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Sample records for alpha-fetoproteins

  1. Subcloning and expression of human alpha-fetoprotein gene in ...

    African Journals Online (AJOL)

    Subcloning and expression of human alpha-fetoprotein gene in Pichia pastoris. ... in inducing protein production in auxotrophic media lacking histidine. This protein could be useful in monoclonal antibody production and in diagnostic kit preparations. Keywords: Alpha-fetoprotein, Pichia pastoris, cloning, expression ...

  2. [Increase of alpha-fetoprotein in pancreatic endocrine tumors with hepatic metastases. Apropos of 2 cases].

    Science.gov (United States)

    Lesur, G; Bergemer, A M; Turner, L; Parlier, H; Bernades, P; Dupuy, P

    1996-03-01

    We report two cases of metastatic non-functioning pancreatic endocrine tumour with very elevated plasma levels of alpha-fetoprotein. In these two cases, serial plasma levels of alpha-fetoprotein, initially normal, correlated well with hepatic tumour progression and were associated with fatal outcome. These results suggest that elevated plasma concentration of alpha-fetoprotein may be caused by metastatic pancreatic endocrine tumour and than alpha-fetoprotein serial measurement may be useful in prognostic evaluation.

  3. Diagnostic value of glypican-3 in alpha fetoprotein negative ...

    African Journals Online (AJOL)

    Background: The prognosis of patients with hepatocellular carcinoma(HCC) is generally very poor with a 5-year survival rate of less than 15% since most of them are diagnosed clinically at their late stage.However,the differential diagnosis between alpha fetoprotein(AFP) negative HCC and cirrhotic nodules is still difficult.

  4. Diagnostic value of glypican-3 in alpha fetoprotein negative ...

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... Background: The prognosis of patients with hepatocellular carcinoma(HCC) is generally very poor with a 5-year survival rate of less than 15% since most of ... antigen (CEA), CD34, alpha fetoprotein (AFP) were usually used to .... and a number of immunomarkers have been widely utilized to facilitate the ...

  5. Dosage of alpha-fetoprotein for radioimmunoassay in maternal blood

    International Nuclear Information System (INIS)

    Pandolfo, J.; Jaumandreu, C.A.; Aguirre de Garcia, B.; Robles, A.M.; Touya, E.

    1981-01-01

    Leigthon, Gordon and col. showed that the determination of serum levels of alpha-fetoprotein was useful as a method for the detection of fetal malformations of the neural tube. Due to its important clinical significance, the study of this simple test in women in different stages of pregnancy has been started. A total of 34 patients from the obstetrical external service were studied, with pregnancy stages between 10 and 40 weeks. Having established the incidence and implications of false positive and principally of false negative results, it has been concluded that this technique should be imposed as routine in the evolutive control of pregnancy. (M.B.) [es

  6. Serum alpha-fetoprotein level is higher in hepatitis C than hepatitis ...

    African Journals Online (AJOL)

    Background: The frequency of raised serum alpha-fetoprotein may vary in relation to hepatitis B or C infection in chronic liver disease (CLD). The study evaluated the frequency of hepatitis B and C in patients with chronic liver disease and correlated the levels of serum alpha-fetoprotein with hepatitis B and C infection in the ...

  7. Cellular immunolocalization of alpha-fetoprotein in rat liver.

    Science.gov (United States)

    Woods, J A

    1983-10-01

    Increased synthesis of alpha-fetoprotein (AFP) was induced in rat liver by the administration of 3'-methyl-4-dimethyl-aminoazobenzene. The indirect immunoperoxidase technique was used to detect AFP. Cellular localization of AFP was studied using a number of different fixation procedures. Serial sections stained with immunoglobulin served to determine the extent of diffusion of serum proteins into liver cells during fixation. Background staining was minimized when Lillie's neutral buffered formalin plus acetic acid was used as the fixative. After 3'-methyl-4-dimethylaminoazobenzene ingestion, bile duct cell proliferation occurred. The serum AFP was positive in all rats after 17 days on the diet. In rats with AFP-positive sera the immunohistochemical reaction in mature hepatocytes was positive while bile duct cells and small hepatocytes were negative for AFP.

  8. The radioimmunoassay of serum alpha-fetoprotein levels

    International Nuclear Information System (INIS)

    Kim, Y. H.; Choi, K. A.; Ahn, K. S.; Suh, W. H.; Lee, M. J.

    1982-01-01

    Alpha-fetoprotein (AFP) was first described in the human fetus in 1956 and became a marker protein of primary liver cancer in adults. Serum AFP levels were measured by radioimmunoassay in 212 patients with a variety of malignant and nonmalignant diseases to determine the incidence of leveis elevated above 40 ng/ml. The results obtained are as follows: In 44 cases of total 212 patients, abnormal AFP levels above 40 ng/ml in serum were measured; 24 of 31 patients with primary hepatocellular carcinoma and primary hepatocellular carcinoma with liver cirrhosis (77.4%), 7 of 51 patients with only liver cirrhosis (13.7%), 4 of 10 patients with metastatic liver cancer (40.0%), 4 of 15 patients with chronic hepatitis (26.7%), 2 of 23 patients with acute hepatitis (8.7%), and each one patient with 6 pancreatic carcinoma and 9 cholangiocarcinoma had elevated serum AFP levels. One pregnant woman with gestation 35 weeks had elevated level, but within normal limit during pregnancy

  9. Intermethod discordance for alpha-fetoprotein measurements in Fanconi anemia.

    Science.gov (United States)

    Cassinat, B; Darsin, D; Guardiola, P; Toubert, M E; Rain, J D; Gluckman, E; Schlageter, M H

    2001-08-01

    The significantly higher serum alpha-fetoprotein (AFP) in patients with Fanconi anemia (FA) than in non-FA aplastic patients has potential diagnostic utility, but the increase is method-dependent. The aim of this study was to compare five AFP assays on FA and non-FA samples and to investigate possible explanations for FA-specific discrepancies. Two methods available in our laboratory (Kryptor and IMx) were compared on 59 FA and 27 non-FA patient samples. Kryptor, Immulite, Elecsys, Immuno-I, and Elsa-2 methods were then compared on 14 FA and 14 non-FA patient samples. The AFP glycosylation profile was analyzed by electrophoretic separation in a lectin-containing gel. With all six methods, AFP values were significantly higher in FA than in non-FA patients, but the diagnostic precision and optimal cutoff values varied. Indeed, two methods reached 100% sensitivity and specificity, but in other methods, one or both of these parameters were significantly <100%. Neither heterophilic antibodies nor a specific glycosylation profile was detected in FA samples. AFP results are method-dependent in FA. New methods must be evaluated before use in differential diagnosis of aplastic patients.

  10. Electrophoresis and electro-affinity transfer with specific antibodies to alpha-fetoprotein for detection of circulating immune complexes of alpha-fetoprotein.

    OpenAIRE

    Taketa, Kazuhisa; Ichikawa, Eriko; Taga, Hiroko; Hirai, Hidematsu

    1984-01-01

    A combination of agarose gel electrophoresis and a newly developed technique of electro-affinity transfer was applied to the detection of circulating immune complexes of human alpha-fetoprotein (AFP) and anti-AFP. After electrophoretic transfer to nitrocellulose membrane, to which affinity-purified polyclonal horse antibodies to human AFP were bound, the membranes were treated with or without rabbit immunoglobulins to human AFP, followed by overlaying with horseradish peroxidase-labeled goat ...

  11. Maternal serum alpha fetoprotein among pregnant females in Alexandria.

    Science.gov (United States)

    Baghagho, Ehssan E; Kharboush, Ibrahim F; El-Kaffash, Dalal M; KarKour, Tarek A; Ismail, Suzan R; Mortada, Mona M

    2004-01-01

    Maternal serum alpha fetoprotein (MSAFP) was introduced as a screening test for congenital malformations especially neural tube defects (NTDs) two decades ago. However, many factors were known to affect its level. From these are racial differences and maternal weight. The aim of the present work is to illustrate the normal distribution of MSAFP among working pregnant women in Alexandria in gestational age 16-18 weeks, to identify some of its determinants, and to determine the specificity and sensitivity of MSAFP for the detection of congenital anomalies and adverse pregnancy outcome. A sample of 608 pregnant working women who were 16-18 week gestation was recruited for the study from the antenatal clinic affiliated to Gamal Abdel Nasser Health Insurance Hospital in Alexandria. The enrolled women were interviewed using a structured questionnaire and a blood sample was collected from each of them to measure the level of MSAFP. At the expected time of delivery, Gamal Abd el Nasser Health Insurance Hospital was visited to collect data about the outcome of pregnancy of the enrolled women. The median of MSAFP level for deliveries with no congenital anomalies were 25.5, 33.5, and 53.2 IU/ml, at gestational weeks 16, 17 and 18 respectively. The significant variables related positively to MSAFP level included abortion or stillbirth, congenital anomalies in the index pregnancy, gestational age, bleeding during pregnancy, gestational diabetes, twin pregnancy, consanguinity between maternal parents, history of congenital or genetic diseases in maternal family, and caesarian section deliveries. Fatigue score was negatively correlated to MSAFP level. Using MSAFP multiples of median (MOM), 42.9 % of abortions and stillbirths, 57.1 % of twin pregnancies, 31.25 % of preterm deliveries and 27.3 % of low birth weight had levels of 3 MOM or more. One fourth of the congenital anomalies were below 0.5 MOM and 41.7 % were at or above 3 MOM. The sensitivity of MSAFP test for the detection

  12. Autism Spectrum Disorders and Maternal Serum alpha-Fetoprotein Levels During Pregnancy

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Grove, Jakob; Hougaard, David M

    2011-01-01

    Objective: Numerous studies have been trying to disentangle the complex pathophysiology of autism spectrum disorders (ASD). In our study, we explored the potential role of maternal serum (MS) alpha-fetoprotein (AFP) in the prediction and the pathophysiology of ASD. Methods: A total of 112 patients...

  13. Fifty years of discovery of alpha-fetoprotein as the first tumor marker

    Directory of Open Access Journals (Sweden)

    Nikulina Dina

    2015-01-01

    Full Text Available Alpha-fetoprotein represents the most prominent oncobiomarker, widely used in the diagnosis of hepatocellular carcinoma for monitoring of tumor progression, presence of metastasis, assessment of cancer prognosis and successful antitumor therapeutic measures. Yuri Semenovich Tatarinov is a Russian scientist who first published antigen specific for human hepatocellular carcinoma in 1963. To commemorate the 50th anniversary of the discovery of alpha-fetoprotein, 9th International Scientific- Practical Conference entitled “Achievements of fundamental science and translational medicine capabilities in solving actual problems of practical public health”, was held from May 6-8th, 2013 in Astrakhan, Russia. The conference was held in memory of historical scientific work of Yuri Semenovich Tatarinov. [Projekat Ministarstva nauke Republike Srbije, br. 175056

  14. The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

    International Nuclear Information System (INIS)

    Arrieta, Oscar; Cacho, Bernardo; Morales-Espinosa, Daniela; Ruelas-Villavicencio, Ana; Flores-Estrada, Diana; Hernández-Pedro, Norma

    2007-01-01

    Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng/mL. Prospective studies are required to

  15. Autism Spectrum Disorders and Maternal Serum alpha-Fetoprotein Levels During Pregnancy

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Grove, Jakob; Hougaard, David M

    2011-01-01

    Objective: Numerous studies have been trying to disentangle the complex pathophysiology of autism spectrum disorders (ASD). In our study, we explored the potential role of maternal serum (MS) alpha-fetoprotein (AFP) in the prediction and the pathophysiology of ASD. Methods: A total of 112 patients...... role in the pathophysiology of ASD makes AFP a good candidate for further larger-scale studies to confirm such an association and to determine whether this pattern is unique to ASD or related to other psychiatric disorders as well....

  16. Alpha fetoprotein

    Science.gov (United States)

    ... Creasy and Resnik's Maternal-Fetal Medicine: Principles and Practice . 7th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 30. Review Date 8/26/2017 Updated by: Peter J Chen, MD, FACOG, Associate Professor of OBGYN at Cooper Medical School at Rowan ...

  17. Regression of hepatocarcinoma cells using RNA aptamer specific to alpha-fetoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Ju [Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin 448-701 (Korea, Republic of); Lee, Seong-Wook, E-mail: SWL0208@dankook.ac.kr [Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin 448-701 (Korea, Republic of)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Identification of RNA aptamer specific to AFP with high affinity. Black-Right-Pointing-Pointer Specific induction of HCC proliferation by AFP. Black-Right-Pointing-Pointer Efficient increase in oncogene expression by AFP. Black-Right-Pointing-Pointer Efficient inhibition of AFP-mediated HCC proliferation by the aptamer. Black-Right-Pointing-Pointer Efficient suppression of AFP-induced oncogene expression of by the aptamer. -- Abstract: Alpha-fetoprotein (AFP) is a cancer-associated fetal protein and has long been utilized as a serum fetal defect/tumor marker to monitor distress/disease progression. In addition, AFP is closely associated with the proliferation of hepatocellular carcinoma. Thus, direct targeting of AFP has been recommended for a therapeutic strategy against hepatocellular carcinoma. In this study, we developed and characterized an RNA aptamer that specifically bound to the alpha-fetoprotein using SELEX technology. The aptamer interacted with the AFP with a K{sub D} of {approx}33 nM. Importantly, the identified aptamer specifically and efficiently inhibited the AFP-mediated proliferation of hepatocarcinoma cells in a dose dependent manner. Moreover, the aptamer efficiently down-regulated AFP-induced expression of oncogenes in the cells. These results indicate that an AFP-specific RNA aptamer could be a useful therapeutic and diagnostic agent against AFP-related hepatocellular carcinoma.

  18. Fabrication of protein microarrays for alpha fetoprotein detection by using a rapid photo-immobilization process

    Directory of Open Access Journals (Sweden)

    Sirasa Yodmongkol

    2016-03-01

    Full Text Available In this study, protein microarrays based on sandwich immunoassays are generated to quantify the amount of alpha fetoprotein (AFP in blood serum. For chip generation a mixture of capture antibody and a photoactive copolymer consisting of N,N-dimethylacrylamide (DMAA, methacryloyloxy benzophenone (MaBP, and Na-4-styrenesulfonate (SSNa was spotted onto unmodified polymethyl methacrylate (PMMA substrates. Subsequently to printing of the microarray, the polymer and protein were photochemically cross-linked and the forming, biofunctionalized hydrogels simultaneously bound to the chip surface by short UV- irradiation. The obtained biochip was incubated with AFP antigen, followed by biotinylated AFP antibody and streptavidin-Cy5 and the fluorescence signal read-out. The developed microarray biochip covers the range of AFP in serum samples such as maternal serum in the range of 5 and 100 ng/ml. The chip production process is based on a fast and simple immobilization process, which can be applied to conventional plastic surfaces. Therefore, this protein microarray production process is a promising method to fabricate biochips for AFP screening processes. Keywords: Photo-immobilization, Protein microarray, Alpha fetoprotein, Hydrogel, 3D surface, Down syndrome

  19. CONCANAVALIN-A VARIANTS OF ALPHA-FETOPROTEIN IN FIRST TRIMESTER FETUSES WITH TRISOMY-21 AND WITH NORMAL KARYOTYPES

    NARCIS (Netherlands)

    LOS, FJ; JANSE, HC; BRANDENBURG, H; DEVRIJ, RW; DEBRUIJN, HWA

    1995-01-01

    Total alpha-fetoprotein (AFP) concentrations and proportions of AFP non-reactive with the lectin concanavalin A (Con A) were studied in extracellular fluid of 22 first-trimester fetuses. Total AFP concentrations were significantly lower in fetuses with Down's syndrome than in those with

  20. Female Mice Deficient in Alpha-Fetoprotein Show Female-Typical Neural Responses to Conspecific-Derived Pheromones

    NARCIS (Netherlands)

    Brock, O.; Keller, M.; Douhard, Q.; Bakker, J.

    2012-01-01

    The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estradiol, that exposure to

  1. Alpha-fetoprotein is a predictor of outcome in acetaminophen-induced liver injury

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2005-01-01

    An increase in alpha-fetoprotein (AFP) following hepatic necrosis is considered indicative of hepatic regeneration. This study evaluated the prognostic value of serial AFP measurements in patients with severe acetaminophen-induced liver injury. Prospectively, serial measurements of AFP were...... performed in 239 patients with acetaminophen intoxication and a peak alanine aminotransferase (ALT) level above 1000 U/L. AFP was measured using an enzyme-linked immunoassay (EIA) with a detection limit below 0.4 microg/L. The optimum threshold of AFP to discriminate nonsurvivors was identified. An increase......%. In conclusion, an increase in AFP was strongly associated with a favorable outcome in patients with acetaminophen-induced liver injury. AFP may be useful as a supplement to existing prognostic criteria. We suggest that the introduction of highly sensitive EIAs for the detection of AFP will require...

  2. Late solitary pelvic metastasis of hepatocellular carcinoma mimicking alpha-fetoprotein-producing gynaecologic tumour

    Directory of Open Access Journals (Sweden)

    Ji He Kim

    2018-01-01

    Full Text Available Extrahepatic spread of hepatocellular carcinoma (HCC is uncommon; and, pelvic metastasis, in particular, is extremely rare. A 71-year-old woman was admitted for evaluation of pelvic solitary solid mass. She had undergone a left lobectomy 28 years previously. Magnetic resonance imaging of the abdomen and pelvis demonstrated a heterogeneous mass in the right pelvic cavity, whereas no space-occupying lesions or ascites were detected in the liver. CA 125 levels were within normal limits; however, serum alpha-fetoprotein levels were markedly elevated. She underwent laparoscopic pelvic mass excision, total hysterectomy, and bilateral salpingo-oophorectomy. Histopathologic findings and immunochemical staining results indicated metastatic HCC. Herein, we report an unusual case of a patient with solitary recurrence in the pelvic cavity 28 years after initial diagnosis and treatment.

  3. Specific Genetic Immunotherapy Induced by Recombinant Vaccine Alpha-Fetoprotein-Heat Shock Protein 70 Complex

    Science.gov (United States)

    Wang, Xiaoping; Lin, Huanping; Wang, Qiaoxia

    Purposes: To construct a recombinant vaccine alpha-fetoprotein (AFP)-heat shock protein (HSP70) complex, and study its ability to induce specific CTL response and its protective effect against AFP-producing tumor. Material/Methods: A recombinant vaccine was constructed by conjugating mouse alpha-fetoprotein to heat shock protein 70. By way of intracutaneous injection, mice were primed and boosted with recombinant vaccine mAFP/HSP70, whereas single mAFP or HSP70 injection as controls. The ELISPOT and ELISA were used to measure the frequency of cells producing the cytokine IFN-γ in splenocytes and the level of anti-AFP antibody of serum from immunized mice respectively. In vivo tumor challenge were carried out to assess the immune effect of the recombinant vaccine. Results: By recombinant mAFP/HSP70 vaccine immunization, the results of ELISPOT and ELISA showed that the number of splenic cells producing IFN-γ and the level of anti-AFP antibody of serum were significantly higher in mAFP/HSP70 group than those in mAFP and HSP70 groups (108.50±11.70 IFN-γ spots/106 cells vs 41.60±10.40 IFN-γ spots/106 cells, 7.32±3.14 IFN-γ spots/106 cells, Pimmune adjuvant. Sequential immunization with recombinant mAFP/HSP70 vaccine could generate effective antitumor immunity on AFP-producing tumor. The recombined mAFP/HSP70 vaccine may be suitable for serving as an immunotherapy for hepatocellular carcinoma.

  4. Validation of the alpha-fetoprotein model for hepatocellular carcinoma recurrence after transplantation in an Asian population.

    Science.gov (United States)

    Rhu, Jinsoo; Kim, Jong Man; Choi, Gyu Seong; Kwon, Choon Hyuck David; Joh, Jae-Won

    2018-02-20

    This study was designed to validate the alpha-fetoprotein model for predicting recurrence after liver transplantation in Korean hepatocellular carcinoma patients. Patients who underwent liver transplantation for hepatocellular carcinoma at Samsung Medical Center between 2007 and 2015 were included. Recurrence, overall survival, and disease-specific survival of patients divided by both the Milan criteria and the alpha-fetoprotein model were compared using Kaplan-Meier log-rank test. The predictability of the alpha-fetoprotein model compared to the Milan criteria was tested by means of net reclassification improvement analysis applied to patients with a follow-up of at least 2 years. A total of 400 patients were included in the study. Patients within Milan criteria had 5-year recurrence, and overall survival rates of 20.9% and 76.3% respectively, compared to corresponding rates of 50.3% and 55.7%, respectively, for patients who were beyond Milan criteria. Alpha-fetoprotein model low risk patients had 5-year recurrence and overall survival rates of 21.1% and 76.2%, respectively, compared to corresponding rates of 57.7% and 52.2%, respectively, in high risk patients (P<0.001, all). Although overall net reclassification improvements were statistically nonsignificant for recurrence (NRI=1.7%, Z=0.30, p=0.7624), and overall survival (NRI=9.0%, Z=1.60, p=0.1098), they were significantly better for predicting no recurrence (NRI=6.6%, Z=3.16, p=0.0016) and no death. (NRI=7.7%, Z=3.65, p=0.0003) CONCLUSIONS: The alpha-fetoprotein model seems to be a promising tool for liver transplantation candidacy, but further investigation is needed.

  5. Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang ZG

    2015-12-01

    Full Text Available Zhiguo Zhang,1 Yanying Zhang,2 Yeying Wang,1 Lingling Xu,3 Wanju Xu3 1Department of Clinical Laboratory, Zhangqiu Maternity and Child Care Hospital, Zhangqiu, 2Department of Clinical Laboratory, Zaozhuang City Wangkai Infection Hospital, Zaozhuang, 3Department of Clinical Laboratory, Qianfoshan Hospital, Jinan, People’s Republic of China Abstract: Currently, there is no reliable biomarker for use in diagnosing alpha-fetoprotein (AFP-negative hepatocellular carcinoma (HCC. Such a biomarker would aid in making an early diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. This study examined AFP-L3 and Golgi protein 73 (GP73 as candidate biomarkers for AFP-negative HCC. The affinity adsorption method and enzyme-linked immunoassays were separately used to determine serum levels of AFP-L3 and GP73 in 50 patients with AFP-negative HCC, 30 non-HCC patients, and 50 healthy subjects. Fifty percent of patients with AFP-negative HCC tested positive for AFP-L3, while 3.33% of non-HCC patients and 2.00% of healthy subjects were AFP-L3 positive. Patients with AFP-negative HCC had significantly higher serum levels of AFP-L3 compared to non-HCC patients and healthy individuals; however, there was no significant difference in the AFP-L3 levels of non-HCC patients and healthy subjects. Sixty-six percent of patients with AFP-negative HCC tested positive for GP73, while 10% of non-HCC patients and 0% of healthy subjects were GP73-positive. Patients with AFP-negative HCC had significantly higher serum levels of GP73 compared to non-HCC patients and healthy subjects, but there was no significant difference between the GP73 levels of non-HCC patients and healthy individuals. Moreover, 20 patients with AFP-negative HCC were both AFP-L3- and GP73-positive, while no non-HCC patients or healthy subjects tested positive for both markers. Either AFP-L3 or GP73 may be used as a biomarker for diagnosing AFP-negative HCC, while their combined use

  6. Hepatocellular carcinoma (HCC) and diagnostic significance of alpha-fetoprotein (AFP)

    International Nuclear Information System (INIS)

    Baig, J.A.; Alam, J.M.; Baig, M.; Mahmood, S.R.; Shaheen, R.; Waheed, A.

    2009-01-01

    Alpha-fetoprotein (alpha-fetoprotein, AFP) is a Glycoprotein, belonging to the intriguing class of onco-development protein. Generally designated as tumour marker, AFP is recognized as an important blood component, having specific diagnostic utilities Elevation of its level up to pathological range in adults correlate with the appearance of several malignant and chronic conditions, such as hepatocellular carcinoma (HCC) and chronic liver disease, respectively. To evaluate the diagnostic significance of AFP in HCC, a study was carried out for a period of two years (Jan. 2004 to Dec. 2005) A brief history of Patients was taken with clinical symptoms and signs and initial diagnosis. Patients admitted in wards or visiting OPDs with diagnosis or suspicions of HCC and additional conditions of Chronic Liver disease (CLDs), hepatitis C (HCV) and hepatitis B viral (HBV) infections, were selected and classified according to gender. When confirmed, their HCC status was evaluated and classified according to clinical condition. In 1012 adults including, males 762 (75.3%) and females 250 (24.7%) patients suspected of or diagnosed with HCC and presence of HBV and HCV infections. Out of 480 males, who depicted elevated AFP levels, 39 (8.13%) were diagnosed with HCC. Similarly, 7 (5.34%) females out of 131 with elevated levels of AFP were diagnosed with HCC. Mean elevated AFP levels in all HCC patients were, 421+-59 mu g/ml (range 157-4019 mu g/ml) in males and 163+-32 mu g/ml (range 101-2341 mu g/ml) in females. In males, the overall estimated mean AFP elevated values were analyzed to be 514 mu g/ml (range 67-4019+-59 mu g/ml), whereas in females it was 396+-42 mu g/ml (range 21-2341 mu g/ml). It was also noted that 43 (8.96%) males and 7 (5.34%) female patients, exhibited elevated levels of AFP, however, found negative for HCV and HBV infections. It is concluded that AFP is a significant markers for Hepatocellular carcinoma, helpful in assessing problems in management of HCC and

  7. Routine ultrasonography compared with maternal serum alpha-fetoprotein for neural tube defect screening.

    Science.gov (United States)

    Norem, Carol T; Schoen, Edgar J; Walton, David L; Krieger, Robyn C; O'Keefe, Jennifer; To, Trinh T; Ray, G Thomas

    2005-10-01

    This study was done to estimate the value of prenatal maternal serum alpha-fetoprotein (MSAFP) screening compared with that of routine ultrasonography in the diagnosis of neural tube defects (NTDs). An integrated database was used retrospectively to identify cases of NTDs among 219,000 consecutive pregnancy outcomes observed during a 7-year period at 40 Kaiser Permanente facilities in Northern California. We specifically examined types of NTD and the tests used to diagnose cases. We identified 189 NTD cases, 102 of which had received MSAFP screening. Results of MSAFP testing were negative in 25 (25%) of these 102 cases. Without other testing, these 25 NTD diagnoses would have been missed. These included 15 (38%) of the 40 spina bifida cases screened, 6 (67%) of the 9 encephalocele cases screened, and 4 (8%) of the 53 anencephaly cases screened. Of the 186 NTD cases diagnosed prenatally, 115 (62%) were initially detected by routine ultrasonography administered during the second trimester without knowledge of MSAFP values; 69 (37%) were diagnosed by targeted ultrasonography after MSAFP screening indicated a higher risk for NTD; and 2 (1%) were diagnosed by pathology examination after miscarriage. Compared with MSAFP performed alone for screening, routine second-trimester ultrasonography was more likely to discover an NTD.

  8. Reference Intervals of Alpha-Fetoprotein and Carcinoembryonic Antigen in the Apparently Healthy Population.

    Science.gov (United States)

    Zhang, Gao-Ming; Guo, Xu-Xiao; Ma, Xiao-Bo; Zhang, Guo-Ming

    2016-12-12

    BACKGROUND The aim of this study was to calculate 95% reference intervals and double-sided limits of serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI EP28-A3 guideline. MATERIAL AND METHODS Serum AFP and CEA values were measured in samples from 26 000 healthy subjects in the Shuyang area receiving general health checkups. The 95% reference intervals and upper limits were calculated by using MedCalc. RESULTS We provided continuous reference intervals from 20 years old to 90 years old for AFP and CEA. The reference intervals were: AFP, 1.31-7.89 ng/ml (males) and 1.01-7.10 ng/ml (females); CEA, 0.51-4.86 ng/ml (males) and 0.35-3.45ng/ml (females). AFP and CEA were significantly positively correlated with age in both males (r=0.196 and r=0.198) and females (r=0.121 and r=0.197). CONCLUSIONS Different races or populations and different detection systems may result in different reference intervals for AFP and CEA. Continuous reference intervals of age changes are more accurate than age groups.

  9. Capillary electrochromatography immunoassay for alpha-fetoprotein based on poly(guanidinium ionic liquid) monolithic material.

    Science.gov (United States)

    Liu, Cuicui; Deng, Qiliang; Fang, Guozhen; Dang, Meng; Wang, Shuo

    2017-08-01

    Alpha-fetoprotein (AFP) is widely used as a tumor marker for the serum diagnosis of primary hepatoma. Sensitive detection of AFP level plays an important role in the early diagnosis of disease and highly reliable prediction. In this study, a novel non-competitive immunoassay (IA) based on poly(guanidinium ionic liquid) monolithic material was developed for detecting ultra trace levels of AFP in capillary electrochromatography (CEC) mode. The AFP was mixed with an excess amount of fluorescently labeled antibody. After incubation, the immunocomplex was separated from the free labeled antibody and detected by CEC coupled with laser-induced fluorescence detector. Under the optimized conditions, the developed CEC-IA performed a low detection limit of 0.05 μg L -1  (S/N = 3) and a wide linearity ranging from 0.1 to 1000 μg L -1 for AFP, which can be largely attributed to the high separation and enrichment efficiency of poly(guanidinium ionic liquid) monolithic material for the targets. The application of this method was demonstrated by determining AFP in human serum. Copyright © 2017. Published by Elsevier Inc.

  10. First trimester maternal serum alpha-fetoprotein is not raised in pregnancies with open spina bifida.

    Science.gov (United States)

    Spencer, Kevin; Khalil, Asma; Brown, Louise; Mills, Ian; Horne, Hannah

    2014-02-01

    Two recent studies have suggested that maternal serum alpha fetoprotein (AFP) levels are increased in the first trimester of pregnancies in which the fetus has an open spina bifida. This is contrary to previously published studies. This study assesses further whether maternal serum AFP is elevated in the first trimester in cases with open spina bifida. Cases with open spina bifida were identified from our fetal database, and corresponding first trimester screening samples were retrieved and analysed for maternal serum AFP. A control group was selected by taking three samples matched for gestational age (exact day), ethnicity and smoking status and received in the laboratory on the same day. AFP was measured with the Kryptor platform and free β-hCG and pregnancy-associated plasma protein A results were available from the fetal database. Thirty-nine open spina bifida cases were identified with a control group of 126 cases. The median multiple of the median AFP in the cases were not significantly different from the controls (0.92 vs 1.06 p = 0.3511) as was the case for free β-hCG (0.87 vs 0.95 p = 0.7146) and pregnancy-associated plasma protein A (1.04 vs 1.04 p = 0.261). Our results confirm that maternal serum biochemical markers in the first trimester are unable to distinguish cases in which the fetus has open spina bifida. © 2013 John Wiley & Sons, Ltd.

  11. Role of Maternal Serum Alpha-Fetoprotein and Ultrasonography in Contemporary Detection of Spina Bifida.

    Science.gov (United States)

    Racusin, Diana A; Villarreal, Sarah; Antony, Kathleen M; Harris, R Alan; Mastrobattista, Joan; Lee, Wesley; Shamshirsaz, Alireza A; Belfort, Michael; Aagaard, Kjersti M

    2015-12-01

    Midtrimester maternal serum alpha-fetoprotein (MSAFP) and sonographic evaluation have been used to screen for spina bifida. With the increased uptake of cell-free DNA (cfDNA) and first trimester screening, MSAFP levels may no longer be obtained routinely. Our aim was to evaluate a pediatric neurosurgical referral center database of spina bifida cases to determine the antenatal detection rate and means of diagnosis. Nested case series of all spina bifida cases referred postnatally from 2007 to 2013. Data were abstracted from the maternal record and rates of antenatal detection with MSAFP and sonographic screening were determined. Of the 105 postnatally referred cases, 11.4% (12/105) were not identified until delivery. Overall, 39% of the cases had MSAFP screening. The odds ratio for sonogram-based detection of spina bifida was 4.9 (95% confidence interval, 2-11.9). Of the neonatally detected cases, 100% had prenatal care and 91.6% (11 of the 12 cases) had documented sonography. We have found that 11.4% of the spina bifida cases were not detected before delivery. Nine out of the 12 cases of antenatally missed spina bifida were not screened using MSAFP. Our findings support the approach of midtrimester MSAFP screening combined with sonographic evaluation. We speculate that prenatal screening with MSAFP is underutilized. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Nanobody medicated immunoassay for ultrasensitive detection of cancer biomarker alpha-fetoprotein.

    Science.gov (United States)

    Chen, Jing; He, Qing-hua; Xu, Yang; Fu, Jin-heng; Li, Yan-ping; Tu, Zhui; Wang, Dan; Shu, Mei; Qiu, Yu-lou; Yang, Hong-wei; Liu, Yuan-yuan

    2016-01-15

    Immunoassay for cancer biomarkers plays an important role in cancer prevention and early diagnosis. To the development of immunoassay, the quality and stability of applied antibody is one of the key points to obtain reliability and high sensitivity for immunoassay. The main purpose of this study was to develop a novel immunoassay for ultrasensitive detection of cancer biomarker alpha-fetoprotein (AFP) based on nanobody against AFP. Two nanobodies which bind to AFP were selected from a phage display nanobody library by biopanning strategy. The prepared nanobodies are clonable, thermally stable and applied in both sandwich enzyme linked immunoassay (ELISA) and immuno-PCR assay for ultrasensitive detection of AFP. The limit detection of sandwich ELISA setup with optimized nanobodies was 0.48ng mL(-1), and the half of saturation concentration (SC50) value was 6.68±0.56ng mL(-1). These nanobodies were also used to develop an immuno-PCR assay for ultrasensitive detection of AFP, its limit detection values was 0.005ng mL(-1), and the linear range was 0.01-10,000ng mL(-1). These established immunoassays based on nanobodies were highly specific to AFP and with negligible cross reactivity with other tested caner biomarkers. Furthermore, this novel concept of nanobodies mediated immunoassay may provide potential applications in a general method for the ultrasensitive detection of various cancer biomarkers. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Fast detection of alpha-fetoprotein-L3 using lens culinaris agglutinin immobilized gold nanoparticles.

    Science.gov (United States)

    Sun, Ying; Qin, Liubin; Liu, Dejun; Liu, Changhong; Sun, Yongwei; Duan, Yourong

    2014-06-01

    Colloidal gold is extensively used for molecular sensing because that the surface plasmon resonance (SPR) bands are affected by changes in the dielectric properties in the close vicinity of these structures due to the binding of ligands to the corresponding receptor molecules immobilized onto the nanostructures through chemi- or physisorption. We describe a simple method for the detection of Alpha-Fetoprotein-L3 which is a new generation of tumor marker for hepatocellular carcinoma (HCC) based on the aggregation of Lens culinaris agglutinin (LCA) Immobilized Gold Nanoparticles. The LCA conjugated GNPs obtained were 15-20 nm in diameter. The visible color change of the gold nanoparticles from purple to blue on interaction with 100 ng/mL of AFP-L3 is the principle applied here for the sensing of AFP-L3 level. UV/Vis spectroscopy also allows assay monitoring by quantifying the red shift of the plasmon resonance wavelength. With this method, the protein AFP-L3 can be rapidly detected as demanded for clinical diagnosis.

  14. Quantum dot-based immunochromatography test strip for rapid, quantitative and sensitive detection of alpha fetoprotein.

    Science.gov (United States)

    Yang, Qiuhua; Gong, Xiaoqun; Song, Tao; Yang, Jiumin; Zhu, Shengjiang; Li, Yunhong; Cui, Ye; Li, Yingxin; Zhang, Bingbo; Chang, Jin

    2011-12-15

    Rapid, quantitative detection of tumor markers with high sensitivity and specificity is critical to clinical diagnosis and treatment of cancer. We describe here a novel portable fluorescent biosensor that integrates quantum dot (QD) with an immunochromatography test strip (ICTS) and a home-made test strip reader for detection of tumor markers in human serum. Alpha fetoprotein (AFP), which is valuable for diagnosis of primary hepatic carcinoma, is used as a model tumor marker to demonstrate the performance of the proposed immunosensor. The principle of this sensor is on the basis of a sandwich immunoreaction that was performed on an ICTS. The fluorescence intensity of captured QD labels on the test line and control line served as signals was determined by the home-made test strip reader. The strong luminescence and robust photostability of QDs combined with the promising advantages of an ICTS and sensitive detection with the test strip reader result in good performance. Under optimal conditions, this biosensor is capable of detecting as low as 1 ng/mL AFP standard analyte in 10 min with only 50 μL sample volume. Furthermore, 1000 clinical human serum samples were tested by both the QD-based ICTS and a commercial electrochemiluminescence immunoassay AFP kit simultaneously to estimate the sensitivity, specificity and concordance of the assays. Results showed high consistency except for 24 false positive cases (false positive rate 3.92%) and 17 false negative cases (false negative rate 4.38%); the error rate was 4.10% in all. This demonstrates that the QD-based ICTS is capable of rapid, sensitive, and quantitative detection of AFP and shows a great promise for point-of-care testing of other tumor markers. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kao, W.-Y. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Chiou, Y.-Y., E-mail: yychiou@vghtpe.gov.tw [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hung, H.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Su, C.-W., E-mail: cwsu2@vghtpe.gov.tw [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Chou, Y.-H. [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, J.-C. [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan (China); Huo, T.-I. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Huang, Y.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, W.-C. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China)

    2012-05-15

    Aims: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). Materials and methods: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of {>=}100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. Results: After a median follow-up of 26.7 {+-} 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and {>=}100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of {>=}100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count {<=}10{sup 5}/mm{sup 3} (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. Conclusions: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

  16. Development of graphite carbon nitride based fluorescent immune sensor for detection of alpha fetoprotein

    Science.gov (United States)

    Li, Yike; Dong, Lingyu; Wang, Xiangfeng; Liu, Yuan; Liu, Hailing; Xie, Mengxia

    2018-05-01

    A novel fluorescent immunosensor for determination of alpha fetoprotein (AFP) in serum samples has been developed based on the nano graphite carbon nitride (g-C3N4) as fluorophore and immunomagnetic beads (MBs) as separation material. The bulk g-C3N4 was obtained by thermal polymerization of melamine, and then carboxylated and exfoliated to acquire the carboxylated nano g-C3N4 (c-n-g-C3N4), which has been characterized and the results showed that it had excellent fluorescent properties. The antibodies of AFP (Ab1, Ab2) were conjugated to the MBs and the c-n-g-C3N4, respectively. In assay of AFP detection, the magnetic part of the immunosensor, MBs-Ab1, would form the sandwich type complex with the signal part of the sensor, c-n-g-C3N4-Ab2. The developed immunosensor could simplify the process of separation due to the MBs. The results illustrated that proposed approach held a good linearity between the fluorescence intensity of the sensor and the AFP concentration ranging from 5-600 ng/mL with the limit of detection as low as 0.43 ng/mL, and its spiking recoveries ranged from 98.2% to 105.9% with RSD from 2.1% to 3.5%. The fabricated fluorescent immunosensor possesses the merits of good sensitivity, excellent selectivity, high biocompatibility and low cost, and the results provide a novel clue to develop immunosensor for determination of the biomarkers in complex matrices.

  17. Measurement of alpha-fetoprotein in maternal serum: three commercial radioimmunoassay kits and two non-commercial radioimmunoassays compared

    International Nuclear Information System (INIS)

    Forest, J.C.; Verreault, F.; Pouliot, M.

    1982-01-01

    We evaluated three commercial radioimmunoassay kits (Amersham, Dainabot, Clinical Assays) and two non-commercial methods for determining alpha-fetoprotein in maternal serum during pregnancy. All five procedures were found to be acceptable with respect to practicability, sensitivity, linearity, and precision. Similar results were obtained with Dainabot, Clinical Assays, and the two non-commercial methods, but the Amersham method revealed a proportional error, results being about 20% lower than those by the other methods. Use of the international unit system is suggested for reporting results for AFP, to facilitate comparison between methods and laboratories

  18. Significance of radioimmunoassay of human chorionic gonadotropin and alpha fetoprotein in nonseminomatous germ cell tumors of the testis

    International Nuclear Information System (INIS)

    Kausitz, J.; Hupka, S.; Cerny, V.; Bohunicky, L.; Korec, S.

    1980-01-01

    Radioimmunoassays human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) made in 49 patients with nonseminomatous testicular tumors showed that these investigations make the diagnosis more precise, permit to follow up the dynamics of the course of the disease and the effectiveness of treatment and may help to reveal the presence of otherwise undetectable tumorous metastases. The significance of these assays is enhanced if the two tumorous proteins are investigated in parallel. The results proved positive in 43 (87.8%) and false negative in 6 (12.2%) of the patients. The absence of HCG and AFP production in some patients with active disorder has not as yet been elucidated. (author)

  19. Significance of radioimmunoassay of human chorionic gonadotropin and alpha fetoprotein in nonseminomatous germ cell tumors of the testis

    Energy Technology Data Exchange (ETDEWEB)

    Kausitz, J.; Hupka, S. (Institute for Postgradual Training of Physicians and Pharmaceutists, Bratislava (Czechoslovakia)); Cerny, V.; Bohunicky, L.; Korec, S. (Ustav Klinickej Onkologie, Bratislava (Czechoslovakia))

    1980-01-01

    Radioimmunoassays human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) made in 49 patients with nonseminomatous testicular tumors showed that these investigations make the diagnosis more precise, permit to follow up the dynamics of the course of the disease and the effectiveness of treatment and may help to reveal the presence of otherwise undetectable tumorous metastases. The significance of these assays is enhanced if the two tumorous proteins are investigated in parallel. The results proved positive in 43 (87.8%) and false negative in 6 (12.2%) of the patients. The absence of HCG and AFP production in some patients with active disorder has not as yet been elucidated.

  20. Quantum-dot-based homogeneous time-resolved fluoroimmunoassay of alpha-fetoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chen Meijun; Wu Yingsong; Lin Guanfeng; Hou Jingyuan; Li Ming [Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515 (China); Liu Tiancai, E-mail: liutc@smu.edu.cn [Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, 510515 (China)

    2012-09-05

    Highlights: Black-Right-Pointing-Pointer QDs-based homogeneous time-resolved fluoroimmunoassay was developed to detect AFP. Black-Right-Pointing-Pointer The conjugates were prepared with QDs-doped microspheres and anti-AFP McAb. Black-Right-Pointing-Pointer The conjugates were prepared with LTCs and another anti-AFP McAb. Black-Right-Pointing-Pointer Excess amounts of conjugates were used for detecting AFP without rinsing. Black-Right-Pointing-Pointer The wedding of QPs and LTCs was suitable for HTRFIA to detect AFP. - Abstract: Quantum dots (QDs) with novel photoproperties are not widely used in clinic diagnosis, and homogeneous time-resolved fluorescence assays possess many advantages over current methods for alpha-fetoprotein (AFP) detection. A novel QD-based homogeneous time-resolved fluorescence assay was developed and used for detection of AFP, a primary marker for many cancers and diseases. QD-doped carboxyl-modified polystyrene microparticles (QPs) were prepared by doping oil-soluble QDs possessing a 605 nm emission peak. The antibody conjugates (QPs-E014) were prepared from QPs and an anti-AFP monoclonal antibody, and luminescent terbium chelates (LTCs) were prepared and conjugated to a second anti-AFP monoclonal antibody (LTCs-E010). In a double-antibodies sandwich structure, QPs-E014 and LTCs-E010 were used for detection of AFP, serving as energy acceptor and donor, respectively, with an AFP bridge. The results demonstrated that the luminescence lifetime of these QPs was sufficiently long for use in a time-resolved fluoroassay, with the efficiency of time-resolved Foerster resonance transfer (TR-FRET) at 67.3% and the spatial distance of the donor to acceptor calculated to be 66.1 Angstrom-Sign . Signals from TR-FRET were found to be proportional to AFP concentrations. The resulting standard curve was log Y = 3.65786 + 0.43863{center_dot}log X (R = 0.996) with Y the QPs fluorescence intensity and X the AFP concentration; the calculated sensitivity was 0

  1. Performance of Alpha Fetoprotein in Combination with Alpha-1-acid Glycoprotein for Diagnosis of Hepatocellular Carcinoma Among Liver Cirrhosis Patients

    Directory of Open Access Journals (Sweden)

    Rino A Gani

    2016-05-01

    Full Text Available Aim: to evaluate the use of alpha-1-acid glycoprotein (AAG for diagnosing hepatocellular carcinoma (HCC, and to combine with alpha fetoprotein (AFP as part of routine examination in liver cirrhosis patients. Methods: this is a diagnostic study using cross-sectional design. A hundred and six patients were included in this study. Baseline data such as age, gender, AFP, AAG, peripheral blood count, AST and ALT were consecutively collected from liver cirrhosis patients with or without HCC. Serum AAG were measured quantitatively using immunoturboditimetric assay and AFP with enzyme immune assay (EIA. Statistical analysis were done using SPSS 13.0. Data comparisons between group were done using Mann-Whitney test. Diagnostic performance for each marker alone was compared to the surrogate use of both markers (combined parallel approach in HCC cases. Results: receiver operating characteristic (ROC analysis showed that area under the curve for AFP AAG combination was 88.1% and higher than AFP only (86.2% or AAG only (76.5% with sensitivity of 83%, 73% and 44%, respectively, at specificity of >80%. Conclusion: our study showed that combination of AFP and AAG is superior than either marker alone in diagnosing HCC in liver cirrhosis patients. Combination of AFP and AAG may be used to prompt early diagnosis screening of HCC. Key words: alpha fetoprotein, alpha-1-acid glycoprotein, biomarker, liver cancer

  2. The association between hypertensive disorders of pregnancy and abnormal second-trimester maternal serum levels of hCG and alpha-fetoprotein

    NARCIS (Netherlands)

    Morssink, LP; Heringa, MP; Beekhuis, [No Value; DeWolf, BTHM; Mantingh, A

    Objective: To examine the association between hypertensive disorders of pregnancy and second-trimester maternal serum alpha-fetoprotein (MSAFP) and hCG levels. Methods: The proportions of abnormal second-trimester MSAFP and hCG levels in the serum samples from 65 women with true pregnancy-induced

  3. ABNORMAL LEVELS OF MATERNAL SERUM HUMAN CHORIONIC-GONADOTROPIN AND ALPHA-FETOPROTEIN IN THE 2ND-TRIMESTER - RELATION TO FETAL WEIGHT AND PRETERM DELIVERY

    NARCIS (Netherlands)

    MORSSINK, LP; KORNMAN, LH; BEEKHUIS, [No Value; DEWOLF, BTHM; MANTINGH, A

    1995-01-01

    The aim of this prospective descriptive cross-sectional study was to examine the clinical significance of abnormal maternal serum human chorionic gonadotropin (MShCG) and alpha-fetoprotein (MSAFP) in the second trimester of pregnancy. The study group comprised 8892 women with a singleton pregnancy,

  4. INCREASED MATERNAL SERUM ALPHA-FETOPROTEIN AND HUMAN CHORIONIC-GONADOTROPIN IN COMPROMISED PREGNANCIES OTHER THAN FOR NEURAL-TUBE DEFECTS OR DOWN-SYNDROME

    NARCIS (Netherlands)

    BEEKHUIS, [No Value; VANLITH, JMM; DEWOLF, BTHM; MANTINGH, A

    Intrauterine fetal death occurred in four women who were 'screen-positive' in a screening programme for neural tube defects (NTDs) and Down syndrome (DS). These women had very high levels of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG). Therefore,

  5. Correlation between preoperative serum alpha-fetoprotein levels and survival with respect to the surgical treatment of hepatocellular carcinoma at a tertiary care hospital in Veracruz, Mexico

    Directory of Open Access Journals (Sweden)

    G. Martínez-Mier

    2017-10-01

    Full Text Available Introduction: Preoperative serum alpha-fetoprotein levels can have predictive value for hepatocellular carcinoma survival. Aim: Our aim was to analyze the correlation between preoperative serum alpha-fetoprotein levels and survival, following the surgical treatment of hepatocellular carcinoma. Methods: Nineteen patients were prospectively followed (07/2005-01/2016. An ROC curve was created to determine the sensitivity and specificity of alpha-fetoprotein in relation to survival (Kaplan-Meier. Results: Of the 19 patients evaluated, 57.9% were men. The mean patient age was 68.1 ± 8.5 years and survival at 1, 3, and 5 years was 89.4, 55.9, and 55.9%. The alpha-fetoprotein cutoff point was 15.1 ng/ml (sensitivity 100%, specificity 99.23%. Preoperative alpha-fetoprotein levels below 15.1, 200, 400, and 463 ng/ml correlated with better 1 and 5-year survival rates than levels above 15.1, 200, 400, and 463 ng/ml (P<.05. Conclusions: Elevated preoperative serum alpha-fetoprotein levels have predictive value for hepatocellular carcinoma survival. Resumen: Introducción: Los niveles séricos de alfafetoproteína (AFP preoperatoria pueden tener valor predictivo para la sobrevida del hepatocarcinoma (HCC. Objetivo: Analizar la correlación entre los niveles séricos de AFP preoperatoria y la sobrevida posterior al tratamiento quirúrgico del HCC. Métodos: Diecinueve pacientes fueron seguidos prospectivamente (julio del 2005-enero del 2016. Se realizó una curva ROC para determinar la sensibilidad y la especificidad de la AFP con relación con la sobrevida (Kaplan-Meier. Resultados: Se evaluó a 19 pacientes, 57.9% hombres, edad media 68.1 ± 8.5 años con sobrevida a 1, 3 y 5 años del 89.4, el 55.9 y el 55.9%. El punto de corte de AFP fue 15.1 ng/ml (sensibilidad 100%, especificidad 99.23%. Los niveles preoperatorios de AFP menores de 15.1, 200, 400 y 463 ng/ml correlacionaron con mejor sobrevida a 1 y 5 años que niveles mayores de AFP (p < 0

  6. Carcinosarcoma of the Uterine Corpus with Alpha-Fetoprotein-Producing Hepatoid Adenocarcinoma: A Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Ryuji Kawaguchi

    2011-07-01

    Full Text Available We report two cases of uterine carcinosarcoma associated with alpha-fetoprotein (AFP-producing hepatoid adenocarcinoma. Samples were obtained from two women aged 63 and 82 years. Serum AFP levels of the two samples were 10,131 and 401 ng/ml, respectively. Histologically, in both cases the tumor cells were composed of hepatoid adenocarcinoma component and sarcoma component including rhabdomyosarcoma. Immunohistochemical analyses revealed that AFP was expressed in the cytoplasm of the carcinomatous component. After surgery, the patients received six courses of carboplatin/paclitaxel chemotherapy, and the serum levels of AFP decreased to normal range. The first patient is alive and well at the 2-year follow-up, while the second patient died of disease 1 year after initial operative treatment. This is, to our knowledge, the second report of carcinosarcoma of the uterine corpus with AFP-producing hepatoid adenocarcinoma, as proven by immunohistochemical analyses.

  7. Binding of alpha-fetoprotein by immobilized monoclonal antibodies during episodes of zero-gravity obtained by parabolic flight

    Science.gov (United States)

    Spooner, Brian S.; Guikema, James A.; Barnes, Grady

    1990-01-01

    Alpha-fetoprotein (AFP), a single-chain polypeptide which is synthesized by the liver and yolk sac of the human fetus, provided a model ligand for assessing the effects of microgravity on ligand binding to surface-immobilized model receptor molecules. Monoclonal antibodies, used as receptors for AFP, were immobilized by covalent attachment to latex microparticles. Zero gravity environment was obtained by parabolic flight aboard NASA 930, a modified KC-135 aircraft. Buring the onset of an episode of zero gravity, ligand and receptor were mixed. Timed incubation (20 s) was terminated by centrifugation, the supernatant removed, and microparticies were assessed for bound AFP by immunochemical methods. The extent of binding was not influenced by microgravity, when compared with 1-G controls, which suggests that aberrant cellular activities observed in microgravity are not the simple expression of altered macromolecular interactions.

  8. Blood Serum Alpha Fetoprotein Enhancer Binding Protein, a Tumor Suppressor, Decreases in Chronic HBV Hepatitis Patients as Hepatocellular Cancer Appears

    Directory of Open Access Journals (Sweden)

    James N. Riggins

    2010-01-01

    Full Text Available Chronic hepatitis increases the risk of hepatocellular carcinoma (HCC. To test whether circulating proteins reflect hepatic carcinogenesis, sera from patients and controls were albumin depleted, enriched for glycoproteins, digested with trypsin, and subjected to reverse phase chromatography and tandem mass spectrometry. Alpha-fetoprotein enhancer binding protein (AFPebp, a tumor suppressor, was repeatedly identified in sera from chronic HBV hepatitis patients. We independently identified and quantified AFPebp with a deuterated, phenylisocyanate-labeled synthetic peptide standard. Elevated AFPebp levels in sera from chronic HBV hepatitis patients decreased as cancer developed. These data suggest that rising AFPebp levels in chronic HBV hepatitis may be protective, while falling levels may contribute to HCC development.

  9. Gastric Composite Tumor of Alpha Fetoprotein-Producing Carcinoma/Hepatoid Adenocarcinoma and Endocrine Carcinoma with Reference to Cellular Phenotypes

    Directory of Open Access Journals (Sweden)

    Akira Suzuki

    2012-01-01

    Full Text Available Alpha-fetoprotein-producing carcinoma (AFPC/hepatoid adenocarcinoma (HAC and neuroendocrine carcinoma (NEC are uncommon in the stomach. Composite tumors consisting of these carcinomas and their histologic phenotypes are not well known. Between 2002 and 2007, to estimate the prevalence of composite tumors consisting of tubular adenocarcinoma, AFPC/HAC and NEC, we reviewed specimens obtained from 294 consecutive patients treated surgically for gastric cancer. We examined histological phenotype of tumors of AFPC or NEC containing the composite tumor by evaluating immunohistochemical expressions of MUC2, MUC5AC, MUC6, CDX2, and SOX2. Immunohistochemically, AFPC/HAC dominantly showed the intestinal or mixed phenotype, and NEC frequently showed the gastric phenotype. In the composite tumor, the tubular and hepatoid components showed the gastric phenotype, and the neuroendocrine component showed the mixed type. The unique composite tumor predominantly showed the gastric phenotype, and the hepatoid and neuroendocrine components were considered to be differentiated from the tubular component.

  10. Diagnostic performance of alpha-fetoprotein, lens culinaris agglutinin-reactive alpha-fetoprotein, des-gamma carboxyprothrombin, and glypican-3 for the detection of hepatocellular carcinoma: a systematic review and meta-analysis protocol.

    Science.gov (United States)

    Huang, Ting-Shuo; Shyu, Yu-Chiau; Turner, Robin; Chen, Huang-Yang; Chen, Pei-Jer

    2013-06-06

    Diagnosis of early-stage hepatocellular carcinoma (HCC) followed by curative resection or liver transplantation offers the best chance for long-term patient survival. Clinically, ultrasonography has suboptimal sensitivity for detecting early-stage HCC. Several serological tests including alpha-fetoprotein (AFP), the ratio of lens culinaris agglutinin-reactive alpha-fetoprotein to total AFP (AFP-L3/AFP), des-gamma carboxyprothrombin (DCP), and glypican-3 (GPC-3) have been widely investigated as diagnostic biomarkers for early-stage HCC in at-risk populations. However, these tests are not recommended for routine HCC screening. Our objective is to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of HCC, particularly early-stage tumors meeting the Milan criteria. We will include cross-sectional studies that consecutively or randomly recruit target populations. We will search the Cochrane Library, Medline, Embase, Science Citation Index, and the Chinese National Knowledge Infrastructure. We will also search the MEDION and ARIF databases to identify diagnostic systematic reviews that include primary studies. Reference lists of relevant reviews will be searched for additional trials. Language restrictions will not be applied. Two reviewers will independently screen study eligibility and extract data. Methodological quality will be assessed according to the revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Two authors will apply the QUADAS-2 assessment to all the included studies, and any discrepancies will be resolved by the third author. The following test characteristics will be extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives, and false negatives. Study-specific estimates of sensitivity and specificity with 95% confidence intervals will be displayed in forest plots. When possible, we will use the bivariate random-effects model or the Rutter

  11. Hepatoid adenocarcinoma of the stomach: an unusual case of elevated alpha-fetoprotein with prior treatment for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Joon Seong Ahn

    2013-06-01

    Full Text Available Hepatoid adenocarcinoma (HAC is a rare type of extrahepatic carcinoma whose morphology is similar to that of hepatocellular carcinoma (HCC. Metachronous HCC and HAC in the same patient is extremely rare. The case of a 68-year-old man with chronic hepatitis B infection who had both HCC and HAC of the stomach is reported herein. Nine years previously this patient had been diagnosed with HCC and received a right lobectomy. HCC that recurred at the caudate lobe at 6 months after the operation was successfully treated with transarterial chemoembolization. The patient was followed up regularly thereafter without evidence of tumor recurrence for 9 years. In July 2010 his serum alpha-fetoprotein (AFP level elevated from 6.5 ng/mL to 625.4 ng/mL, and he developed a probable single metastatic lymph node around the hepatic artery without intrahepatic lesions. Subsequent evaluation with upper endoscopy revealed a 4-cm ulcerative lesion on the antrum of the stomach. Subtotal gastrectomy was performed with lymph-node dissection. Histologic examination revealed a special type of extrahepatic AFP-producing adenocarcinoma-HAC with lymph-node metastasis-which indicates that HAC can be a cause of elevated AFP even in patients with HCC. HAC should be considered if a patient with stable HCC exhibits unusual elevation of AFP.

  12. Screening and Identifying a Novel ssDNA Aptamer against Alpha-fetoprotein Using CE-SELEX

    Science.gov (United States)

    Dong, Lili; Tan, Qiwen; Ye, Wei; Liu, Dongli; Chen, Haifeng; Hu, Hongwei; Wen, Duo; Liu, Yang; Cao, Ya; Kang, Jingwu; Fan, Jia; Guo, Wei; Wu, Weizhong

    2015-01-01

    Alpha-fetoprotein (AFP) is a liver cancer associated protein and has long been utilized as a serum tumor biomarker of disease progression. AFP is usually detected in HCC patients by an antibody based system. Recently, however, aptamers generated from systematic evolution of ligands by exponential enrichment (SELEX) were reported to have an alternative potential in targeted imaging, diagnosis and therapy. In this study, AFP-bound ssDNA aptamers were screened and identified using capillary electrophoresis (CE) SELEX technology. After cloning, sequencing and motif analysis, we successfully confirmed an aptamer, named AP273, specifically targeting AFP. The aptamer could be used as a probe in AFP immunofluorescence imaging in HepG2, one AFP positive cancer cell line, but not in A549, an AFP negative cancer cell line. More interesting, the aptamer efficiently inhibited the migration and invasion of HCC cells after in vivo transfection. Motif analysis revealed that AP273 had several stable secondary motifs in its structure. Our results indicate that CE-SELEX technology is an efficient method to screen specific protein-bound ssDNA, and AP273 could be used as an agent in AFP-based staining, diagnosis and therapy, although more works are still needed. PMID:26497223

  13. Post-synthetic modification of human alpha-fetoprotein revealed by isoelectric focusing controls its immunosuppressive potency

    Energy Technology Data Exchange (ETDEWEB)

    Lester, E. P.; Miller, J. B.; Yachnin, S.

    1977-01-01

    We have demonstrated 3 variants of human alpha-fetoprotein (HAFP) by crossed immunoelectrophoresis, and have correlated the capacity of HAFP isolates to suppress human lymphocyte transformation in vitro with the relative proportion of the electronegative variant, HAFP-3, present in each isolate. We have now isolated HAFP from the serum, ascitic fluid, and saline extract of tumor from a single hepatoma patient, and from an homogenate of fetal livers. When tested for their capacity to inhibit human lymphocyte transformation in vitro, tumor and fetal liver HAFP were found to be extremely potent; serum HAFP had intermediate potency, and ascitic fluid HAFP was the least potent. Analysis of these HAFP isolates by crossed immunoelectrophoresis confirmed the correlation between the proportion of HAFP-3 and the immunosuppressive potency of each isolate. In addition, analysis of these HAFP isolates by isoelectric focusing in polyacrylamide gels containing 8 M urea revealed further evidence of microheterogeneity; at least 6 molecular variants were apparent. The proportion of one of these variants, termed HAFP-3a, in each isolate was correlated with the immunosuppressive potency of the isolate. The sialic acid content of the various HAFP isolates did not vary significantly. Our data suggest that a post-synthetic modification of HAFP occurs, which modulates its immunosuppressive potency.

  14. Enzyme-catalyzed silver deposition on irregular-shaped gold nanoparticles for electrochemical immunoassay of alpha-fetoprotein.

    Science.gov (United States)

    Lai, Wenqiang; Tang, Dianping; Que, Xiaohua; Zhuang, Junyang; Fu, Libing; Chen, Guonan

    2012-11-28

    A new and disposable electrochemical immunosensor was designed for detection of alpha-fetoprotein (AFP), as a model analyte, with sensitivity enhancement based on enzyme-catalyzed silver deposition onto irregular-shaped gold nanoparticles (ISGNPs). The assay was carried out with a sandwich-type immunoassay protocol by using ISGNP-labeled anti-AFP antibodies conjugated with alkaline phosphatase (ALP-Ab(2)) as detection antibodies. The enzymatically catalytic deposition of silver on the electrode could be measured by stripping analysis in KCl solution due to the Ag/AgCl solid-state voltammetric process. Several labeling protocols including spherical gold nanoparticle-labeled ALP-Ab(2) and ISGNP-labeled ALP-Ab(2) were investigated for determination of AFP, and improved analytical properties were achieved with the ISGNP labeling. With the ISGNP labeling method, the effects of incubation time and incubation temperature for antigen-antibody reaction, and deposition time of silver on the current responses of the electrochemical immunosensors were also monitored. Under optimal conditions, the electrochemical immunosensor exhibited a wide dynamic range from 0.01 ng mL(-1) to 200 ng mL(-1) with a detection limit of 5.0 pg mL(-1) AFP. The immunosensor displayed a good stability and acceptable reproducibility and accuracy. No significant differences at the 95% confidence level were encountered in the analysis of 10 clinical serum samples between the developed immunoassay and the commercially available electrochemiluminescent method for determination of AFP. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Oral antiviral therapy improves the diagnostic accuracy of alpha-fetoprotein levels in patients with chronic hepatitis B.

    Science.gov (United States)

    Shim, Jae-Jun; Kim, Jung Wook; Lee, Chang Kyun; Jang, Jae Young; Kim, Byung-Ho

    2014-09-01

    Analysis of alpha-fetoprotein (AFP) levels affords limited diagnostic accuracy because of the high false-positive rates, especially in those with active chronic hepatitis B (CHB). We measured AFP levels before and after commencement of oral antiviral therapy and explored the utility of these data in terms of early detection of hepatocellular carcinoma (HCC) in patients with CHB. A total of 207 patients with CHB who were treated with an oral antiviral agent were consecutively included. Dynamic changes in AFP levels and the diagnostic utility of such changes for HCC detection during the therapy were explored. The proportions of patients showing elevated AFP levels (≥ 20 ng/mL) were 22.2%, 5.5%, and 1.3% at baseline; and at 6 and 12 months after commencement of antiviral therapy, respectively. All patients who did not suffer from HCC exhibited normalization of AFP levels at 12 months. The cumulative incidence of HCC was 9.5% during 36 months of follow-up. If AFP levels were over 20 ng/mL after 12 months of antiviral treatment, the probability of HCC development approached certainty. The positive predictive value for HCC development remained at 100% in patients prescribed long-term (≥ 12 months) antiviral therapy, if AFP levels persistently or abruptly elevated more than 12 ng/mL. In the era of oral antiviral agents, AFP might be a useful biomarker for HCC surveillance in patients with CHB. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  16. Changes in highly sensitive alpha-fetoprotein for the prediction of the outcome in patients with hepatocellular carcinoma after hepatectomy

    International Nuclear Information System (INIS)

    Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Ito, Takanori; Maeda, Atsuyuki; Kaneoka, Yuji; Kagebayashi, Chiaki; Satomura, Shinji

    2014-01-01

    We investigated changes in highly sensitive lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (hsAFP-L3) measured using a novel method and its predictive ability for prognosis in patients with hepatocellular carcinoma (HCC) who underwent curative hepatectomy, comparing to other HCC tumor markers, that is, AFP, des-gamma-carboxy prothrombin (DCP), and AFP-L3 measured with conventional method (cAFP-L3). AFP, DCP, and AFP-L3 including both cAFP-L3 and hsAFP-L3 were measured before and after curative hepatectomy in 187 patients. The percentage of patients with elevated tumor marker levels pre- and postoperatively was compared, and recurrence-free and overall survival rates were analyzed based on changes in tumor markers. The percentages of patients with elevated AFP, DCP, and cAFP-L3 decreased postoperatively. In contrast, the percentage of patients with elevated hsAFP-L3 did not decrease postoperatively. Both recurrence-free and overall survival rates were significantly lower in patients whose tumor marker levels remained elevated postoperatively than patients without tumor marker elevation postoperatively. Recurrence-free and overall survival rates of patients in whom hsAFP-L3 became elevated postoperatively despite normal preoperative hsAFP-L3 levels were significantly lower than those of patients with normal hsAFP-L3 postoperatively, and were similar to those of patients with persistent elevation. Preoperative elevations of AFP, DCP, and cAFP normalized in many patients postoperatively, but not for hsAFP-L3. The elevation of hsAFP-L3 identifies patients with poor prognosis despite the normalization of AFP and DCP

  17. Time of hepatocellular carcinoma recurrence after liver resection and alpha-fetoprotein are important prognostic factors for salvage liver transplantation.

    Science.gov (United States)

    Lee, Sanghoon; Hyuck David Kwon, Choon; Man Kim, Jong; Joh, Jae-Won; Woon Paik, Seung; Kim, Bong-Wan; Wang, Hee-Jung; Lee, Kwang-Woong; Suh, Kyung-Suk; Lee, Suk-Koo

    2014-09-01

    Salvage liver transplantation (LT) is considered a feasible option for the treatment of recurrent hepatocellular carcinoma (HCC). We performed this multicenter study to assess the risk factors associated with the recurrence of HCC and patient survival after salvage LT. Between January 2000 and December 2011, 101 patients who had previously undergone liver resection (LR) for HCC underwent LT at 3 transplant centers in Korea. Sixty-nine patients' data were retrospectively reviewed for the analysis. The recurrence of HCC was diagnosed at a median of 10.6 months after the initial LR, and patients underwent salvage LT. Recurrences were within the Milan criteria in 48 cases and were outside the Milan criteria in 21 cases. After salvage LT, 31 patients had HCC recurrence during a median follow-up period of 24.5 months. There were 24 deaths, and 20 were due to HCC recurrence. The 5-year overall survival rate was approximately 54.6%, and the 5-year recurrence-free survival rate was 49.3%. HCC recurrence within the 8 months after LR [hazard ratio (HR) = 3.124, P = 0.009], an alpha-fetoprotein level higher than 200 ng/mL (HR = 2.609, P = 0.02), and HCC outside the Milan criteria at salvage LT (HR = 2.219, P = 0.03) were independent risk factors for poor recurrence-free survival after salvage LT. In conclusion, the timing and extent of HCC recurrence after primary LR both play significant roles in the outcome of salvage LT. © 2014 American Association for the Study of Liver Diseases.

  18. Female mice deficient in alpha-fetoprotein show female-typical neural responses to conspecific-derived pheromones.

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    Olivier Brock

    Full Text Available The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO and which lack the protective actions of AFP against maternal estradiol, that exposure to prenatal estradiol completely defeminized the potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus, as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

  19. Clinical characteristics of hepatocellular carcinoma patients with normal serum alpha-fetoprotein level: A study of 112 consecutive cases.

    Science.gov (United States)

    Li, Li; Chen, Jinglong; Xu, Weiran; Ding, Xiaosheng; Wang, Xiangyi; Liang, Jun

    2017-10-26

    Serum alpha-fetoprotein (AFP) level is normal in 30-40% of hepatocellular carcinoma (HCC) patients, and knowledge on its characteristics and clinical outcome is limited. The purpose of this observational study was to determine the clinical presentation, biological behavior and outcome of HCC patients with normal AFP level. Data of 112 consecutive HCC patients with normal AFP level were analyzed retrospectively. Statistical analysis including survival and factors associated with serum AFP level were performed by Kaplan-Meier method and t-test, respectively. Hepatitis B virus infection exited in 83.0% of all 112 HCC patients with normal AFP level. During a mean 52 ± 20 months (range 5-85 months) follow-up, the 1-, 2-, 3-year overall survival (OS) rate was 97.2%, 85.3% and 81.7%, respectively. The OS rates at 3 years stratified by stages at diagnosis were 100%, 96.2%, 85.7%, 11.1% and 0%, respectively for Barcelona Clinic Liver Cancer (BCLC) stage 0-D diseases. Significant difference in OS was observed among patients with BCLC stage 0-D diseases, P level elevated beyond normal figure during follow-up (AFP conversion) in 16 patients, which related with deterioration of liver function, quantitative changes of T helper cell subsets, rapid tumor progression and shorter survival. Patients with sustained normal AFP level had better survival than patients with AFP conversion, P level elevation and the time of AFP elevation to death, P level was relatively optimal. Serum AFP level elevation during follow-up was significantly associated with clinical outcome in terms of OS. © 2017 John Wiley & Sons Australia, Ltd.

  20. Serum alpha-fetoprotein in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

    Science.gov (United States)

    Bredaki, F E; Sciorio, C; Wright, A; Wright, D; Nicolaides, K H

    2015-07-01

    To define the contribution of maternal variables which influence the measured level of maternal serum alpha-fetoprotein (AFP) in screening for pregnancy complications. Maternal characteristics and medical history were recorded and serum AFP was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of AFP were determined from a linear mixed-effects multiple regression. Serum AFP was measured in 17 071 cases in the first trimester, 8583 in the second trimester and 8607 in the third trimester. Significant independent contributions to serum AFP were provided by gestational age, maternal weight, racial origin, gestational age at delivery and birth-weight Z-score of the neonate of the previous pregnancy and interpregnancy interval. Cigarette smoking was found to significantly affect serum AFP in the first trimester only. The machine used to measure serum AFP was also found to have a significant effect. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum AFP and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed pre-eclampsia and in those without this pregnancy complication. A model was fitted to express measured serum AFP across the three trimesters of pregnancy as MoMs, after adjusting for variables from maternal characteristics and medical history that affect this measurement. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  1. Synthesis of CdTe/CdS/ZnS quantum dots and their application in imaging of hepatocellular carcinoma cells and immunoassay for alpha fetoprotein

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    Tian Jianniao; Liu Rongjun; Zhao Yanchun; Peng Yan; Hong Xue; Zhao Shulin [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), College of Chemistry and Chemical Engineering of Guangxi Normal University, Guilin 541004 (China); Xu Qing, E-mail: tianjn58@yahoo.com.cn [Pharmacology Department of Guilin Medical College, Guilin 541004 (China)

    2010-07-30

    We report the imaging of hepatocellular carcinoma cells and the immunoassay for alpha fetoprotein (AFP) using CdTe/CdS/ZnS core-shell-shell QDs. Stable and high PLQY (20%-48%) CdTe/CdS/ZnS core-shell-shell QDs were synthesized by a stepwise process. Bioconjugation of the core-shell-shell QDs with streptavidin (SA) was successfully applied in immunofluorescent imaging of the human hepatocellular carcinoma (HCC) cell line HepG2.2.15. Furthermore, the thioglycolic acid (TGA)-capped CdTe/CdS/ZnS core-shell-shell QDs fluorescence lifetime is longer than fluorescein, so it was first engaged to conjugate with antigen for the determination of protein (AFP) by fluorescence polarization immunoassay.

  2. Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice

    Directory of Open Access Journals (Sweden)

    S.J. Guo

    2013-05-01

    Full Text Available We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8 mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m to age-matched SAM-resistant 1 (SAMR1 mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413, chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2_A, alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4+ T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.

  3. Fullerol-fluorescein isothiocyanate-concanavalin agglutinin phosphorescent sensor for the detection of alpha-fetoprotein and forecast of human diseases.

    Science.gov (United States)

    Liu, Jia-ming; Lin, Li-ping; Jiang, Shu-lian; Cui, Ma Lin; Jiao, Li; Zhang, Xiao Yang; Zhang, Li-hong; Zheng, Zhi Yong; Lin, Xuan; Lin, Shao-qin

    2013-11-01

    Based on the reaction of the active -OH group in fullerol (F) with the dissociated -COOH group in fluorescein isothiocyanate (FITC) to form an F-FITC and the enhanced effect of N, N-dimethylaniline (DMA) on phosphorescence signal of F-FITC, a new phosphorescent labeling reagent (DMA-F-FITC) was developed. What's more, a phosphorescent sensor for the determination of alpha-fetoprotein variant (AFP-V) has been designed via the coupling technique of the high sensitivity for affinity adsorption-solid substrate-room temperature phosphorimetry (AA-SS-RTP) with the strong specificity reaction between DMA-F-FITC-Con A and AFP-V. The DMA-F-FITC increased the number of luminescent molecules in the biological target which improved the sensitivity of phosphorescent sensor. The proposed sensor was responsive, simple, selective and sensitive, and it has been applied to the determination of trace AFP-V in human serum and the forecast of human diseases using phosphorescence emission wavelength of F or FITC, with the results agreed well with those obtained by enzyme-linked immunoassay (ELISA). Meanwhile, the mechanisms for the labeling reaction and the sensing detection of AFP-V were discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Magnetic immunoassay coupled with inductively coupled plasma mass spectrometry for simultaneous quantification of alpha-fetoprotein and carcinoembryonic antigen in human serum

    Science.gov (United States)

    Zhang, Xing; Chen, Beibei; He, Man; Zhang, Yiwen; Xiao, Guangyang; Hu, Bin

    2015-04-01

    The absolute quantification of glycoproteins in complex biological samples is a challenge and of great significance. Herein, 4-mercaptophenylboronic acid functionalized magnetic beads were prepared to selectively capture glycoproteins, while antibody conjugated gold and silver nanoparticles were synthesized as element tags to label two different glycoproteins. Based on that, a new approach of magnetic immunoassay-inductively coupled plasma mass spectrometry (ICP-MS) was established for simultaneous quantitative analysis of glycoproteins. Taking biomarkers of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as two model glycoproteins, experimental parameters involved in the immunoassay procedure were carefully optimized and analytical performance of the proposed method was evaluated. The limits of detection (LODs) for AFP and CEA were 0.086 μg L- 1 and 0.054 μg L- 1 with the relative standard deviations (RSDs, n = 7, c = 5 μg L- 1) of 6.5% and 6.2% for AFP and CEA, respectively. Linear range for both AFP and CEA was 0.2-50 μg L- 1. To validate the applicability of the proposed method, human serum samples were analyzed, and the obtained results were in good agreement with that obtained by the clinical chemiluminescence immunoassay. The developed method exhibited good selectivity and sensitivity for the simultaneous determination of AFP and CEA, and extended the applicability of metal nanoparticle tags based on ICP-MS methodology in multiple glycoprotein quantifications.

  5. Shrink-induced graphene sensor for alpha-fetoprotein detection with low-cost self-assembly and label-free assay

    Science.gov (United States)

    Sando, Shota; Zhang, Bo; Cui, Tianhong

    2017-12-01

    Combination of shrink induced nano-composites technique and layer-by-layer (LbL) self-assembled graphene challenges controlling surface morphology. Adjusting shrink temperature achieves tunability on graphene surface morphology on shape memory polymers, and it promises to be an alternative in fields of high-surface-area conductors and molecular detection. In this study, self-assembled graphene on a shrink polymer substrate exhibits nanowrinkles after heating. Induced nanowrinkles on graphene with different shrink temperature shows distinct surface roughness and wettability. As a result, it becomes more hydrophilic with higher shrink temperatures. The tunable wettability promises to be utilized in, for example, microfluidic devices. The graphene on shrink polymer also exhibits capability of being used in sensing applications for pH and alpha-fetoprotein (AFP) detection with advantages of label free and low cost, due to self-assembly technique, easy functionalization, and antigen-antibody reaction on graphene surface. The detection limit of AFP detection is down to 1 pg/mL, and therefore the sensor also has a significant potential for biosensing as it relies on low-cost self-assembly and label-free assay.

  6. Combining des-gamma-carboxyprothrombin and alpha-fetoprotein for hepatocellular carcinoma diagnosing: an update meta-analysis and validation study.

    Science.gov (United States)

    Chen, Huaping; Chen, Siyuan; Li, Shan; Chen, Zhijian; Zhu, Xuan; Dai, Meiyu; Kong, Lingxi; Lv, Xiaodan; Huang, Zhili; Qin, Xue

    2017-10-27

    Controversies about the combination of des-gamma-carboxyprothrombin (DCP) and alpha-fetoprotein (AFP) for hepatocellular carcinoma diagnosing still exist. Hence, we performed this updated meta-analysis to estimate the diagnostic value of DCP , AFP and DCP + AFP in HCC. In addition, we conducted a validation study to analyze the performance of the candidate makers. After a systematic literature review, 27 studies from 20 articles were identified from four major databases. The pooled sensitivity and specificity were 69% and 89%, respectively, for DCP; for AFP, they were 65% and 88%, respectively; and they were 82% and 85%, respectively, for DCP + AFP. The values of the area under the curve (AUC) for DCP, AFP, DCP + AFP, respectively, were 0.88, 0.75, and 0.90. The validation study confirmed that the performance of DCP + AFP (sensitivity = 84%, specificity = 86%; AUC = 0.887) was higher than that of DCP (sensitivity = 76%, specificity = 92%; AUC = 0.843) or AFP (sensitivity = 73%, specificity = 92%; AUC = 0.837) alone.

  7. Second trimester serum alpha-fetoprotein level is a significant positive predictor for intrauterine growth restriction in pregnant women with hyperemesis gravidarum

    Science.gov (United States)

    Özkaya, Enis; Çakır, Evrim; Çınar, Mehmet; Altay, Metin; Gelişen, Orhan; Kara, Fadıl

    2011-01-01

    Objective The aim of this study was to determine the association between three parameters of second trimester serum secreening and preterm labor and intrauterine growth restriction (IUGR) in patients with hyperemesis gravidarum (HG). Material and Methods A prospective study on 429 pregnancies with HG was designed to determine the association between alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (HCG) and pregnancy prognosis in terms of preterm labor, IUGR and birth weight. Results In our study group the mean age of patients was 25.4±3.8 years. Mean birth weight was 3180±555 g. Mean AFP, uE3, hCG levels in the study group were 1.44±0.65 MoM, 0.91±0.38 MoM, 1.09±0.64 MoM, respectively. Twenty nine (6.8%) patients delivered before 37 weeks of gestation and 52 (12.1%) patients developed IUGR. Mean MoM values of AFP among patients with preterm labor, IUGR and normal delivery were 1.35±0.45, 1.97±0.81, 1.34±0.58 MoM, respectively (p1.55 was 3.73 (95% CI, 1.99–6.98, phyperemesis gravidarum. The second trimester screening test can predict poor outcome in HG. PMID:24591998

  8. Development of an automated wax-printed paper-based lateral flow device for alpha-fetoprotein enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Preechakasedkit, Pattarachaya; Siangproh, Weena; Khongchareonporn, Nanthika; Ngamrojanavanich, Nattaya; Chailapakul, Orawon

    2018-04-15

    In this study, a novel wax-printed paper-based lateral flow device has been developed as an alternative approach for an automated and one-step enzyme-linked immunosorbent assay (ELISA). The design pattern consisted of a non-delayed channel, a wax-delayed channel, a test zone and a control zone. This system was easily fabricated on a nitrocellulose membrane using a wax-printing method and then baked in an oven at 100°C for 1min. The four barriers of the wax-delayed channel could delay the flow time for 11s compared to the flow time of the non-delayed channel. To use the device under optimal conditions, alpha-fetoprotein (AFP) was detected at a limit of detection of 1ngmL -1 and assessed with the naked eye within 10min. A colorimetric intensity was also measured using a smart phone and computer software at a linear range of 0.1-100ngmL -1 with a good correlation. Furthermore, the proposed device was successfully applied to detect AFP in human serum. Therefore, the wax-printing demonstrates a user-friendly, easy and quick method for the fabrication of the device, which could be used as a one-step, portable, disposable, low-cost, simple, instrument-free and point-of-care device for the automated ELISA. Copyright © 2017. Published by Elsevier B.V.

  9. Prolonged Survival in a Case of Chemotherapy-Sensitive Gastric Cancer That Produced Alpha-Fetoprotein and Protein Induced by Vitamin K Antagonist-II

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    Naotaka Ogasawara

    2015-04-01

    Full Text Available The number of reported cases of alpha-fetoprotein (AFP-producing gastric cancer has gradually increased, with a reported prevalence of 1.3-1.5% of all gastric cancer cases. However, reports of gastric cancer accompanied by elevated serum levels of both AFP and protein induced by vitamin K antagonist-II (PIVKA-II are rare. The prognosis of AFP- and PIVKA-II-producing gastric cancer has been reported to be very poor because the tumor cells were considered to have a high malignant potential and the cancer progressed rapidly. We described a case of gastric cancer producing AFP and PIVKA-II in which chemotherapy was effective and resulted in prolonged survival, and these two tumor markers were useful for monitoring the treatment response. Routine health screening using upper abdominal ultrasonography revealed hepatic tumors in an apparently healthy 65-year-old man. Whole-body computed tomography (CT revealed multiple hepatic tumors, and an esophagogastroduodenoscopy (EGD revealed a Bormann type 3 tumor in the lower stomach. A biopsy specimen confirmed that the tumor was immunohistochemically positive for AFP, PIVKA-II, and human epidermal growth factor receptor 2. After chemotherapy, the gastric tumor appeared as a small elevated lesion on EGD, and CT revealed a remarkable reduction in the size of the metastatic liver tumors. The patient is still alive, 35 months after the initial chemotherapy.

