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Sample records for cancer diagnostics prognostics

  1. Diagnostic and prognostic epigenetic biomarkers in cancer.

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    Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

    2015-01-01

    Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

  2. DIAGNOSTIC AND PROGNOSTIC UTILITY OF SERUM PSA IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    张淑群; 强水云; 李妙羡; 纪宗正

    2004-01-01

    Objective To investigate the diagnostic and prognostic value of total and free prostate-specific antigen (PSA) in breast cancer women. Methods Using the microparticle enzyme immunoassay system, we measured the concentrations of these markers in the sera of 85 women with breast cancer and in 30 healthy women.Results Free PSA levels were significantly higher in women with breast cancer than healthy women (P <0. 05 ).The percentage of free PSA predominant subjects was 37. 6% in breast cancer patients and 3. 3% in healthy women.In women with breast cancer,total PSA positivity was 23.5% and free PSA positivity was 27. 1%. When compared to negatives,total PSA positive patients had a higher percentage of lymph node involvement tamours ( P >0. 05).However, patients with predominant free PSA had a higher percentage of early stage than patients with predominant PSA-ACT. Conclusion This study indicate clinical significance of preoperative measurement of serum total and free PSA in diagnosis and prognosis of women with breast cancer. The expression of KLKs is correlated with carcinogenesis of breast cancer.

  3. Mean platelet volume provides beneficial diagnostic and prognostic information for patients with resectable gastric cancer

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    Shen, Xiao-Ming; Xia, You-You; Lian, Lian; Zhou, Chong; Li, Xiang-Li; Han, Shu-Guang; Zheng, Yan; Gong, Fei-Ran; Tao, Min; Mao, Zhong-Qi; Li, Wei

    2016-01-01

    Gastric cancer is the fourth most frequent cancer and the second cause of cancer-related mortalities worldwide. Platelets play an important and multifaceted role in cancer progression. Elevated mean platelet volume (MPV) detected in peripheral blood has been identified in various types of cancer. In the present study, we investigated the application value of MPV in early diagnostic and prognostic prediction in patients with resectable gastric cancer. In total, 168 patients with resectable gastric cancer were included and separated into the gastric cancer and healthy control groups according to median pre-operatic MPV value (MPV low, <10.51 or MPV high, ≥10.51). The results showed that the pre-operatic MPV level was significantly higher in gastric cancer patients compared with the healthy subjects. Low pre-operatic MPV level correlated with improved clinicopathological features, including decreased depth of invasion, less lymphonodus metastasis and early tumor stage. The Kaplan-Meier plots showed that the patients with higher pre-operatic MPV had decreased overall survival (OS) and disease-free survival (DFS). Surgical tumor resection resulted in a significant decrease in the MPV level. The patients whose MPV level decreased following surgery had an improved OS. Multivariate Cox regression analysis revealed that the depth of invasion, lymphonodus metastasis, American Joint Committee on Cancer (AJCC) stage, and changes in MPV following surgery were prognostic factors affecting OS, and the AJCC stage and pre-operatic MPV were prognostic factors affecting DFS. In conclusion, MPV measurement can provide important diagnostic and prognostic results in patients with resectable gastric cancer. PMID:27703523

  4. Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer

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    Martens-Uzunova, E S; Jalava, S E; Dits, N F

    2011-01-01

    Prostate cancer (PCa) is the most frequent male malignancy and the second most common cause of cancer-related death in Western countries. Current clinical and pathological methods are limited in the prediction of postoperative outcome. It is becoming increasingly evident that small non-coding RNA...... RNAs (snoRNAs) and transfer RNAs (tRNAs). From microarray analysis, we derived a miRNA diagnostic classifier that accurately distinguishes normal from cancer samples. Furthermore, we were able to construct a PCa prognostic predictor that independently forecasts postoperative outcome. Importantly...

  5. Targeting nuclear transporters in cancer: Diagnostic, prognostic and therapeutic potential.

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    Stelma, Tamara; Chi, Alicia; van der Watt, Pauline J; Verrico, Annalisa; Lavia, Patrizia; Leaner, Virna D

    2016-04-01

    The Karyopherin superfamily is a major class of soluble transport receptors consisting of both import and export proteins. The trafficking of proteins involved in transcription, cell signalling and cell cycle regulation among other functions across the nuclear membrane is essential for normal cellular functioning. However, in cancer cells, the altered expression or localization of nuclear transporters as well as the disruption of endogenous nuclear transport inhibitors are some ways in which the Karyopherin proteins are dysregulated. The value of nuclear transporters in the diagnosis, prognosis and treatment of cancer is currently being elucidated with recent studies highlighting their potential as biomarkers and therapeutic targets.

  6. Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients.

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    Infante, Maurizio; Allavena, Paola; Garlanda, Cecilia; Nebuloni, Manuela; Morenghi, Emanuela; Rahal, Daoud; Roncalli, Massimo; Cavuto, Silvio; Pesce, Samantha; Monari, Marta; Valaperta, Serenella; Montanelli, Alessandro; Solomon, Daniel; Bottoni, Edoardo; Errico, Valentina; Voulaz, Emanuele; Bossi, Manuela; Chiesa, Giuseppe; Passera, Eliseo; Mantovani, Alberto; Alloisio, Marco

    2016-02-15

    There is a well-established link between inflammation and cancer of various organs, but little data are available on inflammation-associated markers of diagnostic and prognostic clinical utility in pulmonary malignancy. Blood samples were prospectively collected from 75 resectable lung cancer patients before surgery and in a cohort of 1,358 high-risk subjects. Serum levels of long pentraxin 3 (PTX3) were determined by high-sensitivity ELISA. PTX3 immunostaining was evaluated by immunohistochemistry in cancer tissue. Serum PTX3 levels in the high-risk population were not predictive of developing subsequent lung cancer or any other malignancy; however, serum PTX3 values in patients with lung cancer were significantly higher compared with cancer-free heavy smokers. With a cutoff of 4.5 ng/ml, specificity was 0.80, sensitivity 0.69, positive predictive value 0.15 and negative predictive value 0.98. The receiver operating curve (ROC) for serum PTX3 had an area under the curve (AUC) of 83.52%. Preoperative serum PTX3 levels in lung cancer patients did not correlate with patient outcome, but high interstitial expression of PTX3 in resected tumor specimens was a significant independent prognostic factor associated with shorter survival (p < 0.001). These results support the potential of serum PTX3 as a lung cancer biomarker in high-risk subjects. Furthermore, PTX3 immunohistochemistry findings support the role of local inflammatory mechanisms in determining clinical outcome and suggest that local expression of PTX3 may be of prognostic utility in lung cancer patients.

  7. SELDI-TOF Serum Profiling for Prognostic and Diagnostic Classification of Breast Cancers

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    Christine Laronga

    2004-01-01

    Full Text Available Surface enhanced laser desorption/ionization (SELDI time-of-flight mass spectrometry has emerged as a successful tool for serum based detection and differentiation of many cancer types, including breast cancers. In this study, we have applied the SELDI technology to evaluate three potential applications that could extend the effectiveness of established procedures and biomarkers used for prognostication of breast cancers. Paired serum samples obtained from women with breast cancers prior to surgery and post-surgery (6–9 mos. were examined. In 14/16 post-treatment patients, serum protein profiles could be used to distinguish these samples from the pre-treatment cancer samples. When compared to serum samples from normal healthy women, 11 of these post-treatment samples retained global protein profiles not found in healthy women, including five low-mass proteins that remained elevated in both pre-treatment and post-treatment serum groups. In another pilot study, serum profiles were compared for a group of 30 women who were known BRCA-1 mutation carriers, half of whom subsequently developed breast cancer within three years of the sample procurement. SELDI protein profiling accurately classified 13/15 women with BRCA-1 breast cancers from the 15 non-cancer BRCA-1 carriers. Additionally, the ability of SELDI to distinguish between the serum profiles from sentinel lymph node positive and sentinel lymph node negative patients was evaluated. In sentinel lymph node positive samples, 22/27 samples were correctly classified, in comparison to the correct classification of 55/71 sentinel lymph node negative samples. These initial results indicate the utility of protein profiling approaches for developing new diagnostic and prognostic assays for breast cancers.

  8. Evaluating the diagnostic and prognostic value of circulating cathepsin S in gastric cancer.

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    Liu, Wan-Li; Liu, Dan; Cheng, Kai; Liu, Yi-Jun; Xing, Shan; Chi, Pei-Dong; Liu, Xiao-Hua; Xue, Ning; Lai, Yan-Zhen; Guo, Ling; Zhang, Ge

    2016-05-10

    To evaluate whether serum Cathepsin S (Cat S) could serve as a biomarker for the diagnosis and prognosis of gastric cancer (GC), Enzyme-linked immuno sorbent assay (ELISA) was used to detect serum Cat S in 496 participants including healthy controls and patients with benign gastric diseases, gastric cancer, esophageal cancer, liver cancer, colorectal cancer, nasopharyngeal cancer and lung cancer. The levels of serum Cat S were significantly increased in cancer patients, especially in GC patients. The qRT-PCR, Western blotting, and immunohistochemical staining revealed the overexpression of Cat S in GC cell lines and tissues. The diagnostic value of serum Cat S for GC patients from controls resulted in an AUC of 0.803 with a sensitivity of 60.7% and a specificity of 90.0%. Moreover, the levels of serum Cat S were associated with GC tumor volume, lymphoid nodal status, metastasis status, and stages. Moreover, the patients with high levels of serum Cat S had a poorer overall survival. Univariate analysis revealed Cat S expression was a prognostic factor. The knockdown of Cat S significantly suppressed the migration and invasion of GC cells. This study suggested serum Cat S may be a potential biomarker for the diagnosis and prognosis of GC.

  9. Expression of tNASP in Prostate Cancer: Opportunities for a Novel Diagnostic and Prognostic Biomarker Development

    Science.gov (United States)

    2013-12-01

    and to distinguish prostate cancer from BPH . Detection of tNASP protein expression levels in needle biopsies and postoperative prostate cancer...samples will be correlated with pathologic indicators of aggressive prostate cancer for diagnostic and prognostic purposes. We propose two specific aims...hypothesis that tNASP-specific antibodies are present in the blood of prostate cancer patients, but not BPH patients or otherwise healthy men. We will test

  10. Serum tumour markers as a diagnostic and prognostic tool in Libyan breast cancer.

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    Elfagieh, Mohamed; Abdalla, Fathi; Gliwan, Asma; Boder, Jamela; Nichols, Wafa; Buhmeida, Abdelbaset

    2012-12-01

    Results from studies on efficacy of carcinoembryonic antigen (CEA), carbohydrate antigen 15.3 (CA 15.3) and thymidine kinase (TK1) as diagnostic and prognostic tools for primary breast cancer (BC) have presented conflicting results, and usefulness of these markers for clinical use in BC remains unclear. The aim of this study is to evaluate potential of concentration of the sera CEA, CA15.3 and TK1 peptides' use as markers in the diagnosis and prognosis of breast lesions of Libyan patients. Serum tumour markers were studied in 20 healthy subjects, 30 patient with benign lesion diseases and 50 patients with histologically confirmed BC diagnosed at the National Cancer Institute (NCI), Misurata, Libya during the period 2005-2009. The concentrations of the BC patients' cutoff points used for diagnostic and prognostic sensitivity were 8.82 ng/ml, 35.57 U/ml and 32.57 U/mg/protein for CEA, CA15.3 and TK1, respectively. Increased CEA (>8.82 ng/ml), CA 15.3 (>35.57 U/ml) and TK1 (>32.57 U/mg/protein) concentrations were found in 62 %, 70 % and 78 % of the BC patients, respectively. For all three tumour markers, increased concentrations correlated increased tumour size and nodal involvement. Significantly higher serum TK1 levels were found in patients with advanced disease (p < 0.0001) and TK1 levels also correlated with disease-specific survival (DSS, p < 0.07). The combined data set of the three markers' data from three markers increased the diagnostic sensitivity to 90 %. The serum marker analysis for CEA, CA 15.3, and S-TK1 concentrations is shown to be a useful tool for identification of malignant cases in our BC population and for the prognostic evaluation of patients with primary BC. Increased concentrations of the markers were also observed to be higher in patients with advanced tumours and indicative of the development of distant metastasis.

  11. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

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    Ming-Ming Tsai

    2016-06-01

    Full Text Available Human gastric cancer (GC is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.

  12. Diagnostic and Prognostic Value of TSH Levels in Differentiated Thyroid Cancers

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    Mazhar Müslüm Tuna

    2014-03-01

    Full Text Available Purpose: The frequency of thyroid surgery for suspected malignancy but with a benign result in pathological examination is increasing in recent years. For this reason, additional preoperative markers are needed for increasing the sensitivity for evaluating the preoperative malignancy risk of thyroid nodules. In this study, we aimed to evaluate the diagnostic value of serum TSH levels for determining the differentiated thyroid cancers (DTC and to identify a proper cut-off value if relevant association is present. Material and Method: Our study included 380 patients who underwent thyroidectomy due to nodular goiter in our hospital between 01.01.2012 and 01.06.2013 retrospectively. 201 patients who were diagnosed with DTC constituted the study group, and 179 consecutive patients with a benign pathology result were included as controls. Patients who had overt hyperthyroidism or hypothyroidism and was taken medicines that affect TSH level were excluded. Results: There were no significant differences between the two groups in terms of age, sex, and family history of thyroid disease. Preoperative TSH levels were 1.66 mIU/lt and 1.59 mIU/lt in patients with DTC and controls, respectively (p=0.641. There was no correlation between TSH and tumor size, and no relationship between TSH and capsular invasion, vascular invasion, extrathyroidal invasion and lymph node metastasis. Discussion: In our study, no relationship was found between preoperative TSH level and DTC. In addition, there was no relationship between TSH and bad prognostic parameters. Turk Jem 2014; 1: 1-4

  13. [The diagnostic value of microsatellite LOH analysis and the prognostic relevance of angiogenic gene expression in urinary bladder cancer].

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    Szarvas, Tibor

    2009-12-01

    Bladder cancer is the second most common malignancy affecting the urinary system. Currently, histology is the only tool that determines therapy and patients' prognosis. As the treatment of non-invasive (Ta/T1) and muscle invasive (T2-T4) bladder tumors are completely different, correct staging is important, although it is often hampered by disturbing factors. Molecular methods offer new prospects for early disease detection, confirmation of unclear histological findings and prognostication. Applying molecular biological methods, the present study is searching for answers to current diagnostic and prognostic problems in bladder carcinoma. We analyzed tumor, blood and/or urine samples of 334 bladder cancer patients and 117 control individuals. Genetic alterations were analyzed in urine samples of patients and controls, both by PCR-based microsatellite loss of heterozigosity (LOH) analysis using 12 fluorescently labeled primers and by DNA hybridization based UroVysion FISH technique using 4 probes, to assess the diagnostic values of these methods. Whole genome microsatellite analysis (with 400 markers) was performed in tumor and blood specimens of bladder cancer patients to find chromosomal regions, the loss of which may be associated with tumor stage. Furthermore, we assessed the prognostic value of Tie2, VEGF, Angiopoietin-1 and -2. We concluded that DNA analysis of voided urine samples by microsatellite analysis and FISH are sensitive and non-invasive methods to detect bladder cancer. Furthermore, we established a panel of microsatellite markers that could differentiate between non-invasive and invasive bladder cancer. However, further analyses in a larger cohort of patients are needed to assess their specificity and sensitivity. Finally, we identified high Ang-2 and low Tie2 gene expression as significant and independent risk factors of tumor recurrence and cancer related survival.

  14. A Case of Urethral Metastasis from Sigmoid Colon Cancer Diagnostically and Prognostically Indicated by F 18 FDG PET/CT

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    Seo, Han Seok; Kim, Eun Sil; Kim, Soyon; Im, Su Jin; Park, Yong Hyun; Lee, Ju Hyoung; Hur, So Chong [National Police Hospital, Seoul (Korea, Republic of)

    2011-12-15

    Urethral metastasis from colorectal cancer is rare and is known to have a poor prognosis. A 72 year old man with a history of colectomy and colostomy due to sigmoid colon cancer was admitted to the emergency room with bowel distension, rectal bleeding and urinary symptoms. Computed tomography of the abdominopelvis showed sigmoid colon cancer with multiple metastases involving the liver. Positron emission tomography with F 18 fluorodeoxyglucose (FDG) showed multiple hypermetabolic foci in the liver, penis and pubic bone, which otherwise could not be diagnosed. The lesions revealed no improvement with chemotherapy and urological surgery on follow up F 18 FDG PET/CT. We present a case of urethral metastasis of sigmoid colon cancer diagnostically and prognostically indicated by F 18 FDG PET/CT.

  15. Diagnostic and prognostic correlates of preoperative FDG PET for breast cancer

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    Vinh-Hung, Vincent [University of Geneva, Department of Imaging and Medical Information Sciences, University Hospitals of Geneva, Geneva (Switzerland); University of Geneva, Radiation Oncology, University Hospitals of Geneva, Geneva (Switzerland); Everaert, Hendrik [Vrije Universiteit Brussel, Department of Nuclear Medicine, UZ Brussel, Brussels (Belgium); Lamote, Jan; Vanhoeij, Marian; Verfaillie, Guy [Vrije Universiteit Brussel, Department of Surgery, UZ Brussel, Brussels (Belgium); Voordeckers, Mia; Parijs, Hilde van; Ridder, Mark de [Vrije Universiteit Brussel, Department of Radiotherapy, UZ Brussel, Brussels (Belgium); Fontaine, Christel [Vrije Universiteit Brussel, Department of Medical Oncology UZ Brussel, Brussels (Belgium); Vees, Hansjoerg; Ratib, Osman [University of Geneva, Department of Imaging and Medical Information Sciences, University Hospitals of Geneva, Geneva (Switzerland); Vlastos, Georges [University of Geneva, Department of Surgical Senology, University Hospitals of Geneva, Geneva (Switzerland)

    2012-10-15

    To explore the preoperative utility of FDG PET for the diagnosis and prognosis in a retrospective breast cancer case series. In this retrospective study, 104 patients who had undergone a preoperative FDG PET scan for primary breast cancer at the UZ Brussel during the period 2002-2008 were identified. Selection criteria were: histological confirmation, FDG PET performed prior to therapy, and breast surgery integrated into the primary therapy plan. Patterns of increased metabolism were recorded according to the involved locations: breast, ipsilateral axillary region, internal mammary chain, or distant organs. The end-point for the survival analysis using Cox proportional hazards was disease-free survival. The contribution of prognostic factors was evaluated using the Akaike information criterion and the Nagelkerke index. PET positivity was associated with age, gender, tumour location, tumour size >2 cm, lymphovascular invasion, oestrogen and progesterone receptor status. Among 63 patients with a negative axillary PET status, 56 (88.9 %) had three or fewer involved nodes, whereas among 41 patients with a positive axillary PET status, 25 (61.0 %) had more than three positive nodes (P < 0.0001). In the survival analysis of preoperative characteristics, PET axillary node positivity was the foremost statistically significant factor associated with decreased disease-free survival (hazard ratio 2.81, 95% CI 1.17-6.74). Preoperative PET axillary node positivity identified patients with a higher burden of nodal involvement, which might be important for treatment decisions in breast cancer patients. (orig.)

  16. Gear Fatigue Diagnostics and Prognostics

    Science.gov (United States)

    2013-01-01

    The first objective was to collect meaningful gear fault progression data starting from healthy NASA-designed spur test gears and ending with failed...and D. P. Townsend, "Analysis of the effects of surface pitting and wear on the vibration of a gear transmission system," Tribology International...Reporting Period: April 15, 2012 to September 27, 2012 Attached is the Gear Fatigue Diagnostics and Prognostics project progress report for the

  17. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Hong Zheng; Jia-Yu Liu; Feng-Ju Song; Ke-Xin Chen

    2013-01-01

    Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70%of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30%because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA (miR) is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injury. Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer.

  18. Prostate Cancer Diagnostics and Prognostics Based on Interphase Spatial Genome Positioning

    Science.gov (United States)

    2016-03-01

    of tissues included twelve breast cancers, six benign breast tissues (hyperplasia and fibroadenoma ), six normal breast tissues, 20 prostate cancers... fibroadenoma ) and malignant breast tissues and, conversely, we positioned breast GPBs in nor- mal, normal adjacent to tumor (NAT) and adenocarcinoma...in abnor- mal, but non-malignant, breast tissue, we positioned these genes in benign hyperplasia and fibroadenoma breast tis- sues (Table 4, Suppl

  19. Diagnostic and Prognostic Biomarkers in Melanoma

    Science.gov (United States)

    Leininger, Jennifer; Hamby, Carl; Safai, Bijan

    2014-01-01

    Melanoma is a lethal melanocytic neoplasm. Unfortunately, the histological diagnosis can be difficult at times. Distinguishing ambiguous melanocytic neoplasms that are benign nevi from those that represent true melanoma is important both for treatment and prognosis. Diagnostic biomarkers currently used to assist in the diagnosis of melanoma are usually specific only for melanocytic neoplasms and not necessarily for their ability to metastasize. Traditional prognostic biomarkers include depth of invasion and mitotic count. Newer diagnostic and prognostic biomarkers utilize immunohistochemical staining as well as ribonucleic acid, micro-ribonucleic acid, and deoxyribonucleic acid assays and fluorescence in situ hybridization. Improved diagnostic and prognostic biomarkers are of increasing importance in the treatment of melanoma with the development of newer and more targeted therapies. Herein, the authors review many of the common as well as newer diagnostic and prognostic biomarkers used in melanoma. PMID:25013535

  20. SULF2 Expression Is a Potential Diagnostic and Prognostic Marker in Lung Cancer.

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    Natalie S Lui

    Full Text Available Lung cancer is one of the most deadly cancers; median survival from diagnosis is less than one year in those with advanced disease. Novel lung cancer biomarkers are desperately needed. In this study, we evaluated SULF2 expression by immunohistochemistry and its association with overall survival in a cohort of patients with non-small cell lung cancer (NSCLC. We also looked for the presence of SULF2 protein in plasma to evaluate its potential as an early detection biomarker for NSCLC.We identified patients who underwent surgical resection for pulmonary adenocarcinoma or squamous cell carcinoma at our institution. A section from each paraffin-embedded specimen was stained with a SULF2 antibody. A pathologist determined the percentage and intensity of tumor cell staining. Survival analysis was performed using a multivariate Cox proportional hazards model. Using a novel SULF2 ELISA assay, we analyzed plasma levels of SULF2 in a small cohort of healthy donors and patients with early stage NSCLC.SULF2 staining was present in 82% of the lung cancer samples. Squamous cell carcinomas had a higher mean percentage of staining than adenocarcinomas (100% vs. 60%; p<0.0005. After adjusting for age, sex, race, histologic type, stage, and neoadjuvant therapy, there was a non-significant (31%; p = 0.65 increase in the risk of death for patients with adenocarcinoma with SULF2 staining in tumor cells. In contrast, there was a significant decrease in the risk of death (89%; p = 0.02 for patients with squamous cell carcinoma with SULF2 staining in tumor cells. SULF2 protein was present in plasma of patients with early stage NSCLC, and soluble SULF2 levels increased with age. Finally, plasma SULF2 levels were significantly elevated in early stage NSCLC patients, compared to healthy controls.Tumor expression of SULF2 may affect prognosis in NSCLC, while blood SULF2 levels may have a significant role in the diagnosis of this fatal disease.

  1. The diagnostic and prognostic value of serum bone Gla protein (osteocalcin) in patients with recurrent breast cancer

    DEFF Research Database (Denmark)

    Kamby, C; Egsmose, C; Söletormos, G

    1993-01-01

    bone survey. The sites of recurrence were bone (61%), bone marrow (46%), soft tissue (52%), lung (13%), pleura (11%), liver (4%), and brain (2%). Radiology and bone biopsy served as key diagnoses as to the presence or absence of bone metastases. The diagnostic efficiency of B-scan and S-AP was greater...... than that of S-BGP, and the result of BGP measurement was associated with neither extent nor number of bone metastases. However, the BGP values were significantly lower in patients who had visceral metastases, and the median duration of survival after recurrence was 13 months for patients with low S......Serum bone Gla protein (S-BGP), a marker of bone metabolism, was measured in 60 patients included in a staging programme for recurrent breast cancer. Other diagnostic procedures comprised S-alkaline phosphatase (S-AP), bone scan (B-scan), bilateral iliac crest bone marrow biopsies, and radiological...

  2. Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer.

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    Zuberi, Mariyam; Khan, Imran; Mir, Rashid; Gandhi, Gauri; Ray, Prakash Chandra; Saxena, Alpana

    2016-01-01

    MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan-Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (pmiR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

  3. A REVIEW OF SLOW SPEED BEARING DIAGNOSTICS AND PROGNOSTICS

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    SYLVESTER A. AYE

    2014-10-01

    Full Text Available This paper reviews the literature in diagnostics and prognostics of slow rotating bearings. Diagnostics and prognostics involve data acquisition and processing. The diagnostics and prognostics of rotating machinery is a subject of much on-going research. There are three approaches to diagnostics and prognostics which include data driven techniques, model based techniques and experience based approach. The review looks at current diagnostics and prognostics approaches to bearings in general and slow rotating bearings in particular and future trends. Bayesian techniques are currently gaining widespread application in diagnostics and prognostics of slow rotating bearings and mechanical systems as a result of their ability to handle the stochastic nature of the data well at varying operating conditions.

  4. PROGNOSTIC FACTORS IN PROSTATE CANCER

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    N. A. Gorban

    2014-08-01

    Full Text Available Prostate cancer is most common and its heterogenicity is presently apparent. There is a continuous search for the factors allowing the prediction of the poor course and biological difference of tumors. The College of American Pathologists classifies the currently known prognostic factors into 3 categories: 1 the factors whose prognostic importance and successful use have been proven in practice; 2 those that have been widely studied biologically and clinically, but the significance of which needs to be proven in extensive statistical studies; 3 all other factors that have been inadequately studied to demonstrate their prognostic value. Category 1 prognostic factors, such as prostate-specific antigen levels, TNM stage, Gleason grading, and the status of surgical margins, enjoy wide application. Category 2 factors are not used IN clinical practice so extensively. The value of some Category 3 factors (the biomarkers p53, Ki-67, Bcl-2, receptors of androgens is indubitably and they claim to be widely applied in clinical practice with time. The clinical significance of molecular biological markers calls for further investigation.

  5. PROGNOSTIC FACTORS IN PROSTATE CANCER

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    N. A. Gorban

    2010-01-01

    Full Text Available Prostate cancer is most common and its heterogenicity is presently apparent. There is a continuous search for the factors allowing the prediction of the poor course and biological difference of tumors. The College of American Pathologists classifies the currently known prognostic factors into 3 categories: 1 the factors whose prognostic importance and successful use have been proven in practice; 2 those that have been widely studied biologically and clinically, but the significance of which needs to be proven in extensive statistical studies; 3 all other factors that have been inadequately studied to demonstrate their prognostic value. Category 1 prognostic factors, such as prostate-specific antigen levels, TNM stage, Gleason grading, and the status of surgical margins, enjoy wide application. Category 2 factors are not used IN clinical practice so extensively. The value of some Category 3 factors (the biomarkers p53, Ki-67, Bcl-2, receptors of androgens is indubitably and they claim to be widely applied in clinical practice with time. The clinical significance of molecular biological markers calls for further investigation.

  6. Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

    DEFF Research Database (Denmark)

    Schultz, Nicolai A; Christensen, Ib Jarle; Werner, Jens;

    2013-01-01

    We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.......We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival....

  7. EEG Abnormalities as Diagnostic and Prognostic Factor for Encephalitis

    Directory of Open Access Journals (Sweden)

    Gavrilovic Aleksandar

    2016-09-01

    Full Text Available The aim of the study is to examine whether EEG abnormalities in patients with encephalitis might be prognostic and diagnostic factors for final epilepsy outcome and/or be correlated with the severity of the disability.

  8. PROGNOSTIC FACTORS ANALYSIS FOR STAGEⅠ RECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    武爱文; 顾晋; 薛钟麒; 王怡; 徐光炜

    2001-01-01

    To explore the death-related factors of stageⅠrectal cancer patients. Methods: 89 cases of stage I rectal cancer patients between 1985 and 2000 were retrospectively studied for prognostic factors. Factors including age, gender, tumor size, circumferential occupation, gross type, pathological type, depth of tumor invasion, surgical procedure, adjuvant chemotherapy and postoperative complication were chosen for cox multivariate analysis (forward procedure) using Spss software (10.0 version). Results: multivariate analysis demonstrated that muscular invasion was an independent negative prognostic factor for stageⅠrectal cancer patients (P=0.003). Conclusion: Muscular invasion is a negative prognostic factor for stage I rectal cancer patients.

  9. Diagnostic and Prognostic Models for Generator Step-Up Transformers

    Energy Technology Data Exchange (ETDEWEB)

    Vivek Agarwal; Nancy J. Lybeck; Binh T. Pham

    2014-09-01

    In 2014, the online monitoring (OLM) of active components project under the Light Water Reactor Sustainability program at Idaho National Laboratory (INL) focused on diagnostic and prognostic capabilities for generator step-up transformers. INL worked with subject matter experts from the Electric Power Research Institute (EPRI) to augment and revise the GSU fault signatures previously implemented in the Electric Power Research Institute’s (EPRI’s) Fleet-Wide Prognostic and Health Management (FW-PHM) Suite software. Two prognostic models were identified and implemented for GSUs in the FW-PHM Suite software. INL and EPRI demonstrated the use of prognostic capabilities for GSUs. The complete set of fault signatures developed for GSUs in the Asset Fault Signature Database of the FW-PHM Suite for GSUs is presented in this report. Two prognostic models are described for paper insulation: the Chendong model for degree of polymerization, and an IEEE model that uses a loading profile to calculates life consumption based on hot spot winding temperatures. Both models are life consumption models, which are examples of type II prognostic models. Use of the models in the FW-PHM Suite was successfully demonstrated at the 2014 August Utility Working Group Meeting, Idaho Falls, Idaho, to representatives from different utilities, EPRI, and the Halden Research Project.

  10. Diagnostic and prognostic value of serum nitric oxide, tumor necrosis factor-alpha, basic fibroblast growth factor and copper as angiogenic markers in premenopausal breast cancer patients: a case-control study.

    Science.gov (United States)

    Hewala, T I; Abd El-Moneim, N A; Ebied, S Abd El-Moneim; Sheta, M I; Soliman, K; Abu-Elenean, A

    2010-01-01

    Many studies demonstrate that increased microvessel density (MVD) surrounding primary tumour is associated with decreased overall survival in patients with breast cancer. This study compares the diagnostic and prognostic values of the angiogenic serum factors nitric oxide (NO), tumour necrosis factor-alpha (TNFalpha), basic fibroblast growth factor (bFGF) and copper with those of serum CA15-3 as the standard tumour marker in breast cancer patients. Microvessel density was estimated in CD31-immunostained sections from breast cancer patients. Before surgery, NO, TNFalpha, bFGF, copper and CA 15-3 were measured in serum samples from 30 premenopausal breast cancer patients in comparison with 15 healthy controls. The diagnostic values of the assayed parameters were compared using receiver operating characteristic (ROC) curve analysis. Univariate survival analysis of patients was assessed using the Kaplan-Meier method. Breast cancer tissues showed higher MVD than did normal breast tissues adjacent to the tumour (P = 0.008). Before surgery, tumour MVD correlated significantly with serum NO, TNFalpha, bFGF and copper (r = 0.458, P = .011; r = 0.379, P = .039; r = 0.513, P = .004 and r = 0.613, P = 0.000, respectively). Serum NO, TNFalpha, bFGF, copper and CA 15-3 levels in patients were significantly elevated compared with controls (P = 0.011, P = 0.004, P = 0.039, P = 0.000 and P = 0.001, respectively). Kaplan-Meier analysis revealed that patients with elevated serum TNFalpha, CA 15-3 and copper (P = 0.035, P = 0.040, P = 0.0339, respectively) had an overall survival significantly shorter than those who had lower levels of these parameters. These data suggest that serum TNFalpha, CA 15-3 and copper are useful predictive markers for overall survival in premenopausal breast cancer patients.

  11. Prognostic Gene Expression Profiles in Breast Cancer

    DEFF Research Database (Denmark)

    Sørensen, Kristina Pilekær

    Each year approximately 4,800 Danish women are diagnosed with breast cancer. Several clinical and pathological factors are used as prognostic and predictive markers to categorize the patients into groups of high or low risk. Around 90% of all patients are allocated to the high risk group...... clinical courses, and they may be useful as novel prognostic biomarkers in breast cancer. The aim of the present project was to predict the development of metastasis in lymph node negative breast cancer patients by RNA profiling. We collected and analyzed 82 primary breast tumors from patients who...... and the time of event. Previous findings have shown that high expression of the lncRNA HOTAIR is correlated with poor survival in breast cancer. We validated this finding by demonstrating that high HOTAIR expression in our primary tumors was significantly associated with worse prognosis independent...

  12. Prognostic DNA Methylation Markers for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Siri H. Strand

    2014-09-01

    Full Text Available Prostate cancer (PC is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181 and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.

  13. Potential Prognostic Markers for Human Prostate Cancer

    Science.gov (United States)

    2001-03-01

    Prostate 35: 185-192, 1998 osteoblasts on prostate carcinoma proliferation and chemo- 32. Trikha M, Cai Y, Grignon D, Honn KV: Identification taxis ...Markers for Human Prostate Cancer PRINCIPAL INVESTIGATOR: Bruce R. Zetter, Ph.D. CONTRACTING ORGANIZATION: Children’s Hospital Boston, Massachusetts...March 2001 Final (1 Sep 98 - 28 Feb 01) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Potential Prognostic Markers for Human Prostate Cancer DAMD17-98-1

  14. Prognostic factors in young ovarian cancer patients

    DEFF Research Database (Denmark)

    Klar, M; Hasenburg, A; Hasanov, M;

    2016-01-01

    OBJECTIVES: We evaluated in a large study meta-database of prospectively randomised phase III trials the prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients 40 years of age with advanced epithelial ovarian cancer. METHODS: A total of 5055 patients...... epithelial ovarian cancer, excellent performance status, who had received complete macroscopic upfront cytoreduction and ≥5 chemotherapy cycles. RESULTS: For patients

  15. Prognostic factors in cervical cancer

    NARCIS (Netherlands)

    Biewenga, P.

    2015-01-01

    Surgery is the standard of care for women with early stage cervical cancer; radiotherapy is the cornerstone in patients with advanced stages of disease. Recent changes in the treatment of cervical cancer involve less radical surgery in early stage cervical cancer, concomitant chemo- and radiotherapy

  16. Conceptualizing prognostic awareness in advanced cancer: a systematic review.

    Science.gov (United States)

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2014-09-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients' understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness.

  17. Diagnostic Reasoning using Prognostic Information for Unmanned Aerial Systems

    Science.gov (United States)

    Schumann, Johann; Roychoudhury, Indranil; Kulkarni, Chetan

    2015-01-01

    With increasing popularity of unmanned aircraft, continuous monitoring of their systems, software, and health status is becoming more and more important to ensure safe, correct, and efficient operation and fulfillment of missions. The paper presents integration of prognosis models and prognostic information with the R2U2 (REALIZABLE, RESPONSIVE, and UNOBTRUSIVE Unit) monitoring and diagnosis framework. This integration makes available statistically reliable health information predictions of the future at a much earlier time to enable autonomous decision making. The prognostic information can be used in the R2U2 model to improve diagnostic accuracy and enable decisions to be made at the present time to deal with events in the future. This will be an advancement over the current state of the art, where temporal logic observers can only do such valuation at the end of the time interval. Usefulness and effectiveness of this integrated diagnostics and prognostics framework was demonstrated using simulation experiments with the NASA Dragon Eye electric unmanned aircraft.

  18. MOLECULAR PROGNOSTIC MARKERS OF URINE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2012-01-01

    Full Text Available Bladder cancer (BC remains a current problem in oncourology. Despite that bladder cancer risk factors have been studied and described in the literature, new molecular and genetic mechanisms have been identified that predisposes to the disease development. There are numerous cellular processes involve in BC pathogenesis. The less-aggressive, non-invasive slow progressing bladder cancer types are defined by Ras-MAPK system activation. Tumors that are more aggressive and have low cancer-specific survival rate are characterized by changes in retinoblastoma genes and p53. Attempts are made to develop prognostic tests to predict tumor behavior, targeted treatment. perspectively, BC patients will be treated using molecular genetic markers allowing the accurate prediction of the patient’s tumor behavior and fitting the treatment tactics on the individual basis.

  19. Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers.

    LENUS (Irish Health Repository)

    Jansen, Michael

    2010-07-01

    Over the past 10 years, there has been an increasing use of molecular markers in the assessment and management of adult malignant gliomas. Some molecular signatures are used diagnostically to help pathologists classify tumours, whereas others are used to estimate prognosis for patients. Most crucial, however, are those markers that are used to predict response to certain therapies, thereby directing clinicians to a particular treatment while avoiding other potentially deleterious therapies. Recently, large-scale genome-wide surveys have been used to identify new biomarkers that have been rapidly developed as diagnostic and prognostic tools. Given these developments, the pace of discovery of new molecular assays will quicken to facilitate personalised medicine in the setting of malignant glioma.

  20. Does the use of diagnostic PET/CT cause stage migration in patients with primary advanced ovarian cancer?

    DEFF Research Database (Denmark)

    Risum, S; Høgdall, C; Loft, Annika

    2010-01-01

    To investigate if the use of diagnostic FDG-PET/CT leads to stage migration in patients with advanced ovarian cancer and to evaluate the prognostic significance of FDG-PET/CT.......To investigate if the use of diagnostic FDG-PET/CT leads to stage migration in patients with advanced ovarian cancer and to evaluate the prognostic significance of FDG-PET/CT....

  1. Prognostic role of syncytin expression in breast cancer

    DEFF Research Database (Denmark)

    Larsson, Lars-Inge; Holck, Susanne; Christensen, Ib Jarle

    2007-01-01

    Breast cancer cells were recently found to produce syncytin, an endogenous retroviral protein implicated in cell fusion, immune regulation, and nitric oxide synthase expression. To determine whether syncytin has a prognostic role in breast cancer, we investigated a series of 165 premenopausal lymph...... prognostic indicator for recurrence-free survival. In addition, we examined a second series of 54 consecutively operated breast cancer patients of all categories and the results supported the conclusions made from the first study. Thus, syncytin expression constitutes a positive prognostic factor in breast...... cancer - a phenomenon that may be related to the involvement of syncytin in mediating fusions between breast cancer cells and entodhelial cells....

  2. Histotype-based prognostic classification of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Anna Maria Chiaravalli; Catherine Klersy; Alessandro Vanoli; Andrea Ferretti; Carlo Capella; Enrico Solcia

    2012-01-01

    T8 cell-rich HLR group,the largest group among low-grade histotypes.Coexisting HLR proved to be a factor in improved prognosis in tumors with microsatellite instability (P =0.0015 vs HLR-/MSI-H tumors) or DR type human leukocyte antigen expression (P =0.033 vs HLR-/HLA-DR+ tumors).CONCLUSION:Identification of low-and high-grade histotypes can improve the prognostic assessment of a substantial proportion of gastric cancers in routine diagnostic practice.

  3. SERUM LACTATE DEHYDROGENASE AS A PROGNOSTIC MARKER IN BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Hardik

    2015-11-01

    Full Text Available : BACKGROUND: Breast cancer a multifactorial disease and one of the most dreaded of human diseases that claims the lives of thousands of women all over the globe every year. This may probably due to the fact that it remains undiagnosed at an early stage perhaps due to lack of awareness amongst the females and the fact that most cancers do not produce any symptoms until the tumour are too large to be removed surgically. Hence there is need to detect cancer at an early stage. AIM: Estimation of diagnostic importance and prognostication of serum Lactate dehydrogenase in cases on breast cancer. SETTINGS AND DESIGN: An observational study was conducted in Acharya Vinoba Bhave Rural Hospital, Sawangi (Meghe, Wardha which included 44 confirmed cases of carcinoma breast and 44 normal healthy females admitted in AVBRH in a span of 2 years. METHODS AND MATERIAL: Determination of serum LDH was done using TC matrix analyser. The values of LDH were obtained on presentation, 21 days after intervention, 2 months after intervention and 6 months after intervention. The values of LDH on presentation in both the groups were compared. The decline in the values of LDH were observed with the due course of treatment. Chisquare test and Student’s Unpaired and paired t test were used for statistical analysis. RESULT: The mean Lactate dehydrogenase on presentation was in study group and control group was 564.38±219.41 IU/L and 404.18±101.32 IU/L respectively (p<0.05. The levels of Lactate dehydrogenase decreased with due course of treatment. The levels of LDH were proportionate to the stage of disease. CONCLUSION: The results of the study concludes cost effective usefulness of serum Lactate dehydrogenase in early detection of breast cancer and to assess its prognostic importance which can be done in smaller laboratories. The traditional model of DS-

  4. Matrix metalloproteinase-9 is a prognostic marker for patients with cervical cancer.

    Science.gov (United States)

    Li, Yi; Wu, Tao; Zhang, Beilei; Yao, Yuanqing; Yin, Guowu

    2012-12-01

    Cervical cancer remains one of the most common malignancies in women. Previous study proved MMP-9 might be prognostic marker for multiple human malignancies. The present study was to investigate the protein expression of MMP-9 in cervical cancer and its association with clinicopathological characteristics as well as prognosis of patients. Cervical cancer specimens from 225 cases who had not received chemotherapy or radiotherapy prior to surgery were collected. Immunochemistry assays were utilized to investigate MMP-9 protein expression. Results showed that MMP-9 expression was increased in cervical cancer and associated with stromal invasion, FIGO stage, lymph node metastasis, and vascular invasion. Kaplan-Meier analysis showed that patients with cervical cancer of positive MMP-9 staining tend to have worse overall survival. In multivariate analysis stratified for known prognostic variables, MMP-9 was proved to be an independent prognostic factor. The present study confirmed that MMP-9 expression in cervical cancer was an independent prognostic factor of patients, which might be a potential diagnostic and even therapeutic target of cervical cancer.

  5. Conforming to cancer staging, prognostic indicators and national treatment guidelines.

    Science.gov (United States)

    Dykstra-Long, Gwendylen R

    2011-01-01

    Clinical cancer staging and prognostic indicators guide treatment planning, and as such the American College of Surgeons Commission on Cancer Commission on Cancer (ACoS CoC) and the American Joint Committee on Cancer (AJCC) have recognized this as quality patient care. Overton Brooks Veterans Administration (OBVAMC) developed an organizational policy and procedure, flow algorithms, treatment plan templates, and education strategies in order to conform to this quality care approach. The purpose of this article is to share this systematic approach that is able to support clinical and working cancer stage and prognostic indicators which have been recognized by national standard setting organizations as quality patient care.

  6. Uncertainty Management for Diagnostics and Prognostics of Batteries using Bayesian Techniques

    Data.gov (United States)

    National Aeronautics and Space Administration — Uncertainty management has always been the key hurdle faced by diagnostics and prognostics algorithms. A Bayesian treatment of this problem provides an elegant and...

  7. Real-Time Adaptive Algorithms for Flight Control Diagnostics and Prognostics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Model-based machinery diagnostic and prognostic techniques depend upon high-quality mathematical models of the plant. Modeling uncertainties and errors decrease...

  8. Accumulated metabolites of hydroxybutyric acid serve as diagnostic and prognostic biomarkers of ovarian high-grade serous carcinomas

    Science.gov (United States)

    Hilvo, Mika; de Santiago, Ines; Gopalacharyulu, Peddinti; Schmitt, Wolfgang D.; Budczies, Jan; Kuhberg, Marc; Dietel, Manfred; Aittokallio, Tero; Markowetz, Florian; Denkert, Carsten; Sehouli, Jalid; Frezza, Christian

    2016-01-01

    Ovarian cancer is a heterogeneous disease of low prevalence, but poor survival. Early diagnosis is critical for survival, but is often challenging because the symptoms of ovarian cancer are subtle and become apparent only during advanced stages of the disease. Therefore, the identification of robust biomarkers of early disease is a clinical priority. Metabolomic profiling is an emerging diagnostic tool enabling the detection of biomarkers reflecting alterations in tumor metabolism, a hallmark of cancer. In this study, we performed metabolomic profiling of serum and tumor tissue from 158 patients with high-grade serous ovarian cancer (HGSOC) and 100 control patients with benign or non-neoplastic lesions. We report metabolites of hydroxybutyric acid (HBA) as novel diagnostic and prognostic biomarkers associated with tumor burden and patient survival. The accumulation of HBA metabolites caused by HGSOC was also associated with reduced expression of succinic semialdehyde dehydrogenase (encoded by ALDH5A1), and with the presence of an epithelial-to-mesenchymal transition (EMT) gene signature, implying a role for these metabolic alterations in cancer cell migration and invasion. In conclusion, our findings represent the first comprehensive metabolomics analysis in HGSOC and propose a new set of metabolites as biomarkers of disease with diagnostic and prognostic capabilities. PMID:26685161

  9. Diagnostic and prognostic biomarkers of sepsis in critical care.

    Science.gov (United States)

    Kibe, Savitri; Adams, Kate; Barlow, Gavin

    2011-04-01

    Sepsis is a leading cause of mortality in critically ill patients. Delay in diagnosis and initiation of antibiotics have been shown to increase mortality in this cohort. However, differentiating sepsis from non-infectious triggers of the systemic inflammatory response syndrome (SIRS) is difficult, especially in critically ill patients who may have SIRS for other reasons. It is this conundrum that predominantly drives broad-spectrum antimicrobial use and the associated evolution of antibiotic resistance in critical care environments. It is perhaps unsurprising, therefore, that the search for a highly accurate biomarker of sepsis has become one of the holy grails of medicine. Procalcitonin (PCT) has emerged as the most studied and promising sepsis biomarker. For diagnostic and prognostic purposes in critical care, PCT is an advance on C-reactive protein and other traditional markers of sepsis, but is not accurate enough for clinicians to dispense with clinical judgement. There is stronger evidence, however, that measurement of PCT has a role in reducing the antibiotic exposure of critical care patients. For units intending to incorporate PCT assays into routine clinical practice, the cost-effectiveness of this is likely to depend on the pre-implementation length of an average antibiotic course and the subsequent impact of implementation on emerging antibiotic resistance. In most of the trials to date, the average baseline duration of the antibiotic course was longer than is currently standard practice in many UK critical care units. Many other biomarkers are currently being investigated. To be highly useful in clinical practice, it may be necessary to combine these with other novel biomarkers and/or traditional markers of sepsis.

  10. Important prognostic factors for the long-term survival of lung cancer subjects in Taiwan

    Directory of Open Access Journals (Sweden)

    Ko Albert

    2008-11-01

    Full Text Available Abstract Background This study used a large-scale cancer database in determination of prognostic factors for the survival of lung cancer subjects in Taiwan. Methods Total of 24,910 subjects diagnosed with lung cancer was analysed. Survival estimates by Kaplan-Meier methods. Cox proportional-hazards model estimated the death risk (hazard ratio (HR for various prognostic factors. Results The prognostic indicators associated with a higher risk of lung cancer deaths are male gender (males versus females; HR = 1.07, 95% confidence intervals (CI: 1.03–1.11, males diagnosed in later periods (shown in 1991–1994 versus 1987–1990; HR = 1.13, older age at diagnosis, large cell carcinoma (LCC/small cell carcinoma (SCC, and supportive care therapy over chemotherapy. The overall 5-year survival rate for lung cancer death was significantly poorer for males (21.3% than females (23.6%. Subjects with squamous cell carcinoma (SQCC and treatment by surgical resection alone had better prognosis. We find surgical resections to markedly increase 5-year survival rate from LCC, decreased risk of death from LCC, and no improved survival from SCC. Conclusion Gender and clinical characteristics (i.e. diagnostic period, diagnostic age, histological type and treatment modality play important roles in determining lung cancer survival.

  11. Prognostic predictors for non-small cell lung cancer patients with brain metastasis after radiotherapy

    Directory of Open Access Journals (Sweden)

    Qiuhong FAN

    2008-06-01

    Full Text Available Background and objective Brain metastasis (BM is often found in the patients with lung cancer. Radiotherapy is regular and effective means of therapy and it aims at palliating symptoms and prolonging survival time. However, now there are different viewpoints on protocols of radiotherapy and prognostic factors. A retrospective analysis is used to evaluate the results of treatment for 82 cases with brain metastasis from non-small cell lung cancer (NSCLC and explore the prognostic factors to establish a prognostic index (PI model. Methods From Feb.1995 to Oct. 2006, 82 patients irradiated for BM from NSCLC, with both complete medical charts and follow-up data available, were eligible for this retrospective analysis. A number of potential factors which might affect prognosis after irradiation were evaluated. The significance of prognostic variables in the survival resulted from both univariate analysis by Kaplan-Meier combining with log-rank test and multivariate Cox regression model. The prognostic index (PI was established based on Cox regression analysis and subgrouping values. Results The follow-up time was 1-120 months. For the entire cohort, the median survival from the start of radiation for BM was 10.5 months, and the actuarial overall survival rate was 50.8%, 23.7% and 5.1% at 0.5, 1 and 2 years respectively. Univariate analysis showed KPS, control of primary tumor, interval from the beginning of diagnostic to BM, extracranial systemic metastasis, counts of lymphocyte and solitary BM were predictors of prognosis. However, in the Cox multivariate analysis, only KPS, control of primary tumor, interval from the beginning of diagnostic to BM and solitary BM were significant prognostic factors. The prognostic index was established based on Cox regression analysis and 82 patients were stratified good, intermediate and poor prognostic sub-groups. The difference of survival rate among 3 subgroups is significant (P<0.001. Conclusion Radiotherapy is

  12. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  13. Predictive and prognostic molecular markers for cancer medicine.

    Science.gov (United States)

    Mehta, Sunali; Shelling, Andrew; Muthukaruppan, Anita; Lasham, Annette; Blenkiron, Cherie; Laking, George; Print, Cristin

    2010-03-01

    Over the last 10 years there has been an explosion of information about the molecular biology of cancer. A challenge in oncology is to translate this information into advances in patient care. While there are well-formed routes for translating new molecular information into drug therapy, the routes for translating new information into sensitive and specific diagnostic, prognostic and predictive tests are still being developed. Similarly, the science of using tumor molecular profiles to select clinical trial participants or to optimize therapy for individual patients is still in its infancy. This review will summarize the current technologies for predicting treatment response and prognosis in cancer medicine, and outline what the future may hold. It will also highlight the potential importance of methods that can integrate molecular, histopathological and clinical information into a synergistic understanding of tumor progression. While these possibilities are without doubt exciting, significant challenges remain if we are to implement them with a strong evidence base in a widely available and cost-effective manner.

  14. Diagnostic and prognostic value of IDH1 mutation in gliomas

    Directory of Open Access Journals (Sweden)

    YANG Yan-wu

    2012-12-01

    Full Text Available Objective To discuss the significance of IDH1 mutation for diagnosis and prognosis of gliomas through detecting of IDH1 mutation in supratentorial glioma cells. Methods IDH1 genes of postoperative pathological samples obtained from 315 patients with supratentorial gliomas (3 cases of WHO Ⅰ, 95 cases of WHO Ⅱ, 37 cases of WHO Ⅲ and 180 cases of WHO Ⅳ were collected for DNA extraction, on which PCR amplification and direct sequencing were done. At the same time, multiple-factor analysis was used on those patients' age, sex, tumor location, excision extension, Karnofsky Performance Status (KPS and progression-free survival time or median survival time, to investigate the influence of IDH1 mutation on the prognosis of patients. Results A total of 112 gene mutations among 315 cases (35.56% were found and they were all R132H type of mutations. Mutation rates in WHOⅡ, Ⅲ and Ⅳ gliomas were 72.63% (69/95, 24.32% (9/37 and 18.89% (34/180 respectively, which were significantly different (P = 0.000, for all. Among patients with IDH1 mutations in WHOⅣ gliomas, there were 18 cases of primary glioblastoma and 16 cases of secondary glioblastoma, the mutation rates of which were 11.39% (18/158 and 72.73% (16/22, respectively. The latter was much higher than the former and the difference was statistically significant ( χ 2 = 23.654,P = 0.001. Survival analysis revealed that IDH1 mutation presented notable effect on the prognosis of patients with gliomas. Conclusion IDH1 mutation can happen in WHO Ⅱ, Ⅲ and Ⅳ gliomas, and the mutation rates of WHOⅡ gliomas and secondary glioblastomas of WHO Ⅳ are higher than others. The survival time of patients are remarkably influenced by IDH1 mutation, and the prognosis of patient with IDH1 mutation is good, which may suggest that IDH1 mutation is an important diagnostic and prognostic biomarker in different grades of gliomas.

  15. Malnutrition in lung cancer: incidence, prognostic implications, and pathogenesis.

    Science.gov (United States)

    Kisner, D L

    1982-01-01

    Malnutrition and weight loss are common in patients with lung cancer. Weight loss is an independent prognostic factor for survival in lung cancer treatment studies. Metabolic disturbances probably play a dominant role in weight loss in these patients rather than reduced food intake. The identification of the pertinent etiologic metabolic abnormalities and development of specific therapeutic intervention should be goals for future research.

  16. Exosomes in Cancer Diagnostics

    Directory of Open Access Journals (Sweden)

    Young Hwa Soung

    2017-01-01

    Full Text Available Exosomes are endosome derived extracellular vesicles of 30–120 nm size ranges. Exosomes have been identified as mediators of cell-to-cell communication by transferring bioactive molecules such as nucleic acids, proteins and lipids into recipient cells. While exosomes are secreted by multiple cell types, cancer derived exosomes not only influence the invasive potentials of proximally located cells, but also affect distantly located tissues. Based on their ability to alter tumor microenvironment by regulating immunity, angiogenesis and metastasis, there has been growing interest in defining the clinical relevance of exosomes in cancers. In particular, exosomes are valuable sources for biomarkers due to selective cargo loading and resemblance to their parental cells. In this review, we summarize the recent findings to utilize exosomes as cancer biomarkers for early detection, diagnosis and therapy selection.

  17. Clinical and prognostic significance of plasma fibrinogen in lung cancer

    OpenAIRE

    Chen YS; Zeng DH; Li HR; Wu YL; Lin X.; Xu NL; Lin M

    2014-01-01

    Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV). However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA) still remains unclear. ...

  18. Molecular Markers with Predictive and Prognostic Relevance in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Alphy Rose-James

    2012-01-01

    Full Text Available Lung cancer accounts for the majority of cancer-related deaths worldwide of which non-small-cell lung carcinoma alone takes a toll of around 85%. Platinum-based therapy is the stronghold for lung cancer at present. The discovery of various molecular alterations that underlie lung cancer has contributed to the development of specifically targeted therapies employing specific mutation inhibitors. Targeted chemotherapy based on molecular profiling has shown great promise in lung cancer treatment. Various molecular markers with predictive and prognostic significance in lung cancer have evolved as a result of advanced research. Testing of EGFR and Kras mutations is now a common practice among community oncologists, and more recently, ALK rearrangements have been added to this group. This paper discusses various predictive and prognostic markers that are being investigated and have shown significant relevance which can be exploited for targeted treatment in lung cancer.

  19. Prognostic impact of prechemotherapy serum levels of HER2, CA125, and HE4 in ovarian cancer patients

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Brandslund, Ivan;

    2011-01-01

    Human epididymis protein 4 (HE4) has attracted a lot of interest as a relatively novel biomarker for ovarian carcinoma. Research focus has been directed at HE4 as a diagnostic tool with potential for better triage of women with adnexal masses but the prognostic aspect of HE4 in ovarian cancer...... patients remains to be elucidated. The aim of the present study was to investigate the prognostic value of prechemotherapy serum HER2, cancer antigen 125 (CA125), and HE4 levels in ovarian cancer patients receiving standard combination chemotherapy....

  20. Novel diagnostic biomarkers for prostate cancer

    Directory of Open Access Journals (Sweden)

    Chikezie O. Madu, Yi Lu

    2010-01-01

    prostate cancer. The purpose of this review is to examine the current status of prostate cancer biomarkers, with special emphasis on emerging markers, by evaluating their diagnostic and prognostic potentials. Both genes and proteins that reveal loss, mutation, or variation in expression between normal prostate and cancerous prostate tissues will be covered in this article. Along with the discovery of prostate cancer biomarkers, we will describe the criteria used when selecting potential biomarkers for further development towards clinical use. In addition, we will address how to appraise and validate candidate markers for prostate cancer and some relevant issues involved in these processes. We will also discuss the new concept of the biomarkers, existing challenges, and perspectives of biomarker development.

  1. Novel diagnostic biomarkers for prostate cancer.

    Science.gov (United States)

    Madu, Chikezie O; Lu, Yi

    2010-10-06

    purpose of this review is to examine the current status of prostate cancer biomarkers, with special emphasis on emerging markers, by evaluating their diagnostic and prognostic potentials. Both genes and proteins that reveal loss, mutation, or variation in expression between normal prostate and cancerous prostate tissues will be covered in this article. Along with the discovery of prostate cancer biomarkers, we will describe the criteria used when selecting potential biomarkers for further development towards clinical use. In addition, we will address how to appraise and validate candidate markers for prostate cancer and some relevant issues involved in these processes. We will also discuss the new concept of the biomarkers, existing challenges, and perspectives of biomarker development.

  2. Autophagy-related prognostic signature for breast cancer.

    Science.gov (United States)

    Gu, Yunyan; Li, Pengfei; Peng, Fuduan; Zhang, Mengmeng; Zhang, Yuanyuan; Liang, Haihai; Zhao, Wenyuan; Qi, Lishuang; Wang, Hongwei; Wang, Chenguang; Guo, Zheng

    2016-03-01

    Autophagy is a process that degrades intracellular constituents, such as long-lived or damaged proteins and organelles, to buffer metabolic stress under starvation conditions. Deregulation of autophagy is involved in the progression of cancer. However, the predictive value of autophagy for breast cancer prognosis remains unclear. First, based on gene expression profiling, we found that autophagy genes were implicated in breast cancer. Then, using the Cox proportional hazard regression model, we detected autophagy prognostic signature for breast cancer in a training dataset. We identified a set of eight autophagy genes (BCL2, BIRC5, EIF4EBP1, ERO1L, FOS, GAPDH, ITPR1 and VEGFA) that were significantly associated with overall survival in breast cancer. The eight autophagy genes were assigned as a autophagy-related prognostic signature for breast cancer. Based on the autophagy-related signature, the training dataset GSE21653 could be classified into high-risk and low-risk subgroups with significantly different survival times (HR = 2.72, 95% CI = (1.91, 3.87); P = 1.37 × 10(-5)). Inactivation of autophagy was associated with shortened survival of breast cancer patients. The prognostic value of the autophagy-related signature was confirmed in the testing dataset GSE3494 (HR = 2.12, 95% CI = (1.48, 3.03); P = 1.65 × 10(-3)) and GSE7390 (HR = 1.76, 95% CI = (1.22, 2.54); P = 9.95 × 10(-4)). Further analysis revealed that the prognostic value of the autophagy signature was independent of known clinical prognostic factors, including age, tumor size, grade, estrogen receptor status, progesterone receptor status, ERBB2 status, lymph node status and TP53 mutation status. Finally, we demonstrated that the autophagy signature could also predict distant metastasis-free survival for breast cancer.

  3. Diagnostic Ultrasound in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael

    2014-01-01

    SUMMARYBackground and purpose Colorectal cancer is a common disease in Denmark with considerable morbidity and mortality. Although survival in recent years has improved, Denmark still has the lowest 5-year survival compared to the other Nordic countries. The treatment of patients depends on local...... the potential to contribute to the staging of colorectal cancer. The purpose of these studies was to determine the usefulness of ultrasound diagnostics in patients with colorectal cancer.The purpose of the TRUS studies was to compare staging of rectal carcinomas using digital rectal exploration...... with the resulting pathological examination in relation to differentiating benign from malignant polyps and determining tumour stage and lymph node status. In this context we also performed an observer comparison using both TRUS and MRI. Consistency of tumour outgrowth of rectal cancer rated by TRUS and MRI...

  4. Multigene prognostic tests in breast cancer: past, present, future.

    Science.gov (United States)

    Győrffy, Balázs; Hatzis, Christos; Sanft, Tara; Hofstatter, Erin; Aktas, Bilge; Pusztai, Lajos

    2015-01-27

    There is growing consensus that multigene prognostic tests provide useful complementary information to tumor size and grade in estrogen receptor (ER)-positive breast cancers. The tests primarily rely on quantification of ER and proliferation-related genes and combine these into multivariate prediction models. Since ER-negative cancers tend to have higher proliferation rates, the prognostic value of current multigene tests in these cancers is limited. First-generation prognostic signatures (Oncotype DX, MammaPrint, Genomic Grade Index) are substantially more accurate to predict recurrence within the first 5 years than in later years. This has become a limitation with the availability of effective extended adjuvant endocrine therapies. Newer tests (Prosigna, EndoPredict, Breast Cancer Index) appear to possess better prognostic value for late recurrences while also remaining predictive of early relapse. Some clinical prediction problems are more difficult to solve than others: there are no clinically useful prognostic signatures for ER-negative cancers, and drug-specific treatment response predictors also remain elusive. Emerging areas of research involve the development of immune gene signatures that carry modest but significant prognostic value independent of proliferation and ER status and represent candidate predictive markers for immune-targeted therapies. Overall metrics of tumor heterogeneity and genome integrity (for example, homologue recombination deficiency score) are emerging as potential new predictive markers for platinum agents. The recent expansion of high-throughput technology platforms including low-cost sequencing of circulating and tumor-derived DNA and RNA and rapid reliable quantification of microRNA offers new opportunities to build extended prediction models across multiplatform data.

  5. Prognostic values of Notch receptors in breast cancer.

    Science.gov (United States)

    Xu, Junming; Song, Fangbin; Jin, Tao; Qin, Jun; Wu, Junyi; Wang, Min; Wang, Ye; Liu, Jun

    2016-02-01

    Notch receptors are frequently deregulated in several human malignancies including human breast cancer. Activation of Notch has been reported to cause mammary carcinomas in mice. However, the prognostic value of individual Notch receptors in breast cancer (BC) patients remains elusive. In the current study, we investigated the prognostic value of Notch receptors in human BC patients. More specifically, we investigated the prognostic value of four Notch receptors in breast cancer patients through "the Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information are from a total of 3554 breast cancer patients. Our results showed that Notch1 messenger RNA (mRNA) high expression was correlated to worsen overall survival (OS) in PgR-negative BC patients. Notch2, Notch3, and Notch4 mRNA high expressions were found to be correlated to better OS for all breast cancer patients. Notch2 was also found to be correlated to better OS in lymph node-negative breast cancer patients and HER2-positive breast cancer patients. These results will be useful for better understanding of the heterogeneity and complexity in the molecular biology of breast cancer and for developing tools to more accurately predict their prognosis and design their customized treatment strategies.

  6. Physical Modeling for Anomaly Diagnostics and Prognostics Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Ridgetop developed an innovative, model-driven anomaly diagnostic and fault characterization system for electromechanical actuator (EMA) systems to mitigate...

  7. The diagnostic and prognostic value of conventional and rapid diagnostic tools in malaria

    Directory of Open Access Journals (Sweden)

    Chandrakanth C.H

    2016-10-01

    Full Text Available Background: The burden of malaria is raising all over the world and India is no exception. Despite well established treatment regimens and diagnostic tools, Malaria is thought to kill between1.1 to 2.7 million people worldwide each year. Rapid diagnosis and early treatment are one of the key factors in controlling the disease burden of malaria. Objective: The study was conducted to investigate the diagnostic and prognostic utility of rapid test (QBC, PLDH, HRP2 with conventional thick and thin films Methods: The present study included clinically suspected cases of malaria referred to Microbiology laboratory at Kempegowda Institute of Medical Sciences, Bangalore during the period from April 2004 to April 2005. Blood samples were collected and were subjected to conventional peripheral smear tests as well as rapid tests by using quantitative buffy coat and Paramax-3 kits. Results: Peripheral smear was 60.78% sensitive to Paramax -3 kit with 59.21% sensitivity for P falciparum and 65.38% for P vivax. Peripheral smear showed more number of false negatives as compared to Paramax-3 kit. QBC is 67.64% (69/102 sensitive to Paramax -3 kit with 60.81% sensitivity for P falciparum and 92.31% for P vivax. Although specificity and sensitivity of QBC higher than peripheral smear, it was not on par with Paramax-3 kit. Conclusion: The QBC method is highly sensitive and specific and provides a reliable, rapid and accurate method for diagnosis of malaria. However, Paramax-3 test was the most sensitive for P falciparum and P vivax.

  8. Prognostic and predictive biomarkers in colorectal cancer. Towards precision medicine

    NARCIS (Netherlands)

    Reimers, Marlies Suzanne

    2015-01-01

    The aim of this thesis was to define prognostic and predictive biomarkers in colorectal cancer for improved risk stratification and treatment benefit in the individual patient, with the introduction of precision medicine in the near future as the ultimate goal. By definition, precision medicine is

  9. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer

    NARCIS (Netherlands)

    Voorwinden, Jan S; Jaspers, Jan P C

    2015-01-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors tha

  10. Breast thermography. A prognostic indicator for breast cancer survival.

    Science.gov (United States)

    Isard, H J; Sweitzer, C J; Edelstein, G R

    1988-08-01

    A prognostic classification for thermographic staging of breast cancer has been applied to a cohort of 70 patients from 5040 screenees enrolled in the Albert Einstein Medical Center (AEMC) Breast Cancer Detection Demonstration Project (BCDDP). A diagnosis of breast cancer was established in each case before December 31, 1980. None of the patients have been lost to follow-up which extended from a minimum of 6 to a maximum of 13 years. Survival rates for those with favorable, equivocal, and poor thermographic factors are compared with each other and with results in accordance with tumor-node-metastasis (TNM) classification. As of December 31, 1986, there have been 22 (31.4%) deaths, all attributed to breast cancer. The thermographic scoring system clearly shows shorter survival for patients with poor thermographic prognostic factors, 30% surviving at 5 years and only 20% at 10 years compared with overall survival of 80% at 5 years and 70% at 10 years.

