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Sample records for human hepatic cancer

  1. Liver Cancer and Hepatitis B

    Science.gov (United States)

    ... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  2. Clinical cancer chemoprevention: From the hepatitis B virus (HBV) vaccine to the human papillomavirus (HPV) vaccine.

    Science.gov (United States)

    Tsai, Horng-Jyh

    2015-04-01

    Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV), a risk factor of hepatocellular cancer, and human papillomavirus (HPV), a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV) vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population), and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer. Copyright © 2015. Published by Elsevier B.V.

  3. Hepatic sarcoidosis mimicking liver cancer

    OpenAIRE

    Yu, Kang-Kang; Liu, Han-Qiu; Zhou, Zhong-Wen; Chen, Ming-Quan

    2015-01-01

    We present a case of a 50-year-old woman with multiple occupations in the liver. Liver cancer was strongly suspected initially according to the results of imaging examination. However, sarcoidosis was confirmed subsequently by liver biopsy, so methylprednisolone was then prescribed and the patient showed favorable therapeutic response. This case report suggests that hepatic mass in Chinese patients without any history of hepatitis virus infection should be carefully investigated before giving...

  4. Murine model of hepatic breast cancer.

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    Rikhi, Rishi; Wilson, Elizabeth M; Deas, Olivier; Svalina, Matthew N; Bial, John; Mansoor, Atiya; Cairo, Stefano; Keller, Charles

    2016-12-01

    Breast cancer is the most common cancer in women and the second leading cause of cancer-related deaths in this population. Breast cancer related deaths have declined due to screening and adjuvant therapies, yet a driving clinical need exists to better understand the cause of the deadliest aspect of breast cancer, metastatic disease. Breast cancer metastasizes to several distant organs, the liver being the third most common site. To date, very few murine models of hepatic breast cancer exist. In this study, a novel murine model of liver breast cancer using the MDA-MB-231 cell line is introduced as an experimental (preclinical) model. Histological typing revealed consistent hepatic breast cancer tumor foci. Common features of the murine model were vascular invasion, lung metastasis and peritoneal seeding. The novel murine model of hepatic breast cancer established in this study provides a tool to be used to investigate mechanisms of hepatic metastasis and to test potential therapeutic interventions.

  5. Viral Hepatitis and Liver Cancer on the Island of Guam

    OpenAIRE

    Haddock, RL; Paulino, YC; Bordallo, R

    2013-01-01

    Patient records from the Guam Cancer Registry were compared with patients listed in a health department viral hepatitis case registry. The number of liver cancer and viral hepatitis cases were compared by ethnicity. Hepatitis C was the form of viral hepatitis most common among liver cancer cases on Guam (63.3% of viral hepatitis-associated liver cancer cases). Since viral hepatitis is an important cause of liver cancer, studies such as the present one may provide the information necessary to ...

  6. Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency ...

    African Journals Online (AJOL)

    Background: The epidemiology of viral hepatitis and Human immunodeficiency virus (HIV) during pregnancy is of great importance for health planners and program managers. However, few published data on viral hepatitis and HIV are available in Sudan especially during pregnancy. Objectives: The current study was ...

  7. Prevalence of hepatitis B surface antigen, hepatitis C and Human ...

    African Journals Online (AJOL)

    Objective: Human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C viruses (HCV) are major causes of mortality and morbidity worldwide. They are also among the commonest transfusiontransmissible infectious agents. Students of higher institutions are often used as voluntary unpaid donors by many ...

  8. Seroprevalence of Hepatitis B Virus among Human ...

    African Journals Online (AJOL)

    The HIV/AIDS pandemic has changed the prevalence of some infectious diseases. Hepatitis B is a very important potentially lethal and presently treatable infection which affects the course of HIV disease. This study was carried out to determine the prevalence of hepatitis B virus [HBV] infection in human immunodeficiency ...

  9. Seroprevalence of Human Immunodeficiency Virus, Hepatitis B ...

    African Journals Online (AJOL)

    Gonçales FL Jr, Pereira JS, Da Silva C, Thomaz GR, Pavan MH,. Fais VC, et al. Hepatitis B virus DNA in sera of blood donors and of patients infected with hepatitis C virus and human immunodeficiency virus. Clin Diagn Lab Immunol. 2003;10:718‑20. 25. Bahaf F, Tanomand A, Montazam H, Sany AA. Seroprevalence.

  10. Inhibitory effects of crude extracts from some edible Thai plants against replication of hepatitis B virus and human liver cancer cells

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    Waiyaput Wanwisa

    2012-12-01

    Full Text Available Abstract Background Edible plants such as Cratoxylum formosum (Jack Dyer, Curcumin longa Lin, Momordica charantia Lin and Moringa oleifera Lam have long been believed in Thai culture to relieve ulcers and the symptoms of liver disease. However, little is known about their anti-liver cancer properties and antiviral activity against hepatitis B virus (HBV. The aim of this study was to investigate the anti-liver cancer and anti-HBV activities of crude extracts from these edible plants on human liver cancer cells. Methods Plant samples were prepared and extracted using buffer and hydro-alcoholic solvents. The MTT assay was performed to investigate the effects of the plant extracts on the cell viability of HepG2 cells. The inhibitory effect on replication of HBV was analysed by determining the level of HBV covalently closed circular DNA (cccDNA in transiently transfected HepG2 cells with the DNA expression plasmid of the HBV genome using a quantitative real-time PCR. Results Buffer and hydroalcoholic extracts from C. formosum (leaf reduced cell viability of HepG2 cells and they also inhibited HBV cccDNA. Crude extracts from C. longa (bulb in both solvents did not have any cytotoxic effects on the HepG2 cells, but they significantly decreased the level of HBV cccDNA. Buffer extracts from the leaves of M. charantia and the fruits of M. oleifera showed to have anti-HBV activity and also a mild cytotoxicity effect on the HepG2 cells. In addition, leaves of M. Oleifera extracted by hydroalcoholic solvent drastically decreased the level of cccDNA in transiently transfected HepG2 cells. Conclusion Some crude extracts of edible plants contain compounds that demonstrate anti-liver cancer and anti-HBV activities.

  11. Prevention of hepatitis B virus infection and liver cancer.

    Science.gov (United States)

    Chang, Mei-Hwei

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the five leading causes of cancer death in human. Hepatitis B virus (HBV) is the most common etiologic agent of HCC in the world, particularly in areas prevalent for HBV infection such as Asia, Africa, southern part of Eastern and Central Europe, and the Middle East. Risk factors of HBV-related HCC include (1) viral factors-persistent high viral replication, HBV genotype C or D, pre-S2 or core promoter mutants; (2) host factors-older age (>40 years old) at HBeAg seroconversion, male gender; (3) mother-to-infant transmission; and (4) other carcinogenic factors-smoking, habitual use of alcohol, etc. Prevention is the best way to control cancer. There are three levels of liver cancer prevention, i.e., primary prevention by HBV vaccination targeting the general population, secondary prevention by antiviral agent for high-risk subjects with chronic HBV infection, and tertiary prevention by antiviral agent to prevent recurrence for patients who have been successfully treated for liver cancer. Primary prevention by hepatitis B vaccination is most cost effective. Its cancer preventive efficacy supports it as the first successful example of cancer preventive vaccine in human. This experience can be extended to the development of other cancer preventive vaccine. Careful basic and clinical research is needed to develop ideal vaccines to induce adequate protection. Understanding the main transmission route and age at primary infection may help to set the optimal target age to start a new cancer preventive vaccination program. Besides timely HBV vaccination, the earlier administration of hepatitis B immunoglobulin immediately after birth, and even antiviral agent during the third trimester of pregnancy to block mother-to-infant transmission of HBV are possible strategies to enhance the prevention efficacy of HBV infection and its related liver cancer.

  12. Human urinary amylolytic enzymes in acute hepatitis

    Science.gov (United States)

    Franzini, C.; Moda, S.

    1965-01-01

    Using paper eletrophoresis two amylolytic enzymes in human urine were demonstrated. A main peak was shown in the gamma globulin zone in normal urine and a second minor peak, in contrast to earlier findings, in the beta globulin zone. The organic source of the minor peak is probably in the liver. Urines from cases of acute hepatitis were studied in the same way and showed that the electrophoretic beta peak was raised in acute hepatitis, also pointing to a possible origin in the liver. Further studies are required to confirm this hypothesis. PMID:5844206

  13. Hepatitis B, C and Human Immunodeficiency Virus (HIV) Co ...

    African Journals Online (AJOL)

    Background: Nigeria which has one of the world's highest burden of children living with Sickle cell anaemia is also endemic for hepatitis B, C and the Human immunodeficiency virus (HIV). This study set out to determine the prevalence of Hepatitis B surface antigen (HBsAg), antibodies to Hepatitis C Virus (HCV) and Human ...

  14. Fulminant hepatitis due to human adenovirus.

    Science.gov (United States)

    Ronan, B A; Agrwal, N; Carey, E J; De Petris, G; Kusne, S; Seville, M T; Blair, J E; Vikram, H R

    2014-02-01

    To describe the demographics, clinical manifestations, treatment and outcomes of patients with human adenovirus (HAdV) hepatitis. A case of fulminant HAdV hepatitis in a patient with chronic lymphocytic leukemia receiving rituximab and fludarabine is described. We conducted a comprehensive review of the English-language literature through May, 2012 in search of definite cases of HAdV hepatitis. Eighty-nine cases were reviewed. Forty-three (48 %) were liver transplant recipients, 19 (21 %) were bone marrow transplant recipients, 11 (12 %) had received chemotherapy, five (6 %) had severe combined immunodeficiency, four (4 %) were HIV infected, two had heart transplantation, and two were kidney transplant recipients. Ninety percent (46/51) of patients presented within 6 months following transplantation. Fever was the most common initial symptom. Abdominal CT scan revealed hypodense lesions in eight of nine patients. Diagnosis was made by liver biopsy in 43 (48 %), and on autopsy in 46 (52 %). The HAdV was isolated at other sites in 54 cases. Only 24 of 89 patients (27 %) survived: 16 whose immunosuppression was reduced, six with liver re-transplantation, and two who received cidofovir and intravenous immunoglobulin. HAdV hepatitis can manifest as a fulminant illness in immunocompromised hosts. Definitive diagnosis requires liver biopsy. Early consideration of a viral etiology, reduction in immunosuppression, and liver transplantation can be potentially life-saving.

  15. Numerical design of RF ablation applicator for hepatic cancer treatment

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    Rakhmadi, Aditya; Basari

    2017-02-01

    Currently, cancer has become one of health problems that is difficult to be overcomed. This disease is not only difficult to be cured, but also to be detected and may cause death. For this reason, RF ablation treatment method is proposed to cure cancer. RF ablation therapy is a method in which an applicator is inserted into the body to kill cancer cells by heating the cells. The cancer cells are exposed to the temperature more than 60°C in short duration (few second to few minutes) so thus cell destruction occurs locally. For the sake of the successful treatment, a minimally invasive method is selected in order for perfect local temperature distribution in cancer cells can be achieved. In this paper, a coax-fed dipole-type applicator with interstitial irradiation technique is proposed aimed at RF ablation into hepatic cells. Numerical simulation is performed to obtain a suitable geometric dimension at operating frequency around 2.45 GHz, in order to localize the ablation area. The proposed applicator is inserted into a simple phantom representing an adult human body model in which normal and cancerous liver cells. The simulated results show that the proposed applicator is able to operate at center frequency of 2.355 GHz with blood droplet-type ablation zone and the temperature around the cancer cell by 60°C can be achieved.

  16. Seroprevalence of Human Immunodeficiency Virus, Hepatitis B ...

    African Journals Online (AJOL)

    Nigeria is also endemic for hepatitis B virus (HBV) infection, ... of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, and co‑infections among ..... Hou J, Liu Z, Gu F. Epidemiology and prevention of hepatitis. B virus infection. Int J Med Sci 2005;2:50‑7. 9. Ogunro PS, Adekanle DA, Fadero FF, Ogungbamigbe TO,.

  17. Low prevalence of hepatitis B virus, hepatitis D virus and hepatitis C virus among patients with human immunodeficiency virus or acquired immunodeficiency syndrome in the Brazilian Amazon basin

    OpenAIRE

    Braga,Wornei Silva Miranda; Castilho,Márcia da Costa; Santos,Isabelle Cristina Vale dos; Moura,Marco Antônio Sabóia; Segurado,Aluisio Cotrim

    2006-01-01

    Comorbidities in human immunodeficiency virus infection are of great interest due to their association with unfavorable outcomes and failure of antiretroviral therapy. This study evaluated the prevalence of coinfection by human immunodeficiency virus and viral hepatitis in an endemic area for hepatitis B in the Western Amazon basin. Serological markers for hepatitis B virus, hepatitis C virus and hepatitis D virus were tested in a consecutive sample of all patients referred for treatment of h...

  18. Hepatic stellate cells in liver development, regeneration, and cancer

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    Yin, Chunyue; Evason, Kimberley J.; Asahina, Kinji; Stainier, Didier Y.R.

    2013-01-01

    Hepatic stellate cells are liver-specific mesenchymal cells that play vital roles in liver physiology and fibrogenesis. They are located in the space of Disse and maintain close interactions with sinusoidal endothelial cells and hepatic epithelial cells. It is becoming increasingly clear that hepatic stellate cells have a profound impact on the differentiation, proliferation, and morphogenesis of other hepatic cell types during liver development and regeneration. In this Review, we summarize and evaluate the recent advances in our understanding of the formation and characteristics of hepatic stellate cells, as well as their function in liver development, regeneration, and cancer. We also discuss how improved knowledge of these processes offers new perspectives for the treatment of patients with liver diseases. PMID:23635788

  19. The Prevalence Of Hepatitis B Surface Antigen And Human ...

    African Journals Online (AJOL)

    Aims: To determine the prevalence of Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) infection among persons with sickle cell anaemia. Methods: Serum samples of 47 non- transfused persons with sickle cell anaemia (controls) and 73 transfused (subjects) were sreened for HIV antibody or the Hepatitis B ...

  20. Prevalence of human immunodeficiency virus, hepatitis C virus ...

    African Journals Online (AJOL)

    Background. Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis remain major infections around the world. In Angola, about 166 000 individuals are living with HIV, representing a prevalence of 1.98% in adults between 15 and 49 years of age. In a 2003 study in Luanda, 4.5% ...

  1. Sero-prevalence of Human Immunodeficiency Virus and hepatitis ...

    African Journals Online (AJOL)

    Sero-prevalence of Human Immunodeficiency Virus and hepatitis viruses and their correlation with CD4 T-cell lymphocyte counts in pregnant women in the Buea Health District of Cameroon. ... Prior to this study, very few studies in Cameroon have addressed co-infection of HIV and hepatitis in pregnancy. The aim of this ...

  2. Synthesis, characterization and dose dependent antimicrobial and anti-cancerous activity of phycogenic silver nanoparticles against human hepatic carcinoma (HepG2 cell line

    Directory of Open Access Journals (Sweden)

    N. Supraja

    2016-10-01

    Full Text Available In the present study silver nanoparticles (AgNPs were successfully synthesized using aqueous extract of sea weed, Gracilaria corticata. The aqueous callus extract (5% treated with 1 mM silver nitrate solution resulted in the formation of AgNPs and the surface plasmon resonance (SPR of the formed AgNPs was recorded at 405 nm using UV-Visible spectrophotometer. The molecules involved in the formation of AgNPs were identified by Fourier transform infrared spectroscopy (FT-IR, surface morphology was studied by using scanning electron microscopy (SEM, and X-ray diffraction spectroscopy (XRD was used to determine the crystalline structure. SEM micrograph clearly revealed the size of the AgNPs was in the range of 20–55 nm with spherical, hexagonal in shape and poly-dispersed nature. High positive Zeta potential (22.9 mV of formed AgNPs indicates the stability and XRD pattern revealed the crystal structure of the AgNPs by showing the Bragg’s peaks corresponding to (111, (200, (220 planes of face-centered cubic crystal phase of silver. The synthesized AgNPs exhibited effective anticancerous activity (at doses 6.25 and 12.5 µg/ml of AgNPs against human hepatic carcinoma cell line (HepG2.

  3. Role of PXR in Hepatic Cancer: Its Influences on Liver Detoxification Capacity and Cancer Progression.

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    Kotiya, Deepak; Jaiswal, Bharti; Ghose, Sampa; Kaul, Rachna; Datta, Kasturi; Tyagi, Rakesh K

    2016-01-01

    The role of nuclear receptor PXR in detoxification and clearance of xenobiotics and endobiotics is well-established. However, its projected role in hepatic cancer is rather illusive where its expression is reported altered in different cancers depending on the tissue-type and microenvironment. The expression of PXR, its target genes and their biological or clinical significance have not been examined in hepatic cancer. In the present study, by generating DEN-induced hepatic cancer in mice, we report that the expression of PXR and its target genes CYP3A11 and GSTa2 are down-regulated implying impairment of hepatic detoxification capacity. A higher state of inflammation was observed in liver cancer tissues as evident from upregulation of inflammatory cytokines IL-6 and TNF-α along with NF-κB and STAT3. Our data in mouse model suggested a negative correlation between down-regulation of PXR and its target genes with that of higher expression of inflammatory proteins (like IL-6, TNF-α, NF-κB). In conjunction, our findings with relevant cell culture based assays showed that higher expression of PXR is involved in reduction of tumorigenic potential in hepatic cancer. Overall, the findings suggest that inflammation influences the expression of hepatic proteins important in drug metabolism while higher PXR level reduces tumorigenic potential in hepatic cancer.

  4. Humanized chimeric mouse models of hepatitis B virus infection

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    Suwan Sun

    2017-06-01

    Full Text Available Hepatitis B virus (HBV infection is associated with an increased risk of hepatic cirrhosis, hepatocellular carcinoma, fulminant hepatitis and end-stage hepatic failure. Despite the availability of anti-HBV therapies, HBV infection remains a major global public health problem. Developing an ideal animal model of HBV infection to clarify the details of the HBV replication process, the viral life cycle, the resulting immunoresponse and the precise pathogenesis of HBV is difficult because HBV has an extremely narrow host range and almost exclusively infects humans. In this review, we summarize and evaluate animal models available for studying HBV infection, especially focusing on humanized chimeric mouse models, and we discuss future development trends regarding immunocompetent humanized mouse models that can delineate the natural history and immunopathophysiology of HBV infection.

  5. Viruses in cancer cell plasticity: the role of hepatitis C virus in hepatocellular carcinoma.

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    Hibner, Urszula; Grégoire, Damien

    2015-01-01

    Viruses are considered as causative agents of a significant proportion of human cancers. While the very stringent criteria used for their classification probably lead to an underestimation, only six human viruses are currently classified as oncogenic. In this review we give a brief historical account of the discovery of oncogenic viruses and then analyse the mechanisms underlying the infectious causes of cancer. We discuss viral strategies that evolved to ensure virus propagation and spread can alter cellular homeostasis in a way that increases the probability of oncogenic transformation and acquisition of stem cell phenotype. We argue that a useful way of analysing the convergent characteristics of viral infection and cancer is to examine how viruses affect the so-called cancer hallmarks. This view of infectious origin of cancer is illustrated by examples from hepatitis C infection, which is associated with a high proportion of hepatocellular carcinoma.

  6. Theories about evolutionary origins of human hepatitis B virus in primates and humans

    Directory of Open Access Journals (Sweden)

    Breno Frederico de Carvalho Dominguez Souza

    2014-09-01

    Conclusion: Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the ‘90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate hosts because of the proximity between the phylogeny of Old and New World non-human primate and their human hepatitis B virus variants. The importance of further research, related to the subject in South American wild fauna, is paramount and highly relevant for understanding the origin of human hepatitis B virus.

  7. Viral hepatitis E: A disease of humans and animals

    Directory of Open Access Journals (Sweden)

    Kureljušić Branislav

    2012-01-01

    Full Text Available The hepatitis E virus is ubiquitous in all parts of the world where pig production exists. The infection occurs in several animal species and its course is mostly asymptomatic. Viral strains isolated from pigs and humans are genetically similar, which indicates a potential zoonotic nature of the disease, and the possibility that pigs, and perhaps also other species of animals diseased with viral hepatitis E are a source of infection to humans. The pig hepatitis E virus, which is similar to the hepatitis E virus in humans, was isolated and described for the first time in the USA in 1997. The infection of pigs with hepatitis E virus occurs through faeco-oral transmission, by ingestion of feed and water contaminated with the virus, or through direct contact between infected and healthy animals. The pathogenesis of this infection in pigs differs from its pathogenesis in humans and it has not been sufficiently examined in all its aspects. Even though viral hepatitis E in pigs has been described as a subclinical disease, some authors describe changes in the concentration of certain biochemical parameters in blood serum of the infected pigs. Histologically, a mild to moderate lymphotic-plasma cellular infiltration is observed in livers of infected pigs, as well as focal areas of hepatocyte necrosis. Viral hepatitis E is an endemic disease of humans in Asia, Africa, and Latin America. In developed countries, hepatitis E sporadically occurs in humans, but it is becoming of increasing importance in particular in Japan, North America, and Europe, because the populations of these areas travel extensively to the endemic regions or as a result of the consumption of thermally untreated meat of wild boar and products made from thermally untreated meat. Pork products can be contaminated with hepatitis E virus. Further proof that indicates the zoonotic potential of this virus and places this diseases among the group of professional diseases of farmers and

  8. Hepatitis C virus reactivation in cancer patients in the era of targeted therapies.

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    Yazici, Ozan; Sendur, Mehmet Ali Nahit; Aksoy, Sercan

    2014-06-14

    reported cases of hepatitis C reactivation with imatinib therapy. However, there are many reports of hepatitis B reactivation with imatinib treatment. Based on the evidence of hepatitis B reactivation with imatinib and the effects of imatinib on immune system functions, we suggest that imatinib therapy might be a risk factor for HCV reactivation. Anti-human epidermal growth factor receptor 2 therapies are not associated with hepatic flare in HCV infected patients. Post-transplant studies reported that mTOR was safely administered to patients with active hepatitis C without causing hepatic flare. Cetuximab and panitumumab have not been associated with HCV reactivation. Two cases of HCV infected melanoma were safely treated with ipilimumab without any HCV reactivation or hepatic flare. Targeted therapies are a new and emerging area of oncology treatment modalities. While treating HCV infected cancer patients, clinicians should be mindful of the immunosuppressive properties of targeted therapies. Further randomized trials are needed to establish algorithms for this issue.

  9. Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer.

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    Zou, Wei; Ma, Xiangdong; Yang, Hong; Hua, Wei; Chen, Biliang; Cai, Guoqing

    2017-03-01

    Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in

  10. Woodchuck hepatitis virus-induced carcinoma as a relevant natural model for therapy of human hepatoma.

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    Gouillat, C; Manganas, D; Zoulim, F; Vitrey, D; Saguier, G; Guillaud, M; Ain, J F; Duque-Campos, R; Jamard, C; Praves, M; Trepo, C

    1997-06-01

    Eastern American woodchuck (Marmota monax), naturally infected with woodchuck hepatitis virus, a virus similar to human hepatitis B virus, develops liver cancer with a high prevalence. The aim of this work was to assess Marmota monax as a model of human hepatocellular carcinoma, especially to assess new potential adjuvant therapies after surgical resection. Forty-four woodchuck hepatitis virus-infected animals were regularly screened by ultrasound examination from the age of 18 months and for a 30-month period. One or more liver tumors were diagnosed in 31 animals (70%). Five of them with multifocal tumor or poor general status were considered unsuitable for surgery. The other 26 were operated on. At laparotomy no tumor was found in three. The 18 liver tumors studied were hepatocellular carcinomas, grossly and microscopically similar to human hepatocellular carcinoma. Peritumoral parenchyma studied in 13 specimens was always non-cirrhotic but adequate staining demonstrated patterns of fibrosis in four cases. Clear evidence of chronic active hepatitis, periportal hepatitis and steatosis were demonstrated in five, seven and one of the 13 specimens, respectively. Tumors were treated by tumorectomy in eight animals, by alcoholization in seven and by laser photocoagulation in one. A simple tumor biopsy was performed in the other seven. Ten animals died postoperatively. All the survivors in the tumorectomy group died from tumor recurrence within 10-18 months after surgery. It is concluded that woodchuck hepatitis virus-induced liver carcinoma is a natural model of human hepatocellular carcinoma with similar pathology and natural history, including early ultrasonic detection and tumor recurrence after resection. Tumor excision is feasible in this animal model, which now provides the basis for assessment of new potential adjuvant therapies for human hepatocellular carcinoma in an attempt to reduce the high recurrence rate after surgical resection in humans.

  11. Viral Hepatitis

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    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  12. Primary hepatic leiomyosarcoma with liver metastasis of rectal cancer

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    Takehara, Kiyoto; Aoki, Hideki; Takehara, Yuko; Yamasaki, Rie; Tanakaya, Kohji; Takeuchi, Hitoshi

    2012-01-01

    Primary hepatic leiomyosarcoma is a particularly rare tumor with a poor prognosis. Curative resection is currently the only effective treatment, and the efficacy of chemotherapy is unclear. This represents the first case report of a patient with primary hepatic leiomyosarcoma co-existing with metastatic liver carcinoma. We present a 59-year-old man who was diagnosed preoperatively with rectal cancer with multiple liver metastases. He underwent a curative hepatectomy after a series of chemotherapy regimens with modified FOLFOX6 consisting of 5-fluorouracil, leucovorin and oxaliplatin plus bevacizumab, FOLFIRI consisting of 5-fluorouracil, leucovorin and irinotecan plus bevacizumab, and irinotecan plus cetuximab. One of the liver tumors showed a different response to chemotherapy and was diagnosed as a leiomyosarcoma following histopathological examination. This case suggests that irinotecan has the potential to inhibit the growth of hepatic leiomyosarcomas. The possibility of comorbid different histological types of tumors should be suspected when considering the treatment of multiple liver tumors. PMID:23082067

  13. Seroprevalence of Human Immunodeficiency Virus, Hepatitis B ...

    African Journals Online (AJOL)

    Nigeria is also endemic for hepatitis B virus (HBV) infection, a virus that shares similar transmission routes with HIV.[4]. Over 2 billion of the world's population have been exposed to HBV and an estimated 387 million of these are now chronically infected with a rate of 10 million new carriers each year.[5] Approximately, 13% ...

  14. Theories about evolutionary origins of human hepatitis B virus in primates and humans

    Directory of Open Access Journals (Sweden)

    Breno Frederico de Carvalho Dominguez Souza

    Full Text Available Introduction: The human hepatitis B virus causes acute and chronic hepatitis and is considered one of the most serious human health issues by the World Health Organization, causing thousands of deaths per year. There are similar viruses belonging to the Hepadnaviridae family that infect non-human primates and other mammals as well as some birds. The majority of non-human primate virus isolates were phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial. However, there is a possibility that human hepatitis B virus originated in primates. Knowing whether these viruses might be common to humans and primates is crucial in order to reduce the risk to humans. Objective: To review the existing knowledge about the evolutionary origins of viruses of the Hepadnaviridae family in primates. Methods: This review was done by reading several articles that provide information about the Hepadnaviridae virus family in non-human primates and humans and the possible origins and evolution of these viruses. Results: The evolutionary origin of viruses of the Hepadnaviridae family in primates has been dated back to several thousand years; however, recent analyses of genomic fossils of avihepadnaviruses integrated into the genomes of several avian species have suggested a much older origin of this genus. Conclusion: Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the '90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly B virus in basal sister-relationship to the Old monkey human hepatitis World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory

  15. Theories about evolutionary origins of human hepatitis B virus in primates and humans.

    Science.gov (United States)

    Souza, Breno Frederico de Carvalho Dominguez; Drexler, Jan Felix; Lima, Renato Santos de; Rosário, Mila de Oliveira Hughes Veiga do; Netto, Eduardo Martins

    2014-01-01

    The human hepatitis B virus causes acute and chronic hepatitis and is considered one of the most serious human health issues by the World Health Organization, causing thousands of deaths per year. There are similar viruses belonging to the Hepadnaviridae family that infect non-human primates and other mammals as well as some birds. The majority of non-human primate virus isolates were phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial. However, there is a possibility that human hepatitis B virus originated in primates. Knowing whether these viruses might be common to humans and primates is crucial in order to reduce the risk to humans. To review the existing knowledge about the evolutionary origins of viruses of the Hepadnaviridae family in primates. This review was done by reading several articles that provide information about the Hepadnaviridae virus family in non-human primates and humans and the possible origins and evolution of these viruses. The evolutionary origin of viruses of the Hepadnaviridae family in primates has been dated back to several thousand years; however, recent analyses of genomic fossils of avihepadnaviruses integrated into the genomes of several avian species have suggested a much older origin of this genus. Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the '90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate

  16. Epidemiology of virus infection and human cancer.

    Science.gov (United States)

    Chen, Chien-Jen; Hsu, Wan-Lun; Yang, Hwai-I; Lee, Mei-Hsuan; Chen, Hui-Chi; Chien, Yin-Chu; You, San-Lin

    2014-01-01

    The International Agency for Research on Cancer (IARC) has comprehensively assessed the human carcinogenicity of biological agents. Seven viruses including Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1), and human papillomavirus (HPV) have been classified as Group 1 human carcinogens by IARC. The conclusions are based on the findings of epidemiological and mechanistic studies. EBV, HPV, HTLV-1, and KSHV are direct carcinogens; HBV and HCV are indirect carcinogens through chronic inflammation; HIV-1 is an indirect carcinogen through immune suppression. Some viruses may cause more than one cancer, while some cancers may be caused by more than one virus. However, only a proportion of persons infected by these oncogenic viruses will develop specific cancers. A series of studies have been carried out to assess the viral, host, and environmental cofactors of EBV-associated nasopharyngeal carcinoma, HBV/HCV-associated hepatocellular carcinoma, and HPV-associated cervical carcinoma. Persistent infection and high viral load are important risk predictors of these virus-caused cancers. Risk calculators incorporating host and viral factors have also been developed for the prediction of long-term risk of hepatocellular carcinoma. These risk calculators are useful for the triage and clinical management of infected patients. Both clinical trials and national programs of immunization or antiviral therapy have demonstrated a significant reduction in the incidence of cancers caused by HBV, HCV, and HPV. Future researches on gene-gene and gene-environment interaction of oncogenic viruses and human host are in urgent need.

  17. Virus infection and human cancer: an overview.

    Science.gov (United States)

    Schiller, John T; Lowy, Douglas R

    2014-01-01

    It is now estimated that approximately 10 % of worldwide cancers are attributable to viral infection, with the vast majority (>85 %) occurring in the developing world. Oncogenic viruses include various classes of DNA and RNA viruses and induce cancer by a variety of mechanisms. A unifying theme is that cancer develops in a minority of infected individuals and only after chronic infection of many years duration. The viruses associated with the greatest number of cancer cases are the human papillomaviruses (HPVs), which cause cervical cancer and several other epithelial malignancies, and the hepatitis viruses HBV and HCV, which are responsible for the majority of hepatocellular cancer. Other oncoviruses include Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). Identification of the infectious cause has led to several interventions that may reduce the risk of developing these tumors. These include preventive vaccines against HBV and HPV, HPV-based testing for cervical cancer screening, anti-virals for the treatment of chronic HBV and HCV infection, and screening the blood supply for the presence of HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may lead to further insight into etiology and pathogenesis as well as to new approaches for therapeutic and prophylactic intervention.

  18. Possible Human Papillomavirus 38 Contamination of Endometrial Cancer RNA Sequencing Samples in The Cancer Genome Atlas Database

    OpenAIRE

    Kazemian, Majid; Ren, Min; Lin, Jian-Xin; Liao, Wei; Spolski, Rosanne; Leonard, Warren J.

    2015-01-01

    Viruses are causally associated with a number of human malignancies. In this study, we sought to identify new virus-cancer associations by searching RNA sequencing data sets from >2,000 patients, encompassing 21 cancers from The Cancer Genome Atlas (TCGA), for the presence of viral sequences. In agreement with previous studies, we found human papillomavirus 16 (HPV16) and HPV18 in oropharyngeal cancer and hepatitis B and C viruses in liver cancer. Unexpectedly, however, we found HPV38, a cuta...

  19. Primary hepatic embryonal sarcoma masquerading as metastatic ovarian cancer

    Directory of Open Access Journals (Sweden)

    Praseedom Raaj

    2009-06-01

    Full Text Available Abstract Background Hepatic embryonal sarcoma (HES is a rare but aggressive primary tumor of the liver occurring most frequently in childhood. Case presentation We report a case of a 52 year old woman having previously undergone treatment for ovarian serous papillary carcinoma who subsequently presented with a large solitary mass in the liver. Initially this was presumed to be metastasis from the ovarian primary however, on further examination it was shown to be a primary hepatic embryonal sarcoma. Conclusion Primary liver tumors should be considered in differential diagnoses in patients with ovarian cancer who subsequently present with liver tumors. This is particularly important when there is no direct evidence of recurrence of ovarian cancer.

  20. Human viruses and cancer.

    Science.gov (United States)

    Morales-Sánchez, Abigail; Fuentes-Pananá, Ezequiel M

    2014-10-23

    The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt's lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers.

  1. Human Viruses and Cancer

    Directory of Open Access Journals (Sweden)

    Abigail Morales-Sánchez

    2014-10-01

    Full Text Available The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt’s lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers.

  2. The use of non-human primates as animal models for the study of hepatitis viruses

    Directory of Open Access Journals (Sweden)

    C.L. Vitral

    1998-08-01

    Full Text Available Hepatitis viruses belong to different families and have in common a striking hepatotropism and restrictions for propagation in cell culture. The transmissibility of hepatitis is in great part limited to non-human primates. Enterically transmitted hepatitis viruses (hepatitis A virus and hepatitis E virus can induce hepatitis in a number of Old World and New World monkey species, while the host range of non-human primates susceptible to hepatitis viruses transmitted by the parenteral route (hepatitis B virus, hepatitis C virus and hepatitis delta virus is restricted to few species of Old World monkeys, especially the chimpanzee. Experimental studies on non-human primates have provided an invaluable source of information regarding the biology and pathogenesis of these viruses, and represent a still indispensable tool for vaccine and drug testing.

  3. Human immunodeficiency virus, hepatitis B virus and syphilis ...

    African Journals Online (AJOL)

    Human immunodeficiency virus, hepatitis B virus and syphilis infections among long-distance truck ... Journal Home > Vol 10, No 1 (2016) > ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed ...

  4. Hepatitis C Virus and Human Immunodeficiency Virus Co-Infection ...

    African Journals Online (AJOL)

    Background: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are major health problems worldwide. HCV/HIV co-infection has been shown to increase the frequency of liver disease and also maternal-fetal transmission of HCV. Little data exist on the prevalence of co-infection of these viruses in ...

  5. Prevalence of Hepatitis C Virus (HCV) and Human ...

    African Journals Online (AJOL)

    Prevalence of Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) Co-Infection Among Pregnant Women Attending Antenatal Clinics in Abuja, Nigeria. ... with this virus complicates issues related to diagnosis, clinical disease progression, monitoring disease activity, treatment options and basic immunology.

  6. Human immunodeficiency virus (HIV) seropositivity and hepatitis B ...

    African Journals Online (AJOL)

    Method: A total of 130 donors comprising 120 commercial donors and 10 voluntary donors were tested for antibodies to human immunodeficiency virus and hepatitis B surface antigen in Benin city using Immunocomb HIV - 1 and 2 Biospot kit and Quimica Clinica Aplicada direct latex agglutination method respectively.

  7. prevalence of hepatitis a, b, c and human immunodeficiency virus ...

    African Journals Online (AJOL)

    hi-tech

    2004-04-01

    Apr 1, 2004 ... PREVALENCE OF HEPATITIS A, B, C AND HUMAN IMMUNODEFICIENCY VIRUS SEROPOSITIVITY AMONG PATIENTS WITH ACUTE ICTERIC .... computer software. The 95% confidence level was used to assess statistical significance. The Pearson chi-square test was utilised in assesing statistical ...

  8. Hepatitis B, C and Human Immunodeficiency Virus (HIV) Co ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    Hepatitis B, C and Human Immunodeficiency Virus (HIV). Co-infection in Nigerian Children with Sickle Cell Anaemia. Type of Article:CSWI. 1Lucy Eberechukwu Yaguo Ide, 2Seye Babatunde. Departments of 1Paediatrics And Child ... of haemolytic anemia and one of the most common in our society.1 It is a major cause of.

  9. Hepatitis E Virus Genotype 3 in Humans and Swine, Bolivia

    Science.gov (United States)

    Cavallo, Annalisa; Gonzales, José Luis; Bonelli, Sara Irene; Valda, Ybar; Pieri, Angela; Segundo, Higinio; Ibañez, Ramón; Mantella, Antonia; Bartalesi, Filippo; Tolari, Francesco; Bartoloni, Alessandro

    2011-01-01

    We determined the seroprevalence of hepatitis E virus (HEV) in persons in 2 rural communities in southeastern Bolivia and the presence of HEV in human and swine fecal samples. HEV seroprevalence was 6.3%, and HEV genotype 3 strains with high sequence homology were detected. PMID:21801630

  10. Epidemiology of Hepatitis B and Hepatitis C Virus infections among ...

    African Journals Online (AJOL)

    Hepatitis B and hepatitis C virus infection are common in Nigeria; where they are a major cause of both acute and chronic liver disease, as well as hepatocellular cancer. Persons at risk of acquisition of Human Immunodeficiency Virus (HIV) infection are also at risk of acquisition of infection with Hepatitis B virus (HBV) and ...

  11. Associations between MTHFR Ala222Val polymorphism and risks of hepatitis and hepatitis-related liver cancer: a meta-analysis.

    Science.gov (United States)

    Zheng, Ruiying; Zhao, Wenyuan; Dai, Dongwei; Li, Chengzhong

    2014-02-01

    Chronic infection of viral hepatitis is the main cause of liver cancer. There were many studies assessing the associations of methylenetetrahydrofolate reductase (MTHFR) Ala222Val polymorphism with risks of hepatitis and hepatitis-related liver cancer, but no consistent results were reported. To investigate the associations of MTHFR Ala222Val polymorphism with risks of hepatitis and hepatitis-related liver cancer, we performed a meta-analysis of published case-control studies. Eligible studies were searched from PubMed and Chinese National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR) and corresponding 95 % confidence interval (95 %CI) were used to assess the associations. Twenty-one individual studies with a total of 8,187 subjects were included. Overall, MTHFR Ala222Val polymorphism was not significantly associated with risks of liver cancer, hepatitis-related liver cancer, and non-hepatitis-related liver cancer. However, MTHFR Ala222Val polymorphism was significantly associated with risk of hepatitis infection (Val vs. Ala: OR = 1.15, 95 %CI 1.01-1.32, P = 0.03; ValVal/AlaVal vs. AlaAla: OR = 1.37, 95 %CI 1.11-1.68, P = 0.003). Therefore, MTHFR Ala222Val polymorphism is significantly associated with risk of hepatitis infection but not liver cancer. More studies are needed to further assess the association between MTHFR Ala222Val polymorphism and hepatitis-related liver cancer.

  12. Viruses and human cancer: from detection to causality.

    Science.gov (United States)

    Sarid, Ronit; Gao, Shou-Jiang

    2011-06-28

    The study of cancer is incomplete without taking into consideration of tumorigenic viruses. Initially, searches for human cancer viruses were fruitless despite an expansion of our knowledge in the same period concerning acute-transforming retroviruses in animals. However, over the last 40 years, we have witnessed rapid progress in the tumor virology field. Currently, acknowledged human cancer viruses include Epstein-Barr virus, hepatitis B virus, hepatitis C virus, high-risk human papilloma viruses, human T-cell lymphotropic virus type 1 and Kaposi's sarcoma-associated herpesvirus. Extensive epidemiological and mechanistic studies have led to the development of novel preventive and therapeutic approaches for managing some of these infections and associated cancers. In addition, recent advances in molecular technologies have enabled the discovery of a new potential human tumor virus, Merkel cell polyomavirus, but its association with cancer remains to be validated. It is anticipated that in the next few decades many additional human cancer viruses will be discovered and the mechanisms underlying viral oncogenesis delineated. Thus, it can be expected that better tools for preventing and treating virus-associated cancer will be available in the near future. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Enzyme-activated nanoconjugates for tunable release of doxorubicin in hepatic cancer cells.

    Science.gov (United States)

    Medina, Scott H; Chevliakov, Maxim V; Tiruchinapally, Gopinath; Durmaz, Yasemin Yuksel; Kuruvilla, Sibu P; Elsayed, Mohamed E H

    2013-06-01

    We report the synthesis of a series of aromatic azo-linkers (L1-L4), which are selectively recognized and cleaved by azoreductase enzymes present in the cytoplasm of hepatic cancer cells via a NADPH-dependent mechanism. We utilized L1-L4 azo-linkers to conjugate doxorubicin to generation 5 (G5) of poly(amidoamine) dendrimers to prepare G5-L(x)-DOX nanoconjugates. We incorporated electron-donating oxygen (O) or nitrogen (N) groups in the para and ortho positions of L1-L4 azo-linkers to control the electronegativity of G5-L(x)-DOX conjugates and investigated their cleavage by azoreductase enzymes and the associated release of loaded DOX molecules. Hammett σ values of G5-L(x)-DOX conjugates ranged from -0.44 to -1.27, which is below the reported σ threshold (-0.37) required for binding to azoreductase enzymes. Results show that incubation of G5-L1-DOX (σ = -0.44), G5-L2-DOX (σ = -0.71), G5-L3-DOX (σ = -1.00), and G5-L4-DOX (σ = -1.27) conjugates with human liver microsomal (HLM) enzymes and the S9 fraction isolated from HepG2 hepatic cancer cells results in release of 4%-8%, 17%, 60%, and 100% of the conjugated DOX molecules, respectively. These results show that increasing the electronegativity (i.e. lower σ value) of L1-L4 azo-linkers increases their susceptibility to cleavage by azoreductase enzymes. Intracellular cleavage of G5-L(x)-DOX nanoconjugates, release of conjugated DOX molecules, and cytotoxicity correlated with conjugate's electronegativity (σ value) was investigated, with G5-L4-DOX conjugate exhibiting the highest toxicity towards hepatic cancer cells with an IC50 of 13 nm ± 5 nm in HepG2 cells. Cleavage of G5-L(x)-DOX conjugates was specific to hepatic cancer cells as shown by low non-specific DOX release upon incubation with non-enzymatic insect proteins and the S9 fraction isolated from rat cardiomyocytes. These enzyme-activated G5-L(x)-DOX conjugates represent a drug delivery platform that can achieve tunable and cell-specific release of

  14. Hepatitis

    Science.gov (United States)

    ... yourself against hepatitis A is by vaccination. Other ways to protect yourself include avoiding rimming and other anal and oral contact. While condom use is essential in preventing the spread of HIV, hepatitis B and other STDs, it does not ...

  15. Age-Dependent Human Hepatic Carboxylesterase 1 (Ces1) ...

    Science.gov (United States)

    Human hepatic carboxylesterase 1 and 2 (CES1 and CES2) are important for ester- and amide- bond containing pharmaceutical and environmental chemical disposition. Despite concern regarding juvenile sensitivity to such compounds, CES1 and CES2 ontogeny has not been well characterized. To define human hepatic microsomal and cytosolic CES1 and CES2 expression during early postnatal life, microsomal and cytosolic fractions were prepared using liver samples from subjects without liver disease [N=165, 1d-18 yrs]. Proteins were fractionated, detected and quantitated by western blotting. Median microsomal CES1 was lower among samples from subjects mg microsomal protein, respectively; pmg cytosolic protein, respectively; p values mg microsomal protein, respectively (p<0.001, both), whereas for cytosolic CES2, only the youngest age group differed from the two older g

  16. Acute hepatic porphyria and cancer risk: a nationwide cohort study.

    Science.gov (United States)

    Baravelli, C M; Sandberg, S; Aarsand, A K; Nilsen, R M; Tollånes, M C

    2017-09-01

    Acute hepatic porphyria (AHP) is considered to be a risk factor for primary liver cancer (PLC), but varying risk estimates have been published. Our aim was to investigate the risk of PLC and other cancers in persons with AHP using a nationwide cohort design. Given that greater numbers of women than men tend to have manifest and more severe AHP, a further aim was to investigate sex differences in this risk. The study sample consisted of all Norwegian residents aged 18 years or older during the period 2000-2011. Persons with AHP (n = 251) were identified through the Norwegian Porphyria Centre, and patients with a cancer diagnosis were identified by linkage to the Cancer Registry of Norway. For persons with AHP, the annual incidence rate of PLC was 0.35%. PLC risk was substantially higher for individuals with an AHP diagnosis compared to the reference population [adjusted hazard ratio (aHR) 108, 95% confidence interval (CI) 56-207]. In a meta-analysis of published studies on PLC and AHP, including ours, women had a higher risk than men. In addition, our results suggested that persons with AHP may have increased risks of kidney (aHR 7.4, 95% CI 2.4-23.1) and endometrial cancers (aHR 6.2, 95% CI 2.0-19.3). Our findings confirmed a substantially higher risk of PLC associated with AHP compared to the general population. In a meta-analysis, the risk was shown to be greater for women than men. The novel findings of a moderate to substantial association between AHP and kidney and endometrial cancers should be investigated further. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  17. Human papillomavirus and oropharyngeal cancer

    DEFF Research Database (Denmark)

    Josiassen, Michael; Larsen, Christian Grønhøj; Lajer, Christel Bræmer

    2017-01-01

    The prevalence of oropharyngeal cancer is increasing in the Western world, and human papillomavirus (HPV) is believed to play a role in this development. Patients with HPV-positive oropharyngeal cancer differ significantly from patients with HPV-negative cancer. They may present solely with a small...

  18. Hepatitis B Virus Seroprevalence Among Children With Cancer in Sudan.

    Science.gov (United States)

    Abdalla, Mohammed; Hamad, Tarig

    2016-01-01

    The seroprevalence of hepatitis B among children with cancer in Sudan is unknown. The aim of this study was to detect the seroprevalence of hepatitis B virus (HBV) infection in children with malignancy and its correlation with different risk factors. This study included 178 children with malignancy presenting to the Radioisotope Center in Khartoum during the period of May-July 2011. Sixty-four healthy children served as controls. Sera from patients and controls were investigated for HBV total anti-core antibody, HBV surface antigen (HBsAg), and HBV e antigen (HBeAg). HBV total anti-core antibody was positive in 71/178 (39.9%), HBsAg was positive in 38 (21.3%), and HBeAg was positive in 19 (10.7%). Blood product transfusion, surgical exposure, chemotherapy, malignancy type, and sex did not affect the seroprevalence of HBV in this study. Vaccinated children had reduced rates of exposure compared to non-vaccinated patients. There is a high seroprevalence of HBV in children with malignancies in Sudan. Vaccination appears to play a major protective role. © 2015 Wiley Periodicals, Inc.

  19. The role of human T cell lymphotrophic virus type 1, hepatitis B virus and hepatitis C virus coinfections in leprosy

    OpenAIRE

    Paulo Roberto Lima Machado; Johnson, Warren D.; Glesby, Marshall J.

    2012-01-01

    Leprosy spectrum and outcome is associated with the host immune response against Mycobacterium leprae. The role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. Leprosy remains endemic in several regions where human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV) are also endemic. We have evaluated the evidence for the possible role of these viruses in the clinical...

  20. Seroprevalence of Hepatitis C, Hepatitis B, Cytomegalovirus, and Human Immunodeficiency Viruses in Multitransfused Thalassemic Children in Upper Egypt

    OpenAIRE

    Mahmoud, Ramadan A.; El-Mazary, Abdel-Azeem M.; Khodeary, Ashraf

    2016-01-01

    Background. Frequent blood transfusions in thalassemia major children expose them to the risk of transfusion-transmitted infections (TTIs). The aim of this study was to estimate the prevalence of hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and cytomegalovirus (CMV) in thalassemic children attending the Pediatrics Departments of both Sohag and Minia Universities of Upper Egypt, during the period from May 2014 to May 2015. Methods. Serum samples were sc...

  1. Interaction of vinyl chloride monomer exposure and hepatitis B viral infection on liver cancer.

    Science.gov (United States)

    Wong, Ruey-Hong; Chen, Pau-Chung; Wang, Jung-Der; Du, Chung-Li; Cheng, Tsun-Jen

    2003-04-01

    Vinyl-chloride monomer (VCM), a human carcinogen, has caused angiosarcoma of the liver. Recent studies have shown that VCM exposure is associated with hepatocellular cancer. In Taiwanese studies, the majority of VCM-exposed workers with liver cancer had history of hepatitis B virus (HBV) infection. To determine the role of HBV on the development of liver cancer in the VCM-exposed workers, we conducted a case-control study from a previously established polyvinyl chloride (PVC) cohort consisting of 4096 male workers from six PVC polymerization plants. A total of 18 patients with liver cancer, and 68 control subjects matched for age and specific plant of employment were selected. Detailed history of the participants that included alcohol consumption status, cigarette use, occupation, and family history of chronic liver disease were obtained using an interviewer-administered questionnaire. When the HBV surface antigen (HBsAg)-negative subjects without history of tank-cleaning were used as the reference, the HBsAg-negative subjects with history of tank-cleaning demonstrated a 4.0-fold greater risk of liver cancer (95% confidence interval: 95% CI = 0.2-69.1). The HBsAg carriers without history of tank-cleaning revealed a 25.7-fold greater risk of liver cancer (95% CI = 2.9-229.4). Whereas the HBsAg carriers with history of tank-cleaning revealed the greatest risk (matched odds ratio (ORm) 396.0, 95% CI = 22.6 -infinity) of developing liver cancer among subjects with different VCM-exposure status and HBsAg status categories. Further analysis showed the interaction term was significant (P < .01). Therefore, our results suggest an interaction between occupational VCM exposure and HBV infection for the development of liver cancer.

  2. Hepatitis C virus infection and risk of cancer: a population-based cohort study

    DEFF Research Database (Denmark)

    Omland, Lars; Farkas, Dora Körmendiné; Jepsen, Peter

    2010-01-01

    Hepatitis C virus (HCV) infection is associated with an increased risk of primary liver cancer; however, 5- and 10-year risk estimates are needed. The association of HCV with non-Hodgkin lymphoma (NHL) is uncertain and the association with other cancers is unknown.......Hepatitis C virus (HCV) infection is associated with an increased risk of primary liver cancer; however, 5- and 10-year risk estimates are needed. The association of HCV with non-Hodgkin lymphoma (NHL) is uncertain and the association with other cancers is unknown....

  3. Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Jianjin Huang

    Full Text Available Liver metastasis is a major cause of mortality from colorectal cancer (CRC. However, mechanisms underlying this process are largely unknown. Osteopontin (OPN is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6 was detected by using an immunohistochemical (IHC method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Fluorescence redistribution after photobleaching (FRAP was used to study gap functional intercellular communication (GJIC among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

  4. Antiviral treatment for chronic hepatitis C in patients with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Iorio, Alfonso; Marchesini, Emanuela; Awad, Tahany

    2010-01-01

    Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV).......Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV)....

  5. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  6. Regulation of human hepatic drug transporter activity and expression by diesel exhaust particle extract.

    Directory of Open Access Journals (Sweden)

    Marc Le Vee

    Full Text Available Diesel exhaust particles (DEPs are common environmental air pollutants primarily affecting the lung. DEPs or chemicals adsorbed on DEPs also exert extra-pulmonary effects, including alteration of hepatic drug detoxifying enzyme expression. The present study was designed to determine whether organic DEP extract (DEPe may target hepatic drug transporters that contribute in a major way to drug detoxification. Using primary human hepatocytes and transporter-overexpressing cells, DEPe was first shown to strongly inhibit activities of the sinusoidal solute carrier (SLC uptake transporters organic anion-transporting polypeptides (OATP 1B1, 1B3 and 2B1 and of the canalicular ATP-binding cassette (ABC efflux pump multidrug resistance-associated protein 2, with IC50 values ranging from approximately 1 to 20 μg/mL and relevant to environmental exposure situations. By contrast, 25 μg/mL DEPe failed to alter activities of the SLC transporter organic cation transporter (OCT 1 and of the ABC efflux pumps P-glycoprotein and bile salt export pump (BSEP, whereas it only moderately inhibited those of sodium taurocholate co-transporting polypeptide and of breast cancer resistance protein (BCRP. Treatment by 25 μg/mL DEPe was next demonstrated to induce expression of BCRP at both mRNA and protein level in cultured human hepatic cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B3, OATP2B1, OCT1 and BSEP. Such changes in transporter expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a reference activator of the aryl hydrocarbon receptor (AhR pathway. This suggests that DEPe, which is enriched in known ligands of AhR like polycyclic aromatic hydrocarbons, alters drug transporter expression via activation of the AhR cascade. Taken together, these data established human hepatic transporters as targets of organic chemicals containing in DEPs, which may contribute

  7. The Human Microbiome and Cancer.

    Science.gov (United States)

    Rajagopala, Seesandra V; Vashee, Sanjay; Oldfield, Lauren M; Suzuki, Yo; Venter, J Craig; Telenti, Amalio; Nelson, Karen E

    2017-04-01

    Recent scientific advances have significantly contributed to our understanding of the complex connection between the microbiome and cancer. Our bodies are continuously exposed to microbial cells, both resident and transient, as well as their byproducts, including toxic metabolites. Circulation of toxic metabolites may contribute to cancer onset or progression at locations distant from where a particular microbe resides. Moreover, microbes may migrate to other locations in the human body and become associated with tumor development. Several case-control metagenomics studies suggest that dysbiosis in the commensal microbiota is also associated with inflammatory disorders and various cancer types throughout the body. Although the microbiome influences carcinogenesis through mechanisms independent of inflammation and immune system, the most recognizable link is between the microbiome and cancer via the immune system, as the resident microbiota plays an essential role in activating, training, and modulating the host immune response. Immunologic dysregulation is likely to provide mechanistic explanations as to how our microbiome influences cancer development and cancer therapies. In this review, we discuss recent developments in understanding the human gut microbiome's relationship with cancer and the feasibility of developing novel cancer diagnostics based on microbiome profiles. Cancer Prev Res; 10(4); 226-34. ©2017 AACR. ©2017 American Association for Cancer Research.

  8. Decorin in Human Colon Cancer

    Science.gov (United States)

    Nyman, Marie C.; Sainio, Annele O.; Pennanen, Mirka M.; Lund, Riikka J.; Vuorikoski, Sanna; Sundström, Jari T. T.

    2015-01-01

    Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational. PMID:26001829

  9. Cancer risk in patients with hepatitis C virus infection: a?population?based study in Sweden

    OpenAIRE

    Liu, Xiangdong; Chen, Yanqing; Wang, Youxin; Dong, Xiaohua; Wang, Junming; Tang, Jianhua; Sundquist, Kristina; Sundquist, Jan; Ji, Jianguang

    2017-01-01

    Abstract Increased risks of certain cancers have been observed in patients with hepatitis C virus (HCV) infection. However, data on other cancer sites/types are lacking. We analyzed systematically the risk of developing 35 common cancers in patients with HCV infection using a nationwide Swedish database. Patients with HCV infection were identified from the Swedish Hospital Inpatient and Outpatient Register and Primary Health Care Database, and followed until the diagnosis of cancer. Standardi...

  10. High-intensity focused ultrasound ablation in hepatic and pancreatic cancer: complications.

    Science.gov (United States)

    Jung, Seung Eun; Cho, Se Hyun; Jang, Jin Hee; Han, Joon-Yeol

    2011-04-01

    To evaluate the complications of high-intensity focused ultrasound (HIFU) in patients with hepatic and pancreatic cancer. From January 2006 to December 2008, 133 sessions of HIFU treatment were performed in 114 consecutive patients with primary hepatic tumor (n = 57), hepatic metastasis (n = 22), and pancreatic cancer (n = 35) under general anesthesia. The extracorporeal, ultrasound-guided Model-JC system (HAIFU, Chongqing, China) was used. Artificial pleural effusion was created to obtain an adequate sonographic window for ablating hepatic dome masses in 53 patients. We reviewed medical records and imaging findings before, during, and after HIFU. All patients had skin redness, edema, and pain in the treatment regions. All hepatic tumor patients had necrosis of the ribs along the main ultrasound beam path that did not require further treatment. Major complications included biliary obstruction, symptomatic pleural effusion, pneumothorax and fistula formation between an abdominal wall abscess and the ablated hepatic tumor. In 35 pancreatic cancer patients, major complications included third-degree burns and fistula formation between the tumor and duodenum. Delayed complications in hepatic tumor patients included a diaphragmatic rupture and rib fractures along the ultrasound pathway. The complications of HIFU develop mainly around the targeted lesions or along the ultrasound beam pathway. It is essential to have awareness of the possible complications related to HIFU and its imaging features for to avoiding serious complications.

  11. Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake.

    Directory of Open Access Journals (Sweden)

    Lídia Cedó

    Full Text Available Human hepatic lipase (hHL is mainly localized on the hepatocyte cell surface where it hydrolyzes lipids from remnant lipoproteins and high density lipoproteins and promotes their hepatic selective uptake. Furthermore, hepatic lipase (HL is closely associated with obesity in multiple studies. Therefore, HL may play a key role on lipid homeostasis in liver and white adipose tissue (WAT. In the present study, we aimed to evaluate the effects of hHL expression on hepatic and white adipose triglyceride metabolism in vivo. Experiments were carried out in hHL transgenic and wild-type mice fed a Western-type diet. Triglyceride metabolism studies included β-oxidation and de novo lipogenesis in liver and WAT, hepatic triglyceride secretion, and adipose lipoprotein lipase (LPL-mediated free fatty acid (FFA lipolysis and influx. The expression of hHL promoted hepatic triglyceride accumulation and de novo lipogenesis without affecting triglyceride secretion, and this was associated with an upregulation of Srebf1 as well as the main genes controlling the synthesis of fatty acids. Transgenic mice also exhibited more adiposity and an increased LPL-mediated FFA influx into the WAT without affecting glucose tolerance. Our results demonstrate that hHL promoted hepatic steatosis in mice mainly by upregulating de novo lipogenesis. HL also upregulated WAT LPL and promoted triglyceride-rich lipoprotein hydrolysis and adipose FFA uptake. These data support the important role of hHL in regulating hepatic lipid homeostasis and confirm the broad cardiometabolic role of HL.

  12. Computed tomography changes following cryotherapy for hepatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, J.; Morris, D. L. [University of NSW, Sydney (Australia). Department of Surgery; Glenn, D. [St George Hospital, Kogarah, Sydney (Australia). Department of Radiology

    1997-05-01

    Encouraging survival and tumour marker results have been described in patients where the focally destructive technique, hepatic cryotherapy, is used to treat primary and secondary hepatic malignancy. Radiology allows assessment of the cryotherapy procedure and follow-up treatment. This paper aims to review and describe the appearance of hepatic cryotherapy by computed tomography which allows assessment of the adequacy of surgical technique and offers the ability to identify recurrences that may be suitable for further treatment. 11 refs., 1 tab., 9 figs.

  13. Hepatitis C, human immunodeficiency virus and metabolic syndrome: interactions.

    Science.gov (United States)

    Kotler, Donald P

    2009-03-01

    Significant concerns have been raised about the metabolic effects of antiretroviral medication, including the classic triad of dyslipidaemia, insulin resistance (IR) and characteristic alterations in fat distribution (lipoatrophy and lipohypertrophy). Co-infection with hepatitis C appears to exacerbate IR, reduce serum lipids and induce prothrombotic changes in the treated human immunodeficiency virus patient. The effects of co-infection are complex. While combination antiretroviral therapy has been shown to be associated with an increased risk of cardiovascular events through promotion of dyslipidaemia, IR and fat redistribution, co-infection exacerbates IR while reducing serum lipids. Co-infection also promotes a prothrombotic state characterized by endothelial dysfunction and platelet activation, which may enhance risk for cardiovascular disease. Consideration must be given to selection of appropriate treatment regimens and timing of therapy in co-infected patients to minimize metabolic derangements and, ultimately, reduce cardiovascular risk.

  14. Seroprevalence of hepatitis and human immuno-deficiency virus in multitransfused patients from a pediatric hematology clinic

    Directory of Open Access Journals (Sweden)

    Suar Çakı Kılıç

    2008-12-01

    Full Text Available OBJECTIVE: Transfusion transmitted hepatitis has been a severe problem in Turkey in pediatric cancer patients and in chronic congenital anemia. The aim of the present study was to investigate the prevalence of hepatitis B, hepatitis C and human immunodeficiency virus infections in these patients in a University Hospital. METHODS: Multi-transfused 66 children (59 acute leukemia, 6 thalassemia major, 1 severe hereditary spherocytosis diagnosed and followed-up between May, 2000 and December, 2006 were evaluated. Screening of all the patients for HbsAg, anti-HBs, anti-HBc, anti-HCV and anti-HIV was performed at presentation and during the last follow-up. Serologic studies of leukemic patients were also repeated at the end of the chemotherapy. Hepatitis B vaccination was administered to unvaccinated patients with anemia. All blood products were provided by Blood Bank of the Center. RESULTS: No patient was found HBsAg, anti-HCV or anti-HIV positive at diagnosis and at the end of the therapy. There was history of hepatitis B vaccination in only 42% of the patients at diagnosis due to administration of this vaccine to newborns since 1998. At the beginning of the study, 45 % (n=27 of the leukemic patients were immune for hepatitis B, but after completion of the intensive chemotherapy seropositivity persisted in only 28.8 % (n=17. CONCLUSION: Transmission of these viruses is no longer a real problem even in multitransfused immunosuppressed children in Pediatric Hematology Units as a result of the improvements in screening of voluntary blood donors, administration of disposable material in clinics and vaccination by hepatitis B.

  15. Prenatal invasive procedures in women with hepatitis B, hepatitis C, and/or human immunodeficiency virus infections.

    Science.gov (United States)

    Gagnon, Alain; Davies, Gregory; Wilson, R Douglas

    2014-07-01

    To review the risk of in utero infection through prenatal invasive procedures in women with hepatitis B, hepatitis C, and/or human immunodeficiency virus (HIV) infections. Fetal and neonatal morbidity and mortality. Published literature was retrieved through searches of Medline, CINAHL, and the Cochrane Library using appropriate controlled vocabulary (amniocentesis, chorionic villus sampling, cordocentesis, fetal and neonatal infection) and key words (hepatitis B, hepatitis C, HIV). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies from 2002 to 2012 published in English or French. (Studies from 1966 to 2002 were previously reviewed in Clinical Practice Guideline No. 123.) Searches were updated on a regular basis and incorporated in the guideline to February 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). Recommendations 1. For women infected with hepatitis B, hepatitis C, and/or human immunodeficiency virus, the use of non-invasive methods of prenatal risk assessment is recommended, using tests with high sensitivity and low false-positive rates, such as serum screening combined (or not) with nuchal translucency, anatomic ultrasound, and non-invasive molecular prenatal testing. (III-B) 2. For women infected with hepatitis B, hepatitis C, and/or human immunodeficiency virus undergoing an amniocentesis, every effort should be made to avoid inserting the needle through, or very close to, the placenta. (II-2B) 3. Little information is available on other prenatal diagnostic and therapeutic invasive procedures

  16. Comparison of accelerated and rapid schedules for monovalent hepatitis B and combined hepatitis A/B vaccines in children with cancer.

    Science.gov (United States)

    Köksal, Yavuz; Varan, Ali; Aydin, G Burca; Sari, Neriman; Yazici, Nalan; Yalcin, Bilgehan; Kutluk, Tezer; Akyuz, Canan; Büyükpamukçu, Münevver

    2007-12-01

    The aim of this study was to determine the efficacy of immunization against hepatitis A and B infections with "rapid" or "accelerated" schedules in children with cancer receiving chemotherapy. Fifty-one children were recruited to receive either vaccination schedule, in the "rapid vaccination schedule"; hepatitis B (group I) or combined hepatitis A/B vaccines (group III) were administered at months 0, 1, 2, and 12; in the "accelerated vaccination schedule," hepatitis B (group II) or combined hepatitis A/B (group IV) vaccines were administered on days 0, 7, 21, and 365 intramuscularly. The seroconversion rates at months 1 and 3 were 35.7 and 57.1% in group I and 25 and 18.8% in group II, respectively. Group I developed higher seroconversion rates at month 3. In group III the seroconversion rates for hepatitis B at months 1 and 3 were 54.5 and 60% and in group IV 50 and 70%, respectively. For hepatitis A, the seroconversion rates at months 1 and 3 were 81.8 and 90% in group III and 80 and 88.9% in group IV, respectively. The accelerated vaccination schedule seems to have no advantage in children receiving cancer chemotherapy except for high antibody levels at month 1. In conclusion, the accelerated vaccination schedules are not good choices for cancer patients. The combined hepatitis A/B vaccine is more effective than monovalent vaccine in cancer patients, which probably can be explained by an adjuvant effect of the antigens. The seroconversion of hepatitis A by the combined hepatitis A/B vaccination is very good in cancer patients.

  17. 20-years of population-based cancer registration in hepatitis B and liver cancer prevention in the Gambia, West Africa.

    Science.gov (United States)

    Bah, Ebrima; Carrieri, Maria Patrizia; Hainaut, Pierre; Bah, Yusupha; Nyan, Ousman; Taal, Makie

    2013-01-01

    The Gambia Hepatitis Intervention Study (GHIS) was designed as a randomised control trial of infant hepatitis B vaccination applied to public health policy, with the main goal of preventing primary liver cancer later in adult life in The Gambia. To that effect, the National Cancer Registry of The Gambia (NCR), a population-based cancer registry (PBCR), was established in 1986 to actively collect data on all cancer diagnosis nation-wide. We extracted 20-years (1990-2009) of data to assess for the first time, the evolution of the most common cancers, also describe and demonstrate the role of the PBCR in a hepatitis B and liver cancer prevention programme in this population. We estimated Age-Standardised Incidence Rates (ASR (W)) of the most common cancers registered during the period by gender. The registration period was divided into four 5-year intervals and incidence rates were estimated for each interval. The most common cancers in males were liver, prostate, lung plus bronchus, non-Hodgkin lymphoma (NHL) and stomach, accounting for 60%, 5%, 4%, 5% and 3%, respectively. Similarly, cancers of the cervix uteri, liver, breast and NHL, were the most common in females, accounting for 33%, 24%, 11% and 4% of the female cancers, respectively. Cancer incidence has remained relatively stable over time, but as shown elsewhere in sub-Saharan Africa the disease is a threat in The Gambia. The infection related cancers which are mostly preventable (HBV in men and HPV/HIV in women) were the most common. At the moment the data is not enough to detect an effect of hepatitis B vaccination on liver cancer incidence in The Gambia. However, we observed that monitoring case occurrence through PBCR is a key public health pre-requisite for rational planning and implementation of targeted interventions for improving the health of the population.

  18. 20-years of population-based cancer registration in hepatitis B and liver cancer prevention in the Gambia, West Africa.