  10. Maternal and fetal mechanisms of B cell regulation during pregnancy: human Chorionic Gonadotropin stimulates B cells to produce IL-10 while alpha-fetoprotein drives them into apoptosis

    Directory of Open Access Journals (Sweden)

    Franziska Fettke

    2016-12-01

    Full Text Available Maternal immune tolerance towards the fetus is an essential requisite for pregnancy. While T cell functions are well documented, little is known about the participation of B cells. We have previously suggested that IL-10 producing B cells are involved in pregnancy tolerance in mice and humans. By employing murine and human systems, we report now that fetal trophoblasts positively regulate the generation of IL-10 producing B cells. We next studied the participation of hormones produced by the placenta as well as the fetal protein alpha-fetoprotein (AFP in B cell modulation. Human Chorionic Gonadotropin (hCG, but not progesterone, estrogen or a combination of both, was able to promote changes in B cell phenotype and boost their IL-10 production, which was abolished after blocking hCG. The hCG-induced B cell phenotype was not associated with augmented galactosylation, sialylation or fucosylation of IgG subclasses in their Fc. In vitro, hCG induced the synthesis of asymmetrically glycosylated antibodies in their Fab region. Interestingly, AFP had dual effects depending on the concentration. At concentrations corresponding to maternal serum levels, it did not modify the phenotype or IL-10 secretion of B cells. At fetal concentrations, however, AFP was able to drive B cells into apoptosis, which may indicate a protective mechanism to avoid maternal B cells to reach the fetus.Our data suggests that the fetus secrete factors that promote a pregnancy-friendly B cell phenotype, unraveling interesting aspects of B cell function and modulation by pregnancy hormones and fetal proteins.

  11. Alpha-fetoprotein (AFP) modulates the effect of serum albumin on brain development by restraining the neurotrophic effect of oleic acid.

    Science.gov (United States)

    García-García, Alejandro G; Polo-Hernández, Erica; Tabernero, Arantxa; Medina, José M

    2015-10-22

    We have previously shown that serum albumin controls perinatal rat brain development through the regulation of oleic acid synthesis by astrocytes. In fact, oleic acid synthesized and released by astrocytes promoted neurite growth, neuron migration and the arrangement of prospective synapses. In this work we show that alpha-fetoprotein (AFP) is also present in the brain during embryonic development, its concentrations peaking at E15.5 and at E19.5. However, after E19.5 AFP concentrations plummeted concurrently with a sharp increase in serum albumin concentrations. At E15.5, AFP is present in caudal regions of the brain, particularly in brain areas undergoing differentiation during this period, such as the thalamic reticular nucleus of the thalamus, the hypothalamus, the amygdala and the hippocampus. Albumin was not detected in the brain at E15.5 but stained brain cells substantially on day E19.5, showing a very similar distribution to that of AFP under the same circumstances. The concentrations of free oleic acid in the brain were inversely correlated with those of AFP, suggesting that the signals elicited by AFP and oleic acid can be inversely associated. GAP-43, a marker of axonal growth that is highly expressed by the presence of oleic acid, was not co-localized with AFP except in the marginal zone and areas delimiting the subplate. AFP prevented the increase in GAP-43 expression caused by the presence of oleic acid in neurons in primary culture in vitro and in organotypic cultures of embryonic rat brain ex vivo, suggesting that AFP may modulate the effect of serum albumin on brain development. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Magnetic immunoassay coupled with inductively coupled plasma mass spectrometry for simultaneous quantification of alpha-fetoprotein and carcinoembryonic antigen in human serum

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xing; Chen, Beibei; He, Man; Zhang, Yiwen; Xiao, Guangyang; Hu, Bin, E-mail: binhu@whu.edu.cn

    2015-04-01

    The absolute quantification of glycoproteins in complex biological samples is a challenge and of great significance. Herein, 4-mercaptophenylboronic acid functionalized magnetic beads were prepared to selectively capture glycoproteins, while antibody conjugated gold and silver nanoparticles were synthesized as element tags to label two different glycoproteins. Based on that, a new approach of magnetic immunoassay-inductively coupled plasma mass spectrometry (ICP-MS) was established for simultaneous quantitative analysis of glycoproteins. Taking biomarkers of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as two model glycoproteins, experimental parameters involved in the immunoassay procedure were carefully optimized and analytical performance of the proposed method was evaluated. The limits of detection (LODs) for AFP and CEA were 0.086 μg L{sup −1} and 0.054 μg L{sup −1} with the relative standard deviations (RSDs, n = 7, c = 5 μg L{sup −1}) of 6.5% and 6.2% for AFP and CEA, respectively. Linear range for both AFP and CEA was 0.2–50 μg L{sup −1}. To validate the applicability of the proposed method, human serum samples were analyzed, and the obtained results were in good agreement with that obtained by the clinical chemiluminescence immunoassay. The developed method exhibited good selectivity and sensitivity for the simultaneous determination of AFP and CEA, and extended the applicability of metal nanoparticle tags based on ICP-MS methodology in multiple glycoprotein quantifications. - Highlights: • 4-Mercaptophenylboronic acid functionalized magnetic beads were prepared and characterized. • ICP-MS based magnetic immunoassay approach was developed for quantification of glycoproteins. • AFP and CEA were quantified simultaneously with Au and Ag NPs as element tags. • The developed method exhibited good selectivity and sensitivity for target glycoproteins.

  13. Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

    Science.gov (United States)

    Alvarez-Nava, Francisco; Soto, Marisol; Lanes, Roberto; Pons, Hector; Morales-Machin, Alisandra; Bracho, Ana

    2015-12-01

    The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P < 0.05), when compared to those of unaffected pregnancies. Levels of β-hCG in pregnancies with hydrops fetalis were significantly higher than in those with cystic hygroma (P <0.0001), as were AF-AFP concentrations (P <0.0015). In addition, abnormalities in both maternal serum β-hCG and AF-AFP predicted fetal death. The relative risk of adverse obstetric outcome was 10.667 (P = 0.0004; 95% confidence interval [CI]: 1.554-73.203) for β-hCG and 2.19 (P = 0.0256; 95% CI: 1.001 to 4.779), for AF-AFP. Maternal serum β-hCG and AF-AFP levels may preferentially identify those Turner syndrome pregnancies with the highest risk of fetal death. © 2015 Japan Society of Obstetrics and Gynecology.

  14. Clinical and molecular sub-classification of hepatocellular carcinoma relative to alpha-fetoprotein level in an Asia-Pacific island cohort.

    Science.gov (United States)

    Nishioka, Scott T; Sato, Miles M; Wong, Linda L; Tiirikainen, Maarit; Kwee, Sandi A

    2018-01-01

    Increased serum alpha-fetoprotein (AFP) levels are associated with specific molecular sub-classes of hepatocellular carcinoma (HCC), supporting AFP as a predictive or therapeutic biomarker for precision treatment of this disease. Considering recent efforts to validate HCC molecular classification systems across different populations, we applied existing signature-based classification templates to Hawaii cohorts and examined whether associations between HCC molecular sub-class, AFP levels, and clinical features found elsewhere can also be found in Hawaii, a region with a unique demographic and risk factor profile for HCC. Whole-genome expression profiling was performed on HCC tumors collected from 40 patients following partial hepatectomy. Tumors underwent transcriptome-based categorization into 3 molecular sub-classes (S1, S2, and S3). Patient groups based on molecular sub-class and AFP level were then compared with regards to clinical features and survival. Differences associated with AFP level and other clinical parameters were also examined at the gene signature level by gene set enrichment analysis. Statistically confident (false discovery rate 400 ng/mL predicted significant tumor enrichment for genes corresponding to MYC target activation, high cell proliferation, poor clinical prognosis, and the S2 sub-class. AFP > 400 ng/mL and non-S3 tumor classification were found to be significant predictors of overall survival. Distinct sub-classes of HCC associated with different molecular features and survival outcomes can be detected with statistical confidence in a Pacific Island cohort. Molecular classification signatures and other predictive markers for HCC that are valid for all patient populations are needed to support multi-center efforts to develop targeted therapies for HCC.

  15. 8-Quinolineboronic acid as a potential phosphorescent molecular switch for the determination of alpha-fetoprotein variant for the prediction of primary hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Liu Jiaming; Li Feiming; Liu Zhenbo; Lin Changqing; Lin Shaoqin; Lin Liping; Wang Xinxing; Li Zhiming

    2010-01-01

    8-Quinolineboronic acid phosphorescent molecular switch (8-QBA-PMS) in the 'off' state emitted weak room temperature phosphorescence (RTP) of 8-QBA on the acetylcellulose membrane (ACM) with the perturbation of Pb 2+ . When 8-QBA-PMS was used to label concanavalin agglutinin (Con A) to form 8-QBA-PMS-Con A based on the reaction between -OH of 8-QBA-PMS and -COOH of Con A, 8-QBA-PMS turned 'on' automatically due to its structure change, and RTP of the system increased 2.7 times. Besides, -NH 2 of 8-QBA-PMS-Con A could carry out affinity adsorption (AA) reaction with the -COOH of alpha-fetoprotein variant (AFP-V) to form the product Con A-AFP-V-Con A-8-QBA-PMS containing -NH-CO- bond, causing the RTP of the system to further increase. Moreover, the amount of AFP-V was linear to the ΔI p of the system in the range of 0.012-2.40 (fg spot -1 ). Thus, a new affinity sensitive adsorption solid substrate room temperature phosphorimetry using 8-QBA-PMS as labelling reagent (8-QBA-PMS-AASSRTP) for the determination of AFP-V was proposed with the detection limit (LD) of 9 x 10 -15 g mL -1 . It had been used to determine AFP-V in human serum with the results agreeing with enzyme-link immunoassay (ELISA), showing promise for the prediction of PHC due to the intimate association between AFP-V and primary hepatocellular carcinoma (PHC). The mechanism of the promethod was also discussed.

  16. Rapid and sensitive lateral flow immunoassay method for determining alpha fetoprotein in serum using europium (III) chelate microparticles-based lateral flow test strips.

    Science.gov (United States)

    Liang, Rong-Liang; Xu, Xu-Ping; Liu, Tian-Cai; Zhou, Jian-Wei; Wang, Xian-Guo; Ren, Zhi-Qi; Hao, Fen; Wu, Ying-Song

    2015-09-03

    Alpha-fetoprotein (AFP), a primary marker for many diseases including various cancers, is important in clinical tumor diagnosis and antenatal screening. Most immunoassays provide high sensitivity and accuracy for determining AFP, but they are expensive, often complex, time-consuming procedures. A simple and rapid point-of-care system that integrates Eu (III) chelate microparticles with lateral flow immunoassay (LFIA) has been developed to determine AFP in serum with an assay time of 15 min. The approach is based on a sandwich immunoassay performed on lateral flow test strips. A fluorescence strip reader was used to measure the fluorescence peak heights of the test line (HT) and the control line (HC); the HT/HC ratio was used for quantitation. The Eu (III) chelate microparticles-based LFIA assay exhibited a wide linear range (1.0-1000 IU mL(-1)) for AFP with a low limit of detection (0.1 IU mL(-1)) based on 5ul of serum. Satisfactory specificity and accuracy were demonstrated and the intra- and inter-assay coefficients of variation (CV) for AFP were both <10%. Furthermore, in the analysis of human serum samples, excellent correlation (n = 284, r = 0.9860, p < 0.0001) was obtained between the proposed method and a commercially available CLIA kit. Results indicated that the Eu (III) chelate microparticles-based LFIA system provided a rapid, sensitive and reliable method for determining AFP in serum, indicating that it would be suitable for development in point-of-care testing. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Alpha-fetoprotein, identified as a novel marker for the antioxidant effect of placental extract, exhibits synergistic antioxidant activity in the presence of estradiol.

    Directory of Open Access Journals (Sweden)

    Hye Yeon Choi

    Full Text Available Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol.

  18. In vitro radionuclide therapy and in vivo scintigraphic imaging of alpha fetoprotein producing hepatocellular carcinoma by targeted sodium iodide symporter gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kwang Il; Lee, Yong Jin; Lee, Tae Sup; Song, Inho; Cheon, Gi Jeong; Lim, Sang Moo; Kang, Joo Hyun [Korea Institute of Radiological and Medical and Medical Sciences, Seoul (Korea, Republic of); Chung, June Key [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2012-03-15

    This study aimed to develop a gene expression targeting method for specific imaging and therapy of alpha fetoprotein (AFP) producing hepatocellular carcinoma (HCC) cells, using an adenovirus vector containing the human sodium/iodide symporter (hNIS) gene driven by an AFP enhancer/promoter. The recombinant adenovirus vector, AdAFPhNIS (containing the hNIS gene driven by human AFP enhancer/promoter) was prepared. After in vitro infection by the adenovirus, hNIS gene expression in AFP producing cells and in AFP nonproducing cells was investigated using {sup 125}I uptake assay and semi quantitative reverse transcription polymerase chain reaction (RT-PCR). The killing effect of {sup 131}I vitro clonogenic assay. In addition, tumor bearing mice were intravenously injected with the adenovirus, and scintigraphic images were obtained. The expression of hNIS was efficiently demonstrated by {sup 125}I uptake assay in AFP producing cells, but not in AFP nonproducing cells. AFP producing HCC targeted gene expression was confirmed at the mRNA level. Furthermore, in vitro clonogenic assay showed that hNIS gene expression induced by AdAFPhNIS infection in AFP producing cells caused more sensitivity to {sup 131}I than that in AFP nonproducing cells. Injected intravenously in HuH-7 tumor xenografts mice by adenovirus, the functional hNIS gene expression was confirmed in tumor by in vivo scintigraphic imaging. An AFP producing HCC was targeted with an adenovirus vector containing the hNIS gene using the AFP enhancer/promoter in vitro and in vivo. These findings demonstrate that AFP producing HCC specific molecular imaging and radionuclide gene therapy are feasible using this recombinant adenovirus vector system.

  19. Análisis de las malformaciones congénitas detectadas por el programa alfafetoproteína-ultrasonido genético Analysis of the congenital malformations detected by the alpha-fetoprotein-genetic ultrasound program

    Directory of Open Access Journals (Sweden)

    Aicha Julia Llamos Paneque

    2007-03-01

    Full Text Available La alfafetoproteína es una glicoproteína específica del plasma fetal, cuya determinación en suero materno se realiza entre las 15 y 19 semanas de gestación. Para conocer el comportamiento del programa alfafetoproteína-ultrasonido genético en el municipio 10 de Octubre se realizó esta investigación. En ella se encontró que 862 gestantes presentaron alfafetoproteína elevada en suero materno en el período analizado, y las principales causas encontradas dependientes de la madre fueron: el error en la fecha de última menstruación, seguida de la amenaza de aborto; y las malformaciones congénitas más frecuentemente encontradas fueron los defectos de cierre del tubo neural, seguidos de las malformaciones cardiovasculares.The alpha-fetoprotein is a specific glycoprotein of the fetal plasma, whose determination in maternal serum is performed from the 15th to the 19th week of gestation. This research was conducted to know the behavior of the alpha-fetoprotein-genetic ultrasound program in “10 de Octubre” municipality. It was found that 108 pregnant women presented elevated alpha-fetoprotein in maternal serum during the analyzed period. The main causes depending on the mother were: error in the date of the last menstruation and threatened abortion. The most frequent congenital malformations were the defects of the neural tube closure, and the cardiovascular malformations.

  20. Rapid and sensitive lateral flow immunoassay method for determining alpha fetoprotein in serum using europium (III) chelate microparticles-based lateral flow test strips

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Rong-Liang; Xu, Xu-Ping; Liu, Tian-Cai; Zhou, Jian-Wei; Wang, Xian-Guo; Ren, Zhi-Qi [Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong (China); Hao, Fen [DaAn Gene Co. Ltd. of Sun Yat-sen University, 19 Xiangshan Road, Guangzhou 510515 (China); Wu, Ying-Song, E-mail: wg@smu.edu.cn [Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou 510515, Guangdong (China)

    2015-09-03

    Alpha-fetoprotein (AFP), a primary marker for many diseases including various cancers, is important in clinical tumor diagnosis and antenatal screening. Most immunoassays provide high sensitivity and accuracy for determining AFP, but they are expensive, often complex, time-consuming procedures. A simple and rapid point-of-care system that integrates Eu (III) chelate microparticles with lateral flow immunoassay (LFIA) has been developed to determine AFP in serum with an assay time of 15 min. The approach is based on a sandwich immunoassay performed on lateral flow test strips. A fluorescence strip reader was used to measure the fluorescence peak heights of the test line (H{sub T}) and the control line (H{sub C}); the H{sub T}/H{sub C} ratio was used for quantitation. The Eu (III) chelate microparticles-based LFIA assay exhibited a wide linear range (1.0–1000 IU mL{sup −1}) for AFP with a low limit of detection (0.1 IU mL{sup −1}) based on 5ul of serum. Satisfactory specificity and accuracy were demonstrated and the intra- and inter-assay coefficients of variation (CV) for AFP were both <10%. Furthermore, in the analysis of human serum samples, excellent correlation (n = 284, r = 0.9860, p < 0.0001) was obtained between the proposed method and a commercially available CLIA kit. Results indicated that the Eu (III) chelate microparticles-based LFIA system provided a rapid, sensitive and reliable method for determining AFP in serum, indicating that it would be suitable for development in point-of-care testing. - Highlights: • Europium (III) chelate microparticles was used as a label for LIFA. • Quantitative detection by using H{sub T}/H{sub C} ratio was achieved. • LIFA for simple and rapid AFP detection in human serum. • The sensitivity and linearity was more excellent compared with QD-based ICTS. • This method could be developed for rapid point-of-care screening.

  1. Cost-effectiveness analysis of hepatocellular carcinoma screening by combinations of ultrasound and alpha-fetoprotein among Alaska Native people, 1983–2012

    Directory of Open Access Journals (Sweden)

    Prabhu P. Gounder

    2016-05-01

    Full Text Available Background: The American Association for the Study of Liver Diseases (AASLD recommends semi-annual hepatocellular carcinoma (HCC screening using ultrasound (US in persons with chronic hepatitis B (CHB virus infection at high risk for HCC such as Asian males aged ≥40 years and Asian females aged ≥50 years. Objective: To analyse the cost-effectiveness of 2 HCC screening methods in the Alaska Native (AN health system: US-alone, or screening by alpha-fetoprotein (AFP initially and switching to US for subsequent screenings if AFP >10 ng/mL (AFP→US. Design: A spreadsheet-based model was developed for accounting the costs of 2 hypothetical HCC screening methods. We used epidemiologic data from a cohort of 839 AN persons with CHB who were offered HCC screening by AFP/US semi-annually during 1983–2012. We assumed that compared with AFP→US, US-alone identifies 33% more tumours at an early stage (defined as a single tumour ≤5 cm or ≤3 tumours ≤3 cm in diameter. Years of life gained (YLG attributed to screening was estimated by comparing additional years of survival among persons with early- compared with late-stage tumours. Screening costs were calculated using Medicare reimbursement rates in 2012. Future screening costs and YLG were projected over a 30-year time horizon using a 3% discount rate. Results: The total cost of screening for the cohort by AFP→US would have been approximately $357,000 ($36,000/early-stage tumour detected compared to $814,000 ($59,000/early-stage tumour detected by US-alone. The AFP→US method would have yielded an additional 27.8 YLG ($13,000/YLG compared with 38.9 YLG ($21,000/YLG for US-alone. Screening by US-alone would incur an additional $114,000 per extra early-tumour detected compared with AFP→US and $41,000 per extra YLG. Conclusions: Although US-alone HCC screening might have yielded more YLG than AFP→US, the reduced costs of the AFP→US method could expand access to HCC screening in resource

  2. Conductive carbon nanoparticles-based electrochemical immunosensor with enhanced sensitivity for alpha-fetoprotein using irregular-shaped gold nanoparticles-labeled enzyme-linked antibodies as signal improvement.

    Science.gov (United States)

    Tang, Juan; Su, Biling; Tang, Dianping; Chen, Guonan

    2010-08-15

    A new electrochemical immunoassay protocol for sensitive detection of alpha-fetoprotein (AFP, as a model) is designed using carbon nanoparticles (CNPs)-functionalized biomimetic interface as immunosensing probe and irregular-shaped gold nanoparticles (ISNGs)-labeled horseradish peroxidase-anti-AFP conjugates (HRP-anti-AFP-ISNG) as trace label. The low-toxic and high-conductive CNPs provided a high capacity nanoparticulate immobilization surface and a facile pathway for electron transfer. In comparison with conventional label methods, i.e. spherical gold nanoparticles-labeled HRP-anti-AFP and HRP-labeled anti-AFP, the electrochemical immunosensor using HRP-anti-AFP-ISNGs as trace labels exhibited high bioelectrocatalytic response toward enzyme substrate and a wide dynamic range from 0.02 to 4.0 ng/mL with a low detection limit of 10 pg/mL toward AFP (at 3sigma). The developed immunoassay method showed good selectivity and acceptable reproducibility. Clinical serum samples with various AFP concentrations were evaluated by using the electrochemical immunosensor and the referenced enzyme-linked immunosorbent assay (ELISA), respectively, and received in good accordance with results obtained from these two methods. Copyright 2010 Elsevier B.V. All rights reserved.

  3. Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways.

    Science.gov (United States)

    Bortel, Nicola; Armeanu-Ebinger, Sorin; Schmid, Evi; Kirchner, Bettina; Frank, Jan; Kocher, Alexa; Schiborr, Christina; Warmann, Steven; Fuchs, Jörg; Ellerkamp, Verena

    2015-12-01

    In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC.

  4. Prognostic Value of Preoperative Serum Levels of Five Tumor Markers (Carcinoembryonic Antigen, CA19-9, Alpha-fetoprotein, CA72-4, and CA125) in Gastric Cancer.

    Science.gov (United States)

    Kim, Ji-Hyun; Jun, Kyong-Hwa; Jung, Hun; Park, In-Soo; Chin, Hyung-Min

    2014-05-01

    There is no known specific tumor marker for gastric cancer, although several tumor markers have been used. The aim of this study was to investigate the prognostic significance of preoperative carcinoembryonic antigen (CEA), CA 19-9, alpha-fetoprotein (AFP), CA 72-4, and CA 125 levels in patients with gastric cancer. Medical records of 1,253 patients who were diagnosed with gastric adenocarcinoma were retrospectively reviewed. The clinicopathologic characteristics and disease-free survival rate of the patients were compared between positive and negative CEA, CA 19-9, AFP, CA 72-4, and CA 125 groups of patients. Additionally, the prognostic significance of each tumor marker was assessed by multivariate analysis. CEA, CA19-9, and CA72-4 were more frequently positive in patients with lymphatic and venous invasion, serosal involvement, and lymph node metastasis. The 5-year overall survival and disease free survival rates were significantly associated with elevated serum levels of CEA, CA 19-9, and CA 72-4. The depth of invasion and CA 19-9 were independent prognostic factors. Patients with elevated serum levels of CA 19-9 showed a 3.35-fold higher risk of death than patients with low levels of the marker. CA 19-9 has prognostic significance in gastric cancer, and a high preoperative serum level of CA 19-9 can be useful for estimating worse prognosis and a higher recurrence of gastric cancer.

  5. Electrochemical immunosensor for alpha-fetoprotein determination based on ZnSe quantum dots/Azure I/gold nanoparticles/poly (3,4-ethylenedioxythiophene) modified Pt electrode

    International Nuclear Information System (INIS)

    Liu, Keke; Zhang, Jianrong; Liu, Qing; Huang, Haiping

    2013-01-01

    A novel amperometric enzyme immunosensor with amplified sensitivity for the determination of alpha-fetoprotein (AFP) was constructed with layer-by-layer assembly of ZnSe quantum dots (ZnSe QDs)/Azure I/gold nanoparticles (nanoAu)/poly (3,4-ethylenedioxythiophene) (PEDOT) on Pt electrode. Firstly, citrate coated nanoAu was immobilized on the PEDOT polymer film, which was electrochemically synthesized in ionic liquid electrolyte of 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF 4 ]). Then, Azure I was immobilized on nanoAu/PEDOT composite matrix as a redox probe and was used to immobilize ZnSe QDs. Subsequently, AFP antibody (anti-AFP) was adsorbed onto the surface of ZnSe layer. Finally, horseradish peroxidase (HRP) was employed to block sites against nonspecific binding and amplify the current signal of the antigen–antibody reaction. The modification processes were characterized by cyclic voltammetry, scanning electron microscopy. The factors influenced the performances of the proposed immunosensors were studied in detail. Because of the synergism between Azure I and nanoAu/PEDOT to facilitate electron-transfer process, and the small diameter of ZnSe QDs favorable for stabilization of biological activity to a large extent, the immunosensor displayed a high sensitivity, fast analytical time, a relatively low detection limit of 1.1 fg/mL at 3 times of signal-to-noise ratio (S/N = 3), and a especially broad linear response to AFP in a ranges from 5 × 10 −5 to 250 ng/mL. Moreover, the selectivity, repeatability, and stability of the proposed immunosensor were acceptable

  6. Simultaneous electrochemical immunosensing of alpha-fetoprotein and prostate specific antigen using a glassy carbon electrode modified with gold nanoparticle-coated silica nanospheres and decorated with Azure A or ferrocene carboxylic acid

    International Nuclear Information System (INIS)

    Zhao, Junqing; Guo, Zilin; Guo, Jinjin; Wang, Junchun; Zhang, Yuzhong; Feng, Dexiang

    2015-01-01

    We describe an electrochemical immunosensor for the simultaneous determination of alpha-fetoprotein (AFP) and prostate specific antigen (PSA) via a modified glassy carbon electrode. Silica nanoparticles (200–300 nm i.d.) with good monodispersity and uniform shape were synthesized, and the following species were then consecutively immobilized on their surface: gold nanoparticles (AuNPs; 5–15 nm i.d.), secondary antibody (Ab 2 ) and the redox-probes Azure A or ferrocenecarboxy acid (Fc). In parallel, two types of primary antibodies (Ab 1 ) were co-immobilized on the surface of the dissolved reduced graphene oxide sheets (rGO) that were also decorated with AuNPs. In the presence of antigens (AFP or PSA), the Ab 2 /Si-AuNPs carrying Azure A and Fc are attached to the AuNP/rGO conjugate via a sandwich type immunoreaction. Differential pulse voltammetry (DPV) was employed to measure the resulting changes in the signal of Fc or Azure A. Two well-resolved oxidation peaks, one at −0.48 V (corresponding to Azure A) and other at + 0.12 V (corresponding to Fc; both vs. SCE) can be observed in the DPV curves. Under optimal conditions, AFP and PSA can be simultaneously determined in the range from 0.01 to 25 ng mL -1 for AFP, and from 0.012 to 25 ng mL -1 for PSA. The detection limits are 3.3 pg mL -1 for AFP and 4.0 pg mL -1 for PSA (at a signal-to-noise ratio of 3). The method was applied to (spiked) real sample analysis, and the recoveries are within 96.0 and 107.2 % for PSA, and within 100.9 and 105.8 % for AFP, indicating that this dual immunosensor matches the requirements of clinical analysis. (author)

  7. The sandwich-type electrochemiluminescence immunosensor for {alpha}-fetoprotein based on enrichment by Fe{sub 3}O{sub 4}-Au magnetic nano probes and signal amplification by CdS-Au composite nanoparticles labeled anti-AFP

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Hankun [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China); Gan Ning, E-mail: ganning@nbu.edu.cn [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China); Li Tianhua; Cao Yuting; Zeng Saolin [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China); Zheng Lei, E-mail: nfyyzl@163.com [Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Guo Zhiyong [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China)

    2012-10-09

    Highlights: Black-Right-Pointing-Pointer Sandwich immunoreaction, testing a large number of samples simultaneously. Black-Right-Pointing-Pointer The magnetic separation and enrichment by Fe{sub 3}O{sub 4}-Au magnetic nano probes. Black-Right-Pointing-Pointer The amplification of detection signal by CdS-Au composite nanoparticles labeled anti-AFP. Black-Right-Pointing-Pointer Almost no background signal, which greatly improve the sensitivity of detection. - Abstract: A novel and sensitive sandwich-type electrochemiluminescence (ECL) immunosensor was fabricated on a glassy carbon electrode (GCE) for ultra trace levels of {alpha}-fetoprotein (AFP) based on sandwich immunoreaction strategy by enrichment using magnetic capture probes and quantum dots coated with Au shell (CdS-Au) as the signal tag. The capture probe was prepared by immobilizing the primary antibody of AFP (Ab1) on the core/shell Fe{sub 3}O{sub 4}-Au nanoparticles, which was first employed to capture AFP antigens to form Fe{sub 3}O{sub 4}-Au/Ab1/AFP complex from the serum after incubation. The product can be separated from the background solution through the magnetic separation. Then the CdS-Au labeled secondary antibody (Ab2) as signal tag (CdS-Au/Ab2) was conjugated successfully with Fe{sub 3}O{sub 4}-Au/Ab1/AFP complex to form a sandwich-type immunocomplex (Fe{sub 3}O{sub 4}-Au/Ab1/AFP/Ab2/CdS-Au), which can be further separated by an external magnetic field and produce ECL signals at a fixed voltage. The signal was proportional to a certain concentration range of AFP for quantification. Thus, an easy-to-use immunosensor with magnetic probes and a quantum dots signal tag was obtained. The immunosensor performed at a level of high sensitivity and a broad concentration range for AFP between 0.0005 and 5.0 ng mL{sup -1} with a detection limit of 0.2 pg mL{sup -1}. The use of magnetic probes was combined with pre-concentration and separation for trace levels of tumor markers in the serum. Due to the

  8. Evaluation of a second trimester triple marker screening test for fetal status using alpha-fetoprotein (aFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3)

    International Nuclear Information System (INIS)

    Mi, Seong Young; Kim, Jong Ho; Choi, Seung Hun

    1997-01-01

    Our purpose was to assess the utility of maternal serum triple-marker screening test using alpha-fetoprotein (aFP), human Chorionic Gonadotropin (hCG) and unconjugated Estriol (uE 3 ) for fetal chromosomal abnormalities. 1,767 venous blood samples (4ml) between 15 and 20 week's gestation for maternal serum screening from January to October 1996, were tested with Kodak Amerix-M triple marker radioimmunoassay kits. Risk analysis was achieved with interpretive software such as Alpha (LMS, Kodak Clinical Diagnostics). Marker levels are transformed into multiples of median (MOM), which represent an interpretation of (weight regressed) patient marker levels relative to regressed median levels for stated gestation. By multivariate anaysis, the three MOM values are combined to generate a liklihood ratio. Calculation of a patient, risk is the product of liklihood ratio and age-related risk. Risk assessment is weight for maternal age. The median values of aFP, hCG and uE 3 were well correlated with gestational age, respectively (r=0.94, p=0.003; r=-0.97, p=0.029; r=0.99, p 3 weren't (r=-0.17, p=0.22; r=0.36, p=0.09, respectively). The values of aFP, CG and uE 3 between pregnancy younger than 35 years-old (n=87) and older than that (n=1640) were 51.67±27.44, vs 54.65±126.36, 46.45±30.08 vs 51.33±38.50 and 8.01±11.01 vs 6.68±7.23, respectively but all of them failed to show significant differences. A second-trimester risk for trisomy 21 > or = 1:270 was considered screen positive. Patients were screen positive for trisomy 21 if aFP or 2.1 MOM and E 3 2.5 MOM. The initial screen-positive rate for both Down' syndrome and neural tube defect were 1.46% (26/1767); 0.73% (13/1767) with each other. Among screen positive 26 patients, three and nine were normal karyotype and normal phenotype, respectively and five patients had still births. Reamining 9 patients underwent terminations. In conclusion, compared with the other group's data even in Koreans (Whang et al, and Song et al

  9. Correlação do nível de alfa-feto proteína, índice de sobrevida e recidiva tumoral em pacientes submetidosa transplante hepático Survival and tumor relapse rate according to alpha-fetoprotein level in patients submitted to liver transplantation

    Directory of Open Access Journals (Sweden)

    Elaine Cristina Ataide

    2011-03-01

    Full Text Available RACIONAL: O transplante hepático para carcinoma hepatocelular pode resultar em potencial cura e melhora da sobrevida comparado com operações conservadoras. OBJETIVO: Analisar os índices de recorrência e sobrevida em pacientes transplantados hepáticos por carcinoma hepatocelular e com níveis séricos de alfa-fetoproteína maiores que 200 ng/ml. MÉTODO: Foram analisados retrospectivamente 90 pacientes cirróticos com carcinoma hepatocelular submetidos à transplante hepático ortotópico entre 1997 e 2009. As lesões hepáticas foram diagnosticadas no pré-operatório por ultrassonografia com Doppler, tomografia computadorizada e níveis séricos de alfa fetoproteína. Os pacientes foram divididos em dois grupos de acordo com o nível de alfa-fetoproteína (menor ou maior que 200 ng/ml. O método de Kaplan-Meier foi usado para calcular a taxa de sobrevida. A análise de regressão Cox estudou os fatores preditivos de sobrevida. RESULTADOS: Pacientes com alfa-fetoproteína maior que 200 ng/ml (n=6 apresentaram menor taxa de sobrevida em um e cinco anos e na média de meses comparados com o grupo com alfa-fetoproteína menor que 200 ng/ml (n=84; respectivamente 35%, 18% e 11,8 meses contra 68%, 43% e 28,1 meses. Além disso, a taxa de recidiva foi 16,6% no primeiro grupo, e de 5,6% no outro. Observouse risco de óbito de 1% para cada 10 u de alfa-fetoproteína>200 ng/ml e para cada mm da maior medida de tumor acima de 28 mm. CONCLUSÃO: Os pacientes com valores séricos de alfa-fetoproteína maiores que 200 ng/ml demonstraram menores taxas de sobrevida, porém não foi preditivo de recidiva tumoral.BACKGROUND: Liver transplantation for hepatocellular carcinoma (HCC can result in a potential cure and greater survival than other less radical techniques. AIM: To analyze the survival and recurrence rate in liver transplant recipients with hepatocellular carcinoma and alpha-fetoprotein over 200 ng/ml. METHOD: Analysis, in this retrospective study

  10. Feto portador de síndrome de turner e tetralogia de fallot associadas à elevação de alfafetoproteína materna Fetal turner syndrome and tetralogy of fallot associated with elevated maternal serum alpha-fetoprotein levels

    Directory of Open Access Journals (Sweden)

    Eduardo Vieira Neto

    1998-06-01

    Full Text Available A síndrome de Turner fetal e suas complicações, a hidropisia e o higroma cístico, podem produzir alteração dos marcadores bioquímicos de soro materno inicialmente utilizados no rastreamento de síndrome de Down e de defeitos de tubo neural (DTN. Os autores relatam o caso de uma gestante de 37 anos, que foi rastreada para síndrome de Down e DTN no início do 2º trimestre. Foi constatado aumento da alfafetoproteína de soro materno (MSAFP e o rastreamento foi considerado positivo para DTN. Foi realizado exame ultra-sonográfico tridimensional, que não demonstrou nenhuma anormalidade fetal ou placentária, caracterizando o caso como elevação idiopática de MSAFP. No 3º trimestre, a gravidez evoluiu com acentuada oligoidrâmnia e alteração do fluxo uteroplacentário, obrigando à instituição de terapia com corticosteróides e parto cesáreo na 34ª semana gestacional. O concepto do sexo feminino foi encaminhado à UTI neonatal, onde foram diagnosticadas tetralogia de Fallot e síndrome de Turner. Esse caso incentivou os autores a rever a literatura sobre marcadores bioquímicos de soro materno na síndrome de Turner e nas malformações cardíacas congênitas. Ao final, propõe-se um protocolo para elevação idiopática de MSAFP.Turner syndrome and its complications, hydrops and cystic hygroma, can produce alterations in maternal serum biochemical markers used in screening for Down's syndrome and neural tube defects (NTD. The authors report the case of a 37-year-old pregnant woman, screened for Down's syndrome and NTD in the second trimester of pregnancy. The maternal serum alpha-fetoprotein (MSAFP level was increased and the test was considered screen positive for NTD. A three-dimensional ultrasound investigation was performed, but no fetal or placental anomalies were found, indicating a case of unexplained increased msafp. In the third trimester severe oligohydramnios and disturbances in uteroplacental arterial circulation

  11. Diagnostic Utility of Alpha-fetoprotein and Des-gamma ...

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... (DCP) have been extensively studied as biomarkers for the diagnosis of and prognostication in hepatocellular carcinoma (HCC). However there are only few reports on the clinical characteristics of hepatocellular carcinoma in relation to .... measured by ultrasound and/or computed tomography scan.

  12. Diagnostic Utility of Alpha-fetoprotein and Des-gamma ...

    African Journals Online (AJOL)

    2018-02-07

    ] High DCP levels also reflect .... using the multiple logistic regression models. P < 0.05 was considered statistically significant. .... that C-reactive protein has significant diagnostic power in AFP-negative, HBV-related HCC.[23].

  13. RIA of alpha-fetoprotein in serum and amniotic fluid

    International Nuclear Information System (INIS)

    Fingerova, H.; Talas, M.; Stroufova, A.

    1979-01-01

    An own modification of the double antibody radioimmunoassay for AFP using 125 I-labelled AFP as a tracer, rabbit anti-AFP obtained from SEVAC, Prague and precipitating antibodies prepared by the authors is described. The AFP levels measured in the serum and the amniotic fluid using the method were in agreement with those obtained by the means of the AFPK RIA kit by SORIN in the Institute for the Care of Mother and Child in Prague. The AFP concentrations found in the cord serum and the amniotic fluid were confirmed also by the rocket electroimmunoassay according to Laurell. The described AFP RIA seems suitable for the clinical application in prenatal screening for congenital malformations, in difficult pregnancies, in hepatology and the diagnosis and the evaluation of therapy of some human malignancies. (author)

  14. Preoperative serum levels of ca 72-4, cea, ca 19-9, and Alpha-fetoprotein in patients with gastric cancer Níveis séricos pré-operatórios de CA 72-4, CEA, CA 19-9 e Alfa-fetoproteína em pacientes com câncer gástrico

    Directory of Open Access Journals (Sweden)

    Rejane Mattar

    2002-06-01

    Full Text Available INTRODUCTION: The clinical importance of preoperative serum levels of CA 72-4, carcinoembryonic antigen (CEA, CA 19-9, and alpha-fetoprotein (AFP was prospectively evaluated in 44 patients with gastric cancer. METHOD: The serum tumor marker levels were determined by commercial radioimmunoassay kits. Positivity for CA 72-4 (>4 U/mL, CEA (>5 ng/mL, CA 19-9 (>37 U/mL, and AFP (>10 ng/mL were correlated according to the stage, histology, and lymph node metastasis. RESULTS AND DISCUSSION: CA 72-4 showed a higher positivity rate for gastric cancer (47.7% than CEA (25%, CA 19-9 (25%, and AFP (0%. The combination of CA 72-4 with CEA and CA 19-9 increased the sensitivity to 61.4%. The positivity rates of CA 72-4 in patients at stages I and II (initial disease and in patients at stages III and IV (advanced disease were 9% and 60.6%, respectively (P INTRODUÇÃO: A importância clínica dos níveis séricos pré-operatórios de CA 72-4, antígeno carcinoembrionário (CEA, CA 19-9 e alfa-fetoproteína (AFPfoi avaliada prospectivamente em 44 pacientes com câncer gástrico. MÉTODOS: Os marcadores tumorais foram quantificados com o emprego de kits comerciais de radioimunoensaio. A positividade dos marcadores, CA 72-4 (>4 U/ml, CEA (>5 ng/ml, CA 19-9 (>37 U/ml e AFP (>10 ng/ml, foi correlacionada com o estágio da doença, a histologia do tumor e comprometimento de linfonodo. RESULTADOS E DISCUSSÃO: O marcador CA 72-4 apresentou maior positividade para o câncer gástrico (47,7% que CEA (25%, CA 19-9 (25% e AFP (0%. A associação de CA 72-4, CEA e CA 19-9 aumentou a sensibilidade para 61,4%. A positividade do CA 72-4 nos pacientes com estágios I e II (Doença Inicial e nos pacientes com estágios III e IV (Doença Avançada foi de 9 e 60,6%, respectivamente (p<0,005. Não foi observada correlação entre os níveis séricos de CEA e CA 19-9 com o estágio do câncer gástrico. O CA 72-4 apresentou tendência de sugerir comprometimento de linfonodo, mas n

  15. Maternal seric alpha-fetoprotein: determination of the medium values in Costa Rican pregnant women

    International Nuclear Information System (INIS)

    Salas Chaves, P.; Villalobos Castro, A.

    1999-01-01

    The present study focuses on the normal mean values of AFP in 124 Costa rican pregnant women. In the women 554 determinations were done between the fifteenth and twentieth week of gestation. For this purpose, and Irma test and normal values were established. The concentration values of AFP were expressed as multiples of the median, considering a value of 2.5 Mm as the normal superior limit and of 0.25 as the inferior limit. The confidence limits of the median were 24-57 Ku/I and the 2.5MM value located between 60-143 Ku/I. (author)

  16. Alpha-fetoprotein, HCV and HBV infections in Nigerian patients with ...

    African Journals Online (AJOL)

    The aim of this study was to determine the relationship of serum AFP with HBV and HCV infections among Nigerian patients with, Primary Hepato-Cellular Carcinoma . Forty-two Nigerian adults comprising of 3 groups – PHCC, Liver cirrhosis (LC) and Controls were recruited into the study. The findings showed that only nine ...

  17. Radioimmunoimaging using F(ab')2 fragment of monoclonal antibodies against human alpha-fetoprotein

    International Nuclear Information System (INIS)

    Sakahara, Harumi; Endo, Keigo; Nakashima, Tetsuo; Koizumi, Mitsuru; Ohta, Hitoya; Torizuka, Kanji; Okada, Kenichiro; Yoshida, Osamu; Nishi, Shinzo.

    1985-01-01

    Using monoclonal antibodies against human α-fetoprotein (AFP), radioiodinated F(ab') 2 fragments were compared with whole IgG as a radiotracer for radioimmunoimaging of cancer. F(ab') 2 fragments were obtained by pepsin digestion of whole IgG (IgGl). IgG and F(ab') 2 were labeled with 125 I or 131 I by the chloramine-T method with almost full retention of antibody activity. F(ab') 2 fragments were cleared more rapidly from the circulation in normal mice with a half life of 6.3 hours than whole IgG with a half life of 5.5 days. Radioactivity of F(ab') 2 in various organs also decreased faster than IgG. In nude mice transplanted with AFP-producing human testicular tumor, F(ab') 2 fragments demonstrated superior scintigrams to whole IgG at 2 days after the injection, because of the fast disappearance of background radioactivity. Although absolute accumulation of 131 I labeled F(ab') 2 in the tumor was less than that of 131 I labeled IgG, tumor to other organ ratios were much higher with F(ab') 2 than those of IgG. The tumor to blood ratio of 131 I labeled F(ab') 2 was 1.04 at day 2, whereas tumor to blood ratio of 131 I labeled IgG was 0.55 at day 2 and 0.92 at day 4, respectively. These results indicated that for the radiolabeling of monoclonal antibodies, F(ab') 2 fragments would be superior to whole IgG in the radioimmunoimaging of cancer. (author)

  18. Alpha-fetoprotein (AFP) Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... Down syndrome. Why do I need an AFP test? The American Pregnancy Association says that all pregnant women should be ... Medicine [Internet]. Johns Hopkins Medicine; Health Library: Common Tests During Pregnancy [cited 2017 Jun 5]; [about 3 screens]. Available ...

  19. An Ultrasensitive Electrochemical Immunosensor for Alpha-Fetoprotein Using an Envision Complex-Antibody Copolymer as a Sensitive Label

    Science.gov (United States)

    Xiong, Ping; Gan, Ning; Cao, Yuting; Hu, Futao; Li, Tianhua; Zheng, Lei

    2012-01-01

    A novel strategy is presented for sensitive detection of alfa-fetoprotein (AFP), using a horseradish peroxidase (HRP)-functionalized Envision antibody complex (EVC) as the label. The Envision-AFP signal antibody copolymer (EVC-AFP Ab2) was composed of a dextran amine skeleton anchoring more than 100 molecules of HRP and 15 molecules of secondary antibody, and acted as a signal tag in the immunosensor. The sensor was constructed using the following steps: First, gold electrode (GE) was modified with nano-gold (AuNPs) by electro-deposition in HAuCl4 solution. The high affinity of the AuNPs surface facilitates direct formation of a self-assembled thiolated protein G layer. Next, the coated GE was incubated in a solution of AFP capture antibody (AFP Ab1); these antibodies attach to the thiolated protein G layer through their non-antigenic regions, leaving the antigen binding sites for binding of target analyte. Following a sandwich immunoreaction, an EVC-AFP Ab2-AFP-AFP Ab1 immunocomplex was formed on the electrode surface, allowing large amounts of HRP on the complex to produce an amplified electrocatalytic current of hydroquinone (HQ) in the presence of hydrogen peroxide (H2O2). Highly amplified detection was achieved, with a detection limit of 2 pg/mL and a linear range of 0.005–0.2 ng/mL for AFP in 10 μL undiluted serum; this is near or below the normal levels of most cancer biomarker proteins in human serum. Measurements of AFP in the serum of cancer patients correlated strongly with standard enzyme-linked immunosorbent assays. These easily fabricated EVC-modified immunosensors show excellent promise for future fabrication of bioelectronic arrays. By varying the target biomolecules, this technique may be easily extended for use with other immunoassays, and thus represents a versatile design route.

  20. An Ultrasensitive Electrochemical Immunosensor for Alpha-Fetoprotein Using an Envision Complex-Antibody Copolymer as a Sensitive Label

    Directory of Open Access Journals (Sweden)

    Lei Zheng

    2012-12-01

    Full Text Available A novel strategy is presented for sensitive detection of alfa-fetoprotein (AFP, using a horseradish peroxidase (HRP-functionalized Envision antibody complex (EVC as the label. The Envision-AFP signal antibody copolymer (EVC-AFP Ab2 was composed of a dextran amine skeleton anchoring more than 100 molecules of HRP and 15 molecules of secondary antibody, and acted as a signal tag in the immunosensor. The sensor was constructed using the following steps: First, gold electrode (GE was modified with nano-gold (AuNPs by electro-deposition in HAuCl4 solution. The high affinity of the AuNPs surface facilitates direct formation of a self-assembled thiolated protein G layer. Next, the coated GE was incubated in a solution of AFP capture antibody (AFP Ab1; these antibodies attach to the thiolated protein G layer through their non-antigenic regions, leaving the antigen binding sites for binding of target analyte. Following a sandwich immunoreaction, an EVC-AFP Ab2-AFP-AFP Ab1 immunocomplex was formed on the electrode surface, allowing large amounts of HRP on the complex to produce an amplified electrocatalytic current of hydroquinone (HQ in the presence of hydrogen peroxide (H2O2. Highly amplified detection was achieved, with a detection limit of 2 pg/mL and a linear range of 0.005–0.2 ng/mL for AFP in 10 μL undiluted serum; this is near or below the normal levels of most cancer biomarker proteins in human serum. Measurements of AFP in the serum of cancer patients correlated strongly with standard enzyme-linked immunosorbent assays. These easily fabricated EVC-modified immunosensors show excellent promise for future fabrication of bioelectronic arrays. By varying the target biomolecules, this technique may be easily extended for use with other immunoassays, and thus represents a versatile design route.

  1. Reference Intervals for Alpha-Fetoprotein (AFP) and Carcinoembryonic Antigen (CEA) in Guangxi Zhuang Ethnic Males from the FAMHES Project.

    Science.gov (United States)

    Lao, Xianjun; Yang, Dongmei; Mo, Zengnan; Gao, Yong; Deng, Yan; Qin, Xue; Li, Shan

    2016-01-01

    Several studies have reported the reference intervals of serum AFP and CEA levels in ethnically diverse populations, but there is a lack of such reference data among Zhuang ethnic males. The aim of this study was to establish the locally validated reference intervals for AFP and CEA in the male population of the Guangxi Zhuang ethnic group. A total of 283 Zhuang ethnic males, aged 22 to 69 years, were included from the Fangchenggang Area Male Health and Examination Survey (FAMHES) project database. The one-sided upper 95th-percentile limit was used to estimate the reference intervals for serum AFP and CEA. The total non-parametric reference intervals for Zhuang ethnic males were reference intervals for serum AFP and CEA values deviated from that reported in previous studies. Age-specific reference intervals should be performed in clinical laboratories to obtain more precise estimations for the clinical conditions of young adults and elderly people.

  2. Use of human chorionic gonadtropin and alpha-fetoprotein radioimmunoassays: specificity and apparent half-life determination after delivery and in patients with germ cell tumors

    International Nuclear Information System (INIS)

    Mann, K.; Lamerz, R.; Hellmann, Th.; Kuemper, H.J.; Staehler, G.; Karl, H.J.

    1980-01-01

    The specificity of commercially available hCG and hCG-β antibodies (anti-hCG-β from N.I.A.M.D.D. (SB6), Serono (S), Biosigma (B), Union Carbide (UC) (I.R.E.) and anti-hCG from Union Carbide) were compared. Using 125 I-hCG (CR 115), the crossreactivity with LH (LER 960) was 5.5% for SB6, 0.25% for S and 0.3% for B. In the homologous hCG system UC, crossreactivity was 0.06% with hCG-β and 1.2% with LH, in the hCG-β system UC, it was 2.2% with hCG and 0.01% with LH. Parallel standard curves for hCG, the 2nd I.R.P. hCG and hCG-β were found exclusively with the 125 I-hCG, anti-hCG-β system S. Consequently accurate estimates of the total hCG or hCG-β content in serum and standardization with the 2nd I.R.P. is possible. This system is the most useful for clinical purposes. The serum half-life of hCG was calculated in 10 pregnant women after delivery and was found to be 10 to 34h. AFP half-life time, determined by the double antibody radioimmunoassay was 4.0+-1.8 (+- SD) days in pregnant women after delivery (n=60) and 3.8+-0.9 days in neonates during the first 16 days of life (n=26). Altogether, apparent half-life determinations were carried out in 29 patients with nonseminomatous germ cell tumours. The results indicate that half-life determinations of hCG and AFP may have a predictive value with respect to the monitoring of therapy. (Auth.)

  3. Simultaneous breast cancer and hepatocellular carcinoma in a male patient with alcoholic liver cirrhosis and a normal serum alpha-fetoprotein level

    Directory of Open Access Journals (Sweden)

    Li-Chun Kao

    2017-06-01

    Laparoscopic cholecystectomy and an excision of the left breast mass were performed. The breast mass was pathologically confirmed to be infiltrating ductal carcinoma not otherwise specified and with predominantly cystic degeneration. The patient received chemotherapy with tamoxifen for the breast cancer, and transarterial chemoembolization for the HCC. Concomitant breast cancer and HCC in a male patient were rarely reported in the literature. Herein, we have discussed the possible relationship of these two disease entities.

  4. Differential vascular endothelial growth factor A protein expression between small hepatocellular carcinoma and cirrhosis correlates with serum vascular endothelial growth factor A and alpha-fetoprotein.

    Science.gov (United States)

    Corradini, Stefano Ginanni; Morini, Sergio; Liguori, Francesca; Carotti, Simone; Muda, Andrea Onetti; Burza, Maria Antonella; Siciliano, Maria; Molinaro, Antonio; Cantafora, Alfredo; Blotta, Ida; Merli, Manuela; Berloco, Pasquale; Rossi, Massimo; Attili, Adolfo Francesco; Gaudio, Eugenio

    2009-01-01

    Drugs with antivascular endothelial growth factor A (anti-VEGF-A) action are under clinical evaluation with encouraging results in advanced hepatocellular carcinoma (HCC). The relative VEGF-A protein expression in non-advanced HCC and in the cirrhotic non-tumoral tissue in the same patient, a variable that could be important for treatment efficacy, has been investigated with conflicting results, only using the cirrhotic tissue surrounding the neoplasm (CS). We measured, for the first time, VEGF-A expression in non-advanced HCC and in the respective CS and cirrhotic tissue at a distance from the tumour (CD), in 24 patients who underwent liver transplantation. VEGF-A protein was more expressed (Pprotein expression in HCC was higher than in the corresponding CD in 83% of cases and AFP and serum VEGF-A corrected for the platelet count positively correlated with the differential VEGF-A protein expression between HCC and CD. Our data provide a rationale for clinical trials involving anti-VEGF-A treatments in patients with non-advanced HCC, and suggest that serum AFP and VEGF-A are variables to be taken into account in these studies.

  5. The value of the indirect immunoradiometric assay of serum alpha - fetoprotein in detecting liver regeneration and neoplastic transformation in chronic liver disease. Part of a coordinated programme on in vitro assay techniques

    International Nuclear Information System (INIS)

    Voiculetz, N.

    1979-07-01

    To investigate the concentration of alphafetoprotein AFP in different liver diseases and above all in liver cancer the immunoradiometric assay was utilized. The results of AFP studies were compared with regeneration index, blastic T lymphocytes transformation as well as other morphological and biochemical data. The results of the investigations indicated that: 38% of chronic benign hepatopathies displayed the values of serum AFP in normal ranges, 54% were in the range of 41 - 200ng/ml, and 8% showed 200 and more ng/ml. The most important conclusion from the work performed was that the elevation of serum AFP level in the evaluation of chronic hepatopathies, especially in cirrhoses, appears as an index of malignancy

  6. ENDODERMAL SINUS TUMOR OF THE OVARY DURING PREGNANCY - A CASE-REPORT

    NARCIS (Netherlands)

    VANDERZEE, AGJ; DEBRUIJN, HWA; BOUMA, J; AALDERS, JG; OOSTERHUIS, JW; DEVRIES, EGE

    Serum alpha-fetoprotein screening led to the detection of an endodermal sinus tumor of the ovary in a 24-year-old female in week 17 of pregnancy. After surgery, chemotherapy was postponed. In week 28 levels of serum alpha-fetoprotein increased, but delivery was delayed until 33 weeks' gestation.

  7. 42 CFR 493.927 - General immunology.

    Science.gov (United States)

    2010-10-01

    ... evaluated include: Analyte or Test Procedure Alpha-l antitrypsin Alpha-fetoprotein (tumor marker... Criteria for acceptable performance Alpha-1 antitrypsin Target value ±3 SD. Alpha-fetoprotein (tumor marker... Hepatitis markers (HBsAg, anti-HBc, HBeAg) IgA IgG IgE IgM Infectious mononucleosis Rheumatoid factor...

  8. Serum and cellular biologic tumor markers in testicular cancer

    International Nuclear Information System (INIS)

    Javadpour, N.; Lalehzarian, M.

    1987-01-01

    Several serum and cellular biologic tumor markers in testicular cancer are studied. The role of alpha-fetoprotein and human chorionic gonadotropin in staying testicular tumors is reported and the use of radioimmunoassay is considered. (M.A.C.) [pt

  9. Prenatal Testing - Multiple Languages

    Science.gov (United States)

    ... AFP (Alpha-Fetoprotein) Test - 简体中文 (Chinese, Simplified (Mandarin dialect)) Bilingual PDF Health Information Translations Non-Stress Test in Pregnancy - 简体中文 (Chinese, Simplified ( ...

  10. CK (Creatine Kinase) Test

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  11. Myasthenia Gravis Tests

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  12. HIV Genotypic Resistance Testing

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  13. With Home Testing, Consumers Take Charge of Their Health

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  14. Liver Panel

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  15. Mono Test

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  16. Pleural Fluid Analysis Test

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  17. Coagulation Factors Test

    Science.gov (United States)

    ... Blood Testing Alpha-1 Antitrypsin Alpha-fetoprotein (AFP) Tumor Marker AMAS Aminoglycoside Antibiotics Ammonia Amniocentesis Amylase ANCA/MPO/ ... Beta-2 Microglobulin Kidney Disease Beta-2 Microglobulin Tumor Marker Bicarbonate (Total CO2) Bilirubin Blood Culture Blood Gases ...

  18. Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients.

    Science.gov (United States)

    Huang, Shujing; Jiang, Feifei; Wang, Ying; Yu, Yanhua; Ren, Siqian; Wang, Xiaowei; Yin, Peng; Lou, Jinli

    2017-06-01

    Alpha-fetoprotein is an effective biomarker as an aid in hepatocellular carcinoma detection in many countries. However, alpha-fetoprotein has its limitations, especially in early hepatocellular carcinoma diagnosis. Protein induced by vitamin K absence or antagonist-II is another biomarker that is used for hepatocellular carcinoma detection. The aim of this study is to compare the diagnostic performance of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II alone and in combination to explore improving biomarker performance as an aid in early hepatocellular carcinoma detection. In this study a total of 582 serum samples including 132 hepatocellular carcinoma patients, 250 non-hepatocellular carcinoma patients, and 200 healthy volunteers were collected. Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were measured by both chemiluminescent enzyme immunoassay on LUMIPULSE platform and by chemiluminescent microparticle immunoassay on ARCHITECT platform. Receiver operation characteristic curve analyses were performed for each biomarker and in combination. The results showed that Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in combination have shown higher area under the curve compared to alpha-fetoprotein alone for diagnosis in whole patients (0.906 vs 0.870) in hepatocellular carcinoma early-stage patients (0.809 vs 0.77) and in hepatitis B virus-related hepatocellular carcinoma patients (0.851 vs 0.788) with ARCHITECT platform. Protein induced by vitamin K absence or antagonist-II showed higher area under the curve than alpha-fetoprotein for diagnosis of hepatitis B virus-related hepatocellular carcinoma patients (0.901 vs 0.788).We conclude that Combining alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II may improve the diagnostic value for early detection of hepatocellular carcinoma. Protein induced by vitamin K absence or antagonist-II performs better

  19. Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver

    DEFF Research Database (Denmark)

    Oertel, Michael; Menthena, Anuradha; Chen, Yuan-Qing

    2008-01-01

    BACKGROUND & AIMS: Previously, we showed high-level, long-term liver replacement after transplantation of unfractionated embryonic day (ED) 14 fetal liver stem/progenitor cells (FLSPC). However, for clinical applications, it will be essential to transplant highly enriched cells, while maintaining....... Rat ED14 FLSPC are alpha-fetoprotein(+)/cytokeratin-19(+) or alpha-fetoprotein(+)/cytokeratin-19(-) and contain all of the normal liver repopulation capacity found in fetal liver. Hematopoietic stem cells, a major component in crude fetal liver cell preparations that engraft in other organs...

  20. Tumor Marker Detection: Ultrasensitive Luminescent In Vitro Detection for Tumor Markers Based on Inorganic Lanthanide Nano?Bioprobes (Adv. Sci. 11/2016)

    OpenAIRE

    Zheng, Wei; Zhou, Shanyong; Xu, Jin; Liu, Yongsheng; Huang, Ping; Liu, Yan; Chen, Xueyuan

    2016-01-01

    In article 1600197, Xueyuan Chen and co?workers report a novel luminescent bioassay technique, namely, dissolution?enhanced luminescence bioassay based on inorganic lanthanide nanoprobes, for ultrasensitive in?vitro detection of tumor markers in human sera or saliva, such as carcinoembryonic antigen, prostate specific antigen and alpha?fetoprotein, with detection sensitivities several orders of magnitude improvement relative to current commercial bioassays.

  1. Browse Title Index

    African Journals Online (AJOL)

    Items 401 - 450 of 1463 ... Vol 13, No 3 (2013), Diagnostic value of glypican-3 in alpha fetoprotein negative hepatocellular carcinoma patients, Abstract PDF. B Li, H Liu, HW Shang, P Li, N Li, HG Ding. Vol 13, No 4 (2013), Differential expressed genes in ECV304 Endothelial-like Cells infected with Human Cytomegalovirus ...

  2. Heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of deleted in malignant brain tumor 1

    DEFF Research Database (Denmark)

    Bisgaard, H.C.; Holmskov, U.; Santoni-Rugiu, E.

    2002-01-01

    DNA library screening approach, we identified 48 enriched, nonredundant gene products associated with liver injury and oval cell proliferation in the adult rat liver. Of these, only two, namely alpha-fetoprotein and a novel transcript with high homology to human DMBT1 (deleted in malignant brain tumor 1...

  3. Occipital Encephalocele: A Case Report

    OpenAIRE

    Aslanova, Rakhshanda; Dolgun, Zehra Nihal; Turhan, Emrah; Ökten, Sabri Berkem

    2015-01-01

    Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the covering membranes through an opening in the skull. In this case we presented a 21-year old 20 weeks pregnant woman with fetal occipital encephalocele accompanying lemon sign, normal posterior fossa imaging and normal level of maternal serum alpha-fetoprotein (MSAFP).

  4. Antenatal Diagnosis and Management of Nuchal Cystic Hygroma: A ...

    African Journals Online (AJOL)

    Differential diagnosis is encephalocele or meningocele. (the mass is posterior and is a single mass. It is associated with a cranial defect) and unfused amniotic membrane. 2.2 Biochemical findings. Fetuses with 45 X karyotype and cystic hygroma are asso- ciated with an elevated amniotic alpha-fetoprotein (AFP).

  5. Cutaneous features seen in primary liver cell (Hepatocellular ...

    African Journals Online (AJOL)

    kemrilib

    biopsy /fine needle aspiration, tumor markers –alpha- fetoprotein, carcinoembryonic antigen, ascitic fluid cytology and other relevant liver function tests. The study was conducted jointly by the GIT and. Dermatology units of the department of medicine of. UCH. The dermatologists recorded the cutaneous findings while the ...

  6. A rare case of ovarian dysgerminoma in a 6-year old child in Lagos ...

    African Journals Online (AJOL)

    Examination findings on presentation to us were that of a full abdomen with obvious suprapubic fullness and a 20-week sized abdominopelvic mass which was firm, non-tender, smooth, and mobile. Tumor markers including beta-human chorionic gonadotrophin and alpha-fetoprotein were essentially normal, but there was a ...

  7. A Rare Case of Immature Ovarian Teratoma with Gliomatosis Peritonei

    African Journals Online (AJOL)

    examination revealed a huge abdominpelvic mass. Ultrasound and CT scan revealed an abdominopelvic mass of 35 cm × 30 cm diameter arising from the left ovary without lymphadenopathy or liver metastasis. Preoperative tumor markers were high with an alpha fetoprotein (AFP) levels of 3100 ng/ml and Ca 125 level of.

  8. Swyer syndrome: The gender swayer?

    African Journals Online (AJOL)

    Jaideep Khare

    2016-06-11

    Jun 11, 2016 ... is a rare type of Disorder of Sex Development (DSD) first ... out mosaicism. A repeat karyotype over 100 cells showed the same result (Fig. 2). Hormonal evaluations were consistent with primary gonadal failure: [TSH 1.59mIU/L, Prolactin ... phatase (PLAP), b-catenin, alpha-fetoprotein (AFP), and stem cell ...

  9. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma.

    NARCIS (Netherlands)

    Perilongo, G.; Maibach, R.; Shafford, E.; Brugieres, L.; Brock, P.; Morland, B.; Camargo, B. de; Zsiros, J.; Roebuck, D.; Zimmermann, A.; Aronson, D.C.; Childs, M.; Widing, E.; Laithier, V.; Plaschkes, J.; Pritchard, J.; Scopinaro, M.; MacKinlay, G.; Czauderna, P.

    2009-01-01

    BACKGROUND: Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter). METHODS: Children with standard-risk

  10. Cisplatin versus Cisplatin plus Doxorubicin for Standard-Risk Hepatoblastoma

    NARCIS (Netherlands)

    Perilongo, Giorgio; Maibach, Rudolf; Shafford, Elisabeth; Brugieres, Laurence; Brock, Penelope; Morland, Bruce; de Camargo, Beatriz; Zsiros, Jozsef; Roebuck, Derek; Zimmermann, Arthur; Aronson, Daniel; Childs, Margaret; Widing, Eva; Laithier, Veronique; Plaschkes, Jack; Pritchard, Jon; Scopinaro, Marcello; MacKinlay, Gordon; Czauderna, Piotr

    2009-01-01

    Background Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter). Methods Children with standard-risk

  11. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma

    NARCIS (Netherlands)

    Perilongo, G.; Maibach, R.; Shafford, E.; Brugieres, L.; Brock, P.; Morland, B.; de Camargo, B.; Zsiros, J.; Roebuck, D.; Zimmermann, A.; Aronson, D.; Childs, M.; Widing, E.; Laithier, V.; Plaschkes, J.; Pritchard, J.; Scopinaro, M.; Czauderna, P.

    2009-01-01

    Background: Preoperative cisplatin alone may be as effective as cisplatin plus doxorubicin in standard-risk hepatoblastoma (a tumor involving three or fewer sectors of the liver that is associated with an alpha-fetoprotein level of >100 ng per milliliter). Methods: Children with standard-risk

  12. OEIS complex (cloacal exstrophy): prenatal diagnosis in the second trimester.

    Science.gov (United States)

    Kutzner, D K; Wilson, W G; Hogge, W A

    1988-05-01

    OEIS complex (exstrophy of the cloaca) is an association of fetal malformations that includes omphalocele, exstrophy of the bladder, imperforate anus, and spinal defects. Most cases should be prenatally detectable by maternal serum alpha-fetoprotein screening, but an accurate diagnosis is essential for appropriate counselling of the family.

  13. Perinatal management of spina bifida | Padayachy | South African ...

    African Journals Online (AJOL)

    The management of patients with myelomeningocele is largely dependent on the timing of the diagnosis, i.e. ante- or postnatally. Antenatal diagnosis can be made using a combination of maternal serum alpha-fetoprotein measurement, fetal ultrasonography and, where necessary, amniocentesis.

  14. The HELLP syndrome : Its association with unexplained elevation of MSAFP and MShCG in the second trimester

    NARCIS (Netherlands)

    Morssink, LP; Heringa, MP; Beekhuis, [No Value; DeWolf, BTHM; Mantingh, A

    In this study, we examined the relationship between concentrations of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG) in the second trimester and the 'haemolysis, elevated liver enzymes, low platelet count' (HELLP) syndrome. The concentrations of both

  15. Identification of Serum Monocyte Chemoattractant Protein-1 and Prolactin as Potential Tumor Markers in Hepatocellular Carcinoma

    NARCIS (Netherlands)

    Wang, Who-Whong; Ang, Soo Fan; Kumar, Rajneesh; Heah, Charmain; Utama, Andi; Tania, Navessa Padma; Li, Huihua; Tan, Sze Huey; Poo, Desmond; Choo, Su Pin; Chow, Wan Cheng; Tan, Chee Kiat; Toh, Han Chong

    2013-01-01

    Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the

  16. common laboratory investigations in obstetrics and gynaecology

    African Journals Online (AJOL)

    Enrique

    Laboratory investigations in obstetrics and gynaecology prac- tice have much in common ... HIV diagnosis and monitoring. These 'universal' tests are ... HIV. • Alpha fetoprotein and Down's screen (α-fetoprotein, β-human chorionic gonadotrophin (HCG) and unconjugated oestriol). • Glucose tolerance test. • Midstream urine.

  17. Serum clusterin as a marker for diagnosing hepatocellular carcinoma

    African Journals Online (AJOL)

    Ragaa A. Ramadan

    2014-06-20

    Jun 20, 2014 ... Clusterin;. Alpha fetoprotein;. Tumor marker;. Hepatitis C virus related liver cirrhosis;. Hepatocellular carcinoma. Abstract Background: Approximately 80% of patients with .... three groups based on clinical and laboratory characteristics: ..... strated in other tumors; such as bladder cancer,29 colorectal.

  18. TJOG Vol 26 No 2.cdr

    African Journals Online (AJOL)

    operatively, serum alpha fetoprotein level was lower abdominal pains. ... measurement of serum TSH in combination with. 123 was discharged on .... Scully RE, Sobin LH. Histological typing. 15. Kurman RJ, Noris HJ. Germ cell tumors of the of ovarian tumors. International histological ovary. In: Somers SAC, Rosen MR, eds.

  19. Significance of detecting circulating hepatocellular carcinoma cells in peripheral blood of hepatocellular carcinoma patients by nested reverse transcription-polymerase chain reaction and its clinical value: a retrospective study.

    Science.gov (United States)

    Liu, Yang; Wang, Yue-ru; Wang, Long; Song, Rui-mei; Zhou, Bo; Song, Zhen-shun

    2014-01-01

    Circulating hepatocellular carcinoma cells may be detected by reverse transcription-polymerase chain reaction. We investigated the relationship between circulating hepatocellular carcinoma cells and hepatoma patient survival after different managements and survival periods. Peripheral vein blood (5 ml) samples were obtained from 113 patients with hepatocellular carcinoma and from 33 control subjects (9 with liver cirrhosis after hepatitis B, 14 with chronic hepatitis B, 10 healthy individuals) between January 1, 2009, and December 31, 2013. To detect circulating hepatocellular carcinoma cells in peripheral blood, alpha-fetoprotein messenger RNA was amplified from total RNA extracted from whole blood by reverse transcription-polymerase chain reaction. Alpha-fetoprotein messenger RNA was detected in 59 blood samples from the hepatocellular carcinoma patients (59/113, 52.2%). In contrast, there were no clinical control subjects whose samples showed detectable alpha-fetoprotein messenger RNA. The presence of alpha-fetoprotein messenger RNA in blood seemed to be correlated with the stage (by TNM classification) of hepatocellular carcinoma, serum alpha-fetoprotein value, and the presence of intrahepatic metastasis, portal vein thrombosis, tumor diameter and/or distant metastasis. In addition, alpha-fetoprotein messenger RNA was detected in the blood of 25 patients showing distant metastasis at extrahepatic organs (100%), in contrast to 32 of 88 cases without metastasis (36.4%). All the patients with hepatocellular carcinoma were followed. Seventeen patients with resection of a T 2 stage hepatocellular carcinoma had a survival of 3.2 years after surgical management, 38 cases with resection of a T3 stage hepatocellular carcinoma had a 1.3-year survival, and only 37 cases with T4 stage disease after different treatments except surgery survived for 0.6 years (P <0.01). The presence of alpha-fetoprotein messenger RNA in peripheral blood may be an indicator of circulating

  20. [Biphasic pulmonary blastoma with germ cell differentiation: a challenge in diagnosis and treatment].

    Science.gov (United States)

    Teixeira, Alexandra; Vieira, Claúdia; Sousa, Nuno; Begonha, Rosa; Afonso, Mariana; Amaro, Teresina; Maurício, Joaquina

    2011-12-01

    Serviço de Oncologia Médica. Instituto Português de Oncologia Francisco Gentil. Porto. Portugal. A 27-year-old man, smoker, presented with three months history of fever. A left pulmonary mass inseparable from the heart was identified and serum alpha-fetoprotein was 4160 ng/ml. The morphologic aspects and immunohistochemistry of the biopsy specimen, in conjunction with the clinical findings were compatible with a diagnosis of pulmonary blastoma with germ cell differentiation. The tumour was considered unresectable. The patient was submitted to two cycles of primary chemotherapy with bleomycin, etoposide and cisplatin. Despite a reduction in serum alpha-fetoprotein, the tumor did not regress. Second line chemotherapy (with paclitaxel, ifosfamide and cisplatin) was instituted, but progressive disease was identified after 2 cycles. Six months after the diagnosis cerebral metastases were found and the patient died. This case illustrates a rare situation of difficult diagnosis and treatment.

  1. Recurrence of acute myeloid leukemia in cryptorchid testis: case report

    OpenAIRE

    Góes, Luccas Santos Patto de; Lopes, Roberto Iglesias; Campos, Octavio Henrique Arcos; Oliveira, Luiz Carlos Neves de; Sant’Anna, Alexandre Crippa; Dall’Oglio, Marcos Francisco; Srougi, Miguel

    2014-01-01

    A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associat...

  2. The Relationship between Preeclampsia and Quadruple Screening Test in Nuliparous

    Directory of Open Access Journals (Sweden)

    Farnaz Zand Vakili

    2017-01-01

    Full Text Available Introduction: Early diagnosis and prediction of preeclampsia needs appropriate obstetric care. Preeclampsia predicting methods are important. This study was designed to determine the correlation between preeclampsia and quadruple screening test in the nulliparous. Materials and Methods:  This case - control study was conducted on 54 pregnant women with preeclampsia (case group and 108 healthy pregnant women (control group who referred to health centers in Sanandaj, Iran. Ultrasonography was performed to determine the gestational age by a radiologist. Maternal serum levels of alpha fetoprotein (AFP, human chorionic gonadotropin (hCG, unconjugated estriol (uE3, and inhibin-A were measured in the second trimester of pregnancy. Data were analyzed using SPSS statistical software and Chi-square test, T-test, sensitivity, specificity, positive and negative predictive values. Results: The results showed that the sensitivity and specificity for the diagnosis of preeclampsia in pregnant women for hCG were 35.2% and 79.6 respectively. These findings for estriol were 20.4% and 88.9%, for inhibin-A were 38.8% and 88% and for alpha fetoprotein were 38.8% and 74.1%. The positive predictive value for hCG, estriol, inhibin-A and alpha fetoprotein were 46.3%, 47.8%, 61.8% and 42.9% respectively. The negative predictive value for hCG, estriol, inhibin-A and alpha fetoprotein were also 71%, 69.1%, 74.2% and 70.8% respectively. Conclusion: There was a relationship between preeclampsia and high levels of inhibin-A and hCG. Further studies on these markers and evaluating their usefulness in the diagnosis and management of preeclampsia are recommended.

  3. Echography of congenital malformations of the central nervous system

    International Nuclear Information System (INIS)

    Toirac Romani, Carlos Andres; Salmon Cruzata, Acelia; Musle Acosta, Mirelvis; Rosales Fargie, Yamile; Dosouto Infante, Vivian

    2010-01-01

    A descriptive and prospective study was conducted in 173 pregnant women attended at the Provincial Department of Clinical Genetics of Santiago de Cuba, from January, 2000 to December, 2004, to identify congenital malformations of the central nervous system detected by means of echography. The most frequent malformation was the hydrocephaly, followed by the fusion defects of the spine, associated with the hydrocephaly and the absence of cranial cavity. There was a prevalence of altered alpha fetoprotein and of elevated amniotic fluid

  4. Research advances in tumor markers for the diagnosis of hepatocellular carcinoma

    OpenAIRE

    YANG Guimin

    2018-01-01

    Hepatocellular carcinoma (HCC) is a malignant tumor with a high fatality rate in the world, and alpha-fetoprotein (AFP) is the most commonly used tumor marker for HCC diagnosis. However, AFP does not have a satisfactory sensitivity or specificity and may lead to missed diagnosis when the tumor is small in the early stage of HCC. This article summarizes the clinical value of new tumor markers in the diagnosis, treatment monitoring, and prognosis judgment of HCC and analyzes the future prospect...

  5. Role of biochemical markers in testicular cancer: diagnosis, staging, and surveillance

    OpenAIRE

    Milose, Jaclyn C; Filson, Christopher P; Weizer, Alon Z; Hafez, Khaled S; Montgomery, Jeffrey S

    2011-01-01

    Jaclyn C Milose, Christopher P Filson, Alon Z Weizer, Khaled S Hafez, Jeffrey S MontgomeryDepartment of Urology, University of Michigan, Ann Arbor, MI, USAAbstract: Testis cancer is one of the few solid organ malignancies for which reliable serum tumor markers are available to help guide disease management. Human chorionic gonadotropin, alpha fetoprotein, and lactate dehydrogenase play crucial roles in diagnosis, staging, prognosis, monitoring treatment response, and surveillance of seminomat...

  6. Novel tumor markers in the serum of testicular germ cell cancer patients: a review

    OpenAIRE

    Syring I; Müller SC; Ellinger J

    2014-01-01

    Isabella Syring, Stefan C Müller, Jörg Ellinger Department for Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany Abstract: Serum tumor markers have an important role in the management of patients with testicular cancer. They are useful for diagnosis, staging and risk assessment, follow-up, evaluation of response, and early detection of relapse. Alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are established serum markers in te...

  7. Liver Rapid Reference Set Application: Kevin Qu-Quest (2011) — EDRN Public Portal

    Science.gov (United States)

    We propose to evaluate the performance of a novel serum biomarker panel for early detection of hepatocellular carcinoma (HCC). This panel is based on markers from the ubiquitin-proteasome system (UPS) in combination with the existing known HCC biomarkers, namely, alpha-fetoprotein (AFP), AFP-L3%, and des-y-carboxy prothrombin (DCP). To this end, we applied multivariate logistic regression analysis to optimize this biomarker algorithm tool.

  8. Posterior midline cervical fetal cystic hygroma.

    Directory of Open Access Journals (Sweden)

    Oak S

    1992-04-01

    Full Text Available Posterior midline cervical cystic hygromas (PMC are frequently found associated with chromosomal aberrations and usually do not survive. The present report illustrates diagnosis of this condition by sonography in an 18 weeks old fetus and an amniocentesis revealed 45 x0 karyotype and increased concentration of alpha-fetoproteins. Pregnancy was terminated in view of Turner′s syndrome. The etiology and natural history of the condition is reviewed.

  9. Intrahepatic recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: Analysis of the pattern and risk factors

    International Nuclear Information System (INIS)

    Kim, Young-sun; Rhim, Hyunchul; Cho, On Koo; Koh, Byung Hee; Kim, Yongsoo

    2006-01-01

    Purpose: To evaluate the pattern and risks for intrahepatic recurrence after percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC). Materials and methods: We studied 62 patients with 72 HCCs (≤4 cm) who were treated with percutaneous RF ablation. The mean follow-up period was 19.1 months (6.0-49.1). We assessed the incidence and cumulative disease-free survival of local tumor progression (LTP) and intrahepatic distant recurrence (IDR). To analyze the risk factors, we examined the following, for the LTP: (1) tumor diameter, (2) contact with vessels, (3) degree of approximation to hepatic hilum, (4) contact with hepatic capsule, (5) presence of ablative safety margin, (6) degree of benign periablational enhancement and (7) serum alpha-fetoprotein; for the IDR: (1) severity of hepatic disease, (2) presence of HBsAg, (3) serum alpha-fetoprotein, (4) whether RF ablation was the initial treatment and (5) multiplicity of tumor for IDR. Results: The incidence of overall recurrence, LTP and IDR was 62.9%, 26.4% and 53.2%, respectively. The cumulative disease-free survival rates were 52%, 82% and 56% at 1 year, 26%, 63% and 30% at 2 years, respectively. Univariate analysis showed that the significant risk factors for LTP were: a tumor with a diameter >3 cm, contact of HCC with a vessel and an insufficient safety margin (p 3 cm and insufficient safety margin were independent factors. Only the increased serum alpha-fetoprotein was a significant risk factor for IDR (p 3 cm) with high serum alpha-fetoprotein should be treated more aggressively because of higher risk for recurrence

  10. A novel embryological theory of autism causation involving endogenous biochemicals capable of initiating cellular gene transcription: a possible link between twelve autism risk factors and the autism 'epidemic'.

    Science.gov (United States)

    King, Chiara R

    2011-05-01

    Human alpha-fetoprotein is a pregnancy-associated protein with an undetermined physiological role. As human alpha-fetoprotein binds retinoids and inhibits estrogen-dependent cancer cell proliferation, and because retinoic acid (a retinol metabolite) and estradiol (an estrogen) can both initiate cellular gene transcription, it is hypothesized here that alpha-fetoprotein functions during critical gestational periods to prevent retinoic acid and maternal estradiol from inappropriately stimulating gene expression in developing brain regions which are sensitive to these chemicals. Prenatal/maternal factors linked to increased autism risk include valproic acid, thalidomide, alcohol, rubella, cytomegalovirus, depression, schizophrenia, obsessive-compulsive disorder, autoimmune disease, stress, allergic reaction, and hypothyroidism. It will be shown how each of these risk factors may initiate expression of genes which are sensitive to retinoic acid and/or estradiol - whether by direct promotion or by reducing production of alpha-fetoprotein. It is thus hypothesized here that autism is not a genetic disorder, but is rather an epigenetic disruption in brain development caused by gestational exposure to chemicals and/or conditions which either inhibit alpha-fetoprotein production or directly promote retinoic acid-sensitive or estradiol-sensitive gene expression. This causation model leads to potential chemical explanations for autistic brain morphology, the distinct symptomatology of Asperger's syndrome, and the differences between high-functioning and low-functioning autism with regard to mental retardation, physical malformation, and sex ratio. It will be discussed how folic acid may cause autism under the retinoic acid/estradiol model, and the history of prenatal folic acid supplementation will be shown to coincide with the history of what is popularly known as the autism epidemic. It is thus hypothesized here that prenatal folic acid supplementation has contributed to the

  11. Intrahepatic chemoembolization in unresectable pediatric liver malignancies

    International Nuclear Information System (INIS)

    Arcement, C.M.; Towbin, R.B.; Meza, M.P.; Kaye, R.D.; Carr, B.I.; Gerber, D.A.; Mazariegos, G.V.; Reyes, J.

