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Sample records for cancer diagnostics prognosis

  1. Understanding Cancer Prognosis

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    Full Text Available ... Overview Research Cancer Screening Cancer Screening Overview Screening Tests Research Diagnosis and Staging Symptoms Diagnosis Staging Prognosis ... Cancer Prevention Overview Screening Cancer Screening Overview Screening Tests Diagnosis & Staging Symptoms Diagnosis Staging Prognosis Treatment Types ...

  2. Understanding Cancer Prognosis

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    Full Text Available ... disease will go for you is called prognosis. It can be hard to understand what prognosis means ... prognosis include: The type of cancer and where it is in your body The stage of the ...

  3. Understanding Cancer Prognosis

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    Full Text Available ... doctor to give you an accurate prognosis. Understanding the Difference Between Cure and Remission Cure means that ... about her colorectal cancer prognosis. Diving Out of the Dark View this video on YouTube. Andrew wants ...

  4. Understanding Cancer Prognosis

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    Full Text Available ... Questions to Ask about Your Diagnosis Research Understanding Cancer Prognosis Oncologist Anthony L. Back, M.D., a ... for provider care teams (PDF-210KB). Understanding Your Cancer Prognosis Video View this video on YouTube. Three ...

  5. Understanding Cancer Prognosis

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    Full Text Available ... to treatment Seeking Information About Your Prognosis Is a Personal Decision When you have cancer, you and ... how long she has to live. For Doctors, a Patient-Centered Approach View this video on YouTube. ...

  6. Understanding Cancer Prognosis

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    Full Text Available ... treatment Seeking Information About Your Prognosis Is a Personal Decision When you have cancer, you and your ... think they are too impersonal to be of value to you. It is up to you to ...

  7. Understanding Cancer Prognosis

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    Full Text Available ... to know more, the doctor who knows the most about your situation is in the best position ... statistics may be used to estimate prognosis. The most commonly used statistics include: Cancer-specific survival This ...

  8. Circulating tumor cells (CTCs) in breast cancer: a diagnostic tool for prognosis and molecular analysis

    Institute of Scientific and Technical Information of China (English)

    Xiaoshen Dong; R.Katherine Alpaugh; Massimo Cristofanilli

    2012-01-01

    Metastatic breast cancer (MBC) is characterized by a combination of tumor growth,proliferation and metastatic progression and is typically managed with palliative intent.The benefit of standard systemic therapies is relatively limited and the disease is considered incurable suggesting the need to investigate the biological drivers of the various phases of the metastatic process in order to improve the selection of molecularly driven therapies.The detection,enumeration and molecular analysis of circulating tumor cells (CTCs) provide an intriguing opportunity to advance this knowledge.CTCs enumerated by the Food and Drugs Administration-cleared CellSearchTM system are an independent prognostic factor of progression-free survival (PFS) and overall survival (OS) in MBC patients.Several published papers demonstrated the poor prognosis for MBC patients that presented basal CTC count ≥5 in 7.5 mL of blood.Therefore,the enumeration of CTCs during treatment for MBC provides a tool with the ability to predict progression of disease earlier than standard timing of anatomical assessment using conventional radiological tests.During the metastatic process cancer cells exhibit morphological and phenotypic plasticity undergoing epithelial-mesenchymal transition (EMT).This important phenomenon is associated with down regulation of epithelial marker (e.g.,EpCAM) with potential limitations in the applicability of current CTCs enrichment methods.Such observations translated in a number of investigations aimed at improving our capabilities to enumerate and perform molecular characterization of CTCs.Theoretically,the phenotypic analysis of CTCs can represent a "liquid" biopsy of breast tumor that is able to identify a new potential target against the metastatic disease and advance the development and monitoring of personalized therapies.

  9. Understanding Your Cancer Prognosis Video

    Science.gov (United States)

    Understanding Your Cancer Prognosis is the main video in the NCI Prognosis Video Series, which offers the perspectives of three cancer patients and their doctor, an oncologist who is also a national expert in doctor-patient communication.

  10. Understanding Cancer Prognosis

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    Full Text Available ... Information Advance Directives Using Trusted Resources Cancer Types Adolescents and Young Adults with Cancer Reports, Research, and ... of Cancers Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Recurrent Cancer Research ...

  11. Understanding Cancer Prognosis

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    Full Text Available ... Talking about Advanced Cancer Coping with Your Feelings Planning for Advanced Cancer Advanced Cancer and Caregivers Questions ... Talking About Advanced Cancer Coping With Your Feelings Planning for Advanced Cancer Advanced Cancer & Caregivers Managing Cancer ...

  12. Understanding Cancer Prognosis

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    Full Text Available ... Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Lung Cancer Lymphoma Pancreatic Cancer ... grade, which refers to how abnormal the cancer cells look under a microscope. Grade provides clues about ...

  13. Understanding Cancer Prognosis

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    Full Text Available ... Effects of Childhood Cancer Treatment Pediatric Supportive Care Unusual Cancers of Childhood Treatment Childhood Cancer Genomics Study ... Genomics Causes of Cancer Diagnosis Prevention Screening & Early Detection Treatment Cancer & Public Health Cancer Health Disparities Childhood ...

  14. Understanding Cancer Prognosis

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  15. Understanding Cancer Prognosis

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    Full Text Available ... Cancers Metastatic Cancer Recurrent Cancer Research NCI’s Role in Cancer Research Intramural Research Extramural Research Bioinformatics and ... Annual Report to the Nation Cancer Snapshots Milestones in Cancer Research and Discovery Stories of Discovery R& ...

  16. Lifestyle influences on the association between pre-diagnostic hormone replacement therapy and breast cancer prognosis - results from The Danish 'Diet, Cancer and Health' prospective cohort

    DEFF Research Database (Denmark)

    Holm, Marianne; Olsen, Anja; Kroman, Niels

    2014-01-01

    OBJECTIVES: The association between pre-diagnostic hormone replacement therapy (HRT) and breast cancer specific mortality as well as potential influences from other lifestyle factors on the association was investigated. STUDY DESIGN: Female participants from the prospective cohort "Diet, Cancer...