  11. Prognostic values of aldehyde dehydrogenase 1 isoenzymes in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Ma YM

    2016-04-01

    Full Text Available Yu-mei Ma,1 Shan Zhao2 1Department of Pathology, 2Department of Cancer Second Division, The Second Hospital of Hebei Medical University, Shijiazhuang City, People’s Republic of China Abstract: Aldehyde dehydrogenase 1 (ALDH1 activity has been used as a functional stem cell marker to isolate cancer stem cells in different cancer types, including ovarian cancer. However, which ALDH1’s isoenzymes are contributing to ALDH1 activity in ovarian cancer remains elusive. In addition, the prognostic value of an individual ALDH1 isoenzyme in ovarian cancer is not clear. Thus, we accessed the prognostic value of ALDH1 isoenzymes in ovarian cancer patients through the “Kaplan–Meier plotter” online database, which can be used to determine the effect of the genes on ovarian cancer prognosis. We found that high mRNA expression of five ALDH1 isoenzymes, such as ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, and ALDH1L1, was not correlated with overall survival (OS for all 1,306 ovarian cancer patients. In addition, all five of the ALDH1 isoenzymes’ high mRNA expression was found to be uncorrelated with OS in serous cancer or endometrioid cancer patients. However, ALDH1A3’s high mRNA expression is associated with worse OS in grade II ovarian cancer patients, hazard ratio (HR 1.53 (1.14–2.07, P=0.005. ALDH1A2’s high mRNA expression is significantly associated with worse OS in TP53 wild-type ovarian cancer patients, HR 2.86 (1.56–5.08, P=0.00036. In addition, ALDH1A3’s high mRNA expression is significantly associated with better OS in TP53 wild-type ovarian cancer patients, HR 0.56 (0.32–1.00, P=0.04. Our results indicate that although ALDH1 isoenzyme mRNA might not be a prognostic marker for overall ovarian cancer patients, some isoenzymes, such as ALDH1A2 and ALDH1A3, might be a good prognostic marker for some types of ovarian cancer patients. Keywords: ALDH1, cancer stem cell, prognosis, KM plotter, hazard ratio

  12. The Prognostic Value of UHRF-1 and p53 in Gastric Cancer

    Science.gov (United States)

    Babacan, Nalan A.; Eğilmez, Hatice Reyhan; Yücel, Birsen; Parlak, Ilknur; Şeker, Mehmet Metin; Kaçan, Turgut; Bahçeci, Aykut; Cihan, Sener; Akinci, Bülent; Eriten, Berna; Kılıçkap, Saadettin

    2016-01-01

    Background/Aims: This study aimed to examine whether UHRF-1 and p53 overexpression is a prognostic marker for gastric cancer. Patients and Methods: Sixty-four patients with gastric cancer (study group) and 23 patients with gastritis (control group) were evaluated. Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis. Results: The median age was 63 years (18-83 years) in the study group. UHRF-1 was positive in 15 (23%) patients with gastric cancer and five (21.7%) patients with gastritis (P = 0.559). UHRF1 expression level in gastric cancer is more powerful than in gastritis (P = 0.046). Thirty-seven (61%) patients with gastric cancer and only one patient with gastritis were p53 positive (P < 0.001). After a median follow-up of 12 months (1–110), the 2-year overall survival rates were 55% and 30% in negative and positive p53, respectively (P = 0.084). Also, the 2-year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (P = 0.132). Conclusion: According to this study, UHRF-1and p53 were not prognostic factors for gastric cancer, whereas they may have a diagnostic value for differantiating between gastric cancer and gastritis. PMID:26831603

  13. The prognostic value of UHRF-1 and p53 in gastric cancer

    Directory of Open Access Journals (Sweden)

    Nalan A Babacan

    2016-01-01

    Full Text Available Background/Aims: This study aimed to examine whether UHRF-1 and p53 overexpression is a prognostic marker for gastric cancer. Patients and Methods: Sixty-four patients with gastric cancer (study group and 23 patients with gastritis (control group were evaluated. Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis. Results: The median age was 63 years (18-83 years in the study group. UHRF-1 was positive in 15 (23% patients with gastric cancer and fi ve (21.7% patients with gastritis (P = 0.559. UHRF1 expression level in gastric cancer is more powerful than in gastritis (P = 0.046. Thirty-seven (61% patients with gastric cancer and only one patient with gastritis were p53 positive (P < 0.001. After a median follow-up of 12 months (1-110, the 2-year overall survival rates were 55% and 30% in negative and positive p53, respectively (P = 0.084. Also, the 2-year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (P = 0.132. Conclusion: According to this study, UHRF-1and p53 were not prognostic factors for gastric cancer, whereas they may have a diagnostic value for differantiating between gastric cancer and gastritis.

  14. Identification of Prostate Cancer Prognostic Markers

    Science.gov (United States)

    2014-10-01

    Assessment post- Surgical ( CAPRA -S) nomogram (pɘ.05 respectively). Importantly, the 16p13.3 gain status was found to significantly predict early...operative PSA levels, GS, T-Stage and CAPRA -S risk scores respectively, improved the overall prognostication in these patients (log rank, Pɘ.001...Risk Assessment post-Surgical ( CAPRA -S) nomogram (pɘ.05 respectively). Importantly, the 16p13.3 gain status was found to significantly predict

  15. Prognostic features and markers for testicular cancer management

    Directory of Open Access Journals (Sweden)

    Eddy S Leman

    2010-01-01

    Full Text Available Testicular neoplasm accounts for about 1% of all cancers in men. Over the last 40 years, the incidence of testicular cancer has increased in northern European male populations for unknown reasons. When diagnosed at early stage, testicular cancer is usually curable with a high survival rate. In the past three decades, successful multidisciplinary approaches for the management of testicular cancer have significantly increased patient survival rates. Utilization of tumor markers and accurate prognostic classification has also contributed to successful therapy. In this article, we highlight the most commonly used tumor markers and several potential "novel" markers for testicular cancer as part of the ongoing effort in biomarker research and discovery. In addition, this article also identifies several key prognostic features that have been demonstrated to play a role in predicting relapse. These features include tumor size, rete testis invasion, lymphovascular invasion, and tumor histology. Together with tumor markers, these prognostic factors should be taken into account for risk-adapted management of testicular cancer.

  16. Diagnostic and prognostic implications of exercise testing in coronary artery disease

    NARCIS (Netherlands)

    J.W. Deckers (Jaap)

    1988-01-01

    textabstractThe clinical indications for exercise testing as a diagnostic and prognostic tool in the assessment of patients with ischemic heart disease have gradually evolved since Master introduced the two-step exercise test in 1929 (1). New information from correlations between electrocardiographi

  17. Prognostic and Predictive Roles of KRAS Mutation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Amanda K. Arrington

    2012-09-01

    Full Text Available The RAS gene family is among the most studied and best characterized of the known cancer-related genes. Of the three human ras isoforms, KRAS is the most frequently altered gene, with mutations occurring in 17%–25% of all cancers. In particular, approximately 30%–40% of colon cancers harbor a KRAS mutation. KRAS mutations in colon cancers have been associated with poorer survival and increased tumor aggressiveness. Additionally, KRAS mutations in colorectal cancer lead to resistance to select treatment strategies. In this review we examine the history of KRAS, its prognostic value in patients with colorectal cancer, and evidence supporting its predictive value in determining appropriate therapies for patients with colorectal cancer.

  18. miR-421 is a diagnostic and prognostic marker in patients with osteosarcoma.

    Science.gov (United States)

    Zhou, Shuguang; Wang, Bing; Hu, Jun; Zhou, Yucheng; Jiang, Mengzhen; Wu, Mingyu; Qin, Liming; Yang, Xuming

    2016-07-01

    MicroRNAs (miRNAs) are a new class of prognostic and diagnostic biomarkers for many cancers. Recent studies have shown that miRNAs are highly stable in plasma/serum. The aim of this study was to investigate the role of miR-421 in osteosarcoma. We found that the serum expression levels of miR-421 were significantly higher in osteosarcoma patients than those in healthy volunteers. Moreover, miR-421 expression was significantly higher in osteosarcoma tissues compared with that in the adjacent normal tissues. Meanwhile, the expression of miR-421 was upregulated in 90 % (36/40) osteosarcoma tissues compared to non-tumor tissues. More importantly, the expression levels of miR-421 in osteosarcoma tissues were correlated with those in patients' serum. In addition, patients with high miR-421 expression had shorter overall survival (OS) than those with low expressions. We also found that overexpression of miR-421 promoted osteosarcoma cell line MG-63 proliferation, migration, and invasion. In conclusion, miR-421 expression levels were upregulated in osteosarcoma tissue and serum and it may be a useful marker for diagnosis of osteosarcoma.

  19. [Molecular diagnostics of lung cancer].

    Science.gov (United States)

    Ryska, A; Dziadziuszko, R; Olszewski, W; Berzinec, P; Öz, B; Gottfried, M; Cufer, T; Samarzija, M; Plank, L; Ostoros, Gy; Tímár, J

    2015-09-01

    Development of the target therapies of lung cancer was a rapid process which fundamentally changed the pathological diagnosis as well. Furthermore, molecular pathology became essential part of the routine diagnostics of lung cancer. These changes generated several practical problems and in underdeveloped countries or in those with reimbursement problems have been combined with further challenges. The central and eastern region of Europe are characterized by similar problems in this respect which promoted the foundation of NSCLC Working Group to provide up to date protocols or guidelines. This present paper is a summary of the molecular pathology and target therapy guidelines written with the notion that it has to be upgraded continuously according to the development of the field.

  20. Evaluation of Prognostic Factors Following Flow-Cytometric DNA Analysis after Cytokeratin Labelling: II. Cervical and Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Pauline Wimberger

    2002-01-01

    Full Text Available In gynecologic oncology valid prognostic factors are necessary to define biologically similar subgroups for analysis of therapeutic efficacy. This study is the first published prospective study concerning prognostic significance of DNA ploidy and S‐phase fraction in cervical and endometrial cancer following enrichment of tumor cells by cytokeratin labelling. Epithelial cells were labeled by FITC‐conjugated cytokeratin antibody (CK 5, 6, 8, and CK 17 prior to flow cytometric cell cycle analysis in 91 specimens of cervical cancer and 73 samples of endometrial cancer. In cervical cancer neither DNA‐ploidy nor S‐phase fraction were relevant prognostic parameters. But CV of the G0G1‐peak showed prognostic relevance in cervical cancer cells, even in multivariate analysis. This interesting observation, however, seems to have no therapeutic consequence due to the small discrimination capacity of CV. In endometrial carcinoma, gross DNA‐aneuploidy (DNA‐index > 1.3 and a high percentage of proliferating cells (>75th percentile were univariate and multivariate highly significant prognostic factors for recurrence‐free survival. Especially DNA‐aneuploidy (DI>1.3 is one of the most important independent molecular biological prognostic factors. While diagnostic curettage we could identify risk patients even preoperatively by determination of the prognostic factors like histologic tumor type, grading, cervical involvement and DNA‐ploidy. Thereby these patients could be treated primarily in an oncologic center. In conclusion, our investigations showed that the determination of DNA‐ploidy should be done in endometrial carcinoma. In cervical cancer no clinical significance for determination of DNA‐parameters was found.

  1. Histopathological prognostic factor comparison of endometrial cancer patients in a tertiary hospital in India

    Directory of Open Access Journals (Sweden)

    P. Swarna Latha

    2014-02-01

    Conclusions: This study highlights the prognostic characteristics of endometrial cancer patients with most of them presenting in early stages thereby having a good prognostic outcome. [Int J Reprod Contracept Obstet Gynecol 2014; 3(1.000: 102-104

  2. Prognostic Factors for Distress After Genetic Testing for Hereditary Cancer.

    Science.gov (United States)

    Voorwinden, Jan S; Jaspers, Jan P C

    2016-06-01

    The psychological impact of an unfavorable genetic test result for counselees at risk for hereditary cancer seems to be limited: only 10-20 % of counselees have psychological problems after testing positive for a known familial mutation. The objective of this study was to find prognostic factors that can predict which counselees are most likely to develop psychological problems after presymptomatic genetic testing. Counselees with a 50 % risk of BRCA1/2 or Lynch syndrome completed questionnaires at three time-points: after receiving a written invitation for a genetic counseling intake (T1), 2-3 days after receiving their DNA test result (T2), and 4-6 weeks later (T3). The psychological impact of the genetic test result was examined shortly and 4-6 weeks after learning their test result. Subsequently, the influence of various potentially prognostic factors on psychological impact were examined in the whole group. Data from 165 counselees were analyzed. Counselees with an unfavorable outcome did not have more emotional distress, but showed significantly more cancer worries 4-6 weeks after learning their test result. Prognostic factors for cancer worries after genetic testing were pre-existing cancer worries, being single, a high risk perception of getting cancer, and an unfavorable test result. Emotional distress was best predicted by pre-existing cancer worries and pre-existing emotional distress. The psychological impact of an unfavorable genetic test result appears considerable if it is measured as "worries about cancer." Genetic counselors should provide additional guidance to counselees with many cancer worries, emotional distress, a high risk perception or a weak social network.

  3. Impaired SNX9 Expression in Immune Cells during Chronic Inflammation: Prognostic and Diagnostic Implications.

    Science.gov (United States)

    Ish-Shalom, Eliran; Meirow, Yaron; Sade-Feldman, Moshe; Kanterman, Julia; Wang, Lynn; Mizrahi, Olga; Klieger, Yair; Baniyash, Michal

    2016-01-01

    Chronic inflammation is associated with immunosuppression and downregulated expression of the TCR CD247. In searching for new biomarkers that could validate the impaired host immune status under chronic inflammatory conditions, we discovered that sorting nexin 9 (SNX9), a protein that participates in early stages of clathrin-mediated endocytosis, is downregulated as well under such conditions. SNX9 expression was affected earlier than CD247 by the generated harmful environment, suggesting that it is a potential marker sensing the generated immunosuppressive condition. We found that myeloid-derived suppressor cells, which are elevated in the course of chronic inflammation, are responsible for the observed SNX9 reduced expression. Moreover, SNX9 downregulation is reversible, as its expression levels return to normal and immune functions are restored when the inflammatory response and/or myeloid-derived suppressor cells are neutralized. SNX9 downregulation was detected in numerous mouse models for pathologies characterized by chronic inflammation such as chronic infection (Leishmania donovani), cancer (melanoma and colorectal carcinoma), and an autoimmune disease (rheumatoid arthritis). Interestingly, reduced levels of SNX9 were also observed in blood samples from colorectal cancer patients, emphasizing the feasibility of its use as a diagnostic and prognostic biomarker sensing the host's immune status and inflammatory stage. Our new discovery of SNX9 as being regulated by chronic inflammation and its association with immunosuppression, in addition to the CD247 regulation under such conditions, show the global impact of chronic inflammation and the generated immune environment on different cellular pathways in a diverse spectrum of diseases.

  4. Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics has received considerable attention recently as an emerging sub-discipline within SHM. Prognosis is here strictly defined as “predicting the time at...

  5. Expert system applications in support of system diagnostics and prognostics at EBR-II

    Energy Technology Data Exchange (ETDEWEB)

    Lehto, W.K.; Gross, K.C. (Argonne National Lab., Idaho Falls, ID (USA); Argonne National Lab., IL (USA))

    1989-01-01

    Expert systems have been developed to aid in the monitoring and diagnostics of the Experimental Breeder Reactor-II (EBR-II) at the Idaho National Engineering Laboratory (INEL) in Idaho Falls, Idaho. Systems have been developed for failed fuel surveillance and diagnostics and reactor coolant pump monitoring and diagnostics. A third project is being done jointly by ANL-W and EG G Idaho to develop a transient analysis system to enhance overall plant diagnostic and prognostic capability. The failed fuel surveillance and diagnosis system monitors, processes, and interprets information from nine key plant sensors. It displays to the reactor operator diagnostic information needed to make proper decisions regarding technical specification conformance during reactor operation with failed fuel. 8 refs., 9 figs., 2 tabs.

  6. Diagnostic and Prognostic Role of Procalcitonin in Infections

    Directory of Open Access Journals (Sweden)

    Maria Hatzistilianou

    2010-01-01

    Full Text Available Despite several consensus conferences, the criteria for the definition of sepsis are still considered too sensitive and insufficiently specific. The traditional clinical signs of infection and routine laboratory tests used to diagnose bacterial infection and sepsis lack diagnostic accuracy and can be misleading, particularly in patients with immunodeficiencies. The problems with sepsis definitions and diagnoses are indications of the need to focus on biochemical mediators capable not only of distinguishing the inflammatory response to infection from other types of inflammation, but also of indicating the severity and prognosis of the disease. Thus, physicians need an early and rapid marker for detecting bacterial infection and distinguishing it from viral infection. Several studies revealed that elevated procalcitonin (PCT levels in human blood could be detected in cases of sepsis and bacterial infection. PCT is a protein that can act as a hormone and a cytokine. It can be produced by several cell types and many organs in response to proinflammatory stimuli, particularly bacterial infection. It provides a rapid diagnostic test, available at the patient's bedside, and its half-life is suitable for daily monitoring of the disease progress.

  7. Multifocality as a prognostic factor in breast cancer patients registered in Danish Breast Cancer Cooperative Group (DBCG) 1996-2001

    DEFF Research Database (Denmark)

    Joergensen, L.E.; Gunnarsdottir, K.A.; Lanng, C.;

    2008-01-01

    The purpose of this study was to investigate the prognostic influence of multifocality in breast cancer patients. In a cohort of 7196 patients there were 945 patients with multifocality. We found no prognostic influence of multifocality on overall survival when controlling for known prognostic......, Gunnarsdottir KA, Rasmussen BB, Moeller S, Lanng C. The prognostic influence of multifocality in breast cancer patients. Breast 2004;13:188-193]....

  8. Predictive and Prognostic Factors in Colorectal Cancer: A Personalized Approach

    Directory of Open Access Journals (Sweden)

    Timothy A. Rockall

    2011-03-01

    Full Text Available It is an exciting time for all those engaged in the treatment of colorectal cancer. The advent of new therapies presents the opportunity for a personalized approach to the patient. This approach considers the complex genetic mechanisms involved in tumorigenesis in addition to classical clinicopathological staging. The potential predictive and prognostic biomarkers which have stemmed from the study of the genetic basis of colorectal cancer and therapeutics are discussed with a focus on mismatch repair status, KRAS, BRAF, 18qLOH, CIMP and TGF-β.

  9. The Prognostic, Diagnostic, and Therapeutic Potential of Tumor Antigens

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn

    or abundance in cancer cells is often unique and their roles and functions in tumorigenesis are, in many cases, studied extensively. They, therefore, have the potential to be highly specific biomarkers as well as therapeutic targets, but complex analysis combining basic science, high-throughput methods...... and therapeutic agents, by developing and implementing several computational tools and databases for immunotherapy target discovery, and have analyzed the potential of tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas. In this analysis I have shown that the combination of proteomics...

  10. Dioxins: diagnostic and prognostic challenges arising from complex mechanisms

    DEFF Research Database (Denmark)

    Rysavy, Noel M.; Maaetoft-Udsen, Kristina; Turner, Helen

    2013-01-01

    such as cancer and diabetes, which are already multifactorial and highly complex, creates the context for the current review paper. Here, we summarize dioxin exposure paradigms and the resulting physiological effects that have been documented in animals and humans. Novel insights into potential endogenous end...... exogenous ligands, as well as the mechanisms by which these ligands impact acute and chronic cellular processes, are discussed. We develop the idea that the diagnosis of dioxin exposure, the subtleties of the cellular effects of the compounds and prognosis of the long-term effects of exposure are problems...

  11. Clinical and prognostic significance of plasma fibrinogen in lung cancer

    Directory of Open Access Journals (Sweden)

    Chen YS

    2014-01-01

    Full Text Available Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV. However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1 further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2 evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3 explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1 The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001, there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001. 2 Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen

  12. Prognostic significance of miR-205 in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Mihriban Karaayvaz

    Full Text Available PURPOSE: microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues. EXPERIMENTAL DESIGN: Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0. RESULTS: The expression levels of miR-200c (P<0.0001 and miR-205 (P<0.0001 were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028. Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues. CONCLUSION: miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

  13. Prognostic value of metastin expression in human pancreatic cancer

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    Kawaguchi Yoshiya

    2009-01-01

    Full Text Available Abstract Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissues obtained from 53 consecutive patients who underwent resection between July 2003 and May 2007 at Kyoto University Hospital. In 23 consecutive patients, the plasma metastin level was measured before surgery by enzyme immunoassay. Results Strong immunohistochemical expression of metastin was detected in 13 tumors (24.5%, while strong expression of GPR54 was detected in 30 tumors (56.6%. Tumors that were negative for both metastin and GPR54 expression were significantly larger than tumors that were positive for either metastin or GPR54 (p = 0.047. Recurrence was less frequent in patients who had metastin-positive tumors compared with those who had metastin-negative tumors (38.5% versus 70.0%, p = 0.04. Strong expression of metastin and GPR54 was significantly correlated with longer survival (p = 0.02. Metastin expression by pancreatic cancer was an independent prognostic factor for longer survival (hazard ratio, 2.1; 95% confidence interval, 1.1–4.7; p = 0.03, and the patients with a high plasma metastin level (n = 6 did not die after surgical resection. Conclusion Strong expression of metastin and GPR54 by pancreatic cancer is associated with longer survival. Metastin expression is an independent prognostic factor for the survival of pancreatic cancer patients. The plasma metastin level could become a noninvasive prognostic factor for the assessment of pancreatic cancer.

  14. The prognostic relevance of estimates of proliferative activity in early breast cancer

    DEFF Research Database (Denmark)

    Offersen, B V; Sørensen, Flemming Brandt; Knoop, A;

    2003-01-01

    clinicopathological parameters at diagnosis in early breast cancer patients. MATERIALS AND METHODS: Tumour specimens from 365 consecutively treated breast cancer patients were immunostained for MIB-1 and evaluated under the microscope using systematic random sampling accomplished by the CAST-grid system. RESULTS...... and number of mitoses included in the analysis, MIB-1 estimates showed no independent prognostic impact. CONCLUSIONS: High MIB-1 estimates did not add independent prognostic information at diagnosis when evaluated together with classical prognostic markers of early breast cancer....

  15. Prognostic value of serum tetranectin in patients with metastatic breast cancer

    DEFF Research Database (Denmark)

    Høgdall, C K; Sölétormos, G; Nielsen, D;

    1993-01-01

    To evaluate serum tetranectin as a prognostic marker before first-line chemotherapy, serum levels were studied in 67 patients with metastatic breast cancer. In the Cox analyses, the relative risk (RR) for death of cancer varied with the cut-off level of serum tetranectin. A maximal RR of 5...... prognostic factor in metastatic breast cancer....

  16. Clinical and prognostic significance of coagulation assays in lung cancer.

    Science.gov (United States)

    Tas, Faruk; Kilic, Leyla; Serilmez, Murat; Keskin, Serkan; Sen, Fatma; Duranyildiz, Derya

    2013-03-01

    Activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are supposed to be associated with higher risk of invasion, metastases and eventually worse outcome. The aim of this study is to explore the prognostic value of blood coagulation tests for lung cancer patients. The study comprised 110 lung cancer patients. Pretreatment blood coagulation tests including PT, aPTT, PTA, INR, D-dimer, fibrinogen levels and platelet counts were evaluated. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group (p coagulation parameters (p = 0.05). In conclusion, elevation of PT and INR are associated with decreased survival in lung cancer patients.

  17. Prognostic factors in 165 elderly colorectal cancer patients

    Institute of Scientific and Technical Information of China (English)

    Ke-Jun Nan; Hai-Xia Qin; Guang Yang

    2003-01-01

    AIM: To analyse the prognostic factors in 165 colorectal patients aged ≥70.METHODS: One hundred and sixty-five elderly patients with colorectal cancer diagnosed by histology were entered into the retrospective study between 1994 and 2001. Patients were given optimal operation alone, chemotherapy after operation, or chemotherapy alone according to tumor stage,histology, physical strength, and co-morbid problems.Survival rate was calculated by Kaplan-Meier method, and compared with meaningful variances by Log-rank method.Prognostic factors were analyzed by Cox regression.RESULTS: The 1,2,3,4,5 year survival rate (all-cause rnortality)was 87.76%, 65.96%, 52.05%, 42.77%, 40.51%,respectively. The mean survival time was 41.89±2.33 months (95% CI: 37.33-46.45 months), and the median survival time was 37 months. Univariate analysis showed that factors such as age, nodal metastasis, treatment method, Duke's stage, gross findings, kind of histology, and degree of differentiation had influences on the survival rate. Multivariate analysis showed that factors such as treatment method,Duke's stage, kind of histology and degree of differentiation were independent prognostic factors.CONCLUSION: This study suggests that the prognosis of elderly colorectal cancer patients is influenced by several factors. Most of elderly patients can endure surgery and/or chemotherapy, and have a long-time survival and good quality of life.

  18. Immunoexpression analysis and prognostic value of BLCAP in breast cancer.

    Directory of Open Access Journals (Sweden)

    Irina Gromova

    Full Text Available Bladder Cancer Associated Protein (BLCAP, formerly Bc10, was identified by our laboratory as being down-regulated in bladder cancer with progression. BLCAP is ubiquitously expressed in different tissues, and several studies have found differential expression of BLCAP in various cancer types, such as cervical and renal cancer, as well as human tongue carcinoma and osteosarcoma. Here we report the first study of the expression patterns of BLCAP in breast tissue. We analyzed by immunohistochemistry tissue sections of normal and malignant specimens collected from 123 clinical high-risk breast cancer patients within the Danish Center for Translational Breast Cancer Research (DCTB prospective study dataset. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. We observed weak immunoreactivity for BLCAP in mammary epithelial cells, almost exclusively localizing to the cytoplasm and found that levels of expression of BLCAP were generally higher in malignant cells as compared to normal cells. Quantitative IHC analysis of BLCAP expression in breast tissues confirmed this differential BLCAP expression in tumor cells, and we could establish, in a 62-patient sample matched cohort, that immunostaining intensity for BLCAP was increased in tumors relative to normal tissue, in more than 45% of the cases examined, indicating that BLCAP may be of value as a marker for breast cancer. We also analyzed BLCAP expression and prognostic value using a set of tissue microarrays comprising an independent cohort of 2,197 breast cancer patients for which we had follow-up clinical information.

  19. Comparison of prognostic and diagnostic surface flux modeling approaches over the Nile River basin

    Science.gov (United States)

    Yilmaz, M. Tugrul; Anderson, Martha C.; Zaitchik, Ben; Hain, Chris R.; Crow, Wade T.; Ozdogan, Mutlu; Chun, Jong Ahn; Evans, Jason

    2014-01-01

    Regional evapotranspiration (ET) can be estimated using diagnostic remote sensing models, generally based on principles of energy balance closure, or with spatially distributed prognostic models that simultaneously balance both energy and water budgets over landscapes using predictive equations for land surface temperature and moisture states. Each modeling approach has complementary advantages and disadvantages, and in combination they can be used to obtain more accurate ET estimates over a variety of land and climate conditions, particularly for areas with limited ground truth data. In this study, energy and water flux estimates from diagnostic Atmosphere-Land Exchange (ALEXI) and prognostic Noah land surface models are compared over the Nile River basin between 2007 and 2011. A second remote sensing data set, generated with Penman-Monteith approach as implemented in the Moderate Resolution Imaging Spectroradiometer (MODIS) MOD16 ET product, is also included as a comparative technique. In general, spatial and temporal distributions of flux estimates from ALEXI and Noah are similar in regions where the climate is temperate and local rainfall is the primary source of water available for ET. However, the diagnostic ALEXI model is better able to retrieve ET signals not directly coupled with the local precipitation rates, for example, over irrigated agricultural areas or regions influenced by shallow water tables. These hydrologic features are not well represented by either Noah or MOD16. Evaluation of consistency between diagnostic and prognostic model estimates can provide useful information about relative product skill, particularly over regions where ground data are limited or nonexistent as in the Nile basin.

  20. Molecular Diagnostic Applications in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Laura Huth

    2014-06-01

    Full Text Available Colorectal cancer, a clinically diverse disease, is a leading cause of cancer-related death worldwide. Application of novel molecular diagnostic tests, which are summarized in this article, may lead to an improved survival of colorectal cancer patients.  Distinction of these applications is based on the different molecular principles found in colorectal cancer (CRC. Strategies for molecular analysis of single genes (as KRAS or TP53 as well as microarray based techniques are discussed. Moreover, in addition to the fecal occult blood testing (FOBT and colonoscopy some novel assays offer approaches for early detection of colorectal cancer like the multitarget stool DNA test or the blood-based Septin 9 DNA methylation test. Liquid biopsy analysis may also exhibit great diagnostic potential in CRC for monitoring developing resistance to treatment. These new diagnostic tools and the definition of molecular biomarkers in CRC will improve early detection and targeted therapy of colorectal cancer.

  1. A diagnostic and prognostic tool for epidemiologic and economic analyses of dairy herd health management

    DEFF Research Database (Denmark)

    Enevoldsen, Carsten; Sørensen, J.T.; Thysen, Iver;

    1995-01-01

    A computer program framework was established to enable a dairy herd production consultant to perform whole-herd analysis. The diagnostic process was an extensive data analysis 1) to derive key parameters related to production, reproduction, and health and 2) to produce input to a prognostic process....... The prognostic process synthesized the obtained information into short- or long-term prognoses for the herd through a complex herd simulation model. Site specificity of parameter estimation and forecasting and explorability of assumptions and results were major characteristics of the approach. A user acceptance...... problem related to the simulation was addressed through a simultaneous process of development and validation during the introduction of the program framework into veterinary practices. The generally slow adoption of herd simulation models in extension work could be due to lack of credibility of the models...

  2. Association of Telomere Length with Breast Cancer Prognostic Factors

    Science.gov (United States)

    Têtu, Bernard; Maunsell, Elizabeth; Poirier, Brigitte; Montoni, Alicia; Rochette, Patrick J.; Diorio, Caroline

    2016-01-01

    Introduction Telomere length, a marker of cell aging, seems to be affected by the same factors thought to be associated with breast cancer prognosis. Objective To examine associations of peripheral blood cell-measured telomere length with traditional and potential prognostic factors in breast cancer patients. Methods We conducted a cross-sectional analysis of data collected before surgery from 162 breast cancer patients recruited consecutively between 01/2011 and 05/2012, at a breast cancer reference center. Data on the main lifestyle factors (smoking, alcohol consumption, physical activity) were collected using standardized questionnaires. Anthropometric factors were measured. Tumor biological characteristics were extracted from pathology reports. Telomere length was measured using a highly reproducible quantitative PCR method in peripheral white blood cells. Spearman partial rank-order correlations and multivariate general linear models were used to evaluate relationships between telomere length and prognostic factors. Results Telomere length was positively associated with total physical activity (rs = 0.17, P = 0.033; Ptrend = 0.069), occupational physical activity (rs = 0.15, P = 0.054; Ptrend = 0.054) and transportation-related physical activity (rs = 0.19, P = 0.019; P = 0.005). Among post-menopausal women, telomere length remained positively associated with total physical activity (rs = 0.27, P = 0.016; Ptrend = 0.054) and occupational physical activity (rs = 0.26, P = 0.021; Ptrend = 0.056) and was only associated with transportation-related physical activity among pre-menopausal women (rs = 0.27, P = 0.015; P = 0.004). No association was observed between telomere length and recreational or household activities, other lifestyle factors or traditional prognostic factors. Conclusions Telomeres are longer in more active breast cancer patients. Since white blood cells are involved in anticancer immune responses, these findings suggest that even regular low

  3. Tumor volume as a prognostic factor for local control and overall survival in advanced larynx cancer

    NARCIS (Netherlands)

    Timmermans, A.J.; Lange, C.A.H.; de Bois, J.A.; van Werkhoven, E.; Hamming-Vrieze, O.; Hilgers, F.J.M.; van den Brekel, M.W.M.

    2015-01-01

    Keywords: Head and neck cancer; larynx cancer; organ preservation; total laryngectomy; imaging; tumor volume;prognosis; outcome Objectives/Hypothesis Tumor volume has been postulated to be an important prognostic factor for oncological outcome after radiotherapy or chemoradiotherapy. This postulate

  4. A Survey of Health Management User Objectives Related to Diagnostic and Prognostic Metrics

    Science.gov (United States)

    Wheeler, Kevin R.; Kurtoglu, Tolga; Poll, Scott D.

    2010-01-01

    One of the most prominent technical challenges to effective deployment of health management systems is the vast difference in user objectives with respect to engineering development. In this paper, a detailed survey on the objectives of different users of health management systems is presented. These user objectives are then mapped to the metrics typically encountered in the development and testing of two main systems health management functions: diagnosis and prognosis. Using this mapping, the gaps between user goals and the metrics associated with diagnostics and prognostics are identified and presented with a collection of lessons learned from previous studies that include both industrial and military aerospace applications.

  5. Review of Histopathological and Molecular Prognostic Features in Colorectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Marzouk, Ola; Schofield, John, E-mail: john.schofield@nhs.net [Department of Cellular Pathology, Maidstone Hospital, Hermitage Lane, Maidstone, Kent ME16 9QQ (United Kingdom)

    2011-06-23

    Prediction of prognosis in colorectal cancer is vital for the choice of therapeutic options. Histopathological factors remain paramount in this respect. Factors such as tumor size, histological type and subtype, presence of signet ring morphology and the degree of differentiation as well as the presence of lymphovascular invasion and lymph node involvement are well known factors that influence outcome. Our understanding of these factors has improved in the past few years with factors such as tumor budding, lymphocytic infiltration being recognized as important. Likewise the prognostic significance of resection margins, particularly circumferential margins has been appreciated in the last two decades. A number of molecular and genetic markers such as KRAS, BRAF and microsatellite instability are also important and correlate with histological features in some patients. This review summarizes our current understanding of the main histopathological factors that affect prognosis of colorectal cancer.

  6. Review of Histopathological and Molecular Prognostic Features in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    John Schofield

    2011-06-01

    Full Text Available Prediction of prognosis in colorectal cancer is vital for the choice of therapeutic options. Histopathological factors remain paramount in this respect. Factors such as tumor size, histological type and subtype, presence of signet ring morphology and the degree of differentiation as well as the presence of lymphovascular invasion and lymph node involvement are well known factors that influence outcome. Our understanding of these factors has improved in the past few years with factors such as tumor budding, lymphocytic infiltration being recognized as important. Likewise the prognostic significance of resection margins, particularly circumferential margins has been appreciated in the last two decades. A number of molecular and genetic markers such as KRAS, BRAF and microsatellite instability are also important and correlate with histological features in some patients. This review summarizes our current understanding of the main histopathological factors that affect prognosis of colorectal cancer.

  7. Prognostic value of serum angiogenic activity in colorectal cancer patients.

    Science.gov (United States)

    Gonzalez, Francisco-Jesus; Quesada, Ana-Rodriguez; Sevilla, Isabel; Baca, Juan-Javier; Medina, Miguel-Angel; Amores, Jose; Diaz, Juan Miguel; Rius-Diaz, Francisca; Marques, Eduardo; Alba, Emilio

    2007-01-01

    Angiogenesis, resulting from an imbalance between angiogenic activator factors and inhibitors, is required for tumour growth and metastasis. The determination of the circulating concentration of all angiogenic factors (activators and inhibitors) is not feasible at present. We have evaluated diagnostic and prognostic values of the measurement of serum angiogenic activity in colorectal carcinoma (CRC) patients. Serum proliferative activity (PA) on human umbilical vein endothelial cells (HUVEC) in vitro, and serum vascular endothelial growth factor (VEGF) levels were determined by ELISA in 53 patients with primary CRC, 16 subjects with non-neoplastic gastrointestinal disease (SC) and 34 healthy individuals. Data were compared with clinical outcome of the patients. Although serum from CRC patients significantly increased the PA of HUVEC, compared to culture control (HUVEC in medium + 10% foetal bovine serum (FBS); P < 0.001); our results indicate that serum PA in CRC patients was similar to that of SC or healthy individuals. There was no correlation between serum PA and circulating VEGF concentrations. Surgery produced a decrease of PA at 8 hrs after tumour resection in CRC patients compared to pre-surgery values (186 +/- 47 versus 213 +/- 41, P < 0.001). However, an increase in serum VEGF values was observed after surgery (280 [176-450] versus 251 [160-357] pg/ml, P = 0.004). Patients with lower PA values after surgery showed a worse outcome that those with higher PA values. Therefore, this study does not support a diagnostic value for serum angiogenic activity measured by proliferative activity on HUVEC but suggests it could have a prognostic value in CRC patients.

  8. Diagnostic Imaging of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Kemal Kara

    2012-12-01

    Full Text Available Lung cancer is the most common cause of cancer related death in men and women. It is frequently seen among men than in women and male-female ratio is 1.5:1. Common epidemiological factors that increase risk of lung cancer is smoking. Early age to start smoking, high number of smoking cigarettes per a day and depth of inhalation increase risk of lung cancer. 25% of patients with lung cancer are nonsmokers that passively exposed to cigarette smoke. Occupational exposure to substances such as asbestos, arsenic, nickel, beryllium, mustard gas increases the risk of lung cancer. The well defined risk factor is exposure to asbestos. In addition advanced age, diffuse pulmonary fibrosis, chronic obstructive pulmonary disease (COPD and genetic predisposition are the risk factors that increases lung cancer. [TAF Prev Med Bull 2012; 11(6.000: 749-756

  9. The diagnostic and prognostic value of neurofilament heavy chain levels in immune-mediated optic neuropathies.

    Science.gov (United States)

    Petzold, Axel; Plant, Gordon T

    2012-01-01

    Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH) in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n = 20), chronic relapsing inflammatory optic neuritis (CRION, n = 19), neuromyelitis optica (NMO, n = 9), and healthy controls (n = 28). Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean 0.79 ± 1.51 ng/mL) compared to patients with CRION (0.13 ± 0.16 ng/mL, P = 0.007), MSON (0.09 ± 0.09, P = 0.008), and healthy controls (0.01 ± 0.02 ng/mL, P = 0.001). High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

  10. The Diagnostic and Prognostic Value of Neurofilament Heavy Chain Levels in Immune-Mediated Optic Neuropathies

    Directory of Open Access Journals (Sweden)

    Axel Petzold

    2012-01-01

    Full Text Available Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n=20, chronic relapsing inflammatory optic neuritis (CRION, n=19, neuromyelitis optica (NMO, n=9, and healthy controls (n=28. Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean 0.79±1.51 ng/mL compared to patients with CRION (0.13±0.16 ng/mL, P=0.007, MSON (0.09±0.09, P=0.008, and healthy controls (0.01±0.02 ng/mL, P=0.001. High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

  11. PROGNOSTIC FACTORS OF TUMORAL PROCESS IN PATIENTS WITH DISSEMINATED COLORECTAL CANCER

    Directory of Open Access Journals (Sweden)

    Ye. Yu. Zorina

    2014-01-01

    Full Text Available New prognostic factors for disseminated colorectal cancer (dCRC are being investigated in this article.Subjects and methods. In this study we have analyzed three clinical groups. First group – 60 patients with dCRC had not specifical therapy. Second group – 200 patients had specifical therapy, but without identification of prognostic and predictive markers. And third group – 93 patients had individual therapy which was based on prognostic and predictive markers of each patient.Results. Definition of prognostic factors (TS, TP, DPD, Ercc-1, СОХ-2, MSI, KRAS in patients with dCRC allowed to prescribe optimal specific therapy and improve results of treatment.Conclusion. Investigation of prognostic markers allowed to differentiate prognostic groups among dCRC patients. Investigation of prognostic factors in patients with intermediate prognosis allows to improve treatment outcome and improve number of liver surgery.

  12. Perspectives of long noncoding RNAs in cancer diagnostics and therapy

    Directory of Open Access Journals (Sweden)

    Eduardo M Reis

    2012-03-01

    Full Text Available Long noncoding RNAs (lncRNAs transcribed from intergenic and intronic regions of the human genome constitute a broad class of cellular transcripts that are under intensive investigation. While only a handful of lncRNAs have been characterized, their involvement in fundamental cellular processes that control gene expression highlight a central role in cell homeostasis. Not surprisingly, aberrant expression of regulatory lncRNAs has been increasingly documented in different types of cancer, where they can mediate both oncogenic or tumor suppressor effects. Interaction with chromatin remodeling complexes that promote silencing of specific genes seems to be a general mode of lncRNA regulation, but it is conceivable that additional mechanisms of action are yet to be unveiled. LncRNAs show greater tissue specificity compared to protein-coding mRNAs making them attractive in the search of novel diagnostics/prognostics cancer biomarkers in body fluid samples. In fact, lncRNA PCA3 can be detected in urine samples and has been shown to improve diagnosis of prostate cancer. Identification of regulatory regions controlling the expression of lncRNAs highly expressed in tumors (e.g. lncRNA H19 holds potential to the development of targeted cancer therapies based on vectors carrying toxin genes under control of tumor-specific promoters. Annotation and functional characterization of the lncRNA complement of the cancer transcriptome will conceivably provide new venues for early diagnosis and treatment of the disease.

  13. ROCK1 as a novel prognostic marker in vulvar cancer

    DEFF Research Database (Denmark)

    Akagi, Erica M; Lavorato-Rocha, André M; Maia, Beatriz de Melo;

    2014-01-01

    infection, but most cases develop in women aged over 50 years through poorly understood genetic mechanisms. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) has been implicated in many cellular processes, but its function in vulvar cancer has never been examined. In this study, we aimed...... to determine the prognostic value of ROCK1 gene and protein analysis in vulvar squamous cell carcinoma (VSCC). METHODS: ROCK1 expression levels were measured in 16 vulvar tumour samples and adjacent normal tissue by qRT-PCR. Further, 96 VSCC samples were examined by immunohistochemistry (IHC) to confirm...... tissue compared with the tumour samples (p = 0.016). By IHC, 100% of invasive front areas of the tumour and 95.8% of central tumour areas were positive for ROCK1. Greater expression of ROCK1 was associated with the absence of lymph node metastasis (p = 0.022) and a lower depth of invasion (p = 0...

  14. Prognostic significance of aberrantly silenced ANPEP expression in prostate cancer

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Abildgaard, Mette Opstrup; Haldrup, Christa;

    2013-01-01

    Background:Novel biomarkers for prostate cancer (PC) are urgently needed. This study investigates the expression, epigenetic regulation, and prognostic potential of ANPEP in PC.Methods:Aminopeptidase N (APN; encoded by ANPEP) expression was analysed by immunohistochemistry using tissue microarrays...... nonmalignant and PC tissue samples, and in cell lines.Results:The APN expression was significantly downregulated in PC compared with nonmalignant prostate tissue samples. Aberrant promoter hypermethylation was frequently observed in PC tissue samples, and 5-aza-2'-deoxycytidine induced ANPEP expression...... in three hypermethylated prostate cell lines, suggesting epigenetic silencing. Negative APN immunoreactivity was significantly associated with short RFS and short CSS in the RP and CT cohort, respectively, independently of routine clinicopathological predictors. Combining APN with a known angiogenesis...

  15. Meta-analysis of several gene lists for distinct types of cancer: A simple way to reveal common prognostic markers

    Directory of Open Access Journals (Sweden)

    Sun Xiao

    2007-04-01

    Full Text Available Abstract Background Although prognostic biomarkers specific for particular cancers have been discovered, microarray analysis of gene expression profiles, supported by integrative analysis algorithms, helps to identify common factors in molecular oncology. Similarities of Ordered Gene Lists (SOGL is a recently proposed approach to meta-analysis suitable for identifying features shared by two data sets. Here we extend the idea of SOGL to the detection of significant prognostic marker genes from microarrays of multiple data sets. Three data sets for leukemia and the other six for different solid tumors are used to demonstrate our method, using established statistical techniques. Results We describe a set of significantly similar ordered gene lists, representing outcome comparisons for distinct types of cancer. This kind of similarity could improve the diagnostic accuracies of individual studies when SOGL is incorporated into the support vector machine algorithm. In particular, we investigate the similarities among three ordered gene lists pertaining to mesothelioma survival, prostate recurrence and glioma survival. The similarity-driving genes are related to the outcomes of patients with lung cancer with a hazard ratio of 4.47 (p = 0.035. Many of these genes are involved in breakdown of EMC proteins regulating angiogenesis, and may be used for further research on prognostic markers and molecular targets of gene therapy for cancers. Conclusion The proposed method and its application show the potential of such meta-analyses in clinical studies of gene expression profiles.

  16. A Modified Nottingham Prognostic Index for Breast Cancer Patients Diagnosed in Denmark 1978-1994

    DEFF Research Database (Denmark)

    Rostgaard, Klaus; Mouridsen, Henning T.; Væth, Michael;

    2001-01-01

    Stage of disease is a predictor of breast cancer survival. We used data from the Danish Cancer Register amd the Daniish Breast Cancer Cooperative Group to study stage distribution in 0-69-years-old Danish breast cancer patients diagnosed in 1978-1994. We constructed a modified Nottingham Prognostic...

  17. Prognostic factors for patients with hepatic metastases from breast cancer.

    Science.gov (United States)

    Wyld, L; Gutteridge, E; Pinder, S E; James, J J; Chan, S Y; Cheung, K L; Robertson, J F R; Evans, A J

    2003-07-21

    Median survival from liver metastases secondary to breast cancer is only a few months, with very rare 5-year survival. This study reviewed 145 patients with liver metastases from breast cancer to determine factors that may influence survival. Data were analysed using Kaplan-Meier survival curves, univariate and multivariate analysis. Median survival was 4.23 months (range 0.16-51), with a 27.6% 1-year survival. Factors that significantly predicted a poor prognosis on univariate analysis included symptomatic liver disease, deranged liver function tests, the presence of ascites, histological grade 3 disease at primary presentation, advanced age, oestrogen receptor (ER) negative tumours, carcinoembryonic antigen of over 1000 ng ml(-1) and multiple vs single liver metastases. Response to treatment was also a significant predictor of survival with patients responding to chemo- or endocrine therapy surviving for a median of 13 and 13.9 months, respectively. Multivariate analysis of pretreatment variables identified a low albumin, advanced age and ER negativity as independent predictors of poor survival. The time interval between primary and metastatic disease, metastases at extrahepatic sites, histological subtype and nodal stage at primary presentation did not predict prognosis. Awareness of the prognostic implications of the above factors may assist in selecting the most appropriate treatment for these patients.British Journal of Cancer (2003) 89, 284-290. doi:10.1038/sj.bjc.6601038 www.bjcancer.com

  18. Prognostic factors for progression-free and overall survival in advanced biliary tract cancer

    DEFF Research Database (Denmark)

    Bridgewater, J; Lopes, A; Wasan, H

    2016-01-01

    BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable...... associated with PFS and OS. ROC analysis suggested the models generated from the ABC-02 study had a limited prognostic value [6-month PFS: area under the curve (AUC) 62% (95% CI 57-68); 1-year OS: AUC 64% (95% CI 58-69)]. CONCLUSION: These data propose a set of prognostic criteria for outcome in advanced...

  19. Diagnostic interval and mortality in colorectal cancer

    DEFF Research Database (Denmark)

    Tørring, Marie Louise; Frydenberg, Morten; Hamilton, William;

    2012-01-01

    Objective To test the theory of a U-shaped association between time from the first presentation of symptoms in primary care to the diagnosis (the diagnostic interval) and mortality after diagnosis of colorectal cancer (CRC). Study Design and Setting Three population-based studies in Denmark...... presentation, the association between the length of the diagnostic interval and 5-year mortality rate after the diagnosis of CRC was the same for all three types of data: displaying a U-shaped association with decreasing and subsequently increasing mortality with longer diagnostic intervals. Conclusion Unknown...... confounding and in particular confounding by indication is likely to explain the counterintuitive findings of higher mortality among patients with very short diagnostic intervals, but cannot explain the increasing mortality with longer diagnostic intervals. The results support the theory that longer...

  20. Imaging diagnostics in ovarian cancer

    DEFF Research Database (Denmark)

    Fog, Sigrid Marie Kasper Kasper; Dueholm, Margit; Marinovskij, Edvard;

    2017-01-01

    OBJECTIVE: To analyze the ability of magnetic resonance imaging (MRI) and systematic evaluation at surgery to predict optimal cytoreduction in primary advanced ovarian cancer and to develop a preoperative scoring system for cancer staging. STUDY DESIGN: Preoperative MRI and standard laparotomy were...... performed in 99 women with either ovarian or primary peritoneal cancer. Using univariate and multivariate logistic regression analysis of a systematic description of the tumor in nine abdominal compartments obtained by MRI and during surgery plus clinical parameters, a scoring system was designed....... MRI is able to assess ovarian cancer with peritoneal carcinomatosis with satisfactory concordance with laparotomic findings. This scoring system could be useful as a clinical guideline and should be evaluated and developed further in larger studies....

  1. Prognostic Values of microRNAs in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Yaguang Xi

    2006-01-01

    Full Text Available The functions of non-coding microRNAs (miRNAs in tumorigenesis are just beginning to emerge. Previous studies from our laboratory have identifi ed a number of miRNAs that were deregulated in colon cancer cell lines due to the deletion of the p53 tumor suppressor gene. In this study, the in vivo signifi cance of some of these miRNAs was further evaluated using colorectal clinical samples. Ten miRNAs (hsa-let-7b, hsa-let-7g, hsa-miR-15b, hsa-miR-181b, hsa-miR-191, hsa-miR-200c, hsa-miR-26a, hsa-miR-27a, hsa-miR-30a-5p and hsa-miR-30c were evaluated for their potential prognostic value in colorectal cancer patients. Forty eight snap frozen clinical colorectal samples (24 colorectal cancer and 24 paired normal patient samples with detailed clinical follow-up information were selected . The expression levels of 10 miRNAs were quantified via qRT-PCR analysis. The statistical signifi cance of these markers for disease prognosis was evaluated using a two tailed paired Wilcoxon test. A Kaplan-Meier survival curve was generated followed by performing a Logrank test. Among the ten miRNAs, hsa-miR-15b (p = 0.0278, hsa-miR-181b (p = 0.0002, hsa-miR-191 (p = 0.0264 and hsa-miR-200c (p = 0.0017 were signifi cantly over-expressed in tumors compared to normal colorectal samples. Kaplan-Meier survival analysis indicated that hsa-miR-200c was signifi cantly associated with patient survival (p = 0.0122. The patients (n = 15 with higher hsa-miR-200c expression had a shorter survival time (median survival = 26 months compared to patients (n = 9 with lower expression (median survival = 38 months. Sequencing analysis revealed that hsa-miR-181b (p = 0.0098 and hsa-miR-200c (p = 0.0322 expression were strongly associated with the mutation status of the p53 tumor suppressor gene. Some of these miRNAs may function as oncogenes due to their over-expression in tumors. hsa-miR-200c may be a potential novel prognostic factor in colorectal cancer.

  2. Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer.

    NARCIS (Netherlands)

    Cohen, S.J.; Punt, C.J.A.; Iannotti, N.; Saidman, B.H.; Sabbath, K.D.; Gabrail, N.Y.; Picus, J.; Morse, M.A.; Mitchell, E.; Miller, M.C.; Doyle, G.V.; Tissing, H.; Terstappen, L.W.; Meropol, N.J.

    2009-01-01

    BACKGROUND: We demonstrated that circulating tumor cell (CTC) number at baseline and follow-up is an independent prognostic factor in metastatic colorectal cancer (mCRC). This analysis was undertaken to explore whether patient and treatment characteristics impact the prognostic value of CTCs. PATIEN

  3. Preoperative plasma TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer

    DEFF Research Database (Denmark)

    Birgisson, Helgi; Nielsen, Hans J.; Christensen, Ib Jarle;

    2010-01-01

    Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent ...

  4. Prognostic effect of estrogen receptor status across age in primary breast cancer

    DEFF Research Database (Denmark)

    Bentzon, N.; During, M.; Rasmussen, B.B.;

    2008-01-01

    Estrogen receptor (ER) status is considered as an important prognostic factor as well as a predictive factor for endocrine responsiveness in breast cancer. We analyzed the distribution of ER status across age and estimated variations in the prognostic impact of ER status related to patients' age...

  5. Predictive and prognostic values of cancer-associated serum antigen (CASA) and cancer antigen 125 (CA 125) levels prior to second-look laparotomy for ovarian cancer.

    Science.gov (United States)

    Kierkegaard, O; Mogensen, O; Mogensen, B; Jakobsen, A

    1995-11-01

    CA 125 and cancer-associated serum antigen (CASA) were measured prior to second-look laparotomy (SLL) to investigate their predictive and prognostic values in 93 patients treated for epithelial ovarian cancer FIGO stage II, III, or IV. Residual tumor was diagnosed at the SLL in 58 patients (62%). The optimal cutoff level was 15 U/ml for CA 125 and 8 U/ml for CASA. Using these levels, the sensitivity for detection of residual tumor was 40% for CA 125 and 22% for CASA. The combined use of the markers resulted in a sensitivity of 47% (diagnostic gain 6.9%; 95% confidence interval (CI), 0.14-13.44%). Microscopic tumor volumes were equally diagnosed by CASA and CA 125. The independent prognostic value of CA 125 (RR = 2.6; 95% CI, 2.0-3.2) and CASA (RR = 2.2; CI, 1.5-2.9) was established by means of Cox regression analysis of the covariation between survival, age, FIGO stage, histopathology, tumor grade, and bulk of residual tumor at the primary operation and CA 125 and CASA before the SLL. In conclusion, we found that CASA could supplement CA 125 measurement prior to SLL and reduce the number of SLLs. Furthermore, CASA had an independent prognostic value for survival which may be used together with other information in the planning of further treatment of the individual patient.

  6. The diagnostic and prognostic role of liquid-based cytology: are we ready to monitor therapy and resistance?

    Science.gov (United States)

    Rossi, Esther Diana; Bizzarro, Tommaso; Longatto-Filho, Adhemar; Gerhard, Rene; Schmitt, Fernando

    2015-01-01

    Here, we evaluate the diagnostic and prognostic role of liquid-based cytology (LBC) in different body lesions, including thyroid, lung, effusions and malignant breast lesions. LBC has gained consensus after being applied to both non-gynecologic and fine-needle aspiration cytology. Although some remain sceptical regarding the diagnostic efficacy of LBC, mainly when used alone, in recent years, good results have been obtained as long as it showed a high diagnostic accuracy. Here, we discuss the additional possibility of storing material for the application of ancillary techniques (immunocytochemistry-molecular analysis) with several diagnostic and prognostic advantages, which may pave the way for the challenging evaluation of both monitoring responses to treatment and resistance to targeted therapies in thyroid, lung, breast carcinoma or malignant effusions. Furthermore, it provides the use of several molecular spots as specific targets for personalized therapy.

  7. Prognostic value of innate and adaptive immunity in colorectal cancer.

    Science.gov (United States)

    Grizzi, Fabio; Bianchi, Paolo; Malesci, Alberto; Laghi, Luigi

    2013-01-14

    Colorectal cancer (CRC) remains one of the major public health problems throughout the world. Originally depicted as a multi-step dynamical disease, CRC develops slowly over several years and progresses through cytologically distinct benign and malignant states, from single crypt lesions through adenoma, to malignant carcinoma with the potential for invasion and metastasis. Moving from histological observations since a long time, it has been recognized that inflammation and immunity actively participate in the pathogenesis, surveillance and progression of CRC. The advent of immunohistochemical techniques and of animal models has improved our understanding of the immune dynamical system in CRC. It is well known that immune cells have variable behavior controlled by complex interactions in the tumor microenvironment. Advances in immunology and molecular biology have shown that CRC is immunogenic and that host immune responses influence survival. Several lines of evidence support the concept that tumor stromal cells, are not merely a scaffold, but rather they influence growth, survival, and invasiveness of cancer cells, dynamically contributing to the tumor microenvironment, together with immune cells. Different types of immune cells infiltrate CRC, comprising cells of both the innate and adaptive immune system. A relevant issue is to unravel the discrepancy between the inhibitory effects on cancer growth exerted by the local immune response and the promoting effects on cancer proliferation, invasion, and dissemination induced by some types of inflammatory cells. Here, we sought to discuss the role played by innate and adaptive immune system in the local progression and metastasis of CRC, and the prognostic information that we can currently understand and exploit.

  8. Embedded diagnostic, prognostic, and health management system and method for a humanoid robot

    Science.gov (United States)

    Barajas, Leandro G. (Inventor); Sanders, Adam M (Inventor); Reiland, Matthew J (Inventor); Strawser, Philip A (Inventor)

    2013-01-01

    A robotic system includes a humanoid robot with multiple compliant joints, each moveable using one or more of the actuators, and having sensors for measuring control and feedback data. A distributed controller controls the joints and other integrated system components over multiple high-speed communication networks. Diagnostic, prognostic, and health management (DPHM) modules are embedded within the robot at the various control levels. Each DPHM module measures, controls, and records DPHM data for the respective control level/connected device in a location that is accessible over the networks or via an external device. A method of controlling the robot includes embedding a plurality of the DPHM modules within multiple control levels of the distributed controller, using the DPHM modules to measure DPHM data within each of the control levels, and recording the DPHM data in a location that is accessible over at least one of the high-speed communication networks.

  9. Family history in breast cancer is not a prognostic factor?

    Science.gov (United States)

    Jobsen, J J; Meerwaldt, J H; van der Palen, J

    2000-04-01

    The aim of this study is to determine if breast conservative treatment is justified for patients with a positive family history of breast cancer and to investigate whether they have a worse prognosis. We performed a prospective cohort study of breast cancer patients, treated with breast conservative treatment with radiotherapy at the Radiotherapy Department of the Medisch Spectrum Twente. Between 1984 and 1996, 1204 patients with T1 and T2 or =2 FDRs. The local recurrence rate was 4.1%, with similar rates for all groups. In young patients, or =2 FDRs. Patients with a positive FH had significantly more contralateral tumours. The 5-year corrected survival was 91.3%. Among patients with a positive FH, a 5-year corrected survival of 91% was observed and the survival 100% among patients with one and > or =2 FDR. Family history is not a contraindication for breast conservative treatment and is not associated with a worse prognosis. Family history is not a prognostic factor for local recurrence rate in patients older than 40 years.

  10. Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer population

    DEFF Research Database (Denmark)

    Kjaer-Frifeldt, Sanne; Fredslund, Rikke; Lindebjerg, Jan;

    2012-01-01

    To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients.......To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients....

  11. Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients.

    Science.gov (United States)

    Satelli, Arun; Batth, Izhar Singh; Brownlee, Zachary; Rojas, Christina; Meng, Qing H; Kopetz, Scott; Li, Shulin

    2016-07-01

    Although circulating tumor cells (CTCs) have potential as diagnostic biomarkers for cancer, determining their prognostic role in cancer patients undergoing treatment is a challenge. We evaluated the prognostic value of programmed death-ligand 1 (PD-L1) expression in CTCs in colorectal and prostate cancer patients undergoing treatment. Peripheral blood samples were collected from 62 metastatic colorectal cancer patients and 30 metastatic prostate cancer patients. CTCs were isolated from the samples using magnetic separation with the cell-surface vimentin(CSV)-specific 84-1 monoclonal antibody that detects epithelial-mesenchymal transitioned (EMT) CTCs. CTCs were enumerated and analyzed for PD-L1 expression using confocal microscopy. PD-L1 expression was detectable in CTCs and was localized in the membrane and/or cytoplasm and nucleus. CTC detection alone was not associated with poor progression-free or overall survival in colorectal cancer or prostate cancer patients, but nuclear PD-L1 (nPD-L1) expression in these patients was significantly associated with short survival durations. These results demonstrated that nPD-L1 has potential as a clinically relevant prognostic biomarker for colorectal and prostate cancer. Our data thus suggested that use of CTC-based models of cancer for risk assessment can improve the standard cancer staging criteria and supported the incorporation of nPD-L1 expression detection in CTCs detection in such models.

  12. Prognostic significance of detection of microscopic peritoneal disease in colorectal cancer: a systematic review.

    LENUS (Irish Health Repository)

    Mohan, Helen M

    2013-06-01

    Free intraperitoneal tumour cells are an independent indicator of poor prognosis, and are encorporated in current staging systems in upper gastrointestinal cancers, but not colorectal cancer. This systematic review aimed to evaluate the role and prognostic significance of positive peritoneal lavage in colorectal cancer.

  13. The ErbB signalling pathway : protein expression and prognostic value in epithelial ovarian cancer

    NARCIS (Netherlands)

    de Graeff, P.; Crijns, A.P.; ten Hoor, K.A.; Klip, H.G.; Hollema, H.; Oien, K.; Bartlett, J.M.; Wisman, G.B.; de Bock, G.H.; de Vries, E.G.; de Jong, S.; van der Zee, A.G.

    2008-01-01

    Ovarian cancer is the most frequent cause of death from gynaecological cancer in the Western world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR) and HER-2/neu are f

  14. Diagnostic and prognostic utility of non-invasive imaging indiabetes management

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Medical imaging technologies are acquiring an increasingrelevance to assist clinicians in diagnosis and to guidemanagement and therapeutic treatment of patients,thanks to their non invasive and high resolution properties.Computed tomography, magnetic resonanceimaging, and ultrasonography are the most usedimaging modalities to provide detailed morphologicalreconstructions of tissues and organs. In addition, theuse of contrast dyes or radionuclide-labeled tracerspermits to get functional and quantitative informationabout tissue physiology and metabolism in normal anddisease state. In recent years, the development ofmultimodal and hydrid imaging techniques is comingto be the new frontier of medical imaging for thepossibility to overcome limitations of single modalitiesand to obtain physiological and pathophysiologicalmeasurements within an accurate anatomical framework.Moreover, the employment of molecular probes,such as ligands or antibodies, allows a selective in vivotargeting of biomolecules involved in specific cellularprocesses, so expanding the potentialities of imagingtechniques for clinical and research applications. Thisreview is aimed to give a survey of characteristicsof main diagnostic non-invasive imaging techniques.Current clinical appliances and future perspectives ofimaging in the diagnostic and prognostic assessment ofdiabetic complications affecting different organ systemswill be particularly addressed.

  15. The Practicability of a Novel Prognostic Index (PI Model and Comparison with Nottingham Prognostic Index (NPI in Stage I-III Breast Cancer Patients Undergoing Surgical Treatment.

    Directory of Open Access Journals (Sweden)

    Jiahuai Wen

    Full Text Available Previous studies have indicated the prognostic value of various laboratory parameters in cancer patients. This study was to establish a prognostic index (PI model for breast cancer patients based on the potential prognostic factors.A retrospective study of 1661 breast cancer patients who underwent surgical treatment between January 2002 and December 2008 at Sun Yat-sen University Cancer Center was conducted. Multivariate analysis (Cox regression model was performed to determine the independent prognostic factors and a prognostic index (PI model was devised based on these factors. Survival analyses were used to estimate the prognostic value of PI, and the discriminatory ability of PI was compared with Nottingham Prognostic Index (NPI by evaluating the area under the receiver operating characteristics curves (AUC.The mean survival time of all participants was 123.6 months. The preoperative globulin >30.0g/L, triglyceride >1.10mmol/L and fibrinogen >2.83g/L were identified as risk factors for shorter cancer-specific survival. The novel prognostic index model was established and enrolled patients were classified as low- (1168 patients, 70.3%, moderate- (410 patients, 24.7% and high-risk groups (83 patients, 5.0%, respectively. Compared with the low-risk group, higher risks of poor clinical outcome were indicated in the moderate-risk group [Hazard ratio (HR: 1.513, 95% confidence interval (CI: 1.169-1.959, p = 0.002] and high-risk group (HR: 2.481, 95%CI: 1.653-3.724, p< 0.001.The prognostic index based on three laboratory parameters was a novel and practicable prognostic tool. It may serve as complement to help predict postoperative survival in breast cancer patients.

  16. PROGNOSTIC FACTORS OF PROSTATE CANCER BEFORE AND AFTER RADICAL PROSTATECTOMY

    Directory of Open Access Journals (Sweden)

    E. I. Veliev

    2011-01-01

    Full Text Available Objective: to assess a correlation between the preoperative prognostic characteristics and the pathologic stage and to determine whether a positive surgical margin is present after radical prostatectomy (RPE.Materials and methods. The materials of 224 patients with prostate cancer (PC who had undergone RPE at the Clinic of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, were analyzed.Results. The patients’ median age was 62 (43–78 years. Sixty-seven (29.9 %, 46 (20.5%, and 111 (49.6 % patients were referred to as low-, moderate-, and high-risk groups, respectively. A positive surgical margin was observed in 11.9, 28.3, and 38.7 % of the patients in the low-, moderate-, and high-risk groups, respectively (р = 0.0003. The predictors of a positive surgical margin were the percent of involved biopsy specimens (R = 0.34 and Gleason score (R = 0.31 and perineural invasion. According to multivariate analysis, neither the preoperative level of prostate-specific antigen, nor the clinical stage showed any correlation with the positive surgical margin and the pathologic stage after RPE.

  17. PROGNOSTIC FACTORS OF PROSTATE CANCER BEFORE AND AFTER RADICAL PROSTATECTOMY

    Directory of Open Access Journals (Sweden)

    E. I. Veliev

    2014-07-01

    Full Text Available Objective: to assess a correlation between the preoperative prognostic characteristics and the pathologic stage and to determine whether a positive surgical margin is present after radical prostatectomy (RPE.Materials and methods. The materials of 224 patients with prostate cancer (PC who had undergone RPE at the Clinic of Urology and Surgical Andrology, Russian Medical Academy of Postgraduate Education, were analyzed.Results. The patients’ median age was 62 (43–78 years. Sixty-seven (29.9 %, 46 (20.5%, and 111 (49.6 % patients were referred to as low-, moderate-, and high-risk groups, respectively. A positive surgical margin was observed in 11.9, 28.3, and 38.7 % of the patients in the low-, moderate-, and high-risk groups, respectively (р = 0.0003. The predictors of a positive surgical margin were the percent of involved biopsy specimens (R = 0.34 and Gleason score (R = 0.31 and perineural invasion. According to multivariate analysis, neither the preoperative level of prostate-specific antigen, nor the clinical stage showed any correlation with the positive surgical margin and the pathologic stage after RPE.

  18. Application of Diagnostic/Prognostic Methods to Critical Equipment for the Spent Nuclear Fuel Cleanup Program

    Energy Technology Data Exchange (ETDEWEB)

    Casazza, Lawrence O.; Jarrell, Donald B.; Koehler, Theresa M.; Meador, Richard J.; Wallace, Dale E.