    2000-01-01

    Objective. To determine the effectiveness of a new miltidisciplinary approach using neoadjuvant intrahepatic chemoembolization (IHCE) and liver transplant (OLTx) in patients with unresectable hepatic tumors who have failed systemic chemotherapy. Materials and methods. From November 1989 to April 1998, 14 children (2-15 years old) were treated with 50 courses of intra-arterial chemotherapy. Baseline and post-treatment contrast-enhanced CT and alpha-fetoprotein levels were performed. Seven had hepatoblastoma, and 7 had hepatocellular carcinoma (1 fibrolamellar variant). All patients had subselective hepatic angiography and infusion of cisplatin and/or adriamycin (36 courses were followed by gelfoam embolization). The procedure was repeated every 3-4 weeks based on hepatic function and patency of the hepatic artery. Results. Six of 14 children received orthotopic liver transplants (31 courses of IHC). Pretransplant, 3 of 6 showed a significant decrease in alpha-fetoprotein, while only 1 demonstrated a significant further reduction in tumor size. Three of 6 patients are disease free at this time. Three of 6 patients died of metastatic tumor 6, 38, and 58 months, respectively post-transplant. One of 14 is currently undergoing treatment, has demonstrated a positive response, and is awaiting OLTx. Three of 14 withdrew from the program and died. Four of 14 patients developed an increase in tumor size, developed metastatic disease, and were not transplant candidates. Two hepatic arteries thrombosed, and one child had a small sealed-off gastric ulcer as complications of intrahepatic chemoembolization. Conclusion. The results of intrahepatic chemoembolization are promising and suggest that some children who do not respond to systemic therapy can be eventually cured by a combination of intrahepatic chemoembolization orthotopic liver transplant. Alpha-fetoprotein and cross-sectional imaging appear to be complementary in evaluating tumor response. IHCE does not appear to convert

  12. Alfa-fetoprotein secreting ovarian sex cord-stromal tumor

    Directory of Open Access Journals (Sweden)

    Kusum D Jashnani

    2013-01-01

    Full Text Available Ovarian sex cord-stromal tumors are relatively infrequent neoplasms that account for approximately 8% of all primary ovarian tumors. They are a heterogeneous group of neoplasms composed of cells derived from gonadal sex cords (granulosa and Sertoli cells, specialized gonadal stroma (theca and Leydig cells, and fibroblasts. They may show androgenic or estrogenic manifestations. We report such a tumor associated with markedly raised serum alpha-fetoprotein (AFP levels in a young female presenting with a mass and defeminising symptoms. Serum AFP levels returned to normal on removal of tumor.

  13. Classical testicular seminoma in young man.

    Science.gov (United States)

    Voinea, F; Vameşu, S; Deacu, Mariana; Aşchie, Mariana; Poinăreanu, I

    2006-01-01

    A 29 year old man was admitted in Urology Department of County Hospital of Constanta for left testicular increased size in last six months, without other symptoms. Testicular tumor was palpated and visualized by ultrasound. Computed tomography did not revealed metastatic lymph nodes. Beta-human chorionic gonadotropin and alpha-fetoprotein were within the normal range. We diagnosed the case as a left testicular tumor and performed high orchiectomy. Histological examination revealed typical seminoma. Subsequently, the patient was given two courses of systemic chemotherapy (bleomycin, etoposide, cisplatin) as an adjuvant therapy. The patient has remained free of disease six months after discharge.

  14. Development of a Computational Assay for the Estrogen Receptor

    Science.gov (United States)

    2006-07-01

    are worse for a coupled cluster energy cal- T .; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challa - combe, M.; Gill, P. M. W.; Johnson, B.; Chen, W...tumors by fourfold." OH3 /H 3 N Taoifn4-hvd..vt ,rmvife n 0 CH3 T a nixife n 0 __ CH3 0 OH / \\/_ __\\\\ o \\/ 0 Hf OH O H3 OH3 H3OH N-de s me thylta mo...Alpha-Fetoprotein" Karl N. Kirschner, Katrina W. Lexa,* Amanda M. Salisburg,* Katherine A. Alser,* Leroy Joseph, Thomas T . Andersen, James A. Bennett

  15. Primary Lymphoma of the Liver: A Case Report and Review

    Directory of Open Access Journals (Sweden)

    Franzjosef Schweiger

    2000-01-01

    Full Text Available The case of a previously healthy man who developed primary non-Hodgkin’s lymphoma of the liver is presented. Biopsy confirmed that the tumour was of the diffuse large cell type and was of apparent T-cell origin. The diagnosis of these rare tumours is suggested by the presence of a hepatic mass without lymphadenopathy, splenomegaly or bone marrow involvement, as well as normal carcinoembryonic antigen and alpha-fetoprotein levels. However, histological examination of tissue is essential to confirm the diagnosis. The response to treatment varies, but surgical resection and/or chemotherapy can result in prolonged remissions. The literature on this topic is briefly reviewed.

  16. Hepatoblastoma associated with Beckwith-Wiedemann syndrome and hemihypertrophy.

    Science.gov (United States)

    Hamada, Y; Takada, K; Fukunaga, S; Hioki, K

    2003-04-01

    Both Beckwith-Wiedemann syndrome (BWS) and hemihypertrophy (HH) have been recognized to be overgrowth syndromes associated with an increased risk of cancer. We report an infant with hepatoblastoma associated with both BWS and HH in whom high serum alpha-fetoprotein (AFP) levels persisted even after complete tumor resection with no tumor recurrence. This phenomenon might be partly due to the nature of the proliferative disease. It is important to recognize that in some infants with BWS prolonged high serum AFP levels mimic the existence of a tumor, and that treatment should be based not only on AFP measurement, but also on repeated radiologic imaging.

  17. Gender impact on first trimester markers in Down syndrome screening

    DEFF Research Database (Denmark)

    Larsen, Severin Olesen; Wøjdemann, Karen R; Shalmi, Anne-Cathrine

    2002-01-01

    with normal outcome. Mean log MoM values for pregnancies with female and male fetuses were calculated using regression of log marker values on gestational age expressed as crown rump length and on maternal weight. A pronounced gender impact was found for free betahCG, being 16% higher for female than for male......The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies...

  18. A giant cord hemangioma with extramedullary hematopoiesis and elevated maternal serum human chorionic gonadotropin: a case report and review of the literature

    OpenAIRE

    Hara, Kieko; Fukumura, Yuki; Saito, Tsuyoshi; Arakawa, Atsushi; Okabe, Hitomi; Takeda, Satoru; Yao, Takashi

    2015-01-01

    A case of prenatally diagnosed, giant cord hemangioma is reported, which was accompanied by the elevation of maternal serum alpha-fetoprotein (MS-AFP) and human chorionic gonadotropin (MS-hCG) levels. A 30-year-old woman without a previous history of gravida or para, presented with intermittent abdominal pain at 26 weeks of gestation. Doppler studies showed the fetus developing heart failure as the tumor grew larger. Caesarian section was performed at 29 weeks of gestation. Macroscopic examin...

  19. Tricuspid valve obstruction by a Tumour Thrombus in primary liver cell carcinoma

    Directory of Open Access Journals (Sweden)

    Basil N Okeahialam

    2015-01-01

    Full Text Available An adult male in his early thirties presented with gradual weight loss over several months; during which he became jaundiced and lately insidious breathlessness. On physical examination, he was cachectic with irregular upper abdominal distension. There was no lower limb oedema or other feature of congestive cardiac failure. There was however a hard, knobbly and tender liver on abdominal palpitation; which on abdominal ultrasound was reported as primary liver cell carcinoma (PLCC. Alpha fetoprotein level was also in support of the diagnosis.

  20. Hepatocellular carcinoma with extensive hepatic artery injury: transcatheter arterial chemoembolization through collaterals after coil embolizatoin of gastric arteries

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Gab Choul; Yoon, Hyun Ki; Hwang, Jae Cheol; Lee, Duck Hee; Song, Ho Young; Suh, Dong Jin; Lee, Yung Sang; Chung, Young Hwa; Sung, Gyu Bo [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of); Ko, Ki Young [Catholic Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-09-01

    To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE) after coil embolization of the gastroduodenal artery in hepatocellular carcinoma cases with multiple collateral arteries caused by proper hepatic artery injury. Between March 1997 and November 1998, a prospective trial of transcatheter arterial chemoembolization (TACE) was performed through collaterals from the gastroduodenal artery of 31 hepatocellular carcinoma patients with extensive proper hepatic artery injury due to repeated TACE. Among this number, 16 (group A) underwent TACE after coil embolization of the right gastric and gastroduodenal artery. The other 15 patients (group B) underwent TACE without coil embolization. The two groups had the same TNM stage and Clild-Pugh status. During the follow-up period, group A underwent additional TACE 3.3 times, and group B 2.8 times. The therapeutic effect of TACE was evaluated with computed tomography and by measuring alpha-fetoprotein levels. Complications were evaluated by means of gastrofibroscopy, laboratory data, and evaluation of the patients' clinical symptoms. The results obtained after six months and one year were compared within and between each group. At six months follow-up, CT findings had improved or were unchanged in 11 patients(69 %) in group A, and four patients(27 %) in group B(p = 0.032). In ten patients in each group, the level of alpha-fetoprotein was above 200 ng/ml. Its level was decreased in five patients(50 %) and three patients(30 %), respectively. The six-month survival rate was 81 % (13/16) in group A and 67% (10/15) in group B (p 0.43), while the one-year survival figures for these two groups were 50 % (8/16) and 20 % (3/15), respectively(p = 0.135). In group A, the CT findings were steady in five out of eight patients(63 %), while in groupB, CT findings showed that tumors with increased alpha-fetoprotein levels had increased in size and/or number. In group A, it was found that in two (33 %) of six

  1. Evaluation of serum protein markers in diagnosis of hepatocellular carcinoma and carcinogenesis risk assessment in chronic liver disease patients

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    Essraa Adel Aly Aly Hegazy

    2017-09-01

    Full Text Available Objective: To assess the diagnostic value of the protein markers in both cirrhotic patients on top of hepatitis C virus (HCV and in hepatocellular carcinoma (HCC patients on top of HCV in comparison to normal controls. Methods: A total number of 100 subjects including HCC, cirrhotic patients on top of HCV and normal controls were subjected to serum protein markers analysis for alpha-fetoprotein, apolipoprotein A1, apolipoprotein A2, insulin like growth factor 1 and insulin like growth factor 1 receptor by western blotting technique. Results: It was found that alpha-fetoprotein alone could not be used as a screening test while apolipoprotein A2 as a serum marker could be used as a non invasive screening test to differentiate a case of HCC from cirrhotic HCV patient. The all four markers were able to discriminate normal persons from HCC and cirrhotic HCV patients effectively. Conclusions: We concluded that proteomics analysis being non invasive, rapid and sensitive is a novel gate that can serve in early diagnosis and screening of HCC and cirrhotic HCV patients

  2. Assaying Biomarkers via Real-Time Measurements of the Effective Relaxation Time of Biofunctionalized Magnetic Nanoparticles Associated with Biotargets

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    Shu-Hsien Liao

    2015-01-01

    Full Text Available An assay of biomarkers consisting of alpha-fetoprotein (AFP is reported. Real-time measurements of the effective relaxation time τeff, when the biofunctionalized magnetic nanoparticles (BMNs were conjugating with biotargets, were made. The BMNs are anti-alpha-fetoprotein (antiAFP coated onto dextran-coated iron oxide nanoparticles labeled as Fe3O4-antiAFP. It was found that the effective relaxation time, τeff, increases as the association of AFP and Fe3O4-antiAFP evolves. We attribute this to the enhanced Brownian motion of BMNs when magnetic clusters are present during the conjugation. We found that saturation magnetization, Ms, increases when the concentration of AFP increases. This is due to the fact that more magnetic clusters are associated in the reagent, and therefore the Ms increases when the concentration of AFP increases. The change of effective relaxation time and saturation magnetization shows a behavior of logistic function, which provides a foundation for assaying an unknown amount of biomolecules. Thus, we demonstrate sensitive platforms for detecting AFP by characterizing τeff. The detection platform is robust and easy to use and shows promise for further use in assaying a broad number of biomarkers.

  3. Programa de pesquisaje por alfafetoproteína en Ciudad de La Habana: Evaluación de aspectos organizativos e impacto psicosocial

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    Celia Llanusa Ruiz

    1998-02-01

    Full Text Available Se realiza en Cuba el pesquisaje de malformaciones congénitas a gestantes desde 1982, y se evalúan los niveles de alfafetoproteína. Por esta razón se aplicó en Ciudad de La Habana, en el Departamento Provincial de Genética, una encuesta a 100 gestantes atendidas en este servicio por alfafetoproteína elevada, con el objetivo de evaluar los aspectos organizativos y el impacto psicosocial de este programa de pesquisaje. Se concluye que debe mejorar la información que se ofrece a la gestante sobre la utilidad de la prueba (el 18 % no había recibido información por parte del médico, aunque el 93 % evaluó bien el pesquisajeThe screening of congenital malformations among pregnant women is conducted in Cuba Since 1982, and their alpha-fetoprotein levels are also evaluated. For this reason, a survey was applied to 100 pregnant women who receive attention at the Provincial Genetics Department, in Havana City, due to their elevated alpha-fetoprotein (AFP with the objective of evaluating the organizational aspects and the psychosocial impact ot this screening program. It was concluded that the information given to the pregnant women about the usefulness of this should be improved (18 % of them had not received any information from the doctor, although 93 % of these patients considered the screening as good

  4. Validation of serological models for staging and prognostication of HCC in patients from a Japanese nationwide survey.

    Science.gov (United States)

    Toyoda, Hienori; Tada, Toshifumi; Johnson, Philip J; Izumi, Namiki; Kadoya, Masumi; Kaneko, Shuichi; Kokudo, Norihiro; Ku, Yonson; Kubo, Shoji; Kumada, Takashi; Matsuyama, Yutaka; Nakashima, Osamu; Sakamoto, Michiie; Takayama, Tadatoshi; Kudo, Masatoshi

    2017-10-01

    Two serology-based scoring models for prognostication of patients with hepatocellular carcinoma (HCC), the BALAD and BALAD-2 models, were applied to a Japanese cohort of a nationwide follow-up survey of HCC. The ability of these models to predict the progression of HCC and the deterioration of liver function and to assess prognosis was evaluated. BALAD and BALAD-2 scores were calculated in 24,029 patients from a cohort of Japanese nationwide survey based on the serum levels of five markers (bilirubin, albumin, lens culinaris agglutinin-reactive alpha-fetoprotein, alpha-fetoprotein, and des-gamma-carboxy prothrombin) measured at the time of HCC diagnosis. The associations of these scores with the progression of HCC and liver function and with survival rates were analyzed. There were good correlations between BALAD and BALAD-2 scores and the progression of HCC and Child-Pugh class. Both scores accurately categorized patients into risk groups with different survival rates. BALAD-2 showed superior discrimination of patient survival compared with the original BALAD. Serology-based scoring models for prognostication, especially the BALAD-2 model, were useful for staging and prognostication of survival in a cohort of Japanese patients with HCC from a nationwide survey.

  5. Surveillance Program for Diagnosis of HCC in Liver Cirrhosis: Role of Ultrasound Echo Patterns.

    Science.gov (United States)

    Soresi, Maurizio; Terranova, Antonino; Licata, Anna; Serruto, Antonietta; Montalto, Giuseppe; Brancatelli, Giuseppe; Giannitrapani, Lydia

    2017-01-01

    International guidelines suggest ultrasound surveillance for hepatocellular carcinoma (HCC) early diagnosis in liver cirrhosis (LC) patients, but 40% of nodules HCC in patients under surveillance. 359 patients with LC (Child-Pugh A-B8) underwent ultrasound screening (median follow-up 54 months, range 12-90 months), liver function tests, alpha-fetoprotein assay, and portal hypertension evaluation. Echo patterns were homogeneous, bright liver, coarse, coarse small nodular pattern, and coarse large nodular pattern. During follow-up 13.9% developed HCC. At multivariate analysis using Cox's model alpha-fetoprotein, coarse large nodular pattern, portal hypertension, and age were independent predictors of HCC development. Kaplan-Meier estimates of HCC cumulative risk in relation to the baseline echo patterns showed risk of 75% in coarse large nodular pattern patients, 23% coarse small nodular pattern, 21% coarse pattern, 0% homogeneous, and bright liver echo patterns (log-rank test = 23.6, P HCC as 40.7% of patients with this pattern developed HCC. Homogeneous and bright liver echo patterns and the absence of portal hypertension were not related to HCC. This observation could raise the question of possibly modifying the follow-up timing in this subset of patients.

  6. ROM Plus®: accurate point-of-care detection of ruptured fetal membranes

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    McQuivey RW

    2016-05-01

    Full Text Available Ross W McQuivey,1 Jon E Block2 1Clinical Affairs, Clinical Innovations, Salt Lake City, UT, 2Independent Clinical Consultant, San Francisco, CA, USAAbstract: Accurate and timely diagnosis of rupture of fetal membranes is imperative to inform and guide gestational age-specific interventions to optimize perinatal outcomes and reduce the risk of serious complications, including preterm delivery and infections. The ROM Plus is a rapid, point-of-care, qualitative immunochromatographic diagnostic test that uses a unique monoclonal/polyclonal antibody approach to detect two different proteins found in amniotic fluid at high concentrations: alpha-fetoprotein and insulin-like growth factor binding protein-1. Clinical study results have uniformly demonstrated high diagnostic accuracy and performance characteristics with this point-of-care test that exceeds conventional clinical testing with external laboratory evaluation. The description, indications for use, procedural steps, and laboratory and clinical characterization of this assay are presented in this article.Keywords: ROM Plus®, premature rupture of membranes, point-of-care immunoassay, insulin-like growth factor binding protein-1, IGFBP-1, placental protein 12, PP12, alpha-fetoprotein, AFP

  7. An inflammation-based prognostic index predicts survival advantage after transarterial chemoembolization in hepatocellular carcinoma.

    Science.gov (United States)

    Pinato, David J; Sharma, Rohini

    2012-08-01

    Transarterial chemoembolization (TACE) is the preferred treatment for unresectable, intermediate-stage hepatocellular carcinoma (HCC). However, survival after TACE can be highly variable, suggesting the need for more accurate patient selection to improve therapeutic outcome. We have explored the prognostic ability of the blood neutrophil-to-lymphocyte ratio (NLR), a biomarker of systemic inflammation, as a predictor of survival after TACE. Fifty-four patients with a diagnosis of HCC eligible for TACE were selected. Clinicopathologic variables were collected, including demographics, tumor staging, liver functional reserve, and laboratory variables. Dynamic changes in the NLR before and after TACE were studied as predictors of survival using both a univariate and multivariate Cox regression model. Patients in whom the NLR remained stable or normalized after TACE showed a significant improvement in overall survival of 26 months compared with patients showing a persistently abnormal index (P = 0.006). Other predictors of survival on univariate analysis were Cancer of the Liver Italian Program score (P = 0.05), intrahepatic spread (P = 0.01), tumor diameter > 5 cm (P = 0.02), > 1 TACE (P = 0.01), alpha-fetoprotein ≥ 400 (P = 0.002), and radiologic response to TACE (P analysis. Changes in alpha-fetoprotein after treatment did not predict survival. Patients with a persistently increased NLR have a worse outcome after TACE. NLR is a simple and universally available stratifying biomarker that can help identify patients with a significant survival advantage after TACE. Copyright © 2012 Mosby, Inc. All rights reserved.

  8. Prenatal aspects of giant fetal cranial haemangio-endothelioma.

    Science.gov (United States)

    Boulot, P; Deschamps, F; Montoya, F; Montoya, P; Couture, A; Ferran, J L; Lefort, G

    1996-04-01

    A case of a large vascular lesion of the skull is reported. The lesion was discovered at 22 weeks' gestation and it rapidly increased in size, reaching 8 cm a month later. Tumor echogenicity was the same as that for soft tissues and colour Doppler examination revealed intense vascularization. Cordocentesis showed features of the Kasabach-Merritt syndrome and very high plasma levels of alpha-fetoprotein. A Caesarean section was performed to avoid dystocia and led to the birth of a baby with cardiac failure in the immediate neonatal period. Biopsies of the mass led to the diagnosis of a non-malignant haemangio-endothelioma. The mass was removed and plastic surgery performed. The baby is alive and well 9 months after the operation.

  9. Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis

    Science.gov (United States)

    Gomez-Ospina, Natalia; Potter, Carol J.; Xiao, Rui; Manickam, Kandamurugu; Kim, Mi-Sun; Kim, Kang Ho; Shneider, Benjamin L.; Picarsic, Jennifer L.; Jacobson, Theodora A.; Zhang, Jing; He, Weimin; Liu, Pengfei; Knisely, A. S.; Finegold, Milton J.; Muzny, Donna M.; Boerwinkle, Eric; Lupski, James R.; Plon, Sharon E.; Gibbs, Richard A.; Eng, Christine M.; Yang, Yaping; Washington, Gabriel C.; Porteus, Matthew H.; Berquist, William E.; Kambham, Neeraja; Singh, Ravinder J.; Xia, Fan; Enns, Gregory M.; Moore, David D.

    2016-01-01

    Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection. PMID:26888176

  10. Portal vein thrombosis in pregnancy caused by hepatocellular carcinoma: A rare case report

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    Nasrin Jalilian

    2014-03-01

    Full Text Available Background: Portal Vein Thrombosis (PVT during pregnancy is very rare. Its most common underlying causes are myeloproliferative disorders, pancreatitis, hepatocellular carcinoma and hereditary deficiency of natural anticoagulants (thrombophilia. Hepatocellular Carcinoma (HCC is one of the most common gastrointestinal malignancies which is caused by toxins, alcohol and hepatitis viruses. Viral hepatitis is the cause of one-third of this carcinoma in China and Asia. Case Report: We reported a case of Portal Vein Thrombosis (PVT in a 31-year-old pregnant woman with an otherwise normal liver function, no risk factors, no hepatitis and no history of thrombophilia. Report of ultrasonography, CT scan and elevated alpha-fetoprotein test, indicated hepatocellular carcinoma and metastases was found in the bone and lungs. Conclusion: This case is very rare in pregnancy so diagnosis and decision to termination of pregnancy is important.

  11. A case of leptospirosis simulating colon cancer with liver metastases.

    Science.gov (United States)

    Granito, Alessandro; Ballardini, Giorgio; Fusconi, Marco; Volta, Umberto; Muratori, Paolo; Sambri, Vittorio; Battista, Giuseppe; Bianchi, Francesco-B

    2004-08-15

    We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; alpha-fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was reevaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospirosis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two mo, biochemical data, CT and colonoscopy were totally normal.

  12. Recurrence of acute myeloid leukemia in cryptorchid testis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Góes, Luccas Santos Patto de [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Lopes, Roberto Iglesias [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Campos, Octavio Henrique Arcos [Hospital do Servidor Público Municipal de São Paulo, São Paulo, SP (Brazil); Oliveira, Luiz Carlos Neves de; Sant' Anna, Alexandre Crippa; Dall' Oglio, Marcos Francisco; Srougi, Miguel [Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-07-01

    A 23-year-old male with a history of bone marrow transplant for acute myeloid leukemia. He presented a large mass in the right inguinal region 5 years ago. Upon physical examination, right-sided cryptorchidism was observed. The tumor markers alpha-fetoprotein and beta-HCG were within normalcy range and lactate dehydrogenase was raised. Computed tomography of the abdomen and pelvis revealed right testicular mass in contiguity with the inguinal canal to the ipsilateral retroperitoneum, associated with right hydronephrosis. Due to the risk of germ-cell tumor in undescended testicle, the patient underwent radical right orchiectomy. The pathological examination showed recurrence of acute myeloid leukemia in the testis. He was referred to oncology for adjuvant therapy. Our literature review found no similar cases described.

  13. MAY GLYPICAN-3 BE A NOVEL BIOMARKER AND POTENTIAL THERAPEUTIC TARGET IN HEPATOCELLULAR CANCER?

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    Irina I. Ivanova

    2018-03-01

    Full Text Available The burden of advanced chronic liver disease is increasing worldwide, despite the recent advances in the management of chronic hepatitis viral infections. The abdominal ultrasound is the only approved method for surveillance of patients with cirrhosis, a premalignant condition for hepatocellular cancer (HCC. Although alpha fetoprotein has been known as a tumour marker for HCC, it is not commonly used for screening due to suboptimal sensitivity and specificity. There is a need to introduce a novel biomarker for definition of HCC in early stage and for prognostic and therapeutic response assessment. A review of the current evidences, encouraging the use of glypican-3 in management of patients with cirrhosis and HCC is presented.

  14. Prognostic value of α-fetoprotein response in treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    JIA Jia

    2013-08-01

    Full Text Available Primary hepatocellular carcinoma (HCC is the most common malignant tumor of the liver. Accurate assessment of treatment outcome and prognosis in HCC patients is very important due to its high malignancy and poor prognosis. Currently, radiological imaging, though a standard method for prognostic evaluation of HCC, has a lot of limitations. As an important serological marker of HCC, alpha-fetoprotein (AFP has been widely used in the screening, diagnosis, and prognostic evaluation of HCC. The studies regarding the prognostic value of AFP response in HCC patients were summarized. Generally, AFP has good prognostic value in HCC patients treated with radiofrequency ablation, transarterial chemoembolization, yttrium-90 radioembolization, molecular targeted agents like sorafenib, systemic chemotherapy, hepatic artery infusion chemotherapy, or concurrent chemoradiotherapy.

  15. Serum ferritin. Its clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Rochna Viola, E.M. (Comision Nacional de Energia Atomica, Buenos Aires (Argentina). Centro de Medicina Nuclear); Diaz de Domingo, N.B.; Lazarowski, A. (Buenos Aires Univ. Nacional (Argentina). Facultad de Farmacia y Bioquimica)

    1981-08-01

    Serum ferritin (SF) concentration as determined by the immunoradiometric method allows the direct measurement of a fraction of the body ferritin pool. In normal subjects, SF is an excellent index of body iron stores. In certain conditions associated with increased ferritin synthesis (such as liver disease, inflammation, malignancy, chronic disorders, ineffective erythropoiesis, or during ferrotherapy), SF may not accurately reflect body iron stores. In hyposideremic anemias SF concentration permits to differentiate those due to iron deficiency from those due to chronic disorders. With a good assay quality, subnormal SF levels are incontrovertible in the diagnosis of iron deficiency. SF determination has been investigated as possible tumor marker. When performed in combination with the alpha-fetoprotein assay, SF enhances the specificity of serodiagnosis of hepatoma. SF results must be interpreted bearing in mind the possible participation of circumstances that i) modify the body iron stores and ii) lead to increased ferritin synthesis.

  16. Primary Hepatic Lymphoma Mimicking Cholangiocarcinoma

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    Foroogh Forghani1,

    2017-07-01

    Full Text Available Primary hepatic lymphoma (PHL presenting with obstructive jaundice is rare and can mimic a preoperative diagnosis of cholangiocarcinoma. We should consider PHL in patients with radiological hepatic disease with normal serum alpha-fetoprotein and carcinoembryonic antigen levels, and elevated lactate dehydrogenase. We present the case of a 67-year-old male with no significant medical history presented with abdominal pain, jaundice, fever, and abnormal liver function tests. Abdominal sonography and computed tomography scan suggested a diagnosis of obstructive jaundice and cholangitis due to cholangiocarcinoma (Klatskin tumor. A subsequent liver biopsy diagnosed PHL, and the patient was treated with combination chemotherapy, including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP. PHL should be considered in patients presenting with biliary obstruction.

  17. Metastatic Granulosa Cell Tumor of the Testis: Clinical Presentation and Management

    Directory of Open Access Journals (Sweden)

    Anand Mohapatra

    2016-01-01

    Full Text Available Granulosa cell tumors (GCTs of the testis are rare sex cord-stromal tumors that are present in both juvenile and adult subtypes. While most adult GCTs are benign, those that present with distant metastases manifest a grave prognosis. Treatments for aggressive GCTs are not well established. Options that have been employed in previous cases include retroperitoneal lymph node dissection (RPLND, radiation, chemotherapy, or a combination thereof. We describe the case of a 57-year-old man who presented with a painless left testicular mass and painful gynecomastia. Serum tumor markers (alpha fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase and computed tomography of the chest and abdomen were negative. The patient underwent left radical orchiectomy. Immunohistochemical staining was consistent with a testicular GCT. He underwent a left-template laparoscopic RPLND which revealed 2/19 positive lymph nodes. Final pathological stage was IIA. He remains free of disease 32 months after surgery.

  18. Research advances in tumor markers for the diagnosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    YANG Guimin

    2018-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a malignant tumor with a high fatality rate in the world, and alpha-fetoprotein (AFP is the most commonly used tumor marker for HCC diagnosis. However, AFP does not have a satisfactory sensitivity or specificity and may lead to missed diagnosis when the tumor is small in the early stage of HCC. This article summarizes the clinical value of new tumor markers in the diagnosis, treatment monitoring, and prognosis judgment of HCC and analyzes the future prospects of the measurement of tumor markers for HCC. It is pointed out that combined determination of several tumor markers helps to improve the sensitivity and specificity of HCC diagnosis, and the screening and optimization of combined determination of tumor markers, noninvasive and efficient tumor markers, and individualized treatment are research hotspots in future.

  19. Pancreatoblastoma, a Rare Childhood Tumor: A Case Report

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    Asuman ARGON

    2017-05-01

    Full Text Available Pancreatoblastoma, rarely encountered in the literature, is a malignant exocrine tumor seen in the pancreas. A 5-year-old boy suffering from abdominal pain was sent to our institute for further examination and treatment. Clinical examination was normal but for a palpable abdominal tumor mass. Abdominal Doppler ultrasonography showed a mass with well-defined margins within the body of the pancreas. Laboratory tests, including lactic dehydrogenase, alpha-fetoprotein and cancer antigen 125 were abnormal. The tumor invading the splenic vein and transverse colon was removed totally. We observed a hypercellular tumor in histopathological examination. The tumor had epithelial acinar cells and squamoid morules (corpuscles separated by stromal bands. Adjuvant chemotherapy was used after surgery. However, the patient died 14 months later. All data about pancreatoblastoma have to be collected in order to choose the treatment to elucidate the molecular pathogenesis of the tumor, to diagnose it early and to develop target-specific treatments.

  20. Radioimmunoassays for tumor diagnosis

    International Nuclear Information System (INIS)

    Dressler, J.

    1983-01-01

    Aside from imaging techniques several (radio-)immunological analyses are used for tumor diagnosis. Oncofetal antigens, for instance the carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP), have become the most important substances for many malignancies. However, nearly all of the so-called tumor markers are not suitable for early diagnosis or screening either because of low sensitivity or low tumor specifity. On the other hand follow-up measurements give a very sensitive index of the success of treatment and may indicate tumor progression when other signs are still not present. In some carcinomas and under some clinical circumstances tumorspecific markers are available and mandatory for detection and/or staging: AFP in hepatoma, acid phosphatase in metastasizing carcinoma of the prostate and serum thyreoglobulin in differentiated thyroid cancer. (orig.) [de

  1. Three equine cases of mixed hepatoblastoma with teratoid features.

    Science.gov (United States)

    Loynachan, A T; Bolin, D C; Hong, C B; Poonacha, K B

    2007-03-01

    Hepatoblastoma was diagnosed in 3 Thoroughbreds at the University of Kentucky Livestock Disease Diagnostic Center (LDDC) since 1997. Case #1 involved a fetus with a well-demarcated, multilobulated, solitary mass that extended from the left liver lobe. Case #2 was observed in a neonate with a primary hepatic mass and multiple metastases in the skin, brain, meninges, and stylohyoid bone. Case #3 was a solitary hepatic mass incidentally discovered in a neonate at necropsy. Microscopically, the masses were similarly composed of sheets and cords of fetal and embryonal epithelial cells that frequently formed sinusoid-like structures. Intermixed with the neoplastic epithelial cells were variable amounts of hemorrhage, necrosis, osteoid, and bone. Immunohistochemically, the epithelial cells stained variably positive for alpha- fetoprotein, frequently positive for vimentin, and occasionally positive for cytokeratin. All 3 cases were diagnosed as mixed hepatoblastoma with teratoid features.

  2. Manejo terapêutico do hepatocarcinoma fibrolamelar

    Directory of Open Access Journals (Sweden)

    Marlus Moreira

    Full Text Available Fibrolamellar carcinoma of the liver is a distinct variant of hepatocellular carcinoma characterized by the lack of association with cirrhosis or other underlying liver diseases, as hepatitis B virus. The serum alpha-fetoprotein level is often not elevated, occuring typically in young patients. Distinction from conventional hepatocellular carcinoma is of clinical significance, because prognosis is far better due to higher ressecability and more indolent growth. We describe a case of a 26-year-old woman free of other liver diseases presenting with a large abdominal palpable mass. After ressection by vascular exclusion technique, the pathologic examination revealed fibrolamellar carcinoma. The former should not be confused with the hepatocellular carcinoma, since it is related with a more favorable prognosis.

  3. Serum ferritin

    International Nuclear Information System (INIS)

    Rochna Viola, E.M.; Diaz de Domingo, N.B.; Lazarowski, A.

    1981-01-01

    Serum ferritin (SF) concentration as determined by the immunoradiometric method allows the direct measurement of a fraction of the body ferritin pool. In normal subjects, SF is an excellent index of body iron stores. In certain conditions associated with increased ferritin synthesis (such as liver disease, inflammation, malignancy, chronic disorders, ineffective erythropoiesis, or during ferrotherapy), SF may not accurately reflect body iron stores. In hyposideremic anemias SF concentration permits to differentiate those due to iron deficiency from those due to chronic disorders. With a good assay quality, subnormal SF levels are incontrovertible in the diagnosis of iron deficiency. SF determination has been investigated as possible tumor marker. When performed in combination with the alpha-fetoprotein assay, SF enhances the specificity of serodiagnosis of hepatoma. SF results must be interpreted bearing in mind the possible participation of circumstances that i) modify the body iron stores and ii) lead to increased ferritin synthesis. (author) [es

  4. Primary Yolk Sac Tumor of the Omentum: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Chang Kyu; Oh, Young Taik; Jung, Dae Chul [Dept. of Radiology, Research Institue of Radiological Science, Yensei University College of Medicine, Seoul (Korea, Republic of); Bae, Yoon Sung [Dept. of Pathology, Yensei University College of Medicine, Seoul (Korea, Republic of)

    2012-01-15

    A 32-year-old woman had been referred to our hospital for lower abdominal pain. Pelvic ultrasonography and magnetic resonance imaging revealed a huge solid mass with an internal cystic portion. The patient underwent a staging laparotomy and subsequent total abdominal hysterectomy with bilateral salpingo-oophorectomy, bilateral pelvic lymph nodes sampling, and total omentectomy. At staging laparotomy, a large omental mass was found. The tumor displayed the typical histological patterns observed in the yolk sac tumor. The alpha-fetoprotein (AFP) serum value on the 10th day after surgery was 11,576.67 IU/mL and decreased to 6.46 IU/mL after chemotherapy. At the end of the treatment, all the findings, including the AFP level, were normal. We report a case of primary yolk sac tumor of the omentum in a 32-year-old woman.

  5. CONGENITAL MALFORMATIONS: PRENATAL DIAGNOSTICS AND NOVEL CONCEPTION OF MEDICAL HELP TO NEWBORNS

    Directory of Open Access Journals (Sweden)

    Yu.F. Isakov

    2007-01-01

    Full Text Available Current views on basic prenatal diagnostics techniques, as ultrasound, maternal serum biochemical markers (alpha fetoprotein, human chorionic gonadotropin, and unconjugated estriol, and fetal biologic material (chorionic villus sampling, placenta, amniotic liquid, fetal blood, obtained with invasive techniques (chorion biopsy, amniocentesis, cordocentesis, its' efficacy and possible practical application are given in the article. These new conception announce to consolidate three branches providing maternal and children — welfare should consolidate maternal welfare outpatient clinics, maternal hospital and newborn surgery hospital — into one institute, thus allowing to success work of all stages, to avoid transportation and late surgical treatment, to reduce lethal outcomes following surgical treatment of congenital malformations. Primary results of implementation of this conception are presented in the article.Key words: prenatal diagnostics, newborns, congenital mal formations, prevention and prophylactics, diagnostics.

  6. An Overview of Biomarkers and Molecular Signatures in HCC

    International Nuclear Information System (INIS)

    Yim, Seon-Hee; Chung, Yeun-Jun

    2010-01-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. Although most HCCs seem to originate from the accumulation of genetic abnormalities induced by various risk factors, underlying mechanisms of hepatocarcinogenesis remain unclear. Long-term survival of HCC patients is also poor, partly due to HCC recurrence. Although serum alpha-fetoprotein (AFP) level is a useful marker for the detection and monitoring of HCC, AFP levels may remain normal in the patients even with advanced HCC. To identify useful biomarkers for HCC, many studies have been conducted on molecular events such as genetic and epigenetic alterations, and gene expression. This review summarizes recent studies of potential molecular markers for diagnosis and monitoring metastasis or recurrence of HCC

  7. The evaluation and presentation of a rare case of gonadal dysgenesis

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    Ghafarnejad M

    1996-07-01

    Full Text Available A seventeen-years old woman was presented with infertility and primary amenorrhea. She had normal stature, femate phenotype and normal development of breasts, external genitalia, vagina and cervix. Pelvic examination showed a large lobulated mass. On sonography there was a mass with probable origin of ovary. Paraclinic tests were carried out. Gonadotropins were in postmeno pausal limits. Alpha Fetoprotein, Beta Subunit (B-HCG assay were normal Laparotomy revealed a gonadat mass on right side, normal uterus and left streak gonad. Pathologic report of tumor was dysgerminoma and teratoma. Due to pathology of tumor and Y chromosome, we advised the patient to remove the other streak gonad and have irradiatio

  8. A review on laboratory liver function tests

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    Shruthi Kulkarni

    2009-11-01

    Full Text Available Laboratory liver tests are broadly defined as tests useful in the evaluation and treatment of patients with hepatic dysfunction. The liver carries out metabolism of carbohydrate, protein and fats. Some of the enzymes and the end products of the metabolic pathway which are very sensitive for the abnormality occurred may be considered as biochemical marker of liver dysfunction. Some of the biochemical markers such as serum bilirubin, alanine amino transferase, aspartate amino transferase, ratio of aminotransferases, alkaline phosphatase, gamma glutamyl transferase, 5´ nucleotidase, ceruloplasmin, alpha-fetoprotein are considered in this article. An isolated or conjugated alteration of biochemical markers of liver damage in patients can challenge the clinicians during the diagnosis of disease related to liver directly or with some other organs. The term “liver chemistry tests” is a frequently used but poorly defined phrase that encompasses the numerous serum chemistries that can be assayed to assess hepatic function and/or injury.

  9. Relapse surveillance in AFP-positive hepatoblastoma: re-evaluating the role of imaging

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    Rojas, Yesenia; Vasudevan, Sanjeev A.; Nuchtern, Jed G. [Baylor College of Medicine, Pediatric Surgery Division, Michael E. DeBakey Department of Surgery, Texas Children' s Hospital, Houston, TX (United States); Guillerman, R.P. [Baylor College of Medicine, Department of Pediatric Radiology, Texas Children' s Hospital, Houston, TX (United States); Zhang, Wei [Texas Children' s Hospital, Surgical Outcomes Center, Houston, TX (United States); Thompson, Patrick A. [Baylor College of Medicine, Hematology-Oncology Division, Department of Pediatrics, Texas Children' s Cancer Center, Texas Children' s Hospital, Houston, TX (United States); University of North Carolina, Hematology-Oncology Division, Department of Pediatrics, North Carolina Children' s Hospital, Chapel Hill, NC (United States)

    2014-10-15

    Children with hepatoblastoma routinely undergo repetitive surveillance imaging, with CT scans for several years after therapy, increasing the risk of radiation-induced cancer. The purpose of this study was to determine the utility of surveillance CT scans compared to serum alpha-fetoprotein (AFP) levels for the detection of hepatoblastoma relapse. This was a retrospective study of all children diagnosed with AFP-positive hepatoblastoma from 2001 to 2011 at a single institution. Twenty-six children with hepatoblastoma were identified, with a mean age at diagnosis of 2 years 4 months (range 3 months to 11 years). Mean AFP level at diagnosis was 132,732 ng/ml (range 172.8-572,613 ng/ml). Five of the 26 children had hepatoblastoma relapse. A total of 105 imaging exams were performed following completion of therapy; 88 (84%) CT, 8 (8%) MRI, 5 (5%) US and 4 (4%) FDG PET/CT exams. A total of 288 alpha-fetoprotein levels were drawn, with a mean of 11 per child. The AFP level was elevated in all recurrences and no relapses were detected by imaging before AFP elevation. Two false-positive AFP levels and 15 false-positive imaging exams were detected. AFP elevation was found to be significantly more specific than PET/CT and CT imaging at detecting relapse. We recommend using serial serum AFP levels as the preferred method of surveillance in children with AFP-positive hepatoblastoma, reserving imaging for the early postoperative period, for children at high risk of relapse, and for determination of the anatomical site of clinically suspected recurrence. Given the small size of this preliminary study, validation in a larger patient population is warranted. (orig.)

  10. Expression of Tight Junction Components in Hepatocyte-Like Cells Differentiated from Human Embryonic Stem Cells.

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    Erdélyi-Belle, Boglárka; Török, György; Apáti, Ágota; Sarkadi, Balázs; Schaff, Zsuzsa; Kiss, András; Homolya, László

    2015-09-01

    Human embryonic stem cells can be differentiated in vitro into a wide variety of progeny cells by addition of different morphogens and growth factors. Our aim was to monitor the expression pattern of tight junction (TJ) components and various cellular markers during differentiation of stem cell lines toward the hepatic lineage. Human embryonic stem cell lines (HUES1, HUES9) were differentiated into endoderm-like cells, and further differentiated to hepatocyte-like cells. Gene expressions of Oct3/4, Nanog, alpha-fetoprotein, albumin, cytokeratins (CK-7, CK-8, CK-18, CK-19), ATP-binding cassette (ABC) transporters (ABCC2, ABCC7, ABCG2), and various TJ components, including claudin-1, claudin-4, claudin-5, claudin-7, and tricellulin, as well as an extracellular matrix component, agrin were monitored during hepatic differentiation by real-time quantitative PCR. The differentiated cells exhibit epithelial morphology and functional assessments similar to that of hepatocytes. The expression level of stem cell marker genes (Oct3/4 and Nanog) significantly and gradually decreased, while liver-associated genes (alpha-fetoprotein, albumin) reached their highest expression at the end of the differentiation. The endoderm-like cells expressed claudin-1, which declined eventually. The expression levels of cholangiocyte markers including claudin-4, CK-7, CK-19, and agrin gradually increased and reached their highest level at the final stage of differentiation. In contrast, these cells did not express notable level of claudin-7, CK-8 and tricellulin. The marker set used for monitoring differentiation revealed both hepatocyte and cholangiocyte characteristics of the differentiated cells at the final stage. This is the first report describing the expression level changes of various TJ components, and underlining their importance in hepatic differentiation.

  11. Differentiation and selection of hepatocyte precursors in suspension spheroid culture of transgenic murine embryonic stem cells.

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    Elke Gabriel

    Full Text Available Embryonic stem cell-derived hepatocyte precursor cells represent a promising model for clinical transplantations to diseased livers, as well as for establishment of in vitro systems for drug metabolism and toxicology investigations. This study aimed to establish an in vitro culture system for scalable generation of hepatic progenitor cells. We used stable transgenic clones of murine embryonic stem cells possessing a reporter/selection vector, in which the enhanced green fluorescent protein- and puromycin N-acetyltransferase-coding genes are driven by a common alpha-fetoprotein gene promoter. This allowed for "live" monitoring and puromycin selection of the desired differentiating cell type possessing the activated alpha-fetoprotein gene. A rotary culture system was established, sequentially yielding initially partially selected hepatocyte lineage-committed cells, and finally, a highly purified cell population maintained as a dynamic suspension spheroid culture, which progressively developed the hepatic gene expression phenotype. The latter was confirmed by quantitative RT-PCR analysis, which showed a progressive up-regulation of hepatic genes during spheroid culture, indicating development of a mixed hepatocyte precursor-/fetal hepatocyte-like cell population. Adherent spheroids gave rise to advanced differentiated hepatocyte-like cells expressing hepatic proteins such as albumin, alpha-1-antitrypsin, cytokeratin 18, E-cadherin, and liver-specific organic anion transporter 1, as demonstrated by fluorescent immunostaining. A fraction of adherent cells was capable of glycogen storage and of reversible up-take of indocyanine green, demonstrating their hepatocyte-like functionality. Moreover, after transplantation of spheroids into the mouse liver, the spheroid-derived cells integrated into recipient. These results demonstrate that large-scale hepatocyte precursor-/hepatocyte-like cultures can be established for use in clinical trials, as well as in

  12. The therapeutic effect of nano-encapsulated and nano-emulsion forms of carvacrol on experimental liver fibrosis.

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    Hussein, Jihan; El-Banna, Mona; Mahmoud, Khaled F; Morsy, Safaa; Abdel Latif, Yasmin; Medhat, Dalia; Refaat, Eman; Farrag, Abdel Razik; El-Daly, Sherien M

    2017-06-01

    The present study aimed to compare the therapeutic efficiency of nano-encapsulated and nano-emulsion carvacrol administration on liver injury in thioacetamide (TAA) treated rats. To fulfill our target, we used sixty male albino rats classified into six groups as follow: control, nano-encapsulated carvacrol, nano-emulsion carvacrol, thioacetamide, treated nano-encapsulated carvacrol and treated nano-emulsion carvacrol groups. Blood samples were collected from all groups and the separated serum was used for analysis of the following biochemical parameters; aspartate aminotransferase (AST), alanine aminotransferase (ALT), S100 B protein, alpha fetoprotein (AFP) and caspase-3. The levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), monocyte chemoattractant protein-1(MCP-1) and hydroxyproline content were all evaluated in liver tissue homogenate. Histopathological examinations for liver tissues were also performed. Thioacetamide induced hepatic damage in rats as revealed by the significant increase in the levels of serum ALT, AST and produced oxidative stress as displayed by the significant elevation in the levels of hepatic MDA and NO concomitant with a significant decrease in GSH. In addition, thioacetamide significantly increased serum S100B protein, alpha fetoprotein and caspase-3 along with hepatic MCP-1 and hydroxyproline; these results were confirmed by the histopathological investigation. In contrast, nano-encapsulated and nano-emulsion carvacrol were able to ameliorate these negative changes in the thioacetamide injected rats. However, the effect of the nano-encapsulated form of carvacrol was more prominent than the nano-emulsion form. Nano-encapsulated and nano-emulsion carvacrol can ameliorate thioacetamide induced liver injury. These results could be attributed to the potential anti-inflammatory, antioxidant, and anti-apoptotic activities of carvacrol in addition to the effectiveness of the encapsulation technique that can protect

  13. A designated centre for people with disabilities operated by St Michael's House, Dublin 9

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    Abdel Aziz, Mohamed T

    2011-05-05

    Abstract Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl 4 , rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation

  14. Vascular Endothelial Growth Factor Level as A Predictor of Hepatocellular Carcinoma in Liver Cirrhosis Patients

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    Benyamin Lukito

    2014-12-01

    Full Text Available BACKGROUND: Alpha-fetoprotein (AFP has been used for hepatocellular carcinoma (HCC diagnosis and screening, however, AFP has poor specificity. The extensive hypervascularity associated with HCC could be driven in part by the pro-angiogenic factor known as vascular endothelial growth factor (VEGF. Furthermore, invasiveness of certain HCC lesions has recently been linked to high levels of VEGF. Therefore, circulating VEGF levels of patients with liver cirrhosis (LC and HCC were investigated and analysed. METHODS: An analytical cross sectional study was designed. Diagnosis of HCC and LC was performed using clinical criteria and findings obtained from B-mode ultrasonography (USG, computed tomography (CT angiography, or magnetic resonance imaging (MRI. Blood were collected intravenously from all subjects. Obtained serum and plasma were stored in -80°C for following analyses: hepatitis B surface antigen (HBSAg, hepatitis C virus (HCV, alanine aminotransferase (ALT, total bilirubin, albumin, VEGF and AFP. RESULTS: Levels of VEGF and AFP were significantly higher in HCC group compared with LC group with p=3.05x10-6 and p=8.74x10-5, respectively. There was a significant positive correlation (p=0.029, r=0.309 between VEGF level and tumor size in HCC group. The area under curve (AUC for VEGF level in HCC and LC groups was 0.771. In the level of median 435.6 pg/mL VEGF, the sensitivity was 50% and specificity was 86%. In the level of 199.99 pg/mL VEGF the sensitivity was 74% and specificity was 76%. CONCLUSIONS: The present findings suggested that VEGF level could be a useful marker for the presence of HCC in patients with LC. KEYWORDS: hepatocellular carcinoma, HCC, liver cirrhosis, LC, vascular endothelial growth factor, VEGF, alpha-fetoprotein, AFP.

  15. Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

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    Sabry Dina

    2011-05-01

    Full Text Available Abstract Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs in an experimental hepatocellular carcinoma (HCC model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA and CCl4, rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA, cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell

  16. Sensitive electrochemical immunosensor based on three-dimensional nanostructure gold electrode

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    Zhong G

    2015-03-01

    Full Text Available Guangxian Zhong,1,2,* Ruilong Lan,3,* Wenxin Zhang,1,4 Feihuan Fu,5 Yiming Sun,1,4 Huaping Peng,1,4 Tianbin Chen,3 Yishan Cai,6 Ailin Liu,1,4 Jianhua Lin,2 Xinhua Lin1,4 1Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, 2Department of Orthopaedics, 3The Centralab, First Affiliated Hospital of Fujian Medical University, 4Nano Medical Technology Research Institute, Fujian Medical University, Fuzhou, 5Department of Endocrinology, The County Hospital of Anxi, Anxi, 6Fujian International Travel Healthcare Center, Fujian Entry-Exit Inspection and Quarantine Bureau, Fuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: A sensitive electrochemical immunosensor was developed for detection of alpha-fetoprotein (AFP based on a three-dimensional nanostructure gold electrode using a facile, rapid, “green” square-wave oxidation-reduction cycle technique. The resulting three-dimensional gold nanocomposites were characterized by scanning electron microscopy and cyclic voltammetry. A “sandwich-type” detection strategy using an electrochemical immunosensor was employed. Under optimal conditions, a good linear relationship between the current response signal and the AFP concentrations was observed in the range of 10–50 ng/mL with a detection limit of 3 pg/mL. This new immunosensor showed a fast amperometric response and high sensitivity and selectivity. It was successfully used to determine AFP in a human serum sample with a relative standard deviation of <5% (n=5. The proposed immunosensor represents a significant step toward practical application in clinical diagnosis and monitoring of prognosis. Keywords: electrochemical immunosensors, three-dimensional nanostructure gold electrode, square-wave oxidation-reduction cycle, alpha-fetoprotein 

  17. The in Vitro Assessment of Biochemical Factors in Hepatocyte like Cells Derived from Umbilical Cord Blood Stem Cells

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    A KHoramroodi

    2009-10-01

    Full Text Available Introduction & Objective: Umbilical cord blood (UCB is a source of Hematopoietic Stem Cells (HSC and progenitor cells that can reconstitute the hematopoietic system in patients with malignant and nonmalignant disorders. Mesenchymal stem cell-derived from umbilical cord blood (UCB have been differentiated to some kind of cells, such as osteobblast, adipoblast and chondroblast in Vitro. This study examined the differentiation of Umbilical Cord Blood (UCB derived stem cells to functional hepatocytes. Materials & Methods: The present study was an experimental study which was carried out in the Payam-e-Noor University of Tehran in cooperation with Hamedan University of Medical Sciences in 2008. Umbilical cord blood (UCB was obtained from Fatemieh hospital (Hamadan, Iran. Stem cells were isolated from the cord blood by combining density gradient centrifugation with plastic adherence. When the isolated cells reached 80% confluence, they differentiated to hepatocyte like cells. The medium which was used was consists of DMEM and 10% Fetal Bovine Serum (FBS supplemented with 20 ng/mL Hepatocyte Growth Factor (HGF, 10 ng/mL basic Fibroblast Growth Factor (bFGF and 20 ng/mL Oncostatin M (OSM.The medium was changed every 3 days and stored for Albumin (ALB, Alpha Fetoprotein (AFP, Alkaline Phosphatase (ALP, and urea assay. Finally PAS stain was done to study Glycogen storage in the differentiated cell. Results: Measurement of biochemical factors in different days showed that concentration of albumin (ALB, alpha fetoprotein (AFP, alkaline phosphatase (ALP, and Urea gradually increased. Also, PAS staining showed the storage of glycogen in these cells. Conclusion: Stem cell-derived from human umbilical cord blood (HUCB is a new source of cell types for cell transplantation therapy of hepatic diseases and under certain conditions these cells can differentiate into liver cells.

  18. Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

    LENUS (Irish Health Repository)

    Abdel Aziz, Mohamed T

    2011-05-05

    Abstract Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl 4 , rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation

  19. IS RESECTION OF HEPATOCELLULAR CARCINOMA IN THE ERA OF LIVER TRANSPLANTATION WORTHWILE? A single center experience

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    Paulo HERMAN

    Full Text Available ABSTRACT Background - Liver resection for hepatocellular carcinoma is a potentially curative therapeutic procedure that can be performed readily after its indication, without the need of a long waiting time and lower costs when compared to liver transplantation, being a good alternative in patients with preserved/good liver function. Objective - Evaluate long-term results of liver resection from a high volume single center for selected patients with hepatocellular carcinoma in a context of a long waiting list for liver transplant. Methods - One hundred and one patients with hepatocellular carcinoma, with a mean age of 63.1 years, and preserved liver function were submitted to liver resection. Clinical and pathological data were evaluated as prognostic factors. Mean follow-up was 39.3 months. Results - All patients had a single nodule and 57 (58.2% patients were within the Milan criteria. The size of the nodule ranged from 1 to 24 cm in diameter. In 74 patients, liver resection was performed with the open approach and in 27 (26.7% was done laparoscopically. Postoperative morbidity was 55.3% being 75.5% of the complications classified as Dindo-Clavien I and II and operative mortality was 6.9%. Five-year overall and disease free survival rates were 49.9% and 40.7%, respectively.After a log-rank univariate analysis, the levels of preoperative alpha-fetoprotein (P=0.043, CA19-9 (P=0.028, capsule invasion (P=0.03, positive margin (R1-R2 (P=0.004 and Dindo-Claviens' morbidity classification IV (P=0.001 were the only parameters that had a significant negative impact on overall survival. On the odds-ratio evaluation, the only significant factors for survival were high levels of alpha-fetoprotein (P=0.037, and absence of free margins (P=0.008. Conclusion - Resection, for selected cases, is a potentially curative treatment with acceptable morbidity and mortality and, in a context of a long waiting list for transplant, plays an important role for the

  20. Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients.

    Science.gov (United States)

    Agopian, Vatche G; Morshedi, Maud M; McWilliams, Justin; Harlander-Locke, Michael P; Markovic, Daniela; Zarrinpar, Ali; Kaldas, Fady M; Farmer, Douglas G; Yersiz, Hasan; Hiatt, Jonathan R; Busuttil, Ronald W

    2015-09-01

    To evaluate the rate, effect, and predictive factors of a complete pathologic response (cPR) in patients with hepatocellular carcinoma (HCC) undergoing locoregional therapy (LRT) before liver transplantation (LT). Eligible patients with HCC receive equal model for end-stage liver disease prioritization, despite variable risks of tumor progression, waitlist dropout, and posttransplant recurrence. Pretransplant LRT mitigates these risks by inducing tumor necrosis. Comparisons were made among HCC recipients with cPR (n = 126) and without cPR (n = 375) receiving pre-LT LRT (1994-2013). Multivariable predictors of cPR were identified. Of 501 patients, 272, 148, and 81 received 1, 2, and 3 or more LRT treatments. The overall, recurrence-free, and disease-specific survival at 1-, 3-, and 5 years was 86%, 71%, 63%; 84%, 67%, 60%; and 97%, 90%, 87%. Compared with recipients without cPR, cPR patients had significantly lower laboratory model for end-stage liver disease scores, pretransplant alpha fetoprotein, and cumulative tumor diameters; were more likely to have 1 lesion, tumors within Milan/University of California, San Francisco (UCSF) criteria, LRT that included ablation, and a favorable tumor response to LRT; and had superior 1-, 3-, and 5-year recurrence-free survival (92%, 79%, and 73% vs 81%, 63%, and 56%; P = 0.006) and disease-specific survival (100%, 100%, and 99% vs 96%, 89%, and 86%; P < 0.001) with only 1 cancer-specific death and fewer recurrences (2.4% vs 15.2%; P < 0.001). Multivariate predictors of cPR included a favorable post-LRT radiologic/alpha fetoprotein tumor response, longer time interval from LRT to LT, and lower model for end-stage liver disease score and maximum tumor diameter (C-statistic 0.75). Achieving cPR in patients with HCC receiving LRT strongly predicts tumor-free survival. Factors predicting cPR are identified, allowing for differential prioritization of HCC recipients based on their variable risks of post-LT recurrence. Improving LRT

  1. Clinical performance of LOCI™-based tumor marker assays for tumor markers CA 15-3, CA 125, CEA, CA 19-9 and AFP in gynecological cancers.

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    Dolscheid-Pommerich, Ramona C; Keyver-Paik, Mignon; Hecking, Thomas; Kuhn, Walther; Hartmann, Gunther; Stoffel-Wagner, Birgit; Holdenrieder, Stefan

    2017-10-01

    Evidence is sparse regarding the clinical performance of luminescent oxygen channeling immunoassays-based tumor marker assays in gynecological cancer. Analyzing serum samples of 336 patients with Dimension™Vista1500, we investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein in patients suffering from different types of gynecological cancer and precancerous gynecological diseases and compared findings to appropriate control groups. The cohort comprised 177 female patients with gynecological cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4 cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24 healthy controls. Discriminative power was assessed by areas under the curve in receiver operating characteristic curves, and sensitivities were determined at a fixed specificity of 95%. Levels of biomarkers in healthy controls were in the expected ranges and a discriminative power between gynecological cancers and healthy controls was observed for several tumor markers. Established tumor type-associated markers were elevated in specific gynecological cancers and benign controls as well as within precancerous gynecological diseases and healthy control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate antigen 15-3 were significantly elevated compared to the respective benign diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer, carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher than in the respective benign diseases. Carcinoembryonic antigen achieved the most conclusive area under the curve (0.65) with 31.5% sensitivity at 95% specificity. None of the investigated markers was found to be of

  2. Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

    Science.gov (United States)

    Combs, C Andrew; Garite, Thomas J; Lapidus, Jodi A; Lapointe, Jerome P; Gravett, Michael; Rael, Julie; Amon, Erol; Baxter, Jason K; Brady, Kim; Clewell, William; Eddleman, Keith A; Fortunato, Stephen; Franco, Albert; Haas, David M; Heyborne, Kent; Hickok, Durlin E; How, Helen Y; Luthy, David; Miller, Hugh; Nageotte, Michael; Pereira, Leonardo; Porreco, Richard; Robilio, Peter A; Simhan, Hyagriv; Sullivan, Scott A; Trofatter, Kenneth; Westover, Thomas

    2015-04-01

    Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in

  3. The Effect of the Bujeonghangam-tang Extract on Hepatocellular Carcinogenesis and Hepatic Cirrhosis Induced by Diethylnitrosamine and CCl4 in Rats

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    Young-Ho Moon

    2010-06-01

    Full Text Available Objective : Bujeonghangam-tang(BH has been used for cure of tumor as a traditional medicine. This study was carried out to clarify the effect of BH extract on hepatocellular carcinogenesis and hepatic cirrhosis induced by Diethylnitrosamine(DENA and CCl4 in Rats. Method : Experimental groups were divided into two, 8th and 12th week groups, and subdivided into four; normal group(Nor, cirrhosis and hepatic cancer inducing control group(Con, and BH extract 320 ㎎/㎏/day(BHA or 640 ㎎/㎏/day(BHB administered groups to Con. Result : In the 8th week group: The body weight decreased significantly in Con compared with the Nor. The activities of transaminase, alkaline phosphatase(ALP, and lactacte dehydrogenase(LDH were significantly increased(p<0.05 in the Con compared with Nor, but decreased in the BHA and BHB compared with Con. Alpha fetoprotein(AFP were the most increased in the Con compared to BHA and BHB. The results of light microscopical observation, a number of hepatocytes were damaged in the Con compared with Nor and BH extract administerd groups. The number of hepatic p53 positive cells was reduced in the BH extract administered groups. According to the electron microscopical observation, hepatocarcinoma cells were observed distinctly in the Con compared with BH extract administered groups. In the 12 weeks group: The results of body were similar to 8th week groups. The activities of transaminase and ALT were significantly increased(p<0.05 in the Con compared with Nor. LDH was significantly(p<0.05 increased in the Con compared with Nor but significantly (p<0.05 decreased in the BHB. Alpha fetoprotein(AFP were the most increased in the Con among experimental groups. The activities of superoxide dismutase(SOD were significantly (p<0.05 increased in the Con, but the activities of catalase were not increased(p<0.05 compared with Nor. The number of hepatic p53 positive cells was increased in the Con. The results of electron microscopical

  4. Camel Milk: Potential Utility as an Adjunctive Therapy to Peg-IFN/RBV in HCV-4 Infected Patients in Egypt.

    Science.gov (United States)

    Mohamed, Walid A; Schaalan, Mona F; El-Abhar, Hanan S

    2015-01-01

    The present prospective study aims to investigate the potential therapeutic effect and the underlying mechanisms of drinking camel milk for 60 days as an adjunctive therapy to the standard treatment PEG/RBV. Twenty-five hepatitis C virus (HCV)-infected Egyptian patients, with mild to moderate parenchymal affection to mild cirrhosis were enrolled in this study after proper history taking and clinical examination. Their biomarkers were evaluated before and after the addition of camel milk. The improving effect of camel milk was reflected on the marked inhibition of the serum levels of the proinflammatory markers, viz., tumor necrosis factor-α, monocyte chemotactic protein-1, hyaluronic acid, and TGF-β1, besides PCR, AST, ALT, GGT, bilirubin, prothrombin time, INR, and alpha-fetoprotein. In addition, camel milk elevated significantly (P camel milk on multiple parameters of inflammatory mediators, immunomodulators, antiapoptosis, and antioxidants, giving insight into the potential therapeutic benefit underlying the anti-HCV actions of camel milk. The limitations of the current study include the small sample size recruited and the failure to test it on cohorts with severe stages of hepatitis; like Child-Pugh stage C, and hepatocellular carcinoma.

  5. Protective Effects of Total Glucosides of Paeony on N-nitrosodiethylamine-induced Hepatocellular Carcinoma in Rats via Down-regulation of Regulatory B Cells.

    Science.gov (United States)

    Song, S S; Yuan, P F; Li, P P; Wu, H X; Ni, W J; Lu, J T; Wei, W

    2015-01-01

    Total glucoside of paeony (TGP), extracted from the root of Paeonia Lactiflora, has been known to show anti-inflammatory, anti-oxidative, hepato-protective and immuno-regulatory activities. The aim of this present study was to determine the anti-tumor effect of TGP against N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) in rats, and to find the related mechanisms. Rat HCC model was established by intragastrically administrating with DEN (8 mg/kg). We found the number of tumor nodules and the index of liver and spleen were increased in the model group compared with the normal group, and was significantly decreased by TGP. Additionally, TGP obviously improved the hepatic pathological lesions induced by DEN, and decreased the elevated levels of serum alanine aminotransferase (ALT), glutamic oxalacetic transaminase (AST), alkaline phosphatase (ALP) and alpha fetoprotein (AFP) by DEN. Moreover, TGP decreased the level of B cell-activating factor (BAFF) and the proportion of IL-10-producing regulatory B cells (Bregs), and the decrease of BAFF by TGP is positively correlated to the decrease of IL-10-producing Bregs by TGP. These results suggest that TGP had a good therapeutic action on DEN-induced HCC rats, which might be due to its down-regulation of Bregs through reducing the level of BAFF.

  6. Surgical outcomes of hepatocellular carcinoma invading hepatocaval confluence.

    Science.gov (United States)

    Li, Wei; Wu, Hong; Han, Jun

    2016-12-01

    Combined liver and inferior vena cava (IVC) resection followed by IVC and/or hepatic vein reconstruction (HVR) is a curative operation for selected patients with hepatocellular carcinoma (HCC) invading the hepatocaval confluence. The present study aimed to elucidate the prognostic factors for patients with HCC invading the hepatocaval confluence. Forty-two consecutive patients underwent hepatectomy, combined with IVC replacement and/or HVR for HCC between January 2009 and December 2014 were included in this study. The cases were divided into three groups based on the surgical approaches of HVR: group 1 (n=13), tumor invaded the hepatocaval confluence but with one or two hepatic veins intact in the residual liver, thus only the replacement of IVC, not HVR; group 2 (n=23), the hepatic vein of the residual liver was also partially invaded, and the hepatic vein defect was repaired with patches locally; group 3 (n=6), three hepatic veins at the hepatocaval confluence were infiltrated, and the hepatic vein remnant was re-implanted onto the side of the tube graft. The patient characteristics, intra- and postoperative results, and long-term overall survival were compared among the three groups. The survival-related factors were analyzed by univariate and multivariate analysis. The group 1 had higher preoperative alpha-fetoprotein level (PHVR (PHVR (group 1). HVR was one of the unfavorable prognostic factors of overall survival.

  7. A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Zamba-Papanicolaou Eleni

    2008-04-01

    Full Text Available Abstract Background Senataxin (chromosome 9q34 was recently identified as the causative gene for an autosomal recessive form of Ataxia (ARCA, termed as Ataxia with Oculomotor Apraxia, type 2 (AOA2 and characterized by generalized incoordination, cerebellar atrophy, peripheral neuropathy, "oculomotor apraxia" and increased alpha-fetoprotein (AFP. Here, we report a novel Senataxin mutation in a Cypriot ARCA family. Methods We studied several Cypriot autosomal recessive cerebellar ataxia (ARCA families for linkage to known ARCA gene loci. We linked one family (909 to the SETX locus on chromosome 9q34 and screened the proband for mutations by direct sequencing. Results Sequence analysis revealed a novel c.5308_5311delGAGA mutation in exon 11 of the SETX gene. The mutation has not been detected in 204 control chromosomes from the Cypriot population, the remaining Cypriot ARCA families and 37 Cypriot sporadic cerebellar ataxia patients. Conclusion We identified a novel SETX homozygous c.5308_5311delGAGA mutation that co-segregates with ARCA with cerebellar atrophy and raised AFP.

  8. Arterial Hepatic Embolization of Unresectable Hepatocellular Carcinoma Using a Cyanoacrylate/Lipiodol Mixture

    International Nuclear Information System (INIS)

    Berghammer, Peter; Pfeffel, Franz; Winkelbauer, Fritz; Wiltschke, Christoph; Schenk, Thomas; Lammer, Johannes; Mueller, Christian; Zielinski, Christoph

    1998-01-01

    Purpose: A survival analysis in 16 patients with unresectable hepatocellular carcinoma (HCC) undergoing transcatheter arterial embolization (TAE) using a combination of lipiodol and N-butyl-2-cyanoacrylate (5 : 1) was performed in a retrospective study. Methods: A combination of lipiodol and N-butyl-2-cyanoacrylate (5 : 1) was used for TAE. All patients had disease compatible with Okuda stages I and II. Results: Twenty-four embolizations were done; five patients had more than one embolization. Median alpha-fetoprotein levels declined from 116 to 48.6 ng/ml. A median of 0.3 ml cyanoacrylate was administered per patient. Median survival was 8.5 months (range 2-49 months). After a median follow-up of 4 years, 12 patients have died (75%). Okuda stage I and II patients had a median survival time of 34.4 and 5.5 months respectively. Few side effects (19%) were seen. Conclusion: We conclude that the TAE procedure used [lipiodol and N-butyl-2-cyanoacrylate (5 : 1)] is safe and produced only few side effects, thus constituting a valuable therapeutic option for patients with Okuda stage I andII HCC

  9. Thymic enlargement in patients with hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Myung, Jae Sung; Goo, Jin Mo; Im, Jung Gi [College of medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of); Kim, Mi Young [Sejong General Hospital, Seoul (Korea, Republic of); Park, Yang Hee [National Police Hospital, Seoul (Korea, Republic of)

    2000-08-01

    To evaluate the radiologic findings and clinical feasibility of thymic enlargement in patients with hyperthyroidism. Seven patients with hyperthyroidism and anterior mediastinal bulging revealed by chest radiography were evaluated. The CT findings were analyzed with regard to the shape of the anterior mediastinal mass, surrounding infiltration, and enlargement of mediastinal lymph nodes. Whether or not tumor markers (alpha-fetoprotein, beta-human chorionic gonadotrophin, and chorionic embryonic antigen) showed increased levels was determined, and the size and thickness of the anterior mediastinal mass were measured and compared with previously described age-matched thymus data. In addition, changes in the thyroid gland were evaluated. In all seven patients, anterior mediastinal masses were bi-lobed, with no surrounding infiltration or enlarged mediastinal lymph node, and tumor marker levels showed no increase. The masses were therefore considered to be thymus. In six patients, the size of the thymus exceeded two upper standard deviations of mean value and in one patient, it was smaller than this. In three patients, PCNB (percutaneous needle biopsy) revealed normal thymic tissue and in two, follow-up chest PA demonstrated no interval change. CT showed that in three patients, the thyroid glands were diffusely enlarged. In patients with hyperthyroidism, an anterior mediastinal mass seen on chest radiographs was due to thymic enlargement. The recognition of CT findings of thymic enlargement in such patients may avoid unnecessary biopsy. (author)

  10. Clinicopathological features and prognosis in elderly gastric cancer patients: a retrospective cohort study.

    Science.gov (United States)

    Xu, Guanghui; Feng, Fan; Liu, Shushang; Wang, Fei; Zheng, Gaozan; Wang, Qiao; Cai, Lei; Guo, Man; Lian, Xiao; Zhang, Hongwei

    2018-01-01

    Little is known about the clinicopathological features and prognosis in elderly gastric cancer (GC) patients aged 65-79 years. The aim of this study was to evaluate clinicopathological features and prognosis in elderly GC patients. From May 2008 to December 2014, a total of 5,282 GC patients were enrolled in our present study. Patients were divided into elderly and middle-aged groups. The clinicopathological features and clinical outcomes were analyzed. The proportion of dysphagia was significantly higher in elderly patients than that in middle-aged patients ( P =0.002), whereas the proportion of abdominal pain and heartburn was significantly lower in elderly patients than that in middle-aged patients ( P elderly patients than that in middle-aged patients ( P =0.009). There was no significant difference in clinicopathological features between elderly and middle-aged patients with D2 gastrectomy (all P >0.05). Age, tumor size, histological type, tumor depth, lymph node metastasis, carcinoembryonic antigen, alpha fetoprotein, CA19-9, and CA125 were independent risk factors for the prognosis of GC patients in univariate and multivariate analyses. Overall survival in elderly patients was significantly reduced compared with middle-aged patients ( P =0.001), especially in patients with tumor size >5 cm ( P =0.002), poorly differentiated tumor ( P elderly patients were different to those of middle-aged patients. The prognosis for elderly GC patients was significantly worse than for middle-aged patients.

  11. Biochemical and molecular evidences for the antitumor potential of Ginkgo biloba leaves extract in rodents.

    Science.gov (United States)

    Ahmed, Hanaa H; Shousha, Wafaa Gh; El-Mezayen, Hatem A; El-Toumy, Sayed A; Sayed, Alaa H; Ramadan, Aesha R

    2017-01-01

    Hepatocellular carcinoma (HCC) is one of the deadliest primary cancers, with a 5-year survival rate of 10% or less. This study was undertaken to elucidate the underlying biochemical and molecular mechanisms in favor of N-nitrosodiethylamine-induced hepatocellular carcinoma. Furthermore, the aim of this work was extended to explore the efficacy of Ginkgo biloba leaves extract in deterioration of HCC in rats. In the current study, HCC group experienced significant downregulation of ING-3 gene expression and upregulation of Foxp-1 gene expression in liver. Treatment of HCC groups with Ginkgo biloba leaves extract resulted in upregulation of ING-3 and downregulation of Foxp-1 gene expression in liver. In addition, there was significant increase in serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and glypican-3 (GPC-3) levels in HCC group versus the negative control group. In contrast, the groups with HCC subjected to either high or low dose of Ginkgo biloba leaves extract elicited significant reduction (PGinkgo biloba leaves extract elicited marked improvement in the histological feature of liver tissue in HCC groups. In conclusion, this research indicated that the carcinogenic potency of N-nitrosodiethylamine targeted multiple systems on the cellular and molecular levels. In addition, the results of the current study shed light on the promising anticancer activity of Ginkgo biloba leaves extract in treatment of hepatocellular carcinoma induced chemically in the experimental model through its apoptotic and antiproliferative properties.

  12. The homeobox gene Hex regulates hepatocyte differentiation from embryonic stem cell-derived endoderm.

    Science.gov (United States)

    Kubo, Atsushi; Kim, Yon Hui; Irion, Stefan; Kasuda, Shogo; Takeuchi, Mitsuaki; Ohashi, Kazuo; Iwano, Masayuki; Dohi, Yoshiko; Saito, Yoshihiko; Snodgrass, Ralph; Keller, Gordon

    2010-02-01

    We investigated the role of the hematopoietically expressed homeobox (Hex) in the differentiation and development of hepatocytes within embryonic stem cell (ESC)-derived embryoid bodies (EBs). Analyses of hepatic endoderm derived from Hex(-/-) EBs revealed a dramatic reduction in the levels of albumin (Alb) and alpha-fetoprotein (Afp) expression. In contrast, stage-specific forced expression of Hex in EBs from wild-type ESCs led to the up-regulation of Alb and Afp expression and secretion of Alb and transferrin. These inductive effects were restricted to c-kit(+) endoderm-enriched EB-derived populations, suggesting that Hex functions at the level of hepatic specification of endoderm in this model. Microarray analysis revealed that Hex regulated the expression of a broad spectrum of hepatocyte-related genes, including fibrinogens, apolipoproteins, and cytochromes. When added to the endoderm-induced EBs, bone morphogenetic protein 4 acted synergistically with Hex in the induction of expression of Alb, Afp, carbamoyl phosphate synthetase, transcription factor 1, and CCAAT/enhancer binding protein alpha. These findings indicate that Hex plays a pivotal role during induction of liver development from endoderm in this in vitro model and suggest that this strategy may provide important insight into the generation of functional hepatocytes from ESCs.

  13. Nitric Oxide Synthase Type III Overexpression By Gene Therapy Exerts Antitumoral Activity In Mouse Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Raúl González

    2015-08-01

    Full Text Available Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO synthase type III (NOS-3 overexpression induces cell death in hepatoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. Hepa 1-6 cells were used for in vitro and in vivo experiments. The first generation adenovirus was designed to overexpress NOS-3 (or GFP and luciferase cDNA under the regulation of murine alpha-fetoprotein (AFP and Rous Sarcoma Virus (RSV promoters, respectively. Both adenoviruses were administered through the tail vein two weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-Luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8 activity in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by l-NAME or p53 siRNA. The tail vein infusion of AFP-NOS- 3/RSV-Luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.

  14. Summary, the 20th quality control survey for radioisotopes in vitro tests in Japan, 1998

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-11-01

    For advancement of radioisotope in vitro tests such as radioimmunoassay and immunoradiometric assay, the Subcommittee for Radioisotope in vitro Test in Medical and Pharmaceutical Committee of Japan Radioisotope Association has conducted the yearly quality control survey for the test facilities in Japan since 1978. This is the summary of the 20th survey in 1998 where non-radioisotope tests like enzyme-immunoassay were involved as well. The survey was done for 143 facilities: 20 national and public university hospitals, 18 private university hospitals, 8 national hospitals, 13 public hospitals, 21 private hospitals, 41 hygienic laboratories and 22 manufacturers of reagents. Facilities examined intra- and between day-reproducibility, freeze-thaw effect and time change of the measured values on the same samples. Assays were for: growth hormone (h), somatomedin C, follicle stimulating h, luteinizing h, prolactin, thyroid stimulating h, triiodothyronines, thyroxines, thyroxine binding protein, calcitonin, insulin, C-peptide, glucagons, gastrin, testosterones, estradiol, progesterone, gonadotropin, 17{alpha}-hydroxyprogesterone, aldosterone, cortisol, dehydroepiandorosterone sulfate, renin, IgE, digoxin, {alpha}-fetoprotein, carcinoembryonic antigen, tissue polypeptide antigen, CA (125, 19-9 and 15-3), prostatic acid phosphatase, prostate specific antigen, {beta}2-microglobulin, ferritin, and neuron specific enolase. There was no great difference between this and last survey results although tendency of improvement was recognized. There were problems to be solved from the standpoint of clinical practice. (K.H.)

  15. Assessment of treatment outcomes based on tumor marker trends in patients with recurrent hepatocellular carcinoma undergoing trans-catheter arterial chemo-embolization.

    Science.gov (United States)

    Arai, Takuma; Kobayashi, Akira; Ohya, Ayumi; Takahashi, Masaaki; Yokoyama, Takahide; Shimizu, Akira; Motoyama, Hiroaki; Furusawa, Norihiko; Notake, Tsuyoshi; Kitagawa, Noriyuki; Sakai, Hiroshi; Imamura, Hiroshi; Kadoya, Masumi; Miyagawa, Shin-Ichi

    2014-10-01

    The aim of the present study was to evaluate whether serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) trends might be correlated with overall survival rates in patients with recurrent hepatocellular carcinoma (HCC) undergoing trans-catheter arterial chemo-embolization (TACE). We performed a retrospective cohort study of 142 patients with recurrent HCC who were treated by TACE at our hospital from April 1990 to December 2011. Patients were divided into three groups, as follows, according to the trends of the two tumor markers AFP and DCP: the low group, comprising patients with tumor marker levels below the cutoff values (AFP 100 ng/mL and DCP 100 mAU/mL) both pre- and post-TACE; the decreased group, comprising patients with elevated tumor marker levels pre-TACE in whom the levels decreased post-TACE; and the elevated group, comprising patients with elevated tumor marker levels post-TACE. Analysis using a Cox proportional hazards model identified the DCP trend (elevated group vs. low group, hazard ratio 8.47, 95 % confidence interval 4.53-15.84, p Tumors (mRECIST; p = 0.041), the DCP trend was strongly associated with both the overall response rate (p = 0.009) and the disease control rate (p = 0.004). The DCP trend might be useful for assessing treatment outcomes after TACE in patients with recurrent HCC.

  16. The tumor marker score is an independent predictor of survival in patients with recurrent hepatocellular carcinoma.

    Science.gov (United States)

    Okamura, Yukiyasu; Ashida, Ryo; Ito, Takaaki; Sugiura, Teiichi; Mori, Keita; Uesaka, Katsuhiko

    2015-12-01

    Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are prognostic factors for hepatocellular carcinoma (HCC). The impact of these tumor markers in recurrent HCC on the prognosis remains to be fully elucidated. Two hundred and seventeen patients whose AFP and DCP levels were measured at recurrence were enrolled in the present study. AFP levels >10 ng/mL and DCP levels ≥40 mAU/mL were defined as AFP positive (AFP+) and DCP positive (DCP+), respectively. The patterns of tumor markers were scored as AFP-/DCP-, 0; AFP+/DCP- or AFP-/DCP+, 1 and AFP+/DCP+, 2. The median survival period after recurrence in patients with a score of 2 (26.6 months) was significantly lower than that in patients with scores of 1 or 0 (43.5 months, P tumor marker score of 2 at recurrence was an independent predictor for poor survival after recurrence (hazard ratio 2.12, P = 0.03). The prognosis after recurrence in the patients with a decreased tumor maker score was significantly better than that in the patients with no change in the tumor marker score compared to the primary surgery (P = 0.048). The present study shows that measurements of both AFP and DCP are useful for predicting the prognosis of recurrent HCC.

  17. Evaluation of molecular targeted cancer drug by changes in tumor marker doubling times.

    Science.gov (United States)

    Enooku, Kenichiro; Tateishi, Ryosuke; Kanai, Fumihiko; Kondo, Yuji; Masuzaki, Ryota; Goto, Tadashi; Shiina, Shuichiro; Yoshida, Haruhiko; Omata, Masao; Koike, Kazuhiko

    2012-01-01

    We evaluated the usefulness of tumor marker doubling time (DT) as an efficacy indicator of a molecular targeted anticancer agent. Twenty-five patients with advanced hepatocellular carcinoma (HCC) received TSU-68, a multiple tyrosine kinase inhibitor. Exponential increase in HCC-specific tumor marker levels (alpha-fetoprotein or des-gamma-carboxyprothrombin) was seen in 15 of them prior to TSU-68 administration. The relationship between tumor marker DT and tumor volume DT was evaluated. Next, tumor marker DT in the first 8 weeks of TSU-68 administration was compared with tumor marker DT before treatment. Efficacy evaluation based on changes in tumor marker DT was compared with Response Evaluation Criteria In Solid Tumors (RECIST). Tumor marker DT and tumor volume DT were almost identical (r(2) = 0.94, P tumor marker DT on TSU-68 administration was in accordance with RECIST in 12/15 cases. Discordance was observed in three cases, for which RECIST indicated disease progression in spite of elongated tumor marker DT. Those cases showed substantial tumor necrosis without volume shrinkage or appearance of new lesions in spite of apparent effects on target lesions. Serum tumor marker DT can be used to evaluate viable tumor burden irrespective of the presence of tumor necrosis which can compromise radiographic evaluation. This approach may be applicable to the evaluation of responses to chemotherapy, particularly to cytostatic agents (ClinicalTrials.gov number, NCT00784290).

  18. Imaging diagnosis of hepatoma

    International Nuclear Information System (INIS)

    Ashizawa, Tatsuto

    1984-01-01

    Nuclear medicine (NM), ultrasonography (US), and computed tomography (CT) were evaluated as screening methods for hepatoma, and the characteristics of each modality were compared. Qualitative diagnosis of hepatoma by measuring the quantitative time-lapse changes in 67 Ga-citrate accumulation was also investigated. A prospective analysis using the above modalities was conducted for 70 patients with hepatoma, with the following results: sensitivities of NM, US and CT were 91.1% ; 91.8% ; and 96.9% respectively. In comparing the characteristics of the three modalities, however, it was concluded that the combined use of NM and US was recommended for screening, and that CT should be used for more detailed examination of a tumor indicated by NM and/or US. In the diagnosis of hepatoma by 67 Ga-citrate, a sensitivity rate of 73.7% and a specificity rate of 92.5% were obtained, indicating 67 Ga-citrate's considerable significance for qualitative diagnosis of hepatoma. A decision tree was also made for those patients with chronic liver disease in whom positive hepatitis B virus (HBV) infection was detected or in whom serum alpha-fetoprotein (AFP) showed an increasing tendency. (author)

  19. Diagnostic accuracy of des-gamma-carboxy prothrombin for hepatocellular carcinoma in a French cohort using the Lumipulse®G600 analyzer.