    Directory of Open Access Journals (Sweden)

    Ebrima Bah

    Full Text Available The Gambia Hepatitis Intervention Study (GHIS was designed as a randomised control trial of infant hepatitis B vaccination applied to public health policy, with the main goal of preventing primary liver cancer later in adult life in The Gambia. To that effect, the National Cancer Registry of The Gambia (NCR, a population-based cancer registry (PBCR, was established in 1986 to actively collect data on all cancer diagnosis nation-wide. We extracted 20-years (1990-2009 of data to assess for the first time, the evolution of the most common cancers, also describe and demonstrate the role of the PBCR in a hepatitis B and liver cancer prevention programme in this population.We estimated Age-Standardised Incidence Rates (ASR (W of the most common cancers registered during the period by gender. The registration period was divided into four 5-year intervals and incidence rates were estimated for each interval. The most common cancers in males were liver, prostate, lung plus bronchus, non-Hodgkin lymphoma (NHL and stomach, accounting for 60%, 5%, 4%, 5% and 3%, respectively. Similarly, cancers of the cervix uteri, liver, breast and NHL, were the most common in females, accounting for 33%, 24%, 11% and 4% of the female cancers, respectively.Cancer incidence has remained relatively stable over time, but as shown elsewhere in sub-Saharan Africa the disease is a threat in The Gambia. The infection related cancers which are mostly preventable (HBV in men and HPV/HIV in women were the most common. At the moment the data is not enough to detect an effect of hepatitis B vaccination on liver cancer incidence in The Gambia. However, we observed that monitoring case occurrence through PBCR is a key public health pre-requisite for rational planning and implementation of targeted interventions for improving the health of the population.

  19. Biliary Secretion of Quasi-Enveloped Human Hepatitis A Virus

    Directory of Open Access Journals (Sweden)

    Asuka Hirai-Yuki

    2016-12-01

    Full Text Available Hepatitis A virus (HAV is an unusual picornavirus that is released from cells cloaked in host-derived membranes. These quasi-enveloped virions (eHAV are the only particle type circulating in blood during infection, whereas only nonenveloped virions are shed in feces. The reason for this is uncertain. Hepatocytes, the only cell type known to support HAV replication in vivo, are highly polarized epithelial cells with basolateral membranes facing onto hepatic (blood sinusoids and apical membranes abutting biliary canaliculi from which bile is secreted to the gut. To assess whether eHAV and nonenveloped virus egress from cells via vectorially distinct pathways, we studied infected polarized cultures of Caco-2 and HepG2-N6 cells. Most (>99% progeny virions were released apically from Caco-2 cells, whereas basolateral (64% versus apical (36% release was more balanced with HepG2-N6 cells. Both apically and basolaterally released virions were predominantly enveloped, with no suggestion of differential vectorial release of eHAV versus naked virions. Basolateral to apical transcytosis of either particle type was minimal (<0.02%/h in HepG2-N6 cells, arguing against this as a mechanism for differences in membrane envelopment of serum versus fecal virus. High concentrations of human bile acids converted eHAV to nonenveloped virions, whereas virus present in bile from HAV-infected Ifnar1−/−Ifngr1−/− and Mavs−/− mice banded over a range of densities extending from that of eHAV to that of nonenveloped virions. We conclude that nonenveloped virions shed in feces are derived from eHAV released across the canalicular membrane and stripped of membranes by the detergent action of bile acids within the proximal biliary canaliculus.

  20. Committee Opinion No. 655: Hepatitis B, Hepatitis C, and Human Immunodeficiency Virus Infections in Obstetrician-Gynecologists.

    Science.gov (United States)

    2016-02-01

    To prevent transmission of bloodborne pathogens, it is important that health care providers adhere to standard precautions, follow fundamental infection-control principles, and use appropriate procedural techniques. All obstetrician-gynecologists who provide clinical care should receive the hepatitis B virus vaccine series. The Society for Healthcare Epidemiology of America has established guidelines for the management of health care providers who are infected with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV). The guidelines categorize representative obstetric and gynecologic procedures according to level of risk of bloodborne pathogen transmission and include recommendations for health care provider clinical activities, based on these categories and viral burden. It is important to note that when no restrictions are recommended, careful supervision should be carried out as highlighted. These recommendations provide a framework within which to consider such cases; however, each case should be independently considered in context by the expert review panel.

  1. Committee Opinion No. 655 Summary: Hepatitis B, Hepatitis C, and Human Immunodeficiency Virus Infections in Obstetrician-Gynecologists.

    Science.gov (United States)

    2016-02-01

    To prevent transmission of bloodborne pathogens, it is important that health care providers adhere to standard precautions, follow fundamental infection-control principles, and use appropriate procedural techniques. All obstetrician-gynecologists who provide clinical care should receive the hepatitis B virus vaccine series. The Society for Healthcare Epidemiology of America has established guidelines for the management of health care providers who are infected with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV). The guidelines categorize representative obstetric and gynecologic procedures according to level of risk of bloodborne pathogen transmission and include recommendations for health care provider clinical activities, based on these categories and viral burden. It is important to note that when no restrictions are recommended, careful supervision should be carried out as highlighted. These recommendations provide a framework within which to consider such cases; however, each case should be independently considered in context by the expert review panel.

  2. Hepatitis B Foundation Newsletter: B Informed

    Science.gov (United States)

    ... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  3. Derivation and characterization of hepatic progenitor cells from human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Dongxin Zhao

    Full Text Available The derivation of hepatic progenitor cells from human embryonic stem (hES cells is of value both in the study of early human liver organogenesis and in the creation of an unlimited source of donor cells for hepatocyte transplantation therapy. Here, we report for the first time the generation of hepatic progenitor cells derived from hES cells. Hepatic endoderm cells were generated by activating FGF and BMP pathways and were then purified by fluorescence activated cell sorting using a newly identified surface marker, N-cadherin. After co-culture with STO feeder cells, these purified hepatic endoderm cells yielded hepatic progenitor colonies, which possessed the proliferation potential to be cultured for an extended period of more than 100 days. With extensive expansion, they co-expressed the hepatic marker AFP and the biliary lineage marker KRT7 and maintained bipotential differentiation capacity. They were able to differentiate into hepatocyte-like cells, which expressed ALB and AAT, and into cholangiocyte-like cells, which formed duct-like cyst structures, expressed KRT19 and KRT7, and acquired epithelial polarity. In conclusion, this is the first report of the generation of proliferative and bipotential hepatic progenitor cells from hES cells. These hES cell-derived hepatic progenitor cells could be effectively used as an in vitro model for studying the mechanisms of hepatic stem/progenitor cell origin, self-renewal and differentiation.

  4. Lipid profile and hepatic steatosis in hepatitis C infected egyptian survivors of childhood cancer.

    Science.gov (United States)

    Al-Tawil, Mohammed Mostafa; Shoeeb, Ahmed Saeed; Abbas, Amal; El-Tawil, Ahmed; El-Sayed, Manal Hamdy

    2015-02-01

    Studies associating chronic hepatitis C virus (HCV) infection with lipid profile and hepatic steatosis in children and adolescents are scarce. This study investigated lipid profile abnormalities and hepatic steatosis among HCV-infected Egyptian children and adolescents who survived leukemia and lymphoma and evaluated impact on response to antiviral therapy. Thirty-six leukemia/lymphoma cured children and adolescents (mean age: 12.47 ± 3.56 years) with chronic HCV infection and 30 healthy controls (mean age: 11.64 ± 3.96 years) were enrolled in this prospective study. Serum lipid profile and abdominal ultrasonography were done for all patients and controls. Guided liver biopsy with histopathological examination was done for 32 (88.9%) patients eligible for antiviral therapy. Total cholesterol, LDL-cholesterol, and apolipoprotein B (apo-B) in patients were significantly lower than in the control group (P ≤ .01, ≤ .01, and ≤ .05, respectively). Among those who underwent liver biopsy (n = 32), macrovesicular hepatic steatosis associated with chronic hepatitis C was documented in 10 children (31.3%). Body mass index was significantly higher (P ≤ .05) and apo-B was significantly lower in steatotic (P ≤ .05) than non-steatotic HCV-infected children. Liver span by ultrasound, alanine aminotransferase (ALT), and apo-B were independent predictors for hepatic steatosis (P lipids in HCV-infected children with cured leukemia/lymphoma. Hepatic steatosis was found in a significant proportion of patients and was associated with a poor response to antiviral treatment.

  5. Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D L; Nørgaard, H; Weber Vestermark, Lene

    2012-01-01

    The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease.......The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease....

  6. Natural history of hepatic metastases from colorectal cancer--pathobiological pathways with clinical significance.

    Science.gov (United States)

    Paschos, Konstantinos A; Majeed, Ali W; Bird, Nigel C

    2014-04-14

    Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.

  7. Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

    Science.gov (United States)

    Paschos, Konstantinos A; Majeed, Ali W; Bird, Nigel C

    2014-01-01

    Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting. PMID:24744570

  8. The impact of PET/CT on the management of hepatic and extra hepatic metastases from gastrointestinal cancers

    Energy Technology Data Exchange (ETDEWEB)

    Polat, Erdal, E-mail: erdal066@yahoo.com [Kartal Kosuyolu High Specialty Training and Research Hospital, Department of Gastrointestinal Surgery, Istanbul (Turkey); Bostanci, Erdal Birol [Sakarya University, Faculty of Medicine, Department of General Surgery, Sakarya (Turkey); Aksoy, Erol [Turkiye Yuksek Ihtisas Teaching and Research Hospital, Department of Gastroenterological Surgery, Ankara (Turkey); Karaman, Kerem [Sakarya University, Faculty of Medicine, Department of General Surgery, Sakarya (Turkey); Poyraz, Nilufer Yildirim [Ataturk Teaching and Research Hospital, Department of Nuclear Medicine, Ankara (Turkey); Duman, Ugur [Sevket Yilmaz Training and Research Hospital, Department of General Surgery, Bursa (Turkey); Gencturk, Zeynep Biyikli [Ankara University, Faculty of Medicine, Department of Biostatistics, Ankara (Turkey); Yol, Sinan [Medeniyet University, Faculty of Medicine, Department of General surgery, Istanbul (Turkey)

    2015-06-15

    Highlights: • CT is more sensitive than PET/CT in detecting hepatic metastases. • PET/CT is more specific in detecting hepatic metastases. • CT and PET/CT have equal sensitivity in detecting extra hepatic metastases. • PET/CT is more specific in detecting extra hepatic metastases. • PET/CT has an impact of about 40% on changing the management strategies. - Abstract: Purpose: To investigate the efficacy of positron emission tomography/computed tomography (PET/CT) in detection and management of hepatic and extrahepatic metastases from gastrointestinal cancers. Materials and methods: Between February 2008 and July 2010, patients histopathologically diagnosed with gastrointestinal cancer and showing suspected metastasis on CT screening were subsequently evaluated with PET/CT. All patients were subgrouped according to histopathological origin and localization of the primary tumor. Localization of gastrointestinal cancers was further specified as lower gastrointestinal system (GIS), upper GIS, or hepato-pancreato-biliary (HPB). Both accuracy and impact of CT and PET/CT on patient management were retrospectively evaluated. Results: One hundred and thirteen patients diagnosed histopathologically with gastrointestinal cancers were retrospectively evaluated. Seventy-nine patients had adenocarcinoma and 34 patients other gastrointestinal tumors. Forty-one patients were in the upper GIS group, 30 patients in the HPB group, and 42 patients in the lower GIS group. Evaluation the diagnostic performance of PET/CT for suspected metastasis according to histopathological origin of the tumor, revealed that the sensitivity of PET/CT – although statistically not different – was higher in adenocarcinomas than in non-adenocarcinomas (90% (95% CI, 0.78–0.96) vs. 71.4% (95% CI, 0.45–0.88), P = 0.86). The specificity was not significantly different (85.7% (95% CI, 0.70–0.93) vs. 85% (95% CI, 0.63–0.94), P = 1.00). In the overall patient group; CT was significantly more

  9. Seroprevalence of Hepatitis B and Human Immunodeficency Virus ...

    African Journals Online (AJOL)

    There is a rising prevalence of blood borne infections such as Hepatitis B (HBV) and HIV worldwide, especially in developing countries. This study was conducted to establish the prevalence rate of HIV and Hepatitis B infections and to determine the risk to which Health workers and neonates are exposed in our centre.

  10. Hepatitis A virus infection and hepatitis A vaccination in human immunodeficiency virus-positive patients: A review

    Science.gov (United States)

    Lin, Kuan-Yin; Chen, Guan-Jhou; Lee, Yu-Lin; Huang, Yi-Chia; Cheng, Aristine; Sun, Hsin-Yun; Chang, Sui-Yuan; Liu, Chun-Eng; Hung, Chien-Ching

    2017-01-01

    Hepatitis A virus (HAV) is one of the most common infectious etiologies of acute hepatitis worldwide. The virus is known to be transmitted fecal-orally, resulting in symptoms ranging from asymptomatic infection to fulminant hepatitis. HAV can also be transmitted through oral-anal sex. Residents from regions of low endemicity for HAV infection often remain susceptible in their adulthood. Therefore, clustered HAV infections or outbreaks of acute hepatitis A among men who have sex with men and injecting drug users have been reported in countries of low endemicity for HAV infection. The duration of HAV viremia and stool shedding of HAV may be longer in human immunodeficiency virus (HIV)-positive individuals compared to HIV-negative individuals with acute hepatitis A. Current guidelines recommend HAV vaccination for individuals with increased risks of exposure to HAV (such as from injecting drug use, oral-anal sex, travel to or residence in endemic areas, frequent clotting factor or blood transfusions) or with increased risks of fulminant disease (such as those with chronic hepatitis). The seroconversion rates following the recommended standard adult dosing schedule (2 doses of HAVRIX 1440 U or VAQTA 50 U administered 6-12 mo apart) are lower among HIV-positive individuals compared to HIV-negative individuals. While the response rates may be augmented by adding a booster dose at week 4 sandwiched between the first dose and the 6-mo dose, the need of booster vaccination remain less clear among HIV-positive individuals who have lost anti-HAV antibodies. PMID:28611512

  11. Hepatitis A virus infection and hepatitis A vaccination in human immunodeficiency virus-positive patients: A review.

    Science.gov (United States)

    Lin, Kuan-Yin; Chen, Guan-Jhou; Lee, Yu-Lin; Huang, Yi-Chia; Cheng, Aristine; Sun, Hsin-Yun; Chang, Sui-Yuan; Liu, Chun-Eng; Hung, Chien-Ching

    2017-05-28

    Hepatitis A virus (HAV) is one of the most common infectious etiologies of acute hepatitis worldwide. The virus is known to be transmitted fecal-orally, resulting in symptoms ranging from asymptomatic infection to fulminant hepatitis. HAV can also be transmitted through oral-anal sex. Residents from regions of low endemicity for HAV infection often remain susceptible in their adulthood. Therefore, clustered HAV infections or outbreaks of acute hepatitis A among men who have sex with men and injecting drug users have been reported in countries of low endemicity for HAV infection. The duration of HAV viremia and stool shedding of HAV may be longer in human immunodeficiency virus (HIV)-positive individuals compared to HIV-negative individuals with acute hepatitis A. Current guidelines recommend HAV vaccination for individuals with increased risks of exposure to HAV (such as from injecting drug use, oral-anal sex, travel to or residence in endemic areas, frequent clotting factor or blood transfusions) or with increased risks of fulminant disease (such as those with chronic hepatitis). The seroconversion rates following the recommended standard adult dosing schedule (2 doses of HAVRIX 1440 U or VAQTA 50 U administered 6-12 mo apart) are lower among HIV-positive individuals compared to HIV-negative individuals. While the response rates may be augmented by adding a booster dose at week 4 sandwiched between the first dose and the 6-mo dose, the need of booster vaccination remain less clear among HIV-positive individuals who have lost anti-HAV antibodies.

  12. Using Bovine Viral Diarrhea Virus (BVDV) As Surrogate for Human Hepatitis C Virus

    Science.gov (United States)

    This test is designed to validate virucidal effectiveness claims for a product to be registered as a virucide. It determines the potential of the test agent to disinfect hard surfaces contaminated with human Hepatitis C virus (HCV).

  13. Seroprevalence of Hepatitis A virus infection in non-human primates in Assam, India

    Directory of Open Access Journals (Sweden)

    B.G. Nath

    2013-08-01

    Full Text Available The present study investigated 37 serum samples of non-human primates in Assam State Zoo and the Department of Forest and Environment, Govt. of Assam for seroprevalence of hepatitis A virus infection during the period from December, 2007 to November, 2009. Four serum samples were also collected from animal keepers of the zoo to investigate transmission of the disease to the attendants working with these primates. Competitive ELISA was performed using hepatitis A virus ELISA kit (Wanti Hep. AV to detect hepatitis A virus antibody in serum samples. Ten (27.21% of the non-human primate samples and three (75% human samples had detectable anti-hepatitis A virus antibodies. Living status of the non-human primates (Free living was a high potential risk for hepatitis A virus infection. Seroprevalence of hepatitis A virus infection had significant difference between free living non-human primates and captive non-human primates (P less than 0.05. No significant difference (p=0.86 was seen between male and female non-human primates

  14. Human papillomavirus and genital cancer

    Directory of Open Access Journals (Sweden)

    Rapose Alwyn

    2009-01-01

    Full Text Available Human papillomavirus (HPV is one of the most common sexually transmitted infections world-wide. Low-risk HPV-types are associated with genital warts. Persistent infection with high-risk HPV-types is associated with genital cancers. Smoking and HIV infection have consistently been associated with longer duration of HPV infection and risk for genital cancer. There is an increasing incidence of anal cancers, and a close association with HPV infection has been demonstrated. Receptive anal sex and HIV-positive status are associated with a high risk for anal cancer. Two HPV vaccines are now available and offer protection from infection by the HPV-types included in the vaccine. This benefit is maximally seen in young women who were uninfected prior to vaccination.

  15. Human mesenchymal stem cell-engineered hepatic cell sheets accelerate liver regeneration in mice

    OpenAIRE

    Noriko Itaba; Yoshiaki Matsumi; Kaori Okinaka; An Afida Ashla; Yohei Kono; Mitsuhiko Osaki; Minoru Morimoto; Naoyuki Sugiyama; Kazuo Ohashi; Teruo Okano; Goshi Shiota

    2015-01-01

    Mesenchymal stem cells (MSCs) are an attractive cell source for cell therapy. Based on our hypothesis that suppression of Wnt/β-catenin signal enhances hepatic differentiation of human MSCs, we developed human mesenchymal stem cell-engineered hepatic cell sheets by a small molecule compound. Screening of 10 small molecule compounds was performed by WST assay, TCF reporter assay, and albumin mRNA expression. Consequently, hexachlorophene suppressed TCF reporter activity in time- and concentrat...

  16. [Hepatic intra-arterial infusion of BAK immune cells to treat metastatic liver cancer].

    Science.gov (United States)

    Ebina, Takusaburo

    2011-11-01

    Based on the "living with cancer" concept while maintaining a favorable QOL and avoiding side effects and drug resistance, we have developed a new immune cell treatment called BAK (BRM activated killer) therapy, primarily using CD56+ cells for a case of advanced progressive solid cancer. In the present case, we administered BAK cells by hepatic intra-arterial infusion to a patient who happened to be a surgeon and wished to undergo this therapy. The patient was a 52-year- old male surgeon who underwent surgery for rectal cancer in April 2007. Heavy particle radiotherapy was administered when liver metastases were identified in July 2008. Starting in December 2008, 10 billion BAK cells were administered each month by hepatic intra-arterial infusion via a catheter on a total of six different occasions. The 10 billion autologous lymphocytes were suspended in 200 mL of Ringer's solution and returned to the patient by hepatic intra-arterial infusion over a period of one hour. Interactions between the activated lymphocytes and liver cancer cells increased levels of serum α1AG, an inflammation marker, but these levels normalized following the sixth and final administration. Conventional drip-infusion BAK therapy was administered thereafter. Diagnostic imaging, including PET-CT and PET, confirmed a complete disappearance of liver metastases. This case suggests the effectiveness of hepatic intra-arterial infusion BAK cell therapy in treating liver cancer.

  17. Colon cancer metastasis mimicking intraductal papillary neoplasm of the extra-hepatic bile duct.

    Science.gov (United States)

    Yamao, Takanobu; Hayashi, Hiromitsu; Higashi, Takaaki; Takeyama, Hideyuki; Kaida, Takayoshi; Nitta, Hidetoshi; Hashimoto, Daisuke; Chikamoto, Akira; Beppu, Toru; Baba, Hideo

    2015-01-01

    An accurate diagnosis of the primary cancer in cases with metastatic lesions is quite important because misdiagnosis may lead to the selection of incorrect adjuvant therapy and worse long-term outcomes after surgery. The metastatic sites associated with the dissemination of colon cancer are well known and normally predictable, which includes the lymphatic, haematogenous, or peritoneal regions, while other locations are quite rare. In this report, we present a case of colon cancer with an unusual metastatic pattern mimicking an intraductal papillary neoplasm of the bile duct (IPNB) present in the extra-hepatic bile duct with a cytokeratin (CK)-7-negative and CK-20-positive profile (intestinal type). In the case of this patient who had a history of colon cancer, immunohistochemical staining for the CKs was useful for distinguishing between primary IPNB and colon cancer metastases. We suspect that the metastatic pattern of this case of colon cancer that mimicked IPNB at the extra-hepatic bile duct developed incidentally via the bile stream. This is a rare case of colon cancer metastasis mimicking IPNB at the extra-hepatic bile duct. Our findings also suggest that there may be an incidental 4th metastatic route via the bile stream. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Hepatic Lesions Detected after Mastectomy, in Breast Cancer Patients with Hepatitis Background May Need to Undergo Liver Biopsy to Rule Out Second Primary Hepatocellular Carcinoma.

    Science.gov (United States)

    Chen, Qi-wen; Li, Hai-jin; Chen, Ya-nan; Ning, Zhou-yu; Gao, Song; Shen, Ye-hua; Meng, Zhi-qiang; Vargulick, Sonya; Wang, Bi-yun; Chen, Hao

    2016-01-01

    Liver metastasis is a common phenomenon in breast cancer patients. Hepatic lesions detected in breast cancer patients may be easily misdiagnosed as metastatic sites, rather than being treated as primary foci. This descriptive study aims to investigate the clinicopathological characteristics of second primary hepatocellular carcinoma in breast cancer patients and to infer in which circumstances liver biopsy is needed. Eighty-one consecutive breast cancer patients with hepatic lesions admitted to our department were retrospectively studied and analyzed from January 2009 to March 2014 according to Warren and Gates' criteria for second primary cancers. Second primary hepatocellular carcinoma was observed in sixteen of seventy eight patients with breast cancer. There was a significant difference in HBV status between the second HCC group and liver metastases group (Phistory (P = 0.1160) between second primary HCC and metastases group. Two of these patients had synchronous second primary hepatocellular carcinoma and the remaining fourteen patients had metachronous second primary HCC. All sixteen patients were infected with hepatitis, including hepatitis virus B and C, or resolved HBV infection. Breast cancer patients with either HBV infection or resolved HBV infection, regardless of an elevated AFP level, may receive liver biopsy to avoid unnecessary and inappropriate treatments for metastasis. Awareness of second primary HCC in breast cancer patients needs to be emphasized.

  19. Septin mutations in human cancers

    Directory of Open Access Journals (Sweden)

    Elias T Spiliotis

    2016-11-01

    Full Text Available Septins are GTP-binding proteins that are evolutionarily and structurally related to the RAS oncogenes. Septin expression levels are altered in many cancers and new advances point to how abnormal septin expression may contribute to the progression of cancer. In contrast to the RAS GTPases, which are frequently mutated and actively promote tumorigenesis, little is known about the occurrence and role of septin mutations in human cancers. Here, we review septin missense mutations that are currently in the Catalog of Somatic Mutations in Cancer (COSMIC database. The majority of septin mutations occur in tumors of the large intestine, skin, endometrium and stomach. Over 25% of the annotated mutations in SEPT2, SEPT4 and SEPT9 belong to large intestine tumors. From all septins, SEPT9 and SEPT14 exhibit the highest mutation frequencies in skin, stomach and large intestine cancers. While septin mutations occur with frequencies lower than 3%, recurring mutations in several invariant and highly conserved amino acids are found across different septin paralogs and tumor types. Interestingly, a significant number of these mutations occur in the GTP-binding pocket and septin dimerization interfaces. Future studies may determine how these somatic mutations affect septin structure and function, whether they contribute to the progression of specific cancers and if they could serve as tumor-specific biomarkers.

  20. DBGC: A Database of Human Gastric Cancer

    Science.gov (United States)

    Wang, Chao; Zhang, Jun; Cai, Mingdeng; Zhu, Zhenggang; Gu, Wenjie; Yu, Yingyan; Zhang, Xiaoyan

    2015-01-01

    The Database of Human Gastric Cancer (DBGC) is a comprehensive database that integrates various human gastric cancer-related data resources. Human gastric cancer-related transcriptomics projects, proteomics projects, mutations, biomarkers and drug-sensitive genes from different sources were collected and unified in this database. Moreover, epidemiological statistics of gastric cancer patients in China and clinicopathological information annotated with gastric cancer cases were also integrated into the DBGC. We believe that this database will greatly facilitate research regarding human gastric cancer in many fields. DBGC is freely available at http://bminfor.tongji.edu.cn/dbgc/index.do PMID:26566288

  1. Isolated varices over hepatic flexure colon indicating superior mesenteric venous thrombosis caused by uncinate pancreatic head cancer - a case report

    OpenAIRE

    Ho, Yu-Pin; Lin, Chun-Jung; Su, Ming-Yao; Tseng, Jeng-Hwei; Chiu, Cheng-Tang; Chen, Pang-Chi

    2005-01-01

    Very rare cases of varices involving right side colon were reported. Most of them were due to cirrhotic portal hypertension or other primary causes. No report case contributed to pancreatic cancer. Here, we reported a case of uncinate pancreatic cancer with the initial finding of isolated hepatic flexure colon varices. Following studies confirmed isolated varices involving hepatic flexure colon due to pancreatic cancer with occlusion of superior mesenteric vein. From this report, superior mes...

  2. Prevalence of human immunodeficiency virus — hepatitis B virus co ...

    African Journals Online (AJOL)

    Azhani Mandiwana

    thirds of new HIV infections by 2020 and to reduce 90% of new cases of chronic hepatitis by 2030.1 Worldwide, about 36.9 million people live with HIV; of these 2.6 million are co-infected with hepatitis B virus (HBV).2,3 Primary modes of the HIV–HBV co- infection transmission include sexual contact, injection drug use,.

  3. Colon cancer presenting as a hepatic mass in pregnancy: A case ...

    African Journals Online (AJOL)

    The incidences of hepatic masses and colon cancer in pregnancy are low. The clinical features of each can mimic those of pregnancy, thereby posing a diagnostic challenge to clinicians, particularly when the clinical scenario is complicated by HIV infection. This report illustrates such diagnostic difficulties, and the need to ...

  4. Profile of hepatitis B virus, hepatitis C virus, hepatitis d virus and human immunodeficiency virus infections in hemodialysis patients of a tertiary care hospital in uttarakhand.

    Science.gov (United States)

    Mittal, Garima; Gupta, Pratima; Thakuria, Bhaskar; Mukhiya, Gulshan K; Mittal, Manish

    2013-03-01

    Viral hepatitis and human immunodeficiency virus (HIV) infection are important causes of morbidity and mortality in hemodialysis (HD) patients. The present study was performed to assess the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and HIV infections in hemodialysis patients of a tertiary care hospital in Uttarakhand. All patients undergoing maintenance HD at our center were screened for hepatitis B surface antigen (HBsAg), antibody to HCV (anti-HCV), antibody to HDV (anti-HDV) and HIV antibody by ELISA. Detailed history regarding age, sex, duration of dialysis, blood transfusions, number of dialysis centers, dialyzer reuse and laboratory data was recorded. A total of 118 patients (79 males and 39 females) were followed for 18 months with screening for the presence of HBV, HCV and HIV infections. At baseline, 12 (10.2%) patients were positive for HBsAg, 19 (16.1%) for anti-HCV and 2 (1.7%) for HIV antibody. Over 18 months, one additional patient became HBsAg positive and an additional 17 became anti-HCV-positive to give a total of 36 HCV-positive patients. Dual HBV and HCV infection was seen in 5 (4.2%) and anti-HDV antibodies were found in 1 (0.9%) patient. History of blood transfusions, duration of HD, dialyzer reuse and dialysis at multiple centers were found to be important risk factors for anti-HCV positivity. Implementation and adherence to universal work precautions by dialysis staff is imperative to prevent transmission of these infections.

  5. Seroprevalence of the Hepatitis B, Hepatitis C, and Human Immunodeficiency Viruses and Treponema pallidum at the Beijing General Hospital from 2010 to 2014: A Cross-Sectional Study.

    Science.gov (United States)

    Xu, Shaoxia; Wang, Qiaofeng; Zhang, Weihong; Qiu, Zhifeng; Cui, Jingtao; Yan, Wenjuan; Ni, Anping

    2015-01-01

    The hepatitis B, hepatitis C, human immunodeficiency viruses and Treponema pallidum are important causes of infectious diseases concern to public health. Between 2010 and 2014, we used an automated chemiluminescence microparticle immunoassay to detect the hepatitis B, hepatitis C, and human immunodeficiency viruses as well as Treponema pallidum (the rapid plasma regain test was used in 2010-2011). Positive human immunodeficiency virus tests were confirmed via western blotting. Among 416,130 subjects, the seroprevalences for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum were 5.72%, 1.23%, 0.196%, and 0.76%, respectively. Among 671 patients with positive human immunodeficiency virus results, 392 cases were confirmed via western blotting. Hepatitis B and human immunodeficiency virus infections were more frequent in men (7.78% and 0.26%, respectively) than in women (4.45% and 0.021%, respectively). The hepatitis B and C virus seroprevalences decreased from 6.21% and 1.58%, respectively, in 2010, to 5.37% and 0.988%, respectively, in 2014. The human immunodeficiency virus seroprevalence increased from 0.04% in 2010 to 0.17% in 2014, and was elevated in the Infectious Disease (2.65%), Emergency (1.71%), and Dermatology and Sexually Transmitted Diseases (1.12%) departments. The specificity of the human immunodeficiency virus screening was 71.4%. The false positive rates for the Treponema pallidum screening tests increased in patients who were 60-70 years old. The co-infection rates for the hepatitis C and human immunodeficiency viruses were 0.47% in hepatitis C virus-positive patients and 7.33% in human immunodeficiency virus-positive patients. During 2010-2014, hepatitis B virus and human immunodeficiency virus infections were more frequent among men at our institution. Although the seroprevalences of hepatitis B and C viruses decreased, the seroprevalence of human immunodeficiency virus infection increased (with higher

  6. Seroprevalence of the Hepatitis B, Hepatitis C, and Human Immunodeficiency Viruses and Treponema pallidum at the Beijing General Hospital from 2010 to 2014: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Shaoxia Xu

    Full Text Available The hepatitis B, hepatitis C, human immunodeficiency viruses and Treponema pallidum are important causes of infectious diseases concern to public health.Between 2010 and 2014, we used an automated chemiluminescence microparticle immunoassay to detect the hepatitis B, hepatitis C, and human immunodeficiency viruses as well as Treponema pallidum (the rapid plasma regain test was used in 2010-2011. Positive human immunodeficiency virus tests were confirmed via western blotting.Among 416,130 subjects, the seroprevalences for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum were 5.72%, 1.23%, 0.196%, and 0.76%, respectively. Among 671 patients with positive human immunodeficiency virus results, 392 cases were confirmed via western blotting. Hepatitis B and human immunodeficiency virus infections were more frequent in men (7.78% and 0.26%, respectively than in women (4.45% and 0.021%, respectively. The hepatitis B and C virus seroprevalences decreased from 6.21% and 1.58%, respectively, in 2010, to 5.37% and 0.988%, respectively, in 2014. The human immunodeficiency virus seroprevalence increased from 0.04% in 2010 to 0.17% in 2014, and was elevated in the Infectious Disease (2.65%, Emergency (1.71%, and Dermatology and Sexually Transmitted Diseases (1.12% departments. The specificity of the human immunodeficiency virus screening was 71.4%. The false positive rates for the Treponema pallidum screening tests increased in patients who were 60-70 years old. The co-infection rates for the hepatitis C and human immunodeficiency viruses were 0.47% in hepatitis C virus-positive patients and 7.33% in human immunodeficiency virus-positive patients.During 2010-2014, hepatitis B virus and human immunodeficiency virus infections were more frequent among men at our institution. Although the seroprevalences of hepatitis B and C viruses decreased, the seroprevalence of human immunodeficiency virus infection increased (with

  7. Dried blood spots, valid screening for viral hepatitis and human immunodeficiency virus in real-life

    DEFF Research Database (Denmark)

    Mössner, Belinda K; Staugaard, Benjamin; Jensen, Janne

    2016-01-01

    AIM: To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS: We included prospective patients with known viral infections from drug treatment......, but correctly classified 95% of the anti-HCV-positive patients with chronic and past infections. Anti-HBc and anti-HBS showed low sensitivity in DBS (68% and 42%). CONCLUSION: DBS sampling, combined with an automated analysis system, is a feasible screening method to diagnose chronic viral hepatitis and HIV...

  8. Cancer Vaccines

    Science.gov (United States)

    ... foreign. Most preventive vaccines, including those aimed at cancer-causing viruses ( hepatitis B virus and human papillomavirus ), stimulate the ... 9 through 25 for the prevention of cervical cancer caused by HPV. Hepatitis B virus (HBV) vaccines. Chronic HBV infection can lead to ...

  9. Seroprevalence of Hepatitis A virus infection in non-human primates in Assam, India

    OpenAIRE

    B.G. NATH; Chakraborty, A.; Sarma, D. K.; Rahman, T; P.K. Boro

    2013-01-01

    The present study investigated 37 serum samples of non-human primates in Assam State Zoo and the Department of Forest and Environment, Govt. of Assam for seroprevalence of hepatitis A virus infection during the period from December, 2007 to November, 2009. Four serum samples were also collected from animal keepers of the zoo to investigate transmission of the disease to the attendants working with these primates. Competitive ELISA was performed using hepatitis A virus ELISA kit (Wanti Hep. AV...

  10. Lung metastasectomy for postoperative colorectal cancer in patients with a history of hepatic metastasis.

    Science.gov (United States)

    Kamiyoshihara, Mitsuhiro; Igai, Hitoshi; Kawatani, Natsuko; Ibe, Takashi; Tomizawa, Naoki; Obayashi, Kai; Shimizu, Kimihiro; Takeyoshi, Izumi

    2014-05-01

    Our objective was to evaluate the efficacy of pulmonary metastasectomy for postoperative colorectal cancer with hepatic metastasis, and to investigate the role of clinicopathological factors as predictors of outcome. Consecutive patients undergoing pulmonary metastasectomy for colorectal cancer with (group PH, n = 27) or without (group P, n = 46) a history of hepatic metastasis were included in the study. Clinicopathological variables, including sex, age, site, carcinoembryonic antigen in the primary tumor, disease-free interval, prior hepatic resection, timing of pulmonary metastases, preoperative chemotherapy, type of pulmonary resection, and number, size, and location of pulmonary metastases were retrospectively collected and investigated for prognostic significance. Five-year survival rates were 59.5 and 70.0 % for patients with and without a history of hepatic metastasis, respectively; these values did not differ significantly. Among all investigated prognostic variables, sex and number of pulmonary metastases (1 vs. >1) were the most important factors affecting the outcome after colorectal and pulmonary resection. There was no significant difference in overall survival whether it was calculated from the time of resection of the primary colorectal cancer or of pulmonary metastases. Pulmonary resection is not contraindicated in clinical practice. Significant factors indicating a good prognosis were female sex and the number of pulmonary metastases. Special attention should be paid to comparison of survival among studies.

  11. Reelin expression in human liver of patients with chronic hepatitis C infection

    Directory of Open Access Journals (Sweden)

    Simone Carotti

    2017-03-01

    Full Text Available Reelin is a secreted extracellular glycoprotein that plays a critical role during brain development. Several studies have described Reelin expression in hepatic stellate cells of the human liver. In order to investigate the possible role of Reelin in the process of hepatic fibrogenesis, in this study we investigated Reelin expression in the liver tissue of patients infected with the Hepatitis C Virus (HCV. On this basis, Reelin expression was analysed by immunohistochemistry during liver biopsies of 81 patients with HCV-related chronic hepatitis. A Knodell score was used to stage liver fibrosis. Hepatic stellate cells/myofibroblast immunohistochemical markers (CRBP-1, alpha-SMA were also evaluated. As further confirmed by co-localization experiments (Reelin +CRBP-1, Reelin protein was expressed by hepatic stellate cells/myofibroblasts, and a significant positive correlation was found between Reelin expression and the stage of liver fibrosis (P=0.002. Moreover, Reelin correlated with CRBP-1 positive cells (P=0.002, but not with alpha-SMA, suggesting that Reelin should not be regarded as a marker of hepatic stellate cells/myofibroblasts differentiation but rather as a functional protein expressed during some phases of liver fibrosis. Furthermore, Disabled-1 (Dab1, a Reelin adaptor protein, was expressed in cells of ductular reaction suggesting a paracrine role for Reelin with regards these elements. In conclusion, Reelin was expressed by human hepatic stellate cells/myofibroblasts and the number of these cells increased significantly in the lobule as the liver fibrosis progressed, suggesting a role for Reelin in the activation of hepatic stellate cells/myofibroblasts during liver injury. Reelin may potentially be incorporated into liver injury evaluations in combination with other histological data.

  12. Laparoscopic radical lymph node dissection for advanced colon cancer close to the hepatic flexure.

    Science.gov (United States)

    Uematsu, Dai; Akiyama, Gaku; Sugihara, Takehiko; Magishi, Akiko; Yamaguchi, Takuya; Sano, Takayuki

    2017-02-01

    Complete mesocolic excision is currently recognized as a standard procedure for colon cancer. Gastroepiploic, infrapyloric, and superficial pancreatic head lymph node metastases in the gastrocolic ligament have been reported for colon cancer close to the hepatic flexure. We sought to investigate metastases in the gastrocolic ligament in colon cancer close to the hepatic flexure. This was a single-center retrospective study. All patients with T2 or deeper invasive colon cancer in the relevant tumor location who underwent laparoscopic right hemicolectomy or extended right hemicolectomy at our institution between 1 April 2011 and 31 March 2015 were included. Lymph node dissection in the gastrocolic ligament was performed in 35 cases. Complications occurred in 11 patients (31%) and were grades I and II according to the Clavien-Dindo classification. Lymph node metastases in the gastrocolic ligament were found in only three patients (9%). Each metastasis was larger than 9 mm. Metastases in the gastrocolic ligament occurred in 9% of patients with T2 or deeper invasive colon cancer close to the hepatic flexure. Laparoscopy was feasible and useful during gastrocolic ligament resection. This study included a small sample and lacked an extended follow-up. Further studies are needed to determine the clinical relevance of this finding, particularly in terms of recurrence and long-term survival. © 2016 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

  13. Hepatic splenosis diagnosed after inappropriate metastatic evaluation in patient with low-risk prostate cancer.

    Science.gov (United States)

    Li, Hanhan; Snow-Lisy, Devon; Klein, Eric A

    2012-05-01

    A man interested in active surveillance of low-risk prostate cancer sought a second opinion after having undergone an inappropriate metastatic evaluation that demonstrated multiple enhancing liver masses. Because of his history of splenectomy for trauma, hepatic splenosis was suspected. Despite reassurance, the patient desired biopsy of the masses to confirm splenosis. The imaging features and pathophysiology of hepatic splenosis are presented. Owing to the low rates of metastatic disease, the current guidelines do not recommend diagnostic imaging for low-risk prostate cancer. The present case illustrates the dangers of the current widespread practice of inappropriate diagnostic imaging of patients with low-risk prostate cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. How do persistent infections with hepatitis C virus cause liver cancer?

    Science.gov (United States)

    Mitchell, Jonathan K; Lemon, Stanley M; McGivern, David R

    2015-10-01

    Persistent infection with hepatitis C virus (HCV) is associated with an increased risk of hepatocellular carcinoma (HCC). Cancer typically develops in a setting of chronic hepatic inflammation and advanced fibrosis or cirrhosis, and such tissue represents a pre-neoplastic 'cancer field'. However, not all persistent infections progress to HCC and a combination of viral and host immune factors likely contributes to carcinogenesis. HCV may disrupt cellular pathways involved in detecting and responding to DNA damage, potentially adding to the risk of cancer. Efforts to unravel how HCV promotes HCC are hindered by lack of a robust small animal model, but a better understanding of molecular mechanisms could identify novel biomarkers for early detection and allow for development of improved therapies. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Examples of Cancer Health Disparities

    Science.gov (United States)

    ... prevalence of infection with human papillomavirus (cervical cancer), hepatitis B virus (liver cancer), and the bacterium H. pylori (stomach cancer) in immigrant countries of origin contributes to these disparities. ( ACS ) Although Hispanics and ...

  16. Seroprevalence of Hepatitis C, Hepatitis B, Cytomegalovirus, and Human Immunodeficiency Viruses in Multitransfused Thalassemic Children in Upper Egypt

    Directory of Open Access Journals (Sweden)

    Ramadan A. Mahmoud

    2016-01-01

    Full Text Available Background. Frequent blood transfusions in thalassemia major children expose them to the risk of transfusion-transmitted infections (TTIs. The aim of this study was to estimate the prevalence of hepatitis C virus (HCV, hepatitis B virus (HBV, human immunodeficiency virus (HIV, and cytomegalovirus (CMV in thalassemic children attending the Pediatrics Departments of both Sohag and Minia Universities of Upper Egypt, during the period from May 2014 to May 2015. Methods. Serum samples were screened for hepatitis B surface antigen (HBsAg, anti-HCV, anti-CMV, and anti-HIV type 1 and type 2 using the Vitek Immunodiagnostic Assay System. Results. The frequencies of anti-HCV, HBsAg, anti-CMV, and anti-HIV type 1 and type 2 were found to be 37.11%, 4.12%, 4.12%, 0.00%, and 0.00%, respectively. Seropositivity for anti-HCV, HBsAg, and anti-CMV increased with increasing age of the patients, duration of the disease, serum ferritin level (ng/mL, and liver enzymes (U/L, while it was not significantly associated with gender, frequency of blood transfusion, or the status of splenectomy operation (P>0.05. Conclusion. The frequency of TTIs, especially HCV, is considerably high among Egyptian children with thalassemia major. It is therefore important to implement measures to improve blood transfusion screening, such as polymerase chain reaction, in order to reduce TTIs from blood donor units.

  17. Hepatitis C virus infection and risk of cancer: a population-based cohort study

    Directory of Open Access Journals (Sweden)

    Lars Haukali Omland

    2010-06-01

    Full Text Available Lars Haukali Omland1, Dora Körmendiné Farkas2, Peter Jepsen2,3, Niels Obel1, Lars Pedersen21Department of Infectious Diseases, Rigshospitalet, Denmark; 2Department of Clinical Epidemiology, 3Department of Medicine V (Hepatology and Gastroenterology, Aarhus University Hospital, DenmarkBackground: Hepatitis C virus (HCV infection is associated with an increased risk of primary liver cancer; however, 5- and 10-year risk estimates are needed. The association of HCV with non-Hodgkin lymphoma (NHL is uncertain and the association with other cancers is unknown.Method: We conducted a nationwide, population-based cohort study of 4,349 HCV-infected patients in Denmark, computing standardized incidence ratios (SIR of cancer incidence in HCV infected patients compared with cancer incidence of the general population. We calculated 5-and 10-year risks of developing cancer, stratifying our analyses based on the presence of HIV coinfection and cirrhosis.Results: We recorded an increased risk of primary liver cancer (SIR: 76.63 [95% CI: 51.69–109.40], NHL (SIR: 1.89 [95% CI: 0.39–5.52], and several smoking- and alcohol-related cancers in HCV infected patients without HIV coinfection. HCV-infected patients without HIV coinfection had a 6.3% (95% CI: 4.6%–8.7% risk of developing cancer and 2.0% (95% CI: 1.1%–3.8% risk of developing primary liver cancer within 10 years.Conclusion: We confirmed the association of HCV infection with primary liver cancer and NHL. We also observed an association between HCV infection and alcohol- and smoking-related cancers.Keywords: hepatitis C virus, non-Hodgkin lymphoma, standardized incidence ratio, cancer

  18. Prevalence of human immunodeficiency virus — hepatitis B virus co ...

    African Journals Online (AJOL)

    virus (HIV) worldwide, with 2.6 million co-infected with the hepatitis B virus (HBV). HBV infection causes 650 000 deaths annually worldwide. Botswana has a high prevalence of HIV and a growing population of patients on highly active ...

  19. A genetically humanized mouse model for hepatitis C virus infection.

    NARCIS (Netherlands)

    Dorner, M.; Horwitz, J.A.; Robbins, J.B.; Barry, W.T.; Feng, Q.; Mu, K.; Jones, C.T.; Schoggins, J.W.; Catanese, M.T.; Burton, D.R.; Law, M.; Rice, C.M.; Ploss, A.

    2011-01-01

    Hepatitis C virus (HCV) remains a major medical problem. Antiviral treatment is only partially effective and a vaccine does not exist. Development of more effective therapies has been hampered by the lack of a suitable small animal model. Although xenotransplantation of immunodeficient mice with

  20. Human immunodeficiency virus, hepatitis B virus and syphilis ...

    African Journals Online (AJOL)

    HIV), hepatitis B virus (HBV) and syphilis infections among longdistance truck drivers has been well documented globally, such data are sparse from Africa, and there has been no such data from Ghana. This study carried out between the months ...

  1. Simultaneous detection of Hepatitis B virus and Hepatitis C virus in human plasma using Taq-man chemistry

    Directory of Open Access Journals (Sweden)

    Khaja M N

    2011-07-01

    Full Text Available Designing a rapid, reliable and sensitive assay, for detection of hepatitis B virus and Hepatitis C virus variants by real-time PCR, is challenging at best. A recent approach for quantifying the viral load using the sensitive fluorescence principle, was used in this study. A total of 350 samples were collected from outpatient unit, Center for Liver Research and Diagnostics (CLRD. Complete Human HBV DNA and HCV sequences were obtained from the National Centre for Biotechnology Information (NCBI; primers and probes were designed and synthesized from core, surface and x region of Hepatitis B and UTR region of HCV. Real-time based detection was done, using standard kit and in-house generated standards and RT-PCR protocols. A standard curve was generated by using the Smart Cycler II software and serial dilution 102 to 108 of cloned viral regions, the calibration curve was linear in a range from 102 to108 cp/ml for both HBV and HCV, with R2 value of 0.999 and 0.995. Out of 100 predetermined HCV negative samples, 02 samples were found positive with in-house developed RT-PCR assay, the positivity of this sample was confirmed by sequencing the amplified product. Low cost of this assay procedure and précised sample volume will permit the assay to be implemented for routine screening of Hepatitis B and C virus mono-infection and co-infection using Real Time PCR , Nucleic acid Chip technology and Fluorescent End Point detection systems. This assay is reproducible showing limited inter and intra assay variability. Our results correlated well with the standard kit for HBV and HCV virus monitor.

  2. Monograph: reassessment of human cancer risk of aldrin/dieldrin.

    Science.gov (United States)

    Stevenson, D E; Walborg, E F; North, D W; Sielken, R L; Ross, C E; Wright, A S; Xu, Y; Kamendulis, L M; Klaunig, J E

    1999-10-05

    In 1987, the US Environmental Protection Agency (EPA) classified aldrin and dieldrin as category B2 carcinogens, i.e. probable human carcinogens, based largely on the increase in liver tumors in mice fed either organochlorine insecticide. At that date, the relevant epidemiology was deemed inadequate to influence the cancer risk assessment. More time has now elapsed since early exposures of manufacturing workers to aldrin/dieldrin; therefore, updated epidemiological data possess more power to detect exposure-related differences in cancer risk and mortality. Also, recent experimental studies provide a plausible mode of action to explain the mouse specificity of dieldrin-induced hepatocarcinogenesis and call into question the relevance of this activity to human cancer risk. This monograph places this new information within the historic and current perspectives of human cancer risk assessment, including EPA's 1996 Proposed Guidelines for Carcinogen Risk Assessment. Updated epidemiological studies of manufacturing workers in which lifetime exposures to aldrin/dieldrin have been quantified do not indicate increased mortality or cancer risk. In fact, at the middle range of exposures, there is evidence of a decrease in both mortality from all causes and cancer. Recent experimental studies indicate that dieldrin-induced hepatocarcinogenesis in mice occurs through a nongenotoxic mode of action, in which the slow oxidative metabolism of dieldrin is accompanied by an increased production of reactive oxygen species, depletion of hepatic antioxidant defenses (particularly alpha-tocopherol), and peroxidation of liver lipids. Dieldrin-induced oxidative stress or its sequelae apparently result in modulation of gene expression that favors expansion of initiated mouse, but not rat, liver cells; thus, dieldrin acts as a nongenotoxic promoter/accelerator of background liver tumorigenesis in the mouse. Within the framework of EPA's Proposed Guidelines for Carcinogen Risk Assessment, it

  3. First-principle, structure-based prediction of hepatic metabolic clearance values in human.

    Science.gov (United States)

    Li, Haiyan; Sun, Jin; Sui, Xiaofan; Liu, Jianfang; Yan, Zhongtian; Liu, Xiaohong; Sun, Yinghua; He, Zhonggui

    2009-04-01

    The first-principle, quantitative structure-hepatic clearance relationship for 50 drugs was constructed based on selected molecular descriptors calculated by TSAR software. The R(2) of the predicted and observed hepatic clearance for the training set (n=36) and test set (n=13) were 0.85 and 0.73, respectively. The average fold error (AFE) of the in silico model was 1.28 (n=50). The prediction accuracy of in silico model was superior to in vitro hepatocytes' model in literature (n=50, AFE=2.55). It is attractive to predict human hepatic clearance based on molecular descriptors merely. The structure-based model can be used as an efficient tool in the rapid identification of hepatic clearance of new drug candidates in drug discovery.

  4. Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans

    DEFF Research Database (Denmark)

    Sundelin, Elias; Gormsen, Lars Christian; Jensen, Jonas Brorson

    2017-01-01

    Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding...... the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed noninvasive 11C-metformin positron emission tomography (PET)/computed tomography (CT) to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin...... was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates...

  5. Long-term survival after an aggressive surgical approach in patients with breast cancer hepatic metastases.

    Science.gov (United States)

    Vlastos, Georges; Smith, David L; Singletary, S Eva; Mirza, Nadeem Q; Tuttle, Todd M; Popat, Reena J; Curley, Steven A; Ellis, Lee M; Roh, Mark S; Vauthey, Jean-Nicolas

    2004-09-01

    Metastatic breast cancer is generally believed to be associated with a poor prognosis. Therapeutic advances over the past two decades, however, have resulted in improved outcomes for selected patients with limited metastatic disease. Between March 1991 and October 2002, 31 patients had hepatic resection for breast cancer metastases limited to the liver. Clinical and pathologic data were collected prospectively from breast and hepatobiliary databases. Median age of patients was 46 years (range, 31 to 70). Liver metastases were solitary in 20 patients and multiple in 11 patients. Median size of the largest liver metastasis was 2.9 cm (range, 1 to 8). Major liver resections (three or more segments resected) were performed in 14 patients, whereas minor resections (fewer than three segments resected) with or without radiofrequency ablation (RFA) were performed in 17 patients. No postoperative mortality occurred. Of the 31 patients, 27 (87%) received either preoperative or postoperative systemic therapy as treatment for metastatic disease. The median survival was 63 months; a single patient died within 12 months of hepatic resection. The overall 2- and 5-year survival rates were 86% and 61%, respectively, whereas the 2- and 5-year disease-free survival rates were 39% and 31%, respectively. No treatment- or patient-specific variables were found to correlate with survival rates. In selected patients with liver metastases from breast cancer, an aggressive surgical approach is associated with favorable long-term survival. Hepatic resection should be considered a component of multimodality treatment of breast cancer in these patients.

  6. Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors.

    Science.gov (United States)

    Rodrigues, Robim M; Sachinidis, Agapios; De Boe, Veerle; Rogiers, Vera; Vanhaecke, Tamara; De Kock, Joery

    2015-09-01

    Besides their role in the elucidation of pathogenic processes of medical and pharmacological nature, biomarkers can also be used to document specific toxicological events. Hepatic cells generated from human skin-derived precursors (hSKP-HPC) were previously shown to be a promising in vitro tool for the evaluation of drug-induced hepatotoxicity. In this study, their capacity to identify potential liver-specific biomarkers at the gene expression level was investigated with particular emphasis on acute liver failure (ALF). To this end, a set of potential ALF-specific biomarkers was established using clinically relevant liver samples obtained from patients suffering from hepatitis B-associated ALF. Subsequently, this data was compared to data obtained from primary human hepatocyte cultures and hSKP-HPC, both exposed to the ALF-inducing reference compound acetaminophen. It was found that both in vitro systems revealed a set of molecules that was previously identified in the ALF liver samples. Yet, only a limited number of molecules was common between both in vitro systems and the ALF liver samples. Each of the in vitro systems could be used independently to identify potential toxicity biomarkers related to ALF. It seems therefore more appropriate to combine primary human hepatocyte cultures with complementary in vitro models to efficiently screen out potential hepatotoxic compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. The role of hepatic ischemia-reperfusion injury and liver parenchymal quality on cancer recurrence.

    Science.gov (United States)

    Orci, Lorenzo A; Lacotte, Stéphanie; Oldani, Graziano; Morel, Philippe; Mentha, Gilles; Toso, Christian

    2014-09-01

    Hepatic ischemia/reperfusion (I/R) injury is a common clinical challenge. Despite accumulating evidence regarding its mechanisms and potential therapeutic approaches, hepatic I/R is still a leading cause of organ dysfunction, morbidity, and resource utilization, especially in those patients with underlying parenchymal abnormalities. In the oncological setting, there are growing concerns regarding the deleterious impact of I/R injury on the risk of post-surgical tumor recurrence. This review aims at giving the last updates regarding the role of hepatic I/R and liver parenchymal quality injury in the setting of oncological liver surgery, using a "bench-to-bedside" approach. Relevant medical literature was identified by searching PubMed and hand scanning of the reference lists of articles considered for inclusion. Numerous preclinical models have depicted the impact of I/R injury and hepatic parenchymal quality (steatosis, age) on increased cancer growth in the injured liver. Putative pathophysiological mechanisms linking I/R injury and liver cancer recurrence include an increased implantation of circulating cancer cells in the ischemic liver and the upregulation of proliferation and angiogenic factors following the ischemic insult. Although limited, there is growing clinical evidence that I/R injury and liver quality are associated with the risk of post-surgical cancer recurrence. In conclusion, on top of its harmful early impact on organ function, I/R injury is linked to increased tumor growth. Therapeutic strategies tackling I/R injury could not only improve post-surgical organ function, but also allow a reduction in the risk of cancer recurrence.

  8. Pharmacokinetics and safety of the anti-human cytomegalovirus drug letermovir in subjects with hepatic impairment.

    Science.gov (United States)

    Kropeit, Dirk; McCormick, David; Erb-Zohar, Katharina; Moiseev, Valentin S; Kobalava, Zhanna D; Stobernack, Hans-Peter; Zimmermann, Holger; Rübsamen-Schaeff, Helga

    2017-07-18

    Human cytomegalovirus constitutes a prevalent and serious threat to immunocompromised individuals and requires new treatments. Letermovir is a novel viral-terminase inhibitor that has demonstrated prophylactic/pre-emptive activity against human cytomegalovirus in Phase 2 and 3 transplant trials. As unchanged letermovir is primarily excreted via the liver by bile, this trial aimed to assess the effect of hepatic impairment on letermovir pharmacokinetics. Phase 1, open-label, parallel-group pharmacokinetic and safety comparison of multiple once-daily oral letermovir in female subjects with hepatic impairment and healthy matched controls. For 8 days, subjects with moderate hepatic impairment (n = 8) and their matched healthy controls (n = 9) received 60 mg letermovir/day and those with severe hepatic impairment (n = 8) and their matched healthy controls (n = 8) received 30 mg letermovir/day. Pharmacokinetic parameters were determined from blood samples. For subjects with moderate hepatic impairment, maximal observed concentration at steady state (Css,max ) and the area under the concentration vs. time curve over a dosing interval at steady state (AUCτ,ss ) for total letermovir were 1.37-fold (90% confidence interval: 0.87, 2.17) and 1.59-fold (0.98, 2.57) higher, respectively, than in healthy subjects. For subjects with severe hepatic impairment, Css,max and AUCτ,ss values of total letermovir were 2.34-fold (1.91, 2.88) and 3.82-fold (2.94, 4.97) higher, respectively, compared with healthy subjects. Moderate hepatic impairment increased exposure to letermovir letermovir exposure approximately 4-fold as compared with healthy subjects. Letermovir 60/30 mg/day was generally well-tolerated in subjects with hepatic impairment. © 2017 The British Pharmacological Society.

  9. Occurrence of human hepatitis E virus in Norway rats: A zoonotic potential with great public health implications

    OpenAIRE

    Nahed Hamed Ghoneim; Khaled Abdel-Aziz Abdel-Moein; Dalia Anwar Hamza; Naglaa Mohamed Hagag

    2016-01-01

    Objective: To investigate the occurrence of human hepatitis E virus genotype I among sheep and rats as well as seroprevalence of hepatitis E virus immunoglobulin G (IgG) antibodies among people live in rural settings. Methods: Fecal samples were collected from 43 Norway rats and 30 sheep. All fecal samples were examined for the presence of human hepatitis E virus genotype I through direct detection using RT-PCR. In addition, serum samples collected from 90 apparently healthy pe...

  10. Photoacoustic tomography of human hepatic malignancies using intraoperative indocyanine green fluorescence imaging.

    Directory of Open Access Journals (Sweden)

    Akinori Miyata

    Full Text Available Recently, fluorescence imaging following the preoperative intravenous injection of indocyanine green has been used in clinical settings to identify hepatic malignancies during surgery. The aim of this study was to evaluate the ability of photoacoustic tomography using indocyanine green as a contrast agent to produce representative fluorescence images of hepatic tumors by visualizing the spatial distribution of indocyanine green on ultrasonographic images. Indocyanine green (0.5 mg/kg, intravenous was preoperatively administered to 9 patients undergoing hepatectomy. Intraoperatively, photoacoustic tomography was performed on the surface of the resected hepatic specimens (n = 10 under excitation with an 800 nm pulse laser. In 4 hepatocellular carcinoma nodules, photoacoustic imaging identified indocyanine green accumulation in the cancerous tissue. In contrast, in one hepatocellular carcinoma nodule and five adenocarcinoma foci (one intrahepatic cholangiocarcinoma and 4 colorectal liver metastases, photoacoustic imaging delineated indocyanine green accumulation not in the cancerous tissue but rather in the peri-cancerous hepatic parenchyma. Although photoacoustic tomography enabled to visualize spatial distribution of ICG on ultrasonographic images, which was consistent with fluorescence images on cut surfaces of the resected specimens, photoacoustic signals of ICG-containing tissues decreased approximately by 40% even at 4 mm depth from liver surfaces. Photoacoustic tomography using indocyanine green also failed to identify any hepatocellular carcinoma nodules from the body surface of model mice with non-alcoholic steatohepatitis. In conclusion, photoacoustic tomography has a potential to enhance cancer detectability and differential diagnosis by ultrasonographic examinations and intraoperative fluorescence imaging through visualization of stasis of bile-excreting imaging agents in and/or around hepatic tumors. However, further technical

  11. Hepatic late adverse effects after antineoplastic treatment for childhood cancer

    NARCIS (Netherlands)

    Mulder, Renée L.; van Dalen, Elvira C.; van den Hof, Malon; Bresters, Dorine; Koot, Bart G. P.; Castellino, Sharon M.; Loke, Yoon; Leclercq, Edith; Post, Piet N.; Caron, Huib N.; Postma, Aleida; Kremer, Leontien C. M.

    2011-01-01

    Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer.

  12. Can the National Health Service Cancer Plan timeline be applied to colorectal hepatic metastases?

    LENUS (Irish Health Repository)

    Jones, Claire

    2012-02-01

    INTRODUCTION: The National Health Service (NHS) Cancer Plan guidelines recommend a maximum 2-week wait from referral to first appointment, and 2 months from referral to treatment for primary cancers. However, there are currently no guidelines available for metastatic disease. In the UK, nearly half of all colorectal cancer patients develop hepatic metastases. Timely, surgical resection offers the potential for cure. The aim of this study was to audit current practice for colorectal liver metastases in a regional hepatobiliary unit, and compare this to the NHS Cancer Plan standards for primary disease. PATIENTS AND METHODS: A retrospective review of the unit\\'s database was performed for all hepatic metastases referrals from January 2006 to December 2008. The dates of referral, first appointment, investigations and initiation of treatment, along with patient\\'s age and sex, were recorded on Microsoft Excel and analysed. Time was expressed as mean +\\/- SD in days. RESULTS: A total of 102 patients with hepatic metastases were identified. Five were excluded due to incomplete data. The average time from referral to first appointment was 10.6 +\\/- 9.4 days and the average time from referral to treatment was 38.5 +\\/- 28.6 days. Seventy-five (72.7%) had surgical intervention, of whom 37 also had chemotherapy. CONCLUSIONS: The data compare favourably to the NHS Cancer Plan guidelines for primary malignancy, demonstrating that a regional hepatobiliary unit is capable of delivering a service for colorectal liver metastases that adheres to the NHS Cancer Plan. Therefore, the NHS Cancer Plan can be applied to this cohort.

  13. Hepatic energy metabolism in human diabetes mellitus, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Koliaki, Chrysi; Roden, Michael

    2013-10-15

    Alterations of hepatic mitochondrial function have been observed in states of insulin resistance and non-alcoholic fatty liver disease (NAFLD). Patients with overt type 2 diabetes mellitus (T2DM) can exhibit reduction in hepatic adenosine triphosphate (ATP) synthesis and impaired repletion of their hepatic ATP stores upon ATP depletion by fructose. Obesity and NAFLD may also associate with impaired ATP recovery after ATP-depleting challenges and augmented oxidative stress in the liver. On the other hand, patients with obesity or NAFLD can present with upregulated hepatic anaplerotic and oxidative fluxes, including β-oxidation and tricarboxylic cycle activity. The present review focuses on the methods and data on hepatic energy metabolism in various states of human insulin resistance. We propose that the liver can adapt to increased lipid exposition by greater lipid storing and oxidative capacity, resulting in increased oxidative stress, which in turn could deteriorate hepatic mitochondrial function in chronic insulin resistance and NAFLD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Novel Radiolytic Rotenone Derivative, Rotenoisin B with Potent Anti-Carcinogenic Activity in Hepatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Srilatha Badaboina

    2015-07-01

    Full Text Available Rotenone, isolated from roots of derris plant, has been shown to possess various biological activities, which lead to attempting to develop a potent drug against several diseases. However, recent studies have demonstrated that rotenone has the potential to induce several adverse effects such as a neurodegenerative disease. Radiolytic transformation of the rotenone with gamma-irradiation created a new product, named rotenoisin B. The present work was designed to investigate the anticancer activity of rotenoisin B with low toxicity and its molecular mechanism in hepatic cancer cells compared to a parent compound, rotenone. Our results showed rotenoisin B inhibited hepatic cancer cells’ proliferation in a dose dependent manner and increased in apoptotic cells. Interestingly, rotenoisin B showed low toxic effects on normal cells compared to rotenone. Mitochondrial transmembrane potential has been decreased, which leads to cytochrome c release. Down regulation of anti-apoptotic Bcl-2 levels as well as the up regulation of proapoptotic Bax levels were observed. The cleaved PARP (poly ADP-ribose polymerase level increased as well. Moreover, phosphorylation of extracellular signal regulated kinase (ERK and p38 slightly up regulated and intracellular reactive oxygen species (ROS increased as well as cell cycle arrest predominantly at the G2/M phase observed. These results suggest that rotenoisin B might be a potent anticancer candidate similar to rotenone in hepatic cancer cells with low toxicity to normal cells even at high concentrations compared to rotenone.

  15. Human Cancer Models Initiative | Office of Cancer Genomics

    Science.gov (United States)

    The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer and other research.

  16. Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells.

    Science.gov (United States)

    Lo Re, Oriana; Panebianco, Concetta; Porto, Stefania; Cervi, Carlo; Rappa, Francesca; Di Biase, Stefano; Caraglia, Michele; Pazienza, Valerio; Vinciguerra, Manlio

    2018-02-01

    Hepatocellular carcinoma (HCC) has a poor outcome. Most HCCs develop in the context of liver fibrosis and cirrhosis caused by chronic inflammation. Short-term fasting approaches enhance the activity of chemotherapy in preclinical cancer models, other than HCC. Multi-tyrosine kinase inhibitor Sorafenib is the mainstay of treatment in HCC. However, its benefit is frequently short-lived. Whether fasting can alleviate liver fibrosis and whether combining fasting with Sorafenib is beneficial remains unknown. A 24 hr fasting (2% serum, 0.1% glucose)-induced changes on human hepatic stellate cells (HSC) LX-2 proliferation/viability/cell cycle were assessed by MTT and flow cytometry. Expression of lypolysaccharide (LPS)-induced activation markers (vimentin, αSMA) was evaluated by qPCR and immunoblotting. Liver fibrosis and inflammation were evaluated in a mouse model of steatohepatitis exposed to cycles of fasting, by histological and biochemical analyses. A 24 hr fasting-induced changes were also analyzed on the proliferation/viability/glucose uptake of human HCC cells exposed to Sorafenib. An expression panel of genes involved in survival, inflammation, and metabolism was examined by qPCR in HCC cells exposed to fasting and/or Sorafenib. Fasting decreased the proliferation and the activation of HSC. Repeated cycles of short term starvation were safe in mice but did not improve fibrosis. Fasting synergized with Sorafenib in hampering HCC cell growth and glucose uptake. Finally, fasting normalized the expression levels of genes which are commonly altered by Sorafenib in HCC cells. Fasting or fasting-mimicking diet diets should be evaluated in preclinical studies as a mean to potentiate the activity of Sorafenib in clinical use. © 2017 Wiley Periodicals, Inc.