  17. Understanding Cancer Prognosis

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    Full Text Available ... Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors Genetics Cancer Prevention Overview Research Cancer Screening Cancer Screening Overview Screening ...

  18. Understanding Cancer Prognosis

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  19. Understanding Cancer Prognosis

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    Full Text Available ... about Advanced Cancer Research Managing Cancer Care Finding Health Care Services Costs & Medical Information Advance Directives Using ... Cancer Advanced Cancer & Caregivers Managing Cancer Care Finding Health Care Services Managing Costs and Medical Information Advance ...

  20. Understanding Cancer Prognosis

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    Full Text Available ... Finding Health Care Services Managing Costs and Medical Information Advance Directives Using Trusted Resources Cancer Types Adolescents and Young Adults with Cancer Reports, Research, and Literature Quiz Cancers by Body Location/System Childhood Cancers Late Effects of Childhood Cancer Treatment ...

  1. Understanding Cancer Prognosis

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    Full Text Available ... Trials Information A to Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about ... Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to ...

  2. Understanding Cancer Prognosis

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  3. Understanding Cancer Prognosis

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    Full Text Available ... type Progress Annual Report to the Nation Cancer Portfolio Snapshots Milestones in Cancer Research & Discovery Stories of ... greatly. Also, it takes years to see the benefit of new treatments and ways of finding cancer. ...

  4. Understanding Cancer Prognosis

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    Full Text Available ... has to live. For Doctors, a Patient-Centered Approach View this video on YouTube. Anthony L. Back, M.D., coaches other oncologists about how to discuss prognosis with their patients. Good communication, he says, is part of providing good care. ...

  5. Understanding Cancer Prognosis

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    Full Text Available ... cancer-specific survival is based on causes of death listed in medical records. Relative survival This statistic ... does not use information about the cause of death. It is the percentage of cancer patients who ...

  6. Understanding Cancer Prognosis

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    Full Text Available ... Conferences Advisory Board Meetings Social Media Events Cancer Currents Blog All Press Releases 2017 2016 2015 2014 ... Lectures Conferences Advisory Board Meetings Social Media Cancer Currents Blog About NCI NCI Overview History Contributing to ...

  7. Understanding Cancer Prognosis

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    Full Text Available ... History Committees of Interest Legislative Resources Recent Public Laws Contact Overview History of NCI Contributing to Cancer ... History Committees of Interest Legislative Resources Recent Public Laws Careers Visitor Information Search Search Home About Cancer ...

  8. Understanding Cancer Prognosis

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    Full Text Available ... Research Managing Cancer Care Finding Health Care Services Costs & Medical Information Advance Directives Using Trusted Resources Understanding ... Managing Cancer Care Finding Health Care Services Managing Costs and Medical Information Advance Directives Using Trusted Resources ...

  9. Understanding Cancer Prognosis

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    Full Text Available ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Events Cancer Currents Blog All Press Releases 2017 ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Cancer Currents Blog About NCI NCI Overview History ...

  10. Understanding Cancer Prognosis

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    Full Text Available ... Research Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information A to Z List of Cancer Drugs Complementary & ... Interest Legislative Resources Recent Public Laws Careers Visitor Information Search ... Oncologist Anthony L. Back, M.D., a national expert on doctor-patient communications, talks with one of his patients about what ...

  11. Understanding Cancer Prognosis

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    Full Text Available ... Report (RPPR) Grant Closeout Grant Resources NCI Grants Management Legal Requirements NCI Grant Policies Grants Management Contacts Training Cancer Training at NCI Funding for ...

  12. Understanding Cancer Prognosis

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    Full Text Available ... cancer’s grade, which refers to how abnormal the cancer cells look under a microscope. Grade provides clues about ... to grow and spread. Certain traits of the cancer cells Your age and how healthy you were before ...

  13. Understanding Cancer Prognosis

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    Full Text Available ... Cancer Research and Discovery Stories of Discovery R&D Resources Conducting Clinical Trials Statistical Tools and Data ... about some of NCI's major research initiatives R&D Resources Tools and data sets for researchers Research ...

  14. Understanding Cancer Prognosis

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    Full Text Available ... M.D., a national expert on doctor-patient communications, talks with one of his patients about what ... is also a national expert in doctor-patient communication share their perspectives on their cancer prognoses. Learn ...

  15. Understanding Cancer Prognosis

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    Full Text Available ... Research Leadership Director's Page Previous NCI Directors NCI Organization Advisory Boards Budget & Appropriations About the Annual Plan & ... Cancer Research Senior Leadership Director Previous Directors NCI Organization Divisions, Offices & Centers Advisory Boards & Groups Budget & Appropriations ...

  16. Understanding Cancer Prognosis

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    Full Text Available ... Resources Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...

  17. MicroRNAs in Testicular Cancer Diagnosis and Prognosis.

    Science.gov (United States)

    Ling, Hui; Krassnig, Lisa; Bullock, Marc D; Pichler, Martin

    2016-02-01

    Testicular cancer processes a unique and clear miRNA expression signature. This differentiates testicular cancer from most other cancer types, which are usually more ambiguous when assigning miRNA patterns. As such, testicular cancer may represent a unique cancer type in which miRNAs find their use as biomarkers for cancer diagnosis and prognosis, with a potential to surpass the current available markers usually with low sensitivity. In this review, we present literature findings on miRNAs associated with testicular cancer, and discuss their potential diagnostic and prognostic values, as well as their potential as indicators of drug response in patients with testicular cancer.