    Science.gov (United States)

    Sultanik, P; Ginguay, A; Vandame, J; Popovici, T; Meritet, J-F; Cynober, L; Pol, S; Bories, P-N

    2017-01-01

    The increasing incidence of hepatocellular carcinoma (HCC) in Western countries requests reliable tumour markers for preclinical diagnosis. We evaluated the diagnostic accuracy of des-gamma-carboxy prothrombin (DCP), in comparison with alpha-fetoprotein (AFP) in a French cohort using a new analyser. One hundred and sixty-two patients with virus-related cirrhosis (46 HCC patients and 116 controls) were recruited in this retrospective proof-of-concept study. DCP was measured on new Lumipulse ® G600 analyzer and AFP on usual Cobas e602 analyzer in serum samples that were collected at the time of HCC diagnosis for HCC patients or during follow-up for controls. DCP and AFP levels were higher in HCC patients. The area under receiver operating characteristic curve was larger for DCP than for AFP (0.89 vs 0.77, P=.03). At the cut-off value of 128 mAU/mL, sensitivity and specificity for DCP were 74% and 92%. At the cut-off value of 20 μg/L, sensitivity and specificity for AFP were 63% and 82%. NRI >0 for the association of "AFP+DCP" were 101%, P<.0001, and 23%, P=.03, compared to "AFP" or "DCP" alone, respectively. We conclude that DCP outperformed AFP for the detection of HCC. © 2016 John Wiley & Sons Ltd.

  20. Analytical and Clinical Performance Evaluation of the Abbott Architect PIVKA Assay.

    Science.gov (United States)

    Ko, Dae-Hyun; Hyun, Jungwon; Kim, Hyun Soo; Park, Min-Jeong; Kim, Jae-Seok; Park, Ji-Young; Shin, Dong Hoon; Cho, Hyoun Chan

    2018-01-01

    Protein induced by vitamin K absence (PIVKA) is measured using various assays and is used to help diagnose hepatocellular carcinoma. The present study evaluated the analytical and clinical performances of the recently released Abbott Architect PIVKA assay. Precision, linearity, and correlation tests were performed in accordance with the Clinical Laboratory Standardization Institute guidelines. Sample type suitability was assessed using serum and plasma samples from the same patients, and the reference interval was established using sera from 204 healthy individuals. The assay had coefficients of variation of 3.2-3.5% and intra-laboratory variation of 3.6-5.5%. Linearity was confirmed across the entire measurable range. The Architect PIVKA assay was comparable to the Lumipulse PIVKA assay, and the plasma and serum samples provided similar results. The lower reference limit was 13.0 mAU/mL and the upper reference limit was 37.4 mAU/mL. The ability of the Architect PIVKA assay to detect hepatocellular carcinoma was comparable to that of the alpha-fetoprotein test and the Lumipulse PIVKA assay. The Architect PIVKA assay provides excellent analytical and clinical performance, is simple for clinical laboratories to adopt, and has improved sample type suitability that could broaden the assay's utility. © 2018 by the Association of Clinical Scientists, Inc.

  1. Factors influencing women's acceptance of prenatal screening tests.

    Science.gov (United States)

    Li, De-Kun; Karlberg, Kristen; Wi, Soora; Norem, Carol

    2008-12-01

    To determine the factors influencing a woman's acceptance of the expanded alpha-fetoprotein (AFP) test. A population-based case-control study. All women (age < 35) who declined the expanded AFP test were identified as eligible cases. Controls were randomly selected from all women (age < 35) who accepted the test. We interviewed 199 cases and 229 controls before 30 weeks of gestation. While 47% of cases reported opposition to abortion as one of their reasons for declining the test (Group A), the remaining 53% of cases had a variety of other reasons for declining (Group B). After controlling for potential confounders, factors significantly associated with declining the test included: skepticism of the usefulness of the test results (odds ratio (OR) = 33.0), influence from family members (OR = 11.4), low educational level (OR = 7.1), willingness to keep a malformed fetus (OR = 6.2), failure to use providers as useful sources of information (OR = 5.0), and misunderstanding of the purpose of the test (OR = 2.0). Polytomous logistic regression revealed that Groups A and B had different determining factors as well as common factors. While many influential factors for participating in prenatal screening remain unmodifiable, some of them may be addressed to improve women's acceptance of prenatal screening tests. Copyright (c) 2008 John Wiley & Sons, Ltd.

  2. Camel milk inhibits murine hepatic carcinogenesis, initiated by diethylnitrosamine and promoted by phenobarbitone

    Directory of Open Access Journals (Sweden)

    Hala M.F. El Miniawy

    2014-12-01

    Full Text Available This study was carried out in order to investigate the possible inhibitory effect of camel milk (CM on induced hepatocarcinogenesis in rats. Twenty-eight male rats were assigned into 4 groups (7 rats per group. Group I served as control negative. Group II treated with camel milk. Group III was injected I/P with diethylnitrosamine (DENA (200 mg/kg as a single dose and after one week received 500 ppm phenobarbitone in drinking water. Group IV injected with DENA as group III and treated with camel milk. Estimation of AST, ALT, albumin, total protein and alpha fetoprotein (AFP in the serum of euthanized rats was performed. Histopathological examination and immunohistochemical staining of AFP and placental glutathione s transferase of the liver were carried out. Biochemical result at 38th week revealed an increase in serum AFP and a decrease in serum albumin on group III although no significance was detected. Histopathologically, the size of altered hepatic foci was smaller in the milk treated group (group IV. The number of mitotic figures observed in group IV was lower than group III. Hepatocellular carcinoma developed only in group III but not group IV. Immunohistochemical staining of AFP demonstrated an intense positive staining in group III and a weak positive staining in group IV. Similarly, the area percent of preneoplastic P-GST positive foci in liver was higher in group III than group IV. In conclusion, camel milk halted the progression of hepatocellular carcinoma.

  3. Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow

    Directory of Open Access Journals (Sweden)

    Vinken Mathieu

    2007-04-01

    Full Text Available Abstract Background The capability of human mesenchymal stem cells (hMSC derived of adult bone marrow to undergo in vitro hepatic differentiation was investigated. Results Exposure of hMSC to a cocktail of hepatogenic factors [(fibroblast growth factor-4 (FGF-4, hepatocyte growth factor (HGF, insulin-transferrin-sodium-selenite (ITS and dexamethasone] failed to induce hepatic differentiation. Sequential exposure to these factors (FGF-4, followed by HGF, followed by HGF+ITS+dexamethasone, however, resembling the order of secretion during liver embryogenesis, induced both glycogen-storage and cytokeratin (CK18 expression. Additional exposure of the cells to trichostatin A (TSA considerably improved endodermal differentiation, as evidenced by acquisition of an epithelial morphology, chronological expression of hepatic proteins, including hepatocyte-nuclear factor (HNF-3β, alpha-fetoprotein (AFP, CK18, albumin (ALB, HNF1α, multidrug resistance-associated protein (MRP2 and CCAAT-enhancer binding protein (C/EBPα, and functional maturation, i.e. upregulated ALB secretion, urea production and inducible cytochrome P450 (CYP-dependent activity. Conclusion hMSC are able to undergo mesenchymal-to-epithelial transition. TSA is hereby essential to promote differentiation of hMSC towards functional hepatocyte-like cells.

  4. Nonalcoholic fatty liver disease and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    LI Liangping

    2016-03-01

    Full Text Available As the etiology of hepatocellular carcinoma (HCC has been changing, the incidence of HCC related to nonalcoholic fatty liver disease (NAFLD is gradually increasing in developed countries in Europe and America and some countries in Asia. This article introduces the close association between NAFLD and HCC, risk factors, clinicopathological features, and prevention and screening, and points out that although the incidence of NAFLD is not as high as that of hepatitis B- or hepatitis C-related HCC, there are a large absolute number of NAFLD patients, especially the high-risk patients with diabetes and obesity, or liver fibrosis/cirrhosis, due to a huge base number of NAFLD patients. NAFLD-related HCC is commonly seen in the elderly with various comorbidities and a poor prognosis. This article also points out that the prevention should focus on the effective treatment of NAFLD. The strict screening of high-risk population is the strategy for the diagnosis of early-stage HCC. At present, the sensitivity of alpha-fetoprotein is relatively low, and imaging examinations including computed tomography are the main screening methods; however, there are no measures for early warning of NAFLD-related HCC.

  5. Persistent Unresolved Inflammation in the Mecp2-308 Female Mutated Mouse Model of Rett Syndrome

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    Alessio Cortelazzo

    2017-01-01

    Full Text Available Rett syndrome (RTT is a rare neurodevelopmental disorder usually caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2. Several Mecp2 mutant mouse lines have been developed recapitulating part of the clinical features. In particular, Mecp2-308 female heterozygous mice, bearing a truncating mutation, are a validated model of the disease. While recent data suggest a role for inflammation in RTT, little information on the inflammatory status in murine models of the disease is available. Here, we investigated the inflammatory status by proteomic 2-DE/MALDI-ToF/ToF analyses in symptomatic Mecp2-308 female mice. Ten differentially expressed proteins were evidenced in the Mecp2-308 mutated plasma proteome. In particular, 5 positive acute-phase response (APR proteins increased (i.e., kininogen-1, alpha-fetoprotein, mannose-binding protein C, alpha-1-antitrypsin, and alpha-2-macroglobulin, and 3 negative APR reactants were decreased (i.e., serotransferrin, albumin, and apolipoprotein A1. CD5 antigen-like and vitamin D-binding protein, two proteins strictly related to inflammation, were also changed. These results indicate for the first time a persistent unresolved inflammation of unknown origin in the Mecp2-308 mouse model.

  6. Effect of HCV Core Antigen and RNA Clearance during Therapy with Direct Acting Antivirals on Hepatic Stiffness Measured with Shear Wave Elastography in Patients with Chronic Viral Hepatitis C

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    Mariusz Łucejko

    2018-01-01

    Full Text Available To assess a combination of novel measures of therapeutic success in the treatment of chronic hepatitis C (CHC infection, we evaluated liver stiffness (LS with shear wave elastography and hepatitis C virus core antigen (HCVcAg concentrations. We followed 34 patients during and after treatment with direct acting antivirals. All patients achieved a sustained virologic and serologic response and a significant increase of albumin levels. Decreases of alanine aminotransferase (ALT activity and alpha-fetoprotein (AFP level were observed during the treatment and follow-up period. A significant decrease in LS was observed between baseline, end of treatment (EOT, and at 24- and 96-week post-treatment follow-up. LS decline between EOT and 96-week follow-up (FU96 was observed in 79% of patients. Significant LS changes were seen in patients with advanced fibrosis, particularly in cirrhotics and in patients with ALT exceeding 100 IU/mL. There was a positive correlation between ALT activity and LS changes at the baseline versus FU96. A negative correlation was demonstrated between individual HCVcAg baseline concentrations and reduction of LS at the baseline versus FU96. In conclusion, we observed that LS significantly declined during and after antiviral treatment. It was accompanied by improvement in some liver function measures, and disappearance of both HCVcAg and HCV ribonucleic acid (HCV RNA.

  7. Liver stiffness measured by magnetic resonance elastography as a risk factor for hepatocellular carcinoma: a preliminary case-control study

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    Motosugi, Utaroh; Ichikawa, Tomoaki; Koshiishi, Tsuyota; Sano, Katsuhiro; Morisaka, Hiroyuki; Ichikawa, Shintaro; Araki, Tsutomu [University of Yamanashi, Department of Radiology, Yamanashi-ken (Japan); Enomoto, Nobuyuki [University of Yamanashi, 1st Department of Internal Medicine, Yamanashi (Japan); Matsuda, Masanori; Fujii, Hideki [University of Yamanashi, 1st Department of Surgery, Yamanashi (Japan)

    2013-01-15

    To examine if liver stiffness measured by magnetic resonance elastography (MRE) is a risk factor for hepatocellular carcinoma (HCC) in patients with chronic liver disease. By reviewing the records of magnetic resonance (MR) examinations performed at our institution, we selected 301 patients with chronic liver disease who did not have a previous medical history of HCC. All patients underwent MRE and gadoxetic acid-enhanced MR imaging. HCC was identified on MR images in 66 of the 301 patients, who were matched to controls from the remaining patients without HCC according to age. MRE images were obtained by visualising elastic waves generated in the liver by pneumatic vibration transferred via a cylindrical passive driver. Risk factors of HCC development were determined by the odds ratio with logistic regression analysis; gender and liver stiffness by MRE and serum levels of aspartate transferase, alanine transferase, alpha-fetoprotein, and protein induced by vitamin K absence-II. Multivariate analysis revealed that only liver stiffness by MRE was a significant risk factor for HCC with an odds ratio (95 % confidence interval) of 1.38 (1.05-1.84). Liver stiffness measured by MRE is an independent risk factor for HCC in patients with chronic liver disease. (orig.)

  8. Klotho-beta overexpression as a novel target for suppressing proliferation and fibroblast growth factor receptor-4 signaling in hepatocellular carcinoma

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    Poh Weijie

    2012-03-01

    Full Text Available Abstract Background We had previously demonstrated overexpression of fibroblast growth factor receptor-4 (FGFR4 in hepatocellular carcinoma (HCC. However, additional molecular mechanisms resulting in amplified FGFR4 signaling in HCC remain under-studied. Here, we studied the mechanistic role of its co-receptor klotho-beta (KLB in driving elevated FGFR4 activity in HCC progression. Results Quantitative real-time PCR analysis identified frequent elevation of KLB gene expression in HCC tumors relative to matched non-tumor tissue, with a more than two-fold increase correlating with development of multiple tumors in patients. KLB-silencing in Huh7 cells decreased cell proliferation and suppressed FGFR4 downstream signaling. While transient repression of KLB-FGFR4 signaling decreased protein expression of alpha-fetoprotein (AFP, a HCC diagnostic marker, prolonged inhibition enriched for resistant HCC cells exhibiting increased liver stemness. Conclusions Elevated KLB expression in HCC tissues provides further credence to the oncogenic role of increased FGFR4 signaling in HCC progression and represents a novel biomarker to identify additional patients amenable to anti-FGFR4 therapy. The restricted tissue expression profile of KLB, together with the anti-proliferative effect observed with KLB-silencing, also qualifies it as a specific and potent therapeutic target for HCC patients. The enrichment of a liver stem cell-like population in response to extended KLB-FGFR4 repression necessitates further investigation to target the development of drug resistance.

  9. Patients with liver FNH and HCC patients with negative AFP: plain and dynamic enhanced MRI and CT findings

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    LI Mingtong

    2015-05-01

    Full Text Available ObjectiveTo investigate plain and dynamic enhanced magnetic resonance imaging (MRI and computed tomography (CT findings in patients with focal nodular hyperplasia (FNH of the liver and hepatocellular carcinoma (HCC patients with negative alpha-fetoprotein (AFP. MethodsA statistical analysis was performed on the clinical data of 124 cases of liver tumor admitted to Beijing Miyun County Hospital from April 2012 to April 2014. ResultsFifty-five of the 74 patients with FNH underwent CT examination, among whom 38 patients received three-phase dynamic enhanced scan and 16 received only plain scan; 62 cases had plain and enhanced MRI with the application of contrast agent Gd-BOPTA in 42 patients. Among the 50 HCC patients with negative AFP, CT examination was performed in 40 and 10 only had plain scan; 46 patients received plain and enhanced MRI with the use of contrast agent Gd-BOPTA in 30. Delayed scan after 1-2 h demonstrated low signal in 30 lesions of the 30 cases. ConclusionFor patients with liver FNH and AFP-negative HCC patients, their plain and dynamic enhanced MRI and CT scan have respective characteristics. A combination of multiple examination methods can significantly improve diagnostic yield of the two diseases.

  10. Prevention of aflatoxin B1-initiated hepatotoxicity in rat by marine algae extracts.

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    Abdel-Wahhab, Mosaad A; Ahmed, Hanaa H; Hagazi, Mohamad M

    2006-01-01

    Chemoprevention by extracts of Laurencia obtusa (E1) and Caulerpa prolifera (E2) collected from the Egyptian coast of the Red Sea against aflatoxin B(1) (AFB(1))-initiated hepatotoxicity in female Sprague-Dawley rats has been studied. Animals were fed aflatoxin-contaminated diet (3 mg kg(-1) diet) for 6 days then treated orally with pure aflatoxin B(1) (AFB(1)) (200 microg kg(-1) b.w.) for 4 days either in combination with or before E1 or E2 administration (50 mg kg(-1) b.w.). AFB(1) resulted in a signicant increase in serum alpha fetoprotein, carcinoembryonic antigen, tumor necrosis factor alpha, nitric oxide, interleukin-1alpha, procollagen III and lipid peroxidation level in the liver. It caused a signicant decrease in food intake, body weight, serum leptin, the activities of glutathione peroxidase, superoxide dismutase and DNA and RNA concentrations in the liver. Cotreatment with AFB(1) and E1 or E2 resulted in an obvious improvement in all tested parameters. Noteworthy, E2 was more effective than E1 in the protection against AFB(1)-induced hepatotoxicity. Copyright 2006 John Wiley & Sons, Ltd.

  11. Surgical resection versus radiofrequency ablation in treatment of small hepatocellular carcinoma

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    HE Xiuting

    2013-08-01

    Full Text Available ObjectiveTo compare clinical efficacy and recurrence between surgical resection and radiofrequency ablation (RFA in the treatment of small hepatocellular carcinoma (HCC. MethodsThe clinical data of 97 patients with small HCC, who underwent surgical resection or RFA as the initial treatment in The First Hospital of Jilin University from January 2002 to December 2008, were collected. Sixty-three cases, who survived 2 years after treatment, were followed up; of the 63 cases, 34 underwent surgical resection, and 29 underwent RFA. The recurrence of these patients was analyzed retrospectively. The measurement data were analyzed by chi-square test. The Cox regression analysis was used for determining the risk factors for recurrence. The log-rank test was used for disease-free survival (DFS difference analysis. ResultsThe 3-month, 1-year, and 2-year intrahepatic recurrence rates for the patients who underwent surgical resection were 15%, 38%, and 64%, respectively, versus 21%, 35%, and 45% for those who underwent RFA, without significant differences between the two groups of patients. The intrahepatic recurrence after initial treatment was not significantly associated with treatment method, sex, age, Child-Pugh grade, tumor size, number of nodules, presence of cirrhosis, and alpha-fetoprotein level. There was no significant difference in DFS between the two groups of patients. ConclusionRFA produces a comparable outcome to that by surgical resection in the treatment of small HCC. RFA holds promise as a substitute for surgical resection.

  12. One-step synthesis of redox-active polymer/AU nanocomposites for electrochemical immunoassay of multiplexed tumor markers.

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    Liu, Zhimin; Rong, Qinfeng; Ma, Zhanfang; Han, Hongliang

    2015-03-15

    In this work, a simple and sensitive multiplexed immunoassay protocol for simultaneous electrochemical determination of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) was designed using redox-active nanocomposites. As the redox-active species, the poly(o-phenylenediamine) (POPD)/Au nanocomposite and poly(vinyl ferrocene-2-aminothiophenol) (poly(VFc-ATP))/Au nanocomposite were obtained by one-step method which HAuCl4 was used as the oxidant. With Au nanoparticles (AuNPs), the nanocomposites were successful to immobilize labeled anti-CEA and anti-AFP as the immunosensing probes. The proposed electrochemical immunoassay enabled the simultaneous monitoring of AFP and CEA in a wide range of 0.01-100ngmL(-1). The detection limits was 0.006ngmL(-1) for CEA and 0.003ngmL(-1) for AFP (S/N=3). The assay results of serum samples with the proposed method were well consistent with the reference values from standard ELISA method. And the negligible cross-reactivity between the two analytes makes it possesses potential promise in clinical diagnosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Clinical and pathologic factors associated with survival in young adult patients with fibrolamellar hepatocarcinoma

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    Moreno-Luna, Laura E; Arrieta, Oscar; García-Leiva, Jorge; Martínez, Braulio; Torre, Aldo; Uribe, Misael; León-Rodríguez, Eucario

    2005-01-01

    Fibrolamellar Carcinoma (FLC), a subtype of hepatocellular carcinoma (HCC), is a rare primary hepatic malignancy. Several aspects of the clinic features and epidemiology of FLC remain unclear because most of the literature on FLC consists of case reports and small cases series with limited information on factors that affect survival. We did a retrospective analysis of the clinical and histological characteristics of FLC. We also determined the rate of cellular proliferation in biopsies of these tumors. We assessed whether these variables were associated with survival. We found 15 patients with FLC out of 174 patients with HCC (8.6%). Between patients with these neoplasms, we found statistically significant survival, age at onset, level of alpha fetoprotein, and an earlier stage of the disease. The 1, 3 and 5 year survival in patients with FLC was of 66, 40 and 26% respectively. The factors associated with a higher survival in patients with FLC were age more than 23 years, feasibility of surgical resection, free surgical borders, absence of thrombosis or invasion to hepatic vessels and the absence of alterations in liver enzymes. The size of the tumor, gender, cellular proliferation and atypia did not affect the prognosis. We concluded that FLC patients diagnosed before 23 years of age have worse prognosis than those diagnosed after age 23. Other factors associated with worse prognosis in this study are: lack of surgical treatment, presence of positive surgical margins, vascular invasion, and altered hepatic enzymes

  14. Cognitive functions in ataxia with oculomotor apraxia type 2.

    Science.gov (United States)

    Klivényi, Peter; Nemeth, Dezso; Sefcsik, Tamas; Janacsek, Karolina; Hoffmann, Ildiko; Haden, Gabor Peter; Londe, Zsuzsa; Vecsei, Laszlo

    2012-01-01

    Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by cerebellar atrophy, peripheral neuropathy, oculomotor apraxia, and elevated serum alpha-fetoprotein (AFP) levels. The disease is caused by a recessive mutation in the senataxin gene. Since it is a very rare cerebellar disorder, no detailed examination of cognitive functions in AOA2 has been published to date. The aim of the present study was to investigate the neuropsychological profile of a 54-year-old patient with AOA2. A broad range of neuropsychological examination protocol was administered including the following domains: short-term, working- and episodic-memories, executive functions, implicit sequence learning, and the temporal parameters of speech. The performance on the Listening Span, Letter Fluency, Serial Reaction Time Task, and pause ratio in speech was 2 or more standard deviations (SD) lower compared to controls, and 1 SD lower on Backward Digit Span, Semantic Fluency, articulation rate, and speech tempo. These findings indicate that the pathogenesis of the cerebrocerebellar circuit in AOA2 is responsible for the weaker coordination of complex cognitive functions such as working memory, executive functions, speech, and sequence learning.

  15. Imaging features of undifferentiated embryonal sarcoma of the liver: a series of 15 children

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    Gabor, Flaviu; Franchi-Abella, Stephanie; Pariente, Daniele; Merli, Laura; Adamsbaum, Catherine

    2016-01-01

    Undifferentiated embryonal sarcoma of the liver is a rare malignant mesenchymal tumour occurring mostly in children ages 6-10 years. The discrepancy between its solid appearance on US and cystic-like appearance on CT has been described. To study the imaging particularities and similarities among our cases of undifferentiated embryonal sarcoma and to report the errors in initial diagnoses. We conducted a retrospective study of 15 children with undifferentiated embryonal sarcoma diagnosed or referred to our hospital during 1997-2015 and analysed the clinical, biological and imaging data. We identified eight boys and seven girls ages 9 months to 14 years. Ten children presented with abdominal pain. Alpha-fetoprotein was slightly increased in one. Initial US and CT had been performed for all, while additional MRI had been done in two children. Initial CT demonstrated a hypoattenuated mass in all. Rupture was seen in five and intratumoural bleeding in seven children. Tumour volumes reduced during neoadjuvant chemotherapy in 10 children. Undifferentiated embryonal sarcoma might be suggested in a non-secreting unifocal tumour with well-defined borders, fluid-filled spaces on US, hypoattenuation and serpiginous vessels on CT, and if there are signs of internal bleeding or rupture on CT or MRI. (orig.)

  16. Yolk sac tumor in a patient with transverse testicular ectopia

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    Zhu Yi-Ping

    2011-08-01

    Full Text Available Abstract Transverse testicular ectopia (TTE is a rare anomaly in which both testes descend through a single inguinal canal. We report a case of yolk sac tumor in the ectopic testis of a patient with TTE. A 24-year-old man presented to our hospital with a left inguinal-mass, right cryptorchidism and elevated alpha-fetoprotein (AFP. A left herniotomy 3 years earlier demonstrated both testes in the left scrotum, one above another positionally. Four months ago, a left scrotal mass appeared and radical orchiectomy of both testes revealed testicular yolk sac tumor of the ectopic testis. An enlarging left inguinal-mass appeared 2 months ago and he was referred to our hospital. Laboratory data showed an elevation of AFP (245.5 ng/ml and a 46 XY karyotype. He underwent bilateral retroperitoneal lymph node dissection and simultaneous left inguinal mass dissection. Histopathologic examination revealed a diagnosis of recurrent yolk sac tumor in the left inguinal mass. The retroperitoneal lymph node was not enlarged and, on histopathology, was not involved. The patient has now been followed up for 8 months without evidence of biochemical or radiological recurrence.

  17. Primary clear cell ductal adenocarcinoma of the pancreas: A case report and clinicopathologic literature review

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    Yashpal Modi

    2014-01-01

    Full Text Available We present a very rare, interesting case of a carcinoma of the pancreas with predominantly abundant clear cell morphology. According to the WHO classification, primary clear cell carcinoma of the pancreas is classified as a rare "miscellaneous" carcinoma. The tumor was observed in the distal body and tail of the pancreas of a 74-year-old woman. The histopathology of tumor cells showed well-defined cell membranes, clear cytoplasm, and prominent cell boundaries. Immunohistochemical (IHC staining showed positive reactions to antibodies against vimentin, cytokeratin 7 (CK-7, mucicarmine (MUC-1, periodic acid-Schiff (PAS, periodic acid-Schiff with diastase (PASD, carcinoembryonic antigen (CEA, and Carbohydrate Antigen 19-9 (CA 19-9. On the other hand, IHC staining was negative for alpha-fetoprotein (AFP, cytokeratin 20 (CK-20, HMB45, chromogranin, and synaptophysin. The patient was subsequently diagnosed with a primary solid-type pancreatic clear cell carcinoma with hepatic metastasis. Herein, we report this rare case and include a review of the current literature of this tumor.

  18. Clinical and pathologic factors associated with survival in young adult patients with fibrolamellar hepatocarcinoma

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    Torre Aldo

    2005-10-01

    Full Text Available Abstract Background Fibrolamellar Carcinoma (FLC, a subtype of hepatocellular carcinoma (HCC, is a rare primary hepatic malignancy. Several aspects of the clinic features and epidemiology of FLC remain unclear because most of the literature on FLC consists of case reports and small cases series with limited information on factors that affect survival. Methods We did a retrospective analysis of the clinical and histological characteristics of FLC. We also determined the rate of cellular proliferation in biopsies of these tumors. We assessed whether these variables were associated with survival. Results We found 15 patients with FLC out of 174 patients with HCC (8.6%. Between patients with these neoplasms, we found statistically significant survival, age at onset, level of alpha fetoprotein, and an earlier stage of the disease. The 1, 3 and 5 year survival in patients with FLC was of 66, 40 and 26% respectively. The factors associated with a higher survival in patients with FLC were age more than 23 years, feasibility of surgical resection, free surgical borders, absence of thrombosis or invasion to hepatic vessels and the absence of alterations in liver enzymes. The size of the tumor, gender, cellular proliferation and atypia did not affect the prognosis. Conclusion We concluded that FLC patients diagnosed before 23 years of age have worse prognosis than those diagnosed after age 23. Other factors associated with worse prognosis in this study are: lack of surgical treatment, presence of positive surgical margins, vascular invasion, and altered hepatic enzymes.

  19. Therapeutic response of untreatable hepatocellular carcinoma after application of the immune modulators IL-2, BCG and melatonin.

    Science.gov (United States)

    Tomov, Bojidar; Popov, Dimitar; Tomova, Radosveta; Vladov, Nicola; Den Otter, Willem; Krastev, Zachary

    2013-10-01

    Application of immunotherapy to a patient with untreatable hepatocellular carcinoma. The patient had a tumor of 60 mm in the liver. The pathological anatomic diagnosis was adenoma. However, after surgery of the tumor seven new lesions arose, showing that the original tumor had been a hepatocellular carcinoma. In addition, when hepatocellular adenomas grow to a size of more than 6-8 cm, they are considered cancerous and thus become a risk for hepatocellular carcinoma. The patient was treated with interleukin-2, Bacillus Calmette Guerin, and melatonin. During treatment, the alpha-fetoprotein levels in blood fell from 5,000 IU/ml to zero, at which level it remained during the follow-up period of two years. No tumor was detectable on MRI and CT. Six years after the diagnosis of untreatable hepatocellular carcinoma, the patient remains in a good condition. In this case, combined immunomodulating therapy was effective. For patients with metastasized tumors of the liver who are not suitable for conventional therapy, immunomodulation may delay tumor progression, induce tumor regression, or even be curative in some patients. Immunotherapeutic approaches combined with conventional methods for hepatocellular carcinoma treatment may be able to improve therapeutic efficacy.

  20. [Comparison liver resection with transarterial chemoembolization for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma patients on long-term survival after SPSS propensity score matching].

    Science.gov (United States)

    Ke, Yang; Zhong, Jianhong; Guo, Zhe; Liang, Yongrong; Li, Lequn; Xiang, Bangde

    2014-03-18

    To compare the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) undergoing either liver resection or transarterial chemoembolization (TACE) after propensity score matching (PSM). One hundred sixty-seven and 70 BCLC-B HCC patients undergoing liver resection and TACE were retrospectively collected. PSM function of SPSS software was conducted to reduce confounding bias between the groups. And then survival analysis was performed for the matched data. Fifty-three pairs of patients were successfully matched. And then survival analysis showed that the median survival periods and their 95% confidence intervals were 35.0 (26.3-43.7)months in the liver resection group versus 20.0(15.0-25.0) months in the TACE group. The 1, 3, 5 and 7-year survival rates were 91.0%, 49.0%, 30.0% and 17.0% in the liver resection group versus 73.0%, 25.0%, 8.0% and 5.0% respectively in the TACE group (P = 0.001). Cox regression analysis revealed that TACE, total bilirubin ≥ 34.2 µmol/L, alpha fetoprotein ≥ 400 ng/ml and tumor number ≥ 3 were independent risk factors of survival (hazard ratio >1, P < 0.05). The balance of covariates may be achieved through PSM. And for patients with BCLC-B HCC, liver resection provides better long-term overall survival than TACE.

  1. Prognostic scores for sorafenib-treated hepatocellular carcinoma patients: A new application for the hepatoma arterial embolisation prognostic score.

    Science.gov (United States)

    Edeline, J; Blanc, J-F; Campillo-Gimenez, B; Ma, Y-T; King, J; Faluyi, O; Mathurin, J; Ghazi, S; Palmer, D H; Meyer, T

    2017-11-01

    No prognostic classification is currently used for patients treated with systemic therapies for Hepatocellular Carcinoma (HCC). We retrospectively analysed data from patients treated with sorafenib for HCC from five centres in France and in the United Kingdom (UK). The training set comprised data from two centres and the validation set from three. Variables independently associated with Overall Survival (OS) in the training set were used to build the SAP (Sorafenib Advanced HCC Prognosis) score. The score was tested in the validation set, then compared with other prognostication systems. The training set and validation set included 370 and 468 patients respectively. In the training set, variables independently associated with OS in multivariable analysis were: performance status (PS) >0, alpha-fetoprotein (AFP) >400 ng/ml, tumour size >7 cm, bilirubin >17 μmol/l and albumin Cancer (BCLC) and albumin-bilirubin (ALBI) scores. However, the hepatoma arterial embolisation prognostic (HAP) score showed greater discriminative abilities than the SAP score. In European patients treated with sorafenib, the HAP was the most discriminant prognostic score and may facilitate stratification in trials and inform clinical decision making. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Phenobarbital at Low Dose in the presence of Curcumin Decreases Progress of Cancer in Rats

    International Nuclear Information System (INIS)

    Mazen, G.M.A.

    2011-01-01

    This current investigation was conducted on male albino rats to elucidate the effects of curcumin alone or in the presence of phenobarbital at low dose to decrease the progress of hepato-gastrointestinal carcinogenesis induced by N-diethylnitrosoamine (DEN) in rats. As a result of cancer induction, the levels of serum tumour markers [carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP) and cancer antigen (CA19.9)] were significantly elevated. On the other hand, glutathione (GSH) and glutathione peroxidase (GPx) were decreased significantly in blood, liver, stomach and intestine whereas the levels of malondialdehyde (MAD) in liver, stomach and intestine were significantly elevated in the cancer group of rats in comparison to their corresponding control group. The administration of curcumin alone or together with phenobarbital ameliorated all these alterations depending on the time of administration. The data of this study suggested that low dose of phenobarbital in the presence of curcumin may inhibit the development of hepato-gastrointestinal carcinogenesis initiated with DEN.

  3. Retroperitoneal liposarcoma associated with small plaque parapsoriasis.

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    Tartaglia, Francesco; Blasi, Sara; Sgueglia, Monica; Polichetti, Paolo; Tromba, Luciana; Berni, Alberto

    2007-07-09

    Extremely rare cases of paraneoplastic syndromes or ectopic production of proteins associated with liposarcoma are reported in literature. Production of Granulocyte-Colony Stimulating Factor, alpha-fetoprotein, paraneoplastic pemphigus and leucocytosis, Acrokeratosis paraneoplastica (Bazex's syndrome) are reported. The present report describes a case of retroperitoneal liposarcoma associated with small plaque parapsoriasis. Our search in the English literature of such a kind of association did not reveal any case reported. A 74 year male patient was admitted to our hospital because of the presence of an abdominal mass in right iliac fossa. He also complained of a two-year history of psoriasiform eruptions. The CT scan showed a retroperitoneal pelvic mass. Therefore surgical resection of the tumor was performed. After surgery, the skin eruptions disappeared completely in seven days and so a diagnosis of parapsoriasis syndrome was done. Parallel disappearing of skin eruptions after surgery, typical clinical picture and not specific histology of the cutaneous lesions suggest the diagnosis of small plaque parapsoriasis. Therefore we propose to add Small Plaque Parapsoriasis to the list of paraneoplastic syndromes associated to liposarcoma.

  4. Retroperitoneal liposarcoma associated with small plaque parapsoriasis

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    Polichetti Paolo

    2007-07-01

    Full Text Available Abstract Background Extremely rare cases of paraneoplastic syndromes or ectopic production of proteins associated with liposarcoma are reported in literature. Production of Granulocyte-Colony Stimulating Factor, alpha-fetoprotein, paraneoplastic pemphigus and leucocytosis, Acrokeratosis paraneoplastica (Bazex's syndrome are reported. The present report describes a case of retroperitoneal liposarcoma associated with small plaque parapsoriasis. Our search in the English literature of such a kind of association did not reveal any case reported. Case presentation A 74 year male patient was admitted to our hospital because of the presence of an abdominal mass in right iliac fossa. He also complained of a two-year history of psoriasiform eruptions. The CT scan showed a retroperitoneal pelvic mass. Therefore surgical resection of the tumor was performed. After surgery, the skin eruptions disappeared completely in seven days and so a diagnosis of parapsoriasis syndrome was done. Conclusion Parallel disappearing of skin eruptions after surgery, typical clinical picture and not specific histology of the cutaneous lesions suggest the diagnosis of small plaque parapsoriasis. Therefore we propose to add Small Plaque Parapsoriasis to the list of paraneoplastic syndromes associated to liposarcoma.

  5. Spontaneous regression of a large hepatocellular carcinoma: case report

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    Alqutub, Adel

    2011-01-01

    Full Text Available The prognosis of untreated advanced hepatocellular carcinoma (HCC is grim with a median survival of less than 6 months. Spontaneous regression of HCC has been defined as the disappearance of the hepatic lesions in the absence of any specific therapy. The spontaneous regression of a very large HCC is very rare and limited data is available in the English literature. We describe spontaneous regression of hepatocellular carcinoma in a 65-year-old male who presented to our clinic with vague abdominal pain and weight loss of two months duration. He was found to have multiple hepatic lesions with elevation of serum alpha-fetoprotein (AFP level to 6,500 µg/L (normal <20 µg/L. Computed tomography revealed advanced HCC replacing almost 80% of the right hepatic lobe. Without any intervention the patient showed gradual improvement over a period of few months. Follow-up CT scan revealed disappearance of hepatic lesions with progressive decline of AFP levels to normal. Various mechanisms have been postulated to explain this rare phenomenon, but the exact mechanism remains a mystery.

  6. Adult Type Granulosa Cell Tumor: A Very Rare Case of Sex-Cord Tumor of the Testis with Review of the Literature

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    Dimosthenis Miliaras

    2013-01-01

    Full Text Available Granulosa cell tumor (GST is a sex-cord/stromal neoplasm of the gonads, more commonly arising in the ovaries, while approximately 80 cases have been reported in the testes. Out of these, 30 cases were of the adult type, while the remainder 50 cases were of the juvenile type. The latter mostly concerned infants and followed a benign course. However, the adult type testicular GCTs may be potentially malignant as it also happens in female patients with such neoplasms. We present a case of an adult type GCT located at the left testis. The patient was subjected to total orchiectomy and received no further treatment. Histology showed typical GCT histomorphology with Call-Exner bodies in some places. The immunoprofile of the tumor was CD99 (+, calretinin (+, inhibin (+, alpha smooth muscle actin (+, vimentin (+, ER (−, PR (−, keratin AE1/AE3 (−, alpha fetoprotein (−, CD117 (−, and placental alkaline phosphatase (−. Two years after surgery, the patient is alive and well with no signs of recurrence.

  7. Heteroassembled gold nanoparticles with sandwich-immunoassay LSPR chip format for rapid and sensitive detection of hepatitis B virus surface antigen (HBsAg).

    Science.gov (United States)

    Kim, Jinwoon; Oh, Seo Yeong; Shukla, Shruti; Hong, Seok Bok; Heo, Nam Su; Bajpai, Vivek K; Chun, Hyang Sook; Jo, Cheon-Ho; Choi, Bong Gill; Huh, Yun Suk; Han, Young-Kyu

    2018-06-01

    This study aimed to develop a more sensitive method for the detection of hepatitis B surface antigen (HBsAg) using heteroassembled gold nanoparticles (AuNPs). A single layered localized surface plasmon resonance (LSPR) chip format was developed with antigen-antibody reaction-based detection symmetry using AuNPs, which detected HBsAg at 10 pg/mL. To further improve the detection limit, a modified detection format was fabricated by fixing a secondary antibody (to form a heteroassembled sandwich format) to the AuNP monolayer, which enhanced the detection sensitivity by about 100 times. The developed heteroassembled AuNPs sandwich-immunoassay LSPR chip format was able to detect as little as 100 fg/mL of HBsAg within 10-15 min. In addition, the heteroassembled AuNPs sandwich-immunoassay LSPR chip format did not show any non-specific binding to other tested antigens, including alpha fetoprotein (AFP), C-reactive protein (CRP), and prostate-specific antigen (PSA). These findings confirm that the proposed detection strategy of heteroassembled AuNPs sandwich-immunoassay LSPR chip format may provide a new platform for early diagnosis of various human diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Differentiation of hamster liver oval cell following Clonorchis sinensis infection.

    Science.gov (United States)

    Yoon, B I; Jung, S Y; Hur, K; Lee, J H; Joo, K H; Lee, Y S; Kim, D Y

    2000-12-01

    Oval cells which appear in the liver after hepatic injuries are suspected to be progenitor cells for both hepatocytes and bile duct cells. Oval cell isolated from the livers of the hamsters treated with diethylnitrosamine and 2-acetylaminofluorene and infected with Clonorchis sinensis (CS). cultured for 2 weeks and evaluated for differentiation and plasticity by electron microscopy and immunohistochemistry. In the CS-uninfected group, glycogen granules and peroxisomes were noted in the cells that were cultured for 2 weeks. Starting at 1 week postculture, immunoreactivity of the cells to cytokeratin 19 markedly decreased but that to albumin and alpha-fetoprotein gradually increased. This means that oval cells isolated from hamsters that were not infected with CS differentiated toward hepatocyte lineage. However, in the CS-infected group, cultured cells contained numerous rough endoplasmic reticulum and showed immunoreactivity that was generally in reverse to that of CS-uninfected group, meaning that cells isolated following CS infection were primed by CS and differentiated toward bile duct cell lineage. The results of this study suggested that oval cells are indeed bipolar progenitor cells for hepatocytes and bile duct cells and can differentiate toward either lineage depending upon the priming factor.

  9. LPAC syndrome associated with deletion of the full exon 4 in a ABCB4 genetic mutation in a patient with hepatitis C

    Directory of Open Access Journals (Sweden)

    Blanca Fombuena

    2014-12-01

    Full Text Available Low-phospholipid-associated cholelithiasis syndrome (LPAC is associated with ABCB4 genetic mutation. ABCB4 encodes MDR3 protein, involved in biliary phosphatidylcholine excretion. Higher prevalence in women, biliary symptoms in young adults and ursodesoxycholic acid (UDCA response are the main features. We report the case of a 48-year-old man with hepatitis C, genotype 1b, fibrosis F3, null responder to Peg-IFNα2b/ribavirin and nephritic colic. In 2011 he developed jaundice, pruritus and epigastric pain. He showed increased serum levels of AST, ALT, GGT, bilirubin and alpha-fetoprotein, and viral load (14,600,000IU/mL. Pancreatic-CT, endoscopic ultrasonography and echo-Doppler showed non-cirrhotic chronic liver disease. The episode resolved spontaneously and one year later he suffered a similar episode. UDCA was started with excellent response. An immunohistochemistry study and sequencing of ABCB4 did not find alteration. MLPA® technique detected heterozygous deletion of the full exon 4 confirming LPAC syndrome diagnosis.

  10. LPAC syndrome associated with deletion of the full exon 4 in a ABCB4 genetic mutation in a patient with hepatitis C.

    Science.gov (United States)

    Fombuena, Blanca; Ampuero, Javier; Álvarez, Luis; Aparcero, Reyes; Llorca, Rocío; Millán, Raquel; Pastor, Helena; Andueza, Sara; Barbu, Veronique; Romero-Gómez, Manuel

    2014-12-01

    Low-phospholipid-associated cholelithiasis syndrome (LPAC) is associated with ABCB4 genetic mutation. ABCB4 encodes MDR3 protein, involved in biliary phosphatidylcholine excretion.Higher prevalence in women, biliary symptoms in young adults and ursodesoxycholic acid (UDCA) response are the main features. We report the case of a 48-year-old man with hepatitis C, genotype 1b, fibrosis F3, null responder to Peg-IFN-alpha-2b/ribavirin and nephritic colic. In 2011 he developed jaundice, pruritus and epigastric pain.He showed increased serum levels of AST, ALT, GGT, bilirubin and alpha-fetoprotein, and viral load (14,600,000 IU/mL). Pancreatic- CT, endoscopic ultrasonography and echo-Doppler showed noncirrhotic chronic liver disease. The episode resolved spontaneously and one year later he suffered a similar episode. UDCA was started with excellent response. An immunohistochemistry study and sequencing of ABCB4 did not find alteration. MLPA® technique detected heterozygous deletion of the full exon 4 confirming LPAC syndrome diagnosis.

  11. Carcinosarcoma of the Liver: A Case Report

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    Kwon, Jung Hyeok; Kang, Yu Na; Kang, Koo Jeong [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2007-08-15

    A 46-year-old woman was referred after having general weakness for one month. Biochemical indices of liver function were normal. The tumor markers revealed the following: alpha-fetoprotein level, 2.1 ng/mL (< 9.6 ng/mL); carcinoembryonic antigen level, 1.5 ng/mL (< 5.0 ng/mL); serum carbohydrate antigen 19 9 level, 13.2 U/mL (< 39 U/mL). Serum markers for hepatitis B and C were negative. Ultrasonography showed a lobulate heterogeneous echogenic solid mass with a highly echogenic lesion with posterior acoustic shadowing within the mass in the left lobe of the liver. Computed tomographic analysis of the mass revealed peripheral enhancing viable portions, large internal non-enhancing necrotic portions, and a dense radiopaque lesion. In conclusion, the imaging findings of hepatic carcinosarcoma presented in this report showed a large mass with large necrotic portions, small cystic portions, calcifications and bone formations. Although, from a clinical standpoint, establishing an accurate preoperative diagnosis is difficult, carcinosarcoma should be included in the differential diagnosis of a large necrotic hepatic mass, especially if rocky calcifications or bone formations are seen.

  12. USE OF SACCHROMYCES CERVISIAE TO SUPPRESS THE EFFECTS OF FUMONISIN MYCOTOXICOSIS IN JAPANESE QUAIL

    International Nuclear Information System (INIS)

    ABU TALEB, A.M.

    2008-01-01

    In this study, 400 unsexed Japanese quail chicks (1 day old) were used. The quail chicks were randomly assigned into four groups of 100 birds in each. The first group was served as control. The other experimental groups were fed on a basal diet supplemented with 0.5% yeast/kg diet (G2), 0.5% yeast/kg diet ± 200 mg fumonicin-B1/kg diet (G3) and 200 mg fumonicin-B1/kg diet (G4). The results showed significant increases in mortality rate, GPT (ALT), GOT (AST), cholesterol, uric acid, creatinine and alpha-fetoprotein (AFP) and decreases in body weight, hatchability, fertility and hatching weight, serum total proteins, globulin and glutathione peroxidase (GPx) activity in group of quails received fumonisin (G4) in comparison with the control group (G1) and all treatments. Yeast led to partial improvement in the parameters in group two (G2). Also, yeast suppressed the toxic effect of fumonisin B-1 (G3)

  13. Recent Advances in Application of Biosensors in Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Anwarul Hasan

    2014-01-01

    Full Text Available Biosensors research is a fast growing field in which tens of thousands of papers have been published over the years, and the industry is now worth billions of dollars. The biosensor products have found their applications in numerous industries including food and beverages, agricultural, environmental, medical diagnostics, and pharmaceutical industries and many more. Even though numerous biosensors have been developed for detection of proteins, peptides, enzymes, and numerous other biomolecules for diverse applications, their applications in tissue engineering have remained limited. In recent years, there has been a growing interest in application of novel biosensors in cell culture and tissue engineering, for example, real-time detection of small molecules such as glucose, lactose, and H2O2 as well as serum proteins of large molecular size, such as albumin and alpha-fetoprotein, and inflammatory cytokines, such as IFN-g and TNF-α. In this review, we provide an overview of the recent advancements in biosensors for tissue engineering applications.

  14. Effects of low concentrations of Regorafenib and Sorafenib on human HCC cell AFP, migration, invasion and growth in vitro

    Science.gov (United States)

    Carr, Brian Irving; D’Alessandro, Rosalba; Refolo, Maria Grazia; Iacovazzi, Palma Aurelia; Lippolis, Catia; Messa, Caterina; Cavallini, Aldo; Correale, Mario; Di Carlo, Antonio

    2012-01-01

    Sorafenib was shown in clinical trial to enhance survival in hepatocellular carcinoma (HCC) patients, but with minimal tumor shrinkage. To correlate several indices of HCC growth at various drug concentrations, HCC cells were grown in various low concentrations of two multi-kinase inhibitors, Regorafenib (Stivarga) and Sorafenib (Nexavar) and their effects were examined on alpha-fetoprotein (AFP), cell growth, migration and invasion. In two AFP positive human HCC cell lines, AFP was inhibited at 0.1–1µM drug concentrations. Cell migration and invasion were also inhibited at similar low drug concentrations. However, 10-fold higher drug concentrations were required to inhibit cell growth in both AFP positive and negative cells. To investigate this concentration discrepancy of effects, cells were then grown for prolonged times and sub-cultured in low drug concentrations and then their growth was re-tested. The growth in these drug-exposed cells was found to be slower than cells without prior drug exposure and they were also more sensitive to subsequent drug challenge. Evidence was also found for changes in cell signaling pathways in these slow-growth cells. Low multi-kinase inhibitor concentrations thus modulate several aspects of HCC cell biology. PMID:23169148

  15. Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease.

    Science.gov (United States)

    Leung, Christopher; Yeoh, Sern Wei; Patrick, Desmond; Ket, Shara; Marion, Kaye; Gow, Paul; Angus, Peter W

    2015-01-28

    To determine characteristics and prognostic predictors of patients with hepatocellular carcinoma (HCC) in association with non-alcoholic fatty liver disease (NAFLD). We reviewed the records of all patients with NAFLD associated HCC between 2000 and 2012. Data collected included demographics; histology; presence or absence of cirrhosis, size and number of HCC, alpha-fetoprotein, body mass index (BMI), and the presence of diabetes, hypertension, or dyslipidaemia. Fifty-four patients with NAFLD associated HCC were identified. Mean age was 64 years with 87% male. Fifteen percent (8/54) were not cirrhotic. 11%, 24% and 50% had a BMI of <25 kg/m2, 25-29 kg/m2 and ≥30 kg/m2 respectively. Fifty-nine percent were diabetic, 44% hypertensive and 26% hyperlipidaemic. Thirty-four percent of the patients had ≤1 of these risk factors. Non-cirrhotics had a significantly larger mean tumour diameter at diagnosis than cirrhotics (P=0.041). Multivariate analysis did not identify any other patient characteristics that predicted the size or number of HCC. HCC can develop in NAFLD without cirrhosis. At diagnosis such tumours are larger than those in cirrhotics, conferring a poorer prognosis.

  16. Facile synthesis of water-soluble Zn-doped AgIn5S8/ZnS core/shell fluorescent nanocrystals and their biological application.

    Science.gov (United States)

    Song, Jiangluqi; Jiang, Tongtong; Guo, Tianyi; Liu, Ling; Wang, Huijie; Xia, Tongyan; Zhang, Wenting; Ye, Xuecheng; Yang, Mingya; Zhu, Lixin; Xia, Ruixiang; Xu, Xiaoliang

    2015-02-16

    Here we demonstrate a novel and facile strategy of highly luminescent water-soluble Zn-doped AgIn5S8 (ZAIS) nanocrystals and ZAIS/ZnS core/shell structures, which were based on hydrothermal reaction between the acetate salts of the corresponding metals and sulfide precursor in the presence of l-cysteine at 110 °C in a Teflon-lined autoclave. The photoluminescent (PL) emission wavelength can be conveniently tuned from 560 to 650 nm by tailoring the stoichiometric ratio of [Ag]/[Zn]. The as prepared nanocrystals were characterized systematically and exhibit long PL lifetimes more than 100 ns. The influence of experimental conditions, including concentration of l-cysteine and reaction temperature, was investigated. In addition, we performed a coating procedure with the ZnS shell outside the ZAIS core and showed excellent PL quantum yields up to 35%. The in vitro experiment exhibited quite low cytotoxicity and marvelous biocompatibility, revealing their promising prospect in bioscience. Furthermore, the obtained ZAIS/ZnS nanocompounds (NCs) were covalently conjugated to alpha-fetoprotein antibodies and targeted fluorescent imaging for hepatocellular carcinoma cells was realized.

  17. A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma with poor liver function

    Directory of Open Access Journals (Sweden)

    Hyun Yang

    2017-06-01

    Full Text Available Background/Aims Metronomic chemotherapy (MET is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The aim of this study was to evaluate the feasibility and overall survival (OS of MET compared to sorafenib for advanced hepatocellular carcinoma (HCC patients with portal vein tumor thrombosis (PVTT. Methods A total of 54 patients with advanced HCC and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53 patients who had undergone sorafenib therapy were analyzed as the control group. The primary endpoint of this study was OS. Results The median number of MET cycles was two (1-15. The OS values for the MET group and sorafenib group were 158 days (132-184 and 117 days (92-142, respectively (P=0.029. The Cox proportional-hazard model showed that a higher risk of death was correlated with higher serum alpha fetoprotein level (≥400 mg/dL, hazard ratio [HR]=1.680, P=0.014 and Child-Pugh class B (HR=1.856, P=0.008. Conclusions MET was associated with more favorable outcomes in terms of overall survival than was sorafenib in patients with advanced HCC with PVTT, especially in patients with poor liver function. Therefore, MET can be considered as a treatment option in patients with advanced HCC with PVTT and poor liver function.

  18. [Hepatocellular carcinoma originated in the caudate lobe. Surgical strategy for resection. A propos of a case].

    Science.gov (United States)

    Martínez-Mier, Gustavo; Esquivel-Torres, Sergio; Calzada-Grijalva, José Francisco; Grube-Pagola, Peter

    2015-01-01

    Hepatocellular carcinoma originating from the caudate lobe has a worse prognosis than other hepatocellular carcinoma in another segment of the liver. An isolated caudate lobe resection of the liver represents a significant technical challenge. Caudate lobe resection can be performed along with a lobectomy or as an isolated liver resection. There are very few reports about isolated caudate lobe liver resection. We report a case of successful isolated resection of hepatocellular carcinoma in the caudate lobe with excellent long-term survival. A 74 years old female with 8cm mass lesion in the caudate lobe without clinical or biochemical evidence of liver cirrhosis, serum alpha-fetoprotein 3.7 U/l, and negative hepatitis serology was evaluated for surgery. Complete resection of the lesion in 270minutes with Pringle maneuver for 13minutes was satisfactorily performed. Patient was discharged ten days after surgery without complications. Patient is currently asymptomatic, without deterioration of liver function and 48 month tumor free survival after the procedure. Isolated caudate lobe resection is an uncommon but technically possible procedure. In order to achieve a successful resection, one must have a detailed knowledge of complete liver anatomy. Tumor free margins must be obtained to provide long survival for these patients who have a malignancy in this anatomic location. Copyright © 2015. Published by Masson Doyma México S.A.

  19. Fibroblast growth factor receptor 4 polymorphism is associated with liver cirrhosis in hepatocarcinoma.

    Directory of Open Access Journals (Sweden)

    Ming-Jen Sheu

    Full Text Available Fibroblast growth factor receptor 4 (FGFR4 polymorphisms are positively correlated with tumor progression in numerous malignant tumors. However, the association between FGFR4 genetic variants and the risk of hepatocellular carcinoma (HCC has not yet been determined. In this study, we investigated the potential associations of FGFR4 single nucleotide polymorphisms (SNPs with HCC susceptibility and its clinicopathological characteristics.Four SNPs in FGFR4 (rs1966265, rs351855, rs2011077, and rs7708357 were analyzed among 884 participants, including 595 controls and 289 patients with HCC. The samples were further analyzed to clarify the associations between these gene polymorphisms and the risk of HCC, and the impact of these SNPs on the susceptibility and clinicopathological characteristics of HCC. After adjusting for other covariants, HCC patients who carrying at least one A genotype (GA and AA at rs351855 were observed to have a higher risk of liver cirrhosis compared with those carrying the wild-type genotype (GG (OR: 2.113, 95% CI: 1.188-3.831. Moreover, the patients with at least one A genotype were particularly showed a high level of alpha-fetoprotein (AFP.Our findings suggest that genetic polymorphism in FGFR4 rs351855 may be associated with the risk of HCC coupled with liver cirrhosis and may markedly increase the AFP level in Taiwanese patients with HCC. In addition, this is the first study that evaluated the risk factors associated with FGFR4 polymorphism variants in Taiwanese patients with HCC.

  20. Cognitive Functions in Ataxia with Oculomotor Apraxia Type 2

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    Péter eKlivényi

    2012-08-01

    Full Text Available Background: Ataxia with oculomotor apraxia type 2 (AOA2 is characterized by cerebellar atrophy, peripheral neuropathy, oculomotor apraxia, and elevated serum alpha-fetoprotein levels. The disease is caused by a recessive mutation in the senataxin gene. Since it is a very rare cerebellar disorder, no detailed examination of cognitive functions in AOA2 has been published to date. The aim of the present study was to investigate the neuropsychological profile of a 54-year-old patient with AOA2. Methods: A broad range of neuropsychological examination protocol was administered including the following domains: short-term, working- and episodic- memories, executive functions, implicit sequence learning, and the temporal parameters of speech. Results: The performance on the Listening Span, Letter Fluency, Serial Reaction Time Task and pause ratio in speech was 2 or more standard deviations (SD lower compared to controls, and 1 SD lower on Backward Digit Span, Semantic Fluency, articulation rate and speech tempo. Conclusions: These findings indicate that the pathogenesis of the cerebrocerebellar circuit in AOA2 is responsible for the weaker coordination of complex cognitive functions such as working memory, executive functions, speech and sequence learning.

  1. Congenital juvenile granulosa cell tumor of the testis: Case report and literature review

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    Carolina Talini

    2016-07-01

    Full Text Available Juvenile granulosa cell tumor (JGCT is a very rarely diagnosed benign tumor, accounting for 1.2% of all prepubertal testicular tumors. A full-term healthy neonate was diagnosed with a painless left scrotal mass. During evaluation it was identified to have about two times the volume of the contralateral testis, presenting a firm consistency, not as hard as the consistency of a prenatal testicular torsion. Doppler ultrasound detected a multicystic left testicular mass, with normal blood flow, but failed in detecting normal-appearing testis. Human chorionic gonadotropin (β-HCG and serum alpha-fetoprotein (AFP were normal. Inguinal approach was performed, section of the lesion was sent to frozen biopsy and excluded yolk sac tumor, and however the impossibility of detecting normal testis tissue indicated orchiectomy with high ligation of the spermatic cord. Histological evaluation demonstrated gray testicular parenchyma with multicystic aspect fulfilled with yellow fluid. The usual clinical presentation of JGCT is a painless scrotal mass, radiological imaging demonstrates a multicystic tumor. Tumoral markers levels are normal and the standard treatment is the inguinal orchiectomy.

  2. Liver transplantation for hepatocellular carcinoma: is zero recurrence theoretically possible?

    Science.gov (United States)

    Irtan, Sabine; Barbier, Louise; Francoz, Claire; Dondero, Federica; Durand, Francois; Belghiti, Jacques

    2016-04-01

    Hepatocellular carcinoma (HCC) recurrence remains a key issue after liver transplantation. This study aimed to determine a subgroup of HCC patients within the Milan criteria who could achieve a theoretical goal of zero recurrence rates after liver transplantation. Between 1999 and 2009, 179 patients who received liver transplantation for HCC within the Milan criteria were retrospectively included. Analysis of the factors associated with HCC recurrence was performed to determine the subgroup of patients at the lowest risk of recurrence. Seventy-two percent of the patients received a bridging therapy, including 54 liver resections. Eleven (6.1%) patients recurred within a delay of 19+/-22 months and ultimately died. Factors associated with recurrence were serum alpha-fetoprotein level >400 ng/mL, satellite nodules, poor differentiation, microvascular invasion and cholangiocarcinoma component. Recurrence rates decreased from 6.1% to 3.1% in patients without any of these factors. Among HCC patients within the Milan criteria, selecting patients with factors based on histology would allow tending towards zero recurrence, and prior histological assessment by liver biopsy or resection may be essential to rule out poorly differentiated tumors, microvascular invasion, and cholangiocarcinoma component.

  3. Recurrent Merkel cell carcinoma of the testis with unknown primary site: a case report.

    Science.gov (United States)

    Mweempwa, Angela; Tan, Alvin; Dray, Michael

    2016-11-05

    Merkel cell carcinoma is a rare and aggressive neuroendocrine tumor that commonly arises in the skin. It is rare for it to occur in the testes. There are only seven cases of testicular Merkel cell carcinoma reported in the literature. A 66-year-old Maori man presented to our hospital with left testicular swelling. His alpha-fetoprotein and beta-human chorionic gonadotrophin levels were within normal limits. His lactate dehydrogenase concentration was elevated to 267 U/L. Ultrasound imaging confirmed a large testicular mass, and he underwent left orchiectomy. His histological examination revealed a neuroendocrine tumor with an immunostaining pattern suggesting Merkel cell carcinoma. He presented to our hospital again 3 months later with right testicular swelling that was confirmed on ultrasound sonography to be a tumor. He underwent a right orchiectomy, and his histological examination revealed metastatic Merkel cell carcinoma. A primary lesion was not identified, and computed tomographic imaging did not reveal spread to other organs. He received six cycles of adjuvant carboplatin and etoposide chemotherapy and remained disease-free 18 months after completion of chemotherapy. Given the paucity of studies, standard adjuvant treatment for testicular Merkel cell carcinoma remains uncertain, although platinum-based chemotherapy seems to be an appropriate option.

  4. Shell-encoded Au nanoparticles with tunable electroactivity for specific dual disease biomarkers detection.

    Science.gov (United States)

    Zhao, Yuan; Yang, Yaxin; Sun, Yali; Cui, Linyan; Zheng, Fangjie; Zhang, Jiru; Song, Qijun; Xu, Chuanlai

    2018-01-15

    The exploration of electroactive labelling with tailorable and strong differential pulse voltammetry (DPV) responses is of great importance in accurate and sensitive screening of a panel of biomarkers related to cancer. Herein, shell-encoded gold nanoparticles (Au NPs) are fabricated and give rise to shell species-dominated DPV peak potentials. Two independent DPV peaks appear at -0.08V for Au@Cu 2 O core-shell NPs and 0.26V for Au@Ag core-shell NPs. Shell-encoded Au NPs drastically exhibit shell thickness-tunable amplified peak currents. The non-interfering and amplified DPV responses enable shell-encoded Au NPs to be an alternative electrochemical signal amplifier for dual screening of carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP). The limits of detection (LODs) are calculated to be 1.8pg/mL for CEA and 0.3pg/mL for AFP. In comparison to the parallel single-analyte assays, shell-encoded Au NPs engineered electrochemical aptasensors offer multiplexing capability and show significant prospects in biomedical research and early diagnosis of diseases. Copyright © 2017. Published by Elsevier B.V.

  5. Recent Advances in Application of Biosensors in Tissue Engineering

    Science.gov (United States)

    Paul, Arghya; Lee, Yong-kyu; Jaffa, Ayad A.

    2014-01-01

    Biosensors research is a fast growing field in which tens of thousands of papers have been published over the years, and the industry is now worth billions of dollars. The biosensor products have found their applications in numerous industries including food and beverages, agricultural, environmental, medical diagnostics, and pharmaceutical industries and many more. Even though numerous biosensors have been developed for detection of proteins, peptides, enzymes, and numerous other biomolecules for diverse applications, their applications in tissue engineering have remained limited. In recent years, there has been a growing interest in application of novel biosensors in cell culture and tissue engineering, for example, real-time detection of small molecules such as glucose, lactose, and H2O2 as well as serum proteins of large molecular size, such as albumin and alpha-fetoprotein, and inflammatory cytokines, such as IFN-g and TNF-α. In this review, we provide an overview of the recent advancements in biosensors for tissue engineering applications. PMID:25165697

  6. Summary. The 19th quality control survey for radioisotope in vitro tests in Japan, 1997

    Energy Technology Data Exchange (ETDEWEB)

    Shishiba, Yoshimasa; Shimizu, Taeko [Toranomon Hospital, Tokyo (Japan); Ichihara, Kiyoshi; Kousaka, Tadako; Kobayashi, Hisae; Tsushima, Toshio; Hoshino, Minoru; Mori, Mikio

    1998-11-01

    This summary concerns results of the survey in the title performed by the Subcommittee for Radioisotope in vitro Test in the Medical and Pharmaceutical Committee, Japan Radioisotope Association. The survey was conducted in 161 facilities in Japan including public and private hospitals, health institutes and reagent manufacturers. Samples were sent to the facilities and subjected to examinations of intra- and inter-day reproducibility, freeze-thawing effects and periodical changes of the measured values. Methods employed were RIA, IRMA, EIA, ELISA, LPIA, PAMIA, FIA, FPIA, NIA, LAT, CLIA and ECLIA. Results were analyzed by variation coefficients in the kit and between the kits. Samples were for: growth hormone, somatomedin C, follicle stimulating hormone, luteinizing hormone, prolactin, thyroid stimulating hormone, triiodothyronine, thyroxine, thyroxine binding globulin, calcitonin, insulin, C-peptide, glucagon, gastrin, testosterone, estradiol, progesterone, {beta}human chorionic gonadotropin, 17{alpha}-hydroxyprogesterone, aldosterone, cortisol, dehydroepiandrosterone, renin, immunogloblin E, digoxin, {alpha}-fetoprotein, carcinoembryonic antigen, tissue polypeptide antigen, CA125, CA19-9, CA15-3, prostatic acid phosphatase, prostate specific antigen, {beta}{sub 2}-microgloblin and ferritin. Results were found rather unsatistactory for some products in the clinical practice, necessary for improvement of detection for some tests and needed for some kits for solving the problems of difference between kits and of matrix effect. (K.H)

  7. Imaging features of undifferentiated embryonal sarcoma of the liver: a series of 15 children

    Energy Technology Data Exchange (ETDEWEB)

    Gabor, Flaviu; Franchi-Abella, Stephanie; Pariente, Daniele [Bicetre Hospital, Department of Pediatric Radiology, Le Kremlin-Bicetre (France); Merli, Laura [Bambino Gesu Children' s Hospital, Unit of Hepato-Biliary and Transplant Surgery, Department of Surgery and Transplantation Centre, Rome (Italy); Adamsbaum, Catherine [Bicetre Hospital, Department of Pediatric Radiology, Le Kremlin-Bicetre (France); Paris Sud University, Faculty of Medicine, Le Kremlin-Bicetre (France); Universite Paris-Saclay, LTCI, CNRS, Telecom Paris Tech, Paris (France)

    2016-11-15

    Undifferentiated embryonal sarcoma of the liver is a rare malignant mesenchymal tumour occurring mostly in children ages 6-10 years. The discrepancy between its solid appearance on US and cystic-like appearance on CT has been described. To study the imaging particularities and similarities among our cases of undifferentiated embryonal sarcoma and to report the errors in initial diagnoses. We conducted a retrospective study of 15 children with undifferentiated embryonal sarcoma diagnosed or referred to our hospital during 1997-2015 and analysed the clinical, biological and imaging data. We identified eight boys and seven girls ages 9 months to 14 years. Ten children presented with abdominal pain. Alpha-fetoprotein was slightly increased in one. Initial US and CT had been performed for all, while additional MRI had been done in two children. Initial CT demonstrated a hypoattenuated mass in all. Rupture was seen in five and intratumoural bleeding in seven children. Tumour volumes reduced during neoadjuvant chemotherapy in 10 children. Undifferentiated embryonal sarcoma might be suggested in a non-secreting unifocal tumour with well-defined borders, fluid-filled spaces on US, hypoattenuation and serpiginous vessels on CT, and if there are signs of internal bleeding or rupture on CT or MRI. (orig.)

  8. Testicular Cancer Presenting as Gastric Variceal Hemorrhage

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Salazar-Mejía

    2017-01-01

    Full Text Available Testicular cancer is the most common solid malignancy affecting males between the ages of 15 and 35. The symptomatology caused by this tumor varies according to the site of metastasis. We present the case of a 26-year-old male who arrived to the emergency department with hematemesis. He had no previous medical history. On arrival, we noted enlargement of the left scrotal sac. There was also a mass in the left scrotum which provoked displacement of the penis and right testis. The serum alpha-fetoprotein level was 17,090 ng/mL, lactate dehydrogenase was 1480 U/L, and human chorionic gonadotropin was 287.4 IU/mL. Upper endoscopy revealed a type 1 isolated gastric varix, treated with cyanoacrylate. A CT scan showed extrinsic compression of the portal vein by lymphadenopathy along with splenic vein partial thrombosis, which caused left-sided portal hypertension. Neoadjuvant chemotherapy was started with etoposide and cisplatin, and seven days later the patient underwent left radical orchiectomy. A postoperative biopsy revealed a pure testicular teratoma. Noncirrhotic left portal hypertension with bleeding from an isolated gastric varix secondary to metastasic testicular cancer has not been described before. Clinicians must consider the possibility of malignancy in the differential diagnosis of a young man presenting with unexplained gastrointestinal bleeding.

  9. Proteomic profiling of facial development in chick embryos.

    Science.gov (United States)

    Mangum, Jonathan E; Farlie, Peter G; Hubbard, Michael J

    2005-07-01

    Craniofacial disorders are associated with one-third of human birth defects but the underlying molecular and cellular causes remain poorly understood. Proteomics seems well-placed to benefit this medically important area but the scarcity of embryonic tissues poses a major challenge. In this study, we applied a microsample proteomics strategy to investigate the first branchial arch, an embryonic structure crucial for facial development, and found that proteome analysis is both practicable and informative despite the scarcity of tissue. Exploiting the embryonic chick as a tractable source of accurately staged tissue, we developed a sequential extraction procedure to interface with one-dimensional polyacrylamide gel electrophoresis (1-D PAGE) and 2-D PAGE. In 2-D gels, about 8% of the visible proteome changed between embryonic days 3 and 5, and the identities determined for 21 proteins accorded with the rapid growth during this period. These results led to the first molecular identification of chicken alpha-fetoprotein, and an unusual localisation of vimentin to endoderm. With over 470 protein spots accessible, this comparative proteomics approach has good prospects for providing new markers, functional hypotheses and genes to target in functional tests. A broader value of extending these approaches to facial development in other species and to other areas in embryology can be anticipated.

  10. Further delineation of the Nijmegen breakage syndrome

    International Nuclear Information System (INIS)

    Taalman, R.D.; Hustinx, T.W.; Weemaes, C.M.; Seemanova, E.; Schmidt, A.; Passarge, E.; Scheres, J.M.

    1989-01-01

    We report on five independent families with a chromosome instability disorder that earlier had been called the Nijmegen breakage syndrome (NBS). These families, two from the Netherlands and three from Czechoslovakia, had a total of eight patients, five of whom are still alive. The main clinical manifestations were microcephaly, short stature, a ''bird-like'' face, immunological defects involving both the humoral and cellular system. In four of the five living patients it has been possible to study the chromosomes of cultured lymphocytes. The basic karyotype in these patients were normal, but in 17% to 35% of the metaphases rearrangements were found, preferentially involving chromosomes 7 and/or 14 at the sites 7p13, 7q34, and 14q11. The chromosomes of all five living patients were very sensitive to ionizing radiation. In addition, the DNA synthesis in their cultured lymphocytes and fibroblasts was more resistant to X-rays than in cells from controls. The NBS shares a number of important features with ataxia telangiectasia (AT). Both syndromes are characterized by the occurrence of typical rearrangements of chromosomes 7 and/or 14, cellular and chromosomal hypersensitivity to X-irradiation, radioresistance of DNA replication and immunodeficiency. However, there are also obvious differences: NBS patients have microcephaly but neither ataxia nor telangiectasia, and in contrast to the situation in AT the alpha-fetoprotein level in their serum is normal

  11. Prognostic Factors for Tumor Recurrence after a 12-Year, Single-Center Experience of Liver Transplantations in Patients with Hepatocellular Carcinoma

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    Matteo Cescon

    2010-01-01

    Full Text Available Background. Factors affecting outcomes after orthotopic liver transplantation (OLT for hepatocellular carcinoma (HCC have been extensively studied, but some of them have only recently been discovered or reassessed. Methods. We analyzed classical and more recently emerging variables with a hypothetical impact on recurrence-free survival (RFS in a single-center series of 283 patients transplanted for HCC between 1997 and 2009. Results. Five-year patient survival and RFS were 75% and 86%, respectively. Thirty-four (12% patients had HCC recurrence. Elevated preoperative alpha-fetoprotein (AFP levels, preoperative treatments of HCC, unfulfilled Milan and up-to-seven criteria at final histology, poor tumor differentiation, and tumor microvascular invasion negatively affected RFS by univariate analysis. Milan and up-to-seven criteria applied preoperatively, and the use of m-TOR inhibitors did not reach statistical significance. Cox's proportional hazard model showed that only elevated AFP levels (Odds Ratio=2.88; 95% C.I.=1.43–5.80; =.003, preoperative tumor treatments (Odds Ratio=4.84; 95% C.I.=1.42–16.42; =.01, and microvascular invasion (Odds Ratio=4.82; 95% C.I.=1.87–12.41; =.001 were predictors of lower RFS. Conclusions. Biological aggressiveness and preoperative tumor treatment, rather than traditional and expanded dimensional criteria, conditioned the outcomes in patients transplanted for HCC.

  12. A Meta-Analysis of Arsenic Trioxide Combined with Transcatheter Arterial Chemoembolization for Treatment of Primary Hepatic Carcinoma

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    Ling He

    2016-01-01

    Full Text Available Primary hepatic carcinoma (PHC is one of the most common malignant tumours in the world. More and more research has shown that As2O3 combined with TACE has a good curative effect in treating PHC. The objectives of this study were to evaluate the therapeutic efficacy and safety of As2O3 combined with TACE in treating PHC. The CNKI, VIP, Wanfang, PubMed, and Cochrane databases were searched from their inception until December 2015. Randomized controlled trials (RCTs comparing As2O3 combined with TACE versus TACE alone in treating PHC were identified. Stata SE 12.0 was used for data analysis. 17 RCTs with 1055 patients were included. Meta-analysis showed that, compared with TACE alone, As2O3 combined with TACE showed significant effects in improving the clinical efficacy rate (P<0.01, decreasing the value of alpha-fetoprotein (P<0.01, increasing the one-year survival rate (P<0.01, and improving the quality of life of PHC patients (P<0.01. Fifteen studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, As2O3 combined with TACE therapy appears to be potentially effective in treating PHC and is generally safe. However, further studies with rigorous designs trials and multiregional cooperation trials are needed.

  13. A Compatible Sensitivity Enhancement Strategy for Electrochemiluminescence Immunosensors Based on the Biomimetic Melanin-Like Deposition.

    Science.gov (United States)

    Ma, Hongmin; Zhao, Yanhua; Liu, Yuanyuan; Zhang, Yong; Wu, Dan; Li, He; Wei, Qin

    2017-12-19

    In this work, a compatible strategy was demonstrated for the enhancement of detection sensitivity of sandwich-type electrochemiluminescence (ECL) immunosensors. The enhanced signal response was based on the combination of biomimetic melanin-like deposition with the effective ECL quenching ability of quinone-rich biopolymers. Gold nanoparticle-loaded horseradish peroxidase (HRP) was used as a catalytic label for the secondary antibodies. The intrinsic catalytic property of HRP toward hydrogen peroxide (H 2 O 2 ) generates reactive oxygen species, which highly promote the autopolymerization of catecholamines. The resulting fast deposition of quinone-rich biopolymers approaching the luminophor-incorporated sensing platform achieves an obvious ECL quenching. A broad-spectrum tumor marker alpha fetoprotein (AFP) was selected as a model analyte to demonstrate the feasibility of the proposed strategy. Under optimal conditions, a very low detection limit of 0.056 pg mL -1 was obtained. Two orders of magnitude enhancement was achieved in contrast to the signal response without the step of catalytic biopolymer deposition. The combination of compatible HRP labeling with unique melanin-like deposition has potential as a universal strategy in other ECL bioassays.

  14. Deciduous and permanent dental pulp mesenchymal cells acquire hepatic morphologic and functional features in vitro.

    Science.gov (United States)

    Ishkitiev, Nikolay; Yaegaki, Ken; Calenic, Bogdan; Nakahara, Taka; Ishikawa, Hiroshi; Mitiev, Vanyo; Haapasalo, Markus

    2010-03-01

    Mesenchymal stem cells display extensive proliferative capacity of multilineage differentiation. The stromal compartment of mesenchymal tissues is considered to harbor stem cells. We assessed the endodermal differentiation of mesenchymal cells from deciduous and wisdom tooth pulp. Dental mesenchymal cells were isolated and expanded in vitro. After cell cultures had been established, cells were characterized using known stem cell markers. For hepatic differentiation the media was supplemented with hepatic growth factor, dexamethasone, Insulin-Transferrin-Selenium-X, and oncostatin. Both cultures showed a number of cells positive for specific hepatic markers including alpha-fetoprotein, albumin, and hepatic nuclear factor 4alpha after differentiation. Also, small clusters of cells positive for insulin-like growth factor 1 were found. The concentration of urea increased significantly in the media. Moreover, a significant amount of glycogen was found in the cells. Because the cells proved to produce specific hepatic proteins and to start functions specific for hepatocytes, such as storing glycogen and urea production, we may state that the mesenchymal cell cultures from wisdom and deciduous tooth pulp acquired morphologic and functional characteristics of hepatocytes. Copyright (c) 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  15. Serum YKL-40 independently predicts outcome after transcatheter arterial chemoembolization of hepatocellular carcinoma.

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    Cheng-Bao Zhu

    Full Text Available Transcatheter arterial chemoembolization (TACE is the most widely used treatment option for unresectable hepatocellular carcinoma (HCC. Elevated serum YKL-40 level has been shown to predict poor prognosis in HCC patients undergoing resection. This study was designed to validate the prognostic significance of serum YKL-40 in patients with HCC undergoing TACE treatment.Serum YKL-40 level was determined by enzyme-linked immunosorbent assay. Overall survival (OS was evaluated with the Kaplan-Meier method and compared by the log-rank test. Multivariate study with Cox proportional hazard model was used to evaluate independent prognostic variables of OS.The median pretreatment serum YKL-40 in HCC patients with was significantly higher than that in healthy controls (P<0.001. The YKL-40 could predict survival precisely either in a dichotomized or continuous fashion (P<0.001 and P = 0.001, respectively. Multivariate Cox regression analysis indicated that serum YKL-40 was an independent prognostic factor for OS in HCC patients (P = 0.001. In further stratified analyses, YKL-40 could discriminate the outcomes of patients with low and high alpha-fetoprotein (AFP level (P = 0.006 and 0.016, respectively. Furthermore, the combination of serum YKL-40 and AFP had more capacity to predict patients' outcomes.Serum YKL-40 was demonstrated to be an independent prognostic biomarker in HCC patients treated with TACE. Our results need confirmation in an independent study.

  16. Intracranial Metastasis in a Patient with Hepatocellular Carcinoma and Gastric Cancer

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    Akinobu Tawada

    2014-03-01

    Full Text Available A 76-year-old man was referred to our hospital with visual disturbance, weakness of the left upper and lower limbs, and gait disturbance. He had previously received transarterial chemoembolization for hepatocellular carcinoma (HCC 3 and 10 years ago. When he had received radiofrequency ablation for HCC recurrence 2 years ago, total gastrectomy was also performed for his gastric cancer. Subsequently, sorafenib had been administrated for concomitant lung metastatic tumors. On admission, MRI revealed an intra-axial tumor with perifocal edema. The level of carcinoembryonic antigen, but not alpha-fetoprotein, markedly increased. The tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of adenocarcinoma, which was consistent with the primary gastric cancer. After surgery, his neurological disturbances rapidly resolved. Additional gamma-knife treatment was also performed for another small brain metastasis detected after craniotomy. Subsequently, sorafenib administration was discontinued and S-1 was administered postoperatively. Successful treatment of intracranial metastasis of gastric cancer is important and meaningful, even in patients with multiple primary malignancies.

  17. Chemo prevention of Tea Polyphenols against Tumor Growth of Hepato-Colon Cancer Induced by Azoxy methane in Rats

    International Nuclear Information System (INIS)

    Heibashy, M.I.A.; Mazen, G.M.A.

    2008-01-01

    This investigation was conducted to evaluate the chemo prevention of tea polyphenols as anticancer agent in rats which were injected with azoxy methane (AOM) which is a potent hepato-colon carcinogen agents in rodents. The obtained data revealed a significant elevation in serum tumor markers, carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP) and cancer antigen (CA 1 9.9) in carcinogenic rats in comparison to their corresponding normal control ones. Also, there was a significant increase in the content of cytochrome P 4 50 and the activity of alcohol dehydrogenase (ADH) in both liver and colon as well as a significant elevation in the activities of methoxyresorufin-O-dealkylase (MRD), ethoxyresorutin-O-dealkylase (ERD) and pentoxyresorufin-O- dealkylase (PRD) in liver microsomes. While, glutathione content (GSH) and glutathione peroxidase (Gp x ) activity were decreased significantly in liver and colon as a result of cancer induction. On the other hand, the supplementation of black or green tea before induction of cancer in rats led to a considerable correction in all previous parameters studied. These amelioration effects dependent on magic biochemical properties of flavanols (catechins) and type of tea. In conclusion, tea polyphenols have appreciable anti-cancer efficacy on hepato colon cancer in rats. The underlying mechanisms of through which tea counteracted hepato-colon cancer were discussed

  18. Validation of a new prognostic staging system for hepatocellular carcinoma: a comparison of the biomarker-combined Japan Integrated Staging Score, the conventional Japan Integrated Staging Score and the BALAD Score.

    Science.gov (United States)

    Kitai, Satoshi; Kudo, Masatoshi; Minami, Yasunori; Haji, Seiji; Osaki, Yukio; Oka, Hiroko; Seki, Toshihito; Kasugai, Hiroshi; Sasaki, Yo; Matsunaga, Takashi

    2008-01-01

    The conventional Japan Integrated Staging (c-JIS) score has been reported to effectively stratify patients with hepatocellular carcinoma (HCC). Recently, two new staging systems, the biomarker-combined JIS (bm-JIS) score and the BALAD score, have been proposed. Both staging systems include three tumor markers: alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP and des-gamma-carboxy prothrombin specific for HCC. The aim of this study is to evaluate the performance of these three staging systems. A total of 1,173 HCC patients were included in this study. The stratification ability and prognostic predictive power were compared between these three staging systems. These three staging systems effectively predicted the patient survival. When accounting for the best prognostic subgroup of each staging systems (i.e. score of 0), there were significant differences between the bm-JIS score and the BALAD score and, likewise, between the c-JIS score and the BALAD score. The likelihood ratio chi(2) test showed the highest value and the Akaike information criterion value was lowest in the bm-JIS score. The bm-JIS score showed good stratification ability and was thus demonstrated to be a better predictor of the prognosis than the c-JIS score and the BALAD score, especially for the patients with a good prognosis. Copyright 2008 S. Karger AG, Basel.