  17. Telomerase activity in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, J.

    2000-10-01

    The overall goal of this collaborative project was to investigate the role in malignant cells of both chromosome telomeres, and telomerase, the enzyme that replicates telomeres. Telomeres are highly conserved nucleoprotein complexes located at the ends of eucaryotic chromosomes. Telomere length in somatic cells is reduced by 40--50 nucleotide pairs with every cell division due to incomplete replication of terminal DNA sequences and the absence of telomerase, the ribonucleoprotein that adds telomere DNA to chromosome ends. Although telomerase is active in cells with extended proliferative capacities, including more than 85% of tumors, work performed under this contract demonstrated that the telomeres of human cancer cells are shorter than those of paired normal cells, and that the length of the telomeres is characteristic of particular types of cancers. The extent of telomere shortening ostensibly is related to the number of cell divisions the tumor has undergone. It is believed that ongoing cell proliferation leads to the accumulation and fixation of new mutations in tumor cell lineages.Therefore, it is not unreasonable to assume that the degree of phenotypic variability is related to the proliferative history of the tumor, and therefore to telomere length, implying a correlation with prognosis. In some human tumors, short telomeres are also correlated with genomic instabilities, including interstitial chromosome translocation, loss of heterozygosity, and aneuoploidy. Moreover, unprotected chromosome ends are highly recombinogenic and telomere shortening in cultured human cells correlates with the formation of dicentric chromosomes, suggesting that critically short telomeres not only identify, but also predispose, cells to genomic instability, again implying a correlation with prognosis. Therefore, telomere length or content could be an important predictor of metastatic potential or responsiveness to various therapeutic modalities.

  18. Effects of intranasal insulin on hepatic fat accumulation and energy metabolism in humans.

    Science.gov (United States)

    Gancheva, Sofiya; Koliaki, Chrysi; Bierwagen, Alessandra; Nowotny, Peter; Heni, Martin; Fritsche, Andreas; Häring, Hans-Ulrich; Szendroedi, Julia; Roden, Michael

    2015-06-01

    Studies in rodents suggest that insulin controls hepatic glucose metabolism through brain-liver crosstalk, but human studies using intranasal insulin to mimic central insulin delivery have provided conflicting results. In this randomized controlled crossover trial, we investigated the effects of intranasal insulin on hepatic insulin sensitivity (HIS) and energy metabolism in 10 patients with type 2 diabetes and 10 lean healthy participants (CON). Endogenous glucose production was monitored with [6,6-(2)H2]glucose, hepatocellular lipids (HCLs), ATP, and inorganic phosphate concentrations with (1)H/(31)P magnetic resonance spectroscopy. Intranasal insulin transiently increased serum insulin levels followed by a gradual lowering of blood glucose in CON only. Fasting HIS index was not affected by intranasal insulin in CON and patients. HCLs decreased by 35% in CON only, whereas absolute hepatic ATP concentration increased by 18% after 3 h. A subgroup of CON received intravenous insulin to mimic the changes in serum insulin and blood glucose levels observed after intranasal insulin. This resulted in a 34% increase in HCLs without altering hepatic ATP concentrations. In conclusion, intranasal insulin does not affect HIS but rapidly improves hepatic energy metabolism in healthy humans, which is independent of peripheral insulinemia. These effects are blunted in patients with type 2 diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  19. Human papillomaviruses and skin cancer.

    Science.gov (United States)

    Smola, Sigrun

    2014-01-01

    Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 120 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood. The clinical relevance of genus beta-PV infection has clearly been demonstrated in patients suffering from epidermodysplasia verruciformis (EV), a rare inherited disease associated with ahigh rate of skin cancer. In the normal population genus beta-PV are suspected to have an etiologic role in skin carcinogenesis as well but this is still controversially discussed. Their oncogenic potency has been investigated in mouse models and in vitro. In 2009, the International Agency for Research on Cancer (IARC) classified the genus beta HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. This chapter will give an overview on the knowns and unknowns of infections with genus beta-PV and discuss their potential impact on skin carcinogenesis in the general population.

  20. Hepatitis B Virus and Human Immunodeficiency Virus co-infection in ...

    African Journals Online (AJOL)

    Hepatitis B Virus(HBV) and Human Immunodeficiency Virus(HIV) share similar properties such as modes of transmission. This study was therefore designed to find out the prevalence of HBV/HIV co-infection in Zawan village. Three hundred subjects were recruited into the study through simple random sampling method ...

  1. Interferon-alpha treatment rapidly clears Hepatitis e virus infection in humanized mice

    NARCIS (Netherlands)

    M.D.B. van de Garde (Martijn D.B.); S.D. Pas (Suzan); G.W. van Oord (Gertine); L. Gama (Lucio); Choi, Y. (Youkyung); R.A. de Man (Robert); P.A. Boonstra (André); T. Vanwolleghem (Thomas)

    2017-01-01

    textabstractAntiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-α (pegIFNα) against HEV infections in humanized mice and modelled

  2. Hepatitis C virus infection in the human immunodeficiency virus infected patient

    DEFF Research Database (Denmark)

    Clausen, Louise Nygaard; Lundbo, Lene Fogt; Benfield, Thomas

    2014-01-01

    Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and...

  3. Transcriptional Regulation of the Human Hepatic Lipase Gene: Relation to Glucose and Lipid Metabolism

    NARCIS (Netherlands)

    D. van Deursen (Diederik)

    2012-01-01

    textabstractHepatic Lipase (HL; EC 3.1.1.3) is an extracellular glycoprotein with phospholipase A1 and triacylglycerol hydrolase activity. The human HL protein is encoded by the LIPC gene on chromosome 15q21. Most of this protein is synthesized in the parenchymal cells of the liver and secreted into

  4. The role of human T cell lymphotrophic virus type 1, hepatitis B virus and hepatitis C virus coinfections in leprosy

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Lima Machado

    2012-12-01

    Full Text Available Leprosy spectrum and outcome is associated with the host immune response against Mycobacterium leprae. The role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. Leprosy remains endemic in several regions where human T cell lymphotrophic virus type 1 (HTLV-1, hepatitis B virus (HBV or hepatitis C virus (HCV are also endemic. We have evaluated the evidence for the possible role of these viruses in the clinical manifestations and outcomes of leprosy. HTLV-1, HBV and HCV are associated with leprosy in some regions and institutionalization is an important risk factor for these viral coinfections. Some studies show a higher prevalence of viral coinfection in lepromatous cases. Although HBV and HCV coinfection were associated with reversal reaction in one study, there is a lack of information about the consequences of viral coinfections in leprosy. It is not known whether clinical outcomes associated with leprosy, such as development of reactions or relapses could be attributed to a specific viral coinfection. Furthermore, whether the leprosy subtype may influence the progression of the viral coinfection is unknown. All of these important and intriguing questions await prospective studies to definitively establish the actual relationship between these entities.

  5. The role of human T cell lymphotrophic virus type 1, hepatitis B virus and hepatitis C virus coinfections in leprosy.

    Science.gov (United States)

    Machado, Paulo Roberto Lima; Johnson, Warren D; Glesby, Marshall J

    2012-12-01

    Leprosy spectrum and outcome is associated with the host immune response against Mycobacterium leprae. The role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. Leprosy remains endemic in several regions where human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV) are also endemic. We have evaluated the evidence for the possible role of these viruses in the clinical manifestations and outcomes of leprosy. HTLV-1, HBV and HCV are associated with leprosy in some regions and institutionalization is an important risk factor for these viral coinfections. Some studies show a higher prevalence of viral coinfection in lepromatous cases. Although HBV and HCV coinfection were associated with reversal reaction in one study, there is a lack of information about the consequences of viral coinfections in leprosy. It is not known whether clinical outcomes associated with leprosy, such as development of reactions or relapses could be attributed to a specific viral coinfection. Furthermore, whether the leprosy subtype may influence the progression of the viral coinfection is unknown. All of these important and intriguing questions await prospective studies to definitively establish the actual relationship between these entities.

  6. Hepatic late adverse effects after antineoplastic treatment for childhood cancer

    NARCIS (Netherlands)

    Mulder, Renee L.; van Dalen, Elvira C.; Van den Hof, Malon; Bresters, Dorine; Koot, Bart G. P.; Castellino, Sharon M.; Loke, Yoon; Leclercq, Edith; Post, Piet N.; Caron, Huib N.; Postma, Aleida; Kremer, Leontien C. M.

    2011-01-01

    Background Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood

  7. Mitophagy Controls the Activities of Tumor Suppressor p53 to Regulate Hepatic Cancer Stem Cells.

    Science.gov (United States)

    Liu, Kai; Lee, Jiyoung; Kim, Ja Yeon; Wang, Linya; Tian, Yongjun; Chan, Stephanie T; Cho, Cecilia; Machida, Keigo; Chen, Dexi; Ou, Jing-Hsiung James

    2017-10-19

    Autophagy is required for benign hepatic tumors to progress into malignant hepatocellular carcinoma. However, the mechanism is unclear. Here, we report that mitophagy, the selective removal of mitochondria by autophagy, positively regulates hepatic cancer stem cells (CSCs) by suppressing the tumor suppressor p53. When mitophagy is enhanced, p53 co-localizes with mitochondria and is removed by a mitophagy-dependent manner. However, when mitophagy is inhibited, p53 is phosphorylated at serine-392 by PINK1, a kinase associated with mitophagy, on mitochondria and translocated into the nucleus, where it binds to the NANOG promoter to prevent OCT4 and SOX2 transcription factors from activating the expression of NANOG, a transcription factor critical for maintaining the stemness and the self-renewal ability of CSCs, resulting in the reduction of hepatic CSC populations. These results demonstrate that mitophagy controls the activities of p53 to maintain hepatic CSCs and provide an explanation as to why autophagy is required to promote hepatocarcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders.

    Science.gov (United States)

    Viganò, Mauro; Serra, Giuseppe; Casella, Giovanni; Grossi, Glenda; Lampertico, Pietro

    2016-07-01

    Targeted therapies have gained popularity in the treatment of several oncologic and immune-mediated diseases. Immunosuppression caused by these drugs has been associated to reactivation of hepatitis B virus (HBV) in both hepatitis B surface antigen (HBsAg) positive patients (overt infection) and HBsAg negative/anti-hepatitis B core antigen (anti-HBc) positive carriers (resolved infection), leading to premature discontinuation of therapy and potentially fatal hepatitis. This review summarizes the evidence of HBV reactivation in patients with overt or resolved HBV infection undergoing targeted therapies for cancer or immune-mediated disorders, providing recommendations for the management of these patients. The risk of HBV reactivation relies on the immunosuppressive potency and duration of these therapies, the underlying disease and the virological patient's profile. However, HBV reactivation is preventable by screening for HBV markers in all patients scheduled to receive targeted therapies, assessing the virological profile and patient's clinical state, followed by appropriate antiviral treatment or prophylaxis in those patients at high risk of HBV reactivation. Close monitoring of HBV carriers at low risk of reactivation is warranted with the aim to start antiviral therapy as soon as HBV reactivates.

  9. Optical diagnostic of hepatitis B (HBV) and C (HCV) from human blood serum using Raman spectroscopy

    Science.gov (United States)

    Anwar, Shahzad; Firdous, Shamaraz

    2015-06-01

    Hepatitis is the second most common disease worldwide with half of the cases arising in the developing world. The mortality associated with hepatitis B and C can be reduced if the disease is detected at the early stages of development. The aim of this study was to investigate the potential of Raman spectroscopy as a diagnostic tool to detect biochemical changes accompanying hepatitis progression. Raman spectra were acquired from 20 individuals with six hepatitis B infected patients, six hepatitis C infected patients and eight healthy patients in order to gain an insight into the determination of biochemical changes for early diagnostic. The human blood serum was examined at a 532 nm excitation laser source. Raman characteristic peaks were observed in normal sera at 1006, 1157 and 1513 cm-1, while in the case of hepatitis B and C these peaks were found to be blue shifted with decreased intensity. New Raman peaks appeared in HBV and HCV infected sera at 1194, 1302, 844, 905, 1065 and 1303 cm-1 respectively. A Mat lab subroutine and frequency domain filter program is developed and applied to signal processing of Raman scattering data. The algorithms have been successfully applied to remove the signal noise found in experimental scattering signals. The results show that Raman spectroscopy displays a high sensitivity to biochemical changes in blood sera during disease progression resulting in exceptional prediction accuracy when discriminating between normal and malignant. Raman spectroscopy shows enormous clinical potential as a rapid non-invasive diagnostic tool for hepatitis and other infectious diseases.

  10. Optimization of human cancer radiotherapy

    CERN Document Server

    Swan, George W

    1981-01-01

    The mathematical models in this book are concerned with a variety of approaches to the manner in which the clinical radiologic treatment of human neoplasms can be improved. These improvements comprise ways of delivering radiation to the malignan­ cies so as to create considerable damage to tumor cells while sparing neighboring normal tissues. There is no unique way of dealing with these improvements. Accord­ ingly, in this book a number of different presentations are given. Each presentation has as its goal some aspect of the improvement, or optimization, of radiotherapy. This book is a collection of current ideas concerned with the optimization of human cancer radiotherapy. It is hoped that readers will build on this collection and develop superior approaches for the understanding of the ways to improve therapy. The author owes a special debt of thanks to Kathy Prindle who breezed through the typing of this book with considerable dexterity. TABLE OF CONTENTS Chapter GENERAL INTRODUCTION 1. 1 Introduction 1...

  11. Human tumor-associated viruses and new insights into the molecular mechanisms of cancer.

    Science.gov (United States)

    Martin, D; Gutkind, J S

    2008-12-01

    The study of acute-transforming retroviruses and their oncogenes and of the multiple mechanisms deployed by DNA viruses to circumvent the growth-suppressive and proapoptotic function of tumor suppressor genes has provided the foundation of our current understanding of cancer biology. Unlike acute-transforming animal viruses, however, human tumor-associated viruses lead to malignancies with a prolonged latency and in conjunction with other environmental and host-related cooperating events. The relevance of viral infection to human cancer development has often been debated. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), human T-cell lymphotropic virus (HTLV-1) and Kaposi's associated sarcoma virus (KSHV) contribute to 10-15% of the cancers worldwide. Hence, the opportunity exists to fight cancer at the global scale by preventing the spread of these viruses, by the development and distribution of effective and safe antiviral vaccines, and by identifying their oncogenic mechanism. Here, we discuss the molecular events underlying the neoplastic potential of the human tumor-associated viruses, with emphasis on the enigmatic KSHV and its numerous virally hijacked proangiogenic, immune-evasive and tumor-promoting genes. The emerging information may facilitate the development of new molecular-targeted approaches to prevent and treat virally associated human malignancies.

  12. Evaluation of melphalan, oxaliplatin, and paclitaxel in colon, liver, and gastric cancer cell lines in a short-term exposure model of chemosaturation therapy by percutaneous hepatic perfusion.

    Science.gov (United States)

    Uzgare, Rajneesh P; Sheets, Timothy P; Johnston, Daniel S

    2013-05-01

    The goal of this study was to determine whether liver, gastric, or colonic cancer may be suitable targets for chemosaturation therapy with percutaneous hepatic perfusion (CS-PHP) and to assess the feasibility of utilizing other cytotoxic agents besides melphalan in the CS-PHP system. Forty human cell lines were screened against three cytotoxic chemotherapeutic agents. Specifically, the dose-dependent effect of melphalan, oxaliplatin, and paclitaxel on proliferation and apoptosis in each cell line was evaluated. These agents were also evaluated for their ability to induce apoptosis in normal primary human hepatocytes. A high-dose short-term drug exposure protocol was employed to simulate conditions encountered during CS-PHP. The average concentration of melphalan required for inducing significant apoptosis was 61 μM, or about 3-fold less than the theoretical concentration of 192 μM, achieved in the hepatic artery during CS-PHP dosing with melphalan. Additionally, we found that gastric cancer cell lines were 2-5 fold more sensitive to apoptosis than liver cancer cell lines to all three compounds, suggesting that in addition to colonic and gastric cancer metastases to the liver, primary gastric cancer may also be amenable to management by CS-PHP using an appropriate therapeutic agent. Significantly, at concentrations that are predicted using the CS-PHP system, these agents caused apoptosis of colonic, gastric, and liver cancer cells but were not toxic to primary human hepatocytes. The compounds tested are potential candidates for use in the CS-PHP system to treat patients with gastric and colonic metastases, and primary cancer of the liver.

  13. Hepatitis B virus exposure in human immunodeficiency virus seropositive Cuban patients

    Directory of Open Access Journals (Sweden)

    Licel Rodríguez

    2000-04-01

    Full Text Available In order to estimate the prevalence of serological markers of exposure to Hepatitis B Virus (HBV, 295 subjects were selected at random from the National Registry of human immunodeficiency virus positive subjects. Evidence of exposure to HBV was defined as: testing Hepatitis B surface antigen (HBsAg and anti-Hepatitis B core antigen (anti-HBc positive or anti-HBc positive only. Overall, 133 (45.5% were positive for anti-HBc and 15 (5.1% resulted positive to HBsAg. Significant statistical association was found between male sex and exposure to HBV (p<0.01. Homosexual or bisexual behavior was found to be strongly associated to HBV exposure (p<0.001. In conclusion, the prevalence of HBV serological markers is higher in Cuban HIV positive subjects compared to the Cuban general population.

  14. Peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Gluud, Lise Lotte; Marchesini, Emanuela; Iorio, Alfonso

    2009-01-01

    OBJECTIVES: The aim of this study was to assess the effects of peginterferon plus ribavirin for chronic hepatitis C in patients with human immunodeficiency virus (HIV). METHODS: Trials were identified through manual and electronic searches. Randomized trials comparing peginterferon plus ribavirin...... with other antiviral treatments for patients with chronic hepatitis C and HIV were included. The primary outcome measure was virological response at the end of treatment and after > or =6 months (sustained). Intention-to-treat meta-analyses including data on all patients who were randomized were carried out....... RESULTS: Seven randomized trials were eligible for inclusion. The patients included had chronic hepatitis C and stable HIV and were not previously treated with interferon or ribavirin (treatment naive). The mean dosages were 180 or 1.5 microg/kg once weekly for peginterferon and 800 mg daily for ribavirin...

  15. 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.

  16. Measurement of hepatic insulin sensitivity early after the bypass of the proximal small bowel in humans.

    Science.gov (United States)

    Miras, A D; Herring, R; Vusirikala, A; Shojaee-Moradi, F; Jackson, N C; Chandaria, S; Jackson, S N; Goldstone, A P; Hakim, N; Patel, A G; Umpleby, A M; Le Roux, C W

    2017-03-01

    Unlike gastric banding or sleeve gastrectomy procedures, intestinal bypass procedures, Roux-en-Y gastric bypass in particular, lead to rapid improvements in glycaemia early after surgery. The bypass of the proximal small bowel may have weight loss and even caloric restriction-independent glucose-lowering properties on hepatic insulin sensitivity. In this first human mechanistic study, we examined this hypothesis by investigating the early effects of the duodeno-jejunal bypass liner (DJBL; GI Dynamics, USA) on the hepatic insulin sensitivity by using the gold standard euglycaemic hyperinsulinaemic clamp methodology. Seven patients with obesity underwent measurement of hepatic insulin sensitivity at baseline, 1 week after a low-calorie liquid diet and after a further 1 week following insertion of the DJBL whilst on the same diet. Duodeno-jejunal bypass liner did not improve the insulin sensitivity of hepatic glucose production beyond the improvements achieved with caloric restriction. Caloric restriction may be the predominant driver of early increases in hepatic insulin sensitivity after the endoscopic bypass of the proximal small bowel. The same mechanism may be at play after Roux-en-Y gastric bypass and explain, at least in part, the rapid improvements in glycaemia.

  17. GFP Labeling and Hepatic Differentiation Potential of Human Placenta-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Yu, Jiong; Su, Xiaoru; Zhu, Chengxing; Pan, Qiaoling; Yang, Jinfeng; Ma, Jing; Shen, Leyao; Cao, Hongcui; Li, Lanjuan

    2015-01-01

    Stem cell-based therapy in liver diseases has received increasing interest over the past decade, but direct evidence of the homing and implantation of transplanted cells is conflicting. Reliable labeling and tracking techniques are essential but lacking. The purpose of this study was to establish human placenta-derived mesenchymal stem cells (hPMSCs) expressing green fluorescent protein (GFP) and to assay their hepatic functional differentiation in vitro. The GFP gene was transduced into hPMSCs using a lentivirus to establish GFP(+) hPMSCs. GFP(+) hPMSCs were analyzed for their phenotypic profile, viability and adipogenic, osteogenic and hepatic differentiation. The derived GFP(+) hepatocyte-like cells were evaluated for their metabolic, synthetic and secretory functions, respectively. GFP(+) hPMSCs expressed high levels of HLA I, CD13, CD105, CD73, CD90, CD44 and CD29, but were negative for HLA II, CD45, CD31, CD34, CD133, CD271 and CD79. They possessed adipogenic, osteogenic and hepatic differentiation potential. Hepatocyte-like cells derived from GFP(+) hPMSCs showed typical hepatic phenotypes. GFP gene transduction has no adverse influences on the cellular or biochemical properties of hPMSCs or markers. GFP gene transduction using lentiviral vectors is a reliable labeling and tracking method. GFP(+) hPMSCs can therefore serve as a tool to investigate the mechanisms of MSC-based therapy, including hepatic disease therapy. © 2015 S. Karger AG, Basel.

  18. Engraftment Potential of Spheroid-Forming Hepatic Endoderm Derived from Human Embryonic Stem Cells

    Science.gov (United States)

    Kim, Sung-Eun; An, Su Yeon; Woo, Dong-Hun; Han, Jiyou; Kim, Jong Hyun; Jang, Yu Jin; Son, Jeong Sang; Yang, Hyunwon; Cheon, Yong Pil

    2013-01-01

    Transplantation and drug discovery programs for liver diseases are hampered by the shortage of donor tissue. While recent studies have shown that hepatic cells can be derived from human embryonic stem cells (hESCs), few cases have shown selective enrichment of hESC-derived hepatocytes and their integration into host liver tissues. Here we demonstrate that the dissociation and reaggregation procedure after an endodermal differentiation of hESC produces spheroids mainly consisted of cells showing hepatic phenotypes in vitro and in vivo. A combined treatment with Wnt3a and bone morphogenic protein 4 efficiently differentiated hESCs into definitive endoderm in an adherent culture. Dissociation followed by reaggregation of these cells in a nonadherent condition lead to the isolation of spheroid-forming cells that preferentially expressed early hepatic markers from the adherent cell population. Further differentiation of these spheroid cells in the presence of the hepatocyte growth factor, oncostatin M, and dexamethasone produced a highly enriched population of cells exhibiting characteristics of early hepatocytes, including glycogen storage, indocyanine green uptake, and synthesis of urea and albumin. Furthermore, we show that grafted spheroid cells express hepatic features and attenuate the serum aspartate aminotransferase level in a model of acute liver injury. These data suggest that hepatic progenitor cells can be enriched by the spheroid formation of differentiating hESCs and that these cells have engraftment potential to replace damaged liver tissues. PMID:23373441

  19. Testosterone prevents protein loss via the hepatic urea cycle in human.

    Science.gov (United States)

    Lam, Teresa; Poljak, Anne; McLean, Mark; Bahl, Neha; Ho, Ken K Y; Birzniece, Vita

    2017-04-01

    The urea cycle is a rate-limiting step for amino acid nitrogen elimination. The rate of urea synthesis is a true indicator of whole-body protein catabolism. Testosterone reduces protein and nitrogen loss. The effect of testosterone on hepatic urea synthesis in humans has not been studied. To determine whether testosterone reduces hepatic urea production. An open-label study. Eight hypogonadal men were studied at baseline, and after two weeks of transdermal testosterone replacement (Testogel, 100 mg/day). The rate of hepatic urea synthesis was measured by the urea turnover technique using stable isotope methodology, with 15 N 2 -urea as tracer. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, were calculated. Testosterone administration significantly reduced the rate of hepatic urea production (from 544.4 ± 71.8 to 431.7 ± 68.3 µmol/min; P  Testosterone treatment significantly reduced net protein loss, as measured by percent Lox/LRa, by 19.3 ± 5.8% ( P  testosterone administration ( r 2  = 0.59, P  Testosterone replacement reduces protein loss and hepatic urea synthesis. We conclude that testosterone regulates whole-body protein metabolism by suppressing the urea cycle. © 2017 European Society of Endocrinology.

  20. Seroprevalence of hepatitis B virus and human immunodeficiency virus among young prisoners

    Directory of Open Access Journals (Sweden)

    Mehdi Ataie

    2013-01-01

    Full Text Available Background: Juveniles in custody are affected by sexually transmitted infections due to risky behaviors. Therefore, they have a disproportionate burden of hepatitis B virus (HBV and human immunodeficiency virus (HIV. In this study, the prevalence and associated characteristics of hepatitis B and HIV infections were assessed in young prisoners. Materials and Methods: In this cross-sectional study, prevalence of HBV and HIV infections was assessed among young prisoners during 2008-2009. A checklist consisting of demographic, social, and risk factors was filled out and blood was drawn for their tests. Sera were analyzed for hepatitis B surface antigen (HBs Ag, hepatitis B surface antibody (HBs Ab, hepatitis B core antibody (HBc Ab and HIV Ab, and Western blot test was performed on antibody-positive HIV. Results: A total number of 160 young prisoners (147 boys and 13 girls were evaluated. The mean age of the subjects was 16.59 ± 1.24 year. HBs Ag, HBc Ab, HBs Ab, and HIV Ab were detected in 1 (0.63%, 1 (0.63%, 52 (32.5%, and 1 (0.63%, respectively. Conclusion: With respect to national vaccination program against HBV infection, the juvenile prisoners had low prevalence of HBs Ab.

  1. Prevalence of Human Papillomavirus in endometrial cancer

    DEFF Research Database (Denmark)

    Olesen, Tina Bech; Svahn, Malene Frøsig; Faber, Mette Tuxen

    2014-01-01

    HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.......HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer....

  2. Hepatitis B or Hepatitis C Virus Infection Is a Risk Factor for Severe Hepatic Cytolysis after Initiation of a Protease Inhibitor-Containing Antiretroviral Regimen in Human Immunodeficiency Virus-Infected Patients

    Science.gov (United States)

    Savès, Marianne; Raffi, François; Clevenbergh, Philippe; Marchou, Bruno; Waldner-Combernoux, Anne; Morlat, Philippe; Le Moing, Vincent; Rivière, Catherine; Chêne, Geneviève; Leport, Catherine

    2000-01-01

    In a cohort of 1,047 human immunodeficiency virus type 1-infected patients started on protease inhibitors (PIs), the incidence of severe hepatic cytolysis (alanine aminotransferase concentration five times or more above the upper limit of the normal level ≥ 5N) was 5% patient-years after a mean follow-up of 5 months. Only positivity for hepatitis C virus antibodies (hazard ratio [HR], 7.95; P < 10−3) or hepatitis B virus surface antigen (HR, 6.67; P < 10−3) was associated with severe cytolysis. Before starting patients on PIs, assessment of liver enzyme levels and viral coinfections is necessary. PMID:11083658

  3. Outcomes of resection for colorectal cancer hepatic metastases stratified by evolving eras of treatment

    Directory of Open Access Journals (Sweden)

    Chan Kun-Ming

    2011-12-01

    Full Text Available Abstract Background and purpose The outcomes and management of colorectal cancer (CRC hepatic metastasis have undergone many evolutionary changes. In this study, we aimed to analyze the outcomes of patients with CRC hepatic metastasis in terms of the era of treatment. Methods We conducted a retrospective review of 279 patients who underwent liver resection (LR for CRC hepatic metastases. The prognoses of patients treated pre-2003 (era 1 and post-2003 (era 2 were examined. Results Of the patients included in the study, 210 (75.3% had CRC recurrence after LR. There was a significant difference in the ratio of CRC recurrence between the 2 eras (82.0% in era 1 vs. 69.5% in era 2; p = 0.008. Analysis of recurrence-free and overall survival rates also showed that the patient outcome was significantly better in the post-2003 era than in the pre-2003 era. Further analysis showed that a significantly higher percentage of patients in era 2 had received modern chemotherapeutic regimens including irinotecan and oxaliplatin, while patients in era 1 were mainly administered fluorouracil and leucovorin for adjuvant chemotherapy. Among patients with CRC recurrence, a significant ratio of those in era 2 underwent surgical resection for recurrent lesions, and these patients had a better survival curve than did patients without resection (34.1% vs. 2.2% for 5-year survival; p Conclusion The incidence of CRC recurrence after LR for hepatic metastasis remains very high. However, the management and outcomes of patients with CRC hepatic metastasis have greatly improved with time, suggesting that the current use of aggressive multimodality treatments including surgical resection combined with modern chemotherapeutic regimens effectively prolongs the life expectancy of these patients.

  4. Cyclooxygenase-2 -765 G/C polymorphisms and susceptibility to hepatitis B-related liver cancer in Han Chinese population.

    Science.gov (United States)

    He, Jianhong; Zhang, Quanbao; Ren, Zhijian; Li, Yumin; Li, Xun; Zhou, Wence; Zhang, Hui; Meng, Wenbo; Yan, Jun; He, Wenting

    2012-04-01

    To investigate the relationship of cyclooxygenase-2 (COX-2) polymorphisms [COX-2 -765 G/C (rs 20417)] and susceptibility to hepatitis B-related liver cancer in Han Chinese population. The polymorphisms of COX-2 -765 G/C was detected by polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in 300 patients with hepatitis B, 300 patients with cirrhosis, 300 patients with primary liver carcinoma and 300 health controls. The COX-2 -765 G/C genotypes were GG, GC and CC. There frequencies in the hepatitis B patients were 80.33, 17.67 and 2.00%; in the cirrhosis patients were 77.67, 18.00 and 4.33%; in the patients with primary liver carcinoma were 65.67, 28.33 and 6.00% and in the heathy controls were 87.00, 12.33 and 0.67%, respectively, COX-2 -765 C allele carriers had an increased risk of hepatitis B-related liver cancer. COX-2 -765 C allele carriers having drinking history or family history of liver cancer had higher risk for HCC. COX-2 -765 C allele genotype, drinking history and family history of liver cancer may increase the susceptibility to hepatitis B-related liver cancer in Gansu province, China.

  5. Hepatic-intestinal disposal of endogenous human alpha atrial natriuretic factor99-126 in patients with cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Bendtsen, Flemming; Schütten, H J

    1990-01-01

    Hepatic-intestinal disposal of endogenous human alpha atrial natriuretic factor99-126 (ANF) was assessed in 13 patients with cirrhosis (six Child-Turcotte class A, five class B, and two class C) and eight control subjects. The Fick principle was applied during hepatic vein catheterization. Arterial...

  6. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  7. [Seroconversion in response to a reinforced primary hepatitis B vaccination in children with cancer].

    Science.gov (United States)

    Villena, Rodolfo; Zubieta, Marcela; Hurtado, Carmen; Salgado, Carmen; Silva, Gladys; Fernández, Jazmine; Villarroel, Milena; Fernández, Marisol; Brahm, Javier; O'Ryan, Miguel; Santolaya, María Elena

    2015-01-01

    Immune response against vaccine antigens may be impaired in children with cancer. The aim of this study was to evaluate the seroconversion response against hepatitis B vaccination (HBV) at the time of chemotherapy onset and/or remission in children with cancer. Prospective, two-centre, controlled, non-randomised study conducted on children recently diagnosed with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6 months with DNA recombinant HBV at a dose of 20 and 40 μg if than 10 years of age, respectively, at the time of diagnosis for solids tumours and after the remission in case of haematological tumours. Controls received the same schedule, but at of 10 and 20 μg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as > 10 mIU/ml at 8th month of follow up. A total of 78 children with cancer and 25 healthy controls were analysed at month 8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no differences by age, gender or type of tumour (P = .13, .29, and .44, respectively). Control group seroconversion was 100% at the 8th month, with P 10 mIU/ml. Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an increased concentration, administrated at the time of onset of chemotherapy and/or remission provided an insufficient immune response in a majority of children with cancer. More immunogenic vaccines should be evaluated in this special population, such as a third generation, with more immunogenic adjuvants, enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8 and 12h to evaluate the need for further booster doses. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Hepatic stellate cells promote upregulation of epithelial cell adhesion molecule and epithelial-mesenchymal transition in hepatic cancer cells.

    Science.gov (United States)

    Nagahara, Teruya; Shiraha, Hidenori; Sawahara, Hiroaki; Uchida, Daisuke; Takeuchi, Yasuto; Iwamuro, Masaya; Kataoka, Junro; Horiguchi, Shigeru; Kuwaki, Takeshi; Onishi, Hideki; Nakamura, Shinichiro; Takaki, Akinobu; Nouso, Kazuhiro; Yamamoto, Kazuhide

    2015-09-01

    promote upregulation of EpCAM and EMT in hepatic cancer cells.

  9. Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans.

    Science.gov (United States)

    Sundelin, Eio; Gormsen, L C; Jensen, J B; Vendelbo, M H; Jakobsen, S; Munk, O L; Christensen, Mmh; Brøsen, K; Frøkiaer, J; Jessen, N

    2017-11-01

    Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed noninvasive 11 C-metformin positron emission tomography (PET)/computed tomography (CT) to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates the application of novel imaging techniques to investigate pharmacogenetic properties in humans. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  10. Adult liver stem cells in hepatic regeneration and cancer

    NARCIS (Netherlands)

    Nantasanti, Sathidpak

    2015-01-01

    An alternative source of livers for transplantation in patients with (genetic) liver diseases and liver failure is needed because liver donors are scarce. HPC-derived hepatocyte-like cells could be one of the options. Because dogs and humans share liver-pathologies and disease-pathways, the dog is

  11. Effect of recombinant human growth hormone and interferon gamma on hepatic collagen synthesis and proliferation of hepatic stellate cells in cirrhotic rats.

    Science.gov (United States)

    Chen, Yong-Hua; Du, Bing-Qing; Zheng, Zhen-Jiang; Xiang, Guang-Ming; Liu, Xu-Bao; Mai, Gang

    2012-06-01

    Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10(-3)-10(-1) mg/100 μL), and interferon gamma (10(-2)-10(-1) μg/100 μL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10(-1) μg/100 μL, P0.05) and a time-dependent manner (Pgrowth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.

  12. The value of gadoxetic acid-enhanced MRI for differentiation between hepatic microabscesses and metastases in patients with periampullary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo-Youn [Soonchunhyang University College of Medicine, Bucheon Hospital, Department of Radiology, Bucheon (Korea, Republic of); Kim, Young Kon; Cha, Dong Ik; Jeong, Woo Kyoung; Lee, Won Jae [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Min, Ji Hye [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Chungnam National University Hospital, Chungnam National University College of Medicine, Department of Radiology, Daejeon (Korea, Republic of)

    2017-10-15

    We aimed to identify features that differentiate hepatic microabscess from hepatic metastasis on gadoxetic acid-enhanced MRI in patients with periampullary cancer. We included 72 patients (31 patients with 83 hepatic microabscesses and 41 patients with 71 hepatic metastases) who had a history of periampullary cancer and underwent gadoxetic acid-enhanced MRI. Image analysis was performed for margin, signal intensity, rim enhancement, perilesional hyperaemia, pattern on DWI and dynamic phases, and size discrepancy between sequences by consensus of two observers. Multivariate analysis revealed that the following significant parameters favour microabscess: a history of bile duct cancer, perilesional hyperaemia, persistent arterial rim enhancement through the transitional phase (TP), and size discrepancy between T1WI and T2WI and between T1WI and hepatobiliary phase image (HBPI). The diagnostic accuracy for microabscess was highest (90.9%) when showing a size discrepancy ≥30% between T1WI and HBPI or persistent arterial rim enhancement through the TP. When the lesion was positive for both these variables, specificity reached 100%. The combination of a size discrepancy between T1WI and HBPI and persistent arterial rim enhancement through the TP represents a reliable MRI feature for distinguishing between hepatic microabscess and metastasis in patients with periampullary cancer. (orig.)

  13. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

    Torrente, Mariela C.; Rodrigo, Juan P.; Haigentz, Missak; Dikkers, Frederik G.; Rinaldo, Alessandra; Takes, Robert P.; Olofsson, Jan; Ferlito, Alfio

    Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we

  14. Prognostic factors in patients with hepatitis B-related primary liver cancer treated with transcatheter arterial chemoembolization

    Directory of Open Access Journals (Sweden)

    YIN Hao

    2014-01-01

    Full Text Available ObjectiveTo analyze the prognostic factors in patients with hepatitis B-related primary liver cancer treated with transcatheter arterial chemoembolization (TACE and to provide a basis for properly selecting indications and treatment regimen in clinical practice. MethodsA total of 140 patients with hepatitis B-related primary liver cancer, who underwent TACE in our hospital from January to December 2010, were enrolled in this study. Follow-up was continued until December 2011 to observe the patients′ survival within 12 months after treatment. The Kaplan-Meier method and log-rank (Mantel-Cox test were used for univariate and multivariate analyses to identify the prognostic factors in patients with hepatitis B-related primary liver cancer treated with TACE. ResultsThe univariate analysis showed that age, portal vein metastasis, peritoneal metastasis, pleural metastasis, Child-Pugh classification, bilirubin, alanine aminotransferase, number of interventional therapies, and antiviral therapy were prognostic factors in patients with hepatitis B-related primary liver cancer treated with TACE. There was significant difference in 12-month survival curve between patients treated with TACE plus antiviral therapy and those who did not receive antiviral therapy (P<0.05. The multivariate analysis showed that portal vein metastasis (P=0.004, peritoneal metastasis (P=0.009, bilirubin level (P=0.017, antiviral therapy (P=0.000, and number of TACE therapies (P=0.000 were prognostic factors in patients with hepatitis B-related primary liver cancer treated with TACE. ConclusionPortal vein metastasis, peritoneal metastasis, and bilirubin level may be independent risk factors in patients with hepatitis B-related primary liver cancer treated with TACE, and antiviral therapy and number of interventional therapies may be protective factors for these patients.

  15. Positive association between hepatitis C infection and oral cavity cancer: a nationwide population-based cohort study in Taiwan.

    Science.gov (United States)

    Su, Fu-Hsiung; Chang, Shih-Ni; Chen, Pei-Chun; Sung, Fung-Chang; Huang, Shiang-Fu; Chiou, Hung-Yi; Su, Chien-Tien; Lin, Cheng-Chieh; Yeh, Chih-Ching

    2012-01-01

    The association between viral hepatitis (B and C) and oral cavity cancer has been widely debated. This nationwide, population-based cohort study assessed the subsequent risk of oral cavity cancer among patients with chronic viral hepatitis infection. Data were retrieved from insurance claims data of 1,000,000 randomly sampled individuals covered under the Taiwan National Health Insurance system. We identified a total of 21,199 adults with chronic viral hepatitis infection (12,369 with HBV alone, 5,311 with HCV alone, and 3,519 with HBV/HCV dual infections) from 2000-2005. Comparison group comprised 84,796 sex- and age-matched subjects without viral hepatitis during the same study period. Incidence and risk of subsequent oral cavity cancer were measured until 2008. The incidence of oral cavity cancers was 2.28-fold higher among patients with HCV alone than non-viral hepatitis group (6.15 versus 2.69 per 10,000 person-years). After adjusting for sociodemographic covariates, HCV alone was significantly associated with an increased risk for oral cavity cancer (hazard ratio (HR) = 1.90, 95% confidence interval (CI) = 1.20-3.02). This positive association was highest among individuals in the 40-49-year age group (HR = 2.57, 95% CI = 1.21-5.46). However, there were no significant associations between HBV alone or HBV/HCV dual infections and risk for oral cavity cancer. Our data suggest that HCV but not HBV infection is a risk factor for oral cavity cancer. In addition, subjects with HCV infection tend to be at early onset risk for oral cavity cancer. This finding needs to be replicated in further studies.

  16. Gastrointestinal stromal tumor (GIST coexisting with pancreatic cancer and hepatic hemangioma

    Directory of Open Access Journals (Sweden)

    M. A. Beltrán

    2014-11-01

    Full Text Available The occurrence of gastric gastrointestinal stromal tumors (GIST associated to pancreatic adenocarcinoma has been reported in 0.2% pancreatic cancers. There are no published reports on distal pancreatic adenocarcinoma associated to gastric antral GIST. Herein, we discuss a 75 years-old female patient who was admitted to our institution with upper digestive hemorrhage. The endoscopy showed large, superficial erosions over the cardias and, on the posterior wall of the antrum, a rounded sub-mucosal non-eroded lesion suspected of gastric GIST. An abdominal computed tomography scan found a hepatic hemangioma on the left hepatic lobe. In the pancreatic distal body and tail a solid exophytic lesion was identified. The surgical findings confirmed the radiologic diagnostic. The biopsy reported a hepatic hemangioma. The pancreatic tail and the proximal part of the body harbored a well-differentiated ductal adenocarcinoma measuring 3.4 cm x 3 cm x 2.5 cm with negative margins. The gastric tumor measured 4 cm x 2.5 cm x 1 cm, was positive for CD117, CD34, and DOG-1; it had a positive Ki67 in less than 2%, and 2 or less mitoses per 50 high-power fields. This uncommon case illustrates the occurrence of synchronous tumors of different cellular origins in the same patient, which were diagnosed during the study for another unrelated condition. The individual incidence of these tumors is low and if associated they probably will continue to be found incidentally.

  17. Direct muscarinic cholinergic inhibition of hepatic glucose production in humans.

    OpenAIRE

    Boyle, P. J.; Liggett, S B; Shah, S D; Cryer, P E

    1988-01-01

    To explore the potential role of the parasympathetic nervous system in human glucoregulatory physiology, responses to the muscarinic cholinergic agonist bethanechol (5.0 mg s.c.) and antagonist atropine (1.0 mg i.v.) were measured in normal humans. There were no changes in the plasma glucose concentration or rates of glucose production or utilization following atropine administration. After bethanechol administration there were no changes in the plasma glucose concentration or fluxes despite ...

  18. Hepatitis B and C Viruses Infections and Their Association with Human Immunodeficiency Virus: A Cross-Sectional Study among Blood Donors in Ethiopia.

    Science.gov (United States)

    Yami, Alemeshet; Alemseged, Fissehaye; Hassen, Alima

    2011-03-01

    Since the introduction of Highly Active Anti-Retroviral Therapy and the dramatic improvement in the prognosis of individuals with Human Immunodeficiency Virus, liver disease due to chronic viral hepatitis has become as important cause of morbidity and mortality in co-infected individuals. The objective of the study was to determine the Sero-prevalence of Hepatitis B Virus, Hepatitis C Virus and Human Immunodeficiency Virus and the association of the virus with Hepatitis B Virus and Hepatitis C Virus infection. As Human Immunodeficiency Virus and Hepatitis B Virus infections are highly prevalent and they are among the major public health concern in developing countries including Ethiopia investigating this problem is of paramount benefit. Although studies on co-infection of Hepatitis C Virus and Human Immunodeficiency Virus have clearly identified adverse effects of co-infection, the prevalence of Hepatitis C Virus infection and the association with Human Immunodeficiency Virus in developing countries including Ethiopia has not been know for sure. A cross sectional study was conducted from January 1 to 31, 2010, in Jimma University specialized hospital Blood Bank. The inclusion criteria of the study was adult who donated blood to Jimma University specialized hospital blood bank any time from establishment of the unit until January 2010 and whose record was retrieved. Accordingly 9,204 adults were included of which 6,063 were selected by lottery method. Data on socio-demographic variables (age and sex), laboratory test result for Hepatitis B surface Antigen, anti-Hepatitis C Virus antibody, anti-Human Immunodeficiency Virus 1 antibody, and Rapid Plasma Reagin tests were collected using structured questionnaire. After the data were collected, they were entered into a computer and analyzed using SPSS -16 for windows. P-Value of Virus, Hepatitis C Virus, Human Immunodeficiency Virus and syphilis infection were 2.1%, 0.2%, 2.1% and 0.7%, respectively. Sex and age had

  19. Liver cancer-derived hepatitis C virus core proteins shift TGF-beta responses from tumor suppression to epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Serena Battaglia

    Full Text Available BACKGROUND: Chronic hepatitis C virus (HCV infection and associated liver cirrhosis represent a major risk factor for hepatocellular carcinoma (HCC development. TGF-beta is an important driver of liver fibrogenesis and cancer; however, its actual impact in human cancer progression is still poorly known. The aim of this study was to investigate the role of HCC-derived HCV core natural variants on cancer progression through their impact on TGF-beta signaling. PRINCIPAL FINDINGS: We provide evidence that HCC-derived core protein expression in primary human or mouse hepatocyte alleviates TGF-beta responses in terms or growth inhibition or apoptosis. Instead, in these hepatocytes TGF-beta was still able to induce an epithelial to mesenchymal transition (EMT, a process that contributes to the promotion of cell invasion and metastasis. Moreover, we demonstrate that different thresholds of Smad3 activation dictate the TGF-beta responses in hepatic cells and that HCV core protein, by decreasing Smad3 activation, may switch TGF-beta growth inhibitory effects to tumor promoting responses. CONCLUSION/SIGNIFICANCE: Our data illustrate the capacity of hepatocytes to develop EMT and plasticity under TGF-beta, emphasize the role of HCV core protein in the dynamic of these effects and provide evidence for a paradigm whereby a viral protein implicated in oncogenesis is capable to shift TGF-beta responses from cytostatic effects to EMT development.

  20. Inorganic Arsenic and Human Prostate Cancer

    Science.gov (United States)

    Benbrahim-Tallaa, Lamia; Waalkes, Michael P.

    2008-01-01

    Objective We critically evaluated the etiologic role of inorganic arsenic in human prostate cancer. Data sources We assessed data from relevant epidemiologic studies concerning environmental inorganic arsenic exposure. Whole animal studies were evaluated as were in vitro model systems of inorganic arsenic carcinogenesis in the prostate. Data synthesis Multiple studies in humans reveal an association between environmental inorganic arsenic exposure and prostate cancer mortality or incidence. Many of these human studies provide clear evidence of a dose–response relationship. Relevant whole animal models showing a relationship between inorganic arsenic and prostate cancer are not available. However, cellular model systems indicate arsenic can induce malignant transformation of human prostate epithelial cells in vitro. Arsenic also appears to impact prostate cancer cell progression by precipitating events leading to androgen independence in vitro. Conclusion Available evidence in human populations and human cells in vitro indicates that the prostate is a target for inorganic arsenic carcinogenesis. A role for this common environmental contaminant in human prostate cancer initiation and/or progression would be very important. PMID:18288312

  1. Fatty Acid Desaturase 1 (FADS1) Gene Polymorphisms Control Human Hepatic Lipid Composition

    Science.gov (United States)

    Wang, Libo; Athinarayanan, Shaminie; Jiang, Guanglong; Chalasani, Naga; Zhang, Min; Liu, Wanqing

    2014-01-01

    Fatty Acid Desaturase (FADS) genes and their variants have been associated with multiple metabolic phenotypes including liver enzymes and hepatic fat accumulation but the detailed mechanism remains unclear. We aimed to delineate the role of FADSs in modulating lipid composition in human liver. We performed a targeted lipidomic analysis of a variety of phospholipids, sphingolipids and ceramides among 154 human liver tissue samples. The associations between previously Genome-wide Association Studies (GWAS)-identified six FADS single nucleotide polymorphisms (SNPs) and these lipid levels as well as total hepatic fat content (HFC) were tested. The potential function of these SNPs in regulating transcription of 3 FADS genes (FADS1, FADS2 and FADS3) in the locus was also investigated. We found that while these SNPs were in high linkage disequilibrium (r2 >0.8), the rare alleles of these SNPs were consistently and significantly associated with the accumulation of multiple very-long-chain fatty acids (VLCFAs), with C47H85O13P (C36:4), a phosphatidylinositol (PI) and C43H80O8PN (C38:3), a phosphatidylethanolamine (PE) reached the Bonferroni corrected significance (pFADS1 (p=0.0018 for rs174556), but not FADS2 or FADS3 (p>0.05). Conclusion Our findings revealed critical insight into the mechanism underlying FADS1 and its polymorphisms in modulating hepatic lipid deposition by altering gene transcription and controlling lipid composition in human livers. PMID:25123259

  2. Discovery of a Novel Hepatovirus (Phopivirus of Seals) Related to Human Hepatitis A Virus.

    Science.gov (United States)

    Anthony, S J; St Leger, J A; Liang, E; Hicks, A L; Sanchez-Leon, M D; Jain, K; Lefkowitch, J H; Navarrete-Macias, I; Knowles, N; Goldstein, T; Pugliares, K; Ip, H S; Rowles, T; Lipkin, W I

    2015-08-25

    Describing the viral diversity of wildlife can provide interesting and useful insights into the natural history of established human pathogens. In this study, we describe a previously unknown picornavirus in harbor seals (tentatively named phopivirus) that is related to human hepatitis A virus (HAV). We show that phopivirus shares several genetic and phenotypic characteristics with HAV, including phylogenetic relatedness across the genome, a specific and seemingly quiescent tropism for hepatocytes, structural conservation in a key functional region of the type III internal ribosomal entry site (IRES), and a codon usage bias consistent with that of HAV. Hepatitis A virus (HAV) is an important viral hepatitis in humans because of the substantial number of cases each year in regions with low socioeconomic status. The origin of HAV is unknown, and no nonprimate HAV-like viruses have been described. Here, we describe the discovery of an HAV-like virus in seals. This finding suggests that the diversity and evolutionary history of these viruses might be far greater than previously thought and may provide insight into the origin and pathogenicity of HAV. Copyright © 2015 Anthony et al.

  3. Trends in the incidence of Hepatitis B, C and Human ...

    African Journals Online (AJOL)

    Background: There have been various claims of reduction in the prevalence of human immunodeficiency virus and other transfusion transmissible viruses in the general population following various interventions including public awareness campaigns, provision of facilities for voluntary counselling and testing, programmes ...

  4. Azadirachta indica exhibits chemopreventive action against hepatic cancer: Studies on associated histopathological and ultrastructural changes.

    Science.gov (United States)

    Bharati, Sanjay; Rishi, Praveen; Koul, Ashwani

    2012-05-01

    The present study was designed to evaluate the anticarcinogenic potential of Azadirachta indica against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. Further, the associated histopathological and ultrastructural changes were also analyzed. Hepatic cancer model was developed by the intraperitoneal administration of NDEA to mice at weekly intervals, in successive increasing doses, for a period of 8 weeks. Aqueous A. indica leaf extract (AAILE) was administered orally at a dosage of 100 μg/g body weight thrice a week till termination of the study. A relationship between histopathological grading and chemopreventive effect of A. indica had been established at various stages of carcinogenesis. Anticancer activity of A. indica was evaluated in terms of tumor incidence, tumor multiplicity, and survival rate. A significant reduction in tumor incidence (33%), tumor multiplicity (42%), and increase in survival (34%) was observed upon administration of AAILE to NDEA-abused mice. Transmission and scanning electron microscopic investigations showed severe alterations in organelle organization, cellular arrangement, degree of differentiation, cellular metabolism, and morphology of the hepatocytes. These changes appeared to be distinctly delayed upon AAILE supplementation. The results suggest A. indica may have anticancer potential against NDEA-induced hepatic cancer. Copyright © 2011 Wiley Periodicals, Inc.

  5. Long-term use of oral nucleos(t)ide analogues for chronic hepatitis B does not increase cancer risk - a cohort study of 44 494 subjects.

    Science.gov (United States)

    Wong, G L-H; Tse, Y-K; Yip, T C-F; Chan, H L-Y; Tsoi, K K-F; Wong, V W-S

    2017-05-01

    Patients with chronic hepatitis B (CHB) need long-term antiviral treatment with nucleos(t)ide analogues (NA). Animal studies suggest that some NA may increase cancer risk, but human data are lacking. To investigate cancer risks in patients with or without NA treatment. We conducted a territory-wide cohort study using the database from Hospital Authority in Hong Kong. The diagnosis of CHB and various malignancies was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes between 2000 and 2012. Patients exposed to any of the oral NA for CHB were included. The primary outcome was incident cancers. A 3-year landmark analysis, with follow-up up to 7 years, was used to evaluate the relative risk of cancers in treated and untreated patients. A total of 44 494 patients (39 712 untreated and 4782 treated) were included in the analysis. During 194 890 patient-years of follow-up, hepatocellular carcinoma developed in 402 (1.0%) untreated patients and 179 (3.7%) treated patients, while other cancers developed in 528 (1.3%) and 128 (2.7%) patients respectively. After propensity score weighting, treated patients had similar risks of all malignancies [weighted hazard ratio (wHR): 1.01, 95% CI: 0.82-1.25, P = 0.899], lung/pleural cancers (wHR: 0.82, 95% CI: 0.52-1.31, P = 0.409) and urinary/renal malignancies (wHR: 1.04, 95% CI: 0.38-2.81, P = 0.944) when compared with untreated patients. Oral nucleos(t)ide analogue treatment does not appear to increase cancer risk in patients with chronic hepatitis B. Given the beneficial effect on liver outcomes, our data support the current practice of long-term anti-viral therapy. © 2017 John Wiley & Sons Ltd.

  6. Relaxin modulates human and rat hepatic myofibroblast function and ameliorates portal hypertension in vivo.

    Science.gov (United States)

    Fallowfield, Jonathan A; Hayden, Annette L; Snowdon, Victoria K; Aucott, Rebecca L; Stutchfield, Ben M; Mole, Damian J; Pellicoro, Antonella; Gordon-Walker, Timothy T; Henke, Alexander; Schrader, Joerg; Trivedi, Palak J; Princivalle, Marc; Forbes, Stuart J; Collins, Jane E; Iredale, John P

    2014-04-01

    Active myofibroblast (MF) contraction contributes significantly to the increased intrahepatic vascular resistance that is the primary cause of portal hypertension (PHT) in cirrhosis. We sought proof of concept for direct therapeutic targeting of the dynamic component of PHT and markers of MF activation using short-term administration of the peptide hormone relaxin (RLN). We defined the portal hypotensive effect in rat models of sinusoidal PHT and the expression, activity, and function of the RLN-receptor signaling axis in human liver MFs. The effects of RLN were studied after 8 and 16 weeks carbon tetrachloride intoxication, following bile duct ligation, and in tissue culture models. Hemodynamic changes were analyzed by direct cannulation, perivascular flowprobe, indocyanine green imaging, and functional magnetic resonance imaging. Serum and hepatic nitric oxide (NO) levels were determined by immunoassay. Hepatic inflammation was assessed by histology and serum markers and fibrosis by collagen proportionate area. Gene expression was analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting and hepatic stellate cell (HSC)-MF contractility by gel contraction assay. Increased expression of RLN receptor (RXFP1) was shown in HSC-MFs and fibrotic liver diseases in both rats and humans. RLN induced a selective and significant reduction in portal pressure in pathologically distinct PHT models, through augmentation of intrahepatic NO signaling and a dramatic reduction in contractile filament expression in HSC-MFs. Critical for translation, RLN did not induce systemic hypotension even in advanced cirrhosis models. Portal blood flow and hepatic oxygenation were increased by RLN in early cirrhosis. Treatment of human HSC-MFs with RLN inhibited contractility and induced an antifibrogenic phenotype in an RXFP1-dependent manner. We identified RXFP1 as a potential new therapeutic target for PHT and MF activation status. Copyright

  7. Human papilloma virus in oral cancer

    Science.gov (United States)

    2016-01-01

    Cervical cancer is the second most prevalent cancer among women, and it arises from cells that originate in the cervix uteri. Among several causes of cervical malignancies, infection with some types of human papilloma virus (HPV) is well known to be the greatest cervical cancer risk factor. Over 150 subtypes of HPV have been identified; more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region and oral cavity. The recently introduced vaccine for HPV infection is effective against certain subtypes of HPV that are associated with cervical cancer, genital warts, and some less common cancers, including oropharyngeal cancer. Two HPV vaccines, quadrivalent and bivalent types that use virus-like particles (VLPs), are currently used in the medical commercial market. While the value of HPV vaccination for oral cancer prevention is still controversial, some evidence supports the possibility that HPV vaccination may be effective in reducing the incidence of oral cancer. This paper reviews HPV-related pathogenesis in cancer, covering HPV structure and classification, trends in worldwide applications of HPV vaccines, effectiveness and complications of HPV vaccination, and the relationship of HPV with oral cancer prevalence. PMID:28053902

  8. Modeling Human Cancers in Drosophila.

    Science.gov (United States)

    Sonoshita, M; Cagan, R L

    2017-01-01

    Cancer is a complex disease that affects multiple organs. Whole-body animal models provide important insights into oncology that can lead to clinical impact. Here, we review novel concepts that Drosophila studies have established for cancer biology, drug discovery, and patient therapy. Genetic studies using Drosophila have explored the roles of oncogenes and tumor-suppressor genes that when dysregulated promote cancer formation, making Drosophila a useful model to study multiple aspects of transformation. Not limited to mechanism analyses, Drosophila has recently been showing its value in facilitating drug development. Flies offer rapid, efficient platforms by which novel classes of drugs can be identified as candidate anticancer leads. Further, we discuss the use of Drosophila as a platform to develop therapies for individual patients by modeling the tumor's genetic complexity. Drosophila provides both a classical and a novel tool to identify new therapeutics, complementing other more traditional cancer tools. © 2017 Elsevier Inc. All rights reserved.

  9. Human sterol regulatory element-binding protein 1a contributes significantly to hepatic lipogenic gene expression.

    Science.gov (United States)

    Bitter, Andreas; Nüssler, Andreas K; Thasler, Wolfgang E; Klein, Kathrin; Zanger, Ulrich M; Schwab, Matthias; Burk, Oliver

    2015-01-01

    Sterol regulatory element-binding protein (SREBP) 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression. © 2015 S. Karger AG, Basel.

  10. Human Sterol Regulatory Element-Binding Protein 1a Contributes Significantly to Hepatic Lipogenic Gene Expression

    Directory of Open Access Journals (Sweden)

    Andreas Bitter

    2015-01-01

    Full Text Available Background/Aims: Sterol regulatory element-binding protein (SREBP 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression.

  11. Novel innate cancer killing activity in humans

    Directory of Open Access Journals (Sweden)

    Lovato James

    2011-08-01

    Full Text Available Abstract Background In this study, we pilot tested an in vitro assay of cancer killing activity (CKA in circulating leukocytes of 22 cancer cases and 25 healthy controls. Methods Using a human cervical cancer cell line, HeLa, as target cells, we compared the CKA in circulating leukocytes, as effector cells, of cancer cases and controls. The CKA was normalized as percentages of total target cells during selected periods of incubation time and at selected effector/target cell ratios in comparison to no-effector-cell controls. Results Our results showed that CKA similar to that of our previous study of SR/CR mice was present in human circulating leukocytes but at profoundly different levels in individuals. Overall, males have a significantly higher CKA than females. The CKA levels in cancer cases were lower than that in healthy controls (mean ± SD: 36.97 ± 21.39 vs. 46.28 ± 27.22. Below-median CKA was significantly associated with case status (odds ratio = 4.36; 95% Confidence Interval = 1.06, 17.88 after adjustment of gender and race. Conclusions In freshly isolated human leukocytes, we were able to detect an apparent CKA in a similar manner to that of cancer-resistant SR/CR mice. The finding of CKA at lower levels in cancer patients suggests the possibility that it may be of a consequence of genetic, physiological, or pathological conditions, pending future studies with larger sample size.

  12. Prevalence of hepatitis B, hepatitis C and human immunodeficiency viral infections in patients with inflammatory bowel disease in north India

    Directory of Open Access Journals (Sweden)

    Parnita Harsh

    2017-01-01

    Full Text Available Background/Aims: Patients with inflammatory bowel disease (IBD often require immunosuppressive therapy and blood transfusions and therefore are at a high risk of contracting infections due to hepatitis B (HBV and hepatitis C (HCV and human immunodeficiency virus (HIV. In the present study, we assessed the prevalence of these infections in patients with IBD.Methods: This retrospective study included 908 consecutive patients with IBD (ulcerative colitis [UC], n=581; Crohn's disease [CD], n=327 who were receiving care at a tertiary care center. Ninety-five patients with intestinal tuberculosis (ITB were recruited as disease controls. Prospectively maintained patient databases were reviewed for the prevalence of HBV surface antigen, anti-HCV antibodies, and HIV (enzyme-linked immunosorbent assay method. HCV RNA was examined in patients who tested positive for anti-HCV antibodies. Prevalence data of the study were compared with that of the general Indian population (HBV, 3.7%; HCV, 1%; HIV, 0.3%.Results: The prevalence of HBV, HCV, and HIV was 2.4%, 1.4%, and 0.1%, respectively, in the 908 patients with IBD. Among the 581 patients with UC, 2.2% (12/541 had HBV, 1.7% (9/517 had HCV, and 0.2% (1/499 had HIV. Among the 327 patients with CD, 2.8% (8/288 had HBV, 0.7% (2/273 had HCV, and 0% (0/277 had HIV. One patient with CD had HBV and HCV coinfection. The prevalence of HBV, HCV, and HIV in patients with ITB was 5.9% (4/67, 1.8% (1/57, and 1.2% (1/84, respectively.Conclusions: The prevalence of HBV, HCV, and HIV in north Indian patients with IBD is similar to the prevalence of these viruses in the general community. Nonetheless, the high risk of flare after immunosuppressive therapy mandates routine screening of patients with IBD for viral markers.

  13. Cytochrome P450 isoform selectivity in human hepatic theobromine metabolism

    Science.gov (United States)

    Gates, Simon; Miners, John O

    1999-01-01

    Aims The plasma clearance of theobromine (TB; 3,7-dimethylxanthine) is known to be induced in cigarette smokers. To determine whether TB may serve as a model substrate for cytochrome P450 (CYP) 1A2, or possibly other isoforms, studies were undertaken to identify the individual human liver microsomal CYP isoforms responsible for the conversion of TB to its primary metabolites. Methods The kinetics of formation of the primary TB metabolites 3-methylxanthine (3-MX), 7-methylxanthine (7-MX) and 3,7-dimethyluric acid (3,7-DMU) by human liver microsomes were characterized using a specific hplc procedure. Effects of CYP isoform-selective xenobiotic inhibitor/substrate probes on each pathway were determined and confirmatory studies with recombinant enzymes were performed to define the contribution of individual isoforms to 3-MX, 7-MX and 3,7-DMU formation. Results The CYP1A2 inhibitor furafylline variably inhibited (0–65%) 7-MX formation, but had no effect on other pathways. Diethyldithiocarbamate and 4-nitrophenol, probes for CYP2E1, inhibited the formation of 3-MX, 7-MX and 3,7-DMU by ≈55–60%, 35–55% and 85%, respectively. Consistent with the microsomal studies, recombinant CYP1A2 and CYP2E1 exhibited similar apparent Km values for 7-MX formation and CYP2E1 was further shown to have the capacity to convert TB to both 3-MX and 3,7-DMU. Conclusions Given the contribution of multiple isoforms to 3-MX and 7-MX formation and the negligible formation of 3,7-DMU in vivo, TB is of little value as a CYP isoform-selective substrate in humans. PMID:10215755

  14. Discovery of a novel hepatovirus (Phopivirus of seals) related to human Hepatitis A Virus

    Science.gov (United States)

    Anthony. S.J.,; St. Leger, J.A; Liang, E.; Hicks, A.L.; Sanchez-Leon, M.D; Ip, Hon S.; Jain, K.; Lefkowitch, J. H.; Navarrete-Macias, I.; Knowles, N.; Goldstein, T.; Pugliares, K.; Rowles, T.; Lipkin, W.I.

    2015-01-01

    Describing the viral diversity of wildlife can provide interesting and useful insights into the natural history of established human pathogens. In this study, we describe a previously unknown picornavirus in harbor seals (tentatively named phopivirus) that is related to human hepatitis A virus (HAV). We show that phopivirus shares several genetic and phenotypic characteristics with HAV, including phylogenetic relatedness across the genome, a specific and seemingly quiescent tropism for hepatocytes, structural conservation in a key functional region of the type III internal ribosomal entry site (IRES), and a codon usage bias consistent with that of HAV.

  15. Stable human lymphoblastoid cell lines constitutively expressing hepatitis C virus proteins.

    Science.gov (United States)

    Wölk, Benno; Gremion, Christel; Ivashkina, Natalia; Engler, Olivier B; Grabscheid, Benno; Bieck, Elke; Blum, Hubert E; Cerny, Andreas; Moradpour, Darius

    2005-06-01

    The cellular immune response plays a central role in virus clearance and pathogenesis of liver disease in hepatitis C. The study of hepatitis C virus (HCV)-specific immune responses is limited by currently available cell-culture systems. Here, the establishment and characterization of stable human HLA-A2-positive B-lymphoblastoid x T hybrid cell lines constitutively expressing either the NS3-4A complex or the entire HCV polyprotein are reported. These cell lines, termed T1/NS3-4A and T1/HCVcon, respectively, were maintained in continuous culture for more than 1 year with stable characteristics. HCV structural and non-structural proteins were processed accurately, indicating that the cellular and viral proteolytic machineries are functional in these cell lines. Viral proteins were found in the cytoplasm in dot-like structures when expressed in the context of the HCV polyprotein or in a perinuclear fringe when the NS3-4A complex was expressed alone. T1/NS3-4A and T1/HCVcon cells were lysed efficiently by HCV-specific cytotoxic T lymphocytes from patients with hepatitis C and from human HLA-A2.1 transgenic mice immunized with a liposomal HCV vaccine, indicating that viral proteins are processed endogenously and presented efficiently via the major histocompatibility complex class I pathway. In conclusion, these cell lines represent a unique tool to study the cellular immune response, as well as to evaluate novel vaccine and immunotherapeutic strategies against HCV.

  16. Splanchnic blood flow and hepatic glucose production in exercising humans

    DEFF Research Database (Denmark)

    Bergeron, R; Kjaer, M; Simonsen, L

    2001-01-01

    The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O(2) consumption (VO(2 max)) followed by 30 min at 70% VO(2 max) either with [angiotensin-converti......The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O(2) consumption (VO(2 max)) followed by 30 min at 70% VO(2 max) either with [angiotensin......-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an approximately 20-fold increase (P ... blockade; 0.74 +/- 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 +/- 0.06, ACE blockade; 0.68 +/- 0.10 mmol/min, control) increased during moderate exercise (1.97 +/- 0.29, ACE blockade; 1.91 +/- 0.41 mmol/min, control). Refuting a major role of the RAS for these responses...

  17. Pesticide exposure: human cancers on the horizon.

    Science.gov (United States)

    Jaga, K; Brosius, D

    1999-01-01

    Dichlorodiphenyltrichlorethane, a halogenated hydrocarbon, was introduced as an insecticide in the 1940s. In her book "Silent Spring", Rachel Carson expressed her concern for the environment, plants, animals, and human health about the potential harmful effects of such chemicals. In 1972, the Environmental Protection Agency banned the chemical in the USA. DDT and its metabolite DDE are lipid soluble compounds that persist in the environment and bioaccumulate in the body in adipose tissue at levels far higher than those in blood and breast milk. This paper evaluates the possibility of cancer occurring in humans from DDT exposure. Some risk of lymphoma, leukemia, pancreatic cancer, and breast cancer was found in humans exposed to DDT. Animal studies showed a significant association between DDT administration and lymphoma, respiratory cancer, liver cancer, and estrogenic effects on mammary tissue. On the basis of on epidemiological principles, human studies were deficient in adequate sample sizes and were not exempt from such confounding factors as multiple chemical exposure, lifestyle factors, genetic, and other environmental influences. Extrapolation of data on DDT toxicity from animals to humans has limitations. With the persistence of DDT and DDE in the environment, the potential risk to the health of man, animals, and the environment remains.