    2002-02-28

    The management of the Spent Nuclear Fuel (SNF) project at the Hanford K-Basin in the 100 N Area has successfully restructured the preventive maintenance, spare parts inventory requirements, and the operator rounds data requirements. In this investigation, they continue to examine the different facets of the operations and maintenance (O&M) of the K-Basin cleanup project in search of additional reliability and cost savings. This report focuses on the initial findings of a team of PNNL engineers engaged to identify potential opportunities for reducing the cost of O&M through the application of advanced diagnostics (fault determination) and prognostics (residual life/reliability determination). The objective is to introduce predictive technologies to eliminate or reduce high impact equipment failures. The PNNL team in conjunction with the SNF engineers found the following major opportunities for cost reduction and/or enhancing reliability: (1) Provide data routing and automated analysis from existing detection systems to a display center that will engage the operations and engineering team. This display will be operator intuitive with system alarms and integrated diagnostic capability. (2) Change operating methods to reduce major transients induced in critical equipment. This would reduce stress levels on critical equipment. (3) Install a limited sensor set on failure prone critical equipment to allow degradation or stressor levels to be monitored and alarmed. This would provide operators and engineers with advance guidance and warning of failure events. Specific methods for implementation of the above improvement opportunities are provided in the recommendations. They include an Integrated Water Treatment System (IWTS) decision support system, introduction of variable frequency drives on certain pump motors, and the addition of limited diagnostic instrumentation on specified critical equipment.

  19. The DSM-5 diagnostic criteria for anorexia nervosa may change its population prevalence and prognostic value.

    Science.gov (United States)

    Mustelin, Linda; Silén, Yasmina; Raevuori, Anu; Hoek, Hans W; Kaprio, Jaakko; Keski-Rahkonen, Anna

    2016-06-01

    The definition of anorexia nervosa was revised for the Fifth Edition of the Diagnostic and Statistical Manual (DSM-5). We examined the impact of these changes on the prevalence and prognosis of anorexia nervosa. In a nationwide longitudinal study of Finnish twins born 1975-1979, the women (N = 2825) underwent a 2-stage screening for eating disorders at mean age 24. Fifty-five women fulfilled DSM-IV criteria for lifetime anorexia nervosa. When we recoded the interviews using DSM-5 criteria, we detected 37 new cases. We contrasted new DSM-5 vs. DSM-IV cases to assess their clinical characteristics and prognosis. We also estimated lifetime prevalences and incidences and tested the association of minimum BMI with prognosis. We observed a 60% increase in the lifetime prevalence of anorexia nervosa using the new diagnostic boundaries, from 2.2% to 3.6%. The new cases had a later age of onset (18.8 y vs. 16.5, p = 0.002), higher minimum BMI (16.9 vs. 15.5 kg/m(2), p = 0.0004), a shorter duration of illness (one year vs. three years, p = 0.002), and a higher 5-year probability or recovery (81% vs. 67%, p = 0.002). Minimum BMI was not associated with prognosis. It therefore appears that the substantial increase in prevalence of anorexia nervosa is offset by a more benign course of illness in new cases. Increased diagnostic heterogeneity underscores the need for reliable indicators of disease severity. Our findings indicate that BMI may not be an ideal severity marker, but should be complemented by prognostically informative criteria. Future studies should focus on identifying such factors in prospective settings.

  20. Prognostic Factors and Recurrence in Breast Cancer: Experience at the National Cancer Institute of Mexico

    OpenAIRE

    Stankov, A.; J. E. Bargallo-Rocha; A. Ñamendys-Silva Silvio; Ramirez, M. T.; Stankova-Ninova, K.; Meneses-Garcia, A.

    2012-01-01

    The purpose of this study was to analyze the prognostic and predictive factors that relate to locoregional or distant recurrences in breast cancer patients who have been treated at the National Cancer Institute of Mexico. Multivariate, time-dependent Cox regression analyses indicate that the pN status (positive versus negative lymph node; P = 0.003; HR (hazard ratio), 3.47; CI (confidence interval), 1.52–7.91) and the pathological complete response of the patient to neoadjuvant chemotherapy (...

  1. Loss of heterozygosity: An independent prognostic factor of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Shih-Ching Chang; Jen-Kou Lin; Tzu-Chen Lin; Wen-Yih Liang

    2005-01-01

    AIM: Colorectal cancers result from the accumulation of several distinct genetic alterations. This study was to investigate the frequency and prognostic value of loss of heterozygosity (LOH) and microsatellite instability (MSI) at 14 genetic loci located near or within regions containing important genes implicated in colorectal tumorigenesis.METHODS: We studied colorectal cancers with corresponding normal mucosae in 207 patients (139 males and 68 females,mean age at the time of tumor resection 66.2±12.4 years,range 22-88 years). There were 37 right-sided colonic tumors, 85 left-sided colonic tumors and 85 rectal tumors.The distribution of tumor staging was stage Ⅰ in 25, stage Ⅱ in 73, stage Ⅲ in 68, and stage Ⅳ in 41. We analyzed the LOH and MSI of HPC1, hMSH2, hMLH1, APC, MET,P53, NH23-H1, DCC, BAT25, BAT26, D17S250, MYCL1 and D8S254 with fluorescent polymerase chain reaction and denatured gel electrophoresis. High-frequency LOH was determined to be greater than three, or more than 50%of the informative marker with LOH. High-frequency MSI (MSI-H) was determined as more than four markers with instability (>30%). Correlations of LOH and MSI with clinical outcomes and pathological features were analyzed and compared.RESULTS: The occurrence of MSI-H was 7.25%, located predominantly in the right colons (7/15) and had a higher frequency of poor differentiation (6/15) and mucin production (7/15). LOH in at least one genetic locus occurred in 78.7% of the tumors and was significantly associated with disease progression. Of the 166 potentially cured patients, 45 developed tumor recurrence within 36 mo of follow-up. Clinicopathological factors affecting 3-year disease-free survival (DFS) were TNM staging, grade of differentiation, preoperative CEA level, and high LOH status. Patients with high LOH tumors had a significantly lower DFS (50%) compared with patients with low LOH tumors (84%). Of the patients developing subsequent tumor recurrence, the number and

  2. Diagnostic and prognostic value of urinary sarcosine for prostatic cancer%尿肌氨酸水平对前列腺癌诊断及预后判断的应用价值

    Institute of Scientific and Technical Information of China (English)

    张晓毅; 邹练; 刘德忠; 高翔; 孙博; 赵国华; 孙家各

    2013-01-01

    Objective To investigate the value of the urinary sarcosine in the diagnosis and prognosis of prostate cancer(PCa). Methods A total of 16 PCa patients, with age ranging from 65 to 89(68.4±10.2)years, diagnosed by prostate biopsy in our department from May 2009 to May 2011, were enrolled in this study. Their blood and urinary samples were collected for detection of sarcosine level by isotope dilution-liquid chromatography mass spectrometry (LC/MS). Electrochemiluminescence assay was used for the detection of serum level of prostate specific antigen (PSA). The results were statistically analyzed with their Gleason scores and with bone metastasis. Results There was significant difference in the total PSA(TPSA) level between the PCa patients with bone metastases [n=9, (203.95±169.68)µg/L] and without [n=7, (35.53±35.77)µg/L, P0.05]. The urinary sarcosine level was significantly higher in the PCa patients with bone metastasis than those without [(1277.67±432.78) vs (494.71±211.35) µg/L, P=0.018]. There was no significant difference in the serum sarcosine level between different pathological Gleason scores, but urinary sarcosine level was significantly elevated with the increase of Gleason score(P>0.05). Urinary sarcosin level was correlated with Gleason score and bone metastasis(P<0.05). Conclusion Urinary sarcosine might be used as a useful tumor marker for the diagnosis and prognosis of PCa.%目的:探讨尿肌氨酸水平对前列腺癌(PCa)的诊断和病情判断方面的应用价值。方法选取我院泌尿外科住院的经前列腺穿刺活检确诊的PCa患者16例,年龄65~89(68.4±10.2)岁。采集PCa患者的血标本和尿标本,然后用同位素稀释液相色谱质谱法检测其血、尿肌氨酸水平,电化学发光法检测血清前列腺特异抗原(PSA)水平,并根据其Gleason评分及是否骨转移进行统计学分析。结果 PCa伴有骨转移患者(n=9)与无转移患者(n=7)血清总前列腺

  3. Transcriptomics in cancer diagnostics: developments in technology, clinical research and commercialization.

    Science.gov (United States)

    Sager, Monica; Yeat, Nai Chien; Pajaro-Van der Stadt, Stefan; Lin, Charlotte; Ren, Qiuyin; Lin, Jimmy

    2015-01-01

    Transcriptomic technologies are evolving to diagnose cancer earlier and more accurately to provide greater predictive and prognostic utility to oncologists and patients. Digital techniques such as RNA sequencing are replacing still-imaging techniques to provide more detailed analysis of the transcriptome and aberrant expression that causes oncogenesis, while companion diagnostics are developing to determine the likely effectiveness of targeted treatments. This article examines recent advancements in molecular profiling research and technology as applied to cancer diagnosis, clinical applications and predictions for the future of personalized medicine in oncology.

  4. Prognostic and therapeutic value of mitochondrial serine hydroxyl-methyltransferase 2 as a breast cancer biomarker

    Science.gov (United States)

    Zhang, Lahong; Chen, Zhaojun; Xue, Dan; Zhang, Qi; Liu, Xiyong; Luh, Frank; Hong, Liquan; Zhang, Hang; Pan, Feng; Liu, Yuhua; Chu, Peiguo; Zheng, Shu; Lou, Guoqiang; Yen, Yun

    2016-01-01

    Mitochondrial serine hydroxylmethyltransferase 2 (SHMT2) is a key enzyme in the serine/glycine synthesis pathway. SHMT2 has been implicated as a critical component for tumor cell survival. The aim of the present study was to evaluate the prognostic value and efficiency of SHMT2 as a biomarker in patients with breast cancer. Individual and pooled survival analyses were performed on five independent breast cancer microarray datasets. Gene signatures enriched by SHMT2 were also analyzed in these datasets. SHMT2 protein expression was detected using immunohistochemistry (IHC) assay in 128 breast cancer cases. Gene set enrichment analysis revealed that SHMT2 was significantly associated with gene signatures of mitochondrial module, cancer invasion, metastasis and poor survival among breast cancer patients (paggressiveness (TNM staging and Elson grade) in a dose-dependent manner (p<0.05). The prognostic performance of SHMT2 mRNA was comparable to other gene signatures and proved superior to TNM staging. Further analysis results indicated that SHMT2 had better prognostic value for estrogen receptor (ER)-negative breast cancer patients, compared to ER-positive patients. In cases involving stage IIb breast cancer, chemotherapy significantly extended survival time among patients with high SHMT2 expression. These results indicate that SHMT2 may be a valuable prognostic biomarker in ER-negative breast cancer cases. Furthermore, SHMT2 may be a potential target for breast cancer treatment and drug discovery. PMID:27666119

  5. Electrochemical sensors in breast cancer diagnostics and follow-up

    Directory of Open Access Journals (Sweden)

    Raquel Marques

    2015-12-01

    Full Text Available Purpose: The detection of tumor biomarkers can have a major contribution to the management of breast cancer. So far the only serum biomarker in current use in breast cancer is the cancer antigen 15-3 (CA15-3. This biomarker is used in advanced breast cancer to monitor patients and to help to identify treatment failure. The human epidermal growth factor receptor 2 (HER 2 is another biomarker whose characterization is usually made in tissue samples from primary tumour or metastasis and has been used as a prognostic factor but mainly as a target in immunotherapy treatment. Some previous studies suggest that the detection of the extracellular domain of HER2 (HER2-ECD in blood can be a prognostic factor, with even better results than its detection in tissue. Recent techniques for circulating protein biomarker detection use immunoassays, but some are, for example, not sufficiently sensitive for the detection of low biomarker concentrations. To overcome some of these problems, electrochemical (biosensors, and especially the ones using voltammetric detection, can be adequate alternatives because of their high selectivity and sensitivity which allows early detection of many diseases. Furthermore, electrochemical (biosensors are excellent to be included into point-of-care devices due to their fast response, simplicity, low cost, easy miniaturization and integration into automatic systems. Another advantage is the possibility of combining individual sensors into multiplexed detection systems. Like this they can provide fast recording of biomarker profiles of tumours which can play an important role in early detection and personalized medicine.Methods: Both individual as well as multiplexed electrochemical immunosensors were developed for the detection of CA15-3 and HER2-ECD. For this purpose a sandwich immunoassay was employed and the analytical signal was based on the voltammetric detection of enzymatically deposited silver. Screen-printed carbon

  6. The prognostic significance of extramural deposits and extracapsular lymph node invasion in colon cancer.

    LENUS (Irish Health Repository)

    Al Sahaf, Osama

    2011-08-01

    The status of resected lymph nodes in colon cancer determines prognosis and further treatment. The American Joint Committee on Cancer staging system has designated extramural nodules as nonnodal disease and classified them as extensions of the T category in the sixth edition and as site-specific tumor deposits in the seventh edition. Extracapsular lymph node extension is an established poor prognostic indicator in many cancers. Its significance in colon cancer has not been extensively investigated.

  7. Homogeneous datasets of triple negative breast cancers enable the identification of novel prognostic and predictive signatures.

    Directory of Open Access Journals (Sweden)

    Thomas Karn

    Full Text Available BACKGROUND: Current prognostic gene signatures for breast cancer mainly reflect proliferation status and have limited value in triple-negative (TNBC cancers. The identification of prognostic signatures from TNBC cohorts was limited in the past due to small sample sizes. METHODOLOGY/PRINCIPAL FINDINGS: We assembled all currently publically available TNBC gene expression datasets generated on Affymetrix gene chips. Inter-laboratory variation was minimized by filtering methods for both samples and genes. Supervised analysis was performed to identify prognostic signatures from 394 cases which were subsequently tested on an independent validation cohort (n = 261 cases. CONCLUSIONS/SIGNIFICANCE: Using two distinct false discovery rate thresholds, 25% and <3.5%, a larger (n = 264 probesets and a smaller (n = 26 probesets prognostic gene sets were identified and used as prognostic predictors. Most of these genes were positively associated with poor prognosis and correlated to metagenes for inflammation and angiogenesis. No correlation to other previously published prognostic signatures (recurrence score, genomic grade index, 70-gene signature, wound response signature, 7-gene immune response module, stroma derived prognostic predictor, and a medullary like signature was observed. In multivariate analyses in the validation cohort the two signatures showed hazard ratios of 4.03 (95% confidence interval [CI] 1.71-9.48; P = 0.001 and 4.08 (95% CI 1.79-9.28; P = 0.001, respectively. The 10-year event-free survival was 70% for the good risk and 20% for the high risk group. The 26-gene signatures had modest predictive value (AUC = 0.588 to predict response to neoadjuvant chemotherapy, however, the combination of a B-cell metagene with the prognostic signatures increased its response predictive value. We identified a 264-gene prognostic signature for TNBC which is unrelated to previously known prognostic signatures.

  8. MALDI TOF imaging mass spectrometry in clinical pathology: a valuable tool for cancer diagnostics (review).

    Science.gov (United States)

    Kriegsmann, Jörg; Kriegsmann, Mark; Casadonte, Rita

    2015-03-01

    Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) imaging mass spectrometry (IMS) is an evolving technique in cancer diagnostics and combines the advantages of mass spectrometry (proteomics), detection of numerous molecules, and spatial resolution in histological tissue sections and cytological preparations. This method allows the detection of proteins, peptides, lipids, carbohydrates or glycoconjugates and small molecules.Formalin-fixed paraffin-embedded tissue can also be investigated by IMS, thus, this method seems to be an ideal tool for cancer diagnostics and biomarker discovery. It may add information to the identification of tumor margins and tumor heterogeneity. The technique allows tumor typing, especially identification of the tumor of origin in metastatic tissue, as well as grading and may provide prognostic information. IMS is a valuable method for the identification of biomarkers and can complement histology, immunohistology and molecular pathology in various fields of histopathological diagnostics, especially with regard to identification and grading of tumors.

  9. Neutropenic enterocolitis in children and young adults with cancer: prognostic value of clinical and image findings.

    Science.gov (United States)

    Rizzatti, Marcelo; Brandalise, Silvia Regina; de Azevedo, Amilcar Cardoso; Pinheiro, Vitória Régia Pereira; Aguiar, Simone dos Santos

    2010-09-01

    Intensive chemotherapy regimens can result in severe toxicities, particularly those that involve the digestive systems, leading to morbidity and mortality in this group of patients. Acute enterocolitis can be a frequent complication. The authors performed a retrospective review or patients treated at their institution to ascertain the prognostic value of the clinical symptoms and signs of acute enterocolitis, the corresponding abdominal ultrasonographic findings, and the impact of previous chemotherapy. Amongst 1159 patients with cancer treated at the Centro Infantil Boldrini from 2003 to 2007, 188 (16.2%) patients had 1 or more episode of enterocolitis. An intestinal wall thickness of >or=3 mm on ultrasound was considered diagnostic of enterocolitis. There were 231 episodes of enterocolitis with a death rate of 11.7%. Previous therapy with cytarabine and the presence of abdominal distention affected survival. An intestinal wall thickness of >or=10 mm in the ultrasonographic examination was associated with greater mortality. In multivariate analysis, age, gender, tumor type, degree of neutropenia, intestinal wall thickness, and number of intestinal segments were not statistically significant difference. In children and young adults with cancer and enterocolitis, the clinical findings of 4 or more symptoms and presence of abdominal distention were associated with higher risk of death. Use of cytarabine and an intestinal wall thickness of >or=10 mm were associated with a higher death rate.

  10. OPTIMIZATION OF DIAGNOSTIC IMAGING IN BREAST CANCER

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    S. A. Velichko

    2015-01-01

    Full Text Available The paper presents the results of breast imaging for 47200 women. Breast cancer was detected in 862 (1.9% patients, fibroadenoma in 1267 (2.7% patients and isolated breast cysts in 1162 (2.4% patients. Different types of fibrocystic breast disease (adenosis, diffuse fibrocystic changes, local fibrosis and others were observed in 60.1% of women. Problems of breast cancer visualization during mammography, characterized by the appearance of fibrocystic mastopathy (sclerosing adenosis, fibrous bands along the ducts have been analyzed. Data on the development of diagnostic algorithms including the modern techniques for ultrasound and interventional radiology aimed at detecting early breast cancer have been presented.  

  11. Building prognostic models for breast cancer patients using clinical variables and hundreds of gene expression signatures

    Directory of Open Access Journals (Sweden)

    Liu Yufeng

    2011-01-01

    Full Text Available Abstract Background Multiple breast cancer gene expression profiles have been developed that appear to provide similar abilities to predict outcome and may outperform clinical-pathologic criteria; however, the extent to which seemingly disparate profiles provide additive prognostic information is not known, nor do we know whether prognostic profiles perform equally across clinically defined breast cancer subtypes. We evaluated whether combining the prognostic powers of standard breast cancer clinical variables with a large set of gene expression signatures could improve on our ability to predict patient outcomes. Methods Using clinical-pathological variables and a collection of 323 gene expression "modules", including 115 previously published signatures, we build multivariate Cox proportional hazards models using a dataset of 550 node-negative systemically untreated breast cancer patients. Models predictive of pathological complete response (pCR to neoadjuvant chemotherapy were also built using this approach. Results We identified statistically significant prognostic models for relapse-free survival (RFS at 7 years for the entire population, and for the subgroups of patients with ER-positive, or Luminal tumors. Furthermore, we found that combined models that included both clinical and genomic parameters improved prognostication compared with models with either clinical or genomic variables alone. Finally, we were able to build statistically significant combined models for pathological complete response (pCR predictions for the entire population. Conclusions Integration of gene expression signatures and clinical-pathological factors is an improved method over either variable type alone. Highly prognostic models could be created when using all patients, and for the subset of patients with lymph node-negative and ER-positive breast cancers. Other variables beyond gene expression and clinical-pathological variables, like gene mutation status or DNA

  12. Prognostic impact of tumor MET expression among patients with stage IV gastric cancer

    DEFF Research Database (Denmark)

    Erichsen, Rune; Kelsh, Michael A; Oliner, Kelly S;

    2016-01-01

    PURPOSE: We aimed to investigate the prevalence and prognostic impact of tumor mesenchymal epithelial transition factor (MET) expression in stage IV gastric cancers in a real-world clinical setting because existing evidence is sparse. METHODS: The study included archived cancer specimens from 103...

  13. Gradually implemented new biomarkers for prognostication of breast cancer : complete case analysis may introduce bias

    NARCIS (Netherlands)

    Pathy, Nirmala Bhoo; Uiterwaal, Cuno S. P. M.; Taib, Nur Aishah; Verkooijen, Helena M.; Yip, Cheng Har

    2012-01-01

    Objective: Many recent studies investigated the prognostic value of new biomarkers in breast cancer using data from cancer registries. Some of these studies were conducted using only patients for whom biomarker status was available (or tested). Using human epidermal growth factor receptor 2 (HER2) a

  14. Disseminated tumor cells in pancreatic cancer-an independent prognosticator of disease progression and survival

    NARCIS (Netherlands)

    Effenberger, Katharina E.; Schroeder, Cornelia; Eulenburg, Christine; Reeh, Matthias; Tachezy, Michael; Riethdorf, Sabine; Vashist, Yogesh K.; Izbicki, Jakob R.; Pantel, Klaus; Bockhorn, Maximilian

    2012-01-01

    Pancreatic cancer is one of the most devastating cancers with a 6-month median survival and a 5-year survival rate of 35%. Still important aspects of its aggressive biology remain elusive and advanced therapeutic regimens have not been substantially successful. We investigated the prognostic role of

  15. Pretreatment serum albumin: a prognostic indicator of survival in oral cancer

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    Saurabh Bobdey

    2016-06-01

    Conclusion: Pretreatment serum albumin levels are of useful prognostic significance in oral cancer patients. Thus, this easily accessible variable may not only serve as a potent marker to predict the outcomes, but more importantly as an indicator for initiating aggressive nutrition intervention in oral cancer patients. [Int J Res Med Sci 2016; 4(6.000: 2135-2141

  16. Aromatase, cyclooxygenase 2, HER-2/neu, and p53 as prognostic factors in endometrioid endometrial cancer

    NARCIS (Netherlands)

    Jongen, Vincent H. W. M.; Briet, Justine M.; de Jong, Renske A.; Joppe, Erna; ten Hoor, Klaske A.; Boezen, H. M.; Evans, Dean B.; Hollema, Harry; van der Zee, Ate G. J.; Nijman, Hans W.

    2009-01-01

    The prognostic value of aromatase, cyclooxygenase 2 (COX-2), HER-2/neu, and p53 expression was determined in endometrioid endometrial cancer. Tissue microarrays were constructed comprising samples from 315 endometrioid endometrial cancer patients. Expression of aromatase, COX-2, HER-2/neu, and p53 w

  17. Vectorcardiographic diagnostic & prognostic information derived from the 12-lead electrocardiogram: Historical review and clinical perspective.

    Science.gov (United States)

    Man, Sumche; Maan, Arie C; Schalij, Martin J; Swenne, Cees A

    2015-01-01

    In the course of time, electrocardiography has assumed several modalities with varying electrode numbers, electrode positions and lead systems. 12-lead electrocardiography and 3-lead vectorcardiography have become particularly popular. These modalities developed in parallel through the mid-twentieth century. In the same time interval, the physical concepts underlying electrocardiography were defined and worked out. In particular, the vector concept (heart vector, lead vector, volume conductor) appeared to be essential to understanding the manifestations of electrical heart activity, both in the 12-lead electrocardiogram (ECG) and in the 3-lead vectorcardiogram (VCG). Not universally appreciated in the clinic, the vectorcardiogram, and with it the vector concept, went out of use. A revival of vectorcardiography started in the 90's, when VCGs were mathematically synthesized from standard 12-lead ECGs. This facilitated combined electrocardiography and vectorcardiography without the need for a special recording system. This paper gives an overview of these historical developments, elaborates on the vector concept and seeks to define where VCG analysis/interpretation can add diagnostic/prognostic value to conventional 12-lead ECG analysis.

  18. Prediction of stroke-related diagnostic and prognostic measures using robot-based evaluation.

    Science.gov (United States)

    Mostafavi, Sayyed Mostafa; Glasgow, Janice I; Dukelow, Sean P; Scott, Stephen H; Mousavi, Parvin

    2013-06-01

    Traditional clinical scores for assessment of impairments resulting from stroke are inherently subjective and limited by inter-rater and intra-rater reliability. In contrast, robotic technologies provide objective, highly repeatable tools for quantification of motor performance of stroke subjects. Although use of robotic technologies has been widely suggested in the literature, they are not an established tool and their relationship to traditional clinical scales for stroke diagnosis and prognosis is mostly unknown. In this study we propose the application of two non-linear system identification methods, Parallel Cascade Identification and Fast Orthogonal Search, for prediction of stroke-related clinical scores using robot-based metrics. We show the suitability of these two methods for prediction of both diagnostic and prognostic scores. We compare our results with a previously applied approach based on linear regression and show the superiority of our modeling approach. Our results also underscore the importance of quantifying proprioceptive deficits in the prediction of motor-related prognosis scores.

  19. Traumatic extremity arterial injury in children: Epidemiology, diagnostics, treatment and prognostic value of Mangled Extremity Severity Score

    OpenAIRE

    Lange Nadine; Khaladj Nawid; Frink Michael; Hildebrand Frank; Zeckey Christian; Mommsen Philipp; Krettek Christian; Probst Christian

    2010-01-01

    Abstract Background Traumatic paediatric arterial injuries are a great challenge due to low incidence and specific characteristics of paediatric anatomy and physiology. The aim of the present study was to investigate their epidemiology, diagnostic and therapeutic options and complications. Furthermore, the prognostic value of the Mangled Extremity Severity Score (MESS) was evaluated. Methods In a retrospective clinical study 44 children aged 9.0 ± 3.2 years treated for traumatic extremity art...

  20. Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential

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    Bendahl Pär-Ola

    2007-03-01

    Full Text Available Abstract Background Soft tissue sarcoma (STS diagnosis is challenging because of a multitude of histopathological subtypes, different genetic characteristics, and frequent intratumoral pleomorphism. One-third of STS metastasize and current risk-stratification is suboptimal, therefore, novel diagnostic and prognostic markers would be clinically valuable. We assessed the diagnostic and prognostic value of array-based gene expression profiles using 27 k cDNA microarrays in 177, mainly high-grade, STS of 13 histopathological subtypes. Results Unsupervised analysis resulted in two major clusters – one mainly containing STS characterized by type-specific genetic alterations and the other with a predominance of genetically complex and pleomorphic STS. Synovial sarcomas, myxoid/round-cell liposarcomas, and gastrointestinal stromal tumors clustered tightly within the former cluster and discriminatory signatures for these were characterized by developmental genes from the EGFR, FGFR, Wnt, Notch, Hedgehog, RAR and KIT signaling pathways. The more pleomorphic STS subtypes, e.g. leiomyosarcoma, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma and dedifferentiated/pleomorphic liposarcoma, were part of the latter cluster and were characterized by relatively heterogeneous profiles, although subclusters herein were identified. A prognostic signature partly characterized by hypoxia-related genes was identified among 89 genetically complex pleomorphic primary STS and could, in a multivariate analysis including established prognostic markers, independently predict the risk of metastasis with a hazard ratio of 2.2 (P = 0.04. Conclusion Diagnostic gene expression profiles linking signaling pathways to the different STS subtypes were demonstrated and a hypoxia-induced metastatic profile was identified in the pleomorphic, high-grade STS. These findings verify diagnostic utility and application of expression data for improved selection of high

  1. Prognostic value of the Glasgow Prognostic Score in metastatic colorectal cancer in the era of anti-EGFR therapies.

    Science.gov (United States)

    Dréanic, Johann; Maillet, Marianne; Dhooge, Marion; Mir, Olivier; Brezault, Catherine; Goldwasser, François; Chaussade, Stanislas; Coriat, Romain

    2013-01-01

    The Glasgow Prognostic Score (GPS), combination of C-reactive protein and albumin, has proven its prognostic value in metastatic colorectal cancer (mCRC) patients receiving conventional cytotoxic therapy. More recently, anti-EGFR therapies have been validated in mCRC and roll forward the patients' overall survival (OS). We aimed to evaluate the prognostic accuracy of the GPS in patients receiving anti-EGFR therapy in addition to conventional chemotherapy. From January 2007 to February 2012, consecutive mCRC patients who received 5-fluorouracil-based chemotherapy plus cetuximab were included in the present analysis. Patients were eligible for the study if they met the following criteria: advanced pathologically proven MCRC, age >18 years, adequate renal function (creatinine clearance >40 ml/min), C-reactive protein and albumin and performance status evaluation before treatment initiation. A total of 49 patients received cetuximab plus 5-fluorouracil-based chemotherapy (colon, n = 34; rectum, n = 15) and were treated with a median follow-up of 35 months (16.5-74.7). Median age was 48 years old. In addition to cetuximab, patients received oxaliplatin- (n = 34, 60%) or irinotecan (n = 15, 30%)-based chemotherapy. At time of diagnosis, 55, 29 and 16% of patients had a GPS of 0 (n = 27), 1 (n = 14) and 2 (n = 8), respectively. Fifty-five, 29 and 14 % of patients add one, two or ≥3 metastatic sites, respectively. Considering two groups (GPS = 0 and GPS ≥1), median progression-free survivals were significantly different (p = 0.0084). Median OS in the GPS 0, 1 and 2 groups were 38.2, 14 and 12.1 months, respectively (p = 0.0093). The results of the present study confirm that the GPS is still a simple and effective prognostic factor in the era of cetuximab therapy in mCRC patients.

  2. A Systems Engineering Approach to Electro-Mechanical Actuator Diagnostic and Prognostic Development

    Data.gov (United States)

    National Aeronautics and Space Administration — The authors have formulated a Comprehensive Systems Engineering approach to Electro-Mechanical Actuator (EMA) Prognostics and Health Management (PHM) system...

  3. Optical spectra analysis for breast cancer diagnostics

    Science.gov (United States)

    Belkov, S. A.; Kochemasov, G. G.; Lyubynskaya, T. E.; Maslov, N. V.; Nuzhny, A. S.; da Silva, L. B.; Rubenchik, A.

    2011-11-01

    Minimally invasive probe and optical biopsy system based on optical spectra recording and analysis seem to be a promising tool for early diagnostics of breast cancer. Light scattering and absorption spectra are generated continuously as far as the needle-like probe with one emitting and several collecting optical fibers penetrates through the tissues toward to the suspicious area. That allows analyzing not only the state of local site, but also the structure of tissues along the needle trace. The suggested method has the advantages of automated on-line diagnosing and minimal tissue destruction and in parallel with the conventional diagnostic procedures provides the ground for decision-making. 165 medical trials were completed in Nizhny Novgorod Regional Oncology Centre, Russia. Independent diagnoses were the results of fine biopsy and histology. Application of wavelet expansion and clasterization techniques for spectra analysis revealed several main spectral types for malignant and benign tumors. Automatic classification algorithm demonstrated specificity ˜90% and sensitivity ˜91%. Large amount of information, fuzziness in criteria and data noisiness make neural networks to be an attractive analytic tool. The model based on three-layer perceptron was tested over the sample of 29 `cancer' and 29 `non-cancer' cases and demonstrated total separation.

  4. Prognostic factors of second primary contralateral breast cancer in early-stage breast cancer

    Science.gov (United States)

    LI, ZHENG; SERGENT, FABRICE; BOLLA, MICHEL; ZHOU, YUNFENG; GABELLE-FLANDIN, ISABELLE

    2015-01-01

    The aim of the present study was to investigate the therapeutic outcome of early-stage breast cancer (pT1aN0M0) and to identify prognostic factors for secondary primary contralateral breast cancer (CBC). A total of 85 patients with mammary carcinomas were included. All patients had undergone breast surgery and adjuvant treatment between January 2001 and December 2008 at the Central Hospital of Grenoble University (Grenoble, France). The primary end-points were disease-free survival and secondary CBC, and the potential prognostic factors were investigated. During a median follow-up of 60 months, 10 of the 85 patients presented with secondary primary cancer, of which six suffered with CBC. No patient mortalities were reported. The rates of CBC were 2.35, 3.53 and 7.06% at one, two and five years, respectively. The cumulative univariate analysis showed that microinvasion and family history are potential risk factors for newly CBC. The current study also demonstrated that secondary CBC was more likely to occur in patients with microinvasion or a family history of hte dise. In addition, the systematic treatment of secondary CBC should include hormone therapy. PMID:25435968

  5. Estimation of the extent of local prostate cancer spread according to magnetic resonance imaging findings and clinical prognostic factors

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    A. T. Kazymov

    2015-01-01

    Full Text Available To estimate the extent of local tumor spread is a main goal in the diagnosis of prostate cancer (PC. The value of this criterion is that its clinical stage plays a key role in choosing a treatment policy. Overestimation of the clinical stage of cancer leads to the fact that specialists refuse radical and its underestimation gives rise to its recurrence. Our trial defined criteria for the diagnostic efficiency of magnetic resonance imaging (MRI in 150 PC patients who had undergone radical prostatectomy. The findings were as follows: the diagnostic sensitivity of the method in determining the spread of the cancer beyond the organ was 76.8 %; its diagnostic specificity and accuracy were 80.2 and 78.7 %, respectively. The positive predictive value in detecting the extra-organ spread of the tumor was equal to 76.8 %; the negative predictive value was 80.2 %. A prognostic classification of a risk for locally advanced PS has been developed using the independent clinical and MRI signs found.

  6. Urokinase plasminogen activator receptor on invasive cancer cells: A prognostic factor in distal gastric adenocarcinoma

    DEFF Research Database (Denmark)

    Alpizar, Warner Enrique Alpizar; Christensen, Ib Jarle; Santoni-Rugiu, Eric

    2012-01-01

    Gastric cancer is the second cancer causing death worldwide. The five-year survival for this malignancy is below 25% and few parameters have shown an impact on the prognosis of the disease. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation...... by mediating cell surface associated plasminogen activation, and its presence on gastric cancer cells is linked to micrometastasis and poor prognosis. Using immunohistochemistry, the prognostic significance of uPAR was evaluated in tissue samples from a retrospective series of 95 gastric cancer patients. u...... association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor...

  7. IGFBP3 methylation is a novel diagnostic and predictive biomarker in colorectal cancer.

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    Lucia Perez-Carbonell

    Full Text Available Aberrant hypermethylation of cancer-related genes has emerged as a promising strategy for the development of diagnostic, prognostic and predictive biomarkers in human cancer, including colorectal cancer (CRC. The aim of this study was to perform a systematic and comprehensive analysis of a panel of CRC-specific genes as potential diagnostic, prognostic and predictive biomarkers in a large, population-based CRC cohort.Methylation status of the SEPT9, TWIST1, IGFBP3, GAS7, ALX4 and miR137 genes was studied by quantitative bisulfite pyrosequencing in a population-based cohort of 425 CRC patients.Methylation levels of all genes analyzed were significantly higher in tumor tissues compared to normal mucosa (p<0.0001; however, cancer-associated hypermethylation was most frequently observed for miR137 (86.7% and IGFBP3 (83% in CRC patients. Methylation analysis using the combination of these two genes demonstrated greatest accuracy for the identification of colonic tumors (sensitivity 95.5%; specificity 90.5%. Low levels of IGFBP3 promoter methylation emerged as an independent risk factor for predicting poor disease free survival in stage II and III CRC patients (HR = 0.49, 95% CI: 0.28-0.85, p = 0.01. Our results also suggest that stage II & III CRC patients with high levels of IGFBP3 methylation do not benefit from adjuvant 5FU-based chemotherapy.By analyzing a large, population-based CRC cohort, we demonstrate the potential clinical significance of miR137 and IGFBP3 hypermethylation as promising diagnostic biomarkers in CRC. Our data also revealed that IGFBP3 hypermethylation may serve as an independent prognostic and predictive biomarker in stage II and III CRC patients.

  8. Short-Term Prognostic Index for Breast Cancer: NPI or Lpi

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    V. Van Belle

    2011-01-01

    Full Text Available Axillary lymph node involvement is an important prognostic factor for breast cancer survival but is confounded by the number of nodes examined. We compare the performance of the log odds prognostic index (Lpi, using a ratio of the positive versus negative lymph nodes, with the Nottingham Prognostic Index (NPI for short-term breast cancer specific disease free survival. A total of 1818 operable breast cancer patients treated in the University Hospital of Leuven between 2000 and 2005 were included. The performance of the NPI and Lpi were compared on two levels: calibration and discrimination. The latter was evaluated using the concordance index (cindex, the number of patients in the extreme groups, and difference in event rates between these. The NPI had a significant higher cindex, but a significant lower percentage of patients in the extreme risk groups. After updating both indices, no significant differences between NPI and Lpi were noted.

  9. Routine ventilation scans in children with cystic fibrosis: diagnostic usefulness and prognostic value

    Energy Technology Data Exchange (ETDEWEB)

    Jaffe, A.; Hamutcu, R.; Adler, B.; Rosenthal, M.; Bush, A. [Dept. of Respiratory Paediatrics, Royal Brompton and Harefield, London (United Kingdom); Dhawan, R.T. [Department of Nuclear Medicine, Royal Brompton and Harefield, London (United Kingdom)

    2001-09-01

    Krypton ventilation scans (VS) provide an index of peripheral lung function, and may be particularly useful in children unable to perform pulmonary function testing. This communication reports on three linked studies which investigated whether a routine VS in young children with cystic fibrosis (CF) is diagnostically or prognostically useful. Study 1: In a preliminary study in 1991, VS were compared with clinical examination and chest radiography (CXR) in 50 CF children (29 females, 21 males) aged 0.4-5.2 years (median 2.2 years). The chest was divided into six zones, and abnormalities scored from 0 (normal) to 2 (very abnormal). Clinical examination was unhelpful in predicting abnormalities on imaging. In five children (10%) with a normal CXR, VS was abnormal, and in a further eight children (16%), CXR markedly underestimated VS changes. Study 2: In order to determine the long-term prognostic significance of VS abnormalities, we followed up 27 (19 females, 8 males) of the children from study 1, who had had their first VS at presentation at median age 1.6 years (range 0.4-5.2), scoring the same six zones from 0 to 2. Follow-up was for a mean of 11.6 years (range 7.8-14.8). Spirometry at age 7 years showed a mean forced expiratory volume in 1 s (FEV{sub 1}) of 96% (range 46%-145%) and a mean forced vital capacity (FVC) of 96% (range 46%-145%). A poor VS score at presentation was correlated with percent predicted FEV{sub 1} at age 7 (r=0.4, P=0.042, 16% of variance explained). Those with a normal VS at presentation had a mean FEV{sub 1} at presentation of 99% (range 80%-129%). Whereas four patients had an abnormal VS, a normal CXR and a low FEV{sub 1} at age 7 years, no patient had a normal VS, an abnormal CXR and a low FEV{sub 1}at age 7 years. Study 3: Fifty children (29 females, 21 males) aged 0.5-6.0 years (median 3.8) were prospectively studied in 1998, to determine whether the findings in study 1 were stable over time, and to assess whether VS altered clinical

  10. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer.

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    Stefanie Aust

    Full Text Available Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC. Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs ascertained by pre-operative computed tomography (CT. Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients.We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient's outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis.Muscle attenuation (MA-a well established BCM parameter-is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028. Low MA-reflecting a state of cachexia-is also associated with residual tumor after cytoreductive surgery (p = 0.046 and with an unfavorable performance status (p = 0.015. Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively.MA-ascertained by routine pre-operative CT-is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA.

  11. CCNA2 Is a Prognostic Biomarker for ER+ Breast Cancer and Tamoxifen Resistance

    OpenAIRE

    Tian Gao; Yong Han; Ling Yu; Sheng Ao; Ziyu Li; Jiafu Ji

    2014-01-01

    Identification of effective prognostic biomarkers and targets are of crucial importance to the management of estrogen receptor positive (ER+) breast cancer. CCNA2 (also known as CyclinA2) belongs to the highly conserved cyclin family and is significantly overexpressed in various cancer types. In this study, we demonstrated that CCNA2 had significant predictive power in distant metastasis free survival, disease free survival, recurrence free survival and overall survival of ER+ breast cancer p...

  12. Current early diagnostic biomarkers of prostate cancer

    Directory of Open Access Journals (Sweden)

    Min Qu

    2014-08-01

    Full Text Available Prostate cancer (PCa has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers.

  13. The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer

    DEFF Research Database (Denmark)

    You, Benoit; Colomban, Olivier; Heywood, Mark;

    2013-01-01

    Unexpected results were recently reported about the poor surrogacy of Gynecologic Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian cancer (ROC) patients. Mathematical modeling may help describe CA-125 decline dynamically and discriminate prognostic kinetic parameters....

  14. Lung cancer symptoms and pulse oximetry in the prognostic assessment of patients with lung cancer

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    Harada Cecilia M

    2005-07-01

    Full Text Available Abstract Background Medical oncologists continue to use performance status as a proxy for quality of life (QOL measures, as completion of QOL instruments is perceived as time consuming, may measure aspects of QOL not affected by cancer therapy, and interpretation may be unclear. The pulse oximeter is widely used in clinical practice to predict cardiopulmonary morbidity after lung resection in cancer patients, but little is known on its role outside the surgical setting. We evaluated whether the Lung Cancer Symptom Scale and pulse oximetry may contribute to the evaluation of lung cancer patients who received standard anticancer therapy. Methods We enrolled forty-one consecutive, newly diagnosed, patients with locally advanced or metastatic lung cancer in this study. We developed a survival model with the variables gender, age, histology, clinical stage, Karnofsky performance status, wasting, LCSS symptom scores, average symptom burden index, and pulse oximetry (SpO2. Results Patient and observer-rated scores were correlated, except for the fatigue subscale. The median SpO2 was 95% (range: 86 to 98, was unrelated to symptom scores, and was weakly correlated with observer cough scores. In a multivariate survival model, SpO2 > 90% and patient scores on the LCSS appetite and fatigue subscales were independent predictors of survival. Conclusion LCSS fatigue and appetite rating, and pulse oximetry should be studied further as prognostic factors in lung cancer patients.

  15. Prognostic impact of metastatic lymph node ratio on gastric cancer after curative distal gastrectomy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the prognostic impact of metastatic lymph node ratio(rN) on gastric cancer after curative distal gastrectomy.METHODS:A total of 634 gastric cancer patients who underwent curative resection(R0) of lymph nodes at distal gastrectomy in 1995-2004.Correlations between positive nodes and retrieved nodes,between rN and retrieved nodes,and between rN and negative lymph node(LN) count were analyzed respectively.Prognostic factors were identif ied by univariate and multivariate analyses.Staging acc...

  16. Novel non invasive diagnostic strategies in bladder cancer.

    Science.gov (United States)

    Truta, Anamaria; Popon, Tudor Adrian Hodor; Saraci, George; Ghervan, Liviu; Pop, Ioan Victor

    2016-01-01

    Bladder cancer is one of the most commonly diagnosed malignancies worldwide, derived from the urothelium of the urinary bladder and defined by long asymptomatic and atypical clinical picture. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. Various genetic polymorphisms and microRNA might represent useful diagnostic or prognostic biomarkers. Genetic and molecular abnormalities - risk factors are represented by miRNA or genetic polymorphisms proved to be part of bladder carcinogenesis such as: genetic mutations of oncogenes TP53, Ras, Rb1 or p21 oncoproteins, cyclin D or genetic polymorhisms of XPD,ERCC1, CYP1B1, NQO1C609T, MDM2SNP309, CHEK2, ERCC6, NRF2, NQO1Pro187Ser polymorphism and microRNA (miR-143, -145, -222, -210, -10b, 576-3p). The aim of our article is to highlight the most recent acquisitions via molecular biomarkers (miRNAs and genetic polymorphisms) involved in bladder cancer in order to provide early diagnosis, precise therapy according to the molecular profile of bladder tumors, as well as to improve clinical outcome, survival rates and life quality of oncological patients. These molecular biomarkers play a key role in bladder carcinogenesis, clinical evolution, prognosis and therapeutic response and explain the molecular mechanisms involved in bladder carcinogenesis; they can also be selected as therapeutic targets in developing novel therapeutic strategies in bladder malignancies. Moreover, the purpose in defining these molecular non invasive biomarkers is also to develop non invasive screening programs in bladder malignancies with the result of decreasing bladder cancer incidence in risk population.

  17. BAP1 facilitates diagnostic objectivity, classification, and prognostication in malignant pleural mesothelioma.

    Science.gov (United States)

    McGregor, Stephanie M; Dunning, Ryan; Hyjek, Elizabeth; Vigneswaran, Wickii; Husain, Aliya N; Krausz, Thomas

    2015-11-01

    BRCA-associated protein 1 (BAP1) has emerged as a promising biomarker for malignant pleural mesothelioma (MPM). Loss of BAP1 expression can occur by a variety of mechanisms, but reports on incidence are variable and the clinical significance is unclear. In order to investigate the diagnostic and prognostic significance of BAP1, we constructed a tissue microarray consisting of 111 MPM cases and performed BAP1 immunohistochemistry. BAP1 was lost in 77% of epithelioid cases (n=58) but was retained in all sarcomatoid cases (n=10); 49% of biphasic cases showed loss (n=43), and BAP1-negative cases demonstrated loss of staining in both the epithelioid and sarcomatoid components. All non-neoplastic mesothelial tissues (n=20) retained BAP1, resulting in a sensitivity, specificity, positive predictive value, and negative predictive value of 61%, 100%, 100%, and 32%, respectively. Moreover, BAP1 expression in spindled mesothelium enabled discrimination of reactive and malignant cells, thus providing a more objective means of distinguishing epithelioid from biphasic morphology compared to histology alone. Nonetheless, BAP1 staining was patchy in some benign mesothelial neoplasms, which raises concern for using BAP1 in small biopsies. Kaplan-Meier analysis demonstrated a significant improvement in overall survival with BAP1 loss, but this did not reach significance in multivariate analysis accounting for histologic subtype. When only epithelioid cases were analyzed there was a trend toward increased survival, but it did not reach significance. We conclude that BAP1 loss is frequent in epithelioid MPM, which is in turn associated with improved survival, and that it can have additional clinical significance by facilitating histologic classification.

  18. Mucins as diagnostic and prognostic biomarkers in a fish-parasite model: transcriptional and functional analysis.

    Directory of Open Access Journals (Sweden)

    Jaume Pérez-Sánchez

    Full Text Available Mucins are O-glycosylated glycoproteins present on the apex of all wet-surfaced epithelia with a well-defined expression pattern, which is disrupted in response to a wide range of injuries or challenges. The aim of this study was to identify mucin gene sequences of gilthead sea bream (GSB, to determine its pattern of distribution in fish tissues and to analyse their transcriptional regulation by dietary and pathogenic factors. Exhaustive search of fish mucins was done in GSB after de novo assembly of next-generation sequencing data hosted in the IATS transcriptome database (www.nutrigroup-iats.org/seabreamdb. Six sequences, three categorized as putative membrane-bound mucins and three putative secreted-gel forming mucins, were identified. The transcriptional tissue screening revealed that Muc18 was the predominant mucin in skin, gills and stomach of GSB. In contrast, Muc19 was mostly found in the oesophagus and Muc13 was along the entire intestinal tract, although the posterior intestine exhibited a differential pattern with a high expression of an isoform that does not share a clear orthologous in mammals. This mucin was annotated as intestinal mucin (I-Muc. Its RNA expression was highly regulated by the nutritional background, whereas the other mucins, including Muc2 and Muc2-like, were expressed more constitutively and did not respond to high replacement of fish oil (FO by vegetable oils (VO in plant protein-based diets. After challenge with the intestinal parasite Enteromyxum leei, the expression of a number of mucins was decreased mainly in the posterior intestine of infected fish. But, interestingly, the highest down-regulation was observed for the I-Muc. Overall, the magnitude of the changes reflected the intensity and progression of the infection, making mucins and I-Muc, in particular, reliable markers of prognostic and diagnostic value of fish intestinal health.

  19. Diagnostic and prognostic value of SHOX2 and SEPT9 DNA methylation and cytology in benign, paramalignant and malignant pleural effusions.

    Directory of Open Access Journals (Sweden)

    Dimo Dietrich

    Full Text Available Pleural effusions (PE are a common clinical problem. The discrimination between benign (BPE, malignant (MPE and paramalignant (PPE pleural effusions is highly important to ensure appropriate patient treatment. Today, cytology is the gold standard for diagnosing malignant pleural effusions. However, its sensitivity is limited due to the sometimes low abundance of tumor cells and the challenging assessment of cell morphology in cytological samples. This study aimed to develop and validate a diagnostic test, which allows for the highly specific detection of malignant cells in pleural effusions based on the DNA methylation biomarkers SHOX2 and SEPT9. A quantitative real-time PCR assay was developed which enabled the accurate and sensitive detection of SHOX2 and SEPT9 in PEs. Cytological and DNA methylation analyses were conducted in a case control study comprised of PEs from 114 patients (58 cases, 56 controls. Cytological analysis as well as SHOX2 and SEPT9 methylation resulted in 100% specificity. 21% of the cases were cytologically positive and 26% were SHOX2 or SEPT9 methylation positive. The combined analysis of cytology and DNA methylation resulted in an increase of 71% positively classified PEs from cancer patients as compared to cytological analysis alone. The absolute sensitivity of cytology and DNA methylation was not determinable due to the lack of an appropriate gold standard diagnostic for distinguishing between MPEs and PPEs. Therefore, it was unclear which PEs from cancer patients were malignant (containing tumor cells and which PEs were paramalignant and resulted from benign conditions in cancer patients, respectively. Furthermore, DNA methylation analysis in PEs allowed the prognosis of the overall survival in cancer patients (Kaplan-Meier analysis, log rank test, p=0.02 (SHOX2, p=0.02 (SEPT9. The developed test may be used as a diagnostic and prognostic adjunct to existing clinical and cytopathological investigations in patients

  20. Diagnostic and prognostic value of SHOX2 and SEPT9 DNA methylation and cytology in benign, paramalignant and malignant pleural effusions.

    Science.gov (United States)

    Dietrich, Dimo; Jung, Maria; Puetzer, Svenja; Leisse, Annette; Holmes, Emily Eva; Meller, Sebastian; Uhl, Barbara; Schatz, Philipp; Ivascu, Claudia; Kristiansen, Glen

    2013-01-01

    Pleural effusions (PE) are a common clinical problem. The discrimination between benign (BPE), malignant (MPE) and paramalignant (PPE) pleural effusions is highly important to ensure appropriate patient treatment. Today, cytology is the gold standard for diagnosing malignant pleural effusions. However, its sensitivity is limited due to the sometimes low abundance of tumor cells and the challenging assessment of cell morphology in cytological samples. This study aimed to develop and validate a diagnostic test, which allows for the highly specific detection of malignant cells in pleural effusions based on the DNA methylation biomarkers SHOX2 and SEPT9. A quantitative real-time PCR assay was developed which enabled the accurate and sensitive detection of SHOX2 and SEPT9 in PEs. Cytological and DNA methylation analyses were conducted in a case control study comprised of PEs from 114 patients (58 cases, 56 controls). Cytological analysis as well as SHOX2 and SEPT9 methylation resulted in 100% specificity. 21% of the cases were cytologically positive and 26% were SHOX2 or SEPT9 methylation positive. The combined analysis of cytology and DNA methylation resulted in an increase of 71% positively classified PEs from cancer patients as compared to cytological analysis alone. The absolute sensitivity of cytology and DNA methylation was not determinable due to the lack of an appropriate gold standard diagnostic for distinguishing between MPEs and PPEs. Therefore, it was unclear which PEs from cancer patients were malignant (containing tumor cells) and which PEs were paramalignant and resulted from benign conditions in cancer patients, respectively. Furthermore, DNA methylation analysis in PEs allowed the prognosis of the overall survival in cancer patients (Kaplan-Meier analysis, log rank test, p=0.02 (SHOX2), p=0.02 (SEPT9)). The developed test may be used as a diagnostic and prognostic adjunct to existing clinical and cytopathological investigations in patients with PEs of

  1. Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Freedland, Stephen J., E-mail: steve.freedland@duke.edu [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Gerber, Leah [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Reid, Julia; Welbourn, William; Tikishvili, Eliso; Park, Jimmy; Younus, Adib; Gutin, Alexander; Sangale, Zaina; Lanchbury, Jerry S. [Myriad Genetics, Inc, Salt Lake City, Utah (United States); Salama, Joseph K. [Department of Radiation Oncology, Durham VA Medical Center, Durham, North Carolina (United States); Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Stone, Steven [Myriad Genetics, Inc, Salt Lake City, Utah (United States)

    2013-08-01

    Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.

  2. A Survey of Attitudes towards the Clinical Application of Systemic Inflammation Based Prognostic Scores in Cancer

    Directory of Open Access Journals (Sweden)

    David G. Watt

    2015-01-01

    Full Text Available Introduction. The systemic inflammatory response (SIR plays a key role in determining nutritional status and survival of patients with cancer. A number of objective scoring systems have been shown to have prognostic value; however, their application in routine clinical practice is not clear. The aim of the present survey was to examine the range of opinions internationally on the routine use of these scoring systems. Methods. An online survey was distributed to a target group consisting of individuals worldwide who have reported an interest in systemic inflammation in patients with cancer. Results. Of those invited by the survey (n=238, 65% routinely measured the SIR, mainly for research and prognostication purposes and clinically for allocation of adjuvant therapy or palliative chemotherapy. 40% reported that they currently used the Glasgow Prognostic Score/modified Glasgow Prognostic Score (GPS/mGPS and 81% reported that a measure of systemic inflammation should be incorporated into clinical guidelines, such as the definition of cachexia. Conclusions. The majority of respondents routinely measured the SIR in patients with cancer, mainly using the GPS/mGPS for research and prognostication purposes. The majority reported that a measure of the SIR should be adopted into clinical guidelines.

  3. Methodological Aspects of Prognostic Classifications: Applications in Testicular Cancer

    NARCIS (Netherlands)

    M.R. van Dijk (Merel)

    2007-01-01

    textabstractPatients with similar characteristics can be grouped together in a prognostic classification to estimate a patient’s prognosis and guide treatment decisions. The topic of this thesis is methodological aspects of defining prognosis classifications. We specifically looked at patients wi

  4. Three dimensional diagnostic, semidiagnostic and prognostic calculations of current in the East China Sea in April of 1994

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Three dimensional diagnostic, semidiagnostic and prognostic models in the a-coordinate are used to compute the current in the Fast China Sea with wind and hydrographic data obtained from the investigation of ocean fluxes in the East China Sea during the cruise of April 1994. The computed results show that: the density and velocity fields and so on have been adjusted when time t≈ 23 d,i. e., the solution of semidiagnostic calculation has been obtained. The quasi-steady state solution also has been reached after about 60 d. Comparing the results of diagnostic calculation with those of semidiagnostic and prognostic calculations, it is found that they agree qualitatively For example, they all show that: (1) The Kuroshio flows along the shelf break of 200~ 1 000m isobaths; (2) In the southeastern part of the computational region there is a stronger counter-current with an anticyclonic eddy; (3) The volume transport through Section lPN is about 30 × 106m3/s and so on. However there are some quantitative differences between them. For example, (1) For the semidiagnostic results the Kuroshio current is stronger and clearer than that for diagnostic results and the Kuroshio width is more narrow than that for diagnostic results. This shows that the semidiagnostic calculation can better reflect the topography effect; (2) In most computed region the vertical component of velocity intensifies for semidiagnostic result, especially on the shelf break. Comparing the results of semidiagnostic calculation with those of prognostic calculation, they agree qualitatively, and also agree quantitatively in the middle of computed region.

  5. Clinical implications of serum N-glycan profiling as a diagnostic and prognostic biomarker in germ-cell tumors.

    Science.gov (United States)

    Narita, Takuma; Hatakeyama, Shingo; Yoneyama, Tohru; Narita, Shintaro; Yamashita, Shinichi; Mitsuzuka, Koji; Sakurai, Toshihiko; Kawamura, Sadafumi; Tochigi, Tatsuo; Takahashi, Ippei; Nakaji, Shigeyuki; Tobisawa, Yuki; Yamamoto, Hayato; Koie, Takuya; Tsuchiya, Norihiko; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara

    2017-03-20

    Serum biomarker monitoring is essential for management of germ-cell tumors (GCT). However, not all GCT are positive for conventional tumor markers. We examined whether serum N-glycan-based biomarkers can be applied for detection and prognosis in patients with GCT. We performed a comprehensive N-glycan structural analysis of sera from 54 untreated GCT patients and 103 age-adjusted healthy volunteers using glycoblotting methods and mass spectrometry. Candidate N-glycans were selected from those with the highest association; cutoff concentration values were established, and an N-glycan score was created based on the number of positive N-glycans present. The validity of this score for diagnosis and prognosis was analyzed using a receiver operating characteristic (ROC) curve. We identified five candidate N-glycans significantly associated with GCT patients. The accuracy of the N-glycan score for GCT was significant with an area-under-the-curve (AUC) value of 0.87. Diagnostically, the N-glycan score detected 10 of 12 (83%) patients with negative conventional tumor markers. Prognostically, the N-glycan score comprised four candidate N-glycans. The predictive value of the prognostic N-glycan score was significant, with an AUC value of 0.89. A high value prognostic N-glycan score was significantly associated with poor prognosis. Finally, to identify a potential carrier protein, immunoglobulin (Ig) fractions of sera were subjected to N-glycan analysis and compared to whole sera. Candidate N-glycans in Ig-fractions were significantly decreased; therefore, the carrier protein for candidate N-glycans is likely not an immunoglobulin. In summary, our newly developed N-glycan score seems to be a practical diagnostic and prognostic method for GCT.

  6. Nestin servers as a promising prognostic biomarker in non-small cell lung cancer.

    Science.gov (United States)

    Liu, Fang; Zhang, Yuan; Lu, Ming; Wang, Cong; Li, Qingbao; Gao, Yongsheng; Mu, Dianbin; Cao, Yan; Li, Miaomiao; Meng, Xiangjiao

    2017-01-01

    Lung cancer is currently the leading cause of cancer-related death worldwide and it is important to identify the predictive and/or prognostic markers for the cancer. Nestin, a proliferative and multipotent biomarker has been reported to be associated with prognosis in non-small cell lung cancer (NSCLC) in a few studies. In the present study, we retrospectively recruited 153 patients with NSCLC. Nestin protein expression in tumor samples was determined by immunohistochemistry staining. Nestin expression was related with tumor differentiation (P=0.036), lymphatic metastasis (N stage, P=0.011), and p-TNM stage (P=0.013), while there was no significant association between Nestin expression level and age, smoking habits, gender, histologic type, and T stage. Nestin was an independent prognostic factor for overall survival in NSCLC with an adjusted hazard ratio of 2.701 (95% CI, 1.616-4.513, PCRISPR/Cas9 mediated genome editing. It was observed that knockout of Nestin caused enhancement of cancer cell apoptosis and inhibition of cell proliferation, colony formation, and invasion in A549 and H1299 cell lines. Furthermore, we examined the expression of epithelial-mesenchymal transition (EMT) related biomarkers such as E-cadherin and Vimentin in Nestin-depleted lung cancer cells and knockout of Nestin was found to inhibit EMT, suggesting the involvement of Nestin mediated EMT signaling in lung cancer. The finding above demonstrated that Nestin might serve as a prognostic factor and therapeutic target in NSCLCs.

  7. The Prognostic Value of Circumferential Resection Margin Involvement in Patients with Extraperitoneal Rectal Cancer.

    Science.gov (United States)

    Shin, Dong Woo; Shin, Jin Yong; Oh, Sung Jin; Park, Jong Kwon; Yu, Hyeon; Ahn, Min Sung; Bae, Ki Beom; Hong, Kwan Hee; Ji, Yong Il

    2016-04-01

    The prognostic influence of circumferential resection margin (CRM) status in extraperitoneal rectal cancer probably differs from that of intraperitoneal rectal cancer because of its different anatomical and biological behaviors. However, previous reports have not provided the data focused on extraperitoneal rectal cancer. Therefore, the aim of this study was to examine the prognostic significance of the CRM status in patients with extraperitoneal rectal cancer. From January 2005 to December 2008, 248 patients were treated for extraperitoneal rectal cancer and enrolled in a prospectively collected database. Extraperitoneal rectal cancer was defined based on tumors located below the anterior peritoneal reflection, as determined intraoperatively by a surgeon. Cox model was used for multivariate analysis to examine risk factors of recurrence and mortality in the 248 patients, and multivariate logistic regression analysis was performed to identify predictors of recurrence and mortality in 135 patients with T3 rectal cancer. CRM involvement for extraperitoneal rectal cancer was present in 29 (11.7%) of the 248 patients, and was the identified predictor of local recurrence, overall recurrence, and death by multivariate Cox analysis. In the 135 patients with T3 cancer, CRM involvement was found to be associated with higher probability of local recurrence and mortality. In extraperitoneal rectal cancer, CRM involvement is an independent risk factor of recurrence and survival. Based on the results of the present study, it seems that CRM involvement in extraperitoneal rectal cancer is considered an indicator for (neo)adjuvant therapy rather than conventional TN status.

  8. Prognostic Significance of p16 Expression in Advanced Cervical Cancer Treated With Definitive Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Lewis, James S. [Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Pfeifer, John [Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States); Huettner, Phyllis [Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States); Grigsby, Perry [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States); Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO (United States)

    2012-09-01

    Purpose: The purpose of this study was to evaluate the prognostic significance of p16 immunohistochemistry (IHC) in patients with advanced cervical cancer treated with radiation therapy. Materials and Methods: This was a retrospective study of 126 patients with International Federation of Gynecology and Obstetrics Stages Ib1-IVb cervical cancer treated with radiation. Concurrent cisplatin chemotherapy was given to 108 patients. A tissue microarray (TMA) was constructed from the paraffin-embedded diagnostic biopsy specimens. Immunoperoxidase staining was performed on the TMA and a p16 monoclonal antibody was utilized. IHC p16 extent was evaluated and scored in quartiles: 0 = no staining, 1 = 1-25% of cells staining, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%. Results: The p16 IHC score was 4 in 115 cases, 3 in 1, 2 in 3 and 0 in 7. There was no relationship between p16 score and tumor histology. Patients with p16-negative tumors were older (mean age at diagnosis 65 vs. 52 years for p16-positive tumors; p = 0.01). The 5-year cause-specific survivals were 33% for p16-negative cases (score = 0) compared with 63% for p16-positive cases (scores 1, 2, 3 or 4; p = 0.07). The 5-year recurrence-free survivals were 34% for those who were p16-negative vs. 57% for those who were p16-positive (p = 0.09). In addition, patients with p16-positive tumors (score > 0) were more likely to be complete metabolic responders as assessed by the 3-month posttherapy 18 [F]-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomograph compared with patients with p16-negative tumors (p = 0.03). Conclusion: p16 expression is predictive of improved survival outcome after chemoradiation therapy for advanced-stage invasive cervical carcinoma. Further testing will be needed to evaluate p16-negative cervical tumors.

  9. Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer

    NARCIS (Netherlands)

    Oort, van I.M.; Witjes, J.A.; Kok, D.E.G.; Kiemeney, L.A.; Hulsbergen-van de Kaa, C.A.

    2008-01-01

    Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localized prostate c

  10. Maximum tumor diameter is not an independent prognostic factor in high-risk localized prostate cancer.

    NARCIS (Netherlands)

    Oort, I.M. van; Witjes, J.A.M.; Kok, D.E.; Kiemeney, L.A.L.M.; Hulsbergen- van de Kaa, C.A.

    2008-01-01

    OBJECTIVES: Previous studies suggest that maximum tumor diameter (MTD) is a predictor of recurrence in prostate cancer (PC). This study investigates the prognostic value of MTD for biochemical recurrence (BCR) in patients with PC, after radical prostatectomy (RP), with emphasis on high-risk localize

  11. The role of genetic breast cancer susceptibility variants as prognostic factors

    DEFF Research Database (Denmark)

    Fasching, Peter A; Pharoah, Paul D P; Cox, Angela

    2012-01-01

    Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 ...

  12. Prognostic and predictive relevance of CA-125 at primary surgery of ovarian cancer

    NARCIS (Netherlands)

    Mury, Dina; Woelber, Linn; Jung, Sabine; Eulenburg, Christine; Choschzick, Matthias; Witzel, Isabell; Schwarz, Joerg; Jaenicke, Fritz; Mahner, Sven

    2011-01-01

    Despite radical surgery and chemotherapy, most patients with ovarian cancer develop recurrence and die due to progressive disease. To stratify patients for optimal therapy, prognostic and predictive factors are needed. We examined the role of pre- and postoperative CA-125 in this context. A total of

  13. An overview of prognostic factors for long-term survivors of breast cancer

    NARCIS (Netherlands)

    I. Soerjomataram (Isabelle); M.W.J. Louwman (Marieke); J.G. Ribot (Jacques); J.A. Roukema; J.W.W. Coebergh (Jan Willem)

    2008-01-01

    textabstractBackground: Numerous studies have examined prognostic factors for survival of breast cancer patients, but relatively few have dealt specifically with 10+-year survivors. Methods: A review of the PubMed database from 1995 to 2006 was undertaken with the following inclusion criteria: media

  14. FDG-PET parameters as prognostic factor in esophageal cancer patients: a review

    NARCIS (Netherlands)

    J.M.T. Omloo; M. van Heijl; O.S. Hoekstra; M.I. van Berge Henegouwen; J.J.B. van Lanschot; G.W. Sloof

    2011-01-01

    (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used extensively to explore whether FDG Uptake can be used to provide prognostic information for esophageal cancer patients. The aim of the present review is to evaluate the literature available to date concerning the potential

  15. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Paulsen, Birgitte Sandfeld; Aggerholm-Pedersen, N; Bæk, R

    2016-01-01

    BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection...