  19. ABO-incompatible Living Donor Liver Transplantation with Rituximab and Total Plasma Exchange Does Not Increase Hepatocellular Carcinoma Recurrence.

    Science.gov (United States)

    Kim, Jong Man; Kwon, Choon Hyuck David; Joh, Jae-Won; Han, Sangbin; Yoo, Jeejin; Kim, Kyunga; Sinn, Dong Hyun; Choi, Gyu-Seong; Gerber, David A; Egawa, Hiroto; Lee, Suk-Koo

    2018-02-28

    ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has a high success rate. This study compares HCC recurrence in ABO-I LDLT with that in ABO-compatible (ABO-C) LDLT and explores the effects of rituximab prophylaxis and total plasma exchange (TPE) on HCC recurrence after LDLT. Two-hundred forty patients with a diagnosis of HCC underwent LDLT between 2010 and 2015. Fifty-nine patients underwent ABO-I LDLT. Baseline, perioperative, and tumor characteristics did not vary between the two groups. The 1-, 2-, and 3-year disease-free survival rates in the ABO-I LDLT and ABO-C LDLT groups were 90.3%, 79.7%, and 73.3% and 86.7%, 79.0%, and 75.3%, respectively (p=0.96). The overall patient survival rates for the same period in the ABO-I LDLT and ABO-C LDLT groups were 90.6%, 85.0%, and 81.9% and 88.0%, 83.5%, and 82.5%, respectively (p=0.77). HCC recurrence after LDLT was associated with preoperative alpha-fetoprotein >35 ng/mL, increased tumor size, encapsulation, and microvascular invasion. ABO-incompatibility was not related to HCC recurrence after LDLT. HCC recurrence and patient survival in the ABO-I LDLT group are comparable to those in the ABO-C LDLT group. Rituximab prophylaxis and TPE do not increase HCC recurrence after LT.

  20. A giant cord hemangioma with extramedullary hematopoiesis and elevated maternal serum human chorionic gonadotropin: a case report and review of the literature.

    Science.gov (United States)

    Hara, Kieko; Fukumura, Yuki; Saito, Tsuyoshi; Arakawa, Atsushi; Okabe, Hitomi; Takeda, Satoru; Yao, Takashi

    2015-09-04

    A case of prenatally diagnosed, giant cord hemangioma is reported, which was accompanied by the elevation of maternal serum alpha-fetoprotein (MS-AFP) and human chorionic gonadotropin (MS-hCG) levels. A 30-year-old woman without a previous history of gravida or para, presented with intermittent abdominal pain at 26 weeks of gestation. Doppler studies showed the fetus developing heart failure as the tumor grew larger. Caesarian section was performed at 29 weeks of gestation. Macroscopic examination of the placenta revealed a 17.0 × 10.0 × 7.0 cm tumor localized at the placental end of the umbilical cord. Microscopically, the tumor was composed of small arborizing vessels proliferating in the myxoid background, and the tumor cells were positive for AFP by immunohistochemistry. Extramedullary hematopoiesis was seen in the tumor vascular channels. The present case is one of the largest umbilical cord hemangiomas reported in the literature, and the first hemangioma case with MS-hCG elevation, extramedullary hematopoiesis, and positive AFP staining in the cord hemangioma. Its clinical course and detailed pathological findings are presented along with a review of the related literature.

  1. [Biologic tests for the diagnosis of amniotic fluid embolism].

    Science.gov (United States)

    Van Cortenbosch, B; Huel, C; Houfflin Debarge, V; Luton, D; Lambaudie, E; Porquet, D; Guibourdenche, J

    2007-01-01

    Amniotic fluid embolism is a rare, unpredictable and often lethal complication of pregnancy and childbirth. Because of its variable presentation, an early biologic test would help to establish the diagnosis. We investigated in maternal serum 4 components of amniotic fluid, i.e., alpha-fetoprotein (AFP), l'insuline like growth factor binding protein-1 (IGFBP-1), fetal fibronectin (fFN) and placental alpha1-microglobulin (PAMG-1). On the 6 cesareans controls involved, none of the makers increased after membranes section. PAMG-1 is unsuitable because its detection is always positive or doubtful even in the baseline. On the 7 cases suspected of amniotic fluid embolism, no detectable increase in any of those markers was noted in 3 cases, which is not in favour of this diagnosis. In the remaining cases, IGFBP-1 and fFN became detectable, confirming histological evidences of amniotic fluid embolism in 2 cases. The follow up of those markers in maternal blood confirmed the suspicion of amniotic fluid embolism at 21 wg in one case of ongoing pregnancy. These preliminary results point out the potential interest to assay maternal serum AFP, IGFBP-1 and fFN to confirm amniotic fluid embolism using rapid laboratory tests.

  2. Liver stiffness measured by magnetic resonance elastography as a risk factor for hepatocellular carcinoma: a preliminary case-control study

    International Nuclear Information System (INIS)

    Motosugi, Utaroh; Ichikawa, Tomoaki; Koshiishi, Tsuyota; Sano, Katsuhiro; Morisaka, Hiroyuki; Ichikawa, Shintaro; Araki, Tsutomu; Enomoto, Nobuyuki; Matsuda, Masanori; Fujii, Hideki

    2013-01-01

    To examine if liver stiffness measured by magnetic resonance elastography (MRE) is a risk factor for hepatocellular carcinoma (HCC) in patients with chronic liver disease. By reviewing the records of magnetic resonance (MR) examinations performed at our institution, we selected 301 patients with chronic liver disease who did not have a previous medical history of HCC. All patients underwent MRE and gadoxetic acid-enhanced MR imaging. HCC was identified on MR images in 66 of the 301 patients, who were matched to controls from the remaining patients without HCC according to age. MRE images were obtained by visualising elastic waves generated in the liver by pneumatic vibration transferred via a cylindrical passive driver. Risk factors of HCC development were determined by the odds ratio with logistic regression analysis; gender and liver stiffness by MRE and serum levels of aspartate transferase, alanine transferase, alpha-fetoprotein, and protein induced by vitamin K absence-II. Multivariate analysis revealed that only liver stiffness by MRE was a significant risk factor for HCC with an odds ratio (95 % confidence interval) of 1.38 (1.05-1.84). Liver stiffness measured by MRE is an independent risk factor for HCC in patients with chronic liver disease. (orig.)

  3. Multiple Ectopic Hepatocellular Carcinomas Arising in the Abdominal Cavity

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    Toru Miyake

    2012-09-01

    Full Text Available Ectopic hepatocellular carcinoma (HCC is a very rare clinical entity that is defined as HCC arising from extrahepatic liver tissue. This report presents a case of ectopic multiple HCC arising in the abdominal cavity. A 42-year-old otherwise healthy male presented with liver dysfunction at a general health checkup. Both HCV antibody and hepatitis B surface antigen were negative. Laboratory examination showed elevations in serum alpha-fetoprotein and PIVKA-II. Ultrasonography and computed tomography revealed multiple nodular lesions in the abdominal cavity with ascites without a possible primary tumor. Exploratory laparoscopy was performed, which revealed bloody ascites and multiple brown nodular tumors measuring approximately 10 mm in size that were disseminated on the perineum and mesentery. A postoperative PET-CT scan was performed but it did not reveal any evidence of a tumor in the liver. The tumors resected from the peritoneum were diagnosed as HCC. The present case of HCC was thought to have possibly developed from ectopic liver on the peritoneum or mesentery.

  4. Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC.

    Science.gov (United States)

    Wang, Mengjun; Sanda, Miloslav; Comunale, Mary Ann; Herrera, Harmin; Swindell, Charles; Kono, Yuko; Singal, Amit G; Marrero, Jorge; Block, Timothy; Goldman, Radoslav; Mehta, Anand

    2017-05-01

    Background: Hepatocellular carcinoma (HCC) has the greatest increase in mortality among all solids tumors in the United States related to low rates of early tumor detection. Development of noninvasive biomarkers for the early detection of HCC may reduce HCC-related mortality. Methods: We have developed an algorithm that combines routinely observed clinical values into a single equation that in a study of >3,000 patients from 5 independent sites improved detection of HCC as compared with the currently used biomarker, alpha-fetoprotein (AFP), by 4% to 20%. However, this algorithm had limited benefit in those with AFP HCC, especially in those with AFP HCC increased from 0% (AFP alone) to 89% (for the new algorithm). Glycan analysis revealed that kininogen has several glycan modifications that have been associated with HCC, but often not with specific proteins, including increased levels of core and outer-arm fucosylation and increased branching. Conclusions: An algorithm combining fucosylated kininogen, AFP, and clinical characteristics is highly accurate for early HCC detection. Impact: Our biomarker algorithm could significantly improve early HCC detection and curative treatment eligibility in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev; 26(5); 795-803. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Sharieff, S.; Burney, I.; Salam, A.; Siddiqui, T.

    2002-01-01

    Objective: To describe the etiology, clinico pathological features and outcome of hepatocellular carcinoma (HCC). Design: A retrospective study. Place and Duration of Study: The study was conducted at the Aga Khan University Hospital, Karachi, on patients admitted between January 1994 and December 1998. Subjects and Methods: A total of 201 consecutive patients diagnosed to have primary HCC on liver biopsy were the subjects of this study. Data included clinical and physical examination, routine hematological and bio-chemical investigations along with alpha-fetoprotein (alpha-FP or AFP) and imaging studies. Results: The mean age at the time of diagnosis was 56 years (24 to 85 year). There was a male preponderance (74%). The mean alpha FP was 17, 027 plus minus 68,853 ng/ml. The viral hepatitis profile was: HbsAg positive = 36% anti-HCV positive = 41%; both positive =7%: both negative = 16%. HBV-related HCC patients were found to be younger than HCV-related HCC patients (49.7 v/s 56.3 years: p =ns). However there was no significant difference in the survival rates of either group of patients. The median survival time was 16 weeks. Conclusion: HBV and HCV account for 84.% of HCC in Pakistan. Majority of the patients had advanced stage of HCC. The median survival was 16 weeks. (author)

  6. Tuning the EDTA-induced self-assembly and plasmonic spectral properties of gold nanorods: application in surface-enhanced Raman scattering

    International Nuclear Information System (INIS)

    Li, Jian-jun; Zhang, Ning; Wang, Jingyuan; Yang, Chun-yu; Zhu, Jian; Zhao, Jun-wu

    2016-01-01

    Self-assembly of cetyl trimethyl ammonium bromide-protected colloidal gold nanorods with different aspect ratios has been studied by adding the ethylene diamine tetraacetic acid (EDTA). Both the assembly strength and assembly configuration fashion of the gold nanorods could be tuned by changing the aspect ratio. For gold nanorods with small aspect ratio, side-by-side assembly takes the major role in the aggregation. In this case, the blue shift of the longitudinal absorption and the increase of the transverse absorption lead to the great uplift of the middle spectrum dip as the EDTA is increased. For gold nanorods with large aspect ratio, end-to-end assembly takes the major role in the aggregation. In this case, the longitudinal absorption peak fades down rapidly and a tailing absorption peak at longer wavelength uplifts greatly as the EDTA is increased. The surface-enhanced Raman scattering (SERS) activity of the assembled gold nanorods has been studied using alpha-fetoprotein (AFP) as the Raman active probe. It has been found that both the side-by-side assembly and end-to-end assembly of the gold nanorods could effectively improve the Raman signal of the AFP. And the gold nanorod substrate with side-by-side assembly has higher SERS activity. Graphical Abstract: Side-by-side assembly of gold nanorods leads to the middle spectrum dip of LSPR uplift greatly as the EDTA is increased, which also effectively improves the SERS activity

  7. Simultaneous electrochemical detection of multiple tumor markers using metal ions tagged immunocolloidal gold.

    Science.gov (United States)

    Xu, Teng; Jia, Xinle; Chen, Xia; Ma, Zhanfang

    2014-06-15

    In this work, a sandwich-format electrochemical immunosensor has been fabricated in the aim of simultaneous detection of carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) using metal ions tagged immunocolloidal gold nanocomposites as signal tags. The capture anti-CEA and anti-AFP were immobilized onto the chitosan-Au nanoparticles (CHIT-AuNPs) membrane modified glassy carbon electrode through glutaraldehyde (GA). The metal ion labels could be detected directly through differential pulse voltammetry (DPV) without metal pre-concentration, and the distinct voltammetric peaks had a close relationship with each sandwich-type immunoreaction. Under the optimized conditions, the multiplexed immunoassay exhibited good sensitivity and selectivity for the simultaneous determination of CEA and AFP with linear ranges of 0.01-50 ng mL(-1). The detection limits for CEA and AFP are 4.6 pg mL(-1) and 3.1 pg mL(-1), respectively. The method was successfully applied for the determination of AFP and CEA levels in clinical serum samples, and the results were in good agreement with standard enzyme linked immunosorbent assay (ELISA). This approach gives a promising simple and sensitive immunoassay strategy for clinical applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Influence of Behçet's disease on first and second trimester serum screening markers.

    Science.gov (United States)

    Yılmaz, Zehra Vural; Türkmen, Gülenay Gençosmanoğlu; Yılmaz, Elif; Dağlar, Korkut; Kırbaş, Ayşe; Sanhal, Cem; Yücel, Aykan; Uygur, Dilek

    2017-03-01

    Behçet's disease (BD) is a rare and multisystemic vasculitis disease. In this study, we investigated whether BD had any effect on the biochemical components of first and second trimester aneuploidy screening tests. A case-control retrospective study was conducted with 32 pregnant women with BD and 60 healthy pregnant women as controls. All pregnant womens' first trimester maternal serum pregnancy-associated plasma protein-A, free β-human chorionic gonadotropin and second trimester serum alpha-fetoprotein, unconjugated estriol and total human chorionic gonadotropin levels were examined from medical records. First and second serum screening markers were compared between pregnancies with BD and without. There was no difference in age, body mass index and obstetric history between the groups. No significant difference was observed between the groups in terms of first and second trimester serum screening test results in the absence of aneuploidy or neural tube defect. Gestational age at birth, birth weight and neonatal intensive care admission rate were also similar between the groups. Both first and second serum screening tests for Down syndrome may be recommended to pregnant women with BD without the need to readjust these markers. Pregnancy with BD was not associated with adverse perinatal outcome with respect to gestational age at birth or birth weight. © 2016 Japan Society of Obstetrics and Gynecology.

  9. Down syndrome screening marker levels in women with a previous aneuploidy pregnancy.

    Science.gov (United States)

    Cuckle, Howard S; Spencer, K; Nicolaides, K H

    2005-01-01

    In Down syndrome screening programmes, women with a previous affected pregnancy are assumed to have the same marker distribution as those without a family history. This assumption needs to be tested. Information on previous aneuploidy pregnancies was routinely sought on the test request forms in three centres, Leeds, Romford and the Fetal Medicine Centre, London. For each woman with a previous aneuploidy (case), five unaffected pregnancies to women without a history were selected as controls. The markers tested included maternal serum free beta-human chorionic gonadotrophin (hCG), pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein, unconjugated estriol and ultrasound nuchal translucency thickness. There were 375 cases: 303 with previous Down syndrome, 63 with Edwards syndrome and 9 with Patau's syndrome. There was a statistically significant difference between cases and controls, in the distribution of free beta-hCG and PAPP-A levels, adjusted for gestation. On average, free beta-hCG was increased by 10% in a subsequent pregnancy after aneuploidy (p pregnancies are available for study, it would be prudent to assume that the same increase as in unaffected pregnancies applies. Copyright (c) 2005 John Wiley & Sons, Ltd.

  10. Screening for Down syndrome.

    Science.gov (United States)

    Spencer, Kevin

    2014-01-01

    Screening for Down Syndrome was initially only related to maternal age and has successively developed by introducing biochemical markers and algorithms to estimate the risk for particularly trisomy 21 and 18. We now have a long experience of screening with four biochemical markers, alpha-fetoprotein, total hCG, unconjugated estriol and free β-hCG during the second trimester. Screening is now moving towards screening in the first trimester using a combination of ultrasound (Nuchal Translucency) and the maternal serum biochemical markers free β-hCG and Pregnancy Associated Plasma Protein-A (PAPP-A). This has become known as the combined test. Several maternal and pregnancy factors which can influence the concentrations of biochemical markers are discussed. The possibilities of screening for other aneuploidies in the first trimester and an outline of recent methods to improve overall screening performance are highlighted and the review will suggest some possible options for the future in which Cell Free DNA techniques may become part of an improved overall screening strategy. In conclusion it is emphasized that the time has come to invert the Pyramid of Antenatal Care to focus on the 11-13 week assessment.

  11. Reprogramming factors involved in hybrids and cybrids of human embryonic stem cells fused with hepatocytes.

    Science.gov (United States)

    Guo, Jitong; Tecirlioglu, R Tayfur; Nguyen, Linh; Koh, Karen; Jenkin, Graham; Trounson, Alan

    2010-10-01

    Embryonic stem cells (ESCs) have the potential to reprogram somatic cells into ESC-like cells through cell fusion. In the present study, the potential of human (h)ESC cytoplasts and karyoplasts to reprogram human hepatocytes was evaluated. Green fluorescent protein (GFP) transfected hESCs (ENVY cells) were fused with SNARF-1 (CellTracker)-labeled human hepatocytes using polyethylene glycol (PEG) and fluorescence-activated cell sorting (FACS) to produce hESC-hepatocyte hybrids. Immunocytochemical analysis of ESC markers showed that the hybrids expressed OCT4, TRA-1-60, TRA-1-81, SSEA-4, and GCTM-2. However, SSEA-1, which is typically low or absent on hESCs, was detected on hESC–hepatocyte hybrids. Moreover, reverse transcriptase polymerase chain reaction (RT-PCR) showed that alpha-fetoprotein, which is highly expressed in hepatocytes, was erased in the hybrids. These results indicated that hESCs have the potential to reprogram hepatocyte phenotype to a relatively undifferentiated state, but such hybrid cells are not identical to hESCs. Although hESC–hepatocyte hybrids were aneuploid, they were able to differentiate into embryoid bodies and some types of somatic cells. Furthermore, cybrids of enucleated hESCs and hepatocytes were produced by cell fusion, but the cybrids were unable to self-renew in the same way as hESCs. Presumably, the reprogramming factors are associated with the karyoplast and not the cytoplast of hESCs.

  12. Cryopreservation and re-culture of a 2.3 litre biomass for use in a bioartificial liver device

    Science.gov (United States)

    Kilbride, Peter; Lamb, Stephen; Gibbons, Stephanie; Bundy, James; Erro, Eloy; Selden, Clare; Fuller, Barry; Morris, John

    2017-01-01

    For large and complex tissue engineered constructs to be available on demand, long term storage using methods, such as cryopreservation, are essential. This study optimised parameters such as excess media concentration and warming rates and used the findings to enable the successful cryopreservation of 2.3 litres of alginate encapsulated liver cell spheroids. This volume of biomass is typical of those required for successful treatment of Acute Liver Failure using our Bioartificial Liver Device. Adding a buffer of medium above the biomass, as well as slow (0.6°C/min) warming rates was found to give the best results, so long as the warming through the equilibrium melting temperature was rapid. After 72 h post thaw-culture, viable cell number, glucose consumption, lactate production, and alpha-fetoprotein production had recovered to pre-freeze values in the 2.3 litre biomass (1.00 ± 0.05, 1.19 ± 0.10, 1.23 ± 0.18, 2.03 ± 0.04 per ml biomass of the pre-cryopreservation values respectively). It was also shown that further improvements in warming rates of the biomass could reduce recovery time to cryopreserved in a single cassette and re-cultured. It demonstrates that a bioartificial liver device can be cryopreserved, and has wider applications to scale-up large volume cryopreservation. PMID:28841674

  13. Impact on spina bifida screening of shifting prenatal Down syndrome maternal serum screening from the second trimester to the first.

    Science.gov (United States)

    Spaggiari, Emmanuel; Dreux, Sophie; Stirnemann, Julien J; Czerkiewicz, Isabelle; Houfflin-Debarge, Véronique; Segonne, Alexandra; Jouannic, Jean-Marie; Ville, Yves; Muller, Francoise

    2017-07-01

    Shifting screening for trisomy 21 to the first trimester has resulted in the loss of maternal serum alpha-fetoprotein screening for spina bifida. The aim of this study was to study the impact on open spina bifida prenatal screening. We reviewed prenatally diagnosed cases of spina bifida over three years: 2009 (only second-trimester screening, MSM2T), 2010 (transient period) and 2011 (majority first-trimester screening, MSM1T). Cases were assigned to three groups based on maternal serum markers (MSM2T, MSM1T and 'not performed'). Gestational age at diagnosis of spina bifida was compared between these three groups and between the years 2009 and 2011. Median gestational ages at diagnosis of the 742 spina bifida cases between the three groups were 22 weeks [18 +6 -23], 22 +1  weeks [21 +3 -23] and 21 +4  weeks [14 +1 -23], respectively (P Spina bifida diagnosis at 14-20 weeks declined from 38.8% in 2009 to 13.3% in 2011 (P spina bifida and resulted in a decrease of 25% of cases of spina bifida detected before 20 weeks. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

  14. Guidelineness of the parameters using integrated test in down syndrome risk prediction

    International Nuclear Information System (INIS)

    Lee, Jin Won; Go, Sung Jin; Kang, Se Sik; Kim, Chang Soo

    2016-01-01

    This study was an evaluation of the significance of each parameter through aimed at pregnant women subjected to screening test(integrated test) in predicting risk of Down syndrome. We retrospectively analysed the correlation of risk of Down's syndrome with Nuchal Translucency(NT) images measured by ultrasound, Pregnancy Associated Plasma Protein A(PAPP-A), alpha-fetoprotein(AFP), unconjugated estriol(uE3), human chorionic gonadotrophin(hCG) and Inhibin A by maternal serum. As a result, a significant correlation with NT, uE3, hCG, Inhibin A is revealed with Down's syndrome risk(P<.001). In ROC analysis, AUC of Inhibin A is analysed as the biggest predictor of Down's syndrome(0.859). And the criterion for cut-off was inhibin A 1.4 MoM(sensitivity 81.8%, specificity 75.9%). In conclusion, Inhibin A was the most useful in parameters to predict Down's syndrome in the integrated test. If we make up for the weakness based on the cut-off value of parameters they will be able to be used as an independent indicator in the risk of Down's syndrome screening

  15. Guidelineness of the parameters using integrated test in down syndrome risk prediction

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jin Won [Graduate School of Catholic University of Pusan, Busan (Korea, Republic of); Go, Sung Jin; Kang, Se Sik; Kim, Chang Soo [Dept. Radiological Science, College of Health Sciences, Catholic University of Pusan, Busan (Korea, Republic of)

    2016-12-15

    This study was an evaluation of the significance of each parameter through aimed at pregnant women subjected to screening test(integrated test) in predicting risk of Down syndrome. We retrospectively analysed the correlation of risk of Down's syndrome with Nuchal Translucency(NT) images measured by ultrasound, Pregnancy Associated Plasma Protein A(PAPP-A), alpha-fetoprotein(AFP), unconjugated estriol(uE3), human chorionic gonadotrophin(hCG) and Inhibin A by maternal serum. As a result, a significant correlation with NT, uE3, hCG, Inhibin A is revealed with Down's syndrome risk(P<.001). In ROC analysis, AUC of Inhibin A is analysed as the biggest predictor of Down's syndrome(0.859). And the criterion for cut-off was inhibin A 1.4 MoM(sensitivity 81.8%, specificity 75.9%). In conclusion, Inhibin A was the most useful in parameters to predict Down's syndrome in the integrated test. If we make up for the weakness based on the cut-off value of parameters they will be able to be used as an independent indicator in the risk of Down's syndrome screening.

  16. Amniotic fluid biochemistry in isolated polyhydramnios: a series of 464 cases.

    Science.gov (United States)

    Allaf, Bichr; Dreux, Sophie; Schmitz, Thomas; Czerkiewicz, Isabelle; Le Vaillant, Claudine; Benachi, Alexandra; Houfflin-Debarge, Véronique; Maréchaud, Martine; Oury, Jean-François; Muller, Françoise

    2015-12-01

    To report amniotic fluid biochemistry in a large series of 464 cases of isolated polyhydramnios in order to analyze both the outcome and the benefit of amniotic fluid biochemistry. This retrospective cohort (2008-2012) included polyhydramnios cases for which amniotic fluid samples were sent to our laboratory for biochemical analysis (total protein, alpha-fetoprotein and gamma-glutamyl transpeptidase) so as to investigate the etiology. A Bartter index and an esophageal atresia index were defined. Final diagnoses were compared between groups to determine the association between these indices and the frequency and type of adverse outcomes. Among 464 cases of polyhydramnios considered isolated at ultrasound examination, severe fetal diseases were diagnosed in 136 (29.3%): 46 (9.9%) chromosomal anomalies, 28 (6%) Bartter syndrome, 23 (4.95%) other genetic syndromes, 22 (4.75%) swallowing disorders and 17 (3.7%) uro-nephrological disorders. Amniotic fluid biochemistry identified esophageal atresia with 66.6% (10/15) sensitivity and 100% specificity and Bartter syndrome with 85.7% (24/28) sensitivity and 84.2% specificity. Isolated polyhydramnios is associated with a high risk of severe fetal diseases. Molecular cytogenetics and amniotic fluid biochemistry are helpful tools. © 2015 John Wiley & Sons, Ltd.

  17. The ultrasonographic diagnosis of fetal encephalocele at 13th gestational week

    Directory of Open Access Journals (Sweden)

    Šorak Marija

    2010-01-01

    Full Text Available Background. Encephalocele presents a rare anomaly of central nervous system, developed as a consequence of neural tube closing defect during early embrional development, and it is described by a baggy formation which prolaborates through the pores of the scull, filled with brain tissue, cerebrospinal liquor and entwined with meninges. According to literature search, until this day, the earliest it can be ultrasonically detected is the 13th gestation week, with the appliance of three-dimensional ultrasound. Case report. We presented 25 years old patient, ultrasonically diagnosed with occipital fetal encephalocela at the 13th gestation week. A gestation sack was located in the right uteral corn of the two-corned uterus with one cervix. The diagnosis was confirmed also by trippled value of alpha-fetoprotein in maternal serum: 75,98 IU/mL. Conclusion. Ultrasonic examination is the method of choice for prenatal detection of a fetal anomaly. It is possible to diagnose encephalocele if it prominates above the limits of the scull.

  18. Sub-tesla-field magnetization of vibrated magnetic nanoreagents for screening tumor markers

    Science.gov (United States)

    Chieh, Jen-Jie; Huang, Kai-Wen; Shi, Jin-Cheng

    2015-02-01

    Magnetic nanoreagents (MNRs), consisting of liquid solutions and magnetic nanoparticles (MNPs) coated with bioprobes, have been widely used in biomedical disciplines. For in vitro tests of serum biomarkers, numerous MNR-based magnetic immunoassay methods or schemes have been developed; however, their applications are limited. In this study, a vibrating sample magnetometer (VSM) was used for screening tumor biomarkers based on the same MNRs as those used in other immunoassay methods. The examination mechanism is that examined tumor biomarkers are typically conjugated to the bioprobes coated on MNPs to form magnetic clusters. Consequently, the sub-Tesla-field magnetization (Msub-T) of MNRs, including magnetic clusters, exceeds that of MNRs containing only separate MNPs. For human serum samples, proteins other than the targeted biomarkers induce the formation of magnetic clusters with increased Msub-T because of weak nonspecific binding. In this study, this interference problem was suppressed by the vibration condition in the VSM and analysis. Based on a referenced Msub-T,0 value defined by the average Msub-T value of a normal person's serum samples, including general proteins and few tumor biomarkers, the difference ΔMsub-T between the measured Msub-T and the reference Msub-T,0 determined the expression of only target tumor biomarkers in the tested serum samples. By using common MNRs with an alpha-fetoprotein-antibody coating, this study demonstrated that a current VSM can perform clinical screening of hepatocellular carcinoma.

  19. Expression of Fra-1 in human hepatocellular carcinoma and its prognostic significance.

    Science.gov (United States)

    Gao, Xiao-Qiang; Ge, Yong-Sheng; Shu, Qing-Hua; Ma, Hua-Xing

    2017-06-01

    This study aimed to explore the clinical significance and prognostic value of Fra-1 in hepatocellular carcinoma patients after curative resection. Fra-1 expression was investigated using a combination of techniques: immunohistochemistry for 66 samples of hepatocellular carcinoma and quantitative real-time polymerase chain reaction and western blotting assays for 19 matched hepatocellular carcinoma specimens. Fra-1 was present in 38 of 66 (57.6%) tumor tissues, with intense staining in the nuclei. There was also positive staining in 14 of 66 (21.2%) adjacent peritumoral tissues, with weak staining in the cytoplasm. Quantitative real-time polymerase chain reaction and western blotting assays confirmed higher expression of Fra-1 messenger RNA and Fra-1 protein in tumor tissues than adjacent non-tumor tissues for 19 hepatocellular carcinoma samples (p expression of Fra-1 was significantly related to vascular invasion and serum alpha-fetoprotein. Kaplan-Meier survival analysis found that overexpressed Fra-1 was correlated with poor overall survival and disease-free survival. Multivariate analysis identified Fra-1 as an independent prognostic factor. Fra-1 may be involved in the progress of hepatocellular carcinoma and could be a promising molecular candidate in the diagnosis and treatment of hepatocellular carcinoma.

  20. [The methylation of ZHX2 gene promoter enhances AFP gene expression in hepatocellular carcinoma].

    Science.gov (United States)

    Lv, Zili; DU, Yangjun; Wen, Jianming

    2013-07-01

    To investigate the relationship between Zinc-fingers and homeoboxes 2 (ZHX2) promoter methylation and alpha-fetoprotein (AFP) gene expression, and analyze the mechanism of AFP gene expression. HepG2 cell line was cultured with 0.5, 1.0 or 5.0 μmol/L of 5-aza-deoxycytidine (5-Aza-Dc). RT-PCR and Western blotting were used to detect the expressions of ZHX2 and AFP in HepG2 cell line. Methylation-specific PCR was used to detect ZHX2 promoter methylation in 38 hepatocellular carcinoma tissues. The HepG2 cell line showed a low level of ZHX2 mRNA, negative expression of ZHX2 protein, but high expression of AFP at both mRNA and protein levels. After the HepG2 cells were treated with 1.0 or 5.0 μmol/L 5-Aza-Dc for 6 d, the expression of ZHX2 mRNA and protein increased and the expression of AFP mRNA and protein decreased. Among 38 hepatocellular carcinoma tissues, ZHX2 promoter methylation was found in 16 hepatocellular carcinoma tissues with AFP>25 ng/mL in serum. No methylation of ZHX2 promoter was found in 8 hepatocellular carcinoma tissues with AFPexpression.

  1. [Epidemiology and risk factors of hepatocellular carcinoma].

    Science.gov (United States)

    Budny, Agnieszka; Kozłowski, Piotr; Kamińska, Marzena; Jankiewicz, Małgorzata; Kolak, Agnieszka; Budny, Bożena; Budny, Witold; Niemunis-Sawicka, Joanna; Szczypiór, Grzegorz; Kurniawka, Bartosz; Burdan, Franciszek

    2017-09-29

    Primary liver neoplasms occurs relatively rarely in Poland. The most frequently occurring type of cancer is hepatocellular carcinoma (HCC), which globally constitutes 7% of all the occurrences of cancer. The incidence increases with age and is the highest in patients around the age of 70. It also varies significantly depending on the geographic location. The main factors that cause HCC are infection of HBV and HCV, whose genome integrates into the DNA of the host, causing mutations. The other factors include excessive alcohol consumption, contact or consumption of Aspergillus toxins as well as various metabolic disorders, such as α1-antitrypsin deficiency, hemochromatosis, tyrosinemia, porphyria, von Gierke disease and in person with gene mutation p.I148M of adiponutrin. HCC is usually detected incidentally, during ultrasound examination or during clinical diagnosis of liver failure. HCC can be diagnosed using computed tomography (CT) or magnetic resonance imaging (MRI), which is considered the most accurate diagnostic method. A core needle biopsy or the examination of the level of markers such as: alpha-fetoprotein (AFP), D-gamma-carboxy prothrombin (DCP), tumourassociated glycoprotein 72 (CA 72-4, TAG-72), are advised for a complete diagnostics.

  2. Squamous Cell Carcinoma Antigen: A Novel Tumor Marker for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Abdel Messeih, Ph.L.

    2009-01-01

    Serum Squamous Cell Carcinoma Antigen (SCC-Ag) by ELISA technique and Alpha-fetoprotein (AFP) by IRMA technique were measured in 65 patients with hepatic focal lesion. 49 patients suffered from proved hepatocellular carcinoma and 16 patients were having cirrhosis and 20 normal controls. Median levels of serum AFP and SCC-Ag in HCC patients was significantly higher when compared with both cirrhotic patients and controls. On using receiver operator characteristic curve to improve sensitivity and specificity of AFP and SCC-Ag for detection of HCC, the best chosen cut-off values were 40 IU/mL for AFP and 2.55 ng/L for SCC-Ag, these yielded a sensitivity of 67.2% and 61.2% respectively and specificity 100%. The diagnostic sensitivity of them increased to 87.7% when they was combiendly calculated. It was found that the combined use of AFP and SCC-Ag is useful in screening patients with hepatic focal lesion to increase the chance of early diagnosis of HCC patients.

  3. Macro- and micro-environmental factors in clinical hepatocellular cancer.

    Science.gov (United States)

    Pancoska, Petr; Carr, Brian I

    2014-04-01

    We previously developed a network phenotyping strategy (NPS), a graph theory-based transformation of clinical practice data, for recognition of two primary subgroups of hepatocellular cancer (HCC), called S and L, which differed significantly in their tumor masses. In the current study, we have independently validated this result on 641 HCC patients from another continent. We identified the same HCC subgroups with mean tumor masses 9 cm x n (S) and 22 cm x n (L), Penvironment factors, identifying four subtypes for S and five subtypes for L phenotypes, respectively. In L phenotype, all reference patterns were portal vein thrombosis (PVT)-positive, all platelet/alpha fetoprotein (AFP) levels were high, and all were chronic alcohol consumers. L had phenotype landmarks with worst survival. S phenotype interaction patterns were PVT-negative, with low platelet/AFP levels. We demonstrated that tumor-clinical environment interaction patterns explained how a given parameter level can have a different significance within a different overall context. Thus, baseline bilirubin is low in S1 and S4, but high in S2 and S3, yet all are S subtype patterns, with better prognosis than in L. Gender and age, representing macro-environmental factors, and bilirubin, prothrombin time, and AST levels representing micro-environmental factors, had a major impact on subtype characterization. Clinically important HCC phenotypes are therefore represented by complete parameter relationship patterns and cannot be replaced by individual parameter levels. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Liver Full Reference Set Application: Hiro Yamada - Wako (2011) — EDRN Public Portal

    Science.gov (United States)

    Wako has received new 510(k) clearance for Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and Des-gamma-carboxy prothrombin (DCP) tests on an innovative μTASWako i30 analyzer from FDA. The AFP-L3 and DCP assayed on an older platform LiBASys have been cleared with indication of use for risk assessment of hepatocellular carcinoma (HCC) in patient at risk for the liver malignancy. Wako believes that early detection of HCC is critical for improving HCC patient outcome. Therefore, Wako is currently seeking collaborative opportunities to retrospectively measure clinical samples using the AFP-L3 and DCP for further determining of effectiveness of the HCC biomarkers in early detection which are collected prospectively during HCC surveillance. The Reference Sample Set in the EDRN biorepository are well characterized and studied. Access to these samples would allow Wako to quickly determine the clinical effectiveness of AFP-L3 and DCP in detecting early HCC

  5. Clinical and Biological Manifestation of RNF168 Deficiency in Two Polish Siblings

    Directory of Open Access Journals (Sweden)

    Barbara Pietrucha

    2017-12-01

    Full Text Available Germline mutations in the RING finger protein gene RNF168 have been identified in a combined immunodeficiency disorder called RIDDLE syndrome. Since only two patients have been described with somewhat different phenotypes, there is need to identify further patients. Here, we report on two Polish siblings with RNF168 deficiency due to homozygosity for a novel frameshift mutation, c.295delG, that was identified through exome sequencing. Both patients presented with immunoglobulin deficiency, telangiectasia, cellular radiosensitivity, and increased alpha-fetoprotein (AFP levels. The younger sibling had a more pronounced neurological and morphological phenotype, and she also carried an ATM gene mutation in the heterozygous state. Immunoblot analyses showed absence of RNF168 protein, whereas ATM levels and function were proficient in lymphoblastoid cells from both patients. Consistent with the absence of RNF168 protein, 53BP1 recruitment to DNA double-strand breaks (DSBs after irradiation was undetectable in lymphoblasts or primary fibroblasts from either of the two patients. γH2AX foci accumulated normally but they disappeared with significant delay, indicating a severe defect in DSB repair. A comparison with the two previously identified patients indicates immunoglobulin deficiency, cellular radiosensitivity, and increased AFP levels as hallmarks of RNF168 deficiency. The variability in its clinical expression despite similar cellular phenotypes suggests that some manifestations of RNF168 deficiency may be modified by additional genetic or epidemiological factors.

  6. Engineered measles virus Edmonston strain used as a novel oncolytic viral system against human hepatoblastoma

    International Nuclear Information System (INIS)

    Zhang, Shu-Cheng; Wang, Wei-Lin; Cai, Wei-Song; Jiang, Kai-Lei; Yuan, Zheng-Wei

    2012-01-01

    Hepatoblastoma (HB) is the most common primary, malignant pediatric liver tumor in children. The treatment results for affected children have markedly improved in recent decades. However, the prognosis for high-risk patients who have extrahepatic extensions, invasion of the large hepatic veins, distant metastases and very high alpha-fetoprotein (AFP) serum levels remains poor. There is an urgent need for the development of novel therapeutic approaches. An attenuated strain of measles virus, derived from the Edmonston vaccine lineage, was genetically engineered to produce carcinoembryonic antigen (CEA). We investigated the antitumor potential of this novel viral agent against human HB both in vitro and in vivo. Infection of the Hep2G and HUH6 HB cell lines, at multiplicities of infection (MOIs) ranging from 0.01 to 1, resulted in a significant cytopathic effect consisting of extensive syncytia formation and massive cell death at 72–96 h after infection. Both of the HB lines overexpressed the measles virus receptor CD46 and supported robust viral replication, which correlated with CEA production. The efficacy of this approach in vivo was examined in murine Hep2G xenograft models. Flow cytometry assays indicated an apoptotic mechanism of cell death. Intratumoral administration of MV-CEA resulted in statistically significant delay of tumor growth and prolongation of survival. The engineered measles virus Edmonston strain MV-CEA has potent therapeutic efficacy against HB cell lines and xenografts. Trackable measles virus derivatives merit further exploration in HB treatment

  7. In vitro differentiation and maturation of mouse embryonic stem cells into hepatocytes

    International Nuclear Information System (INIS)

    Ishii, Takamichi; Yasuchika, Kentaro; Fujii, Hideaki; Hoppo, Toshitaka; Baba, Shinji; Naito, Masato; Machimoto, Takafumi; Kamo, Naoko; Suemori, Hirofumi; Nakatsuji, Norio; Ikai, Iwao

    2005-01-01

    It is difficult to induce the maturation of embryonic stem (ES) cells into hepatocytes in vitro. We previously reported that Thy1-positive mesenchymal cells derived from the mouse fetal liver promote the maturation of hepatic progenitor cells. Here, we isolated alpha-fetoprotein (AFP)-producing cells from mouse ES cells for subsequent differentiation into hepatocytes in vitro by coculture with Thy1-positive cells. ES cells expressing green fluorescent protein (GFP) under the control of an AFP promoter were cultured under serum- and feeder layer-free culture conditions. The proportion of GFP-positive cells plateaued at 41.6 ± 12.2% (means ± SD) by day 7. GFP-positive cells, isolated by flow cytometry, were cultured in the presence or absence of Thy1-positive cells as a feeder layer. Isolated GFP-positive cells were stained for AFP, Foxa2, and albumin. The expression of mRNAs encoding tyrosine amino transferase, tryptophan 2,3-dioxygenase, and glucose-6-phosphatase were only detected following coculture with Thy1-positive cells. Following coculture with Thy1-positive cells, the isolated cells produced and stored glycogen. Ammonia clearance activity was also enhanced following coculture. Electron microscopic analysis indicated that the cocultured cells exhibited the morphologic features of mature hepatocytes. In conclusion, coculture with Thy1-positive cells in vitro induced the maturation of AFP-producing cells isolated from ES cell cultures into hepatocytes

  8. Novel electrochemical redox-active species: one-step synthesis of polyaniline derivative-Au/Pd and its application for multiplexed immunoassay

    Science.gov (United States)

    Wang, Liyuan; Feng, Feng; Ma, Zhanfang

    2015-01-01

    Electrochemical redox-active species play crucial role in electrochemically multiplexed immunoassays. A one-pot method for synthesizing four kinds of new electrochemical redox-active species was reported using HAuCl4 and Na2PdCl4 as dual oxidating agents and aniline derivatives as monomers. The synthesized polyaniline derivative-Au/Pd composites, namely poly(N-methyl-o-benzenediamine)-Au/Pd, poly(N-phenyl-o-phenylenediamine)-Au/Pd, poly(N-phenyl-p-phenylenediamine)-Au/Pd and poly(3,3’,5,5’-tetramethylbenzidine)-Au/Pd, exhibited electrochemical redox activity at −0.65 V, −0.3 V, 0.12 V, and 0.5 V, respectively. Meanwhile, these composites showed high H2O2 electrocatalytic activity because of the presence of Au/Pd. The as-prepared composites were used as electrochemical immunoprobes in simultaneous detection of four tumor biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199), carbohydrate antigen 72-4 (CA724), and alpha fetoprotein (AFP)). This immunoassay shed light on potential applications in simultaneous gastric cancer (related biomarkers: CEA, CA199, CA724) and liver cancer diagnosis (related biomarkers: CEA, CA199, AFP). The present strategy to the synthesize redox species could be easily extended to other polymers such as polypyrrole derivatives and polythiophene derivatives. This would be of great significance in the electrochemical detection of more analytes. PMID:26577799

  9. Characteristics of thymoma successfully resected by videothoracoscopic surgery.

    Science.gov (United States)

    Cheng, Yu-Jen; Hsu, Jui-Sheng; Kao, Eing-Long

    2007-01-01

    The inclusion criteria were established for a videothoracoscopic resection of early-stage thymoma. We retrospectively evaluated the validity of these criteria in the treatment of early-stage thymoma. The computed tomography (CT) image characteristics and clinical information comprised these criteria. The image considerations included the location of the tumor in the anterior mediastinum, a distinct fat plane between the tumor and vital organs, unilateral tumor predominance, tumor encapsulation, the existence of residual normal-appearing thymic tissue, and no mass compression effect. All enrollees were expected to be free of pleural effusion, pericardial effusion, paralysis of the hemidiaphragm, and the encasement of great vessels. An elevation of either the serum alpha-fetoprotein or beta-human chorionic gonadotropin levels, severe chest pain, superior vena cava syndrome, hoarseness, and age less than 20 years excluded the patient from enrollment. The heterogeneous content of the tumor was not an exclusion criterion, and the tumor size was not considered important. According to the above criteria, 44 patients were enrolled between November 1999 and November 2005. Twenty-seven patients had stage I thymoma and 17 had stage II thymoma. All patients successfully underwent a complete tumor resection using a three-port endoscopic technique. There was no open conversion. Based on these criteria, we can select suitable patients to confidently perform a thoracoscopic resection of early-stage thymoma.

  10. Lymphoepithelioma-like hepatocellular carcinoma without Epstein-Barr virus infection: A case report and a review of the literature

    Directory of Open Access Journals (Sweden)

    Jianguo Wei

    2015-01-01

    Full Text Available Lymphoepithelioma-like carcinoma (LELC of the liver is uncommon, only 20 cases have been reported in the English-language literature so far, and the majority has been identified as cholangiocarcinomas, only four cases were hepatocellular LELC. Here we described a rare case of lymphoepithelioma-like hepatocellular carcinoma (HCC. A 42-year-old Chinese female who was incidentally found to have a liver-occupying lesion during a routine medical examination. Ultrasonography revealed a 47 mm × 33 mm × 36 mm hypoechoic mass in the left lobe. Computed tomography and magnetic resonance imaging displayed a nodular lesions in the left liver lobe. The patient underwent a left-side hepatectomy. Histopathological examination of the resected specimen revealed an undifferentiated carcinoma with a dense lymphocytic infiltrate, predominantly composed of CD3(+ T cells, morphologically similar to nasopharyngeal carcinoma. Immunohistochemically, the tumor cells were positive for CK, EMA, Glypican-3 and hepatocyte, but negative for alpha-fetoprotein, CK19, CK7 and CK20. Epstein–Barr virus (EBV in situ hybridization was negative. The final histopathological diagnosis was lymphoepithelioma-like HCC without EBV infection.

  11. A case of intracranial teratoma

    International Nuclear Information System (INIS)

    Shiota, Madoka; Ando, Yukinori; Takashima, Sachio; Hori, Tomokatsu; Hiramoto, Shinsuke.

    1985-01-01

    A case of neonatal intracranial teratoma was examined on ultrasonography (US), computed tomography (CT) and tumor markers in serum, CSF and tumor tissue. This 27-day-old male infant was pointed out a head enlargement by prenatal sonography at 39 weeks' gestation. He admitted to our hospital at the age of one day after cesarean section. His birth weight was 4430 g and head circumstance 47.5 cm. On admission, physical and neurological examinations reveled big head, weak crying, twiching and sun set phenomenon. The optic fundi were normal. The CT scan at 1 day demonstrated the marked enlargement of lateral ventricles and the supratentorial large polycystic mass with calcifications at midline area. Transfontanelle sonography also delineated the polycystic mass and enlarged ventricle. Ventricular tap showed bloody CSF. Alpha-Fetoprotein and carcinoembryonic antigen level in CSF was higher than those in serum. Postmortam tumor necropsy revealed a teratoma including mature squamous epithelium, muscle, cartilage, bone, lymphoid and nervous tissue. There were immature mesenchymal cells in some parts. The immune histochemical method showed positive staining to AFP in intestinal and respiratory epithelium, and to CEA in intestinal epithelium and immature mesenchymal cells. In summary, these characteristic findings of US, CT and tumor marker in CSF have a diagnostic value of intracranial teratoma. (author)

  12. Kinetic Consideration of AFP irma assay

    International Nuclear Information System (INIS)

    Aly, M. A.; Moustafa, K.A.

    2003-01-01

    Alpha-fetoprotein (AFP) is a glycoprotein produced by the yolk sac and later by the fetal liver during pregnancy. When the neural tube is not properly formed, by the fetal liver during pregnancy. When the neural tube is not properly formed, large amounts of AFP pass into the amniotic fluid and reach the mother's blood. During pregnancy, the major interest in AFP determination in maternal serum and amniotic fluid is on the early diagnosis of fetal abnormalities. AFP also used as a tumor marker for hepatocellular carcinoma. There are many different techniques for measuring AFP in blood, but the more accurate one is the immunoassay technique. The kinetics of the interaction between AFP antigen and two matched antibodies, one labeled with radioactive isotope 1 25I (tracer) and the other is unlabelled and attached to a solid support (tube), are studied using the more recently, two sites (sandwich) immunoradiometric assay (IRMA) technique. We present here a method for determining the rate constants, using an advanced computer program (RKY), which based on the nelder-mead optimization principle. The rate constant, at three variable temperatures and three different antigen concentrations, as well as the half time of exchange (t 1/2 ) were calculated

  13. Use of Yttrium-90 TheraSphere for the treatment of unresectable hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Michael D; Uaje, Michelle B; Al-Ghazi, Muthana S; Fields, Denise; Herman, June; Kuo, Jeffrey V; Milne, Norah; Nguyen, Thong H; Ramsinghani, Nilam S; Tokita, Kenneth M; Tsai, Fong Y; Vajgrt, Duane J; Imagawa, David K

    2004-11-01

    This is a retrospective analysis of a new treatment modality, intra-arterial administration of Yttrium-90 TheraSphere, for unresectable hepatocellular carcinoma (HCC). Patients with HCC not amenable to surgical treatment who had satisfactory physiological function without comorbid disease or significant pulmonary shunting were eligible for treatment. Patients were categorized into complete, partial, or no response based on serum alpha-fetoprotein (AFP) levels and CT or MRI imaging. Fourteen patients were considered candidates for treatment. Three patients were excluded due to significant hepatopulmonary shunting. Eleven patients were treated with TheraSphere. One patient (9%) had a complete response, eight patients (78%) had a partial response, and two patients (18%) showed no response. Partial and complete responders with AFP-associated HCC demonstrated a median decrease in AFP levels of 79 per cent at 73 days. No patients developed liver toxicity nor died due to treatment. Five patients (45%) died of progressive disease at a median of 7 months post-treatment. Six patients (54%) were alive at a median of 11 months (range, 9 to 20 months). Okuda stage 2 and 3 patients showed a median survival of 11 months and 7 months, respectively. Yttrium-90 TheraSphere treatment for unresectable hepatocellular carcinoma is well tolerated and appears to extend survival.

  14. Comparative proteomic analysis of human amniotic fluid supernatants with Down syndrome using mass spectrometry.

    Science.gov (United States)

    Park, Jisook; Cha, Dong-Hyun; Jung, Jin Woo; Kim, Young Hwan; Lee, Sook Hwan; Kim, Youngjun; Kim, Kwang Pyo

    2010-06-01

    Down syndrome (DS) is an abnormality of the 21st chromosome that commonly occurs in children born to advanced age women. Amniotic fluid (AF) is usually collected from such women for prenatal diagnosis. This study analyzed human AF supernatants (AFS) by mass spectrometric (MS) approach to search for candidate biomarkers of DS pregnancy. AFS were collected from advanced age pregnant women at 16-18th weeks of gestation by amniocentesis for cytogenetic analysis. AFS from pregnancies carrying DS (n=4) or chromosomally normal (n=6) fetuses, as revealed by cytogenetic analysis, were then subjected to global protein profiling by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Affinity chromatography was applied prior to LC-ESI-MS/MS to minimize the masking effect of highly abundant albumin and immunoglobulin and thereby, increased the diversity of identified proteins. Hereby, at least 30 AFS proteins were newly identified and 44 AFS proteins were found to be differentially expressed between DS and normal cases. Six of these proteins were unique to DS cases while 11 proteins were unique to chromosomally normal cases. In addition, 19 AFS proteins were down-regulated and 8 were up-regulated in DS cases with varying fold changes. A western blot analysis confirmed the LC-ESI-MS/MS data that combined detection of Apolipoprotein A-II (apo A-II) and alpha-fetoprotein (AFP) could be a potential tool for diagnosing DS cases.

  15. CA 125 and other tumor markers in uterine leiomyomas and their association with lesion characteristics.

    Science.gov (United States)

    Babacan, Ali; Kizilaslan, Cem; Gun, Ismet; Muhcu, Murat; Mungen, Ercument; Atay, Vedat

    2014-01-01

    The aim of this study was to investigate the factors associated with serum levels of several tumor markers in a group of patients operated for uterine myoma. One hundred thirty-seven female patients operated for uterine myoma were included. Serum samples were examined for CA 125, CA 19-9, CA 15-3, carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) levels as part of routine workup. Pathological and morphological characteristics of the patients were retrieved from medical records. The mean age was 46.7 ± 8.8 years (range, 22-85 y). Abnormally high levels of CA 125, CA 19-9, CA 15-3, CEA, and AFP were found in 19.7%, 6.6%, 5.1%, 3.7%, and 1.5% of the patients, respectively. Patients with additional adenomyosis and patients with at least one large myoma (≥ 5 cm diameter) had significantly higher levels of CA 125. Multivariate analysis identified coexistence of adenomyosis (OR 7.7 [95% CI, 2.6-23.0], p CA 125 levels. CA 125 levels are affected by the tumor size and coexistence of adenomyosis in uterine leiomyomas. Indirect mechanisms caused by large myoma size such as peritoneal irritation may be responsible for CA 125 elevations.

  16. Lactate Dehydrogenase Is an Important Prognostic Indicator for Hepatocellular Carcinoma after Partial Hepatectomy

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    Jing-Ping Zhang

    2015-12-01

    Full Text Available Preoperative serum lactate dehydrogenase (LDH has been used as a prognostic indicator for patients with hepatocellular carcinoma (HCC treated with sorafenib or undergoing transcatheter arterial chemoembolization, but its significance in predicting survival of HCC patients who received curative resection remains undefined. A total of 683 patients with histopathologically confirmed HCC were enrolled in this study. The prognostic significance of preoperative serum LDH was determined by Kaplan-Meier analysis and a Cox proportional hazards regression model. The association between the preoperative serum LDH and clinicopathological parameters was evaluated by the χ2 test or linear regression analysis when appropriate. Higher preoperative serum LDH level was associated with worse prognosis. In a multivariate Cox proportional hazards analysis, the preoperative serum LDH level could predict overall survival and recurrence independently. Higher preoperative serum LDH level is associated with the elevated serum alpha-fetoprotein, the presence of hepatitis B surface antigen, larger tumor size, the presence of macrovascular invasion, the advanced tumor–lymph node–metastasis stage, worse tumor differentiation, and Child-Pugh B. Preoperative serum LDH level was an inexpensive, simple, convenient, and routinely measured biomarker exhibiting a potential to select patients at high risk with poor clinical outcome for appropriate treatment strategies.

  17. Doppler e marcadores séricos maternos na predição de complicações da gestação Doppler and maternal serum screening in the prediction of pregnancy complications

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    Fabrício da Silva Costa

    2008-02-01

    Full Text Available OBJETIVO: Comparar a eficácia do Doppler das artérias uterinas e de marcadores séricos maternos na predição de complicações da gestação. MATERIAIS E MÉTODOS: Trata-se de um estudo prospectivo com 49 primigestas, incluídas no estudo na 18ª semana, sendo coletada a amostra sanguínea para a realização das dosagens séricas, realizadas pelo método de quimioluminescência (alfa-fetoproteína, gonadotrofina coriônica humana e óxido nítrico e radioimunoensaio (peptídio atrial natriurético. O Doppler das artérias uterinas foi realizado entre 24-26 semanas, determinando a presença ou ausência de incisura na onda de velocidade de fluxo. Na análise estatística utilizou-se o teste de Mann-Whitney, para amostras não-paramétricas, e o teste exato de Fisher, para parâmetros qualitativos. RESULTADOS: Os valores de sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo foram, respectivamente, de 8,3%, 97,0%, 50,0% e 74,4% para a alfa-fetoproteína; 8,3%, 87,9%, 20,0% e 72,5% para a gonadotrofina coriônica humana; 16,7%, 97,0%, 33,3% e 76,2% para o peptídio atrial natriurético; e 16,7%, 93,9%, 50,0% e 75,6% para o óxido nítrico. A sensibilidade do Doppler foi de 75,0%, especificidade de 63,6%, valor preditivo positivo de 57,1% e valor preditivo negativo de 87,5%. CONCLUSÃO: O Doppler das artérias uterinas é melhor preditor de complicações da gestação quando comparado a alguns marcadores séricos em populações de baixo risco.OBJECTIVE: To compare the effectiveness of uterine artery Doppler and maternal serum screening in the prediction of pregnancy complications. MATERIALS AND METHODS: Prospective study with 49 primigravidae at their 18th gestational week, when a blood sample was collected for serum dosage by chemiluminescence (alpha-fetoprotein, human chorionic gonadotropin and nitric oxide and radioimmunoassay (atrial natriuretic peptide. Uterine artery Doppler was performed between the 24th

  18. Exposure-response relationship of regorafenib efficacy in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Solms, Alexander; Reinecke, Isabel; Fiala-Buskies, Sabine; Keunecke, Anne; Drenth, Henk-Jan; Bruix, Jordi; Meinhardt, Gerold; Cleton, Adriaan; Ploeger, Bart

    2017-11-15

    To explore the relationship between regorafenib exposure and efficacy in patients with hepatocellular carcinoma (HCC) who had disease progression during sorafenib treatment (RESORCE). Exposure-response (ER) analyses for regorafenib were performed using data from a phase 3, randomized, placebo-controlled trial (RESORCE). Patients received 160mg regorafenib or placebo once daily (3weeks on/1week off in a 4-week cycle) with best supportive care until disease progression, death, or unacceptable toxicity. Kaplan-Meier analyses for overall survival (OS) and time-to-progression (TTP) were performed in which regorafenib-treated patients were grouped into four categories according to their estimated average exposure over 4weeks in cycle 1. While this analysis primarily focused on efficacy, a potential correlation between exposure and treatment-emergent adverse events (TEAEs) was also evaluated. If any differences were observed between Kaplan-Meier plots, the ER analysis continued with a multivariate Cox regression analysis to evaluate the correlation between exposure quartile categories and the efficacy and safety parameters while taking into consideration the effect of the predefined clinically relevant demographic and baseline covariates. The functional form of the ER relationship within the regorafenib treatment group was subsequently evaluated. Based on visual assessment of the Kaplan-Meier plots, no meaningful relationship between the exposure categories and TEAEs were observed, although median OS and TTP tended to be longer in the higher exposure categories. Further ER analyses, which considered the effects of predefined covariates and the different shapes of the ER relationship, focused on efficacy. The baseline risk factors Eastern Cooperative Oncology Group (ECOG) performance status ≥1, alpha-fetoprotein levels ≥400ng/ml, and aspartate transaminase or alanine transaminase levels >3×upper limit of normal were significantly associated with OS (Pregorafenib

  19. Contribuição da quimioembolização de hepatocarcinomas em pacientes cirróticos na espera pelo transplante hepático Contribution of transcatheter arterial chemoembolization of hepatocellular carcinomas in cirrhotic patients awaiting liver transplantation

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    Luís Francisco Langer

    2005-02-01

    using mitomycin C and lipiodol. A prospective evaluation of the following factors was performed: a serum levels of alpha-fetoprotein; b tumor size; c maintenance of the viability criteria for hepatic transplantation; d degree of liver dysfunction. RESULTS: The mean serum levels of alpha-fetoprotein were reduced by 43% during the first 13 months. The mean tumor size, as measured by the long axis, after a mean follow-up period of 13.5 months was 3.2 cm, which is considered stable for the period according to the World Health Organization criteria. The mean survival rate was 14 months. CONCLUSION: In this trial, pre-transplantation use of chemoembolization in combination with an adequately chosen therapy showed few complications and contra-indications as well as a considerable anti-tumor efficacy. Despite the fact that the adopted therapy increased survival rates in comparison to historical evolution data in hepatocellular carcinoma, this increase had not the same dimension if the median waiting time for transplantation is taken into consideration. Therefore, other strategies need to be associated to either make survival rate longer or to reduce transplantation waiting time.

  20. Uterine artery Doppler and adverse pregnancy outcome in women with extreme levels of fetoplacental proteins used for Down syndrome screening.

    Science.gov (United States)

    Filippi, E; Staughton, J; Peregrine, E; Jones, P; Huttly, W; Peebles, D M; Pandya, P; David, A L

    2011-05-01

    To evaluate the use of second-trimester uterine artery (UtA) Doppler to predict adverse pregnancy outcome in women with extreme levels of fetoplacental proteins used for Down syndrome screening. At a single institution, women screened for Down syndrome were offered second-trimester UtA Doppler examination if they had one of the following on analysis of maternal serum: pregnancy-associated plasma protein-A ≤ 0.28 multiples of the median (MoM) (1% of screened population), inhibin ≥ 3.0 MoM (2%), human chorionic gonadotropin ≥ 4.0 MoM (2%), alpha-fetoprotein (AFP) ≥ 2.5 MoM (2%), estriol ≤ 0.5 MoM (1%). Abnormal UtA Doppler was defined as bilateral or unilateral notching or mean pulsatility index ≥ 1.45. Of 240 women studied, 92 (38.3%) had an adverse pregnancy outcome: small for gestational age (either one marker (61.1% vs. 35.6%, P = 0.04). UtA Doppler was abnormal in 20% (32 of 159 women screened) and increased the risk of adverse pregnancy outcome (RR 2.5, 65.6% vs. 26.0%, P UtA Doppler (RR 2.98, 56.2% vs. 18.9%, P UtA Doppler examination confers a high risk of adverse pregnancy outcome and SGA in particular, but a normal examination does not rule out an adverse pregnancy outcome. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

  1. LDH inhibition impacts on heat shock response and induces senescence of hepatocellular carcinoma cells.

    Science.gov (United States)

    Manerba, Marcella; Di Ianni, Lorenza; Govoni, Marzia; Roberti, Marinella; Recanatini, Maurizio; Di Stefano, Giuseppina

    2017-07-15

    In normal cells, heat shock response (HSR) is rapidly induced in response to a variety of harmful conditions and represents one of the most efficient defense mechanism. In cancer tissues, constitutive activation converts HSR into a life-threatening process, which plays a major role in helping cell survival and proliferation. Overexpression of heat shock proteins (HSPs) has been widely reported in human cancers and was found to correlate with tumor progression. Hepatocellular carcinoma is one of the conditions in which HSR activation was shown to have the highest clinical significance. Transcription of HSPs is induced by HSF-1, which also activates glycolytic metabolism and increases the expression of LDH-A, the master regulator of the Warburg effect. In this paper, we tried to explore the relationship between HSR and LDH-A. In cultured hepatocellular carcinoma cells, by using two enzyme inhibitors (oxamate and galloflavin), we found that the reduction of LDH-A activity led to decreased level and function of the major HSPs involved in tumorigenesis. Galloflavin (a polyphenol) also inhibited the ATPase activity of two of the examined HSPs. Finally, hindering HSR markedly lowered the alpha-fetoprotein cellular levels and induced senescence. Specific inhibitors of single HSPs are currently under evaluation in different neoplastic diseases. However, one of the effects usually observed during treatment is a compensatory elevation of other HSPs, which decreases treatment efficacy. Our results highlight a connection between LDH and HSR and suggest LDH inhibition as a way to globally impact on this tumor promoting process. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Accuracy of serum markers, progesterone and vitamins measurements for early screening of abortions in the eastern region of Algeria (Batna

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    Sara Mouffouk

    2018-02-01

    Full Text Available Spontaneous abortion is an involuntary interruption of pregnancy before 22 weeks of gestation. According to the Algerian National Institute of Public Health the percentage of women suffering from permanent complications during pregnancy is approximately 15%. The aim of this study is the determination of some biochemical analytes, including folic acid, vitamin B12, alphafoetoproteine, beta human chorionic gonadotropin (β-hCG, progesterone and oestradiol (uE3, which are involved in the detection of pregnancy failures. This case-control study was carried out on women in the process of abortion and a control group with viable pregnancies in the East region of Algeria (Batna during the year 2015. In the present investigation, 69 pregnant women during the first and second trimester were recruited during the first and second trimesters as cases (with miscarriages and the control group (n=69 was constituted of women who had normal ultrasound. The average concentration of alpha-fetoprotein is significantly low during the first trimester, but it is very high during the second trimester between cases and controls. The median values of β- hCG, uE3 and progesterone decrease very significantly. The mean concentration of serum folate and vitamin B12 did not change significantly between cases and controls in the first and second trimesters. The results of this study revealed that, spontaneous abortions are associated with changes in serum markers and progesterone, which could form an important part in the early diagnosis of non-viable pregnancies. However, vitamins levels have no significant effects on these pregnancies.

  3. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.

    Science.gov (United States)

    Church, Rachel J; Kullak-Ublick, Gerd A; Aubrecht, Jiri; Bonkovsky, Herbert L; Chalasani, Naga; Fontana, Robert J; Goepfert, Jens C; Hackman, Frances; King, Nicholas M P; Kirby, Simon; Kirby, Patrick; Marcinak, John; Ormarsdottir, Sif; Schomaker, Shelli J; Schuppe-Koistinen, Ina; Wolenski, Francis; Arber, Nadir; Merz, Michael; Sauer, John-Michael; Andrade, Raul J; van Bömmel, Florian; Poynard, Thierry; Watkins, Paul B

    2018-01-22

    Current blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of fourteen promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n=192 and =81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n=55 and =92) and DILI patients (n=98, =28, and =143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total keratin 18 (K18), caspase cleaved K18 (ccK18), glutathione S-transferase alpha (GSTα), alpha fetoprotein (AFP), arginase-1 (ARG1), osteopontin (OPN), sorbitol dehydrogenase (SDH), fatty acid binding protein (FABP1), cadherin-5 (CDH5), macrophage colony stimulating factor receptor (MCSFR), paraoxonase 1 (PON1, normalized to prothrombin protein), and leucocyte cell-derived chemotaxin-2 (LECT2). Most candidate biomarkers were significantly altered in DILI cases compared to healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase (ALT) than miR-122 and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among the healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplant within 6 months of DILI-onset. Prediction of prognosis among DILI patients using Model for End-stage Liver Disease (MELD) was improved by incorporation of K18 and MCSFR levels. GLDH appears to be more useful than miR-122 in identifying DILI patients. K18, OPN and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  4. HBx induced AFP receptor expressed to activate PI3K/AKT signal to promote expression of Src in liver cells and hepatoma cells

    International Nuclear Information System (INIS)

    Zhu, Mingyue; Guo, Junli; Li, Wei; Xia, Hua; Lu, Yan; Dong, Xu; Chen, Yi; Xie, Xieju; Fu, Shigan; Li, Mengsen

    2015-01-01

    Hepatitis B virus (HBV)-X protein(HBx) is a transactivator of host several cellular genes including alpha-fetoprotein(AFP) and AFP receptor(AFPR) which contributes to HBV-associated tumor development. The expression of AFP/AFPR are correlated with hepatocellular carcinoma(HCC)-initial cells. But the role of AFP and AFPR in promoting occurrence of HBV-related HCC were still unclear. A total of 71 clinical patients’ liver specimens, normal human liver cells L-02 and HCC cell lines, PLC/PRF/5 were selected for analyzing the effects of HBx on expression of AFP, AFPR and Src. The expression of goal proteins were detected by Immunohistochemical stained and Western blotting; HBx-expressed vectors were constructed and transfected into L-02 cells, laser confocal microscopy was applied to observe expression and location of AFP, AFPR and Src in the normal liver cells and HCC cells, soft agar colony formation assay was used to observe colonies formed of the cells. We confirmed HBx gives preference to promote the expression of AFP and AFPR; HBx priors to up-regulate the expression of AFPR and AFP in L-02 cells and in normal liver specimens; AFPR signal been able to stimulate Src expression. The results also indicated that phosphatidylinositol 3-kinase(PI3K) inhibitors Ly294002 and GDC0941 effectively suppress AFPR mediated up-regulation expression of Src in AFPR positive HCC lines. HBx priors to drive the expression of AFP and AFPR to promote expression of Src in normal liver cells and hepatoma cells; AFP and AFPR maybe play pivotal role in HBV-related hepatocarcinogenesis; Targeting AFPR is an available therapeutic strategy of HCC. The online version of this article (doi:10.1186/s12885-015-1384-9) contains supplementary material, which is available to authorized users

  5. Birth weight, breast cancer and the potential mediating hormonal environment.

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    Radek Bukowski

    Full Text Available Previous studies have shown that woman's risk of breast cancer in later life is associated with her infants birth weights. The objective of this study was to determine if this association is independent of breast cancer risk factors, mother's own birth weight and to evaluate association between infants birth weight and hormonal environment during pregnancy. Independent association would have implications for understanding the mechanism, but also for prediction and prevention of breast cancer.Risk of breast cancer in relation to a first infant's birth weight, mother's own birth weight and breast cancer risk factors were evaluated in a prospective cohort of 410 women in the Framingham Study. Serum concentrations of estriol (E3, anti-estrogen alpha-fetoprotein (AFP, and pregnancy-associated plasma protein-A (PAPP-A were measured in 23,824 pregnant women from a separate prospective cohort, the FASTER trial. During follow-up (median, 14 years 31 women (7.6% were diagnosed with breast cancer. Women with large birth weight infants (in the top quintile had a higher breast cancer risk compared to other women (hazard ratio (HR, 2.5; 95% confidence interval (CI, 1.2-5.2; P = 0.012. The finding was not affected by adjustment for birth weight of the mother and traditional breast cancer risk factors (adjusted HR, 2.5; 95% CI, 1.2-5.6; P = 0.021. An infant's birth weight had a strong positive relationship with the mother's serum E3/AFP ratio and PAPP-A concentration during pregnancy. Adjustment for breast cancer risk factors did not have a material effect on these relationships.Giving birth to an infant with high birth weight was associated with increased breast cancer risk in later life, independently of mother's own birth weight and breast cancer risk factors and was also associated with a hormonal environment during pregnancy favoring future breast cancer development and progression.

  6. Predictive models for lymph node metastases in patients with testicular germ cell tumors.

    Science.gov (United States)

    Mao, Yun; Hedgire, Sandeep; Prapruttam, Duangkamon; Harisinghani, Mukesh

    2015-10-01

    To develop predictive models for lymph node (LN) metastasis in testicular germ cell tumors. 291 patients with testicular germ cell tumors were included, which were divided into seminomatous and nonseminomatous groups. For screening the risk factors for LN metastasis, the tumor-related characteristics (including histopathological information and tumor markers) alpha fetoprotein and the lymph node-related features on CT were compared between metastatic cases and nonmetastatic cases. Two logistic regression models were built for each histological group, one depending on all tumor- and lymph node-related risk factors (Model 1) and another only on tumor-related factors (Model 2). Receivers operating characteristic curves were used to evaluate the predictive abilities of these models. 117 positive nodes/regions were identified in 68 patients, including 51 metastases and 17 occult metastases. Based on the selected independent risk factors, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of Models 1 and 2 in seminomatous and nonseminomatous groups were (95.5%, 95.3%, 95.3%, 77.8%, and 99.2%), (63.6%, 83.6%, 80.7%, 40.0%, and 93.0%), (93.5%, 94.7%, 94.3%, 89.6%, and 96.8%), and (89.1%, 44.2%, 58.9%, 43.6%, and 89.4%), respectively. Two predictive models for each seminomatous and nonseminomatous testicular tumor were established based on lymph node- and tumor-related risk factors. In patients with tumor and lymph node-related risk factors, regular CT surveillance is likely sufficient for predicting LN status, while in the patients without any tumor and lymph node-related risk factors a long interval-time CT follow-up should be considered. Additionally, right side tumors tend to involve contralateral LNs compared to left side ones. Positive inguinal LNs more frequently occur in patients with a history of groin surgery.

  7. Transarterial chemoembolization through collateral vessels in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kim, Ji Hye; Han, Joon Koo; Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung

    1993-01-01

    We performed 70 procedures of transarterial chemoembolization (TAE) through extrahepatic collateral vessels (n=27) or parasitic feeders (n=18) in 45 hepatocellular carcinoma patients. The collaterals developed after interruption of the hepatic artery due to repeated TAE (n=17), surgical ligation (n=7)and primary celiac occlusion (n=3). Radiologic findings suggest the existence of parasitic or collateral supply for hepatocellular carcinoma were 1) a focal defect of Lipiodol retention on CT or plain film after TAE via the hepatic artery, 2) dilated and tortuous vessels around the mass on angiography, 3) persistent elevation of the level of serum alpha-fetoprotein or continuous clinical symptoms in spite of sufficient devascularization of the tumor via the hepatic artery, and 4) radiological findings of direct invasion into adjacent organ. The sites of the catheter placement were the inferior phrenic artery(n=19), omental branches(n=16), periportal collaterals (n=6), pancreaticodenal arcade (n=3), gastroduodenal artery(n=3), internal mammary artery (n=2), intercosal artery (n=2), lateral thoracic artery (n=1), bronchial artery (n=1), and colic branches (n=1). Masses feeded by the inferior phrenic and chest wall collaterals were usually located at the dome area of the liver, and the omental and gastroduodenal collaterals developed in the masses located at the inferior tip of the liver. After TAE via collateral vessels, 37 patients underwent follow-up study. In 18 cases(48%), the tumor favorably responded to TAE. Specific complications of collateral TAE were epigastric soreness (n=10), severe shoulder pain (n=4), and embolization of the spinal artery during embolization through the intercostal artery (n=1). In conclusion, various extrahepatic collateals are important alternative or addition routes for effective chemoembolization in patients with advanced hepatoma, and early recognition of the parasitic supply and the effort to perform TAE via collaterals is very

  8. Effect of the Wnt/β-catenin signaling pathway on apoptosis, migration, and invasion of transplanted hepatocellular carcinoma cells after transcatheter arterial chemoembolization in rats.

    Science.gov (United States)

    Wang, Bao-Ming; Li, Nuo

    2018-05-01

    This study aims to investigate the influence of the Wnt/β-catenin signaling pathway on apoptosis, migration, and invasion of transplanted hepatocellular carcinoma (HCC) cells after transcatheter arterial chemoembolization (TACE) in rat models. A total of 80 rats were grouped into sham, TACE, Wnt-C59, and TACE + Wnt-C59 groups (n = 20). Ten days after model establishment, 10 rats in each group were executed to perform pathological examination and follow-up experiment, and the remaining 10 rats in each group were reared to observe the survival condition. RT-qPCR and Western blotting were applied to determine the expressions of Wnt1, β-catenin, cyclin D1, c-met, vimentin, E-cadherin, and vascular endothelial growth factor (VEGF). ELISA was performed to measure the serum alpha-fetoprotein (AFP) content of rats. Flow cytometry was used to evaluate cell apoptosis rate and transwell assay to examine cell migration and invasion. Compared with the TACE group, the Wnt-C59 and TACE + Wnt-C59 groups showed increased apoptosis and survival time (the TACE + Wnt-C59 group > the Wnt-C59 group). Compared with the sham group, the TACE + Wnt-C59 groups showed decreased cancer tissue weight and expressions of Wnt1, β-catenin, cyclin D1, vimentin, c-met, and VEGF, but increased E-cadherin expression. Compared with the TACE group, the Wnt-C59 and TACE + Wnt-C59 groups showed decreased AFP level, migration, and invasion (the TACE + Wnt-C59 group Wnt-C59 group). These findings indicate inhibition of the Wnt/β-catenin signaling pathway improves therapeutic effect on TACE via suppressing migration, invasion, and promoting apoptosis of transplanted HCC cells in rats. © 2017 Wiley Periodicals, Inc.

  9. High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zijian; Huang, Shanzhou [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Wang, Huanyu [Department of Thyroid and Breast Surgery, Nanshan District People’s Hospital, Shenzhen, 518000 (China); Wu, Jian [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Chen, Dong [Department of Biliopancreatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Peng, Baogang [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Zhou, Qi, E-mail: hnzhouqi@163.com [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China)

    2016-06-10

    Rapid progress and metastasis remain the major treatment failure modes of hepatocarcinoma (HCC). Unfortunately, the underlying molecular mechanisms of hepatoma cell proliferation and migration are poorly understood. Metabolic abnormalities play critical roles in tumorigenesis and progression. Hexokinase domain containing 1 (HKDC1) catalyzes the phosphorylation of glucose. However, the functions and mechanisms of HKDC1 in cancer remain unknown. In this study, real-time RT-PCR and Western blotting assays were used to detect the HKDC1 expression levels in HCC tissues and cell lines. The Oncomine™ Cancer Microarray Database was applied to analysis the correlations between HKDC1 expression and HCC clinical characteristics. MTT and Transwell migration assays were performed to determine the functions of HKDC1 in HCC cells. The effect of HKDC1 on Wnt/β-catenin signaling pathway was assessed using Western blotting assay. In this study, we found that HKDC1 expression levels were elevated in HCC tissues compared with the adjacent tissues. HCC patients with high expression levels of HKDC1 had poor overall survival (OS). Furthermore, higher HKDC1 levels also predicted a worse OS of patients within solitary, elevated pre-operated serum alpha fetoprotein (AFP) level and higher tumor diameter. Moreover, silencing HKDC1 suppressed HCC cells proliferation and migration in vitro. Downregulated HKDC1 expression repressed β-Catenin and c-Myc expression, which indicates that silencing HKDC1 may reduce proliferation and migration via inhibiting the Wnt/β-catenin signaling pathway in HCC. In summary, HKDC1 provides further insight into HCC tumor progression and may provide a novel prognostic biomarker and therapeutic target for HCC treatment. -- Highlights: •HKDC1 is upregulated in HCC. •Patients with high HKDC1 expressions perform worse OS. •Silencing HKDC1 suppresses proliferation and migration. •Silencing HKDC1 represses Wnt/β-catenin signaling pathway.

  10. The membrane protein melanoma cell adhesion molecule (MCAM) is a novel tumor marker that stimulates tumorigenesis in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, J; Tang, X; Weng, W; Qiao, Y; Lin, J; Liu, W; Liu, R; Ma, L; Yu, W; Yu, Y; Pan, Q; Sun, F

    2015-11-19

    Yes-associated protein (YAP) is overexpressed and has an oncogenic role in hepatocellular carcinoma (HCC). However, whether membrane protein can serve not only as a tumor marker that reflects YAP function but also as a therapeutic target that stimulates tumorigenesis in HCC remains unknown. Here we report that the membrane protein melanoma cell adhesion molecule (MCAM) was under positive regulation by YAP and was highly elevated in HCC cells. Within the MCAM promoter, we found the presence of a cAMP Response Element (CRE; -32 to -25 nt), which is conserved among species and is essential for YAP- and CREB-dependent regulation. Moreover, the interaction between CREB and YAP at the CRE site was dependent on PTPIY-WW domain interactions. However, MCAM expression was low and could not be regulated by YAP in breast and colon cancer cells because of the low levels of the acetyltransferase p300. In HCC cells, high levels of p300 facilitated the binding of YAP to the MCAM promoter, which in turn enhanced histone acetylation and polymerase II recruitment through the dissociation of the deacetylase Sirt1. These results suggest that MCAM is an HCC-specific target of YAP. In clinical serum samples, we found that the serum levels of MCAM were highly elevated in patients with HCC compared with healthy controls and with patients with cirrhosis, hepatitis, colon cancer and breast cancer. MCAM levels were shown to be a slightly better indicator than serum alpha-fetoprotein for predicting HCC. We further demonstrated that MCAM is essential for the survival and transformation of HCC. Mechanistically, MCAM induced translation initiation and the transcriptional activities of c-Jun/c-Fos. In addition, AKT activation had an essential role in the MCAM-promoted binding of eukaryotic initiation factor 4E to c-Jun/c-Fos mRNA. In conclusion, we demonstrated that MCAM may be a potential tumor marker and therapeutic target for the diagnosis and treatment of HCC.

  11. Establishment and characterization of 7 novel hepatocellular carcinoma cell lines from patient-derived tumor xenografts.

    Directory of Open Access Journals (Sweden)

    Hong Xin

    Full Text Available Hepatocellular carcinoma (HCC is a common cancer with poor prognosis worldwide and the molecular mechanism is not well understood. This study aimed to establish a collection of human HCC cell lines from patient-derived xenograft (PDX models. From the 20 surgical HCC sample collections, 7 tumors were successfully developed in immunodeficient mice and further established 7 novel HCC cell lines (LIXC002, LIXC003, LIXC004, LIXC006, LIXC011, LIXC012 and CPL0903 by primary culture. The characterization of cell lines was defined by morphology, growth kinetics, cell cycle, chromosome analysis, short tandem repeat (STR analysis, molecular profile, and tumorigenicity. Additionally, response to clinical chemotherapeutics was validated both in vitro and in vivo. STR analysis indicated that all cell lines were unique cells different from known cell lines and free of contamination by bacteria or mycoplasma. The other findings were quite heterogeneous between individual lines. Chromosome aberration could be found in all cell lines. Alpha-fetoprotein was overexpressed only in 3 out of 7 cell lines. 4 cell lines expressed high level of vimentin. Ki67 was strongly stained in all cell lines. mRNA level of retinoic acid induced protein 3 (RAI3 was decreased in all cell lines. The 7 novel cell lines showed variable sensitivity to 8 tested compounds. LIXC011 and CPL0903 possessed multiple drug resistance property. Sorafenib inhibited xenograft tumor growth of LIXC006, but not of LIXC012. Our results indicated that the 7 novel cell lines with low passage maintaining their clinical and pathological characters could be good tools for further exploring the molecular mechanism of HCC and anti-cancer drug screening.

  12. A new therapeutic assessment score for advanced hepatocellular carcinoma patients receiving hepatic arterial infusion chemotherapy.

    Directory of Open Access Journals (Sweden)

    Issei Saeki

    Full Text Available Hepatic arterial infusion chemotherapy (HAIC is an option for treating advanced hepatocellular carcinoma (HCC. Because of the poor prognosis in HAIC non-responders, it is important to identify patients who may benefit from continuous HAIC treatment; however, there are currently no therapeutic assessment scores for this identification. Therefore, we aimed to establish a new therapeutic assessment score for such patients.We retrospectively analyzed 90 advanced HCC patients with elevated baseline alpha-fetoprotein (AFP and/or des-gamma-carboxy prothrombin (DCP levels and analyzed various parameters for their possible use as predictors of response and survival. AFP and DCP responses were assessed after half a course of HAIC (2 weeks; a positive-response was defined as a reduction of ≥ 20% from baseline.Multivariate analysis identified DCP response (odds ratio 16.03, p < 0.001 as an independent predictor of treatment response. In multivariate analysis, Child-Pugh class A (hazard ratio [HR] 1.99, p = 0.018, AFP response (HR 2.17, p = 0.007, and DCP response (HR 1.90, p = 0.030 were independent prognostic predictors. We developed an Assessment for Continuous Treatment with HAIC (ACTH score, including the above 3 factors, which ranged from 0 to 3. Patients stratified into two groups according to this score showed significantly different prognoses (≤ 1 vs. ≥ 2 points: median survival time, 15.1 vs. 8.7 months; p = 0.003.The ACTH score may be useful in the therapeutic assessment of HCC patients receiving HAIC.