  18. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of

  19. High frequency of hepatitis E virus infection in swine from South Brazil and close similarity to human HEV isolates

    Directory of Open Access Journals (Sweden)

    Ana Maria Passos-Castilho

    Full Text Available Abstract Hepatitis E virus is responsible for acute and chronic liver infections worldwide. Swine hepatitis E virus has been isolated in Brazil, and a probable zoonotic transmission has been described, although data are still scarce. The aim of this study was to investigate the frequency of hepatitis E virus infection in pigs from a small-scale farm in the rural area of Paraná State, South Brazil. Fecal samples were collected from 170 pigs and screened for hepatitis E virus RNA using a duplex real-time RT-PCR targeting a highly conserved 70 nt long sequence within overlapping parts of ORF2 and ORF3 as well as a 113 nt sequence of ORF2. Positive samples with high viral loads were subjected to direct sequencing and phylogenetic analysis. hepatitis E virus RNA was detected in 34 (20.0% of the 170 pigs following positive results in at least one set of screening real-time RT-PCR primers and probes. The swine hepatitis E virus strains clustered with the genotype hepatitis E virus-3b reference sequences in the phylogenetic analysis and showed close similarity to human hepatitis E virus isolates previously reported in Brazil.

  20. Hepatic metabolism of toluene after gastrointestinal uptake in humans

    DEFF Research Database (Denmark)

    Bælum, Jesper; Mølhave, Lars; Honoré Hansen, S

    1993-01-01

    The metabolism of toluene and the influence of small doses of ethanol were measured in eight male volunteers after gastrointestinal uptake, the toluene concentration in alveolar air and the urinary excretion of hippuric acid and ortho-cresol being used as the measures of metabolism. During toluene...... exposure to 2 mg.min-1 for 3 h the alveolar toluene concentration was 0.07 (range 0-0.11) mg.m-3; exposure to 6 mg.min-1 for 30 min increased the alveolar concentration to 0.9 (range 0.03-2.6) mg.m-3. Ingestion of 0.08, 0.16, and 0.32 g of ethanol per kilogram of body weight during toluene exposure of 2 mg...... doses of ethanol inhibit toluene metabolism, and the procedure is sensitive enough to measure metabolic interactions between solvents and other xenobiotics in humans....

  1. Cancer risk in patients with hepatitis C virus infection: a population-based study in Sweden.

    Science.gov (United States)

    Liu, Xiangdong; Chen, Yanqing; Wang, Youxin; Dong, Xiaohua; Wang, Junming; Tang, Jianhua; Sundquist, Kristina; Sundquist, Jan; Ji, Jianguang

    2017-05-01

    Increased risks of certain cancers have been observed in patients with hepatitis C virus (HCV) infection. However, data on other cancer sites/types are lacking. We analyzed systematically the risk of developing 35 common cancers in patients with HCV infection using a nationwide Swedish database. Patients with HCV infection were identified from the Swedish Hospital Inpatient and Outpatient Register and Primary Health Care Database, and followed until the diagnosis of cancer. Standardized incidence ratios (SIRs) were calculated for subsequent 35 common cancer sites/types between 1990 and 2010 in patients with HCV infection in Sweden. Increased risks were recorded for six cancers. The highest SIR was seen for liver cancer (36.67; 95% CI: 33.20-40.40). The decreased risk was for prostate cancer (0.73; 95% CI: 0.59-0.90) and melanoma (0.50; 95% CI: 0.30-0.79). A significant sex-difference for cancer was observed only for liver cancer (40.72; 95% CI: 36.36-45.45 for men and 27.21; 95% CI: 21.90-33.41 for women). Also, increased SIRs were noted only for liver cancer during the entire period of follow-up. HCV infection was associated with an increased incidence of liver cancer and additionally five other types of cancer. Active surveillance of other cancers may be needed in order to be diagnosed at an earlier stage. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  2. Immunogenicity and safety of heat-inactivated hepatitis B vaccine (CLB) in low risk human volunteers and in patients treated with chronic haemodialysis in the Netherlands

    NARCIS (Netherlands)

    Reerink-Brongers, E. E.; Lelie, P. N.; Reesink, H. W.; Dees, P. J.; Brummelhuis, H. G.; van Aken, W. G.

    1983-01-01

    The immunogenicity and safety of a heat-inactivated hepatitis B vaccine (HB-vaccine) were studied in healthy human volunteers (n = 471) at a low risk to be infected with hepatitis B virus (HBV) and in patients on chronic haemodialysis (n = 227), who were treated in hepatitis B free centres. After

  3. Prevalence of Telomerase Activity in Human Cancer

    Directory of Open Access Journals (Sweden)

    Chi-Hau Chen

    2011-05-01

    Full Text Available Telomerase activity has been measured in a wide variety of cancerous and non-cancerous tissue types, and the vast majority of clinical studies have shown a direct correlation between it and the presence of cancerous cells. Telomerase plays a key role in cellular immortality and tumorigenesis. Telomerase is activated in 80–90% of human carcinomas, but not in normal somatic cells, therefore, its detection holds promise as a diagnostic marker for cancer. Measurable levels of telomerase have been detected in malignant cells from various samples: tissue from gestational trophoblastic neoplasms; squamous carcinoma cells from oral rinses; lung carcinoma cells from bronchial washings; colorectal carcinoma cells from colonic luminal washings; bladder carcinoma cells from urine or bladder washings; and breast carcinoma or thyroid cancer cells from fine needle aspirations. Such clinical tests for telomerase can be useful as non-invasive and cost-effective methods for early detection and monitoring of cancer. In addition, telomerase activity has been shown to correlate with poor clinical outcome in late-stage diseases such as non-small cell lung cancer, colorectal cancer, and soft tissue sarcomas. In such cases, testing for telomerase activity can be used to identify patients with a poor prognosis and to select those who might benefit from adjuvant treatment. Our review of the latest medical advances in this field reveals that telomerase holds great promise as a biomarker for early cancer detection and monitoring, and has considerable potential as the basis for developing new anticancer therapies.

  4. Bioenergetic Changes during Differentiation of Human Embryonic Stem Cells along the Hepatic Lineage

    DEFF Research Database (Denmark)

    Hopkinson, Branden M; Madsen, Claus Desler; Kalisz, Mark

    2017-01-01

    of embryonic origin differentiating along the hepatic lineage. Our study reveals especially the transition between hepatic specification and hepatic maturation as dependent on mitochondrial respiration and demonstrates that even though differentiating cells are primarily dependent on glycolysis until induction...

  5. General Information about Liver (Hepatocellular) Cancer

    Science.gov (United States)

    ... Hepatitis C Hepatitis D Hepatitis E Hepatitis G Liver cancer is a disease in which malignant (cancer) cells ... Primary Liver Cancer Treatment Childhood Liver Cancer Treatment Liver cancer is not common in the United States. Liver ...

  6. ODAM Expression Inhibits Human Breast Cancer Tumorigenesis

    OpenAIRE

    Kestler, Daniel P; Foster, James S.; Bruker, Charles T.; Prenshaw, John W.; Kennel, Stephen J.; Wall, Jonathan S.; Weiss, Deborah T.; Alan Solomon

    2011-01-01

    We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, an...

  7. Human Papillomavirus in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Anna Rosa Garbuglia

    2014-08-01

    Full Text Available Human papillomavirus (HPV is currently considered to be a major etiologic factor, in addition to tobacco and alcohol, for oropharyngeal cancer (OPC development. HPV positive OPCs are epidemiologically distinct from HPV negative ones, and are characterized by younger age at onset, male predominance, and strong association with sexual behaviors. HPV16 is the most prevalent types in oral cavity cancer (OCC, moreover the prevalence of beta, and gamma HPV types is higher than that of alpha HPV in oral cavity.

  8. Co-infection of syphilis and hepatitis B with carcinoma penis in a human immunodeficiency virus male.

    Science.gov (United States)

    Govindan, Balaji; Subramanian, Kalaivani; Karunakaran, Maduravasagam

    2017-01-01

    Human immunodeficiency virus (HIV) infections have a high probability of co-infections with Syphilis and hepatitis B virus since they share the common routes of transmission. We report a 41-year-old HIV male (on antiretroviral therapy for the past 6 years) admitted for a complaint of penile ulcer for 2 months. Serology for syphilis and hepatitis B were positive. Skin biopsy of the penile ulcer confirmed squamous cell carcinoma. Henceforth, the patient was referred to oncology department for further management. We present this rare combination of syphilis and hepatitis B with carcinoma penis in an HIV patient.

  9. Hepatic-intestinal disposal of endogenous human alpha atrial natriuretic factor99-126 in patients with cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Bendtsen, F; Schütten, H J

    1990-01-01

    Hepatic-intestinal disposal of endogenous human alpha atrial natriuretic factor99-126 (ANF) was assessed in 13 patients with cirrhosis (six Child-Turcotte class A, five class B, and two class C) and eight control subjects. The Fick principle was applied during hepatic vein catheterization. Arterial...... ANF concentration in patients with cirrhosis [11.1 +/- 1.6 (SEM) pmol/L] was not significantly different from that of the control subjects (14.9 +/- 4.2 pmol/L, NS). Arteriohepatic venous extraction ratio of ANF (0.43 +/- 0.05 in cirrhosis vs 0.37 +/- 0.09 in controls, NS), hepatic...

  10. Ulinastatin Reduces Cancer Recurrence after Resection of Hepatic Metastases from Colon Cancer by Inhibiting MMP-9 Activation via the Antifibrinolytic Pathway

    Directory of Open Access Journals (Sweden)

    Bo Xu

    2013-01-01

    Full Text Available High recurrence of colon cancer liver metastasis is observed in patients after hepatic surgery, and the cause is believed to be mostly due to the growth of residual microscopic metastatic lesions within the residual liver. Therefore, triggering the progression of occult metastatic foci may be a novel strategy for improving survival from colon cancer liver metastases. In the present study, we identified an anti-recurrence effect of ulinastatin on colon cancer liver metastasis in mice after hepatectomy. Transwell cell invasion assays demonstrated that ulinastatin significantly inhibited the in vitro invasive ability of colon cancer HCT116 cells. Moreover, gelatin zymography and ELISA analysis showed that MMP-9 activity and plasmin activity of colon cancer HCT116 cells were inhibited by ulinastatin, respectively. Furthermore, in vivo BALB/C nu/nu mice model indicated that ulinastatin effectively reduced recurrence after resection of hepatic metastases from colon cancer. The optimum timing for ulinastatin administration was one week after hepatectomy. Taken together, our findings point to the potential of ulinastatin as an effective approach in controlling recurrence of hepatic metastases from colon cancer after hepatectomy via its anti-plasmin activity.

  11. Metabolism of oxycodone in human hepatocytes from different age groups and prediction of hepatic plasma clearance

    Directory of Open Access Journals (Sweden)

    Timo eKorjamo

    2012-01-01

    Full Text Available Oxycodone is commonly used to treat severe pain in adults and children. It is extensively metabolized in the liver in adults, but the maturation of metabolism is not well understood. Our aim was to study the metabolism of oxycodone in cryopreserved human hepatocytes from different age groups (3 days, 2 and 5 months, 4 years, adult pool and predict hepatic plasma clearance of oxycodone using these data. Oxycodone (0.1, 1 and 10 µM was incubated with hepatocytes for 4 hours, and 1 µM oxycodone also with CYP3A inhibitor ketoconazole (1 µM. Oxycodone and noroxycodone concentrations were determined at several time points with liquid chromatography-mass spectrometry. In vitro clearance of oxycodone was used to predict hepatic plasma clearance, using the well-stirred model and published physiological parameters. Noroxycodone was the major metabolite in all batches and ketoconazole inhibited the metabolism markedly in most cases. A clear correlation between in vitro oxycodone clearance and CYP3A4 activity was observed. The predicted hepatic plasma clearances were typically much lower than the published median total plasma clearance from pharmacokinetic studies. In general, this in vitro to in vivo extrapolation method provides valuable information on the maturation of oxycodone metabolism that can be utilized in the design of clinical pharmacokinetic studies in infants and young children.

  12. Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients.

    Science.gov (United States)

    Alvarez-Muñoz, Ma Teresa; Maldonado-Rodriguez, Angelica; Rojas-Montes, Othon; Torres-Ibarra, Rocio; Gutierrez-Escolano, Fernanda; Vazquez-Rosales, Guillermo; Gomez, Alejandro; Muñoz, Onofre; Torres, Javier; Lira, Rosalia

    2014-10-07

    To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico. We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson's χ(2) and/or Fisher's exact test. We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05). The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.

  13. Quantifying the Contribution of the Liver to Glucose Homeostasis: A Detailed Kinetic Model of Human Hepatic Glucose Metabolism

    Science.gov (United States)

    König, Matthias; Bulik, Sascha; Holzhütter, Hermann-Georg

    2012-01-01

    Despite the crucial role of the liver in glucose homeostasis, a detailed mathematical model of human hepatic glucose metabolism is lacking so far. Here we present a detailed kinetic model of glycolysis, gluconeogenesis and glycogen metabolism in human hepatocytes integrated with the hormonal control of these pathways by insulin, glucagon and epinephrine. Model simulations are in good agreement with experimental data on (i) the quantitative contributions of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic glucose production and hepatic glucose utilization under varying physiological states. (ii) the time courses of postprandial glycogen storage as well as glycogen depletion in overnight fasting and short term fasting (iii) the switch from net hepatic glucose production under hypoglycemia to net hepatic glucose utilization under hyperglycemia essential for glucose homeostasis (iv) hormone perturbations of hepatic glucose metabolism. Response analysis reveals an extra high capacity of the liver to counteract changes of plasma glucose level below 5 mM (hypoglycemia) and above 7.5 mM (hyperglycemia). Our model may serve as an important module of a whole-body model of human glucose metabolism and as a valuable tool for understanding the role of the liver in glucose homeostasis under normal conditions and in diseases like diabetes or glycogen storage diseases. PMID:22761565

  14. Risk of all-type cancer, hepatocellular carcinoma, non-Hodgkin lymphoma and pancreatic cancer in patients infected with hepatitis B virus

    DEFF Research Database (Denmark)

    Andersen, E S; Omland, L H; Jepsen, Peter

    2015-01-01

    The increased risk of hepatocellular carcinoma (HCC) among patients infected with hepatitis B virus (HBV) is well established; however, long-term risk estimates are needed. Recently, it has been suggested that HBV is associated with non-Hodgkin lymphoma (NHL) and pancreatic cancer (PC). The aim o...

  15. Differences in Radiation Activity Between Glass and Resin 90Y Microspheres in Treating Unresectable Hepatic Cancer.

    Science.gov (United States)

    James, Trent; Hill, Jacqueline; Fahrbach, Thomas; Collins, Zachary

    2017-03-01

    The purpose of this study was to compare the difference in prescribed radiation activity between glass and resin yttrium-90 (Y) microspheres for radioembolization of unresectable hepatocellular carcinoma (HCC) or liver metastases at a tertiary care teaching institution. The authors performed a retrospective analysis on 126 patients with primary HCC and hepatic metastatic disease from extrahepatic primary cancers who underwent radioembolization with glass or resin particles between 2008 and 2013 at their institution. Radiation activity estimates for prescribed treatments, as well as for the alternate embolization particles, were calculated using commonly employed formulae for both glass and resin particles for all treatments. A total of 217 treatments were performed on 126 patients, with 136 (62.7%) using glass particles and 81 (37.3%) using resin particles. Forty-six (36.5%) patients had metastatic colorectal cancer (CRC), 51 (40.5%) had primary HCC, while 11 (8.7%) had neuroendocrine carcinoma, and 18 (14.3%) had metastases from other primary tumors. The average prescribed activity was 2.66 GBq for glass treatments and 1.06 GBq for resin treatments across all cancer types. When the alternative treatment activity was calculated, activities were projected to decrease by an average of 1.52 GBq per treatment if resin microspheres were used instead of glass microspheres (-52.5%), while activities were projected to increase by an average of 1.57 GBq per treatment if glass microspheres were used instead of resin microspheres (148.9%; p glass microspheres.

  16. Hematologic safety of breast cancer chemotherapies in patients with hepatitis B or C virus infection.

    Science.gov (United States)

    Shoji, Hirokazu; Hashimoto, Kenji; Kodaira, Makoto; Yunokawa, Mayu; Yonemori, Kan; Shimizu, Chikako; Tamura, Kenji; Ando, Masashi; Fujiwara, Yasuhiro

    2012-01-01

    Information regarding hematological toxicities in breast cancer chemotherapy patients with hepatitis B (HBV) or C virus (HCV) infection is limited. We retrospectively reviewed the presence of hepatotoxicities (i.e. aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin elevation) and hematotoxicities (i.e. leukopenia and thrombocytopenia) among breast cancer patients with HBV or HCV infection who received chemotherapy from 1999 to 2010. All of the patients included in this analysis were classified as Child-Pugh A. Among 32 patients with HBV infection who underwent chemotherapy (total cycles, 378), 3 experienced grade 3/4 hepatotoxicities, requiring 2 treatment delays and 1 treatment revision. Further, 9 patients experienced grade 3/4 hematotoxicities; of these, 2 required treatment delays and 3 required treatment revisions. Fifty-two HCV patients underwent a total of 570 cycles of chemotherapy. Five patients experienced grade 3/4 hepatotoxicities and required treatment delays, whereas 10 patients experienced grade 3 hematotoxicities; 3 of these patients required treatment delays. Hematotoxicities requiring chemotherapy dose or treatment revision were not highly prevalent among breast cancer chemotherapy patients with HBV or HCV infection and a normal range of liver function. Under careful monitoring, chemotherapy dosage or schedule adjustments may not be necessary in similar patients positive for HBV or HCV. Copyright © 2012 S. Karger AG, Basel.

  17. Differential expression proteomics of human colon cancer.

    Science.gov (United States)

    Mazzanti, Roberto; Solazzo, Michela; Fantappié, Ornella; Elfering, Sarah; Pantaleo, Pietro; Bechi, Paolo; Cianchi, Fabio; Ettl, Adam; Giulivi, Cecilia

    2006-06-01

    The focus of this study was to use differential protein expression to investigate operative pathways in early stages of human colon cancer. Colorectal cancer represents an ideal model system to study the development and progression of human tumors, and the proteomic approach avoids overlooking posttranslational modifications not detected by microarray analyses and the limited correlation between transcript and protein levels. Colon cancer samples, confined to the intestinal wall, were analyzed by expression proteomics and compared with matched samples from normal colon tissue. Samples were processed by two-dimensional gel electrophoresis, and spots differentially expressed and consistent across all patients were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analyses and by Western blot analyses. After differentially expressed proteins and their metabolic pathways were analyzed, the following main conclusions were achieved for tumor tissue: 1) a shift from beta-oxidation, as the main source of energy, to anaerobic glycolysis was observed owed to the alteration of nuclear- versus mitochondrial-encoded proteins and other proteins related to fatty acid and carbohydrate metabolism; 2) lower capacity for Na(+) and K(+) cycling; and 3) operativity of the apoptosis pathway, especially the mitochondrial one. This study of the human colon cancer proteome represents a step toward a better understanding of the metabolomics of colon cancer at early stages confined to the intestinal wall.

  18. Hepatitis B virus reactivation and antiviral prophylaxis during lung cancer chemotherapy: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yu-Tuan Wu

    Full Text Available Antiviral drugs have been recommended as prophylaxis for the reactivation of hepatitis B virus (HBV infection in cancer patients undergoing chemotherapy. However, screening and antiviral prophylaxis for lung cancer remain controversial because of insufficient evidence.In this study, we investigate the absolute risk for HBV reactivation and the prophylactic effects of antiviral drugs in hepatitis B surface antigen (HBsAg-positive lung cancer patients during chemotherapy.We searched Pubmed, Embase, Cochrane, Web of Science and SinoMed from inception until 28 November 2016, and identified all potential relevant references with or without prophylactic use of antiviral therapy in HBsAg-positive lung cancer patients during chemotherapy. The primary outcome was the incidence of HBV reactivation, the secondary outcomes were the incidence of hepatitis, chemotherapy disruption and mortality.Eleven studies involving 794 patients were analyzed. The incidences of HBV reactivation in control group and antiviral prophylaxis group ranged from 0% to 38% (median, 21%, 95% CI: 0.17-0.25 and 0% to 7% (median, 4%, 95% CI: 0.02-0.06, respectively. Antiviral prophylaxis had significantly reduced the risk for HBV reactivation (RR, 0.22 [95% CI: 0.13-0.37], p< 0.0001, hepatitis (RR, 0.35 [95% CI: 0.22-0.56], p<0.0001 and chemotherapy disruption (RR: 0.29 [95% CI, 0.15-0.55], p<0.0002 compared to those without antiviral prophylaxis. There was no significant heterogeneity in the comparisons, and a fixed-model was used.The risks of HBV reactivation and relevant complications are high in HBsAg-positive lung cancer patients receiving chemotherapy, and available evidences support HBV screening for antiviral prophylaxis before initiation of chemotherapy for lung cancer patients.

  19. Virosomes of hepatitis B virus envelope L proteins containing doxorubicin: synergistic enhancement of human liver-specific antitumor growth activity by radiotherapy.

    Science.gov (United States)

    Liu, Qiushi; Jung, Joohee; Somiya, Masaharu; Iijima, Masumi; Yoshimoto, Nobuo; Niimi, Tomoaki; Maturana, Andrés D; Shin, Seol Hwa; Jeong, Seong-Yun; Choi, Eun Kyung; Kuroda, Shun'ichi

    2015-01-01

    Bionanocapsules (BNCs) are hollow nanoparticles consisting of hepatitis B virus (HBV) envelope L proteins and have been shown to deliver drugs and genes specifically to human hepatic tissues by utilizing HBV-derived infection machinery. The complex of BNCs with liposomes (LPs), the BNC-LP complexes (a LP surrounded by BNCs in a rugged spherical form), could also become active targeting nanocarriers by the BNC function. In this study, under acidic conditions and high temperature, BNCs were found to fully fuse with LPs (smooth-surfaced spherical form), deploying L proteins with a membrane topology similar to that of BNCs (ie, virosomes displaying L proteins). Doxorubicin (DOX) was efficiently encapsulated via the remote loading method at 14.2%±1.0% of total lipid weight (mean ± SD, n=3), with a capsule size of 118.2±4.7 nm and a ζ-potential of -51.1±1.0 mV (mean ± SD, n=5). When mammalian cells were exposed to the virosomes, the virosomes showed strong cytotoxicity in human hepatic cells (target cells of BNCs), but not in human colon cancer cells (nontarget cells of BNCs), whereas LPs containing DOX and DOXOVES (structurally stabilized PEGylated LPs containing DOX) did not show strong cytotoxicity in either cell type. Furthermore, the virosomes preferentially delivered DOX to the nuclei of human hepatic cells. Xenograft mice harboring either target or nontarget cell-derived tumors were injected twice intravenously with the virosomes containing DOX at a low dose (2.3 mg/kg as DOX, 5 days interval). The growth of target cell-derived tumors was retarded effectively and specifically. Next, the combination of high dose (10.0 mg/kg as DOX, once) with tumor-specific radiotherapy (3 Gy, once after 2 hours) exhibited the most effective antitumor growth activity in mice harboring target cell-derived tumors. These results demonstrated that the HBV-based virosomes containing DOX could be an effective antitumor nanomedicine specific to human hepatic tissues, especially in

  20. Gene Expression Variability in Human Hepatic Drug Metabolizing Enzymes and Transporters

    Science.gov (United States)

    Yang, Lun; Price, Elvin T.; Chang, Ching-Wei; Li, Yan; Huang, Ying; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang

    2013-01-01

    Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications. PMID:23637747

  1. MALDI profiling of human lung cancer subtypes.

    Directory of Open Access Journals (Sweden)

    Angelo Gámez-Pozo

    Full Text Available BACKGROUND: Proteomics is expected to play a key role in cancer biomarker discovery. Although it has become feasible to rapidly analyze proteins from crude cell extracts using mass spectrometry, complex sample composition hampers this type of measurement. Therefore, for effective proteome analysis, it becomes critical to enrich samples for the analytes of interest. Despite that one-third of the proteins in eukaryotic cells are thought to be phosphorylated at some point in their life cycle, only a low percentage of intracellular proteins is phosphorylated at a given time. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we have applied chromatographic phosphopeptide enrichment techniques to reduce the complexity of human clinical samples. A novel method for high-throughput peptide profiling of human tumor samples, using Parallel IMAC and MALDI-TOF MS, is described. We have applied this methodology to analyze human normal and cancer lung samples in the search for new biomarkers. Using a highly reproducible spectral processing algorithm to produce peptide mass profiles with minimal variability across the samples, lineal discriminant-based and decision tree-based classification models were generated. These models can distinguish normal from tumor samples, as well as differentiate the various non-small cell lung cancer histological subtypes. CONCLUSIONS/SIGNIFICANCE: A novel, optimized sample preparation method and a careful data acquisition strategy is described for high-throughput peptide profiling of small amounts of human normal lung and lung cancer samples. We show that the appropriate combination of peptide expression values is able to discriminate normal lung from non-small cell lung cancer samples and among different histological subtypes. Our study does emphasize the great potential of proteomics in the molecular characterization of cancer.

  2. Human epidermal growth factor receptor2 expression in unresectable gastric cancers: Relationship with CT characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Sub [Dept. of Radiology, Jeju National University Hospital, Jeju (Korea, Republic of); Kim, Se Hyung; Im, Seock Ah; Kim, Min A; Han, Joon Koo [Seoul National University Hospital, Seoul (Korea, Republic of)

    2017-09-15

    To retrospectively analyze the qualitative CT features that correlate with human epidermal growth factor receptor 2 (HER2)-expression in pathologically-proven gastric cancers. A total of 181 patients with pathologically-proven unresectable gastric cancers with HER2-expression (HER2-positive [n = 32] and negative [n = 149]) were included. CT features of primary gastric and metastatic tumors were reviewed. The prevalence of each CT finding was compared in both groups. Thereafter, binary logistic regression determined the most significant differential CT features. Clinical outcomes were compared using Kaplan-Meier method. HER2-postive cancers showed lower clinical T stage (21.9% vs. 8.1%; p = 0.015), hyperattenuation on portal phase (62.5% vs. 30.9%; p = 0.003), and was more frequently metastasized to the liver (62.5% vs. 32.2%; p = 0.001), than HER2-negative cancers. On binary regression analysis, hyperattenuation of the tumor (odds ratio [OR], 4.68; p < 0.001) and hepatic metastasis (OR, 4.43; p = 0.001) were significant independent factors that predict HER2-positive cancers. Median survival of HER2-positive cancers (13.7 months) was significantly longer than HER2-negative cancers (9.6 months) (p = 0.035). HER2-positive gastric cancers show less-advanced T stage, hyperattenuation on the portal phase, and frequently metastasize to the liver, as compared to HER2-negative cancers.

  3. Dating the origin and dispersal of hepatitis B virus infection in humans and primates.

    Science.gov (United States)

    Paraskevis, Dimitrios; Magiorkinis, Gkikas; Magiorkinis, Emmanouil; Ho, Simon Y W; Belshaw, Robert; Allain, Jean-Pierre; Hatzakis, Angelos

    2013-03-01

    The origin of hepatitis B virus (HBV) infection in humans and other primates remains largely unresolved. Understanding the origin of HBV is crucial because it provides a framework for studying the burden, and subsequently the evolution, of HBV pathogenicity with respect to changes in human population size and life expectancy. To investigate this controversy we examined the relationship between HBV phylogeny and genetic diversity of modern humans, investigated the timescale of global HBV dispersal, and tested the hypothesis of HBV-human co-divergence. We find that the global distribution of HBV genotypes and subgenotypes are consistent with the major prehistoric modern human migrations. We calibrate the HBV molecular clock using the divergence times of different indigenous human populations based on archaeological and genetic evidence and show that HBV jumped into humans around 33,600 years ago; 95% higher posterior density (HPD): 22,000-47,100 years ago (estimated substitution rate: 2.2 × 10(-6) ; 95% HPD: 1.5-3.0 × 10(-6) substitutions/site/year). This coincides with the origin of modern non-African humans. Crucially, the most pronounced increase in the HBV pandemic correlates with the global population increase over the last 5,000 years. We also show that the non-human HBV clades in orangutans and gibbons resulted from cross-species transmission events from humans that occurred no earlier than 6,100 years ago. Our study provides, for the first time, an estimated timescale for the HBV epidemic that closely coincides with dates of human dispersals, supporting the hypothesis that HBV has been co-expanding and co-migrating with human populations for the last 40,000 years. (HEPATOLOGY 2013). Copyright © 2012 American Association for the Study of Liver Diseases.

  4. Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms.

    Science.gov (United States)

    Bitter, Andreas; Rümmele, Petra; Klein, Kathrin; Kandel, Benjamin A; Rieger, Jessica K; Nüssler, Andreas K; Zanger, Ulrich M; Trauner, Michael; Schwab, Matthias; Burk, Oliver

    2015-11-01

    In addition to its well-characterized role in the regulation of drug metabolism and transport by xenobiotics, pregnane X receptor (PXR) critically impacts on lipid homeostasis. In mice, both ligand-dependent activation and knockout of PXR were previously shown to promote hepatic steatosis. To elucidate the respective pathways in human liver, we generated clones of human hepatoma HepG2 cells exhibiting different PXR protein levels, and analyzed effects of PXR activation and knockdown on steatosis and expression of lipogenic genes. Ligand-dependent activation as well as knockdown of PXR resulted in increased steatosis in HepG2 cells. Activation of PXR induced the sterol regulatory element-binding protein (SREBP) 1-dependent lipogenic pathway via PXR-dependent induction of SREBP1a, which was confirmed in primary human hepatocytes. Inhibiting SREBP1 activity by blocking the cleavage-dependent maturation of SREBP1 protein impaired the induction of lipogenic SREBP1 target genes and triglyceride accumulation by PXR activation. On the other hand, PXR knockdown resulted in up-regulation of aldo-keto reductase (AKR) 1B10, which enhanced the acetyl-CoA carboxylase (ACC)-catalyzed reaction step of de novo lipogenesis. In a cohort of human liver samples histologically classified for non-alcoholic fatty liver disease, AKR1B10, SREBP1a and SREBP1 lipogenic target genes proved to be up-regulated in steatohepatitis, while PXR protein was reduced. In summary, our data suggest that activation and knockdown of PXR in human hepatic cells promote de novo lipogenesis and steatosis by induction of the SREBP1 pathway and AKR1B10-mediated increase of ACC activity, respectively, thus providing mechanistic explanations for a putative dual role of PXR in the pathogenesis of steatohepatitis.

  5. Know HBV: What Every Asian and Pacific Islander Should Know About Hepatitis B and Liver Cancer

    Science.gov (United States)

    ... your family to get tested for HBV because hepatitis B is one of the KNOW greatest health threats ... Ask your doctor for these blood tests: HBV Hepatitis B sur face antigen (HBs Ag) : Tells if you ...

  6. Prediction of hepatic microsomal intrinsic clearance and human clearance values for drugs.

    Science.gov (United States)

    Nikolic, Katarina; Agababa, Danica

    2009-10-01

    Twenty-nine drugs of different structures were used in theoretical QSAR analysis of human hepatic microsomal intrinsic clearance (in vitro T(1/2) and in vitro CL'(int)) and whole body clearance (CL(blood)). The examined compounds demonstrated a wide range of scaled intrinsic clearance values. Constitutional, geometrical, physico-chemical and electronic descriptors were computed for the examined structures by use of the Marvin Sketch 5.1.3_2, the Chem3D Ultra 7.0.0 and the Dragon 5.4 program. Partial least squares regression (PLSR), has been applied for selection of the most relevant molecular descriptors and development of quantitative structure-activity relationship (QSAR) model for human hepatic microsomal intrinsic clearance (in vitro T(1/2)). Optimal QSAR models with nine and ten variables, R(2)>0.808 and cross-validation parameter q(pre)(2)>0.623, were selected and compared. Since the microsomal in vitro T(1/2) data can be used for calculation of in vitro CL'(int) and in vivo CL(blood), the developed QSAR model will enable one to analyze the kinetics of cytochrome P450-mediated reactions in term of intrinsic clearance and whole body clearance. A comparison is made between predictions produced from the QSAR analysis and experimental data, and there appears to be generally satisfactory correlations with the literature values for intrinsic clearance data.

  7. Genetic heterogeneity and subtyping of human Hepatitis E virus isolates from Uruguay.

    Science.gov (United States)

    Mirazo, Santiago; Ramos, Natalia; Russi, José Carlos; Arbiza, Juan

    2013-05-01

    Hepatitis E virus (HEV) infection is an important public health concern in many developing countries causing waterborne outbreaks, as well as sporadic autochthonous hepatitis. It is transmitted primarily by the fecal-oral route. However, zoonotic transmission from animal reservoirs to human has also been suggested. Genotype 3 is the most frequent genotype found in South America and the HEV epidemiology in this region seems to be very complex. However, data about the molecular characterization of HEV isolates of the region is still lacking and further investigation is needed. Our study characterized human HEV strains detected in a 1-year period in Uruguay, by extensive sequence analysis of three regions of the HEV genome. Uruguayan strains were closely related to a set of European strains and in turn, were dissimilar to Brazilian, Argentinean and Bolivian isolates. Additionally, the co-circulation of viral subtypes 3i and 3h was observed. Circulation of subtype 3i had been reported in Argentina and Bolivia whereas sequences of subtype 3h are rare and had never been reported in Latin America. In order to contribute to shedding light over the molecular epidemiology of this emergent infection in the region, we thoroughly analyzed the genetic variability of HEV strains detected in Uruguay, providing the largest dataset of sequences of HEV ever reported in a country in South America. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Know More Hepatitis

    Science.gov (United States)

    ... death. In fact, Hepatitis C is a leading cause of liver cancer and the #1 cause of liver transplants. Many people can get lifesaving care and treatment. Knowing you have Hepatitis C can help you make important decisions about your health. Successful treatments can eliminate the ... “Hepatitis C: Did You Know?” Watch this video ...

  9. Mitomycin-based hepatic arterial infusion chemotherapy for solitary ampullary cancer liver metastasis: an unusual treatment for an uncommon disease.

    Science.gov (United States)

    Vitale, Felice V; Romeo, Placido; Luciani, Bruno; Raffaele, Mario; Colina, Paolo; Ferraù, Francesco

    2015-10-01

    Ampullary carcinoma is an uncommon gastrointestinal disease. Its natural history is often characterized by the occurrence of liver metastases. Among patients who undergo pancreatoduodenectomy, those presenting with lymph nodes involvement are more prone to early distant disease relapse. In this report, a patient previously diagnosed with ampullary carcinoma had been treated with curative surgery. After subsequent adjuvant gemcitabine, the patient developed significant myelotoxicity and suffered from a single liver metastasis a few months later. A hepatic intra-arterial mitomycin plus fluorouracil-based chemotherapy was administered in order to avoid any serious systemic toxicity. The treatment was well tolerated and no serious side effects occurred. Extra-hepatic cancer relapse, involving intra-thoracic and abdominal lymph nodes, was observed not long after the initial intra-hepatic almost complete response. In conclusion, the locoregional chemotherapy administration was effective in overcoming any systemic toxicities and showed activity against the liver metastasis but it did not prevent extra-hepatic cancer dissemination. © The Author(s) 2014.

  10. [Hepatic intra-arterial infusion of biological response modifier (BRM)-activated killer immune lymphocytes to treat liver cancer].

    Science.gov (United States)

    Ebina, Takusaburo

    2012-11-01

    To enable "life with cancer" while maintaining quality of life(QOL) and freedom from adverse effects, we have devised biological response modifier (BRM)-activated killer (BAK) therapy, a new immune cell therapy using CD56-positive lymphocytes designed to treat advanced solid cancers. This treatment is yet to be applied to liver cancer, because BAK cells administered by intravenous infusion are unlikely to reach lesions via the complex vascular and lymphatic systems. Here, we report a case in which the patient, a surgeon, requested that we attempt to deliver BAK cells to cancer lesions in the liver via hepatic intra-arterial infusion. In 2005, with the patient's consent, we injected autologous lymphocytes intra-arterially into the liver using a catheter and confirmed the absence of adverse effects. In December 2008, we began injecting BAK cells intra-arterially into the liver of the patient, a male physician aged 52 years at the time, after identifying liver metastases following surgery for rectal cancer. We injected 10 billion cells intra-arterially into the liver via a catheter once a month for 6 months, and then undertook conventional BAK therapy by monthly intravenous infusion. Based on images obtained by positron emission tomography-computed tomography, BAK therapy led to complete remission and disappearance of the liver metastases. This case highlights the effectiveness of hepatic intra-arterial infusion of BAK cells in cases of liver cancer.

  11. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy.

    Science.gov (United States)

    Kopetz, Scott; Chang, George J; Overman, Michael J; Eng, Cathy; Sargent, Daniel J; Larson, David W; Grothey, Axel; Vauthey, Jean-Nicolas; Nagorney, David M; McWilliams, Robert R

    2009-08-01

    Fluorouracil/leucovorin as the sole therapy for metastatic colorectal cancer (CRC) provides an overall survival of 8 to 12 months. With an increase in surgical resections of metastatic disease and development of new chemotherapies, indirect evidence suggests that outcomes for patients are improving in the general population, although the incremental gain has not yet been quantified. We performed a retrospective review of patients newly diagnosed with metastatic CRC treated at two academic centers from 1990 through 2006. Landmark analysis evaluated the association of diagnosis year and liver resection with overall survival. Additional survival analysis of the Surveillance Epidemiology and End Results (SEER) database evaluated a similar population from 1990 through 2005. Two thousand four hundred seventy patients with metastatic CRC at diagnosis received their primary treatment at the two institutions during this time period. Median overall survival for those patients diagnosed from 1990 to 1997 was 14.2 months, which increased to 18.0, 18.6, and 29.3 months for patients diagnosed in 1998 to 2000, 2001 to 2003, and 2004 to 2006, respectively. Likewise, 5-year overall survival increased from 9.1% in the earliest time period to 19.2% in 2001 to 2003. Improved outcomes from 1998 to 2004 were a result of an increase in hepatic resection, which was performed in 20% of the patients. Improvements from 2004 to 2006 were temporally associated with increased utilization of new chemotherapeutics. In the SEER registry, overall survival for the 49,459 identified patients also increased in the most recent time period. Profound improvements in outcome in metastatic CRC seem to be associated with the sequential increase in the use of hepatic resection in selected patients (1998 to 2006) and advancements in medical therapy (2004 to 2006).

  12. Hepatitis C virus infection and the risk of cancer among elderly US adults: A registry-based case-control study.

    Science.gov (United States)

    Mahale, Parag; Torres, Harrys A; Kramer, Jennifer R; Hwang, Lu-Yu; Li, Ruosha; Brown, Eric L; Engels, Eric A

    2017-04-01

    Hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC) and subtypes of non-Hodgkin lymphoma (NHL). Associations with other cancers are not established. The authors systematically assessed associations between HCV infection and cancers in the US elderly population. This was a registry-based case-control study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data in US adults aged ≥66 years. Cases (n = 1,623,538) were patients who had first cancers identified in SEER registries (1993-2011). Controls (n = 200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race, and calendar year. Associations with HCV (documented by Medicare claims) were determined using logistic regression. HCV prevalence was higher in cases than in controls (0.7% vs 0.5%). HCV was positively associated with cancers of the liver (adjusted odds ratio [aOR] = 31.5; 95% confidence interval [CI], 29.0-34.3), intrahepatic bile duct (aOR, 3.40; 95% CI, 2.52-4.58), extrahepatic bile duct (aOR, 1.90; 95% CI, 1.41-2.57), pancreas (aOR, 1.23; 95% CI, 1.09-1.40), and anus (aOR, 1.97; 95% CI, 1.42-2.73); nonmelanoma nonepithelial skin cancer (aOR, 1.53; 95% CI, 1.15-2.04); myelodysplastic syndrome (aOR, 1.56; 95% CI, 1.33-1.83); and diffuse large B-cell lymphoma (aOR, 1.57; 95% CI, 1.34-1.84). Specific skin cancers associated with HCV were Merkel cell carcinoma (aOR, 1.92; 95% CI, 1.30-2.85) and appendageal skin cancers (aOR, 2.02; 95% CI, 1.29-3.16). Inverse associations were observed with uterine cancer (aOR, 0.64; 95% CI, 0.51-0.80) and prostate cancer (aOR, 0.73; 95% CI, 0.66-0.82). Associations were maintained in sensitivity analyses conducted among individuals without documented alcohol abuse, cirrhosis, or hepatitis B or human immunodeficiency virus infections and after adjustment for socioeconomic status. Associations of HCV with other cancers were not observed. HCV is associated with increased risk of

  13. Metabolism of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) by murine and human hepatic preparations.

    Science.gov (United States)

    Egorin, M J; Rosen, D M; Wolff, J H; Callery, P S; Musser, S M; Eiseman, J L

    1998-06-01

    17-(Allylamino)-17-demethoxygeldanamycin (17AAG), a compound that is proposed for clinical development, shares the ability of geldanamycin to bind to heat shock protein 90 and GRP94, thereby depleting cells of p185erbB2, mutant p53, and Raf-1. Urine and plasma from mice treated i.v. with 17AAG contained six materials with absorption spectra similar to that of 17AAG. Therefore, in vitro metabolism of 17AAG by mouse and human hepatic preparations was studied to characterize: (a) the enzymes responsible for 17AAG metabolism; and (b) the structures of the metabolites produced. These materials had retention times on high-performance liquid chromatography of approximately 2, 4, 5, 6, 7, and 9 min. When incubated in an aerobic environment with 17AAG, murine hepatic supernatant (9000 x g) produced each of these compounds; the 4-min metabolite was the major product. This metabolism required an electron donor, and NADPH was favored over NADH. Metabolic activity resided predominantly in the microsomal fraction. Metabolism was decreased by approximately 80% in anaerobic conditions and was essentially ablated by CO. Microsomes prepared from human livers produced essentially the same metabolites as produced by murine hepatic microsomes, but the 2-min metabolite was the major product, and the 4-min metabolite was next largest. There was no metabolism of 17AAG by human liver cytosol. Metabolism of 17AAG by human liver microsomes also required an electron donor, with NADPH being preferred over NADH, was inhibited by approximately 80% under anaerobic conditions, and was essentially ablated by CO. Liquid chromatography/mass spectrometry analysis of human and mouse in vitro reaction mixtures indicated the presence of materials with molecular weights of 545, 601, and 619, compatible with 17-(amino)-17-demethoxygeldanamycin (17AG), an epoxide, and a diol, respectively. The metabolite with retention time of 4 min was identified as 17AG by cochromatography and mass spectral concordance

  14. The Human Amnion Epithelial Cell Secretome Decreases Hepatic Fibrosis in Mice with Chronic Liver Fibrosis

    Directory of Open Access Journals (Sweden)

    Majid Alhomrani

    2017-10-01

    Full Text Available Background: Hepatic stellate cells (HSCs are the primary collagen-secreting cells in the liver. While HSCs are the major cell type involved in the pathogenesis of liver fibrosis, hepatic macrophages also play an important role in mediating fibrogenesis and fibrosis resolution. Previously, we observed a reduction in HSC activation, proliferation, and collagen synthesis following exposure to human amnion epithelial cells (hAEC and hAEC-conditioned media (hAEC-CM. This suggested that specific factors secreted by hAEC might be effective in ameliorating liver fibrosis. hAEC-derived extracellular vesicles (hAEC-EVs, which are nanosized (40–100 nm membrane bound vesicles, may act as novel cell–cell communicators. Accordingly, we evaluated the efficacy of hAEC-EV in modulating liver fibrosis in a mouse model of chronic liver fibrosis and in human HSC.Methods: The hAEC-EVs were isolated and characterized. C57BL/6 mice with CCl4-induced liver fibrosis were administered hAEC-EV, hAEC-CM, or hAEC-EV depleted medium (hAEC-EVDM. LX2 cells, a human HSC line, and bone marrow-derived mouse macrophages were exposed to hAEC-EV, hAEC-CM, and hAEC-EVDM. Mass spectrometry was used to examine the proteome profile of each preparation.Results: The extent of liver fibrosis and number of activated HSCs were reduced significantly in CCl4-treated mice given hAEC-EVs, hAEC-CM, and hAEC EVDM compared to untreated controls. Hepatic macrophages were significantly decreased in all treatment groups, where a predominant M2 phenotype was observed. Human HSCs cultured with hAEC-EV and hAEC-CM displayed a significant reduction in collagen synthesis and hAEC-EV, hAEC-CM, and hAEC-EVDM altered macrophage polarization in bone marrow-derived mouse macrophages. Proteome analysis showed that 164 proteins were unique to hAEC-EV in comparison to hAEC-CM and hAEC-EVDM, and 51 proteins were co-identified components with the hAEC-EV fraction.Conclusion: This study provides novel data

  15. Viruses and Human Cancers: a Long Road of Discovery of Molecular Paradigms

    Science.gov (United States)

    White, Martyn K.; Pagano, Joseph S.

    2014-01-01

    SUMMARY About a fifth of all human cancers worldwide are caused by infectious agents. In 12% of cancers, seven different viruses have been causally linked to human oncogenesis: Epstein-Barr virus, hepatitis B virus, human papillomavirus, human T-cell lymphotropic virus, hepatitis C virus, Kaposi's sarcoma herpesvirus, and Merkel cell polyomavirus. Here, we review the many molecular mechanisms of oncogenesis that have been discovered over the decades of study of these viruses. We discuss how viruses can act at different stages in the complex multistep process of carcinogenesis. Early events include their involvement in mutagenic events associated with tumor initiation such as viral integration and insertional mutagenesis as well as viral promotion of DNA damage. Also involved in tumor progression is the dysregulation of cellular processes by viral proteins, and we describe how this has been investigated by studies in cell culture and in experimental animals and by molecular cellular approaches. Also important are the molecular mechanisms whereby viruses interact with the immune system and the immune evasion strategies that have evolved. PMID:24982317

  16. A transcriptome anatomy of human colorectal cancers

    Directory of Open Access Journals (Sweden)

    Zhang Hao

    2006-02-01

    Full Text Available Abstract Background Accumulating databases in human genome research have enabled integrated genome-wide study on complicated diseases such as cancers. A practical approach is to mine a global transcriptome profile of disease from public database. New concepts of these diseases might emerge by landscaping this profile. Methods In this study, we clustered human colorectal normal mucosa (N, inflammatory bowel disease (IBD, adenoma (A and cancer (T related expression sequence tags (EST into UniGenes via an in-house GetUni software package and analyzed the transcriptome overview of these libraries by GOTree Machine (GOTM. Additionally, we downloaded UniGene based cDNA libraries of colon and analyzed them by Xprofiler to cross validate the efficiency of GetUni. Semi-quantitative RT-PCR was used to validate the expression of β-catenin and. 7 novel genes in colorectal cancers. Results The efficiency of GetUni was successfully validated by Xprofiler and RT-PCR. Genes in library N, IBD and A were all found in library T. A total of 14,879 genes were identified with 2,355 of them having at least 2 transcripts. Differences in gene enrichment among these libraries were statistically significant in 50 signal transduction pathways and Pfam protein domains by GOTM analysis P Conclusion Colorectal cancers are genetically heterogeneous. Transcription variants are common in them. Aberrations of ribosome and glycolysis pathway might be early indicators of precursor lesions in colon cancers. The electronic gene expression profile could be used to highlight the integral molecular events in colorectal cancers.

  17. Chlorella sorokiniana induces mitochondrial-mediated apoptosis in human non-small cell lung cancer cells and inhibits xenograft tumor growth in vivo

    National Research Council Canada - National Science Library

    Lin, Ping-Yi; Tsai, Ching-Tsan; Chuang, Wan-Ling; Chao, Ya-Hsuan; Pan, I-Horng; Chen, Yu-Kuo; Lin, Chi-Chen; Wang, Bing-Yen

    2017-01-01

    ..., minerals, vitamins, fatty acids, and antioxidants [3]. Chlorella is a unicellular green microalgae and is widely consumed as a nutritional supplement in East Asian countries. Chlorella or Chlorella extracts have been demonstrated to modulate immune response [4, 5], decrease hepatitis C virus viral load [6], and to have anti-cancer effects in human...

  18. Nuclear Matrix Proteins in Human Colon Cancer

    Science.gov (United States)

    Keesee, Susan K.; Meneghini, Marc D.; Szaro, Robert P.; Wu, Ying-Jye

    1994-03-01

    The nuclear matrix is the nonchromatin scaffolding of the nucleus. This structure confers nuclear shape, organizes chromatin, and appears to contain important regulatory proteins. Tissue specific nuclear matrix proteins have been found in the rat, mouse, and human. In this study we compared high-resolution two-dimensional gel electropherograms of nuclear matrix protein patterns found in human colon tumors with those from normal colon epithelia. Tumors were obtained from 18 patients undergoing partial colectomy for adenocarcinoma of the colon and compared with tissue from 10 normal colons. We have identified at least six proteins which were present in 18 of 18 colon tumors and 0 of 10 normal tissues, as well as four proteins present in 0 of 18 tumors and in 10 of 10 normal tissues. These data, which corroborate similar findings of cancer-specific nuclear matrix proteins in prostate and breast, suggest that nuclear matrix proteins may serve as important markers for at least some types of cancer.

  19. A case of the hepatic hilar bile duct cancer with external radiation. Efficacy and severe side effect of external radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Andoh, Hideaki; Yasui, Ouki; Ise, Norihito [Akita Univ. (Japan). School of Medicine

    2003-04-01

    Hepatic hilar bile duct cancer was difficult to cure by surgical treatment and its prognosis was very poor. We present the case of non-curative resection of hepatic hilar bile duct cancer, controlled with external radiation. 72 years-old-female, she complained jaundice and diagnosed hepatic hilar bile duct cancer with abdominal ultrasonography. Hepatic hilar resection was performed but curative resection could not be done, because cancer was diffusely spreaded to the hepatic and duodenal ends of the bile duct. After surgery, external radiation (1.8 Gy/day; total 50.4 Gy) was performed. Three months after operation, sometimes, cholangitis was occurred but we could not detect the intrahepatic bile duct dilatation and improved with antibiotics. After seven months, she was dead for sepsis, liver abscess and biliary cirrhosis. From autopsy findings, severe hepatic hilar fibrosis around the irradiation area, stenosis of the hepatico-jejunostomy and portal vein were existed but could not detect the remnant cancer cells. External radiation was sometimes effective, especially for this case. But we should consider the side effect of fibrosis and preventive treatments such as biliary stenting or early biliary drainage. (author)

  20. Hepatic differentiation of human pluripotent stem cells in miniaturized format suitable for high-throughput screen

    Directory of Open Access Journals (Sweden)

    Arnaud Carpentier

    2016-05-01

    Full Text Available The establishment of protocols to differentiate human pluripotent stem cells (hPSCs including embryonic (ESC and induced pluripotent (iPSC stem cells into functional hepatocyte-like cells (HLCs creates new opportunities to study liver metabolism, genetic diseases and infection of hepatotropic viruses (hepatitis B and C viruses in the context of specific genetic background. While supporting efficient differentiation to HLCs, the published protocols are limited in terms of differentiation into fully mature hepatocytes and in a smaller-well format. This limitation handicaps the application of these cells to high-throughput assays. Here we describe a protocol allowing efficient and consistent hepatic differentiation of hPSCs in 384-well plates into functional hepatocyte-like cells, which remain differentiated for more than 3 weeks. This protocol affords the unique opportunity to miniaturize the hPSC-based differentiation technology and facilitates screening for molecules in modulating liver differentiation, metabolism, genetic network, and response to infection or other external stimuli.

  1. Genetic characteristics of the human hepatic stellate cell line LX-2.

    Directory of Open Access Journals (Sweden)

    Ralf Weiskirchen

    Full Text Available The human hepatic cell line LX-2 has been described as tool to study mechanisms of hepatic fibrogenesis and the testing of antifibrotic compounds. It was originally generated by immortalisation with the Simian Vacuolating Virus 40 (SV40 transforming (T antigen and subsequent propagation in low serum conditions. Although this immortalized line is used in an increasing number of studies, detailed genetic characterisation has been lacking. We here have performed genetic characterisation of the LX-2 cell line and established a single-locus short tandem repeat (STR profile for the cell line and characterized the LX-2 karyotype by several cytogenetic and molecular cytogenetic techniques. Spectral karyotyping (SKY revealed a complex karyotype with a set of aberrations consistently present in the metaphases analyses which might serve as cytogenetic markers. In addition, various subclonal and single cell aberrations were detected. Our study provides criteria for genetic authentication of LX-2 and offers insights into the genotype changes which might underlie part of its phenotypic features.

  2. Liver cancer and non-hodgkin lymphoma in hepatitis C virus-infected patients: results from the danvir cohort study

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; Jepsen, Peter; Krarup, Henrik Bygum

    2012-01-01

    Hepatitis C virus (HCV)-infection can cause hepatocellular carcinoma (HCC) and most likely non-Hodgkin lymphoma (NHL). No studies have compared the risk of these cancers between patients with chronic and cleared HCV-infection. The aim of this study was to estimate the 10-year risk of HCC and NHL...... in HCV-infected patients and to compare the risk of these cancers between HCV-infected patients and the general population in Denmark and between patients with chronic and cleared HCV-infection. Nationwide cohorts were used: 11,975 HCV-infected patients in the DANVIR cohort and 71,850 individuals from...

  3. Hepatitis B or hepatitis C co-infection in individuals infected with human immunodeficiency virus and effect of anti-tuberculosis drugs on liver function

    Directory of Open Access Journals (Sweden)

    Padmapriyadarsini C

    2006-01-01

    Full Text Available Background: Tuberculosis (TB and hepatitis are the two common co-infections in patients infected with human immunodeficiency virus (HIV. Anti-tuberculosis treatment (ATT may have an effect on the liver enzymes in these co-infected HIV patients. Aims: To determine the prevalence of Hepatitis B and C virus coinfection in HIV infected patients in Tamilnadu and assess effects of anti-tuberculosis drugs on their liver function. Settings: HIV positive subjects referred to the Tuberculosis Research Centre, Chennai Materials and Methods: All HIV infected patients referred to the Tuberculosis Research centre, from March 2000 to May 2004, were screened for Hepatitis B surface antigen (HBsAg & Hepatitis C virus (HCV antibodies by enzyme linked immunoabsorbent assay (ELISA. HIV infection was confirmed using two rapid tests and one ELISA. Patients were given either short- course anti-tuberculosis treatment or preventive therapy for tuberculosis, depending on the presence or absence of active TB, if their baseline liver functions were within normal limits. None of these patients were on antiretroviral therapy during the study period. Statistical Analysis: Paired t-test was used to find the significance between baseline and end of treatment liver enzymes levels, while logistic regression was done for assessing various associations. Results: Of the 951 HIV-infected patients, 61 patients (6.4% were HBsAg positive, 20 (2.1% had demonstrable anti HCV antibodies in their blood. Serial estimation of liver enzymes in 140 HIV patients (81 being co-infected with either HBV or HCV showed that 95% did not develop any liver toxicity while they were on anti-tuberculosis treatment or prophylaxis. Conclusions: The prevalence of hepatitis B and C coinfection was fairly high in this largely heterosexually infected population supporting the use of more careful screening for these viruses in HIV positive persons in this region. Anti-tuberculosis therapy as well as TB preventive

  4. Prevalence of human immunodeficiency virus, hepatitis C virus, hepatitis B virus and syphilis among individuals attending anonymous testing for HIV in Luanda, Angola.

    Science.gov (United States)

    Guimarães Nebenzahl, H; Lopes, A; Castro, R; Pereira, F

    2013-01-24

    Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis remain major infections around the world. In Angola there are about 166 000 individuals living with HIV, representing a prevalence of 1.98% in adults between 15 and 49 years of age. In a 2003 study in Luanda, 4.5% of pregnant women had antibodies to HIV and 8.1% to HBV, and 5.4% were infected with Treponema pallidum. Objectives. The aim of this study was to determine the prevalence of HIV-1 and 2, HBV, HCV and T. pallidum serological markers, and hence the prevalence of these infections, in individuals attending a sexually transmitted disease clinic in Luanda, Angola, and the burden of these infections in the Angolan population. Methods. Individuals attending a centre for anonymous testing for HIV were randomly included in the study. All samples were tested for HBV surface antigen (HBsAg), anti-HCV and anti-HIV-1 and 2 antibodies and antibodies to T. pallidum. Results. A total of 431 individuals (262 women and 169 men) were studied, of whom 10.0% (43/431) were seropositive for T. pallidum and 4.6% had active syphilis; 8.8% (38/431) were seropositive for HIV-1 and/or HIV-2 (of these, 78.9% were HIV-1-positive, 2.6% HIV-2-positive and 18.4% co-infected); 9.3% (40/431) were HBsAg-positive, while 8.1% (35/431) had antibodies to HCV. Of 102 patients with positive results, 26 (25.5%, or 6.0% of the total of 431 patients) were positive for more than one of the organisms studied. Rates of co-infection were as follows: 2.3% (10/431) for HIV/HBV, 0.9% (4/431) for HIV/HCV, and 0.9% (4/431) for HCV/HBV. Three individuals with active syphilis had viral co-infection, hepatitis B in 1 case and HIV in 2. Five individuals (1.2% of the total) were seropositive for three infections, HIV, hepatitis B and hepatitis C in 3 cases and HIV, hepatitis C and syphilis in 2. Conclusions. A high prevalence of co-infection with the infections studied was found in this population, including HIV

  5. Hepatitis B Vaccination Protection

    Science.gov (United States)

    Fact Sheet Hepatitis B Vaccination Protection Hepatitis B virus (HBV) is a pathogenic microorganism that can cause potentially life- threatening disease in humans. HBV infection is transmitted through exposure ...

  6. Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Roskams, Tania [Department of Morphology and Molecular Pathology, University of Leuven (Belgium); Oben, Jude A., E-mail: j.oben@ucl.ac.uk [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Department of Gastroenterology and Hepatology, Guy' s and St Thomas' Hospital, London SE1 7EH (United Kingdom)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Cigarette smoke may induce liver fibrosis via nicotine receptors. Black-Right-Pointing-Pointer Nicotine induces proliferation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Nicotine activates hepatic fibrogenic pathways. Black-Right-Pointing-Pointer Nicotine receptor antagonists attenuate HSC proliferation. Black-Right-Pointing-Pointer Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine - which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed - RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-{alpha}2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-{beta}1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type ({alpha}1, {beta}1, delta and epsilon) and neuronal type ({alpha}3, {alpha}6, {alpha}7, {beta}2 and {beta}4) nAChR subunits at the mRNA level. Among these subunits, {alpha}3, {alpha}7, {beta}1 and {epsilon} were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-{alpha}2 and TGF-{beta}1 mRNA expression were significantly upregulated by nicotine and inhibited by

  7. New models of hepatitis E virus replication in human and porcine hepatocyte cell lines

    Science.gov (United States)

    Hepatitis E virus (HEV) causes acute, enterically-transmitted hepatitis. It is associated with large epidemics in tropical and subtropical regions where it is endemic or with sporadic cases in non-endemic regions. Unlike other hepatitis viruses, HEV has several animal reservoirs. Phylogenetic studie...

  8. Factors in enhancing blood safety by nucleic acid technology testing for human immunodeficiency virus, hepatitis C virus and hepatitis B virus

    Science.gov (United States)

    Shyamala, Venkatakrishna

    2014-01-01

    In the last few decades through an awareness of transfusion transmitted infections (TTI), a majority of countries have mandated serology based blood screening assays for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and Hepatitis B virus (HBV). However, despite improved serology assays, the transfusion transmission of HIV, HCV, and HBV continues, primarily due to release of serology negative units that are infectious because of the window period (WP) and occult HBV infections (OBI). Effective mode of nucleic acid technology (NAT) testing of the viruses can be used to minimize the risk of TTIs. This review compiles the examples of NAT testing failures for all three viruses; analyzes the causes for failure, and the suggestions from retrospective studies to minimize such failures. The results suggest the safest path to be individual donation testing (ID) format for highest sensitivity, and detection of multiple regions for rapidly mutating and recombining viruses. The role of blood screening in the context of the donation and transfusion practices in India, the donor population, and the epidemiology is also discussed. World wide, as the public awareness of TTIs increases, as the recipient rights for safe blood are legally upheld, as the possibility to manage diseases such as hepatitis through expensive and prolonged treatment becomes accessible, and the societal responsibility to shoulder the health costs as in the case for HIV becomes routine, there is much to gain by preventing infections than treating diseases. PMID:24678167

  9. Factors in enhancing blood safety by nucleic acid technology testing for human immunodeficiency virus, hepatitis C virus and hepatitis B virus

    Directory of Open Access Journals (Sweden)

    Venkatakrishna Shyamala

    2014-01-01

    Full Text Available In the last few decades through an awareness of transfusion transmitted infections (TTI, a majority of countries have mandated serology based blood screening assays for Human immunodeficiency virus (HIV, Hepatitis C virus (HCV, and Hepatitis B virus (HBV. However, despite improved serology assays, the transfusion transmission of HIV, HCV, and HBV continues, primarily due to release of serology negative units that are infectious because of the window period (WP and occult HBV infections (OBI. Effective mode of nucleic acid technology (NAT testing of the viruses can be used to minimize the risk of TTIs. This review compiles the examples of NAT testing failures for all three viruses; analyzes the causes for failure, and the suggestions from retrospective studies to minimize such failures. The results suggest the safest path to be individual donation testing (ID format for highest sensitivity, and detection of multiple regions for rapidly mutating and recombining viruses. The role of blood screening in the context of the donation and transfusion practices in India, the donor population, and the epidemiology is also discussed. World wide, as the public awareness of TTIs increases, as the recipient rights for safe blood are legally upheld, as the possibility to manage diseases such as hepatitis through expensive and prolonged treatment becomes accessible, and the societal responsibility to shoulder the health costs as in the case for HIV becomes routine, there is much to gain by preventing infections than treating diseases.

  10. A prominent role of Hepatitis D Virus in liver cancers documented in Central Africa

    Directory of Open Access Journals (Sweden)

    Marie Atsama Amougou

    2016-11-01

    Full Text Available Abstract Background Hepatocellular Carcinoma (HCC is one of the commonest cancers in Central Africa, a region with the unusual peculiarity to be hyperendemic for infections with Hepatitis B, C and D viruses. However, data estimating the respective proportions of HCC cases attributable to these viruses are still limited in this area. The current study was undertaken to determine the role of these viruses in HCC compared to non-HCC Cameroonian patients. Methods A case–control study was conducted in the Gastroenterology Unit of Central Hospital of Yaounde in collaboration with Centre Pasteur of Cameroon. Blood samples of all HCC cases (n = 88 and matched control individuals without known liver disease (n = 85 were tested for serological markers of Hepatitis B, C and D viral infections using commercially available enzyme immune-assay kits. Hepatitis B and C viral loads were quantified for positive patients by real-time PCR using commercial kits. Results The mean age was 46.0 ± 18 and 42.1 ± 16 years old for HCC-patients and controls, respectively for a 2.3 Male/Female sex ratio. The prevalence of hepatitis B surface antigen, antibody to HCV and antibody to HDV were significantly higher in HCC patients (65.90, 20.26 and 26 % respectively than in control patients (9.23, 4.62 and 1 % (P < 2.5 10−5. The risk factors analysis showed that both HBV and HCV infections were strongly associated with HCC development in Cameroon with crude odds ratios of 15.98 (95 % CI 6.19-41.25 and 7.33 (95 % CI 2.09-25.77, respectively. Furthermore, the risk of developing HCC increased even more significantly in case of HBV and HDV co-infections with the odd ratio of 29.3 (95 % CI, 4.1-1231. HBV-DNA level was significantly higher in HBsAg-positive HCC-patients than in HBsAg-positive controls with (6.3 Log IU/mL and 5.7 Log IU/mL respectively (P < 0.05. Conclusion HBV and HCV infections are the mains factors of HCC development in Cameroon

  11. Release of Virus from Lymphoid Tissue Affects Human Immunodeficiency Virus Type 1 and Hepatitis C Virus Kinetics in the Blood

    NARCIS (Netherlands)

    Müller, Viktor; Marée, Athanasius F.M.; Boer, R.J. de

    2000-01-01

    Kinetic parameters of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections have been estimated from plasma virus levels following perturbation of the chronically infected (quasi-) steady state. We extend previous models by also considering the large pool of virus

  12. [Phylogenetic analysis indicates human origin of rotavirus and hepatitis A virus strains found in the drinking water of western Colombia].

    Science.gov (United States)

    Moreno, Sandra; Alvarado, Mónica Viviana; Bermúdez, Andrea; Gutiérrez, María Fernanda

    2009-06-01

    Quibdó, the capital of Chocó Province, is one of the poorest cities in Colombia. Enteric viruses such as rotavirus and hepatitis A virus was found to occur commonly in city drinking water and indicated poor water quality and high risk of becoming infected. The source of these viruses was unknown, but humans and cattle were suspect sources. City water was assessed to determine source and persistence of diarrhea and hepatitis among the human populations in the environs of Quibdó. Four thousand liters of water were collected, filtered by tangential ultrafiltration and centrifuged in Centriprep Ultracel YM-50 tubes. Sixty samples of untreated and 20 of treated water were probed by RT-PCR. Six samples were positive for rotavirus and 2 for hepatitis A virus in both, treated and non treated water. DNA sequence analysis identified the presence of human G2 rotavirus and human hepatitis A virus. The evidence indicated a high level of contamination with pathogenic viruses in consumable water sources in Quibdó, Colombia.

  13. Direct assessment of hepatic mitochondrial oxidative and anaplerotic fluxes in humans using dynamic 13C magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Befroy, Douglas E; Perry, Rachel J; Jain, Nimit

    2014-01-01

    Despite the central role of the liver in the regulation of glucose and lipid metabolism, there are currently no methods to directly assess hepatic oxidative metabolism in humans in vivo. By using a new (13)C-labeling strategy in combination with (13)C magnetic resonance spectroscopy, we show that...

  14. Isolation and characterization of broadly neutralizing human monoclonal antibodies to the e1 glycoprotein of hepatitis C virus

    DEFF Research Database (Denmark)

    Meunier, Jean-Christophe; Russell, Rodney S.; Goossens, Vera

    2008-01-01

    The relative importance of humoral and cellular immunity in the prevention or clearance of hepatitis C virus (HCV) infection is poorly understood. However, there is considerable evidence that neutralizing antibodies are involved in disease control. Here we describe the detailed analysis of human...