  18. Statins and breast cancer prognosis

    DEFF Research Database (Denmark)

    Ahern, Thomas P; Lash, Timothy L; Damkier, Per

    2014-01-01

    Much preclinical and epidemiological evidence supports the anticancer effects of statins. Epidemiological evidence does not suggest an association between statin use and reduced incidence of breast cancer, but does support a protective effect of statins-especially simvastatin-on breast cancer...... recurrence. Here, we argue that the existing evidence base is sufficient to justify a clinical trial of breast cancer adjuvant therapy with statins and we advocate for such a trial to be initiated without delay. If a protective effect of statins on breast cancer recurrence is supported by trial evidence......, then the indications for a safe, well tolerated, and inexpensive treatment can be expanded to improve outcomes for breast cancer survivors. We discuss several trial design opportunities-including candidate predictive biomarkers of statin safety and efficacy-and off er solutions to the key challenges involved...

  19. Prognosis of synchronous bilateral breast cancer

    DEFF Research Database (Denmark)

    Holm, Marianne; Tjønneland, Anne; Balslev, Eva

    2014-01-01

    Currently, no consistent evidence-based guidelines for the management of synchronous bilateral breast cancer (SBBC) exist and it is uncertain how presenting with SBBC affects patients' prognosis. We conducted a review of studies analyzing the association between SBBC and prognosis. The studies...... that reported adjusted effect measures were included in meta-analyses of effect of bilaterality on breast cancer mortality. From 57 initially identified records 17 studies from 11 different countries including 8,050 SBBC patients were included. The quality of the studies varied but was generally low with small...... sample sizes, and lack of consistent, detailed histo-pathological information. When doing meta-analysis on the subgroup of studies that provided adjusted effect estimates on breast cancer mortality (nine studies including 3,631 SBBC cases), we found that bilaterality in itself had a negative impact...

  20. Endometrial cancer, types, prognosis, female hormones and antihormones

    DEFF Research Database (Denmark)

    Ulrich, L S G

    2011-01-01

    . Prognosis is also dependent on tumor differentiation and stage, and treatment should be adjusted accordingly. In this paper, the different types of endometrial cancer, staging, prognosis, diagnosis, prevention, treatment and their relationship to estrogen and other female hormones are reviewed....

  1. Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort - Differential effects by tumour subtype, NAT2 status, BMI and alcohol intake

    NARCIS (Netherlands)

    Seibold, P.; Vrieling, A.; Heinz, J.; Obi, N.; Sinn, H.P.; Flesch-Janys, D.; Chang-Claude, J.

    2014-01-01

    BACKGROUND: Inconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking. METHODS: We used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50-74 and diagnosed

  2. Recurrent cervical cancer : detection and prognosis

    NARCIS (Netherlands)

    Duyn, A; Van Eijkeren, M; Kenter, G; Zwinderman, K; Ansink, A

    2002-01-01

    Background. Only a small proportion of cervical cancer recurrences is detected during routine follow-up. We investigated which percentage of recurrences is detected during follow-up, which diagnostic tools are helpful to detect recurrent disease and which factors are of prognostic significance once

  3. Constructive Technology Assessment (CTA) as a tool in coverage with evidence development: the case of the 70-gene prognosis signature for breast cancer diagnostics

    NARCIS (Netherlands)

    Retèl, Valesca P.; Bueno-de-Mesquita, Jolien M.; Hummel, Marjan J.M.; Vijver, van de Marc J.; Douma, Kirsten F.L.; Karsenberg, Kim; Dam, van Frits S.A.M.; Krimpen, van Cees; Bellot, Frank E.; Roumen, Rudi M.H.; Linn, Sabine C.; Harten, van Wim H.

    2009-01-01

    Objectives: Constructive Technology Assessment (CTA) is a means to guide early implementation of new developments in society, and can be used as an evaluation tool for Coverage with Evidence Development (CED). We used CTA for the introduction of a new diagnostic test in the Netherlands, the 70-gene

  4. Tumor Volumes and Prognosis in Laryngeal Cancer

    Directory of Open Access Journals (Sweden)

    Mohamad R. Issa

    2015-11-01

    Full Text Available Tumor staging systems for laryngeal cancer (LC have been developed to assist in estimating prognosis after treatment and comparing treatment results across institutions. While the laryngeal TNM system has been shown to have prognostic information, varying cure rates in the literature have suggested concern about the accuracy and effectiveness of the T-classification in particular. To test the hypothesis that tumor volumes are more useful than T classification, we conducted a retrospective review of 78 patients with laryngeal cancer treated with radiation therapy at our institution. Using multivariable analysis, we demonstrate the significant prognostic value of anatomic volumes in patients with previously untreated laryngeal cancer. In this cohort, primary tumor volume (GTVP, composite nodal volumes (GTVN and composite total volume (GTVP + GTVN = GTVC had prognostic value in both univariate and multivariate cox model analysis. Interestingly, when anatomic volumes were measured from CT scans after a single cycle of induction chemotherapy, all significant prognosticating value for measured anatomic volumes was lost. Given the literature findings and the results of this study, the authors advocate the use of tumor anatomic volumes calculated from pretreatment scans to supplement the TNM staging system in subjects with untreated laryngeal cancer. The study found that tumor volume assessment after induction chemotherapy is not of prognostic significance.