  13. Evaluation of a CLEIA automated assay system for the detection of a panel of tumor markers.

    Science.gov (United States)

    Falzarano, Renato; Viggiani, Valentina; Michienzi, Simona; Longo, Flavia; Tudini, Silvestra; Frati, Luigi; Anastasi, Emanuela

    2013-10-01

    Tumor markers are commonly used to detect a relapse of disease in oncologic patients during follow-up. It is important to evaluate new assay systems for a better and more precise assessment, as a standardized method is currently lacking. The aim of this study was to assess the concordance between an automated chemiluminescent enzyme immunoassay system (LUMIPULSE® G1200) and our reference methods using seven tumor markers. Serum samples from 787 subjects representing a variety of diagnoses, including oncologic, were analyzed using LUMIPULSE® G1200 and our reference methods. Serum values were measured for the following analytes: prostate-specific antigen (PSA), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9), and cytokeratin 19 fragment (CYFRA 21-1). For the determination of CEA, AFP, and PSA, an automatic analyzer based on chemiluminescence was applied as reference method. To assess CYFRA 21-1, CA125, CA19-9, and CA15-3, an immunoradiometric manual system was employed. Method comparison by Passing-Bablok analysis resulted in slopes ranging from 0.9728 to 1.9089 and correlation coefficients from 0.9977 to 0.9335. The precision of each assay was assessed by testing six serum samples. Each sample was analyzed for all tumor biomarkers in duplicate and in three different runs. The coefficients of variation were less than 6.3 and 6.2 % for within-run and between-run variation, respectively. Our data suggest an overall good interassay agreement for all markers. The comparison with our reference methods showed good precision and reliability, highlighting its usefulness in clinical laboratory's routine.

  14. Protein induced by vitamin K absence or antagonist-II (PIVKA-II) specifically increased in Italian hepatocellular carcinoma patients.

    Science.gov (United States)

    Viggiani, Valentina; Palombi, Sara; Gennarini, Giuseppina; D'Ettorre, Gabriella; De Vito, Corrado; Angeloni, Antonio; Frati, Luigi; Anastasi, Emanuela

    2016-10-01

    As a marker for Hepatocellular Carcinoma (HCC), Protein Induced by Vitamin K Absence II (PIVKA-II) seems to be superior to alpha fetoprotein (AFP). To better characterize the role of PIVKA-II, both AFP and PIVKA-II have been measured in Italian patients with diagnosis of HCC compared with patients affected by non-oncological liver pathologies. Sixty serum samples from patients with HCC, 60 samples from patients with benign liver disease and 60 samples obtained from healthy blood donors were included in the study. PIVKA-II and AFP were measured by LUMIPULSE(®) G1200 (Fujirebio-Europe, Belgium). We considered as PIVKA-II cutoff 70 mAU/ml (mean +3SD) of the values observed in healthy subjects. The evaluation of PIVKA-II showed a positivity of 70% in patients with HCC and 5% in patients with benign diseases (p < 0.0001) whereas high levels of AFP were observed in 55% of HCC patients and in 47% of patients with benign diseases. The combined Receiver Operating Characteristic (ROC) analysis of the two analytes revealed a higher sensitivity (75%) compared to those observed for the individual biomarkers. In conclusion, we demonstrate that as a marker for HCC, PIVKA-II is more specific for HCC and less prone to elevation during chronic liver diseases. The combination of the two biomarkers, evaluated by the ROC analysis, improved the specificity compared to a single marker. These data suggest that the combined analysis of the two markers could be a useful tool in clinical practice.

  15. Maternal serum unconjugated estriol as a predictor for Smith-Lemli-Opitz syndrome and other fetal conditions.

    Science.gov (United States)

    Schoen, Edgar; Norem, Carol; O'Keefe, Jennifer; Krieger, Robyn; Walton, David; To, Trinh T

    2003-07-01

    To assess the clinical value of low maternal serum unconjugated estriol (E3) level for diagnosing Smith-Lemli-Opitz syndrome and other fetal clinical conditions in pregnant members of a large health maintenance organization. We studied serum unconjugated E3 levels in 120,071 gravidas having California Expanded Alpha-Fetoprotein prenatal screening at 15-20 weeks' gestation during a 5-year period. Of the 120,071 women, 323 (0.27%) had low unconjugated E3 levels (less than or equal to 0.2 ng/mL, or 0.15 multiples of the median). Excluding women who were screened too early or who had indeterminate screening results, 103 (0.08%) women with unexplained low unconjugated E3 level remained; of these 103 women, 33 had negative screening results and 68 had positive screening results, and two were tested too late for interpretation. Intrauterine fetal death occurred in 39 (57%) of the 68 women with low unconjugated E3 and positive screening results and occurred in two (6%) of the 33 women with low unconjugated E3 levels and negative screening results, a significant difference (P <.001). Two cases of Smith-Lemli-Opitz syndrome were identified and the patients did not survive the neonatal period; one was a therapeutic abortion for severe oligohydramnios, and the other died at age 48 hours. Low unconjugated E3 level also predicted presence of steroid sulfatase deficiency, a much more common X-linked skin disorder characterized by ichthyosis. Low maternal serum unconjugated E3 diagnosed more cases of steroid sulfatase deficiency and undetected intrauterine fetal death than Smith-Lemli-Opitz syndrome (1:60,000 prevalence), although the clinical importance of having this information prenatally is uncertain.

  16. Cytology of mixed germ cell tumor with mediastinal metastasis

    Directory of Open Access Journals (Sweden)

    Dagli Adile

    2009-01-01

    Full Text Available Nonseminomatous germ cell tumors of the testis are common and are very aggressive malignant tumors. Most of the cases have metastases at the time of diagnosis, and involvement of the posterior mediastinum in particular is well known. A 33 year-old male patient presented with complaints of a swelling on the right side of the neck that had been growing for the last month, as well as shortness of breath and cough. His thoracic computed tomography (CT showed a 1.5 cm lymph node on the anterior mediastinum and a mass of about 11 x 10 x 8 cm extending from the right lung apex to the right hilus, with regular contours and without contrast enhancement. The patient, who was given the preliminary diagnosis of a mixture metastatic bronchial tumor plus lymphoma, was subjected to transthoracic fine needle aspiration cytology (FNAC. His abdominal CT revealed a hypodense, heterogeneous and cystic necrotic mass of about 10 x 7 x 5 cm that was para-aortic at the infrarenal level (initially predicted as a lymphoma. The patient, who could not be typed in his cytopathological examination, was diagnosed with malignant epithelial tumor and was recommended to undergo a genitourinary system examination. Upon finding a high alpha fetoprotein (AFP value, a scrotal ultra sonography was performed which showed a mass filling the right testis. Histopathological examination of the orchiectomy material resulted in the diagnosis of mixed germ cell tumor (60% mature teratoma and 40% yolk sac tumor. Even though metastatic lesions are mostly seen in the posterior mediastinum, our findings reveal that specimens obtained with FNAC from the anterior mediastinum bear discohesive, pleomorphic, small nuclei in epithelial cells with microvacoules in the cytoplasm. These cytopathological alterations in specimens from the anterior mediastinum might promote germ cell and yolk sac tumors.

  17. Generation of human hepatocytes by stem cell technology: definition of the hepatocyte.

    Science.gov (United States)

    Hengstler, Jan G; Brulport, Marc; Schormann, Wiebke; Bauer, Alexander; Hermes, Matthias; Nussler, Andreas K; Fandrich, Fred; Ruhnke, Maren; Ungefroren, Hendrik; Griffin, Louise; Bockamp, Ernesto; Oesch, Franz; von Mach, Marc-Alexander

    2005-06-01

    Since 1999, numerous articles have reported the generation of hepatocytes from different types of extrahepatic stem or precursor cells. This opens exciting new possibilities for pharmacology and toxicology, as well as for cell therapy. Hepatocyte marker expression, including albumin, cytokeratin 18, c-met, alpha-fetoprotein and cytochrome P450 3A4 and -2B6, has been observed after transplantation of different types of human stem cells into the liver of laboratory animals or in vitro after incubation with cytokines. These intriguing observations have prompted scientists to classify stem cell-derived cell populations as hepatocytes. However, this conclusion may be premature. It has been shown that factors of the liver microenvironment can induce expression of a limited number of hepatocyte marker genes in nonhepatic cell types. To conclude on the grounds of a limited number of markers that these cells are true hepatocytes is not indicated. In this case one should carefully evaluate crucial hepatocyte-defining enzymatic properties. The present article: i) reviews studies describing the fate of extrahepatic human stem and precursor cells in livers of laboratory animals, including the possibility of cell fusion; and ii) critically discusses the phenotype of stem cells after application of various differentiation protocols aimed at generating human hepatocytes. In addition, the necessary criteria needed for defining a true hepatocyte are suggested. Establishing the necessary properties for stem cell-derived hepatocytes is timely and reasonable, and thus avoids further misleading semantic confusion. Finally, it is essential to understand that the definition of a bona fide hepatocyte should not be limited to qualitative assays, such as reverse transcriptase polymerase chain reaction and immunohistochemistry, but has to include a quantitative analysis of enzymatic activities, which allows direct comparison with primary hepatocytes. Although the stem cell

  18. Clinical factors related to recurrence after hepatic arterial concurrent chemoradiotherapy for advanced but liver-confined hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Cha, Hyejung; Yoon, Hong In; Lee, Ik Jae; Koom, Woong Sub; Seong, Jinsil; Han, Kwang-Hyub

    2013-01-01

    Before the sorafenib era, advanced but liver-confined hepatocellular carcinoma (HCC) was treated by liver-directed therapy. Hepatic arterial concurrent chemoradiotherapy (CCRT) has been performed in our group, giving substantial local control but frequent failure. The aim of this study was to analyze patterns of failure and find out predictive clinical factors in HCC treated with a liver-directed therapy, CCRT. A retrospective analysis was done for 138 HCC patients treated with CCRT between May 2001 and November 2009. Protocol-based CCRT was performed with local radiotherapy (RT) and concurrent 5-fluorouracil (5-FU) hepatic arterial infusion chemotherapy (HAIC), followed by monthly HAIC (5-FU and cisplatin). Patterns of failure were categorized into three groups: infield, intrahepatic-outfield and extrahepatic failure. Treatment failure occurred in 34.0% of patients at 3 months after RT. Infield, intrahepatic-outfield and extrahepatic failure were observed in 12 (8.6%), 26 (18.7%) and 27 (19.6%) patients, respectively. Median progression-free survival for infield, outfield and extrahepatic failure was 22.4, 18 and 21.5 months, respectively. For infield failure, a history of pre-CCRT treatment was a significant factor (P=0.020). Pre-CCRT levels of alpha-fetoprotein and prothrombin induced by vitamin K absence or antagonist-II were significant factors for extrahepatic failure (P=0.029). Treatment failures after CCRT were frequent in HCC patients, and were more commonly intrahepatic-outfield and extrahepatic failures than infield failure. A history of pre-CCRT treatment and levels of pre-CCRT tumor markers were identified as risk factors that could predict treatment failure. More intensified treatment is required for patients presenting risk factors. (author)

  19. Malignant ovarian germ cell tumors in pediatric patients: The AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) study.

    Science.gov (United States)

    Terenziani, M; Bisogno, G; Boldrini, R; Cecchetto, G; Conte, M; Boschetti, L; De Pasquale, M D; Biasoni, D; Inserra, A; Siracusa, F; Basso, M E; De Leonardis, F; Di Pinto, D; Barretta, F; Spreafico, F; D'Angelo, P

    2017-11-01

    Malignant ovarian germ cell tumors (MOGCT) carry an excellent prognosis, and the treatment aims to achieve results with the least possible treatment-related morbidity. The aim of this study was to assess the outcomes of pediatric patients with MOGCT. Patients were treated according to their stage: surgery and surveillance for stage I; a modified bleomycin-etoposide-cisplatin (BEP) regimen for stages II (three cycles), III, and IV (three cycles) with surgery on residual disease. Seventy-seven patients were enrolled (median age 11.8 years), 26 with dysgerminoma (Dysg), 13 with immature teratoma and elevated serum alpha-fetoprotein levels (IT + AFP), and 38 with nondysgeminoma (Non-Dysg) staged as follows: 27 stage I, 13 stage II, 32 stage III, 5 stage IV. Among evaluable patients in stage I (5-year event-free survival [EFS] 72.1% [95% CI: 56.4-92.1%]; 5-year overall survival [OS] 100%), seven relapsed (three patients with Dysg and four patients with Non-Dysg) and were rescued with chemotherapy (plus surgery in three patients). Among the evaluable patients with stages II-IV, 48 (98%) achieved complete remission after chemotherapy ± surgery, one (IT + AFP, stage IV) had progressive disease. In the whole series (median follow-up 80 months), the 5-year OS and EFS were 98.5% (95% CI: 95.6-100%) and 84.5% (95% CI: 76.5-93.5%). We confirm the excellent outcome for MOGCT. Robust data are lacking on surgical staging, surveillance for Non-Dysg with stage I, the management of IT + AFP, and the most appropriate BEP regimen. As pediatric oncologists, we support the role of surveillance after proper surgical staging providing cases are managed by experts at specialized pediatric centers. © 2017 Wiley Periodicals, Inc.

  20. Molecular analysis of Hepatitis B virus sub-genotypes and incidence of preS1/preS2 region mutations in HBV-infected Egyptian patients from Mansoura.

    Science.gov (United States)

    El-Mowafy, Mohammed; Elgaml, Abdelaziz; El-Mesery, Mohamed; Elegezy, Mohamed

    2017-09-01

    Hepatitis B virus (HBV) is one of the major causes of viral hepatitis worldwide. Despite the prevalence of HBV infection in Egypt, few studies have focused on sub-genotyping of the virus. Moreover, no studies are available regarding the mutational analysis of the preS1/preS2 region of the viral genome, or its impact on hepatocellular carcinoma (HCC) development in Egypt. In this study, we have analyzed the sub-genotypes and incidence of mutations in the preS1/preS2 region of HBV present in HBV-infected patients, from Mansoura city (located in the center of Nile Delta region of Egypt), via partial sequencing of this specific region. Moreover, we have investigated the impact of these mutations on HCC development by measuring serum alpha fetoprotein (AFP) level and abdominal ultrasound examination of the HBV-infected patients. According to our results, all samples were genotype D in which sub-genotype D1 was predominant. In addition, the results revealed mutations in the preS1/preS2 region, which could result in either immature preS1 protein or completely inhibit the translation of the preS2 protein. However, there was no incidence of HCC development in patients infected with mutated HBV in the preS1/preS2 region. In summary, for the first time our work has proved the predominance of sub-genotype D1 among HBV-infected Egyptian patients in Mansoura city, Nile Delta region, Egypt, and incidence of mutations in the preS1/preS2 region of HBV genome. This current study opens up research opportunities to discuss the impact of HBV mutations on the development of HCC in Egypt. © 2017 Wiley Periodicals, Inc.

  1. A long-term study of the effects of antiviral therapy on survival of patients with HBV-associated hepatocellular carcinoma (HCC) following local tumor ablation

    International Nuclear Information System (INIS)

    The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed after 1999 received antiviral treatment. Survival between the treated and untreated groups was compared. Among 555 HCC patients seen at our clinic between 1991 and 2013, 25 subjects were eligible. Nine subjects (all male patients, median age 53 years [46–66]) did not receive antiviral therapy while 16 (14 male patients, median age 56 years [20–73]) received treatment. Between the two groups, there was no difference in their median tumor size and levels of alpha-fetoprotein and albumin. However, the survival was significantly different (P = 0.001): the median survival of the untreated was 16 months (3–36 months) while that of the treated was 80 months (15–152 months). Fourteen of 16 treated patients are alive to date with two longest survivors alive for ≥151 months. In conclusion, concomitant antiviral therapy for CHB patients with HCC reduces and prevents new/recurrent tumor and improves survival. This novel treatment strategy offers an alternative to liver transplantation in patients with HBV-associated HCC

  2. Elevated serum levels of Chromogranin A in hepatocellular carcinoma.

    Science.gov (United States)

    Biondi, Antonio; Malaguarnera, Giulia; Vacante, Marco; Berretta, Massimiliano; D'Agata, Velia; Malaguarnera, Michele; Basile, Francesco; Drago, Filippo; Bertino, Gaetano

    2012-01-01

    During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages. The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed. The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001). Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.

  3. Identification of race-associated metabolite biomarkers for hepatocellular carcinoma in patients with liver cirrhosis and hepatitis C virus infection.

    Science.gov (United States)

    Di Poto, Cristina; He, Shisi; Varghese, Rency S; Zhao, Yi; Ferrarini, Alessia; Su, Shan; Karabala, Abdullah; Redi, Mesfin; Mamo, Hassen; Rangnekar, Amol S; Fishbein, Thomas M; Kroemer, Alexander H; Tadesse, Mahlet G; Roy, Rabindra; Sherif, Zaki A; Kumar, Deepak; Ressom, Habtom W

    2018-01-01

    Disparities in hepatocellular carcinoma (HCC) incidence and survival have been observed between ethnic groups including African-Americans (AA) and European-Americans (EA). The evaluation of the changes in the levels of metabolites in samples stratified by race could provide a snapshot of ethnically diverse disease related pathways and identify reliable biomarkers. In this study, we considered AA and EA to investigate metabolites that may be associated with HCC in a race-specific manner. The levels of 46 metabolites in plasma samples, collected from patients recruited at MedStar Georgetown University Hospital, were analyzed by Agilent GC-qMS in selected ion monitoring (SIM) mode. A least absolute shrinkage and selection operator (LASSO) regression model was applied to select metabolites with significant changes in HCC vs. cirrhosis in three groups: (1) AA and EA combined; (2) AA separately; and (3) EA separately. In addition, metabolites that distinguish HCC cases from cirrhosis in these three groups were selected by excluding those without HCV infection. The performances of the metabolites selected by LASSO in each group were evaluated through a leave-one-out cross-validation. We identified race-specific metabolites that differentiated HCC cases from cirrhotic controls, yielding better area under the receiver operating characteristics (ROC) curve (AUC) compared to alpha-fetoprotein (AFP), the serological marker widely used for the diagnosis of HCC. This study sheds light on metabolites that could potentially be used as biomarkers for HCC by monitoring their levels in high-risk population of cirrhotic patients in a race-specific manner.

  4. Effect of Direct-Acting Agents on Fibrosis Regression in Chronic Hepatitis C Virus Patients' Treatment Compared with Interferon-Containing Regimens.

    Science.gov (United States)

    El-Raziky, Maissa; Khairy, Marwa; Fouad, Ahmed; Salama, Ahmed; Elsharkawy, Aisha; Tantawy, Omnia

    2018-03-01

    Hepatitis C virus (HCV) treatment is aiming to cure and prevent the development, progression of fibrosis, and related complications. Interferon-based therapy was claimed to reduce or even reverse fibrosis. Although direct-acting agents have a better cure rate, we still lack the knowledge of their effect on fibrosis regression. We aim to assess fibrosis regression in direct-acting agents compared with interferon-based treatment regimens in the treatment of chronic HCV patients. The 204 chronic HCV patients were divided into 3 groups; group 1(N = 68) received Peg-IFN and ribavirin, group 2 (N = 69) received sofosbuvir and ribavirin, and group 3 (N = 67) received Peg-IFN, ribavirin, and sofosbuvir. Fibrosis assessment was performed by transient elastography (TE), APRI and FIB 4, in the pretreatment and at least 3 months after end of treatment. Of these, 66.2% of the patients did not show significant fibrosis changes, 6.4% fibrosis progressed, and 27.5% of fibrosis regressed (P < 0.0001) by TE. Similar results were detected in the different treatment regimens with no statistically significant difference between the regimens. Fibrosis regression was detected in 43.3% of cirrhotic patients who achieved sustained virological response (SVR) and only in 27.4% with significant fibrosis. Significant improvement of posttreatment aspartate transaminase, alanine transaminase, and alpha fetoprotein as well as APRI and FIB 4 scores were detected. Fibrosis regression (TE, APRI and FIB 4) was detected with direct-acting agents and interferon-based therapy. Treated patients with significant fibrosis will benefit of fibrosis regression irrespective to their treatment response, whereas fibrosis regression was associated with SVR in cirrhotic patients.

  5. Serum Transforming Growth Factor Beta-1 as an Index of Chemical Hepato carcinogenesis in Rats

    International Nuclear Information System (INIS)

    Abdelgawad, M.R.; Fekry, A.E.; Edrees, G.; Ali, M.A.; Ghareeb, N.A.

    2008-01-01

    Transforming growth factor beta-1 (TGF β1) is an important mediator which controls liver cell proliferation and replication. The relation between TGF β1, Alpha-fetoprotein (AFP) and clinically thought hepatocellular carcinoma (HCC) in rats were investigated to clarify the clinical value of measuring peripheral serum TGF β1 and AFP in evaluation of HCC. Peripheral serum TGF β1 and AFP were measured during chemically induced hepato carcinogenesis. Male rats were given a genotoxic compound diethylnitrosamine (DEN) in drinking water for 149 days with control receiving drinking water only. Animals were killed at different times intervals 54, 86 and 149 days, serum TGF β1 levels were measured by, Enzyme Linked Immunosorbent Assay (ELISA) and AFP levels were assayed by immunoradiometric assay (IRMA). In DEN treated rats 54 days, there was mild portal tract inflammatory cellular infiltrate, serum TGF β1 and AFP levels were both significantly elevated above control (P>0.05 and P<0.001). At 86 days there were moderate inflammation (portal and peri portal), serum TGF β1 and AFP levels were significantly increased, (P<0.001). At 149 days typical HCC were present in ten of ten rats and serum TGF β1 and AFP were both significantly elevated compared with controls, (P<0.001). It can be concluded that serum TGF β1 and AFP levels are elevated during chemically induced HCC and have roles during the stages of process (initiation, promotion and progression); both serum TGF β1 and AFP levels can be used in parallel as a non invasive tumor markers for early diagnosis and prognosis of HCC

  6. Do HIV care providers appropriately manage hepatitis B in coinfected patients treated with antiretroviral therapy?

    Science.gov (United States)

    Jain, Mamta K; Opio, Christopher K; Osuagwu, Chukwuma C; Pillai, Rathi; Keiser, Philip; Lee, William M

    2007-04-01

    The common occurrence of hepatitis B virus (HBV) infection in patients who carry the human immunodeficiency virus (HIV) demands that both viruses be recognized, evaluated, and treated when appropriate. We identified 357 HIV- and hepatitis B surface antigen-positive patients who underwent testing from 1999 to 2003; 155 patients who were new to our clinic and who initiated therapy for HIV and HBV coinfection were considered for inclusion in the study. The frequency of HIV testing (to determine HIV load and CD4+ cell count) performed during the first year of therapy was compared with the frequency of HBV measurements (to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load), abdominal ultrasound examination, and measurement of levels of alpha-fetoprotein in serum. HBV load data were obtained for only 16% of patients before initiation of antiretroviral therapy (ART), whereas HIV load was determined for 99% of patients before initiation of ART. The total number of HIV load measurements obtained during the first year after ART initiation was 497 (median number of HIV load measurements per patient, 3.0), compared with 85 measurements of HBV load (median number of HBV load measurements per patient, <1; P<.001). The percentage of patients who received any level of HBV monitoring (i.e., tests to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load) after ART initiation increased from 7% in 1999 to 52% in 2001 (P<.001), whereas the percentage of patients who underwent HIV load testing remained at 80%-90% during the same period. Health care providers treating patients with HIV infection during the period 1999-2003 infrequently monitored HBV response in coinfected patients, but they systematically monitored HIV response after ART initiation. Improved physician adherence to guidelines that better delineate HBV treatment and monitoring for patients with HIV-HBV coinfection is needed.

  7. Hepatectomy for Hepatocellular Carcinoma with Bile Duct Tumor Thrombus, Including Cases with Obstructive Jaundice.

    Science.gov (United States)

    Orimo, Tatsuya; Kamiyama, Toshiya; Yokoo, Hideki; Wakayama, Kenji; Shimada, Shingo; Tsuruga, Yosuke; Kamachi, Hirofumi; Taketomi, Akinobu

    2016-08-01

    This study aimed to evaluate the short- and long-term outcomes of hepatectomy for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT), including cases with obstructive jaundice. The study reviewed 42 HCC patients with BDTT, including six patients who needed preoperative biliary drainage due to obstructive jaundice, and 732 HCC patients without BDTT. The authors analyzed the impact of BDTT on the surgical outcomes and assessed the outcomes of hepatectomy for patients presenting with obstructive jaundice. The HCC patients with BDTT, almost all with stage 3 or 4 disease, had increased alpha-fetoprotein expression, larger tumors, and more portal vein invasion status. The survival of the HCC patients with BDTT was significantly inferior to that of the patients without BDTT (p = 0.0003). Survival did not differ significantly between the HCC patients with BDTT and those without BDTT when the two groups were matched by stage (p = 0.3366). The HCC patients with BDTT who presented with obstructive jaundice demonstrated outcomes similar to those for the HCC patients with BDTT who did not present with obstructive jaundice in terms of the overall survival rate (p = 0.5469). The perioperative outcomes for the HCC patients with BDTT did not depend on the presence or absence of preoperative jaundice. No patients in either BDTT group demonstrated 90-day mortality in this study. Hepatectomy should be considered for HCC patients with BDTT, even for patients with obstructive jaundice, because the surgical outcomes equivalent to those for HCC without BDTT can be achieved.

  8. Expression of MAGE, GAGE and BAGE genes in human liver diseases: utility as molecular markers for hepatocellular carcinoma.

    Science.gov (United States)

    Kobayashi, Y; Higashi, T; Nouso, K; Nakatsukasa, H; Ishizaki, M; Kaneyoshi, T; Toshikuni, N; Kariyama, K; Nakayama, E; Tsuji, T

    2000-04-01

    The MAGE, GAGE and BAGE genes encode tumor antigens recognized by autologous cytotoxic T lymphocytes. The aim of this study was to evaluate the possibility of using these genes as molecular markers and as the targets of specific immunotherapy for human hepatocellular carcinoma (HCC). The expressions of MAGE-1, MAGE-3, GAGE1-6, GAGE1-2 and BAGE mRNA in 33 surgically resected HCC samples and 26 of their corresponding non-cancerous samples (11 liver cirrhosis and 15 chronic hepatitis) were studied by a reverse-transcription polymerase chain reaction, and were compared with clinicopathological parameters. The expression of MAGE-1 was also examined in 16 biopsied HCC samples. MAGE-1, MAGE-3, GAGE1-6, GAGE1-2 and BAGE mRNA were expressed in 67%, 39%, 36%, 30%, and 21% of the HCC, respectively. At least one transcript was detected in 88% of the HCC, while no expression was observed in the non-cancerous livers. There was no significant correlation between the expression of any of the tumor antigens examined and the differentiation stage or size of the HCC. Especially, MAGE-1 was highly expressed in small HCC with a diameter of less than 2 cm and in well-differentiated HCC (81% and 70%, respectively), and was also expressed even in alpha-fetoprotein-negative and PIVKA-II-negative HCC (58% and 76%, respectively). The MAGE-1 expression was detected in 69% of biopsied HCC samples and the expression was high in both small and well-differentiated HCC. These tumor-specific antigens can be useful as molecular markers and as the possible target molecules for the specific immunotherapy of human HCC.

  9. Non-germ cell tumours arising in germ cell tumours (teratoma with malignant transformation) in men: CT and MR findings

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    Athanasiou, A. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Institut Curie, Paris (France)], E-mail: alexandra.athanasiou@curie.net; Vanel, D. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Istituti Ortopedici Rizzoli, Bologna (Italy); El Mesbahi, O. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Theodore, C. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Department of Oncology, Hopital Foch, Suresnes (France); Fizazi, K. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France)

    2009-02-15

    Purpose: To describe the imaging findings of germ cell tumours (GCT) containing non-germ cell malignant components (also designated teratoma with malignant transformation or TMT). Patients and methods: The records of 14 male patients with GCT and a non-germ cell histological component TMT were retrospectively reviewed. All patients had computed tomography (CT) and/or magnetic resonance (MR) studies before and after initial surgery and chemotherapy, as well as during follow-up. Imaging findings were correlated with the response to treatment and with overall survival. Pathological evaluation, immunohistochemistry, serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were also taken into consideration. Sarcoma was identified in 10 out of 14 patients, with rhabdomyosarcoma ranking first (n = 4), followed by osteosarcoma (n = 2), fusiform cell sarcoma (n = 1), undifferentiated sarcoma (n = 1), neurosarcoma (n = 1) and myxoid sarcoma (n = 1). Other histological types of malignant transformation included adenocarcinoma (n = 3) and bronchoalveolar carcinoma (n = 1). Overall, 9 patients relapsed at a median time of 84 months (range 60-168). Results: Non-GCT malignant transformation was identified in the retroperitoneum (5), testis (3), mediastinum (3), peritoneum (2) and lungs (1). The CT and MR imaging findings before treatment and after relapse were evaluated with emphasis on imaging features that could possibly imply the presence of malignant transformation (heterogeneously enhancing soft-tissue masses, ossified masses with calcified lymph nodes, diffuse epiploic thickening associated with ascites and peritoneal nodules, pulmonary alveolar infiltration with septal thickening). All but 1 patient with TMT presented with nodal and distant metastases. The prognosis was poor: within a median follow-up of 59 months (range 3-180), 4 out of 14 patients were alive. Conclusion: TMT is rare and associated with poorer survival compared to GCT. Imaging can be useful

  10. Serum human chorionic gonadotropin is associated with angiogenesis in germ cell testicular tumors

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    Avilés-Salas Alejandro

    2009-08-01

    Full Text Available Abstract Background Germ cell testicular tumors have survival rate that diminishes with high tumor marker levels, such as human chorionic gonadotropin (hCG. hCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF. Our purpose was to determine the relationship between hCG serum levels, angiogenesis, and VEGF expression in germ cell testicular tumors. Methods We conducted a retrospective study of 101 patients. Serum levels of hCG, alpha-fetoprotein (AFP, and lactate dehydrogenase were measured prior to surgery. Vascular density (VD and VEGF tissue expression were determined by immunohistochemistry and underwent double-blind analysis. Results Histologically, 46% were seminomas and 54%, non-seminomas. Median follow-up was 43 ± 27 months. Relapse was present in 7.5% and mortality in 11.5%. Factors associated with high VD included non-seminoma type (p = 0.016, AFP ≥ 14.7 ng/mL (p = 0.0001, and hCG ≥ 25 mIU/mL (p = 0.0001. In multivariate analysis, the only significant VD-associated factor was hCG level (p = 0.04. When hCG levels were stratified, concentrations ≥ 25 mIU/mL were related with increased neovascularization (p Conclusion This is the first study that relates increased serum hCG levels with vascularization in testicular germ cell tumors. Hence, its expression might play a role in tumor angiogenesis, independent of VEGF expression, and may explain its association with poor prognosis. hCG might represent a molecular target for therapy.

  11. Assessment and association of two useful tumour markers: alpha feto protein and human chornionic gonodotropin (beta hCG) hormone

    International Nuclear Information System (INIS)

    Subhan, F.; Tahir, F.; Sultan, S.; Subhan, K.

    2008-01-01

    This study was designed to determine serum Alpha-fetoprotein (AFP) and beta-h Chornionic Gonodotropin hormone (beta-hCG) levels among adult Pakistani population, and to observe their correlation. Serum AFP and beta-hCG levels were evaluated, using Micro-particle Enzyme Immuno Assay (MEIA) technology of M/s Abbott Laboratories. Data were compared using students t-test and correlation was computed. In the patients advised serum AFP assessment, 52% had normal AFP levels. comprising 37% male and 63% female subjects. For patients having a non-pathological picture, AFP levels varied non-significantly (p>0.05) between the Genders however, age varied highly significantly (p 0.05) and highly significant (p 0.05). Comparison of the population in the same age groups of both genders revealed significant (p 0.05), due to a large standard error. Although the differences in beta-hCG levels were highly significant (p 0.05). Among the studied cases, 67% patients had normal and 33% patients had raised beta-hCG levels. Beta-hCG levels show a decreasing trend with increasing age and beta-hCG levels were statistically significant (p<0.05) when patients under 50 years of age were compared with patients above 50 years. The coefficient of correlation between serum AFP and beta- hCG levels was 0.996454, which indicated a very strong. Significant positive correlation between the two tumour markers. The study showed that both serum AFP and beta-hCG are useful tumour markers and had a very strong positive correlation. (author)

  12. Testicular parenchymal abnormalities in Klinefelter syndrome: a question of cancer? Examination of 40 consecutive patients

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    Giacomo Accardo

    2015-02-01

    Full Text Available Klinefelter syndrome (KS is a hypergonadotropic hypogonadism characterized by a 47, XXY karyotype. The risk of testicular cancer in KS is of interest in relation to theories about testicular cancer etiology generally; nevertheless it seems to be low. We evaluated the need for imaging and serum tumor markers for testicular cancer screening in KS. Participants were 40 consecutive KS patients, enrolled from December 2009 to January 2013. Lactate dehydrogenase (LDH, alpha-fetoprotein (AFP, and beta-human chorionic gonadotrophin subunit (β-HCG serum levels assays and testicular ultrasound (US with color Doppler, were carried out at study entry, after 6 months and every year for 3 years. Abdominal magnetic resonance (MR was performed in KS when testicular US showed micro-calcifications, testicular nodules and cysts. Nearly 62% of the KS had regular testicular echotexture, 37.5% showed an irregular echotexture and 17.5% had micro-calcifications and cysts. Eighty seven percent of KS had a regular vascular pattern, 12.5% varicocele, 12.5% nodules 1 cm. MR ruled out the diagnosis of cancer in all KS with testicular micro calcifications, nodules and cysts. No significant variations in LDH, AFP, and β-HCG levels and in US pattern have been detected during follow-up. We compared serum tumor markers and US pattern between KS with and without cryptorchidism and no statistical differences were found. We did not find testicular cancer in KS, and testicular US, tumor markers and MR were, in selected cases, useful tools for correctly discriminating benign from malignant lesions.

  13. Chemoembolization Decreases Drop-Off Risk of Hepatocellular Carcinoma Patients on the Liver Transplant List

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    Frangakis, Constantine; Geschwind, Jean-Francois; Kim, Daniel; Chen, Yong; Koteish, Ayman; Hong, Kelvin; Liapi, Eleni; Georgiades, Christos S.

    2011-01-01

    Introduction: The drop-off risk for patients awaiting liver transplantation for hepatocellular carcinoma (HCC) is 22%. Transplant liver availability is expected to worsen, resulting in longer waiting times and increased drop-off rates. Our aim was to determine whether chemoembolization can decrease this risk. Patients and Methods: Eighty-seven consecutive HCC patients listed for liver transplant (Milan criteria) underwent statistical comparability adjustments using the propensity score (Wilcoxon, Fisher’s, and chi-square tests). Forty-three nonchemoembolization patients and 22 chemoembolization patients were comparable for Child-Pugh and Model for End-Stage Liver Disease scores, tumor size and number, alpha fetoprotein (AFP) levels, and cause of cirrhosis. We calculated the risk of dropping off the transplant list by assigning a transplant time to those who dropped off (equal probability with patients who were on the list longer than the patient in question). The significance level was obtained by calculating the simulation distribution of the difference compared with the permutations of chemoembolization versus nonchemoembolization assignment of the patients. Kaplan–Meier estimators (log-rank test) were used to determine survival rates. Results: Median follow-up was 187 ± 110 weeks (range 38 to 435, date of diagnosis). The chemoembolization group had an 80% drop-off risk decrease (15% nonchemoembolization versus 3% chemoembolization, p = 0.04). Although survival was better for the chemoembolization group, it did not reach statistical significance. Two-year survival for the nonchemoembolization and chemoembolization group was 57.3% ± 7.1% and 76.0% ± 7.9%, respectively (p = 0.078). Conclusions: Chemoembolization appears to result in a significant decrease in the risk of dropping off liver transplant list for patients with HCC and results in a tendency toward longer survival.

  14. Feasibility of conducting a randomized control trial for liver cancer screening: is a randomized controlled trial for liver cancer screening feasible or still needed?

    Science.gov (United States)

    Poustchi, Hossein; Farrell, Geoffrey C; Strasser, Simone I; Lee, Alice U; McCaughan, Geoffrey W; George, Jacob

    2011-12-01

    Screening for hepatocellular carcinoma (HCC) is commonly practiced and recommended in published guidelines, but evidence for its efficacy has been controversial. We tested the feasibility of conducting a randomized controlled trial (RCT) of HCC surveillance in patients with cirrhosis and followed up those offered screening to detect clinical outcomes. Participation was offered to patients with cirrhosis attending liver clinics at three university hospitals. Following discussion, patients received a decision aid (DA) that outlined the risks and benefits of surveillance. The proposed screening program comprised ultrasonography 6-monthly and serum alpha-fetoprotein every 3 months. We envisaged five groups of patients: those who agreed to randomization, those choosing nonrandomized screening, those wanting continuation of usual care, those who were undecided, and those refusing participation. Among 205 patients, 204 (99.5%) declined randomization. Of these, 181 (88%) elected for a nonrandomized screening program, 10% chose usual care (which typically included ad hoc screening), and two were undecided. Among 176 patients fluent in English communication skills, 160 (91%) preferred nonrandomized screening compared with 22/29 (76%) patients needing an interpreter (P < 0.026). Of 173 patients in nonrandomized screening followed up for a mean 13.5 ± 6.04 months, three developed HCC, two died from nonliver-related causes, and one underwent liver transplantation for liver failure. Eighteen of 21 patients in "usual care" received ad hoc screening. A simultaneous survey on the quality of the DA showed that the majority of participants believed that the information provided was unbiased. Although an RCT is theoretically ideal for determining the efficacy, efficiency, and cost-effectiveness of HCC screening, informed patients prefer surveillance. A randomized study of HCC screening is not feasible when informed consent is imparted. Copyright © 2011 American Association for the

  15. Fetal Alcohol Syndrome (FAS) in C57BL/6 Mice Detected through Proteomics Screening of the Amniotic Fluid

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    Datta, Susmita; Turner, Delano; Singh, Reetu; Ruest, L. Bruno; Pierce, William M.; Knudsen, Thomas B.

    2009-01-01

    BACKGROUND Fetal Alcohol Syndrome (FAS), a severe consequence of the Fetal Alcohol Spectrum Disorders, is associated with craniofacial defects, mental retardation, and stunted growth. Previous studies in C57BL/6J and C57BL/6N mice provide evidence that alcohol-induced pathogenesis follows early changes in gene expression within specific molecular pathways in the embryonic headfold. Whereas the former (B6J) pregnancies carry a high-risk for dysmorphogenesis following maternal exposure to 2.9 g/kg alcohol (two injections spaced 4.0 h apart on gestation day 8), the latter (B6N) pregnancies carry a low-risk for malformations. The present study used this murine model to screen amniotic fluid for biomarkers that could potentially discriminate between FAS-positive and FAS-negative pregnancies. METHODS B6J and B6N litters were treated with alcohol (exposed) or saline (control) on day 8 of gestation. Amniotic fluid aspirated on day 17 (n = 6 replicate litters per group) was subjected to trypsin digestion for analysis by matrix-assisted laser desorption–time of flight mass spectrometry with the aid of denoising algorithms, statistical testing, and classification methods. RESULTS We identified several peaks in the proteomics screen that were reduced consistently and specifically in exposed B6J litters. Preliminary characterization by liquid chromatography tandem mass spectrometry and multidimensional protein identification mapped the reduced peaks to alpha fetoprotein (AFP). The predictive strength of AFP deficiency as a biomarker for FAS-positive litters was confirmed by area under the receiver operating characteristic curve. CONCLUSIONS These findings in genetically susceptible mice support clinical observations in maternal serum that implicate a decrease in AFP levels following prenatal alcohol damage. PMID:18240165

  16. A long-term study of the effects of antiviral therapy on survival of patients with HBV-associated hepatocellular carcinoma (HCC) following local tumor ablation.

    Science.gov (United States)

    Hann, Hie-Won; Coben, Robert; Brown, Daniel; Needleman, Laurence; Rosato, Ernest; Min, Albert; Hann, Richard S; Park, Kyong Bin; Dunn, Stephen; DiMarino, Anthony J

    2014-04-01

    The ultimate goal of antiviral therapy for chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC). Earlier we reported favorable effects of antiviral therapy on survival of HCC patients following curative tumor ablation (Int J Cancer online 14 April 2010; doi: 10.1002/ijc.25382). It was the first observation made in the United States. We now report 12 year follow-up of this patient group. CHB patients with no prior antiviral therapy with a single HCC (≤ 7 cm) were studied. All patients underwent local tumor ablation as their first option. Patients diagnosed before 1999 received no antiviral treatment while those diagnosed after 1999 received antiviral treatment. Survival between the treated and untreated groups was compared. Among 555 HCC patients seen at our clinic between 1991 and 2013, 25 subjects were eligible. Nine subjects (all male patients, median age 53 years [46-66]) did not receive antiviral therapy while 16 (14 male patients, median age 56 years [20-73]) received treatment. Between the two groups, there was no difference in their median tumor size and levels of alpha-fetoprotein and albumin. However, the survival was significantly different (P = 0.001): the median survival of the untreated was 16 months (3-36 months) while that of the treated was 80 months (15-152 months). Fourteen of 16 treated patients are alive to date with two longest survivors alive for ≥ 151 months. In conclusion, concomitant antiviral therapy for CHB patients with HCC reduces and prevents new/recurrent tumor and improves survival. This novel treatment strategy offers an alternative to liver transplantation in patients with HBV-associated HCC. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  17. A clear cell adenocarcinoma of the gallbladder with hepatoid differentiation: case report and review of literature

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    Zhang C

    2016-09-01

    Full Text Available Chengsheng Zhang,1,2 Wei Zhang,1,2 Dianbin Mu,1 Xuetao Shi,1 Lei Zhao1,2 1Department of Hepatobiliary Surgery, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Science, 2School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China Abstract: An 80-year-old male was referred to our department for a gallbladder mass. He denied any history of alcohol consumption or cholecystitis and smoking. Hepatitis B surface antigen test and antihepatitis C antibody test were found to be negative. Serum carbohydrate antigen 19-9 (CA19-9 and carcinoembryonic antigen were elevated (CA19-9 was 59.92 U/mL and carcinoembryonic antigen was 12.64 ng/mL, whereas alpha-fetoprotein was below the normal limit (2.46 ng/mL. Computed tomography scan revealed a solid mass with measurements of 4.6×5.6×7.1 cm, which nearly filled the whole gallbladder space. Radical cholecystectomy, including segments IV B and V of the liver and lymphadenectomy, was performed. The neoplasm in gallbladder was completely resected, and the patient obtained a negative margin. Histological and immunohistochemical profile suggested a clear cell adenocarcinoma of the gallbladder with hepatoid differentiation. After reviewing the literature, we reported that this case is the first identified case of cell adenocarcinoma of the gallbladder with extensive hepatoid differentiation. However, clinical features of clear cell adenocarcinoma with hepatoid differentiation remain unclear due to the extremely rare incidence. There was no indication of adjuvant chemotherapy and no literature has been reported on the application of chemotherapy. This case showed a promising clinical outcome after curative resection, which indicated that surgical treatment could be potentially considered for suitable patients. Keywords: gallbladder, clear cell adenocarcinoma, hepatoid differentiation 

  18. Tumors of the liver; a ten year study in Children Medical Center

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    Farahmand F

    2007-06-01

    Full Text Available Background: The aim of this study was to review the frequency, histopathology and outcome in children with tumors of the liver. Methods: Included in this retrospective/descriptive study were 30 children treated for liver tumors from 1375-1384 (ca. 1996-2005, at Children’s Hospital Medical Center, Tehran, Iran. We included the clinical, radiologic, and pathologic data of our patients, focusing on the frequency, etiology and outcome. Results: Patient ages ranged from three months to 12 years (median 3.8 years, with 18 males (60% and 12 females (40%. Of these, 17 patients had hepatoblastoma (55.66%, including 13 males and four females, with an age range of six months to five years. Four cases (13.33% had neuroblastoma. Hepatocellular carcinoma (HCC was found in three cases (10%, all of whom were carriers of hepatitis B. Two cases (6.66% were diagnosed with mesenchymal hamartoma, two cases (6.66% with hemangioendothelioma and two cases (6.66% with rhabdomyosarcoma and leiomyosarcoma of the biliary tract. Abdominal swelling and hepatomegaly were seen in all of patients. Jaundice was observed in two cases. Serum alpha-fetoprotein levels greater than 500 ng/ml were seen in 17 cases (56.66%. All patients were receiving specific treatment. The three-year survival rate was 65% for hepatoblastoma and 2% for HCC Conclusion: With the introduction of specific treatment, the survival rate for children with tumors of the liver has significantly increased. Further improvement can be achieved using diagnostic biopsy for hepatoblastoma, although it may result in complications, and preoperative chemotherapy followed by complete surgical excision (per International Society of Pediatric Oncology guidelines, yielding an outstanding survival rate of 80%.

  19. PIVKA-II is a useful tool for diagnostic characterization of ultrasound-detected liver nodules in cirrhotic patients.

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    Saitta, Carlo; Raffa, Giuseppina; Alibrandi, Angela; Brancatelli, Santa; Lombardo, Daniele; Tripodi, Gianluca; Raimondo, Giovanni; Pollicino, Teresa

    2017-06-01

    Protein induced by vitamin K absence-II (PIVKA-II) is a potential screening marker for hepatocellular carcinoma (HCC). Limited data are available about its utility in discriminating neoplastic from regenerative nodules at ultrasonography (US) evaluation in cirrhotic patients. Aim of this study was to investigate the diagnostic utility of PIVKA-II in cases showing liver nodules of uncertain diagnosis at US.Ninety cirrhotics with US evidence of liver nodule(s) were enrolled. All patients underwent blood sampling within 1 week of US and were thereafter followed up. HCC was confirmed in 40/90 cases, and in all cases it was in a very early/early stage. All sera were tested for PIVKA-II and alpha-fetoprotein (AFP) at the end of follow-up. PIVKA-II at a cut off of 60 mAU/mL was significantly associated with HCC at both univariate and multivariate analysis (P = .016 and P = .032, respectively). AFP at a cut off of 6.5 ng/mL was not associated with HCC at univariate analysis (P = .246). ROC curves showed that PIVKA-II had 60% sensitivity, 88% specificity, 80% positive predictive value (PPV), and 73% negative predictive value (NPV), whereas AFP had 67% sensitivity, 68% specificity, 63% PPV, and 72% NPV. AUROC curves showed that the combination of both biomarkers increased the diagnostic accuracy for HCC (AUC 0.76; sensitivity 70%, specificity 94%, PPV 91%, and NPV 79%).In conclusion, PIVKA-II is a useful tool for the diagnostic definition of US-detected liver nodules in cirrhotic patients, and it provides high diagnostic accuracy for HCC when combined with AFP.

  20. Analysis of RIA standard curve by log-logistic and cubic log-logit models

    International Nuclear Information System (INIS)

    Yamada, Hideo; Kuroda, Akira; Yatabe, Tami; Inaba, Taeko; Chiba, Kazuo

    1981-01-01

    In order to improve goodness-of-fit in RIA standard analysis, programs for computing log-logistic and cubic log-logit were written in BASIC using personal computer P-6060 (Olivetti). Iterative least square method of Taylor series was applied for non-linear estimation of logistic and log-logistic. Hear ''log-logistic'' represents Y = (a - d)/(1 + (log(X)/c)sup(b)) + d As weights either 1, 1/var(Y) or 1/σ 2 were used in logistic or log-logistic and either Y 2 (1 - Y) 2 , Y 2 (1 - Y) 2 /var(Y), or Y 2 (1 - Y) 2 /σ 2 were used in quadratic or cubic log-logit. The term var(Y) represents squares of pure error and σ 2 represents estimated variance calculated using a following equation log(σ 2 + 1) = log(A) + J log(y). As indicators for goodness-of-fit, MSL/S sub(e)sup(2), CMD% and WRV (see text) were used. Better regression was obtained in case of alpha-fetoprotein by log-logistic than by logistic. Cortisol standard curve was much better fitted with cubic log-logit than quadratic log-logit. Predicted precision of AFP standard curve was below 5% in log-logistic in stead of 8% in logistic analysis. Predicted precision obtained using cubic log-logit was about five times lower than that with quadratic log-logit. Importance of selecting good models in RIA data processing was stressed in conjunction with intrinsic precision of radioimmunoassay system indicated by predicted precision. (author)

  1. Surveillance after initial surgery for pediatric and adolescent girls with stage I ovarian germ cell tumors: report from the Children's Oncology Group.

    Science.gov (United States)

    Billmire, Deborah F; Cullen, John W; Rescorla, Frederick J; Davis, Mary; Schlatter, Marc G; Olson, Thomas A; Malogolowkin, Marcio H; Pashankar, Farzana; Villaluna, Doojduen; Krailo, Mark; Egler, Rachel A; Rodriguez-Galindo, Carlos; Frazier, A Lindsay

    2014-02-10

    To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection. Between November 2003 and July 2011, girls age 0 to 16 years with stage I MOGCT were enrolled onto Children's Oncology Group study AGCT0132. Required histology included yolk sac, embryonal carcinoma, or choriocarcinoma. Surveillance included measurement of serum tumor markers and radiologic imaging at defined intervals. In those with residual or recurrent disease, chemotherapy with compressed PEB (cisplatin, etoposide, and bleomycin) was initiated every 3 weeks for three cycles (cisplatin 33 mg/m(2) on days 1 to 3, etoposide 167 mg/m(2) on days 1 to 3, bleomycin 15 U/m(2) on day 1). Survivor functions for event-free survival (EFS) and OS were estimated using the Kaplan-Meier method. Twenty-five girls (median age, 12 years) with stage I MOGCT were enrolled onto AGCT0132. Twenty-three patients had elevated alpha-fetoprotein (AFP) at diagnosis. Predominant histology was yolk sac. After a median follow-up of 42 months, 12 patients had evidence of persistent or recurrent disease (4-year EFS, 52%; 95% CI, 31% to 69%). Median time to recurrence was 2 months. All patients had elevated AFP at recurrence; six had localized disease, two had metastatic disease, and four had tumor marker elevation only. Eleven of 12 patients experiencing relapse received successful salvage chemotherapy (4-year OS, 96%; 95% CI, 74% to 99%). Fifty percent of patients with stage I pediatric MOGCT can be spared chemotherapy; treatment for those who experience recurrence preserves OS. Further study is needed to identify the factors that predict recurrence and whether this strategy can be extended successfully to older adolescents and young adults.

  2. Hepatocyte growth factor incorporated chitosan nanoparticles augment the differentiation of stem cell into hepatocytes for the recovery of liver cirrhosis in mice

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    Rose Chellan

    2011-04-01

    Full Text Available Abstract Background Short half-life and low levels of growth factors in the niche of injured microenvironment necessitates the exogenous and sustainable delivery of growth factors along with stem cells to augment the regeneration of injured tissues. Methods Here, recombinant human hepatocyte growth factor (HGF was incorporated into chitosan nanoparticles (CNP by ionic gelation method and studied for its morphological and physiological characteristics. Cirrhotic mice received either hematopoietic stem cells (HSC or mesenchymal stemcells (MSC with or without HGF incorporated chitosan nanoparticles (HGF-CNP and saline as control. Biochemical, histological, immunostaining and gene expression assays were carried out using serum and liver tissue samples. One way analysis of variance was used for statics application Results Serum levels of selected liver protein and enzymes were significantly increased in the combination of MSC and HGF-CNP (MSC+HGF-CNP treated group. Immunopositive staining for albumin (Alb and cytokeratin 18 (CK18, and reverse transcription-polymerase chain reaction (RT-PCR for Alb, alpha fetoprotein (AFP, CK18, cytokeratin 19 (CK19 ascertained that MSC-HGF-CNP treatment could be an effective combination to repopulate liver parenchymal cells in the liver cirrhosis. Zymogram and western blotting for matrix metalloproteinases 2 and 9 (MMP2 and MMP9 revealed that MMP2 actively involved in the fibrolysis of cirrhotic tissue. Immunostaining for alpha smooth muscle actin (αSMA and type I collagen showed decreased expression in the MSC+HGF-CNP treatment. These results indicated that HGF-CNP enhanced the differentiation of stem cells into hepatocytes and supported the reversal of fibrolysis of extracellular matrix (ECM. Conclusion Bone marrow stem cells were isolated, characterized and transplanted in mice model. Biodegradable biopolymeric nanoparticles were prepared with the pleotrophic protein molecule and it worked well for the

  3. Volumetric parameters on FDG PET can predict early intrahepatic recurrence-free survival in patients with hepatocellular carcinoma after curative surgical resection

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    Lee, Jeong Won [Catholic Kwandong University College of Medicine, Department of Nuclear Medicine, Incheon (Korea, Republic of); Hwang, Sang Hyun; Kim, Hyun Jeong; Kim, Dongwoo; Cho, Arthur; Yun, Mijin [Yonsei University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of)

    2017-11-15

    This study assessed the prognostic values of volumetric parameters on {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting early intrahepatic recurrence-free survival (RFS) after curative resection in patients with hepatocellular carcinoma (HCC). A retrospective analysis was performed on 242 patients with HCC who underwent staging FDG PET and subsequent curative surgical resection. The tumor-to-non-tumorous liver uptake ratio, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the HCC lesions on PET were measured. The prognostic values of clinical factors and PET parameters for predicting overall RFS, overall survival (OS), extrahepatic RFS, and early and late intrahepatic RFS were assessed. The median follow-up period was 54.7 months, during which 110 patients (45.5%) experienced HCC recurrence and 62 (25.6%) died. Patients with extrahepatic and early intrahepatic recurrence showed worse OS than did those with no recurrence or late intrahepatic recurrence (p < 0.001). Serum bilirubin level, MTV, and TLG were independent prognostic factors for overall RFS and OS (p < 0.05). Only MTV and TLG were prognostic for extrahepatic RFS (p < 0.05). Serum alpha-fetoprotein and bilirubin levels, MTV, and TLG were prognostic for early intrahepatic RFS (p < 0.05) and hepatitis C virus (HCV) positivity and serum albumin level were independently prognostic for late intrahepatic RFS (p < 0.05). Intrahepatic recurrence showed different prognoses according to the time interval of recurrence in which early recurrence had as poor survival as extrahepatic recurrence. MTV and TLG on initial staging PET were significant independent factors for predicting early intrahepatic and extrahepatic RFS in patients with HCC after curative resection. Only HCV positivity and serum albumin level were significant for late intrahepatic RFS, which is mainly attributable to the de novo formation of new primary HCC. (orig.)

  4. Review of Growth Inhibitory Peptide as a biotherapeutic agent for tumor growth, adhesion, and metastasis.

    Science.gov (United States)

    Muehlemann, M; Miller, K D; Dauphinee, M; Mizejewski, G J

    2005-09-01

    This review surveys the biological activities of an alpha-fetoprotein (AFP) derived peptide termed the Growth Inhibitory Peptide (GIP), which is a synthetic 34 amino acid segment produced from the full length 590 amino acid AFP molecule. The GIP has been shown to be growth-suppressive in both fetal and tumor cells but not in adult terminally-differentiated cells. The mechanism of action of this peptide has not been fully elucidated; however, GIP is highly interactive at the plasma membrane surface in cellular events such as endocytosis, cell contact inhibition and cytoskeleton-induced cell shape changes. The GIP was shown to be growth-suppressive in nine human tumor types and to suppress the spread of tumor infiltrates and metastases in human and mouse mammary cancers. The AFP-derived peptide and its subfragments were also shown to inhibit tumor cell adhesion to extracellular matrix (ECM) proteins and to block platelet aggregation; thus it was expected that the GIP would inhibit cell spreading/migration and metastatic infiltration into host tissues such as lung and pancreas. It was further found that the cyclic versus linear configuration of GIP determined its biological and anti-cancer efficacy. Genbank amino acid sequence identities with a variety of integrin alpha/beta chain proteins supported the GIP's linkage to inhibition of tumor cell adhesion and platelet aggregation. The combined properties of tumor growth suppression, prevention of tumor cell-to-ECM adhesion, and inhibition of platelet aggregation indicate that tumor-to-platelet interactions present promising targets for GIP as an anti-metastatic agent. Finally, based on cholinergic studies, it was proposed that GIP could influence the enzymatic activity of membrane acetylcholinesterases during tumor growth and metastasis. It was concluded that the GIP derived from full-length AFP represents a growth inhibitory motif possessing instrinsic properties that allow it to interfere in cell surface events such

  5. Proliferation and differentiation potential of mouse adult hepatic progenitor cells cultured in vitro.

    Science.gov (United States)

    Song, Lujun; Wang, Hongshan; Gao, Xiaodong; Shen, Kuntang; Niu, Weixin; Qin, Xinyu

    2010-02-01

    This study aimed to isolate the stem cells or progenitors, if exist, from normal adult mouse liver and investigate their potential of proliferation and differentiation. Hepatocytes were isolated by modified two-step liver perfusion method and centrifugation, and then cultured in modified serumcontaining DMEM for observation more than 60 days. Immunofluorescence technique was applied to check the hepatocytes and to examine the formation of colonies with albumin, alpha-fetoprotein (AFP) and cytokeratin 19 (CK19). Results showed that some hepatocytes that were strongly positive for hepatocyte specific markers albumin on Day 1 in culture, could be activated at Days 2-3, followed by rapid proliferation and formation of colonies. The colonies could expand continually for more than 60 days. On Day 5, all the cells in the colony expressed hepatic stem cell (HSC) markers AFP. With the time of culture, some cells in colonies lost ability to divide at Days 13-15, and differentiated into cells which had a large cytoplasm and some two nuclei, similar to the appearance of mature hepatocytes morphologically. These differentiated cells demonstrated strong expression of albumin. Around Day 30, some big cells appeared in colonies and expressed bile duct cell marker CK19. Therefore, this subpopulation of mouse hepatocytes could acquire some characteristics of immature hepatocytes and showed the profile of hepatic progenitor cells with a high proliferating ability and bi-potential of differentiation. They were isolated from normal adult mouse, hence, named adult hepatic progenitor cells (AHPCs). Mouse AHPCs may be used as an HSC model for hepatocytes transplantation and hepatopathy study.

  6. Evaluation of the Clinical Significance of Serum Carcinoembryonic Antigen in Patients with Resectable Gastric Adenocarcinoma.

    Science.gov (United States)

    Dang, Yuan; Ouyang, Xiaojuan; Wang, Kai; Zhang, Fan; Huang, Qiaojia

    2016-04-01

    Carcinoembryonic antigen (CEA) is the most commonly used tumor marker for gastrointestinal cancers but its value for resectable gastric adenocarcinoma (RGA) patients in areas of high GA incidence is uncertain. We retrospectively studied 400 subjects with RGA from the Fujian Province in China, which has a high incidence of GA. Patients had surgery between January 2010 and December 2013. CEA was measured and correlated to pathology. High pretreatment serum CEA (>5 ng/mL) was associated with patient age (p = 0.000), tumor size (p = 0.008), and T and N stages (p = 0.002, p = 0.032, respectively), alpha fetoprotein (p = 0.014), and CA19-9 (p = 0.000). High CEA was significantly associated with poor overall survival. Overall survival in the whole group of patients was 63.8%, whereas it was only 42.9% in the high CEA group (p = 0.0001). Mean overall survival for high CEA patients was significantly shorter than patients with low CEA (36.5 ± 2.63 months vs. 47.4 ± 0.98 months, p = 0.000). Multivariate analysis confirmed that pretreatment serum CEA was an independent prognostic factor for increased death risk. Additionally, mean CEA in 45 high CEA patients was reduced after surgery. Pretreatment serum CEA may help to predict survival for patients with RGA in high GA incidence areas. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  7. Cross-talk-free simultaneous fluoroimmunoassay of two biomarkers based on dual-color quantum dots

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    Cao Zhijuan; Li Huan [School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Lau Choiwan, E-mail: cyliu@shmu.edu.cn [School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Zhang Yuhao, E-mail: zhang.yuhao@zs-hospital.sh.cn [Department of Neurology, Zhongshan Hospital, 180 Fenglin Road, Shanghai 200032 (China)

    2011-07-18

    Highlights: {yields} A new cross-talk-free duplex fluoroimmunoassay for cancer related biomarkers was developed using multiple QD as detection elements with the LOD of 0.625 ng/mL. {yields} A fast homogeneous immunoreaction as well as a simple heterogeneous separation process was achieved by the coupling of the submicrometer-sized polystyrene microspheres as the carrier and the 96-well filter plate as the reaction and separation container. {yields} This new approach could also be extended to detect other biomarkers relating to other cancers, such as alpha fetoprotein and prostate specific antigen associated with liver cancer and prostrate cancer, etc. - Abstract: In this article, we demonstrate the fabrication and simultaneous fluorescent detection of two biomarkers related to lung cancer. Polystyrene microspheres (PSM) were introduced as biomolecular immobilizing carriers and a 96-well filter plate was used as the separation platform. The whole experiment could be effectively carried out in a homogeneous system, as exemplified by the detection of carcinoembryonic antigen (CEA) and neuron specific enolase (NSE). First, two capture antibodies for CEA and NSE were immobilized on the PSM surface. Next, they reacted successively with two antigens and two modified detection antibodies. Finally, these two biomarkers could be recognized by streptavidin-conjugated quantum dots (QD) and goat-anti-FITC conjugated QD with a detection limit of 0.625 ng mL{sup -1}, which was lower than the clinical cut-off level. The protocol showed good precision within 6.36% and good recovery in the range of 90.86-105.02%. Compared with several other assay formats reported previously, our new technique is competitive or even better. Furthermore, the immunosensor was successfully illustrated in 20 serum samples. Overall, this new immunoassay offers a promising alternative for the detection of biomarkers related to cancer diseases, taking advantage of simplicity, specificity, sensitivity and

  8. Intraoperative blood salvage during liver transplantation in patients with hepatocellular carcinoma: efficiency of leukocyte depletion filters in the removal of tumor cells.

    Science.gov (United States)

    Liang, Ting-Bo; Li, Dong-Lin; Liang, Liang; Li, Jun-Jian; Bai, Xue-Li; Yu, Wei; Wang, Wei-Lin; Shen, Yan; Zhang, Min; Zheng, Shu-Sen

    2008-03-27

    Intraoperative blood salvage (IBS) reduces homologous transfusion in orthotopic liver transplantation (OLT), but may carry with it the risk of reinfusing tumor cells in patients with hepatocellular carcinoma (HCC). The use of leukocyte depletion filters (LDFs) for the removal of tumor cells is rarely reported in clinical OLT. The aims of this study were to evaluate the frequency of tumor cell contamination in surgical field during OLT for HCC recipients and to investigate the efficiency of additional LDFs for eliminating tumor cells from IBS. Thirty-two HCC patients with preoperatively elevated serum alpha-fetoprotein (AFP) underwent OLT. The blood from the surgical field was collected and processed by an autotransfusion device (Cell Saver 5), followed by 2 consecutive LDF filtrations. The HCC cells in IBS samples and filtered samples were determined using a nested RT-PCR technique to detect the AFP mRNA. The shed blood samples from 20 (62.5%) of the 32 HCC patients were contaminated with HCC cells and 15 of them remained positive after Cell Saver processing. Patients within the Milan or UCSF criteria were less likely to have HCC cell contamination and the contaminated HCC cells were more likely to be removed by the Cell Saver in these patients as compared to other patients (P<0.01). After filtration through an additional LDF, most cases (13/15) became negative except for those with ruptured tumors (P<0.05). Our results suggest that blood filtration with the LDF can efficiently remove tumor cells and the use of an additional LDF after use of the Cell Saver could markedly reduce the risk of tumor cell reintroduction during the OLT in HCC recipients with nonruptured tumors.

  9. Specific diagnosis of hepatocellular carcinoma by delayed hepatobiliary imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Y.; Nakano, S.; Ibuka, K.; Hashizume, T.; Noguchi, A.; Sasaki, Y.; Imaoka, S.; Fujita, M.; Kawamoto, S.; Kasugai, H.

    1986-01-15

    For assessment of the value of delayed hepatobiliary imaging with technetium 99m (/sup 99m/Tc)-(Sn)-N-pyridoxyl-5-methyltryptophan (/sup 99m/Tc-PMT) for specific diagnosis of hepatocellular carcinoma, 88 patients with various malignant and benign liver diseases (49 with hepatocellular carcinoma, 4 with cholangiocellular carcinoma, 10 with metastatic liver carcinoma, 2 with liver cysts, 2 with liver hemangioma, 1 with liver abscess, 2 with intrahepatic lithiasis, 12 with liver cirrhosis, and 6 with chronic hepatitis) were studied. In 20 (41%) of the 49 patients with hepatocellular carcinoma, greater uptake of /sup 99m/Tc-PMT by the tumor than by the surrounding liver tissue was seen in delayed hepatobiliary images, whereas in eight patients (16%), equilibrated uptake was seen. No increased uptake of the radioisotope by hepatic lesions was seen in 21 patients with localized liver diseases other than hepatoma. Moreover, in 18 patients with diffuse liver diseases, no focal accumulation of the radioisotope was seen in delayed /sup 99m/Tc-PMT images. In addition, of 28 patients with hepatocellular carcinoma in whom the serum alpha-fetoprotein level showed little or no increase, 12 showed increased uptake of /sup 99m/Tc-PMT by the tumor. In assessing delayed /sup 99m/Tc-PMT images, however, it was necessary to consider following complications: accumulation of tracer in obstructed and dilated biliary trees; retention of radioactivity in nonneoplastic liver tissues; difficulties in evaluating /sup 99m/Tc-PMT uptake by small hepatic tumors; overlapping of radioactivity in the gut and gallbladder in delayed /sup 99m/Tc-PMT images of tumors. This study indicates that delayed /sup 99m/Tc-PMT images can be useful in the diagnosis of hepatocellular carcinoma.

  10. Current concepts in rational therapy for haemochromatosis.

    Science.gov (United States)

    Crawford, D H; Halliday, J W

    1991-06-01

    Genetic haemochromatosis is characterised by an inappropriately high rate of iron absorption by the small intestine. The disease is transmitted as an autosomal recessive condition. The gene frequency in the Caucasian population is approximately 1 in 20 and the disease frequency is 1 in 400. Excessive iron deposition occurs in the liver, pancreas, heart, pituitary and joints and hepatic iron concentrations above approximately 400 mumol/g dry weight are always associated with fibrosis and usually with cirrhosis and progressive liver failure. Accurate diagnosis depends upon the demonstration of elevated hepatic iron stores. An hepatic iron index [hepatic iron concentration (in mumol/g dry weight) divided by patient age] of greater than 2.0 distinguishes homozygous subjects from the other conditions in which slight increases in hepatic iron concentration may occur, e.g. in a subject heterozygous for haemochromatosis or alcoholic liver disease. If cirrhosis is present, patients are at a high risk of developing hepatocellular carcinoma. Therefore, they should undergo regular abdominal ultrasound and alpha-fetoprotein estimation. In the absence of cirrhosis, phlebotomy restores life expectancy to normal. Venesection should be continued until all excess iron stores are removed as judged by failure of a rise in haemoglobin concentration on cessation of phlebotomy. Screening of first degree relatives should commence from a young age (e.g. 10 years). If serum ferritin or transferrin saturation are abnormal, liver biopsy should be undertaken. HLA typing of the family allows for the identification of those siblings who are most likely to develop the disease. Secondary iron overload is often multifactorial in origin. Iron chelation therapy with subcutaneous deferoxamine (desferrioxamine) should only commence after careful consideration of the potential benefits in each individual patient.

  11. Adult-derived human liver mesenchymal-like cells as a potential progenitor reservoir of hepatocytes?

    Science.gov (United States)

    Najimi, Mustapha; Khuu, Dung Ngoc; Lysy, Philippe Antoine; Jazouli, Nawal; Abarca, Jorge; Sempoux, Christine; Sokal, Etienne Marc

    2007-01-01

    It is currently accepted that adult tissues may develop and maintain their own stem cell pools. Because of their higher safety profile, adult stem cells may represent an ideal candidate cell source to be used for liver cell therapies. We therefore evaluated the differentiation potential of mesenchymal-like cells isolated from adult human livers. Mesenchymal-like cells were isolated from enzymatically digested adult human liver and expanded in vitro. Cell characterization was performed using flow cytometry, RT-PCR, and immunofluorescence, whereas the differentiation potential was evaluated both in vitro after incubation with specific media and in vivo after intrasplenic transplantation of uPA(+/+)-SCID and SCID mice. Adult-derived human liver mesenchymal-like cells expressed both hepatic and mesenchymal markers among which albumin, CYP3A4, vimentin, and alpha-smooth muscle actin. In vitro differentiation studies demonstrated that these mesenchymal-like cells are preferentially determined to differentiate into hepatocyte-like cells. Ten weeks following intrasplenic transplantation into uPA(+/+)-SCID mice, recipient livers showed the presence of human hepatocytic cell nodules positive for human albumin, prealbumin, and alpha-fetoprotein. In SCID transplanted liver mice, human hepatocyte-like cells were mostly found near vascular structures 56 days posttransplantation. In conclusion, the ability of isolated adult-derived liver mesenchymal stem-like cells to proliferate and differentiate into hepatocyte-like cells both in vitro and in vivo leads to propose them as an attractive expandable cell source for stem cell therapy in human liver diseases.

  12. Transarterial chemoembolization versus resection for intermediate-stage (BCLC B hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Jun Young Kim

    2016-06-01

    Full Text Available Background/Aims: Several studies have suggested that surgical resection (SR can provide a survival benefit over transarterial chemoembolization (TACE for hepatocellular carcinoma (HCC at the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC staging system. However, the criteria for SR remain to be determined. This study compared the long-term outcome of intermediate-stage HCC patients treated by either TACE or SR as a primary treatment modality, with the aim of identifying the patient subgroup that gained a survival benefit by either modality. Methods: In total, 277 BCLC intermediate-stage HCC patients treated by either TACE (N=225 or SR (N=52 were analyzed. Results: The overall median survival time was significantly better for SR than TACE (61 vs. 30 months, P=0.002. Decision-tree analysis divided patients into seven nodes based on tumor size and number, serum alpha-fetoprotein (AFP level, and Child-Pugh score, and these were then simplified into four subgroups (B1–B4 based on similarities in the overall hazard rate. SR provided a significant survival benefit in subgroup B2, characterized by ‘oligo’ (2–4 nodules of intermediate size (5–10 cm when the AFP levels was <400 ng/ml, or ‘oligo’ (2–4 nodules of small to intermediate size (<10 cm plus a Child-Pugh score of 5 when the AFP level was ≥400 ng/mL (median survival 73 vs. 28 months for SR vs. TACE respectively; P=0.014. The survival rate did not differ significantly between SR and TACE in the other subgroups (B1 and B3. Conclusion: SR provided a survival benefit over TACE in intermediate-stage HCC, especially for patients meeting certain criteria. Re-establishing the criteria for optimal treatment modalities in this stage of HCC is needed to improve survival rates.

  13. Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association.

    Science.gov (United States)

    Shimada, Hideaki; Noie, Tamaki; Ohashi, Manabu; Oba, Koji; Takahashi, Yutaka

    2014-01-01

    The aim of this review was to evaluate the clinical significance of serum tumor markers, particularly CEA, CA19-9, and CA72-4, in patients with gastric cancer. A systematic literature search was performed using PubMed/MEDLINE with the keywords "gastric cancer" and "tumor marker," to select 4,925 relevant reports published before the end of November 2012. A total of 187 publications contained data for CEA and CA19-9, and 19 publications contained data related to all three tumor markers. The positive rates were 21.1 % for CEA, 27.8 % for CA19-9, and 30.0 % for CA72-4. These three markers were significantly associated with tumor stage and patient survival. Serum markers are not useful for early cancer, but they are useful for detecting recurrence and distant metastasis, predicting patient survival, and monitoring after surgery. Tumor marker monitoring may be useful for patients after surgery because the positive conversion of tumor markers usually occurs 2-3 months before imaging abnormalities. Among other tumor markers, alpha-fetoprotein (AFP) is useful for detecting and predicting liver metastases. Moreover, CA125 and sialyl Tn antigens (STN) are useful for detecting peritoneal metastases. Although no prospective trial has yet been completed to evaluate the clinical significance of these serum markers, this literature survey suggests that combinations of CEA, CA19-9, and CA72-4 are the most effective ways for staging before surgery or chemotherapy. In particular, monitoring tumor markers that were elevated before surgery or chemotherapy could be useful for detection of recurrence or evaluation of the response.

  14. Simultaneous quantitative detection of multiple tumor markers with a rapid and sensitive multicolor quantum dots based immunochromatographic test strip.

    Science.gov (United States)

    Wang, Chunying; Hou, Fei; Ma, Yicai

    2015-06-15

    A novel multicolor quantum dots (QDs) based immunochromatographic test strip (ICTS) was developed for simultaneous quantitative detection of multiple tumor markers, by utilizing alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) as models. The immunosensor could realize simultaneous quantitative detection of tumor markers with only one test line and one control line on the nitrocellulose membrane (NC membrane) due to the introduction of multicolor QDs. In this method, a mixture of mouse anti-AFP McAb and mouse anti-CEA McAb was coated on NC membrane as test line and goat anti-mouse IgG antibody was coated as control line. Anti-AFP McAb-QDs546 conjugates and anti-CEA McAb-QDs620 conjugates were mixed and applied to the conjugate pad. Simultaneous quantitative detection of multiple tumor markers was achieved by detecting the fluorescence intensity of captured QDs labels on test line and control line using a test strip reader. Under the optimum conditions, AFP and CEA could be detected as low as 3 ng/mL and 2 ng/mL in 15 min with a sample volume of 80 μL, and no obvious cross-reactivity was observed. The immunosensor was validated with 130 clinical samples and in which it exhibited high sensitivity (93% for AFP and 87% for CEA) and specificity (94% for AFP and 97% for CEA). The immunosensor also demonstrated high recoveries (87.5-113% for AFP and 90-97.3% for CEA) and low relative standard deviations (RSDs) (2.8-6.2% for AFP and 4.9-9.6% for CEA) when testing spiked human serum. This novel multicolor QDs based ICTS provides an easy and rapid, simultaneous quantitative detecting strategy for point-of-care testing of tumor markers. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Multiplex detection of tumor markers with photonic suspension array

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Yuanjin; Zhao Xiangwei [State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Pei Xiaoping [Department of Hematology, Affiliated Zhongda Hospital, Southeast University, Nanjing 210009 (China); Hu Jing; Zhao Wenju [State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Chen Baoan [Department of Hematology, Affiliated Zhongda Hospital, Southeast University, Nanjing 210009 (China); Gu Zhongze [State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Laboratory of Environment and Biosafety, Research Institute of Southeast University in Suzhou, Dushu Lake Higher Education Town, Suzhou 215123 (China)], E-mail: gu@seu.edu.cn

    2009-02-02

    A novel photonic suspension array was developed for multiplex immunoassay. The carries of this array were silica colloidal crystal beads (SCCBs). The codes of these carriers are the characteristic reflection peak originated from their structural periodicity, and therefore they do not suffer from fading, bleaching, quenching, and chemical instability. In addition, because no dyes or materials related with fluorescence are included, the fluorescence background of SCCBs is very low. With a sandwich format, the proposed suspension array was used for simultaneous multiplex detection of tumor markers in one test tube. The results showed that the four tumor markers, {alpha}-fetoprotein (AFP), carcinoembryonic antigen (CEA), carcinoma antigen 125 (CA 125) and carcinoma antigen 19-9 (CA 19-9) could be assayed in the ranges of 1.0-500 ng mL{sup -1}, 1.0-500 ng mL{sup -1}, 1.0-500 U mL{sup -1} and 3.0-500 U mL{sup -1} with limits of detection of 0.68 ng mL{sup -1}, 0.95 ng mL{sup -1}, 0.99 U mL{sup -1} and 2.30 U mL{sup -1} at 3{sigma}, respectively. The proposed array showed acceptable accuracy, detection reproducibility, storage stability and the results obtained were in acceptable agreement with those from parallel single-analyte test of practical clinical sera. This technique provides a new strategy for low cost, automated, and simultaneous multiplex immunoassay.

  16. Targeting Gene-Viro-Therapy with AFP driving Apoptin gene shows potent antitumor effect in hepatocarcinoma

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    Zhang Kang-Jian

    2012-02-01

    Full Text Available Abstract Background Gene therapy and viral therapy are used for cancer therapy for many years, but the results are less than satisfactory. Our aim was to construct a new recombinant adenovirus which is more efficient to kill hepatocarcinoma cells but more safe to normal cells. Methods By using the Cancer Targeting Gene-Viro-Therapy strategy, Apoptin, a promising cancer therapeutic gene was inserted into the double-regulated oncolytic adenovirus AD55 in which E1A gene was driven by alpha fetoprotein promoter along with a 55 kDa deletion in E1B gene to form AD55-Apoptin. The anti-tumor effects and safety were examined by western blotting, virus yield assay, real time polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide assay, Hoechst33342 staining, Fluorescence-activated cell sorting, xenograft tumor model, Immunohistochemical assay, liver function analysis and Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling assay. Results The recombinant virus AD55-Apoptin has more significant antitumor effect for hepatocelluar carcinoma cell lines (in vitro than that of AD55 and even ONYX-015 but no or little impair on normal cell lines. Furthermore, it also shows an obvious in vivo antitumor effect on the Huh-7 liver carcinoma xenograft in nude mice with bigger beginning tumor volume till about 425 mm3 but has no any damage on the function of liver. The induction of apoptosis is involved in AD55-Apoptin induced antitumor effects. Conclusion The AD55-Apoptin can be a potential anti-hepatoma agent with remarkable antitumor efficacy as well as higher safety in cancer targeting gene-viro-therapy system.

  17. Pineal yolk sac tumor: correlation between neuroimaging and pathological findings Tumor do seio endodérmico da pineal: correlação entre os achados patológicos e de neuroimagem

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    Taísa Davaus

    2007-06-01

    Full Text Available A 17-year-old boy presented with somnolence and mental confusion. Physical examination demonstrated motor disturbances. Laboratorial investigation showed elevated levels of alpha-fetoprotein in serum and cerebrospinal fluid. The CT scan revealed a heterogeneous mass at the pineal region. At the MRI, this lesion was hypointense on T1 and hyperintense on T2-weighted images, enhancing after contrast administration. The patient underwent a surgical biopsy, which defined the diagnosis of yolk sac tumor. We emphasize the correlation of neuroimaging and pathological findings of this rare pineal region tumor.Um menino de 17 anos de idade apresentou-se com sonolência e confusão mental. O exame físico demonstrou distúrbios motores. A investigação laboratorial revelou aumento dos níveis de alfafetoproteína no soro e no líquor. A TC de crânio revelou massa heterogênea na região pineal. À RM, a lesão era hipointensa em T1 e hiperintensa em T2, com realce após a administração de contraste. O paciente foi submetido a biópsia cirúrgica, a qual definiu o diagnóstico de tumor do seio endodérmico. Enfatizamos a correlação entre os achados patológicos e de neuroimagem deste raro tumor da região pineal.

  18. Proximity Hybridization-Regulated Immunoassay for Cell Surface Protein and Protein-Overexpressing Cancer Cells via Electrochemiluminescence.

    Science.gov (United States)

    Wang, Xiaofei; Gao, Hongfang; Qi, Honglan; Gao, Qiang; Zhang, Chengxiao

    2018-03-06

    A simple electrochemiluminescence (ECL) immunoassay based on a proximity hybridization-regulated strategy was developed for highly sensitive and specific detection of cell surface protein and protein-overexpressing cancer cells. A biosensor was fabricated by self-assembling a thiolated capture ss-DNA3 (partially hybridize with ss-DNA1 and ss-DNA2) and blocking with 6-mercapto-1-hexanol on a gold electrode surface. Target protein was simultaneously bound by two ss-DNA-tagged antibody probes (DNA1-Ab1 and DNA2-Ab2), while DNA1 and DNA2 were brought in sufficient proximity and hybridized with capture DNA3 on the surface of the biosensor. After ECL signal reagent Ru(phen) 3 2+ was intercalated into the hybridized ds-DNAs, ECL measurement was performed in the coreactant solution. A "signal on" proximity hybridization-regulated ECL immunoassay for alpha-fetoprotein (AFP) was developed. The ECL intensity increased with the increase of AFP concentration in the range of 0.05-20.0 ng/mL with a detection limit of 6.2 pg/mL. Moreover, the developed ECL method was successfully used to detect AFP-overexpressing cancer cells (MCF-7 cancer cells as model) with a detection limit of 620 cells/mL (∼60 MCF-7 cells in 100 μL of cell suspension) and discriminate AFP expression on different types of the living cell surface. This work for the first time reports a proximity hybridization-regulated ECL immunoassay for the detection of the cell surface protein on a living cell surface with good specificity and sensitivity. This simple, specific, and sensitive strategy is greatly promising for the detection of proteins and specific cells.