  15. A long-term hepatitis B viremia model generated by transplanting nontumorigenic immortalized human hepatocytes in Rag-2-deficient mice

    NARCIS (Netherlands)

    Parashar, B; Moshage, H; Tanaka, KE; Engelhardt, D; Rabbani, E; Roy-Chowdhury, N; Roy-Chowdhury, J

    Development of new therapies for human hepatitis B virus infection (HBV) would be greatly facilitated by the availability of a suitable small-animal model for HBV virus production in vivo. To develop a murine model for HBV production, we established an immortalized, cloned liver cell line by

  16. Three-Dimensional Culture of Human Embryonic Stem Cell Derived Hepatic Endoderm and Its Role in Bioartificial Liver Construction

    Directory of Open Access Journals (Sweden)

    Ruchi Sharma

    2010-01-01

    Full Text Available The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

  17. Maintenance of Hepatic Functions in Primary Human Hepatocytes Cultured on Xeno-Free and Chemical Defined Human Recombinant Laminins.

    Science.gov (United States)

    Watanabe, Masaaki; Zemack, Helen; Johansson, Helene; Hagbard, Louise; Jorns, Carl; Li, Meng; Ellis, Ewa

    2016-01-01

    Refined methods for maintaining specific functions of isolated hepatocytes under xeno-free and chemical defined conditions is of great importance for the development of hepatocyte research and regenerative therapy. Laminins, a large family of heterotrimeric basement membrane adhesion proteins, are highly cell and tissue type specific components of the extracellular matrix and strongly influence the behavior and function of associated cells and/or tissues. However, detailed biological functions of many laminin isoforms are still to be evaluated. In this study, we determined the distribution of laminin isoforms in human liver tissue and isolated primary human hepatocytes by western blot analysis, and investigated the efficacy of different human recombinant laminin isoforms on hepatic functions during culture. Protein expressions of laminin-chain α2, α3, α4, β1, β3, γ1, and γ2 were detected in both isolated human hepatocytes and liver tissue. No α1 and α5 expression could be detected in liver tissue or hepatocytes. Hepatocytes were isolated from five different individual livers, and cultured on human recombinant laminin isoforms -111, -211, -221, -332, -411, -421, -511, and -521 (Biolamina AB), matrigel (extracted from Engelbreth-Holm-Swarm sarcoma), or collagen type IV (Collagen). Hepatocytes cultured on laminin showed characteristic hexagonal shape in a flat cell monolayer. Viability, double stranded DNA concentration, and Ki67 expression for hepatocytes cultured for six days on laminin were comparable to those cultured on EHS and Collagen. Hepatocytes cultured on laminin also displayed production of human albumin, alpha-1-antitrypsin, bile acids, and gene expression of liver-enriched factors, such as hepatocyte nuclear factor 4 alpha, glucose-6-phosphate, cytochrome P450 3A4, and multidrug resistance-associated protein 2. We conclude that all forms of human recombinant laminin tested maintain cell viability and liver-specific functions of primary human

  18. Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer

    Science.gov (United States)

    Ding, Lin; El Zaatari, Mohamad

    2017-01-01

    Overview Gastric cancer has been traditionally defined by the Correa paradigm as a progression of sequential pathological events that begins with chronic inflammation [1]. Infection with Helicobacter pylori (H. pylori) is the typical explanation for why the stomach becomes chronically inflamed. Acute gastric inflammation then leads to chronic gastritis, atrophy particularly of acid-secreting parietal cells, metaplasia due to mucous neck cell expansion from trans-differentiation of zymogenic cells to dysplasia and eventually carcinoma [2]. The chapter contains an overview of gastric anatomy and physiology to set the stage for signaling pathways that play a role in gastric tumorigenesis. Finally, the major known mouse models of gastric transformation are critiqued in terms of the rationale behind their generation and contribution to our understanding of human cancer subtypes. PMID:27573785

  19. Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus

    DEFF Research Database (Denmark)

    Giang, Erick; Dorner, Marcus; Prentoe, Jannick C

    2012-01-01

    Hepatitis C virus (HCV) infects ∼2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable......, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human m......bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies...

  20. The laboratory diagnosis of acute viral hepatitis

    African Journals Online (AJOL)

    Arbuthnot P, Kew MC, Fitschen W. c-fos and c-myc oncoprotein expression in human hepatocellular carcinomas ... Abelson murine leukemia virus encoded protein present in transformed fibroblasts and lymphoid cells. ... hepatocellular carcinoma from liver cirrhosis with persistent hepatitis S virus infection.lnt J Cancer 1980; ...

  1. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor

    Directory of Open Access Journals (Sweden)

    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

  2. Cancer history and other personal factors affect quality of life in patients with hepatitis C

    Directory of Open Access Journals (Sweden)

    Toro Charlene

    2005-06-01

    Full Text Available Abstract Background Although patients with chronic hepatitis C (CHC have been found to have reduced quality of life, little is known about how other characteristics affect their quality of life. The purpose of this study was to investigate the effect of other characteristics, including history of cancer, on quality of life in patients with CHC. Methods One hundred forty patients from clinics at three hospitals in New York City completed a detailed epidemiologic interview about demographic and lifestyle characteristics and the SF-36 measuring health-related quality of life. We compared results from our patients to normative data using t-tests of differences between means. We used multivariate analyses to determine other personal and health-related factors associated with quality of life outcomes. Results Compared to normative data, these patients had reduced quality of life, particularly on physical functioning. The summary Physical Component Score (PCS was 45.4 ± 10.6 and the Mental Component Score (MCS was 48.2 ± 11.1, vs norms of 50 ± 10.0; p-values were Conclusion Several health and lifestyle factors independently influence quality of life in CHC patients. Different factors are important for men and women.

  3. Nomogram including pretherapeutic parameters for prediction of survival after SIRT of hepatic metastases from colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fendler, Wolfgang Peter [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Klinik und Poliklinik fuer Nuklearmedizin, Munich (Germany); Ilhan, Harun [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Paprottka, Philipp M. [Ludwig-Maximilians-University of Munich, Department of Clinical Radiology, Munich (Germany); Jakobs, Tobias F. [Hospital Barmherzige Brueder, Department of Diagnostic and Interventional Radiology, Munich (Germany); Heinemann, Volker [Ludwig-Maximilians-University of Munich, Department of Internal Medicine III, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Bartenstein, Peter; Haug, Alexander R. [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Ludwig-Maximilians-University of Munich, Comprehensive Cancer Center, Munich (Germany); Khalaf, Feras [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Ezziddin, Samer [Saarland University Medical Center, Department of Nuclear Medicine, Homburg (Germany); Hacker, Marcus [Vienna General Hospital, Department of Nuclear Medicine, Vienna (Austria)

    2015-09-15

    Pre-therapeutic prediction of outcome is important for clinicians and patients in determining whether selective internal radiation therapy (SIRT) is indicated for hepatic metastases of colorectal cancer (CRC). Pre-therapeutic characteristics of 100 patients with colorectal liver metastases (CRLM) treated by radioembolization were analyzed to develop a nomogram for predicting survival. Prognostic factors were selected by univariate Cox regression analysis and subsequent tested by multivariate analysis for predicting patient survival. The nomogram was validated with reference to an external patient cohort (n = 25) from the Bonn University Department of Nuclear Medicine. Of the 13 parameters tested, four were independently associated with reduced patient survival in multivariate analysis. These parameters included no liver surgery before SIRT (HR:1.81, p = 0.014), CEA serum level ≥ 150 ng/ml (HR:2.08, p = 0.001), transaminase toxicity level ≥2.5 x upper limit of normal (HR:2.82, p = 0.001), and summed computed tomography (CT) size of the largest two liver lesions ≥10 cm (HR:2.31, p < 0.001). The area under the receiver-operating characteristic curve for our prediction model was 0.83 for the external patient cohort, indicating superior performance of our multivariate model compared to a model ignoring covariates. The nomogram developed in our study entailing four pre-therapeutic parameters gives good prediction of patient survival post SIRT. (orig.)

  4. Hepatic colon cancer metastases in mice: dynamic in vivo correlation with hypoechoic rims visible at US.

    Science.gov (United States)

    Kruskal, J B; Thomas, P; Nasser, I; Cay, O; Kane, R A

    2000-06-01

    To use videomicroscopy of tumor-bearing livers of live mice to depict tumors directly to determine the exact nature of rims seen on corresponding ultrasonographic (US) scans. Seventy-six hepatic colorectal cancer metastases were studied in exteriorized livers of 18 mice by using intravital microscopy, US, and histologic examination of the same tumors. Hypoechoic rims correlated with distended sinusoidal spaces in vivo. These spaces surrounded only locally invasive tumors (mean diameter, 0.85 mm) that had obstructed the supplying terminal portal venules. These spaces, containing adherent leukocytes and tumor cells, gave rise to new tumor vasculature. Results of histologic examination of rims (portal inflammation, congested or compressed sinusoids, cell atrophy) correlated with leukocyte endothelial adherence, occluded sinusoids, and new vessel formation in vivo. Unlike results from previous studies, dynamic in vivo observations of peritumoral rims demonstrated distended sinusoidal spaces giving rise to new tumor-penetrating vessels. These sinusoids arose around locally invasive tumors and were associated with more advanced intrahepatic disease. These dynamic observations provide a pathophysiologic explanation for previous histologic correlates of peritumoral rims.

  5. Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting

    Science.gov (United States)

    Ma, Xuanyi; Qu, Xin; Zhu, Wei; Li, Yi-Shuan; Yuan, Suli; Zhang, Hong; Liu, Justin; Wang, Pengrui; Lai, Cheuk Sun Edwin; Zanella, Fabian; Feng, Gen-Sheng; Sheikh, Farah; Chien, Shu; Chen, Shaochen

    2016-01-01

    The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling. PMID:26858399

  6. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused Three-Dimensional Multicompartment Bioreactor

    Science.gov (United States)

    Freyer, Nora; Knöspel, Fanny; Strahl, Nadja; Amini, Leila; Schrade, Petra; Bachmann, Sebastian; Damm, Georg; Seehofer, Daniel; Jacobs, Frank; Monshouwer, Mario; Zeilinger, Katrin

    2016-01-01

    Abstract 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 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 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 systems in stem cell differentiation approaches for improved formation of differentiated tissue structures. PMID:27610270

  7. Endotoxin administration to humans inhibits hepatic cytochrome P450-mediated drug metabolism.

    Science.gov (United States)

    Shedlofsky, S I; Israel, B C; McClain, C J; Hill, D B; Blouin, R A

    1994-12-01

    In experimental animals, injection of gram-negative endotoxin (LPS) decreases hepatic cytochrome P450-mediated drug metabolism. To evaluate this phenomenon in a human model of gram-negative sepsis, LPS was administered on two consecutive days to healthy male volunteers during which time a cocktail of antipyrine (AP-250 mg), hexobarbital (HB-500 mg), and theophylline (TH-150 mg) was ingested and the apparent oral clearance of each drug determined. Each subject had a control drug clearance study with saline injections. In the first experiment, six subjects received the drug cocktail 0.5 h after the first dose of LPS. In the second experiment, another six subjects received the drug cocktail 0.5 h after the second dose of LPS. In both experiments, LPS caused the expected physiologic responses of inflammation including fever with increases in serum concentrations of TNF alpha, IL-1 beta, IL-6, and acute phase reactants. In the first experiment, only minor decreases in clearances of the probe drugs were observed (7-12%). However in the second experiment, marked decreases in the clearances of AP (35, 95% CI 18-48%), HB (27, 95% CI 14-34%), and TH (22, 95% CI 12-32%) were seen. The decreases in AP clearance correlated with initial peak values of TNF alpha (r = 0.82) and IL-6 (r = 0.86). These data show that in humans the inflammatory response to even a very low dose of LPS significantly decreases hepatic cytochrome P450-mediated drug metabolism and this effect evolves over a 24-h period. It is likely that septic patients with much higher exposures to LPS have more profound inhibition of drug metabolism.

  8. Applications of human hepatitis B virus preS domain in bio- and nanotechnology.

    Science.gov (United States)

    Toita, Riki; Kawano, Takahito; Kang, Jeong-Hun; Murata, Masaharu

    2015-06-28

    Human hepatitis B virus (HBV) is a member of the family Hepadnaviridae, and causes acute and chronic infections of the liver. The hepatitis B surface antigen (HBsAg) contains the large (L), middle (M), and small (S) surface proteins. The L protein consists of the S protein, preS1, and preS2. In HBsAg, the preS domain (preS1 + preS2) plays a key role in the infection of hepatocytic cells by HBV and has several immunogenic epitopes. Based on these characteristics of preS, several preS-based diagnostic and therapeutic materials and systems have been developed. PreS1-specific monoclonal antibodies (e.g., MA18/7 and KR127) can be used to inhibit HBV infection. A myristoylated preS1 peptide (amino acids 2-48) also inhibits the attachment of HBV to HepaRG cells, primary human hepatocytes, and primary tupaia hepatocytes. Antibodies and antigens related to the components of HBsAg, preS (preS1 + preS2), or preS1 can be available as diagnostic markers of acute and chronic HBV infections. Hepatocyte-targeting delivery systems for therapeutic molecules (drugs, genes, or proteins) are very important for increasing the clinical efficacy of these molecules and in reducing their adverse effects on other organs. The selective delivery of diagnostic molecules to target hepatocytic cells can also improve the efficiency of diagnosis. In addition to the full-length HBV vector, preS (preS1 + preS2), preS1, and preS1-derived fragments can be useful in hepatocyte-specific targeting. In this review, we discuss the literature concerning the applications of the HBV preS domain in bio- and nanotechnology.

  9. Randomized Trial: Immunogenicity and Safety of Coadministered Human Papillomavirus-16/18 AS04-Adjuvanted Vaccine and Combined Hepatitis A and B Vaccine in Girls

    DEFF Research Database (Denmark)

    Pedersen, Court; Breindahl, Morten; Aggarwal, Naresh

    2012-01-01

    This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A......, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone....

  10. ODAM Expression Inhibits Human Breast Cancer Tumorigenesis

    Science.gov (United States)

    Kestler, Daniel P.; Foster, James S.; Bruker, Charles T.; Prenshaw, John W.; Kennel, Stephen J.; Wall, Jonathan S.; Weiss, Deborah T.; Solomon, Alan

    2011-01-01

    We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes. Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions. Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import. PMID:21603257

  11. Prevention of hepatitis B.

    Science.gov (United States)

    Chang, Mei-Hwei; Chen, Ding-Shinn

    2015-03-02

    Hepatitis B virus (HBV) causes life-threatening liver disease. It is transmitted through a horizontal route or a mother-to-infant route, and the latter is the major route in endemic areas. Prevention of HBV infection by immunization is the best way to eliminate HBV-related diseases. The HBV vaccine is the first human vaccine using a viral antigen from infected persons, which is safe and effective. Either passive immunization by hepatitis B immunoglobulin (HBIG) or active immunization by HBV vaccine is effective, and a combination of both yields the best efficacy in preventing HBV infection. The impact of universal HBV immunization is huge, with 90%-95% effectiveness in preventing chronic HBV infection. It is the first cancer preventive vaccine with a protective efficacy against hepatocellular carcinoma (HCC) of ∼ 70%. Nevertheless, further effort is still needed to avoid vaccine failure and to increase the global coverage rate. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  12. Partial isolation and identification of hepatic stimulator substance mRNA extracted from human fetal liver

    Science.gov (United States)

    Yang, Xiao-Ming; Xie, Ling; Xing, Gui-Chun; Wu, Zu-Ze; He, Fu-Chu

    1998-01-01

    AIM: To partially isolate and identify hepatic stimulator substance mRNA from human fetal liver tissues. METHODS: The poly (A) mRNA was extracted from human fetal liver tissues of 4-5 month gestation, fractionated by size on sucrose gradient centrifugation, translated into protein from each fraction in vitro and then its products were tested for HSS activity. RESULTS: Twenty-two 500 μg total RNA was obtained from human fetal liver tissues and pooled. mRNA of 420 μg was yielded, processed by oligo (dT)-cellulose column chromatography, then was size-fractionated by ultracentrifution on a continuous sucrose density gradient (5%-25%), and separated into 18 fractions. Translated products of mRNA in fraction 8 and 9 could produce a two-fold increase in the incorporation of 3H-TdR into DNA of SMMC-7721 hepatoma cells and in a heat resistant and organ-specific way. CONCLUSION: The partially purified HSS mRNA was obtained and this would facilitate the cloning of HSS using expression vectors. PMID:11819247

  13. Human Cancer Classification: A Systems Biology- Based Model Integrating Morphology, Cancer Stem Cells, Proteomics, and Genomics

    Directory of Open Access Journals (Sweden)

    Halliday A Idikio

    2011-01-01

    Full Text Available Human cancer classification is currently based on the idea of cell of origin, light and electron microscopic attributes of the cancer. What is not yet integrated into cancer classification are the functional attributes of these cancer cells. Recent innovative techniques in biology have provided a wealth of information on the genomic, transcriptomic and proteomic changes in cancer cells. The emergence of the concept of cancer stem cells needs to be included in a classification model to capture the known attributes of cancer stem cells and their potential contribution to treatment response, and metastases. The integrated model of cancer classification presented here incorporates all morphology, cancer stem cell contributions, genetic, and functional attributes of cancer. Integrated cancer classification models could eliminate the unclassifiable cancers as used in current classifications. Future cancer treatment may be advanced by using an integrated model of cancer classification.

  14. A nested case-control study on association between hepatitis C virus antibodies and primary liver cancer in a cohort of 9,775 men in Taiwan.

    Science.gov (United States)

    Chang, C C; Yu, M W; Lu, C F; Yang, C S; Chen, C J

    1994-07-01

    Most studies on the association between antibodies against hepatitis C virus (anti-HCV) and primary liver cancer (PLC) were limited to case-series, or cross-sectional case-control studies leaving a controversy on causal temporality. A nested case-control study on 38 newly-developed PLC patients and 152 matched controls selected from a cohort of 9,775 men in Taiwan recruited from September, 1984, to February, 1986, was carried out to examine the relation between HCV infection and PLC. Case-control pairs were matched on age (+/- 1 year), residence, and the date at recruitment. Serum samples collected from study subjects at the initial recruitment were examined for anti-HCV by enzyme immunoassay and hepatitis B surface antigen (HBsAg) by reverse passive hemagglutination assay combined with radioimmunoassay. History of cigarette smoking, alcohol consumption, vegetable consumption, vegetarian habit, and chronic liver diseases were also obtained through standardized interviews according to a structured questionnaire at the recruitment. After adjusting for HBsAg status and other risk factors, the anti-HCV was significantly associated with the development of PLC showing a multivariate-adjusted relative risk of 88.24. The results suggest that HCV infection may play an important role in the etiology of human PLC in Taiwan.

  15. A consensus for occupational health management of healthcare workers infected with human immunodeficiency virus, hepatitis B virus, and / or hepatitis C virus.

    Science.gov (United States)

    Ishimaru, Tomohiro; Wada, Koji; Smith, Derek R

    2017-05-25

    Occupational health management plays an important role in the prevention of provider-to-patient transmission in healthcare workers infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV). Therefore, the Japan Society for Occupational Health's Research Group on Occupational Health for Health Care Workers has proposed a consensus for the management of healthcare workers infected with HIV, HBV, and/or HCV based on recent evidence for each concerned group. The consensus recommends that: (1) employers in medical institutions should establish a policy of respecting the human rights of healthcare workers, management strategies for occupational blood exposure, and occupational health consultation; (2) occupational health staff should appropriately assess the risk of provider-to-patient transmission of HIV, HBV, and/or HCV infection and rearrange their tasks if necessary. When conducting risk assessment, occupational health staff should obtain informed consent and then cooperate with the physician in charge as well as infection control experts in the workplace; (3) healthcare workers infected with HIV, HBV, and/or HCV should disclose their employment to their treating physician and consult with their doctor regarding the need for special considerations at work; and (4) supervisors and colleagues in medical institutions should correctly understand the risks of HIV, HBV, and HCV infection and should not engage in any behavior that leads to discrimination against colleagues infected with HIV, HBV, and/or HCV.

  16. Human Cancer Classification: A Systems Biology- Based Model Integrating Morphology, Cancer Stem Cells, Proteomics, and Genomics

    OpenAIRE

    Halliday A Idikio

    2011-01-01

    Human cancer classification is currently based on the idea of cell of origin, light and electron microscopic attributes of the cancer. What is not yet integrated into cancer classification are the functional attributes of these cancer cells. Recent innovative techniques in biology have provided a wealth of information on the genomic, transcriptomic and proteomic changes in cancer cells. The emergence of the concept of cancer stem cells needs to be included in a classification model to capture...

  17. Alterations of 5-Hydroxymethylcytosine in Human Cancers

    Directory of Open Access Journals (Sweden)

    Ali Yesilkanal

    2013-06-01

    Full Text Available Prior to 2009, 5-methylcytosine (5-mC was thought to be the only biologically significant cytosine modification in mammalian DNA. With the discovery of the TET enzymes, which convert 5-methylcytosine (5-mC to 5-hydroxymethylcytosine (5-hmC, however, intense interest has emerged in determining the biological function of 5-hmC. Here, we review the techniques used to study 5-hmC and evidence that alterations to 5-hmC physiology play a functional role in the molecular pathogenesis of human cancers.

  18. PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells

    Science.gov (United States)

    Pirazzi, Carlo; Valenti, Luca; Motta, Benedetta Maria; Pingitore, Piero; Hedfalk, Kristina; Mancina, Rosellina Margherita; Burza, Maria Antonella; Indiveri, Cesare; Ferro, Yvelise; Montalcini, Tiziana; Maglio, Cristina; Dongiovanni, Paola; Fargion, Silvia; Rametta, Raffaela; Pujia, Arturo; Andersson, Linda; Ghosal, Saswati; Levin, Malin; Wiklund, Olov; Iacovino, Michelina; Borén, Jan; Romeo, Stefano

    2014-01-01

    Retinoids are micronutrients that are stored as retinyl esters in the retina and hepatic stellate cells (HSCs). HSCs are key players in fibrogenesis in chronic liver diseases. The enzyme responsible for hydrolysis and release of retinyl esters from HSCs is unknown and the relationship between retinoid metabolism and liver disease remains unclear. We hypothesize that the patatin-like phospholipase domain-containing 3 (PNPLA3) protein is involved in retinol metabolism in HSCs. We tested our hypothesis both in primary human HSCs and in a human cohort of subjects with non-alcoholic fatty liver disease (N = 146). Here we show that PNPLA3 is highly expressed in human HSCs. Its expression is regulated by retinol availability and insulin, and increased PNPLA3 expression results in reduced lipid droplet content. PNPLA3 promotes extracellular release of retinol from HSCs in response to insulin. We also show that purified wild-type PNPLA3 hydrolyzes retinyl palmitate into retinol and palmitic acid. Conversely, this enzymatic activity is markedly reduced with purified PNPLA3 148M, a common mutation robustly associated with liver fibrosis and hepatocellular carcinoma development. We also find the PNPLA3 I148M genotype to be an independent (P = 0.009 in a multivariate analysis) determinant of circulating retinol-binding protein 4, a reliable proxy for retinol levels in humans. This study identifies PNPLA3 as a lipase responsible for retinyl-palmitate hydrolysis in HSCs in humans. Importantly, this indicates a potential novel link between HSCs, retinoid metabolism and PNPLA3 in determining the susceptibility to chronic liver disease. PMID:24670599

  19. Hepatitis B viral core protein disrupts human host gene expression by binding to promoter regions

    Directory of Open Access Journals (Sweden)

    Guo Yanhai

    2012-10-01

    Full Text Available Abstract Background The core protein (HBc of hepatitis B virus (HBV has been implicated in the malignant transformation of chronically-infected hepatocytes and displays pleiotropic functions, including RNA- and DNA-binding activities. However, the mechanism by which HBc interacts with the human genome to exert effects on hepatocyte function remains unknown. This study investigated the distribution of HBc binding to promoters in the human genome and evaluated its effects on the related genes’ expression. Results Whole-genome chromatin immunoprecipitation microarray (ChIP-on-chip analysis was used to identify HBc-bound human gene promoters. Gene Ontology and pathway analyses were performed on related genes. The quantitative polymerase chain reaction assay was used to verify ChIP-on-chip results. Five novel genes were selected for luciferase reporter assay evaluation to assess the influence of HBc promoter binding. The HBc antibody immunoprecipitated approximately 3100 human gene promoters. Among these, 1993 are associated with known biological processes, and 2208 regulate genes with defined molecular functions. In total, 1286 of the related genes mediate primary metabolic processes, and 1398 encode proteins with binding activity. Sixty-four of the promoters regulate genes related to the mitogen-activated protein kinase (MAPK pathways, and 41 regulate Wnt/beta-catenin pathway genes. The reporter gene assay indicated that HBc binding up-regulates proto-oncogene tyrosine-protein kinase (SRC, type 1 insulin-like growth factor receptor (IGF1R, and neurotrophic tyrosine kinase receptor 2 (NTRK2, and down-regulates v-Ha-ras Harvey rat sarcoma viral oncogene (HRAS. Conclusion HBc has the ability to bind a large number of human gene promoters, and can disrupt normal host gene expression. Manipulation of the transcriptional profile in HBV-infected hepatocytes may represent a key pathogenic mechanism of HBV infection.

  20. In vivo activity of a mixture of two human monoclonal antibodies (anti-HBs) in a chronic hepatitis B virus carrier chimpanzee

    NARCIS (Netherlands)

    R. Heijtink; W. Paulij; P.A.C. van Bergen (Patrick); M.H. van Roosmalen (Mark); D. Rohm; B. Eichentopf; E. Muchmore; A.D.M.E. Osterhaus (Albert); R.A. de Man (Robert)

    1999-01-01

    textabstractA 35-year-old female hepatitis B virus carrier chimpanzee was infused with one dose of a mixture of human monoclonal antibodies 9H9 and 4-7B (antibodies against hepatitis B virus surface antigen; HBsAg). Blood samples were taken before and up to 3 weeks

  1. Analysis of antiviral response in human epithelial cells infected with hepatitis E virus.

    Directory of Open Access Journals (Sweden)

    Pradip B Devhare

    Full Text Available Hepatitis E virus (HEV is a major cause of enterically transmitted acute hepatitis in developing nations and occurs in sporadic and epidemic forms. The disease may become severe with high mortality (20% among pregnant women. Due to lack of efficient cell culture system and small animal model, early molecular events of HEV infection are not yet known. In the present study, human lung epithelial cells, A549, were infected with HEV to monitor expression levels of genes/proteins in antiviral pathways. Both live and UV inactivated virus elicited robust induction of inflammatory cytokines/chemokines such as IL-6, IL-8, TNF-α, and RANTES within 12 h of infection. Cells exposed to soluble capsid protein showed no induction suggesting the capsid structure and not the protein being detected as the pathogen pattern by cells. A delayed up-regulation of type I interferon genes only by the live virus at 48 h post HEV infection indicated the need of virus replication. However, absence of secreted interferons till 96 h suggested possible involvement of post-transcriptional regulation of type I IFN expression. HEV infected cells showed activation of both NF-κB and IRF3 transcription factors when seen at protein levels; however, reporter gene assays showed predominant expression via NF-κB promoter as compared to IRF3 promoter. Knockdown experiments done using siRNAs showed involvement of MyD88 and TRIF adaptors in generating antiviral response thus indicating role of TLR2, TLR4 and TLR3 in sensing viral molecules. MAVS knockdown surprisingly enhanced only proinflammatory cytokines and not type I IFNs. This suggested that HEV not only down-regulates RIG-I helicase like receptor mediated IFN induction but also employs MAVS in curtailing host inflammatory response. Our findings uncover an early cellular response in HEV infection and associated molecular mechanisms suggesting the potential role of inflammatory response triggered by HEV infection in host immune

  2. Mutations in human CPO gene predict clinical expression of either hepatic hereditary coproporphyria or erythropoietic harderoporphyria.

    Science.gov (United States)

    Schmitt, Caroline; Gouya, Laurent; Malonova, Eva; Lamoril, Jérôme; Camadro, Jean-Michel; Flamme, Magali; Rose, Christian; Lyoumi, Said; Da Silva, Vasco; Boileau, Catherine; Grandchamp, Bernard; Beaumont, Carole; Deybach, Jean-Charles; Puy, Hervé

    2005-10-15

    Hereditary coproporphyria (HCP), an autosomal dominant acute hepatic porphyria, results from mutations in the gene that encodes coproporphyrinogen III oxidase (CPO). HCP (heterozygous or rarely homozygous) patients present with an acute neurovisceral crisis, sometimes associated with skin lesions. Four patients (two families) have been reported with a clinically distinct variant form of HCP. In such patients, the presence of a specific mutation (K404E) on both alleles or associated with a null allele, produces a unifying syndrome in which hematological disorders predominate: 'harderoporphyria'. Here, we report the fifth case (from a third family) with harderoporphyria. In addition, we show that harderoporphyric patients exhibit iron overload secondary to dyserythropoiesis. To investigate the molecular basis of this peculiar phenotype, we first studied the secondary structure of the human CPO by a predictive method, the hydrophobic cluster analysis (HCA) which allowed us to focus on a region of the enzyme. We then expressed mutant enzymes for each amino acid of the region of interest, as well as all missense mutations reported so far in HCP patients and evaluated the amount of harderoporphyrin in each mutant. Our results strongly suggest that only a few missense mutations, restricted to five amino acids encoded by exon 6, may accumulate significant amounts of harderoporphyrin: D400-K404. Moreover, all other type of mutations or missense mutations mapped elsewhere throughout the CPO gene, lead to coproporphyrin accumulation and subsequently typical HCP. Our findings, reinforced by recent crystallographic results of yeast CPO, shed new light on the genetic predisposition to HCP. It represents a first monogenic metabolic disorder where clinical expression of overt disease is dependent upon the location and type of mutation, resulting either in acute hepatic or in erythropoietic porphyria.

  3. Peromyscus as a model system for human hepatitis C: An opportunity to advance our understanding of a complex host parasite system.

    Science.gov (United States)

    Vandegrift, Kurt J; Critchlow, Justin T; Kapoor, Amit; Friedman, David A; Hudson, Peter J

    2017-01-01

    Worldwide, there are 185 million people infected with hepatitis C virus and approximately 350,000 people die each year from hepatitis C associated liver diseases. Human hepatitis C research has been hampered by the lack of an appropriate in vivo model system. Most of the in vivo research has been conducted on chimpanzees, which is complicated by ethical concerns, small sample sizes, high costs, and genetic heterogeneity. The house mouse system has led to greater understanding of a wide variety of human pathogens, but it is unreasonable to expect Mus musculus to be a good model system for every human pathogen. Alternative animal models can be developed in these cases. Ferrets (influenza), cotton rats (human respiratory virus), and woodchucks (hepatitis B) are all alternative models that have led to a greater understanding of human pathogens. Rodent models are tractable, genetically amenable and inbred and outbred strains can provide homogeneity in results. Recently, a rodent homolog of hepatitis C was discovered and isolated from the liver of a Peromyscus maniculatus. This represents the first small mammal (mouse) model system for human hepatitis C and it offers great potential to contribute to our understanding and ultimately aid in our efforts to combat this serious public health concern. Peromyscus are available commercially and can be used to inform questions about the origin, transmission, persistence, pathology, and rational treatment of hepatitis C. Here, we provide a disease ecologist's overview of this new virus and some suggestions for useful future experiments. Copyright © 2016. Published by Elsevier Ltd.

  4. The role of human papillomaviruses in anogenital cancers.

    Science.gov (United States)

    Melbye, M; Frisch, M

    1998-08-01

    There is substantial evidence to suggest that common risk factors exist for cancer of the cervix and other anogenital cancers. Cervical cancer has been etiologically linked with venereal types of human papillomavirus (HPV) and the same types of HPV are being found in other anogenital tissues. The question is to what extent these HPV types may also contribute to carcinogenesis in anogenital cancer other than cervical cancer. In this review some general aspects of the natural history of HPV are presented followed by a description of the incidence and risk factors for anal, vulvar, and penile cancer. Main focus is given to the evidence for an association between these cancers and HPV.

  5. Primary liver cancer deaths and related years of life lost attributable to hepatitis B and C viruses in India.

    Science.gov (United States)

    Islami, Farhad; Dikshit, Rajesh; Mallath, Mohandas K; Jemal, Ahmedin

    2016-02-01

    More than 25,000 people die of liver cancer annually in India. There is little information about the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to these deaths. We conducted a systematic review of published studies on HBV or HCV infection and liver cancer in India and estimated the population attributable fraction (PAF) of liver cancer deaths caused by these infections and the corresponding annual number of deaths and years of life lost (YLL) in the country. We searched the PubMed and Scopus databases, as well as the reference list of relevant articles in the systematic review. For calculation of the number of liver cancer deaths attributable to HBV and HCV, we used two sources of outcome data and two relative risks for the association between HCV and liver cancer. The PAF was 67% for HBV, 17-19% for HCV, and 71-72% for HBV and/or HCV. The annual attributable number of liver cancer deaths was approximately 17,000 for HBV; 4500 for HCV; and 18,500 for HBV and/or HCV, corresponding to approximately 297,000, 75,000, and 315,000 YLL, respectively. There was little difference in these numbers using the two sources of outcome data or the two risk estimates for HCV. Our findings underscore the importance of primary prevention of HBV and HCV by appropriate measures, including vaccination (HBV only), prevention of transfusion-related infections, and increased awareness of the routes of transmission and long-term health outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Human immunodeficiency virus (HIV) seropositivity and hepatitis B surface antigenemia (HBSAG) among blood donors in Benin city, Edo state, Nigeria.

    Science.gov (United States)

    Umolu, Patience Idia; Okoror, Lawrence Ehis; Orhue, Philip

    2005-03-01

    Human Immunodeficiency Virus and Hepatitis B virus are blood borne pathogens that can be transmitted through blood transfusion and could pose a huge problem in areas where mechanisms of ensuring blood safety are suspect. This study became necessary in a population where most of the blood for transfusion is from commercial blood donors. A total of 130 donors comprising 120 commercial donors and 10 voluntary donors were tested for antibodies to human immunodeficiency virus and hepatitis B surface antigen in Benin city using Immunocomb HIV - 1 and 2 Biospot kit and Quimica Clinica Aplicada direct latex agglutination method respectively. Thirteen (10%) samples were HIV seropositive and 7(5.8%) were HBsAg positive. The age bracket 18 - 25years had the highest numbers of donors and also had the highest number of HBsAg positive cases (7.8%) while the age group 29 - 38years had highest number of HIV seropositive cases. High prevalence of HIV antibodies and Hepatitis B surface antigen was found among commercial blood donors. Appropriate and compulsory screening of blood donors using sensitive methods, must be ensured to prevent post transfusion hepatitis and HIV.

  7. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis.

    Science.gov (United States)

    Koliaki, Chrysi; Szendroedi, Julia; Kaul, Kirti; Jelenik, Tomas; Nowotny, Peter; Jankowiak, Frank; Herder, Christian; Carstensen, Maren; Krausch, Markus; Knoefel, Wolfram Trudo; Schlensak, Matthias; Roden, Michael

    2015-05-05

    The association of hepatic mitochondrial function with insulin resistance and non-alcoholic fatty liver (NAFL) or steatohepatitis (NASH) remains unclear. This study applied high-resolution respirometry to directly quantify mitochondrial respiration in liver biopsies of obese insulin-resistant humans without (n = 18) or with (n = 16) histologically proven NAFL or with NASH (n = 7) compared to lean individuals (n = 12). Despite similar mitochondrial content, obese humans with or without NAFL had 4.3- to 5.0-fold higher maximal respiration rates in isolated mitochondria than lean persons. NASH patients featured higher mitochondrial mass, but 31%-40% lower maximal respiration, which associated with greater hepatic insulin resistance, mitochondrial uncoupling, and leaking activity. In NASH, augmented hepatic oxidative stress (H2O2, lipid peroxides) and oxidative DNA damage (8-OH-deoxyguanosine) was paralleled by reduced anti-oxidant defense capacity and increased inflammatory response. These data suggest adaptation of the liver ("hepatic mitochondrial flexibility") at early stages of obesity-related insulin resistance, which is subsequently lost in NASH. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Effects of radiation from a radiofrequency identification (RFID) microchip on human cancer cells.

    Science.gov (United States)

    Lai, Henry C; Chan, Ho Wing; Singh, Narendra P

    2016-01-01

    Radiofrequency identification (RFID) microchips are used to remotely identify objects, e.g. an animal in which a chip is implanted. A passive RFID microchip absorbs energy from an external source and emits a radiofrequency identification signal which is then decoded by a detector. In the present study, we investigated the effect of the radiofrequency energy emitted by a RFID microchip on human cancer cells. Molt-4 leukemia, BT474 breast cancer, and HepG2 hepatic cancer cells were exposed in vitro to RFID microchip-emitted radiofrequency field for 1 h. Cells were counted before and after exposure. Effects of pretreatment with the spin-trap compound N-tert-butyl-alpha-phenylnitrone or the iron-chelator deferoxamine were also investigated. Results We found that the energy effectively killed/retarded the growth of the three different types of cancer cells, and the effect was blocked by the spin-trap compound or the iron-chelator, whereas an inactive microchip and energy from the external source had no significant effect on the cells. Conclusions Data of the present study suggest that radiofrequency field from the microchip affects cancer cells via the Fenton Reaction. Implantation of RFID microchips in tumors may provide a new method for cancer treatment.

  9. Persistence of hepatitis C virus in a white population: associations with human leukocyte antigen class 1.

    LENUS (Irish Health Repository)

    Fanning, Liam J

    2012-02-03

    The aim of this study was to define novel associations between human leukocyte antigen (HLA) class 1 alleles and persistence or clearance of the hepatitis C virus (HCV) in a white population. All individuals in the study were seropositive for anti-HCV antibodies. Viral status was determined by the Roche HCV Amplicor test. HLA-A, -B, -C allelic group profile was molecularly defined by reverse line probe hybridization. The strongest individual allelic group associations with persistent HCV infection were HLA A*11 (p = 0.044) and Cw*04 (p = 0.006). However, only the HLA C*04 association survived correction for multiple comparisons. Further analysis of alleles in linkage with HLA Cw*04 revealed that the haplotype HLA A*11, Cw*04 was present in 11 individuals, 10 of whom were viremic (p = 0.05). No gene dosage effect was observed. No association between HLA class 1 allelic groups and aviremia and virus load was evident in this white population. HLA B*44 is associated with low virus load in human immunodeficiency virus disease, but this association was not evident in this HCV-infected population. Novel HLA class 1 alleles associated with persistence of HCV have been identified.

  10. Dried human skin fibroblasts as a new substratum for functional culture of hepatic cells.

    Science.gov (United States)

    Wencel, Agnieszka; Zakrzewska, Karolina Ewa; Samluk, Anna; Noszczyk, Bartłomiej Henryk; Pijanowska, Dorota Genowefa; Pluta, Krzysztof Dariusz

    2017-01-01

    The primary hepatocytes culture is still one of the main challenges in toxicology studies in the drug discovery process, development of in vitro models to study liver function, and cell-based therapies. Isolated hepatocytes display a rapid decline in viability and liver-specific functions including albumin production, conversion of ammonia to urea, and activity of the drug metabolizing enzymes. A number of methods have been developed in order to maintain hepatocytes in their highly differentiated state in vitro. Optimization of culture conditions includes a variety of media formulations and supplements, growth surface coating with the components of extracellular matrix or with synthetic polymers, three-dimensional growth scaffolds and decellularized tissues, and coculture with other cell types required for the normal cell-cell interactions. Here we propose a new substratum for hepatic cells made by drying confluent human skin fibroblasts' culture. This growth surface coating, prepared using maximally simplified procedure, combines the advantages of the use of extracellular matrices and growth factors/cytokines secreted by the feeder layer cells. In comparison to the hepatoma cells grown on a regular tissue culture plastic, cells cultured on the dried fibroblasts were able to synthesize albumin in larger quantities and to form greater number of apical vacuoles. Unlike the coculture with the living feeder layer cells, the number of cells grown on the new substratum was not reduced after fourteen days of culture. This fact could make the dried fibroblasts coating an ideal candidate for the substrate for non-dividing human hepatocytes.

  11. Endogenous retroviral promoter exaptation in human cancer

    Directory of Open Access Journals (Sweden)

    Artem Babaian

    2016-12-01

    Full Text Available Abstract Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.

  12. Replicating poxviruses for human cancer therapy.

    Science.gov (United States)

    Kim, Manbok

    2015-04-01

    Naturally occurring oncolytic viruses are live, replication-proficient viruses that specifically infect human cancer cells while sparing normal cell counterparts. Since the eradication of smallpox in the 1970s with the aid of vaccinia viruses, the vaccinia viruses and other genera of poxviruses have shown various degrees of safety and efficacy in pre-clinical or clinical application for human anti-cancer therapeutics. Furthermore, we have recently discovered that cellular tumor suppressor genes are important in determining poxviral oncolytic tropism. Since carcinogenesis is a multi-step process involving accumulation of both oncogene and tumor suppressor gene abnormalities, it is interesting that poxvirus can exploit abnormal cellular tumor suppressor signaling for its oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ATM, and RB are known to play important roles in genomic fidelity/maintenance. Thus, tumor suppressor gene abnormality could affect host genomic integrity and likely disrupt intact antiviral networks due to accumulation of genetic defects, which would in turn result in oncolytic virus susceptibility. This review outlines the characteristics of oncolytic poxvirus strains, including vaccinia, myxoma, and squirrelpox virus, recent progress in elucidating the molecular connection between oncogene/tumor suppressor gene abnormalities and poxviral oncolytic tropism, and the associated preclinical/clinical implications. I would also like to propose future directions in the utility of poxviruses for oncolytic virotherapy.

  13. Increased incidence of cancer observed in HIV/hepatitis C virus-coinfected patients versus HIV-monoinfected.

    Science.gov (United States)

    Meijide, Héctor; Pértega, Sonia; Rodríguez-Osorio, Iria; Castro-Iglesias, Ángeles; Baliñas, Josefa; Rodríguez-Martínez, Guillermo; Mena, Álvaro; Poveda, Eva

    2017-05-15

    Cancer is a growing problem in persons living with HIV infection (PLWH) and hepatitis C virus (HCV) coinfection could play an additional role in carcinogenesis. Herein, all cancers in an HIV-mono and HIV/HCV-coinfected cohort were evaluated and compared to identify any differences between these two populations. A retrospective cohort study was conducted including all cancers in PLWH between 1993 and 2014. Cancers were classified in two groups: AIDS-defining cancer (ADC) and non-AIDS-defining cancer (NADC). Cancer incidence rates were calculated and compared with that observed in the Spanish general population (GLOBOCAN, 2012), computing the standardized incidence ratios (SIRs). A competing risk approach was used to estimate the probability of cancer after HIV diagnosis. Cumulative incidence in HIV-monoinfected and HIV/HCV-coinfected patients was also compared using multivariable analysis. A total of 185 patients (117 HIV-monoinfected and 68 HIV/HCV) developed cancer in the 26 580 patient-years cohort, with an incidence rate of 696 cancers per 100 000 person-years, higher than in the general population (SIR = 3.8). The incidence rate of NADC in HIV/HCV-coinfected patients was 415.0 (SIR = 3.4), significantly higher than in monoinfected (377.3; SIR = 1.8). After adjustments, HIV/HCV-coinfected patients had a higher cumulative incidence of NADC than HIV-monoinfected (adjusted hazard ratio = 1.80), even when excluding hepatocellular carcinomas (adjusted hazard ratio = 1.26). PLWH have a higher incidence of NADC than the general population and HCV-coinfection is associated with a higher incidence of NADC. These data justify the need for prevention strategies in these two populations and the importance of eradicating HCV.

  14. Postoperative radiotherapy dose correlates with locoregional control in patients with extra-hepatic bile duct cancer

    Energy Technology Data Exchange (ETDEWEB)

    Im, Jung Ho; Seong, Jinsil; Lee, Jeong Shim; Kim, Yong Bae; Kim, Kyung Sik; Lee, Woo Jung [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Ik Jae; Park, Jun Sung; Yoon, Dong Sup [Sangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival. Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%). The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (≥50 Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively). In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection.

  15. Prediction of human drug clearance by multiple metabolic pathways: integration of hepatic and intestinal microsomal and cytosolic data.

    Science.gov (United States)

    Cubitt, Helen E; Houston, J Brian; Galetin, Aleksandra

    2011-05-01

    The current study assesses hepatic and intestinal glucuronidation, sulfation, and cytochrome P450 (P450) metabolism of raloxifene, quercetin, salbutamol, and troglitazone using different in vitro systems. The fraction metabolized by conjugation and P450 metabolism was estimated in liver and intestine, and the importance of multiple metabolic pathways on accuracy of clearance prediction was assessed. In vitro intrinsic sulfation clearance (CL(int, SULT)) was determined in human intestinal and hepatic cytosol and compared with hepatic and intestinal microsomal glucuronidation (CL(int, UGT)) and P450 clearance (CL(int, CYP)) expressed per gram of tissue. Hepatic and intestinal cytosolic scaling factors of 80.7 mg/g liver and 18 mg/g intestine were estimated from published data. Scaled CL(int, SULT) ranged between 0.7 and 11.4 ml · min(-1) · g(-1) liver and 0.1 and 3.3 ml · min(-1) · g(-1) intestine (salbutamol and quercetin were the extremes). Salbutamol was the only compound with a high extent of sulfation (51 and 28% of total CL(int) for liver and intestine, respectively) and also significant renal clearance (26-57% of observed plasma clearance). In contrast, the clearance of quercetin was largely accounted for by glucuronidation. Drugs metabolized by multiple pathways (raloxifene and troglitazone) demonstrated improved prediction of intravenous clearance using data from all hepatic pathways (44-86% of observed clearance) compared with predictions based only on the primary pathway (22-36%). The assumption of no intestinal first pass resulted in underprediction of oral clearance for raloxifene, troglitazone, and quercetin (3-22% of observed, respectively). Accounting for the intestinal contribution to oral clearance via estimated intestinal availability improved prediction accuracy for raloxifene and troglitazone (within 2.5-fold of observed). Current findings emphasize the importance of both hepatic and intestinal conjugation for in vitro-in vivo extrapolation

  16. Whole-liver radiotherapy for end-stage colorectal cancer patients with massive liver metastases and advanced hepatic dysfunction

    Directory of Open Access Journals (Sweden)

    Kim Sun Young

    2010-10-01

    Full Text Available Abstract Background To investigate whether whole-liver radiotherapy (RT is beneficial in end-stage colorectal cancer with massive liver metastases and severe hepatic dysfunction. Methods Between June 2004 and July 2008, 10 colorectal cancer patients, who exhibited a replacement of over three quarters of their normal liver by metastatic tumors and were of Child-Pugh class B or C in liver function with progressive disease after undergoing chemotherapy, underwent whole-liver RT. RT was administered using computed tomography-based three-dimensional planning and the median dose was 21 Gy (range, 21-30 in seven fractions. Improvement in liver function tests, defined as a decrease in the levels within 1 month after RT, symptom palliation, toxicity, and overall survival were analyzed retrospectively. Results Levels of alkaline phosphatase, total bilirubin, aspartate transaminase, and alanine transaminase improved in 8, 6, 9, and all 10 patients, respectively, and the median reduction rates were 42%, 68%, 50%, and 57%, respectively. Serum carcinoembryonic antigen level decreased after RT in three of four assessable patients. For all patients, pain levels decreased and acute toxicity consisted of nausea/vomiting of grade ≤ 2. Further chemotherapy became possible in four of 10 patients. Mean survival after RT was 80 ± 80 days (range, 20-289; mean survival for four patients who received post-RT chemotherapy was 143 ± 100 days (range, 65-289, versus 38 ± 16 days (range, 20-64 for the six patients who did not receive post-RT chemotherapy (p = 0.127. Conclusions Although limited by small case number, this study demonstrated a possible role of whole-liver RT in improving hepatic dysfunction and delaying mortality from hepatic failure for end-stage colorectal cancer patients with massive liver metastases. Further studies should be followed to confirm these findings.

  17. Long-term Effects of Hepatitis B Immunization of Infants in Preventing Liver Cancer.

    Science.gov (United States)

    Chang, Mei-Hwei; You, San-Lin; Chen, Chien-Jen; Liu, Chun-Jen; Lai, Ming-Wei; Wu, Tzee-Chung; Wu, Shu-Fen; Lee, Chuan-Mo; Yang, Sheng-Shun; Chu, Heng-Cheng; Wang, Tsang-Eng; Chen, Bor-Wen; Chuang, Wan-Long; Soon, Maw-Soan; Lin, Ching-Yih; Chiou, Shu-Ti; Kuo, Hsu-Sung; Chen, Ding-Shinn

    2016-09-01

    The incidence of hepatocellular carcinoma (HCC) increases with age, but protective antibody responses decrease with time after infants are immunized against hepatitis B virus (HBV). We investigated whether immunization of infants against HBV prevents their developing HCC as adults. We also searched for strategies to maximize the cancer-preventive effects. We collected data from 2 Taiwan HCC registry systems on 1509 patients (6-26 years old) diagnosed with HCC from 1983 through 2011. Data on history of HBV immunization and prenatal maternal levels of HBV antigens of all HCC patients born after July 1984 were retrieved from the HBV immunization data bank of the Taiwan Center for Disease Control. We collected data on birth cohort-specific populations (6-26 years old) of Taiwan using the National Household Registry System. Rates of HCC incidence per 10(5) person-years were derived by dividing the number of patients with HCC by the person-years of the general population. Relative risks (RR) for HCC were estimated by Poisson regression analysis in vaccinated vs unvaccinated birth cohorts. We stratified patients by age group to evaluate the association of birth cohorts and HCC risks. Of the 1509 patients with HCC, 1343 were born before, and 166 were born after, the HBV vaccination program began. HCC incidence per 10(5) person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. The RRs for HCC in patients 6-9 years old, 10-14 years old, 15-19 years old, and 20-26 years old who were vaccinated vs unvaccinated were 0.26 (95% confidence interval [CI], 0.17-0.40), 0.34 (95% CI, 0.25-0.48), 0.37 (95% CI, 0.25-0.51), and 0.42 (95% CI, 0.32-0.56), respectively. The RR for HCC in 6- to 26-year-olds was lower in the later vs the earlier cohorts (born in 1992-2005 vs 1986-1992; P liver cancer. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples

    Directory of Open Access Journals (Sweden)

    Robim M. Rodrigues

    2016-06-01

    Full Text Available This data set is composed of transcriptomics analyses of (i liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF and (ii hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC. Data from primary human hepatocytes was also added to the data set “Open TG-GATEs: a large-scale toxicogenomics database” (Igarashi et al., 2015 [1]. Changes in gene expression due to acetaminophen intoxication as well as comparative information between human in vivo and in vitro samples are provided. The microarray data have been deposited in NCBI׳s Gene Expression Omnibus and are accessible through GEO Series accession number GEO: GSE74000. The provided data is used to evaluate the predictive capacity of each hepatic in vitro system and can be directly compared with large-scale publically available toxicogenomics databases. Further interpretation and discussion of these data feature in the corresponding research article “Toxicogenomics-based prediction of acetaminophen-induced liver injury using human hepatic cell systems” (Rodrigues et al., 2016 [2].

  19. Novel resveratrol-based substrates for human hepatic, renal, and intestinal UDP-glucuronosyltransferases.

    Science.gov (United States)

    Greer, Aleksandra K; Madadi, Nikhil R; Bratton, Stacie M; Eddy, Sarah D; Mazerska, Zofia; Hendrickson, Howard P; Crooks, Peter A; Radominska-Pandya, Anna

    2014-04-21

    Trans-Resveratrol (tRes) has been shown to have powerful antioxidant, anti-inflammatory, anticarcinogenic, and antiaging properties; however, its use as a therapeutic agent is limited by its rapid metabolism into its conjugated forms by UDP-glucuronosyltransferases (UGTs). The aim of the current study was to test the hypothesis that the limited bioavailability of tRes can be improved by modifying its structure to create analogs which would be glucuronidated at a lower rate than tRes itself. In this work, three synthetic stilbenoids, (E)-3-(3-hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)acrylic acid (NI-12a), (E)-2,4-dimethoxy-6-(4-methoxystyryl)benzaldehyde oxime (NI-ST-05), and (E)-4-(3,5-dimethoxystyryl)-2,6-dinitrophenol (DNR-1), have been designed based on the structure of tRes and synthesized in our laboratory. UGTs recognize and glucuronidate tRes at each of the 3 hydroxyl groups attached to its aromatic rings. Therefore, each of the above compounds was designed with the majority of the hydroxyl groups blocked by methylation and the addition of other novel functional groups as part of a drug optimization program. The activities of recombinant human UGTs from the 1A and 2B families were examined for their capacity to metabolize these compounds. Glucuronide formation was identified using HPLC and verified by β-glucuronidase hydrolysis and LC-MS/MS analysis. NI-12a was glucuronidated at both the -COOH and -OH functions, NI-ST-05 formed a novel N-O-glucuronide, and no product was observed for DNR-1. NI-12a is primarily metabolized by the hepatic and renal enzyme UGT1A9, whereas NI-ST-05 is primarily metabolized by an extrahepatic enzyme, UGT1A10, with apparent Km values of 240 and 6.2 μM, respectively. The involvement of hepatic and intestinal UGTs in the metabolism of both compounds was further confirmed using a panel of human liver and intestinal microsomes, and high individual variation in activity was demonstrated between donors. In summary, these

  20. Co‑infections of hepatitis B and C with human immunodeficiency ...

    African Journals Online (AJOL)

    2015-01-04

    sectional study was carried out on 342 ... Patients' sera were screened for hepatitis B surface antigen (HBsAg) and anti‑hepatitis C virus (HCV) using immunochromatographic‑based kits. Clinical stage of HIV and CD4+ cell ...

  1. Acute hypoxia and cytochrome P450-mediated hepatic drug metabolism in humans

    DEFF Research Database (Denmark)

    Jürgens, Gesche; Christensen, Hanne Rolighed; Brøsen, Kim

    2002-01-01

    Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes.......Our objective was to investigate the effect of acute hypoxia on the activity of hepatic cytochrome P450 (CYP) enzymes....

  2. PKCδ regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans

    DEFF Research Database (Denmark)

    Bezy, Olivier; Tran, Thien T; Pihlajamäki, Jussi

    2011-01-01

    and circulating triglycerides. Mice with global or liver-specific inactivation of the Prkcd gene displayed increased hepatic insulin signaling and reduced expression of gluconeogenic and lipogenic enzymes. This resulted in increased insulin-induced suppression of hepatic gluconeogenesis, improved glucose...

  3. Molecular status of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus among transgender commercial sex workers in Surakarta, Indonesia

    Science.gov (United States)

    Prasetyo, Afiono Agung; Sari, Yulia; Dharmawan, Ruben; Marwoto

    2017-02-01

    Sexual contact and other risk behavior among transgender working as commercial sex workers are important factors for sexual and blood-borne virus (BBV) infections. However, there no data concerning the molecular status of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) circulated among transgender working as commercial sex workers. Blood samples obtained from transgender working as commercial sex workers in Surakarta were examined for HIV antibodies, HBsAg and HCV antibodies, respectively, by immunological assays. All blood samples were also subjected for viral nucleic acid extraction and molecular detection of HIV, HBV and HCV by nested RT-PCR. The PCR products were purified from agarose gels, and the nucleotide sequences were retrieved and molecular analyzed. HIV, HBV and HCV was detected in 26.9% (7/26), 19.2% (5/26) and 46.2% (12/26), respectively. HIV CRF01_AE and B were found to be circulating in the community. HBV genotype B3 predominated, followed by C1. HCV genotype 1a predominated among HCV-infected transgender working as commercial sex workers, followed by 1c, 3a, and 4a. HIV, HBV, and HCV were found circulating in the transgender working as commercial sex workers in Surakarta, Indonesia.

  4. Human immunodeficiency virus, hepatitis B and hepatitis C in an Indonesian prison: prevalence, risk factors and implications of HIV screening.

    Science.gov (United States)

    Nelwan, Erni J; Van Crevel, Reinout; Alisjahbana, Bachti; Indrati, Agnes K; Dwiyana, Reiva F; Nuralam, Nisaa; Pohan, Herdiman T; Jaya, Ilham; Meheus, Andre; Van Der Ven, Andre

    2010-12-01

    To determine the prevalence and behavioural correlates of HIV, HBV and HCV infections among Indonesian prisoners and to examine the impact of voluntary counselling and testing for all incoming prisoners on access to antiretroviral treatment (ART). In a non-anonymous survey in an Indonesian prison for drug-related offences, all incoming prisoners and symptomatic resident prisoners were counselled and offered testing for HIV, hepatitis B and C. Screening was performed in 679 incoming prisoners, of whom 639 (94.1%) agreed to be tested, revealing a seroprevalence of 7.2% (95% CI 5.2-9.2) for HIV, 5.8% (95% CI 3.9-7.6) for HBsAg and 18.6% (95% CI 15.5-21.6) for HCV. Of 57 resident prisoners tested, 29.8% were HIV-positive. HIV infection was strongly associated with injecting drug use (IDU; P prisoners was responsible for diagnosing and treating HIV in 73.0%, respectively, and 68.0% of HIV-positive individuals. HIV and HCV are highly prevalent among incoming Indonesian prisoners and almost entirely explained by IDU. Our study is the first to show that voluntary HIV counselling and testing during the intake process in prison may greatly improve access to ART in a developing country. © 2010 Blackwell Publishing Ltd.

  5. Protection against aflatoxin B1-induced hepatic toxicity as short-term screen of cancer chemopreventive dithiolethiones.

    Science.gov (United States)

    Maxuitenko, Y Y; Curphey, T J; Kensler, T W; Roebuck, B D

    1996-08-01

    Dithiolethiones are an important class of cancer chemopreventive agents. More than 50 new dithiolethione analogs were synthesized for structure-activity studies. Using selected dithiolethiones, studies were designed to measure protection against the hepatotoxicity of aflatoxin B1 (AFB1) and relate it to the protection against carcinogenicity. Young male F344 rats were pretreated with 0.1 or 0.3 mmol dithiolethiones/kg body wt and challenged with toxic doses of AFB1 (50 micrograms/100 g rat/day) on 2 successive days. One day later, the protection from hepatotoxicity was assessed by measuring serum hepatic enzymes, hepatic necrosis, and degree of bile duct cell proliferation. The ability of these dithiolethiones to prevent AFB1-induced tumorigenicity was assessed by quantifying the hepatic burden of putative preneoplastic lesions [placental glutathione S-transferase (GST-P)-positive foci]. Significant correlations (p bile duct cell proliferation, r = 0.933). These results imply that inhibition of hepatotoxicity affords protection against hepatocarcinogenicity. The extent of protection from acute hepatotoxicity offers a simple, short-term biological endpoint to screen dithiolethiones and related compounds for their chemopreventive properties.

  6. RNA Editing Modulates Human Hepatic Aryl Hydrocarbon Receptor Expression by Creating MicroRNA Recognition Sequence.

    Science.gov (United States)

    Nakano, Masataka; Fukami, Tatsuki; Gotoh, Saki; Takamiya, Masataka; Aoki, Yasuhiro; Nakajima, Miki

    2016-01-08

    Adenosine to inosine (A-to-I) RNA editing is the most frequent type of post-transcriptional nucleotide conversion in humans, and it is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes. In this study we investigated the effect of RNA editing on human aryl hydrocarbon receptor (AhR) expression because the AhR transcript potentially forms double-stranded structures, which are targets of ADAR enzymes. In human hepatocellular carcinoma-derived Huh-7 cells, the ADAR1 knockdown reduced the RNA editing levels in the 3'-untranslated region (3'-UTR) of the AhR transcript and increased the AhR protein levels. The ADAR1 knockdown enhanced the ligand-mediated induction of CYP1A1, a gene downstream of AhR. We investigated the possibility that A-to-I RNA editing creates miRNA targeting sites in the AhR mRNA and found that the miR-378-dependent down-regulation of AhR was abolished by ADAR1 knockdown. These results indicated that the ADAR1-mediated down-regulation of AhR could be attributed to the creation of a miR-378 recognition site in the AhR 3'-UTR. The interindividual differences in the RNA editing levels within the AhR 3'-UTR in a panel of 32 human liver samples were relatively small, whereas the differences in ADAR1 expression were large (220-fold). In the human liver samples a significant inverse association was observed between the miR-378 and AhR protein levels, suggesting that the RNA-editing-dependent down-regulation of AhR by miR-378 contributes to the variability in the constitutive hepatic expression of AhR. In conclusion, this study uncovered for the first time that A-to-I RNA editing modulates the potency of xenobiotic metabolism in the human liver. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Immunoblotting with Human Native Antigen Shows Stage-Related Sensitivity in the Serodiagnosis of Hepatic Cystic Echinococcosis

    OpenAIRE

    Mariconti, Mara; Bazzocchi, Chiara; Tamarozzi, Francesca; Meroni, Valeria; Genco, Francesca; Maserati, Roberta; Brunetti, Enrico

    2014-01-01

    The diagnosis of hepatic cystic echinococcosis is based on ultrasonography and confirmed by serology. However, no biological marker of cyst viability is currently available implying years-long patient follow-up, which is not always feasible in endemic areas. We characterized the performance of an immunoblotting test based on human hydatid cyst fluid with particular regard to its ability to distinguish between cyst stages. Sera from patients with cysts in different stages showed distinctive ba...

  8. Impact of the timing of hepatitis B virus identification and anti-hepatitis B virus therapy initiation on the risk of adverse liver outcomes for patients receiving cancer therapy.

    Science.gov (United States)

    Hwang, Jessica P; Suarez-Almazor, Maria E; Cantor, Scott B; Barbo, Andrea; Lin, Heather Y; Ahmed, Sairah; Chavez-MacGregor, Mariana; Donato-Santana, Christian; Eng, Cathy; Ferrajoli, Alessandra; Fisch, Michael J; McLaughlin, Peter; Simon, George R; Rondon, Gabriela; Shpall, Elizabeth J; Lok, Anna S

    2017-09-01

    Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]-positive/hepatitis B core antibody [anti-HBc]-positive) or past (HBsAg-negative/anti-HBc-positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients

  9. Acceptability of human papilloma virus vaccine and cervical cancer ...

    African Journals Online (AJOL)

    2012-07-14

    Jul 14, 2012 ... [3] Human papilloma virus (HPV), a sexually transmitted virus has been implicated as the causative agent. ... Acceptability of human papilloma virus vaccine and cervical cancer screening among female ..... IIiyasu Z, Abubakar IS, Aliyu MH, Galadanci HS. Cervical cancer risk perception and predictors of ...

  10. Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II activity in human hepatic cells.

    Science.gov (United States)

    Zhang, Zhuhong; Chen, Si; Mei, Hu; Xuan, Jiekun; Guo, Xiaoqing; Couch, Letha; Dobrovolsky, Vasily N; Guo, Lei; Mei, Nan

    2015-09-30

    Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a 2-year bioassay conducted by the National Toxicology Program. In this study, the DNA damaging effects of Ginkgo biloba leaf extract and many of its constituents were evaluated in human hepatic HepG2 cells and the underlying mechanism was determined. A molecular docking study revealed that quercetin, a flavonoid constituent of Ginkgo biloba, showed a higher potential to interact with topoisomerase II (Topo II) than did the other Ginkgo biloba constituents; this in silico prediction was confirmed by using a biochemical assay to study Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the induction of γ-H2A.X, quercetin, followed by keampferol and isorhamnetin, appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II knockdown cells, DNA damage triggered by Ginkgo biloba leaf extract or quercetin was dramatically decreased, indicating that DNA damage is directly associated with Topo II. DNA damage was also observed when cells were treated with commercially available Ginkgo biloba extract product. Our findings suggest that Ginkgo biloba leaf extract- and quercetin-induced in vitro genotoxicity may be the result of Topo II inhibition.

  11. Hepatitis C and Human Immunodeficiency Virus Kidney Transplantation: The Mount Sinai Experience.

    Science.gov (United States)

    Nair, Vinay; Khaim, Rafael; El-Salem, Fadi; Kent, Rebecca; Lerner, Susan; Berger, Amnon; Miko, Leandra; Rollins, Brett; Ebcioglu, Zeynep; Delaney, Veronica; Sehgal, Vinita; Menon, Madhav; Ames, Scott; Benvenisty, Alan; Wadhera, Vikram; Arvelakas, Antonious; Schiano, Thomas; Rana, Meena; Huprikar, Shirish; Florman, Sander; Shapiro, Ron

    2015-01-01

    Mount Sinai Hospital in New York has a long history in the field of organ transplantation. The first kidney transplant at Mount Sinai was performed in 1967 by the late Dr. Lewis Burrows and the first laparoscopic donor nephrectomy in New York was performed at Mount Sinai in 1996. Over 3000 kidney transplantations have been performed at Mount Sinai. In the early 1990s, the first hepatitis C virus (HCV) positive patient at Mount Sinai underwent a kidney transplant and the first kidney transplant in a patient with human immunodeficiency virus (HIV) in New York was performed at Mount Sinai in 2001. In general, these patients have done well after renal transplantation, with outcomes similar to those seen in non-infected patients. This chapter will describe the evolution of immunosuppressive regimens in HCV positive and HIV positive patients, and will describe the outcomes of kidney transplantation in these patients. Given the favorable outcomes, it is reasonable to continue to offer renal transplantation as a treatment for end stage renal disease patients with HCV and/or HIV. Copyright© 2016 by the Terasaki Foundation Laboratory.

  12. The depuration dynamics of oysters (Crassostrea gigas artificially contaminated with hepatitis A virus and human adenovirus

    Directory of Open Access Journals (Sweden)

    Adriana de Abreu Corrêa

    2012-02-01

    Full Text Available Within the country of Brazil, Santa Catarina is a major shellfish producer. Detection of viral contamination is an important step to ensure production quality and consumer safety during this process. In this study, we used a depuration system and ultraviolet (UV disinfection to eliminate viral pathogens from artificially infected oysters and analysed the results. Specifically, the oysters were contaminated with hepatitis A virus (HAV or human adenovirus type 5 (HAdV5. After viral infection, the oysters were placed into a depuration tank and harvested after 48, 72 and 96 h. After sampling, various oyster tissues were dissected and homogenised and the viruses were eluted with alkaline conditions and precipitated with polyethylene glycol. The oyster samples were evaluated by cell culture methods, as well as polymerase chain reaction (PCR and quantitative-PCR. Moreover, at the end of the depuration period, the disinfected seawater was collected and analysed by PCR. The molecular assays showed that the HAdV5 genome was present in all of the depuration time samples, while the HAV genome was undetectable after 72 h of depuration. However, viral viability tests (integrated cell culture-PCR and immunofluorescence assay indicated that both viruses were inactivated with 96 h of seawater recirculation. In conclusion, after 96 h of UV treatment, the depuration system studied in this work purified oysters that were artificially contaminated with HAdV5 and HAV.