  5. Tumor Volumes and Prognosis in Laryngeal Cancer

    Science.gov (United States)

    Issa, Mohamad R.; Samuels, Stuart E.; Bellile, Emily; Shalabi, Firas L.; Eisbruch, Avraham; Wolf, Gregory

    2015-01-01

    Tumor staging systems for laryngeal cancer (LC) have been developed to assist in estimating prognosis after treatment and comparing treatment results across institutions. While the laryngeal TNM system has been shown to have prognostic information, varying cure rates in the literature have suggested concern about the accuracy and effectiveness of the T-classification in particular. To test the hypothesis that tumor volumes are more useful than T classification, we conducted a retrospective review of 78 patients with laryngeal cancer treated with radiation therapy at our institution. Using multivariable analysis, we demonstrate the significant prognostic value of anatomic volumes in patients with previously untreated laryngeal cancer. In this cohort, primary tumor volume (GTVP), composite nodal volumes (GTVN) and composite total volume (GTVP + GTVN = GTVC) had prognostic value in both univariate and multivariate cox model analysis. Interestingly, when anatomic volumes were measured from CT scans after a single cycle of induction chemotherapy, all significant prognosticating value for measured anatomic volumes was lost. Given the literature findings and the results of this study, the authors advocate the use of tumor anatomic volumes calculated from pretreatment scans to supplement the TNM staging system in subjects with untreated laryngeal cancer. The study found that tumor volume assessment after induction chemotherapy is not of prognostic significance. PMID:26569309

  6. Irritable bowel syndrome--prognosis and diagnostic safety. A 5-year follow-up study

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Munck, L K; Andersen, J R

    1985-01-01

    The irritable bowel syndrome is the commonest diagnosis in gastroenterological clinics, although diagnostic criteria and investigatory programs vary. To elucidate the diagnostic safety and prognosis of the syndrome, a retrospective study was conducted. One hundred and twelve consecutive patients ...

  7. Risk, characteristics, and prognosis of breast cancer after Hodgkin's lymphoma

    OpenAIRE

    Veit-rubin, Nikolaus; Rapiti Aylward, Elisabetta; Usel, Massimo; Benhamou, Simone; Vinh Hung, Vincent; Vlastos, Georges; Bouchardy Magnin, Christine

    2012-01-01

    Patients with breast cancer after Hodgkin's lymphoma were compared with patients with other breast cancers using the Surveillance, Epidemiology and End Results dataset. Hodgkin's lymphoma survivors had a higher risk for breast cancer, more aggressive breast cancers, a higher risk for a second breast cancer, and a poorer prognosis.

  8. 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.

  9. Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Qiu-Li; Xu, Wang-Hong, E-mail: mtao@buffalo.edu [Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032 (China); Tao, Meng-Hua, E-mail: mtao@buffalo.edu [Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214 (United States)

    2010-04-28

    In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS) is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of the MS in the prognosis of breast cancer.

  10. Novel diagnostic biomarkers for prostate cancer

    Directory of Open Access Journals (Sweden)

    Chikezie O. Madu, Yi Lu

    2010-01-01

    Full Text Available Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of

  11. Novel diagnostic biomarkers for prostate cancer.

    Science.gov (United States)

    Madu, Chikezie O; Lu, Yi

    2010-10-06

    Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The

  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. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Torres

    2015-01-01

    Full Text Available The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients’ outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox’s proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

  14. Diabetes mellitus and prognosis in women with breast cancer

    Science.gov (United States)

    Zhao, Xiao-Bo; Ren, Guo-Sheng

    2016-01-01

    Abstract Background: Diabetes mellitus is associated with an increased risk of breast cancer, but studies of the effects of diabetes on the prognosis of women with breast cancer have yielded inconsistent findings. The present meta-analysis aimed to investigate the impact of preexisting diabetes on the prognosis in terms of overall survival (OS), disease-free survival (DFS), and relapse-free period (RFP) in women with breast cancer. Methods: We searched the Embase and PubMed databases until June 2016 for cohort or case–control studies assessing the impact of diabetes on the prognosis of women with breast cancer. The pooled multivariate adjusted hazard ratio (HR) and their 95% confidence intervals (CIs) for OS, DFS, and RFP were used to analyze the impact of diabetes on the prognosis of breast cancer patients. Results: Seventeen studies involving 48,315 women with breast cancer met our predefined inclusion criteria. Meta-analysis showed that the pooled adjusted HR was 1.51 (95% CI 1.34–1.70) for OS and 1.28 (95% CI 1.09–1.50) for DFS in breast cancer patients with diabetes compared to those without diabetes. However, RFP did not differ significantly between patients with and without diabetes (HR 1.42; 95% CI 0.90–2.23). Conclusions: The present meta-analysis suggests that preexisting diabetes is independently associated with poor OS and DFS in female breast cancer patients. However, the impact of diabetes on RFP should be further verified. More prospective studies are warranted to investigate whether appropriate glycemic control with modification of antihyperglycemic agents can improve the prognosis of female breast cancer patients with diabetes. PMID:27930583

  15. Significance of humoral neopterin in clinical diagnostics and prognosis

    Institute of Scientific and Technical Information of China (English)

    Li Yanchun; Hu Zhidong

    2011-01-01

    Neopterin is bioactive substance released by the activated monocyte/macrophage,and an early and sensitive marker used for reflection of cellular immune activation status induced by the lymphocyte macrophage system.Observation of neopterin levels is conducive to the diagnosis and prognosis of various diseases. This article reviews the existing evidence that neopterin has an important role in cardiovascular risk,infectious diseases,malignancy,autoimmune diseases and transplantaiton.

  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. ProGRP对小细胞肺癌的疗效与预后评价的价值%Diagnostic value and prognosis assessment of ProGRP for small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    荆结线; 杜丽莉; 徐晓琴; 田保国; 孙婷; 赵先文; 韩存芝