  16. A patient-centered methodology that improves the accuracy of prognostic predictions in cancer.

    Directory of Open Access Journals (Sweden)

    Mohammed Kashani-Sabet

    Full Text Available Individualized approaches to prognosis are crucial to effective management of cancer patients. We developed a methodology to assign individualized 5-year disease-specific death probabilities to 1,222 patients with melanoma and to 1,225 patients with breast cancer. For each cancer, three risk subgroups were identified by stratifying patients according to initial stage, and prediction probabilities were generated based on the factors most closely related to 5-year disease-specific death. Separate subgroup probabilities were merged to form a single composite index, and its predictive efficacy was assessed by several measures, including the area (AUC under its receiver operating characteristic (ROC curve. The patient-centered methodology achieved an AUC of 0.867 in the prediction of 5-year disease-specific death, compared with 0.787 using the AJCC staging classification alone. When applied to breast cancer patients, it achieved an AUC of 0.907, compared with 0.802 using the AJCC staging classification alone. A prognostic algorithm produced from a randomly selected training subsample of 800 melanoma patients preserved 92.5% of its prognostic efficacy (as measured by AUC when the same algorithm was applied to a validation subsample containing the remaining patients. Finally, the tailored prognostic approach enhanced the identification of high-risk candidates for adjuvant therapy in melanoma. These results describe a novel patient-centered prognostic methodology with improved predictive efficacy when compared with AJCC stage alone in two distinct malignancies drawn from two separate populations.

  17. Prognostic value of p53 for high risk superficial bladder cancer with long-term followup.

    NARCIS (Netherlands)

    Moonen, P.M.J.; Balken-Ory, B. van; Kiemeney, L.A.L.M.; Schalken, J.A.; Witjes, J.A.

    2007-01-01

    PURPOSE: The risk of muscle invasive disease in a high risk patient with superficial bladder cancer is up to 50%. Identifying patients at risk for progression remains an unsolved problem. A suggested prognosticator is mutations in the p53 tumor suppressor gene. We determined the value of p53 mutatio

  18. FDG-PET parameters as prognostic factor in esophageal cancer patients: A review

    NARCIS (Netherlands)

    J.M. Omloo (Jikke); M. van Heijl (Mark); O.S. Hoekstra (Otto); M.I. van Berge Henegouwen (Mark); J.J.B. van Lanschot (Jan); G.W. Sloof (Gerrit)

    2011-01-01

    textabstractBackground:18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used extensively to explore whether FDG Uptake can be used to provide prognostic information for esophageal cancer patients. The aim of the present review is to evaluate the literature available to date con

  19. Serum cathepsin H as a potential prognostic marker in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Schweiger, A; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2005-01-01

    Cathepsin H is a lysosomal cysteine protease that may participate in tumor progression. In order to evaluate its potential as a prognostic marker, its protein levels were measured by ELISA in preoperative sera from 324 patients with colorectal cancer. The level of cathepsin H was significantly...

  20. The comparison of thrombocytosis and platelet-lymphocyte ratio as potential prognostic markers in colorectal cancer

    DEFF Research Database (Denmark)

    Baranyai, Zsolt; Krzystanek, Marcin; Josa, Valeria;

    2014-01-01

    The aim of the present study was to analyse the preoperative platelet count and the platelet-lymphocyte ratio (PLR) in patients with colorectal cancer (CRC) of different stages and with hepatic metastasis of CRC (mCRC) and to compare these factors as potential prognostic markers. Clinicopathologi...

  1. Limited independent prognostic value of MMP-14 and MMP-2 expression in ovarian cancer

    NARCIS (Netherlands)

    Vos, M.C.; Wurff, A.A. van der; Bulten, J.; Kruitwagen, R.; Feijen, H.; Kuppevelt, T.H. van; Hendriks, T.; Massuger, L.F.

    2016-01-01

    BACKGROUND: In cancer, various MMPs play a role in progression and metastasis and their overexpression generally indicates a poor prognosis. MMP-14 is the main activator of MMP-2 and both molecules play a role in normal ovarian follicular development. Earlier reports indicated a prognostic value for

  2. YKL-40 protein expression is not a prognostic marker in patients with primary breast cancer

    DEFF Research Database (Denmark)

    Roslind, A.; Knoop, A.S.; Jensen, Maiken Brit;

    2008-01-01

    YKL-40 is a new biomarker in serum with a prognostic value in several localized and metastatic malignancies. The current knowledge regarding the biological functions of YKL-40 in cancer links YKL-40 to increased aggressiveness of the tumor. Utilizing tissue microarrays, YKL-40 protein expression...

  3. Identification of potential prognostic markers for vulvar cancer using immunohistochemical staining of tissue microarrays.

    NARCIS (Netherlands)

    Fons, G.; Burger, M.P.; Kate, F.J. ten; Velden, J. van der

    2007-01-01

    The aim of this study is to determine immunohistochemical markers with prognostic significance for disease-specific survival in patients with squamous cell cancer of the vulva. The study material consisted of slides and paraffin blocks of 50 vulvectomy specimens. A tissue microarray was constructed

  4. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Torben F., E-mail: torben.hansen@slb.regionsyddanmark.dk; Spindler, Karen-Lise G. [Department of Oncology, Vejle Hospital, Vejle (Denmark); Andersen, Rikke F. [Department of Biochemistry, Vejle Hospital, Vejle (Denmark); Lindebjerg, Jan [Department of Clinical Pathology, Vejle Hospital, Vejle (Denmark); Kølvraa, Steen [Department of Clinical Genetics, Vejle Hospital, Vejle (Denmark); Brandslund, Ivan [Department of Biochemistry, Vejle Hospital, Vejle (Denmark); Jakobsen, Anders [Department of Oncology, Vejle Hospital, Vejle (Denmark)

    2010-06-28

    New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study was to investigate the prognostic importance of haplotypes in the VEGF-A gene in patients with CRC. The study included 486 patients surgically resected for stage II and III CRC, divided into two independent cohorts. Three SNPs in the VEGF-A gene were analyzed by polymerase chain reaction. Haplotypes were estimated using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible for this effect, was present in approximately 30% of the patients and demonstrated a significant relationship with poor survival, and it remained an independent prognostic marker after multivariate analysis, hazard ratio 2.46 (95% confidence interval 1.49–4.06), p < 0.001. Validation was provided by consistent findings in a second and independent cohort. Haplotype combinations call for further investigation.

  5. Terminology and details of the diagnostic process for testis cancer.

    LENUS (Irish Health Repository)

    Connolly, Stephen S

    2011-03-01

    We examined the process and causes of diagnostic delay, defined as the interval from symptom onset to diagnosis, for testis (germ cell) cancer and the change with time. Diagnostic delay influences disease burden and may be subdivided into symptomatic interval, defined as symptom onset to first presentation, and diagnostic interval, defined as first presentation to diagnosis.

  6. Pre-diagnostic cruciferous vegetables intake and lung cancer survival among Chinese women.

    Science.gov (United States)

    Wu, Qi-Jun; Yang, Gong; Zheng, Wei; Li, Hong-Lan; Gao, Jing; Wang, Jing; Gao, Yu-Tang; Shu, Xiao-Ou; Xiang, Yong-Bing

    2015-05-19

    No study to date has prospectively evaluated the association between pre-diagnostic cruciferous vegetables intake and lung cancer survival among women. This analysis included 547 incident lung cancer cases identified from the Shanghai Women's Health Study (SWHS) during the follow-up period of 1997-2011. Dietary intake was assessed for all SWHS participants at enrollment and reassessed 2-3 years later. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. Of the 547 lung cancer patients, 412 patients died during the follow-up. A total of 393 (95.4%) deaths from lung cancer were documented with median survival time of 10.3 months (interquartile range, 3.6-21.1 months). High cruciferous vegetables intake was significantly associated with improved lung cancer-specific survival after adjusting for all nonclinical prognostic factors (n = 547, HR = 0.69; 95%CI = 0.49-0.95; P trend = 0.02) for the highest versus lowest quartile. A slightly stronger association of cruciferous vegetables intake with lung cancer-specific survival was observed in analyses restricted to patients with known clinical prognostic factors (n = 331, HR = 0.63; 95%CI = 0.41-0.97; P trend = 0.03) or never smokers (n = 308, HR = 0.58; 95%CI = 0.37-0.91; P trend = 0.02). In conclusion, pre-diagnostic cruciferous vegetables intake is associated with better survival of lung cancer in Chinese women.

  7. Prognostic significance of new onset ascites in patients with pancreatic cancer

    OpenAIRE

    Luzardo German; Boe Brian A; Osborne Dana; Zervos Emmanuel E; Goldin Steven B; Rosemurgy Alexander S

    2006-01-01

    Abstract Background The purpose of this study was to determine risk factors for development of malignant ascites and its prognostic significance in patients with pancreatic cancer. Methods A prospective database was queried to identify patients with pancreatic cancer who develop ascites. Stage at presentation, size, and location of primary tumor, treatment received and length of survival after onset of ascites were determined. Results A total of 15 patients were identified. Of which 4 patient...

  8. Prognostic and therapeutic value of mitochondrial serine hydroxyl-methyltransferase 2 as a breast cancer biomarker.

    Science.gov (United States)

    Zhang, Lahong; Chen, Zhaojun; Xue, Dan; Zhang, Qi; Liu, Xiyong; Luh, Frank; Hong, Liquan; Zhang, Hang; Pan, Feng; Liu, Yuhua; Chu, Peiguo; Zheng, Shu; Lou, Guoqiang; Yen, Yun

    2016-11-01

    Mitochondrial serine hydroxylmethyltransferase 2 (SHMT2) is a key enzyme in the serine/glycine synthesis pathway. SHMT2 has been implicated as a critical component for tumor cell survival. The aim of the present study was to evaluate the prognostic value and efficiency of SHMT2 as a biomarker in patients with breast cancer. Individual and pooled survival analyses were performed on five independent breast cancer microarray datasets. Gene signatures enriched by SHMT2 were also analyzed in these datasets. SHMT2 protein expression was detected using immunohistochemistry (IHC) assay in 128 breast cancer cases. Gene set enrichment analysis revealed that SHMT2 was significantly associated with gene signatures of mitochondrial module, cancer invasion, metastasis and poor survival among breast cancer patients (prelevance of SHMT2 was validated on IHC data. The mitochondrial localization of SHMT2 protein was visualized on IHC staining. Independent and pooled analysis confirmed that SHMT2 expression was associated with breast cancer tumor aggressiveness (TNM staging and Elson grade) in a dose-dependent manner (pvalue for estrogen receptor (ER)-negative breast cancer patients, compared to ER-positive patients. In cases involving stage IIb breast cancer, chemotherapy significantly extended survival time among patients with high SHMT2 expression. These results indicate that SHMT2 may be a valuable prognostic biomarker in ER-negative breast cancer cases. Furthermore, SHMT2 may be a potential target for breast cancer treatment and drug discovery.

  9. Prognostic Significance of Apoptosis Related Gene Family bcl-2 in Human Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the prognostic effect of bcl-2 oncogene and its gene family members bax, bcl-x expression in breast cancer patients. Methods: expression of bcl-2, bax proteins in 91 human breast cancer tissue sections were studied by immunohistochemical method. Bcl-x1 mRNA expression in frozen tissues from 16 breast cancer patients were detected using Northern blot method. Results: bcl-2 protein positivity was found in 60/91 (65.9%) patients, and bax positivity 59/91 (64.8%). Bcl-2 and bax expression levels were associated with apoptotic index(AI), histological grade, axillary lymph node metastasis, postoperative local recurrence and metastasis. Bcl-2 expression was related to ER positivity. In univariate analysis for disease free survival (DFS), bcl-2 and bax protein levels, and Al were all found to have prognostic value. The result of Cox's model multivariate analysis showed that bcl-2 protein level was an independent prognostic factor. In 16 frozen breast cancer tissues, 8/16(50%) had higher level of bcl-x1 mRNA, which showed correlation with bcl-2 protein expression and axillary lymph node metastasis. Conclusion: The findings indicate that dysregulated expressions of bcl-2, bax and bcl-x1 apoptosis-related genes, suggestive of serious deregulation of apoptotic process, may contribute to the biologic aggressiveness of breast cancer. Bcl-2 protein is an independent indicator of prognosis in breast cancer patients.

  10. [Prognostic value of cell heterogeneity in cervical cancer determined by digital image analyzer of DNA content].

    Science.gov (United States)

    Pete, I; Gaudi, I; Szerdahelyi, A; Tóth, E; Pulay, T; Szentirmay, Z

    2000-10-01

    Frequency and prognostic value of cell heterogeneity in FIGO 1a-2a cervical cancer was examined, in 66 of patients underwent Wertheim type hysterectomy between 1989 and 1995 in National Institute of Cancer, Budapest, Hungary. A newly developed DNA image analyses (DNACE) was used in paraffin embedded tissues after enzymatic hydrolyses for evaluation of the DNA content in cervical cancer. In 30.3% of examined tissues (20/66) two subgroups was found. There was significant differences in the DNA indexes (DI) between the subgroups (p = 0.0001). In the remaining 69.7% of the cases only one subgroup was present. The frequency of two subgroups was higher between aneuploid (78.4%), or hyperploid (81.5%) type cervical cancer, however there was no significant difference between the two groups. On the other hand there was significant difference in the presence of two subgroups between the well and less differentiated cervical cancer. The frequency was higher between the less differentiated groups (p = 0.02). Looking at the prognostic value of subgroups, there was no significant correlation between the heterogeneity of cervical cancer and FIGO stage, or lymph node metastasis (p = 0.6855), or vascular/lymphatic space infiltration (p = 0.2558), or invasiveness of cancer (0.0823). There was neither significant value found between the outcome of disease and the number of subgroups present (p = 0.8738). It is though that the present of cellular heterogeneity in cervical cancer is connected with the differentiation of the cancer cells, and can be a good prognostic value in the anticipation of the aggressiveness of cervical cancer. Looking at the present result, there was no significant connection between the heterogeneity of cervical cancer and the outcome of the disease, so further examination should be done.

  11. Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Thomsen, Maria; Kersten, Christian; Sorbye, Halfdan

    2016-01-01

    OBJECTIVES: The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status. RESULTS...... 24.3 months to 12.3 months, (P BRAF mutation (interaction P = 0.004). MATERIALS AND METHODS: IL-6 and CRP were determined in pre-treatment serum samples...... with impaired prognosis in mCRC. IL-6 and CRP give independent prognostic information in addition to RAS and BRAF mutation status....

  12. Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

    DEFF Research Database (Denmark)

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke

    2016-01-01

    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways...... prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here...

  13. Clinical and pathological characteristics, and prognostic factors for gastric cancer survival in 155 patients in Bulgaria.

    Science.gov (United States)

    Angelov, Kostadin Georgiev; Vasileva, Mariela Borisova; Grozdev, Konstantin Savov; Sokolov, Manol Bonev; Todorov, Georgi

    2014-01-01

    Almost one million new cases of gastric cancer were estimated to have occurred in 2012, making it the fifth most common malignancy in the world. It is also the third leading cause of cancer death of people of both genders worldwide. The aim of this study is to evaluate the significance of some prognostic factors for gastric cancer survival in 155 patients treated at Aleksandrovska University Hospital, Sofia, Bulgaria. This retrospective study includes patients diagnosed and treated at Department of Surgery of Aleksandrovska University Hospital for the 9-years period of time between January 2005 and December 2013. We classified the prognostic factors as patient-related (age at diagnosis specification, gender, and blood type), tumor-related (N-stage, tumor differentiation, process localization), and treatment related (patients who had radical surgery and adjuvant therapy). We found that blood type is the only statistically significant prognostic factor for overall survival from the patients-related group of factors (p = 0.030). The only prognostic factor from the ones in the tumor related group remains the N-stage according to the TNM classification (p = 0.003). Adjuvant could not prove its value for overall survival (p = 0.675).

  14. Fuzzy logic-based prognostic score for outcome prediction in esophageal cancer.

    Science.gov (United States)

    Wang, Chang-Yu; Lee, Tsair-Fwu; Fang, Chun-Hsiung; Chou, Jyh-Horng

    2012-11-01

    Given the poor prognosis of esophageal cancer and the invasiveness of combined modality treatment, improved prognostic scoring systems are needed. We developed a fuzzy logic-based system to improve the predictive performance of a risk score based on the serum concentrations of C-reactive protein (CRP) and albumin in a cohort of 271 patients with esophageal cancer before radiotherapy. Univariate and multivariate survival analyses were employed to validate the independent prognostic value of the fuzzy risk score. To further compare the predictive performance of the fuzzy risk score with other prognostic scoring systems, time-dependent receiver operating characteristic curve (ROC) analysis was used. Application of fuzzy logic to the serum values of CRP and albumin increased predictive performance for 1-year overall survival (AUC=0.773) compared with that of a single marker (AUC=0.743 and 0.700 for CRP and albumin, respectively), where the AUC denotes the area under curve. This fuzzy logic-based approach also performed consistently better than the Glasgow Prognostic Score (GPS) (AUC=0.745). Thus, application of fuzzy logic to the analysis of serum markers can more accurately predict the outcome for patients with esophageal cancer.

  15. Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review

    Science.gov (United States)

    Fan, Gaowei; Zhang, Kuo; Yang, Xin; Ding, Jiansheng; Wang, Zujian; Li, Jinming

    2017-01-01

    The application of circulating tumor DNA(ctDNA) represents a non-invasive method for tumor detection. Its prognostic significance in patients with colorectal cancer is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in patients with colorectal cancer. We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to December 6, 2016. We evaluated the quality and design of these studies. A total of 22 studies were eligible for systematic review. Among them, 11 studies investigated the prognostic value of ctDNA on disease-free survival (DFS). Seven of 11 studies showed that ctDNA was an independent variable to estimate the probability of DFS by multivariate analyses. Thirteen studies assessed the relationship between ctDNA and overall survival (OS). Eight of 13 studies showed that ctDNA was an independent predictor of worse OS through the use of multivariate analyses. This analysis provides evidence that ctDNA may be a prognostic biomarker, negatively correlated with the survival of patients with colorectal cancer. PMID:28187169

  16. Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients.

    Science.gov (United States)

    Simpson, K; Jones, R E; Grimstead, J W; Hills, R; Pepper, C; Baird, D M

    2015-06-01

    Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.

  17. Superparamagnetic nanoparticles for cancer diagnostics and therapeutics

    Science.gov (United States)

    Kohler, Nathan

    2005-11-01

    This dissertation describes the development of a magnetic nanoparticle conjugate that can potentially serve as both a contrast enhancement agent in magnetic resonance imaging (MRI) and as a drug carrier in controlled drug release, targeted for cancer diagnostics and therapeutics. In this work, we developed a unique method to synthesize well-dispersed 10-nm superparamagnetic iron oxide nanoparticles (SPION) without using chemical surfactants. This approach is especially advantageous for subsequent surface modification of nanoparticles with functional coatings. To target the SPION for cancer cells in vivo to facilitate MRI contrast enhancement of tumors, we immobilized folic acid on the particle surface. Folic acid is a low molecular weight growth factor over-expressed on many forms of cancer. The covalent immobilization of folic acid to the nanoparticle surface was characterized with FTIR and the intracellular uptake of the folic acid nanoparticles was visualized with scanning confocal microscopy. To use SPION for controlled drug release, we immobilized methotrexate (MTX), a chemotherapeutic drug, to the nanoparticle surface. MTX-modified nanoparticles have several combined advantages including real-time monitoring of drug delivery using MRI, higher intracellular concentrations of methotrexate that increase cellular cytotoxicity, and reduced non-specific uptake by healthy cells within the body. We successfully conducted drug release experiments demonstrating that MTX was released under low pH conditions that mimic the intracellular conditions in the lysozome. To assess cellular cytotoxicity, we tested MTX-nanoparticle conjugates in human breast cancer cells (MCF-7), human cervical cancer cells (HeLa), and glioma cells (9L), and showed that the drug efficacy of MTX-nanoparticle conjugates was similar to that of free MTX. To improve nanoparticle circulation time and intracellular uptake, we developed a novel bifunctional poly(ethylene glycol) (PEG) SAM capable of

  18. Prognostic factors in a series of 504 breast cancer patients with metastatic spinal cord compression

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D.; Douglas, S. [University Hospital Schleswig-Holstein, Luebeck (Germany). Dept. of Radiation Oncology; Veninga, T. [Dr. Bernard Verbeeten Institute, Tilburg (Netherlands). Dept. of Radiation Oncology; Stalpers, L.J.A. [Academic Medical Center, Amsterdam (Netherlands). Dept. of Radiotherapy; Bajrovic, A. [University Hospital Hamburg-Eppendorf, Hamburg (Germany). Dept. of Radiation Oncology; Rudat, V. [Saad Specialist Hospital Al-Khobar, Al-Khobar (Saudi Arabia). Dept. of Radiation Oncology; Schild, S.E. [Mayo Clinic Scottsdale, Scottsdale, AZ (United States). Dept. of Radiation Oncology

    2012-04-15

    This study was performed to identify new significant prognostic factors in breast cancer patients irradiated for metastatic spinal cord compression (MSCC). The data of 504 patients with breast cancer patients with MSCC were retrospectively analyzed with respect to posttreatment motor function, local control of MSCC, and survival. The investigated potential prognostic factors included age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, other bone metastases, visceral metastases, pretreatment ambulatory status, interval from cancer diagnosis to radiotherapy of MSCC, time developing motor deficits before radiotherapy, and the radiation schedule. On multivariate analysis, better functional outcome was associated with ambulatory status prior to RT (estimate - 1.29, p < 0.001), no visceral metastases (estimate - 0.52, p = 0.020), and slower development of motor deficits (estimate + 2.47, p < 0.001). Improved local control was significantly associated with no other bone metastases (risk ratio (RR) 4.33, 95% confidence interval (CI) 1.36-14.02, p = 0.013) and no visceral metastases (RR 3.02, 95% CI 1.42-6.40, p = 0.005). Improved survival was significantly associated with involvement of only 1-2 vertebrae (RR 1.27, 95% CI 1.01-1.60, p = 0.044), ambulatory status before radiotherapy (RR 1.75, 95% CI 1.23-2.50, p = 0.002), no other bone metastases (RR 1.93, 95% CI 1.18-3.13, p = 0.009), no visceral metastases (RR 7.60, 95% CI 5.39-10.84, p < 0.001), and time developing motor deficits before radiotherapy (RR 1.55, 95% CI 1.30-1.86, p < 0.001). Several new independent prognostic factors were identified for treatment outcomes. These prognostic factors should be considered in future trials and may be used to develop prognostic scores for breast cancer patients with MSCC. (orig.)

  19. Prognostic Impact of VEGFA Germline Polymorphisms in Patients with HER2-positive Primary Breast Cancer

    DEFF Research Database (Denmark)

    Maae, Else; Andersen, Rikke Fredslund; Dahl Steffensen, Karina;

    2012-01-01

    Background: Vascular endothelial growth factor A (VEGFA) is essential in tumour angiogenesis, and polymorphisms in the VEGFA gene have been associated with breast cancer prognosis. The human epidermal growth factor receptor 2 (HER2) is overexpressed in breast tumours and is also associated...... multivariate analysis, only the -634CC genotype remained an independent prognostic factor (p=0.008). Conclusion: The VEGFA -634CC genotype was found to be associated with an inferior prognosis for patients with HER2-positive breast cancer....... with angiogenesis. We investigated the possible prognostic impact of VEGFA single nucleotide polymorphisms (SNPs) in patients with HER2-positive primary breast cancer. Patients and Methods: DNA was isolated from venous blood samples from 116 HER2-positive patients and genotyped for VEGFA -2578C>A, -1498T>C, -1154G...

  20. Results of chemo-radiotherapy and prognostic factors of small cell lung cancer.

    Science.gov (United States)

    Shikaura, S; Kawa, S; Yoshida, M; Yonezu, S

    1991-01-01

    We studied the therapeutic results and prognostic factors in 63 cases of small cell lung cancer (SCLC) experienced in our hospital over the past eight years. In the group initially treated with combination chemotherapy using COMP-VAD, the survival period was significantly prolonged. Use of adjuvant radiotherapy from the beginning had no effect on improvement in the survival period, but the period until local recurrences tended to be prolonged. Prognostic factors influencing survival were analyzed by the log rank test and generalized Wilcoxon test and multivariate analysis by the proportional hazard model of Cox. Statistical significance using univariate analysis was found for six factors (PS, clinical stage, LDH, albumin, treatment protocols, treatment response). The strong prognostic factors determined by multivariate analysis were, in the order of importance, chemotherapy protocol, initial PS, and treatment response.

  1. Stage II colorectal cancer: lack of prognostic model

    Directory of Open Access Journals (Sweden)

    Abdelbaset Buhmeida

    2007-01-01

    Full Text Available TO THE EDITOR: Colorectal cancer (CRC is one of the most common malignant tumors worldwide (Gatta et al. 1998 [1], Repetto et al. 2003 [2] with the disease incidence rising along with an advanced age (Wymenga et al. 2001 [3], Franceschi et al. 2001 [4]. The overall mortality from CRC is 60%, which represents the second leading cause of cancer death in western societies. In Finland, the incidence of CRC is 25/100.000, and 20/100.000 among males and females, respectively. Annually, 1.150 new cases are detected among males and 1.200 among women, representing 9.2% and 10% of all cancer cases, respectively (Finnish Cancer Registry, 2005. On the other hand, according to Benghazi Cancer Registry, 2003 [5] the colorectal cancer in eastern part of Libya is the most second frequent cancer after lung cancer in males and breast cancer in females. The average crude incidence rate is 6.4 (male and 5.2 (female cases per 100,000 inhabitants, representing 10.1% of male patients and 9.3% of female patients of all cancer cases.

  2. Prognostic value of PLR in various cancers: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xin Zhou

    Full Text Available BACKGROUND: Recently, more and more studies investigated the association of inflammation parameters such as the Platelet Lymphocyte Ratio (PLR and the prognosis of various cancers. However, the prognostic role of PLR in cancer remains controversial. METHODS: We conducted a meta-analysis of published studies to evaluate the prognostic value of PLR in various cancers. In order to investigate the association between PLR and overall survival (OS, the hazard ratio (HR and its 95% confidence interval (CI were calculated. RESULTS: A total of 13,964 patients from 26 studies were included in the analysis. The summary results showed that elevated PLR was a negative predictor for OS with HR of 1.60 (95%CI: 1.35-1.90; Pheterogeneity <0.001. Subgroup analysis revealed that increased PLR was a negative prognostic marker in patients with gastric cancer (HR = 1.35, 95%CI: 0.80-2.25, Pheterogeneity = 0.011, colorectal cancer (HR = 1.65, 95%CI: 1.33-2.05, Pheterogeneity = 0.995, hepatocellular carcinoma (HR = 3.07, 95% CI: 2.04-4.62, Pheterogeneity = 0.133, ovarian cancer (HR = 1.57, 95%CI: 1.07-2.31, Pheterogeneity = 0.641 and non-small cell lung cancer (NSCLC (HR = 1.85, 95% CI: 1.42-2.41, Pheterogeneity = 0.451 except for pancreatic cancer (HR = 1.00, 95%CI: 0.92-1.09, Pheterogeneity = 0.388. CONCLUSION: The meta-analysis demonstrated that PLR could act as a significant biomarker in the prognosis of various cancers.

  3. Identification of prognostic and diagnostic biomarkers of glucose intolerance in ApoE3Leiden mice

    NARCIS (Netherlands)

    Wopereis, S.; Radonjic, M.; Rubingh, C.; Erk, M. van; Smilde, A.; Duyvenvoorde, W. van; Cnubben, N.; Kooistra, T.; Ommen, B. van; Kleemann, R.

    2012-01-01

    The prevalence of diabetes mellitus Type 2 could be significantly reduced by early identification of subjects at risk, allowing for better prevention and earlier treatment. Glucose intolerance (GI) is a hallmark of the prediabetic stage. This study aims at identifying 1) prognostic biomarkers predic

  4. Waldenström macroglobulinemia. Development of diagnostic criteria and identification of prognostic factors.

    Science.gov (United States)

    Owen, R G; Barrans, S L; Richards, S J; O'Connor, S J; Child, J A; Parapia, L A; Morgan, G J; Jack, A S

    2001-09-01

    To establish whether a combination of morphologic and immunophenotypic criteria could be developed to more precisely define Waldenström macroglobulinemia (WM) and prognostic factors, we retrospectively assessed the clinical and laboratory features of 111 cases of WM. Bone marrow infiltration by small lymphocytes was documented in each case; and diffuse, interstitial, nodular, and paratrabecular patterns of infiltration were documented in 58%, 32%, 6%, and 4% of cases, respectively. Ninety percent were characterized by a surface immunoglobulin-positive, CD19+CD20+CD5-CD10-CD23- immunophenotype. The median overall survival from diagnosis was 60 months; univariate analysis revealed the following adverse prognostic factors: older than 60 years, performance status more than 1, platelet count less than 100 x 10(3)/microL (< 100 x 10(9)/L), pancytopenia, and diffuse bone marrow infiltration. Associated median survival was 40, 38, 46, 28, and 59 months, respectively. Multivariate analysis revealed age, performance status, and platelet count as prognostically significant, but stratification of patients according to the International Prognostic Index had limited value. We suggest defining WM by the following criteria: IgM monoclonal gammopathy; bone marrow infiltration by small lymphocytes, plasmacytoid cells, and plasma cells in a diffuse, interstitial, or nodular pattern; and a surface immunoglobulin-positive, CD19+CD20+CD5-CD10-CD23- immunophenotype.

  5. Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients

    DEFF Research Database (Denmark)

    Liu, Na; Cox, Thomas R; Cui, Weiyingqi;

    2016-01-01

    Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we anal...... the nucleus of colon cancer cell lines by confocal microscopy and Western blot. Our results show a powerful link between nuclear LOX expression in tumours and patient survival, and offer a promising prognostic biomarker for rectal cancer patients....

  6. Prognostic Significance and Clinicopathological Associations of COX-2 SNP in Patients with Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Peter P. Grimminger

    2009-01-01

    Full Text Available Background. To further improve the screening, diagnosis, and therapy of patients with nonsmall cell lung cancer (NSCLC additional diagnostic tools are urgently needed. Gene expression of Cyclooxygenase-2 (COX-2 has been linked to prognosis in patients with NSCLC. The role of the COX-2 926G>C Single Nucleotide Polymorphism (SNP in patients with NSCLC remains unclear. The aim of this study was to investigate the potential of the COX-2 926G>C SNP as a molecular marker in this disease. Methods. COX-2 926G>C SNP was analyzed in surgically resected tumor tissue of 85 patients with NSCLC using a PCR-based RFLP technique. Results. The COX-2 926G>C SNP genotypes were detected with the following frequencies: GG n=62 (73%, GC n=20 (23%, CC n=3 (4%. There were no associations between COX-2 SNP genotype and histology, grading or gender detectable. COX-2 SNP was significantly associated with tumor stage (P=.032 and lymph node status (P=.016, Chi-square test. With a median followup of 85.9 months, the median survival was 59.7 months. There were no associations seen between the COX-2 SNP genotype and patients prognosis. Conclusions. The COX-2 926G>C SNP is detectable at a high frequency in patients with NSCLC. The COX-2 926G>C SNP genotype is not a prognostic molecular marker in this disease. However, patients with the GC or CC genotype seem more susceptible to lymph node metastases and higher tumor stage than patients with the GG genotype. The results suggest COX-2 926G>C SNP as a molecular marker for lymph node involvement in this disease.

  7. Prognostic protein markers for triple negative breast cancer

    NARCIS (Netherlands)

    A. Umar (Arzu); N.Q. Liu (Ning Qing); R.B.H. Braakman (René)

    2010-01-01

    textabstractBreast cancer is the most commonly diagnosed malignancy in women in the Western world, with 13,000 new patients each year in the Netherlands alone. Extensive research on gene expression profiling has shown that breast cancer is a mixture of biologically different disease entities, referr

  8. DNA methylation in serum of breast cancer patients: an independent prognostic marker.

    Science.gov (United States)

    Müller, Hannes M; Widschwendter, Andreas; Fiegl, Heidi; Ivarsson, Lennart; Goebel, Georg; Perkmann, Elisabeth; Marth, Christian; Widschwendter, Martin

    2003-11-15

    Changes in the status of DNA methylation are one of the most common molecular alterations in human neoplasia. Because it is possible to detect these epigenetic alterations in the bloodstream of patients, we investigated whether aberrant DNA methylation in patient pretherapeutic sera is of prognostic significance in breast cancer. Using MethyLight, a high-throughput DNA methylation assay, we analyzed 39 genes in a gene evaluation set, consisting of 10 sera from metastasized patients, 26 patients with primary breast cancer, and 10 control patients. To determine the prognostic value of genes identified within the gene evaluation set, we finally analyzed pretreatment sera of 24 patients having had no adjuvant treatment (training set) to determine their prognostic value. An independent test set consisting of 62 patients was then used to test the validity of genes and combinations of genes, which in the training set were found to be good prognostic markers. In the gene evaluation set we identified five genes (ESR1, APC, HSD17B4, HIC1, and RASSF1A). In the training set, patients with methylated serum DNA for RASSF1A and/or APC had the worst prognosis (P < 0.001). This finding was confirmed by analyzing serum samples from the independent test set (P = 0.007). When analyzing all 86 of the investigated patients, multivariate analysis showed methylated RASSF1A and/or APC serum DNA to be independently associated with poor outcome, with a relative risk for death of 5.7. DNA methylation of particular genes in pretherapeutic sera of breast cancer patients, especially of RASSF1A/APC, is more powerful than standard prognostic parameters.

  9. Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).

    Science.gov (United States)

    Marsoni, S; Torri, V; Valsecchi, M G; Belloni, C; Bianchi, U; Bolis, G; Bonazzi, C; Colombo, N; Epis, A; Favalli, G

    1990-09-01

    The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed.

  10. Methylation of serum SST gene is an independent prognostic marker in colorectal cancer

    Science.gov (United States)

    Liu, Yanqun; Chew, Min Hoe; Tham, Chee Kian; Tang, Choong Leong; Ong, Simon YK; Zhao, Yi

    2016-01-01

    There is an increasing demand for accurate prognostication for colorectal cancer (CRC). This study sought to assess prognostic potentials of methylation targets in the serum of CRC patients. A total of 165 CRC patients were enrolled in this prospective study. Promoter methylation levels of seven genes in pre-operative sera and matched tumor tissues were evaluated by quantitative methylation-specific PCR. Kaplan-Meier test, and univariate and multivariate Cox proportional hazards regression models were used for survival analyses. After a median follow-up of 56 months, 43 patients (28.7%) experienced tumor recurrence. In univariate survival analyses, serum methylation levels of SST and MAL were significantly predictive of cancer-specific death (Pcancer death and recurrence, respectively). When focusing on stage II and III patients, prognostication with serum methylated SST remained significant. Methylated SST detected in all serum samples can be traced back to the matched primary tumor tissues. We believe that methylated SST detected in the pre-operative sera of CRC patients appear to be a novel promising prognostic marker and probably can be auxiliary to tumor staging system and serum carcinoembryonic antigen towards better risk stratification.

  11. Prognostic value of the lymphocyte monocyte ratio in patients with colorectal cancer

    Science.gov (United States)

    Song, Wei; Wang, Kai; Zhang, Run-jin; Zou, Shu-bing

    2016-01-01

    Abstract Background: Inflammation plays a critical role in the pathogenesis and progression of cancer. A low lymphocyte-to-monocyte ratio (LMR) is reported be a poor prognostic factor in multiple malignancies. We performed a meta-analysis to evaluate the prognostic role of preoperative LMR in colorectal cancer (CRC). Methods: Studies investigating the prognostic role of preoperative LMR on survival in patients with CRC were systematically searched for in MEDLINE, EMBASE, Cochrane databases from inception up to August 2016. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were calculated using fixed-effects/random-effects models. Results: A total of nine studies comprising 8626 patients with CRC were included in the meta-analysis. The pooled analysis demonstrated that low LMR was significantly associated with decreased OS (HR: 0.63, 95% CI: 0.56–0.70, P < 0.001) and DFS/RFS (HR: 0.76, 95% CI: 0.68–0.84, P < 0.001). The negative prognostic impact of low LMR on OS was observed in patients with different ethnicity, treatment methods, cut-off values, and across disease stages. Conclusions: This meta-analysis demonstrates that low preoperative LMR is associated with worse survival in patients with CRC. PMID:27930549

  12. A profile of prognostic and molecular factors in European and Māori breast cancer patients

    Directory of Open Access Journals (Sweden)

    Cheale Michelle

    2010-10-01

    Full Text Available Abstract Background New Zealand Māori have a poorer outcome from breast cancer than non-Māori, yet prognostic data are sparse. The objective of this study was to quantify levels of prognostic factors in a cohort of self-declared Māori and European breast cancer patients from Christchurch, New Zealand. Methods and Results Clinicopathological and survival data from 337 consecutive breast cancer patients (27 Māori, 310 European were evaluated. Fewer tumours were high grade in Māori women than European women (p = 0.027. No significant ethnic differences were detected for node status, tumour type, tumour size, human epidermal growth factor receptor, oestrogen and progesterone receptor (ER/PR status, or survival. In addition, tumour and serum samples from a sub-cohort of 14 Māori matched to 14 NZ European patients were analyzed by immunohistochemistry and enzyme linked immunosorbent assay for molecular prognostic factors. Significant correlations were detected between increased grade and increased levels of hypoxia inducible factor-1 (HIF-1α, glucose transporter-1 (GLUT-1, microvessel density (MVD and cytokeratins CK5/6 (p Conclusions In this Christchurch cohort of breast cancer patients, Māori women were no more likely than European women to have pathological or molecular factors predictive of poor prognosis. These data contrast with data from the North Island NZ, and suggest potential regional differences.

  13. Deregulated Expression of Aurora Kinases Is Not a Prognostic Biomarker in Papillary Thyroid Cancer Patients

    Science.gov (United States)

    Prinzi, Natalie; Sorrenti, Salvatore; Falvo, Laura; De Vito, Corrado; Catania, Antonio; Tartaglia, Francesco; Mocini, Renzo; Coccaro, Carmela; Alessandrini, Stefania; Barollo, Susi; Mian, Caterina; Antonelli, Alessandro; De Antoni, Enrico; D’Armiento, Massimino; Ulisse, Salvatore

    2015-01-01

    A number of reports indicated that Aurora-A or Aurora-B overexpression represented a negative prognostic factor in several human malignancies. In thyroid cancer tissues a deregulated expression of Aurora kinases has been also demonstrated, butno information regarding its possible prognostic role in differentiated thyroid cancer is available. Here, weevaluated Aurora-A and Aurora-B mRNA expression and its prognostic relevance in a series of 87 papillary thyroid cancers (PTC), with a median follow-up of 63 months. The analysis of Aurora-A and Aurora-B mRNA levels in PTC tissues, compared to normal matched tissues, revealed that their expression was either up- or down-regulatedin the majority of cancer tissues. In particular, Aurora-A and Aurora-B mRNA levels were altered, respectively, in 55 (63.2%) and 79 (90.8%) out of the 87 PTC analyzed.A significant positive correlation between Aurora-A and Aurora-B mRNAswas observed (p=0.001). The expression of both Aurora genes was not affected by the BRAFV600E mutation. Univariate, multivariate and Kaplan-Mayer analyses documented the lack of association between Aurora-A or Aurora-B expression and clinicopathological parameterssuch as gender, age, tumor size, histology, TNM stage, lymph node metastasis and BRAF status as well asdisease recurrences or disease-free interval. Only Aurora-B mRNA was significantly higher in T(3-4) tissues, with respect to T(1-2) PTC tissues. The data reported here demonstrate that the expression of Aurora kinases is deregulated in the majority of PTC tissues, likely contributing to PTC progression. However, differently from other human solid cancers, detection of Aurora-A or Aurora-B mRNAs is not a prognostic biomarker inPTC patients. PMID:25807528

  14. Prognostic factors of T4 gastric cancer patients undergoing potentially curative resection

    Institute of Scientific and Technical Information of China (English)

    Naoto Fukuda; Yasuyuki Sugiyama; Joji Wada

    2011-01-01

    AIM: To investigate the prognostic factors of T4 gas-tric cancer patients without distant metastasis who could undergo potentially curative resection. METHODS: We retrospectively analyzed the clinical data of 71 consecutive patients diagnosed with T4 gas-tric cancer and who underwent curative gastrectomy at our institutions. The clinicopathological factors that could be associated with overall survival were evalu-ated. The cumulative survival was determined by the Kaplan-Meier method, and univariate comparisons be-tween the groups were performed using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard model and a step-wise procedure.RESULTS: The study patients comprised 53 men (74.6%) and 18 women (25.4%) aged 39-89 years (mean, 68.9 years). Nineteen patients (26.8%) had postoperative morbidity: pancreatic fistula developed in 6 patients (8.5%) and was the most frequent compli-cation, followed by anastomosis stricture in 5 patients (7.0%). During the follow-up period, 28 patients (39.4%) died because of gastric cancer recurrence, and 3 (4.2%) died because of another disease or accident. For all patients, the estimated overall survival was 34.1% at 5 years. Univariate analyses identified the following statis-tically significant prognostic factors in T4 gastric cancer patients who underwent potentially curative resection: peritoneal washing cytology (P < 0.01), number of met-astatic lymph nodes (P < 0.05), and venous invasion (P < 0.05). In multivariate analyses, only peritoneal wash-ing cytology was identified as an independent prognos-tic factor (HR = 3.62, 95% CI = 1.37-9.57) for long-term survival. CONCLUSION: Positive peritoneal washing cytology was the only independent poor prognostic factor for T4 gastric cancer patients who could be treated with potentially curative resection.

  15. Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers

    Energy Technology Data Exchange (ETDEWEB)

    Arrebola, J.P., E-mail: jparrebola@ugr.es [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); CIBER en Epidemiología y Salud Pública (CIBERESP) (Spain); Fernández-Rodríguez, M.; Artacho-Cordón, F. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); University of Granada, Radiology and Physical Medicine Department (Spain); Garde, C. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Perez-Carrascosa, F.; Linares, I.; Tovar, I. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); González-Alzaga, B. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Escuela Andaluza de Salud Pública, Granada (Spain); Expósito, J. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); Torne, P. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); and others

    2016-10-01

    This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends = 0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends = 0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend = 0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends = 0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend = 0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis. - Highlights: • The role of POP exposure on the pathogenesis breast cancer is still controversial. • POPs were analyzed in serum and adipose tissue from breast cancer patients. • POP concentrations were associated with breast cancer prognostic markers. • POPs in serum and adipose tissue of breast cancer patients may provide different clues.

  16. Her-2/neu expression is a negative prognosticator in ovarian cancer cases that do not express the follicle stimulating hormone receptor (FSHR

    Directory of Open Access Journals (Sweden)

    Heublein Sabine

    2013-01-01

    Full Text Available Abstract Background Anti-Her-2 treatment is successfully administered to Her-2 overexpressing breast cancer patients and significantly implicates upon their survival. Building on these promising results, anti-Her-2 treatment protocols were tested as an option for epithelial ovarian cancer (EOC as well. However Her-2 signalling is known to be modulated by G-protein coupled receptors (GPCR. Since a common GPCR in ovarian cancer is the FSH receptor (FSHR, we investigated the prognostic significance of Her-2 in patients that had been stratified according to their FSHR status. Findings A total number of 153 EOC patients were included in this study. Her-2 positivity was assessed using a standard protocol. Intriguingly Her-2 turned out to be an independent prognostic marker for poor overall survival only in those patients that did not express FSHR. This did neither apply for the whole panel nor in case of FSHR co-expression. Conclusions We thus conclude that Her-2 can be a negative prognosticator only in FSHR negative EOC cases. Hence by stratifying EOC patients according to their FSHR expression status, we introduce a diagnostic protocol to effectively select EOC patients that would most probably respond to anti-Her-2 treatment. This observation could be of clinical importance in terms of selecting the patient that would most likely benefit from anti-Her-2 treatment.

  17. Clinicodemographic aspect of resectable pancreatic cancer and prognostic factors for resectable cancer

    Directory of Open Access Journals (Sweden)

    Chiang Kun-Chun

    2012-05-01

    Full Text Available Abstract Background Pancreatic adenocarcinoma (PCA is one of the most lethal human malignancies, and radical surgery remains the cornerstone of treatment. After resection, the overall 5-year survival rate is only 10% to 29%. At the time of presentation, however, about 40% of patients generally have distant metastases and another 40% are usually diagnosed with locally advanced cancers. The remaining 20% of patients are indicated for surgery on the basis of the results of preoperative imaging studies; however, about half of these patients are found to be unsuitable for resection during surgical exploration. In the current study, we aimed to determine the clinicopathological characteristics that predict the resectability of PCA and to conduct a prognostic analysis of PCA after resection to identify favorable survival factors. Methods We retrospectively reviewed the medical files of 688 patients (422 men and 266 women who had undergone surgery for histopathologically proven PCA in the Department of Surgery at Chang Gung Memorial Hospital in Taiwan from 1981 to 2006. We compared the clinical characteristics of patients who underwent resection and patients who did not undergo resection in order to identify the predictive factors for successful resectability of PCA, and we conducted prognostic analysis for PCA after resection. Results A carbohydrate antigen 19–9 (CA 19–9 level of 37 U/ml or greater and a tumor size of 3 cm or more independently predicted resectability of PCA. In terms of survival after resection, PCA patients with better nutritional status (measured as having an albumin level greater than 3.5 g/dl, radical resection, early tumor stage and better-differentiated tumors were associated with favorable survival. Conclusions Besides traditional imaging studies, preoperative CA 19–9 levels and tumor size can also be used to determine the resectability of PCA. Better nutritional status, curative resection, early tumor stage and well

  18. Prognostic value of hedgehog signaling pathway in patients with colon cancer.

    Science.gov (United States)

    Xu, Meihua; Li, Xinhua; Liu, Ting; Leng, Aimin; Zhang, Guiying

    2012-06-01

    Hedgehog signaling pathway plays an important role in normal mammalian gastrointestinal development and is implicated in the oncogenesis of various tumors. However, its correlation with progression and prognosis of colon cancer has not been well documented. This study was designed to investigate expression patterns of related proteins in hedgehog signaling pathway in colon cancer to elucidate its prognostic value in this tumor. Using human colon cancer and their corresponding non-diseased colon from 228 patients' biopsies, the expression of sonic hedgehog, its receptor Patched, and downstream transcription factor Gli1 was investigated by immunohistochemical staining to assess their association with the clinicopathological characteristics of colon cancer. Disease-free survival and overall survival were examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by multivariate Cox analysis. One hundred and thirty-eight patients (59.6%) had sonic hedgehog-positive tumors and that the disease-free survival (43.5 vs. 73.3%, P colon cancer (50.0 vs. 89.3%, P colon cancer. This is the first report describing about the relationship between hedgehog signaling pathway and the prognosis of colon cancer.

  19. DEK: A novel early screening and prognostic marker for breast cancer.

    Science.gov (United States)

    Ying, Guo; Wu, Yonghui

    2015-11-01

    The present study aimed to investigate the expression status and clinical implications of DEK in breast cancer, in order to contribute to developments in breast cancer management. DEK expression status was detected in 628 breast cancer specimens by western blot analysis and immunohistochemistry staining, and the correlation between DEK protein and clinico‑pathological parameters and prognosis of breast cancer was subsequently determined. In comparison to para-carcinoma tissues, DEK protein was highly expressed in breast cancer specimens and was correlated with chemotherapy resistance. In total, 61.94% (389/628) of breast cancer cases exhibited high expression of DEK. According to universal analysis, it was observed that age, tumor size, histological grade, metastatic nodes and distant metastasis (P=0.024, 0.001, 0.001, 0.001 and 0.001 respectively) are key factors associated with DEK. Furthermore, compared with samples with no or low DEK protein expression, high DEK expression resulted in a significantly increased distant metastasis rate and poor disease‑specific survival (P=0.001). In addition, DEK protein was detected as an independent prognostic factor (P=0.001) in the Cox regression analysis. DEK was correlated with chemotherapy resistance and may be an independent prognostic factor for breast cancer, as well as a potential therapeutic target.

  20. Current Challenges in Development of Differentially Expressed and Prognostic Prostate Cancer Biomarkers

    Directory of Open Access Journals (Sweden)

    Steven M. Lucas

    2012-01-01

    Full Text Available Introduction. Predicting the aggressiveness of prostate cancer at biopsy is invaluable in making treatment decisions. In this paper we review the differential expression of genes and microRNAs identified through microarray analysis as potentially useful markers for prostate cancer prognosis and discuss some of the challenges associated with their development. Methods. A review of the literature was conducted through Medline. Articles were identified through searches of the following terms: “prostate cancer AND differential expression”, “prostate cancer prognosis”, and “prostate cancer AND microRNAs”. Results. Though numerous differentially expressed genes and microRNAs were identified as possible prognostic markers, the significance of several of these genes is either debated due to conflicting results or is not validated in other study populations. A few of the articles constructed predictive nomograms using a panel of biomarkers which require further validation. Challenges to the development of useful markers include different methodology, cancer heterogeneity, and sampling error. These can be overcome by categorizing prognostic factors into particular gene pathways or by supplementing biopsy information with blood or urine-based biomarkers. Conclusion. Though biomarkers based on differential expression offer the potential to improve decision making concerning prostate cancer, further validation of their utility and accuracy at the biopsy level is needed.

  1. Prognostic significance of discoidin domain receptor 2 (DDR2) expression in ovarian cancer.

    Science.gov (United States)

    Fan, Yi; Xu, Zhe; Fan, Jin; Huang, Liu; Ye, Ming; Shi, Kun; Huang, Zheng; Liu, Yaqiong; He, Langchi; Huang, Jiezhen; Wang, Yibin; Li, Qiufeng

    2016-01-01

    Increasing evidence has suggested that discoidin domain receptor 2 (DDR2) plays an important role in cancer development and metastasis. However, the correlation between DDR2 expression and clinical outcome in ovarian cancer has not been investigated. In this study, DDR2 expression was examined by Real-time PCR in surgically resected ovarian cancer and normal ovary tissues. Besides, DDR2 expression was analyzed immunohistochemically in 103 ovarian cancer patients, and the correlation between DDR2 expression with clinicopathologic factors was analyzed. The result showed that DDR2 mRNA expression was upregulated in ovarian cancer tissues compared with normal ovary tissues. Statistical analysis revealed that DDR2 expression correlated with tumor stage (P = 0.008) and peritoneal metastasis (P = 0.009). Patients with high DDR2 expression showed poorer 5-year overall survival (P = 0.005), and DDR2 remained an independent prognostic marker for OS (P = 0.013) in multivariate analysis. Our results suggest that DDR2 might be closely associated with ovarian cancer progression and metastasis. Its high expression may serve as a potential prognostic biomarker in human ovarian cancer.

  2. Prognostic value of PDL1 expression in pancreatic cancer.

    Science.gov (United States)

    Birnbaum, David J; Finetti, Pascal; Lopresti, Alexia; Gilabert, Marine; Poizat, Flora; Turrini, Olivier; Raoul, Jean-Luc; Delpero, Jean-Robert; Moutardier, Vincent; Birnbaum, Daniel; Mamessier, Emilie; Bertucci, François

    2016-11-01

    Pancreatic cancer is one of the most aggressive human cancers. PD1/PDL1-inhibitors recently showed promising results in different cancers with correlation between PDL1 tumor expression and responses. Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in pancreatic cancer. In this retrospective study, we analyzed PDL1 mRNA expression in 453 clinical pancreatic cancer samples profiled using DNA microarrays and RNASeq. Compared to normal pancreatic samples, PDL1 expression was upregulated in 19% of cancer samples. Upregulation was not associated with clinicopathological features such as patients' age and sex, pathological type, tumor size, lymph node status, and grade, but was associated with shorter disease-free survival and overall survival in multivariate analyses. Analysis of correlations with biological parameters showed that PDL1 upregulation was associated with some degree of lymphocyte infiltration and signs of anti-tumor T-cell response, but to a lesser extent than what has been reported in breast cancer and GIST. PDL1-up pancreatic cancers displayed profiles of lymphocyte exhaustion, were more enriched in inhibitory molecules and pro-tumor populations (Tregs with upregulation of FOXP3 and IL10, myeloid-derived suppressor cells with upregulation of CD33 and S100A8/A9), and demonstrated a down-modulation of most MHC class I members (HLA-A/B/C, HLA-E/F/G) suggestive of a defect in antigen processing and presentation. In conclusion, our results suggest that PDL1 expression might refine the prediction of metastatic relapse in operated pancreatic cancer, and that PD1/PDL1 inhibitors might reactivate inhibited T-cells to increase the anti-tumor immune response in PDL1-upregulated tumors.

  3. Depression as a prognostic factor for breast cancer mortality

    DEFF Research Database (Denmark)

    Hjerl, Karen; Andersen, Elisabeth W; Keiding, Niels

    2003-01-01

    of data from three central registers and found that breast cancer patients with depression had a modestly but significantly higher risk of mortality depending on stage of breast cancer and time of depression. The same result was found after censoring unnatural causes of death such as accident, suicide......It is unclear if depression or depressive symptoms have an effect on mortality in breast cancer patients. In this population-based, nationwide, retrospective cohort study in Denmark, depression was defined as affective or anxiety disorders that necessitated psychiatric hospital admission. All...

  4. The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rolff, Hans Christian; Christensen, Ib Jarle; Vainer, Ben

    2016-01-01

    PURPOSE: To investigate the prognostic and predictive biomarker value of type IV collagen in colorectal cancer. EXPERIMENTAL DESIGN: Retrospective evaluation of two independent cohorts of patients with colorectal cancer included prospectively in 2004-2005 (training set) and 2006-2008 (validation...... set). Plasma samples were available from 297 (training set) and 482 (validation set) patients. Type IV collagen determinations were performed using an ELISA. From the training set, 222 tumors were available for IHC. Clinical and follow-up data were retrieved from patient files and national registries....... RESULTS: High levels of type IV collagen showed independent prognostic significance in both cohorts with hazard ratios (HRs; for a one-unit change on the log base 2 scale) of 2.25 [95% confidence intervals (CIs), 1.78-2.84; P

  5. Molecular markers for thyroid cancer diagnosis, prognosis, and targeted therapy.

    Science.gov (United States)

    Yip, Linwah

    2015-01-01

    Molecular markers including gene expression profiles, somatic gene alterations, and circulating peripheral markers have augmented diagnostic, prognostic, and therapeutic options for thyroid cancer patients.

  6. Nestin servers as a promising prognostic biomarker in non-small cell lung cancer

    Science.gov (United States)

    Liu, Fang; Zhang, Yuan; Lu, Ming; Wang, Cong; Li, Qingbao; Gao, Yongsheng; Mu, Dianbin; Cao, Yan; Li, Miaomiao; Meng, Xiangjiao

    2017-01-01

    Lung cancer is currently the leading cause of cancer-related death worldwide and it is important to identify the predictive and/or prognostic markers for the cancer. Nestin, a proliferative and multipotent biomarker has been reported to be associated with prognosis in non-small cell lung cancer (NSCLC) in a few studies. In the present study, we retrospectively recruited 153 patients with NSCLC. Nestin protein expression in tumor samples was determined by immunohistochemistry staining. Nestin expression was related with tumor differentiation (P=0.036), lymphatic metastasis (N stage, P=0.011), and p-TNM stage (P=0.013), while there was no significant association between Nestin expression level and age, smoking habits, gender, histologic type, and T stage. Nestin was an independent prognostic factor for overall survival in NSCLC with an adjusted hazard ratio of 2.701 (95% CI, 1.616-4.513, Pcell proliferation, colony formation, invasion, and apoptosis by knockout of Nestin with a new developed method, CRISPR/Cas9 mediated genome editing. It was observed that knockout of Nestin caused enhancement of cancer cell apoptosis and inhibition of cell proliferation, colony formation, and invasion in A549 and H1299 cell lines. Furthermore, we examined the expression of epithelial-mesenchymal transition (EMT) related biomarkers such as E-cadherin and Vimentin in Nestin-depleted lung cancer cells and knockout of Nestin was found to inhibit EMT, suggesting the involvement of Nestin mediated EMT signaling in lung cancer. The finding above demonstrated that Nestin might serve as a prognostic factor and therapeutic target in NSCLCs.

  7. Treatment for liver metastases from breast cancer: Results and prognostic factors

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Li; Zhi-Qiang Meng; Wei-Jian Guo; Jie Li

    2005-01-01

    AIM: Liver metastases from breast cancer (BCLM) are associated with poor prognosis. Cytotoxic chemotherapy can result in regression of tumor lesions and a decrease in symptoms. Available data, in the literature, also suggest a subgroup of patients rraay berefit from surgery, but few talked about transcatheter arterial chemoembolization (TACE).We report the results of TACE and systemic chemotherapy for patients with liver metastases from breast cancer and evaluate the prognostic factors. METHODS: Forty-eight patients with liver metastases, from proved breast primary cancer were treated with TACEor systemic chemotherapy between January 1995 and December 2000. Treatment results were assessed according to WHO criteria, along with analysis of prognostic factors for survival using Cox regression model.RESULTS: The median follow-up was 28 mo (1-72 mo). Response rates were calculated for the TACE group and chemotherapy group, being 35.7% and 7.1%,respectively. The difference was significant. The one-, two- and three-year Survival rates for the TACE group were 63.04%, 30.35%, and 13.01%, and those for the systemic chemotherapy group were 33.88%, 11.29%, and 0%. According to univariate analysis, variables significantly associated with survival were the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight. Other factors such as age, the intervals between the primary to the metastases, the maximal diameter of the liver metastases, the number of liver metastases, extrahepatic metastasis showed no prognostic significances. These factors mentioned above such as the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight were also independent factors in multivariate analysis.CONCLUSION: TACE treatment of liver metastases from breast cancer may prolong survival in certain patients. This approach offers new promise for the curative treatment of the patients

  8. Prognostic relevance of cyclooxygenase-2 (COX-2) expression in Chinese patients with prostate cancer.

    Science.gov (United States)

    Bin, Wu; He, Wang; Feng, Zhang; Xiangdong, Lu; Yong, Chen; Lele, Kou; Hongbin, Zhang; Honglin, Guo

    2011-02-01

    Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, has been reported to be correlated with tumorigenesis, tumor progression and metastasis. The present study was designed to investigate the clinicopathological and prognostic significance of COX-2 in Chinese patients with prostate cancer. Firstly, RT-PCR and Western blot assays were performed to detect the expression of COX-2 mRNA and protein in prostate cancer cell lines and 20 tissue samples (tumor or corresponding non-tumor). Next, immunohistochemistry was performed to detect the expression of COX-2 protein in 88 prostate cancer tissue samples. Finally, the correlation between COX-2 expression and clinicopathological factors and patient survival was evaluated. We found that the expression levels of COX-2 mRNA and protein showed significant difference among four prostate cancer cell lines. Moreover, the levels of COX-2 mRNA and protein were significantly higher in prostate cancer tissues than in corresponding non-tumor tissues. COX-2 staining was positive in the cytoplasm of prostate cancer cells. High-COX-2 expression was correlated with the Gleason score (P=0.009), tumor stage (P=0.012), and lymph-node status (P=0.036). Furthermore, patients with high-COX-2 expression showed lower disease-free (P=0.014) and overall survival (P=0.047) rates than those with low-COX-2 expression. Univariate and multivariate analyses suggested that the status of COX-2 protein expression was an independent prognostic indicator for patients' survival. Taken together, higher COX-2 protein expression might provide an independent prognostic marker for Chinese patients with prostate cancer who have undergone surgery.

  9. Prognostic Significance of MiR-34a Expression in Patients with Gastric Cancer after Radical Gastrectomy

    Institute of Scientific and Technical Information of China (English)

    Wen-Tao Hui; Xiao-Bin Ma; Ying Zan; Xi-Jing Wang; Lei Dong

    2015-01-01

    Background:MiR-34a dysregulation has been implicated in tumorigenesis and progression of gastric cancer,but its role in prognosis of patients with gastric cancer remains unknown.The aim of this study was to investigate the expression and prognostic significance of miR-34a in gastric cancer patients after radical gastrectomy.Methods:Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-34a in human gastric cancer cell lines and tissues in 76 patients with gastric adenocarcinoma from China.Results are assessed for association with clinical features and overall survival (OS) using Kaplan-Meier analysis.Prognostic values of miR-34a expression and clinical outcomes were evaluated by Cox regression analysis.A molecular prognostic stratification scheme incorporating miR-34a expression was determined using receiver operating characteristic analysis.Results:The results show that the expression level of miR-34a was decreased in human gastric cancer cell lines and tissues,and down-regulated expression of miR-34a was associated with Lauren classification (P =0.034).Decreased miR-34a expression in gastric cancer tissues was positively correlated with poor OS of gastric cancer patients (P =0.013).Further multivariate Cox regression analysis suggested that miR-34a expression was an independent prognostic indicator for gastric cancer (P=0.027).Applying the prognostic value of miR-34a expression to tumor node metastasis (TNM) stage system showed a better prognostic value in patients with gastric cancer than miR-34a expression (P =0.0435) or TNM stage (P =0.0249) alone.Conclusion:The results reinforce the critical role for the down-regulated miR-34a expression in gastric cancer and suggest that miR-34a could be a prognostic indicator for this disease.

  10. An Institutional Retrospective Analysis of 93 Patients with Brain Metastases from Breast Cancer: Treatment Outcomes, Diagnosis-Specific Prognostic Factors

    OpenAIRE

    2012-01-01

    To evaluate the prognostic factors and indexes of a series of 93 patients with breast cancer and brain metastases (BM) in a single institution. Treatment outcomes were evaluated according to the major prognostic indexes (RPA, BSBM, GPA scores) and breast cancer subtypes. Independent prognostic factors for overall survival (OS) were identified. The median OS values according to GPA 0–1, 1.5–2, 2.5–3 and 3.5–4, were 4.5, 9.5, 14.2 and 19.1 months, respect...

  11. A new method for analyzing diagnostic delay in gynecological cancer

    DEFF Research Database (Denmark)

    Vandborg, Mai Partridge; Edwards, Kasper; Kragtrup, Jakob;

    2012-01-01

    OBJECTIVE: The aim of this article is to present a new methodology to illustrate, understand, and measure delay in health care. The method is inspired by process mapping tools as analytical framework and demonstrates its usefulness for studying diagnostic delay in gynecological cancer. MATERIALS...... AND METHODS: Six women with a diagnostic delay of 6 weeks or more before treatment of gynecological cancer at a specialized regional department (the Department of Gynecology and Obstetrics, Odense University Hospital, Denmark) were included in the study. Maps of existing processes were performed for each...... to responsibilities and was shown to recurrently influence and contribute to the delay in the diagnostic process. Some important contributors to diagnostic delay in gynecological cancer, such as lack of cancer suspicion, competing diseases, negative test results, inexpedient referral patterns, and referrals without...

  12. A New Method for Analyzing Diagnostic Delay in Gynecological Cancer

    DEFF Research Database (Denmark)

    Vandborg, Mai Partridge; Edwards, Kasper; Kragstrup, Jakob;

    2012-01-01

    OBJECTIVE: The aim of this article is to present a new methodology to illustrate, understand, and measure delay in health care. The method is inspired by process mapping tools as analytical framework and demonstrates its usefulness for studying diagnostic delay in gynecological cancer. MATERIALS...... AND METHODS: Six women with a diagnostic delay of 6 weeks or more before treatment of gynecological cancer at a specialized regional department (the Department of Gynecology and Obstetrics, Odense University Hospital, Denmark) were included in the study. Maps of existing processes were performed for each...... to responsibilities and was shown to recurrently influence and contribute to the delay in the diagnostic process. Some important contributors to diagnostic delay in gynecological cancer, such as lack of cancer suspicion, competing diseases, negative test results, inexpedient referral patterns, and referrals without...

  13. Magnetic Resonance Imaging of Breast Cancer and Correlation with Prognostic Factors

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yun-Woo; Kwon, Kui Hyang; Choi, Deuk Lin; Lee, Dong Wha; Lee, Min Hyuk (College of Medicine, Soonchunhyang Univ. Hospital, Seoul (Korea)); Lee, Hye Kyung (Dept. of Radiology, Soonchunhyang Bucheon Hospital, Kyonggi (Korea)); Yang, Seung Boo (Dept. of Radiology, Soonchunhyang Gumi Hospital, Kyungbook (Korea)); Kim, Yongbae (Dept. of Preventive Medicine, Soonchunhyang Univ., Chungnam (Korea)); Seo, Dae Young (Dept. of Computer Engineering (KO) Polytechnic Univ., Kyonggi (Korea))

    2009-11-15

    Background: Prognostic factors of breast cancer have been used for the prediction of clinical outcome or selection of patients for complementary treatment. Some of the imaging features of breast cancer, e.g. magnetic resonance imaging (MRI), are associated with these prognostic factors. Purpose: To evaluate the relationship between dynamic enhanced MR features and prognostic factors of clinical outcome of breast cancer. Material and Methods: A total of 136 patients with 151 breast cancers underwent 1.5T dynamic MR imaging with the use of a dynamic T1-weighted three-dimensional fast low-angle shot (FLASH) subtraction imaging technique. Morphological and kinetic analyses of MR features were evaluated using the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) MRI lexicon. Pathological prognostic factors were correlated with MR imaging characteristics, including tumor size, histological grade, lymph node status, expression of estrogen receptor (ER), expression of progesterone receptor (PR), expression of c-erbB2, determination of Ki-67 index, and microvascular density (MVD), using univariate and multivariate statistical analyses. Results: Based on univariate and multivariate analyses, spiculated tumor margins correlated significantly with lower histological grade (I-II) and positive PR expression. Rim enhancement was significantly correlated with high histological grade, presence of axillary lymph node metastasis, large tumor size, increased Ki-67 index, and increased MVD. Early peak enhancement, as seen on the first scan after contrast medium injection, was correlated with negative ER expression. Conclusion: The presence of a lesion with a spiculated margin may predict a relatively good prognosis, and the presence of a lesion with rim enhancement may predict a relatively poor prognosis

  14. The prognostic impact of epidermal growth factor receptor in patients with metastatic gastric cancer

    Directory of Open Access Journals (Sweden)

    Atmaca Akin

    2012-11-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is a potential target of anticancer therapy in gastric cancer. However, its prognostic role in metastatic gastric or gastroesophageal junction (GE cancer has not been established yet. Methods EGFR status was analyzed by immunohistochemistry (IHC in paraffin-embedded samples from 357 patients who received chemotherapy in 4 first-line trials. Automated RNA extraction from paraffin and RT-quantitative PCR were additionally used to evaluate EGFR mRNA expression in 130 patients. Results EGFR protein expression (any grade and overexpression (3+ were observed in 43% and 11% of patients, respectively. EGFR positivity correlated with intestinal type histology (p = 0.05, but not with other clinicopathologic characteristics. Median follow-up was 18.2 months. Median overall survival (OS was similar in patients with EGFR positive vs. those with EGFR negative tumors, regardless whether positivity was defined as ≥1+ (10.6 vs. 10.9 months, p = 0.463 or as 3+ (8.6 vs. 10.8 months, p = 0.377. The multivariate analysis indicated that EGFR status is not an independent prognostic factor (hazard ratio 0.85, 0.56 to 1.12, p = 0.247. There were also no significant differences in overall survival when patients were categorized according to median (p = 0.116 or quartile (p = 0.767 distribution of EGFR mRNA gene expression. Similar distributions of progression-free survival according to EGFR status were observed. Conclusions Unlike different cancer types where EGFR-positive disease is associated with an adverse prognostic value, EGFR positivity is not prognostic of patient outcome in metastatic gastric or GE cancer.