  13. Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Clément Guillot

    Full Text Available Hepatitis B virus (HBV infection remains a major public health concern worldwide with 240 million individuals chronically infected and at risk of developing cirrhosis and hepatocellular carcinoma. Current treatments rarely cure chronic hepatitis B infection, highlighting the need for new anti-HBV drugs. Nucleic acid polymers (NAPs are phosphorothioated oligonucleotides that have demonstrated a great potential to inhibit infection with several viruses. In chronically infected human patients, NAPs administration lead to a decline of blood HBsAg and HBV DNA and to HBsAg seroconversion, the expected signs of functional cure. NAPs have also been shown to prevent infection of duck hepatocytes with the Avihepadnavirus duck hepatitis B virus (DHBV and to exert an antiviral activity against established DHBV infection in vitro and in vivo. In this study, we investigated the specific anti-HBV antiviral activity of NAPs in the HepaRG human hepatoma cell line and primary cultures of human hepatocytes. NAPs with different chemical features (phosphorothioation, 2'O-methyl ribose, 5-methylcytidine were assessed for antiviral activity when provided at the time of HBV inoculation or post-inoculation. NAPs dose-dependently inhibited HBV entry in a phosphorothioation-dependent, sequence-independent and size-dependent manner. This inhibition of HBV entry by NAPs was impaired by 2'O-methyl ribose modification. NAP treatment after viral inoculation did not elicit any antiviral activity.

  14. Prediction of interindividual differences in hepatic functions and drug sensitivity by using human iPS-derived hepatocytes.

    Science.gov (United States)

    Takayama, Kazuo; Morisaki, Yuta; Kuno, Shuichi; Nagamoto, Yasuhito; Harada, Kazuo; Furukawa, Norihisa; Ohtaka, Manami; Nishimura, Ken; Imagawa, Kazuo; Sakurai, Fuminori; Tachibana, Masashi; Sumazaki, Ryo; Noguchi, Emiko; Nakanishi, Mahito; Hirata, Kazumasa; Kawabata, Kenji; Mizuguchi, Hiroyuki

    2014-11-25

    Interindividual differences in hepatic metabolism, which are mainly due to genetic polymorphism in its gene, have a large influence on individual drug efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells have the potential to predict interindividual differences in drug metabolism capacity and drug response. However, it remains uncertain whether human iPSC-derived HLCs can reproduce the interindividual difference in hepatic metabolism and drug response. We found that cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary human hepatocytes (PHH)-iPS-HLCs were highly correlated with those of PHHs, suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity and drug responsiveness. We also demonstrated that the interindividual differences, which are due to the diversity of individual SNPs in the CYP gene, could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our knowledge, the first PHH-iPS-HLC panel that reflects the interindividual differences of hepatic drug-metabolizing capacity and drug responsiveness.

  15. An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice.

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    Martha J Harding

    2010-04-01

    Full Text Available Widely accessible small animal models suitable for the study of hepatitis C virus (HCV in vivo are lacking, primarily because rodent hepatocytes cannot be productively infected and because human hepatocytes are not easily engrafted in immunodeficient mice.We report here on a novel approach for human hepatocyte engraftment that involves subcutaneous implantation of primary human fetal hepatoblasts (HFH within a vascularized rat collagen type I/human fibronectin (rCI/hFN gel containing Bcl-2-transduced human umbilical vein endothelial cells (Bcl-2-HUVEC in severe combined immunodeficient X beige (SCID/bg mice. Maturing hepatic epithelial cells in HFH/Bcl-2-HUVEC co-implants displayed endocytotic activity at the basolateral surface, canalicular microvilli and apical tight junctions between adjacent cells assessed by transmission electron microscopy. Some primary HFH, but not Huh-7.5 hepatoma cells, appeared to differentiate towards a cholangiocyte lineage within the gels, based on histological appearance and cytokeratin 7 (CK7 mRNA and protein expression. Levels of human albumin and hepatic nuclear factor 4alpha (HNF4alpha mRNA expression in gel implants and plasma human albumin levels in mice engrafted with HFH and Bcl-2-HUVEC were somewhat enhanced by including murine liver-like basement membrane (mLBM components and/or hepatocyte growth factor (HGF-HUVEC within the gel matrix. Following ex vivo viral adsorption, both HFH/Bcl-2-HUVEC and Huh-7.5/Bcl-2-HUVEC co-implants sustained HCV Jc1 infection for at least 2 weeks in vivo, based on qRT-PCR and immunoelectron microscopic (IEM analyses of gel tissue.The system described here thus provides the basis for a simple and robust small animal model of HFH engraftment that is applicable to the study of HCV infections in vivo.

  16. An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice.

    Science.gov (United States)

    Harding, Martha J; Lepus, Christin M; Gibson, Thomas F; Shepherd, Benjamin R; Gerber, Scott A; Graham, Morven; Paturzo, Frank X; Rahner, Christoph; Madri, Joseph A; Bothwell, Alfred L M; Lindenbach, Brett D; Pober, Jordan S

    2010-04-01

    Widely accessible small animal models suitable for the study of hepatitis C virus (HCV) in vivo are lacking, primarily because rodent hepatocytes cannot be productively infected and because human hepatocytes are not easily engrafted in immunodeficient mice. We report here on a novel approach for human hepatocyte engraftment that involves subcutaneous implantation of primary human fetal hepatoblasts (HFH) within a vascularized rat collagen type I/human fibronectin (rCI/hFN) gel containing Bcl-2-transduced human umbilical vein endothelial cells (Bcl-2-HUVEC) in severe combined immunodeficient X beige (SCID/bg) mice. Maturing hepatic epithelial cells in HFH/Bcl-2-HUVEC co-implants displayed endocytotic activity at the basolateral surface, canalicular microvilli and apical tight junctions between adjacent cells assessed by transmission electron microscopy. Some primary HFH, but not Huh-7.5 hepatoma cells, appeared to differentiate towards a cholangiocyte lineage within the gels, based on histological appearance and cytokeratin 7 (CK7) mRNA and protein expression. Levels of human albumin and hepatic nuclear factor 4alpha (HNF4alpha) mRNA expression in gel implants and plasma human albumin levels in mice engrafted with HFH and Bcl-2-HUVEC were somewhat enhanced by including murine liver-like basement membrane (mLBM) components and/or hepatocyte growth factor (HGF)-HUVEC within the gel matrix. Following ex vivo viral adsorption, both HFH/Bcl-2-HUVEC and Huh-7.5/Bcl-2-HUVEC co-implants sustained HCV Jc1 infection for at least 2 weeks in vivo, based on qRT-PCR and immunoelectron microscopic (IEM) analyses of gel tissue. The system described here thus provides the basis for a simple and robust small animal model of HFH engraftment that is applicable to the study of HCV infections in vivo.

  17. 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

  18. Long-term follow-up for incident cirrhosis among pediatric cancer survivors with hepatitis C virus infection.

    Science.gov (United States)

    Stallings-Smith, Sericea; Krull, Kevin R; Brinkman, Tara M; Hudson, Melissa M; Ojha, Rohit P

    2015-10-01

    Pediatric cancer patients who received blood transfusions were potentially exposed to hepatitis C virus (HCV) prior to second-generation HCV screening of blood products in 1992. Limited evidence is available about long-term incident cirrhosis in this population. We aimed to estimate the overall and sex-specific incidence of cirrhosis among HCV-seropositive survivors of pediatric cancer. We identified 113HCV-seropositive pediatric cancer patients treated at St. Jude Children's Research Hospital between 1962 and 1997, who survived ≥5 years post-diagnosis, and were followed through 2014. Our outcome was cirrhosis determined by liver biopsy or diagnostic imaging. We used a competing-risk framework to estimate the overall and sex-specific cumulative incidence and 95% confidence limits (CL) of cirrhosis at 10-year follow-up intervals. The median duration of follow-up was 30 years (interquartile range=28-36) post-cancer diagnosis. Cumulative incidence of cirrhosis increased at each 10-year interval from 0% after 10 years to 13% after 40 years (Ptrendpediatric cancer survivors and the general population given similar duration of follow-up, but survivors may be diagnosed with cirrhosis at an earlier age. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Proteomic Profiling of Human Liver Biopsies: Hepatitis C Virus-Induced Fibrosis and Mitochondrial Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Diamond, Deborah L.; Jacobs, Jon M.; Paeper, Bryan; Proll, Sean; Gritsenko, Marina A.; Carithers, Jr., Robert L.; Larson , Anne M.; Yeh, Matthew M.; Camp, David G.; Smith, Richard D.; Katze, Michael G.

    2007-09-01

    Liver biopsies from HCV-infected patients offer the unique opportunity to study human liver biology and disease in vivo. However, the low protein yields associated with these small samples present a significant challenge for proteomic analysis. In this study we describe the application of an ultra-sensitive proteomics platform for performing robust quantitative proteomic studies on microgram amounts of HCV-infected human liver tissue from 15 patients at different stages of fibrosis. A high quality liver protein data base containing 5,920 unique protein identifications supported high throughput quantitative studies using 16O:18O stable isotope labeling in combination with the accurate mass and time (AMT) tag approach. A total of 1,641 liver biopsy proteins were quantified and ANOVA identified 210 proteins exhibiting statistically significant differences associated with fibrosis stage. Hierarchical clustering revealed that biopsies representative of later fibrosis stages (e.g. Batts-Ludwig stages 3-4) exhibited a distinct protein expression profile indicating an apparent down-regulation of many proteins when compared to samples from earlier fibrosis stages (e.g. Batts-Ludwig stages 0-2). Functional analysis of these signature proteins suggests that impairment of key mitochondrial processes including fatty acid oxidation and oxidative phosphorylation, and response to oxidative stress and reactive oxygen species occurs during advanced stage 3-4 fibrosis. In conclusion, the results reported here represent a significant advancement in clinical proteomics providing to our knowledge, the first demonstration of global proteomic alterations accompanying liver disease progression in patients chronically infected with HCV. Our findings contribute to a generally emerging theme associating oxidative stress and hepatic mitochondrial dysfunction with HCV pathogenesis.

  20. Quantitative evaluation of human bone mesenchymal stem cells rescuing fulminant hepatic failure in pigs.

    Science.gov (United States)

    Shi, Dongyan; Zhang, Jianing; Zhou, Qian; Xin, Jiaojiao; Jiang, Jing; Jiang, Longyan; Wu, Tianzhou; Li, Jiang; Ding, Wenchao; Li, Jun; Sun, Suwan; Li, Jianzhou; Zhou, Ning; Zhang, Liyuan; Jin, Linfeng; Hao, Shaorui; Chen, Pengcheng; Cao, Hongcui; Li, Mingding; Li, Lanjuan; Chen, Xin; Li, Jun

    2017-05-01

    Stem cell transplantation provides a promising alternative for the treatment of fulminant hepatic failure (FHF). However, it lacks fundamental understanding of stem cells' activities. Our objective was to clarify stem cell-recipient interactions for overcoming barriers to clinical application. We used an in-house large-animal (pig) model of FHF rescue by human bone marrow mesenchymal stem cells (hBMSCs) and profiled the cells' activities. The control and transplantation groups of pigs (n=15 per group) both received a D-galactosamine (D-Gal) injection (1.5 g/kg). The transplantation group received hBMSCs via intraportal vein infusion (3×10(6) cells/kg) immediately after D-Gal administration. The stem cell-recipient interactions were quantitatively evaluated by biochemical function, cytokine array, metabolite profiling, transcriptome sequencing and immunohistochemistry. All pigs in the control group died within an average of 3.22 days, whereas 13/15 pigs in the transplantation group lived >14 days. The cytokine array and metabolite profiling analyses revealed that hBMSC transplantation suppressed D-Gal-induced life-threatening cytokine storms and stabilised FHF within 7 days, while human-derived hepatocytes constituted only ∼4.5% of the pig hepatocytes. The functional synergy analysis of the observed profile changes indicated that the implanted hBMSCs altered the pigs' cytokine responses to damage through paracrine effects. Delta-like ligand 4 was validated to assist liver restoration in both pig and rat FHF models. Our results delineated an integrated model of the multifaceted interactions between stem cells and recipients, which may open a new avenue to the discovery of single molecule-based therapeutics that simulate stem cell actions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis.

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    Itaru Kato

    Full Text Available In acute lymphoblastic leukemia (ALL patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc (null mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis.

  2. Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection.

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    Michael G Berg

    2015-12-01

    Full Text Available Hepatitis C virus (HCV and human pegivirus (HPgV, formerly GBV-C, are the only known human viruses in the Hepacivirus and Pegivirus genera, respectively, of the family Flaviviridae. We present the discovery of a second pegivirus, provisionally designated human pegivirus 2 (HPgV-2, by next-generation sequencing of plasma from an HCV-infected patient with multiple bloodborne exposures who died from sepsis of unknown etiology. HPgV-2 is highly divergent, situated on a deep phylogenetic branch in a clade that includes rodent and bat pegiviruses, with which it shares <32% amino acid identity. Molecular and serological tools were developed and validated for high-throughput screening of plasma samples, and a panel of 3 independent serological markers strongly correlated antibody responses with viral RNA positivity (99.9% negative predictive value. Discovery of 11 additional RNA-positive samples from a total of 2440 screened (0.45% revealed 93-94% nucleotide identity between HPgV-2 strains. All 12 HPgV-2 RNA-positive cases were identified in individuals also testing positive for HCV RNA (12 of 983; 1.22%, including 2 samples co-infected with HIV, but HPgV-2 RNA was not detected in non-HCV-infected individuals (p<0.0001, including those singly infected by HIV (p = 0.0075 or HBV (p = 0.0077, nor in volunteer blood donors (p = 0.0082. Nine of the 12 (75% HPgV-2 RNA positive samples were reactive for antibodies to viral serologic markers, whereas only 28 of 2,429 (1.15% HPgV-2 RNA negative samples were seropositive. Longitudinal sampling in two individuals revealed that active HPgV-2 infection can persist in blood for at least 7 weeks, despite the presence of virus-specific antibodies. One individual harboring both HPgV-2 and HCV RNA was found to be seronegative for both viruses, suggesting a high likelihood of simultaneous acquisition of HCV and HPgV-2 infection from an acute co-transmission event. Taken together, our results indicate that HPgV-2 is a

  3. Ecological integrity of streams related to human cancer mortality rates.

    Science.gov (United States)

    Hitt, Nathaniel P; Hendryx, Michael

    2010-08-01

    Assessments of ecological integrity have become commonplace for biological conservation, but their role for public health analysis remains largely unexplored. We tested the prediction that the ecological integrity of streams would provide an indicator of human cancer mortality rates in West Virginia, USA. We characterized ecological integrity using an index of benthic macroinvertebrate community structure (West Virginia Stream Condition Index, SCI) and quantified human cancer mortality rates using county-level data from the Centers for Disease Control and Prevention. Regression and spatial analyses revealed significant associations between ecological integrity and public health. SCI was negatively related to age-adjusted total cancer mortality per 100,000 people. Respiratory, digestive, urinary, and breast cancer rates increased with ecological disintegrity, but genital and oral cancer rates did not. Smoking, poverty, and urbanization were significantly related to total cancer mortality, but did not explain the observed relationships between ecological integrity and cancer. Coal mining was significantly associated with ecological disintegrity and higher cancer mortality. Spatial analyses also revealed cancer clusters that corresponded to areas of high coal mining intensity. Our results demonstrated significant relationships between ecological integrity and human cancer mortality in West Virginia, and suggested important effects of coal mining on ecological communities and public health. Assessments of ecological integrity therefore may contribute not only to monitoring goals for aquatic life, but also may provide valuable insights for human health and safety.

  4. Viral Hepatitis: A through E and Beyond

    Science.gov (United States)

    Viral Hepatitis: A through E and Beyond NATIONAL INSTITUTES OF HEALTH U.S. Department of Health and Human Services National Digestive Diseases Information Clearinghouse What is viral hepatitis? Viral hepatitis is inflammation of the liver caused ...

  5. The effect of recombinant human growth hormone with or without rosiglitazone on hepatic fat content in HIV-1-infected individuals: a randomized clinical trial.

    Science.gov (United States)

    Kotler, Donald P; He, Qing; Engelson, Ellen S; Albu, Jeanine B; Glesby, Marshall J

    2016-01-01

    Hepatic fat is related to insulin resistance (IR) and visceral adipose tissue (VAT) in HIV+ and uninfected individuals. Growth hormone (GH) reduces VAT but increases IR. We evaluated the effects of recombinant human GH (rhGH) and rosiglitazone (Rosi) on hepatic fat in a substudy of a randomized controlled trial. HIV+ subjects with abdominal obesity and IR (QUICKI≤0.33) were randomized to rhGH 3 mg daily, Rosi 4 mg twice daily, the combination or double placebo. Hepatic fat was measured by magnetic resonance spectroscopy, visceral fat by MRI and IR by frequently sampled intravenous glucose tolerance tests at baseline and week 12. 31 subjects were studied at both time points. Significant correlations between hepatic fat and VAT (r=0.41; P=0.02) and QUICKI (r=0.39; P<0.05) were seen at baseline. IR rose with rhGH but not Rosi. When rhGH treatment groups were combined, hepatic fat expressed as percentage change decreased significantly (P<0.05) but did not change in Rosi (P=0.71). There were no correlations between changes in hepatic fat and VAT (P=0.4) or QUICKI (P=0.6). In a substudy of 21 subjects, a trend was noticed between changes in hepatic fat and serum insulin-like growth factor-1 (IGF-1; P=0.09). Hepatic fat correlates significantly with both VAT and IR, but changes in hepatic fat do not correlate with changes in VAT and glucose metabolism. Hepatic fat content is reduced by rhGH but Rosi has no effect. These results suggest an independent effect of GH or IGF-1 on hepatic fat. The study was registered at Clinicaltrials.gov (NCT00130286).

  6. Tumor endothelial inflammation predicts clinical outcome in diverse human cancers.

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    Sean P Pitroda

    Full Text Available Vascular endothelial cells contribute to the pathogenesis of numerous human diseases by actively regulating the stromal inflammatory response; however, little is known regarding the role of endothelial inflammation in the growth of human tumors and its influence on the prognosis of human cancers.Using an experimental model of tumor necrosis factor-alpha (TNF-α-mediated inflammation, we characterized inflammatory gene expression in immunopurified tumor-associated endothelial cells. These genes formed the basis of a multivariate molecular predictor of overall survival that was trained and validated in four types of human cancer.We report that expression of experimentally derived tumor endothelial genes distinguished pathologic tissue specimens from normal controls in several human diseases associated with chronic inflammation. We trained these genes in human cancer datasets and defined a six-gene inflammatory signature that predicted significantly reduced overall survival in breast cancer, colon cancer, lung cancer, and glioma. This endothelial-derived signature predicted outcome independently of, but cooperatively with, standard clinical and pathological prognostic factors. Consistent with these findings, conditioned culture media from human endothelial cells stimulated by pro-inflammatory cytokines accelerated the growth of human colon and breast tumors in immunodeficient mice as compared with conditioned media from untreated endothelial cells.This study provides the first prognostic cancer gene signature derived from an experimental model of tumor-associated endothelial inflammation. These findings support the notion that activation of inflammatory pathways in non-malignant tumor-infiltrating endothelial cells contributes to tumor growth and progression in multiple human cancers. Importantly, these results identify endothelial-derived factors that could serve as potential targets for therapy in diverse human cancers.

  7. Detection of human parvovirus B19 in a patient with hepatitis

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    J.R.R. Pinho

    2001-09-01

    Full Text Available Parvovirus B19 has been associated by some investigators with cases of severe hepatitis. The aim of the present study was to determine the presence of active parvovirus B19 infection among 129 Brazilian patients with non-A-E hepatitis. The patients were assayed for antibodies against parvovirus B19, IgM class, by ELISA. In IgM-positive cases, parvovirus B19 DNA was assayed by PCR in serum and liver tissue and parvovirus VP1 antigen in liver tissue was assayed by immunohistochemistry. Antibodies against parvovirus B19, IgM class, were detected in 3 (2.3% of 129 patients with non-A-E hepatitis. Previous surgery and blood transfusions were reported by these 3 patients. One patient was a 56-year-old female with severe hepatitis, with antimitochondrial antibody seropositivity and submassive necrosis at liver biopsy, who responded to corticosteroid therapy. Strong evidence for active parvovirus B19 infection was found in this patient, with parvovirus B19 DNA being detected by PCR in liver tissue. Furthermore, parvovirus VP1 antigen was also detected in liver tissue by immunohistochemistry. The other two IgM-positive patients were chronic hepatitis cases, but active infection was not proven, since neither viral DNA nor antigen were detected in their liver tissues. This and other reports suggest a possible relation between parvovirus B19 infection and some cases of hepatitis.

  8. The global cancer burden and human development: A review.

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    Fidler, Miranda M; Bray, Freddie; Soerjomataram, Isabelle

    2017-06-01

    This review examines the links between human development and cancer overall and for specific types of cancer, as well as cancer-related risk-factors and outcomes, such as disability and life expectancy. To assess human development, the Human Development Index was utilized continuously and according to four levels (low, medium, high, very high), where the low and very high categories include the least and most developed countries, respectively. All studies that assessed aspects of the global cancer burden using this measure were reviewed. Although the present cancer incidence burden is greater in higher Human Development Index countries, a greater proportion of the global mortality burden is observed in less developed countries, with a higher mean fatality rate in the latter countries. Further, the future cancer burden is expected to disproportionally affect less developed regions; in particular, it has been estimated that low and medium Human Development Index countries will experience a 100% and 81% increase in cancer incidence from 2008 to 2030, respectively. Disparities were also observed in risk factors and average health outcomes, such as a greater number of years of life lost prematurely and fewer cancer-related gains in life expectancy observed in lower versus higher Human Development Index settings. From a global perspective, there remain clear disparities in the cancer burden according to national Human Development Index scores. International efforts are needed to aid countries in social and economic transition in order to efficiently plan, implement and evaluate cancer control initiatives as a means to reduce the widening gap in cancer occurrence and survival worldwide.

  9. Reprogramming of human cancer cells to pluripotency for models of cancer progression

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    Kim, Jungsun; Zaret, Kenneth S

    2015-01-01

    The ability to study live cells as they progress through the stages of cancer provides the opportunity to discover dynamic networks underlying pathology, markers of early stages, and ways to assess therapeutics. Genetically engineered animal models of cancer, where it is possible to study the consequences of temporal-specific induction of oncogenes or deletion of tumor suppressors, have yielded major insights into cancer progression. Yet differences exist between animal and human cancers, such as in markers of progression and response to therapeutics. Thus, there is a need for human cell models of cancer progression. Most human cell models of cancer are based on tumor cell lines and xenografts of primary tumor cells that resemble the advanced tumor state, from which the cells were derived, and thus do not recapitulate disease progression. Yet a subset of cancer types have been reprogrammed to pluripotency or near-pluripotency by blastocyst injection, by somatic cell nuclear transfer and by induced pluripotent stem cell (iPS) technology. The reprogrammed cancer cells show that pluripotency can transiently dominate over the cancer phenotype. Diverse studies show that reprogrammed cancer cells can, in some cases, exhibit early-stage phenotypes reflective of only partial expression of the cancer genome. In one case, reprogrammed human pancreatic cancer cells have been shown to recapitulate stages of cancer progression, from early to late stages, thus providing a model for studying pancreatic cancer development in human cells where previously such could only be discerned from mouse models. We discuss these findings, the challenges in developing such models and their current limitations, and ways that iPS reprogramming may be enhanced to develop human cell models of cancer progression. PMID:25712212

  10. Inhibition of hepatitis B virus surface gene expression by antisense oligodeoxynucleotides in a human hepatoma cell line.

    Science.gov (United States)

    Reinis, M; Reinisová, M; Korec, E; Hlozánek, I

    1993-01-01

    We have studied the inhibitory effect of antisense oligodeoxynucleotides on the expression of hepatitis B virus surface antigens. Human hepatoma cell line PLC/PRF/5 harbors several integrated copies of the HBV genome and produces and secretes hepatitis B virus surface antigen (HBsAg) to the medium. Synthetic antisense oligodeoxynucleotides complementary to various regions of the surface antigen gene were synthesized and their ability to block its expression was tested. Oligodeoxynucleotides (17- and 21-mers) complementary to regions covering ATG codons of both preS2 and S genes significantly inhibited preS2 and S protein production. Less efficient inhibition was achieved when the oligonucleotide complementary to the inside S gene region was assayed.

  11. A plasma metabolomic signature discloses human breast cancer.

    Science.gov (United States)

    Jové, Mariona; Collado, Ricardo; Quiles, José Luís; Ramírez-Tortosa, Mari-Carmen; Sol, Joaquim; Ruiz-Sanjuan, Maria; Fernandez, Mónica; de la Torre Cabrera, Capilla; Ramírez-Tortosa, Cesar; Granados-Principal, Sergio; Sánchez-Rovira, Pedro; Pamplona, Reinald

    2017-03-21

    Metabolomics is the comprehensive global study of metabolites in biological samples. In this retrospective pilot study we explored whether serum metabolomic profile can discriminate the presence of human breast cancer irrespective of the cancer subtype. Plasma samples were analyzed from healthy women (n = 20) and patients with breast cancer after diagnosis (n = 91) using a liquid chromatography-mass spectrometry platform. Multivariate statistics and a Random Forest (RF) classifier were used to create a metabolomics panel for the diagnosis of human breast cancer. Metabolomics correctly distinguished between breast cancer patients and healthy control subjects. In the RF supervised class prediction analysis comparing breast cancer and healthy control groups, RF accurately classified 100% both samples of the breast cancer patients and healthy controls. So, the class error for both group in and the out-of-bag error were 0. We also found 1269 metabolites with different concentration in plasma from healthy controls and cancer patients; and basing on exact mass, retention time and isotopic distribution we identified 35 metabolites. These metabolites mostly support cell growth by providing energy and building stones for the synthesis of essential biomolecules, and function as signal transduction molecules. The collective results of RF, significance testing, and false discovery rate analysis identified several metabolites that were strongly associated with breast cancer. In breast cancer a metabolomics signature of cancer exists and can be detected in patient plasma irrespectively of the breast cancer type.

  12. FYN is overexpressed in human prostate cancer

    Science.gov (United States)

    Posadas, Edwin M.; Al-Ahmadie, Hikmat; Robinson, Victoria L.; Jagadeeswaran, Ramasamy; Otto, Kristen; Kasza, Kristen E.; Tretiakova, Maria; Siddiqui, Javed; Pienta, Kenneth J.; Stadler, Walter M.; Rinker-Schaeffer, Carrie; Salgia, Ravi

    2009-01-01

    Objective FYN is a member of the SRC family of kinases (SFKs), functionally distinct from other SFKs. It interacts with FAK and paxillin (PXN)- regulators of cell morphology and motility. We hypothesized that FYN is upregulated in prostate cancer (CaP). Patients and Methods Through datamining in Oncomine; cell line profiling with immunoblotting and quantitative RT-PCR; and immunohistochemical analysis, we describe FYN expression in CaP. This analysis included 32 cases of CaP, 9 prostatic intraepithelial neoplasia (PIN), and 19 normal. Samples were scored for the percentage of stained glands and intensity of staining (from 0-3). Each sample was assigned a composite score generated by multiplying percentage and intensity. Results Datamining showed an 8-fold increase in FYN expression in CaP compared to normal tissue. This was specific to FYN and not present for other SFKs. Expression of FYN in CaP cell lines (LNCaP, 22Rv1, PC3, DuPro) was detected using quantitative RT-PCR and immunoblot. Expression of FYN and its signaling partners FAK and PXN was demonstrated in human tissue. Comparing normal to cancer, there was a 2.1-fold increase in median composite score for FYN (p<0.001) 1.7-fold increase in FAK (p<0.001), and a 2-fold increase in PXN (p<0.05). There was a 1.7-fold increase in FYN (p<0.05), a 1.6-fold increase in FAK (p<0.01) in CaP as compared to PIN. Conclusions These studies support the hypothesis that the FYN and its related signaling partners are upregulated in CaP and supports further investigation into the role of the FYN as a therapeutic target. PMID:18990162

  13. Seroprevalence of Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus, and Treponema pallidum Infections among Blood Donors on Bioko Island, Equatorial Guinea.

    Directory of Open Access Journals (Sweden)

    Dong-De Xie

    Full Text Available Regular screening of transfusion-transmissible infections (TTIs, such as human immunodeficiency virus (HIV, hepatitis B and hepatitis C virus (HBV and HCV, respectively, and Treponema pallidum, in blood donors is essential to guaranteeing clinical transfusion safety. This study aimed to determine the seroprevalence of four TTIs among blood donors on Bioko Island, Equatorial Guinea (EG.A retrospective survey of blood donors from January 2011 to April 2013 was conducted to assess the presence of HIV, HBV, HCV and T. pallidum. The medical records were analyzed to verify the seroprevalence of these TTIs among blood donations stratified by gender, age and geographical region.Of the total 2937 consecutive blood donors, 1098 (37.39% had a minimum of one TTI and 185 (6.29% harbored co-infections. The general seroprevalence of HIV, HBV, HCV and T. pallidum were 7.83%, 10.01%, 3.71% and 21.51%, respectively. The most frequent TTI co-infections were HBV-T. pallidum 60 (2.04% and HIV-T. pallidum 46 (1.57%. The seroprevalence of HIV, HBV, HCV and T. pallidum were highest among blood donors 38 to 47 years, 18 to 27 years and ≥ 48 years age, respectively (P<0.05. The seroprevalence of TTIs varied according to the population from which the blood was collected on Bioko Island.Our results firstly provide a comprehensive overview of TTIs among blood donors on Bioko Island. Strict screening of blood donors and improved hematological examinations using standard operating procedures are recommended.

  14. Seroprevalence of Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus, and Treponema pallidum Infections among Blood Donors on Bioko Island, Equatorial Guinea.

    Science.gov (United States)

    Xie, Dong-De; Li, Jian; Chen, Jiang-Tao; Eyi, Urbano Monsuy; Matesa, Rocio Apicante; Obono, Maximo Miko Ondo; Ehapo, Carlos Sala; Yang, Li-Ye; Yang, Hui; Yang, Hui-Tian; Lin, Min

    2015-01-01

    Regular screening of transfusion-transmissible infections (TTIs), such as human immunodeficiency virus (HIV), hepatitis B and hepatitis C virus (HBV and HCV, respectively), and Treponema pallidum, in blood donors is essential to guaranteeing clinical transfusion safety. This study aimed to determine the seroprevalence of four TTIs among blood donors on Bioko Island, Equatorial Guinea (EG). A retrospective survey of blood donors from January 2011 to April 2013 was conducted to assess the presence of HIV, HBV, HCV and T. pallidum. The medical records were analyzed to verify the seroprevalence of these TTIs among blood donations stratified by gender, age and geographical region. Of the total 2937 consecutive blood donors, 1098 (37.39%) had a minimum of one TTI and 185 (6.29%) harbored co-infections. The general seroprevalence of HIV, HBV, HCV and T. pallidum were 7.83%, 10.01%, 3.71% and 21.51%, respectively. The most frequent TTI co-infections were HBV-T. pallidum 60 (2.04%) and HIV-T. pallidum 46 (1.57%). The seroprevalence of HIV, HBV, HCV and T. pallidum were highest among blood donors 38 to 47 years, 18 to 27 years and ≥ 48 years age, respectively (P<0.05). The seroprevalence of TTIs varied according to the population from which the blood was collected on Bioko Island. Our results firstly provide a comprehensive overview of TTIs among blood donors on Bioko Island. Strict screening of blood donors and improved hematological examinations using standard operating procedures are recommended.

  15. Genetic variants in human leukocyte antigen-DP influence both hepatitis C virus persistence and hepatitis C virus F protein generation in the Chinese Han population.

    Science.gov (United States)

    Xu, Xiaodong; Yue, Ming; Jiang, Longfeng; Deng, Xiaozhao; Zhang, Yongxiang; Zhang, Yun; Zhu, Danyan; Xiao, Wen; Zhou, Zhenxian; Yao, Wenjuan; Kong, Jing; Yu, Xiaojie; Wei, Juan

    2014-06-03

    Chronic hepatitis C is a serious liver disease that often results in cirrhosis or hepatocellular carcinoma. The aim of this study was to assess the association of human leukocyte antigen-DP (HLA-DP) variants with risk of chronic hepatitis C virus (HCV) or anti-F antibody generation. We selected two single nucleotide polymorphisms (SNPs) in a region including HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277534) and genotyped SNPs in 702 cases and 342 healthy controls from the Chinese population using TaqMan SNP genotyping assay. Moreover, the exon 2 of the HLA-DPA1 and HLA-DPB1 genes were amplified and determined by sequencing-based typing (SBT). The results showed that rs3077 significantly increased the risk of chronic HCV infection in additive models and dominant models (odds ratio (OR) = 1.32 and 1.53). The rs3077 also contributed to decrease the risk of anti-F antibody generation in additive models and dominant models (OR = 0.46 and 0.56). Subsequent analyses revealed the risk haplotypes (DPA1*0103-DPB1*0501 and DPA1*0103-DPB1*0201) and protective haplotypes (DPA1*0202-DPB1*0501 and DPA1*0202-DPB1*0202) to chronic HCV infection. Moreover, we also found that the haplotype of DPA1*0103-DPB1*0201 and DPA1*0202-DPB1*0202 were associated with the anti-F antibody generation. Our findings show that genetic variants in HLA-DP gene are associated with chronic HCV infection and anti-F antibody generation.

  16. Short and Long-Term Postoperative Complications Following Total Joint Arthroplasty in Patients With Human Immunodeficiency Virus, Hepatitis B, or Hepatitis C.

    Science.gov (United States)

    Kildow, Beau J; Politzer, Cary S; DiLallo, Marcus; Bolognesi, Michael P; Seyler, Thorsten M

    2017-11-13

    Due to advancement in treatment against human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), the prevalence of this patient population electing to undergo total joint arthroplasty (TJA) is increasing. Current literature is scarce and conflicting especially when evaluating long-term surgical complications. The purpose of this study is to assess the postoperative medical and surgical complications following TJA in these patient populations. Using a nationwide database between 2005 and 2012, 4 cohorts were created: patients with HIV, HCV, HBV, and HIV and HBV or HCV who underwent TJA. Cohorts were matched to a control group by age, gender, and Charlson Comorbidity Index. Thirty-day and 90-day medical complications and 90-day and 2-year surgical complications were evaluated using odds ratios with 95% confidence intervals. Following TJA, patients with HCV or HBV had increased risk of pneumonia, sepsis, joint infection, and revision surgery at 90 days and 2 years. Patients with HIV did not have increased risk of infection at 90 days and 2 years but did have increased risk of revision at 90 days (odds ratio 3.21, 95% confidence interval 1.31-7.84) following total hip arthroplasty. Patients with HIV, HBV, or HCV have an overall increased risk of postoperative medical and surgical complications following TJA. Patients with HBV or HCV are at risk of more complications than patients with HIV especially for infection within 90 days after TJA. Patients with HIV are at risk of mechanical complications but do not appear to be at significant risk for infection following total hip arthroplasty. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The impact on blood donor screening for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus using plasma from frozen-thawed plasma preparation tubes.

    Science.gov (United States)

    Allison, Kirsty M; Faddy, Helen M; Margaritis, Angelo; Ismay, Susan; Marks, Denese C

    2016-02-01

    Blood services are required to maintain repositories of frozen samples for confirmation of results and/or retrospective testing. The Australian Red Cross Blood Service archives donor samples in plasma preparation tubes (PPTs). This study aims to evaluate the effect of freeze-thawing and extended frozen storage on the ability to detect human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) using blood donation screening assays in samples stored in PPTs. Whole blood was spiked with HIV-, HCV-, or HBV-reactive plasma at high and low viral loads and stored in PPTs or as plasma aliquots. All samples were frozen and stored at not more than -30°C. At 0, 3, 6, 12, 18, and 36 months, samples were tested for HIV and HCV antibodies, HBV surface antigen, and viral nucleic acid. Additional samples were thawed and refrozen either once or twice before testing to simulate up to three freeze-thaw cycles. All PPT and plasma aliquots retained appropriate viral reactivity, including those with multiple freeze-thaw cycles, on both nucleic acid testing and serology platforms. Frozen storage of biologicals in PPTs, as opposed to plasma aliquots, does not affect the ability to detect HIV, HCV, and HBV using viral nucleic acid or serology donation screening systems for up to 36 months. Freezing and thawing PPT samples did not impact the ability to detect these viruses. Our study demonstrates that PPTs appear to be an appropriate receptacle for frozen plasma sample archiving for up to 3 years. © 2015 AABB.

  18. Thy-1 (CD90)-Positive Hepatic Progenitor Cells, Hepatoctyes, and Non-parenchymal Liver Cells Isolated from Human Livers.

    Science.gov (United States)

    Weiss, Thomas S; Dayoub, Rania

    2017-01-01

    In response to liver injury, hepatic cells, especially hepatocytes, can rapidly proliferate to repair liver damage. Additionally, it was shown that under certain circumstances liver resident cells with progenitor capabilities are involved in liver cell proliferation and differentiation. These hepatic progenitor cells (HPCs), known as oval cells in rodents, are derived from the canals of Hering, which are located in the periportal region of the liver. Regarding to different cell niches, which were defined for human HPCs, several markers have been used to identify these cells such as CD34, c-kit, OV-6, and Thy-1 (CD90). The latter was shown to be expressed on HPCs in human liver tissue with histological signs of regeneration. In this chapter we describe a detailed method for the isolation of Thy-1 positive cells from human resected liver tissue. Based on a procedure for isolating primary human hepatocytes and non-parenchymal cells (NPCs) we expanded this protocol to additional enzymatic dissociation, filtration, and centrifugation steps. This results in a bile duct cell enriched fraction of NPCs from which Thy-1 (CD90) positive cells were purified by Thy-1 positivity selection using MACS technique. Bipotential progenitor cells from human liver resections can be isolated using Thy-1 and was shown to be a suitable tool for the enrichment of liver resident progenitor cells for xenotransplantation.

  19. Effect of a Liver Cancer Education Program on Hepatitis B Screening Among Asian Americans in the Baltimore–Washington Metropolitan Area, 2009–2010

    OpenAIRE

    Juon, Hee-Soon; Lee, Sunmin; Strong, Carol; Rimal, Rajiv; Kirk, Gregory D.; Bowie, Janice

    2014-01-01

    Introduction Asian Americans have the highest incidence of hepatocellular carcinoma (HCC), the major form of primary liver cancer, of all ethnic groups in the United States. Chronic hepatitis B virus (HBV) infection is the most common cause of HCC, and as many as 1 in 10 foreign-born Asian Americans are chronically infected with HBV. We tested the effectiveness of a culturally tailored liver cancer education program for increasing screening for HBV among Chinese, Korean, and Vietnamese Americ...

  20. Successful treatment of hepatic oligometastases with stereotactic ablative radiotherapy and radiofrequency ablation in an anaplastic lymphoma kinase fusion-positive lung cancer patient

    DEFF Research Database (Denmark)

    Weber, Britta; Liu, Mitchell; Sobkin, Paul

    2016-01-01

    Local ablative therapy with stereotactic ablative radiotherapy may improve survival in oncogene‐addicted lung cancer patients with extracranial oligometastatic disease treated with targeted therapies. There is limited data on the use of radiofrequency ablation (RFA) in this same setting. We present...... a case of an anaplastic lymphoma kinase (ALK)‐positive lung cancer patient with hepatic oligometastatic progression who was successfully treated with both stereotactic ablative radiation and RFA while continuing with an ALK inhibitor....

  1. Landscape of DNA Virus Associations across Human Malignant Cancers: Analysis of 3,775 Cases Using RNA-Seq

    Science.gov (United States)

    Tannir, Nizar M.; Williams, Michelle D.; Chen, Yunxin; Yao, Hui; Zhang, Jianping; Thompson, Erika J.; Meric-Bernstam, Funda; Medeiros, L. Jeffrey; Weinstein, John N.

    2013-01-01

    Elucidation of tumor-DNA virus associations in many cancer types has enhanced our knowledge of fundamental oncogenesis mechanisms and provided a basis for cancer prevention initiatives. RNA-Seq is a novel tool to comprehensively assess such associations. We interrogated RNA-Seq data from 3,775 malignant neoplasms in The Cancer Genome Atlas database for the presence of viral sequences. Viral integration sites were also detected in expressed transcripts using a novel approach. The detection capacity of RNA-Seq was compared to available clinical laboratory data. Human papillomavirus (HPV) transcripts were detected using RNA-Seq analysis in head-and-neck squamous cell carcinoma, uterine endometrioid carcinoma, and squamous cell carcinoma of the lung. Detection of HPV by RNA-Seq correlated with detection by in situ hybridization and immunohistochemistry in squamous cell carcinoma tumors of the head and neck. Hepatitis B virus and Epstein-Barr virus (EBV) were detected using RNA-Seq in hepatocellular carcinoma and gastric carcinoma tumors, respectively. Integration sites of viral genes and oncogenes were detected in cancers harboring HPV or hepatitis B virus but not in EBV-positive gastric carcinoma. Integration sites of expressed viral transcripts frequently involved known coding areas of the host genome. No DNA virus transcripts were detected in acute myeloid leukemia, cutaneous melanoma, low- and high-grade gliomas of the brain, and adenocarcinomas of the breast, colon and rectum, lung, prostate, ovary, kidney, and thyroid. In conclusion, this study provides a large-scale overview of the landscape of DNA viruses in human malignant cancers. While further validation is necessary for specific cancer types, our findings highlight the utility of RNA-Seq in detecting tumor-associated DNA viruses and identifying viral integration sites that may unravel novel mechanisms of cancer pathogenesis. PMID:23740984

  2. Synchronous hepatic metastasis and metachronous Krukenberg tumor from advanced colon cancer. A case report with an unexpected disease-free survival

    Directory of Open Access Journals (Sweden)

    Giovanni Li Destri

    2017-01-01

    Conclusion: The authors emphasize that the long term survival in colon cancer with hepatic and ovarian metastases is possible as long as it has an adequate surgical approach, a tailored chemotherapy and an intensive follow-up. Most likely new prognostic markers will have to be identified.

  3. Surveillance of hepatic late adverse effects in a large cohort of long-term survivors of childhood cancer: prevalence and risk factors

    NARCIS (Netherlands)

    Mulder, Renée L.; Kremer, Leontien C. M.; Koot, Bart G. P.; Benninga, Marc A.; Knijnenburg, Sebastiaan L.; van der Pal, Helena J. H.; Koning, Caro C. E.; Oldenburger, Foppe; Wilde, James C. H.; Taminiau, Jan A. J. M.; Caron, Huib N.; van Dalen, Elvira C.

    2013-01-01

    Childhood cancer survivors (CCS) are a growing group of young individuals with a high risk of morbidity and mortality. We evaluated the prevalence and risk factors of hepatic late adverse effects, defined as elevated liver enzymes, in a large cohort of CCS. The cohort consisted of all five-year CCS

  4. Isolation of viable human hepatic progenitors from adult livers is possible even after 48 hours of cold ischemia.

    Science.gov (United States)

    Aupet, Sophie; Simoné, Gael; Heyd, Bruno; Bachellier, Philippe; Vidal, Isabelle; Richert, Lysiane; Martin, Hélène

    2013-07-01

    Liver transplantation, utilized routinely for end-stage liver disease, has been constrained by the paucity of organ donors, and is being complemented by alternative strategies such as liver cell transplantation. One of the most promising forms of liver cell transplantation is hepatic stem cell therapies, as the number of human hepatic stem cells (hHpSCs) and other early hepatic progenitor cells (HPCs) are sufficient to provide treatment for multiple patients from a single liver source. In the present study, human adult livers were exposed to cold ischemia and then processed after numbers, albeit somewhat lower, were obtained from those exposed to 48 h of cold ischemia. The yields are similar to those reported from livers with minimal exposure to ischemia. When cultured on plastic dishes and in Kubota's Medium, a serum-free medium designed for early lineage stage HPCs, colonies of rapidly expanding cells formed. They were confirmed to be probable hHpSCs by their ability to survive and expand on plastic and in Kubota's Medium for months, by co-expression of EpCAM and neural cell adhesion molecule, minimal if any albumin expression, with EpCAM found throughout the cells, and no expression of alpha-fetoprotein. The yields of viable EpCAM(+) cells were surprisingly large, and the numbers from a single donor liver are sufficient to treat approximately 50-100 patients given the numbers of EpCAM(+) cells currently used in hepatic stem cell therapies. Thus, cold ischemic livers for up to 48 h are a new source of cells that might be used for liver cell therapies.

  5. Human rights and access to hepatitis C treatment for people who inject drugs.

    Science.gov (United States)

    Wolfe, D; Luhmann, N; Harris, M; Momenghalibaf, A; Albers, E; Byrne, J; Swan, T

    2015-11-01

    People who inject drugs (PWID) achieve adherence to and outcomes from hepatitis C virus (HCV) treatment comparable to other patients. Nonetheless, this population has been excluded from treatment by regulation or practice. Approval of safer and more effective oral HCV medicines should offer greater treatment options for PWID, although high medicine prices have led to continued treatment rationing and exclusion in developed countries. In middle-income countries (MICS), treatment is largely unavailable and unaffordable for most PWID. Human rights analysis, with its emphasis on the universal and interconnected nature of the economic, social and political spheres, offers a useful framework for HCV treatment reform. Using peer-reviewed and grey literature, as well as community case reports, we discuss barriers to treatment, correlate these barriers to rights violations, and highlight examples of community advocacy to increase treatment for PWID. Structural drivers of lack of treatment access for PWID include stigma in health settings; drug use status as a criterion for treatment exclusion; requirements for fees or registration by name as a drug user prior to treatment initiation; and incarceration/detention in prisons and rehabilitation centers where treatment is unavailable. High medicine prices force further exclusion of PWID, with cost containment masked as concern about treatment adherence. These barriers correlate to multiple rights violations, including of the rights to privacy; non-discrimination; health; freedom of information; fair trial; and freedom from cruel, inhuman and degrading treatment. Needed reforms include decriminalization of drug use, possession of drugs and drug injecting equipment; removal of exclusionary or discriminatory treatment protocols; approaches to strengthen links between health providers and increase participation of PWID in treatment design and implementation; and measures to increase transparency in government/pharmaceutical company

  6. Transmission dynamics of hepatitis E among swine: potential impact upon human infection

    Directory of Open Access Journals (Sweden)

    Nishiura Hiroshi

    2007-05-01

    Full Text Available Abstract Background Hepatitis E virus (HEV infection is a zoonosis for which pigs play a role as a reservoir. In Japan, the infection has been enzootic in swine. Clarifying the detailed mechanisms of transmission within farms is required in order to facilitate an understanding of the age-specific patterns of infection, especially just prior to slaughter. Results Here we reanalyze a large-scale seroprevalence survey dataset from Japanese pig farms to estimate the force of infection. The forces of infection of swine HEV were estimated to be 3.45 (95% confidence interval: 3.17, 3.75, 2.68 (2.28, 3.14 and 3.11 (2.76, 3.50 [×10-2 per day] in Hokkaido, Honshu and Kyushu, respectively. The estimates with our model assumptions indicated that the average ages at infection ranged from 59.0–67.3 days and that the basic reproduction number, R0, was in the order of 4.02–5.17. Sensitivity analyses of age-specific incidence at different forces of infection revealed that a decline in the force of infection would elevate the age at infection and could increase the number of virus-excreting pigs at the age of 180 days. Conclusion Although our estimates imply that more than 95% of pigs are infected before the age of 150 days, the model shows that a decline in the force of infection could increase the risk of pig-to-human transmission. If the force of infection started to decline, it might be necessary to implement radical countermeasures (e.g. separation of uninfected pigs from infected herds beginning from the end of the suckling stage to minimize the number of virus-positive pigs at the finishing stage.

  7. Hybrid hepatitis B virus-host transcripts in a human hepatoma cell.

    Science.gov (United States)

    Ou, J; Rutter, W J

    1985-01-01

    The human PLC/PRF/5 hepatoma cell line (the Alexander cell) contains at least seven copies of hepatitis B virus (HBV) DNA integrated in its genome; but it selectively expresses the HBV surface antigen (HBsAg) gene and perhaps low levels of the core gene. We have prepared a cDNA library from PLC/PRF/5 cell poly(A)+ RNA and isolated clones containing HBV sequences. Hybridization experiments show that the great majority of HBV-specific RNAs in this cell line contain HBsAg coding sequences and are presumably derived from the HBsAg gene. Primer extension experiments show that these HBsAg mRNAs are, however, derived from multiple initiation sites in the HBsAg gene and involve two promoters: one at the 5' end of the gene that can produce a protein of 45 kDa, and one located in the pre-S region that can produce two proteins of 31 kDa and the mature HBsAg, 25 kDa, respectively. The HBV RNAs are hybrid RNA species that contain HBV sequences at their 5' ends and host DNA sequences at the 3' ends. The great majority of these hybrid RNAs are transcribed from two closely related yet distinct HBV integrants. The viral-host sequences of these two related hybrid RNAs suggest that the related HBV sequences were generated from a parental fragment via duplication, translocation, and mutagenesis. These processes may play a role in HBV-related oncogenesis. Images PMID:2982146

  8. Affinity maturation to improve human monoclonal antibody neutralization potency and breadth against hepatitis C virus.

    Science.gov (United States)

    Wang, Yong; Keck, Zhen-yong; Saha, Anasuya; Xia, Jinming; Conrad, Fraser; Lou, Jianlong; Eckart, Michael; Marks, James D; Foung, Steven K H

    2011-12-23

    A potent neutralizing antibody to a conserved hepatitis C virus (HCV) epitope might overcome its extreme variability, allowing immunotherapy. The human monoclonal antibody HC-1 recognizes a conformational epitope on the HCV E2 glycoprotein. Previous studies showed that HC-1 neutralizes most HCV genotypes but has modest potency. To improve neutralization, we affinity-matured HC-1 by constructing a library of yeast-displayed HC-1 single chain Fv (scFv) mutants, using for selection an E2 antigen from one of the poorly neutralized HCVpp. We developed an approach by parallel mutagenesis of the heavy chain variable (VH) and κ-chain variable (Vk) genes separately, then combining the optimized VH and Vk mutants. This resulted in the generation of HC-1-related scFv variants exhibiting improved affinities. The best scFv variant had a 92-fold improved affinity. After conversion to IgG1, some of the antibodies exhibited a 30-fold improvement in neutralization activity. Both surface plasmon resonance and solution kinetic exclusion analysis showed that the increase in affinity was largely due to a lowering of the dissociation rate constant, Koff. Neutralization against a panel of HCV pseudoparticles and infectious 2a HCV virus improved with the affinity-matured IgG1 antibodies. Interestingly, some of these antibodies neutralized a viral isolate that was not neutralized by wild-type HC-1. Moreover, propagating 2a HCVcc under the selective pressure of WT HC-1 or affinity-matured HC-1 antibodies yielded no viral escape mutants and, with the affinity-matured IgG1, needed 100-fold less antibody to achieve complete virus elimination. Taken together, these findings suggest that affinity-matured HC-1 antibodies are excellent candidates for therapeutic development.

  9. Aqueous Extracts of Hibiscus sabdariffa Calyces Decrease Hepatitis A Virus and Human Norovirus Surrogate Titers.

    Science.gov (United States)

    Joshi, Snehal S; Dice, Lezlee; D'Souza, Doris H

    2015-12-01

    Hibiscus sabdariffa extract is known to have antioxidant, anti-diabetic, and antimicrobial properties. However, their effects against foodborne viruses are currently unknown. The objective of this study was to determine the antiviral effects of aqueous extracts of H. sabdariffa against human norovirus surrogates (feline calicivirus (FCV-F9) and murine norovirus (MNV-1)) and hepatitis A virus (HAV) at 37 °C over 24 h. Individual viruses (~5 log PFU/ml) were incubated with 40 or 100 mg/ml of aqueous hibiscus extract (HE; pH 3.6), protocatechuic acid (PCA; 3 or 6 mg/ml, pH 3.6), ferulic acid (FA; 0.5 or 1 mg/ml; pH 4.0), malic acid (10 mM; pH 3.0), or phosphate buffered saline (pH 7.2 as control) at 37 °C over 24 h. Each treatment was replicated thrice and plaque assayed in duplicate. FCV-F9 titers were reduced to undetectable levels after 15 min with both 40 and 100 mg/ml HE. MNV-1 was reduced by 1.77 ± 0.10 and 1.88 ± 0.12 log PFU/ml after 6 h with 40 and 100 mg/ml HE, respectively, and to undetectable levels after 24 h by both concentrations. HAV was reduced to undetectable levels by both HE concentrations after 24 h. PCA at 3 mg/ml reduced FCV-F9 titers to undetectable levels after 6 h, MNV-1 by 0.53 ± 0.01 log PFU/ml after 6 h, and caused no significant change in HAV titers. FA reduced FCV-F9 to undetectable levels after 3 h and MNV-1 and HAV after 24 h. Transmission electron microscopy showed no conclusive results. The findings suggest that H. sabdariffa extracts have potential to prevent foodborne viral transmission.

  10. Routine extra-hepatic bile duct resection in gallbladder cancer patients without bile duct infiltration: A systematic review.

    Science.gov (United States)

    Nigri, Giuseppe; Berardi, Giammauro; Mattana, Chiara; Mangogna, Livia; Petrucciani, Niccolò; Sagnotta, Andrea; Aurello, Paolo; D'Angelo, Francesco; Ramacciato, Giovanni

    2016-12-01

    The optimal treatment for advanced gallbladder cancer, in particular T2 stage cancer, is unclear. The use of "radical cholecystectomy" or more extended procedures with extra-hepatic bile duct resection are matter of debate. Due to the lack of consensus regarding the oncological significance of routine extra-hepatic bile duct (EBD) resection for gallbladder carcinoma, we decided to perform a systematic review investigating the real benefit of this procedure focusing on the primary outcomes of overall survival and disease-free survival. A systematic literature search was performed using PubMed, EMBASE, Scopus and the Cochrane Library Central according to the PRISMA statement guidelines for conducting and reporting systematic reviews. Multiple primary and secondary outcomes were analyzed. The selected articles included 424 patients who underwent routine EBD resection without bile duct infiltration. Only two papers discussed the number of dissected lymph nodes during EBD resection for gallbladder carcinoma. Four of the seven included papers reported on tumor involvement in lymph nodes at rates ranging between 39% and 83%. All of the studies included in this systematic review reported on results of overall survival. In general, 5-years OS rate of the EBD-resected patients was not significantly different than that of the EBD-preservation group, while the mobility was significantly higher in the EBD resection group. Routine EBD resection in gallbladder cancer patients without bile duct infiltration is not associated with improved overall survival, improved lymph-node harvesting or with minor recurrence rate, but it is associated with higher morbidity rates. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  11. Hepatitis E

    Science.gov (United States)

    ... sheets Fact files Questions & answers Features Multimedia Contacts Hepatitis E Fact sheet Updated July 2017 Key facts ... in 2005 . Report Global hepatitis report, 2017 World Hepatitis Day Know hepatitis - Act now Event notice Key ...

  12. Hepatitis A

    Science.gov (United States)

    ... or care for someone who has hepatitis A People who travel to developing countries are more likely to get hepatitis A. What are the complications of hepatitis A? People typically recover from hepatitis A without complications. In ...

  13. Evidence for two modes of synergistic induction of apoptosis by mapatumumab and oxaliplatin in combination with hyperthermia in human colon cancer cells.

    Science.gov (United States)

    Song, Xinxin; Kim, Seog-Young; Lee, Yong J

    2013-01-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world--the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway.

  14. Evidence for two modes of synergistic induction of apoptosis by mapatumumab and oxaliplatin in combination with hyperthermia in human colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Xinxin Song

    Full Text Available Colorectal cancer is the third leading cause of cancer-related mortality in the world--the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP. Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP, we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4 antibody mapatumumab (Mapa, and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R and Bcl-xL mutant (S62A completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway.

  15. Human induced hepatic lineage-oriented stem cells: autonomous specification of human iPS cells toward hepatocyte-like cells without any exogenous differentiation factors.

    Directory of Open Access Journals (Sweden)

    Tetsuya Ishikawa

    Full Text Available Preparing targeted cells for medical applications from human induced pluripotent stem cells (hiPSCs using growth factors, compounds, or gene transfer has been challenging. Here, we report that human induced hepatic lineage-oriented stem cells (hiHSCs were generated and expanded as a new type of hiPSC under non-typical coculture with feeder cells in a chemically defined hiPSC medium at a very high density. Self-renewing hiHSCs expressed markers of both human embryonic stem cells (hESCs and hepatocytes. Those cells were highly expandable, markedly enhancing gene expression of serum hepatic proteins and cytochrome P450 enzymes with the omission of FGF-2 from an undefined hiPSC medium. The hepatic specification of hiHSCs was not attributable to the genetic and epigenetic backgrounds of the starting cells, as they were established from distinct donors and different types of cells. Approximately 90% of hiHSCs autonomously differentiated to hepatocyte-like cells, even in a defined minimum medium without any of the exogenous growth factors necessary for hepatic specification. After 12 days of this culture, the differentiated cells significantly enhanced gene expression of serum hepatic proteins (ALB, SERPINA1, TTR, TF, FABP1, FGG, AGT, RBP4, and AHSG, conjugating enzymes (UGT2B4, UGT2B7, UGT2B10, GSTA2, and GSTA5, transporters (SULT2A1, SLC13A5, and SLCO2B1, and urea cycle-related enzymes (ARG1 and CPS1. In addition, the hepatocyte-like cells performed key functions of urea synthesis, albumin secretion, glycogen storage, indocyanine green uptake, and low-density lipoprotein uptake. The autonomous hepatic specification of hiHSCs was due to their culture conditions (coculture with feeder cells in a defined hiPSC medium at a very high density in self-renewal rather than in differentiation. These results suggest the feasibility of preparing large quantities of hepatocytes as a convenient and inexpensive hiPSC differentiation. Our study also suggests the

  16. Recapitulation of treatment response patterns in a novel humanized mouse model for chronic hepatitis B virus infection.

    Science.gov (United States)

    Winer, Benjamin Y; Huang, Tiffany; Low, Benjamin E; Avery, Cindy; Pais, Mihai-Alexandru; Hrebikova, Gabriela; Siu, Evelyn; Chiriboga, Luis; Wiles, Michael V; Ploss, Alexander

    2017-02-01

    There are ~350 million chronic carriers of hepatitis B (HBV). While a prophylactic vaccine and drug regimens to suppress viremia are available, chronic HBV infection is rarely cured. HBV's limited host tropism leads to a scarcity of susceptible small animal models and is a hurdle to developing curative therapies. Mice that support engraftment with human hepatoctyes have traditionally been generated through crosses of murine liver injury models to immunodeficient backgrounds. Here, we describe the disruption of fumarylacetoacetate hydrolase directly in the NOD Rag1-/- IL2RγNULL (NRG) background using zinc finger nucleases. The resultant human liver chimeric mice sustain persistent HBV viremia for >90 days. When treated with standard of care therapy, HBV DNA levels decrease below detection but rebound when drug suppression is released, mimicking treatment response observed in patients. Our study highlights the utility of directed gene targeting approaches in zygotes to create new humanized mouse models for human diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Towards the human colorectal cancer microbiome.

    Directory of Open Access Journals (Sweden)

    Julian R Marchesi

    Full Text Available Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC. To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.

  18. Percutaneous radiofrequency ablation of liver cancer in the hepatic dome using the intrapleural fluid infusion technique.

    Science.gov (United States)

    Kondo, Y; Yoshida, H; Tateishi, R; Shiina, S; Kawabe, T; Omata, M

    2008-08-01

    Intrapleural fluid infusion improves ultrasonographic visualization of tumours in the hepatic dome. The aim of this study was to assess the safety and long-term efficacy of ultrasonographically guided percutaneous radiofrequency ablation for tumours in the hepatic dome with intrapleural infusion. Of 2575 patients with hepatocellular carcinoma or hepatic metastases treated with radiofrequency ablation, intrapleural fluid infusion was performed in 587 patients for tumours in the hepatic dome. After the tip of a 14-G metallic needle was positioned in the pleural cavity under ultrasonographic guidance, 500-1000 ml of 5 per cent glucose solution was infused in 5-15 min. Radiofrequency ablation was performed using an internally cooled electrode. Long-term results were evaluated in 347 patients with a single hepatocellular carcinoma who were naive to any treatment. Intrapleural fluid infusion was successfully performed in all 587 patients. The major complication rate on a per tumour basis was similar for patients treated with and without intrapleural infusion (1.6 versus 1.6 per cent; P = 0.924). The overall and recurrence-free survival were both similar for naive patients with a single hepatocellular carcinoma treated with and without intrapleural infusion (P = 0.429 and P = 0.109 respectively). Intrapleural infusion was not associated with lower overall survival in multivariable analysis. With intrapleural fluid infusion, radiofrequency ablation for tumours in the hepatic dome was safe and effective, resulting in satisfactory overall and recurrence-free survival. Copyright (c) 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  19. Design of a PROTAC that antagonizes and destroys the cancer-forming X-protein of the hepatitis B virus

    Energy Technology Data Exchange (ETDEWEB)

    Montrose, Kristopher; Krissansen, Geoffrey W., E-mail: gw.krissansen@auckland.ac.nz

    2014-10-31

    Highlights: • A novel proteolysis targeting chimeric molecule (PROTAC) to treat hepatitis B. • The PROTAC antagonizes and destroys the X-protein of the hepatitis B virus. • The PROTAC is a fusion of the X-protein oligomerization and instability domains. • The oligomerization domain is a dominant-negative inhibitor of X-protein function. • X-protein-targeting PROTACs have potential to prevent hepatocellular carcinoma. - Abstract: The X-protein of the hepatitis B virus (HBV) is essential for virus infection and contributes to the development of HBV-induced hepatocellular carcinoma (HCC), a disease which causes more than one million deaths each year. Here we describe the design of a novel PROTAC (proteolysis targeting chimeric molecule) capable of simultaneously inducing the degradation of the X-protein, and antagonizing its function. The PROTAC was constructed by fusing the N-terminal oligomerization and C-terminal instability domains of the X-protein to each other, and rendering them cell-permeable by the inclusion of a polyarginine cell-penetrating peptide (CPP). It was predicted that the oligomerization domain would bind the X-protein, and that the instability domain would cause the X-protein to be targeted for proteasomal degradation. Addition of the PROTAC to HepG2 liver cancer cells, engineered to express full-length and C-terminally truncated forms of the X-protein, resulted in the degradation of both forms of the X-protein. A cell-permeable stand-alone form of the oligomerization domain was taken up by HepG2 cells, and acted as a dominant-negative inhibitor, causing inhibition of X-protein-induced apoptosis. In summary, the PROTAC described here induces the degradation of the X-protein, and antagonizes its function, and warrants investigation in a preclinical study for its ability to prevent or treat HBV infection and/or the development of HCC.

  20. Hepatic resection versus transarterial chemoembolization for patients with Barcelona Clinic Liver Cancer intermediate stage Child-Pugh A hepatocellular carcinoma.

    Science.gov (United States)

    Zhao, Yin-Nong; Zhang, Yong-Quan; Ye, Jia-Zhou; Liu, Xing; Yang, Hong-Zhi; Cong, Feng-Yun; Xiang, Bang-De; Wu, Fei-Xiang; Ma, Liang; Li, Le-Qun; Ye, Hai-Hong

    2016-12-01

    The present study aimed to compare the overall and recurrence-free survival rates following hepatic resection (HR) and transcatheter arterial chemoembolization (TACE) in patients with Barcelona Clinic Liver Cancer (BCLC) classified intermediate-stage Child-Pugh A hepatocellular carcinoma (HCC). A total of 443 patients were examined, among whom 274 underwent HR, whereas 169 received TACE. The overall survival, recurrence-free survival between groups and subgroups, and risk factors with respect to mortality and recurrence, were analyzed. The 1-, 3- and 5-year overall and recurrence-free survival rates were 70, 46 and 37% and 73, 52, and 37%, respectively after HR, compared with 38, 15, and 12% and 44, 25 and 16%, respectively after TACE. Overall and recurrence-free survival rates were significantly increased following HR compared with TACE. Subgroup analysis in the multi-nodule group showed that the 1-, 3- and 5-year overall survival rates were 68, 38 and 30% after HR, compared with 36, 10 and 0% following TACE. In the solitary tumor group, 1-, 3- and 5-year overall survival rates were 71, 50 and 38% after HR, and 41, 22 and 15% after TACE. The overall survival rate after HR was significantly increased compared with that after TACE in the solitary tumor and multi-nodule groups. The risk factors for mortality include solitary tumor diameter >10 cm, multi-nodules, serum albumin level ≥35 g/l, prothrombin time >13 sec, alphafetoprotein levels >400 ng/ml, and patients with hepatitis B virus. Solitary tumor diameter >10 cm, multi-nodules, and hepatitis B virus (P<0.001) were found to be associated with higher recurrence of HCC. Overall and recurrence-free survival rates were improved after HR compared with those after TACE in BCLC stage B, Child-Pugh A, HCC patients.

  1. Expression of Matrix Metalloproteinases in Human Breast Cancer Tissues

    OpenAIRE

    Benson, Chellakkan Selvanesan; Babu, Somasundaram Dinesh; Radhakrishna, Selvi; Selvamurugan, Nagarajan; Sankar, Bhaskaran Ravi

    2013-01-01

    BACKGROUND: Breast cancer is the most common cancer affecting women in the world today. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can degrade extracellular matrix proteins and promote cell invasion and metastasis. MMPs are differentially expressed and their expressions are often associated with a poor prognosis for patients. OBJECTIVE: The aim of this study is to investigate and compare the expression of MMPs in different grades of human breast cancer tissues with n...

  2. Knowledge of hepatitis C virus screening in long-term pediatric cancer survivors: a report from the Childhood Cancer Survivor Study.