    2013-01-01

    Objective The purpose of this study was to discuss the clinical significance of serum levels of Pro-gastrin-releasing peptide (ProGRP) in diagnosis,therapy monitoring and prognosis in patients with small cell lung cancer (SCLC).Methods Clinical diagnostic trial.Serum levels of ProGRP were measured by ELISA assays in 413 SCLC patients,418 NSCLC,120 with benign pulmonary diseases patients and 200 healthy subjects.Patients were recuited by the Shanxi Cancer Hospital from Dec.2005 to Oct.2008.Three hundreds and sixty-eight patients with SCLC were followed up from Dec.2005 to Oct.2011.The receiver operating characteristic curves (ROC) was used to set the cut-off value of ProGRP and the area under ROC (ROC-AUC).The sensitivity and specificity of ProGRP were analyzed for diagnosing SCLC.The survival analysis was performed by the Kaplan-Meier method and Cox's proportional hazards model for multivariate analysis of prognosis.Results Using healthy subjects group as control,the largest Youden index point of ROC was used to set the cut-off values of ProGRP and NSE (45.3 ng/L and 12.4 ng/L).The ROC-AUC of ProGRP was 0.798 (95% CI:0.746-0.850)the sensitivity and specificity were 79.2%,98.1% respectively.The AUC of NSE was 0.786(95% CI:0.726-0.746),the sensitivity and specificity were 71.9%,96.7% respectively; Combing detection of ProGRP and NSE,the sensitivity and specificity were 88.1%,95.8% respectively.Serum levels of ProGRP in healthy subjects,benign pulmonary diseases,NSCLC and SCLC groups were 6.9 (5.3-8.6),36.8 (26.3-43.4),21.3 (18.6-35.2) and 1758.7 (368.4-2967.3) μg/L respectively.The serum levels of ProGRP in SCLC groups were significantly higher than those in the healthy group,benign pulmonary diseases group and NSCLC group (H =103.66,P =0.000).Serum levels of ProGRP in SCLC at stage Ⅰ-],stage m,stage Ⅳ were 543.3 (256.8-843.2),1440.6 (1042.4-2543.3) and 1897.6 (1586.5-3958.7) μg/L,respectively (H =25.974,P =0.000).Serum levels of ProGRP in 165

  18. A mathematical prognosis model for pancreatic cancer patients receiving immunotherapy.

    Science.gov (United States)

    Li, Xuefang; Xu, Jian-Xin

    2016-10-07

    Pancreatic cancer is one of the most deadly types of cancer since it typically spreads rapidly and can seldom be detected in its early stage. Pancreatic cancer therapy is thus a challenging task, and appropriate prognosis or assessment for pancreatic cancer therapy is of critical importance. In this work, based on available clinical data in Niu et al. (2013) we develop a mathematical prognosis model that can predict the overall survival of pancreatic cancer patients who receive immunotherapy. The mathematical model incorporates pancreatic cancer cells, pancreatic stellate cells, three major classes of immune effector cells CD8+ T cells, natural killer cells, helper T cells, and two major classes of cytokines interleukin-2 (IL-2) and interferon-γ (IFN-γ). The proposed model describes the dynamic interaction between tumor and immune cells. In order for the model to be able to generate appropriate prognostic results for disease progression, the distribution and stability properties of equilibria in the mathematical model are computed and analysed in absence of treatments. In addition, numerical simulations for disease progression with or without treatments are performed. It turns out that the median overall survival associated with CIK immunotherapy is prolonged from 7 to 13months compared with the survival without treatment, this is consistent with the clinical data observed in Niu et al. (2013). The validity of the proposed mathematical prognosis model is thus verified. Our study confirms that immunotherapy offers a better prognosis for pancreatic cancer patients. As a direct extension of this work, various new therapy methods that are under exploration and clinical trials could be assessed or evaluated using the newly developed mathematical prognosis model.

  19. Prognosis of Lung Cancer: Heredity or Environment

    Science.gov (United States)

    2015-06-01

    Service Career Development Award (10–024), and a Department of Defense Early Investigator Synergistic Idea Award (W18XWH-12-1-0544). The authors...Nurgalieva Z, Du XL. Racial dis- parities and survival for nonsmall-cell lung cancer in a large cohort of black and white elderly patients. Cancer 2009;115

  20. Breast cancer prognosis predicted by nuclear receptor-coregulator networks.

    Science.gov (United States)

    Doan, Tram B; Eriksson, Natalie A; Graham, Dinny; Funder, John W; Simpson, Evan R; Kuczek, Elizabeth S; Clyne, Colin; Leedman, Peter J; Tilley, Wayne D; Fuller, Peter J; Muscat, George E O; Clarke, Christine L

    2014-07-01

    Although molecular signatures based on transcript expression in breast cancer samples have provided new insights into breast cancer classification and prognosis, there are acknowledged limitations in current signatures. To provide rational, pathway-based signatures of disrupted physiology in cancer tissues that may be relevant to prognosis, this study has directly quantitated changed gene expression, between normal breast and cancer tissue, as a basis for signature development. The nuclear receptor (NR) family of transcription factors, and their coregulators, are fundamental regulators of every aspect of metazoan life, and were rigorously quantified in normal breast tissues and ERα positive and ERα negative breast cancers. Coregulator expression was highly correlated with that of selected NR in normal breast, particularly from postmenopausal women. These associations were markedly decreased in breast cancer, and the expression of the majority of coregulators was down-regulated in cancer tissues compared with normal. While in cancer the loss of NR-coregulator associations observed in normal breast was common, a small number of NR (Rev-ERBβ, GR, NOR1, LRH-1 and PGR) acquired new associations with coregulators in cancer tissues. Elevated expression of these NR in cancers was associated with poorer outcome in large clinical cohorts, as well as suggesting the activation of ERα -related, but ERα-independent, pathways in ERα negative cancers. In addition, the combined expression of small numbers of NR and coregulators in breast cancer was identified as a signature predicting outcome in ERα negative breast cancer patients, not linked to proliferation and with predictive power superior to existing signatures containing many more genes. These findings highlight the power of predictive signatures derived from the quantitative determination of altered gene expression between normal breast and breast cancers. Taken together, the findings of this study identify networks

  1. Validation of Biomarkers for Prostate Cancer Prognosis

    Science.gov (United States)

    2013-10-01

    incontinence and urinary urgency as well as sexual dysfunction. Furthermore, evidence from many sources suggests that most prostate cancers are...mainly surgery and radiation therapy, result in well documented significant morbidities, including significant lower urinary tract symptoms such as

  2. 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...