  15. Distinct prognostic values of four-Notch-receptor mRNA expression in ovarian cancer.

    Science.gov (United States)

    Zhou, Xinling; Teng, Lingling; Wang, Min

    2016-05-01

    Notch signaling pathway includes ligands and Notch receptors, which are frequently deregulated in several human malignancies including ovarian cancer. Aberrant activation of Notch signaling has been linked to ovarian carcinogenesis and progression. In the current study, we used the "Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information from a total of 1306 ovarian cancer patients were used to access the prognostic value of four Notch receptors in ovarian cancer patients. Hazard ratio (HR), 95 % confidence intervals, and log-rank P were calculated. Notch1 messenger RNA (mRNA) high expression was not found to be correlated to overall survival (OS) for all ovarian cancer, as well as in serous and endometrioid cancer patients followed for 20 years. However, Notch1 mRNA high expression is significantly associated with worsen OS in TP53 wild-type ovarian cancer patients, while it is significantly associated with better OS in TP53 mutation-type ovarian cancer patients. Notch2 mRNA high expression was found to be significantly correlated to worsen OS for all ovarian cancer patients, as well as in grade II ovarian cancer patients. Notch3 mRNA high expression was found to be significantly correlated to better OS for all ovarian cancer patients, but not in serous cancer patients and endometrioid cancer patients. Notch4 mRNA high expression was not found to be significantly correlated to OS for all ovarian cancer patients, serous cancer patients, and endometrioid cancer patients. These results indicate that there are distinct prognostic values of four Notch receptors in ovarian cancer. This information will be useful for better understanding of the heterogeneity and complexity in the molecular biology of ovarian cancer and for developing tools to more accurately predict their prognosis. Based on our results, Notch1 could be a potential drug target of TP53 wild-type ovarian cancer and Notch2 could be a potential drug

  16. Prognostic Value of Homotypic Cell Internalization by Nonprofessional Phagocytic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Manuela Schwegler

    2015-01-01

    Full Text Available Background. In this study, we investigated the prognostic role of homotypic tumor cell cannibalism in different cancer types. Methods. The phenomenon of one cell being internalized into another, which we refer to as “cell-in-cell event,” was assessed in 416 cases from five head and neck cancer cohorts, as well as one anal and one rectal cancer cohort. The samples were processed into tissue microarrays and immunohistochemically stained for E-cadherin and cleaved caspase-3 to visualize cell membranes and apoptotic cell death. Results. Cell-in-cell events were found in all of the cohorts. The frequency ranged from 0.7 to 17.3 cell-in-cell events per mm2. Hardly any apoptotic cells were found within the cell-in-cell structures, although apoptotic cell rates were about 1.6 to two times as high as cell-in-cell rates of the same tissue sample. High numbers of cell-in-cell events showed adverse effects on patients’ survival in the head and neck and in the rectal cancer cohorts. In multivariate analysis, high frequency was an adverse prognostic factor for overall survival in patients with head and neck cancer (p=0.008. Conclusion. Cell-in-cell events were found to predict patient outcomes in various types of cancer better than apoptosis and proliferation and might therefore be used to guide treatment strategies.

  17. Nottingham prognostic index plus (NPI+) predicts risk of distant metastases in primary breast cancer.

    Science.gov (United States)

    Green, Andrew R; Soria, D; Powe, D G; Nolan, C C; Aleskandarany, M; Szász, M A; Tőkés, A M; Ball, G R; Garibaldi, J M; Rakha, E A; Kulka, J; Ellis, I O

    2016-05-01

    The Nottingham prognostic index plus (NPI+) is based on the assessment of biological class combined with established clinicopathologic prognostic variables providing improved patient outcome stratification for breast cancer superior to the traditional NPI. This study aimed to determine prognostic capability of the NPI+ in predicting risk of development of distant disease. A well-characterised series of 1073 primary early-stage BC cases treated in Nottingham and 251 cases from Budapest were immunohistochemically assessed for cytokeratin (Ck)5/6, Ck18, EGFR, oestrogen receptor (ER), progesterone receptor, HER2, HER3, HER4, Mucin 1 and p53 expression. NPI+ biological class and prognostic scores were assigned using individual algorithms for each biological class incorporating clinicopathologic parameters and investigated in terms of prediction of distant metastases-free survival (MFS). The NPI+ identified distinct prognostic groups (PG) within each molecular class which were predictive of MFS providing improved patient outcome stratification superior to the traditional NPI. NPI+ PGs, between series, were comparable in predicting patient outcome between series in luminal A, basal p53 altered and HER2+/ER+ (p > 0.01) tumours. The low-risk groups were similarly validated in luminal B, luminal N, basal p53 normal tumours (p > 0.01). Due to small patient numbers the remaining PGs could not be validated. NPI+ was additionally able to predict a higher risk of metastases at certain distant sites. This study may indicate the NPI+ as a useful tool in predicting the risk of metastases. The NPI+ provides accurate risk stratification allowing improved individualised clinical decision making for breast cancer.

  18. Tumor-Associated Macrophages Provide Significant Prognostic Information in Urothelial Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Minna M Boström

    Full Text Available Inflammation is an important feature of carcinogenesis. Tumor-associated macrophages (TAMs can be associated with either poor or improved prognosis, depending on their properties and polarization. Current knowledge of the prognostic significance of TAMs in bladder cancer is limited and was investigated in this study. We analyzed 184 urothelial bladder cancer patients undergoing transurethral resection of a bladder tumor or radical cystectomy. CD68 (pan-macrophage marker, MAC387 (polarized towards type 1 macrophages, and CLEVER-1/Stabilin-1 (type 2 macrophages and lymphatic/blood vessels were detected immunohistochemically. The median follow-up time was 6.0 years. High macrophage counts associated with a higher pT category and grade. Among patients undergoing transurethral resection, all studied markers apart from CLEVER-1/Stabilin-1 were associated with increased risk of progression and poorer disease-specific and overall survival in univariate analyses. High levels of two macrophage markers (CD68/MAC387+/+ or CD68/CLEVER-1+/+ groups had an independent prognostic role after transurethral resection in multivariate analyses. In the cystectomy cohort, MAC387, alone and in combination with CD68, was associated with poorer survival in univariate analyses, but none of the markers were independent predictors of outcome in multivariate analyses. In conclusion, this study demonstrates that macrophage phenotypes provide significant independent prognostic information, particularly in bladder cancers undergoing transurethral resection.

  19. The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

    Science.gov (United States)

    Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

    2015-01-01

    Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

  20. Long Non-Coding RNAs As Potential Novel Prognostic Biomarkers in Colorectal Cancer.

    Science.gov (United States)

    Saus, Ester; Brunet-Vega, Anna; Iraola-Guzmán, Susana; Pegueroles, Cinta; Gabaldón, Toni; Pericay, Carles

    2016-01-01

    Colorectal cancer (CRC) is the fourth most common cause of death worldwide. Surgery is usually the first line of treatment for patients with CRC but many tumors with similar histopathological features show significantly different clinical outcomes. The discovery of robust prognostic biomarkers in patients with CRC is imperative to achieve more effective treatment strategies and improve patient's care. Recent progress in next generation sequencing methods and transcriptome analysis has revealed that a much larger part of the genome is transcribed into RNA than previously assumed. Collectively referred to as non-coding RNAs (ncRNAs), some of these RNA molecules such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been shown to be altered and to play critical roles in tumor biology. This discovery leads to exciting possibilities for personalized cancer diagnosis, and therapy. Many lncRNAs are tissue and cancer-type specific and have already revealed to be useful as prognostic markers. In this review, we focus on recent findings concerning aberrant expression of lncRNAs in CRC tumors and emphasize their prognostic potential in CRC. Further studies focused on the mechanisms of action of lncRNAs will contribute to the development of novel biomarkers for diagnosis and disease progression.

  1. Soluble urokinase plasminogen activator receptor as a prognostic marker in men participating in prostate cancer screening

    DEFF Research Database (Denmark)

    Kjellman, A; Akre, O; Gustafsson, O;

    2011-01-01

    with prostate cancer and cardiovascular disease mortality. METHODS: Using time-resolved fluorescence immunoassays, we measured intact suPAR [suPAR(I-III)] and intact plus cleaved suPAR [suPAR(I-III) + suPAR(II-III)] and thus calculated the amount of suPAR(II-III) in serum samples from 375 men participating...... cardiovascular disease. No similar association was found for prostate cancer after adjustment for other prognostic factors....... in a prostate cancer screening trial. A total of 312 men were free of prostate cancer and 63 men had prostate cancer diagnosed at the time of screening. The cohort was followed for 15 years. We assessed survival using Kaplan-Meier estimation and Cox proportional hazards regression. RESULTS: The mean age...

  2. Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, A T; Andersen, Zorana Jovanovic;

    2004-01-01

    The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were...... retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk...... of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2...

  3. Immunoexpression analysis and prognostic value of BLCAP in breast cancer

    DEFF Research Database (Denmark)

    Gromova, Irina; Gromov, Pavel; Kroman, Niels;

    2012-01-01

    patients within the Danish Center for Translational Breast Cancer Research (DCTB) prospective study dataset. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. We observed weak immunoreactivity for BLCAP in mammary epithelial cells, almost exclusively......, such as cervical and renal cancer, as well as human tongue carcinoma and osteosarcoma. Here we report the first study of the expression patterns of BLCAP in breast tissue. We analyzed by immunohistochemistry tissue sections of normal and malignant specimens collected from 123 clinical high-risk breast cancer...... localizing to the cytoplasm and found that levels of expression of BLCAP were generally higher in malignant cells as compared to normal cells. Quantitative IHC analysis of BLCAP expression in breast tissues confirmed this differential BLCAP expression in tumor cells, and we could establish, in a 62-patient...

  4. Breast cancer in neurofibromatosis type 1: overrepresentation of unfavourable prognostic factors

    Science.gov (United States)

    Uusitalo, Elina; Kallionpää, Roope A; Kurki, Samu; Rantanen, Matti; Pitkäniemi, Janne; Kronqvist, Pauliina; Härkönen, Pirkko; Huovinen, Riikka; Carpen, Olli; Pöyhönen, Minna; Peltonen, Sirkku; Peltonen, Juha

    2017-01-01

    Background: An increased breast cancer incidence and poor survival have been reported for women with neurofibromatosis 1 (NF1). To explain the poor survival, we aimed to link the histopathology and clinical characteristics of NF1-associated breast cancers. Methods: The Finnish Cancer Registry and the Finnish NF Registry were cross-referenced to identify the NF1 patients with breast cancer. Archival NF1 breast cancer specimens were retrieved for histopathological typing and compared with matched controls. Results: A total of 32 breast cancers were diagnosed in 1404 NF1 patients during the follow-up. Women with NF1 had an estimated lifetime risk of 18.0% for breast cancer, and this is nearly two-fold compared with that of the general Finnish female population (9.74%). The 26 successfully retrieved archival NF1 breast tumours were more often associated with unfavourable prognostic factors, such as oestrogen and progesterone receptor negativity and HER2 amplification. However, survival was worse in the NF1 group (P=0.053) even when compared with the control group matched for age, diagnosis year, gender and oestrogen receptor status. Scrutiny of The Cancer Genome Atlas data set showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population. Conclusions: These results emphasise the role of the NF1 gene in the pathogenesis of breast cancer and a need for active follow-up for breast cancer in women with NF1. PMID:27931045

  5. Prognostic impact of Metadherin-SND1 interaction in colon cancer.

    Science.gov (United States)

    Wang, Nan; Du, Xilin; Zang, Li; Song, Nuan; Yang, Tao; Dong, Rui; Wu, Tao; He, Xianli; Lu, Jianguo

    2012-12-01

    The interaction between Metadherin (MTDH) and Staphylococcal nuclease homology domain containing 1 (SND1) is involved in tumorigenesis and tumor progression of several human malignancies. However, its roles in colon cancer are still unclear. To investigate the clinical value of MTDH and SND1 expression in colon cancer. Immunohistochemical staining was performed to detect the expression of MTDH and SND1 using human colon cancer and their corresponding non-cancerous colon tissues from 196 patients' biopsies. Positive expression of MTDH and SND1 were both increased in colon cancer tissues compared to paired non-cancerous colon tissues. There was a positive correlation between MTDH and SND1 expression in colon cancer tissues (r = 0.86, p colon cancer patients with positive expression of MTDH and SND1 were significantly shorter than those without their expression (both p = 0.01). Furthermore, multivariate Cox regression analysis suggested that positive expression of MTDH and SND1 was an independent poor prognostic predictor in colon cancer. Our data suggest that the increased expression of MTDH and/or SND1 is closely related to carcinogenesis, progression, and prognosis of colon cancer. The co-expression of MTDH/SND1 may be a novel distinctive marker to benefit us in prediction of the prognosis in colon cancer.

  6. Cyr61 is a potential prognostic marker for prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Naoki Terada; Prakash Kulkarni; Robert H Getzenberg

    2012-01-01

    Cysteine-rich angiogenic inducer 61 (Cyr61) is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling that is frequently altered in expression in several types of cancers.In prostate cancer (PCa),Cyr61 is highly expressed in organ-confined disease.Further,Cyr61 expression levels are associated with a lower risk of disease recurrence,and can be quantitatively measured in the serum.Considered together,these results indicate that Cyr61 is a potential and clinically useful tissue,as well as serum-based biomarker for differentiating lethal and non-lethal PCa.

  7. MDSCs in cancer: Conceiving new prognostic and therapeutic targets.

    Science.gov (United States)

    De Sanctis, Francesco; Solito, Samantha; Ugel, Stefano; Molon, Barbara; Bronte, Vincenzo; Marigo, Ilaria

    2016-01-01

    The incomplete clinical efficacy of anti-tumor immunotherapy can depend on the presence of an immunosuppressive environment in the host that supports tumor progression. Tumor-derived cytokines and growth factors induce an altered hematopoiesis that modifies the myeloid cell differentiation process, promoting proliferation and expansion of cells with immunosuppressive skills, namely myeloid derived suppressor cells (MDSCs). MDSCs promote tumor growth not only by shaping immune responses towards tumor tolerance, but also by supporting several processes necessary for the neoplastic progression such as tumor angiogenesis, cancer stemness, and metastasis dissemination. Thus, MDSC targeting represents a promising tool to eliminate host immune dysfunctions and increase the efficacy of immune-based cancer therapies.

  8. Traumatic extremity arterial injury in children: Epidemiology, diagnostics, treatment and prognostic value of Mangled Extremity Severity Score

    Directory of Open Access Journals (Sweden)

    Lange Nadine

    2010-04-01

    Full Text Available Abstract Background Traumatic paediatric arterial injuries are a great challenge due to low incidence and specific characteristics of paediatric anatomy and physiology. The aim of the present study was to investigate their epidemiology, diagnostic and therapeutic options and complications. Furthermore, the prognostic value of the Mangled Extremity Severity Score (MESS was evaluated. Methods In a retrospective clinical study 44 children aged 9.0 ± 3.2 years treated for traumatic extremity arterial lesions in our Level I trauma center between 1971 and 2006 were enrolled. Exclusion criteria were age > 14, venous and iatrogenic vascular injury. Demographic data, mechanism of injury, severity of arterial lesions (by Vollmar and MESS, diagnostic and therapeutic management, complications and outcome were evaluated. Results The most commonly injured vessel was the femoral artery (25% followed by the brachial artery (22.7%. The mechanism of injury was penetrating (31.8%, isolated severe blunt extremity trauma (29.6%, multiple trauma (25% and humeral supracondylar fractures (13.6%. In 63.6% no specific vascular diagnostic procedure was performed in favour of emergency surgery. Surgical reconstructive strategies were preferred (68.2%. A MESS Conclusions Traumatic paediatric vascular injuries are very rare. The most common situations of vascular lesions in childhood were penetrating injuries and fractures of the extremities either as isolated injuries or in multiply injured patients. In paediatric patients, the MESS could serve as a basis for decision making for limb salvage or amputation.

  9. Diagnostic and prognostic value of circulating micro RNAs in heart failure with preserved and reduced ejection fraction

    Institute of Scientific and Technical Information of China (English)

    Christian Schulte; Dirk Westermann; Stefan Blankenberg; Tanja Zeller

    2015-01-01

    micro RNAs(mi RNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating mi RNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease mi RNAs have been proven to be reliable diagnostic biomarkers for different disease entities. In cardiac fibrosis(CF) and heart failure(HF) dysregulated circulating mi RNAs have been identified,indicating their promising applicability as diagnostic biomarkers. Some mi RNAs were successfully tested in risk stratification of HF implementing their potential use as prognostic biomarkers. In this respect mi RNAs might soon be implemented in diagnostic clinical routine. In the young field of mi RNA based research advances have been made in identifying mi RNAs as potential targets for the treatment of experimental CF and HF. Promising study results suggest their potential future application as therapeutic agents in treatment of cardiovascular disease. This article summarizes the current state of the various aspects of mi RNA research in the field of CF and HF with reduced ejection fraction as well as preserved ejection fraction. The review provides an overview of the application of circulating mi RNAs as biomarkers in CF and HF and current approaches to therapeutically utilize mi RNAs in this field of cardiovascular disease.

  10. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications.

    Science.gov (United States)

    Janik, S; Schiefer, A I; Bekos, C; Hacker, P; Haider, T; Moser, J; Klepetko, W; Müllauer, L; Ankersmit, H J; Moser, B

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated.

  11. HSP27 and 70 expression in thymic epithelial tumors and benign thymic alterations: diagnostic, prognostic and physiologic implications

    Science.gov (United States)

    Janik, S.; Schiefer, A. I.; Bekos, C.; Hacker, P.; Haider, T.; Moser, J.; Klepetko, W.; Müllauer, L.; Ankersmit, H. J.; Moser, B.

    2016-01-01

    Thymic Epithelial Tumors (TETs), the most common tumors in the anterior mediastinum in adults, show a unique association with autoimmune Myasthenia Gravis (MG) and represent a multidisciplinary diagnostic and therapeutic challenge. Neither risk factors nor established biomarkers for TETs exist. Predictive and diagnostic markers are urgently needed. Heat shock proteins (HSPs) are upregulated in several malignancies promoting tumor cell survival and metastases. We performed immunohistochemical staining of HSP27 and 70 in patients with TETs (n = 101) and patients with benign thymic alterations (n = 24). Further, serum HSP27 and 70 concentrations were determined in patients with TETs (n = 46), patients with benign thymic alterations (n = 33) and volunteers (n = 49) by using ELISA. HSPs were differentially expressed in histologic types and pathological tumor stages of TETs. Weak HSP tumor expression correlated with worse freedom from recurrence. Serum HSP concentrations were elevated in TETs and MG, correlated with clinical tumor stage and histologic subtype and decreased significantly after complete tumor resection. To conclude, we found HSP expression in the vast majority of TETs, in physiologic thymus and staining intensities in patients with TETs have been associated with prognosis. However, although interesting and promising the role of HSPs in TETs as diagnostic and prognostic or even therapeutic markers need to be further evaluated. PMID:27097982

  12. Expression status of cyclase‑associated protein 2 as a prognostic marker for human breast cancer.

    Science.gov (United States)

    Xu, Lihua; Peng, Sida; Huang, Qunai; Liu, Yu; Jiang, Hua; Li, Xi; Wang, Jiani

    2016-10-01

    Cyclase-associated protein 2 (CAP2) protein is reported to be upregulated in hepatocellular carcinoma (HCC). However, data regarding its expression pattern and clinical relevance in breast cancer are unknown. The aim of this study was to investigate CAP2 expression and its prognostic significance in breast cancer. CAP2 expression at the mRNA and protein levels was examined by real‑time quantitative-polymerase chain reaction and western blotting in 10 paired breast cancer tissues and adjacent normal tissues. The expression level of CAP2 protein in normal breast epithelial cells and breast cancer cell lines was quantified by western blotting. CAP2 protein expression was analyzed in paraffin‑embedded breast cancer samples, paired adjacent non‑tumor and normal breast tissues by immunohistochemical analysis. Statistical analyses were also performed to evaluate the clinicopathological significance of CAP2 expression. The results showed that the expression of CAP2 mRNA and protein was higher in breast cancer than that noted in the adjacent normal tissues in 10 paired samples. The expression level of CAP2 protein in breast cancer cell lines was higher than that in normal breast epithelial cells. In paraffin‑embedded tissue samples, the expression of CAP2 was higher in breast cancer than that found in the adjacent non‑cancerous tissues and normal breast tissues. Compared with the adjacent non‑cancerous tissues, overexpression of CAP2 was detected in 29.4% (37/126) of the patients. Overexpression of CAP2 was significantly associated with progesterone receptor (PR) expression (p<0.05), and decreased overall survival (OS) (p<0.05). In multivariate analysis, expression of CAP2 was an independent prognostic factor for OS [hazard ratio (HR), 4.821; 95% confidence interval (CI), 2.442‑9.518; p<0.001]. CAP2 is upregulated in breast cancer and is associated with the expression of PR and patient survival. CAP2 may serve as a prognostic indicator for patients

  13. Prognostic Implications of Important Genetic Alterations in Prostate Cancer

    NARCIS (Netherlands)

    J.L. Boormans (Joost)

    2011-01-01

    textabstractThe prostate is a walnut-sized gland that is located caudally from the urinary bladder. It excretes fluid as a part of the semen of men. Prostatic neoplasia is common; in Western developed countries prostate cancer is the most common non-cutaneous malignancy in men and it is the second l

  14. Prognostic relevance of acquired uniparental disomy in serous ovarian cancer

    NARCIS (Netherlands)

    M. Tuna (Musaffe); Z. Ju (Zhenlin); M. Smid (Marcel); C.I. Amos (Christopher I.); G.B. Mills (Gordon B.)

    2015-01-01

    textabstractBACKGROUND: Acquired uniparental disomy (aUPD) can lead to homozygosity for tumor suppressor genes or oncogenes. Our purpose is to determine the frequency and profile aUPD regions in serous ovarian cancer (SOC) and investigated the association of aUPD with clinical features and patient o

  15. Prognostic relevance of acquired uniparental disomy in serous ovarian cancer

    NARCIS (Netherlands)

    M. Tuna (Musaffe); Z. Ju (Zhenlin); M. Smid (Marcel); W. Amos; G. Mills

    2015-01-01

    textabstractBackground: Acquired uniparental disomy (aUPD) can lead to homozygosity for tumor suppressor genes or oncogenes. Our purpose is to determine the frequency and profile aUPD regions in serous ovarian cancer (SOC) and investigated the association of aUPD with clinical features and patient o

  16. Cervical cancer, quality issues in early detection and prognostic factors

    NARCIS (Netherlands)

    Zaal, A.

    2014-01-01

    It is expected that cervical cancer incidence will reduce in The Netherlands over the next decades, as a result of hrHPV vaccination and hrHPV-based screening. Untill then, quality of care could need some improvements as suggested by the work described in this thesis. Novel tools are being indicated

  17. Centrosome-Based Mechanisms, Prognostics and Therapeutics in Prostate Cancer

    Science.gov (United States)

    2007-12-01

    centrosomes creating polyploid with amplified centrosomes. The extra centrosomes can, in turn, form multipolar spindles that missegregate chromosomes...which were dramatically reduced when cells were induced to differentiate into neurons . Importantly, MBds were also found in cancer cells of...Snapin was originally considered to be a neuron -spe- cific protein, but recent studies demonstrated that it is also expressed in nonneuronal cells

  18. Prognostic relevance of glycosylation-associated genes in breast cancer

    NARCIS (Netherlands)

    Milde-Langosch, Karin; Karn, Thomas; Schmidt, Marcus; Eulenburg, Christine Zu; Oliveira-Ferrer, Leticia; Wirtz, Ralph M.; Schumacher, Udo; Witzel, Isabell; Schuetze, Dina; Mueller, Volkmar

    2014-01-01

    Glycosylation of cellular proteins has important impact on their stability and functional properties, and glycan structures strongly influence cell adhesion. Many enzymes are involved in glycoconjugate synthesis and degradation, but there is only limited information about their role in breast cancer

  19. Can metabolomics in addition to genomics add to prognostic and predictive information in breast cancer?

    Science.gov (United States)

    Howell, Anthony

    2010-11-16

    Genomic data from breast cancers provide additional prognostic and predictive information that is beginning to be used for patient management. The question arises whether additional information derived from other 'omic' approaches such as metabolomics can provide additional information. In an article published this month in BMC Cancer, Borgan et al. add metabolomic information to genomic measures in breast tumours and demonstrate, for the first time, that it may be possible to further define subgroups of patients which could be of value clinically. See research article: http://www.biomedcentral.com/1471-2407/10/628.

  20. The prognostic value of tumour regression grade following neoadjuvant chemoradiation therapy for rectal cancer.

    LENUS (Irish Health Repository)

    Abdul-Jalil, K I

    2014-01-01

    To date, there is no uniform consensus on whether tumour regression grade (TRG) is predictive of outcome in rectal cancer. Furthermore, the lack of standardization of TRG grading is a major source of variability in published studies. The aim of this study was to evaluate the prognostic impact of TRG in a cohort of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy (CRT). In addition to the Mandard TRG, we utilized four TRG systems modified from the Mandard TRG system and applied them to the cohort to assess which TRG system is most informative.

  1. The prognostic significance of protein tyrosine phosphatase 4A2 in breast cancer

    Directory of Open Access Journals (Sweden)

    Zhao D

    2015-07-01

    Full Text Available Duanzheng Zhao,1 Libin Guo,2,* Henrique Neves,3,* Hiu-Fung Yuen,4 Shu-Dong Zhang,5 Cian M McCrudden,6 Qing Wen,5 Jin Zhang,2 Qi Zeng,4 Hang Fai Kwok,3,5,6 Yao Lin2 1College of Continuing Education, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, People’s Republic of China; 2College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, People’s Republic of China; 3Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau Special Administrative Region, People’s Republic of China; 4Institute of Molecular and Cell Biology, Biopolis Drive, Proteos, Singapore; 5Center for Cancer Research and Cell Biology, 6School of Pharmacy, Queen’s University of Belfast, Belfast, UK *These authors have contributed equally to this work Abstract: Although PTP4A3 has been shown to be a very important factor in promoting cancer progression, the role of its close family member PTP4A2 is still largely unknown. Recent reports have shown contradicting results on the role of PTP4A2 in breast cancer progression. Considering this, we aimed to investigate the prognostic value of PTP4A2 in five independent breast cancer data sets (minimum 198 patients per cohort, totaling 1,124 patients in the Gene Expression Omnibus Database. We found that high expression of PTP4A2 was a favorable prognostic marker in all five independent breast cancer data sets, as well as in the combined cohort, with a hazard ratio of 0.68 (95% confidence interval =0.56–0.83; P<0.001. Low PTP4A2 expression was associated with estrogen receptor-negative tumors and tumors with higher histological grading; furthermore, low expression was inversely correlated with the expression of genes involved in proliferation, including MKI67 and the MCM gene family encoding the minichromosome maintenance proteins. These findings suggest that PTP4A2 may play a role in breast cancer progression by dysregulating cell proliferation. PTP4A2 expression was

  2. Log-normal censored regression model detecting prognostic factors in gastric cancer: A study of 3018 cases

    Institute of Scientific and Technical Information of China (English)

    Bin-Bin Wang; Cai-Gang Liu; Ping Lu; A Latengbaolide; Yang Lu

    2011-01-01

    AIM: To investigate the efficiency of Cox proportional hazard model in detecting prognostic factors for gastric cancer.METHODS: We used the log-normal regression model to evaluate prognostic factors in gastric cancer and compared it with the Cox model. Three thousand and eighteen gastric cancer patients who received a gastrectomy between 1980 and 2004 were retrospectively evaluated. Clinic-pathological factors were included in a log-normal model as well as Cox model. The akaike information criterion (AIC) was employed to compare the efficiency of both models. Univariate analysis indicated that age at diagnosis, past history, cancer location, distant metastasis status, surgical curative degree, combined other organ resection, Borrmann type, Lauren's classification, pT stage, total dissected nodes and pN stage were prognostic factors in both log-normal and Cox models.RESULTS: In the final multivariate model, age at diagnosis,past history, surgical curative degree, Borrmann type, Lauren's classification, pT stage, and pN stage were significant prognostic factors in both log-normal and Cox models. However, cancer location, distant metastasis status, and histology types were found to be significant prognostic factors in log-normal results alone.According to AIC, the log-normal model performed better than the Cox proportional hazard model (AIC value:2534.72 vs 1693.56).CONCLUSION: It is suggested that the log-normal regression model can be a useful statistical model to evaluate prognostic factors instead of the Cox proportional hazard model.

  3. Host-guest supramolecular nanosystems for cancer diagnostics and therapeutics.

    Science.gov (United States)

    Wang, Lei; Li, Li-li; Fan, Yun-shan; Wang, Hao

    2013-07-26

    Extensive efforts have been devoted to the construction of functional supramolecular nanosystems for applications in catalysis, energy conversion, sensing and biomedicine. The applications of supramolecular nanosystems such as liposomes, micelles, inorganic nanoparticles, carbon materials for cancer diagnostics and therapeutics have been reviewed by other groups. Here, we will focus on the recent momentous advances in the implementation of typical supramolecular hosts (i.e., cyclodextrins, calixarenes, cucurbiturils and metallo-hosts) and their nanosystems in cancer diagnostics and therapeutics. We discuss the evolutive process of supramolecular nanosystems from the structural control and characterization to their diagnostic and therapeutic function exploitation and even the future potentials for clinical translation.

  4. Polo-like kinase 1 expression is a prognostic factor in human colon cancer

    Institute of Scientific and Technical Information of China (English)

    Wilko Weichert; Glen Kristiansen; Mathias Schmidt; Volker Gekeler; Aurelia Noske; Silvia Niesporek; Manfred Dietel; Carsten Denkert

    2005-01-01

    AIM: To clarify the expression patterns and prognostic implications of the mitotic regulator Polo-like kinase 1(PLK1) in colon cancer.METHODS: Expression of PLK1 was investigated by immunohistochemistry (158 cases) and immunoblotting in tissue of colon adenomas and adenocarcinomas. PLK1expression patterns were correlated with clinicopathological parameters and patient prognosis. In addition, expression of PLK1 was evaluated by immunoblot and PCR in colon carcinoma cell lines, and coexpression of PLK1 with the proliferation marker Ki-67 was investigated.RESULTS: Weak PLK1 expression was observed in normal colon mucosa and adenomas. In contrast, 66.7% of carcinomas showed strong expression of PLK1.Overexpression of PLK1 correlated positively with Dukes stage (P<0.001), tumor stage (P = 0.001) and nodal status (P<0.05). Additionally, PLK1 expression was a prognostic marker in univariate survival analysis (P<0.01) and had independent prognostic significance (RR = 3.3, P = 0.02)in patients with locoregional disease. Expression of PLK1 mRNA and protein was detected in all cell lines investigated. Coexpression of PLK1 and Ki-67 was observed in the majority of colon cancer cells, but a considerable proportion of cells showed PLK1 positivity without Ki-67expression.CONCLUSION: PLK1 is a new prognostic marker for colon carcinoma patients and may be involved in tumorigenesis and progression of colon cancer. Strategies focusing on PLK1 inhibition in vivo might therefore represent a promising new therapeutic approach for this tumor entity.

  5. Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer

    Science.gov (United States)

    Yu, Jun; Wu, William K K; Li, Xiangchun; He, Jun; Li, Xiao-Xing; Ng, Simon S M; Yu, Chang; Gao, Zhibo; Yang, Jie; Li, Miao; Wang, Qiaoxiu; Liang, Qiaoyi; Pan, Yi; Tong, Joanna H; To, Ka F; Wong, Nathalie; Zhang, Ning; Chen, Jie; Lu, Youyong; Lai, Paul B S; Chan, Francis K L; Li, Yingrui; Kung, Hsiang-Fu; Yang, Huanming; Wang, Jun; Sung, Joseph J Y

    2015-01-01

    Background Characterisation of colorectal cancer (CRC) genomes by next-generation sequencing has led to the discovery of novel recurrently mutated genes. Nevertheless, genomic data has not yet been used for CRC prognostication. Objective To identify recurrent somatic mutations with prognostic significance in patients with CRC. Method Exome sequencing was performed to identify somatic mutations in tumour tissues of 22 patients with CRC, followed by validation of 187 recurrent and pathway-related genes using targeted capture sequencing in additional 160 cases. Results Seven significantly mutated genes, including four reported (APC, TP53, KRAS and SMAD4) and three novel recurrently mutated genes (CDH10, FAT4 and DOCK2), exhibited high mutation prevalence (6–14% for novel cancer genes) and higher-than-expected number of non-silent mutations in our CRC cohort. For prognostication, a five-gene-signature (CDH10, COL6A3, SMAD4, TMEM132D, VCAN) was devised, in which mutation(s) in one or more of these genes was significantly associated with better overall survival independent of tumor-node-metastasis (TNM) staging. The median survival time was 80.4 months in the mutant group versus 42.4 months in the wild type group (p=0.0051). The prognostic significance of this signature was successfully verified using the data set from the Cancer Genome Atlas study. Conclusions The application of next-generation sequencing has led to the identification of three novel significantly mutated genes in CRC and a mutation signature that predicts survival outcomes for stratifying patients with CRC independent of TNM staging. PMID:24951259

  6. The diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in Urinary Tract Infection (UTI) in camels.

    Science.gov (United States)

    El-Deeb, Wael M; Buczinski, Sébastien

    2015-01-01

    The present study aimed to investigate the diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in urinary tract infection (UTI) in camels. We describe the clinical, bacteriological and biochemical findings in 89 camels. Blood and urine samples from diseased (n = 74) and control camels (n = 15) were submitted to laboratory investigations. The urine analysis revealed high number of RBCS and pus cells. The concentrations of serum and erythrocytic malondialdehyde (sMDA & eMDA), Haptoglobin (Hp), serum amyloid A (SAA), Ceruloplasmin (Cp), fibrinogen (Fb), albumin, globulin and interleukin 6 (IL-6) were higher in diseased camels when compared to healthy ones. Catalase, super oxide dismutase and glutathione levels were lower in diseased camels when compared with control group. Forty one of 74 camels with UTI were successfully treated. The levels of malondialdehyde, catalase, super oxide dismutase, glutathione, Hp, SAA, Fb, total protein, globulin and IL-6 were associated with the odds of treatment failure. The MDA showed a great sensitivity (Se) and specificity (Sp) in predicting treatment failure (Se 85%/Sp 100%) as well as the SAA (Se 92%/Sp 87%) and globulin levels (Se 85%/Sp 100%) when using the cutoffs that maximizes the sum of Se + Sp. Multivariate logistic regression analysis revealed that two models had a high accuracy to predict failure with the first model including sex, sMDA and Hp as covariates (area under the receiver operating characteristic curve (AUC) = 0.92) and a second model using sex, SAA and Hp (AUC = 0.89). Conclusively, the oxidative stress biomarkers and acute phase proteins could be used as diagnostic and prognostic biomarkers in camel UTI management. Efforts should be forced to investigate such biomarkers in other species with UTI.

  7. The Eag potassium channel as a new prognostic marker in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Schalkwyk Gerhard V

    2010-12-01

    Full Text Available Abstract Background Ovarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK, accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K+ channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression. Objectives To determine the expression of the potassium channels Eag and HERG in ovarian cancer tissue and to assess their role in cell proliferation. Methods The expression of Eag and HERG potassium channels was examined in an ovarian cancer tissue microarray. Their role in cell proliferation was investigated by blocking voltage-gated potassium channels in an ovarian cancer cell line (SK-OV-3. Results We show for the first time that high expression of Eag channels in ovarian cancer patients is significantly associated with poor survival (P = 0.016 unlike HERG channel expression where there was no correlation with survival. There was also a significant association of Eag staining with high tumour grade (P = 0.014 and presence of residual disease (P = 0.011. Proliferation of SK-OV-3 cells was significantly (P + channel blockers. Conclusion This novel finding demonstrates a role for Eag as a prognostic marker for survival in patients with ovarian cancer.

  8. Integration of estrogen and progesterone receptors with pathological and molecular prognostic factors in breast cancer patients.

    Science.gov (United States)

    Gago, F E; Tello, O M; Diblasi, A M; Ciocca, D R

    1998-12-01

    In this study we have examined biopsies from women with localized primary breast cancer to investigate the prognostic performance of estrogen receptors (ER) and progesterone receptors (PR) for estimating the metastatic probability of the patients, and to explore whether discrimination gets better by combining clinicopathological and other molecular parameters into a score. This prospective study involved 205 patients with a median follow-up of 5 y. Among the evaluated clinicopathological data were: patient's age; tumor size; axillary lymph node involvement; and tumor grade. The most representative tumor samples were derived to a single laboratory for immunohistochemical evaluation of the following molecular markers: ER, PR, proliferating cell nuclear antigen (PCNA), p53 protein product, erbB-2 (HER-2/neu) oncoprotein, and P170 glycoprotein (mdrl gen product). Distant metastases (study endpoint) appeared in 19.5% (40/205) of the patients, most of these patients presented a mixture of poor, regular and good prognostic factors. Disease-free survival analysis procedures (Kaplan-Meier method) identified tumor size, axillary lymph node involvement, tumor grade, receptor status, PCNA, p53, erbB-2 and P170 as useful prognostic factors. Proportional hazard regression analysis (Cox) identified in order of importance erbB-2, tumor size, receptors status, tumor grade and PCNA as useful prognostic factors. To facilitate the evaluation of the prognostic factors, a practical and simple score system was derived. A high pathological score identified 65% of the patients that developed distant metastases, while a high molecular score was obtained in 57% of patients with metastatic disease. There was a significant improvement in the diagnosis of probability of being with distant metastases when the pathological score was combined with the molecular score, 82% of the patients with distant metastases showed an elevated combined score. Validation of this scoring system will need further

  9. Diagnostic and prognostic value of a careful symptom evaluation and high sensitive troponin in patients with suspected stable angina pectoris without prior cardiovascular disease

    DEFF Research Database (Denmark)

    Madsen, Debbie M; Diederichsen, Axel C P; Hosbond, Susanne E

    2017-01-01

    BACKGROUND AND AIMS: Typical angina pectoris (AP) and high-sensitive troponin I (hs-TnI) are independently associated with coronary artery disease (CAD) and future cardiovascular events (CVE). This study aimed to assess the individual and combined diagnostic and prognostic impact of symptoms and hs...

  10. PTIP associated protein 1, PA1, is an independent prognostic factor for lymphnode negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Takashi Takeshita

    Full Text Available Pax transactivation domain interacting protein (PTIP associated protein 1, PA1, was a newly found protein participating in the modulation of transactivity of nuclear receptor super family members such as estrogen receptor (ER, androgen receptor (AR and glucocorticoid receptor (GR. Breast cancer is one of the most life threatening diseases for women and has tight association with estrogen and ER. This study was performed to understand the function of PA1 in breast cancer. The expression of PA1 had been evaluated in a total of 344 primary invasive breast cancer samples and examined the relationship with clinical output, relapse free survival (RFS, breast cancer-specific survival (BCSS. PA1 expression was observed in both nucleus and cytoplasm, however, appeared mainly in nuclear. PA1 nuclear expression was correlated with postmenopausal (P = 0.0097, smaller tumor size (P = 0.0025, negative Ki67 (P = 0.02, positive AR (P = 0.049 and positive ERβ (P = 0.0020. Kaplan-Meier analysis demonstrated PA1 nuclear positive cases seemed to have a longer survival than negative ones for RFS (P = 0.023 but not for BCSS (P = 0.23. In the Cox hazards model, PA1 nuclear protein expression proved to be a significant prognostic univariate parameter for RFS (P = 0.03, but not for BCSS (P = 0.20. In addition, for those patients without lymphnode metastasis PA1 was found to be an independent prognostic factor for RFS (P = 0.025, which was verified by univariate and multivariate analyses. These investigations suggested PA1 expression could be a potential prognostic indicator for RFS in breast cancer.

  11. Prognostic value of the lymph node ratio in stage Ⅲcolorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Jing-Qing Ren; Jian-Wei Liu; Zhi-Tang Chen; Shao-Jie Liu; Shi-Jie Huang; Yong Huang; Jing-Song Hong

    2012-01-01

    The nodal stage of colorectal cancer is based on the number of positive nodes.It is inevitably affected by the number of removed lymph nodes,but lymph node ratio can be unaffected.We investigated the value of lymph node ratio in stage Ⅲ colorectal cancer in this study.The clinicopathologic factors and follow-up data of 145 cases of stage Ⅲ colorectal cancer between January 1998 and December 2008 were analyzed retrospectively.The Pearson and Spearman correlation analyses were used to determine the correlation coefficient,the Kaplan-Meier method was used to analyze survival,and the Cox proportional hazard regression model was used for multivariate analysis in forward stepwise regression.We found that lymph node ratio was not correlated with the number of removed lymph nodes (r =-0.154,P =0.065),but it was positively correlated with the number of positive lymph nodes (r =0.739,P <0.001) and N stage (r =0.695,P < 0.001),Kaplan-Meier survival analysis revealed that tumor configuration,intestinal obstruction,serum carcinoembryonic antigen (CEA) concentration,T stage,N stage,and lymph node ratio were associated with disease-free survival of patients with stage Ⅲ colorectal cancer (P < 0.05).Multivariate analysis showed that serum CEA concentration,T stage,and lymph node ratio were prognostic factors for disease-free survival (P < 0.05),whereas N stage failed to achieve significance (P =0.664).We confirmed that lymph node ratio was a prognostic factor in stage Ⅲ colorectal cancer and had a better prognostic value than did N stage.

  12. Prognostic evaluation of the B cell/IL-8 metagene in different intrinsic breast cancer subtypes.

    Science.gov (United States)

    Hanker, Lars C; Rody, Achim; Holtrich, Uwe; Pusztai, Lajos; Ruckhaeberle, Eugen; Liedtke, Cornelia; Ahr, Andre; Heinrich, Tomas M; Sänger, Nicole; Becker, Sven; Karn, Thomas

    2013-01-01

    We recently reported that a ratio of high B cell and low IL-8 metagene expression identified 32 % of triple negative breast cancers (TNBC) with good prognosis and was the only significant predictor in multivariate analysis including routine clinicopathological variables. However, the clinical relevance of this signature in other breast cancer subtypes remains unclear. We compiled Affymetrix gene expression datasets from 4,467 primary breast cancer samples and excluded 329 triple negative samples which were used as discovery cohort in our previous study. Molecular classification of the remaining 4,138 samples was performed by two methods, including single genes (ER, PgR, HER2, and Ki67) and a centroid-based method using the intrinsic gene list. The prognostic value within the respective subtypes was assessed by analyzing the event-free survival of patients as a function of the B cell/IL-8 metagene ratio using previously published cutoff. ER-negative subtypes had the highest expression of the B cell and the IL-8 metagenes. The IL-8/B cell signature assigned a considerable fraction of samples (range 20.7-42.0 %) into the "good prognosis" group. However, a significant prognostic value was only observed in the subgroup of triple negative breast cancer (P = 0.035). The prognostic value of the B cell/IL-8 ratio is mainly confined to the basal-like and TNBC subtypes of breast cancer. This result underlines the importance of subtype-specific analyses and suggests a sequential multistep approach to developing and applying outcome predictors in the clinic.

  13. Prognostic and predictive roles of MIR-383 in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Alavieh Fateh

    2016-08-01

    Full Text Available MicroRNAs (miRNAs are impressive regulators of gene expression that have a critical role in the pathogenesis of Colorectal Cancer (CRC. With respect to the aberrant expression of microRNA-383 (miR-383 in some types of human malignancy, this prospective study characterized its contribution to CRC tumorigenesis. The real-time reverse transcription–polymerase chain reaction was used to examine miR-383 expression levels prospectively in 40 sample pairs of CRC tissues and adjacent noncancerous tissues (>2 cm from cancer tissue. No significant relationship was found between miR-383 expression levels and clinicopathological features. The ability of miR-383 to function as a tumor marker was also examined. Showing significant changes overall, miR-383 expression levels were significantly down regulated in the group of CRC samples compared with matched noncancerous tissue samples. A receiver operating characteristic (ROC curve also showed ROC area (AROC of 70% for miR-383 with 68% and 75% sensitivity and specificity, respectively. Therefore, miR-383 can be considered as a tumor marker in CRC and help as a potential predictive biomarker in the diagnosis of colorectal cancer.

  14. [New prognostic and predictive markers for breast cancer].

    Science.gov (United States)

    Wachter, D L

    2016-11-01

    Breast cancer can be divided into four molecular subtypes with different prognoses using immunohistochemical markers in the routine clinicopathological work-up. The protein Ki-67 is of central importance in this context, in particular to distinguish between luminal A and luminal B carcinomas. Determination of the Ki-67 index of a carcinoma also allows a prediction of the likelihood of the response to chemotherapy. Additionally, the expression of certain cytokeratins in tumor cells is associated with a poor response to chemotherapy. The heterogeneity of molecular subtypes with regard to the histological appearance indicates an even greater diversity of breast cancer. We were able to show that a high proportion of luminal B carcinomas display neuroendocrine differentiation. Further studies with particular emphasis on histomorphological criteria should be performed to attain a more accurate classification of breast cancer and to pave the way towards targeted therapies for a better prognosis in the future.

  15. Prognostic impact of vitamin B6 metabolism in lung cancer.

    Science.gov (United States)

    Galluzzi, Lorenzo; Vitale, Ilio; Senovilla, Laura; Olaussen, Ken André; Pinna, Guillaume; Eisenberg, Tobias; Goubar, Aïcha; Martins, Isabelle; Michels, Judith; Kratassiouk, Gueorgui; Carmona-Gutierrez, Didac; Scoazec, Marie; Vacchelli, Erika; Schlemmer, Frederic; Kepp, Oliver; Shen, Shensi; Tailler, Maximilien; Niso-Santano, Mireia; Morselli, Eugenia; Criollo, Alfredo; Adjemian, Sandy; Jemaà, Mohamed; Chaba, Kariman; Pailleret, Claire; Michaud, Mickaël; Pietrocola, Federico; Tajeddine, Nicolas; de La Motte Rouge, Thibault; Araujo, Natalia; Morozova, Nadya; Robert, Thomas; Ripoche, Hugues; Commo, Frederic; Besse, Benjamin; Validire, Pierre; Fouret, Pierre; Robin, Angélique; Dorvault, Nicolas; Girard, Philippe; Gouy, Sébastien; Pautier, Patricia; Jägemann, Nora; Nickel, Ann-Christin; Marsili, Sabrina; Paccard, Caroline; Servant, Nicolas; Hupé, Philippe; Behrens, Carmen; Behnam-Motlagh, Parviz; Kohno, Kimitoshi; Cremer, Isabelle; Damotte, Diane; Alifano, Marco; Midttun, Oivind; Ueland, Per Magne; Lazar, Vladimir; Dessen, Philippe; Zischka, Hans; Chatelut, Etienne; Castedo, Maria; Madeo, Frank; Barillot, Emmanuel; Thomale, Juergen; Wistuba, Ignacio Ivan; Sautès-Fridman, Catherine; Zitvogel, Laurence; Soria, Jean-Charles; Harel-Bellan, Annick; Kroemer, Guido

    2012-08-30

    Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.

  16. Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Lorenzo Galluzzi

    2012-08-01

    Full Text Available Patients with non-small cell lung cancer (NSCLC are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK, the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.

  17. Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Ju; Rhee, Woo Joong; Choi, Seo Hee; Kim, Gwi Eon; Kim, Yong Bae [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, EunJi; Kim, Sang Wun; Kim, Sung Hoon [Dept. of Radiation Oncology, Obstetrics and Gynecology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic

  18. The prognostic significance of apoptosis-related biological markers in Chinese gastric cancer patients.

    Directory of Open Access Journals (Sweden)

    Xiaowen Liu

    Full Text Available BACKGROUND AND OBJECTIVE: The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as p53, bcl-2, bax, and c-myc, and clinicopathological features and their prognostic value. METHODS: From 1996 to 2007, 4426 patients had undergone curative D2 gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 501 patients, the expression levels of p53, bcl-2, bax, and c-myc were examined by immunohistochemistry. The prognostic value of biological markers and the correlation between biological markers and other clinicopathological factors were investigated. RESULTS: There were 339 males and 162 females with a mean age of 57. The percentages of positive expression of p53, bcl-2, bax, and c-myc were 65%, 22%, 43%, and 58%, respectively. There was a strong correlation between p53, bax, and c-myc expression (P=0.00. There was significant association between bcl-2, and bax expression (P<0.05. p53 expression correlated with histological grade (P=0.01; bcl-2 expression with pathological stage (P=0.00; bax expression with male (P=0.02, histological grade (P=0.01, Borrmann type (P=0.01, tumor location (P=0.00, lymph node metastasis (P=0.03, and pathological stage (P=0.03; c-myc expression with Borrmann type (P=0.00. bcl-2 expression was related with good survival in univariate analysis (P=0.01. Multivariate analysis showed that bcl-2 expression and pathological stage were defined as independent prognostic factors. There were significant differences of overall 5-year survival rates according to bcl-2 expression or not in stage IIB (P=0.03. CONCLUSION: The expression of bcl-2 was an independent prognostic factor for patients with gastric cancer; it might be a candidate for the gastric cancer staging system.

  19. Prognostic value of microRNA-126 and CRK expression in gastric cancer

    Science.gov (United States)

    Yue, Shun; Shi, Huichang; Han, Jun; Zhang, Tiecheng; Zhu, Weiguo; Zhang, Dahong

    2016-01-01

    Background MicroRNA (miR)-126, acting as a tumor suppressor, has been reported to inhibit the invasion of gastric cancer cells in part by targeting v-crk sarcoma virus CT10 oncogene homologue (CRK). The aim of this study was to investigate the clinical significance of miR-126/CRK axis in gastric cancer. Methods miR-126 and CRK mRNA expression levels were detected by real-time quantitative reverse transcription polymerase chain reaction in 220 self-pairs of gastric cancer and adjacent noncancerous tissues. Results Expression levels of miR-126 and CRK mRNA in gastric cancer tissues were, respectively, lower and higher than those in adjacent noncancerous tissues (both P<0.001). Low miR-126 expression and high CRK expression, alone or in combination, were all significantly associated with positive lymph node and distant metastases and advanced TNM stage of human gastric cancer (all P<0.05). We also found that the overall survival rates of the patients with low miR-126 expression and high CRK expression were, respectively, shorter than those with high miR-126 expression and low CRK expression. Interestingly, miR-126-low/CRK-high expression was associated with a significantly worse overall survival of all miR-126/CRK groups (P<0.001). Moreover, multivariate analysis identified miR-126 and/or CRK expression as independent prognostic factors for patients with gastric cancer. Notably, the prognostic relevance of miR-126 and/or CRK expression was more obvious in the subgroup of patients with TNM stage IV. Conclusion Dysregulation of miR-126/CRK axis may promote the malignant progression of human gastric cancer. miR-126 and CRK combined expression may serve as an independent predictor of overall survival in patients with advanced gastric cancer.

  20. Expression of CRM1 and CDK5 shows high prognostic accuracy for gastric cancer

    Science.gov (United States)

    Sun, Yu-Qin; Xie, Jian-Wei; Xie, Hong-Teng; Chen, Peng-Chen; Zhang, Xiu-Li; Zheng, Chao-Hui; Li, Ping; Wang, Jia-Bin; Lin, Jian-Xian; Cao, Long-Long; Huang, Chang-Ming; Lin, Yao

    2017-01-01

    AIM To evaluate the predictive value of the expression of chromosomal maintenance (CRM)1 and cyclin-dependent kinase (CDK)5 in gastric cancer (GC) patients after gastrectomy. METHODS A total of 240 GC patients who received standard gastrectomy were enrolled in the study. The expression level of CRM1 and CDK5 was detected by immunohistochemistry. The correlations between CRM1 and CDK5 expression and clinicopathological factors were explored. Univariate and multivariate survival analyses were used to identify prognostic factors for GC. Receiver operating characteristic analysis was used to compare the accuracy of the prediction of clinical outcome by the parameters. RESULTS The expression of CRM1 was significantly related to size of primary tumor (P = 0.005), Borrmann type (P = 0.006), degree of differentiation (P = 0.004), depth of invasion (P = 0.008), lymph node metastasis (P = 0.013), TNM stage (P = 0.002) and distant metastasis (P = 0.015). The expression of CDK5 was significantly related to sex (P = 0.048) and Lauren’s classification (P = 0.011). Multivariate Cox regression analysis identified that CRM1 and CDK5 co-expression status was an independent prognostic factor for overall survival (OS) of patients with GC. Integration of CRM1 and CDK5 expression could provide additional prognostic value for OS compared with CRM1 or CDK5 expression alone (P = 0.001). CONCLUSION CRM1 and CDK5 co-expression was an independent prognostic factors for GC. Combined CRM1 and CDK5 expression could provide a prognostic model for OS of GC. PMID:28373767

  1. Synchronous, bilateral breast cancer: prognostic value and incidence.

    Science.gov (United States)

    Jobsen, J J; van der Palen, J; Ong, F; Meerwaldt, J H

    2003-04-01

    The purpose of this study was to address the question whether patients with bilateral breast cancer (BBC) have a worse prognosis in terms of recurrence and survival than patients with primarily unilateral breast cancer (UBC) following breast-conserving treatment (BCT). From 1983 to 2000, a total of 1760 BCT were registered in the Radiotherapy Department of the Medisch Spectrum Twente. We defined synchronous a BBC as cancer diagnosed in both breasts at the same time or within a period of 3 months of diagnosis of the first tumor. One thousand seven hundred and sixty BCT were performed on 1705 patients, 26 of whom presented with BBC. Of these 26 patients, 18 had BCT for both breasts. A higher proportion of patients with BBC showed more tubular carcinoma (P=0.029) and medially located tumors (P=0.076) than those with UBC did. The 5- and 10-year local recurrence rates (LRRs) were 4.5% and 9.1%, respectively, in BBC patients, as against 3.3% and 7.6% for UBC after BCT. The 5- and 10-year distant metastasis rates were 26.9% and 50.7%, respectively, for BBC as against 13.4% and 21.1% for UBC after BCT (P=0.065 and P=0.014, respectively). The 5- and 10-year disease-specific survival (DSS) rates for the 1705 patients were 82.1% and 41%, respectively, after BBC, and 91.4% and 84% after UBC (P=0.086 and P=0.0045, respectively). Patients with BBC have a higher rate of distant metastasis and a worse DSS than those with UBC. As the LRR is similar for BBC and UBC, BCT is not contraindicated in BBC. The incidence of BBC is low, at 1.5% which makes it difficult to reach any more definitive conclusions on outcome and treatment.

  2. Prognostic value of metastin expression in human pancreatic cancer

    OpenAIRE

    Nagai, Kazuyuki; Doi, Ryuichiro; Katagiri, Fumihiko; Ito, Tatsuo; Kida, Atsushi; Koizumi, Masayuki; Masui, Toshihiko; Kawaguchi, Yoshiya; Tomita, Kenji; Oishi, Shinya; Fujii, Nobutaka; Uemoto, Shinji

    2009-01-01

    Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissue...

  3. Prognostic value of metastin expression in human pancreatic cancer.

    OpenAIRE

    Nagai, Kazuyuki; Doi, Ryuichiro; Katagiri, Fumihiko; Ito, Tatsuo; Kida, Atsushi; Koizumi, Masayuki; Masui, Toshihiko; Kawaguchi, Yoshiya; Tomita, Kenji; Oishi, Shinya; Fujii, Nobutaka; Uemoto, Shinji

    2009-01-01

    [Background]KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. [Methods]We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tiss...

  4. Prognostic value of metastin expression in human pancreatic cancer

    OpenAIRE

    Kawaguchi Yoshiya; Masui Toshihiko; Koizumi Masayuki; Kida Atsushi; Ito Tatsuo; Katagiri Fumihiko; Doi Ryuichiro; Nagai Kazuyuki; Tomita Kenji; Oishi Shinya; Fujii Nobutaka; Uemoto Shinji

    2009-01-01

    Abstract Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcino...

  5. Prognostic and predictive value of liver volume on colorectal cancer patients with unresectable liver metastases

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jun Su; Park, Hee Chul; Choi, Doo Ho; Park, Won; Yu, Jeong Il; Park, Young Suk; Kang, Won Ki; Park, Joon Oh [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    To determine the prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Sixteen patients received whole liver radiotherapy (WLRT) between January 1997 and June 2013. A total dose of 21 Gy was delivered in 7 fractions. The median survival time after WLRT was 9 weeks. In univariate analysis, performance status, serum albumin and total bilirubin level, liver volume and extrahepatic metastases were associated with survival. The mean liver volume was significantly different between subgroups with and without pain relief (3,097 and 4,739 mL, respectively; p = 0.002). A larger liver volume is a poor prognostic factor for survival and also a negative predictive factor for response to WLRT. If patients who are referred for WLRT have large liver volume, they should be informed of the poor prognosis and should be closely observed during and after WLRT.

  6. Limited prognostic value of tissue protein expression levels of cyclin E in Danish ovarian cancer patients

    DEFF Research Database (Denmark)

    Heeran, Mel C; Høgdall, Claus K; Kjaer, Susanne K

    2012-01-01

    The primary objective of this study was to assess the expression of cyclin E in tumour tissues from 661 patients with epithelial ovarian tumours. The second was to evaluate whether cyclin E tissue expression levels correlate with clinico-pathological parameters and prognosis of the disease. Using...... tissue arrays (TA), we analysed the cyclin E expression levels in tissues from 168 women with borderline ovarian tumours (BOT) (147 stage I, 4 stage II, 17 stage III) and 493 Ovarian cancer (OC) patients (127 stage I, 45 stage II, 276 stage III, 45 stage IV). Using a 10% cut-off level for cyclin E......-off value showed that cyclin E had no independent prognostic value. In conclusion, we found cyclin E expression in tumour tissue to be of limited prognostic value to Danish OC patients....

  7. Prognostic impact of splenectomy on advanced proximal gastric cancer with No.10 lymph node metastasis

    Institute of Scientific and Technical Information of China (English)

    HUANG Chang-ming; WANG Jia-bin; LU Hui-shan; ZHENG Chao-hui; LI Ping; XIE Jian-wei; ZHANG Xiang-fu

    2009-01-01

    Background This study evaluated the prognostic impact of D2 lymphadenectomy combined with splenectomy in patients with advanced proximal gastric cancer and lymph node metastasis at the splenic hilum (No. 10 lymph nodes).Methods The clinical records of 216 patients with advanced proximal gastric cancer and No.10 lymph node metastasis who underwent D2 curative resection were retrospectively analyzed. Seventy-three patients underwent simultaneous splenectomy (splenectomy group), while 143 patients did not (spleen-preserving group). Five-year survival rates, mean numbers of dissected No.10 lymph nodes and metastatic No.10 lymph nodes, and operative morbidity and mortality were calculated and compared between the two groups. Potential prognostic factors were evaluated by univariate and multivariate analysis.Results The 5-year survival rate was 30.0% for the splenectomy group and 19.7% for the spleen-preserving group (X~2=14.73, P 0.05).Conclusions Splenectomy is beneficial for No.10 lymph node dissection in patients with advanced proximal gastric cancer. To improve patient prognosis, total gastrectomy with splenectomy is recommended for patients with T3 proximal gastric cancer who have No. 10 lymph node metastasis.

  8. Prognostic value of stem cell quantification in stage II colon cancer.

    Directory of Open Access Journals (Sweden)

    Maria Angeles Vaz

    Full Text Available BACKGROUND: Cancer stem cells (CSCs are a subset of tumor cells with capacity to self-renew and generate the diverse cells that make up the tumor. The aim of this study is to evaluate the prognostic value of CSCs in a highly homogeneous population of stage II colon cancer. METHODS: One hundred stage II colon cancer patients treated by the same surgical team between 1977 and 2005 were retrospectively analyzed. None of the patients received adjuvant chemotherapy. Inmunohistochemistry expression of CD133, NANOG and CK20 was scored, using four levels: 50% positivity. Kaplan-Meier analysis and log rank test were used to compare survival. RESULTS: The average patient age was 68 years (patients were between 45-92 years of age and median follow up was 5.8 years. There was recurrent disease in 17 (17%; CD133 expression (defined by >10% positivity was shown in 60% of the tumors, in 95% for NANOG and 78% for CK20. No correlation was found among expression levels of CD133, NANOG or CK20 and relapse-free survival (RFS or overall survival (OS. However, a statistical significant correlation was found between established pathological prognostic factors and RFS and OS. CONCLUSIONS: Stem Cell quantification defined by CD133 and NANOG expression has no correlation with RFS or OS in this cohort of Stage II colon cancer.

  9. Diagnostic and prognostic impact of {sup 18}F-FDG PET/CT in follicular lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Le Dortz, Ludovic; Garin, Etienne [Eugene Marquis Anticancer Centre, Nuclear Medicine Department, Rennes (France); Inserm U991, Rennes (France); Guibert, Sophie de; Houot, Roch [CHU Pontchaillou, Haematological Department, Rennes (France); Bayat, Sahar; Cuggia, Marc [CHU Pontchaillou, Medical Information Department, Rennes (France); Devillers, Anne; Le Jeune, Florence; Bahri, Haifa; Barge, Marie-Luce [Eugene Marquis Anticancer Centre, Nuclear Medicine Department, Rennes (France); Rolland, Yan [Eugene Marquis Anticancer Centre, Medical Imaging Department, Rennes (France); Lamy, Thierry [CHU Pontchaillou, Haematological Department, Rennes (France); Inserm U917, Rennes (France)

    2010-12-15

    The aim of this study was to assess the usefulness of positron emission tomography/computed tomography in staging, prognosis evaluation and restaging of patients with follicular lymphoma. A retrospective study was performed on 45 patients with untreated biopsy-proven follicular lymphoma who underwent {sup 18}F-fluorodeoxyglucose PET/CT (FDG PET/CT) and CT before and after chemoimmunotherapy induction treatment (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone). PET/CT detected more nodal (+51%) and extranodal (+89%) lesions than CT. PET/CT modified Ann Arbor staging in eight patients (18%). Five patients (11%) initially considered as being early stage (I/II) were eventually treated as advanced stage (III/IV). In this study, an initial PET/CT prognostic score was significantly more accurate than the Follicular Lymphoma International Prognostic Index score in identifying patients with poor prognosis (i.e. patients with incomplete therapeutic response or early relapse). The accuracy of PET/CT for therapeutic response assessment was higher than that of CT (0.97 vs 0.64), especially due to its ability to identify inactive residual masses. In addition, post-treatment PET/CT was able to predict patients' outcomes. The median progression-free survival was 48 months in the PET/CT-negative group as compared with 17.2 months for the group with residual uptake (p < 10{sup -4}). FDG PET/CT is useful for staging and assessing the prognosis and therapeutic response of patients with follicular lymphoma. (orig.)

  10. PAI-1 -675 4G/5G polymorphism as a prognostic biomarker in breast cancer.

    Science.gov (United States)

    Lei, Haixin; Hemminki, Kari; Johansson, Robert; Altieri, Andrea; Enquist, Kerstin; Henriksson, Roger; Lenner, Per; Försti, Asta

    2008-05-01

    Extracellular matrix degradation, mediated by the urokinase plasminogen activation (uPA) system, is a critical step in tumor invasion and metastasis. High tumor levels of uPA and its inhibitor PAI-1 have been correlated with poor prognosis in breast cancer. We examined whether genetic variation in the genes of the uPA system affect breast cancer susceptibility and prognosis. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in six genes of the uPA system in 959 Swedish breast cancer patients with detailed clinical data and up to 15 years of follow-up together with 952 matched controls. We used the unconditional logistic regression models to evaluate the associations between genotypes and breast cancer risk and tumor characteristics. The Kaplan-Meier method was used to estimate the survival probabilities; the log-rank test was used to test differences between subgroups. None of the SNPs conferred an increased breast cancer risk, but correlation with some traditional prognostic factors was observed for several SNPs. Most importantly, we identified the -675 4G/5G SNP in the PAI-1 gene as a promising prognostic biomarker for breast cancer. Compared to the 4G/4G and 4G/5G genotypes 5G/5G homozygosity correlated significantly with worse survival (RR 2.04, 95% CI 1.45-2.86, P5G/5G homozygotes were also the group with worse survival among lymph node negative cases. Our finding suggests that genotyping PAI-1 -675 4G/5G may help in clinical prognosis of breast cancer.