  19. Simulation analysis of 9033 cases of second trimester maternal serum screening for Down’s syndrome

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    Shu-fang JIANG

    2017-06-01

    Full Text Available Objective To reduce the screening positive rate (SPR and improve clinical efficiency of maternal serum screening for Down's syndrome. Methods Nine thousand and thirty-three cases of second trimester maternal serum screening for Down's syndrome were included from Apr. 2013 to Apr. 2014 in the present study. The screening results, all basic data and equation curves were analyzed retrospectively. Based on the data from the authors' laboratory, the important adjustment parameters were simulated. Combined with postnatal follow-up results, the quality and clinical performance of second trimester serum screening for Down's syndrome were evaluated. Results The SPR of second trimester serum screening for Down's syndrome was 6.69%(604/9033, the detection rate (DR was 75%(3/4, and FPR was 6.65%(601/9033. The median multiple of median (MOM of alpha-fetoprotein (AFP was low and SPR was high, and MOM of free human chorionic gonadotropin β subunit (free hCGβ were high and SPR was high, while MOM of unconjugated estriol (uE3 were a little bit low, and SPR was slightly high. Considering these three factors, it is believed that the screening positive rate is high. By the simulation adjustments of MOM value equations (AFP and free hCGβ and weight correction equation, the SPR reduced to 4.11%(371/9033 after recalculating the risk, FPR declined to 4.07%(368/9033, and no more Down's syndrome fetus were missed compared with postnatal follow-up results. Conclusion Based on a localized setting depending on the local laboratory data, we suggest that the MOM value distributions(AFP, free hCGβ and uE3 and maternal weight should be regularly adjusted since it is a useful way to reduce the false-positive rate and improve clinical efficiency of maternal serum screening for Down's syndrome. DOI: 10.11855/j.issn.0577-7402.2017.04.13

  20. Computer-aided assessment of hepatic contour abnormalities as an imaging biomarker for the prediction of hepatocellular carcinoma development in patients with chronic hepatitis C

    Energy Technology Data Exchange (ETDEWEB)

    Goshima, Satoshi [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, 501-1194 Gifu (Japan); Kanematsu, Masayuki, E-mail: masa_gif@yahoo.co.jp [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, 501-1194 Gifu (Japan); Kondo, Hiroshi; Watanabe, Haruo; Noda, Yoshifumi [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, 501-1194 Gifu (Japan); Fujita, Hiroshi [Department of Intelligent Image Information Division of Regeneration and Advanced Medical Sciences, Graduate School of Medicine, Gifu University, Gifu (Japan); Bae, Kyongtae T. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

    2015-05-15

    Highlights: • Hepatic contour was quantified and converted to hepatic fibrosis index (HFI). • HFI was a significant risk factor for HCC with an odds ratio of 26.4. • HFI may be an important imaging biomarker for managing cirrhotic patients. - Abstract: Purpose: To evaluate whether a hepatic fibrosis index (HFI), quantified on the basis of hepatic contour abnormality, is a risk factor for the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. Materials and methods: Our institutional review board approved this retrospective study and written informed consent was waved. During a 14-month period, consecutive 98 patients with chronic hepatitis C who had no medical history of HCC treatment (56 men and 42 women; mean age, 70.7 years; range, 48–91 years) were included in this study. Gadoxetic acid-enhanced hepatocyte specific phase was used to detect and analyze hepatic contour abnormality. Hepatic contour abnormality was quantified and converted to HFI using in-house proto-type software. We compared HFI between patients with (n = 54) and without HCC (n = 44). Serum levels of albumin, total bilirubin, aspartate transferase, alanine transferase, percent prothrombin time, platelet count, alpha-fetoprotein, protein induced by vitamin K absence-II, and HFI were tested as possible risk factors for the development of HCC by determining the odds ratio with logistic regression analysis. Results: HFIs were significantly higher in patients with HCC (0.58 ± 0.86) than those without (0.36 ± 0.11) (P < 0.001). Logistic analysis revealed that only HFI was a significant risk factor for HCC development with an odds ratio (95% confidence interval) of 26.4 (9.0–77.8) using a cutoff value of 0.395. Conclusion: The hepatic fibrosis index, generated using a computer-aided assessment of hepatic contour abnormality, may be a useful imaging biomarker for the prediction of HCC development in patients with chronic hepatitis C.

  1. The impact of severe hyperemesis gravidarum on the triple test screening results.

    Science.gov (United States)

    Peled, Yoav; Melamed, Nir; Krissi, Haim; Eitan, Ram; Yogev, Yariv; Pardo, Joseph

    2012-06-01

    we aimed to determine the influence of severe hyperemesis gravidarum on the interpretation of the triple test screen results. A retrospective, case control study. The study group included 73 women who were hospitalized due to severe hyperemesis gravidarum and data regarding triple screening test was available. Data was compared with a control group consisting of low-risk patients without hyperemesis gravidarum, who underwent the triple screening test in the same laboratory and matched to the study group by maternal age and gestational age at the time of screening in a 2:1 ratio. Overall, 219 gravid patients were included in the study, of whom 73 were diagnosed with severe hyperemesis gravidarum. Patients in the control group were characterized by higher weight at the time of triple test screen (53.7 ± 10.9 vs. 59.7 ± 14.3 years, p = 0.043). No difference was found in the level of Alpha-fetoprotein or unconjugated estriol (uE3) between the groups; however the level of hCG was significantly increased in women with severe hyperemesis gravidarum (1.2977 ± 0.82 vs. 1.0662 ± 0.53 MoM, p = 0.013). Increase in the level of hCG in women with severe hyperemesis gravidarum alter the results of triple test screen. This data should be incorporated when counseling patients regarding overall risk for chromosomal abnormalities.

  2. Radiofrequency ablation assisted by real-time virtual sonography for hepatocellular carcinoma inconspicuous under sonography and high-risk locations

    Directory of Open Access Journals (Sweden)

    Cheng-Han Lee

    2015-08-01

    Full Text Available Radiofrequency ablation (RFA is an effective and real-time targeting modality for small hepatocellular carcinomas (HCCs. However, mistargeting may occur when the target tumor is confused with cirrhotic nodules or because of the poor conspicuity of the index tumor under ultrasonography (US. Real-time virtual sonography (RVS can provide the same reconstruction computed tomography images as US images. The aim of this study is to investigate the usefulness of RVS-assisted RFA for HCCs that are inconspicuous or conspicuous under US. A total of 21 patients with 28 HCC tumors—divided into US inconspicuous and high-risk subgroup (3 tumors in 3 patients, US inconspicuous and nonhigh-risk subgroup (5 tumors in 4 patients, US conspicuous and high-risk subgroup (16 tumors in 14 patients, and US conspicuous and nonhigh-risk subgroup (4 tumors in 3 patients—underwent RVS-assisted RFA between May 2012 and June 2014 in our institution. The mean diameter of the nodules was 2.0 ± 1.1 cm. The results showed that the complete ablation rate is 87.5% (7/8 in the US undetectable group and 75% (15/20 in the US detectable group. A comparison between six tumors with incomplete ablation and 22 tumors with complete ablation showed higher alpha-fetoprotein level (mean, 1912 ng/mL vs. 112 ng/mL and larger tumor size (mean diameter, 26 mm vs. 16 mm in the incomplete ablation nodules (both p < 0.05. In conclusion, RVS-assisted RFA is useful for tumors that are difficult to detect under conventional US and may also be useful for tumors in high-risk locations because it may prevent complication induced by mistargeting.

  3. Role of MTDH, FOXM1 and microRNAs in Drug Resistance in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Xiangbing Meng

    2014-07-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most lethal malignancies due to underlying co-morbid cirrhosis and chemo-resistance. Vaccination and improved treatment for hepatitis are the most effective means to reduce the burden of liver cancer worldwide. Expression of biomarkers such as AFP (alpha-fetoprotein, DDK1 (Dickkopf WNT Signaling Pathway Inhibitor 1 and microRNAs in blood are being tested for early screening of liver cancer. Since 2008, sorafenib has been used as the standard molecular targeting agent for HCC. However, overall outcomes for sorafenib alone or in combination with other tyrosine kinase inhibitors are unsatisfactory. Whether simultaneously or sequentially, addiction switches and compensatory pathway activation in HCC, induced by sorafenib treatment, may induce acquired resistance. Forkhead box M1 (FOXM1 and metadherin (MTDH have been shown to be master regulators of different aspects of tumorigenesis, including angiogenesis, invasion, metastasis and drug resistance. Elevated expression of both FOXM1 and MTDH is known to be a consequence of both activating mutations in oncogenes such as PI3K, Ras, myc and loss of function mutations in tumor suppressor genes such as p53 and PTEN in various types of cancers including HCC. The role of FOXM1 and MTDH as potential prognostic markers as well as therapeutic targets in HCC will be discussed. In addition, microRNAs (miRNAs, endogenous small non-coding RNAs involved in the regulation of gene expression, are involved in HCC and interact with both FOXM1 and MTDH in several ways. Thus, altered expression of miRNAs in HCCs will also be discussed as potential tools for diagnosis, prognosis and therapy in HCC.

  4. Serum apolipoprotein B-100 concentration predicts the virological response to pegylated interferon plus ribavirin combination therapy in patients infected with chronic hepatitis C virus genotype 1b.

    Science.gov (United States)

    Yoshizawa, Kai; Abe, Hiroshi; Aida, Yuta; Ishiguro, Haruya; Ika, Makiko; Shimada, Noritomo; Tsubota, Akihito; Aizawa, Yoshio

    2013-07-01

    Host lipoprotein metabolism is associated closely with the life cycle of hepatitis C virus (HCV), and serum lipid profiles have been linked to the response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy. Polymorphisms in the human IL28B gene and amino acid substitutions in the core and interferon sensitivity-determining region (ISDR) in NS5A of HCV genotype 1b (G1b) were also shown to strongly affect the outcome of Peg-IFN plus RBV therapy. In this study, an observational cohort study was performed in 247 HCV G1b-infected patients to investigate whether the response to Peg-IFN and RBV combination therapy in these patients is independently associated with the level of lipid factors, especially apolipoprotein B-100 (apoB-100), an obligatory structural component of very low density lipoprotein and low density lipoprotein. The multivariate logistic analysis subsequently identified apoB-100 (odds ratio (OR), 1.602; 95% confidence interval (CI), 1.046-2.456), alpha-fetoprotein (OR, 0.764; 95% CI, 0.610-0.958), non-wild-type ISDR (OR, 5.617; 95% CI, 1.274-24.754), and the rs8099917 major genotype (OR, 34.188; 95% CI, 10.225-114.308) as independent factors affecting rapid initial virological response (decline in HCV RNA levels by ≥3-log10 at week 4). While lipid factors were not independent predictors of complete early or sustained virological response, the serum apoB-100 level was an independent factor for sustained virological response in patients carrying the rs8099917 hetero/minor genotype. Together, we conclude that serum apoB-100 concentrations could predict virological response to Peg-IFN plus RBV combination therapy in patients infected with HCV G1b, especially in those with the rs8099917 hetero/minor genotype. Copyright © 2013 Wiley Periodicals, Inc.

  5. Carbon nanotubes multifunctionalized by rolling circle amplification and their application for highly sensitive detection of cancer markers.

    Science.gov (United States)

    Zhao, Bin; Yan, Juan; Wang, Dongfang; Ge, Zhilei; He, Shijiang; He, Dannong; Song, Shiping; Fan, Chunhai

    2013-08-12

    There are still challenges for the development of multifunctional carbon nanotubes (CNTs). Here, a multiwalled carbon nanotube (MWCNT)-based rolling circle amplification system (CRCAS) is reported which allows in situ rolling circle replication of DNA primer on the surface of MWCNTs to create a long single-strand DNA (ssDNA) where a large number of nanoparticles or proteins could be loaded, forming a nano-biohybridized 3D structure with a powerful signal amplification ability. In this strategy, the binding ability of proteins, hybridization, replication ability of DNA, and the catalytical ability of enzymes are integrated on a single carbon nanotube. The CRCAS is then used to develop colorimetric and chemiluminescent assays for the highly sensitive and specific detection of cancer protein markers, alpha-fetoprotein (AFP) and prostate specific antigen (PSA). The colorimetric CRCAS assay is 4000 times more sensitive than a conventional enzyme-linked immunosorbent assay (ELISA), and its concentration range is 10,000 times wider. Control experiments show that as low as 10 pg mL⁻¹ AFP or PSA could be detected even in the presence of interfering protein markers with a more than 10⁵-fold greater concentration in the sample, demonstrating the high specificity of the CRCAS assay. The limit of detection of the chemiluminescent CRCAS assays for AFP and PSA are 5 fg mL⁻¹ (70 aM) and 10 fg mL⁻¹ (0.29 fM), respectively, indicating that the sensitivity is much higher than that of the colorimetric CRCAS assay. Importantly, CRCAS works well with real biological samples. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Association of 5-methylcytosine and 5-hydroxymethylcytosine with mitochondrial DNA content and clinical and biochemical parameters in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Fan Shen

    Full Text Available Increasing epidemiological evidence has indicated that inherited variations of mitochondrial DNA (mtDNA copy number affect the genetic susceptibility of many malignancies in a tumour-specific manner and that DNA methylation also plays an important role in controlling gene expression during the differentiation and development of hepatocellular carcinoma (HCC. Our previous study demonstrated that HCC tissues showed a lower 5-hydroxymethylcytosine (5-hmC content when compared to tumour-adjacent tissues, but the relationship among 5-hmC, 5-methylcytosine (5-mC and mtDNA content in HCC patients is still unknown. This study aimed to clarify the correlation among mtDNA content, 5-mC and 5-hmC by quantitative real-time PCR and liquid chromatography tandem mass spectrometry analysis. We demonstrated that 5-hmC correlated with tumour size [odds ratio (OR 0.847, 95% confidence interval (CI 0.746-0.962, P = 0.011], and HCC patients with a tumour size ≥ 5.0 cm showed a lower 5-hmC content and higher levels of fasting plasma aspartate aminotransferase, the ratio of alanine aminotransferase to aspartate aminotransferase, γ-glutamyltransferase, alpha-fetoprotein than those with a tumour size <5 cm (all P<0.05. We further revealed that the mtDNA content of HCC tumour tissues was 225.97(105.42, 430.54 [median (25th Percentile, 75th Percentile] and was negatively correlated with 5-mC content (P = 0.035, but not 5-hmC content, in genomic DNA from HCC tumour tissues.

  7. Efficient refolding of a hydrophobic protein with multiple S-S bonds by on-resin immobilized metal affinity chromatography.

    Science.gov (United States)

    Sharapova, Olga A; Yurkova, Maria S; Laurinavichyute, Daniela K; Andronova, Svetlana M; Fedorov, Alexey N; Severin, Sergey E; Severin, Evgeny S

    2011-08-05

    The efficient refolding of recombinant proteins produced in the form of inclusion bodies (IBs) in Escherichia coli still is a complicated experimental problem especially for large hydrophobic highly disulfide-bonded proteins. The aim of this work was to develop highly efficient and simple refolding procedure for such a protein. The recombinant C-terminal fragment of human alpha-fetoprotein (rAFP-Cterm), which has molecular weight of 26 kDa and possesses 6 S-S bonds, was expressed in the form of IBs in E. coli. The C-terminal 7× His tag was introduced to facilitate protein purification and refolding. The refolding procedure of the immobilized protein by immobilized metal chelating chromatography (IMAC) was developed. Such hydrophobic highly disulfide-bonded proteins tend to irreversibly bind to traditionally used agarose-based matrices upon attempted refolding of the immobilized protein. Indeed, the yield of rAFP-Cterm upon its refolding by IMAC on agarose-based matrix was negligible with bulk of the protein irreversibly stacked to the resin. The key has occurred to be using IMAC based on silica matrix. This increased on-resin refolding yield of the target protein from almost 0 to 60% with purity 98%. Compared to dilution refolding of the same protein, the productivity of the developed procedure was two orders higher. There was no need for further purification or concentration of the renatured protein. The usage of silica-based matrix for the refolding of immobilized proteins by IMAC can improve and facilitate the experimental work for difficult-to-refold proteins. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment.

    Science.gov (United States)

    Valla, D C; Chevallier, M; Marcellin, P; Payen, J L; Trepo, C; Fonck, M; Bourliere, M; Boucher, E; Miguet, J P; Parlier, D; Lemonnier, C; Opolon, P

    1999-06-01

    To examine the effects of interferon (IFN) therapy on clinical, biochemical, and histological features in patients with compensated hepatitis C virus (HCV)-related cirrhosis, we have conducted a randomized, controlled trial of IFN therapy versus observation. Eight centers included a total of 99 patients with biopsy-proven cirrhosis. IFN-alpha2b, 3 million units three times per week, or no antiviral therapy was given for 48 weeks. Twenty-three patients dropped out. End-of-treatment biochemical response was not observed in any of the 39 controls but was observed in 6 of the 47 treated patients (P <.02); sustained biochemical response was obtained in only 2 treated patients. Controls and treated patients did not significantly differ with regard to the changes in serum level of albumin, bilirubin, alpha-fetoprotein, in plasma prothrombin, in histological activity, or liver collagen content. During trial or follow-up (160 +/- 57 weeks), hepatocellular carcinoma developed in 9 controls and 5 treated patients (NS); decompensation of cirrhosis occurred in 5 controls and 7 treated patients. Seven controls and 10 treated patients died. In conclusion, in patients with compensated HCV-related cirrhosis, a 48-week course of IFN therapy is safe and is able to induce end-of-treatment biochemical response in a significant proportion of patients. However, a 48-week course of IFN therapy usually fails to achieve sustained response and, within the limit of this study, did not significantly improve the 3-year outcome. Therefore, a longer course of IFN therapy or combination therapy with ribavirin should be evaluated in patients with HCV-related cirrhosis.

  9. Constitutive Notch2 signaling induces hepatic tumors in mice.

    Science.gov (United States)

    Dill, Michael T; Tornillo, Luigi; Fritzius, Thorsten; Terracciano, Luigi; Semela, David; Bettler, Bernhard; Heim, Markus H; Tchorz, Jan S

    2013-04-01

    Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCC) are the most common liver tumors and a leading cause for cancer-related death in men. Notch2 regulates cellular differentiation in the developing and adult liver. Although aberrant Notch signaling is implicated in various cancers, it is still unclear whether Notch2 regulates proliferation and differentiation in liver carcinogenesis and thereby contributes to HCC and CCC formation. Here, we investigated the oncogenic potential of constitutive Notch2 signaling in the liver. We show that liver-specific expression of the intracellular domain of Notch2 (N2ICD) in mice is sufficient to induce HCC formation and biliary hyperplasia. Specifically, constitutive N2ICD signaling in the liver leads to up-regulation of pro-proliferative genes and proliferation of hepatocytes and biliary epithelial cells (BECs). Using the diethylnitrosamine (DEN) HCC carcinogenesis model, we further show that constitutive Notch2 signaling accelerates DEN-induced HCC formation. DEN-induced HCCs with constitutive Notch2 signaling (DEN(N2ICD) HCCs) exhibit a marked increase in size, proliferation, and expression of pro-proliferative genes when compared with HCCs from DEN-induced control mice (DEN(ctrl) HCCs). Moreover, DEN(N2ICD) HCCs exhibit increased Sox9 messenger RNA (mRNA) levels and reduced Albumin and Alpha-fetoprotein mRNA levels, indicating that they are less differentiated than DEN(ctrl) HCCs. Additionally, DEN(N2ICD) mice develop large hepatic cysts, dysplasia of the biliary epithelium, and eventually CCC. CCC formation in patients and DEN(N2ICD) mice is accompanied by re-expression of hepatocyte nuclear factor 4α(HNF4α), possibly indicating dedifferentiation of BECs. Our data establish an oncogenic role for constitutive Notch2 signaling in liver cancer development. Copyright © 2012 American Association for the Study of Liver Diseases.

  10. Short- and long-term cytotoxic effects of doxorubicin conjugates with dendrimers and vector protein on MCF-7/MDR1 chemoresistant breast cancer cells

    Science.gov (United States)

    Zamulaeva, I. A.; Matchuk, O. N.; Churyukina, K. A.; Kudryavtzev, V. A.; Yabbarov, N. G.; Nikolskaya, E. D.; Zhunina, O. A.; Kondrasheva, I. G.; Severin, E. S.

    2017-09-01

    The dendritic polymers (dendrimers) are perspective nanocontainers for targeted transport of anticancer drugs to tumor cells. We used polyamidoamine dendrimers of the second generation (G2) covalently conjugated with doxorubicin (Dox) and vector protein - recombinant third domain (3D) of alpha-fetoprotein. The objects of the study were MCF-7/MDR1 breast cancer cells, which demonstrated resistance to traditional anticancer agents due to high expression of P-glycoprotein. Effects of free Dox, G2 dendrimers loaded with Dox (G2-Dox), or conjugates of dendrimers with the vector protein and Dox (3D-G2-Dox) were assessed by the criteria of surviving cell number and clonogenic activity 24 hours and 11 days after treatment with the agents at Dox concentration of 2.5 μM, correspondingly. Flow cytometry was used to evaluate accumulation of Dox immediately after the treatment with the agents and removal of Dox during 24 hours of incubation in agent-free medium following by the treatment. Intracellular localization of Dox was studied using laser scanning microscopy. 3D-G2-Dox demonstrated the highest accumulation and the weakest removal from the cells in comparison with all other agents. The use of free Dox, G2-Dox, or 3D-G2-Dox resulted in a significant decrease in number of surviving cells by approximately 25-30% compared to the control (p ≤ 0.01). However, the most pronounced decrease in the clonogenic ability of cells was observed in the 3D-G2-Dox group (to 19% compared to the control, p < 0.01). Taking into account the previously obtained data on the extremely low 3D-G2-Dox accumulation in normal cells, it can be concluded that further development of 3D-G2-Dox as a possible anticancer drug is a promising way to overcome multiple drug resistance with minimal impact on normal cells.

  11. Massive fetomaternal hemorrhage as a cause of severe fetal anemia

    Directory of Open Access Journals (Sweden)

    Dobrosavljević Aleksandar

    2016-01-01

    Full Text Available Introduction. Fetomaternal hemorrhage (FMH is a transfu-sion of fetal blood into the maternal circulation. A volume of transfused fetal blood required to cause severe, life-threatening fetal anemia, is not clearly defined. Some authors suggest vol-umes of 80 mL and 150 mL as a threshold which defines mas-sive FMH. Therefore, a rate of massive FMH is 1 : 1,000 and 1 : 5,000 births, respectively. Fetal and neonatal anemia is one of the most serious complications of the FMH. Clinical manifesta-tions of FMH are nonspecific, and mostly it presented as re-duced fetal movements and changes in cardiotocography (CTG. The standard for diagnosing FMH is Kleihaurer-Betke test. Case report. A 34-year-old gravida (G 1, para (P 1 was hospitalized due to uterine contractions at 39 weeks of gesta-tion. CTG monitoring revealed sinusoidal fetal heart rate and clinical examination showed complete cervical dilatation. Im-mediately after admission, the women delivered vaginally. Ap-gar scores were 1 and 2 at the first and fifth minute, respec-tively. Immediately baby was intubated and mechanical ventila-tion started. Initial analysis revealed pronounced acidosis and severe anemia. The patient received intravenous fluid therapy with sodium-bicarbonate as well as red cell transfusion. With all measures, the condition of the baby improved with normaliza-tion of hemoglobin level and blood pH. Kleihaurer-Betke test revealed the presence of fetal red cells in maternal circulation, equivalent to 531 mL blood loss. The level of maternal fetal hemoglobin (HbF and elevated alpha fetoprotein also con-firmed the diagnosis of massive FMH. Conclusion. For the successful diagnosis and management of FMH direct commu-nication between the obstetrician and the pediatrician is neces-sary as presented in this report.

  12. Massive fetomaternal hemorrhage as a cause of severe fetal anemia.

    Science.gov (United States)

    Dobrosavljević, Aleksandar; Martić, Jelena; Rakić, Snežana; Pažin, Vladimir; Janković-Ražnatović, Svetlana; Srećković, Svetlana; Dobrosavljević, Branko

    2016-11-01

    Fetomaternal hemorrhage (FMH) is a transfu-sion of fetal blood into the maternal circulation. A volume of transfused fetal blood required to cause severe, life-threatening fetal anemia, is not clearly defined. Some authors suggest vol-umes of 80 mL and 150 mL as a threshold which defines mas-sive FMH. Therefore, a rate of massive FMH is 1 : 1,000 and 1 : 5,000 births, respectively. Fetal and neonatal anemia is one of the most serious complications of the FMH. Clinical manifesta-tions of FMH are nonspecific, and mostly it presented as re-duced fetal movements and changes in cardiotocography (CTG). The standard for diagnosing FMH is Kleihaurer-Betke test. A 34-year-old gravida (G) 1, para (P) 1 was hospitalized due to uterine contractions at 39 weeks of gesta-tion. CTG monitoring revealed sinusoidal fetal heart rate and clinical examination showed complete cervical dilatation. Im-mediately after admission, the women delivered vaginally. Ap-gar scores were 1 and 2 at the first and fifth minute, respec-tively. Immediately baby was intubated and mechanical ventila-tion started. Initial analysis revealed pronounced acidosis and severe anemia. The patient received intravenous fluid therapy with sodium-bicarbonate as well as red cell transfusion. With all measures, the condition of the baby improved with normaliza-tion of hemoglobin level and blood pH. Kleihaurer-Betke test revealed the presence of fetal red cells in maternal circulation, equivalent to 531 mL blood loss. The level of maternal fetal hemoglobin (HbF) and elevated alpha fetoprotein also con-firmed the diagnosis of massive FMH. For the successful diagnosis and management of FMH direct commu-nication between the obstetrician and the pediatrician is neces-sary as presented in this report.

  13. GPC-HCC model: a combination of glybican-3 with other routine parameters improves the diagnostic efficacy in hepatocellular carcinoma.

    Science.gov (United States)

    Attallah, Abdelfattah M; El-Far, Mohamed; Omran, Mohamed M; Abdelrazek, Mohamed A; Attallah, Ahmed A; Saeed, Aya M; Farid, Khaled

    2016-09-01

    Conflicting results for circulating glypican-3 (GPC3) were reported in hepatocellular carcinoma (HCC) diagnosis. We aimed to improve the diagnostic power of GPC3 by developing a GPC-HCC model for diagnosing HCC. GPC3 was tested for HCC (138), liver cirrhosis (56), and fibrosis (62) patients by ELISA. Data from patient groups were retrospectively analyzed. A novel score, GPC-HCC, based on combination of GPC3 and routine laboratory tests, was developed for HCC diagnosis. The GPC-HCC model values produced a significant 1.7-fold increase in liver cirrhosis and 3.2-fold increase in HCC, in comparison with liver fibrosis. In contrast to GPC3 and alpha fetoprotein (AFP), the GPC-HCC model showed high HCC diagnostic power with area under the curve (AUC) of 0.939, sensitivity 93 %, specificity 93 %, positive predictive value 89 %, negative predictive value 95 %, and efficiency 93 %. GPC-HCC AUC in HCC with single tumor, absent vascular invasion, and tumor size ≤3 cm were 0.93, 0.92, and 0.92, respectively, compared with 0.63, 0.63, and 0.64, respectively, for GPC3 and 0.69, 0.70, 0.55, respectively, for AFP. In conclusion, owing to these promising findings, the combination of GPC3 with other laboratory simple routine tests (GPC-HCC model) could improve the diagnostic power of GPC3 in HCC screening and follow up of cirrhotic patients.

  14. Cytokeratin-18 in Diagnosis of HCC in Patients with Liver Cirrhosis

    Science.gov (United States)

    Ismail, Saber A; El Saadany, Sherif; Ziada, Dina H; Zakaria, Soha S; Mayah, Wael W; Elashry, Heba; Arafa, Mona; Elmashad, Nehal

    2017-04-01

    Background: Hepatocellular carcinoma (HCC) is a common malignancy that occurs secondary to viral hepatitis B and C cirrhosis under the influence of environmental factors. In early stages, clinical diagnosis is often difficult and distinguishing HCC from cirrhosis and other hepatic masses by conventional tests is frequently not feasible. Physicians usually depend on measuring serum alpha-fetoprotein (AFP), but this marker has low sensitivity and specificity. The aim of this research was to determine any role of serum cytokeratin-18(Ck-18) as a marker for diagnosis of HCC in patients with liver cirrhosis. Patients and methods: We used ELISA to measure the serum levels of AFP and CK 18 in 60 Egyptian patients (30 cirrhotic and 30 with HCC) and 30 controls. Results: The Ck-18 level was significantly elevated in the HCC group (1247.8± 105.3U/L) when compared to the liver cirrhosis (834.1± 38.8 U/L) and control groups (265.2±83.1U/L). Ck-18 as a marker showed 95.6% sensitivity, 93.3% specificity and 98.8% accuracy. The mean serum AFP was 4901.4±2185.8ng/ml in the HCC group, 100.7±71.7 ng/ml in the cirrhotic group, and 4.0±1.2ng/ ml in controls. AFP showed 55. 7% sensitivity, 97. 7% specificity and 84.4% accuracy. Combined use of both Ck-18 and AFP improved the sensitivity to 98%. Conclusion: Serum cytokeratin-18 level can be used as a diagnostic biomarker for HCC with a higher sensitivity than AFP. Creative Commons Attribution License

  15. AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Beale, Gary; Reeves, Helen; Chattopadhyay, Dipankar; Gray, Joe; Stewart, Stephen; Hudson, Mark; Day, Christopher; Trerotoli, Paolo; Giannelli, Gianluigi; Manas, Derek

    2008-01-01

    The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD. Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP. Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination. We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests that the choice of optimal biomarkers for HCC

  16. Committee Opinion No. 640: Cell-Free DNA Screening For Fetal Aneuploidy.

    Science.gov (United States)

    2015-09-01

    Noninvasive prenatal screening that uses cell-free DNA from the plasma of pregnant women offers tremendous potential as a screening method for fetal aneuploidy. A number of laboratories have validated different techniques for the use of cell-free DNA as a screening test for fetal aneuploidy. All tests have a high sensitivity and specificity for trisomy 18 and trisomy 21, regardless of which molecular technique is used. Women whose results are not reported, indeterminate, or uninterpretable (a "no call" test result) from cell-free DNA screening should receive further genetic counseling and be offered comprehensive ultrasound evaluation and diagnostic testing because of an increased risk of aneuploidy. Patients should be counseled that cell-free DNA screening does not replace the precision obtained with diagnostic tests, such as chorionic villus sampling or amniocentesis and, therefore, is limited in its ability to identify all chromosome abnormalities. Cell-free DNA screening does not assess risk of fetal anomalies such as neural tube defects or ventral wall defects. Patients who are undergoing cell-free DNA screening should be offered maternal serum alpha-fetoprotein screening or ultrasound evaluation for risk assessment. The cell-free DNA screening test should not be considered in isolation from other clinical findings and test results. Management decisions, including termination of the pregnancy, should not be based on the results of the cell-free DNA screening alone. Patients should be counseled that a negative cell-free DNA test result does not ensure an unaffected pregnancy. Given the performance of conventional screening methods, the limitations of cell-free DNA screening performance, and the limited data on cost-effectiveness in the low-risk obstetric population, conventional screening methods remain the most appropriate choice for first-line screening for most women in the general obstetric population.

  17. Committee Opinion Summary No. 640: Cell-Free DNA Screening For Fetal Aneuploidy.

    Science.gov (United States)

    2015-09-01

    Noninvasive prenatal screening that uses cell-free DNA from the plasma of pregnant women offers tremendous potential as a screening method for fetal aneuploidy. A number of laboratories have validated different techniques for the use of cell-free DNA as a screening test for fetal aneuploidy. All tests have a high sensitivity and specificity for trisomy 18 and trisomy 21, regardless of which molecular technique is used. Women whose results are not reported, indeterminate, or uninterpretable (a "no call" test result) from cell-free DNA screening should receive further genetic counseling and be offered comprehensive ultrasound evaluation and diagnostic testing because of an increased risk of aneuploidy. Patients should be counseled that cell-free DNA screening does not replace the precision obtained with diagnostic tests, such as chorionic villus sampling or amniocentesis and, therefore, is limited in its ability to identify all chromosome abnormalities. Cell-free DNA screening does not assess risk of fetal anomalies such as neural tube defects or ventral wall defects. Patients who are undergoing cell-free DNA screening should be offered maternal serum alpha-fetoprotein screening or ultrasound evaluation for risk assessment. The cell-free DNA screening test should not be considered in isolation from other clinical findings and test results. Management decisions, including termination of the pregnancy, should not be based on the results of the cell-free DNA screening alone. Patients should be counseled that a negative cell-free DNA test result does not ensure an unaffected pregnancy. Given the performance of conventional screening methods, the limitations of cell-free DNA screening performance, and the limited data on cost-effectiveness in the low-risk obstetric population, conventional screening methods remain the most appropriate choice for first-line screening for most women in the general obstetric population.

  18. Human EGF-derived direct and reverse short linear motifs: conformational dynamics insight into the receptor-binding residues.

    Science.gov (United States)

    Moldogazieva, Nurbubu T; Shaitan, Konstantin V; Antonov, Mikhail Yu; Mokhosoev, Innokenty M; Levtsova, Olga V; Terentiev, Alexander A

    2018-04-01

    Short linear motifs (SLiMs) have been recognized to perform diverse functions in a variety of regulatory proteins through the involvement in protein-protein interactions, signal transduction, cell cycle regulation, protein secretion, etc. However, detailed molecular mechanisms underlying their functions including roles of definite amino acid residues remain obscure. In our previous studies, we demonstrated that conformational dynamics of amino acid residues in oligopeptides derived from regulatory proteins such as alpha-fetoprotein (AFP), carcino-embryonic antigen (CEA), and pregnancy specific β1-glycoproteins (PSGs) contributes greatly to their biological activities. In the present work, we revealed the 22-member linear modules composed of direct and reverse AFP 14-20 -like heptapeptide motifs linked by CxxGY/FxGx consensus motif within epidermal growth factor (EGF), growth factors of EGF family and numerous regulatory proteins containing EGF-like modules. We showed, first, the existence of similarity in amino acid signatures of both direct and reverse motifs in terms of their physicochemical properties. Second, molecular dynamics (MD) simulation study demonstrated that key receptor-binding residues in human EGF in the aligned positions of the direct and reverse motifs may have similar distribution of conformational probability densities and dynamic behavior despite their distinct physicochemical properties. Third, we found that the length of a polypeptide chain (from 7 to 53 residues) has no effect, while disulfide bridging and backbone direction significantly influence the conformational distribution and dynamics of the residues. Our data may contribute to the atomic level structure-function analysis and protein structure decoding; additionally, they may provide a basis for novel protein/peptide engineering and peptide-mimetic drug design.

  19. Clinical characteristics of patients with HBsAg(+ versus HBsAg(-/HBcAb(+ primary hepatic carcinoma treated by hepatectomy: a comparative analysis

    Directory of Open Access Journals (Sweden)

    YANG Keli

    2015-06-01

    Full Text Available ObjectiveTo explore the differences in clinical characteristics between patients with HBsAg(+ and HBsAg(-/HBcAb(+ primary hepatic carcinoma (PHC treated by hepatectomy. MethodsForty-three HBsAg(+ and 18 HBsAg(-/HBcAb(+ patients who underwent liver resection against PHC from October 2009 to November 2014 in Guangzhou 8th People′s Hospital were selected for the study. The clinical data of the subjects, including sex, age, histological differentiation, intravascular tumor thrombi, and hepatic cirrhosis, were compared, using t test for continuous data, chi-square test for categorical data, and Mann-Whitney U test for non-parametric data. ResultsNo significant differences existed between patients with HBsAg(+ and HBsAg(-/HBcAb(+ PHC in terms of the age of onset (50.77±12.93 years vs 54.28±9.89 years, t=-1.031, P>0.05, the incidence of cholangiocarcinoma (2.3% vs 167%, χ2=2.24, P>0.05, the incidence of hepatic cirrhosis (62.8% vs 44.4%, χ2=1.746, P>0.05, alpha-fetoprotein level (3638±7869 ng/ml vs 3577±9628 ng/ml, t=0.026, P>0.05, histological differentiation (Z=-1.085, P>0.05, and the rate of intravascular tumor thrombi (34.9% vs 22.2%, χ2=0.949, P>0.05. ConclusionThere are no significant differences in the age of onset and progression of disease between patients with HBsAg(+ and HBsAg(-/HBcAb(+ PHC treated by hepatectomy. However, given the possibility of occult hepatitis B virus infection, it is necessary to monitor hepatic carcinoma even post HBsAg seroconversion

  20. Hepatitis B Virus Reactivation during Treatment with Multi-Tyrosine Kinase Inhibitor for Hepatocellular Carcinoma

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    Satoshi Shiba

    2012-09-01

    Full Text Available Hepatitis B virus (HBV reactivation is well documented in individuals with cancer who receive certain cytotoxic or immunosuppressive therapies including rituximab treatment. As a general rule, the risk is greatest upon withdrawal of chemotherapy. The risk ranges from approximately 20 to 50% among HBsAg-positive carriers. A 67-year-old man was diagnosed with inoperable multiple hepatocellular carcinoma accompanied by an increase in alpha-fetoprotein and protein induced by vitamin K absence or antagonist II level. Eighteen weeks after starting on the oral multi-tyrosine kinase inhibitor TSU-68, laboratory investigations showed a substantial increase in serum transaminase levels (AST: 302 IU/l; ALT: 324 IU/l and an elevation of the HBV-DNA level (6.9 log copies/ml. The diagnosis was that the cause of the acute hepatitis was HBV reactivation and we immediately administered entecavir. Two months after the initiation of daily entecavir treatment, laboratory findings showed that the serum levels of transaminases and ALP had improved (AST: 18 IU/l; ALT: 10 IU/l; ALP: 197 U/l. When the HBV markers were examined 4 months later, they were altered: HBeAg was negative and HBeAb was positive. Entecavir treatment was discontinued after 6 months. Although reactivation with rituximab has been reported, reactivation with a tyrosine kinase inhibitor is extremely unusual in a patient who is HBsAg negative but anti-HBc positive. This is the first report describing HBV reactivation with an increasing HBV-DNA level in a HBsAg-negative/HBcAb-positive/HBsAb-positive patient who was treated with TSU-68 for hepatocellular carcinoma.

  1. Liquidus Tracking: Large scale preservation of encapsulated 3-D cell cultures using a vitrification machine.

    Science.gov (United States)

    Puschmann, Eva; Selden, Clare; Butler, Steve; Fuller, Barry

    2017-06-01

    Currently, cryo-banking of multicellular structures such as organoids, especially in large volumes at clinical scale >1 L, remains elusive for reasons such as insufficient dehydration and cryoprotectant additive (CPA 1 ) penetration, slow cooling and warming rates and devitrification processes. Here we introduce the concept of Liquidus Tracking (LT) using a semi-automated process for liquid volumes of up to 450 ml including 130 ml of alginate encapsulated liver cells (AELC) that archived controlled and reversible vitrification with minimized toxicity. First a CPA solution with optimal properties for LT was developed by employing different small scale test systems. Combining sugars such as glucose and raffinose with Me 2 SO improved post-exposure (at +0.5 °C) viabilities from 6% ±3.6 for Me 2 SO alone up to 58% ±6.1 and 65% ±14.2 respectively (p ethylene glycol, propylene glycol, methanol) were investigated as partial replacements for Me 2 SO. A mixture of Me 2 SO, ethylene glycol and glucose (ratio 4:2:1- termed LTdeg) supported glass-forming tendencies with appropriate low viscosities and toxicities required for LT. When running the full LT process, using Me 2 SO alone, no viable cells were recovered; using LTdeg, viable recoveries were improved to 40% ±8 (psynthesis of albumin and alpha-fetoprotein (AFP) were retained in post thaw cultures. In summary: By developing a low-toxicity CPA solution of low viscosity (LTdeg) suitable for LT and by improving the stirring system, post-warming viability of AELC of up to 90% and a AFP secretion of 89% were reached. Results show that it may be possible to develop LT as a suitable cryogenic preservation process for different cell therapy products at large scale. Copyright © 2017. Published by Elsevier Inc.

  2. Formation of human hepatocyte-like cells with different cellular phenotypes by human umbilical cord blood-derived cells in the human-rat chimeras

    International Nuclear Information System (INIS)

    Sun, Yan; Xiao, Dong; Zhang, Ruo-Shuang; Cui, Guang-Hui; Wang, Xin-Hua; Chen, Xi-Gu

    2007-01-01

    We took advantage of the proliferative and permissive environment of the developing pre-immune fetus to develop a noninjury human-rat xenograft small animal model, in which the in utero transplantation of low-density mononuclear cells (MNCs) from human umbilical cord blood (hUCB) into fetal rats at 9-11 days of gestation led to the formation of human hepatocyte-like cells (hHLCs) with different cellular phenotypes, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), cytokeratin 19 (CK19), cytokeratin 8 (CK8), cytokeratin 18 (CK18), and albumin (Alb), and with some animals exhibiting levels as high as 10.7% of donor-derived human cells in the recipient liver. More interestingly, donor-derived human cells stained positively for CD34 and CD45 in the liver of 2-month-old rat. Human hepatic differentiation appeared to partially follow the process of hepatic ontogeny, as evidenced by the expression of AFP gene at an early stage and albumin gene at a later stage. Human hepatocytes generated in this model retained functional properties of normal hepatocytes. In this xenogeneic system, the engrafted donor-derived human cells persisted in the recipient liver for at least 6 months after birth. Taken together, these findings suggest that the donor-derived human cells with different cellular phenotypes are found in the recipient liver and hHLCs hold biological activity. This humanized small animal model, which offers an in vivo environment more closely resembling the situations in human, provides an invaluable approach for in vivo investigating human stem cell behaviors, and further in vivo examining fundamental mechanisms controlling human stem cell fates in the future

  3. Prognostic factors for long-term outcome after percutaneous thermal ablation for hepatocellular carcinoma: a survival analysis of 137 consecutive patients

    International Nuclear Information System (INIS)

    Xu, H.-X.; Lu, M.-D.; Xie, X.-Y.; Yin, X.-Y.; Kuang, M.; Chen, J.-W.; Xu, Z.-F.; Liu, G.-J.

    2005-01-01

    AIM: To identify prognostic factors for long-term outcome for patients with hepatocellular carcinoma (HCC) after percutaneous microwave or radiofrequency ablation. MATERIALS AND METHODS: In total, 137 consecutive patients with HCC underwent microwave or radiofrequency ablation with curative intent; 16 possible prognostic factors were evaluated for their association with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analysis. RESULTS: The median OS and DFS were 27.0 months and 8.2 months, respectively. OS rates for all patients at 1, 2, 3, 4 and 5 years were 73.9%, 52.1%, 42.8%, 26.2% and 20.1%, respectively. DFS rates at 1, 2, 3 and 4 years were 38.1%, 21.9%, 18.8%, and 14.1%, respectively. Pretreatment serum alpha-fetoprotein (AFP) >200 ng/ml, pretreatment serum albumin ≤35 g/dl, liver function Child's class C and incomplete ablation were found to be significant predictors for OS by univariate analysis. Using multivariate analysis, incomplete ablation was identified to be the most significant independent predictor for OS. Other independent predictors for OS were serum albumin level, serum AFP level and Child-Pugh classification. Recurrence after hepatectomy and prothrombin time >14 s were identified to be significant predictors for DFS by univariate analysis, and the former was the only independent predictor for DFS by multivariate analysis. CONCLUSION: Prognosis for patients with HCC after thermal ablation with curative intent was determined by treatment response to ablation, pretreatment serum AFP, and liver function reserve. Tumour response to treatment was the most predictive factor for long-term survival and was related to tumour size, thus careful selection of patients for ablation therapy is recommended

  4. Reproductive health and genetic testing in the Third World.

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    Penchaszadeh, V B

    1993-09-01

    New reproductive genetics means recently developed techniques to prevent the birth of children with specific defects or genetic diseases by testing individuals for sickle cell anemia, the thalassemias, Tay-Sachs disease, cystic fibrosis, or Down syndrome. Third World health services have many deficiencies with high maternal mortality rates (30-40 fold higher than in developed countries), the low percentage of births delivered by health personnel, the high rates of low birth weight babies, and high child malnutrition and infant mortality rates. The main issues in women's reproductive health are fertility regulation, abortion, maternal mortality, sexually transmitted diseases, and infertility. As a result of expansion in contraceptive use worldwide, the total fertility rate in developing countries has declined from 6.1 in 1965 to 3.9 in 1990. It is estimated that, worldwide, 36-53 million induced abortions are performed each year, most of them in developing nations. WHO estimates that more than 500,000 women die each year because of complications of pregnancy, most in developing countries. More than 95% of the 13 million estimated deaths of children under 5 years of age have occurred in these countries. Approximately 200 million people carry a potentially pathologic hemoglobinopathy gene, and about 250,000 children are born every year with hemoglobinopathy, most of them in the developing world. Reproductive genetic testing in big cities and in private for-profit ventures cater to the socioeconomic elite. Amniocentesis is often misused for fetal sex determination to abort female fetuses in India. Currently, in Cuba virtually every pregnant woman is tested for sickle cell trait and maternal serum alpha-fetoprotein levels between 15 and 20 weeks of gestation. It is predicted that the judicious use of reproductive genetic testing will be possible when health and quality of life issues are addressed properly.

  5. [Diagnosis and treatment of yolk sac tumor of the testis with hydrocele in children: report of 7 cases].

    Science.gov (United States)

    Huang, Sheng-Song; Wu, Deng-Long; Gui, Ya-Ping; Zhao, Xin; Xie, Hua

    2013-11-01

    To study the clinical characteristics of yolk sac tumor of the testis with concomitant testicular hydrocele in children and the association between the two conditions in order to improve the diagnosis and treatment of the disease. We retrospectively analyzed the clinical data of 7 cases of stage-I yolk sac tumor of the testis with concomitant testicular hydrocele. The patients ranged in age from 6 to 14 (mean 11) months. As treatment, we performed radical high spermatic cord orchiectomy after diagnosis established on intraoperative frozen sections, and conducted follow-up visits by medical examination, serum alpha-fetoprotein (AFP) detection, chest X-ray, ultrasonography and CT for 3-41 (mean 17) months, every month in the first year, every 3 months in the second year and every 6 months in the third year after surgery. Postoperative pathology confirmed yolk sac tumor in all the cases, with negative incisal margin. The level of serum AFP were decreased to normal in 6 cases within 1 month after surgery, all diagnosed as at stage I, and cured without chemotherapy. The other 1 case, with the serum AFP level of 116 microg/L at 1 month after operation, was diagnosed as at stage II and received PVC chemotherapy, but lost to follow-up at 3 months post-operatively. Yolk sac tumor of the testis with concomitant testicular hydrocele is easily misdiagnosed in children. Ultrasonography is necessitated as routine examination in its diagnosis. Radical high spermatic cord orchiectomy can be performed for patients in stage I, and chemotherapy should follow for those in stage II. Its prognosis is similar to that of other yolk sac tumors. Hitherto, there has been no evidence for a definitive correlation between yolk sac tumor of the testis and hydrocele in children.

  6. Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.

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    Kiichiro Kaji

    Full Text Available Squamous cell carcinoma antigen recognized by T cells 3 (SART3, a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC.The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315 were used for immunological analysis. T-cell responses were investigated by interferon-gamma (IFN-γ enzyme-linked immunospot and cytotoxic T lymphocyte (CTL assays using peripheral blood mononuclear cells (PBMCs in 47 patients, and tumor-infiltrating lymphocytes in 8 of 47 patients with HCC. The safety of immunotherapy using a SART3-derived peptide was investigated by vaccinations of SART3109 in 12 patients with HCC (trial registration: UMIN000005677.The immunofluorescence and immunohistochemical analyses showed that SART3 was expressed in six HCC cell lines, and in HCC tissues including of alpha-fetoprotein-negative individuals. SART3-specific CTLs were generated by stimulating PBMCs with the peptides, and they showed cytotoxicity against HCC cells expressing the protein. Of the 47 HCC patients, 25.5% and 10.6% showed significant responses to SART3109 and SART3315, respectively. The infiltration of SART3109-specific IFN-γ-producing CTLs into the tumor site was confirmed. In the vaccination study, no severe adverse events were observed, and the peptide-specific CTLs were newly induced in four of five patients tested.SART3 is an immunotherapeutic candidate, and peptides from this antigen may be applied in HCC immunotherapy.UMIN000005677.

  7. Dyskerin overexpression in human hepatocellular carcinoma is associated with advanced clinical stage and poor patient prognosis.

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    Bei Liu

    Full Text Available BACKGROUND: Dyskerin (encoded by the DKC1 gene is an essential nucleolar protein involved in cell proliferation, where it is required for the pseudo-uridylation of ribosomal RNA (rRNA molecules and the stabilization of the telomerase RNA component. Dyskerin expression has been reported to predict poor survival in some cancer patients. The aim of the present study was to analyze the expression of dyskerin in hepatocellular carcinoma (HCC and to determine its correlation with clinicopathologic features, including the survival of patients with HCC. METHODOLOGY/PRINCIPAL FINDINGS: Dyskerin protein expression was detected by immunohistochemistry in paraffin sections of 252 HCC cases and 80 noncancerous liver tissues. The correlation was analyzed between dyskerin expression levels and clinicopathologic variables and prognosis. Dyskerin protein was significantly overexpressed in HCC tissues when compared to noncancerous liver tissue. Dyskerin overexpression was positively correlated with the hepatitis B surface antigen status, serum alpha-fetoprotein, and advanced clinical stage in HCC patients. A survival analysis indicated that HCC patients with higher dyskerin expression had a significantly shorter overall survival and 5-year survival time when compared to those with low expression. A multivariate analysis suggested that dyskerin overexpression was an independent factor for prognosis (hazard risk, 2.912; P = 0.007. Expression of DKC1 mRNA was measured by quantitative RT-PCR in 80 HCC and 50 non-cancerous tissues. The relationship between DKC1, TERT, MKI67, and MYC mRNA expression in HCC tissues was also evaluated. DKC1 mRNA was significantly overexpressed in HCC tissues and showed a significant correlation with MKI67 and MYC mRNA but a weak correlation with TERT mRNA. CONCLUSIONS/SIGNIFICANCE: Dyskerin overexpression in HCC patients was correlated with MYC and MKI67 expression and showed a possible involvement in the tumorigenic process. Dyskerin

  8. Hepatoblastoma in a 15-month-old female with trisomy 13.

    Science.gov (United States)

    Shah, Rachana; Tran, Hung Chi; Randolph, Linda; Mascarenhas, Leo; Venkatramani, Rajkumar

    2014-02-01

    Trisomy 13 (T13) is a rare autosomal aneuploidy. Greater than 90% of patients die during the first year of life. Malignancies reported in association with T13 include two cases of Wilms tumor and one case of pilocytic astrocytoma. There is no previous report of hepatoblastoma in patients with T13. We report a unique case of hepatoblastoma in a 15-month-old female with constitutional T13. Our patient was born at 38 weeks gestation and was noted to have phenotypic features consistent with T13. Genetic testing confirmed an abnormal karyotype of 47,XX,+13 in all cells. At fifteen months of age she was noted to have a right hepatic lobe mass on a routine follow-up renal ultrasound for hydronephrosis. Serum alpha-fetoprotein level was 55,300 ng/ml. Staging work-up revealed the absence of metastases. She underwent a complete surgical resection with right hepatic lobectomy. Histopathology was consistent with hepatoblastoma, mixed epithelial and mesenchymal type. She had a protracted postoperative course complicated by Enterobacter aerogenes urosepsis, a significant biloma, chronic pancreatitis, and apneic episodes of uncertain etiology. She received four courses of doxorubicin monotherapy without any severe or unexpected toxicity. She continues to be in remission 8 months following diagnosis. This is the first reported case of hepatoblastoma in a child with constitutional T13. This may represent a non-random association, as somatic trisomy of chromosome 13 in hepatoblastoma tumors has been previously described in the literature. Prolonged survival may have allowed for hepatoblastoma to present in our patient. © 2013 Wiley Periodicals, Inc.

  9. Specific diagnosis of hepatocellular carcinoma by delayed hepatobiliary imaging

    International Nuclear Information System (INIS)

    Hasegawa, Y.; Nakano, S.; Ibuka, K.

    1986-01-01

    For assessment of the value of delayed hepatobiliary imaging with technetium 99m (/sup 99m/Tc)-(Sn)-N-pyridoxyl-5-methyltryptophan (/sup 99m/Tc-PMT) for specific diagnosis of hepatocellular carcinoma, 88 patients with various malignant and benign liver diseases (49 with hepatocellular carcinoma, 4 with cholangiocellular carcinoma, 10 with metastatic liver carcinoma, 2 with liver cysts, 2 with liver hemangioma, 1 with liver abscess, 2 with intrahepatic lithiasis, 12 with liver cirrhosis, and 6 with chronic hepatitis) were studied. In 20 (41%) of the 49 patients with hepatocellular carcinoma, greater uptake of /sup 99m/Tc-PMT by the tumor than by the surrounding liver tissue was seen in delayed hepatobiliary images, whereas in eight patients (16%), equilibrated uptake was seen. No increased uptake of the radioisotope by hepatic lesions was seen in 21 patients with localized liver diseases other than hepatoma. Moreover, in 18 patients with diffuse liver diseases, no focal accumulation of the radioisotope was seen in delayed /sup 99m/Tc-PMT images. In addition, of 28 patients with hepatocellular carcinoma in whom the serum alpha-fetoprotein level showed little or no increase, 12 showed increased uptake of /sup 99m/Tc-PMT by the tumor. In assessing delayed /sup 99m/Tc-PMT images, however, it was necessary to consider following complications: accumulation of tracer in obstructed and dilated biliary trees; retention of radioactivity in nonneoplastic liver tissues; difficulties in evaluating /sup 99m/Tc-PMT uptake by small hepatic tumors; overlapping of radioactivity in the gut and gallbladder in delayed /sup 99m/Tc-PMT images of tumors. This study indicates that delayed /sup 99m/Tc-PMT images can be useful in the diagnosis of hepatocellular carcinoma

  10. Molecular mechanisms underlying antiproliferative and differentiating responses of hepatocarcinoma cells to subthermal electric stimulation.

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    María Luisa Hernández-Bule

    Full Text Available Capacitive Resistive Electric Transfer (CRET therapy applies currents of 0.4-0.6 MHz to treatment of inflammatory and musculoskeletal injuries. Previous studies have shown that intermittent exposure to CRET currents at subthermal doses exert cytotoxic or antiproliferative effects in human neuroblastoma or hepatocarcinoma cells, respectively. It has been proposed that such effects would be mediated by cell cycle arrest and by changes in the expression of cyclins and cyclin-dependent kinase inhibitors. The present work focuses on the study of the molecular mechanisms involved in CRET-induced cytostasis and investigates the possibility that the cellular response to the treatment extends to other phenomena, including induction of apoptosis and/or of changes in the differentiation stage of hepatocarcinoma cells. The obtained results show that the reported antiproliferative action of intermittent stimulation (5 m On/4 h Off with 0.57 MHz, sine wave signal at a current density of 50 µA/mm(2, could be mediated by significant increase of the apoptotic rate as well as significant changes in the expression of proteins p53 and Bcl-2. The results also revealed a significantly decreased expression of alpha-fetoprotein in the treated samples, which, together with an increased concentration of albumin released into the medium by the stimulated cells, can be interpreted as evidence of a transient cytodifferentiating response elicited by the current. The fact that this type of electrical stimulation is capable of promoting both, differentiation and cell cycle arrest in human cancer cells, is of potential interest for a possible extension of the applications of CRET therapy towards the field of oncology.

  11. New Solid Phases for Estimation of Hormones by Radioimmunoassay Technique

    International Nuclear Information System (INIS)

    Sheha, R.R.; Ayoub, H.S.M.; Shafik, M.

    2013-01-01

    The efforts in this study were initiated to develop and validate new solid phases for estimation of hormones by radioimmunoassay (RIA). The study argued the successful application of different hydroxy apatites (HAP) as new solid phases for estimation of Alpha fetoprotein (AFP), Thyroid Stimulating hormone (TSH) and Luteinizing hormone (LH) in human serum. Hydroxy apatites have different alkali earth elements were successfully prepared by a well-controlled co-precipitation method with stoichiometric ratio value 1.67. The synthesized barium and calcium hydroxy apatites were characterized using XRD and Ftir and data clarified the preparation of pure structures of both BaHAP and CaHAP with no evidence on presence of other additional phases. The prepared solid phases were applied in various radioimmunoassay systems for separation of bound and free antigens of AFP, TSH and LH hormones. The preparation of radiolabeled tracer for these antigens was carried out using chloramine-T as oxidizing agent. The influence of different parameters on the activation and coupling of the used apatite particles with the polyclonal antibodies was systematically investigated and the optimum conditions were determined. The assay was reproducible, specific and sensitive enough for regular estimation of the studied hormones. The intra-and inter-assay variation were satisfactory and also the recovery and dilution tests indicated an accurate calibration. The reliability of these apatite particles had been validated by comparing the results that obtained by using commercial kits. The results finally authenticates that hydroxyapatite particles would have a great potential to address the emerging challenge of accurate quantitation in laboratory medical application

  12. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Geschwind, Jean Francois H; Salem, Riad; Carr, Brian I; Soulen, Michael C; Thurston, Kenneth G; Goin, Kathleen A; Van Buskirk, Mark; Roberts, Carol A; Goin, James E

    2004-11-01

    Unresectable hepatocellular carcinoma is extremely difficult to treat. TheraSphere consists of yttrium-90 (a pure beta emitter) microspheres, which are injected into the hepatic arteries. This article reviews the safety and survival of patients with hepatocellular carcinoma who were treated with yttrium-90 microspheres. Eighty patients were selected from a database of 108 yttrium-90 microsphere-treated patients and were staged by using Child-Pugh, Okuda, and Cancer of the Liver Italian Program scoring systems. Patients were treated with local, regional, and whole-liver approaches. Survival from first treatment was analyzed with Kaplan-Meier and Cox regression methods. Adverse events and complications of treatment were coded by using the Southwest Oncology Group toxicity scoring system. Patients received liver doses ranging from 47 to 270 Gy. Thirty-two patients (40%) received more than 1 treatment. Survival correlated with pretreatment Cancer of the Liver Italian Program scores ( P = .002), as well as with the individual Cancer of the Liver Italian Program components, Child-Pugh class, alpha-fetoprotein levels, and percentage of tumor replacement. Patients classified as Okuda stage I (n = 54) and II (n = 26) had median survival durations and 1-year survival rates of 628 days and 63%, and 384 days and 51%, respectively ( P = .02). One patient died of liver failure judged as possibly related to treatment. Thus, in selected patients with hepatocellular carcinoma, yttrium-90 microsphere treatment is safe and well tolerated. On the basis of these results, a randomized controlled trial is warranted comparing yttrium-90 microsphere treatment with transarterial chemoembolization by using the Cancer of the Liver Italian Program system for prospective stratified randomization.

  13. Hepatocellular carcinoma treated by conventional transarterial chemoembolization in field-practice: Serum sodium predicts survival

    Science.gov (United States)

    Biolato, Marco; Miele, Luca; Vero, Vittoria; Racco, Simona; Di Stasi, Carmine; Iezzi, Roberto; Zanché, Andrea; Pompili, Maurizio; Rapaccini, Gian Ludovico; La Torre, Giuseppe; Gasbarrini, Antonio; Grieco, Antonio

    2014-01-01

    AIM: To assess the prognostic role of baseline clinical, biochemical and radiological characteristics of patients with hepatocellular carcinoma (HCC) treated with the first transarterial chemoembolization (TACE) procedure. METHODS: Patients with HCC treated with conventional TACE in a tertiary care setting from 1997 to 2008 were retrospectively reviewed. Predictors of survival were identified using the Cox proportional regression model. RESULTS: Two hundred and seventy patients were included. Median age was 66 years, 81% were male, 58% were HCV-positive, 18% hepatitis B surface antigen-positive, 64% had a Child A status, 40% patients had a largest nodule diameter ≥ 5 cm and 32% had more than 3 tumor nodules. Median overall survival of the whole cohort was 25 mo (95%CI: 21.8-28.2) and the 1-, 2- and 3-year probability of survival was 80%, 50% and 31%, respectively. Non-tumor segmental portal vein thrombosis (HR = 1.76, 95%CI: 1.22-2.54), serum sodium (HR = 1.65, 95%CI: 1.25-2.18), diameter of largest nodule (HR = 1.59, 95%CI: 1.22-2.091), number of nodules (HR = 1.41, 95%CI: 1.06-1.88), alpha-fetoprotein (HR = 1.35, 95%CI: 1.03-1.76) and alkaline phosphatase (HR = 1.33, 95%CI: 1.01-1.74) were independent prognostic factors for overall survival on multivariate analysis. CONCLUSION: The inclusion of serum sodium alongside the already known prognostic factors may allow a better prognostic definition of patients with HCC as candidates for conventional TACE. PMID:25009388

  14. New insights on non-B non-C hepatocellular carcinoma in mid Delta Region, Egypt.

    Science.gov (United States)

    Abou El Azm, Abdel Raouf; Yousef, Mohamed; Mansour, Nagwa; Awad, Aymen; El Dardiry, Samia; Abdel Aziz, Ibrahim

    2014-09-01

    The rate of hepatocellular carcinoma (HCC) is increasing worldwide, including in Egypt. Hepatitis B (HBV) and C (HCV) viruses are major risks. Non-B non-C HCC was reported in some countries. We investigated non-B non-C HCC-independent risk factors and associated profiles in viral hepatitis endemic region. In a consecutive series, 281 patients were diagnosed with HCC and received for management, at Tanta University Hospitals, within the past 3 years. Demographic variables and environmental exposures were recorded by direct application of a modified questionnaire. Sera were tested for HCV (antibodies by ELISA and RNA by RT-PCR) and HBV (HBs Ag by ELISA and HBV DNA). Antinuclear antibody, serum copper, and iron were assessed in non-viral HCC. Liver biopsy was performed for HCC diagnosis and grading and liver tissue in all patients by histopathological and immunohistochemical methods to assess HBV and/or HCV etiology. Non-B non-C HCC patients were 13.87% of the total and were associated with multiple risks, predominantly pesticides (100%, p fertilizers (94.87%, p farming, and residence. Their tumors were mainly solitary, smaller sizes, and of lower alpha-fetoprotein titers. The study showed insignificant increase in prevalence of non-B non-C HCC and had special characters. Multivariate analysis showed significance of pesticides and smoking as independent risks for non-B non-C HCC. Pesticides and smoking heavy exposure can be considered as primary risks for non-B non-C HCC. Phosphate and ammonium sulfate fertilizers were associations. The study will increase awareness for better prevention and management.

  15. α-Fetoprotein promoter-driven Cre/LoxP-switched RNA interference for hepatocellular carcinoma tissue-specific target therapy.

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    Yuan-Fei Peng

    Full Text Available RNA interference (RNAi has recently emerged as a potential treatment modality for hepatocellular carcinoma (HCC therapy, but the lack of cellular targets and sustained efficacy limits its application. The purpose of this study is to develop an HCC tissue-specific RNAi system and investigate its possibility for HCC treatment.Two different HCC-specific RNAi systems in which therapeutic miRNA or shRNA against target gene (Beclin 1 was directly or indirectly driven by alpha-fetoprotein promoter (AFP-miRNA and AFP-Cre/LoxP-shRNA were constructed. Human HCC cell lines (HepG2, Hep3B and HCCLM3 and non-HCC cell lines (L-02, Hela and SW1116 were infected with the systems. The effectiveness and tissue-specificity of the systems were examined by Q-PCR and western blot analysis. The efficacy of the systems was further tested in mouse model of HCC by intravenous or intratumoral administration. The feasibility of the system for HCC treatment was evaluated by applying the system as adjuvant therapy to enhance sorafenib treatment. An AFP-Cre/LoxP-shRNA system targeting Atg5 gene (AFP-Cre/LoxP-shRNA-Atg5 was constructed and its efficacy in sensitizing HCC cells (MHCC97L/PLC to sorafenib treatment was examined by apoptosis assay in vitro and tumorigenesis assay in vivo.The AFP-miRNA system could silence target gene (Beclin 1 but required a high titer which was lethal to target cells. The AFP-Cre/LoxP-shRNA system could efficiently knockdown target gene while maintain high HCC specificity. Intratumoral injection of the AFP-Cre/LoxP-shRNA system could efficiently silence target gene (Beclin 1 in vivo while intravenous administration could not. The AFP-Cre/LoxP-shRNA system target Atg5 gene could significantly sensitize MHCC97L/PLC cells to sorafenib-induced apoptosis in vitro and tumor growth suppression in vivo.An efficient HCC tissue-specific RNAi system (AFP-Cre/LoxP-shRNA was successfully established. The system provides a usable tool for HCC-specific RNAi

  16. Selective Toxicity of Persian Gulf Sea Cucumber (Holothuria parva) and Sponge (Haliclona oculata) Methanolic Extracts on Liver Mitochondria Isolated from an Animal Model of Hepatocellular Carcinoma.

    Science.gov (United States)

    Seydi, Enayatollah; Motallebi, Abbasali; Dastbaz, Maryam; Dehghan, Sahar; Salimi, Ahmad; Nazemi, Melika; Pourahmad, Jalal

    2015-12-01

    Natural products isolated from marine environments are well known for their pharmacodynamic potential in diverse disease treatments, such as for cancer or inflammatory conditions. Sea cucumbers are marine animals of the phylum Echinoderm and the class Holothuroidea, with leathery skin and gelatinous bodies. Sponges are important components of Persian Gulf animal communities, and the marine sponges of the genus Haliclona have been known to display broad-spectrum biological activity. Many studies have shown that sea cucumbers and sponges contain antioxidants and anti-cancer compounds. This study was designed to determine the selective toxicity of Persian Gulf sea cucumber (Holothuria parva) and sponge (Haliclona oculata) methanolic extracts on liver mitochondria isolated from an animal model of hepatocellular carcinoma, as part of a national project that hopes to identify novel potential anticancer candidates among Iranian Persian Gulf flora and fauna. To induce hepatocarcinogenesis, rats were given diethylnitrosamine (DEN) injections (200 mg/kg i.p. by a single dose), and then the cancer was promoted with 2-acetylaminofluorene (2-AAF) (0.02 w/w) for two weeks. Histopathological evaluations were performed, and levels of liver injury markers and a specific liver cancer marker (alpha-fetoprotein), were determined for confirmation of hepatocellular carcinoma induction. Finally, mitochondria were isolated from cancerous and non-cancerous hepatocytes. Our results showed that H. parva methanolic extracts (250, 500, and 1000 µg/mL) and H. oculata methanolic extracts (200, 400, and 800 µg/mL) increased reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP), mitochondrial swelling, and cytochrome c release in the mitochondria obtained from cancerous hepatocytes, but not in mitochondria obtained from non-cancerous liver hepatocytes. These extracts also induced caspase-3 activation, which is known as a final mediator of apoptosis, in the hepatocytes

  17. First-trimester screening for early and late preeclampsia using maternal characteristics, biomarkers, and estimated placental volume.

    Science.gov (United States)

    Sonek, Jiri; Krantz, David; Carmichael, Jon; Downing, Cathy; Jessup, Karen; Haidar, Ziad; Ho, Shannon; Hallahan, Terrence; Kliman, Harvey J; McKenna, David

    2018-01-01

    Preeclampsia is a major cause of perinatal morbidity and mortality. First-trimester screening has been shown to be effective in selecting patients at an increased risk for preeclampsia in some studies. We sought to evaluate the feasibility of screening for preeclampsia in the first trimester based on maternal characteristics, medical history, biomarkers, and placental volume. This is a prospective observational nonintervention cohort study in an unselected US population. Patients who presented for an ultrasound examination between 11-13+6 weeks' gestation were included. The following parameters were assessed and were used to calculate the risk of preeclampsia: maternal characteristics (demographic, anthropometric, and medical history), maternal biomarkers (mean arterial pressure, uterine artery pulsatility index, placental growth factor, pregnancy-associated plasma protein A, and maternal serum alpha-fetoprotein), and estimated placental volume. After delivery, medical records were searched for the diagnosis of preeclampsia. Detection rates for early-onset preeclampsia (preeclampsia (≥34 weeks' gestation) for 5% and 10% false-positive rates using various combinations of markers were calculated. We screened 1288 patients of whom 1068 (82.99%) were available for analysis. In all, 46 (4.3%) developed preeclampsia, with 13 (1.22%) having early-onset preeclampsia and 33 (3.09%) having late-onset preeclampsia. Using maternal characteristics, serum biomarkers, and uterine artery pulsatility index, the detection rate of early-onset preeclampsia for either 5% or 10% false-positive rate was 85%. With the same protocol, the detection rates for preeclampsia with delivery preeclampsia were 15% and 48% for 5% and 10%, while for preeclampsia at ≥37 weeks' gestation the detection rates were 24% and 43%, respectively. The detection rates for late-onset preeclampsia and preeclampsia with delivery at >37 weeks' gestation were not improved by the addition of biomarkers. Screening

  18. Risk of hepatocellular carcinoma in HBV cirrhotic patients assessed by the combination of miR-122, AFP and PIVKA-II.

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    Caviglia, Gian P; Abate, Maria L; Gaia, Silvia; Petrini, Elisa; Bosco, Caterina; Olivero, Antonella; Rosso, Chiara; Ciancio, Alessia; Pellicano, Rinaldo; Saracco, Giorgio M; Rizzetto, Mario; Smedile, Antonina

    2017-12-01

    Reliable biomarkers for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis are lacking. We evaluated the use of miR-122, alpha-fetoprotein (AFP) and protein induced by vitamin k absence/antagonist II (PIVKA-II) for HCC risk prediction in patients with HBV-related cirrhosis under surveillance. We first analyzed a group of 63 patients with HBV-related liver cirrhosis of whom 33 had HCC. Then we performed a retrospective analysis on another group of 13 cirrhotic patients who developed HCC during surveillance, of whom serial serum samples were available (at time of HCC diagnosis [T0], 6-9 months [T-1] and 12-18 months [T-2] before HCC detection). Serum miR-122 levels were assessed by quantitative real time-PCR, whereas AFP and PIVKA-II were measured by fully automated chemiluminescent enzyme immunoassay. Serum levels of miR-122, AFP and PIVKA-II were different between patients with cirrhosis and those with HCC (P=0.024, P<0.001 and P<0.001, respectively). Areas under the curve (AUC) were 0.675 for miR-122, 0.791 for AFP and 0.846 for PIVKA-II, while their combination improved the discrimination power between cirrhosis and HCC (AUC=0.918). In the longitudinal study, we found a significant variation overtime for the biomarkers combination (P=0.011) but not for each single biomarker (miR-122, P=0.163; AFP, P=0.170; PIVKA-II, P=0.447). Combined miR-122+AFP+PIVKA-II adjusted Hazard Ratio for HCC development was 10.63, 95% confidence interval 1.87-60.28 (P<0.001). In HBV-related cirrhosis, the combination of miR-122, AFP and PIVKA-II enables the identification of patients at higher risk of HCC development that could benefit from closer monitoring.

  19. Real-world efficacy and safety of ledipasvir and sofosbuvir in patients with hepatitis C virus genotype 1 infection: a nationwide multicenter study by the Japanese Red Cross Liver Study Group.

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    Tsuji, Keiji; Kurosaki, Masayuki; Itakura, Jun; Mori, Nami; Takaki, Shintaro; Hasebe, Chitomi; Akahane, Takehiro; Joko, Kouji; Yagisawa, Hitoshi; Takezawa, Jirou; Nakata, Ryou; Kusakabe, Atsunori; Kojima, Yuji; Kimura, Hiroyuki; Tamada, Takashi; Kobashi, Haruhiko; Mitsuda, Akeri; Kondou, Masahiko; Ogawa, Chikara; Uchida, Yasushi; Sohda, Tetsuro; Narita, Ryouichi; Izumi, Namiki

    2018-04-06

    We aimed to describe the real-world efficacy and safety of combination therapy with ledipasvir and sofosbuvir (LDV/SOF) for chronic hepatitis C virus (HCV) genotype 1 (GT1) infection. This retrospective analysis of a prospective, nationwide, multicenter registry included GT1-infected patients treated with LDV/SOF for 12 weeks. We assessed the rate of sustained virological response at 12 weeks post-treatment (SVR12), incidence of adverse events, and serum markers of hepatocellular carcinoma (HCC). Among the 1461 patients included (mean age, 69 years; 29.5% aged > 75 years; cirrhosis, 23.8%; history of treatment for HCC, 10.9%), the overall SVR12 rate was 98.4% (1438/1461). Factors associated with treatment failure were cirrhosis (odds ratio, 4.19; p = 0.014) and resistance-associated substitutions (RASs) in NS5A at baseline (odds ratio, 7.78; p = 0.0004). The SVR12 rate in patients with cirrhosis and NS5A RASs was 93.0% compared to 100% in patients without cirrhosis or NS5A RASs. In patients with SVR, the levels of alpha-fetoprotein (AFP), AFP-L3, and Mac-2 binding protein glycosylation isomer (M2BPGi) decreased from baseline to end of treatment (from 13.4 ± 37.6 to 6.0 ± 10.6 ng/mL, p < 0.0001; from 2.2 ± 4.9 to 1.5 ± 6.3%, p < 0.005; and from 3.6 ± 3.7 to 2.0 ± 3.5 cut-off index, p < 0.0001; respectively). Adverse events were rare and not associated with age. No decrease in estimated glomerular filtration rate was observed in patients with baseline chronic kidney disease stage 3. LDV/SOF therapy is highly effective and safe in elderly Japanese patients with HCV GT1, even in the presence of cirrhosis or NS5A RASs. Patients with SVR may have a lower risk of HCC.

  20. Protein phosphatase magnesium-dependent 1δ (PPM1D mRNA expression is a prognosis marker for hepatocellular carcinoma.

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    Guang-Bing Li

    Full Text Available Protein phosphatase magnesium-dependent 1δ (PPM1D is an oncogene, overexpressed in many solid tumors, including ovarian cancer and breast cancer. The current study examined the expression and the prognostic value of PPM1D mRNA in human hepatocellular carcinoma (HCC.Total RNA was extracted from 86 HCC and paired non-cancerous liver tissues. PPM1D mRNA expression was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qPCR. Immunohistochemistry assay was used to verify the expression of ppm1d protein in the HCC and non-cancerous liver tissues. HCC patients were grouped according to PPM1D mRNA expression with the average PPM1D mRNA level in non-cancerous liver tissue samples as the cut-off. Correlations between clinicopathologic variables, overall survival and PPM1D mRNA expression were analyzed.PPM1D mRNA was significantly higher in HCC than in the paired non-cancerous tissue (p<0.01. This was confirmed by ppm1d staining. 56 patients were classified as high expression group and the other 30 patients were categorized as low expression group. There were significant differences between the two groups in term of alpha-fetoprotein (α-FP level (p<0.01, tumor size (p<0.01, TNM stage (p<0.01, recurrence incidence (p<0.01 and family history of liver cancer (p<0.01. The current study failed to find significant differences between the two groups in the following clinical characteristics: age, gender, portal vein invasion, lymphnode metastasis, hepatitis B virus (HBV infection and alcohol intake. Survival time of high expression group was significantly shorter than that of low expression group (median survival, 13 months and 32 months, respectively, p<0.01.Up-regulation of PPM1D mRNA was associated with progressive pathological feature and poor prognosis in HCC patients. PPM1D mRNA may serve as a prognostic marker in HCC.

  1. A prospective clinical trial to compare the performance of dried blood spots prenatal screening for Down's syndrome with conventional non-invasive testing technology.

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    Hu, Huiying; Jiang, Yulin; Zhang, Minghui; Liu, Shanying; Hao, Na; Zhou, Jing; Liu, Juntao; Zhang, Xiaojin; Ma, Liangkun

    2017-03-01

    To evaluate, side by side, the efficiency of dried blood spots (DBSs) against serum screening for Down's syndrome, and then, to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. One thousand eight hundred and thirty-seven low-risk Chinese women, with singleton pregnancy, were enrolled for the study. Alpha-fetoprotein and free beta human chorionic gonadotropin were measured for the serum as well as for the parallel DBS samples. Partial high-risk pregnant women identified by primary blood testing (n = 38) were also subject to the secondary cfDNA screening. Diagnostic amniocentesis was utilized to confirm the screening results. The true positive rate for Down's syndrome detection was 100% for both blood screening methods; however, the false-positive rate was 3.0% for DBS and 4.0% for serum screening, respectively. DBS correlated well with serum screening on Down's syndrome detection. Three out of 38 primary high-risk women displayed chromosomal abnormalities by cfDNA analysis, which were confirmed by amniocentesis. Either the true detection rate or the false-positive rate for Down's syndrome between DBS and the serum test is comparable. In addition, blood primary screening aligned with secondary cfDNA analysis, a "before and after" two-tier screening strategy, can massively decrease the false-positive rate, which, then, dramatically reduces the demand for invasive diagnostic operation. Impact statement Children born with Down's syndrome display a wide range of mental and physical disability. Currently, there is no effective treatment to ease the burden and anxiety of the Down's syndrome family and the surrounding society. This study is to evaluate the efficiency of dried blood spots against serum screening for Down's syndrome and to construct a two-tier strategy by topping up the fetal

  2. Value of contrast-enhanced intraoperative ultrasound for cirrhotic patients with hepatocellular carcinoma: A report of 20 cases

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    Lu, Qiang; Luo, Yan; Yuan, Chao-Xin; Zeng, Yong; Wu, Hong; Lei, Zheng; Zhong, Yao; Fan, Yu-Ting; Wang, Hong-Hao; Luo, Yang

    2008-01-01

    AIM: To assess the clinical value of contrast-enhanced intraoperative ultrasound (CE-IOUS) as a novel tool in partial hepatectomy for cirrhotic patients with hepatocellular carcinoma (HCC). METHODS: From January 2007 to September 2007, a total of 20 consecutive cirrhotic patients with HCC scheduled to undergo partial hepatectomy were studied. Preoperative contrast enhanced computer tomography (CT) and/or magnetic resonance (MR) scans were performed within 1-2 wk before operation. Intraoperative ultrasound (IOUS) and CE-IOUS were carried out after mobilization of the liver. Lesions on precontrast and postcontrast scans were counted and mapped. CE-IOUS was performed with intravenous injection of ultrasound contrast agents SonoVue (Bracco Imaging, Milan, Italy). Arterial, portal and late phases of contrast enhancement were recorded and analyzed. Nodules showing arterial phase hyper-enhancing and/or hypo-enhancing in late parenchymal phase were considered malignant and removed surgically. Ultrasound-guided biopsy and ethanol ablation would be an option if the nodule could not be removed surgically. Newly detected nodules on IOUS showing iso-enhancement in both arterial and late phases were considered benign. These nodules were either removed surgically if they were close to the main lesion or followed by examinations of alpha-fetoprotein (AFP) level and ultrasound and/or CT/MR every 3 mo. RESULTS: IOUS found 41 nodules in total, among which 17 (41.46%) were newly detected compared to preoperative imaging. Thirty-three nodules were diagnosed malignant by CE-IOUS, including one missed by IOUS. The sensitivity and specificity of CE-IOUS on detecting HCC nodules are 100% (33/33 and 100% (9/9), respectively. Nine nodules were considered benign by CE-IOUS, four was confirmed at histology and five by follow-up. CE-IOUS changed the surgical strategy in 35% (7/20) of patients and avoid unnecessary intervention in 30% (6/20) of patients. CONCLUSION: CE-IOUS is a useful means to

  3. A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation: analysis of 865 consecutive liver transplant recipients.

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    Agopian, Vatche G; Harlander-Locke, Michael; Zarrinpar, Ali; Kaldas, Fady M; Farmer, Douglas G; Yersiz, Hasan; Finn, Richard S; Tong, Myron; Hiatt, Jonathan R; Busuttil, Ronald W

    2015-04-01

    Although radiologic size criteria (Milan/University of California, San Francisco [UCSF]) have led to improved outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC), recurrence remains a significant challenge. We analyzed our 30-year experience with LT for HCC to identify predictors of recurrence. A novel clinicopathologic risk score and prognostic nomogram predicting post-transplant HCC recurrence was developed from a multivariate competing-risk Cox regression analysis of 865 LT recipients with HCC between 1984 and 2013. Overall patient and recurrence-free survivals were 83%, 68%, 60% and 79%, 63%, and 56% at 1-, 3-, and 5-years, respectively. Hepatocellular carcinoma recurred in 117 recipients, with a median time to recurrence of 15 months, involving the lungs (59%), abdomen/pelvis (38%), liver (35%), bone (28%), pleura/mediastinum (12%), and brain (5%). Multivariate predictors of recurrence included tumor grade/differentiation (G4/poor diff hazard ratio [HR] 8.86; G2-3/mod-poor diff HR 2.56), macrovascular (HR 7.82) and microvascular (HR 2.42) invasion, nondownstaged tumors outside Milan criteria (HR 3.02), nonincidental tumors with radiographic maximum diameter ≥ 5 cm (HR 2.71) and <5 cm (HR 1.55), and pretransplant neutrophil-to-lymphocyte ratio (HR 1.77 per log unit), maximum alpha fetoprotein (HR 1.21 per log unit), and total cholesterol (HR 1.14 per SD). A pretransplantation model incorporating only known radiographic and laboratory parameters had improved accuracy in predicting HCC recurrence (C statistic 0.79) compared with both Milan (C statistic 0.64) and UCSF (C statistic 0.64) criteria alone. A novel clinicopathologic prognostic nomogram included explant pathology and had an excellent ability to predict post-transplant recurrence (C statistic 0.85). In the largest single-institution experience with LT for HCC, excellent long-term survival was achieved. Incorporation of routine pretransplantation biomarkers to existing

  4. Value of serum GP73, AFP, and AFP-L3 in diagnosis of liver cancer and recurrence monitoring after radiofrequency ablation

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    ZHANG Qin

    2015-02-01

    Full Text Available ObjectiveTo explore the clinical value of three serum tumor markers, Golgi protein 73 (GP73, alpha-fetoprotein (AFP, and AFP-L3, in the diagnosis of liver cancer and recurrence monitoring after radio frequency ablation. MethodsA total of 174 patients who visited our hospital from July 2012 to October 2013 were included in the study, consisting of 86 patients with newly diagnosed liver cancer, 39 with liver cirrhosis, 29 with hepatitis, and 20 healthy controls. Among the patients with newly diagnosed liver cancer, 37 were followed up for three months after the radiofrequency ablation. Serum levels of GP73, AFP, and AFP-L3 were measured by ELISA, electrochemiluminescence, and affinity adsorption chromatography, respectively. Nonparametric tests were performed on the results of serum samples from the four groups which showed skewed distribution and were represented by median (quartile interval [M(P25-P75]. Overall comparison was made by Kruskal-Wallis H test, and comparison between groups was made by Mann-Whitney U test. Pair-matching rank-sum test was performed using Wilcoxon Signed Ranks, and categorical data were analyzed by χ2 test. ResultsThe levels of GP73, AFP, and AFP-L3 in the liver cancer group were significantly higher than those in other groups (all P<0.05. The positive rates of GP73 and AFP-L3 in the liver cancer group were significantly higher than those in other groups (all P<0.05, and the positive rates of the two markers were significantly higher than that of AFP among patients with liver cancer (P<0.05. Thirty-seven patients with newly diagnosed liver cancer were reexamined three months after radiofrequency ablation, and the preoperational AFP-L3 level in the patients who had recurrence was significantly higher than that in the patients without recurrence (P<0.05. ConclusionSerum GP73, AFP, and AFP-L3 show great values in the diagnosis of liver cancer. AFP-L3 can be used as an indicator for the identification of

  5. Systemic administration of a novel human umbilical cord mesenchymal stem cells population accelerates the resolution of acute liver injury

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    Burra Patrizia

    2012-07-01

    Full Text Available Abstract Background Hepatocytes and stem cells transplantation may be an alternative to liver transplantation in acute or chronic liver disease. We aimed to evaluate the therapeutic potential of mesenchymal stem cells from human umbilical cord (UCMSCs, a readily available source of mesenchymal stem cells, in the CCl4-induced acute liver injury model. Methods Mesenchymal stem cells profile was analyzed by flow cytometry. In order to evaluate the capability of our UCMSCs to differentiate in hepatocytes, cells were seeded on three different supports, untreated plastic support, MatrigelTM and human liver acellular matrix. Cells were analyzed by immunocitochemistry for alpha-fetoprotein and albumin expression, qPCR for hepatocyte markers gene expression, Periodic Acid-Schiff staining for glycogen storage, ELISA for albumin detection and colorimetric assay for urea secretion. To assess the effects of undifferentiated UCMSCs in hepatic regeneration after an acute liver injury, we transplanted them via tail vein in mice injected intraperitoneally with a single dose of CCl4. Livers were analyzed by histological evaluation for damage quantification, immunostaining for Kupffer and stellate cells/liver myofibroblasts activation and for UCMSCs homing. Pro- and anti-inflammatory cytokines gene expression was evaluated by qPCR analysis and antioxidant enzyme activity was measured by catalase quantification. Data were analyzed by Mann–Whitney U-test, Kruskal-Wallis test and Cuzick’s test followed by Bonferroni correction for multiple comparisons. Results We have standardized the isolation procedure to obtain a cell population with hepatogenic properties prior to in vivo transplantation. When subjected to hepatogenic differentiation on untreated plastic support, UCMSCs differentiated in hepatocyte-like cells as demonstrated by their morphology, progressive up-regulation of mature hepatocyte markers, glycogen storage, albumin and urea secretion. However

  6. Postoperative Albumin-Bilirubin Grade Change Predicts the Prognosis of Patients with Hepatitis B-Related Hepatocellular Carcinoma Within the Milan Criteria.