  3. Nuclear volume and prognosis in ovarian cancer

    DEFF Research Database (Denmark)

    Mogensen, O.; Sørensen, Flemming Brandt; Bichel, P.;

    1992-01-01

    The prognostic value of the volume-weighted mean nuclear volume (MNV) was investigated retrospectively in 100 ovarian cancer patients with FIGO-stage IB-II (n = 51) and stage III-IV (n = 49) serous tumors. No association was demonstrated between the MNV and the survival or between the MNV and two...

  4. Subsequent pregnancy and prognosis in breast cancer survivors.

    Science.gov (United States)

    Kasum, Miro; Beketić-Orešković, Lidija; Orešković, Slavko

    2014-09-01

    An increase in the incidence of breast cancer in women aged breast cancer in women of childbearing age has significantly improved, they are often concerned whether subsequent pregnancy will alter their risk of disease recurrence. In the modern era, the prognosis of pregnancy-associated breast cancer is comparable to non-pregnancy-associated breast cancer and women can bear children after breast cancer treatment without compromising their survival. Therefore, they should not be discouraged from becoming pregnant, and currently the usual waiting time of at least 2 years after the diagnosis of breast cancer is recommended. However, a small, nonsignificant adverse effect of pregnancy on breast carcinoma prognosis among women who conceive within 12 months of breast cancer diagnosis and a higher risk of relapse in women younger than 35 up to 5 years of the diagnosis may be found. Fortunately, for women with localized disease, earlier conception up to six months after completing their treatment seems unlikely to reduce their survival. Ongoing and future prospective studies evaluating the risks associated with pregnancy in young breast cancer survivors are required.

  5. Validation of Biomarkers for Prostate Cancer Prognosis

    Science.gov (United States)

    2015-11-01

    example the OncotypeDx assay has been calibrated and already validated precisely for this purpose. In addition, multiparametric MRI shows good ...testing. Cancer 119: 3906-3909, 2013. Zuxiong Chen, Zulfiqar G. Gulzar, Catherine A. St. Hill, Bruce Walcheck, James D. Brooks: Increased expression...Jamaspishvili T, Wei W, Feng Z, Good J, Hawley S, Fazli L, McKenney J, Simko J, Hurtado-Coll A, Carroll P, Gleave M, Lance R, Lin D, Nelson P, Thompson I

  6. The role of metallothionein in oncogenesis and cancer prognosis

    DEFF Research Database (Denmark)

    Pedersen, Mie Ø; Larsen, Agnete; Stoltenberg, Meredin

    2009-01-01

    /stage, chemotherapy/radiation resistance, and poor prognosis. However, MT-I+II are downregulated in other types of tumors (e.g. hepatocellular, gastric, colorectal, central nervous system (CNS), and thyroid cancers) where MT-I+II is either inversely correlated or unrelated to mortality. Large discrepancies exist...... in various human cancers; such as breast, kidney, lung, nasopharynx, ovary, prostate, salivary gland, testes, urinary bladder, cervical, endometrial, skin carcinoma, melanoma, acute lymphoblastic leukemia (ALL), and pancreatic cancers, where MT-I+II expression is sometimes correlated to higher tumor grade...

  7. Improvement of prognosis in breast cancer in Denmark 1977-2006, based on the nationwide reporting to the DBCG Registry

    DEFF Research Database (Denmark)

    Mouridsen, H.T.; Bjerre, K.D.; Christiansen, Peter

    2008-01-01

    were registered in the DBCG Database. Since 1977 the prognosis has improved significantly, thus 5 year survival for the total population of patients with primary breast cancer has increased from 65 to 81%. DISCUSSION: According to the present analysis diagnosis at an earlier stage in the natural course......INTRODUCTION: Since 30 years DBCG (Danish Breast Cancer Coperative Group) has maintained, on a nation-wide basis, a clinical database of diagnostic procedures, therapeutic interventions, and clinical outcome in patients with primary breast cancer. The present analysis was undertaken to evaluate...... the development of the prognosis since 1977, and to analyse factors potentially contributing to the change of the prognosis. MATERIAL AND METHODS: All cases of invasive breast cancer reported to DBCG during the period 1977-2006 were included in the present analysis. RESULTS: A total of close to 80 000 patients...

  8. Immune cell interplay in colorectal cancer prognosis

    Institute of Scientific and Technical Information of China (English)

    Samuel; E; Norton; Kirsten; A; Ward-Hartstonge; Edward; S; Taylor; Roslyn; A; Kemp

    2015-01-01

    The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, par-ticularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship betweencancer associated fibroblasts and macrophages, as well as between macrophages and T cells, and demonstrate how each population may support or prevent tumour growth in a different immune environment.

  9. Colorectal cancer prognosis twenty years later

    Institute of Scientific and Technical Information of China (English)

    Luis; Bujanda; Cristina; Sarasqueta; Elisabeth; Hijona; Lander; Hijona; Angel; Cosme; Ines; Gil; Jose; Luis; Elorza; Jose; I; Asensio; Santiago; Larburu; José; M; Enríquez-Navascués; Rodrigo; Jover; Francesc; Balaguer; Xavier; Llor; Xavier; Bessa; Montserrat; Andreu; Artemio; Paya; Antoni; Castells; Gastrointestinal; Oncology; Group; of; the; Spanish; Gastroenterological; Association

    2010-01-01

    AIM:To evaluate changes in colorectal cancer(CRC) survival over the last 20 years.METHODS:We compared two groups of consecutive CRC patients that were prospectively recruited:Group Ⅰincluded 1990 patients diagnosed between 1980 and 1994.GroupⅡincluded 871 patients diagnosed in 2001.RESULTS:The average follow up time was 21 mo(1-229)for GroupⅠand 50 mo(1-73.4)for GroupⅡ.Overall median survival was significantly longer in Group Ⅱthan in GroupⅠ(73 mo vs 25 mo,P<0.001)and the difference was significant for all ...