  11. The Transcription Factor ZNF217 Is a Prognostic Biomarker and Therapeutic Target during Breast Cancer Progression

    Science.gov (United States)

    Littlepage, Laurie E.; Adler, Adam S.; Kouros-Mehr, Hosein; Huang, Guiqing; Chou, Jonathan; Krig, Sheryl R.; Griffith, Obi L.; Korkola, James E.; Qu, Kun; Lawson, Devon A.; Xue, Qing; Sternlicht, Mark D.; Dijkgraaf, Gerrit J. P.; Yaswen, Paul; Rugo, Hope S.; Sweeney, Colleen A.; Collins, Colin C.; Gray, Joe W.; Chang, Howard Y.; Werb, Zena

    2013-01-01

    The transcription factor ZNF217 is a candidate oncogene in the amplicon on chromosome 20q13 that occurs in 20% to 30% of primary human breast cancers and that correlates with poor prognosis. We show that Znf217 overexpression drives aberrant differentiation and signaling events, promotes increased self-renewal capacity, mesenchymal marker expression, motility, and metastasis, and represses an adult tissue stem cell gene signature downregulated in cancers. By in silico screening, we identified candidate therapeutics that at low concentrations inhibit growth of cancer cells expressing high ZNF217. We show that the nucleoside analogue triciribine inhibits ZNF217-induced tumor growth and chemotherapy resistance and inhibits signaling events [e.g., phospho-AKT, phospho-mitogen-activated protein kinase (MAPK)] in vivo. Our data suggest that ZNF217 is a biomarker of poor prognosis and a therapeutic target in patients with breast cancer and that triciribine may be part of a personalized treatment strategy in patients overexpressing ZNF217. Because ZNF217 is amplified in numerous cancers, these results have implications for other cancers. SIGNIFICANCE This study finds that ZNF217 is a poor prognostic indicator and therapeutic target in patients with breast cancer and may be a strong biomarker of triciribine treatment efficacy in patients. Because previous clinical trials for triciribine did not include biomarkers of treatment efficacy, this study provides a rationale for revisiting triciribine in the clinical setting as a therapy for patients with breast cancer who overexpress ZNF217. PMID:22728437

  12. Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer.

    LENUS (Irish Health Repository)

    2012-02-01

    Colorectal cancer is a leading cause of cancer-related deaths worldwide. Early diagnosis and treatment of colorectal cancer is the key to improving survival rates and as such a need exists to identify patients who may benefit from adjuvant chemotherapy. The dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in oncogenesis and cancer cell survival, and proteasome inhibitors are in clinical use for a number of malignancies including multiple myeloma. In our study, we examined the protein expression of several key components of the UPS in colorectal cancer using immunohistochemistry to determine expression levels of ubiquitinylated proteins and the proteasomal subunits, 20S core and Rpt4 in a cohort of 228 patients with colon cancer. Multivariate Cox analysis revealed that neither the intensity of either ubiquitinylated proteins or the 20S core was predictive in either Stage II or III colon cancer for disease free survival or overall survival. In contrast, in Stage II patients increased Rpt4 staining was significantly associated with disease free survival (Cox proportional hazard ratio 0.605; p = 0.0217). Our data suggest that Rpt4 is an independent prognostic variable for Stage II colorectal cancer and may aid in the decision of which patients undergo adjuvant chemotherapy.

  13. Expression of Bmi-1 is a prognostic marker in bladder cancer

    Directory of Open Access Journals (Sweden)

    Xu Li-Hua

    2009-02-01

    Full Text Available Abstract Background The molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer. Methods We examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis. Results Expression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (P P P P P > 0.5. In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, P P P > 0.05. Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (P P Conclusion Expression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.

  14. Cancer testis antigens in newly diagnosed and relapse multiple myeloma: Prognostic markers and potential targets for immunotherapy

    NARCIS (Netherlands)

    M. van Duin (Mark); A. Broyl (Annemiek); Y. de Knegt (Yvonne); H. Goldschmidt (Hartmut); P.G. Richardson (Paul); B. van der Holt (Bronno); W.C.J. Hop (Wim); D. Joseph-Pietras (Debora); G. Mulligan (George); R. Neuwirth (Rachel); S.S. Sahota (Surinder); P. Sonneveld (Pieter)

    2011-01-01

    textabstractBackground In multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens which can be classified by varying expression in norma

  15. A Novel Prognostic Score, Based on Preoperative Nutritional Status, Predicts Outcomes of Patients after Curative Resection for Gastric Cancer.

    Science.gov (United States)

    Liu, Xuechao; Qiu, Haibo; Liu, Jianjun; Chen, Shangxiang; Xu, Dazhi; Li, Wei; Zhan, Youqing; Li, Yuanfang; Chen, Yingbo; Zhou, Zhiwei; Sun, Xiaowei

    2016-01-01

    PURPOSE: We aimed to determine whether preoperative nutritional status (PNS) was a valuable predictor of outcome in patients with gastric cancer (GC). METHODS: We retrospectively evaluated 1320 patients with GC undergoing curative resection. The PNS score was constructed based on four objective and easily measurable criteria: prognostic nutritional index (PNI) score 1, serum albumin nutritional-based prognostic score, is independently associated with OS in GC. Prospective studies are needed to validate its clinical utility.

  16. Developing and comparing two different prognostic indexes for predicting disease-free survival of nonmetastatic breast cancer patients

    OpenAIRE

    TOKATLI, Zehra Füsun; Türe, Mevlüt; Ömürlü, İmran Kurt; ALAS, Ruşen Çoşar; Uzal, Mustafa Cem

    2011-01-01

    To determine 2 different prognostic indexes (PI) for the differentiation of subgroups of nonmetastatic breast cancer patients with the Cox regression analysis and survival tree (ST) methods and the additional usage of the Kaplan-Meier estimates to investigate the predictive power of these methods. Materials and methods: Prognostic factors data were collected for 410 patients. The Cox regression analysis examines the relationship of the survival distribution and covariates. The ST method is ...

  17. Prognostic factors affecting disease-free survival rate following surgical resection of primary breast cancer

    Directory of Open Access Journals (Sweden)

    K Horita

    2009-12-01

    Full Text Available In order to identify the prognostic factors that significantly influence the disease-free survival rate after surgical resection of primary breast cancers, we determined tumour and lymph node grades, and immunohistochemical staining for estrogen and progesterone receptors (ER and PR, c-erbB-2, p53, bcl-2, bax and PCNA in 76 patients. Univariate analysis showed that increased grade of tumour and lymph nodes, negative immunostaining for ER, positive immunostaining for c-erbB-2, and a high PCNA index (³30% negatively influenced the disease- free survival rate, but PR, p53, bcl-2 and bax had no predictive value. Although p53 was not an independent prognostic factor by itself, the combination of p53, bcl-2, and bax proved to correlate with the disease-free survival, with the best prognosis noted in tumours negative for p53 and positive for both bcl-2 and bax, intermediate prognosis in tumours negative for p53 and positive for either bcl- 2 or bax and worst prognosis in tumors negative for p53 as well as bcl-2 and bax. Tumour grade correlated positively with PCNA index, while positive staining for ER correlated negatively with tumour grade as well as with PCNA index, although this was statistically insignificant. Immunostaining of breast cancers for Bcl-2 correlated negatively with tumour grade and PCNA index. Immunostaining for c-erbB-2 correlated positively with PCNA but not with tumour grade. Immunostaining for p53 tended to correlate positively with PCNA, but not with tumour grade. Immunostaining for PR and bax did not correlate with tumour grade and PCNA index. These results suggest that in addition to tumour size and lymph node involvement, immunostaining for ER, c-erbB-2, and a high PCNA index are important prognostic factors in human breast cancer. Wild-type p53 with preserved bcl-2 and bax gene products is also a favorable prognostic factor indicating breast cancer at an early stage of cancer progression.

  18. Overview of diagnostic/targeted treatment combinations in personalized medicine for breast cancer patients

    Directory of Open Access Journals (Sweden)

    Tessari A

    2013-12-01

    Full Text Available Anna Tessari,1 Dario Palmieri,2 Serena Di Cosimo11Division of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 2Molecular Biology and Cancer Genetics, Comprehensive Cancer Center, The Ohio State University College of Medicine, Columbus, OH, USAAbstract: Breast cancer includes a body of molecularly distinct subgroups, characterized by different presentation, prognosis, and sensitivity to treatments. Significant advances in our understanding of the complex architecture of this pathology have been achieved in the last few decades, thanks to new biotechnologies that have recently come into the research field and the clinical practice, giving oncologists new instruments that are based on biomarkers and allowing them to set up a personalized approach for each individual patient. Here we review the main treatments available or in preclinical development, the biomolecular diagnostic and prognostic approaches that changed our perspective about breast cancer, giving an overview of targeted therapies that represent the current standard of care for these patients. Finally, we report some examples of how new technologies in clinical practice can set in motion the development of new drugs.Keywords: breast cancer, biomarkers, gene expression profile, next generation sequencing, targeted therapy

  19. Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients

    DEFF Research Database (Denmark)

    Hansen, S.; Overgaard, Jens; Rose, C.

    2003-01-01

    Tumour angiogenesis and the levels of plasminogen activator inhibitor type 1 (PAI-1) are both informative prognostic markers in breast cancer. In cell cultures and in animal model systems, PAI-1 has a proangiogenic effect. To evaluate the interrelationship of angiogenesis and the PAI-1 level in b...... and the Chalkley count are independent prognostic markers for recurrence-free survival in patients with primary breast cancer, suggesting that the prognostic impact of PAI-1 is not only based on its involvement in angiogenesis.......Tumour angiogenesis and the levels of plasminogen activator inhibitor type 1 (PAI-1) are both informative prognostic markers in breast cancer. In cell cultures and in animal model systems, PAI-1 has a proangiogenic effect. To evaluate the interrelationship of angiogenesis and the PAI-1 level...... in breast cancer, we have evaluated the prognostic value of those factors in a total of 228 patients with primary, unilateral, invasive breast cancer, evaluated at a median follow-up time of 12 years. Microvessels were immunohistochemically stained by antibodies against CD34 and quantitated by the Chalkley...

  20. Prognostic Aspects of DCE-MRI in Recurrent Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gollub, M.J.; Gultekin, D.H.; Sohn, M. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Cao, K. [Peking University Cancer Hospital and Institute, Department of Radiology, Beijing (China); Kuk, D.; Gonen, M. [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Schwartz, L.H. [Columbia University Medical Center/New York Presbyterian Hospital, Department of Radiology, New York, NY (United States); Weiser, M.R.; Temple, L.K.; Nash, G.M.; Guillem, J.G.; Garcia-Aguilar, J.; Paty, P.B. [Memorial Sloan-Kettering Cancer Center, Department of Surgery, New York, NY (United States); Wang, M. [Fudan University Shanghai Cancer Center, Department of Colorectal Surgery, Shanghai (China); Goodman, K. [Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY (United States)

    2013-12-15

    To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K{sup trans}, K{sub ep}, V{sub e}, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K{sup trans} (0.55, P = 0.012) and K{sub ep} (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K{sup trans}, K{sub ep}, V{sub e}, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. K{sup trans} and K{sub ep} were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation. (orig.)

  1. RELATIONSHIP BETWEEN THE EXPRESSIONS OF SURVIVIN AND THE PROGNOSTIC RELATED FACTORS IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    SHEN Jing-hua; WANG Xiao-juan; SU He-ba-te; ZHAO Xiao-xia; TAO Ge-si

    2005-01-01

    Objective: To study the relationship between the Survivin expression and the histological grade, status of ER,expression of PS2 and the prognosis of patients with primary invasive breast cancer. Method: By using LSAB and SP immunohistochemical method, the expression of Survivin, PS2 and ER in 95 cases of invasive breast cancer were detected.Results: the positive rate of Survivin was 70.5% (67/95) and the expression of Survivin was positively related to the histological grade and status of PS2 and ER. The survival time after operation of patients without expression of Survivin was longer than those with positive Survivin. Conclusion: These data suggest that Survivin expression may be considered as a new unfavorable prognostic factor of breast cancer.

  2. Clinical and Prognostic Implications of Transcription Factor SOX4 in Patients with Colon Cancer.

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    Chun-Mao Lin

    Full Text Available Colon cancer is one of the most common malignant cancers worldwide but the current therapeutic approaches for advanced colon cancer are less efficient. This study investigated associations between the expression of nuclear transcription factor SOX4 and various clinicopathologic parameters as well as patients' survival. Expression levels of nuclear SOX4 were analyzed by immunohistochemistry; the data comprised colon tissues from 263 patients with colon cancer. Paired t tests were used to analyze the differences in nuclear SOX4 expression between tumor and non-tumor tissues from each patient. Two-tailed Χ(2 tests were performed to determine whether the differences in nuclear SOX4 expression and clinicopathologic parameters were significant. Time-to-event endpoints for clinicopathologic parameters were plotted using the Kaplan-Meier method, and statistical significance was determined using univariate log-rank tests. Cox proportional hazard model was used for multivariate analysis to determine the independence of prognostic effects of nuclear SOX4 expression. Overexpression of nuclear SOX4 was significantly correlated with depth of invasion (P = 0.0041, distant metastasis (P<0.0001, and stage (P = 0.0001. Patients who displayed high expression levels of nuclear SOX4 achieved a significantly poorer disease-free survival rate, compared with patients with low SOX4 expression levels (P<0.001. Univariate Cox regression analysis showed that overexpression of nuclear SOX4 was a clear prognostic marker for colon cancer (P = 0.001. Overexpression of nuclear SOX4 may be used as a marker to predict the outcome of patients with colon cancer.

  3. Vascular endothelial growth factor and microvessel density for detection and prognostic evaluation of invasive breast cancer

    Institute of Scientific and Technical Information of China (English)

    Lukui Yang; Long Li; Xiangyu Cui; Dalei Yang

    2015-01-01

    Objective The purpose of this study was to evaluate the distribution of vascular endothelial growth factor (VEGF) and CD105-microvessel density (MVD) in invasive breast carcinomas. We also aimed to analyze the relationship between VEGF and MVD expression with other standard prognostic parameters associated with invasive breast cancer, such as size, grade, stage of the cancer, metastases, and tumor recurrence. Methods Immunohistochemistry via the Ultra SensitiveTM S-P method was used to detect VEGF and MVD expression in 128 cases of invasive breast carcinoma. Specimens were evaluated for CD105 expres-sion. Positively stained microvessels were counted in dense vascular foci under 400× magnification. MVD in the peripheral area adjacent to the lesion and in the central area within the lesion in invasive breast carcinomas and benign leisions groups were also assessed. Fifty cases of benign breast disease tissue were selected as the control group. Results Results showed that 64.1% of invasive breast cancer samples were VEGF-positive, higher than in benign breast disease tissue (22.0%, P 0.05). MVD of the peripheral area adja-cent to the lesion was significantly higher than those central area within the lesion in both invasive breast cancer and benign breast disease groups (P 50 years) or the two tumor diameter groups (≤2 cm vs.>2 cm), P > 0.05. Conclusion Overexpression of VEGF and MVD may be important biological markers for invasion and lymph node and distant metastases of invasive breast cancer. Combined detection of the two tumor mark-ers could provide better prognostic monitoring for disease recurrence and metastasis, as wel as aid with clinical staging of breast tumors. Prediction of the risk for metastasis and recurrence, as wel as recurrence patterns based on VEGF and MVD post-surgery, could aid design of better fol ow-up regimens and appro-priate treatment strategies for breast cancer patients.

  4. The prognostic significance of fibroblast growth factor receptor 4 in non-small-cell lung cancer

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    Huang H

    2015-05-01

    Full Text Available Hong-ping Huang, Hui Feng, Hong-bo Qiao, Ze-xiang Ren, Ge-dong ZhuDepartment of General Medicine, Linyi Hospital Affiliated to Shandong University, Linyi City, People’s Republic of China Background: Fibroblast growth factor receptor 4 (FGFR4 has been proved to be correlated with progression and prognosis in many cancers. However, the significance of FGFR4 in non-small-cell lung cancer (NSCLC is still not well elucidated.Methods: In our experiment, we detected FGFR4 expression in 237 samples of NSCLC with immunohistochemistry, and further analyzed the correlation between FGFR4 and clinicopathologic features of NSCLC with chi-square test. Moreover, we evaluated the prognostic value of FGFR4 by Kaplan–Meier survival curve and Cox regression model. By regulating the expression of FGFR4 by overexpression or knockdown, we assessed the role of FGFR4 on NSCLC cell proliferation.Results: FGFR4 expression was high in NSCLC (46.8%, 111/237. FGFR4 expression was significantly associated with tumor diameter (P=0.039. With univariate (P=0.009 and multivariate (P=0.002 analysis, FGFR4 was identified as an independent prognostic factor in NSCLC (P=0.009. Moreover, FGFR4 can promote the proliferation of NSCLC cell lines.Conclusion: FGFR4 is an independent prognostic biomarker in NSCLC. FGFR4 can accelerate the proliferation of NSCLC cell lines, indicating FGFR4 could be a potential drug target of NSCLC.Keywords: fibroblast growth factor 4, non-small-cell lung cancer, prognosis, proliferation

  5. Expression of connective tissue growth factor in male breast cancer: clinicopathologic correlations and prognostic value.

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    Miangela M Lacle

    Full Text Available Connective tissue growth factor (CTGF/CCN2 is a member of the CCN family of secreted proteins that are believed to play an important role in the development of neoplasia. In particular, CTGF has been reported to play an important role in mammary tumorigenesis and to have prognostic value in female breast cancer (FBC. The aim of the present study was to investigate clinicopathologic correlations and prognostic value of CTGF in male breast cancer (MBC and to compare these findings with FBC. For this, we studied CTGF protein expression by immunohistochemistry in 109 MBC cases and 75 FBC cases. In MBC, stromal CTGF expression was seen in the majority of the cases 78% (85/109 with high expression in 31/109 cases (28.4%, but expression in tumor cells was only seen in 9.2% (10/109 of cases. High stromal CTGF expression correlated with high grade and high proliferation index (>15% assessed by MIB-1 immunohistochemical staining. CTGF expression in tumor epithelial cells did not correlate with any of the clinicopathologic features. In FBC, stromal CTGF expression positively correlated with mitotic count and tumor CTGF expression was associated with triple negative status of the tumor (p = 0.002. Neither stromal nor tumor epithelial cell CTGF expression had prognostic value in MBC and FBC. In conclusion, stromal CTGF expression was seen in a high percentage of MBC and was correlated with high grade and high proliferation index. In view of the important role of the microenvironment in cancer progression, this might suggest that stromal CTGF could be an interesting target for novel therapies and molecular imaging. However, the lack of association with prognosis warrants caution. The potential role of CTGF as a therapeutic target for triple negative FBC deserves to be further studied.

  6. DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF INTRATHECAL SYNTHESIS OF IMMUNOGLOBULIN FREE LIGHT CHAINS IN MULTIPLE SCLEROSIS

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    V. D. Nazarov

    2015-01-01

    Full Text Available Increased intrathecal synthesis and oligoclonal banding of immunoglobulins (Ig in cerebrospinal fluid (CSF are major immunological findings in multiple sclerosis. Free light chains are fragments of Ig molecules that are produced in parallel to oligoclonal Ig, and their production reflects total Ig synthesis within central nervous system. Assessment of intrathecal kappaand lambda free light chain production within CNS compartment will help to improve diagnosis and prediction of outcomes in multiple sclerosis. Concentrations of kappa and lambda free light chains and clonality of immunoglobulin pattern synthesis were studied in paired CSF and serum samples of 151 patients, including 92 patients with multiple sclerosis, and 33 patients with clinically isolated syndrome which later was transformed into the definite multiple sclerosis. A control group consisted of 26 patients with other inflammatory diseases of central nervous system. Several Ig parameters have been determined in the patients, i.e., Ig clonality in CSF; concentrations of free light chains (both kappaand lambda- in CSF; as well as their indexes and ratios. It was established that synthesis of kappa free light chains were significantly elevated in patients with multiple sclerosis. Moreover, the amounts of free light Ig chains in patients with positive oligoclonality test were significantly higher than in cases without intrathecal oligoclonal synthesis. With respect to diagnostic significance, the kappa quotient proved the best available option for diagnosis of multiple sclerosis. Its combination with Ig oligoclonality assays caused a decrease in false-negative diagnostics by 42%. Diagnostic benefit of the kappa quotient could be also confirmed by the data of ROC analysis. Also concentration of lambda free light chains in cerebrospinal fluid showed a negative correlation with conversion terms of clinically isolated syndrome to evident multiple sclerosis. Therefore, the indexes of free Ig

  7. Prognostic factors of overall survival in renal cancer patients – single oncological center study

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    Kajetan Juszczak

    2013-08-01

    Full Text Available Introduction. The clinical course of renal cancer remains difficult to predict. Attempts to appoint new independent prognostic factors (IPFs and comparisons of already identified ones among populations are inevitable to develop more effective prognostic instruments. The aim of this study was to evaluate IPFs of overall survival in a given population of patients with renal cancer.Materials and methods. Retrospective analysis of 148 patients with renal cancer treated at the Oncological Institute in Cracow from 2000 to 2007 was performed. Mean follow–up was 51 months. Using the log–rang test, a group of clinicopathological and biochemical features was analyzed in respect to their influence on overall survival. Results were presented as Kaplan–Meier curves. Final identification of IPFs was made by multivariate Cox regression analysis.Results. Overall survival rate at 1, 2, and 5–year follow–up was 58.8%, 38.2%, and 21.4%, respectively. The set of identified IPFs consisted of performance status, smoking history, hemoglobin concentration, anatomical staging, tumor grade, and the presence of microvascular invasion. It was confirmed that only nephrectomy increases significantly overall survival.Conclusions. Apart from smoking history, the role of all other IPFs identified in our study is well documented in the literature. Smoking history seems to be a new IPF with strong negative impact on survival in patients with RCC.

  8. P53 and Ki-67 as prognostic markers in triple-negative breast cancer patients

    Science.gov (United States)

    Pan, Yunbao; Yuan, Yufen; Liu, Guoshi; Wei, Yongchang

    2017-01-01

    Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer lack of effective target therapy. This study was to investigate the prognostic role of p53 and Ki-67 in 156 cases of TNBC patients. Logistic regression analysis was used to examine the association between clinical parameters and recurrence. Univariate and multivariate analyses were used to examine the association between clinical characteristics and disease-free survival (DFS) or overall survival (OS). Survival analyses using the Kaplan-Meier method were performed to examine the association between p53/Ki-67 and DFS and OS. Our data showed that p53 was positive in 71.3% and the Ki-67 high index was in 82.8% of TNBC. Elevated p53 and Ki-67 were associated with histological grade. The tumor size, lymph node involvement, and p53 expression are associated with risk of recurrence. Tumor size, lymph node involvement, family history, Ki-67 and p53 are independent variables associated with either DFS or OS. TNBC patients with positive p53 or Ki-67 high index or family history of cancer have a significant association with worse prognosis. This study suggests that p53, Ki-67 and family history are useful prognostic markers in TNBC. PMID:28235003

  9. Circulating Haptoglobin Is an Independent Prognostic Factor in the Sera of Patients with Epithelial Ovarian Cancer*

    Science.gov (United States)

    Zhao, Changqing; Annamalai, Loganath; Guo, Changfa; Kothandaraman, Narasimhan; Koh, Stephen Chee Liang; Zhang, Huoming; Biswas, Arijit; Choolani, Mahesh

    2007-01-01

    Abstract OBJECTIVE This study was conducted to evaluate the prognostic significance of haptoglobin levels in the overall survival of patients presenting with various stages of epithelial ovarian cancer. MATERIALS AND METHODS We employed an in-house sandwich enzyme-linked immunosorbent assay method to determine the concentrations of preoperative haptoglobin and C-reactive protein (CRP) in sera samples obtained from 66 malignant tumors, 60 benign tumors, and 10 normal healthy women. RESULTS Levels of serum haptoglobin significantly correlated with tumor type (P < .001) and International Federation of Gynecology and Obstetrics stage (P < .05). A significant correlation was observed between clinical stage and patient survival (r = 5.99, P = .026). Our data also indicated that elevated serum haptoglobin levels were associated with poor outcome for overall survival using both univariate and multivariate analyses (P = .048 and P = .036 respectively). Using Pearson's correlation, we have noted that serum CRP concentrations significantly correlated with haptoglobin levels (r2 = 0.22, P < .001). Immunohistochemical findings and Western blot analyses were compatible with sera levels of haptoglobin in which a higher intensity of staining occurred in late-stage epithelial ovarian cancers. CONCLUSION This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer. PMID:17325738

  10. Circulating Haptoglobin Is an Independent Prognostic Factor in the Sera of Patients with Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Changqing Zhao

    2007-01-01

    Full Text Available OBJECTIVE: This study was conducted to evaluate the prognostic significance of haptoglobin levels in the overall survival of patients presenting with various stages of epithelial ovarian cancer. MATERIALS AND METHODS: We employed an in-house sandwich enzyme-linked immunosorbent assay method to determine the concentrations of preoperative haptoglobin and C-reactive protein (CRP in sera samples obtained from 66 malignant tumors, 60 benign tumors, and 10 normal healthy women. RESULTS: Levels of serum haptoglobin significantly correlated with tumor type (P < .001 and International Federation of Gynecology and Obstetrics stage (P < .05. A significant correlation was observed between clinical stage and patient survival (r = 5.99, P = .026. Our data also indicated that elevated serum haptoglobin levels were associated with poor outcome for overall survival using both univariate and multivariate analyses (P = .048 and P = .036 respectively. Using Pearson's correlation, we have noted that serum CRP concentrations significantly correlated with haptoglobin levels (r2 = 0.22, P < .001. Immunohistochemical findings and Western blot analyses were compatible with sera levels of haptoglobin in which a higher intensity of staining occurred in late-stage epithelial ovarian cancers. CONCLUSION: This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer.

  11. Regional cerebral blood flow in normal pressure hydrocephalus: diagnostic and prognostic aspects

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    Larsson, A. (Dept. of Neurology, Sahlgren Hospital, Goeteborg (Sweden)); Bergh, A.C. (Dept. of Clinical Physiology, Sahlgren Hospital, Goeteborg (Sweden)); Bilting, M. (Dept. of Neurosurgery, Sahlgren Hospital, Goeteborg (Sweden)); Aerlig, AA. (Dept. of Radiation Physics, Sahlgren Hospital, Goeteborg (Sweden)); Jacobsson, L. (Dept. of Radiation Physics, Sahlgren Hospital, Goeteborg (Sweden)); Stephensen, H. (Dept. of Neurosurgery, Sahlgren Hospital, Goeteborg (Sweden)); Wikkelsoe, C. (Dept. of Neurology, Sahlgren Hospital, Goeteborg (Sweden))

    1994-02-01

    Relative regional cerebral blood flow (rrCBF) was measured by SPET using [sup 99m]Tc-HMPAO as flow tracer, in 23 patients with normal pressure hydrocephalus (NPH). 1000 MBq [sup 99m]Tc-HMPAO was given intravenously and the rrCBF calculated as regional/cerebellar count level ratios. The patients were examined before and 3-12 months after ventriculoperitoneal shunt surgery. rrCBF was also determined in ten healthy aged matched volunteers who served as controls. The NPH patients had decreased rrCBF in the hippocampal regions and in the frontal and parietal white matter as compared to the controls. The frontal/parietal rrCBF ratio correlated with both psychiatric disability and the preoperative degree of incontinence. Decreased flow in frontal white matter, frontoparietal and hippocampal grey matter and a low frontalparietal grey matter flow ratio preoperatively correlated with improvement in both Mini Mental State score and psychiatric disability after shunt surgery. After shunt surgery the rrCBF increased in the mesencephalon, frontal grey and white matter, parietal white matter and hippocampus. The flow increase in hippocampal regions and frontal white matter correlated with improvement in psychiatric symptomatology. The results of this study regarding the frontal and hippocampal rrCBF patterns, and the clinical correlation, support the hypothesis that CBF changes in these regions are of patohphysiological and prognostic importance in NPH. (orig./MG)

  12. Coronary CT Angiography as a Diagnostic and Prognostic Tool: Perspectives from the SCOT-HEART Trial.

    Science.gov (United States)

    Doris, Mhairi; Newby, David E

    2016-02-01

    Coronary artery disease is the leading cause of death worldwide. Many trials to date have investigated the diagnostic accuracy of coronary computed tomography angiography (CCTA) when compared to the gold standard diagnostic test, invasive coronary angiography. However, whether the use of a non-invasive anatomical test, such as CCTA, can translate into improved patient risk stratification, management and outcome has yet to be established. The Scottish COmputed Tomography of the HEART (SCOT-HEART) trial sought to address these questions and determined whether CCTA, when used in addition to standard care, could aid the diagnosis, further investigation and treatment of patients referred to the cardiology clinic with suspected angina due to coronary heart disease. In this trial, CCTA clarified the diagnosis of angina due to coronary heart disease in a quarter of patients and this led to major alterations in treatment and management that appeared to reduce the risk of subsequent coronary heart disease death or non-fatal myocardial infarction. The SCOT-Heart trial has established that CCTA is a valuable diagnostic test in patients with suspected angina pectoris due to coronary heart disease and leads to greater clarity, more focused appropriate treatments and better coronary heart disease outcomes.

  13. Empiric reliability of diagnostic and prognostic estimations of physical standards of children, going in for sports.

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    Zaporozhanov V.A.

    2012-12-01

    Full Text Available In the conditions of sporting-pedagogical practices objective estimation of potential possibilities gettings busy already on the initial stages of long-term preparation examined as one of issues of the day. The proper quantitative information allows to individualize preparation of gettings in obedience to requirements to the guided processes busy. Research purpose - logically and metrical to rotin expedience of metrical method of calculations of reliability of results of the control measurings, in-use for diagnostics of psychophysical fitness and prognosis of growth of trade gettings busy in the select type of sport. Material and methods. Analysed the results of the control measurings on four indexes of psychophysical preparedness and estimation of experts of fitness 24th gettings busy composition of children of gymnastic school. The results of initial and final inspection of gymnasts on the same control tests processed the method of mathematical statistics. Expected the metrical estimations of reliability of measurings is stability, co-ordination and informing of control information for current diagnostics and prognosis of sporting possibilities inspected. Results. Expedience of the use in these aims of metrical operations of calculation of complex estimation of the psychophysical state of gettings busy is metrology grounded. Conclusions. Research results confirm expedience of calculation of complex estimation of psychophysical features gettings busy for diagnostics of fitness in the select type of sport and trade prognosis on the subsequent stages of preparation.

  14. Diagnostic utility of DTI in prostate cancer

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    Guerses, Bengi, E-mail: bengur0@yahoo.com [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Tasdelen, Neslihan [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Yencilek, Faruk [Yeditepe University Medical Faculty, Department of Urology, Istanbul (Turkey); Kilickesmez, N. Ozguer [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Alp, Turgut [Fatih Sultan Mehmet Training and Research Hospital, Division of Urology, Istanbul (Turkey); Firat, Zeynep [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Albayrak, M. Selami [Kartal Training and Research Hospital, Division of Urology, Istanbul (Turkey); Ulug, Aziz M. [Yeditepe University Department of Biomedical Engineering, Istanbul (Turkey); The Feinstein Institute for Medical Research, Manhasset, New York (United States); Guermen, A. Nevzat [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey)

    2011-08-15

    Purpose: The aim of this study was to compare the diffusion tensor parameters of prostate cancer, prostatitis and normal prostate tissue. Materials and Methods: A total of 25 patients with the suspicion of prostate cancer were included in the study. MRI was performed with 3 T system (Intera Achieva, Philips Medical Systems, The Netherlands). T2 TSE and DTI with ss-EPI were obtained in each subject. TRUS-guided prostate biopsy was performed after the MRI examination. Images were analyzed by two radiologists using a special software system. ROI's were drawn according to biopsy zones which are apex, midgland, base and central zone on each sides of the gland. FA and ADC values in areas of cancer, chronic prostatitis and normal prostate tissue were compared using Student's t-test. Results: Histopathological analysis revealed carcinoma in 68, chronic prostatitis in 67 and was reported as normal in 65 zones. The mean FA of cancerous tissue was significantly higher (p < 0.01) than the FA of chronic prostatitis and normal gland. The mean ADC of cancerous tissue was found to be significantly lower (p < 0.01), compared with non-cancerous tissue. Conclusion: Decreased ADC and increased FA are compatible with the hypercellular nature of prostate tumors. These differences may increase the accuracy of MRI in the detection of carcinoma and to differentiate between cancer and prostatitis.

  15. Clinical features and prognostic factors for patients with bone metastases from prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Jian He; Zhao-Chong Zeng; Ping Yang; Bing Chen; We Jiang; Shi-Suo Du

    2012-01-01

    To identify the clinical features and independent predictors of survival in patients with bone metastases from prostate cancer (PCa).We retrospectively analysed 115 PCa patients with bone metastases between 1997 and 2009.The overall survival rate after bone metastases was calculated using the Kaplan-Meier method.The prognostic factors were identified by univariate analysis using a log-rank test and by multivariate analysis using Cox proportional hazards regression models.The follow-up rate was 100%,the follow-up cases during 1,3 and 5 years were 103,79 and 55,respectively.The 1-,3- and 5-year survival rates were 89.1%,60.9% and 49.8%,respectively,with a median survival time of 48.5 months for patients with bone metastases from PCa.In univariate analysis,age,Gleason score,clinical stage,the number of bone lesions,alkaline phosphatase (ALP) level,invasion of neighbouring organs and non-regional lymph node metastases were correlated with prognosis.By multivariate analysis using Cox regression,ALP level,Gleason score and non-regional lymph node metastases were independent prognostic factors.These prognostic factors will help us to determine the appropriate dose and fraction of radiotherapy for these patients.

  16. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors

    Directory of Open Access Journals (Sweden)

    Kanas GP

    2012-11-01

    Full Text Available Gena P Kanas,1 Aliki Taylor,2 John N Primrose,3 Wendy J Langeberg,4 Michael A Kelsh,4 Fionna S Mowat,1 Dominik D Alexander,5 Michael A Choti,6 Graeme Poston71Health Sciences, Exponent, Menlo Park, CA, USA; 2Centre for Observational Research, Amgen, Uxbridge, UK; 3Department of Surgery, Southampton General Hospital, Southampton, UK; 4Center for Observational Research, Amgen, Thousand Oaks, CA, USA; 5Health Sciences, Exponent, Chicago, IL, USA; 6Johns Hopkins Hospital, Baltimore, MD, USA; 7Department of Surgery, Aintree University Hospitals NHS, Liverpool, UKBackground: Hepatic metastases develop in approximately 50% of colorectal cancer (CRC cases. We performed a review and meta-analysis to evaluate survival after resection of CRC liver metastases (CLMs and estimated the summary effect for seven prognostic factors.Methods: Studies published between 1999 and 2010, indexed on Medline, that reported survival after resection of CLMs, were reviewed. Meta-relative risks for survival by prognostic factor were calculated, stratified by study size and annual clinic volume. Cumulative meta-analysis results by annual clinic volume were plotted.Results: Five- and 10-year survival ranged from 16% to 74% (median 38% and 9% to 69% (median 26%, respectively, based on 60 studies. The overall summary median survival time was 3.6 (range: 1.7–7.3 years. Meta-relative risks (95% confidence intervals by prognostic factor were: node positive primary, 1.6 (1.5–1.7; carcinoembryonic antigen level, 1.9 (1.1–3.2; extrahepatic disease, 1.9 (1.5–2.4; poor tumor grade, 1.9 (1.3–2.7; positive margin, 2.0 (1.7–2.5; >1 liver metastases, 1.6 (1.4–1.8; and >3 cm tumor diameter, 1.5 (1.3–1.8. Cumulative meta-analyses by annual clinic volume suggested improved survival with increasing volume.Conclusion: The overall median survival following CLM liver resection was 3.6 years. All seven investigated prognostic factors showed a modest but significant predictive

  17. Circulating protein fragments of cartilage and connective tissue degradation are diagnostic and prognostic markers of rheumatoid arthritis and ankylosing spondylitis.

    Directory of Open Access Journals (Sweden)

    Anne C Bay-Jensen

    Full Text Available Inflammation driven connective tissue turnover is key in rheumatic diseases, such as ankylosing spondylitis (AS. Few biomarkers are available for measuring disease prognosis or the efficacy of interventions applied in these tissue-related conditions. Type II collagen is the primary structural protein of cartilage and type III collagen of connective tissues, and obvious targets for the collagenalytic, which increase during tissue inflammation. The objective of the study was to investigate the diagnostic and prognostic utility of cartilage, C2M, and synovial, C3M, turnover biomarkers in AS. Serum samples were retrieved from patients suffering from AS (n = 103, RA (n = 47 and healthy controls (n = 56. AS progressors were defined as having new vertebral syndesmophytes or more that 3 unit change in mSASSS over a two-year period. Type II collagen degradation markers in serum were measured by the C2M ELISA, and type III collagen degradation by the C3M ELISA. Logistic regression and dichotomized decision tree were used to analyze the prognostic value of the markers individually or in combination. Both C2M and C3M levels were significantly higher in RA patients than in healthy controls (p<0.0001. Diagnostic utility was analyzed by ROC and areas under the curve (AUCs were 72% and 89% for C2M and C3M, respectively. Both C2M and C3M, were significantly higher in serum samples from AS patient than from healthy controls (p<0.0001. The AUCs of C2M and C3M, respectively, were 70% and 81% for AS. A combination of C2M and C3M, dichotomized according to best cut-offs for individual markers, could correctly identify 80% of the progressors and 61% of the non-progressors. The present study is the first to show that specific biomarkers of cartilage and connective tissue degradation facilitate both diagnosis and prediction of progression of RA and AS.

  18. Single Gene Prognostic Biomarkers in Ovarian Cancer: A Meta-Analysis

    Science.gov (United States)

    Willis, Scooter; Villalobos, Victor M.; Gevaert, Olivier; Abramovitz, Mark; Williams, Casey; Sikic, Branimir I.; Leyland-Jones, Brian

    2016-01-01

    Purpose To discover novel prognostic biomarkers in ovarian serous carcinomas. Methods A meta-analysis of all single genes probes in the TCGA and HAS ovarian cohorts was performed to identify possible biomarkers using Cox regression as a continuous variable for overall survival. Genes were ranked by p-value using Stouffer’s method and selected for statistical significance with a false discovery rate (FDR) <.05 using the Benjamini-Hochberg method. Results Twelve genes with high mRNA expression were prognostic of poor outcome with an FDR <.05 (AXL, APC, RAB11FIP5, C19orf2, CYBRD1, PINK1, LRRN3, AQP1, DES, XRCC4, BCHE, and ASAP3). Twenty genes with low mRNA expression were prognostic of poor outcome with an FDR <.05 (LRIG1, SLC33A1, NUCB2, POLD3, ESR2, GOLPH3, XBP1, PAXIP1, CYB561, POLA2, CDH1, GMNN, SLC37A4, FAM174B, AGR2, SDR39U1, MAGT1, GJB1, SDF2L1, and C9orf82). Conclusion A meta-analysis of all single genes identified thirty-two candidate biomarkers for their possible role in ovarian serous carcinoma. These genes can provide insight into the drivers or regulators of ovarian cancer and should be evaluated in future studies. Genes with high expression indicating poor outcome are possible therapeutic targets with known antagonists or inhibitors. Additionally, the genes could be combined into a prognostic multi-gene signature and tested in future ovarian cohorts. PMID:26886260

  19. Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Seung-Gu [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan (Korea, Republic of); Kim, Dae Yong, E-mail: radiopiakim@hanmail.net [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Park, Ji Won; Oh, Jae Hwan; Kim, Sun Young; Chang, Hee Jin; Kim, Tae Hyun; Kim, Byung Chang; Sohn, Dae Kyung; Kim, Min Ju [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2012-02-01

    Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

  20. Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Prognostic Markers for Metastasis and Death

    Science.gov (United States)

    Heaphy, Christopher M.; Yoon, Ghil Suk; Peskoe, Sarah B.; Joshu, Corinne E.; Lee, Thomas K.; Giovannucci, Edward; Mucci, Lorelei A.; Kenfield, Stacey A.; Stampfer, Meir J.; Hicks, Jessica L.; De Marzo, Angelo M.; Platz, Elizabeth A.; Meeker, Alan K.

    2013-01-01

    Current prognostic indicators are imperfect predictors of outcome in men with clinicallylocalized prostate cancer. Thus, tissue-based markers are urgently needed to improve treatment and surveillance decision-making. Given that shortened telomeres enhance chromosomal instability and such instability is a hallmark of metastatic lesions, we hypothesized that alterations in telomere length in the primary cancer would predict risk of progression to metastasis and prostate cancer death. To test this hypothesis, we conducted a prospective cohort study of 596 surgically treated men who participated in the ongoing Health Professionals Follow-up Study. Men who had the combination of more variable telomere length among prostate cancer cells (cell-to-cell) and shorter telomere length in prostate cancer-associated stromal cells were substantially more likely to progress to metastasis or die of their prostate cancer. These findings point to the translational potential of this telomere biomarker for prognostication and risk stratification for individualized therapeutic and surveillance strategies. PMID:23779129

  1. Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure.

    Science.gov (United States)

    van Veldhuisen, Dirk J; Ruilope, Luis M; Maisel, Alan S; Damman, Kevin

    2016-09-01

    Heart failure guidelines suggest evaluating renal function as a routine work-up in every patient with heart failure. Specifically, it is advised to calculate glomerular filtration rate and determine blood urea nitrogen. The reason for this is that renal impairment and worsening renal function (WRF) are common in heart failure, and strongly associate with poor outcome. Renal function, however, consists of more than glomerular filtration alone, and includes tubulointerstitial damage and albuminuria. For each of these renal entities, different biomarkers exist that have been investigated in heart failure. Hypothetically, and in parallel to data in nephrology, these markers may aid in the diagnosis of renal dysfunction, or for risk stratification, or could help in therapeutic decision-making. However, as reviewed in the present manuscript, while these markers may carry prognostic information (although not always additive to established markers of renal function), their role in predicting WRF is limited at best. More importantly, none of these markers have been evaluated as a therapeutic target nor have their serial values been used to guide therapy. The evidence is most compelling for the oldest-serum creatinine (in combination with glomerular filtration rate)-but even for this biomarker, evidence to guide therapy to improve outcome is circumstantial at best. Although many new renal biomarkers have emerged at the horizon, they have only limited usefulness in clinical practice until thoroughly and prospectively studied. For now, routine measurement of (novel) renal biomarkers can help to determine cardiovascular risk, but there is no role for these biomarkers to change therapy to improve clinical outcome in heart failure.

  2. Diastolic dysfunction and diastolic heart failure: diagnostic, prognostic and therapeutic aspects

    Directory of Open Access Journals (Sweden)

    Galderisi Maurizio

    2005-04-01

    Full Text Available Abstract Left ventricular (LV diastolic dysfunction (DD and diastolic heart failure (HF, that is symptomatic DD, are due to alterations of myocardial diastolic properties. These alterations involve relaxation and/or filling and/or distensibility. Arterial hypertension associated to LV concentric remodelling is the main determinant of DD but several other cardiac diseases, including myocardial ischemia, and extra-cardiac pathologies involving the heart are other possible causes. In the majority of the studies, isolated diastolic HF has been made equal to HF with preserved systolic function (= normal ejection fraction but the true definition of this condition needs a quantitative estimation of LV diastolic properties. According to the position of the European Society of Cardiology and subsequent research refinements the use of Doppler echocardiography (transmitral inflow and pulmonary venous flow and the new ultrasound tools has to be encouraged for diagnosis of DD. In relation to uncertain definitions, both prevalence and prognosis of diastolic heart failure are very variable. Despite an apparent lower death rate in comparison with LV systolic HF, long-term follow-up (more than 5 years show similar mortality between the two kinds of HF. Recent studies performed by Doppler diastolic indexes have identified the prognostic power of both transmitral E/A ratio 1.5 (restrictive patterns. The therapy of LV DD and HF is not well established but ACE-inhibitors, angiotensin inhibitors, aldosterone antagonists and β-blockers show potential beneficial effect on diastolic properties. Several trials, completed or ongoing, have been planned to treat DD and diastolic HF.

  3. Molecular cytogenetics of cutaneous melanocytic lesions - diagnostic, prognostic and therapeutic aspects.

    Science.gov (United States)

    Blokx, Willeke Am M; van Dijk, Marcory C R F; Ruiter, Dirk J

    2010-01-01

    This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect these cytogenetic alterations in melanocytic tumours are described. In addition, the potential value of more novel techniques such as multiplex ligation-dependent probe amplification is pointed out. This review demonstrates that at present cytogenetics has mainly increased our understanding of the pathogenesis of melanocytic tumours, with an important role for activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the initiation of melanocytic tumours. Mutations in BRAF (in common naevocellular naevi), NRAS (congenital naevi), HRAS (Spitz naevi) and GNAQ (blue naevi) can all cause MAPK activation. All these mutations seem early events in the development of melanocytic tumours, but by themselves are insufficient to cause progression towards melanoma. Additional molecular alterations are implicated in progression towards melanoma, with different genetic alterations in melanomas at different sites and with varying levels of sun exposure. This genetic heterogeneity in distinct types of naevi and melanomas can be used for the development of molecular tests for diagnostic purposes. However, at the moment only few molecular tests have become of diagnostic value and are performed in daily routine practice. This is caused by lack of large prospective studies on the diagnostic value of molecular tests including follow-up, and by the low prevalence of certain molecular alterations. For the future we foresee an increasing role for cytogenetics in the treatment of melanoma patients with the increasing availability of targeted therapy. Potential targets for metastatic melanoma include genes involved in the MAPK pathway, such as BRAF and RAS. More recently, KIT

  4. Bioelectrical impedance phase angle as a prognostic indicator in breast cancer

    Directory of Open Access Journals (Sweden)

    Dahlk Sadie L

    2008-08-01

    Full Text Available Abstract Background Bioelectrical impedance analysis (BIA is an easy-to-use, non-invasive, and reproducible technique to evaluate changes in body composition and nutritional status. Phase angle, determined by bioelectrical impedance analysis (BIA, detects changes in tissue electrical properties and has been hypothesized to be a marker of malnutrition. Since malnutrition can be found in patients with breast cancer, we investigated the prognostic role of phase angle in breast cancer. Methods We evaluated a case series of 259 histologically confirmed breast cancer patients treated at Cancer Treatment Centers of America. Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of phase angle independent of stage at diagnosis and prior treatment history. Survival was calculated as the time interval between the date of first patient visit to the hospital and the date of death from any cause or date of last contact/last known to be alive. Results Of 259 patients, 81 were newly diagnosed at our hospital while 178 had received prior treatment elsewhere. 56 had stage I disease at diagnosis, 110 had stage II, 46 had stage III and 34 had stage IV. The median age at diagnosis was 49 years (range 25 – 74 years. The median phase angle score was 5.6 (range = 1.5 – 8.9. Patients with phase angle 5.6 had 49.9 months (95% CI: 35.6 to 77.8; n = 130; the difference being statistically significant (p = 0.031. Multivariate Cox modeling, after adjusting for stage at diagnosis and prior treatment history found that every one unit increase in phase angle score was associated with a relative risk of 0.82 (95% CI: 0.68 to 0.99, P = 0.041. Stage at diagnosis (p = 0.006 and prior treatment history (p = 0.001 were also predictive of survival independent of each other and phase angle. Conclusion This study demonstrates that BIA-derived phase angle is an independent prognostic indicator in patients

  5. Prognostic association of YB-1 expression in breast cancers: a matter of antibody.

    Directory of Open Access Journals (Sweden)

    Adele G Woolley

    Full Text Available The literature concerning the subcellular location of Y-box binding protein 1 (YB-1, its abundance in normal and cancer tissues, and its prognostic significance is replete with inconsistencies. An explanation for this could be due in part to the use of different antibodies in immunohistochemical and immunofluorescent labeling of cells and tissues. The inconsistencies could also be due to poor resolution of immunohistochemical data. We analyzed two cohorts of breast tumours for both abundance and subcellular location of YB-1 using three different antibodies; two targeting N-terminal epitopes (AB-a and AB-b and another (AB-c targeting a C-terminal epitope. We also investigated stress-induced nuclear translocation of YB-1 in cell culture. We report that both AB-a and AB-c detected increased YB-1 in the cytoplasm of high-grade breast cancers, and in those lacking estrogen and progesterone receptors; however the amount of YB-1 detected by AB-a in these cancers is significantly greater than that detected by AB-c. We confirm our previously published findings that AB-b is also detecting hnRNP A1, and cannot therefore be used to reliably detect YB-1 by immunohistochemistry. We also report that AB-a detected nuclear YB-1 in some tumour tissues and stress treated cells, whereas AB-c did not. To understand this, cancer cell lines were analyzed using native gel electrophoresis, which revealed that the antibodies detect different complexes in which YB-1 is a component. Our data suggest that different YB-1 antibodies show different staining patterns that are determined by the accessibility of epitopes, and this depends on the nature of the YB-1 complexes. It is important therefore to standardize the protocols if YB-1 is to be used reproducibly as a prognostic guide for different cancers.

  6. BRG1 is a prognostic marker and potential therapeutic target in human breast cancer.

    Directory of Open Access Journals (Sweden)

    Jin Bai

    Full Text Available BRG1, a core component of the SWI/SNF chromatin-remodeling complex, has been implicated in cancer development; however, the biological significance of BRG1 in breast cancer remains unknown. We explored the role of BRG1 in human breast cancer pathogenesis. Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 437 breast cancer specimens and investigated its role in breast cancer cell proliferation, migration and invasion. Our Kaplan-Meier survival curves showed that high BRG1 expression is inversely correlated with both overall (P = 0.000 and disease-specific (P = 0.000 5-year patient survival. Furthermore, we found that knockdown of BRG1 by RNA interference markedly inhibits cell proliferation and causes cessation of cell cycle. This reduced cell proliferation is due to G1 phase arrest as cyclin D1 and cyclin E are diminished whereas p27 is upregulated. Moreover, BRG1 depletion induces the expression of TIMP-2 but reduces MMP-2, thereby inhibiting the ability of cells to migrate and to invade. These results highlight the importance of BRG1 in breast cancer pathogenesis and BRG1 may serve as a prognostic marker as well as a potentially selective therapeutic target.

  7. Prognostic Significance of Immunoreactive Neutrophil Elastase in Human Breast Cancer: Long-Term Follow-Up Results in 313 Patients

    Directory of Open Access Journals (Sweden)

    Miwa Akizuki

    2007-03-01

    Full Text Available OBJECTIVE: We have measured the concentration of immunoreactive neutrophil elastase (ir-NE in the tumor extracts of 313 primary human breast cancers. Sufficient time has elapsed, and we are now ready to analyze its prognostic value in human breast cancer. METHODS: ir-NE concentration in tumor extracts was determined with an enzyme-linked immunosorbent assay that enables a rapid measurement of both free-form ir-NE and the α1-protease inhibitor-complexed form of ir-NE. We analyzed the prognostic value of this enzyme in human breast cancer in univariate and multivariate analyses. RESULTS: Patients with breast cancer tissue containing a high concentration of ir-NE had poor survival compared to those with a low concentration of ir-NE at the cutoff point of 9.0 µg/100 mg protein (P = .0012, which had been previously determined in another group of 49 patients. Multivariate stepwise analysis selected lymph node status (P= .0004; relative risk = 1.46 and ir-NE concentration (P= .0013; relative risk = 1.43 as independent prognostic factors for recurrence. CONCLUSIONS: Tumor ir-NE concentration is an independent prognostic factor in patients with breast cancer who undergo curative surgery. This enzyme may play an active role in tumor progression that leads to metastasis in human breast cancer.

  8. Small-Fiber Neuropathy: A Diabetic Microvascular Complication of Special Clinical, Diagnostic, and Prognostic Importance.

    Science.gov (United States)

    Körei, A E; Istenes, I; Papanas, N; Kempler, P

    2016-01-01

    Damage of small nerve fibers may lead to a large variety of clinical symptoms. Small-fiber neuropathy underlies the symptoms of painful diabetic neuropathy, which may decrease quality of life. It also contributes to the poor prognosis of diabetic neuropathy because it plays a key role in the pathogenesis of foot ulceration and autonomic neuropathy. Impairment of small nerve fibers is considered the earliest alteration in the course of diabetic neuropathy. Therefore, assessment of functional and morphological abnormalities of small nerve fibers may enable timely diagnosis. The definition, symptoms, and clinical significance of small-fiber neuropathy are considered in the present review. An apparently more complex interaction between small-fiber impairment and microcirculation is extensively discussed. Diagnostic modalities include morphometric and functional methods. Corneal confocal microscopy and punch skin biopsy are considered gold standards, but noninvasive functional tests are also diagnostically useful. However, in routine clinical practice, small-fiber neuropathy is diagnosed by its typical clinical presentation. Finally, prompt treatment should be initiated following diagnosis.

  9. PROGNOSTIC FACTORS OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY FOR LOCALIZED AND LOCALLY-ADVANCED PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    V. A. Chernyaev

    2014-08-01

    Full Text Available Purpose. To reveal prognostic factors of PSA-failure following radical prostatectomy in patients with localized and locally-advanced prostate cancer.Materials and methods. Medical data of 386 consecutive patients with localized and locally-advanced prostate cancer who underwent radical prostatectomy from 1997 to 2011 were analyzed. Median age was 61.0 years. Median PSA before surgery – 10.3 ng/ml. Plasma levels of VEGF, VEGFR2, VEGFR3, TGF-β1, CD105, IL-6 were measured using Enzyme Linked-Immuno-Sorbent Assay (ELISA before radical prostatectomy in 77 patients. Postoperatively the tumours were categorized as pT2 in 288 (59.1 %, pT3 – in 144 (37.3 %, pT4 – in 14 (3.6; pN+ – in 34 (8.8 % cases. Gleason score < 7 was present in 254 (65.8 %,  7 – in 132 (34.2 % specimens. Perineural invasion was identified in 188 (48.7 %, angiolymphatic invasion – in 126 (32.6 cases.Results. Biochemical recurrence occurred in 64 (16.6 % out of 386 patients at a median follow-up of 30.5 (12−164 months. Independent predictors of biochemical recurrence were PSA (HR 0.161 (95% CI:0.058−0.449; р = 0.001, Gleason sum in surgical specimens (HR 0.496 (95 % CI:0.268−0.917; p = 0.025, pN (HR 0.415 (95 % CI:0.181−0.955; p = 0.039. The patients were divided into 3 prognostic groups: good (0 factor, intermediate (1 factor, poor (2 factors and very poor (3 factors (AUC – 0.720 (95% CI: 0.656−0.784. High preoperative levels VEGF ( 67 pg/ml (р = 0.005, VEGFR2 ( 3149 pg/ml (р = 0.036, VEGFR3 ( 2268 pg/ml (р = 0.001, TGF-β1 ( 14473 pg/ml (р = 0.052 were identified as unfavorable prognostic factors for survival without PSA-failure. Conclusion. Independent prognostic factors of biochemical recurrence after prostatectomy were PSA, Gleason sum and pN. Joint effect of the factors allows to predict PSA-relapse with accuracy 0.720. Preoperative serum levels VEGF, VEGFR2, VEGFR3, TGF-β1 potentially are perspective markers for PSA-failure after

  10. PROGNOSTIC FACTORS OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY FOR LOCALIZED AND LOCALLY-ADVANCED PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    V. A. Chernyaev

    2012-01-01

    Full Text Available Purpose. To reveal prognostic factors of PSA-failure following radical prostatectomy in patients with localized and locally-advanced prostate cancer.Materials and methods. Medical data of 386 consecutive patients with localized and locally-advanced prostate cancer who underwent radical prostatectomy from 1997 to 2011 were analyzed. Median age was 61.0 years. Median PSA before surgery – 10.3 ng/ml. Plasma levels of VEGF, VEGFR2, VEGFR3, TGF-β1, CD105, IL-6 were measured using Enzyme Linked-Immuno-Sorbent Assay (ELISA before radical prostatectomy in 77 patients. Postoperatively the tumours were categorized as pT2 in 288 (59.1 %, pT3 – in 144 (37.3 %, pT4 – in 14 (3.6; pN+ – in 34 (8.8 % cases. Gleason score < 7 was present in 254 (65.8 %,  7 – in 132 (34.2 % specimens. Perineural invasion was identified in 188 (48.7 %, angiolymphatic invasion – in 126 (32.6 cases.Results. Biochemical recurrence occurred in 64 (16.6 % out of 386 patients at a median follow-up of 30.5 (12−164 months. Independent predictors of biochemical recurrence were PSA (HR 0.161 (95% CI:0.058−0.449; р = 0.001, Gleason sum in surgical specimens (HR 0.496 (95 % CI:0.268−0.917; p = 0.025, pN (HR 0.415 (95 % CI:0.181−0.955; p = 0.039. The patients were divided into 3 prognostic groups: good (0 factor, intermediate (1 factor, poor (2 factors and very poor (3 factors (AUC – 0.720 (95% CI: 0.656−0.784. High preoperative levels VEGF ( 67 pg/ml (р = 0.005, VEGFR2 ( 3149 pg/ml (р = 0.036, VEGFR3 ( 2268 pg/ml (р = 0.001, TGF-β1 ( 14473 pg/ml (р = 0.052 were identified as unfavorable prognostic factors for survival without PSA-failure. Conclusion. Independent prognostic factors of biochemical recurrence after prostatectomy were PSA, Gleason sum and pN. Joint effect of the factors allows to predict PSA-relapse with accuracy 0.720. Preoperative serum levels VEGF, VEGFR2, VEGFR3, TGF-β1 potentially are perspective markers for PSA-failure after

  11. Targeting SR-BI for cancer diagnostics, imaging and therapy

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    Maneesha Amrita Rajora

    2016-09-01

    Full Text Available Scavenger receptor class B type I (SR-BI plays an important role in trafficking cholesteryl esters between the core of high density lipoprotein and the liver. Interestingly, this integral membrane protein receptor is also implicated in the metabolism of cholesterol by cancer cells, whereby overexpression of SR-BI has been observed in a number of tumours and cancer cell lines, including breast and prostate cancers. Consequently, SR-BI has recently gained attention as a cancer biomarker and exciting target for the direct cytosolic delivery of therapeutic agents. This brief review highlights these key developments in SR-BI-targeted cancer therapies and imaging probes. Special attention is given to the exploration of high density lipoprotein nanomimetic platforms that take advantage of upregulated SR-BI expression to facilitate targeted drug-delivery and cancer diagnostics, and promising future directions in the development of these agents.

  12. State Space Formulation of Nonlinear Vibration Responses Collected from a Dynamic Rotor-Bearing System: An Extension of Bearing Diagnostics to Bearing Prognostics

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    Peter W. Tse

    2017-02-01

    Full Text Available Bearings are widely used in various industries to support rotating shafts. Their failures accelerate failures of other adjacent components and may cause unexpected machine breakdowns. In recent years, nonlinear vibration responses collected from a dynamic rotor-bearing system have been widely analyzed for bearing diagnostics. Numerous methods have been proposed to identify different bearing faults. However, these methods are unable to predict the future health conditions of bearings. To extend bearing diagnostics to bearing prognostics, this paper reports the design of a state space formulation of nonlinear vibration responses collected from a dynamic rotor-bearing system in order to intelligently predict bearing remaining useful life (RUL. Firstly, analyses of nonlinear vibration responses were conducted to construct a bearing health indicator (BHI so as to assess the current bearing health condition. Secondly, a state space model of the BHI was developed to mathematically track the health evolution of the BHI. Thirdly, unscented particle filtering was used to predict bearing RUL. Lastly, a new bearing acceleration life testing setup was designed to collect natural bearing degradation data, which were used to validate the effectiveness of the proposed bearing prognostic method. Results show that the prediction accuracy of the proposed bearing prognostic method is promising and the proposed bearing prognostic method is able to reflect future bearing health conditions.

  13. Macrophage markers in serum and tumor have prognostic impact in American Joint Committee on Cancer stage I/II melanoma

    DEFF Research Database (Denmark)

    Jensen, T.O.; Schmidt, H.; Moller, H.J.;

    2009-01-01

    PURPOSE: To evaluate the prognostic role of soluble CD163 (sCD163) in serum and macrophage infiltration in primary melanomas from patients with American Joint Committee on Cancer (AJCC) stage I/II melanoma. The scavenger receptor CD163 is associated with anti-inflammatory macrophages, and it is s......PURPOSE: To evaluate the prognostic role of soluble CD163 (sCD163) in serum and macrophage infiltration in primary melanomas from patients with American Joint Committee on Cancer (AJCC) stage I/II melanoma. The scavenger receptor CD163 is associated with anti-inflammatory macrophages...

  14. Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer.

    LENUS (Irish Health Repository)

    Wang, Lai Mun

    2012-02-01

    BACKGROUND: Tumor budding along the advancing front of colorectal adenocarcinoma is an early event in the metastatic process. A reproducible, prognostic budding scoring system based on outcomes in early stage colorectal cancer has not been established. DESIGN: One hundred twenty-eight T3N0M0 colorectal carcinoma patients with known outcome were identified. Tumor budding was defined as isolated tumor cells or clusters of <5 cells at the invasive tumor front. Tumor bud counts were generated in 5 regions at 200x by 2 pathologists (conventional bud count method). The median bud count per case was used to divide cases into low (median=0) and high budding (median > or =1) groups. Forty cases were reevaluated to assess reproducibility using the conventional and a novel rapid bud count method. RESULTS: Fifty-seven (45%) carcinomas had high and 71 (55%) had low budding scores. High budding was associated with an infiltrative growth pattern (P<0.0001) and lymphovascular invasion (P=0.005). Five-year cancer-specific survival was significantly poorer in high compared with low budding groups: 63% versus 91%, respectively, P<0.0001. Multivariate analysis demonstrated tumor budding to be independently prognostic (hazard ratio=4.76, P<0.001). Interobserver agreement was at least equivalent comparing the conventional to the rapid bud count methods: 87.5% agreement (kappa=0.75) versus 92.5% agreement (kappa=0.85), respectively. CONCLUSIONS: Tumor budding is a strong, reproducible, and independent prognostic marker of outcome that is easily assessed on hematoxylin and eosin slides. This may be useful for identifying the subset of T3N0M0 patients at high risk of recurrence who may benefit from adjuvant therapy.

  15. Analysis of Prognostic Factors in 541 Female Patients with Advanced Non-small Cell Lung Cancer

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    Meina WU

    2011-03-01

    Full Text Available Background and objective As there is a sharp increase in the incidence of lung cancer in women in recent years, it has brought broad concerns with its unique clinical and epidemiological characteristics and better prognosis. The aim of this study is to analyze the clinical data of women with advanced non-small cell lung cancer (NSCLC retrospectively to explore the prognostic factors. Methods Clinical data of 541 female patients with advanced NSCLC were collected and followed up till death. The primary endpoint is overall survival (OS. SPSS 11.0 statistical analysis software was used for univariate and multivariate analysis. Results The mean age is 59 years (20 years-86 years, adenocarcinoma account for 80.2% (434/541. The median OS was 15 months (95%CI: 13.87-16.13, and 1, 2, 5-year survival rates were 58.8%, 23.7% and 3.20% respectively. Univariate analysis showed that clinical stage, ECOG score, weight loss, clinical symptoms, liver/bone/brain metastasis and received more than one chemotherapy regimen, good response to the first-line chemotherapy, EGFR-TKI targeted therapy and radiotherapy treatment were significantly correlated with the OS and survival rate (P < 0.05. Combined with multivariate analysis, weight loss before treatment, ECOG score, received EGFR-TKI targeted therapy and response to first-line chemotherapy were independent prognostic factor for survival (P < 0.05. Conclusion There is a higher percentage of adenocarcinoma in female NSCLC. Weight loss before treatment, ECOG score, EGFR-TKI targeted therapy and response to first-line chemotherapy may become independent prognostic factors for survival of female patients with advanced NSCLC.

  16. Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients

    Science.gov (United States)

    Vincenzi, Bruno; Cremolini, Chiara; Sartore-Bianchi, Andrea; Russo, Antonio; Mannavola, Francesco; Perrone, Giuseppe; Pantano, Francesco; Loupakis, Fotios; Rossini, Daniele; Ongaro, Elena; Bonazzina, Erica; Dell'Aquila, Emanuela; Imperatori, Marco; Zoccoli, Alice; Bronte, Giuseppe; De Maglio, Giovanna; Fontanini, Gabriella; Natoli, Clara; Falcone, Alfredo; Santini, Daniele; Onetti-Muda, Andrea; Siena, Salvatore; Tonini, Giuseppe; Aprile, Giuseppe

    2015-01-01

    Introduction: Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/tumor sample, are available. We aimed to evaluate the prognostic value of K-Rasmutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. Patients and Methods: This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. Results: At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Discussion: Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set. PMID:26384309

  17. Polymorphisms in the mitochondrial oxidative phosphorylation chain genes as prognostic markers for colorectal cancer

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    Lascorz Jesus

    2012-04-01

    Full Text Available Abstract Background Currently, the TNM classification of malignant tumours based on clinicopathological staging remains the standard for colorectal cancer (CRC prognostication. Recently, we identified the mitochondrial oxidative phosphorylation chain as a consistently overrepresented category in the published gene expression profiling (GEP studies on CRC prognosis. Methods We evaluated associations of putative regulatory single nucleotide polymorphisms (SNPs in genes from the oxidative phosphorylation chain with survival and disease prognosis in 613 CRC patients from Northern Germany (PopGen cohort. Results Two SNPs in the 3′ untranslated region of UQCRB (complex III, rs7836698 and rs10504961, were associated with overall survival (HR = 0.52, 95% CI 0.32–0.85 and HR = 0.64, 95% CI 0.42–0.99, for TT carriers. These associations were restricted to the group of patients with cancer located in the colon (HR = 0.42, 95% CI 0.22–0.82 and HR = 0.46, 95% CI 0.25–0.83. Multivariate analysis indicated that both markers might act as independent prognostic markers. Additionally, the TT carriers were ~2 times more likely to develop tumours in the colon than in the rectum. Two SNPs in COX6B1 (complex IV were associated with lymph node metastasis in a dominant model (rs6510502, OR = 1.75, 95% CI 1.20–2.57; rs10420252, OR = 1.68, 95% CI 1.11–2.53; rs6510502 was associated also with distant metastasis (OR = 1.67, 95% CI 1.09–2.56 in a dominant model. Conclusions This is the first report suggesting that markers in genes from the mitochondrial oxidative chain might be prognostic factors for CRC. Additional studies replicating the presented findings are needed.