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    Li, Chuan; Zhang, Xiao-Yun; Peng, Wei; Wen, Tian-Fu; Yan, Lu-Nan; Li, Bo; Yang, Jia-Yin; Wang, Wen-Tao; Xu, Ming-Qing

    2017-11-14

    Albumin-bilirubin (ALBI) grade has been validated as a simple, evidence-based, and objective prognostic tool for patients with hepatocellular carcinoma (HCC). However, minimal information is available concerning postoperative ALBI grade changes in HCC. This study aimed to investigate the prognostic value of postoperative ALBI grade changes in patients with hepatitis B virus (HBV)-related HCC within the Milan criteria after liver resection. Patients with HBV-related HCC within the Milan criteria who underwent liver resection between 2010 and 2016 at West China Hospital were reviewed (N = 258). A change in ALBI grade was defined as first postoperative month ALBI grade-preoperative ALBI grade. If the value was >0, postoperative worsening of ALBI grade was considered; otherwise, stable ALBI grade was considered. Cox proportional hazard regression analyses were used to determine the factors that influence recurrence and survival. During the follow-up, 130 patients experienced recurrence and 47 patients died. Multivariate analyses revealed that postoperative worsening of ALBI grade (HR 1.541, 95% CI 1.025-2.318, P = 0.038), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, P = 0.004), and multiple tumors (HR 1.676, 95% CI 1.075-2.615, P = 0.023) were associated with postoperative recurrence, whereas MVI (HR 2.737, 95% CI 1.475-5.080, P = 0.001), postoperative worsening of ALBI grade (HR 2.268, 95% CI 1.227-4.189, P = 0.009), high alpha-fetoprotein level (HR 2.055, 95% CI 1.136-3.716, P = 0.017), and transfusion (HR 2.597, 95% CI 1.395-4.834, P = 0.003) negatively influenced long-term survival. Patients with postoperative worsening of ALBI grade exhibited increased incidence of recurrence and worse long-term survival. Postoperative worsening of ALBI grade was associated with increased recurrence and poorer overall survival for patients with HBV-related HCC within the Milan criteria. We should pay attention to liver function changes in HCC patients

  7. Preliminary investigation of hybrid bioartificial liver support system in treatment of HBV-related acute-on-chronic liver failure

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    YOU Shaoli

    2013-09-01

    Full Text Available ObjectiveTo construct a hybrid bioartificial liver support system and to investigate its safety and efficacy in patients with hepatitis B virus (HBV-related acute-on-chronic liver failure (ACLF. MethodsA hollow fiber bioreactor was constructed using cultured HepG2 cells transfected with human augmenter of liver regeneration gene. Patients with HBV-related ACLF who were hospitalized in our hospital from May 2009 to August 2011 were randomly divided into treatment group (n=10 and control group (n=10. The treatment group was treated using the hybrid bioartificial liver support system, while the control group was treated with conventional plasma exchange. Comparison of means between the two groups was made by independent-samples t test, and comparison of variables before and after treatment was made by paired t test. ResultsOf the 10 patients in treatment group, 7 had improvement in clinical symptoms and were discharged, 1 died of hepatic encephalopathy, 1 died of hepatorenal syndrome, and 1 died of liver failure after discharge. Of the 10 patients in control group, 5 survived, 1 underwent liver transplantation, and 4 died of liver failure. Before treatment, the treatment group and control group had model for end-stage liver disease (MELD scores of 24.26±2.54 and 24.71±2.79, respectively, without significant difference between the two groups (t=1.971, P=0.064. The treatment group had MELD scores of 21.71±2.92, 22.10±4.46, and 19.90±5.43 after 3 days, 1 week, and 4 weeks, respectively, of treatment. At the end of one-year follow-up, the mean serum alpha-fetoprotein levels were 14.24 ng/ml in treatment group and 11.32 ng/ml in control group, and no space-occupying lesions in the liver were found through abdominal ultrasound. ConclusionThe constructed hybrid bioartificial liver support system is effective and safe in the treatment of HBV-related ACLF.

  8. Precocious puberty secondary to a mixed germ cell-sex cord-stromal tumor associated with an ovarian yolk sac tumor: a case report

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    Metwalley Kotb

    2012-06-01

    Full Text Available Abstract Introduction Ovarian tumors are the least common cause of sexual precocity in girls. Mixed germ cell-sex cord-stromal tumors associated with a yolk sac tumor of the ovary are rare neoplasms, of which only a small number of well-documented cases have been described so far. Here, we report precocious puberty in a four-year-old Egyptian girl caused by a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary. Case presentation A four-year-old Egyptian girl was referred to our pediatric endocrinology unit for evaluation of bilateral breast budding, pubic hair and vaginal bleeding. On examination, we found that her breast enlargement and pubic hair were compatible with Tanner III. A thorough workup revealed a large mass in her right ovary. Magnetic resonance imaging ofher brain showed that her pituitary gland was normal. A hormonal assay revealed high levels of estradiol, 280 to 375pmol/L; progesterone, 5.3 nmol/L; testosterone 38.9 pg/mL; and androstenedione, 4.1 ng/mL. Her basal and stimulated levels of luteinizing hormone and follicle-stimulating hormone were low. Tumor markers levels were high, with a total inhibin of 1,069U/L and an alpha-fetoprotein of 987 μg/L. Her chromosomes were normal (46XX. Our patient underwent an explorative laparotomy and a solid tumor localized to her right ovary was identified. A right salpingo-oophorectomy was performed and the histopathological diagnosis was a mixed germ cell-sex cord-stromal tumorwith a yolk sac tumor of the ovary. Postoperatively, she was started on treatment with chemotherapy. Our patient is doing well without evidence of tumor recurrence or metastasis during eight months of postoperative follow-up. Conclusion Although a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary is a rare occurrence, it should be considered in the differential diagnosis for a prepubescent girl with an abdominal mass and precocious puberty.

  9. Predictability of liver-related seromarkers for the risk of hepatocellular carcinoma in chronic hepatitis B patients.

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    Yu-Ju Lin

    Full Text Available BACKGROUND: Hepatitis B virus (HBV-related hepatocellular carcinoma (HCC is a major global health problem. A few risk calculators have been developed using mainly HBV seromarkers as predictors. However, serum HBV DNA level, HBV genotype, and mutants are not routinely checked in regular health examinations. This study aimed to assess the predictability of HCC risk in chronic hepatitis B patients, using a combination of liver-related seromarkers combined with or without HBV seromarkers. METHODS: A prospective cohort of 1,822 anti-HCV-seronegative chronic HBV carriers was included in this study. Liver-related seromarkers including aspartate aminotransferase (AST, alanine aminotransferase (ALT, alpha-fetoprotein (AFP, gamma-glutamyltransferase (GGT, total bilirubin, total protein, albumin, serum globulins, apolipoprotein A1, and apolipoprotein B were examined. Hazard ratios of HCC with 95% confidence intervals were estimated using Cox proportional hazards regression models. Regression coefficients of seromarkers significantly associated with HCC risk in multivariate analyses were used to create integer risk scores. The predictability of various risk models were assessed by area under receiver operating characteristic curves (AUROCs. RESULTS: During a median follow-up of 5.9 years, 48 newly-developed HCC cases were ascertained. Elevated serum levels of ALT (≥ 28 U/L, AFP (≥ 5 ng/mL, and GGT (≥ 41 U/L, an increased AST/ALT ratio (AAR, ≥ 1, and lowered serum levels of albumin (≤ 4.1 g/dL and alpha-1 globulin (≤ 0.2 g/dL were significantly associated with an increased HCC risk (P<0.05 in multivariate analysis. The risk model incorporating age, gender, AAR, and serum levels of ALT, AFP, GGT, albumin, and alpha-1 globulin had an AUROC of 0.89 for predicting 6-year HCC incidence. The AUROC was 0.91 after the addition of HBV seromarkers into the model, and 0.83 for the model without liver-related seromarkers, with the exception of ALT

  10. Intervention of raltitrexed combined with epirubicin in hepatic arterial infusion and embolization in treatment of primary liver cancer

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    WANG Baoxin

    2015-05-01

    Full Text Available ObjectiveTo evaluate the therapeutic effect of intervention of raltitrexed combined with epirubicin in hepatic arterial infusion and embolization in the treatment of advanced primary liver cancer. MethodsA total of 80 patients with advanced primary liver cancer who were admitted to the Central Hospital of China National Petroleum Corporation from January 2011 to May 2013 and not suitable for surgical treatment were selected and randomly divided into study group (n=40 and control group (n=40. The study group was treated with intervention of raltitrexed combined with epirubicin in hepatic arterial infusion and embolization, while the control group was treated with intervention of fluorouracil (5-FU combined with epirubicin in hepatic arterial infusion and embolization. The treatment was given once every four weeks for a total of three to six circles. The response rate (RR, disease control rate (DCR, median time to progression, survival rate, and the decreases in alpha fetoprotein (AFP, carcinoembryonic antigen (CEA, transaminase, and bilirubin of the two groups were observed. Comparison of categorical data between the two groups was made by chi-square test, and comparison of continuous data was made by t test. ResultsThe RRs of the study group and control group were 52.5% and 22.5%, respectively, and the difference was significant (χ2=7.680, P=0.006; the DCRs of the study group and control group were 87.5% and 60.0%, respectively, and the difference was significant (χ2=7.813, P=0.005; the median time to progression of the study group and control group was 12.2 and 8.0 months, respectively, and the difference was significant (t=5.118, P=0.00; the 1- and 2-year survival rates of the study group were 85.0% and 60.0%, respectively, with the control group being 65.0% and 37.5%, and the difference was significant (χ2=4.267, P=0.039; χ2=4.053, P=0.044. One month after chemoembolization, the number of patients whose AFP, transaminase, and bilirubin

  11. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor

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    Nora Freyer

    2016-08-01

    Full Text Available The hepatic differentiation of human induced pluripotent stem cells (hiPSC holds great potential for application in regenerative medicine, pharmacological drug screening, and toxicity testing. However, full maturation of hiPSC into functional hepatocytes has not yet been achieved. In this study, we investigated the potential of a dynamic three-dimensional (3D hollow fiber membrane bioreactor technology to improve the hepatic differentiation of hiPSC in comparison to static two-dimensional (2D cultures. A total of 100 × 106 hiPSC were seeded into each 3D bioreactor (n = 3. Differentiation into definitive endoderm (DE was induced by adding activin A, Wnt3a, and sodium butyrate to the culture medium. For further maturation, hepatocyte growth factor and oncostatin M were added. The same differentiation protocol was applied to hiPSC maintained in 2D cultures. Secretion of alpha-fetoprotein (AFP, a marker for DE, was significantly (p < 0.05 higher in 2D cultures, while secretion of albumin, a typical characteristic for mature hepatocytes, was higher after hepatic differentiation of hiPSC in 3D bioreactors. Functional analysis of multiple cytochrome P450 (CYP isoenzymes showed activity of CYP1A2, CYP2B6, and CYP3A4 in both groups, although at a lower level compared to primary human hepatocytes (PHH. CYP2B6 activities were significantly (p < 0.05 higher in 3D bioreactors compared with 2D cultures, which is in line with results from gene expression. Immunofluorescence staining showed that the majority of cells was positive for albumin, cytokeratin 18 (CK18, and hepatocyte nuclear factor 4-alpha (HNF4A at the end of the differentiation process. In addition, cytokeratin 19 (CK19 staining revealed the formation of bile duct-like structures in 3D bioreactors similar to native liver tissue. The results indicate a better maturation of hiPSC in the 3D bioreactor system compared to 2D cultures and emphasize the potential of dynamic 3D culture

  12. Proteomic Analysis of Fetal Ovary Reveals That Ovarian Developmental Potential Is Greater in Meishan Pigs than in Yorkshire Pigs.

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    Mengmeng Xu

    Full Text Available Time-dependent expression of functional proteins in fetal ovaries is important to understand the developmental process of the ovary. This study was carried out to enhance our understanding of the developmental process of porcine fetal ovaries and to better address the differences in fetal ovary development of local and foreign pigs. The objective of the present study is to test the expression of key proteins that regulate the growth and development of fetal ovaries in Meishan and Yorkshire porcine breeds by using proteomics technology. Six Meishan and 6 Yorkshire pregnant gilts were used in this experiment. Fetal ovaries were obtained from Yorkshire and Meishan gilts on days 55 and 90 of the gestation period. Using 2D-DIGE (two dimensional-difference in gel electrophoresis analysis, the results showed that there are about 1551 and 1400 proteins in gilt fetal ovaries on days 55 and 90, respectively of the gestation. Using MALDI TOF-TOF MS analysis, 27 differentially expressed proteins were identified in the fetal ovaries of the 2 breeds on day 55 of gestation, and a total of 18 proteins were identified on day 90 of gestation. These differentially expressed proteins were involved in the regulation of biological processes (cell death, stress response, cytoskeletal proteins and molecular functions (enzyme regulator activity. We also found that alpha-1-antitrypsin, actin, vimentin, and PP2A proteins promote the formation of primordial follicles in the ovaries of Yorkshire pigs on day 55 of gestation while low expression heat shock proteins and high expression alpha-fetoproteins (AFP may promote Meishan fetal ovarian follicular development on day 90 of gestation. These findings provide a deeper understanding of how reduced expression of heat shock proteins and increased expression of AFP can significantly reduce the risk of reproductive disease in obese Meishan sows. Our study also shows how these proteins can increase the ovulation rate and may be

  13. Proteomic Analysis of Fetal Ovary Reveals That Ovarian Developmental Potential Is Greater in Meishan Pigs than in Yorkshire Pigs.

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    Xu, Mengmeng; Che, Long; Wang, Dingyue; Yang, Zhenguo; Zhang, Pan; Lin, Yan; Fang, Zhengfeng; Che, Lianqiang; Li, Jian; Chen, Daiwen; Wu, De; Xu, Shengyu

    2015-01-01

    Time-dependent expression of functional proteins in fetal ovaries is important to understand the developmental process of the ovary. This study was carried out to enhance our understanding of the developmental process of porcine fetal ovaries and to better address the differences in fetal ovary development of local and foreign pigs. The objective of the present study is to test the expression of key proteins that regulate the growth and development of fetal ovaries in Meishan and Yorkshire porcine breeds by using proteomics technology. Six Meishan and 6 Yorkshire pregnant gilts were used in this experiment. Fetal ovaries were obtained from Yorkshire and Meishan gilts on days 55 and 90 of the gestation period. Using 2D-DIGE (two dimensional-difference in gel electrophoresis) analysis, the results showed that there are about 1551 and 1400 proteins in gilt fetal ovaries on days 55 and 90, respectively of the gestation. Using MALDI TOF-TOF MS analysis, 27 differentially expressed proteins were identified in the fetal ovaries of the 2 breeds on day 55 of gestation, and a total of 18 proteins were identified on day 90 of gestation. These differentially expressed proteins were involved in the regulation of biological processes (cell death, stress response, cytoskeletal proteins) and molecular functions (enzyme regulator activity). We also found that alpha-1-antitrypsin, actin, vimentin, and PP2A proteins promote the formation of primordial follicles in the ovaries of Yorkshire pigs on day 55 of gestation while low expression heat shock proteins and high expression alpha-fetoproteins (AFP) may promote Meishan fetal ovarian follicular development on day 90 of gestation. These findings provide a deeper understanding of how reduced expression of heat shock proteins and increased expression of AFP can significantly reduce the risk of reproductive disease in obese Meishan sows. Our study also shows how these proteins can increase the ovulation rate and may be responsible for

  14. Diagnóstico laboratorial do líquido amniótico Laboratory diagnosis of amniotic fluid

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    Sabrina Gonçalves Campana

    2003-09-01

    Full Text Available O presente trabalho tem como objetivos a definição e a fisiologia do líquido amniótico, ressaltando aspectos citológicos e principais técnicas para diagnóstico laboratorial das patologias mais freqüentes. A metodologia utilizada foi a revisão bibliográfica atualizada relacionando os aspectos citológicos com a idade gestacional e técnicas laboratoriais para diagnóstico das principais patologias em que são observadas alterações do líquido amniótico, concluindo-se que este é um importante componente do ambiente intra-uterino. Sua produção e absorção dependem de uma série de mecanismos interdependentes entre o feto, a placenta, as membranas e o organismo materno. Atualmente este fluido pode fornecer inúmeras informações sobre a saúde fetal, realizando-se diversas técnicas, entre elas a amniocentese e a dosagem de alfafetoproteína, que pode detectar defeitos do tubo neural e trissomia do cromossomo 21. A análise do líquido amniótico reforça a importância da realização adequada de um pré-natal, sendo importante relacionar os resultados laboratoriais com a clínica.This present paper aims the definition of the amniotic fluid and its physiology standing out cytological aspects and main techniques for laboratorial diagnosis of the most frequent pathologies. The methodology was based on updated bibliographical research relating the cytological aspects with the pregnancy age and laboratorial techniques for diagnosis of the main pathologies in which alterations of the amniotic fluid are observed, concluding that this is an important component of the intrauterine environment. Its production and absorption depend on a series of interdependent mechanisms among the fetus, the placenta, the membranes and the maternal organism. Currently this fluid can supply innumerable information on the fetal health by the use of diverse techniques, among which, amniocentesis and dosage of alpha-fetoprotein, which can detect defects of the

  15. Gonadal germ cell tumors in children and adolescents

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    Giovanni Cecchetto

    2014-01-01

    Full Text Available Pediatric germ cell tumors (GCT are rare tumors: 80% are benign, 20% malignant (2-3% of all malignant pediatric tumors. The gonadal sites (ovary and testis account for 40% of cases. Ovarian GCTs: Represent 30% of GCTs and 70% of neoplastic ovarian masses, being the most common ovarian neoplasms in children and teenagers. Benign and immature forms (teratomas constitute about 80% of all ovarian GCTs, malignant forms represent 20% increasing during adolescence. The most common malignant entity in children is the yolk sac tumors (YST; dysgerminoma is frequent during adolescence and being bilateral in 10% of cases. Presentation is similar in malignant and benign lesions; abdominal pain (70-80% and lower abdominal mass are common symptoms. Evaluation of alpha-fetoprotein (αFP or beta subunit of human chorionic gonadotropin (βHCG is essential to address the nature of the tumors: Their elevation means presence of malignancy. Surgery includes intraoperative staging procedures and requires ovariectomy or ovarosalpingectomy for malignant lesions, but may be conservative in selected benign tumors. Since malignant GCTs are very chemosensitive, primary chemotherapy is recommended in metastatic or locally advanced tumors. Testicular GCT: Represent 10% of pediatric GCT, and about 30% of malignant GCT with two age peaks: Children <3 years may experience mature teratoma and malignant GCTs, represented almost exclusively by YST, while adolescents may also show seminomas or other mixed tumors. The main clinical feature is a painless scrotal mass. Surgery represents the cornerstone of the management of testicular GCTs, with an inguinal approach and a primary high orchidectomy for malignant tumors, while a testis-sparing surgery can be considered for benign lesions. A retroperitoneal lymph node (LN biopsy may be necessary to define the staging when the involvement of retroperitoneal LN is uncertain at imaging investigations. Conclusion: Patients with gonadal

  16. Values of serum AFP, GGTⅡ and GP73 in diagnosis of primary hepatocellular carcinoma

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    ZHU Chen

    2014-10-01

    Full Text Available ObjectiveTo explore the early diagnostic values of serum alpha-fetoprotein (AFP, gamma-glutamyltransferase Ⅱ (GGTⅡ, and Golgi protein 73 (GP73 in patients with primary hepatocellular carcinoma (PHC. MethodsThe serum specimens of 100 patients with liver diseases (50 cases of hepatitis and liver cirrhosis and 50 cases of PHC and 50 healthy people were collected in our hospital from February 2013 to February 2014. Electrochemical luminescence technique, specific immuno-membrane adsorption assay, and enzyme-linked immunosorbent assay were used to measure the serum levels of AFP, GGTⅡ, and GP73. Comparison of continuous data between multiple groups was made by analysis of variance, and comparison between two groups was made by q test. The receiver operating characteristic (ROC curves of single or combined test results were made, and the areas under the ROC curves (AUCs were calculated. The sensitivity, specificity, and AUCs of AFP, GGTⅡ, GP73, and the combined test were analyzed and compared. ResultsThe level of serum GGTⅡ in the PHC group was significantly different compared with those in the other two groups (F=16.224, P<0.05, but there was no significant difference between the normal group and the hepatitis and liver cirrhosis group (P>0.05. Significant differences in serum levels of AFP and GP73 were observed by paired comparison between the PHC group, hepatitis and liver cirrhosis group, and normal group (F=193.128, F=20.231, P<0.05 for both. When assayed alone, the specificities of GP73, GGTⅡ, and AFP were 69%, 64% and 51%, respectively, and the sensitivities were 92%, 84%, and 76%, respectively. In combined test, the specificity was 94.6% and the sensitivity was 98.8%. ConclusionThe GP73 test is the best performer in the single assays. Combined test of serum AFP, GGTⅡ, and GP73 shows a good diagnostic value for PHC with greatly improved specificity and sensitivity.

  17. Evaluation of Individual and Combined Applications of Serum Biomarkers for Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis

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    Bin Hu

    2013-12-01

    Full Text Available The clinical value of Serum alpha-fetoprotein (AFP to detect early hepatocellular carcinoma (HCC has been questioned due to its low sensitivity and specificity found in recent years. Other than AFP, several new serum biomarkers including the circulating AFP isoform AFP-L3, des-gamma-carboxy prothrombin (DCP and Golgi protein-73 (GP73 have been identified as useful HCC markers. In this investigation, we review the current knowledge about these HCC-related biomarkers, and sum up the results of our meta-analysis on studies that have addressed the utility of these biomarkers in early detection and prognostic prediction of HCC. A systematic search in PubMed, Web of Science, and the Cochrane Library was performed for articles published in English from 1999 to 2012, focusing on serum biomarkers for HCC detection. Data on sensitivity and specificity of tests were extracted from 40 articles that met the inclusion criteria, and the summary receiver operating characteristic curve (sROC was obtained. A meta-analysis was carried out in which the area under the curve (AUC for each biomarker or biomarker combinations (AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73 was used to compare the diagnostic accuracy of different biomarker tests. The AUC of AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73 are 0.835, 0.797, 0.914, 0.710, 0.874, 0.748, and 0.932 respectively. A combination of AFP + GP73 is superior to AFP in detecting HCC and differentiating HCC patients from non-HCC patients, and may prove to be a useful marker in the diagnosis and screening of HCC. In addition, the AUC of GP73, AFP + DCP and AFP + GP73 are better than that of AFP. The clinical value of GP73, AFP + DCP, or AFP + GP73 as serological markers for HCC diagnosis needs to be addressed further in future studies.

  18. Efficacy and safety of TACE in combination with sorafenib for the treatment of TACE-refractory advanced hepatocellular carcinoma in Chinese patients: a retrospective study

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    Wu J

    2017-05-01

    Full Text Available Jianbing Wu,* An Li,* Jiajin Yang,* Yanjun Lu, Jie Li Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Background: Transarterial chemoembolization (TACE and sorafenib (SOR are well-established treatments for hepatocellular carcinoma (HCC. This study evaluates the efficacy and safety of SOR combined with TACE in the treatment of patients with TACE-refractory, advanced-stage HCC. Methods: This retrospective study included 61 patients with TACE-refractory advanced HCC. Patients were divided into TACE + SOR (n=30 and TACE (n=31 treatment groups. Patient demographic and clinical characteristics, overall survival (OS, time to progression (TTP, disease control rate (DCR, and adverse events (AEs were compared between the two groups. Results: Compared with TACE alone, the 5-year OS and TTP were prolonged in the TACE + SOR group (median OS: 17.9 vs 7.1 months, P<0.001; median TTP: 9.3 vs 3.4 months, P<0.001. Multivariate analysis showed that Child–Pugh class A (hazard ratio [HR], 0.234; 95% confidence interval [CI], 0.092–0.595, Eastern Cooperative Oncology Group performance status 1 (HR, 0.355; 95% CI, 0.153–0.826, alpha-fetoprotein <400 ng/mL (HR, 0.349; 95% CI, 0.177–0.689, and TACE + SOR treatment (HR, 0.151; 95% CI, 0.071–0.322 were independent, positive predictive factors of OS. Conclusion: The OS and TTP in the combined treatment group were significantly improved when compared with the TACE group. However, no significant difference in DCR was found between these two groups. While no AEs occurred in the TACE group, two patients in the TACE + SOR group experienced severe AEs which were effectively mitigated by lowering the dose of SOR. Thus, SOR in combination with TACE is a safe and effective treatment for advanced-stage, prior-TACE-resistant HCC. Keywords: hepatocellular carcinoma, sorafenib, transarterial

  19. Quantitative morphometric analysis of hepatocellular carcinoma: development of a programmed algorithm and preliminary application.

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    Yap, Felix Y; Bui, James T; Knuttinen, M Grace; Walzer, Natasha M; Cotler, Scott J; Owens, Charles A; Berkes, Jamie L; Gaba, Ron C

    2013-01-01

    The quantitative relationship between tumor morphology and malignant potential has not been explored in liver tumors. We designed a computer algorithm to analyze shape features of hepatocellular carcinoma (HCC) and tested feasibility of morphologic analysis. Cross-sectional images from 118 patients diagnosed with HCC between 2007 and 2010 were extracted at the widest index tumor diameter. The tumor margins were outlined, and point coordinates were input into a MATLAB (MathWorks Inc., Natick, Massachusetts, USA) algorithm. Twelve shape descriptors were calculated per tumor: the compactness, the mean radial distance (MRD), the RD standard deviation (RDSD), the RD area ratio (RDAR), the zero crossings, entropy, the mean Feret diameter (MFD), the Feret ratio, the convex hull area (CHA) and perimeter (CHP) ratios, the elliptic compactness (EC), and the elliptic irregularity (EI). The parameters were correlated with the levels of alpha-fetoprotein (AFP) as an indicator of tumor aggressiveness. The quantitative morphometric analysis was technically successful in all cases. The mean parameters were as follows: compactness 0.88±0.086, MRD 0.83±0.056, RDSD 0.087±0.037, RDAR 0.045±0.023, zero crossings 6±2.2, entropy 1.43±0.16, MFD 4.40±3.14 cm, Feret ratio 0.78±0.089, CHA 0.98±0.027, CHP 0.98±0.030, EC 0.95±0.043, and EI 0.95±0.023. MFD and RDAR provided the widest value range for the best shape discrimination. The larger tumors were less compact, more concave, and less ellipsoid than the smaller tumors (P < 0.0001). AFP-producing tumors displayed greater morphologic irregularity based on several parameters, including compactness, MRD, RDSD, RDAR, entropy, and EI (P < 0.05 for all). Computerized HCC image analysis using shape descriptors is technically feasible. Aggressively growing tumors have wider diameters and more irregular margins. Future studies will determine further clinical applications for this morphologic analysis.

  20. Relationships between Cell-Free DNA and Serum Analytes in First and Second Trimesters of Pregnancy

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    Vora, Neeta L.; Johnson, Kirby L.; Lambert-Messerlian, Geralyn; Tighiouart, Hocine; Peter, Inga; Urato, Adam C.; Bianchi, Diana W.

    2010-01-01

    Objective Circulating cell-free DNA and maternal serum analytes are indicators of fetal and placental condition. Little is known about the relationship of these noninvasive markers to each other, particularly in the first trimester. Our goal was to assess the relationship between first and second trimester cell-free DNA levels and maternal serum screening markers. Methods First and second trimester residual maternal serum samples from 50 women were obtained. First trimester (pregnancy-associated plasma protein A [PAPP-A] and β-hCG), and second trimester serum analytes (β-hCG, alpha-fetoprotein [AFP], unconjugated estriol and inhibin A) had been measured at the time of sample receipt. All fetuses were male, as confirmed by birth records. Cell-free DNA was extracted and measured by real-time quantitative polymerase chain reaction (PCR) amplification using glyceraldehyde phosphate dehydrogenase (GAPDH) and DYS1 as markers of total DNA and fetal DNA, respectively. Determination of linear associations between first and second trimester serum markers and cell-free DNA levels using Pearson correlations was performed. Results Statistically significant correlations between first trimester PAPP-A multiples of the median (MoMs) and both total (r=0.36, p=0.016) and fetal (r= 0.41, p=0.006) DNA in the first trimester were observed. There were no significant correlations between first trimester serum hCG or any second trimester serum marker with DNA levels. Conclusions Correlation between serum PAPP-A and first trimester circulating cell-free fetal and total DNA levels is a novel finding. PAPP-A is a glycoprotein of placental origin, and its correlation to cell-free fetal DNA in maternal serum suggests a common tissue origin, through apoptosis of placental cells. However, since PAPP-A and cell-free DNA were only marginally correlated and cell-free DNA can be reliably detected in the first trimester, the addition of cell-free DNA to serum screening strategies may be helpful in

  1. Triploidia fetal associada à diminuição da subunidade beta e do estriol não-conjugado no soro materno Fetal triploidy associated with low levels of unconjugated estriol and beta-subunit in maternal serum

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    Eduardo Vieira Neto

    1999-05-01

    Full Text Available Relatamos um caso de triploidia fetal não-molar detectada na 20ª semana gestacional por cordocentese realizada em razão de estudo ultra-sonográfico que revelou retardo do crescimento intra-uterino e grave oligoidrâmnio. Na 19ª semana foram verificados acentuada diminuição da subunidade beta livre da gonadotrofina coriônica humana e do estriol não-conjugado e níveis de alfa-fetoproteína normais, apontando para um risco aumentado de síndrome de Edwards. Houve morte fetal um dia após a cordocentese e a resolução do caso foi por parto vaginal induzido com misoprostol e ocitocina, sob analgesia peridural. Estudo cromossômico das células sangüíneas fetais revelou o cariótipo 69,XXX. O grave retardo do crescimento intra-uterino, a macrocefalia, constatada no estudo anatomopatológico do feto, e os níveis muito baixos de hCG e de estriol não-conjugado sugerem um caso de triploidia por diginia, fertilização de um óvulo diplóide por um espermatozóide haplóide.We report a case of nonmolar fetal triploidy detected by fetal blood sampling at 20 weeks of gestation, performed as an investigation of intrauterine growth retardation and severe oligohydramnios found by ultrasound scan. At 19 weeks of gestation very low levels of maternal free serum beta-subunit of human chorionic gonadotropin and unconjugated estriol, and normal levels of alpha-fetoprotein were found, which were interpreted as a high risk of fetal Edwards syndrome. Fetal death supervened the day after fetal blood sampling, and the pregnancy was terminated by vaginal delivery induced by misoprostol and oxytocin, under epidural anesthesia. Chromosome study of the fetal blood cells showed a 69,XXX karyotype. The severe intrauterine growth retardation and macrocephaly noted on pathological review plus the very low levels of hCG and unconjugated estriol suggest a fetal gynoid triploidy case, caused by the fertilization of a diploid egg by a haploid sperm.

  2. Effect of postoperative adjuvant transarterial chemoembolization on postoperative survival of patients with liver cancer and related influencing factors for prognosis

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    XING Zhixiang

    2017-12-01

    group, and there was a significant difference between the two groups (χ2=4.942, P=0.027. Preoperative alpha-fetoprotein >400 μg/L, TNM stage III, multiple tumors, tumor diameter >5 cm, positive HBsAg, and vascular invasion were independent prognostic factors in patients after hepatectomy, while TACE was a protective factor for long-term survival of these patients. ConclusionAdjuvant TACE after hepatectomy can significantly improve the survival rate and disease-free survival rate of HCC patients and has great significance in improving surgical outcome.

  3. Factors Predicting Survival after Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma

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    Farina M. Hanif

    2014-10-01

    Full Text Available Background: Transarterial chemoembolization is the preferred treatment for unresectable, intermediate-stage hepatocellular carcinoma. Survival after transarterial chemoembolization can be highly variable. The purpose of this study is to identify the factors that predict overall survival of patients with unresectable hepatocellular carcinoma who undergo transarterial chemoembolization as the initial therapy. Methods:We included patients who underwent transarterial chemoembolization from 2007 to 2012 in this study. Patient’s age, gender, cause of cirrhosis, Child-Turcotte-Pugh score, model of end-stage liver disease score, Cancer of the Liver Italian Program score, Okuda stage, alpha- fetoprotein level, site, size and number of tumors were recorded. Radiological response to transarterial chemoembolization was assessed by computerized tomography scan at 1 and 3 months after the procedure. Repeat sessions of transarterial chemoembolization were performed according to the response. We performed survival assessment and all patients were assessed for survival at the last follow-up. Results: Included in this study were 71 patients of whom there were 57 (80.3 % males, with a mean age of 51.9±12.1 years (range: 18-76 years. The mean follow-up period was 12.5±10.7 months. A total of 31 (43.7% patients had only one session of transarterial chemoembolization, 17 (23.9% underwent 2 and 11 (15.5% had 3 or more sessions. On univariate analysis, significant factors that predicted survival included serum bilirubin (P=0.02, esophageal varices (P=0.002, Cancer of the Liver Italian Program score (P=0.003, tumor size (P=0.005, >3 sessions of transarterial chemoembolization (P=0.006 and patient's age (P=0.001. Cox regression analysis showed that tumor size of 1 transarterial chemoembolization session (P=0.004 were associated with better survival. Conclusion: Our study demonstrates that survival after transarterial chemoem- bolization is predicted by tumor size

  4. Are hepatocellular carcinoma surveillance programs effective at improving the therapeutic options?: ¿mejoran las opciones terapéuticas de estos pacientes? Eficacia de los programas de cribado de hepatocarcinoma

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    E. Zapata

    2010-08-01

    Full Text Available Aim: to evaluate whether the current surveillance programs (ultrasonography and alpha-fetoprotein testing every six months are successful in detecting patients in the early stages. Material and methods: the health records of all patients diagnosed with hepatocellular carcinoma in Donostia Hospital between 2003 and 2005 were reviewed retrospectively. Eighty-five patients (11 women and 74 men were included in the study and demographic data, risk factors and clinical data were obtained. Patients were split into two groups according to whether or not they had been included in a surveillance program. Results: seventy per cent of patients of the surveillance group is diagnosed in early stage opposite to 26.7% of patients in no surveillance group (p Objetivo: determinar si la utilización en nuestro medio del programa de cribado de HCC establecido -alfa-fetoproteína (AFP y ecografia semestral- en pacientes con hepatopatía crónica permite detectar pacientes en estadios precoces de la enfermedad. Material y métodos: Diseño experimental: estudio retrospectivo. Criterios diagnósticos de HCC: 2 o más técnicas de imagen con lesión hipervascular mayor de 2 cm o 1 técnica de imagen con lesión hipervascular mayor de 2 cm asociado a AFP mayor de 400 ng/ml. Pacientes: 85 pacientes diagnosticados de HCC en el Hospital Donostia entre los años 2003 y 2005. Datos analizados: información demográfica (sexo, edad, factores de riesgo (alcohol, virus de hepatitis, hemocromatosis, otras enfermedades asociadas, e información clínica (etiología de la hepatopatía, estadio de Child-Pugh, determinación de AFP, hallazgos radiológicos, criterios de resecabilidad, tratamiento recibido, evolución. Se divide la muestra en dos grupos según hubieran seguido o no un programa de cribado. Resultados: el 70% de los pacientes del grupo de cribado se diagnostican en estadio precoz frente al 26,7% del grupo de no cribado (p < 0,05. Trece pacientes no pueden recibir

  5. Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma.

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    Who-Whong Wang

    Full Text Available Early diagnosis of hepatocellullar carcinoma (HCC remains a challenge. The current practice of serum alpha-fetoprotein (AFP measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV carrier samples from the Singapore General Hospital (SGH using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group, confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1 were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974 had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001. In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as

  6. Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma.

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    Wang, Who-Whong; Ang, Soo Fan; Kumar, Rajneesh; Heah, Charmain; Utama, Andi; Tania, Navessa Padma; Li, Huihua; Tan, Sze Huey; Poo, Desmond; Choo, Su Pin; Chow, Wan Cheng; Tan, Chee Kiat; Toh, Han Chong

    2013-01-01

    Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential

  7. Clinicopathological features and prognosis of gastric cancer in young patients

    International Nuclear Information System (INIS)

    Liu, Shushang; Feng, Fan; Xu, Guanghui; Liu, Zhen; Tian, Yangzi; Guo, Man; Lian, Xiao; Cai, Lei; Fan, Daiming; Zhang, Hongwei

    2016-01-01

    The clinicopathological features and prognosis of gastric cancer in young patients are both limited and controversial. Therefore, the aim of this study was to define the clinicopathological features and prognosis of gastric cancer in young patients after curative resection. From May 2008 to December 2014, 198 young patients (age ≤ 40 years) and 1096 middle-aged patients (55 ≤ age ≤ 64 years) were enrolled in this study. The clinicopathological features and prognosis of gastric cancer in these patients were analyzed. Compared with middle-aged patients, the proportion of females, lower third tumors, tumor size less than 5 cm, poorly differentiated tumors and T1 tumors were significantly higher in young patients (all P < 0.05). The proportions of comorbidity, upper third tumors, well and moderately differentiated tumors, T4 tumors, and positive carcinoembryonic antigen (CEA), alpha fetoprotein (AFP) and carbohydrate antigen (CA) 19–9 were significantly lower in young patients (all P < 0.05). The distributions of N status and CA125 were comparable between young and middle-aged patients (all P > 0.05). The five-year overall survival rates were comparable between young patients and middle-aged patients (62.8 vs 54.7 %, P = 0.307). The tumor location, T status, N status and CA125 were independent predictors of prognosis in young patients. The overall survival of patients with tumors located in the upper or middle third was significantly lower than for those located in the lower third (60.8 vs 50.6 % vs 68.4 %, P = 0.016). The overall survival of CA125-positive patients was significantly lower than CA125-negative patients (49.0 vs 64.4 %, P = 0.001). The clinicopathological features were significantly different between young and middle-aged patients. The prognosis of gastric cancer in young patients was equivalent to that of middle-aged patients. Tumor location, T status, N status and CA125 were independent risk factors for prognosis in young patients. The online

  8. Biparietal diameter at 11-13 weeks' gestation in fetuses with open spina bifida.

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    Khalil, A; Coates, A; Papageorghiou, A; Bhide, A; Thilaganathan, B

    2013-10-01

    To ascertain the reported association between reduced biparietal diameter (BPD) at 11-13 weeks' gestation and open spina bifida and to investigate its predictive value in a single-center study. This was a retrospective study of fetuses in which BPD was measured at 11-13 weeks' gestation, including 27 fetuses with isolated open spina bifida subsequently diagnosed at 16-24 weeks and 7775 unaffected controls. BPD values were converted into multiples of the expected median (MoM) after adjustment for crown-rump length and maternal characteristics. Multivariable logistic regression analysis was used to determine the maternal characteristics significantly associated with spina bifida. The performance of screening was determined by receiver-operating characteristics curve analysis. BPD values at 11-13 weeks' gestation were compared with those measured in the second trimester using Z-scores. BPD values at 11-13 weeks' gestation were below the 5(th) centile in 44.4% of cases of open spina bifida. In these fetuses, the median BPD MoM value was significantly smaller than that in the control group (0.930 vs 0.998 MoM; P spina bifida. The detection rate using BPD measurements in the first trimester was 55.6% with a false-positive rate of 11.6%. In fetuses with open spina bifida, the BPD Z-scores were significantly lower at 16-24 weeks compared to those recorded at 11-13 weeks (median, -1.71 (range, -3.98 to -0.20) vs -1.30 (-3.75 to 2.61); P = 0.006). Fetuses with open spina bifida have a smaller BPD in the first trimester. This observation may be useful in early screening. It is likely that a combination of maternal characteristics such as age and BMI, fetal BPD and maternal serum alpha-fetoprotein measured in the first trimester would provide a clinically useful screening test for open spina bifida. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

  9. Adenomatous hyperplasia of the rete testis: A rare intrascrotal lesion managed with limited testicular excision.

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    Catanzariti, Francesco; Servi, Lucilla; Fabiani, Andrea; Filosa, Alessandra; Mammana, Gabriele

    2016-10-05

    Testicular cancer is one of the most frequent in young men and its incidence is increasing in recent years because of incidental finding during routine ultrasound exams. Adenomatous hyperplasia of the rete testis is one of the benign and rare pathological types incidentally detected and very few cases are described in the literature. A 40 years old man come to our attention for a balanoposthitis without testicular pain. During andrological examination we performed palpation of the testes and we noticed a palpable nodule of hard consistency in the left testicle. We then performed an ultrasound exam of the testis which highlighted the presence of an intra-didymus neoformation with diameters of 1.2 x 1.6 cm and with the presence of cysts inside. We also performed blood tests to check tumor markers alpha fetoprotein, beta hCG and LDH which resulted inside the normal range. We then conducted a chest and abdomen CT scan that showed no pathological elements. Therefore, as we suspected that this tumor was benign, we performed an enucleation of the neoplasm. The definitive histological examination revealed the presence of dilated ducts lined with epithelial cubic-columnar cells with clear cytoplasm rich in glycogen and the pathologist so concluded that the tumor could be classified as adenomatous hyperplasia of the rete testis. At three months of follow up, the patient doesn't have any recurrent lesion to either testicles. Adenomatous hyperplasia of the rete testis is a very rare intrascrotal lesion. This histological type is the most frequent between benign lesion of the ovary, but few works in literature reported this histological type in the male gonad and, in most of these works, authors described these lesion at epididymis. We believe that a conservative approach must be considered mandatory in case of testicular lesions 1.5 cm in diameter. A radical approach might have alterate fertility of the patient and also have caused psychological trauma more than an enucleation

  10. Adenomatous hyperplasia of the rete testis: A rare intrascrotal lesion managed with limited testicular excision

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    Francesco Catanzariti

    2016-10-01

    Full Text Available Introduction: Testicular cancer is one of the most frequent in young men and its incidence is increasing in recent years because of incidental finding during routine ultrasound exams. Adenomatous hyperplasia of the rete testis is one of the benign and rare pathological types incidentally detected and very few cases are described in the literature. Case report: A 40 years old man come to our attention for a balanoposthitis without testicular pain. During andrological examination we performed palpation of the testes and we noticed a palpable nodule of hard consistency in the left testicle. We then performed an ultrasound exam of the testis which highlighted the presence of an intra-didymus neoformation with diameters of 1.2 x 1.6 cm and with the presence of cysts inside. We also performed blood tests to check tumor markers alpha fetoprotein, beta hCG and LDH which resulted inside the normal range. We then conducted a chest and abdomen CT scan that showed no pathological elements. Therefore, as we suspected that this tumor was benign, we performed an enucleation of the neoplasm. The definitive histological examination revealed the presence of dilated ducts lined with epithelial cubic-columnar cells with clear cytoplasm rich in glycogen and the pathologist so concluded that the tumor could be classified as adenomatous hyperplasia of the rete testis. At three months of follow up, the patient doesn’t have any recurrent lesion to either testicles. Discussion: Adenomatous hyperplasia of the rete testis is a very rare intrascrotal lesion. This histological type is the most frequent between benign lesion of the ovary, but few works in literature reported this histological type in the male gonad and, in most of these works, authors described these lesion at epididymis. Conclusion: We believe that a conservative approach must be considered mandatory in case of testicular lesions 1.5 cm in diameter. A radical approach might have alterate fertility of the

  11. Assessment of hepatic fibrosis by fibroscan in egyptian chronic hemodialysis patients with chronic Hepatitis C (genotype 4: A single-center study

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    Bahaa El-Din Moustafa Zayed

    2017-01-01

    Full Text Available Assessing hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC can help to evaluate the long-term prognosis, complications of hepatitis C virus (HCV as well as eligibility for renal transplantation,. Our aim was to assess liver fibrosis in Egyptian hemodialysis (HD patients infected with CHC genotype 4 using a fibroscan. This cross-sectional observational study was conducted over two years on a cohort of 134 Egyptian patients on prevalent HD at Kasr Al Ainy Hospital. All patients were subjected to routine laboratory evaluation including, hepatitis B surface antigen, hepatitis B core antibody, hepatitis Be antigen, hepatitis C antibody (HCVAb and human immunodeficiency virus antibody, quantitative polymerase chain reaction (PCR for both HCV and hepatitis B virus (HBV, serum hyaluronic acid level, and alpha-fetoprotein (AFP. Fibroscan was performed on all HCV-positive patients. The mean age was 47.43 ± 12.65 years, 50.7% were male, and 49.3% were female. The most common causes of end-stage renal disease were hypertensive nephropathy (32.1% and diabetic nephropathy (18.7%. HCVAb was positive in 57.5% of the patients and HBV was positive in 3%. Forty HCV-positive patients (57.1% who underwent fibroscan had mild to significant fibrosis, and thirty patients (42.9% had advanced fibrosis. There was significant correlation between HCV PCR and duration on HD, number of blood transfusions, and hyaluronic acid (HA level. In addition, there was a significant correlation between serum HA and HD duration as well as liver fibrosis. No significant correlation was found between duration on HD and fibrosis stage (P = 0.619; also, no significant correlation was noted between the age of the patients and HA level or stage of fibrosis (P = 0.970. Fibro-scan is a simple noninvasive test that can be used to assess liver fibrosis in HD patients with CHC. Most of the study patients had mild to significant fibrosis.

  12. Analysis of association between HSP70 expression in tumor tissues and clinicopathological characteristics of HBV-related hepatocellular carcinoma

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    GAO Jialin

    2015-05-01

    Full Text Available ObjectiveTo investigate the relationship between heat shock protein 70 (HSP70 expression and clinicopathological characteristics of hepatitis virus B (HBV-induced hepatocellular carcinoma (HCC. MethodsStatistical analysis was conducted to explore the association between the data of HSP70 obtained from the gene expression omnibus (GEO and the clinicopathological characteristics of HCC. As for categorical data, frequency (proportion was used to describe and chi-square test or Fisher′s exact test was applied to analyze. Univariate and multivariate logistic regression analyses were used to investigate the relationship between HSP expression and the clinicopathological characteristics of HCC. The variables with a P value less than 0.10 were included for subsequent multivariate analysis. Results1 The percentage of the HCC patients whose primary tumor sizes were more than 5 cm was significantly higher in the group with high expression of HSPA4L, HSPA6, and HSPA13 than in the group with low expression (P<0.05; in comparison with the group with high expression of HSPA1A and HSPA6, the group with low expression had a significantly lower percentage of patients accompanied by liver cirrhosis (P<0.05; there was a significantly higher percentage of patients with alpha-fetoprotein (AFP levels more than 300 ng/ml in the group with high expression of HSPA5 and HSA13 compared with the group with low expression (P<0.01. 2 The survival rates of HCC patients with liver cirrhosis and/or primary tumor that was more than 5 cm significantly decreased (P<0.05. 3 Highly expressed HSPA4L might promote the growth of HCC (OR=1.019, 95% CI:1.006-10.032, P=0.003; the patients with high expression of HSPA1B might have a higher risk of developing multiple nodules (OR=1.002, 95%CI:1.000-1.004, P=0.003. ConclusionThe expression of HSPA4L and HSPA1B is, to some extent, associated with the clinicopathological characteristics of HCC, which might be a therapeutic target and

  13. Clinical features of primary hepatic carcinoma: An analysis of 90 cases

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    ZHU Wei

    2013-06-01

    Full Text Available ObjectiveTo investigate the clinical features of primary hepatic carcinoma (PHC and to improve the early diagnosis of the disease. MethodsA retrospective analysis was performed on the clinical data of 90 inpatients with PHC (PHC group; the clinical data of 45 patients with liver cirrhosis (LC who were hospitalized in the same period (LC group were also collected for comparison, and 45 healthy persons in physical examination were selected as a control group. The collected data of patients included general information, tumor markers: alpha-fetoprotein (AFP and alpha-L-fucosidase (AFU, biochemical indices: hepatitis B virus (HBV markers, total bilirubin (TBil, alanine aminotransferase (ALT, albumin (Alb, prealbumin (PAB, alkaline phosphatase (ALP, gamma-glutamyl transpeptidase (GGT, and HBV DNA, and imaging findings. These groups were compared by t-test and analysis of variance (for measurement data and chi-square test (for numeration data. ResultsThe 90 PHC patients had different initial symptoms, without specificity, and most cases were in advanced stage. The total HBV infection rate was 88.9%, and the hepatitis B surface antigen (HBsAg-positive, hepatitis B e antibody (HBeAb-positive, and hepatitis B c antibody (HBcAb-positive cases accounted for 55.6% of all infected ones. The 40-69 years age group accounted for 76.7% of all PHC cases. There were no significant differences in HBV DNA level and serum TBil and ALT levels between the PHC group and LC group, but the PHC group had significantly higher serum Alb, PAB, GGT, and ALP levels than the LC group (P<0.01. The serum AFP and AFU levels were significantly higher in PHC group than in LC group and control group (P<0001, and the positive rate in joint detection of AFP and AFU was significantly higher than that in detection of either AFP or AFU (P<005. ConclusionRegular follow-up should be performed in people with high risk of PHC to find clinical symptoms in time, and various tumor

  14. Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

    International Nuclear Information System (INIS)

    Tacke, Frank; Kanig, Nicolas; En-Nia, Abdelaziz; Kaehne, Thilo; Eberhardt, Christiane S; Shpacovitch, Victoria; Trautwein, Christian; Mertens, Peter R

    2011-01-01

    Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases. We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n = 33), patients with non-cancerous, mostly inflammatory diseases (n = 60), hepatocellular carcinoma (HCC; n = 25) and advanced solid tumors (n = 20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation. We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients. Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should

  15. Serum AFU, 5’-NT and AFP as biomarkers for primary hepatocellular carcinoma diagnosis

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    Junna Zhu

    2017-10-01

    Full Text Available To evaluate the clinical value of serum α-L-fucosidase (AFU, 5’-nucleotidase (5’-NT and alpha fetoprotein (AFP as biomarkers for primary hepatocellular carcinoma (PHC diagnosis. Methods: Thirty six primary hepatocellular carcinoma (PHC patients and 36 healthy controls were recruited in this study from February 2014 to January 2016 in the Second People’s Hospital of Tianjin. The serum level of AFU, 5’-NT and AFP were examined and compared between the two groups. The diagnostic sensitivity, specificity area under the receiver operating characteristic (ROC curve were calculated by STATA11.0 software. Results: The serum level of AFU, 5’-NT, AFP were 30.87±10.43(U/L, 5.58±3.89(U/L, 233.60±226.60 (μg/L respectively for primary hepatocellular carcinoma group and 19.96±6.73 (U/L, 1.87±0.84 (U/L, 16.64±14.17 (μg/L for healthy control groups. The serum level of AFU, 5’-NT and AFP in primary hepatocellular carcinoma group were significant higher than those of healthy control group (P<0.001. The diagnostic sensitivity and specificity were 0.78 (95%CI:l0.61-0.90, 0.64 (95%CI:0.46-0.79 for serum AFU, 0.75(95%CI:0.58-0.88, 0.72(95%CI:0.55- 0.86 for serum 5’-NT and 0.72 (95%CI:0.55-0.86, 0.92 (95%CI:0.78-0.98 for serum AFP respectively. The AUC under the ROC curve were 0.80 (0.69-0.90, 0.80 (0.69-0.91 and 0.87 (0.780-0.96 for serum AFU, 5’-NT and AFP respectively. Positive correlation between AFU and 5’-NT (rpearson=0.63, P<0.05, AFU and AFP (rpearson=0.49, P<0.05, 5’-NT and AFP(rpearson=0.44, P<0.05 were found in the primary hepatocellular carcinoma patients. Conclusion: Serum AFU, 5’-NT and AFP were higher in PHC patients than those of healthy controls. The difference between PHC patients and healthy controls made serum AFU, 5’-NT and AFP potential biomarker for PHC diagnosis.

  16. [Surgical treatment of hepatocellular carcinoma. Long term results].

    Science.gov (United States)

    Figueras, Juan; Ramos, Emilio; Ibáñez, Luis; Valls, Carles; Serrano, Teresa; Rafecas, Antonio; Casanovas, Teresa; Fabregat, Juan; Xiol, Xavier; Torras, Jaume; Baliellas, Carmen; Jaurrieta, Eduardo; Casais, Luis

    2002-03-30

    Surgical treatment for hepatocellular carcinoma remains controversial due to a lack of prospective randomized studies. Between January 1990 and December 2000, 121 liver transplantations (group 1) and 52 hepatectomies (group 2) were performed for hepatocellular carcinoma. Each surgical treatment was carried out depending on patients' and tumor's characteristics. Patients from group 1 had a more advanced tumoral grade, with higher involvement of two lobes (19 vs 4%; p = 0.015) and higher number of nodules (1.9 DE [2] vs 1.2 [0.6]; p = 0.001); yet the mean tumor size was lower (3 cm [1.5] vs 4.2 [3.2]; p = 0.006). Operative mortality (4% vs 2%; p = 0.66) and 5- and 10-years survival (68% and 42% vs 63% and 45%; p = 0.23) were similar between both groups. Nevertheless, 5- and 10-years recurrence rates (10.6% and 10.6% vs 50% and 65.5%; p < 0.0001) were more favourable in group 1. Prognostic factors of recurrence included microscopic vascular invasion (RR = 12.12; CI, 2.02-75.52) and alpha-fetoprotein levels higher than 300 ng/mL (RR = 7.12; 95% CI, 1.08-47.02) in group 1, and the pT3-4 stage (RR = 3.86; 95% CI, 1.06-14.03) in group 2. Mean time on waiting lists for liver transplantation was 3.06 (2.66) months and it has increased significantly in last years, especially among blood group 0 patients. However, this fact has not been associated with a worsening of survival rates (p = 0.98). After a good patient selection, either liver transplantation or hepatectomy achieve excellent long term survival rates in patients with hepatocellular carcinoma, though the former allows a better control of the tumoral disease. The increase of mean time on waiting lists for liver transplantation during the last years has not led to a worsening of survival results.

  17. Use of Yttrium-90 glass microspheres (TheraSphere) for the treatment of unresectable hepatocellular carcinoma in patients with portal vein thrombosis.

    Science.gov (United States)

    Salem, Riad; Lewandowski, Robert; Roberts, Carol; Goin, James; Thurston, Kenneth; Abouljoud, Marwan; Courtney, Angi

    2004-04-01

    Intra-arterial injection of Yttrium-90 glass microspheres ((90)Y- microS; TheraSphere, MDS Nordion, Ottawa, Canada) is indicated for treatment of unresectable hepatocellular carcinoma (HCC) in the presence of acceptable liver function. This study presents hepatic toxicity results after unilobar and bilobar intra-arterial administration of (90)Y- microS in patients with unresectable HCC who had known portal vein thrombosis (PVT) without evidence of cavernous transformation. Fifteen patients with unresectable HCC and PVT of one or both first order and related segmental portal venous branches received a total of 29 infusions of (90)Y- microS for treatment of HCC. All patients had pretreatment evaluation including: computed tomography (CT) imaging, alpha-fetoprotein (AFP) levels, liver function tests, technetium-99m macroaggregated albumin ((99)Tc-MAA) scan for evaluation of lung and visceral shunting, and angiography with visualization into the portal venous phase. (90)Y- micro S dose was based on lobar hepatic volume with adjustment for lung shunt activity. Liver toxicity was assessed by serum total bilirubin graded for severity according to the NIH NCI Clinical Toxicity Criteria (CTC version 2.0). Other adverse events were reported according to the standards established by the Society of Interventional Radiology. There were no procedural complications with delivery of (90)Y- microS, and treatment was well tolerated by all patients. Increased post-treatment bilirubin levels were observed across all treatments in five patients, four of whom had CT or AFP evidence of intrahepatic disease progression. After initial treatment, two patients developed bilirubin toxicity (grades 1 and 2); one patient demonstrated an increment in bilirubin toxicity grade (grade 1 to grade 3) and one patient had an improvement in grade after initial treatment. There were no new treatment-related toxicities in nine patients after a second treatment. (90)Y- microS treatment was well tolerated

  18. Epidemiological and clinical features of primary liver cancer: an analysis of 236 patients

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    ZHAO Rongrong

    2016-08-01

    Full Text Available ObjectiveTo investigate the epidemiological and clinical features of patients with primary liver cancer (PLC. MethodsA retrospective analysis was performed for the clinical data of 236 patients with complete information who were admitted to The First Hospital of Lanzhou University and diagnosed with PLC for the first time form August 2012 to August 2014, and their epidemiological and clinical features were analyzed. The chi-square test was used for comparison of categorical data between groups. ResultsAmong the 236 PLC patients, there were 198 male patients (83.9% and 38 female patients (16.1%, and the patients aged 41-60 years has the highest incidence rate (58.5%, 138/236. Nineteen patients had a family history of liver cancer, 28 had a history of heavy drinking, 34 were complicated by type 2 diabetes, and 44 were complicated by hypertension. Among these patients, 232 (98.3% developed PLC on the basis of chronic liver disease, and 4 (1.7% had no chronic liver disease. There were 207 patients (87.7% with chronic HBV infection, and most of them had HBeAg-negative infection. Fourteen patients (5.9% had chronic HCV infection, 5 (2.1% had HBV/HCV co-infection, and 6 (2.5% had chronic alcoholic hepatitis. Among the 212 patients with HBV infection, 51(241% had HBeAg-positive chronic hepatitis B, and 95(448% had HBeAg-negative chronic hepatitis B; there was significant difference in HBV DNA level between the two groups (χ2=40687,Ρ=0001. Among all the PLC patients, 104 had an alpha-fetoprotein(AFP level of >400 IU/ml, 48 had an AFP level of 200-400 IU/ml, and 84 had an AFP level of <200 IU/ml; 154 (62.3% had a single lesion, and 72 (30.5% had multiple lesions; most (72.7% of patients with a single lesion had the single lesion in the right lobe, and the proportions of patients with multiple lesions in the right lobe and in both lobes accounted for 58.3% and 41.7%, respectively. Among the 80 PLC patients with

  19. Isoforms of thyroxine-binding globulin as a model for molecular epidemiology of human cancer risk

    International Nuclear Information System (INIS)

    Golovaty, A.S.; Lapko, A.G.

    2000-01-01

    The novel field of molecular epidemiology of human cancer risk has added a new branch to classical epidemiology by providing a direct link between human cancer and carcinogen exposure. It was estimated that about 80% of cancers are due to environmental factors. The blood proteins are almost certainly targets for modification in human cancer, and their identification and characterization will be of primary importance in the development of the new and rapidly evolving field of molecular epidemiology. Among blood proteins that are altered in human cancer, TBG occupies a special place because the level of human blood TBG is the most sensitive to intensification of biosynthesis and proliferation processes in organisms in different types of cancer. The increase of TBG concentration in cancer can be result from both activation of TBG biosynthesis in liver or altering of post translation glycosylation that prolongs protein survival time. The molecular basis for the change in the properties of TBG in cancer is unknown. These distinctive changes could have important consequences for the function of TBG in cancer and may help to develop more precise markers for monitoring pathological progression in this disease. Considerable variability and subtlety can occur in the carbohydrate composition and structure of serum glycoproteins in disease. This can be either as a major change, such as an increase in the number of oligosaccharide branches at a particular glycosylation site or as a minor change such as the addition of an extra fucose or sialic acid residue. Increased fucosylation has also been reported for transferrin and alpha-fetoprotein in liver cancer; thyroglobulin in thyroid cancer, IgG in myeloma, haptoglobin in ovarian cancer. The last own studies have shown that in clinically healthy teenagers born in Khojniki (137 Cs 185-555 kBq/m), we have found an unusual thyroid profile exhibiting increased levels of total triiodothyronine (T3), total thyroxine (T4), and thyroxine

  20. Effect of Ganoderma lucidum (G. lucidum) on the Liver of Mice Bearing Ehrlich Solid Tumor (EST) and Exposed to γ-Radiation

    International Nuclear Information System (INIS)

    Ibrahim, S.I.; El-Kabany, H.

    2013-01-01

    ) activity and glutathione (GSH) content in liver tissues. A remarkable increase was observed in alpha-fetoprotein (AFP) and interleukin-2 (IL-2) concentration in serum as compared to normal control. Liver of tumor bearing mice showed focal tubular necrosis associated with inflammatory cells infiltration, and vacuolation of the hepatic cells. Furthermore, an elevation of tail DNA % was recorded in the tumor tissue of mice treated with G.lucidum and /or γ-irradiation compared to EST control group. Treatment of EST bearing mice with G. lucidum and/or irradiation ameliorated the change in biochemical parameters and improved the histopathological changes in EST bearing mice. It could be concluded that G. lucidum might have anti-tumor properties and a radio protective role in normal tissues as well as a radio sensitizing effect in tumor tissues

  1. Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Alongi, Pierpaolo [IRCSS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Evangelista, Laura [Veneto Institute of Oncology IOV - IRCCS, Nuclear Medicine and Molecular Imaging Unit, Padua (Italy); Caobelli, Federico [Basel University Hospital, Department of Nuclear Medicine, Basel (Switzerland); Spallino, Marianna [University of Milano-Bicocca, Milan (Italy); Gianolli, Luigi; Picchio, Maria [IRCSS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Midiri, Massimo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); University of Palermo, Department of Radiology, DIBIMED, Palermo (Italy)

    2018-01-15

    38%, respectively; p = 0.02). An unremarkable scan was associated also with a longer OS (98% after 2 years and 95% after 5 years, p = 0.02). At univariate Cox regression analysis, a pathological {sup 18}F-FDG PET/CT scan was associated with an increased risk of disease progression (HR = 24.3, CI 95% 14.1-40.6; p = 0.03) and lower OS (HR = 17.3 CI 95% 4,9-77; p < 0.001). Its prognostic value was confirmed also if tested against advanced disease at diagnosis and rising Human Chorionic Gonadotropin Beta (HCGB) or Alpha-Fetoprotein (AFP) (HR = 7.3 for STAGE III-PET+, p = 0.03; HR = 14.3 elevated HCGB-PET+, p = 0.02; HR 10.7 elevated AFP-PET+, p = 0.01) At multivariate analysis, only a pathological {sup 18}F-FDG PET/CT scan and advanced disease in terms of TNM staging were predictors of disease progression and OS. {sup 18}F-FDG PET/CT showed incremental value over other variables both in predicting PFS (chi-square from 24 to 40, p < 0.001) and OS (chi-square from 32 to 38, p = 0.003). {sup 18}F-FDG PET/CT has a very good diagnostic performance in patients with suspected recurrent GCT and has an important prognostic value in assessing the rate of PFS and OS. Furthermore, {sup 18}F-FDG PET/CT impacted the therapeutic regimen in 23% of patients, thus providing a significant impact in the restaging process. (orig.)

  2. Tumor features and correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus-associated primary liver cancer with Yin deficiency

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    YANG Zhiyun

    2016-03-01

    Full Text Available ObjectiveTo investigate the tumor features and the correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus-associated primary liver cancer (PLC with yin deficiency. MethodsA total of 148 PLC patients who were treated in Beijing Ditan Hospital, Capital Medical University, from July 2013 to February 2015 were enrolled and divided into yin-deficiency PLC group (52 patients and non-yin-deficiency PLC group (96 patients. The patients′ general information and laboratory markers were collected, including oncological parameters (alpha-fetoprotein, carcinoembryonic antigen (CEA, and carbohydrate antigen 199 (CA19-9, virological parameter (HBsAg, gross type (nodular type, massive type, bulky type, and diffuse type, radiological features (main portal vein diameter, portal vein tumor thrombus, and extrahepatic metastasis, biochemical parameters (Model for End-Stage Liver Disease (MELD score, white blood cell, red blood cell, platelet (PLT, alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBil, gamma-glutamyl transpeptidase, alkaline phosphatase, albumin, cholinesterase, prothrombin time (PT, and prothrombin time activity (PTA, and lymphocyte count. The t-test was applied for comparison of normally distributed continuous data between groups, and the Pearson correlation analysis was applied for correlation analysis. The Mann-Whitney U test was applied for comparison of non-normally distributed continuous data between groups, and the Spearman correlation analysis was applied for correlation analysis. The chi-square test was applied for comparison of categorical data between groups. ResultsHBsAg showed a significant difference between the two groups (χ2=5.658, P=0.017. Compared with the non-yin-deficiency PLC group, the yin-deficiency PLC group had significantly increased CEA and CA19-9 (U=-2.200 and -2.194, both P<0.05, significantly increased MELD score, TBil, and PT (t=2.2, U=-2.0, U=-2

  3. Significance of serum tumor markers monitoring in carcinomas of unknown primary site

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    Pejčić Ivica

    2010-01-01

    Full Text Available Background/Aim. Unknown primary tumors represent a heterogeneous group of malignancies that are indicative of ominous prognosis. Cancer of unknown primary site (CUP is defined as the lack of any detectable primary site after full evaluation, and accounts for approximately 3-5% of all newly diagnosed patients with malignancies. The aim of this report was to present the prognostic and predictive value of 8 serum tumor markers in this group of patients. Methods. The study involved 63 patients. On histological examination, all the patients were presented with metastatic tumors whose primary site (origin could not be detected with noninvasive diagnostic techniques. Following the routine light microscopy, all histological findings were classified into one of the following three groups: plano-cellular carcinoma - 8 patients; adenocarcinoma - 33 patients; unclassifiable (undifferentiated carcinoma - 22 patients. In all the cases we evaluated 8 serum tumor markers: alpha-fetoproteins (AFP, chronic gonadotrophin beta submit, human (beta-HCG, neuron specific enolase (NSE, marker of malignant ovarian tumors (CA 125, prostate-specific antigene (PSA, marker of malignant brest tumor (CA 15-3, marker of malignant pancreas tumor and gastrointestinal tumor (Ca 19-9, carcinoembryonic antigen (CEA at the time of diagnosis. The patients on chemotherapy had the markers determined after the third and sixth chemocycle, i.e. at the time of illness progression observation, if present. The patients responding to chemotherapy with complete response (CR, partial response (PR or stable disease (SD had the markers determined after three-month periods until the time of relapse or progression. Chemotherapy was applied in 32 patients (20 females and 12 males, aged 29-70 years, who met the inclusion criteria. The following chemotherapy regimen was used: doxorubicin 50mg/m2 (day 1, cisplatin 60mg/m2 (day 1, and etoposide 120 mg/m2 (days 1-3. The period between two chemotherapy

  4. [Family history of liver cancer increases the risk of liver cancer incidence: a 20-year prospective cohort study in Qidong, China].

    Science.gov (United States)

    Sun, Yan; Tu, Hong; Lu, Peixin; Wang, Jinbing; Wu, Yan; Zhang, Qinan; Qian, Gengsun; Chen, Taoyang

    2014-10-01

    To evaluate whether first-degree family history of liver cancer plays a role in liver cancer incidence by prospective evaluation of a patient cohort in Qidong, China over a 20-year period. In May 1992, 708 hepatitis B surface antigen (HBsAg) carriers and 730 HBsAg-negadve controls from Qidong city were enrolled for participation in a prospective cohort study ending in November 2012.Follow-up was carried out every 6 to 12 months, and evaluations included serum assays to measure concentrations of alpha fetoprotein (AFP), HBsAg and alanine aminotransferase (ALT), as well as abdominal ultrasound to assess liver disease.The relationship between baseline (study entry) information of patients with first-degree family history of liver cancer and liver cancer incidence during the two decades of study was statistically assessed. There were 172 newly diagnosed liver cancer cases in the cohort during 25 753 person-years (py) of follow-up, representing an incidence of 667.88/100 000 py.The incidence rates of liver cancer among participants with or without liver cancer family history were 1 244.36/100 000 py and 509.70/100 000 py respectively, and the between-group difference reached the threshold for statistical significance (P less than 0.01, Relative Risk (RR):2.44, 95% Confidence Interval (CI):1.80-3.31).The incidence rates of liver cancer among participants who had a sibling with liver cancer and participants who had a parent with liver cancer were not significantly different (P > 0.05), but the liver cancer incidence among participants who had a mother with liver cancer was significantly higher than that of participants who had a father with liver cancer (P history, 56.52% (39/69) were diagnosed before 50 years old, and this rate was significantly higher than that of participants without a family history of liver cancer (40.78%, 42/103, P less than 0.05).The incidence rate of liver cancer among the participants who were family history-positive and HBsAg-positive was

  5. HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma

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    Aref AM

    2014-06-01

    Full Text Available Ahmed M Aref,1–3 Neil T Hoa,3 Lisheng Ge,3 Anshu Agrawal,4 Maria Dacosta-Iyer,5,6 Nils Lambrecht,5,6 Yi Ouyang,5,6 Andrew N Cornforth,7 Martin R Jadus5,6,8 1Biological Science Department, Modern Sciences and Arts University, Faculty of Dentistry, Cairo, Egypt; 2Southern California Institute for Research and Education, Veterans Affairs Medical Center, Long Beach, CA, USA; 3Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA, USA; 4Department of Medicine, Division of Basic and Clinical Immunology, University of California, Irvine, CA, USA; 5Pathology and Laboratory Medicine Department, Veterans Affairs Medical Center Long Beach, CA, USA; 6Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA; 7California Stem Cells, Inc., CA, USA; 8Neuro-Oncology Program, Chao Comprehensive Cancer Center, University of California, Irvine, CA, USA Background: Immunotherapy for human hepatocellular cancer (HCC is slowly making progress towards treating these fatal cancers. The identification of new antigens can improve this approach. We describe a possible new antigen, hepatocellular carcinoma-associated antigen-519/targeting protein for Xklp-2 (HCA519/TPX2, for HCC that might be beneficial for T-cell specific HCC immunotherapy. Methods: HCC was studied for the expression for 15 tumor-associated antigens considered useful for immunotherapy within three HCC cell lines (HepG2, Hep3B, and PLC/PRF/5, lymphocytes, non-cancerous livers, and clinical HCC. The expression of tumor antigenic precursor proteins (TAPPs messenger RNA was first screened by reverse transcriptase quantitative real-time polymerase chain reaction. Results: Four antigens (alpha fetoprotein, aspartyl/asparaginyl β-hydroxylase, glypican-3 and HCA519/TPX2 proved to be the best expressed TAPPs within the HCC specimens by molecular analyses. HCA519/TPX2 was detected by intracellular cell flow cytometry within HCC cell lines by using a specific

  6. Open-label phase II clinical trial in 75 patients with advanced hepatocellular carcinoma receiving daily dose of tableted liver cancer vaccine, hepcortespenlisimut-L

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    Tarakanovskaya MG

    2017-04-01

    Full Text Available Marina G Tarakanovskaya,1 Jigjidsuren Chinburen,2 Purev Batchuluun,2 Chogsom Munkhzaya,2 Genden Purevsuren,2 Dorjiin Dandii,3 Tsogkhuu Hulan,3 Dandii Oyungerel,4 Galyna A Kutsyna,5 Alan A Reid,6 Vika Borisova,6 Allen I Bain,7 Vichai Jirathitikal,7 Aldar S Bourinbaiar6–8 1Ekomed LLC, 2National Cancer Center, 3Monserum LLC, 4National Center for Public Health, Ulaanbaatar, Mongolia; 5Department of Infectious Diseases, Luhansk State Medical University, Luhansk, Ukraine; 6Immunitor China Ltd, Beijing, People’s Republic of China; 7Immunitor Inc, Vancouver, BC, Canada; 8Immunitor LLC, Ulaanbaatar, Mongolia Background: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5]—an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA as an orphan drug for treatment of hepatocellular carcinoma (HCC. V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis.Methods: The outcome of open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively. Over a period of 5 years, 75 patients with advanced HCC were enrolled, consisting of 29 (38.7% females and 46 (61.3% males with a median age of 60 years (mean 61.6±8.1 years. Out of these, 23 (30.7% had hepatitis B and 34 (45.3% had hepatitis C infections, including 9 (12% with dual infection, 4 (5.3% negative for both viruses, and 5 (6.7% without established viral diagnosis. Most patients (94.7% had underlying liver cirrhosis of varying severity.Results: After a median of 2 months of treatment, 50 out of 75 patients had experienced a decline in serum levels of the tumor marker, alpha-fetoprotein (AFP (66.7%; P=0.006 by Wilcoxon signed rank test. Baseline median AFP levels were 245.2 IU/mL (mean 4,233; range 7.2–92,407; 95% confidence interval [CI] 1,186–7,280 and post-treatment values were 102.3 IU

  7. Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma.

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    Fabio Farinati

    2016-04-01

    Full Text Available Prognostic assessment in patients with hepatocellular carcinoma (HCC remains controversial. Using the Italian Liver Cancer (ITA.LI.CA database as a training set, we sought to develop and validate a new prognostic system for patients with HCC.Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555 and Taiwan (external validation cohort, n = 2,651 were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases. A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG performance status, Child-Pugh score (CPS, and alpha-fetoprotein (AFP in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS. Median follow-up was 58 mo for Italian patients (interquartile range, 26-106 mo and 39 mo for Taiwanese patients (interquartile range, 12-61 mo. The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score ≤ 1, 43 and 38 mo in quartile 2 (ITA.LI.CA score 2-3, 23 and 23 mo in quartile 3 (ITA.LI.CA score 4-5, and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5. Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001 in Italian than in Taiwanese patients, the ITA.LI.CA score maintained

  8. Ataxia telangiectasia: a review

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    Cynthia Rothblum-Oviatt

    2016-11-01

    Full Text Available Abstract Definition of the disease Ataxia telangiectasia (A-T is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome. Epidemiology The world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births. Clinical description A-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages. Neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities including immunoglobulin and antibody deficiencies and lymphopenia. People with A-T have an increased predisposition for cancers, particularly of lymphoid origin. Pulmonary disease and problems with feeding, swallowing and nutrition are common, and there also may be dermatological and endocrine manifestations. Etiology A-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated gene which encodes a protein of the same name. The primary role of the ATM protein is coordination of cellular signaling pathways in response to DNA double strand breaks, oxidative stress and other genotoxic stress. Diagnosis The diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability with one or more of the following which may vary in their appearance: telangiectasia, frequent sinopulmonary infections and specific laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T lymphocytes and increased alpha-fetoprotein levels. Because certain neurological features may arise later, a diagnosis of A-T should be carefully considered for any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be confirmed by the

  9. Avaliação hormonal e de marcadores séricos em pacientes com abortamento Hormonal and serum marker evaluation in patients with abortion

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    Eddie Fernando Candido Murta

    1998-03-01

    the subject of numerous investigations with controversial results. The aim of this study was to evaluate the serum levels of CA-125, CA-19.9, CA-15.3, beta-hCG, estradiol, progesterone, alpha-fetoprotein and CEA in women with abortion (n=18 and with pregnancy complicated by bleeding (n=6, in comparison to the serum levels of the control group (n=7. The results showed that the serum levels of CA-125 were significantly increased in the abortion group (153.9 ± 43.3 IU/ml, but no difference was detected in pregnancy complicated by bleeding (17.4 ± 2.6 IU/ml, as compared to control (24.7 ± 13.4 IU/ml. However, high serum levels of CA-19.9 were found in the group with pregnancy complicated by bleeding in comparison with the abortion group (20.2 ± 11.4 IU/ml versus 6.6 ± 1.4 IU/ml, respectively. In relation to hormone serum levels, both, the abortion (17.38 ± 9.4 ng/ml and bleeding (18.3 ± 8.9 ng/ml groups showed lower serum levels of progesterone, as compared to control (60.4 ± 26.8 ng/ml. Besides, women with abortion had additional low estradiol serum levels, when compared to controls (1,327 ± 1,015 ng/ml versus 10,774 ± 9,244 ng/ml. It was concluded that the serum levels of progesterone, CA-19.9 and beta-hCG seem to add valuable information to the evaluation of a pregnancy complicated by bleeding.

  10. Performance of transient elastography in diagnosis of nonalcoholic fatty liver disease

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    ZHUANG Xiaofang

    2017-12-01

    Full Text Available ObjectiveTo investigate the value of transient elastography (TE in the diagnosis of nonalcoholic fatty liver disease (NAFLD. MethodsA total of 21 patients without fatty liver disease and 92 patients with NAFLD, who visited Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from June to December, 2016, were enrolled. Their general information was collected and body mass index (BMI was calculated. Routine blood test, liver function evaluation, and measurement of blood lipid, serum insulin, and alpha-fetoprotein were performed, and liver CT and FibroTouch were performed. The receiver operating characteristic (ROC curve was plotted with liver/spleen CT ratio as diagnostic criteria, and the ROC curve was used to evaluate the ability of controlled attenuation parameter (CAP to diagnose NAFLD. The area under the ROC curve (AUC was calculated, the Z test was used to evaluate diagnostic effectiveness, and Youden index was used to determine the optimal cut-off value. The t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between any two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test was used for comparison of categorical data between groups. ResultsThere were significant differences in age, alanine aminotransferase (ALT, aspartate aminotransferase (AST, serum insulin, fat attenuation, and liver stiffness measurement (LSM between the patients without fatty liver disease and those with varying degrees of NAFLD (all P<0.05. The severe NAFLD group had a significantly lower mean age than the non-fatty liver disease group (P<0.001. There was a significant difference in CAP

  11. Clinical and laboratory features of hepatocellular carcinoma

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    Andrés Cárdenas

    2007-02-01

    have electrolyte disturbances like hyponatremia, hypokalemia, and metabolic alkalosis, associated with defective water handling or with diuretic use. Serum aminotransferases, alkaline phosphatase and gammaglutamyl transpeptidase are often abnormal in a nonspecific pattern. Some serum markers are useful in diagnosis of HCC. The most commonly used is alpha-fetoprotein (AFP. AFP is a glycoprotein that is normally produced during gestation by the fetal liver and the yolk sac.

    In adults, normal values are less than 20 ng/ml and AFP is often elevated in patients with HCC. Serum concentrations of AFP do not correlate with clinical features of HCC, such as size, stage and prognosis but is generally accepted that serum levels greater than 500 ng/ml in a high risk patient is diagnosis of HCC.

    Other serum markers - Because of the limitations of serum AFP measurements, other serum markers of HCC used alone or in combination with the serum AFP have been evaluated for diagnosis or determining prognosis in patients with HCC. These include lens culinaris agglutinin-reactive AFP and des-gamma carboxyprothrombin, glypican-3, human hepatocyte growth factor, and insulin-like growth factor.

     

  12. Prenatal screening for fetal aneuploidy in singleton pregnancies.

    Science.gov (United States)

    Chitayat, David; Langlois, Sylvie; Douglas Wilson, R

    2011-07-01

    for aneuploidy, and it should not be used a basis for recommending invasive testing when non-invasive prenatal screening for aneuploidy is available. (II-2A) 4. Invasive prenatal diagnosis for cytogenetic analysis should not be performed without multiple marker screening results except for women who are at increased risk of fetal aneuploidy (a) because of ultrasound findings, (b) because the pregnancy was conceived by in vitro fertilization with intracytoplasmic sperm injection, or (c) because the woman or her partner has a history of a previous child or fetus with a chromosomal abnormality or is a carrier of a chromosome rearran