  10. Model Comparison for Breast Cancer Prognosis Based on Clinical Data.

    Directory of Open Access Journals (Sweden)

    Sabri Boughorbel

    Full Text Available We compared the performance of several prediction techniques for breast cancer prognosis, based on AU-ROC performance (Area Under ROC for different prognosis periods. The analyzed dataset contained 1,981 patients and from an initial 25 variables, the 11 most common clinical predictors were retained. We compared eight models from a wide spectrum of predictive models, namely; Generalized Linear Model (GLM, GLM-Net, Partial Least Square (PLS, Support Vector Machines (SVM, Random Forests (RF, Neural Networks, k-Nearest Neighbors (k-NN and Boosted Trees. In order to compare these models, paired t-test was applied on the model performance differences obtained from data resampling. Random Forests, Boosted Trees, Partial Least Square and GLMNet have superior overall performance, however they are only slightly higher than the other models. The comparative analysis also allowed us to define a relative variable importance as the average of variable importance from the different models. Two sets of variables are identified from this analysis. The first includes number of positive lymph nodes, tumor size, cancer grade and estrogen receptor, all has an important influence on model predictability. The second set incudes variables related to histological parameters and treatment types. The short term vs long term contribution of the clinical variables are also analyzed from the comparative models. From the various cancer treatment plans, the combination of Chemo/Radio therapy leads to the largest impact on cancer prognosis.

  11. Generalized Caseview applied to prostate cancer prognosis.

    Science.gov (United States)

    Levy, Pierre P; Bardier, Armelle; Doublet, Jean-Dominique; Sibony, Mathilde

    2008-01-01

    The interpretation of results of any study using large tables with series of numbers is always difficult. Generalized Case View Method (GCm) allows translating these tables of numbers into an image. The Method identifies each informational entity in the table with a 'pixel', forming what we call an 'infoxel'. The sum of all informational entities becomes an image, the Generalized Caseview. The method consists of two steps: the first one is to define the reference frame while the second is to visualize data through the reference frame. The 'infoxels' that constitute the reference frame should be organized according to three criteria: binary, nominal and ordinal. Here this method has been applied to visualize the results of a study about prostate cancer spread. This paper exemplifies the usefulness of associating a classical statistical tool with Generalized Caseview method to solve a biomedical problem.

  12. [Genomic Tests as Predictors of Breast Cancer Patients Prognosis].

    Science.gov (United States)

    Bielčiková, Z; Petruželka, L

    2016-01-01

    Hormonal dependent breast cancer is a heterogeneous disease from a molecular and clinical perspective. The relapse risk of early breast cancer patients treated with adjuvant hormonal therapy varies. Validated predictive markers concerning adjuvant cytotoxic treatment are still lacking in ER+/ HER2-  breast cancer, which has a good prognosis in general. This can lead to the inefficient chemotherapy indication. Molecular classification of breast cancer reports evidence about the heterogeneity of hormonal dependent breast cancer and its stratification to different groups with different characteristics. Multigene assays work on the molecular level, and their aim is to provide patients risk stratification and therapy efficacy prediction. The position of multigene assays in clinical practice is not stabile yet. Non uniform level of evidence connected to patients prognosis interpretations and difficult comparison of tests are the key problems, which prevent their wide clinical use. The article is a summary of some of the most important multigene assays in breast cancer and their current position in oncology practice.

  13. Screening for genes associated with ovarian cancer prognosis

    Institute of Scientific and Technical Information of China (English)

    CHANG Xiao-hong; ZHANG Li; YANG Rong; FENG Jie; CHENG Ye-xia; CHENG Hong-yan; YE Xue; FU Tian-yun; CUI Heng

    2009-01-01

    Background Human epithelial ovarian cancer cell line SKOV3.ipl is more invasive and metastatic compared with its parental line SKOV3. A total of 17 000 human genome complementary DNA microarrays were used to compare the gene expression patterns of the two cell lines. Based on this, the gene expression profiles of 22 patients with ovarian cancer were analyzed by cDNA microarray, and screened the 2-fold differentially expressed genes compared with the normal ones. We screened genes relevant to clinical prognosis of serous ovarian cancer by determining the expression profiles of ovarian cancer genes to investigate cell receptor and immunity-associated genes, and as groundwork, identify ovarian cancer-associated antigens at the gene level.Methods Total RNA was extracted from 22 patients with ovarian cancer and DNA microarrays were prepared. After scanning, hybridization signals were collected and the genes that were differentially expressed twice as compared with the normal ones were screened.Results We screened 236 genes relevant to the prognosis of ovarian cancer from the 17 000 human genome cDNA microarrays. According to gene classification, 48 of the 236 genes were cell receptor or immunity-associatad genes,including 2 genes related to the International Federation of Gynecology and Obstetrics (FIGO) stage, 4 genes to histological grade, 18 genes to lymph node metastasis, 11 genes to residual disease, and 13 genes to the reactivity to chemotherapy. Several functionally important genes including fibronectin 1, pericentriolar material 1, beta-2-microglobulin,PPAR binding protein were identified through review of the literature.Conclusions The cDNA microarray of ovarian cancer genes developed in this study was effective and high throughput in screening the ovarian cancer-associated genes differentially expressed. Through the studies of the cell receptor and immunity-associated genes we expect to identify the molecular biology index of ovarian cancer-associated antigens.

  14. [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.

  15. Delayed breast reconstruction with implants after invasive breast cancer does not impair prognosis

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Düring, Maria; Henriksen, Trine Foged;

    2008-01-01

    We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women......We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women...

  16. 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...