  18. Low Programmed Cell Death 5 Expression is a Prognostic Factor in Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    Li Gao; Xue Ye; Rui-Qiong Ma; Hong-Yan Cheng; Hong-Jing Han; Heng Cui; Li-Hui Wei

    2015-01-01

    Background:Ovarian cancer is a leading gynecological malignancy.We investigated the prognostic value of programmed cell death 5 (PDCD5) in patients with ovarian cancer.Methods:Expression levels ofPDCD5 mRNA and protein were examined in six ovarian cancer cell lines (SKOV3,CAOV3,ES2,OV1,3AO,and HOC1A) and one normal ovarian epithelial cell line (T29) using reverse transcription polymerase chain reaction,Westem blotting,and flow cytometry.After inducing PDCD5 induction in SKOV3 cells or treating this cell line with taxol or doxorubicin (either alone or combined),apoptosis was measured by Annexin V-FITC/propidium iodide staining.Correlations between PDCD5 protein expression and pathological features,histological grade,FIGO stage,effective cytoreductive surgery,and serum cancer antigen-125 values were evaluated in patients with ovarian cancer.Results:PDCD5 mRNA and protein expression were downregulated in ovarian cancer cells.Recombinant human PDCD5 increased doxorubicin-induced apoptosis in SKOV3 cells (15.96 ± 2.07%,vs.3.17 ± 1.45% in controls).In patients with ovarian cancer,PDCD5 expression was inversely correlated with FIGO stage,pathological grade,and patient survival (P < 0.05,R =0.7139 for survival).Conclusions:PDCD5 expression is negatively correlated with disease progression and stage in ovarian cancer.Therefore,measuring PDCD5 expression may be a good method of determining the prognosis of ovarian cancer patients.

  19. Prognostic significance of Notch ligands in patients with non-small cell lung cancer.

    Science.gov (United States)

    Pancewicz-Wojtkiewicz, Joanna; Eljaszewicz, Andrzej; Kowalczuk, Oksana; Niklinska, Wieslawa; Charkiewicz, Radoslaw; Kozłowski, Miroslaw; Miasko, Agnieszka; Moniuszko, Marcin

    2017-01-01

    The Notch signaling pathway is deregulated in numerous solid types of cancer including non-small cell lung cancer (NSCLC). However, the profile of Notch ligand expression remains unclear. Therefore, the present study aimed to determine the profile of Notch ligands in NSCLC patients and to investigate whether quantitative assessment of Notch ligand expression may have prognostic significance in NSCLC patients. The study was performed in 61 pairs of tumor and matched unaffected lung tissue specimens obtained from patients with various stages of NSCLC, which were analyzed by reverse transcription-polymerase chain reaction. The marked expression levels of certain analyzed genes were detected in NSCLC samples and in noncancerous lung samples. Of the five Notch ligands, jagged 1 (Jag1), jagged 2, delta-like protein 1 and delta-like protein 4 were expressed in the majority of tissues, but their expression levels were reduced in NSCLC when compared with noncancerous lung tissue (PNotch ligands are expressed in NSCLC. However, the expression level is reduced when compared to noncancerous tissue. Furthermore, the present study revealed that quantitative assessment of Jag1 expression in NSCLC may improve prognostication of patient survival.

  20. Diagnosis of medullary thyroid cancer and prognostic factors of disease aggressiveness

    Directory of Open Access Journals (Sweden)

    D O Gazizova

    2013-12-01

    Full Text Available In the study were enrolled 137 patients with medullary thyroid cancer (MTC. Low 35%-sensitivity of FNAC and high accuracy of basal calcitonin in MTC diagnostics were found. Mutation analysis of the RET pro- tooncogene in familial and sporadic MTC, RAS -gene in sporadic MTC were done. The correlation between type of the mutation and disease aggressiveness was found.

  1. The prognostic value ofserum C-reactive protein-bound serum amyloid A inearly-stage lung cancer

    Institute of Scientific and Technical Information of China (English)

    XueYanZhang; GeZhang; YingJiang; DanLiu; ManZhiLi; QianZhong; ShanQiZeng; WanLiLiu; MuShengZeng

    2015-01-01

    Background:Elevated levels of serum C‑reactive protein (CRP) have been reported to have prognostic signiifcance in lung cancer patients. This study aimed to further identify CRP‑bound components as prognostic markers for lung cancer and validate their prognostic value. Methods:CRP‑bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis. CRP‑bound serum amyloid A (CRP‑SAA) was evaluated by co‑immunoprecipitation (IP). Serum samples from two independent cohorts with lung cancer (retrospective cohort, 242 patients; prospective cohort, 222 patients) and healthy controls (159 subjects) were used to evaluate the prognostic value of CRP‑SAA by enzyme‑linked immunosorbent assay. Results:CRP‑SAA was identiifed speciifcally in serum samples from lung cancer patients by proteomic analysis. CRP binding to SAA was conifrmed by co‑IP in serum samples from lung cancer patients and cell culture media. The level of CRP‑SAA was signiifcantly higher in patients than in healthy controls (0.37±0.58 vs. 0.03±0.04,P<0.001). Elevated CRP‑SAA levels were signiifcantly associated with severe clinical features of lung cancer. The elevation of CRP‑SAA was associated with lower survival rates for both the retrospective (hazard ration [HR]=2.181, 95% conifdence interval [CI]=1.641–2.897,P<0.001) and the prospective cohorts (HR=2.744, 95% CI=1.810–4.161,P<0.001). Multivariate Cox analysis showed that CRP‑SAA was an independent prognostic marker for lung cancer. Remarkably, in stages I–II patients, only CRP‑SAA, not total SAA or CRP, showed signiifcant association with overall survival in two cohorts. Moreover, univariate and multivariate Cox analyses also showed that only CRP‑SAA could be used as an inde‑pendent prognostic marker for early‑stage lung cancer patients. Conclusion:CRP‑SAA could be a better prognostic marker for lung cancer than total SAA or CRP

  2. Long non-coding RNA expression profiles predict metastasis in lymph node-negative breast cancer independently of traditional prognostic markers

    DEFF Research Database (Denmark)

    Sørensen, Kristina P; Thomassen, Mads; Tan, Qihua;

    2015-01-01

    INTRODUCTION: Patients with clinically and pathologically similar breast tumors often have very different outcomes and treatment responses. Current prognostic markers allocate the majority of breast cancer patients to the high-risk group, yielding high sensitivities in expense of specificities be...... cancer patients eligible for adjuvant therapy, as well as early breast cancer patients that could avoid unnecessary systemic adjuvant therapy. This study emphasizes the potential role of lncRNAs in breast cancer prognosis.......INTRODUCTION: Patients with clinically and pathologically similar breast tumors often have very different outcomes and treatment responses. Current prognostic markers allocate the majority of breast cancer patients to the high-risk group, yielding high sensitivities in expense of specificities...... of traditional prognostic markers and time to metastasis. CONCLUSIONS: To our knowledge, this is the first study investigating the prognostic potential of lncRNA profiles. Our study suggest that lncRNA profiles provide additional prognostic information and may contribute to the identification of early breast...

  3. Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer

    Science.gov (United States)

    Sperduti, Isabella; Iapicca, Pierluigi; Visca, Paolo; Alessandrini, Gabriele; Antoniani, Barbara; Pilotto, Sara; Ludovini, Vienna; Vannucci, Jacopo; Bellezza, Guido; Sidoni, Angelo; Tortora, Giampaolo; Radisky, Derek C.; Crinò, Lucio; Cognetti, Francesco; Facciolo, Francesco; Mottolese, Marcella

    2014-01-01

    Risk assessment and treatment choice remain a challenge in early non-small-cell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low pan-hMENA/high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk. PMID:25373410

  4. ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer.

    Science.gov (United States)

    Choe, Min Ho; Min, Joong Won; Jeon, Hong Bae; Cho, Dong-Hyung; Oh, Jeong Su; Lee, Hyun Gyu; Hwang, Sang-Gu; An, Sungkwan; Han, Young-Hoon; Kim, Jae-Sung

    2015-02-20

    Although targeting radioresistant tumor cells is essential for enhancing the efficacy of radiotherapy, the signals activated in resistant tumors are still unclear. This study shows that ERp57 contributes to radioresistance of laryngeal cancer by activating STAT3. Increased ERp57 was associated with the radioresistant phenotype of laryngeal cancer cells. Interestingly, increased interaction between ERp57 and STAT3 was observed in radioresistant cells, compared to the control cells. This physical complex is required for the activation of STAT3 in the radioresistant cells. Among STAT3-regulatory genes, Mcl-1 was predominantly regulated by ERp57. Inhibition of STAT3 activity with a chemical inhibitor or siRNA-mediated depletion of Mcl-1 sensitized radioresistant cells to irradiation, suggesting that the ERp57-STAT3-Mcl-1 axis regulates radioresistance of laryngeal cancer cells. Furthermore, we observed a positive correlation between ERp57 and phosphorylated STAT3 or Mcl-1 and in vivo interactions between ERp57 and STAT3 in human laryngeal cancer. Importantly, we also found that increased ERp57-STAT3 complex was associated with poor prognosis in human laryngeal cancer, indicating the prognostic role of ERp57-STAT3 regulation. Overall, our data suggest that ERp57-STAT3 regulation functions in radioresistance of laryngeal cancer, and targeting the ERp57-STAT3 pathway might be important for enhancing the efficacy of radiotherapy in human laryngeal cancer.

  5. Data fusion in metabolomic cancer diagnostics

    DEFF Research Database (Denmark)

    Bro, Rasmus; Nielsen, Hans Jørgen; Savorani, Francesco

    2013-01-01

    We have recently shown that fluorescence spectroscopy of plasma samples has promising abilities regarding early detection of colorectal cancer. In the present paper, these results were further developed by combining fluorescence with the biomarkers, CEA and TIMP-1 and traditional metabolomic...

  6. Alloy metal nanoparticles for multicolor cancer diagnostics

    Science.gov (United States)

    Baptista, Pedro V.; Doria, Gonçalo; Conde, João

    2011-03-01

    Cancer is a multigenic complex disease where multiple gene loci contribute to the phenotype. The ability to simultaneously monitor differential expression originating from each locus results in a more accurate indicator of degree of cancerous activity than either locus alone. Metal nanoparticles have been thoroughly used as labels for in vitro identification and quantification of target sequences. We have synthesized nanoparticles with assorted noble metal compositions in an alloy format and functionalized them with thiol-modified ssDNA (nanoprobes). These nanoprobes were then used for the simultaneous specific identification of several mRNA targets involved in cancer development - one pot multicolor detection of cancer expression. The different metal composition in the alloy yield different "colors" that can be used as tags for identification of a given target. Following a non-cross-linking hybridization procedure previously developed in our group for gold nanoprobes, these multicolor nanoprobes were used for the molecular recognition of several different targets including differently spliced variants of relevant genes (e.g. gene products involved in chronic myeloid leukemia BCR, ABL, BCR-ABL fusion product). Based on the spectral signature of mixtures, before and after induced aggregation of metal nanoparticles, the correct identification could be made. Further application to differentially quantify expression of each locus in relation to another will be presented. The differences in nanoparticle stability and labeling efficiency for each metal combination composing the colloids, as well as detection capability for each nanoprobe will be discussed. Additional studies will be conducted towards allele specific expression studies.

  7. Cancer risks following diagnostic and therapeutic radiation exposure in children

    Energy Technology Data Exchange (ETDEWEB)

    Kleinerman, Ruth A. [National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, EPS 7044, Rockville, MD (United States)

    2006-09-15

    The growing use of interventional and fluoroscopic imaging in children represents a tremendous benefit for the diagnosis and treatment of benign conditions. Along with the increasing use and complexity of these procedures comes concern about the cancer risk associated with ionizing radiation exposure to children. Children are considerably more sensitive to the carcinogenic effects of ionizing radiation than adults, and children have a longer life expectancy in which to express risk. Numerous epidemiologic cohort studies of childhood exposure to radiation for treatment of benign diseases have demonstrated radiation-related risks of cancer of the thyroid, breast, brain and skin, as well as leukemia. Many fewer studies have evaluated cancer risk following diagnostic radiation exposure in children. Although radiation dose for a single procedure might be low, pediatric patients often receive repeated examinations over time to evaluate their conditions, which could result in relatively high cumulative doses. Several cohort studies of girls and young women subjected to multiple diagnostic radiation exposures have been informative about increased mortality from breast cancer with increasing radiation dose, and case-control studies of childhood leukemia and postnatal diagnostic radiation exposure have suggested increased risks with an increasing number of examinations. Only two long-term follow-up studies of cancer following cardiac catheterization in childhood have been conducted, and neither reported an overall increased risk of cancer. Most cancers can be induced by radiation, and a linear dose-response has been noted for most solid cancers. Risks of radiation-related cancer are greatest for those exposed early in life, and these risks appear to persist throughout life. (orig.)

  8. Diagnostic and treatment procedures induced by cervical cancer screening

    NARCIS (Netherlands)

    M. van Ballegooijen (Marjolein); M.A. Koopmanschap (Marc); G.J. van Oortmarssen (Gerrit); J.D.F. Habbema (Dik); N. van der Lubbe (Nils); H.M.A. van Agt (H. M A)

    1990-01-01

    markdownabstractAbstract The amount of diagnostic and treatment procedures induced by cervical cancer screening has been assessed prospectively and related to mortality reduction. Assumptions are based on data from Dutch screening programmes and on a scenario for future developments. With 5 invita

  9. Delay in diagnostic workup and treatment of esophageal cancer

    NARCIS (Netherlands)

    B.A. Grotenhuis (Brechtje); P. van Hagen (Pieter); B.P.L. Wijnhoven (Bas); V.M.C.W. Spaander (Manon); H.W. Tilanus (Hugo); J.J-B. van Lanschot (Jan)

    2010-01-01

    textabstractIntroduction: Esophageal cancer should preferably be detected and treated at an early stage, but this may be prohibited by late onset of symptoms and delays in referral, diagnostic workup, and treatment. The aim of this study was to investigate the impact of these delays on outcome in pa

  10. Prognostic and predictive value of circulating tumor cell analysis in colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    de Albuquerque Andreia

    2012-11-01

    Full Text Available Abstract Objective The aim of this study was to assess the prognostic and predictive values of circulating tumor cell (CTC analysis in colorectal cancer patients. Patients and methods Presence of CTCs was evaluated in 60 colorectal cancer patients before systemic therapy - from which 33 patients were also evaluable for CTC analysis during the first 3 months of treatment - through immunomagnetic enrichment, using the antibodies BM7 and VU1D9 (targeting mucin 1 and EpCAM, respectively, followed by real-time RT-PCR analysis of the tumor-associated genes KRT19, MUC1, EPCAM, CEACAM5 and BIRC5. Results Patients were stratified into groups according to CTC detection (CTC negative, when all marker genes were negative; and CTC positive when at least one of the marker genes was positive. Patients with CTC positivity at baseline had a significant shorter median progression-free survival (median PFS 181.0 days; 95% CI 146.9-215.1 compared with patients with no CTCs (median PFS 329.0 days; 95% CI 299.6-358.4; Log-rank P Conclusion The present study provides evidence of a strong correlation between CTC detection and radiographic disease progression in patients receiving chemotherapy for colorectal cancer. Our results suggest that in addition to the current prognostic factors, CTC analysis represent a potential complementary tool for prediction of colorectal cancer patients’ outcome. Moreover, the present test allows for molecular characterization of CTCs, which may be of relevance to the creation of personalized therapies.

  11. Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer.

    Science.gov (United States)

    Labovsky, Vivian; Martinez, Leandro Marcelo; Calcagno, María de Luján; Davies, Kevin Mauro; García-Rivello, Hernán; Wernicke, Alejandra; Feldman, Leonardo; Giorello, María Belén; Matas, Ayelén; Borzone, Francisco Raúl; Howard, Scott C; Chasseing, Norma Alejandra

    2016-10-01

    Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.

  12. Genetic signatures shared in embryonic liver development and liver cancer define prognostically relevant subgroups in HCC

    Directory of Open Access Journals (Sweden)

    Becker Diana

    2012-08-01

    Full Text Available Abstract Multiple activations of individual genes during embryonic liver and HCC development have repeatedly prompted speculations about conserved embryonic signatures driving cancer development. Recently, the emerging discussion on cancer stem cells and the appreciation that generally tumors may develop from progenitor cells of diverse stages of cellular differentiation has shed increasing light on the overlapping genetic signatures between embryonic liver development and HCC. However there is still a lack of systematic studies investigating this area. We therefore performed a comprehensive analysis of differentially regulated genetic signaling pathways in embryonic and liver cancer development and investigated their biological relevance. Genetic signaling pathways were investigated on several publically available genome wide microarray experiments on liver development and HCC. Differentially expressed genes were investigated for pathway enrichment or underrepresentation compared to KEGG annotated pathways by Fisher exact evaluation. The comparative analysis of enrichment and under representation of differentially regulated genes in liver development and HCC demonstrated a significant overlap between multiple pathways. Most strikingly we demonstrated a significant overlap not only in pathways expected to be relevant to both conditions such as cell cycle or apoptosis but also metabolic pathways associated with carbohydrate and lipid metabolism. Furthermore, we demonstrated the clinical significance of these findings as unsupervised clustering of HCC patients on the basis of these metabolic pathways displayed significant differences in survival. These results indicate that liver development and liver cancer share similar alterations in multiple genetic signaling pathways. Several pathways with markedly similar patterns of enrichment or underrepresentation of various regulated genes between liver development and HCC are of prognostic relevance in

  13. Overweight as a Prognostic Factor for Triple-Negative Breast Cancers in Chinese Women.

    Directory of Open Access Journals (Sweden)

    Shuang Hao

    Full Text Available Obesity is associated with poorer outcomes in patients with hormone receptor-positive breast cancers, but this association is not well established for women with triple-negative breast cancers (TNBC. Here, we investigated the prognostic effects of body mass index (BMI on clinical outcomes in patients with TNBC.We identified 1106 patients with TNBC who met the inclusion criteria and were treated between January 2002 and June 2012. Clinical and biological features were collected to evaluate the relation between BMI and breast cancer-specific survival (BCSS and overall survival (OS after controlling for other clinically significant variables.Of 1106 patients, 656 (59.3% were normal weight (BMI ≤24 and 450 patients (40.7% were overweight(BMI>24. Median follow-up time was 44.8 months. Breast cancer specific death was observed in 140 patients. After adjusting for clinicopathologic risk factors, overweight was associated with OS (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.04-2.06, P =0.028 but not BCSS (HR: 1.34, 95% CI: 0.90-2.01, P =0.15in all the patients with TNBC. When stratified with menopausal status, overweight was associated with BCSS and OS (HR: 2.27, 95% CI: 1.11-4.63, P = 0.024 and HR: 2.16, 95% CI: 1.21-3.87, P = 0.010, respectively in premenopausal women. BMI was not associated with BCSS or OS in postmenopausal women.Overweight is an independent prognostic factor of OS in all women with TNBC, and menopause status may be a mitigating factor. Among premenopausal women, overweight women are at a greater risk of poor prognosis than normal weight women. If validated, these findings should be considered in developing preventive programs.

  14. Prognostic factors and survival of patients with brain metastasis from breast cancer who underwent craniotomy.

    Science.gov (United States)

    Leone, José Pablo; Lee, Adrian V; Brufsky, Adam M

    2015-07-01

    Brain metastasis (BM) in patients with breast cancer is a catastrophic event that results in poor prognosis. Identification of prognostic factors associated with breast cancer brain metastases (BCBM) could help to identify patients at risk. The aim of this study was to assess clinical characteristics, prognostic factors, and survival of patients with BCBM who had craniotomy and resection in a series of patients treated with modern multimodality therapy. We analyzed 42 patients with BCBM who underwent resection. Patients were diagnosed with breast cancer between April 1994 and May 2010. Cox proportional hazards regression was selected to describe factors associated with time to BM, survival from the date of first recurrence, and overall survival (OS). Median age was 51 years (range 24-74). Median follow-up was 4.2 years (range 0.6-18.5). The proportion of the biological subtypes of breast cancer was ER+/HER2- 25%, ER+/HER2+ 15%, ER-/HER2+ 30%, and ER-/HER2- 30%. Median OS from the date of primary diagnosis was 5.74 years. Median survival after diagnosis of BM was 1.33 years. In multivariate Cox regression analyses, stage was the only factor associated with shorter time to the development of BM (P = 0.033), whereas age was the only factor associated with survival from the date of recurrence (P = 0.027) and with OS (P = 0.037). Stage at primary diagnosis correlated with shorter time to the development of BM, while age at diagnosis was associated with shorter survival in BCBM. None of the other clinical factors had influence on survival.

  15. Advanced Gastric Cancer and Perfusion Imaging Using a Multidetector Row Computed Tomography: Correlation with Prognostic Determinants

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Huan; Pan, Zilai; Du, Lianjun; Yan, Chao; Ding, Bei; Song, Qi; Ling, Huawei; Chen, Kemin [Jiaotong University, Jiaotong (China)

    2008-04-15

    Objective : To investigate the relationship between the perfusion CT features and the clinicopathologically determined prognostic factors in advanced gastric cancer cases. Materials and Methods : A perfusion CT was performed on 31 patients with gastric cancer one week before surgery using a 16-channel multi-detector CT (MDCT) instrument. The data were analyzed with commercially available software to calculate tumor blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS). The microvessel density (MVD), was evaluated by immunohistochemical staining of the surgical specimens with anti-CD34. All of the findings were analyzed prospectively and correlated with the clinicopathological findings, which included histological grading, presence of lymph node metastasis, serosal involvement, distant metastasis, tumor, node, metastasis (TNM) staging, and MVD. The statistical analyses used included the Student's t-test and the Spearman rank correlation were performed in SPSS 11.5. Result : The mean perfusion values and MVD for tumors were as follows: BF (48.14+/-16.46 ml/100 g/min), BV (6.70+/-2.95 ml/100 g), MTT (11.75+/-4.02 s), PS (14.17+/-5.23 ml/100 g/min) and MVD (41.7+/-11.53). Moreover, a significant difference in the PS values was found between patients with or without lymphatic involvement (p = 0.038), as well as with different histological grades (p 0.04) and TNM stagings (p = 0.026). However, BF, BV, MTT, and MVD of gastric cancer revealed no significant relationship with the clinicopathological findings described above (p > 0.05). Conclusion : The perfusion CT values of the permeable surface could serve as a useful prognostic indicator in patients with advanced gastric cancer.

  16. Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Huberman Joel

    2006-08-01

    Full Text Available Abstract Background Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC. Methods 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. Results Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01, and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22. Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01. Ki-67 did not display apparent prognostic

  17. Prognostic value of plasma levels of HIF-1a and PGC-1a in breast cancer.

    Science.gov (United States)

    Cai, Feng-Feng; Xu, Cheng; Pan, Xin; Cai, Lu; Lin, Xiao-Yan; Chen, Su; Biskup, Ewelina

    2016-11-22

    Cellular adaptive mechanisms are crucial for tumorigenesis and a common feature in solid tumor progression. Hypoxia-inducible factor-1α (HIF-1α) facilitates the biological response to hypoxia, advancing angiogenesis and metastatic potential of the tumor. The peroxisome proliferator-activated receptor γ coactivators 1α (PGC-1α) enhances mitochondrial biogenesis, favored by migratory/invasive cancer cells. We conducted a prospective, long-term follow up study to determine whether HIF-1α and PGC-1α can be implemented as predictive biomarker in breast cancer. HIF-1α and PGC-1α plasma concentrations were measured in patients and in healthy controls by enzyme linked immune sorbent assay. Breast cancer patients had significantly higher HIF-1α and PGC-1α levels, which correlated with clinicopathological features, overall with more aggressive cancer characteristics. Disease free and overall survival of breast cancer patients with high HIF-1α and PGC-1α were significantly poorer than in patients with low plasma levels. In multivariate analysis, high amount of PGC-1α showed independent prognostic value. Our data suggests that HIF-1α and PGC-1α may be promising, noninvasive, biomarkers with a high potential for future clinical implication to identify subgroups of patients with poorer prognosis and to indicate early, subclinical metastasis.

  18. The application of microRNAs in cancer diagnostics

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Ostenfeld, Marie Stampe; Kristensen, Helle

    2012-01-01

    MicroRNAs (miRNAs) play important biological roles in cancer development and progression. During the past decade, widespread use of novel high-throughput technologies for miRNA profiling (e.g., microarrays and next-generation sequencing) has revealed deregulation of miRNA expression as a common...... hallmark of human cancer. Furthermore, miRNAs have been found to be a new class of promising cancer biomarkers with potential to improve the accuracy of diagnosis and prognosis in several hematologic and solid malignancies, as well as to predict response to specific treatments. Recent studies have...... identified exosome-associated tumor-derived miRNAs in, e.g., blood samples from cancer patients, suggesting that miRNAs may be useful as circulation biomarkers for noninvasive diagnostic testing. In this chapter, we review the current state of development of miRNAs as cancer biomarkers with examples from...

  19. Prognostic Role of the Pretreatment C-Reactive Protein/Albumin Ratio in Solid Cancers: A Meta-Analysis

    Science.gov (United States)

    Li, Nan; Tian, Guang-Wei; Wang, Ying; Zhang, Hui; Wang, Zi-hui; Li, Guang

    2017-01-01

    The C-reactive protein/albumin ratio (CAR) has been shown to play a significant prognostic role in several cancers. We aimed to comprehensively explore the potential role of the CAR as a prognostic indicator in solid cancers. In this meta-analysis, we collected data from 10 studies that examined the association between serum CAR and overall survival in patients with cancer. This meta-analysis included 4592 tumor patients. The eligible studies were found through the PubMed and Web of Science databases updated on 6 Oct 2016. The pooled hazard ratio (2.01, 95% CI: 1.58–2.56, p < 0.001) indicated that high CAR yielded worse survival in different cancers. Subgroup analyses showed a significant association between CAR and prognosis, regardless of the cutoff value, cutoff value selection, treatment method, country, sample size, stage and cancer type. This meta-analysis suggests that CAR may be a potential prognostic marker in solid cancers. However, further large prospective studies should be conducted to explore the critical role of CAR in survival of cancer patients. PMID:28128229

  20. Prognostic role of lemur tyrosine kinase-3 germline polymorphisms in adjuvant gastric cancer in Japan and the United States.

    Science.gov (United States)

    Wakatsuki, Takeru; LaBonte, Melissa J; Bohanes, Pierre O; Zhang, Wu; Yang, Dongyun; Azuma, Mizutomo; Barzi, Afsaneh; Ning, Yan; Loupakis, Fotios; Saadat, Siamak; Volz, Nico; Stintzing, Sebastian; El-Khoueiry, Rita; Koizumi, Wasaburo; Watanabe, Masahiko; Shah, Manish; Stebbing, Justin; Giamas, Georgios; Lenz, Heinz-Josef

    2013-10-01

    Lemur tyrosine kinase-3 (LMTK3) was recently identified as an estrogen receptor (ER)-α modulator related to endocrine therapy resistance, and its polymorphisms rs9989661 (T>C) T/T genotype and rs8108419 (G>A) G/G or A/G genotype predicted improved outcomes in breast cancer. Because different predominant ER distributions link to breast and gastric cancer and little is known of the prognostic role of LMTK3 in gastric cancer, this study was carried out to clarify the prognostic role of these polymorphisms in gastric cancer. One-hundred and sixty-nine Japanese and 137 U.S. patients with localized gastric adenocarcinoma were enrolled. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA sequencing. Overall, these polymorphisms were not associated with survival in both cohorts. When gender was considered, in multivariate analysis, harboring rs9989661 T/T genotype was associated with disease-free survival [HR, 4.37; 95% confidence interval (CI), 2.08-9.18; P role of these polymorphisms may be negative in gastric cancer. These findings suggest that the estrogen pathway may play a prognostic role in patients with gastric cancer but this may be dependent on the regional differences both in physiology and genetic alterations of gastric cancer.

  1. Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer.

    Science.gov (United States)

    Oliveira-Ferrer, L; Heßling, A; Trillsch, F; Mahner, S; Milde-Langosch, K

    2015-11-01

    Ovarian cancer (OvCa) accounts for the highest tumor-related mortality among gynecological malignancies, but the underlying mechanisms are poorly understood. Glycosaminoglycans are abundantly present in ovarian tumors, and there is rising evidence that chondroitin sulfate (CS) as well as diverse carbohydrate sulfotransferases (CHSTs), the enzymes involved in the sulfation process of these structures, plays an important role in metastatic spread of tumor cells. mRNA expression levels of CHST3/7/11/12/13/15 were compared between malignant (86 OvCas) and non-malignant tumors (6 borderline tumors and 3 cystadenomas). CHST11 and CHST15 were further chosen for Western blot analysis in a cohort of 216 OvCas. Protein expression levels were correlated with clinicopathologic prognostic parameters and survival data. A significantly higher mRNA expression of CHST11, CHST12, and CHST15 was measured in ovarian cancer samples in comparison to non-malignant ones, and the same trend was observed for CHST13. For CHST3 and CHST7, no significant differences were found between the two groups. At protein level, high CHST11 expression was independently associated with unfavorable progression-free survival (PFS; p = 0.027). A similar trend was observed for CHST15, showing a nearly significant correlation between high expression levels and shorter recurrence-free survival in patients without macroscopic residual tumor after surgery (p = 0.053). We conclude that CHSTs involved in the synthesis of CS-A and CS-E might influence ovarian cancer progression, and we suggest CHST11 as independent unfavorable prognostic factor in this entity.

  2. Prognostic impact of ReTURB in high grade T1 primary bladder cancer

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    Roberto Sanseverino

    2016-07-01

    Full Text Available Purpose: To evaluate whether pathological outcomes of ReTURB have a prognostic impact on recurrence and progression of primitive T1HG bladder cancer. Material and methods: Patients affected by primitive T1HG TCC of bladder underwent restaging TURB (ReTURB. Patients with muscle invasive disease at ReTURB underwent radical cystectomy; those with non-muscle invasive residual (NMI-RT and those with no residual tumour (NRT received an intravesical BCG therapy. We compared recurrence and progression in NMIRT patients and NRT patients at restaging TURB. Patients were followed every 3-6 months with cystoscopy and urine cytology. Results: 212 patients were enrolled in the study. At ReTURB, residual cancer was detected in 92 of 196 (46.9% valuable patients: 14.3% of these were upstaged to T2. At follow up of 26.3 ± 22.8 months, there were differences in recurrence and progression rates between NRT and NMIRT patients: 26.9% and 45.3% (p < 0.001, 10.6% and 23.4% (p 0.03, respectively. Recurrence-free and progression-free survivals were significantly higher in NRT compared to NMIRT patients: 73.1% and 54.7% (p < 0.001, 89.4% and 76.6 (p 0.03, respectively. Conclusions: ReTURB allows to identify a considerable number of residual and understaged cancer. Patients with NMIRT on ReTURB have worse prognosis than those with NRT in terms of recurrence and progression free survival. These outcomes seem to suggest a prognostic impact of findings on ReTURB that could be a valid tool in management of high grade T1 TCC.

  3. Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer.

    Science.gov (United States)

    Peixoto, Renata D'Alpino; Speers, Caroline; McGahan, Colleen E; Renouf, Daniel J; Schaeffer, David F; Kennecke, Hagen F

    2015-08-01

    Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001-2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan-Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6-12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57-4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28-2.23), CA 19.9 > 1000 versus ≤ 1000 (HR 1.59, 95% CI 1.19-2.14) and female gender, (HR 1.57, 95% CI 1.19-2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.

  4. Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer.

    Science.gov (United States)

    Nie, Wei; Xu, Mi-die; Gan, Lu; Huang, Hai; Xiu, Qingyu; Li, Bing

    2015-01-01

    Stathmin 1 (STMN1), a major microtubule-depolymerizing protein, is involved in cell cycle progression and cell motility. However, the clinical significance of STMN1 expression in non-small cell lung cancer (NSCLC) has not been determined. The expression pattern of STMN1 mRNA was analyzed by quantitative real-time PCR (qRT-PCR) in 37 cases of NSCLC and in the corresponding non-tumor tissue samples. Furthermore, immunohistochemistry was performed to detect STMN1 protein expression in 113 primary NSCLC tissues. The functional role of STMN1 in lung cancer cell lines was evaluated by small interfering RNA-mediated depletion followed by analyses of cell proliferation and invasion. We found that the STMN1 mRNA and protein levels in NSCLC tissues were significantly higher than those in the corresponding non-tumor tissues (P<0.001). In addition, increased STMN1 expression was correlated with poor tumor differentiation (P<0.001), large tumor size (P=0.022), advanced N stage (P=0.033), and advanced TNM stage (P<0.001). Kaplan-Meier analysis indicates that NSCLC patients with higher STMN1 expression showed significantly worse survival. Moreover, multivariate analysis indicates that higher STMN1 protein expression was an independent prognostic factor of disease-specific survival (HR 2.247, 95%CI 1.320-3.825, P=0.003). Finally, the knockdown of STMN1 in lung cancer cells resulted in a decrease in cellular proliferation and invasion. Our findings suggest that STMN1 may have an important role in NSCLC progression and could serve as a potential prognostic marker for patients with NSCLC.

  5. Prognostic role of tumor volume for radiotherapy outcome in patient with T2 laryngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rutkowski, T.; Wygoda, A.; Skladowski, K.; Rutkowski, R.; Maciejewski, B. [Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice (Poland). Dept. of Radiation Oncology; Hejduk, B. [Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice (Poland). Dept. of Radiodiagnostic; Kolosza, Z. [Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice (Poland). Dept. of Epidemiology

    2013-10-15

    Background and purpose: Tumor volume (TV) is recognized as a prognostic factor of treatment outcome for head and neck tumors but is not routinely included in the treatment decision-making process. The purpose of the study was to define its prognostic role for patients with T2 laryngeal cancer. Material and methods: TV of 160 patients who underwent RT between 2002 and 2006 for T2 laryngeal squamous cell carcinoma were reviewed. The tumor was located in the glottis and epiglottis in 82 (51 %) and 78 (49 %) patients, respectively. TV was manually contoured on pretreatment, planning, contrast-enhanced CT scans and the volumetric measurement (cm{sup 3}) was calculated by the volume algorithm. Results: The median TV value was 2.01 cm{sup 3} (range 0.15-21.68 cm{sup 3}). The median TV was significantly lower in patients with glottic tumors (p < 0.0001), N0 (p < 0.001), or well histopatologically differentiated tumors (p = 0.01). A significant correlation between TV, hemoglobin concentration (p < 0.01), and total dose (TD; p < 0.001) was observed. On univariate analyses, TV influenced local control (LC; p = 0.02) and overall survival (OS, p < 0.001). On multivariate analysis, both age (HR 1.038, p = 0.03) and TV (HR = 1.075, p = 0.01) remained significantly related to LC and OS (age: HR 1.038, p = 0.005; TV: HR 1.097, p = 0.0001). Conclusion: Large TV worsen prognosis of patients with T2 laryngeal cancer. A large TV is more common for supraglottic, poorly differentiated tumors and may suggest higher risk of nodal spread. The routine estimation of TV prior to therapy may be essential in order to select the best treatment option for patients with T2 laryngeal cancer. (orig.)

  6. Blood pyrrole-protein adducts as a diagnostic and prognostic index in pyrrolizidine alkaloid-hepatic sinusoidal obstruction syndrome

    Directory of Open Access Journals (Sweden)

    Gao H

    2015-08-01

    Full Text Available Hong Gao,1,* Jianqing Q Ruan,2,* Jie Chen,1 Na Li,2 Changqiang Q Ke,3 Yang Ye,3–5 Ge Lin,2,4,5 Jiyao Y Wang1,61Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong; 3Shanghai Institute of Materia Medica, Shanghai, People’s Republic of China; 4Joint Research Laboratory for Promoting Globalization of Traditional Chinese Medicines, Shanghai Institute of Materia Medica, 5Chinese University of Hong Kong, Hong Kong; 6Center of Evidence-Based Medicine Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this work and share first authorship Background: The diagnosis of hepatic sinusoidal obstruction syndrome (HSOS induced by pyrrolizidine alkaloids is mainly based on clinical investigation. There is currently no prognostic index. This study evaluated the quantitative measurement of blood pyrrole-protein adducts (PPAs as a diagnostic and prognostic index for pyrrolizidine alkaloid-induced HSOS.Methods: Suspected drug-induced liver injury patients were prospectively recruited. Blood PPAs were quantitatively measured using ultra-performance liquid chromatography-tandem mass spectrometry. Patients’ age, sex, biochemistry test results, and a detailed drug history were recorded. The patients were divided into two groups, ie, those with HSOS induced by pyrrolizidine alkaloid-containing drugs and those with liver injury induced by drugs without pyrrolizidine alkaloids. The relationship between herb administration, clinical outcomes, blood sampling time, and blood PPA concentration in pyrrolizidine alkaloid-associated HSOS patients was analyzed using multiple linear regression analysis.Results: Forty patients met the entry criteria, among whom 23 had pyrrolizidine alkaloid-associated HSOS and 17 had liver injury caused by drugs without pyrrolizidine alkaloids. Among the 23

  7. XIAP as a prognostic marker of early recurrence of nonmuscular invasive bladder cancer

    Institute of Scientific and Technical Information of China (English)

    LI Ming; SONG Tao; YIN Zhen-fei; NA Yan-qun

    2007-01-01

    Background Dysregulation of apoptosis has been implicated not only in carcinogenesis and tumor progression but also in tumor recurrence. We investigated whether the expression of X-linked inhibitor of apoptosis (XIAP) might predict early recurrence in patients with non-muscular invasive bladder cancer.Methods The cohort comprised 176 consecutive patients with primary superficial bladder cancer treated with transurethral resection. Immunohistochemical staining using the standard avidin-biotin-peroxidase technique and RT-PCR were used to detect XIAP protein and mRNA expressions in cancer tissues. The relationship between XIAP expression and clinicopathological characteristics, cancer recurrence were analyzed.Results XIAP expression was observed in 108 cases (61.4%) and no expression in 68. There was no correlation between XIAP expression rate and the tumor pathological grade, but was an apparent trend toward the increased XIAP levels from well (G1) to poor (G3) differentiated cancer. Eighty-two (46.6%) patients experienced tumor recurrence at a mean of 28.6 months of the follow-up; 66 of them expressed XIAP (61.1%) and 16 were XIAP negative (23.5%). Twelve patients presented with invasive disease at the time of relapse and all of them expressed XIAP. Patients without XIAP expression or with low tumor grades had significantly higher recurrence-free survival than those with XIAP expression(log rank test P=0.0015) or high tumor grades (log rank test P<0.001). Multivariate analysis revealed that XIAP expression, tumor grade, and tumor number were independent predictors for the recurrence of non-muscular invasive bladder cancer (P=-0.004, 0.016, and 0.043, respectively).Conclusions XIAP may be considered as a new independent prognostic marker for early recurrence of non-muscular invasive bladder cancer.

  8. Potential usage of ING family members in cancer diagnostics and molecular therapy.

    Science.gov (United States)

    Gunduz, Mehmet; Demircan, Kadir; Gunduz, Esra; Katase, Naoki; Tamamura, Ryo; Nagatsuka, Hitoshi

    2009-05-01

    The Inhibitor of Growth (ING) gene family is an emerging putative type II tumor suppressor gene (TSG). Proteins of INGs (ING1-5), critical modulator of the histone code via PHD fingers, are able to suppress cell growth and proliferation, induce apoptosis, and modulate cell cycle progression. ING proteins are involved in transcriptional regulation of genes, such as the p53-inducible gene p21. ING proteins also serve as shuttling proteins between nucleus and cytoplasm, and dysregulation of this nucleocytoplasmic traffic has been shown in some cancer cells. In cancer cells, ING mRNA levels are often lost or suppressed but the genes are rarely mutated. Recently the potential roles of ING proteins as prognostic biomarkers, detection of aggressive behavior of the tumor as well as prediction of chemo-radiotherapy response have also emerged. In this review, we summarize the up-to-date knowledge on functions of the ING proteins, the protein status in human tumors and discuss as a potential target in the molecular diagnostics and therapy of cancer.

  9. Are KRAS/BRAF mutations potent prognostic and/or predictive biomarkers in colorectal cancers?

    Science.gov (United States)

    Yokota, Tomoya

    2012-02-01

    KRAS and BRAF mutations lead to the constitutive activation of EGFR signaling through the oncogenic Ras/Raf/Mek/Erk pathway. Currently, KRAS is the only potential biomarker for predicting the efficacy of anti-EGFR monoclonal antibodies (mAb) in colorectal cancer (CRC). However, a recent report suggested that the use of cetuximab was associated with survival benefit among patients with p.G13D-mutated tumors. Furthermore, although the presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC, it remains unknown whether patients with BRAF-mutated tumors experience a survival benefit from treatment with anti-EGFR mAb. Thus, the prognostic or predictive relevance of the KRAS and BRAF genotype in CRC remains controversial despite several investigations. Routine KRAS/BRAF screening of pathological specimens is required to promote the appropriate clinical use of anti-EGFR mAb and to determine malignant phenotypes in CRC. The significance of KRAS/BRAF mutations as predictive or prognostic biomarkers should be taken into consideration when selecting a KRAS/BRAF screening assay. This article will review the spectrum of KRAS/BRAF genotype and the impact of KRAS/BRAF mutations on the clinicopathological features and prognosis of patients with CRC, particularly when differentiating between the mutations at KRAS codons 12 and 13. Furthermore, the predictive role of KRAS/BRAF mutations in treatments with anti-EGFR mAb will be verified, focusing on KRAS p.G13D and BRAF mutations.

  10. Prognostic Value of Preoperative Serum Levels of Periostin (PN in Early Breast Cancer (BCa

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    Pier Vitale Nuzzo

    2015-07-01

    Full Text Available PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005, adjuvant systemic therapy (p = 0.04 and progesterone receptor (PgR status (p = 0.02. No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05 and in those with a low PgR expression (p = 0.03. Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04. Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients.

  11. Prognostic Value of Preoperative Serum Levels of Periostin (PN) in Early Breast Cancer (BCa).

    Science.gov (United States)

    Nuzzo, Pier Vitale; Rubagotti, Alessandra; Argellati, Francesca; Di Meglio, Antonio; Zanardi, Elisa; Zinoli, Linda; Comite, Paola; Mussap, Michele; Boccardo, Francesco

    2015-01-01

    PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005), adjuvant systemic therapy (p = 0.04) and progesterone receptor (PgR) status (p = 0.02). No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05) and in those with a low PgR expression (p = 0.03). Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04). Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients.

  12. Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

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    Cory D. Bovenzi

    2015-01-01

    Full Text Available Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147. Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses. Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p<0.001 for all analyses. Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p<0.0001 for both analyses. Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival. Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations.

  13. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

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    Dimitrios Mougiakakos

    2011-03-01

    Full Text Available Regulatory T cells (Tregs were initially described as "suppressive" lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

  14. Common genetic variants in Wnt signaling pathway genes as potential prognostic biomarkers for colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Wen-Chien Ting

    Full Text Available Compelling evidence has implicated the Wnt signaling pathway in the pathogenesis of colorectal cancer. We assessed the use of tag single nucleotide polymorphisms (tSNPs in adenomatous polyposis coli (APC/β-catenin (CTNNB1 genes to predict outcomes in patients with colorectal cancer. We selected and genotyped 10 tSNP to predict common variants across entire APC and CTNNB1 genes in 282 colorectal cancer patients. The associations of these tSNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis, Cox regression model, and survival tree analysis. The 5-year overall survival rate was 68.3%. Survival tree analysis identified a higher-order genetic interaction profile consisting of the APC rs565453, CTNNB1 2293303, and APC rs1816769 that was significantly associated with overall survival. The 5-year survival overall rates were 89.2%, 66.1%, and 58.8% for the low-, medium-, and high-risk genetic profiles, respectively (log-rank P = 0.001. After adjusting for possible confounders, including age, gender, carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion, perineural invasion, and lymph node involvement, the genetic interaction profile remained significant. None of the studied SNPs were individually associated with distant metastasis-free survival and overall survival. Our results suggest that the genetic interaction profile among Wnt pathway SNPs might potentially increase the prognostic value in outcome prediction for colorectal cancer.

  15. EVALUATION OF THE PROGNOSTIC VALUE OF nm23 GENE EXPRESSION IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    刘红; 毛慧生; 傅西林; 方志沂; 冯玉梅; 范宇; 李树玲

    2002-01-01

    Objective: To investigate the expression of nm23 gene and evaluate its prognostic value in breast cancer. Methods: nm23 expressions were detected in 101 breast cancer patients (group 1) by immunohistochemistry. RT-PCR and immunohistochemistry were used to measure expressions of nm23 gene in another 68 patients with breast cancer (group 2). Results: nm23 gene expression in group 1 was inversely associated with distant metastasis and lymph node metastasis (P<0.05). In 44 patients with negative lymph node, 9 cases progressed to distant metastasis, 7 of them (77.8%) showed low expression of nm23 gene (P<0.05). In 57 patients with positive lymph node, 24 our of 29 patients who had no distant metastasis (82.8%) expressed nm23 gene at high level (P<0.05). Meanwhile, there were 6 patients with distant metastasis in the group 2, all of thenm expressed nm23 gene mRNA at low level. Conclusion: The results showed that nm23 gene might play an independent role in predicting prognosis of breast cancer.

  16. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

    Energy Technology Data Exchange (ETDEWEB)

    Mougiakakos, Dimitrios [Department of Oncology and Pathology, Immune and Gene Therapy Unit, Cancer Centre Karolinska, CCK R8:01, 17176 Stockholm (Sweden)

    2011-03-29

    Regulatory T cells (Tregs) were initially described as “suppressive” lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

  17. Prognostic impact of hexokinase and glucose transporter expressions and clinicopathologic features related to F-18-FDG uptake in esophageal cancer

    NARCIS (Netherlands)

    Schreurs, Liesbeth M; Pultrum, Bareld B; Pavlov, Kirill; Pruim, Jan; Groen, Henk; Hollema, Harry; Plukker, John Theodorus

    2012-01-01

    39 Background: Elucidation of prognostic predictors based on biological viability may be useful for a better detection of patients with a high risk of relapse or death from esophageal cancer. METHODS: Maximum standardized uptake values (SUVmax) were measured in the preoperative 18F-FDG positron emis

  18. Prognostic cell biological markers in cervical cancer patients primarily treated with (chemo)radiation : a systematic review

    NARCIS (Netherlands)

    Noordhuis, Maartje G; Eijsink, Jasper J H; Roossink, Frank; de Graeff, Pauline; Pras, Elisabeth; Schuuring, Ed; Wisman, G Bea A; de Bock, Geertruida H; van der Zee, Ate G J

    2011-01-01

    The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell b

  19. Serum alpha fetoprotein surge after the initiation of chemotherapy for non-seminomatous testicular cancer has an adverse prognostic significance

    NARCIS (Netherlands)

    de Wit, R; Collette, L; Sylvester, R; de Mulder, PHM; Sleijfer, DT; Huinink, WWT; Kaye, SB; van Oosterom, AT; Boven, E; Stoter, G

    1998-01-01

    It has been recognized that the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) may show a transient elevation after the initiation of chemotherapy in non-seminomatous testicular cancer. We investigated the prognostic importance of these so-called marker surges in a co

  20. The prognostic value of positron emission tomography in non-small cell lung cancer : Analysis of 266 cases

    NARCIS (Netherlands)

    Kramer, H.; Post, W.J.; Pruim, J.; Groen, H.J.M.

    2006-01-01

    Positron emission tomography (PET) is more accurate than computed tomography (CT) in the staging of non-small cell lung cancer (NSCLC). We analyzed the prognostic value of PET for survival in NSCLC patients. Methods: Consecutive patients with proven NSCLC with PET for staging were selected. Staging

  1. Circulating vascular endothelial growth factor six months after primary surgery as a prognostic marker in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Werther, Kim; Sørensen, Steen; Christensen, Ib Jarle;

    2003-01-01

    High preoperative circulating vascular endothelial growth factor (VEGF) is predictive of poor prognosis in patients with colorectal cancer (CRC). However, postoperative circulating VEGF has not yet been evaluated as a prognostic marker in CRC patients. In 318 consecutive patients who had undergone...

  2. Prospective Dutch colorectal cancer cohort : an infrastructure for long-term observational, prognostic, predictive and (randomized) intervention research

    NARCIS (Netherlands)

    Burbach, J P M; Kurk, S A; Coebergh van den Braak, R R J; Dik, V K; May, A M; Meijer, G. A.; Punt, C J A; Vink, G R; Los, M; Hoogerbrugge, N; Huijgens, P C; Ijzermans, J N M; Kuipers, E J; de Noo, M E; Pennings, J P; van der Velden, A M T; Verhoef, C; Siersema, P D; van Oijen, M G H; Verkooijen, H M; Koopman, M

    2016-01-01

    BACKGROUND: Systematic evaluation and validation of new prognostic and predictive markers, technologies and interventions for colorectal cancer (CRC) is crucial for optimizing patients' outcomes. With only 5-15% of patients participating in clinical trials, generalizability of results is poor. Moreo

  3. The prognostic value of microRNA-126 and microvessel density in patients with stage II colon cancer

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Kjær-Frifeldt, Sanne; Morgenthaler, Søren

    2014-01-01

    were correlated with recurrence-free cancer specific survival (RF-CSS) and overall survival (OS). RESULTS: Low miRNA-126 expression was significantly correlated to T4, high malignancy grade, tumour perforation, fixation, and the presence of microsatellite instability. A prognostic impact on OS...

  4. A novel prognostic index in colorectal cancer defined by serum carcinoembryonic antigen and plasma tissue inhibitor of metalloproteinases-1

    DEFF Research Database (Denmark)

    Nielsen, Hans J.; Christensen, Ib J.; Brunner, Nils

    2010-01-01

    The introduction of stage-independent prognostic markers may play a significant role in future selection for adjuvant treatment for early-stage colorectal cancer (CRC). The purpose of this study was to assess the combination of preoperative serum carcinoembryonic antigen (CEA) and plasma tissue i...

  5. Treatment outcome and prognostic variables for local control and survival in patients receiving radical radiotherapy for urinary bladder cancer

    DEFF Research Database (Denmark)

    Fokdal, Lars; Høyer, Morten; Maase, Hans von der

    2004-01-01

    The aim of this retrospective study was to analyze the outcome of radical radiotherapy in 292 patients with bladder cancer and to identify prognostic factors for local control and survival. Median age was 72.3 years (range 45-83 years). Median follow up was 66 months (range 18-121 months). All pa...

  6. Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients

    Science.gov (United States)

    Pilanci, Kezban N.; Avcı, Nilüfer; Yıldız, İbrahim; Alço, Gül; Demirhan, Özkan; Köksal, Ülkühan I.; Elbüken, Filiz; Tecimer, Coskun; Demir, Gökhan

    2016-01-01

    Aim of the study Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Material and methods Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Results Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12–61) and 19 months (5–45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. Conclusions As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients. PMID:27358594

  7. THE PROGNOSTIC AND DIAGNOSTIC VALUE OF REPEATED TRANSRECTAL PROSTATE SATURATION BIOPSY

    Directory of Open Access Journals (Sweden)

    M. A. Kurdzhiev

    2014-08-01

    Full Text Available Objective: to determine the rate of prostate cancer (PC development after repeated transrectal saturation prostate biopsy (RTRSPB, to study the characteristics of diagnosed tumors, and to estimate their clinical significance from the data of radical retropubic prostatectomy (RRP.Materials and methods. The results of RTRSPB were analyzed in 226 patients with a later evaluation of a tumor from the results of RRP. All the patients underwent at least 2 prostate biopsies (mean 2.4. The average number of biopsy cores was 26.7 (range 24—30. The average value of total prostate-specific antigen before saturation biopsy was 7.5 (range 7.5 to 28.6 ng/ml. The mean age of patients was 62 years (range 53 to 70.  Results. PC was diagnosed in 14.6% of cases (33/226. An isolated lesion of the prostatic transition zone was in 12.1% of cases. If this zone had been excluded from the biopsy scheme, the detection rate of PC during saturation biopsy should be reduced by 13.8%. Better PC detectability during repeated saturation biopsy generally occurred due to the localized forms of the disease (93.3%. The agreement of Gleason tumor grading in the biopsy and prostatectomy specimens was noted in 66.7% of cases.Conclusion. Saturation biopsy allows prediction of a pathological stage of PC, Gleason grade of a tumor and its site localization with a greater probability. Most tumors detectable by saturation biopsy were clinically significant, which makes it possible to recommend RTRSPB to some cohort of high PC-risk patients 

  8. Prognostic Impact of the 6th and 7th American Joint Committee on Cancer TNM Staging Systems on Esophageal Cancer Patients Treated With Chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Motoo, E-mail: excell@hkg.odn.ne.jp [Department of Clinical Oncology, Aichi Cancer Center Hospital (Japan); Department of Radiation Oncology, Aichi Cancer Center Hospital (Japan); Shitara, Kohei [Department of Clinical Oncology, Aichi Cancer Center Hospital (Japan); Kodaira, Takeshi [Department of Radiation Oncology, Aichi Cancer Center Hospital (Japan); Hatooka, Shunzo [Department of Thoracic Surgery, Aichi Cancer Center Hospital (Japan); Mizota, Ayako; Kondoh, Chihiro; Yokota, Tomoya; Takahari, Daisuke; Ura, Takashi; Muro, Kei [Department of Clinical Oncology, Aichi Cancer Center Hospital (Japan)

    2012-02-01

    Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of the 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT.

  9. Prognostic value of cancer stem cell markers CD133, ALDH1 and nuclearβ-catenin in colon cancer

    Institute of Scientific and Technical Information of China (English)

    Eman H.Abdelbary; Hayam E.Rashed; Eman I.Ismail; Mohamed Abdelgawad

    2014-01-01

    Colon cancer is one of the most common human malignancies. Cancer stem cells (CSCs), despite being only a smal subset of cancer cells, have the capability to self renew and sustain the tumor. They also have the ability to proliferate. Multiple CSCs associated markers have been identified in colon cancer including CD133, ALDH1 andβ catenin. The aim of the work was to study the prognostic value of CSCs markers (CD133, ALDH1 andβ catenin), as wel as their rela tionship to clinicopathological features of colon cancer. Methods:CD133, ALDH1 andβ catenin proteins expression was as sessed immunohistochemical y in a series of colon cancers and their prognostic significance was evaluated. Results:CD133 expression showed significant relationship to tumor stage and lymph node metastasis (P value 0.004&<0.001 respectively), and near significant relationship to liver metastasis (P value 0.092). ALDH1 was significantly associated with tumor grade, stage and nodal metastasis (P value 0.021, 0.001 and 0.026 respectively), but its relationship to liver metastasis was near sig nificant (P value 0.068). Nuclearβ catenin was significantly related to tumor grade, stage, nodal and liver metastasis (P value 0.001,<0.001,<0.001 and 0.008 respectively). Overal survival (OS) was associated inversely with CD133, ALDH1 positivity, and directly with nuclearβ catenin positivity (P value<0.001, 0.0001 and<0.001 respectively). Also recurrence free survival (RFS) was associated inversely with CD133, ALDH1 and directly with nuclearβ catenin positivity (P value 0.0001, 0.001 and<0.001 respectively). Conclusion:CD133, ALDH1 andβ catenin expressions of tumor cells have significant impact upon malignant progression of colon cancer and thus patient survival and tumor recurrence. Hence they can be used to predict outcome of colon cancer patients.

  10. The G Protein-Coupled Receptor RAI3 Is an Independent Prognostic Factor for Pancreatic Cancer Survival and Regulates Proliferation via STAT3 Phosphorylation

    Science.gov (United States)

    Jahny, Elisabeth; Yang, Hai; Liu, Bin; Jahnke, Beatrix; Lademann, Franziska; Knösel, Thomas; Rümmele, Petra; Grützmann, Robert; Aust, Daniela E.; Denz, Axel

    2017-01-01

    Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest tumors worldwide. Understanding the function of gene expression alterations is a prerequisite for developing new strategies in diagnostic and therapy. GPRC5A (RAI3), coding for a seven transmembrane G protein-coupled receptor is known to be overexpressed in pancreatic cancer and might be an interesting candidate for therapeutic intervention. Expression levels of RAI3 were compared using a tissue microarray of 435 resected patients with pancreatic cancer as well as 209 samples from chronic pancreatitis (CP), intra-ductal papillary mucinous neoplasm (IPMN) and normal pancreatic tissue. To elucidate the function of RAI3 overexpression, siRNA based knock-down was used and transfected cells were analyzed using proliferation and migration assays. Pancreatic cancer patients showed a statistically significant overexpression of RAI3 in comparison to normal and chronic pancreatitis tissue. Especially the loss of apical RAI3 expression represents an independent prognostic parameter for overall survival of patients with pancreatic cancer. Suppression of GPRC5a results in decreased cell growth, proliferation and migration in pancreatic cancer cell lines via a STAT3 modulated pathway, independent from ERK activation. PMID:28114355

  11. Prognostic value of neutrophil-to-lymphocyte ratio in metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Qianqian Yu; Hong Qiu; Mingsheng Zhang; Guangyuan Hu; Liu Huang; Xianglin Yuan 

    2016-01-01

    Objective This study investigated the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in predicting clinical outcomes of patients with metastatic colorectal cancer (mCRC) undergoing irinotecan-based first-line chemotherapy. Methods This study was based on a Chinese prospective multicenter trial (NCT01282658). Baseline complete blood cel counts were performed. Survival was determined using the Kaplan-Meier method. Multivariate analyses based on the Cox regression model were performed to determine the ef ects of inde-pendent biomarkers. Results A total of 139 patients were evaluated. Values below the median NLR were associated with bet-ter progression-free survival (PFS) (9.9 vs 7.7 months, P = 0.043) and overal survival (OS) (21.8 vs 15.1 months, P = 0.013). These ef ects remained significant in multivariate analysis. Conclusion NLR is an independent prognostic marker of mCRC treated with first-line irinotecan-based therapy in a Chinese population.

  12. Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer.

    LENUS (Irish Health Repository)

    Cathcart, Mary-Clare

    2011-03-01

    Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and\\/or a survival factor in the disease.

  13. Enhancer of zeste homolog 2 as an independent prognostic marker for cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Shuling Chen

    Full Text Available Novel biomarkers are of particular interest for predicting cancer prognosis. This study aimed to explore the associations between enhancer of zeste homolog 2 (EZH2 and patient survival in various cancers.Relevant literature was retrieved from PubMed and Web of Science databases. Pooled hazard ratios (HRs, odds ratios (ORs, and 95% confidence intervals (CIs were calculated.Forty-nine studies (8,050 patients were included. High EZH2 expression was significantly associated with shorter overall (hazard ratio [HR] 1.74, 95% CI: 1.46-2.07, disease-free (HR 1.59, 95% CI: 1.27-1.99, metastasis-free (HR 2.19, 95% CI: 1.38-3.47, progression-free (HR 2.53, 95% CI: 1.52-4.21, cancer-specific (HR 3.13, 95% CI: 1.70-5.74, and disease-specific (HR 2.29, 95% CI: 1.56-3.35 survival, but not recurrence-free survival (HR 1.38, 95% CI: 0.93-2.06. Moreover, EZH2 expression significantly correlated with distant metastasis (OR 3.25, 95% CI: 1.07-9.87 in esophageal carcinoma; differentiation (OR 3.00, 95% CI: 1.37-6.55 in non-small cell lung cancer; TNM stage (OR 3.18, 95% CI: 2.49-4.08 in renal cell carcinoma; and histological grade (OR 4.50, 95% CI: 3.33-6.09, estrogen receptor status (OR 0.15, 95% CI: 0.11-0.20 and progesterone receptor status (OR 0.30, 95% CI: 0.23-0.39 in breast cancer.Our results suggested that EZH2 might be an independent prognostic factor for multiple survival measures in different cancers.

  14. A comparison of the prognostic value of preoperative inflammation-based scores and TNM stage in patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    Pan QX

    2015-06-01

    Full Text Available Qun-Xiong Pan,* Zi-Jian Su,* Jian-Hua Zhang, Chong-Ren Wang, Shao-Ying KeDepartment of Oncosurgery, Quanzhou First Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of China*These authors contributed equally to this workBackground: People’s Republic of China is one of the countries with the highest incidence of gastric cancer, accounting for 45% of all new gastric cancer cases in the world. Therefore, strong prognostic markers are critical for the diagnosis and survival of Chinese patients suffering from gastric cancer. Recent studies have begun to unravel the mechanisms linking the host inflammatory response to tumor growth, invasion and metastasis in gastric cancers. Based on this relationship between inflammation and cancer progression, several inflammation-based scores have been demonstrated to have prognostic value in many types of malignant solid tumors.Objective: To compare the prognostic value of inflammation-based prognostic scores and tumor node metastasis (TNM stage in patients undergoing gastric cancer resection.Methods: The inflammation-based prognostic scores were calculated for 207 patients with gastric cancer who underwent surgery. Glasgow prognostic score (GPS, neutrophil lymphocyte ratio (NLR, platelet lymphocyte ratio (PLR, prognostic nutritional index (PNI, and prognostic index (PI were analyzed. Linear trend chi-square test, likelihood ratio chi-square test, and receiver operating characteristic were performed to compare the prognostic value of the selected scores and TNM stage.Results: In univariate analysis, preoperative serum C-reactive protein (P<0.001, serum albumin (P<0.001, GPS (P<0.001, PLR (P=0.002, NLR (P<0.001, PI (P<0.001, PNI (P<0.001, and TNM stage (P<0.001 were significantly associated with both overall survival and disease-free survival of patients with gastric cancer. In multivariate analysis, GPS (P=0.024, NLR (P=0.012, PI (P=0.001, TNM stage (P<0.001, and degree of

  15. Prognostic significance of TAZ expression in various cancers: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Feng J

    2016-08-01

    Full Text Available Juntao Feng,1 Pengwei Ren,2 Jinhai Gou,1 Zhengyu Li1,3 1Department of Gynecology and Obstetrics, West China Second University Hospital, 2Department of Evidence-Based Medicine and Clinical Epidemiology, West China Hospital, 3Sichuan Key Laboratory of Gynecologic Oncology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China Background: The overexpression of transcriptional coactivator with PDZ-binding motif (TAZ, a Hippo pathway effector, was detected in a variety of cancers. However, controversies remain in published studies on the prognostic value of TAZ expression in cancer. We performed a meta-analysis to demonstrate the prognostic significance of TAZ in overall survival (OS and its association with clinicopathologic characteristics. Methods: A systematic literature search was performed by using PubMed, EMBASE, and Web of Science databases for eligible studies investigating the association between TAZ and survival. After extracting data, we used hazard ratio (HR, odds ratio (OR and 95% confidence intervals (95% CIs for association evaluation, I2 for heterogeneity across studies, and Egger’s test and Begg’s funnel plot for publication bias assessment. Results: A total of 15 studies including 2,881 patients were analyzed. Pooled results showed that a high TAZ was significantly associated with poor OS (HR =1.82, 95% CI =1.58–2.11; I2=33%; P=0.11. Subgroup analysis indicated significant correlation between TAZ overexpression and OS in patients stratified by ethnicity, sample size, sample source, and staining location. Furthermore, TAZ overexpression was associated with worse OS in hepatocellular carcinoma (HR =2.26, 95% CI =1.43–3.57; P=0.49 and gastrointestinal cancers (HR =2.00, 95% CI =1.54–2.58; P=0.97, but not in non-small-cell lung cancer (HR =1.71, 95% CI =0.93–3.14; P=0.08. TAZ overexpression was also found to be significantly associated with some clinicopathologic characteristics

  16. Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Hansen, Ulla; Christensen, Ib Jarle;

    1999-01-01

    -assisted microscope, which allowed semi-automated quantification of cells within a fixed area. Total white cells and individual counts of eosinophils, neutrophils, mast cells, lymphocytes, and plasma cells were evaluated in every tumour specimen. Stratification into four groups with similar numbers of events was used...... age ( p=0.0003), and tumour location in the rectum predicted poor survival, while high counts of eosinophils ( p=0.006) and mast cells ( p=0.02) predicted good survival. Tumour-associated eosinophilia and mastocytosis appear to be independent prognostic variables in colorectal cancer. Future studies...... should investigate the potential biological role of tumour tissue eosinophils and mast cells in the modulation of tumour growth....

  17. Preoperative Concurrent Radiochemotherapy for Locally Advanced Esophageal Cancer: Treatment Outcome and Prognostic Factors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hae Young; Ahn, Yong Chan; Kim, Kwan Min; Kim, Jhing Ook; Shim, Young Mog; Im, Young Hyuck [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2007-09-15

    Purpose: This study reports the results of the use of preoperative concurrent radiochemotherapy (CRCT) for the treatment of locoregionally advanced esophageal cancer. Materials and Methods: From 1998 through 2005, 61 patients with intrathoracic esophageal cancer at stages II-IVB (without distant organ metastasis and presumed to be respectable) received preoperative CRCT. CRCT consisted of radiotherapy (45 Gy /25 fractions /5 weeks) and FP chemotherapy (5-FU 1 g/m2/day, days 1-4 and 29-32, Cisplatin 60 mg/m2/day, days 1 and 29). An esophagectomy was planned in 4 {approx} 6 weeks after the completion of CRCT. Results: There were two treatment-related deaths. Among the 61 patients, 53 patients underwent surgery and 17 patients achieved a pathological complete response (pCR). The overall survival (OS) rates of all 61 patients at 2 and 5 years were 59.0% and 38.0%, respectively. The rates of OS and disease-free survival (DFS) of the surgically resected patients at 2 and 5 years were 61.6%, 40.1% and 53.3%, 41.8%, respectively. By univariate analysis, achievement of pCR and a clinically uninvolved distant lymph node (cM0) were favorable prognostic factors for OS and DFS. There were 27 patients that experienced a relapse-a locoregional relapse occurred in 5 patients, a distant metastasis occurred in 12 patients and combined failure occurred in 10 patients. Conclusion: The results of the current study are favorable. pCR and an uninvolved distant lymph node were found to be favorable prognostic factors.

  18. Clinical and prognostic association of transcription factor SOX4 in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Chia-Lang Fang

    Full Text Available Gastric cancer (GC is one of the most common malignant cancers worldwide. However, little is known about the molecular process by which this disease develops and progresses. This study investigated correlations between the expression of nuclear transcription factor SOX4 and various clinicopathologic parameters as well as patients' survival. Expression levels of nuclear SOX4 were analyzed by immunohistochemistry; the data comprised gastric tissues from 168 patients with GC. Paired t tests were used to analyze the differences in nuclear SOX4 expression between tumor and non-tumor tissues from each patient. Two-tailed Χ(2 tests were performed to determine whether the differences in nuclear SOX4 expression and clinicopathologic parameters were significant. Time-to-event endpoints for clinicopathologic parameters were plotted using the Kaplan-Meier method, and statistical significance was determined using univariate log-rank tests. Cox proportional hazard model was used for multivariate analysis to determine the independence of prognostic effects of nuclear SOX4 expression. Overexpression of nuclear SOX4 was significantly correlated with depth of invasion (P<0.0001, nodal status (P=0.0055, distant metastasis (P=0.0195, stage (P=0.0003, and vascular invasion (P=0.0383. Patients who displayed high expression levels of nuclear SOX4 achieved a significantly poorer disease-free survival rate, compared with patients with low SOX4 expression levels (P=0.003. Univariate Cox regression analysis showed that overexpression of nuclear SOX4 was a clear prognostic marker for GC (P=0.004. Overexpression of nuclear SOX4 can be used as a marker to predict the outcome of patients with GC.