    Science.gov (United States)

    Lansdale, Meagan; Castellino, Sharon; Marina, Neyssa; Goodman, Pamela; Hudson, Melissa M; Mertens, Ann C; Smith, Stephanie M; Leisenring, Wendy; Robison, Leslie L; Oeffinger, Kevin C

    2010-02-15

    Pediatric cancer survivors who were treated before routine hepatitis C virus (HCV) screening of blood donors in 1992 have an elevated risk of transfusion-acquired HCV. To assess long-term pediatric cancer survivors' knowledge of HCV testing and blood transfusion history, a questionnaire was administered to 9242 participants in the Childhood Cancer Survivor Study who are at risk for transfusion-acquired HCV after cancer therapy from 1970 to 1986. More than 70% of survivors reported either no prior HCV testing (41%) or uncertainty about testing (31%), with only 29% reporting prior testing. One half recalled having a treatment-related blood transfusion; those who recalled a transfusion were more likely to report HCV testing (39%) than those who did not (18%) or were unsure (20%). In multivariate models, survivors who reported no prior HCV testing were more likely to be older (odds ratio [OR] per 5-year increase, 1.1; 95% confidence interval [CI], 1.0-1.1) and to report no care at a cancer center within the past 2 years (OR, 1.2; 95% CI, 1.0-1.4), no cancer treatment summary (OR, 1.3; 95% CI, 1.2-1.5), and no transfusions (OR, 2.6; 95% CI, 2.3-3.0) or uncertainty about transfusions (OR, 2.2; 95% CI, 1.9-2.6), and less likely to be racial/ethnic minorities (OR, 0.9; 95% CI, 0.8-1.0) or survivors of acute myeloid leukemia (OR, 0.7; 95% CI, 0.5-1.0). Many pediatric cancer survivors at risk for transfusion-acquired HCV are unaware of their transfusion history and prior testing for HCV and would benefit from programs to increase HCV knowledge and screening.

  3. Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans.

    Directory of Open Access Journals (Sweden)

    Michiko Itoh

    Full Text Available Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH is poorly understood. Here we report the unique histological structure termed "hepatic crown-like structures (hCLS" in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH.

  4. Hepatitis B virus and human T-cell lymphotropic virus type 1 co-infection in the Northern Territory, Australia.

    Science.gov (United States)

    Marr, Ian; Davies, Jane; Baird, Rob W

    2017-05-01

    To establish the relationship between hepatitis B virus (HBV) and human T-cell lymphotropic virus type 1 (HTLV-1) serological markers in the Northern Territory, Australia. A retrospective serological study of patients presenting to public healthcare facilities in the Northern Territory between 2008 and 2015 was performed in order to determine the presence and relationships of serological markers of HBV and HTLV-1. Seven hundred and forty individual patients were found to be serologically positive for HTLV-1 in the Northern Territory over the 8-year period. Hepatitis B results were available for 521 of these patients. Hepatitis B surface antigen (HBsAg) positivity was demonstrated in 15.9% (83/521) of this cohort, which was significantly different to the HTLV-1-negative group (3.7%, 125/3354) (pTerritory. When considering the higher exposure to HBV in HTLV-1-positive individuals, the clearance of HBV appears lower than in those individuals testing HTLV-1-negative. A lower prevalence of clearance in HTVL-1-positive individuals than in HTLV-1-negative individuals, as signified by formation of HBVcAb and HBVsAb in HTVL-1 positive individual's may equate to higher prevalence of ongoing coinfection. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Earlier Detection of Hepatitis C Virus Infection Through Routine Hepatitis C Virus Antibody Screening of Human Immunodeficiency Virus-Positive Men Who Have Sex With Men Attending A Sexually Transmitted Infection Outpatient Clinic: A Longitudinal Study

    NARCIS (Netherlands)

    van Rooijen, Martijn; Heijman, Titia; de Vrieze, Nynke; Urbanus, Anouk; Speksnijder, Arjen; van Leeuwen, Petra; de Vries, Henry; Prins, Maria

    2016-01-01

    In 2007, routine hepatitis C virus (HCV) antibody testing was introduced for men who have sex with men (MSM) with a human immunodeficiency virus (HIV)-positive or unknown status attending a Dutch sexually transmitted infection (STI) outpatient clinic. We evaluated whether this screening resulted in

  6. Branched chain amino acid suppressed insulin-initiated proliferation of human cancer cells through induction of autophagy.

    Science.gov (United States)

    Wubetu, Gizachew Yismaw; Utsunomiya, Tohru; Ishikawa, Daichi; Ikemoto, Tetsuya; Yamada, Shinichiro; Morine, Yuji; Iwahashi, Shuichi; Saito, Yu; Arakawa, Yusuke; Imura, Satoru; Arimochi, Hideki; Shimada, Mitsuo

    2014-09-01

    Branched chain amino acid (BCAA) dietary supplementation inhibits activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis in diabetic animal models. However, the in vitro effect of BCAA on human cancer cell lines under hyper-insulinemic conditions remains unclear. Colon (HCT-116) and hepatic (HepG2) tumor cells were treated with varying concentrations of BCAA with or without fluorouracil (5-FU). The effect of BCAA on insulin-initiated proliferation was determined. Gene and protein expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. BCAA supplementation had no significant effect on cell proliferation and did not show significant synergistic or antagonistic effects with 5-FU. However, BCAA significantly decreased insulin-initiated proliferation of human colon and hepatic cancer cell lines in vitro. BCAA supplementation caused a marked decrease in activated IGF-IR expression and significantly enhanced both mRNA and protein expression of LC3-II and BECN1 (BECLIN-1). BCAA could be a useful chemopreventive modality for cancer in hyperinsulinemic conditions. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Human immunodeficiency virus infection and autoimmune hepatitis during highly active anti-retroviral treatment: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Higgins Martha

    2011-06-01

    Full Text Available Abstract Introduction The emergence of hepatic injury in patients with human immunodeficiency virus infection during highly active therapy presents a diagnostic dilemma. It may represent treatment side effects or autoimmune disorders, such as autoimmune hepatitis, emerging during immune restoration. Case presentation We present the case of a 42-year-old African-American woman with human immunodeficiency virus infection who presented to our emergency department with severe abdominal pain and was found to have autoimmune hepatitis. A review of the literature revealed 12 reported cases of autoimmune hepatitis in adults with human immunodeficiency virus infection, only three of whom were diagnosed after highly active anti-retroviral treatment was initiated. All four cases (including our patient were women, and one had a history of other autoimmune disorders. In our patient (the one patient case we are reporting, a liver biopsy revealed interface hepatitis, necrosis with lymphocytes and plasma cell infiltrates and variable degrees of fibrosis. All four cases required treatment with corticosteroids and/or other immune modulating agents and responded well. Conclusion Our review suggests that autoimmune hepatitis is a rare disorder which usually develops in women about six to eight months after commencing highly active anti-retroviral treatment during the recovery of CD4 lymphocytes. It represents either re-emergence of a pre-existing condition that was unrecognized or a de novo manifestation during immune reconstitution.

  8. Identification of hormonal receptors in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rosa Pascual, M.; Lage, A.; Diaz, J.W.; Moreno, L.; Marta Diaz, T. (Instituto de Oncologia y Radiobiologia, La Habana (Cuba))

    1981-01-01

    The experience in the implementation of a technique for determining hormono-dependence of human breast cancer is presented. The results found with the use of the technique in 50 patients with malignant breast cancer treated at IOR are examined and discussed.

  9. Apoptosis induction of epifriedelinol on human cervical cancer cell line

    African Journals Online (AJOL)

    Background: Present investigation evaluates the antitumor activity of epifriedelinol for the management of cervical cancer by inducing process of apoptosis. Methods: Human Cervical Cancer Cell Line, C33A and HeLa were selected for study and treated with epifriedelinol at a concentration of (50-1000 μg/ml). Cytotoxicity of ...

  10. Effects of recombinant human nerve growth factor on cervical cancer ...

    African Journals Online (AJOL)

    Nerve growth factor (NGF) plays a crucial role in the life of the sympathetic and sensory nervous systems. However, the roles of NGF to cervical cancer remain deeply unknown. This study investigated the effect of recombinant human nerve growth factor (rhNGF) on cervical cancer. It was found that the proliferation of hela ...

  11. Proteome analysis of human colorectal cancer tissue using 2-D ...

    African Journals Online (AJOL)

    Proteome analysis of human colorectal cancer tissue using 2-D DIGE and tandem mass spectrometry for identification of disease-related proteins. ... African Journal of Biotechnology ... The cDNA of the differential protein was transfected into colorectal cancer cells, and the biological behavior of these cells was observed.

  12. Deciphering Signatures of Mutational Processes Operative in Human Cancer

    Science.gov (United States)

    Alexandrov, Ludmil B.; Nik-Zainal, Serena; Wedge, David C.; Campbell, Peter J.; Stratton, Michael R.

    2013-01-01

    Summary The genome of a cancer cell carries somatic mutations that are the cumulative consequences of the DNA damage and repair processes operative during the cellular lineage between the fertilized egg and the cancer cell. Remarkably, these mutational processes are poorly characterized. Global sequencing initiatives are yielding catalogs of somatic mutations from thousands of cancers, thus providing the unique opportunity to decipher the signatures of mutational processes operative in human cancer. However, until now there have been no theoretical models describing the signatures of mutational processes operative in cancer genomes and no systematic computational approaches are available to decipher these mutational signatures. Here, by modeling mutational processes as a blind source separation problem, we introduce a computational framework that effectively addresses these questions. Our approach provides a basis for characterizing mutational signatures from cancer-derived somatic mutational catalogs, paving the way to insights into the pathogenetic mechanism underlying all cancers. PMID:23318258

  13. Exclusive destruction of mitotic spindles in human cancer cells.

    Science.gov (United States)

    Visochek, Leonid; Castiel, Asher; Mittelman, Leonid; Elkin, Michael; Atias, Dikla; Golan, Talia; Izraeli, Shai; Peretz, Tamar; Cohen-Armon, Malka

    2017-03-28

    We identified target proteins modified by phenanthrenes that cause exclusive eradication of human cancer cells. The cytotoxic activity of the phenanthrenes in a variety of human cancer cells is attributed by these findings to post translational modifications of NuMA and kinesins HSET/kifC1 and kif18A. Their activity prevented the binding of NuMA to α-tubulin and kinesins in human cancer cells, and caused aberrant spindles. The most efficient cytotoxic activity of the phenanthridine PJ34, caused significantly smaller aberrant spindles with disrupted spindle poles and scattered extra-centrosomes and chromosomes. Concomitantly, PJ34 induced tumor growth arrest of human malignant tumors developed in athymic nude mice, indicating the relevance of its activity for cancer therapy.

  14. Calorimetric signatures of human cancer cells and their nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Todinova, S. [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, Sofia 1113 (Bulgaria); Stoyanova, E. [Department of Molecular Immunology, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Tzarigradsko shose Blvd. 73, Sofia 1113 (Bulgaria); Krumova, S., E-mail: sakrumo@gmail.com [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, Sofia 1113 (Bulgaria); Iliev, I. [Institute of Experimental Morphology, Pathology and Anthropology with Museum, Acad. G. Bonchev Str., Bl. 25, Sofia 1113 (Bulgaria); Taneva, S.G. [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, Sofia 1113 (Bulgaria)

    2016-01-10

    Graphical abstract: - Highlights: • Two temperature ranges are distinguished in the thermograms of cells/nuclei. • Different thermodynamic properties of cancer and normal human cells/nuclei. • Dramatic reduction of the enthalpy of the low-temperature range in cancer cells. • Oxaliplatin and 5-FU affect the nuclear matrix proteins and the DNA stability. - Abstract: The human cancer cell lines HeLa, JEG-3, Hep G2, SSC-9, PC-3, HT-29, MCF7 and their isolated nuclei were characterized by differential scanning calorimetry. The calorimetric profiles differed from normal human fibroblast (BJ) cells in the two well distinguished temperature ranges—the high-temperature range (H{sub T}, due to DNA-containing structures) and the low-temperature range (L{sub T}, assigned to the nuclear matrix and cellular proteins). The enthalpy of the L{sub T} range, and, respectively the ratio of the enthalpies of the L{sub T}- vs. H{sub T}-range, ΔH{sub L}/ΔH{sub H}, is strongly reduced for all cancer cells compared to normal fibroblasts. On the contrary, for most of the cancer nuclei this ratio is higher compared to normal nuclei. The HT-29 human colorectal cancer cells/nuclei differed most drastically from normal human fibroblast cells/nuclei. Our data also reveal that the treatment of HT-29 cancer cells with cytostatic drugs affects not only the DNA replication but also the cellular proteome.

  15. S-adenosylmethionine Regulates Ubiquitin-Conjugating Enzyme 9 Protein Expression and Sumoylation in Murine Liver and Human Cancers

    Science.gov (United States)

    Tomasi, Maria Lauda; Tomasi, Ivan; Ramani, Komal; Pascale, Rosa Maria; Xu, Jun; Giordano, Pasquale; Mato, José M.; Lu, Shelly C.

    2012-01-01

    Background and rationale Ubiquitin-conjugating enzyme 9 (Ubc9) is required for sumoylation and overexpressed in several malignancies but its expression in hepatocellular carcinoma (HCC) is unknown. Hepatic S-adenosylmethionine (SAMe) level falls in methionine adenosyltransferase 1A (Mat1a) knockout (KO) mice, which develop HCC, and in ethanol fed mice. Here we examined regulation of Ubc9 by SAMe in murine liver and human HCC, breast and colon carcinoma cell lines and specimens. Methods Real-time PCR and Western blotting measured gene and protein expression, respectively. Immunoprecipitation followed by Western blotting examined protein-protein interactions. Results Ubc9 expression is increased in HCC and when hepatic SAMe level falls. SAMe treatment in Mat1a KO mice reduced Ubc9 protein but not mRNA level and lowered sumoylation. Similarly, treatment of liver cancer cell lines HepG2 and Huh-7, colon cancer cell line RKO and breast cancer cell line MCF-7 with SAMe or its metabolite methylthioadenosine (MTA) reduced only Ubc9 protein level. Ubc9 post-translational regulation is unknown. Ubc9 sequence predicts a possible phosphorylation site by cell division cycle 2 (Cdc2), which directly phosphorylated recombinant Ubc9. Mat1a KO mice have higher phospho-Ubc9 level, which normalized after SAMe treatment. SAMe and MTA treatment lowered Cdc2 mRNA and protein levels, phospho-Ubc9 and protein sumoylation in liver, colon and breast cancer cells. Serine 71 of Ubc9 is required for phosphorylation, interaction with Cdc2 and protein stability. Cdc2, Ubc9 and phospho-Ubc9 levels are increased in human liver, breast and colon cancers. Conclusions Cdc2 expression is increased and Ubc9 is hyperphosphorylated in several cancers and this represents a novel mechanism to maintain high Ubc9 protein expression that can be inhibited by SAMe and MTA. PMID:22407595

  16. Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain.

    Science.gov (United States)

    Vanwolleghem, Thomas; Bukh, Jens; Meuleman, Philip; Desombere, Isabelle; Meunier, Jean-Christophe; Alter, Harvey; Purcell, Robert H; Leroux-Roels, Geert

    2008-06-01

    The role of the humoral immune response in the natural course of hepatitis C virus (HCV) infection is widely debated. Most chronically infected patients have immunoglobulin G (IgG) antibodies capable of neutralizing HCV pseudoparticles (HCVpp) in vitro. It is, however, not clear whether these IgG can prevent a de novo HCV infection in vivo and contribute to the control of viremia in infected individuals. We addressed this question with homologous in vivo protection studies in human liver-urokinase-type plasminogen activator (uPA)(+/+) severe combined immune deficient (SCID) mice. Chimeric mice were loaded with chronic phase polyclonal IgG and challenged 3 days later with a 100% infectious dose of the acute phase H77C virus, both originating from patient H. Passive immunization induced sterilizing immunity in five of eight challenged animals. In the three nonprotected animals, the HCV infection was attenuated, as evidenced by altered viral kinetics in comparison with five control IgG-treated animals. Plasma samples obtained from the mice at viral challenge neutralized H77C-HCVpp at dilutions as high as 1/400. Infection was completely prevented when, before administration to naïve chimeric mice, the inoculum was pre-incubated in vitro at an IgG concentration normally observed in humans. Polyclonal IgG from a patient with a long-standing HCV infection not only displays neutralizing activity in vitro using the HCVpp system, but also conveys sterilizing immunity toward the ancestral HCV strain in vivo, using the human liver-chimeric mouse model. Both experimental systems will be useful tools to identify neutralizing antibodies for future clinical use.

  17. Hepatocyte nuclear factor 4A improves hepatic differentiation of immortalized adult human hepatocytes and improves liver function and survival.

    Science.gov (United States)

    Hang, Hua-Lian; Liu, Xin-Yu; Wang, Hai-Tian; Xu, Ning; Bian, Jian-Min; Zhang, Jian-Jun; Xia, Lei; Xia, Qiang

    2017-11-15

    Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH. Cells were analyzed for telomerase activity, proliferative capacity, hepatocyte markers, and tumorigenicity (c-myc) expression. Hepatocyte markers, hepatocellular functions, and morphology were studied in the HNF4A-overexpressing IHH. Hepatocyte markers and karyotype analysis were completed in the primary hepatocytes using shRNA knockdown of HNF4A. Nuclear translocation of β-catenin was assessed. Rat models of ALF were treated with encapsulated IHH or HNF4A-overexpressing IHH. A HNF4A-positive IHH line was established, which was non-tumorigenic and conserved properties of primary hepatocytes. HNF4A overexpression significantly enhanced mRNA levels of genes related to hepatic differentiation in IHH. Urea levels were increased by the overexpression of HNF4A, as measured 24h after ammonium chloride addition, similar to that of primary hepatocytes. Chromosomal abnormalities were observed in primary hepatocytes transfected with HNF4A shRNA. HNF4α overexpression could significantly promote β-catenin activation. Transplantation of HNF4A overexpressing IHH resulted in better liver function and survival of rats with ALF compared with IHH. HNF4A improved hepatic differentiation of IHH. Transplantation of HNF4A-overexpressing IHH could improve the liver function and survival in a rat model of ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Side Population Cells From an Immortalized Human Liver Epithelial Cell Line Exhibit Hepatic Stem-Like Cell Properties.

    Science.gov (United States)

    Tokiwa, Takayoshi; Yamazaki, Taisuke; Enosawa, Shin

    2012-01-01

    The existence of hepatic stem cells in human livers is controversial. We investigated whether the side population (SP) cells derived from an immortalized human liver epithelial cell line THLE-5b possess the properties of hepatic stem-like cells. SP cells derived from THLE-5b were isolated using flow cytometry and were assayed for the expression of phenotypic markers by reverse transcription polymerase chain reaction and immunostaining. THLE-5b SP cells retained the capacity to generate both SP and non-SP cells, showed a capacity for self-renewal, and were more efficient in colony formation than non-SP cells. Neither the SP nor the non-SP cells formed tumors when transplanted into athymic nude mice or severe combined immunodeficient mice. The expression level of stem cell-associated markers such as an ATP-binding cassette membrane transporter, epithelial cell adhesion molecule, c-kit, Thy-1, and octomer binding transcription factor 4 was higher in SP cells than in non-SP cells. When cultivated as rotation-mediated aggregates, the expression of liver-specific genes including tryptophan oxygenase and CYP3A4 was up-regulated in SP cells, suggesting that THLE-5b SP cells have the ability to differentiate into a hepatocyte phenotype. One of the clonal cell lines derived from the SP cells expressed stem cell-associated markers. These results indicate that SP cells derived from THLE-5b possess hepatic stem-like cell properties and suggest that THLE-5b can be used as a model of normal human liver progenitor or stem cell line.

  19. Telmisartan inhibits human urological cancer cell growth through early apoptosis

    Science.gov (United States)

    MATSUYAMA, MASAHIDE; FUNAO, KIYOAKI; KURATSUKURI, KATSUYUKI; TANAKA, TOMOAKI; KAWAHITO, YUTAKA; SANO, HAJIME; CHARGUI, JAMEL; TOURAINE, JEAN-LOUIS; YOSHIMURA, NORIO; YOSHIMURA, RIKIO

    2010-01-01

    Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agents. In addition, studies have provided evidence that ARBs have the potential to inhibit the growth of several types of cancer cells. It was reported that telmisartan (a type of ARB) has peroxisome proliferator-activated receptor (PPAR)-γ activation activity. We previously reported that the PPAR-γ ligand induces growth arrest in human urological cancer cells through apoptosis. In this study, we evaluated the effects of telmisartan and other ARBs on cell proliferation in renal cell carcinoma (RCC), bladder cancer (BC), prostate cancer (PC) and testicular cancer (TC) cell lines. The inhibitory effects of telmisartan and other ARBs (candesartan, valsartan, irbesartan and losartan) on the growth of the RCC, BC, PC and TC cell lines was investigated using an MTT assay. Flow cytometry and Hoechst staining were used to determine whether the ARBs induced apoptosis. Telmisartan caused marked growth inhibition in the urological cancer cells in a dose- and time-dependent manner. Urological cancer cells treated with 100 μM telmisartan underwent early apoptosis and DNA fragmentation. However, the other ARBs had no effect on cell proliferation in any of the urological cancer cell lines. Telmisartan may mediate potent anti-proliferative effects in urological cancer cells through PPAR-γ. Thus, telmisartan is a potent target for the prevention and treatment of human urological cancer. PMID:22993542

  20. Resources for Precision Analysis of Human Breast Cancer

    Science.gov (United States)

    2000-08-01

    Leygue, P. Watson, and L. C. Murphy. The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue. Clin. Cancer...antibody (Sigma, St. cluded an estimate of the cellular composition (including Louis, MO) as well as a rabbit polyclonal antibody, raised the percentage...Mississauga, ON). After blocking in controls for tumor assays, MCF7 human breast cancer 10% skimmed milk powder in Tris-buffered saline-0.05% cells obtained

  1. Risk of selected gastrointestinal and hepatic toxicities in cancer patients treated with nintedanib: a meta-analysis.

    Science.gov (United States)

    Abdel-Rahman, Omar; Bahie Eldin, Nermean; ElHalawani, Hesham

    2016-09-01

    A meta-analysis of the risk of selected gastrointestinal and hepatic toxicities associated with nintedanib has been conducted. Randomized Phase II/III trials of cancer patients on nintedanib; describing events of diarrhea, vomiting, elevated ALT and elevated AST constituted the eligible studies. The odds ratio for high-grade diarrhea was 3.76 (95% CI: 1.42-9.96; p = 0.008); high-grade vomiting: 1.38 (95% CI: 0.76-2.51; p = 0.28); high-grade elevated ALT: 4.36 (95% CI: 2.14-8.85; p Nintedanib-based regimens are associated with a higher risk of high-grade diarrhea, elevated ALT and elevated AST. Moreover, there is a proportional relationship between nintedanib dose and the risk of elevated transaminases.

  2. Effects of nucleoside analogue prescription for hepatitis B on the incidence of liver cancer in Hong Kong: a territory-wide ecological study.

    Science.gov (United States)

    Seto, W-K; Lau, E H Y; Wu, J T K; Hung, I F N; Leung, W K; Cheung, K-S; Fung, J; Lai, C-L; Yuen, M-F

    2017-02-01

    The temporal relationship between nucleoside analogue therapy for chronic hepatitis B (CHB) and liver cancer development has not been evaluated at a population level. To investigate the impact of nucleoside analogue prescription on liver cancer incidence in a CHB-prevalent region. We obtained territory-wide nucleoside analogue prescription data from 1999, when nucleoside analogue was first available in Hong Kong, to 2012 and the population-based liver cancer incidence data from 1990 to 2012. We compared the liver cancer incidences from 1990 to 1998 and 1999 to 2012 with adjustment for local hepatitis B surface antigen seroprevalence. Nucleoside analogue prescription patient headcount increased from 2006 per year in 1999 to 26 411 in 2012. Prescription volume in 2012 was highest among 55-64 years (30.3%), higher than 65-74 years (13.0%) and ≥75 years (5.8%). Age-standardised liver cancer incidence 1999-2012 decreased by 1.88%/year (95% CI 3.34% to 0.42%/year). NA therapy was associated with decline in age-adjusted liver cancer incidence (2.7 per 100 000 persons, P 0.05). Nucleoside analogue prescription was associated with a reduction of overall liver cancer incidence in a CHB-prevalent region. The lack of association among individuals of ≥65 years was consistent with the low nucleoside analogue prescription volume in elderly patients, mitigating the impact of CHB treatment on liver cancer. © 2016 John Wiley & Sons Ltd.

  3. Hepatitis B surface antigen fusions delivered by DNA vaccination elicit CTL responses to human papillomavirus oncoproteins associated with tumor protection.

    Science.gov (United States)

    Haigh, O; Kattenbelt, J; Cochrane, M; Thomson, S; Gould, A; Tindle, R

    2010-10-01

    We describe the construction and evaluation of a recombinant hepatitis B surface antigen (HBsAg)-vectored DNA vaccine encoding the E7 and E6 tumor-associated oncoproteins of human papillomavirus (HPV) type 16. We show the induction of effector and memory cytotoxic T lymphocyte responses to E7 and E6 class I-restricted epitopes after a single immunization, which were associated with tumor prevention and therapy. The findings vindicate the use of a HBsAg-based DNA vaccine as a vehicle to elicit responses to co-encoded tumor antigens, and have specific implications for the development of a therapeutic vaccine for HPV-associated squamous carcinomas.

  4. Clock gene expression in human and mouse hepatic models shows similar periodicity but different dynamics of variation.

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Rubino, Rosa; Tiberio, Cristiana; Giuliani, Francesco; Vinciguerra, Manlio; Oben, Jude; De Cata, Angelo; Tarquini, Roberto; De Cosmo, Salvatore; Liu, Shu; Cai, Yanning

    2016-01-01

    The biological hard-wiring of 24-hour rhythmicity relies on the circadian clock circuitry, made of peripheral oscillators operated by molecular clockworks and synchronized through humoral and neural outputs by central oscillators located in the hypothalamic suprachiasmatic nuclei. Metabolically active tissues, such as the liver, are entrained also by local cues represented by metabolic flux related to feeding. The mechanics of the molecular clockwork have been explored by studies using cell lines and wild type or genetically engineered mouse models. There is a compelling need to reduce the use of animals in experimental settings. The aim of our study was to evaluate the periodicity and dynamics of functioning of the hepatic clock gene machinery in human and mouse hepatic models. We compared the results obtained in human hepatoma cells (HepG2 cells) and in mouse liver, and a significant 24-hour rhythmic component was found for five clock genes in the HepG2 cells (Bmal1, Cry1, Per1, Per2, NR1D1) and for six clock genes in the mouse liver (Bmal1, Clock, Cry1, Per1, Per2, NR1D1). The amplitude of oscillation rendered by the cosine curve and the dynamics of expression rendered by the rate of change (the derivative of gene expression level with respect to time) were greater in the mouse liver than in the HepG2 cells for Bmal1, Per1, Per2 and NR1D1, and the cosine curve phase was different for many of them. In conclusion, the periodicity of expression of the clock genes showed similar patterns when the two experimental models were compared, whereas the dynamics of transcription in human hepatoma cells cultured in vitro were less vigorous and phased in a different way when compared to mouse hepatic tissue. The results support the reliability of the human hepatic in vitro model as an alternative to animal models only to study the periodicity of function of the molecular clockwork, but not to evaluate the dynamics of clock gene expression.

  5. Hepatic maturation of human iPS cell-derived hepatocyte-like cells by ATF5, c/EBPα, and PROX1 transduction.

    Science.gov (United States)

    Nakamori, Daiki; Takayama, Kazuo; Nagamoto, Yasuhito; Mitani, Seiji; Sakurai, Fuminori; Tachibana, Masashi; Mizuguchi, Hiroyuki

    2016-01-15

    Hepatocyte-like cells differentiated from human iPS cells (human iPS-HLCs) are expected to be utilized in drug development and research. However, recent hepatic characterization of human iPS-HLCs showed that these cells resemble fetal hepatocytes rather than adult hepatocytes. Therefore, in this study, we aimed to develop a method to enhance the hepatic function of human iPS-HLCs. Because the gene expression levels of the hepatic transcription factors (activating transcription factor 5 (ATF5), CCAAT/enhancer-binding protein alpha (c/EBPα), and prospero homeobox protein 1 (PROX1)) in adult liver were significantly higher than those in human iPS-HLCs and fetal liver, we expected that the hepatic functions of human iPS-HLCs could be enhanced by adenovirus (Ad) vector-mediated ATF5, c/EBPα, and PROX1 transduction. The gene expression levels of cytochrome P450 (CYP) 2C9, 2E1, alpha-1 antitrypsin, transthyretin, Na+/taurocholate cotransporting polypeptide, and uridine diphosphate glucuronosyl transferase 1A1 and protein expression levels of CYP2C9 and CYP2E1 were upregulated by ATF5, c/EBPα, and PROX1 transduction. These results suggest that the hepatic functions of the human iPS-HLCs could be enhanced by ATF5, c/EBPα, and PROX1 transduction. Our findings would be useful for the hepatic maturation of human iPS-HLCs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Seroprevalence of hepatitis B Surface antigen among apparently ...

    African Journals Online (AJOL)

    Introduction: Hepatitis B virus infection is a major public health problem worldwide. It is more infectious and more in Nigeria than the Human Immunodeficiency Virus (HIV). It is a major risk factor for the development of liver cirrhosis and hepatocellular cancer in hyperendemic areas. This study was carried out between 8th ...

  7. Reframing cervical cancer prevention. Expanding the field towards prevention of human papillomavirus infections and related diseases.

    Science.gov (United States)

    Bosch, F Xavier; Tsu, Vivien; Vorsters, Alex; Van Damme, Pierre; Kane, Mark A

    2012-11-20

    The reframed paradigm of cervical cancer prevention will include strategic combinations of at least four major components: 1) routine introduction of human papillomavirus (HPV) vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. On a global scale, vaccination of newborns and infants is well established and has developed a successful working infrastructure. The hepatitis B virus (HBV) vaccination programs offer a model for HPV introduction in which newborn and infant immunization achieves a rapid reduction in the prevalence of the HBV carrier rates in immunized cohorts of children, and of liver cirrhosis and liver cancer decades later. In contrast, screening for cervical pre-cancer is largely restricted to industrialized populations and upper social classes in developing countries. The expertise gained by vaccination programs worldwide needs to be coordinated with the traditional cervical cancer prevention community of gynecologists and pathologists. Significant political and advocacy efforts at the Global level (World Health Organization, other United Nations agencies and The GAVI Alliance) need to be organized and reinforced to achieve a meaningful reduction in HPV transmission and its related health conditions and cancers. This desirable goal is now scientifically and technologically attainable, and great progress is being made in obtaining financing for global HPV immunization. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Hepatitis C Virus and Human Immunodeficiency Virus-I (HIV) Co ...

    African Journals Online (AJOL)

    Rev Olaleye

    vaccine against it. (Enamoto and Sato, 1995). Transmission of HCV was mainly via infected blood products, prior to HCV testing. In 1990, the risk was 8 ..... professional. Pp. 1 — 18. Donahue, J.G.., Munoz, A., Ness, P. (1992): The declining risk of post transfusion hepatitis C virus infection. N. Engi. J. Med. 327, 369 — 373.

  9. Buprenorphine for human immunodeficiency virus/hepatitis C virus-coinfected patients: does it serve as a bridge to hepatitis C virus therapy?

    Science.gov (United States)

    Taylor, Lynn E; Maynard, Michaela A; Friedmann, Peter D; Macleod, Cynthia J; Rich, Josiah D; Flanigan, Timothy P; Sylvestre, Diana L

    2012-09-01

    Buprenorphine is associated with enhanced human immunodeficiency virus (HIV) treatment outcomes including increased antiretroviral therapy initiation rates, adherence, and CD4 cell counts among HIV-infected opioid-dependent individuals. Buprenorphine facilitates hepatitis C virus (HCV) treatment in opioid-dependent patients with HCV monoinfection. Less is known about buprenorphine's role in HIV/HCV coinfection. We conducted a retrospective chart review to evaluate HCV care for HIV-infected buprenorphine patients in the first 4 years of buprenorphine's integration into a Rhode Island HIV clinic. Sixty-one patients initiated buprenorphine. All had HCV antibody testing; 57 (93%) were antibody-positive. All antibody-positive patients underwent HCV RNA testing; 48 (84%) were RNA-positive. Of these, 15 (31%) were not referred to HCV care. Among chronically infected patients, 3 received HCV treatment after buprenorphine; all had cirrhosis and none achieved viral eradication. At buprenorphine induction, most patients had inadequately controlled HIV infection, with detectable HIV RNA (59%) or CD4 cell count less than or equal to 350/μL (38%). Buprenorphine has shown limited success to date as a bridge to HCV treatment within an HIV clinic. Buprenorphine's stabilization of opioid dependence and HIV disease may permit the use of HCV therapy over time.

  10. Epigenetic modifications in human thyroid cancer

    Science.gov (United States)

    FAAM, BITA; GHAFFARI, MOHAMMAD ALI; GHADIRI, ATA; AZIZI, FEREIDOUN

    2015-01-01

    Thyroid carcinoma is the most common endocrine malignancy of the endocrine organs, and its incidence rate has steadily increased over the last decade. Over 95% of thyroid carcinoma is derived from follicular cells that have a spectrum of differentiation to the most invasive malignancy. The molecular pathogenesis of thyroid cancer remains to be clarified, although activating the RET, RAS and BRAF oncogenes have been well characterized. Increasing evidence from previous studies demonstrates that acquired epigenetic abnormalities participating with genetic alteration results in altered patterns of gene expression/function. Aberrant DNA methylation has been established in the CpG regions and microRNAs (miRNAs) expression profile recognized in cancer development. In the present review, a literature review was performed using MEDLINE and PubMed with the terms ‘epigenetic patterns in thyroid cancer [or papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid cancer (MTC), anaplastic thyroid cancer (ATC)]’, ‘DNA methylation in thyroid cancer (or PTC, FTC, MTC, ATC)’, ‘miRNA expression in thyroid cancer (or PTC, FTC, MTC, ATC)’, ‘epigenetic patterns in cancer’ and the current understanding of epigenetic patterns in thyroid cancer was discussed. PMID:25469237

  11. HCSD: the human cancer secretome database

    DEFF Research Database (Denmark)

    Feizi, Amir; Banaei-Esfahani, Amir; Nielsen, Jens

    2015-01-01

    types. It has a simple and user friendly query system for basic and advanced search based on gene name, cancer type and data type as the three main query options. The results are visualized in an explicit and interactive manner. An example of a result page includes annotations, cross references, cancer...

  12. Endocrine therapy of human breast cancer grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Osborne, C K; Spang-Thomsen, M

    1987-01-01

    mice bearing transplanted human breast tumors have been proposed as such a model. This review therefore discusses the use of the athymic nude mouse model of the study of human breast cancer biology, and focuses on four subjects: 1. biological characteristics of heterotransplanted breast tumors; 2......Although there have been extensive studies of rodent breast tumor models, and of human breast cancer cell lines in culture, there is still need for a human tumor model which can be manipulated experimentally but also provides a valid expression of the tumor cells in a host environment. Athymic nude....... endocrinology and pharmacology of hormonal agents in the nude mouse; 3. endocrine sensitivity of heterotransplanted tumors; and 4. applicability and limitations of this model for the study of human breast cancer....

  13. Mutations of the BRAF gene in human cancer

    OpenAIRE

    Davies, H.; Bignell, G.R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H.; Garnett, M.J.; Bottomley, W.; Davis, N.; Dicks, E.; Ewing, R.; Floyd, Y.; Gray, K.

    2002-01-01

    Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF ge...

  14. The adult livers of immunodeficient mice support human hematopoiesis: evidence for a hepatic mast cell population that develops early in human ontogeny.

    Directory of Open Access Journals (Sweden)

    Marcus O Muench

    Full Text Available The liver plays a vital role in hematopoiesis during mammalian prenatal development but its hematopoietic output declines during the perinatal period. Nonetheless, hepatic hematopoiesis is believed to persist into adulthood. We sought to model human adult-liver hematopoiesis by transplantation of fetal and neonatal hematopoietic stem cells (HSCs into adult immunodeficient mice. Livers were found to be engrafted with human cells consisting primarily of monocytes and B-cells with lesser contributions by erythrocytes, T-cells, NK-cells and mast-cells. A resident population of CD117(++CD203c(+ mast cells was also documented in human midgestation liver, indicating that these cells comprise part of the liver's resident immune cell repertoire throughout human ontogeny. The murine liver was shown to support human multilineage hematopoiesis up to 321 days after transplant. Evidence of murine hepatic hematopoiesis was also found in common mouse strains as old as 2 years. Human HSC engraftment of the murine liver was demonstrated by detection of high proliferative-potential colony-forming cells in clonal cultures, observation of CD38-CD34(++ and CD133(+CD34(++ cells by flow cytometry, and hematopoietic reconstitution of secondary transplant recipients of chimeric liver cells. Additionally, chimeric mice with both hematopoietic and endothelial reconstitution were generated by intrasplenic injection of immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA transgene. In conclusion, the murine liver is shown to be a hematopoietic organ throughout adult life that can also support human hematopoiesis in severely immunodeficient strains. Further humanization of the murine liver can be achieved in mice harboring an uPA transgene, which support engraftment of non-hematopoietic cells types. Thus, offering a model system to study the interaction of diverse human liver cell types that regulate hematopoiesis and immune

  15. Investigation of the inhibitory effects of various drugs on the hepatic uptake of fexofenadine in humans.

    Science.gov (United States)

    Matsushima, Soichiro; Maeda, Kazuya; Ishiguro, Naoki; Igarashi, Takashi; Sugiyama, Yuichi

    2008-04-01

    Fexofenadine (FEX), an H(1)-receptor antagonist, is eliminated from the liver mainly in an unchanged form. Our previous study suggested that organic anion-transporting polypeptide (OATP) 1B3 contributes mainly to the hepatic uptake of FEX. On the other hand, a clinical report demonstrated that a T521C mutation of OATP1B1 increased its plasma area under the plasma concentration-time curve. Several compounds are reported to have a drug interaction with FEX, and some of this may be caused by the inhibition of its hepatic uptake. We determined which transporters are involved in the hepatobiliary transport of FEX by using double transfectants and examined whether clinically reported drug interactions with FEX could be explained by the inhibition of its hepatic uptake. Vectorial basal-to-apical transport of FEX was observed in double transfectants expressing OATP1B1/multidrug resistance-associated protein 2 (MRP2) and OATP1B3/MRP2, suggesting that OATP1B1 as well as OATP1B3 is involved in the hepatic uptake of FEX and that MRP2 can recognize FEX as a substrate. The inhibitory effects of compounds on FEX uptake in OATP1B3-expressing HEK293 cells were investigated, and the maximal degree of increase in plasma AUC of FEX by drug interaction in clinical situations was estimated. As a result, cyclosporin A and rifampicin were found to have the potential to interact with OATP1B3-mediated uptake at clinical concentrations. From these results, most of the reported drug interaction cannot be explained by the inhibition of hepatic uptake of FEX, and different mechanisms such as the inhibition of intestinal efflux should be considered.

  16. Current understanding of mdig/MINA in human cancers.

    Science.gov (United States)

    Thakur, Chitra; Chen, Fei

    2015-07-01

    Mineral dust-induced gene, mdig has recently been identified and is known to be overexpressed in a majority of human cancers and holds predictive power in the poor prognosis of the disease. Mdig is an environmentally expressed gene that is involved in cell proliferation, neoplastic transformation and immune regulation. With the advancement in deciphering the prognostic role of mdig in human cancers, our understanding on how mdig renders a normal cell to undergo malignant transformation is still very limited. This article reviews the current knowledge of the mdig gene in context to human neoplasias and its relation to the clinico-pathologic factors predicting the outcome of the disease in patients. It also emphasizes on the promising role of mdig that can serve as a potential candidate for biomarker discovery and as a therapeutic target in inflammation and cancers. Considering the recent advances in understanding the underlying mechanisms of tumor formation, more preclinical and clinical research is required to validate the potential of using mdig as a novel biological target of therapeutic and diagnostic value. Expression level of mdig influences the prognosis of several human cancers especially cancers of the breast and lung. Evaluation of mdig in cancers can offer novel biomarker with potential therapeutic interventions for the early assessment of cancer development in patients.

  17. BMI-1, a promising therapeutic target for human cancer

    Science.gov (United States)

    WANG, MIN-CONG; LI, CHUN-LI; CUI, JIE; JIAO, MIN; WU, TAO; JING, LI; NAN, KE-JUN

    2015-01-01

    BMI-1 oncogene is a member of the polycomb-group gene family and a transcriptional repressor. Overexpression of BMI-1 has been identified in various human cancer tissues and is known to be involved in cancer cell proliferation, cell invasion, distant metastasis, chemosensitivity and patient survival. Accumulating evidence has revealed that BMI-1 is also involved in the regulation of self-renewal, differentiation and tumor initiation of cancer stem cells (CSCs). However, the molecular mechanisms underlying these biological processes remain unclear. The present review summarized the function of BMI-1 in different human cancer types and CSCs, and discussed the signaling pathways in which BMI-1 is potentially involved. In conclusion, BMI-1 may represent a promising target for the prevention and therapy of various cancer types. PMID:26622537

  18. Seroprevalence of hepatitis B, hepatitis C, human immunodeficiency virus, Treponema pallidum, and co-infections among blood donors in Kyrgyzstan: a retrospective analysis (2013-2015).

    Science.gov (United States)

    Karabaev, Bakyt B; Beisheeva, Nurgul J; Satybaldieva, Aiganysh B; Ismailova, Aikul D; Pessler, Frank; Akmatov, Manas K

    2017-02-21

    Post-Soviet Kyrgyzstan has experienced a major surge in blood-borne infections, but data from adequately powered, up-to-date studies are lacking. We thus examined a) the seroprevalences of hepatitis B virus surface antigen (HBsAg), HIV-1 p24 antigen and antibodies against hepatitis C virus (anti-HCV), human immunodeficiency viruses (anti-HIV-1/2, HIV-1 group O), and Treponema pallidum among blood donors in Kyrgyzstan and assess their distribution according to sex, age, and provinces of residence; b) trends in the respective seroprevalences; and c) co-infection rates among the pathogens studied. Serological screening was performed on 37 165 blood donors at the Republican Blood Centre in Bishkek, Kyrgyzstan, between January 2013 and December 2015. We applied poststratification weights to control for sampling bias and used logistic regression analyses to examine the association of seropositivity and co-infections with sex, age, provinces of residence, and year of blood donation. Twenty nine thousand and one hundred forty-five (78%) donors were males and 8 020 (22%) were females. The median age was 27 years (range: 18 - 64). The prevalences of HBsAg, anti-HCV, HIV (p24 Ag and anti-HIV), and anti-T. pallidum were 3.6% (95%CI: 3.4 - 3.8%), 3.1% (3.0 - 3.3%), 0.78% (0.69 - 0.87%), and 3.3% (3.1 - 3.5%), respectively. Males were more likely to be seropositive for HBsAg than females (OR: 1.63; 95%CI: 1.40 - 1.90), but less likely to be seropositive for anti-HCV (0.85; 0.74 - 0.98) and HIV (0.65; 0.49 - 0.85). Prevalences were lower in the capital than in the other provinces. There was a decreasing trend in the seroprevalences of HBsAg, anti-HCV, and anti-T. pallidum from 2012 to 2015 (P-value for trend, P = 0.01, P Kyrgyzstan can be reclassified from high to lower-intermediate HBsAg endemicity, whereas the high HIV prevalence with a rising trend is an alarming finding that needs to be urgently addressed by public health authorities. The observed co-infections suggest

  19. Safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in hepatitis C virus/human immunodeficiency virus co-infected patients.

    Science.gov (United States)

    He, Xiaoping; Hopkins, Lynne; Everett, George; Carter, Willie M; SchroppDyce, Cynthia; Abusaada, Khalid; Hsu, Vincent

    2017-10-28

    To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection in an urban HIV clinic. A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016. All patients included were receiving antiretroviral therapy (ART) with HIV RNA values of 100 copies/mL or fewer regardless of baseline HCV RNA level. The primary end point was a sustained virologic response of HCV at 12 wk (SVR12) after the end of therapy. Of the 40 patients enrolled, 55% were black, 22.5% had been previously treated for HCV, and 25% had cirrhosis. The patients were on a wide range of ART. Overall, 39 patients (97.5%) had a SVR 12 after the end of therapy, including rates of 97.1% in patients with HCV genotype 1a and 100% in those with HCV genotype 1b. One patient with HCV genotype 3a was included and achieved SVR12. Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis. Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn't reveal any resistance associated mutation in the NS5A or NS5B region. Interestingly, 7 (17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen. Two (5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy, which resolved after resuming the same ART regimen. No severe adverse events were observed and no patient discontinued treatment because of adverse events. The most common adverse events included headache (12.5%), fatigue (10%), and diarrhea (2.5%). This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV, regardless of HCV baseline levels, HCV treatment history or cirrhosis

  20. Cytotoxic effect of co-expression of human hepatitis A virus 3C protease and bifunctional suicide protein FCU1 genes in a bicistronic vector.

    Science.gov (United States)

    Komissarov, Alexey; Demidyuk, Ilya; Safina, Dina; Roschina, Marina; Shubin, Andrey; Lunina, Nataliya; Karaseva, Maria; Kostrov, Sergey

    2017-08-01

    Recent reports on various cancer models demonstrate a great potential of cytosine deaminase/5-fluorocytosine suicide system in cancer therapy. However, this approach has limited success and its application to patients has not reached the desirable clinical significance. Accordingly, the improvement of this suicide system is an actively developing trend in gene therapy. The purpose of this study was to explore the cytotoxic effect observed after co-expression of hepatitis A virus 3C protease (3C) and yeast cytosine deaminase/uracil phosphoribosyltransferase fusion protein (FCU1) in a bicistronic vector. A set of mono- and bicistronic plasmid constructs was generated to provide individual or combined expression of 3C and FCU1. The constructs were introduced into HEK293 and HeLa cells, and target protein synthesis as well as the effect of 5-fluorocytosine on cell death and the time course of the cytotoxic effect was studied. The obtained vectors provide for the synthesis of target proteins in human cells. The expression of the genes in a bicistronic construct provide for the cytotoxic effect comparable to that observed after the expression of genes in monocistronic constructs. At the same time, co-expression of FCU1 and 3C recapitulated their cytotoxic effects. The combined effect of the killer and suicide genes was studied for the first time on human cells in vitro. The integration of different gene therapy systems inducing cell death (FCU1 and 3C genes) in a bicistronic construct allowed us to demonstrate that it does not interfere with the cytotoxic effect of each of them. A combination of cytotoxic genes in multicistronic vectors can be used to develop pluripotent gene therapy agents.

  1. Isolation and expansion of human pluripotent stem cell-derived hepatic progenitor cells by growth factor defined serum-free culture conditions.

    Science.gov (United States)

    Fukuda, Takayuki; Takayama, Kazuo; Hirata, Mitsuhi; Liu, Yu-Jung; Yanagihara, Kana; Suga, Mika; Mizuguchi, Hiroyuki; Furue, Miho K

    2017-03-15

    Limited growth potential, narrow ranges of sources, and difference in variability and functions from batch to batch of primary hepatocytes cause a problem for predicting drug-induced hepatotoxicity during drug development. Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells in vitro are expected as a tool for predicting drug-induced hepatotoxicity. Several studies have already reported efficient methods for differentiating hPSCs into hepatocyte-like cells, however its differentiation process is time-consuming, labor-intensive, cost-intensive, and unstable. In order to solve this problem, expansion culture for hPSC-derived hepatic progenitor cells, including hepatic stem cells and hepatoblasts which can self-renewal and differentiate into hepatocytes should be valuable as a source of hepatocytes. However, the mechanisms of the expansion of hPSC-derived hepatic progenitor cells are not yet fully understood. In this study, to isolate hPSC-derived hepatic progenitor cells, we tried to develop serum-free growth factor defined culture conditions using defined components. Our culture conditions were able to isolate and grow hPSC-derived hepatic progenitor cells which could differentiate into hepatocyte-like cells through hepatoblast-like cells. We have confirmed that the hepatocyte-like cells prepared by our methods were able to increase gene expression of cytochrome P450 enzymes upon encountering rifampicin, phenobarbital, or omeprazole. The isolation and expansion of hPSC-derived hepatic progenitor cells in defined culture conditions should have advantages in terms of detecting accurate effects of exogenous factors on hepatic lineage differentiation, understanding mechanisms underlying self-renewal ability of hepatic progenitor cells, and stably supplying functional hepatic cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Human dental pulp stem cells derived from cryopreserved dental pulp tissues of vital extracted teeth with disease demonstrate hepatic-like differentiation.

    Science.gov (United States)

    Chen, Y K; Huang, Anderson H C; Chan, Anthony W S; Lin, L M

    2016-06-01

    Reviewing the literature, hepatic differentiation of human dental pulp stem cells (hDPSCs) from cryopreserved dental pulp tissues of vital extracted teeth with disease has not been studied. This study is aimed to evaluate the hypothesis that hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease could possess potential hepatic differentiation. Forty vital extracted teeth with disease recruited for hDPSCs isolation, stem cell characterization and hepatic differentiation were randomly and equally divided into group A (liquid nitrogen-stored dental pulp tissues) and group B (freshly derived dental pulp tissues). Samples of hDPSCs isolated from groups A and B but without hepatic growth factors formed negative controls. A well-differentiated hepatocellular carcinoma cell line was employed as a positive control. All the isolated hDPSCs from groups A and B showed hepatic-like differentiation with morphological change from a spindle-shaped to a polygonal shape and normal karyotype. Differentiated hDPSCs and the positive control expressed hepatic metabolic function genes and liver-specific genes. Glycogen storage of differentiated hDPSCs was noted from day 7 of differentiation-medium culture. Positive immunofluorescence staining of low-density lipoprotein and albumin was observed from day 14 of differentiation-medium culture; urea production in the medium was noted from week 6. No hepatic differentiation was observed for any of the samples of the negative controls. We not only demonstrated the feasibility of hepatic-like differentiation of hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease but also indicated that the differentiated cells possessed normal karyotype and were functionally close to normal hepatic-like cells. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Rhein Induces Apoptosis in Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ching-Yao Chang

    2012-01-01

    Full Text Available Human breast cancers cells overexpressing HER2/neu are more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2 and control vector MCF-7 (MCF-7/VEC cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

  4. The Modulatory Role of Endogenous IL-24/mda-7 in Inflammatory Response of Human Hepatic Stellate Cell (HSC, LX2

    Directory of Open Access Journals (Sweden)

    Iman Jamhiri

    2018-02-01

    Full Text Available Abstract Background: High morbidity and limited therapies of hepatic fibro genesis are important factor for better understanding the molecular mechanisms of the disease. Advances in the understanding of the molecular behavior of hepatic stellate cells (HSC allow the progress of a field dedicated to anti-fibrotic therapy. Melanoma differentiation associated gene-7 (IL-24/mda-7 as a gene induced during terminal differentiation in human melanoma cells, but the inflammatory response of cells to IL-24/mda-7 is not entirely cleared. Materias and Methods: LX-2 cells (a human hepatic stellate cell were treated by leptin (positive control, media (control negative, or were transfected by empty plasmid and pcDNA3.1/mda-7. The inflammatory state was evaluated through measuring the mRNA expression level of inflammatory molecule, IL-1β. The role of IL-24/mda-7 modulation on inflammatory response was assayed using SOCS1 and SOCS3 gene expressions. Results: The expression levels of IL-1β, SOCS1 and SOCS3 were compared in LX-2 cell line groups. The expression of the IL-1β in the transfected cells was higher than the control cell, but it was not significant. The results indicated that the expressions of SOCS1 and SOCS3 were up-regulated following pcDNA 3.1/mda-7 transfection into LX-2 cells compared to control plasmids (p=0.0179, p=0.0428. Conclusion: The endogenous IL-24/mda-7 exhibited a significant modulatory effect on stellate cells. Therefore, IL-24/mda-7 and relevant signaling pathways could be employed as a target for fibrosis treatment.

  5. Defining the cellular precursors to human breast cancer

    Science.gov (United States)

    Keller, Patricia J.; Arendt, Lisa M.; Skibinski, Adam; Logvinenko, Tanya; Klebba, Ina; Dong, Shumin; Smith, Avi E.; Prat, Aleix; Perou, Charles M.; Gilmore, Hannah; Schnitt, Stuart; Naber, Stephen P.; Garlick, Jonathan A.; Kuperwasser, Charlotte

    2012-01-01

    Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM+) and basal/myoepithelial (CD10+). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM+ epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10+ cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10+ breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues. PMID:21940501

  6. Discovery of Human-Similar Gene Fusions in Canine Cancers.

    Science.gov (United States)

    Ulvé, Ronan; Rault, Mélanie; Bahin, Mathieu; Lagoutte, Laetitia; Abadie, Jérôme; De Brito, Clotilde; Coindre, Jean-Michel; Botherel, Nadine; Rousseau, Audrey; Wucher, Valentin; Cadieu, Edouard; Thieblemont, Catherine; Hitte, Christophe; Cornevin, Laurence; Cabillic, Florian; Bachelot, Laura; Gilot, David; Hennuy, Benoit; Guillaudeux, Thierry; Le Goff, Arnaud; Derrien, Thomas; Hédan, Benoît; André, Catherine

    2017-11-01

    Canine cancers represent a tremendous natural resource due to their incidence and striking similarities to human cancers, sharing similar clinical and pathologic features as well as oncogenic events, including identical somatic mutations. Considering the importance of gene fusions as driver alterations, we explored their relevance in canine cancers. We focused on three distinct human-comparable canine cancers representing different tissues and embryonic origins. Through RNA-Seq, we discovered similar gene fusions as those found in their human counterparts: IGK-CCND3 in B-cell lymphoma, MPB-BRAF in glioma, and COL3A1-PDGFB in dermatofibrosarcoma protuberans-like. We showed not only similar partner genes but also identical breakpoints leading to oncogene overexpression. This study demonstrates similar gene fusion partners and mechanisms in human-dog corresponding tumors and allows for selection of targeted therapies in preclinical and clinical trials with pet dogs prior to human trials, within the framework of personalized medicine. Cancer Res; 77(21); 5721-7. ©2017 AACR. ©2017 American Association for Cancer Research.

  7. Imaging of dihydrofolate reductase fusion gene expression in xenografts of human liver metastases of colorectal cancer in living rats

    Energy Technology Data Exchange (ETDEWEB)

    Mayer-Kuckuk, Philipp; Bertino, Joseph R.; Banerjee, Debabrata [Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); The Cancer Institute of New Jersey, Robert Wood Johnson Medical School/UMDNJ, 195 Little Albany Street, NJ 08903, New Brunswick (United States); Doubrovin, Mikhail; Blasberg, Ronald; Tjuvajev, Juri Gelovani [Department of Neurooncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Gusani, Niraj J.; Fong, Yuman [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Gade, Terence; Koutcher, Jason A. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Balatoni, Julius; Finn, Ronald [Radiochemistry/Cyclotron Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Akhurst, Tim; Larson, Steven [Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2003-09-01

    Radionuclide imaging has been demonstrated to be feasible to monitor transgene expression in vivo. We hypothesized that a potential application of this technique is to non-invasively detect in deep tissue, such as cancer cells metastatic to the liver, a specific molecular response following systemic drug treatment. Utilizing human colon adenocarcinoma cells derived from a patient's liver lesion we first developed a nude rat xenograft model for colorectal cancer metastatic to the liver. Expression of a dihydrofolate reductase-herpes simplex virus 1 thymidine kinase fusion (DHFR-HSV1 TK) transgene in the hepatic tumors was monitored in individual animals using the tracer [{sup 124}I]2'-fluoro-2'-deoxy-5-iodouracil-{beta}-d-arabinofuranoside (FIAU) and a small animal micro positron emission tomograph (microPET), while groups of rats were imaged using the tracer [{sup 131}I]FIAU and a clinical gamma camera. Growth of the human metastatic colorectal cancer cells in the rat liver was detected using magnetic resonance imaging and confirmed by surgical inspection. Single as well as multiple lesions of different sizes and sites were observed in the liver of the animals. Next, using a subset of rats bearing hepatic tumors, which were retrovirally bulk transduced to express the DHFR-HSV1 TK transgene, we imaged the fusion protein expression in the hepatic tumor of living rats using the tracer [{sup 124}I]FIAU and a microPET. The observed deep tissue signals were highly specific for the tumors expressing the DHFR-HSV1 TK fusion protein compared with parental untransduced tumors and other tissues as determined by gamma counting of tissue samples. A subsequent study used the tracer [{sup 131}I]FIAU and a gamma camera to monitor two groups of transduced hepatic tumor-bearing rats. Prior to imaging, one group was treated with trimetrexate to exploit DHFR-mediated upregulation of the fusion gene product. Imaging in the living animal as well as subsequent gamma

  8. Cancer-associated loss of TARSH gene expression in human primary lung cancer.

    Science.gov (United States)

    Terauchi, Kunihiko; Shimada, Junichi; Uekawa, Natsuko; Yaoi, Takeshi; Maruyama, Mitsuo; Fushiki, Shinji

    2006-01-01

    We have previously identified mouse Tarsh as one of the cellular senescence-related genes and showed the loss of expression of TARSH mRNA in four human lung cancer cell lines. TARSH is a presumptive signal transduction molecule interacting with NESH, which is implicated to have some roles in lung cancer metastasis. The amplification of complete ORF-encoding TARSH cDNA was done with reverse transcription-PCR. Northern blotting was carried out using TARSH cDNA probes. To clarify the relationship between TARSH and lung cancer, we quantified TARSH mRNA expression in 15 human lung cancer cell lines and 32 primary non-small cell lung cancers. We first determined the complete ORF-encoding cDNA sequence which is expressed in the human lung. On the Northern hybridization analysis, TARSH was strongly expressed in the human lung. The expression of TARSH mRNA is remarkably downregulated in all the lung cancer cell lines examined. Furthermore, TARSH expression was significantly low in all of the tumor specimens when compared to the expression in corresponding non-neoplastic lung tissue specimens. The cancer-associated transcriptional inactivation of TARSH suggests that TARSH could be used as a biomarker for lung cancer development as well as a molecular adjunct for lung carcinogenesis in human.

  9. Broad-spectrum antiviral activity including human immunodeficiency and hepatitis C viruses mediated by a novel retinoid thiosemicarbazone derivative.

    Science.gov (United States)

    Kesel, Andreas J

    2011-05-01

    Aromatic aldehyde-derived thiosemicarbazones 4-6, the S-substituted modified thiosemicarbazones 7/8, and a vitamin A-derived (retinoid) thiosemicarbazone derivative 12 were investigated as inhibitors of human hepatitis C virus (HCV) subgenomic RNA replicon Huh7 ET (luc-ubi-neo/ET) replication. Compounds 4-6 and 12 were found to be potent suppressors of HCV RNA replicon replication. The trifluoromethoxy-substituted thiosemicarbazone 6 and the retinoid thiosemicarbazone derivative 12 were even superior in selectivity to the included reference agent recombinant human alpha-interferon-2b, showing potencies in the nanomolar range of concentration. In addition, compounds 5, 6, 8 and 12 were tested as inhibitors of cytopathic effect (CPE) induced by human varicella-zoster virus (VZV) and/or human cytomegalovirus (HCMV). Compounds 4-6, 8 and 12 were additionally examined as inhibitors of CPE induced by cowpox virus and vaccinia virus. Thiosemicarbazone 4 was inhibitory on cowpox and vaccinia virus replication comparable in potency and selectivity to the reference agent cidofovir. Retinoid thiosemicarbazone derivative 12 was active as micromolar inhibitor of VZV, HCMV, and, in addition, human immunodeficiency virus type 1 (HIV-1) replication. These results indicate that thiosemicarbazone derivatives are appropriate lead structures to be evaluated in targeted antiviral therapies for hepatitis C (STAT-C), and that the vitamin A-related thiosemicarbazone derivative 12 emerges as a broad-spectrum antiviral agent, co-suppressing the multiplication of important RNA and DNA viruses. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  10. DIVERSITY OF ARSENIC METABOLISM IN CULTURED HUMAN CANCER CELL LINES

    Science.gov (United States)

    Diversity of arsenic metabolism in cultured human cancer cell lines. Arsenic has been known to cause a variety of malignancies in human. Pentavalent As (As 5+) is reduced to trivalent As (As3+) which is further methylated by arsenic methyltransferase(s) to monomethylarson...

  11. Novel Oncogene Induced Metastatic Prostate Cancer Cell Lines Define Human Prostate Cancer Progression Signatures

    Science.gov (United States)

    Ju, Xiaoming; Ertel, Adam; Casimiro, Mathew; Yu, Zuoren; Meng, Hui; McCue, Peter A.; Walters, Rhonda; Fortina, Paolo; Lisanti, Michael P.; Pestell, Richard G.

    2013-01-01

    Herein, murine prostate cancer cell lines, generated via selective transduction with a single oncogene (c-Myc, Ha-Ras, and v-Src), demonstrated oncogene-specific prostate cancer molecular signatures that were recapitulated in human prostate cancer, and developed lung metastasis in immune competent mice. Interrogation of two independent retrospective cohorts of patient samples using the oncogene signature demonstrated an ability to distinguish tumor from normal prostate with a predictive value for prostate cancer of 98 – 99%. In a blinded study, the signature algorithm demonstrated independent substratification of reduced recurrence free survival by Kaplan-Meier analysis. The generation of new oncogene-specific prostate cancer cell lines that recapitulate human prostate cancer gene expression, that metastasize in immune-competent mice, are a valuable new resource for testing targeted therapy while the molecular signatures identified herein provides further value over current gene signature markers of prediction and outcome. PMID:23204233

  12. Endogenous retroviral promoter exaptation in human cancer

    National Research Council Canada - National Science Library

    Babaian, Artem; Mager, Dixie L

    2016-01-01

      Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes...

  13. Virus, Oncolytic Virus and Human Prostate Cancer.

    Science.gov (United States)

    Liu, Guang Bin; Zhao, Liang; Zhang, Lifang; Zhao, Kong-Nan

    2017-01-01

    Prostate cancer (PCa), a disease, is characterized by abnormal cell growth in the prostate - a gland in the male reproductive system. Although older age and a family history of the disease have been recognized as the risk factors of PCa, the cause of this cancer remains unclear. Currently, PCa is one of the leading causes of cancer death among men of all races. In this review study, we first discuss the controversy of the contribution of virus infection to PCa, and subsequently summarize the development of oncolytic virotherapy for PCa in the past several years. Mounting evidence suggests that infections with various viruses are causally linked to PCa pathogenesis. Published studies have provided strong evidence that at least two viruses (RXMV and HPV) contribute to prostate tumourigenicity and impact on the survival of patients with malignant PCa. Traditional therapies including chemotherapy and radiotherapy are unable to distinguish cancer cells from normal cells, which are a significant drawback and leads to toxicities for PCa patients undergoing treatment. So far, few other options are available for treating patients with advanced PCa. For PCa treatment, oncolytic virotherapy appears to be much more attractive, which uses live viruses to selectively kill cancer cells. Oncolytic viruses can be genetically engineered to induce cancer cell lysis through virus replication and expression of cytotoxic proteins. Virotherapy is being developed to be a novel therapy for cancers, which uses oncotropic and oncolytic viruses with their abilities to find and destroy malignant cells in the body. As oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents, several important barriers still exist on the road to the use of oncolytic viruses for PCa therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Polymorphic expression of UDP-glucuronosyltransferase UGTlA gene in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Min Wang

    Full Text Available BACKGROUND: Polymorphism of genes encoding drug-metabolizing enzymes is known to play an important role in increased susceptibility of colorectal cancer. UGT1A gene locus has been suggested to define tissue-specific glucuronidation activity. Reduced capacity of glucuronidation is correlated with the development of colorectal cancer. Therefore, we sought to explore polymorphism of UGTlA gene in human colorectal cancer. METHODS: Cancerous and healthy tissues were obtained from selectedpatients. Blood samples were collected and UGTlA mRNA transcriptions were analyzed. Genomic DNA was prepared and UGTlA8 exon-1 sequences were amplified, visualized and purified. The extracted DNA was subcloned and sequenced. Two-tailed Fisher's exact test, Odds ratios (ORs, confidence interval (CIs and Logistics Regression Analysis were used for statistical analysis. RESULTS: UGTlA mRNA expression was reduced in cancerous tissues compared with healthy tissues from the same patient . The UGTlA mRNA expression of healthy tissue in study patients was lower than control . The mRNA expression of cancerous tissue was down-regulated in UGTlAl, 1A3, 1A4, lA6, 1A9 and up-regulated in UGTlA8 and UGTlAl0 UGT1A5 and UGT1A7 were not expressed in colonic tissue of either group. The allele frequency of WT UGTlA8*1 was higher (p = 0.000, frequency of UGTlA8*3 was lowered in control group (p = 0.000. The expression of homozygous UGTlA8*1 was higher in control group (p = 0.000. Higher frequency of both heterozygous UGTlA8*1/*3 and UGTlA8*2/*3 were found in study group (p = 0.000; p = 0.000. The occurrence of colorectal cancer was mainly related to the presence of polymorphic UGTlA8*3 alleles (p = 0.000. CONCLUSION: Regulation of human UGT1A genes is tissue-specific. Individual variation in polymorphic expressions of UGTlA gene locus was noted in all types of colonic tissue tested, whereas hepatic tissue expression was uniform. The high incidence of UGTlA8

  15. Human cancer protein-protein interaction network: a structural perspective.

    Directory of Open Access Journals (Sweden)

    Gozde Kar

    2009-12-01

    Full Text Available Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi-interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network. The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%. We illustrate the interface related affinity properties of two cancer-related hub

  16. Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development

    Science.gov (United States)

    Mueller, Kristina M.; Themanns, Madeleine; Friedbichler, Katrin; Kornfeld, Jan-Wilhelm; Esterbauer, Harald; Tuckermann, Jan P.; Moriggl, Richard

    2012-01-01

    Growth hormone (GH) and glucocorticoids (GCs) are involved in the control of processes that are essential for the maintenance of vital body functions including energy supply and growth control. GH and GCs have been well characterized to regulate systemic energy homeostasis, particular during certain conditions of physical stress. However, dysfunctional signaling in both pathways is linked to various metabolic disorders associated with aberrant carbohydrate and lipid metabolism. In liver, GH-dependent activation of the transcription factor signal transducer and activator of transcription (STAT) 5 controls a variety of physiologic functions within hepatocytes. Similarly, GCs, through activation of the glucocorticoid receptor (GR), influence many important liver functions such as gluconeogenesis. Studies in hepatic Stat5 or GR knockout mice have revealed that they similarly control liver function on their target gene level and indeed, the GR functions often as a cofactor of STAT5 for GH-induced genes. Gene sets, which require physical STAT5–GR interaction, include those controlling body growth and maturation. More recently, it has become evident that impairment of GH-STAT5 signaling in different experimental models correlates with metabolic liver disease, ranging from hepatic steatosis to hepatocellular carcinoma (HCC). While GH-activated STAT5 has a protective role in chronic liver disease, experimental disruption of GC-GR signaling rather seems to ameliorate metabolic disorders under metabolic challenge. In this review, we focus on the current knowledge about hepatic GH-STAT5 and GC-GR signaling in body growth, metabolism, and protection from fatty liver disease and HCC development. PMID:22564914

  17. Hedgehog signaling regulates telomerase reverse transcriptase in human cancer cells.

    Directory of Open Access Journals (Sweden)

    Tapati Mazumdar

    Full Text Available The Hedgehog (HH signaling pathway is critical for normal embryonic development, tissue patterning and cell differentiation. Aberrant HH signaling is involved in multiple human cancers. HH signaling involves a multi-protein cascade activating the GLI proteins that transcriptionally regulate HH target genes. We have previously reported that HH signaling is essential for human colon cancer cell survival and inhibition of this signal induces DNA damage and extensive cell death. Here we report that the HH/GLI axis regulates human telomerase reverse transcriptase (hTERT, which determines the replication potential of cancer cells. Suppression of GLI1/GLI2 functions by a C-terminus truncated GLI3 repressor mutant (GLI3R, or by GANT61, a pharmacological inhibitor of GLI1/GLI2, reduced hTERT protein expression in human colon cancer, prostate cancer and Glioblastoma multiforme (GBM cell lines. Expression of an N-terminus deleted constitutively active mutant of GLI2 (GLI2ΔN increased hTERT mRNA and protein expression and hTERT promoter driven luciferase activity in human colon cancer cells while GANT61 inhibited hTERT mRNA expression and hTERT promoter driven luciferase activity. Chromatin immunoprecipitation with GLI1 or GLI2 antibodies precipitated fragments of the hTERT promoter in human colon cancer cells, which was reduced upon exposure to GANT61. In contrast, expression of GLI1 or GLI2ΔN in non-malignant 293T cells failed to alter the levels of hTERT mRNA and protein, or hTERT promoter driven luciferase activity. Further, expression of GLI2ΔN increased the telomerase enzyme activity, which was reduced by GANT61 administration in human colon cancer, prostate cancer, and GBM cells. These results identify hTERT as a direct target of the HH signaling pathway, and reveal a previously unknown role of the HH/GLI axis in regulating the replication potential of cancer cells. These findings are of significance in understanding the important regulatory

  18. Ocular input for human melatonin regulation: relevance to breast cancer

    Science.gov (United States)

    Glickman, Gena; Levin, Robert; Brainard, George C.