  19. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Directory of Open Access Journals (Sweden)

    Mirco Pistelli

    2014-06-01

    Full Text Available Background: Triple-negative breast cancers (TNBC are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001 and a lympho-vascular invasion (p = 0.01, but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72 or overall survival (p = 0.93. Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

  20. Evaluation of the prognostic benefit of identifying the probable primary site in cancer of unknown primary

    Directory of Open Access Journals (Sweden)

    Das Joyutpal

    2015-09-01

    Full Text Available With the development of site-specific cancer therapy, identifying the primary origin allows the oncologist to personalise therapy for patients with the cancer of unknown primaries (CUPs. At present, immunohistochemistry (IHC screening is the standard method used to postulate the primary site in CUP. In this retrospective study, we evaluated the prognostic benefit of identifying the primary site in CUP. All 84 patients who presented with suspected CUP to the Royal Stoke University Hospital between 2011 and 2012 were included in our study. Forty-eight percent (40/84 of these patients were unable to undergo necessary investigations to identify primary sites because of poor performance status. IHC screening was able to postulate the primary site in 59% (26/44 of the remaining patients with confirmed CUP. Therefore, the primary site was not identified in a significant proportion of patients with CUP. The median survival of confirmed CUP with probable primary site was 2.0 months (95% confidence interval (CI: 1.2 to 2.9 months, whereas the median survival of confirmed CUP with no probable primary site was 4.1 months (95% CI: 1.5 to 9.7 months. This difference in survival time was statistically significant. In addition, using the Cox regression model, we found that patients with confirmed CUP with primary sites had prognostically unfavourable diseases with a shorter median survival, regardless of the age of disease onset, gender, sites of metastases or number of metastases. One approach to improve the survival would be to start systemic therapy at the earliest possible opportunity rather than waiting for all investigation results, such as IHC.

  1. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Science.gov (United States)

    Pistelli, Mirco; Caramanti, Miriam; Biscotti, Tommasina; Santinelli, Alfredo; Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano

    2014-01-01

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target. PMID:24978437

  2. The MicroRNAs as Prognostic Biomarkers for Survival in Esophageal Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Wenbo Fu

    2014-01-01

    Full Text Available Objectives. We performed this meta-analysis to summarize all the results from available studies, aiming delineating the prognostic role of miRNA in esophageal cancer. Design and Methods. We searched the electronic databases PubMed, EMBASE, and ISI Web of Science without time restrictions for the correlative literature to aggregate the survival results. Relevant data were extracted from studies investigating the relationship between miRNAs expression and survival in esophageal cancer patients. Pooled hazard ratios of miR-21and miR-375 for OS in ESCC were calculated. Results. A total of 25 studies involving 2,258 subjects analyzed the relationship between miRNA and prognosis of EC. In all, thirty-nine miRNAs associated with prognosis were reported in these studies. The pooled HR of higher miR-21 expression compared with lower miR-21 expression in ESCC was 1.84 (95% CI: 1.41–2.40, P<0.001, which could significantly predict poorer OS in ESCC. Besides, higher miR-375 was also a significant predictor for OS in ESCC, with a pooled HR of 0.55 (95% CI: 0.42–0.72, P<0.001. Conclusions. Our results support that miR-21 and miR-375 have a prognostic role in ESCC and may be useful therapeutic targets for the treatment of ESCC and meticulous follow-up for early detection of recurrence.

  3. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Energy Technology Data Exchange (ETDEWEB)

    Pistelli, Mirco, E-mail: mirco.pistelli@alice.it; Caramanti, Miriam [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Biscotti, Tommasina; Santinelli, Alfredo [Anatomia Patologica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy)

    2014-06-27

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

  4. Usefulness of tumor volumetry as a prognostic factor of survival in head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kurek, R.; Roeddiger, S.; Martin, T.; Zamboglou, N. [Dept. of Radiotherapy, Klinikum Offenbach (Germany); Kalogera-Fountzila, A.; Fountzilas, G. [AHEPA Hospital, Aristotle Univ. of Thessaloniki, School of Medicine, Thessaloniki, Macedonia (Greece); Muskalla, K. [Dept. of Radiotherapy, Heinrich Heine Univ. Duesseldorf (Germany); Dafni, U. [Dept. of Public Health, School of Nursing, Univ. of Athens (Greece); Schnabel, T. [Dept. of Radiotherapy, Clinic for Radiooncology and Nuclear Medicine, Ludwigshafen (Germany); Kober, B. [Dept. of Radiotherapy, Klinikum Darmstadt (Germany)

    2003-05-01

    Background: The TNM classification system of tumor stage does not always reflect the actual tumor mass present at diagnosis. This study aimed at evaluating the prognostic value of volumetric data regarding survival in head and neck cancer patients being treated with either cisplatin or carboplatin administered concomitantly with radiotherapy. Patients and Methods: We retrospectively analyzed 107 patients suffering from squamous cell carcinoma of the head and neck in a Greek-German cooperational study (see Table 1). All patients were treated by radiotherapy and concomitant chemotherapy. 65 patients received chemotherapy with carboplatin and 42 with cisplatin. More than 6,200 CT scans were analyzed by digitalization of contours which subsequently led to the computation of the tumor volume (primary and macroscopic lymph node metastases). Results: Median follow-up was 43 months and median survival 30 months. Median initial tumor volume was 32.5 ml (range 2.1-220.1 ml) in the carboplatin and 44.4 ml (range 3.2-202.5 ml) in the cisplatin group (see Figure 1). After treatment, tumor volumes did not differ significantly (median of 3.1 ml [range 0.0-167.1 ml] and 3.5 ml [range 0.0-166.0 ml], respectively). 41 patients (63.1%) died in the carboplatin group and 22 patients (52.4%) in the cisplatin group (see Figure 2). Pretherapeutic tumor volume was prognostic with respect to survival while TNM classification and age were not. Pretherapeutic tumor volume was negatively and percent decrease in tumor volume positively associated with survival (see Tables 2 and 3). Conclusion: Knowledge of the initial tumor volume adds valuable information in terms of prognosis. Initial tumor volume should be included in all future clinical trials regarding head and neck cancer patients. (orig.)

  5. Significant prognostic value of circulating tumor cells in esophageal cancer patients: A meta-analysis.

    Science.gov (United States)

    Wang, Shuyu; Du, Hongyang; Li, Guixia

    2017-02-02

    Esophageal cancer is the sixth leading cause of cancer death worldwide. Detection of circulating tumor cells (CTCs) is emerging as a novel strategy for predicting cancer patient prognosis. Here we performed a comprehensive literature search to identify relevant articles in EMbase, PubMed, EBSCO, OVID, Cochrane Database, CNKI, WanFangdata and VIPdata. Meta-analysis was conducted using Stata12.0 software, according to the inclusion and exclusion criteria, extracted data and assessment methodology. Thirteen eligible literature studies were included with a total of 979 esophageal squamous cell carcinoma patients, including 424 CTC-positive and 684 CTC-negative cases. Meta-analysis showed that the presence of CTCs was associated with both worse progression-free/disease-free survival [hazard ration (HR) = 2.32, 95% confidence interval (CI) = 1.57 - 3.43, p < 0.001] and poorer overall survival [HR = 2.64, 95% CI = 1.69 - 4.14, p < 0.001]. Further subgroup analyses demonstrated that CTC-positive patients also showed worse progression-free/disease-free survival and poorer overall survival in different subsets. In summary, our meta-analysis provides strong evidence that detection of CTCs in the peripheral blood is an independent prognostic indicator of poor outcome for esophageal squamous cell carcinoma patients.

  6. Functional analysis of prognostic gene expression network genes in metastatic breast cancer models.

    Directory of Open Access Journals (Sweden)

    Thomas R Geiger

    Full Text Available Identification of conserved co-expression networks is a useful tool for clustering groups of genes enriched for common molecular or cellular functions [1]. The relative importance of genes within networks can frequently be inferred by the degree of connectivity, with those displaying high connectivity being significantly more likely to be associated with specific molecular functions [2]. Previously we utilized cross-species network analysis to identify two network modules that were significantly associated with distant metastasis free survival in breast cancer. Here, we validate one of the highly connected genes as a metastasis associated gene. Tpx2, the most highly connected gene within a proliferation network specifically prognostic for estrogen receptor positive (ER+ breast cancers, enhances metastatic disease, but in a tumor autonomous, proliferation-independent manner. Histologic analysis suggests instead that variation of TPX2 levels within disseminated tumor cells may influence the transition between dormant to actively proliferating cells in the secondary site. These results support the co-expression network approach for identification of new metastasis-associated genes to provide new information regarding the etiology of breast cancer progression and metastatic disease.

  7. Circulating Tumor Cells in Metastatic Breast Cancer: A Prognostic and Predictive Marker

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    Sayyed Farshid Moussavi-Harami

    2014-05-01

    Full Text Available The role of circulating tumor cells (CTCs as a marker for disease progression in metastatic cancer is controversial. The current review will serve to summarize the evidence on CTCs as a marker of disease progression in patients with metastatic breast cancer. The immunohistochemistry (IHC-based CellSearch® is the only FDA-approved isolation technique for quantifying CTCs in patients with metastatic breast cancer. We searched PubMed and Web of Knowledge for clinical studies that assessed the prognostic and predictive value of CTCs using IHC-based isolation. The patient outcomes reported include median and Cox-proportional hazard ratios for overall survival (OS and progression-free survival (PFS. All studies reported shorter OS for CTC-positive patients versus CTC-negative. A subset of the selected trials reported significant lower median PFS for CTC-positive patients. The reported trials support the utility of CTC enumeration for patient prognosis. But further studies are required to determine the utility of CTC enumeration for guiding patient therapy. There are three clinical trials ongoing to test this hypothesis. These studies, and others, will further establish the role of CTCs in clinical practice.

  8. Prognostic significance of new onset ascites in patients with pancreatic cancer

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    Luzardo German

    2006-03-01

    Full Text Available Abstract Background The purpose of this study was to determine risk factors for development of malignant ascites and its prognostic significance in patients with pancreatic cancer. Methods A prospective database was queried to identify patients with pancreatic cancer who develop ascites. Stage at presentation, size, and location of primary tumor, treatment received and length of survival after onset of ascites were determined. Results A total of 15 patients were identified. Of which 4 patients (1 stage II, 3 stage III underwent pancreaticoduodenectomy and manifested with ascites 2, 3, 24 and 47 months after surgery (tumor size 2.9 ± 1.32 cm. All but one of the remaining 11 patients (tumor size 4.4 ± 3.38 cm presented with metastatic disease, and all developed malignant ascites 9 months after diagnosis, dying 2 months later. Resected patients lived longer before the onset of ascites, but not after. Conclusion Once diagnosed, ascites in pancreatic cancer patients heralds imminent death. Limited survival should be considered when determining the aggressiveness of further intervention.

  9. Chemosensitivity profile assay of circulating cancer cells: prognostic and predictive value in epithelial tumors.

    Science.gov (United States)

    Gazzaniga, Paola; Naso, Giuseppe; Gradilone, Angela; Cortesi, Enrico; Gandini, Orietta; Gianni, Walter; Fabbri, Maria Agnese; Vincenzi, Bruno; di Silverio, Franco; Frati, Luigi; Aglianò, Anna Maria; Cristofanilli, Massimo

    2010-05-15

    The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch technology raise additional issues regarding the biological value of this information. We postulated that a drug-resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.

  10. Prognostic impact of dissected lymph node count on patients with node-negative gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Chang-Ming Huang; Jian-Xian Lin; Chao-Hui Zheng; Ping Li; Jian-Wei Xie; Bi-Juan Lin; Hui-Shan Lu

    2009-01-01

    AIM: To investigate the long-term effect of the number of resected lymph nodes (LNs) on the prognosis of patients with node-negative gastric cancer. METHODS: Clinical data of 211 patients with gastric cancer, without nodal involvement, were analyzed retrospectively after D2 radical operation. We analyzed the relationship between the number of resected LNs with the 5-year survival, the recurrence rate and the post-operative complication rate.RESULTS: The 5-year survival of the entire cohort was 82.2%. The total number of dissected LNs was one of the independent prognostic factors. Among patients with comparable depth of invasion, the larger the number of resected LNs, the better the survival ( P 0.05).CONCLUSION: For node-negative gastric cancer,sufficient number of dissected LNs is recommended during D2 lymphadenectomy, to improve the long-term survival and reduce the recurrence. Suitable increments of the dissected LN count would not increase the postoperative complication rate.

  11. The Prognostic Value of Polycomb Group Protein BMI1 in Stage II Colon Cancer Patients

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Linnemann, Dorte; Christensen, Ib J.;

    2016-01-01

    The aim of this study was to investigate the prognostic value of B-cell-specific moloney murine leukemia virus insertion site 1 (BMI1) protein expression in primary tumors of stage II colon cancer patients. BMI1 protein expression was assessed by immunohistochemistry in a retrospective patient...... cohort consisting of 144 stage II colon cancer patients. BMI1 expression at the invasive front of the primary tumors correlated with mismatch repair status of the tumors. Furthermore, BMI1 expression at the luminal surface correlated with T-stage, tumor location, and the histological subtypes....... Likewise, there was no association between 5-year overall survival and BMI1 expression at the invasive front (HR: 1.12; 95% CI 0.80-1.56; p = 0.46) or at the luminal surface of the tumor (HR: 1.16; 95% CI 0.86-1.60; p = 0.33). In conclusion, BMI1 expression in primary tumors of stage II colon cancer...

  12. The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer.

    LENUS (Irish Health Repository)

    d'Adhemar, Charles J

    2014-01-01

    The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact\\/functioning TLR4\\/MyD88

  13. Thioredoxin and thioredoxin-interacting protein as prognostic markers for gastric cancer recurrence

    Institute of Scientific and Technical Information of China (English)

    Jae Yun Lim; Sun Och Yoon; Soon Won Hong; Jong Won Kim; Seung Ho Choi; Jae Yong Cho

    2012-01-01

    related to energy,protein synthesis and autophagy.CONCLUSION:TXN and TXNIP are promising prognostic markers for gastric cancer,and performing personalized adjuvant treatment based on TXN and TXNIP expression levels would be an effective practice in the treatment of gastric cancer.

  14. The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Charles J d'Adhemar

    Full Text Available The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4, and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic, whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05, indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2 cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4

  15. HER2 as a Prognostic Marker in Gastric Cancer - A Systematic Analysis of Data from the Literature

    DEFF Research Database (Denmark)

    Jørgensen, Jan Trøst; Hersom, Maria Nathalie Selch

    2012-01-01

    Through the recent conduct of the ToGA trial, HER2 has shown to be predictive for the treatment with trastuzumab in advanced gastric and gastro-oesophageal cancer. When it comes to the prognostic properties the situation is different. Despite the fact that it is more than 20 years ago since...... the first studies demonstrating an association between a positive HER2 status and poor prognosis were published the issue is still controversial. In this current systematic review a large number of studies on HER2 and gastric cancer have been reviewed. The studies included in this review should fulfill...... with poor survival and/or clinicopathological characteristics, such as serosal invasion, lymph node metastases, disease stage, or distant metastases. Based on the current analysis a clear trend towards a potential role for HER2 as a negative prognostics factor in gastric cancer was shown, suggesting...

  16. Renal Cancer Biomarkers | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute's Laboratory of Proteomics and Analytical Technologies is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic, therapeutic and prognostic cancer biomarkers from clinical specimens.

  17. Prognostic significance of TAZ expression in various cancers: a meta-analysis

    Science.gov (United States)

    Feng, Juntao; Ren, Pengwei; Gou, Jinhai; Li, Zhengyu

    2016-01-01

    Background The overexpression of transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo pathway effector, was detected in a variety of cancers. However, controversies remain in published studies on the prognostic value of TAZ expression in cancer. We performed a meta-analysis to demonstrate the prognostic significance of TAZ in overall survival (OS) and its association with clinicopathologic characteristics. Methods A systematic literature search was performed by using PubMed, EMBASE, and Web of Science databases for eligible studies investigating the association between TAZ and survival. After extracting data, we used hazard ratio (HR), odds ratio (OR) and 95% confidence intervals (95% CIs) for association evaluation, I2 for heterogeneity across studies, and Egger’s test and Begg’s funnel plot for publication bias assessment. Results A total of 15 studies including 2,881 patients were analyzed. Pooled results showed that a high TAZ was significantly associated with poor OS (HR =1.82, 95% CI =1.58–2.11; I2=33%; P=0.11). Subgroup analysis indicated significant correlation between TAZ overexpression and OS in patients stratified by ethnicity, sample size, sample source, and staining location. Furthermore, TAZ overexpression was associated with worse OS in hepatocellular carcinoma (HR =2.26, 95% CI =1.43–3.57; P=0.49) and gastrointestinal cancers (HR =2.00, 95% CI =1.54–2.58; P=0.97), but not in non-small-cell lung cancer (HR =1.71, 95% CI =0.93–3.14; P=0.08). TAZ overexpression was also found to be significantly associated with some clinicopathologic characteristics, including TNM stage (OR =2.56, 95% CI =1.60–4.11; P=0.52), tumor differentiation (OR =3.08, 95% CI =1.25–7.63; P=0.01), and lymph node metastasis (OR =2.53, 95% CI =1.81–3.53; P=0.58). Conclusion TAZ overexpression is not only a predictive factor of poor prognosis but also associated with advanced TNM stage, poor tumor differentiation, and lymph node metastasis. PMID:27601916

  18. Prognostic value of serum level of interleukin-6 and interleukin-8 in metastatic breast cancer patients.

    Science.gov (United States)

    Ahmed, Olal I; Adel, Azza M; Diab, Dina R; Gobran, Nagy S

    2006-01-01

    Previous studies indicated that interleukins may stimulate cancer cells growth and contribute to loco regional relapse as well as metastasis. The aim in this study was to investigate the level of interleukin-6 (IL-6) and interleukin-8 (IL-8) in metastatic breast cancer patients and find out the relation between the levels of these cytokines and the clinical out come of patients and to predict the value of these cytokines as independent prognostic factors. The present study was carried out on 40 women divided into two groups; the first group included 30 patients diagnosed as having metastatic breast cancer. The second group included 10 healthy women as controls. An immunoenzymometric assays for the quantitative measurement of human IL-6 and IL-8 were used. The serum level of IL-6 and IL-8 were measured for patients and controls. Serum level of both IL-6 and IL-8 were found to be higher in patients than in healthy volunteers. Serum IL-6 was detected in all patients and controls with a mean value of (25.3 pg/ml) versus (1.5 pg/ml) for patients and controls respectively and this difference was statistically highly significant (P IL-8 was detected in 26 patients (86.7%) and 7 controls (70%) with a mean value of (8.96 pg/ml) versus (3.9 pg/ml) for patients and controls respectively and this difference was also statistically highly significant (P IL-8 (10.2 pg/ml) in comparison with those with size less than 5cm (IL-6 14 pg/ml) and (IL-8 7.2 pg/ml) and the difference in both cases was statistically significant (P IL-8 with a mean value of 32.8 pg/ml and 10.2 pg/ml for IL-6 and IL-8 respectively, than those with less than 3 positive lymph nodes with mean value of 14 pg/ml and 6.9 pg/ml for IL-6 and IL-8 respectively and this difference was statistically significant (P IL-8 (P IL-8 was 6.2 pg/ml versus 11.3 pg/ml for patients with one metastatic site and patients with more than one metastatic site respectively. However, the level of IL-6 and IL-8 did not correlate with

  19. Prealbumin/CRP Based Prognostic Score, a New Tool for Predicting Metastasis in Patients with Inoperable Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Ali Esfahani

    2016-01-01

    Full Text Available Background. There is a considerable dissimilarity in the survival duration of the patients with gastric cancer. We aimed to assess the systemic inflammatory response (SIR and nutritional status of these patients before the commencement of chemotherapy to find the appropriate prognostic factors and define a new score for predicting metastasis. Methods. SIR was assessed using Glasgow Prognostic Score (GPS. Then a score was defined as prealbumin/CRP based prognostic score (PCPS to be compared with GPS for predicting metastasis and nutritional status. Results. 71 patients with gastric cancer were recruited in the study. 87% of patients had malnutrition. There was a statistical difference between those with metastatic (n=43 and those with nonmetastatic (n=28 gastric cancer according to levels of prealbumin and CRP; however they were not different regarding patient generated subjective global assessment (PG-SGA and GPS. The best cut-off value for prealbumin was determined at 0.20 mg/dL and PCPS could predict metastasis with 76.5% sensitivity, 63.6% specificity, and 71.4% accuracy. Metastatic and nonmetastatic gastric cancer patients were different in terms of PCPS (P=0.005. Conclusion. PCPS has been suggested for predicting metastasis in patients with gastric cancer. Future studies with larger sample size have been warranted.

  20. Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue.

    LENUS (Irish Health Repository)

    Kennedy, Richard D

    2011-12-10

    Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples.

  1. Prognostic Value of Cancer Stem Cell Marker ALDH1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Jinhuang Chen

    Full Text Available Many studies have indicated the prognostic and clinicopathological value of aldehyde dehydrogenase 1 (ALDH1 in colorectal cancer (CRC patients still remains controversial. Thus we performed this study to clarify the relationship between high ALDH1 expression in CRC and its impact on survival and clinicopathological features.Publications for relevant studies in Pubmed, the Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI through April 2015 were identified. Only articles describing ALDH1 antigen with immunohistochemistry in CRC were included. The software RevMan 5.1 was used to analyze the outcomes, including 5-year overall survival (OS, disease-free survival (DFS and clinicopathological features.9 studies with 1203 patients satisfying the criteria were included. The overall rate of high ALDH1 expression was 46.5% by immunohistochemical staining. High ALDH1 expression as an independent prognostic factor was significantly associated with the 5-year OS and DFS (OR = 0.42, 95%CI: 0.26-0.68, P = 0.0004; OR = 0.38, 95%CI: 0.24-0.59, P 60 years old vs. <60 years old; OR = 1.11, 95%CI: 0.63-1.94, P = 0.72.High ALDH1 expression indicates a poor prognosis in CRC patients. Moreover, high ALDH1 expression correlates with the T stage, N stage, and tumor differentiation, but not with age.

  2. Invasive breast cancer in Argentine women: association between risk and prognostic factors with antigens of a peptidic and carbohydrate nature

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    Croce MV

    2011-12-01

    Full Text Available Sandra O Demichelis, Marina T Isla-Larrain, Luciano Cermignani, Cecilio G Alberdi, Amada Segal-Eiras, María Virginia CroceCentre of Basic and Applied Immunological Research, Faculty of Medical Sciences, National University of La Plata, La Plata, ArgentinaObjective: In breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis.Results: All the antigens showed an increased expression according to tumor size increment; moreover, sialyl Lewis x expression showed a significant increase in relation to disease stage, whereas Tn and TF presented a positive tendency. Vascular invasion was related to sialyl Lewis x expression and number of metastatic lymph nodes. Taking into account risk factors, when a patient had at least one child, Lewis antigens diminished their expression. In relation to breastfeeding, sialyl Lewis x expression diminished, although its apical expression increased.Conclusion: Associations between MUC1 and carbohydrate antigens and risk and prognostic factors show the complexity of the cellular biological behavior that these antigens modulate in breast cancer.Keywords: breast cancer, Argentine women, risk factors, prognostic factors, antigenic expression

  3. Personalized cancer medicine: from molecular diagnostics to targeted therapy with natural products.

    Science.gov (United States)

    Efferth, Thomas

    2010-08-01

    Personalized cancer medicine aims to develop individualized treatment options adapted to factors relevant for the prognosis of each patient. Molecular biomarkers are required to predict the likelihood of an individual tumor's responsiveness or of toxicity in normal organs and to advise optimized treatments with improved efficacy at reduced side effects for each cancer patient. In the present review, we present a concept, which takes advantage of methods of molecular diagnostics to identify predictive markers at the DNA, mRNA, and protein levels. Markers with prognostic value concerning treatment response and patient survival can then be used as targets to develop optimized drugs. We focus on three examples to illustrate this strategy: (i) chemoselective treatment of tumors with 9p21 deletion by L-alanosine, (ii) treatment of multidrug-resistant P-glycoprotein-expressing tumor cells by non-cross-resistant natural products or by inhibitors of P-glycoprotein to overcome multidrug resistance, and (iii) natural products that inhibit the epidermal growth factor receptor (EGFR) in EGFR-overexpressing tumor cells.

  4. AGR3 in breast cancer: prognostic impact and suitable serum-based biomarker for early cancer detection.

    Science.gov (United States)

    Garczyk, Stefan; von Stillfried, Saskia; Antonopoulos, Wiebke; Hartmann, Arndt; Schrauder, Michael G; Fasching, Peter A; Anzeneder, Tobias; Tannapfel, Andrea; Ergönenc, Yavuz; Knüchel, Ruth; Rose, Michael; Dahl, Edgar

    2015-01-01

    Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (Pbreast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, Pbreast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer.

  5. The Largest Known Survival Analysis of Patients with Brain Metastasis from Thyroid Cancer Based on Prognostic Groups.

    Directory of Open Access Journals (Sweden)

    Jinhyun Choi

    Full Text Available To analyze the clinical features and prognostic factors associated with the survival of patients with a very rare occurrence of brain metastasis (BM from differentiated thyroid cancer (DTC.A total of 37 patients with DTC who were diagnosed with BM between 1995 and 2014 were included. We reviewed the clinical characteristics, treatment modalities, and image findings of BM. Factors associated with survival were evaluated, and the patients were divided into three prognostic groups (Groups A, B, and C for comparative analysis.The median age at BM was 63 years, and the median time from initial thyroid cancer diagnosis to BM was 3.8 years. The median survival and the 1-year actuarial survival rate after BM were 8.8 months and 47%, respectively. According to univariate and multivariate analyses, four good prognostic factors (GPFs were identified including age ≤ 60 years, PS ≤ ECOG 2, ≤ 3 BM sites, and without extracranial metastasis prior to BM. Three prognostic groups were designed based on age and number of remaining GPFs: patients ≤ 60 years of age with at least 2 GPFs (Group A had the most favorable prognosis with a median survival of 32.8 months; patients ≤ 60 years of age with fewer than 2 GPFs and those > 60 years of age with at least 2 GPFs (Group B had an intermediate prognosis with a median survival of 9.4 months; and patients > 60 years of age with fewer than 2 GPFs (Group C had the least favorable prognosis with a median survival of 1.5 months.The survival of patients with BM form DTC differed among the prognostic groups based on the total number of good prognostic factors.

  6. Towards a simple objective framework for the investigation and treatment of cancer cachexia: the Glasgow Prognostic Score.

    Science.gov (United States)

    Douglas, Euan; McMillan, Donald C

    2014-07-01

    Progress in the treatment of progressive involuntary weight loss in patients with cancer (cancer cachexia) remains dismally slow. Cancer cachexia and its associated clinical symptoms, including weight loss, altered body composition, poor functional status, poor food intake, and poorer quality of life, have long been recognised as indicators of poorer prognosis in the patient with cancer. In order to make some progress a starting point is to have general agreement on what constitutes cancer cachexia. In recent years a plethora of different definitions and consensus statements have been proposed as a framework for investigation and treatment of this debilitating and terminal condition. However, there are significant differences in the criteria used in these and all include poorly defined or subjective criteria and their prognostic value has not been established. The aim of the present review was to examine the hypothesis that a systemic inflammatory response accounts for most of the effect of cancer cachexia and its associated clinical symptoms on poor outcome in patients with cancer. Furthermore, to put forward the case for the Glasgow Prognostic Score to act a simple objective framework for the investigation and treatment of cancer cachexia.

  7. An Apta-Biosensor for Colon Cancer Diagnostics.

    Science.gov (United States)

    Raji, Mojgan Ahmadzadeh; Amoabediny, Ghasem; Tajik, Parviz; Hosseini, Morteza; Ghafar-Zadeh, Ebrahim

    2015-09-03

    This paper reports the design and implementation of an aptasensor using a modified KCHA10a aptamer. This aptasensor consists of a functionalized electrodes using various materials including 11-mercaptoandecanoic acid (11-MUA) and modified KCHA10a aptamer. The HCT 116, HT 29 and HEp-2 cell lines are used in this study to demonstrate the functionality of aptasensor for colon cancer detection purposes. Flow cytometry, fluorescence microscopy and electrochemical cyclic voltammetry are used to verify the binding between the target cells and aptamer. The limit of detection (LOD) of this aptasensor is equal to seven cancer cells. Based on the experimental results, the proposed sensor can be employed for point-of-care cancer disease diagnostics.

  8. An Apta-Biosensor for Colon Cancer Diagnostics

    Directory of Open Access Journals (Sweden)

    Mojgan Ahmadzadeh Raji

    2015-09-01

    Full Text Available This paper reports the design and implementation of an aptasensor using a modified KCHA10a aptamer. This aptasensor consists of a functionalized electrodes using various materials including 11-mercaptoandecanoic acid (11-MUA and modified KCHA10a aptamer. The HCT 116, HT 29 and HEp-2 cell lines are used in this study to demonstrate the functionality of aptasensor for colon cancer detection purposes. Flow cytometry, fluorescence microscopy and electrochemical cyclic voltammetry are used to verify the binding between the target cells and aptamer. The limit of detection (LOD of this aptasensor is equal to seven cancer cells. Based on the experimental results, the proposed sensor can be employed for point-of-care cancer disease diagnostics.

  9. The molecular biology of cancer and its diagnostic implications.

    Science.gov (United States)

    Aw, S E

    1981-07-01

    The origin of cancer is discussed from the view of the two-stage model of malignant transformation. Environmental carcinogens play an integral part in the process. When the cell is transformed, cell surface changes are found for such components as fibronectin, collagen, actin, myosin, glycopeptides and enzyme activities. Hormone receptors are a fruitful line for research. Both qualitative and quantitative alterations are also seen with cancer cell enzymes. Among enzymes that can be used as markers of malignancy are the protease. A group of oncodevelopmental proteins, hormonal and non-hormonal, are in regular service for the management of cancer. Improvements in diagnostic specificity can be expected as the newer technologies are harnessed for medical use.

  10. Survival Prognostic Factors of Male Breast Cancer in Southern Iran: a LASSO-Cox Regression Approach.

    Science.gov (United States)

    Shahraki, Hadi Raeisi; Salehi, Alireza; Zare, Najaf

    2015-01-01

    We used to LASSO-Cox method for determining prognostic factors of male breast cancer survival and showed the superiority of this method compared to Cox proportional hazard model in low sample size setting. In order to identify and estimate exactly the relative hazard of the most important factors effective for the survival duration of male breast cancer, the LASSO-Cox method has been used. Our data includes the information of male breast cancer patients in Fars province, south of Iran, from 1989 to 2008. Cox proportional hazard and LASSO-Cox models were fitted for 20 classified variables. To reduce the impact of missing data, the multiple imputation method was used 20 times through the Markov chain Mont Carlo method and the results were combined with Rubin's rules. In 50 patients, the age at diagnosis was 59.6 (SD=12.8) years with a minimum of 34 and maximum of 84 years and the mean of survival time was 62 months. Three, 5 and 10 year survival were 92%, 77% and 26%, respectively. Using the LASSO-Cox method led to eliminating 8 low effect variables and also decreased the standard error by 2.5 to 7 times. The relative efficiency of LASSO-Cox method compared with the Cox proportional hazard method was calculated as 22.39. The19 years follow of male breast cancer patients show that the age, having a history of alcohol use, nipple discharge, laterality, histological grade and duration of symptoms were the most important variables that have played an effective role in the patient's survival. In such situations, estimating the coefficients by LASSO-Cox method will be more efficient than the Cox's proportional hazard method.

  11. Prognostic value of bcl-2 expression among women with breast cancer in Libya.

    Science.gov (United States)

    Ermiah, Eramah; Buhmeida, Abdelbaset; Khaled, Ben Romdhane; Abdalla, Fathi; Salem, Nada; Pyrhönen, Seppo; Collan, Yrjö

    2013-06-01

    We studied the association of the immunohistochemical bcl-2 expression in Libyan breast cancer with clinicopathological variables and patient outcome. Histological samples from 170 previously untreated primary Libyan breast carcinoma patients were examined. In immunohistochemistry, the NCL-L-bcl-2-486 monoclonal antibody was used. Positive expression of bcl-2 was found in 106 patients (62.4 %). The bcl-2 expression was significantly associated with estrogen receptor (p50 years; p=0.04). Histological subtypes and family history of breast cancer did not have significant relationship with bcl-2. Patients with positive expression of bcl-2 had lower recurrence rate than bcl-2-negative patients and better survival after median follow-up of 47 months. Patients with high bcl-2 staining were associated with the best survival. The role of bcl-2 as an independent predictor of disease-specific survival was assessed in a multivariate survival (Cox) analysis, including age, hormonal status, recurrence, histological grade, and clinical stage variables. Bcl-2 (p<0.0001) and clinical stage (p=0.016) were independent predicators of disease-specific survival. For analysis of disease-free survival, the same variables were entered to the model and only bcl-2 proved to be an independent predictor (p=0.002). Patients with positive expression of bcl-2 were associated with low grade of malignancy, with lower recurrence rate, with lower rate of death, and with longer survival time. Bcl-2 is an independent predictor of breast cancer outcome, and it provides useful prognostic information in Libyan breast cancer. Thus, it could be used with classical clinicopathological factors to improve patient selection for therapy.

  12. Prognostic factors in breast cancer with extracranial oligometastases and the appropriate role of radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Gyu Sang; Yu, Jeong Il; Park, Won; Huh, Seung Jae; Choi, Doo Ho [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-12-15

    To identify prognostic factors for disease progression and survival of patients with extracranial oligometastatic breast cancer (EOMBC), and to investigate the role of radiation therapy (RT) for metastatic lesions. We retrospectively reviewed the medical records of 50 patients who had been diagnosed with EOMBC following standard treatment for primary breast cancer initially, and received RT for metastatic lesions, with or without other systemic therapy between January 2004 and December 2008. EOMBC was defined as breast cancer with five or less metastases involving any organs except the brain. All patients had bone metastasis (BM) and seven patients had pulmonary, hepatic, or lymph node metastasis. Median RT dose applied to metastatic lesions was 30 Gy (range, 20 to 60 Gy). The 5-year tumor local control (LC) and 3-year distant progression-free survival (DPFS) rate were 66.1% and 36.8%, respectively. High RT dose (> or =50 Gy10) was significantly associated with improved LC. The 5-year overall survival (OS) rate was 49%. Positive hormone receptor status, pathologic nodal stage of primary cancer, solitary BM, and whole-lesion RT (WLRT), defined as RT whose field encompassed entire extent of disease, were associated with better survival. On analysis for subgroup of solitary BM, high RT dose was significantly associated with improved LC and DPFS, shorter metastasis-to-RT interval (< or =1 month) with improved DPFS, and WLRT with improved DPFS and OS, respectively. High-dose RT in solitary BM status and WLRT have the potential to improve the progression-free survival and OS of patients with EOMBC.

  13. Serum nucleosomes during neoadjuvant chemotherapy in patients with cervical cancer. Predictive and prognostic significance

    Directory of Open Access Journals (Sweden)

    Cetina Lucely

    2005-06-01

    Full Text Available Abstract Background It has been shown that free DNA circulates in serum plasma of patients with cancer and that at least part is present in the form of oligo- and monucleosomes, a marker of cell death. Preliminary data has shown a good correlation between decrease of nucleosomes with response and prognosis. Here, we performed pre- and post-chemotherapy determinations of serum nucleosomes with an enzyme-linked immunosorbent assay (ELISA method in a group of patients with cervical cancer receiving neoadjuvant chemotherapy. Methods From December 2000 to June 2001, 41 patients with cervical cancer staged as FIGO stages IB2-IIIB received three 21-day courses of carboplatin and paclitaxel, both administered at day 1; then, patients underwent radical hysterectomy. Nucleosomes were measured the day before (baseline, at day seven of the first course and day seven of the third course of chemotherapy. Values of nucleosomes were analyzed with regard to pathologic response and to time to progression-free and overall survival. Results All patients completed chemotherapy, were evaluable for pathologic response, and had nucleosome levels determined. At a mean follow-up of 23 months (range, 7–26 months, projected progression time and overall survival were 80.3 and 80.4%, respectively. Mean differential values of nucleosomes were lower in the third course as compared with the first course (p >0.001. The decrease in the third course correlated with pathologic response (p = 0.041. Survival analysis showed a statistically significant, better progression-free and survival time in patients who showed lower levels at the third course (p = 0.0243 and p = 0.0260, respectively. Cox regression analysis demonstrated that nucleosome increase in the third course increased risk of death to 6.86 (95% confidence interval [CI 95%], 0.84–56.0. Conclusion Serum nucleosomes may have a predictive role for response and prognostic significance in patients with cervical cancer

  14. Mucin secretion activity of gastric cancer as a prognostic factor: a clinicopathological analysis

    Science.gov (United States)

    Mrochen-Domin, Izolda; Zembala-Nożyńska, Ewa; Tukiendorf, Andrzej; Lange, Dariusz; Nowara, Elżbieta

    2012-01-01

    Aim of the study Gastric cancer is characterized by varying secretion of mucus. Mucin producing gastric carcinoma (MUC) is thought to be a histological subtype with a worse prognosis. The aim of this study was to compare the clinicopathological differences between MUC and other types of gastric carcinoma without secretion of mucus (NMUC). Material and methods We reviewed two groups of patients with pathologically confirmed gastric cancer: 34 patients with MUC and 36 cases with NMUC. Patients’ sex, age, tumor location, stage of disease and type in the Lauren classification were examined. We analyzed the presence of lymph node metastasis, peritoneal dissemination and liver metastasis. Additionally, treatment response, toxicity and survival rates were evaluated. Results We observed a statistically significant relationship between MUC subtype and patients’ sex: MUC was found mostly in women (p = 0.017). There were no significant differences between the two gastric cancer groups according to age, tumor location, size of tumor or stage of disease. In the NMUC group the rate of liver metastasis was significantly higher (p = 0.001). The overall survival rate and progression-free survival for MUC patients were lower than those for NMUC patients. There was no significant difference in survival rates between the two groups. In analysis of logistic regression we distinguished significantly advantageous (number of chemotherapy cycles) and disadvantageous parameters (advanced stage in TNM), which influenced the chemotherapy effect. Conclusions The MUC type itself is not an unequivocally negative prognostic agent. Poor prognosis was correlated with more advanced stages at diagnosis, particularly with dissemination of cancer. PMID:23788870

  15. Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis

  16. A Survey of Artificial Intelligence for Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Integrated Systems Health Management includes as key elements fault detection, fault diagnostics, and failure prognostics. Whereas fault detection and diagnostics...

  17. Toward noninvasive microspectrofluorometry of skin lesions for diagnostic and prognostic evaluation of cell metabolism and organelle interactions

    Science.gov (United States)

    Hirschberg, Joseph G.; Schachtschabel, Astrid; Kohen, Elli; Kohen, Cahide; Schachtschabel, Dietrich O.

    1995-02-01

    studies with the new highly sensitive cyanine nucleic acid dyes and their dimers, but caution should be exerted in the use of such compounds because of cytotoxicity (e.g., limiting it to cellular studies used in the interpretation of dermatological findings). Parallel cellular and non-invasive dermatological studies will help to define the most specific set of parameters to be used in diagnostic and prognostic evaluations of skin lesions.

  18. Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zaizen, Yoshiaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Azuma, Koichi, E-mail: azuma@med.kurume-u.ac.jp [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kurata, Seiji [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Sadashima, Eiji; Hattori, Satoshi [Biostatistics Center, Kurume University, Kurume (Japan); Sasada, Tetsuro [Department of Immunology and Immunotherapy, Kurume University School of Medicine, Kurume (Japan); Imamura, Yohei [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Kaida, Hayato [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Kawahara, Akihiko [Department of Pathology, Kurume University School of Medicine, Kurume (Japan); Kinoshita, Takashi [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan); Ishibashi, Masatoshi [Department of Radiology, Kurume University School of Medicine, Kurume (Japan); Hoshino, Tomoaki [Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume (Japan)

    2012-12-15

    Background: [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors. Methods: We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy. Results: This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio = 2.34; 95% confidence interval, 1.18–4.64; P = 0.015] and OS (hazard ratio = 2.80; 95% confidence interval, 1.12–6.96; P = 0.003), whereas SUVmean and SUVmax had no significant association with PFS (P = 0.693 and P = 0.322, respectively) or OS (P = 0.587 and P = 0.214, respectively). Conclusions: Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.

  19. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.

    Directory of Open Access Journals (Sweden)

    Laetitia Marisa

    -free survival, even after adjusting for age, sex, stage, and the emerging prognostic classifier Oncotype DX Colon Cancer Assay recurrence score (hazard ratio 1.5, 95% CI 1.1-2.1, p = 0.0097. However, a limitation of this study is that information on tumor grade and number of nodes examined was not available. CONCLUSIONS: We describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways.

  20. Prognostic impact of metastatic lymph node ratio in advanced gastric cancer from cardia and fundus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the prognostic impact of the metastatic lymph node ratio (MLR) in advanced gastric cancer from the cardia and fundus. METHODS: Two hundred and thirty-six patients with gastric cancer from the cardia and fundus who underwent D2 curative resection were analyzed ret- rospectively. The correlations between MLR and the total lymph nodes, positive nodes and the total lymph nodes were analyzed respectively. The influence of MLR on the survival time of patients was determined with univariate Kaplan-Meier survival analysis and mul- tivariate Cox proportional hazard model analysis. And the multiple linear regression was used to identify the relation between MLR and the 5-year survival rate of the patients. RESULTS: The MLR did not correlate with the total lymph nodes resected (r = -0.093, P = 0.057). The 5-year overall survival rate of the whole cohort was 37.5%. Kaplan-Meier survival analysis identified that the following eight factors influenced the survival time of the patients postoperatively: gender (X2 = 4.26, P = 0.0389), tumor size (X2 = 18.48, P < 0.001), Borrmann type (X2 = 7.41, P = 0.0065), histological grade (X2 =5.07, P = 0.0243), pT category (X2 = 49.42, P < 0.001), pN category (X2 = 87.7, P < 0.001), total number of re- trieved lymph nodes (X2 = 8.22, P = 0.0042) and MLR (X2 = 34.3, P < 0.001). Cox proportional hazard model showed that tumor size (X2 = 7.985, P = 0.018), pT category (X2 = 30.82, P < 0.001) and MLR (X2 = 69.39, P < 0.001) independently influenced the prognosis. A linear correlation between MLR and the 5-year survival was statistically significant based on the multiple lin- ear regression (β = -0.63, P < 0.001). Hypothetically, the 5-year survival would surpass 50% when MLR was lower than 10%. CONCLUSION: The MLR is an independent prognostic factor for patients with advanced gastric cancer from the cardia and fundus. The decrease of MLR due to adequate number of total resected lymph nodes can improve the survival.

  1. Characteristics and prognostic factors for pain management in 152 patients with lung cancer

    Directory of Open Access Journals (Sweden)

    Shi L

    2016-04-01

    Full Text Available Lei Shi,1,* Yumei Liu,2,* Hua He,1 Cong Wang,1 Hongwei Li,1 Nanya Wang1 1Cancer Center, The First Hospital of Jilin University, Changchun, 2Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: The objective of this study was to analyze the pain characteristics and factors influencing the outcome of pain control in patients with lung cancer having pain. Methods: Pain characteristics, the effectiveness, and prognostic factors for pain control were analyzed in 152 patients with lung cancer having moderate or severe chronic pain admitted to Cancer Center of The First Hospital of Jilin University, People’s Republic of China, between January 2012 and May 2013. Information about sex, age, pathological type, TNM stage, presence/absence of bone metastases, characteristics of pain, methods, and effectiveness of pain management was recorded. Results: Patients with non-small-cell lung cancer and small-cell carcinoma accounted for 132/152 (86.8% and 20/152 (13.2% cases, respectively. Among them, moderate (72.4% or severe pain (27.6% was reported in 73.7% of the cases at stage IV, chest or back pain was reported in 76.3% of the cases, and pain in other locations in the rest of the cases. Bone metastases were apparent in 44.1% of the patients. Neuropathic pain was noted in 46.7% of the patients, and frequent breakthrough pain was noted in 25.7% of the patients. High pain intensity was associated with frequent breakthrough pain. Pain was adequately controlled in 81.6% of the patients prescribed 3 days of analgesics. More patients reported a KPS higher than or equal to 80 after 3 days of analgesic treatment (P<0.001. Severe pain, frequent breakthrough pain, and presence of bone metastases were independent risk factors for poor pain control. Severe pain, frequent breakthrough pain, or neuropathic pain in the patients using opioids required higher

  2. Prognostic value of a cell cycle progression score for men with prostate cancer.

    Science.gov (United States)

    Cuzick, Jack

    2014-01-01

    A new prognostic score called the cell cycle progression or CCP score has been evaluated for predicting outcome in men with prostate cancer. The score is based on 31 cell cycle progression genes and 15 housekeeper control genes. Results on 5 cohorts have been reported. In all cases the CCP score was strongly predictive of outcome both in univariate models and in multvariate models incorporating standard factors such as Gleason grade, PSA levels and extent of disease. Two cohorts evaluated patients managed by active surveillance where the outcome was death from prostate cancer, two cohorts examined patients treated by radical prostatectomy where biochemical recurrence was the primary endpoint, and one smaller cohort looked at patients treated with radiotherapy where again biochemical recurrence was used as the endpoint. In all cases a unit change in CCP score was associated with an approximate doubling of risk of an event. These data provide strong event to support use of the CCP score to help guide clinical management.

  3. Prognostic value of preoperative intratumoral FDG uptake heterogeneity in patients with epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Maria; Kim, Hee Seung; Chung, Hyun Hoon; Kim, Jae-Weon; Park, Noh-Hyun; Song, Yong Sang [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of); Lee, Hyunjong; Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Cancer Research Institute, Seoul (Korea, Republic of)

    2017-01-15

    To investigate the prognostic value of intratumoral FDG uptake heterogeneity (IFH) derived from PET/CT in patients with epithelial ovarian cancer (EOC). We retrospectively reviewed patients with pathologically proven epithelial ovarian cancer who underwent preoperative {sup 18}F-FDG PET/CT scans. PET/CT parameters such as maximum and average standardized uptake values (SUV{sub max} and SUV{sub avg}), sum of all metabolic tumour volume (MTV), cumulative total lesion glycolysis (TLG) and IFH were assessed. Regression analyses were used to identify clinicopathological and imaging variables associated with disease-free survival (DFS). Clinicopathological data were reviewed for 61 eligible patients. The median duration of DFS was 13 months (range, 6-26 months), and 18 (29.5 %) patients experienced recurrence. High IFH values were associated with tumour recurrence (P = 0.005, hazard ratio 4.504, 95 % CI 1.572-12.902). The Kaplan-Meier survival graphs showed that DFS significantly differed in groups categorized based on IFH (P = 0.002, log-rank test). Moreover, there were significant differences in DFS (P = 0.009) and IFH (P = 0.040) between patients with and without recurrence. Preoperative IFH measured by {sup 18}F-FDG PET/CT was significantly associated with EOC recurrence. FDG-based heterogeneity could be a useful and potential predicator of EOC recurrence before treatment. (orig.)

  4. Lipid peroxidation and antioxidants in different stages of cervical cancer: Prognostic significance

    Directory of Open Access Journals (Sweden)

    S Srivastava

    2009-01-01

    Full Text Available Background: Free radical Injury is associated with cancer, but how the extent of oxidative stress correlates with the FIGO (International Federation of Gynecology and Obstetrics stage in Carcinoma Cervix (Ca Cx, and its significance as a prognostic marker, is not clear and needs an in-depth study. Aim: To correlate the blood levels of Lipid Peroxidation (LPO, Reduced Glutathione (GSH, Superoxide Dismutase (SOD, and Vitamin A and E levels with the clinical stage in Ca Cx. Settings and Design: This is a Prospective Case Control Study. Materials and Methods: LPO, SOD, reduced GSH were estimated by Bio Chemical Assays and Vitamins by High Performance Liquid Chromatography (HPLC. Statistical Analysis: The cases and controls were compared using One Way ANOVA and different stages over different time periods were individually compared by Repeated Measure Analysis of Variance. Results: The results indicated a statistically significant increase of LPO vis-a-vis the FIGO stage of Ca Cx and control, while the antioxidant status as depicted by GSH and SOD decreased. Vitamin A and E levels were significantly lower in cancer cases as compared to the control. Conclusion: Increased LPO and reduced antioxidant levels may be taken as associated predictive markers, thus suggesting that Ca Cx cases should get nutritive supplements to contain the blood LPO level and maintain a positive balance of antioxidants for a better outcome in terms of delayed recurrence and better Quality of Life (QOL.

  5. Natural History of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer in Men with Favorable Prognostic Indicators

    Directory of Open Access Journals (Sweden)

    Neil E. Martin

    2014-01-01

    Full Text Available Background and Purpose. Life expectancy data could identify men with favorable post-radiation prostate-specific antigen (PSA failure kinetics unlikely to require androgen deprivation therapy (ADT. Materials and Methods. Of 206 men with unfavorable-risk prostate cancer in a randomized trial of radiation versus radiation and ADT, 53 experienced a PSA failure and were followed without salvage ADT. Comorbidity, age and established prognostic factors were assessed for relationship to death using Cox regression analyses. Results. The median age at failure, interval to PSA failure, and PSA doubling time were 76.6 years (interquartile range [IQR]: 71.8–79.3, 49.1 months (IQR: 37.7–87.4, and 25 months (IQR: 13.1–42.8, respectively. After a median follow up of 4.0 years following PSA failure, 45% of men had died, none from prostate cancer and no one had developed metastases. Both increasing age at PSA failure (HR: 1.14; 95% CI: 1.03–1.25; P=0.008 and the presence of moderate to severe comorbidity (HR: 12.5; 95% CI: 3.81–41.0; P2 years following post-radiation PSA failure appear to be good candidates for observation without ADT intervention.

  6. Prognostic and predictive value of DAMPs and DAMP-associated processes in cancer

    Directory of Open Access Journals (Sweden)

    Jitka eFucikova

    2015-08-01

    Full Text Available It is now clear that human neoplasms form, progress and respond to therapy in the context of an intimate crosstalk with the host immune system. In particular, accumulating evidence demonstrates that the efficacy of most, if not all, chemo- and radiotherapeutic agents commonly employed in the clinic critically depends on the (reactivation of tumor-targeting immune response. One of the mechanisms whereby conventional chemotherapeutics, targeted anticancer agents and radiotherapy can provoke a therapeutically relevant, adaptive immune response against malignant cells is commonly known as „immunogenic cell death (ICD. Importantly, dying cancer cells are perceived as immunogenic only when they emit a set of immunostimulatory signals upon the activation of intracellular stress response pathways. The emission of these signals, which are generally referred to as „damage-associated molecular patterns (DAMPs, may therefore predict whether patients will respond to chemotherapy or not, at least in some settings. Here, we review clinical data indicating that DAMPs and DAMP-associated stress responses might have prognostic or predictive value for cancer patients.

  7. Prognostic significance of osteopontin expression in non-small-cell lung cancer: A meta-analysis.

    Science.gov (United States)

    Zou, Xue-Lin; Wang, Chun; Liu, K E; Nie, Wen; Ding, Zhen-Yu

    2015-05-01

    Osteopontin (OPN) plays an important role in the progression and metastasis of cancer. However, the role of OPN as a prognostic factor in non-small-cell lung cancer (NSCLC) remains controversial. The aim of this study was to investigate the association between OPN expression and prognosis in patients with NSCLC using a meta-analysis. Based on PubMed, Ovid Medline, Embase, ISI, ScienceDirect and SpringerLink databases, related articles published prior to January, 2013 were collected. A meta-analysis was conducted to investigate the association of OPN expression with overall survival (OS) and progression-free survival (PFS) in patients with NSCLC. Hazard ratio (HR) with 95% confidence interval (CI) was used to assess the strength of this association. A total of 6 studies, including 776 patients, were found to be eligible for the meta-analysis. No heterogeneity was observed in OS or PFS, whereas low OPN expression was found to be correlated with better OS (HR=0.57, 95% CI: 0.46-0.70) and PFS (HR=0.62, 95% CI: 0.49-0.77). This meta-analysis demonstrated an association of OPN with poor prognosis in NSCLC patients. However, prospective studies are required to confirm these findings.

  8. Correlation of cytokines and inducible nitric oxide synthase expression with prognostic factors in ovarian cancer.

    Science.gov (United States)

    Martins Filho, Agrimaldo; Jammal, Millena Prata; Côbo, Eliângela de Castro; Silveira, Thales Parenti; Adad, Sheila Jorge; Murta, Eddie Fernando Candido; Nomelini, Rosekeila Simões

    2014-01-01

    The study related the immunohistochemical staining of cytokines (IL2, IL5, IL6, IL8, IL10, and TNF-alpha), and iNOS staining with clinical and pathological parameters of patients with primary ovarian malignancy. We prospectively evaluated 40 patients who underwent surgical treatment in accordance with pre-established criteria and later confirmed diagnosis of ovarian cancer. Immunohistochemistry study for cytokines (IL2, IL5, IL6, IL8, IL10, TNF-alpha) and iNOS was performed. The evaluation of prognostic factors was performed using the Fisher's exact test. The significance level was less than 0.05. Histological grade 1 was significantly correlated with strong intensity for TNF-α (p=0.0028). In addition, early stages showed strong expression intensity of TNF-α, but this was at the limit of significance (p=0.0525). Strong staining immunohistochemical IL5 was related to disease-free survival less than or equal to 24 months, suggesting that a factor of poor prognosis, but there was no statistical significance (p=0.1771). There was no statistical significance in relation at other cytokines studied. Therefore, immunohistochemical staining in strong intensity for TNF-α was related to histological grade 1 and early stages of ovarian cancer in our sample of patients.

  9. The prognostic value of KRAS mutated plasma DNA in advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    Nygaard, Anneli Dowler; Garm Spindler, Karen-Lise; Pallisgaard, Niels

    2013-01-01

    DNA) in the blood allows for tumour specific analyses, including KRAS-mutations, and the aim of the study was to investigate the possible prognostic value of plasma mutated KRAS (pmKRAS) in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients with newly diagnosed, advanced NSCLC eligible......BACKGROUND: Lung cancer is one of the most common malignant diseases worldwide and associated with considerable morbidity and mortality. New agents targeting the epidermal growth factor system are emerging, but only a subgroup of the patients will benefit from the therapy. Cell free DNA (cf...... for chemotherapy were enrolled in a prospective biomarker trial. A pre-treatment blood sample was drawn and subsequently DNA was extracted and pmKRAS analysed. The patients received carboplatin (AUC5) i.v. day 1 and vinorelbine (30mg/m(2) i.v. day 1 and 60mg/m(2) p.o. day 8) for a maximum of six cycles. Response...

  10. Prognostic value of MGMT methylation in colorectal cancer: a meta-analysis and literature review.

    Science.gov (United States)

    Li, Yanliang; Lyu, Zhongchuan; Zhao, Lixin; Cheng, Hong; Zhu, Dongyuan; Gao, Yongsheng; Shang, Xiuwan; Shi, Huaijie

    2015-03-01

    The development of colorectal cancer (CRC) spans about 5-10 years, making early detection and prevention beneficial to the survival of CRC patients. To address inconsistencies in evidence regarding O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation as a potential prognostic factor in CRC, we conducted a meta-analysis to evaluate MGMT methylation in CRC patients. Fourteen studies were included in the meta-analysis after screening 120 articles. The following items were collected from each study: author, published year, country, patient gender, MGMT methylation status, and patients' disease progression. Pooled hazard ratios and odd ratios with 95% confidence intervals (CIs) were calculated using fixed or random effect models depending on the heterogeneity between studies. The overall survival of CRC patients was found not to be significantly associated with MGMT methylation. Further subgroup analysis showed that the frequency of MGMT methylation was significantly higher in CRC than in normal tissues (p MGMT promoter in CRC patients was more frequently methylated than in adenoma patients. In addition, MGMT methylation was significantly increased in adenoma than in normal tissues (p MGMT methylation is central to the development of cancer that involves a stepwise carcinogenesis of normal adenoma carcinoma cascade. However, MGMT methylation is not associated with the prognosis of CRC.

  11. Prognostic Significance of Promoter DNA Hypermethylation of cysteine dioxygenase 1 (CDO1 Gene in Primary Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Naoko Minatani

    Full Text Available Using pharmacological unmasking microarray, we identified promoter DNA methylation of cysteine dioxygenase 1 (CDO1 gene in human cancer. In this study, we assessed the clinicopathological significance of CDO1 methylation in primary breast cancer (BC with no prior chemotherapy. The CDO1 DNA methylation was quantified by TaqMan methylation specific PCR (Q-MSP in 7 BC cell lines and 172 primary BC patients with no prior chemotherapy. Promoter DNA of the CDO1 gene was hypermethylated in 6 BC cell lines except SK-BR3, and CDO1 gene expression was all silenced at mRNA level in the 7 BC cell lines. Quantification of CDO1 methylation was developed using Q-MSP, and assessed in primary BC. Among the clinicopathologic factors, CDO1 methylation level was not statistically significantly associated with any prognostic factors. The log-rank plot analysis elucidated that the higher methylation the tumors harbored, the poorer prognosis the patients exhibited. Using the median value of 58.0 as a cut-off one, disease specific survival in BC patients with CDO1 hypermethylation showed significantly poorer prognosis than those with hypomethylation (p = 0.004. Multivariate Cox proportional hazards model identified that CDO1 hypermethylation was prognostic factor as well as Ki-67 and hormone receptor status. The most intriguingly, CDO1 hypermethylation was of robust prognostic relevance in triple negative BC (p = 0.007. Promoter DNA methylation of CDO1 gene was robust prognostic indicator in primary BC patients with no prior chemotherapy. Prognostic relevance of the CDO1 promoter DNA methylation is worthy of being paid attention in triple negative BC cancer.

  12. beta(2)microglobulin mRNA expression levels are prognostic for lymph node metastasis in colorectal cancer patients.

    Science.gov (United States)

    Shrout, J; Yousefzadeh, M; Dodd, A; Kirven, K; Blum, C; Graham, A; Benjamin, K; Hoda, R; Krishna, M; Romano, M; Wallace, M; Garrett-Mayer, E; Mitas, M

    2008-06-17

    Colorectal cancer (CRC) is the fourth most common non-cutaneous malignancy in the United States and the second most frequent cause of cancer-related death. One of the most important determinants of CRC survival is lymph node metastasis. To determine whether molecular markers might be prognostic for lymph node metastases, we measured by quantitative real-time RT-PCR the expression levels of 15 cancer-associated genes in formalin-fixed paraffin-embedded primary tissues derived from stage I-IV CRC patients with (n=20) and without (n=18) nodal metastases. Using the mean of the 15 genes as an internal reference control, we observed that low expression of beta(2)microglobulin (B2M) was a strong prognostic indicator of lymph node metastases (area under the curve (AUC)=0.85; 95% confidence interval (CI)=0.69-0.94). We also observed that the expression ratio of B2M/Spint2 had the highest prognostic accuracy (AUC=0.87; 95% CI=0.71-0.96) of all potential two-gene combinations. Expression values of Spint2 correlated with the mean of the entire gene set at an R(2) value of 0.97, providing evidence that Spint2 serves not as an independent prognostic gene, but rather as a reliable reference control gene. These studies are the first to demonstrate a prognostic role of B2M at the mRNA level and suggest that low B2M expression levels might be useful for identifying patients with lymph node metastasis and/or poor survival.

  13. Prognostic factors to predict survival in non-small-cell lung cancer with brain metastasis

    Institute of Scientific and Technical Information of China (English)

    Tiantian Li; Xuezhen Ma; Yuan Yao

    2014-01-01

    Objective:The purpose of the study was to assess prognostic factors to predict overal survival (OS) and progres-sion-free survival (PFS) in non-smal-celllung cancer (NSCLC) with brain metastasis (BM). Methods:From November 2011 to March 2013, the clinical data of 31 NSCLC cases with BM treated with multiple modalities including brain radiotherapy alone, systemic chemotherapy, whole brain radiotherapy (WBRT) combined with tyrosine kinase inhibitor (TKIs). The ef icacy and adverse reaction were evaluated after treatment. Results:In terms of intracranial lesions, the objective response rate (ORR) and the disease control rate (DCR) were 22.6%and 90.3%, respectively. As for systemic disease, ORR and DCR were 32.3%and 93.5%, respectively. The median time to progression-free survival (PFS) was 298 days (95%CI:258.624-337.376 days), whereas in the epidermal growth factor receptor (EGFR) mutation patients was 331 days. Patients who received EGFR-TKIs combined with brain radiation had better response rate (RR) than those only brain radiation. Univariate analysis showed that the EGFR-mutations could predictive factors for PFS, and not to other clinical pathological features. The most common toxici-ties were rash and diarrhea, but al were wel-tolerated. Conclusion:EGFR-mutations is the independent prognostic factors af ecting the survival rates of NSCLC patients with BM. Through the clinical observation, icotinib combined with WBRT may be ef ective on brain metastases in NSCLC patients, and toxicities are tolerable, which worth further study.

  14. Outcome and Prognostic Factors in Endometrial Stromal Tumors: A Rare Cancer Network Study

    Energy Technology Data Exchange (ETDEWEB)

    Schick, Ulrike, E-mail: Ulrike.schick@icr.ac.uk [Department of Radiation Oncology, University Hospital, Geneva (Switzerland); Bolukbasi, Yasmin [Department of Radiation Oncology, Ege University Hospital, Izmir (Turkey); Thariat, Juliette [Department of Radiation Oncology, Antoine Lacassagne Center, Nice (France); Abdah-Bortnyak, Roxolyana; Kuten, Abraham [Department of Radiation Oncology, Rambam Medical Center, Haifa (Israel); Igdem, Sefik [Department of Radiation Oncology, Metropolitan Hospital, Istanbul (Turkey); Caglar, Hale [Department of Radiation Oncology, Marmara University Hospital, Istanbul (Turkey); Ozsaran, Zeynep [Department of Radiation Oncology, Ege University Hospital, Izmir (Turkey); Loessl, Kristina [Department of Radiation Oncology, University Hospital, Bern (Switzerland); Schleicher, Ursula [Department of Radiation Oncology, Dueren Hospital, Dueren (Germany); Zwahlen, Daniel [Department of Radiation Oncology, William Buckland Radiotherapy Centre, Melbourne (Australia); Villette, Sylviane [Department of Radiation Oncology, Rene Huguenin Center, Saint-Cloud (France); Vees, Hansjoerg [Department of Radiation Oncology, University Hospital, Geneva (Switzerland); Department of Radiation Oncology, Sion Hospital, Sion (Switzerland)

    2012-04-01

    Purpose: To provide further understanding regarding outcome and prognostic factors of endometrial stromal tumors (EST). Methods and Materials: A retrospective analysis was performed on the records of 59 women diagnosed with EST and treated with curative intent between 1983 and 2007 in the framework of the Rare Cancer Network. Results: Endometrial stromal sarcomas (ESS) were found in 44% and undifferentiated ESS (UES) in 49% of the cases. In 7% the grading was unclear. Of the total number of patients, 33 had Stage I, 4 Stage II, 20 Stage III, and 1 presented with Stage IVB disease. Adjuvant chemotherapy was administered to 12 patients, all with UES. External-beam radiotherapy (RT) was administered postoperatively to 48 women. The median follow-up was 41.4 months. The 5-year overall survival (OS) rate was 96.2% and 64.8% for ESS and UES, respectively, with a corresponding 5-year disease-free survival (DFS) rate of 49.4% and 43.4%, respectively. On multivariate analysis, adjuvant RT was an independent prognostic factor for OS (p = 0.007) and DFS (p = 0.013). Locoregional control, DFS, and OS were significantly associated with age ({<=}60 vs. >60 years), grade (ESS vs. UES), and International Federation of Gynecology and Obstetrics stage (I-II vs. III-IV). Positive lymph node staging had an impact on OS (p < 0.001). Conclusion: The prognosis of ESS differed from that of UES. Endometrial stromal sarcomas had an excellent 5-year OS, whereas the OS in UES was rather low. However, half of ESS patients had a relapse. For this reason, adjuvant treatment such as RT should be considered even in low-grade tumors. Multicenter randomized studies are still warranted to establish clear guidelines.

  15. Procalcitonin Improves the Glasgow Prognostic Score for Outcome Prediction in Emergency Patients with Cancer: A Cohort Study

    Directory of Open Access Journals (Sweden)

    Anna Christina Rast

    2015-01-01

    Full Text Available The Glasgow Prognostic Score (GPS is useful for predicting long-term mortality in cancer patients. Our aim was to validate the GPS in ED patients with different cancer-related urgency and investigate whether biomarkers would improve its accuracy. We followed consecutive medical patients presenting with a cancer-related medical urgency to a tertiary care hospital in Switzerland. Upon admission, we measured procalcitonin (PCT, white blood cell count, urea, 25-hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and calculated the GPS. Of 341 included patients (median age 68 years, 61% males, 81 (23.8% died within 30 days after admission. The GPS showed moderate prognostic accuracy (AUC 0.67 for mortality. Among the different biomarkers, PCT provided the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to 1.9, P<0.001, AUC 0.69 and significantly improved the GPS to a combined AUC of 0.74 (P=0.007. Considering all investigated biomarkers, the AUC increased to 0.76 (P<0.001. The GPS performance was significantly improved by the addition of PCT and other biomarkers for risk stratification in ED cancer patients. The benefit of early risk stratification by the GPS in combination with biomarkers from different pathways should be investigated in further interventio