    2002-01-01

    The impact of breast cancer on women across the world has been extensive and severe. As prevalence of breast cancer is greatest in industrialized regions, exposure to light at night has been proposed as a potential risk factor. This theory is supported by the epidemiological observations of decreased breast cancer in blind women and increased breast cancer in women who do shift-work. In addition, human, animal and in vitro studies which have investigated the melatonin-cancer dynamic indicate an apparent relationship between light, melatonin and cancer, albeit complex. Recent developments in understanding melatonin regulation by light in humans are examined, with particular attention to factors that contribute to the sensitivity of the light-induced melatonin suppression response. Specifically, the role of spectral characteristics of light is addressed, and recent relevant action spectrum studies in humans and other mammalian species are discussed. Across five action spectra for circadian and other non-visual responses, a peak sensitivity between 446-484 nm was identified. Under highly controlled exposure circumstances, less than 1 lux of monochromatic light elicited a significant suppression of nocturnal melatonin. In view of the possible link between light exposure, melatonin suppression and cancer risk, it is important to continue to identify the basic related ocular physiology. Visual performance, rather than circadian function, has been the primary focus of architectural lighting systems. It is now necessary to reevaluate lighting strategies, with consideration of circadian influences, in an effort to maximize physiological homeostasis and health.

  19. Dietary Acrylamide and Human Cancer: A Systematic Review of Literature

    Science.gov (United States)

    Nagy, Tim R.; Barnes, Stephen; Groopman, John

    2014-01-01

    Cancer remains the second leading cause of death in the United States, and the numbers of cases are expected to continue to rise worldwide. Cancer prevention strategies are crucial for reducing the cancer burden. The carcinogenic potential of dietary acrylamide exposure from cooked foods is unknown. Acrylamide is a by-product of the common Maillard reaction where reducing sugars (i.e., fructose and glucose) react with the amino acid, asparagine. Based on the evidence of acrylamide carcinogenicity in animals, the International Agency for Research on Cancer has classified acrylamide as a group 2A carcinogen for humans. Since the discovery of acrylamide in foods in 2002, a number of studies have explored its potential as a human carcinogen. This paper outlines a systematic review of dietary acrylamide and human cancer, acrylamide exposure and internal dose, exposure assessment methods in the epidemiologic studies, existing data gaps, and future directions. A majority of the studies reported no statistically significant association between dietary acrylamide intake and various cancers, and few studies reported increased risk for renal, endometrial, and ovarian cancers; however, the exposure assessment has been inadequate leading to potential misclassification or underestimation of exposure. Future studies with improved dietary acrylamide exposure assessment are encouraged. PMID:24875401

  20. Colon cancer presenting as a hepatic mass in pregnancy: A case ...

    African Journals Online (AJOL)

    A colonoscopic biopsy subsequently confirmed cancer of the colon. At laparotomy the cancer was found to be inoperable, and a defunctioning illeo- stomy was done and palliative chemotherapy planned. Discussion. Establishing a diagnosis of CRC presenting as a liver mass in pregnancy requires a high index of suspicion ...

  1. HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis.

    Science.gov (United States)

    Harrington, Willie; Bond, Vincent; Huang, Ming Bo; Powell, Michael; Lillard, James; Manne, Upender; Bumpers, Harvey

    2009-08-05

    CXCR4 receptors have been implicated in tumorigenesis and proliferation, making it a potential target for colorectal cancer therapy. Expression of this chemokine receptor on cellular surfaces appears to promote metastasis by directly stimulating tumor cell migration and invasion. The receptor/ligand, CXCR4/SDF-1alpha, pair are critically important to angiogenesis and vascular remodeling which supports cancer proliferation. Our work has shown that a novel apoptotic peptide of HIV-1, Nef-M1, can act as a CXCR4 antagonist, inducing apoptosis in CXCR4 containing cells. Four colorectal tumor cell lines (HT-29, LS174t, SW480, WiDr), were evaluated for their response to Nef-M1 peptide via in vivo and in vitro. The presence of CXCR4 receptors on tumor cells was determined using immunohistochemical and RT-PCR analyses. Solid xenografts derived from tumor cell lines grown in SCID mice, were evaluated for the persistence of the receptor. Xenografts propagated in SCID mice from each of the four cell lines demonstrated high levels of receptor expression as well. The effects of Nef-M1 in vivo via splenic injected mice and subsequent hepatic metastasis also demonstrated dramatic reduction of primary tumor growth in the spleen and secondary invasion of the liver. We concluded that Nef-M1 peptide, through physical interaction(s) with CXCR4, drives apoptotic reduction in in vivo primary tumor growth and metastasis.

  2. Prevalence of high-risk human papilloma virus among women with hepatitis C virus before liver transplantation.

    Science.gov (United States)

    Tarallo, P A; Smolowitz, J; Carriero, D; Tarallo, J; Siegel, A; Jia, H; Emond, J C

    2013-08-01

    We sought to assess the prevalence and risk factors for high-risk human papillomavirus (HPV) infection among female liver transplant (LT) candidates. Traditional health screening before LT listing has included Pap smear and is typically carried out by the patient's local provider. The prevalence of high-risk HPV in this population has not been studied. With Institutional Review Board approval, 62 LT candidates received a liquid-based Pap smear with high-risk HPV testing as part of their pre-transplant evaluation by a single provider. Clinical variables included age, ethnicity, insurance status, prior Pap smear, and HPV results, HPV risk factors including age of first intercourse, number of lifetime partners, last sexual activity, smoking, birth control pill use, history of sexually transmitted infections, human immunodeficiency virus status, immunosuppressive medication, medical diagnoses, prescribed medications, and history of hepatitis A, B, C, or D. The 62 women had a median age of 56 years, and 39% had high-risk behavior known to be associated with HPV. Ten of 62 patients (16.1%) had high-risk HPV at baseline screening, 5 of whom had atypical cytology. All of the patients who were positive for high-risk HPV had an etiology of hepatitis C virus (HCV) as the underlying cause of liver disease, with the majority (90%) having no history of high-risk behavior for HPV. In contrast, all patients with high-risk behavior who were HCV negative were HPV negative. Fisher's exact test demonstrated a statistically significant relationship between HPV and HCV; odds ratio = 24.4, 95% confidence interval, 1.4, 438.7, P-value = 0.0013. None of the other potential risk factors were associated with HPV in this cohort. In this study, we provide evidence of a strong association between HCV and HPV in LT candidates, which has not been previously reported. HPV positivity was observed in non-sexually active women, suggesting a reactivation of dormant HPV. An association between

  3. Cellular responses induced by Cu(II quinolinonato complexes in human tumor and hepatic cells

    Directory of Open Access Journals (Sweden)

    Trávníček Zdeněk

    2012-12-01

    Full Text Available Abstract Background Inspired by the unprecedented historical success of cisplatin, one of the most important research directions in bioinorganic and medicinal chemistry is dedicated to the development of new anticancer compounds with the potential to surpass it in antitumor activity, while having lower unwanted side-effects. Therefore, a series of copper(II mixed-ligand complexes of the type [Cu(qui(L]Y · xH2O (1–6, where Hqui = 2-phenyl-3-hydroxy-4(1H-quinolinone, Y = NO3 (1, 3, 5 or BF4 (2, 4, 6, and L = 1,10-phenanthroline (phen (1, 2, 5-methyl-1,10-phenanthroline (mphen (3, 4 and bathophenanthroline (bphen (5, 6, was studied for their in vitro cytotoxicity against several human cancer cell lines (A549 lung carcinoma, HeLa cervix epitheloid carcinoma, G361 melanoma cells, A2780 ovarian carcinoma, A2780cis cisplatin-resistant ovarian carcinoma, LNCaP androgen-sensitive prostate adenocarcinoma and THP-1 monocytic leukemia. Results The tested complexes displayed a stronger cytotoxic effect against all the cancer cells as compared to cisplatin. The highest cytotoxicity was found for the complexes 4 (IC50 = 0.36 ± 0.05 μM and 0.56 ± 0.15 μM, 5 (IC50 = 0.66 ± 0.07 μM and 0.73 ± 0.08 μM and 6 (IC50 = 0.57 ± 0.11 μM and 0.70 ± 0.20 μM against A2780, and A2780cis respectively, as compared with the values of 12.0 ± 0.8 μM and 27.0 ± 4.6 μM determined for cisplatin. Moreover, the tested complexes were much less cytotoxic to primary human hepatocytes than to the cancer cells. The complexes 5 and 6 exhibited significantly high ability to modulate secretion of the pro-inflammatory cytokines TNF-α (2873 ± 238 pg/mL and 3284 ± 139 pg/mL for 5, and 6 respectively and IL-1β (1177 ± 128 pg/mL and 1087 ± 101 pg/mL for 5, and 6 respectively tested on the lipopolysaccharide (LPS-stimulated THP-1 cells as compared with the values of 1173

  4. Binding of human lipoproteins (low, very low, high density lipoproteins) to recombinant envelope proteins of hepatitis C virus.

    Science.gov (United States)

    Monazahian, M; Kippenberger, S; Müller, A; Seitz, H; Böhme, I; Grethe, S; Thomssen, R

    2000-06-01

    Heterogeneities in the density of hepatitis C virus (HCV)-RNA-carrying material from human sera (1.03-1.20 g/ml) are partially due to the binding of lipoproteins [low density (LDL), very low density (VLDL), high density (HDL) lipoproteins] and immunoglobulins. In this study we demonstrate the binding of recombinant HCV envelope protein (El/E2) to human LDL, VLDL and HDL on a molecular basis. The binding of lipoproteins was restricted to the middle part of the El gene product (amino acids 222-336) and the C-terminal part of the E2 protein (amino acids 523-809). Lipoproteins did not bind to recombinant HCV core protein.

  5. Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer

    NARCIS (Netherlands)

    Garcia, M.B.; Blankenstein, M.A.; Wall, E. van der; Nortier, J.W.R.; Schornagel, J.H.; Thijssen, J.H.H.

    1990-01-01

    The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15-3, another member of the human mammary epithelial antigen

  6. Human papillomavirus in cervical cancer and oropharyngeal cancer: One cause, two diseases.

    Science.gov (United States)

    Berman, Tara A; Schiller, John T

    2017-06-15

    Human papillomavirus (HPV) causes greater than 5% of cancers worldwide, including all cervical cancers and an alarmingly increasing proportion of oropharyngeal cancers (OPCs). Despite markedly reduced cervical cancer incidence in industrialized nations with organized screening programs, cervical cancer remains the second most common cause of death from cancer in women worldwide, as developing countries lack resources for universal, high-quality screening. In the United States, HPV-related OPC is only 1 of 5 cancers with a rising incidence since 1975 and now has taken over the cervix as the most common site of HPV-related cancer. Similar trends follow throughout North America and Europe. The need for early detection and prevention is paramount. Despite the common etiologic role of HPV in the development of cervical cancer and HPV-associated OPC, great disparity exists between incidence, screening modalities (or lack thereof), treatment, and prevention in these 2 very distinct cohorts. These differences in cervical cancer and HPV-associated OPC and their impact are discussed here. Cancer 2017;123:2219-2229. © 2017 American Cancer Society. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  7. Urinary acylcarnitines are altered in human kidney cancer.

    Science.gov (United States)

    Ganti, Sheila; Taylor, Sandra L; Kim, Kyoungmi; Hoppel, Charles L; Guo, Lining; Yang, Joy; Evans, Christopher; Weiss, Robert H

    2012-06-15

    Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at concentrations different from control patients. Here, we collected urine samples from kidney cancer patients and analyzed them by chromatography coupled to mass spectrometry. Once normalized to control for urinary concentration, samples were analyzed by two independent laboratories. After technical validation, we now show differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades. This finding was validated in a mouse xenograft model of human kidney cancer. Biological validation shows carbon chain length-dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher chain length acylcarnitines demonstrated inhibitory effects on NF-κB activation, suggesting an immune modulatory effect of these compounds. Thus, acylcarnitines in the kidney cancer urine may reflect alterations in metabolism, cell component synthesis and/or immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites which may lead to new therapeutic approaches for cancer and may prove useful in cancer biomarker studies. Furthermore, these findings open up a new area of investigation into the metabolic basis of kidney cancer. Copyright © 2011 UICC.

  8. Human tissue models in cancer research: looking beyond the mouse

    Directory of Open Access Journals (Sweden)

    Samuel J. Jackson

    2017-08-01

    Full Text Available Mouse models, including patient-derived xenograft mice, are widely used to address questions in cancer research. However, there are documented flaws in these models that can result in the misrepresentation of human tumour biology and limit the suitability of the model for translational research. A coordinated effort to promote the more widespread development and use of ‘non-animal human tissue’ models could provide a clinically relevant platform for many cancer studies, maximising the opportunities presented by human tissue resources such as biobanks. A number of key factors limit the wide adoption of non-animal human tissue models in cancer research, including deficiencies in the infrastructure and the technical tools required to collect, transport, store and maintain human tissue for lab use. Another obstacle is the long-standing cultural reliance on animal models, which can make researchers resistant to change, often because of concerns about historical data compatibility and losing ground in a competitive environment while new approaches are embedded in lab practice. There are a wide range of initiatives that aim to address these issues by facilitating data sharing and promoting collaborations between organisations and researchers who work with human tissue. The importance of coordinating biobanks and introducing quality standards is gaining momentum. There is an exciting opportunity to transform cancer drug discovery by optimising the use of human tissue and reducing the reliance on potentially less predictive animal models.

  9. A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Rebecca Lim

    2017-08-01

    Full Text Available Liver cirrhosis is the 6th leading cause of death in adults aged 15–59 years in high-income countries. For many who progress to cirrhosis, the only prospect for survival is liver transplantation. While there is some indication that mesenchymal stem cells may be useful in reversing established liver fibrosis, there are limitations to their widespread use – namely their rarity, the need for extensive serial passaging and the associated potential for genomic instability and cellular senescence. To this end, we propose the use of allogeneic amnion epithelial cells. This clinical trial will assess the safety of intravenously delivered allogeneic human amnion epithelial cells (hAECs in patients with compensated liver cirrhosis. This will also provide clinical data that will inform phases 2 and 3 clinical trials with the ultimate goal of developing hAECs as a therapeutic option for patients with cirrhosis who are at significant risk of disease progression. We will recruit 12 patients with compensated cirrhosis, based on their hepatic venous pressure gradient, for a dose escalation study. Patients will be closely monitored in the first 24 h post-infusion, then via daily telephone interviews until clinical assessment on day 5. Long term follow up will include standard liver tests, transient elastography and hepatic ultrasound. Ethics approval was obtained from Monash Health for this trial 16052A, “A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Liver Fibrosis, A First in Adult Human Study.” The trial will be conducted in accordance to Monash Health Human Ethics guidelines. Outcomes from this study will be disseminated in the form of conference presentations and submission to a peer reviewed journal. This trial has been registered on the Australian and New Zealand Clinical Trials Registry ACTRN12616000437460.

  10. Endocrine Disruption and Human Prostate Cancer

    National Research Council Canada - National Science Library

    Risbridger, Gail

    2008-01-01

    .... In order to test the concept that Vinclozolin alters human prostate development and induces disease, we used our model system to study human prostate development and maturation over 8-12 weeks...

  11. Human Papillomavirus (HPV) and Oropharyngeal Cancer

    Science.gov (United States)

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Human papillomavirus (HPV) can cause serious health problems, including ... any health problems. What is genital HPV? Genital human papillomavirus (also called HPV) is the most common ...

  12. [A case of hepatitis B virus/human immunodeficiency virus coinfection in a patient who achived hepatitis B surface antigen seroclearance after interferon therapy followed by antiretroviral therapy without developing immune reconstitution inflammatory syndrome].

    Science.gov (United States)

    Mitsumoto, Fujiko; Murata, Masayuki; Ikezaki, Hiroaki; Ogawa, Eiichi; Taniai, Hiroaki; Toyoda, Kazuhiro; Otaguro, Shigeru; Kainuma, Mosaburo; Okada, Kyoko; Furusyo, Norihiro; Hayashi, Jun

    2012-11-01

    Coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) is common worldwide. The current guidelines for the treatment of HIV infection recommend that HIV patients coinfected with HBV receive antiretoroviral therapy (ART) with two nucleoside analogs against HBV. However, an increase in liver enzymes that is usually attributed to HBV immune reconstitution inflammatory syndrome (IRIS) sometimes occurs in HBV/HIV-coinfected patients after the commencement of ART. We report a case of HBV/HIV-coinfection in which the chronic hepatitis B was successfully treated using interferon (IFN) therapy followed by ART without the development of IRIS. A Japanese man in thirties was referred to our hospital because of an acute HIV infection two months after the diagnosis of an acute HBV infection, which had progressed to a chronic HBV infection. The laboratory test results were as follows:hepatitis B surface antigen (HBsAg) positive, hepatitis B e antigen (HBeAg) positive, HBV DNA level of 8.8 Log copies/mL, HBV genotype A, alanine aminotransferase of 834 IU/L, HIV RNA level of 5 Log copies/mL, and a CD4+ T cell count of 437/microL. The initial treatment was natural IFNalpha therapy for chronic hepatitis B, and HBeAg seroclearance was achieved 20 weeks after the start of therapy. Four months after the end of IFN therapy for 24 weeks, ART including tenofovir and emtricitabine against HBV was commenced. Six months after starting ART, the patient's serum HBV DNA level had decreased and become undetectable and HBsAg seroclearance was achieved without an elevation in liver enzymes. The present case suggests that IFN therapy prior to ART contributes to a successful outcome for chronic hepatitis B patients coinfected with HIV, if the HIV status does not require the immediate start of ART.

  13. Thermal Inactivation Kinetics of Human Norovirus Surrogates and Hepatitis A Virus in Turkey Deli Meat

    Science.gov (United States)

    Bozkurt, Hayriye; Davidson, P. Michael

    2015-01-01

    Human noroviruses (HNoV) and hepatitis A virus (HAV) have been implicated in outbreaks linked to the consumption of presliced ready-to-eat deli meats. The objectives of this research were to determine the thermal inactivation kinetics of HNoV surrogates (murine norovirus 1 [MNV-1] and feline calicivirus strain F9 [FCV-F9]) and HAV in turkey deli meat, compare first-order and Weibull models to describe the data, and calculate Arrhenius activation energy values for each model. The D (decimal reduction time) values in the temperature range of 50 to 72°C calculated from the first-order model were 0.1 ± 0.0 to 9.9 ± 3.9 min for FCV-F9, 0.2 ± 0.0 to 21.0 ± 0.8 min for MNV-1, and 1.0 ± 0.1 to 42.0 ± 5.6 min for HAV. Using the Weibull model, the tD = 1 (time to destroy 1 log) values for FCV-F9, MNV-1, and HAV at the same temperatures ranged from 0.1 ± 0.0 to 11.9 ± 5.1 min, from 0.3 ± 0.1 to 17.8 ± 1.8 min, and from 0.6 ± 0.3 to 25.9 ± 3.7 min, respectively. The z (thermal resistance) values for FCV-F9, MNV-1, and HAV were 11.3 ± 2.1°C, 11.0 ± 1.6°C, and 13.4 ± 2.6°C, respectively, using the Weibull model. The z values using the first-order model were 11.9 ± 1.0°C, 10.9 ± 1.3°C, and 12.8 ± 1.7°C for FCV-F9, MNV-1, and HAV, respectively. For the Weibull model, estimated activation energies for FCV-F9, MNV-1, and HAV were 214 ± 28, 242 ± 36, and 154 ± 19 kJ/mole, respectively, while the calculated activation energies for the first-order model were 181 ± 16, 196 ± 5, and 167 ± 9 kJ/mole, respectively. Precise information on the thermal inactivation of HNoV surrogates and HAV in turkey deli meat was generated. This provided calculations of parameters for more-reliable thermal processes to inactivate viruses in contaminated presliced ready-to-eat deli meats and thus to reduce the risk of foodborne illness outbreaks. PMID:25956775

  14. Decorin in Human Colon Cancer: Localization In Vivo and Effect on Cancer Cell Behavior In Vitro.

    Science.gov (United States)

    Nyman, Marie C; Sainio, Annele O; Pennanen, Mirka M; Lund, Riikka J; Vuorikoski, Sanna; Sundström, Jari T T; Järveläinen, Hannu T

    2015-09-01

    Decorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational. © The Author(s) 2015.

  15. Cell Pleomorphism and Cytoskeleton Disorganization in Human Liver Cancer.

    Science.gov (United States)

    Cheng, Chiung-Chi; Lai, Yen-Chang Clark; Lai, Yih-Shyong; Chao, Wei-Ting; Tseng, Yu-Hui; Hsu, Yung-Hsiang; Chen, You-Yin; Liu, Yi-Hsiang

    Nucleoskeleton maintains the framework of a cell nucleus that is required for a variety of nuclear functions. However, the nature of nucleoskeleton structure has not been yet clearly elucidated due to microscopy visualization limitations. Plectin, a nuclear pore-permeable component of cytoskeleton, exhibits a role of cross-linking between cytoplasmic intermediate filaments and nuclear lamins. Presumably, plectin is also a part of nucleoskeleton. Previously, we demonstrated that pleomorphism of hepatoma cells is the consequence of cytoskeletal changes mediated by plectin deficiency. In this study, we applied a variety of technologies to detect the cytoskeletons in liver cells. The images of confocal microscopy did not show the existence of plectin, intermediate filaments, microfilaments and microtubules in hepatic nuclei. However, in the isolated nuclear preparation, immunohistochemical staining revealed positive results for plectin and cytoskeletal proteins that may contribute to the contamination derived from cytoplasmic residues. Therefore, confocal microscopy provides a simple and effective technology to observe the framework of nucleoskeleton. Accordingly, we verified that cytoskeletons are not found in hepatic cell nuclei. Furthermore, the siRNA-mediated knockdown of plectin in liver cells leads to collapsed cytoskeleton, cell transformation and pleomorphic nuclei. Plectin and cytoskeletons were not detected in the nuclei of liver cells compared to the results of confocal microscopy. Despite the absence of nuclear plectin and cytoskeletal filaments, the evidence provided support that nuclear pleomorphism of cancer cells is correlated with the cytoplasmic disorganization of cytoskeleton. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Hepatitis D virus infections among injecting drug users with and without human immunodeficiency virus infection in Taiwan

    Directory of Open Access Journals (Sweden)

    Meng-Hsuan Hsieh

    2016-10-01

    Full Text Available In Taiwan, injecting drug use has been the main route of human immunodeficiency virus (HIV transmission since 2005, with hepatitis B virus (HBV and hepatitis D virus (HDV also having similar transmission routes. This has now become an important public health issue. The aim of this study is to explore the conditions of HDV infections between injecting drug users (IDUs with and without HIV infection in Southern Taiwan. In this study, 87 IDUs were enrolled, including 27 anti-HDV seronegative IDUs and 60 anti-HDV seropositive IDUs, and the results of their liver function tests, CD4 cell counts, and anti-HIV and HIV RNA levels were analyzed. The prevalence of anti-HDV seropositivity among hepatitis B surface antigen (HBsAg seropositive IDUs in this study was 68.9% (60/87. The prevalence rate of anti-HDV seropositive IDUs among anti-HIV seronegative and anti-HIV seropositive cases was 40.0% (12/30 and 84.2% (48/57, respectively. Anti-HIV seropositivity was related to anti-HDV seropositivity (odds ratio = 9.34, 95% confidence interval = 2.67–31.59, p < 0.001. Among IDUs with HIV infection, there was no significant difference in CD4 cell counts and HIV RNA viral load between HBsAg-positive patients with anti-HDV seronegativity and those with anti-HDV seropositivity. In conclusion, the prevalence of HDV infection among IDUs is higher among IDUs with HIV infection. Because anti-HIV seropositivity is significantly related to anti-HDV seropositivity, HDV infection among IDUs is still important. We suggest that for IDUs, HBsAg and anti-HDV should be monitored closely.

  17. Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach.

    Directory of Open Access Journals (Sweden)

    Dong Ding

    Full Text Available Integration of the viral DNA into host chromosomes was found in most of the hepatitis B virus (HBV-related hepatocellular carcinomas (HCCs. Here we devised a massive anchored parallel sequencing (MAPS method using next-generation sequencing to isolate and sequence HBV integrants. Applying MAPS to 40 pairs of HBV-related HCC tissues (cancer and adjacent tissues, we identified 296 HBV integration events corresponding to 286 unique integration sites (UISs with precise HBV-Human DNA junctions. HBV integration favored chromosome 17 and preferentially integrated into human transcript units. HBV targeted genes were enriched in GO terms: cAMP metabolic processes, T cell differentiation and activation, TGF beta receptor pathway, ncRNA catabolic process, and dsRNA fragmentation and cellular response to dsRNA. The HBV targeted genes include 7 genes (PTPRJ, CNTN6, IL12B, MYOM1, FNDC3B, LRFN2, FN1 containing IPR003961 (Fibronectin, type III domain, 7 genes (NRG3, MASP2, NELL1, LRP1B, ADAM21, NRXN1, FN1 containing IPR013032 (EGF-like region, conserved site, and three genes (PDE7A, PDE4B, PDE11A containing IPR002073 (3', 5'-cyclic-nucleotide phosphodiesterase. Enriched pathways include hsa04512 (ECM-receptor interaction, hsa04510 (Focal adhesion, and hsa04012 (ErbB signaling pathway. Fewer integration events were found in cancers compared to cancer-adjacent tissues, suggesting a clonal expansion model in HCC development. Finally, we identified 8 genes that were recurrent target genes by HBV integration including fibronectin 1 (FN1 and telomerase reverse transcriptase (TERT1, two known recurrent target genes, and additional novel target genes such as SMAD family member 5 (SMAD5, phosphatase and actin regulator 4 (PHACTR4, and RNA binding protein fox-1 homolog (C. elegans 1 (RBFOX1. Integrating analysis with recently published whole-genome sequencing analysis, we identified 14 additional recurrent HBV target genes, greatly expanding the HBV recurrent target list

  18. The oncogenic potential of human cytomegalovirus and breast cancer.

    Directory of Open Access Journals (Sweden)

    Georges eHerbein

    2014-08-01

    Full Text Available Breast cancer is among the leading causes of cancer-related death among women. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. Numerous articles indicate that breast tumors exhibit diverse phenotypes depending on their distinct physiopathological signatures, clinical courses and therapeutic possibilities. The human cytomegalovirus (HCMV is a multifaceted highly host specific betaherpesvirus that is regarded as asymptomatic or mildly pathogenic virus in immunocompetent host. HCMV may cause serious in utero infections as well as acute and chronic complications in immunocompromised individual. The involvement of HCMV in late inflammatory complications underscores its possible role in inflammatory diseases and cancer. HCMV targets a variety of cell types in vivo, including macrophages, epithelial cells, endothelial cells, fibroblasts, stromal cells, neuronal cells, smooth muscle cells, and hepatocytes. HCMV can be detected in the milk after delivery and thereby HCMV could spread to adjacent mammary epithelial cells. HCMV also infects macrophages and induces an atypical M1/M2 phenotype, close to the tumor associated macrophage phenotype, which is associated with the release of cytokines involved in cancer initiation or promotion and breast cancer of poor prognosis. HCMV antigens and DNA have been detected in tissue biopsies of breast cancers and elevation in serum HCMV IgG antibody levels has been reported to precede the development of breast cancer in some women. In this review, we will discuss the potential role of HCMV in the initiation and progression of breast cancer.

  19. Long non-coding RNA CASC2 in human cancer.

    Science.gov (United States)

    Palmieri, Giuseppe; Paliogiannis, Panagiotis; Sini, Maria Cristina; Manca, Antonella; Palomba, Grazia; Doneddu, Valentina; Tanda, Francesco; Pascale, Maria Rosa; Cossu, Antonio

    2017-03-01

    Long non-coding RNAs cover large part of the non-coding information of the human DNA, which represents more than 90% of the whole genome. They constitute a wide and complex group of molecules with more than 200 nucleotides, which generally lack an open reading frame, and are involved in various ways in the pathophysiology of cancer. Their roles in the regulation of gene expression, imprinting, transcription, and post-translational processing have been described in several types of cancer. CASC2 was discovered in 2004 in patients with endometrial carcinoma as a potential tumor suppressor. Since then, additional studies in other types of neoplasia have been carried out, and both mechanisms and interactions of CASC2 in cancer have been better elucidated. In this review, we summarize the current knowledge on the role of CASC2 in the genesis, progression, and clinical management of human cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Human Equilibrative Nucleoside Transporter 1, as a Predictor of 5-Fluorouracil Resistance in Human Pancreatic Cancer

    National Research Council Canada - National Science Library

    MASANORI TSUJIE; SHOJI NAKAMORI; SHIN NAKAHIRA; YUJI TAKAHASHI; NOBUYASU HAYASHI; JIRO OKAMI; HIROAKI NAGANO; KEIZO DONO; KOJI UMESHITA; MASATO SAKON; MORITO MONDEN

    2007-01-01

    ...€²-difluoro-deoxycytidine) sensitivity in pancreatic cancer. Materials and Methods: The relationship between 5-FU and gemcitabine sensitivity and the mRNA levels of human equilibrative nucleoside transporter 1 (hENT1...

  1. Low-dose adenovirus vaccine encoding chimeric hepatitis B virus surface antigen-human papillomavirus type 16 E7 proteins induces enhanced E7-specific antibody and cytotoxic T-cell responses.

    Science.gov (United States)

    Báez-Astúa, Andrés; Herráez-Hernández, Elsa; Garbi, Natalio; Pasolli, Hilda A; Juárez, Victoria; Zur Hausen, Harald; Cid-Arregui, Angel

    2005-10-01

    Induction of effective immune responses may help prevent cancer progression. Tumor-specific antigens, such as those of human papillomaviruses involved in cervical cancer, are targets with limited intrinsic immunogenicity. Here we show that immunization with low doses (10(6) infectious units/dose) of a recombinant human adenovirus type 5 encoding a fusion of the E7 oncoprotein of human papillomavirus type 16 to the carboxyl terminus of the surface antigen of hepatitis B virus (HBsAg) induces remarkable E7-specific humoral and cellular immune responses. The HBsAg/E7 fusion protein assembled efficiently into virus-like particles, which stimulated antibody responses against both carrier and foreign antigens, and evoked antigen-specific kill of an indicator cell population in vivo. Antibody and T-cell responses were significantly higher than those induced by a control adenovirus vector expressing wild-type E7. Such responses were not affected by preexisting immunity against either HBsAg or adenovirus. These data demonstrate that the presence of E7 on HBsAg particles does not interfere with particle secretion, as it occurs with bigger proteins fused to the C terminus of HBsAg, and results in enhancement of CD8(+)-mediated T-cell responses to E7. Thus, fusion to HBsAg is a convenient strategy for developing cervical cancer therapeutic vaccines, since it enhances the immunogenicity of E7 while turning it into an innocuous secreted fusion protein.

  2. Adjuvant Hepatic Arterial Infusion Chemotherapy After Resection for Pancreatic Cancer Using Coaxial Catheter-Port System Compared with Conventional System

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Aya; Tanaka, Toshihiro, E-mail: toshihir@bf6.so-net.ne.jp [Nara Medical University, Department of Radiology (Japan); Sho, Masayuki [Nara Medical University, Department of Surgery (Japan); Nishiofuku, Hideyuki; Masada, Tetsuya; Sato, Takeshi; Marugami, Nagaaki [Nara Medical University, Department of Radiology (Japan); Anai, Hiroshi [Nara City Hospital, Department of Radiology (Japan); Sakaguchi, Hiroshi [Nara Prefectural Western Medical Center, Department of Radiology (Japan); Kanno, Masatoshi [Nara Medical University, Oncology Center (Japan); Tamamoto, Tetsuro; Hasegawa, Masatoshi [Nara Medical University, Department of Radiation Oncology (Japan); Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery (Japan); Kichikawa, Kimihiko [Nara Medical University, Department of Radiology (Japan)

    2016-06-15

    PurposePrevious reports have shown the effectiveness of adjuvant hepatic arterial infusion chemotherapy (HAIC) in pancreatic cancer. However, percutaneous catheter placement is technically difficult after pancreatic surgery. The purpose of this study was to evaluate the feasibility and outcome of HAIC using a coaxial technique compared with conventional technique for postoperative pancreatic cancer.Materials and Methods93 consecutive patients who received percutaneous catheter-port system placement after pancreatectomy were enrolled. In 58 patients from March 2006 to August 2010 (Group A), a conventional technique with a 5-Fr indwelling catheter was used and in 35 patients from September 2010 to September 2012 (Group B), a coaxial technique with a 2.7-Fr coaxial catheter was used.ResultsThe overall technical success rates were 97.1 % in Group B and 86.2 % in Group A. In cases with arterial tortuousness and stenosis, the success rate was significantly higher in Group B (91.7 vs. 53.8 %; P = 0.046). Fluoroscopic and total procedure times were significantly shorter in Group B: 14.7 versus 26.7 min (P = 0.001) and 64.8 versus 80.7 min (P = 0.0051), respectively. No differences were seen in the complication rate. The 1 year liver metastasis rates were 9.9 % using the conventional system and 9.1 % using the coaxial system (P = 0.678). The overall median survival time was 44 months. There was no difference in the survival period between two systems (P = 0.312).ConclusionsThe coaxial technique is useful for catheter placement after pancreatectomy, achieving a high success rate and reducing fluoroscopic and procedure times, while maintaining the safety and efficacy for adjuvant HAIC in pancreatic cancer.

  3. Evaluation of hepatic calcifications in cancer patients with ultrasonography and computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Oehl, S.; Rehwald, U.; Heckemann, R.

    1985-02-01

    Eight patients with metastatic solid tumours had calcified liver metastases. These infiltrates can be demonstrated by plain X-ray pictures, however, they may be differentiated earlier by sonography and computed tomography. Their appearance does not necessarily correlate with the histology or response to treatment. In addition to cases of colorectal malignancy, this unusual finding occurred in association with breast cancer, thyroid and ovarian cancer.

  4. Multimodal nonlinear optical microscopy used to discriminate human colon cancer

    Science.gov (United States)

    Adur, Javier; Pelegati, Vitor B.; Bianchi, Mariana; de Thomaz, André A.; Baratti, Mariana O.; Carvalho, Hernandes F.; Casco, Víctor H.; Cesar, Carlos L.

    2013-02-01

    Colon cancer is one of the most diffused cancers in the Western World, ranking third worldwide in frequency of incidence after lung and breast cancers. Even if it is curable when detected and treated early, a more accurate premature diagnosis would be a suitable aim for both cancer prognostic and treatment. Combined multimodal nonlinear optical (NLO) microscopies, such as two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third harmonic generation (THG), and fluorescence lifetime imaging microscopy (FLIM) can be used to detect morphological and metabolic changes associated with stroma and epithelial transformation in colon cancer disease. NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns between normal and malignant human colonic mucosa. Using a set of scoring methods significant differences both in the content, distribution and organization of stroma collagen fibrils, and lifetime components of NADH and FAD cofactors of human colon mucosa biopsies were found. Our results provide a framework for using NLO techniques as a clinical diagnostic tool for human colon cancer, and also suggest that the SHG and FLIM metrics could be applied to other intestinal disorders, which are characterized by abnormal cell proliferation and collagen assembly.

  5. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

    Directory of Open Access Journals (Sweden)

    G-Andre Banat

    Full Text Available Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+, cytotoxic-T cells (CD8+, T-helper cells (CD4+, B cells (CD20+, macrophages (CD68+, mast cells (CD117+, mononuclear cells (CD11c+, plasma cells, activated-T cells (MUM1+, B cells, myeloid cells (PD1+ and neutrophilic granulocytes (myeloperoxidase+ compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

  6. Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yung-Lin Chu

    2013-07-01

    Full Text Available Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic 大 蒜 Dà Suàn; Allium sativum, is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients.

  7. Fraction against Human Cancer Cell Lines

    African Journals Online (AJOL)

    Purpose: To investigate the anti-proliferative and apoptotic activity of crude and dichloromethane fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and. L929). Methods: A. sieberi was extracted with methanol and further purification was carried out using liquid-.

  8. DNA methylation analysis in human cancer

    OpenAIRE

    O'Sullivan, Eileen; Goggins, Michael

    2013-01-01

    The functional impact of aberrant DNA methylation and the widespread alterations in DNA methylation in cancer development has led to the development of a variety of methods to characterize the DNA methylation patterns. This chapter will critique and describe the major approaches to analyzing DNA methylation.

  9. Endocrine Disruption and Human Prostate Cancer

    Science.gov (United States)

    2008-03-01

    Committee. Cancer research 64:2270-2305 4. Hamilton PW, Allen DC, Watt PC 1990 A combination of cytological and architectural morphometry in assessing...of 66 Gynecology , Schering AG. It was funded following a bid for funds from the International Pool of Funds for Corporate Research at Schering AG

  10. cervical cancer and the human immunodeficiency

    African Journals Online (AJOL)

    trol and possibly other sexually transmitted infections such as Chlamydia.7,8. According to Denny et al.,10 a ... HIV and HPV. Cervical cancer was made an AIDS-de- fining diagnosis by the Centers for Disease Control ..... follow-up visits cause and reducing the inconvenience of work, child-care and transportation issues.

  11. Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines

    Directory of Open Access Journals (Sweden)

    Nidal Ghosheh

    2016-01-01

    Full Text Available Human pluripotent stem cells- (hPSCs- derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4 which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models.

  12. Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines

    Science.gov (United States)

    Ghosheh, Nidal; Olsson, Björn; Edsbagge, Josefina; Küppers-Munther, Barbara; Van Giezen, Mariska; Asplund, Annika; Andersson, Tommy B.; Björquist, Petter; Carén, Helena; Simonsson, Stina; Sartipy, Peter; Synnergren, Jane

    2016-01-01

    Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models. PMID:26949401

  13. Cytotoxicity, genotoxicity and gene expression changes elicited by exposure of human hepatic cells to Ginkgo biloba leaf extract.

    Science.gov (United States)

    Grollino, Maria Giuseppa; Raschellà, Giuseppe; Cordelli, Eugenia; Villani, Paola; Pieraccioli, Marco; Paximadas, Irene; Malandrino, Salvatore; Bonassi, Stefano; Pacchierotti, Francesca

    2017-11-01

    The use of Ginkgo biloba leaf extract as nutraceutical is becoming increasingly common. As a consequence, the definition of a reliable toxicological profile is a priority for its safe utilization. Recently, contrasting data have been reported on the carcinogenic potential of Ginkgo biloba extract in rodent liver. We measured viability, Reactive Oxygen Species (ROS), apoptosis, colony-forming efficiency, genotoxicity by comet assay, and gene expression changes associated with hepato-carcinogenicity in human cells of hepatic origin (HepG2 and THLE-2) treated with different concentrations (0.0005-1.2 mg/mL) of Ginkgoselect ® Plus. Our analyses highlighted a decrease of cell viability, not due to apoptosis, after treatment with high doses of the extract, which was likely due to ROS generation by a chemical reaction between extract polyphenols and some components of the culture medium. Comet assay did not detect genotoxic effect at any extract concentration. Finally, the array analysis detected a slight decrease in the expression of only one gene (IGFBP3) in Ginkgo-treated THLE-2 cells as opposed to changes in 28 genes in Aflatoxin B1 treated-cells. In conclusion, our results did not detect any significant genotoxic or biologically relevant cytotoxic effects and gross changes in gene expression using the Ginkgo extract in the hepatic cells tested. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. [The immunogenicity of the hepatitis B vaccine in drug addicts with human immunodeficiency virus infection].

    Science.gov (United States)

    Menicagli, V; Barbanera, M; Menicagli, S

    1991-02-01

    In order to evaluate the antibody response to anti-hepatitis B vaccine, 21 heroin addicted with HIV infection previously vaccinated, were studied. 18 patients were asymptomatic and 3 were at the LAS stage. An antibody response was estimated at 1 and 12 months after the end of the vaccination. The first control showed that 62% presented a protective anti-HBs (higher than 10 mU/ml); after one year 70% of responders had a persistent immunity. The antibody response showed no correlation with the value of immunologic tests; the vaccine showed neither a significant evidence of side-effects nor a negative influence on the HIV infection.

  15. Aquaporins in human breast cancer: identification and involvement in carcinogenesis of breast cancer.

    Science.gov (United States)

    Shi, Zhonghua; Zhang, Ting; Luo, Liang; Zhao, Hua; Cheng, Jing; Xiang, Jingying; Zhao, Chun

    2012-09-01

    Aquaporins (AQPs) play important roles in water and glycerol transport. Recently, the role of AQPs in human carcinogenesis has become an area of great interest. However, little is known about the function of AQPs in human breast cancer. The aim of this study was to investigate the expression profile of AQPs in human breast cancer and its significance. In this study, we screened the expression profile of AQP0-12 in breast cancer tissues and corresponding normal tissues by RT-PCR, Western blotting and immunohistochemistry. AQP1, 3-5, and 10-12 were expressed in human breast cancer and/or normal breast tissues, and AQP1 and 3-5 exhibited differential expression. AQP1 was expressed in cell membranes and its expression was higher in cancer than that in normal tissues. AQP4 was expressed in the cell membrane and cytoplasm and was detected markedly stronger in normal than in cancer tissues. AQP5 was expressed mainly in cell membranes in carcinoma tissues, but was almost absent in normal breast tissues. Expression of AQP5 was associated with cellular differentiation, lymph node invasion, and clinicopathological staging. These observations suggested that several subtypes of the AQP family play a role in human breast carcinogenesis. Copyright © 2011 Wiley Periodicals, Inc.

  16. Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

    Science.gov (United States)

    Chitose, Shun-ichi; Sakazaki, T; Ono, T; Kurita, T; Mihashi, H; Nakashima, T

    2010-06-01

    This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity

  17. The role of triple infection with hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV type-1 on CD4+ lymphocyte levels in the highly HIV infected population of North-Central Nigeria

    Directory of Open Access Journals (Sweden)

    JC Forbi

    2007-06-01

    Full Text Available We set out to determine the seroprevalence of hepatitis B and C among human immunodeficiency virus type-1 (HIV-1 infected individuals in North-Central Nigeria to define the influence of these infections on CD4+ lymphocytes cells among our patients as access to antiretroviral therapy improves across the Nigerian nation. The CD4+ values of 180 confirmed HIV-1 infected individuals were enumerated using a superior fluorescence-activated cell sorter system. These patients were tested for the presence of hepatitis B surface antigen and anti-hepatitis C virus (HCV using third generation enzyme-linked immunosorbent assays. Fifty (27.8% patients had active hepatitis B virus (HBV infection while 33 (18.3% tested positive for anti-HCV antibody. Of these infections, 110 (61.1%, 37 (20.6%, and 20 (11.1% had HIV only, HBV/HIV-only, and HCV/HIV-only respectively. A HBV/HCV/HIV coinfection prevalence of 7.2% (13 patients was recorded. Patients coinfected with HIV/HBV/HCV appeared to have lower CD4+ counts (mean = 107 cells/µl; AIDS defining when compared to HBV/HIV-only (mean = 377 cells/µl, HCV/HIV-only (mean = 373 cells/µl and patients with mono HIV infection (mean = 478 cells/µl. Coinfection with HBV or HCV is relatively common among HIV-infected patients in Nigeria and should be a big consideration in the initiation and choice of therapy.

  18. The role of triple infection with hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV) type-1 on CD4+ lymphocyte levels in the highly HIV infected population of North-Central Nigeria.

    Science.gov (United States)

    Forbi, J C; Gabadi, S; Alabi, R; Iperepolu, H O; Pam, C R; Entonu, P E; Agwale, S M

    2007-06-01

    We set out to determine the seroprevalence of hepatitis B and C among human immunodeficiency virus type-1 (HIV-1) infected individuals in North-Central Nigeria to define the influence of these infections on CD4+ lymphocytes cells among our patients as access to antiretroviral therapy improves across the Nigerian nation. The CD4+ values of 180 confirmed HIV-1 infected individuals were enumerated using a superior fluorescence-activated cell sorter system. These patients were tested for the presence of hepatitis B surface antigen and anti-hepatitis C virus (HCV) using third generation enzyme-linked immunosorbent assays. Fifty (27.8%) patients had active hepatitis B virus (HBV) infection while 33 (18.3%) tested positive for anti-HCV antibody. Of these infections, 110 (61.1%), 37 (20.6%), and 20 (11.1%) had HIV only, HBV/HIV-only, and HCV/HIV-only respectively. A HBV/HCV/HIV coinfection prevalence of 7.2% (13 patients) was recorded. Patients coinfected with HIV/HBV/HCV appeared to have lower CD4+ counts (mean = 107 cells/microl; AIDS defining) when compared to HBV/HIV-only (mean = 377 cells/microl), HCV/HIV-only (mean = 373 cells/microl) and patients with mono HIV infection (mean = 478 cells/microl). Coinfection with HBV or HCV is relatively common among HIV-infected patients in Nigeria and should be a big consideration in the initiation and choice of therapy.

  19. Proteomic analysis of differentially expressed proteins in hepatitis B virus-related hepatocellular carcinoma tissues

    OpenAIRE

    Li, Ning; Long, Yunzhu; Fan, Xuegong; Liu, Hongbo; Li, Cui; Chen, Lizhang; Wang, Zhiming

    2009-01-01

    Abstract Background Hepatocellular carcinoma (HCC), a major cause of cancer death in China, is preceded by chronic hepatitis and liver cirrhosis (LC). Although hepatitis B virus (HBV) has been regarded as a clear etiology of human hepatocarcinogenesis, the mechanism is still needs to be further clarified. In this study, we used a proteomic approach to identify the differential expression protein profiles between HCC and the adjacent non-tumorous liver tissues. Methods Eighteen cases of HBV-re...

  20. Cancer genetics and genomics of human FOX family genes.

    Science.gov (United States)

    Katoh, Masuko; Igarashi, Maki; Fukuda, Hirokazu; Nakagama, Hitoshi; Katoh, Masaru

    2013-01-28

    Forkhead-box (FOX) family proteins, involved in cell growth and differentiation as well as embryogenesis and longevity, are DNA-binding proteins regulating transcription and DNA repair. The focus of this review is on the mechanisms of FOX-related human carcinogenesis. FOXA1 is overexpressed as a result of gene amplification in lung cancer, esophageal cancer, ER-positive breast cancer and anaplastic thyroid cancer and is point-mutated in prostate cancer. FOXA1 overexpression in breast cancer and prostate cancer is associated with good or poor prognosis, respectively. Single nucleotide polymorphism (SNP) within the 5'-UTR of the FOXE1 (TTF2) gene is associated with thyroid cancer risk. FOXF1 overexpression in breast cancer is associated with epithelial-to-mesenchymal transition (EMT). FOXM1 is overexpressed owing to gene amplification in basal-type breast cancer and diffuse large B-cell lymphoma (DLBCL), and it is transcriptionally upregulated owing to Hedgehog-GLI, hypoxia-HIF1α or YAP-TEAD signaling activation. FOXM1 overexpression leads to malignant phenotypes by directly upregulating CCNB1, AURKB, MYC and SKP2 and indirectly upregulating ZEB1 and ZEB2 via miR-200b downregulation. Tumor suppressor functions of FOXO transcription factors are lost in cancer cells as a result of chromosomal translocation, deletion, miRNA-mediated repression, AKT-mediated cytoplasmic sequestration or ubiquitination-mediated proteasomal degradation. FOXP1 is upregulated as a result of gene fusion or amplification in DLBCL and MALT lymphoma and also repression of miRNAs, such as miR-1, miR-34a and miR-504. FOXP1 overexpression is associated with poor prognosis in DLBCL, gastric MALT lymphoma and hepatocellular carcinoma but with good prognosis in breast cancer. In neuroblastoma, the entire coding region of the FOXR1 (FOXN5) gene is fused to the MLL or the PAFAH1B gene owing to interstitial deletions. FOXR1 fusion genes function as oncogenes that repress transcription of FOXO target

  1. Cytotoxicity of dietary flavonoids on different human cancer types.

    Science.gov (United States)

    Sak, Katrin

    2014-07-01

    Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. While luteolin and kaempferol can be considered as promising candidate agents for treatment of gastric and ovarian cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as potent antitumor agents for cervical cancer; cells from main sites of flavonoid metabolism (colon and liver) reveal rather large fluctuations in anticancer activity probably due to exposure to various metabolites with different activities. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue-specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment.

  2. Expression of matrix metalloproteinases in human breast cancer tissues.

    Science.gov (United States)

    Benson, Chellakkan Selvanesan; Babu, Somasundaram Dinesh; Radhakrishna, Selvi; Selvamurugan, Nagarajan; Ravi Sankar, Bhaskaran

    2013-01-01

    Breast cancer is the most common cancer affecting women in the world today. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can degrade extracellular matrix proteins and promote cell invasion and metastasis. MMPs are differentially expressed and their expressions are often associated with a poor prognosis for patients. The aim of this study is to investigate and compare the expression of MMPs in different grades of human breast cancer tissues with normal breast tissues. We collected 39 breast cancer samples (24 grade II and 15 grade III) along with 16 normal breast tissues from outside the tumor margin during cancer removal surgery. The samples were analysed for the expression of all known MMPs using real-time quantitative PCR. The results indicate that mRNA expressions of MMP-1, -9,-11,-15,-24 and -25 were upregulated in breast cancer tissues when compared to normal breast tissues. But, the mRNA expressions of MMP-10 and MMP-19 were downregulated in cancer tissue. In membrane associated MMPs like MMP-15 and MMP-24 we found a grade dependent increase of their mRNA expression. Our studies demonstrate that MMPs are differentially regulated in breast cancer tissues and they might play various roles in tumor invasion, metastasis and angiogenesis. Thus, MMPs are of immense value to be studied as diagnostic markers and drug target.

  3. Expression profiles of SnoN in normal and cancerous human tissues support its tumor suppressor role in human cancer.

    Directory of Open Access Journals (Sweden)

    Nadine S Jahchan

    Full Text Available SnoN is a negative regulator of TGF-β signaling and also an activator of the tumor suppressor p53 in response to cellular stress. Its role in human cancer is complex and controversial with both pro-oncogenic and anti-oncogenic activities reported. To clarify its role in human cancer and provide clinical relevance to its signaling activities, we examined SnoN expression in normal and cancerous human esophageal, ovarian, pancreatic and breast tissues. In normal tissues, SnoN is expressed in both the epithelium and the surrounding stroma at a moderate level and is predominantly cytoplasmic. SnoN levels in all tumor epithelia examined are lower than or similar to that in the matched normal samples, consistent with its anti-tumorigenic activity in epithelial cells. In contrast, SnoN expression in the stroma is highly upregulated in the infiltrating inflammatory cells in high-grade esophageal and ovarian tumor samples, suggesting that SnoN may potentially promote malignant progression through modulating the tumor microenvironment in these tumor types. The overall levels of SnoN expression in these cancer tissues do not correlate with the p53 status. However, in human cancer cell lines with amplification of the snoN gene, a strong correlation between increased SnoN copy number and inactivation of p53 was detected, suggesting that the tumor suppressor SnoN-p53 pathway must be inactivated, either through downregulation of SnoN or inactivation of p53, in order to allow cancer cell to proliferate and survive. These data strongly suggest that SnoN can function as a tumor suppressor at early stages of tumorigenesis in human cancer tissues.

  4. Canine cancer immunotherapy studies: linking mouse and human.

    Science.gov (United States)

    Park, Jiwon S; Withers, Sita S; Modiano, Jaime F; Kent, Michael S; Chen, Mingyi; Luna, Jesus I; Culp, William T N; Sparger, Ellen E; Rebhun, Robert B; Monjazeb, Arta M; Murphy, William J; Canter, Robert J

    2016-01-01

    Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will respond and who will experience at times significant toxicities. Although advances in cancer immunotherapy depend on preclinical testing, the majority of in-vivo testing currently relies on genetically identical inbred mouse models which, while offering critical insights regarding efficacy and mechanism of action, also vastly underrepresent the heterogeneity and complex interplay of human immune cells and cancers. Additionally, laboratory mice uncommonly develop spontaneous tumors, are housed under specific-pathogen free conditions which markedly impacts immune development, and incompletely model key aspects of the tumor/immune microenvironment. The canine model represents a powerful tool in cancer immunotherapy research as an important link between murine models and human clinical studies. Dogs represent an attractive outbred combination of companion animals that experience spontaneous cancer development in the setting of an intact immune system. This allows for study of complex immune interactions during the course of treatment while also directly addressing long-term efficacy and toxicity of cancer immunotherapies. However, immune dissection requires access to robust and validated immune assays and reagents as well as appropriate numbers for statistical evaluation. Canine studies will need further optimization of these important mechanistic tools for this model to fulfill its promise as a model for immunotherapy. This review aims to discuss the canine model in the context of existing preclinical cancer immunotherapy models to evaluate both its advantages and limitations, as well as highlighting its growth as a powerful tool in the burgeoning field of both human and veterinary immunotherapy.

  5. Resource Manual for Handling Body Fluids in the School Setting To Prevent Transmission of Human Immunodeficiency Virus and Hepatitis B Virus. Revised Edition.

    Science.gov (United States)

    Maryland State Dept. of Health and Mental Hygiene, Baltimore.

    This Maryland resource manual provides local education agencies with guidelines on how to handle body fluids to prevent the transmission of diseases, especially Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV), in the school setting. The first section summarizes the reasons for development of the manual. The second section summarizes…

  6. Resource Manual for Handling Body Fluids in the School Setting To Prevent the Transmission of Human Immunodeficiency Virus and Hepatitis B Virus.

    Science.gov (United States)

    Maryland State Dept. of Health and Mental Hygiene, Baltimore.

    Guidelines to prevent the transmission of blood-borne diseases, especially those caused by the Human Immunodeficiency Virus (HIV) and the Hepatitis B Virus (HBV), in the school setting are provided in this resource manual for school staff. Sections include information on the reasons for the development of this manual; a summary of the means of HIV…

  7. Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls.

    NARCIS (Netherlands)

    Schmeink, C.E.; Bekkers, R.L.M.; Josefsson, A.; Richardus, J.H.; Berndtsson Blom, K.; David, M.P.; Dobbelaere, K.; Descamps, D.

    2011-01-01

    BACKGROUND: To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB). METHODS: This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV

  8. Sexual Transmission of Hepatitis C Virus in Human Immunodeficiency Virus-Negative Men Who Have Sex With Men: A Series of Case Reports

    NARCIS (Netherlands)

    van de Laar, Thijs J. W.; Paxton, William A.; Zorgdrager, Fokla; Cornelissen, Marion; de Vries, Henry J. C.

    2011-01-01

    Hepatitis C Virus (HCV) has recently emerged as sexual transmitted infection among (human immunodeficiency virus) HIV-positive but not HIV-negative men who have sex with men (MSM). We present 4 case reports showing that HIV-infection is not an absolute prerequisite for sexual HCV transmission in

  9. Multicenter evaluation of the new Abbott RealTime assays for quantitative detection of human immunodeficiency virus type 1 and hepatitis C virus RNA

    NARCIS (Netherlands)

    Schutten, Martin; Peters, D; Back, N K T; Beld, M; Beuselinck, K; Foulongne, V; Geretti, A-M; Pandiani, L; Tiemann, C; Niesters, H G M

    The analytical performances of the new Abbott RealTime hepatitis C virus (HCV) and human immunodeficiency virus type 1 viral load assays were compared at nine laboratories with different competitor assays. These included the Abbott LcX, Bayer Versant bDNA, Roche COBAS Amplicor, and Roche COBAS

  10. Hepatic proteome sensitivity in rainbow trout after chronically exposed to a human pharmaceutical verapamil.

    Science.gov (United States)

    Li, Zhi-Hua; Li, Ping; Sulc, Miroslav; Hulak, Martin; Randak, Tomas

    2012-01-01

    Verapamil (VRP), a cardiovascular pharmaceutical widely distributed and persistent in the aquatic environment, has potential toxicity to fish and other aquatic organisms. However, the molecular mechanisms that lead to these toxic effects are not well known. In the present study, proteomic analysis has been performed to investigate the protein patterns that are differentially expressed in liver of rainbow trout exposed to sublethal concentrations of VRP (0.5, 27.0, and 270 μg/liter) for 42 days. Two-dimensional electrophoresis coupled with MALDI-TOF/TOF mass spectrometry was employed to detect and identify the protein profiles. The analysis revealed that the expression of six hepatic acidic proteins were markedly altered in the treatment groups compared with the control group; three proteins especially were significantly down-regulated in fish exposed to VRP at environmental related concentration (0.5 μg/liter). These results suggested that the VRP induce mechanisms against oxidative stress (glucose-regulated protein 78 and 94 and protein disulfide-isomerase A3) and adaptive changes in ion transference regulation (calreticulin, hyperosmotic glycine-rich protein). Furthermore, for the first time, protein Canopy-1 was found to be significantly down-regulated in fish by chronic exposure to VRP at environmental related levels. Overall, our work supports that fish hepatic proteomics analysis serves as an in vivo model for monitoring the residual pharmaceuticals in aquatic environment and can provide valuable insight into the molecular events in VRP-induced toxicity in fish and other organisms.

  11. Rapid fabricating technique for multi-layered human hepatic cell sheets by forceful contraction of the fibroblast monolayer.

    Directory of Open Access Journals (Sweden)

    Yusuke Sakai

    Full Text Available Cell sheet engineering is attracting attention from investigators in various fields, from basic research scientists to clinicians focused on regenerative medicine. However, hepatocytes have a limited proliferation potential in vitro, and it generally takes a several days to form a sheet morphology and multi-layered sheets. We herein report our rapid and efficient technique for generating multi-layered human hepatic cell (HepaRG® cell sheets using pre-cultured fibroblast monolayers derived from human skin (TIG-118 cells as a feeder layer on a temperature-responsive culture dish. Multi-layered TIG-118/HepaRG cell sheets with a thick morphology were harvested on day 4 of culturing HepaRG cells by forceful contraction of the TIG-118 cells, and the resulting sheet could be easily handled. In addition, the human albumin and alpha 1-antitrypsin synthesis activities of TIG-118/HepaRG cells were approximately 1.2 and 1.3 times higher than those of HepaRG cells, respectively. Therefore, this technique is considered to be a promising modality for rapidly fabricating multi-layered human hepatocyte sheets from cells with limited proliferation potential, and the engineered cell sheet could be used for cell transplantation with highly specific functions.

  12. Synthetic rabbit-human antibody conjugate as a control in immunoassays for immunoglobulin M specific to hepatitis E virus

    Directory of Open Access Journals (Sweden)

    Zhang Rui

    2010-05-01

    Full Text Available Abstract Background In assays for anti-hepatitis E virus (HEV immunoglobulin M (IgM, large volumes of the patient's sera cannot be easily obtained for use as a positive control. In this study, we investigated an alternative chemical method in which rabbit anti-HEV IgG was conjugated with human IgM and was used as a positive control in the anti-HEV IgM assay. Rabbit anti-HEV IgG was isolated from immune sera by chromatography on protein A-Sepharose and was conjugated with human IgM by using 1-ethyl-3-(3-dimethylaminopropylcarbodiimide (EDC as a crosslinker. Results The specific anti-HEV IgG antibody titer was 100,000 times that of the negative control, i.e., prebleed rabbit serum. The results of anti-HEV IgM enzyme-linked immunosobent assay showed that the antibody conjugate was similar to anti-HEV IgM antibodies produced in humans. The results of a stability experiment showed that the antibody conjugate was stable for use in external quality assessment or internal quality control trials. Conclusions We concluded that the chemically conjugated rabbit-human antibody could be used instead of the traditional serum control as a positive control in the anti-HEV IgM assay.

  13. Purification of human hepatic glutathione S-transferases and the development of a radioimmunoassay for their measurement in plasma

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, J.D.; Gilligan, D.; Beckett, G.J. (Edinburgh Univ. (UK). Dept. of Clinical Chemistry); Chapman, B.J. (Royal Infirmary, Edinburgh (UK))

    1983-10-31

    A purification scheme is described for six human hepatic glutathione S-transferases from a single liver. Five of the transferases comprised Ya monomers and had a molecular mass of 44000. The remaining enzyme comprised Yb monomers and had a molecular mass of 47000. Data are presented demonstrating that there are at least two distinct Ya monomers. A radioimmunoassay has been developed that has sufficient precision and sensitivity to allow direct measurement of glutathione S-transferase concentrations in unextracted plasma. A comparison of aminotransferase and glutathione S-transferase levels, in three patients who had taken a paracetamol overdose, indicated that glutathione S-transferase measurements provided a far more sensitive index of hepatocellular integrity than the more conventional aminotransferase measurements.

  14. Dengue Infection in a Human Immunodeficiency Virus-1 Positive Patient Chronically Infected with Hepatitis B Virus in Western Mexico.

    Science.gov (United States)

    Delgado-Enciso, Iván; Espinoza-Gómez, Francisco; Ochoa-Jiménez, Rodolfo; Valle-Reyes, Salvador; Vásquez, Clemente; López-Lemus, Uriel A

    2017-01-11

    Human immunodeficiency virus (HIV) and dengue coinfection has not been extensively studied. We report herein a case of dengue serotype 1 infection in an HIV-1-positive patient coinfected with hepatitis B virus (HBV) in Colima State, Mexico. CD4+ cells and HIV-1 viremia remained at normal levels, and no severe complications were observed during this multiple viral infection. The alanine transaminase and aspartate transaminase values were elevated before and during dengue infection. Surprisingly, these parameters were significantly reduced 2 months later. Because of the lack of evidence regarding this multiple viral interaction, further research is required to understand the biologic and clinical course of dengue infection in HIV-1/HBV coinfected patients, especially in tropical regions where dengue virus transmission is highly active. © The American Society of Tropical Medicine and Hygiene.

  15. Hepatic Differentiation of Human Induced Pluripotent Stem Cells in a Perfused 3D Porous Polymer Scaffold for Liver Tissue Engineering

    DEFF Research Database (Denmark)

    Hemmingsen, Mette; Muhammad, Haseena Bashir; Mohanty, Soumyaranjan

    to limitations of primary hepatocytes regarding availability and maintenance of functionality, stem cells and especially human induced pluripotent stem cells (hIPS cells) are an attractive cell source for liver tissue engineering. The aim of this part of NanoBio4Trans is to optimize culture and hepatic......A huge shortage of liver organs for transplantation has motivated the research field of tissue engineering to develop bioartificial liver tissue and even a whole liver. The goal of NanoBio4Trans is to create a vascularized bioartificial liver tissue, initially as a liver-support system. Due...... differentiation of hIPS-derived definitive endoderm (DE) cells in a 3D porous polymer scaffold built-in a perfusable bioreactor. The use of a microfluidic bioreactor array enables the culture of 16 independent tissues in one experimental run and thereby an optimization study to be performed....

  16. Milk Donor Blood Screening for HIV, Syphilis and Hepatitis B Markers in a Brazilian Human Milk Bank: Prevalence Time-trends Over the 2005- 2015 Period.

    Science.gov (United States)

    Kupek, Emil; Savi, Estela Olivo

    2017-01-01

    Human milk banking has been promoted to provide donated breast milk for at-risk children whose mothers cannot breastfeed them but this effort was hindered by the advent of HIV epidemic. To estimate the seroprevalence of HIV, syphilis and hepatitis B in the blood of human milk donors registered in a major maternity hospital in the northern region of the Santa Catarina State, Brazil. A retrospective study included serological tests for HIV, syphilis and hepatitis B screening of milk donor candidates in the 2005-2015 period. The 95% confidence intervals were calculated using the Poisson distribution. For HIV, the prevalence per 100.000 pregnant women was 155, 170 and zero over the three periods analyzed (2005-2009, 2010-2012 and 2013-2015), respectively. Syphilis prevalence per 100,000 pregnant women was 509, 460 and 1749 in the three periods analyzed. For the HBsAg marker of recent hepatitis B infection, the prevalence on the same scale was 254, 231 and 299, respectively, while the anti-HBc prevalence, a marker of lifetime risk for hepatitis B infection, was 7339 in the 2010-2012 period and 3874 in the 2013-2015 period. High prevalence of HIV, syphilis and hepatitis B was found for the 2005-2015 period among breastfeeding mothers who offered to donate their exceeding milk to a human milk bank in Brazil. Despite apparent elimination of the HIV by the end of the period, the decline was not statistically significant. There was no significant change in the acute hepatitis B prevalence over time but the increased syphilis prevalence in the most recent period was statistically significant. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Thalidomide Increases Human Hepatic Cytochrome P450 3A Enzymes by Direct Activation of Pregnane X Receptor

    Science.gov (United States)

    Suemizu, Hiroshi; Guillouzo, Christiane Guguen; Shibata, Norio; Yajima, Kanako; Utoh, Masahiro; Shimizu, Makiko; Chesné, Christophe; Nakamura, Masato; Guengerich, F. Peter; Houtman, René; Yamazaki, Hiroshi

    2014-01-01

    Heterotropic cooperativity of human cytochrome P450 (P450) 3A4/3A5 by the teratogen thalidomide was recently demonstrated by H. Yamazaki et al. (2013) using the