  17. Using data mining techniques for diagnosis and prognosis of cancer disease

    OpenAIRE

    2012-01-01

    Breast cancer is one of the leading cancers for women in developed countries including India. It is the second most common cause of cancer death in women. The high incidence of breast cancer in women has increased significantly in the last years. In this paper we have discussed various data mining approaches that have been utilized for breast cancer diagnosis and prognosis. Breast Cancer Diagnosis is distinguishing of benign from malignant breast lumps and Breast Cancer Prognosis predicts whe...

  18. Kinome expression profiling and prognosis of basal breast cancers

    Directory of Open Access Journals (Sweden)

    Jacquemier Jocelyne

    2011-07-01

    Full Text Available Abstract Background Basal breast cancers (BCs represent ~15% of BCs. Although overall poor, prognosis is heterogeneous. Identification of good- versus poor-prognosis patients is difficult or impossible using the standard histoclinical features and the recently defined prognostic gene expression signatures (GES. Kinases are often activated or overexpressed in cancers, and constitute targets for successful therapies. We sought to define a prognostic model of basal BCs based on kinome expression profiling. Methods DNA microarray-based gene expression and histoclinical data of 2515 early BCs from thirteen datasets were collected. We searched for a kinome-based GES associated with disease-free survival (DFS in basal BCs of the learning set using a metagene-based approach. The signature was then tested in basal tumors of the independent validation set. Results A total of 591 samples were basal. We identified a 28-kinase metagene associated with DFS in the learning set (N = 73. This metagene was associated with immune response and particularly cytotoxic T-cell response. On multivariate analysis, a metagene-based predictor outperformed the classical prognostic factors, both in the learning and the validation (N = 518 sets, independently of the lymphocyte infiltrate. In the validation set, patients whose tumors overexpressed the metagene had a 78% 5-year DFS versus 54% for other patients (p = 1.62E-4, log-rank test. Conclusions Based on kinome expression, we identified a predictor that separated basal BCs into two subgroups of different prognosis. Tumors associated with higher activation of cytotoxic tumor-infiltrative lymphocytes harbored a better prognosis. Such classification should help tailor the treatment and develop new therapies based on immune response manipulation.

  19. Applications of Machine Learning in Cancer Prediction and Prognosis

    Directory of Open Access Journals (Sweden)

    Joseph A. Cruz

    2006-01-01

    Full Text Available Machine learning is a branch of artificial intelligence that employs a variety of statistical, probabilistic and optimization techniques that allows computers to “learn” from past examples and to detect hard-to-discern patterns from large, noisy or complex data sets. This capability is particularly well-suited to medical applications, especially those that depend on complex proteomic and genomic measurements. As a result, machine learning is frequently used in cancer diagnosis and detection. More recently machine learning has been applied to cancer prognosis and prediction. This latter approach is particularly interesting as it is part of a growing trend towards personalized, predictive medicine. In assembling this review we conducted a broad survey of the different types of machine learning methods being used, the types of data being integrated and the performance of these methods in cancer prediction and prognosis. A number of trends are noted, including a growing dependence on protein biomarkers and microarray data, a strong bias towards applications in prostate and breast cancer, and a heavy reliance on “older” technologies such artificial neural networks (ANNs instead of more recently developed or more easily interpretable machine learning methods. A number of published studies also appear to lack an appropriate level of validation or testing. Among the better designed and validated studies it is clear that machine learning methods can be used to substantially (15-25% improve the accuracy of predicting cancer susceptibility, recurrence and mortality. At a more fundamental level, it is also evident that machine learning is also helping to improve our basic understanding of cancer development and progression.

  20. Yin Yang gene expression ratio signature for lung cancer prognosis.

    Directory of Open Access Journals (Sweden)

    Wayne Xu

    Full Text Available Many studies have established gene expression-based prognostic signatures for lung cancer. All of these signatures were built from training data sets by learning the correlation of gene expression with the patients' survival time. They require all new sample data to be normalized to the training data, ultimately resulting in common problems of low reproducibility and impracticality. To overcome these problems, we propose a new signature model which does not involve data training. We hypothesize that the imbalance of two opposing effects in lung cancer cells, represented by Yin and Yang genes, determines a patient's prognosis. We selected the Yin and Yang genes by comparing expression data from normal lung and lung cancer tissue samples using both unsupervised clustering and pathways analyses. We calculated the Yin and Yang gene expression mean ratio (YMR as patient risk scores. Thirty-one Yin and thirty-two Yang genes were identified and selected for the signature development. In normal lung tissues, the YMR is less than 1.0; in lung cancer cases, the YMR is greater than 1.0. The YMR was tested for lung cancer prognosis prediction in four independent data sets and it significantly stratified patients into high- and low-risk survival groups (p = 0.02, HR = 2.72; p = 0.01, HR = 2.70; p = 0.007, HR = 2.73; p = 0.005, HR = 2.63. It also showed prediction of the chemotherapy outcomes for stage II & III. In multivariate analysis, the YMR risk factor was more successful at predicting clinical outcomes than other commonly used clinical factors, with the exception of tumor stage. The YMR can be measured in an individual patient in the clinic independent of gene expression platform. This study provided a novel insight into the biology of lung cancer and shed light on the clinical applicability.

  1. Machine learning applications in cancer prognosis and prediction.

    Science.gov (United States)

    Kourou, Konstantina; Exarchos, Themis P; Exarchos, Konstantinos P; Karamouzis, Michalis V; Fotiadis, Dimitrios I

    2015-01-01

    Cancer has been characterized as a heterogeneous disease consisting of many different subtypes. The early diagnosis and prognosis of a cancer type have become a necessity in cancer research, as it can facilitate the subsequent clinical management of patients. The importance of classifying cancer patients into high or low risk groups has led many research teams, from the biomedical and the bioinformatics field, to study the application of machine learning (ML) methods. Therefore, these techniques have been utilized as an aim to model the progression and treatment of cancerous conditions. In addition, the ability of ML tools to detect key features from complex datasets reveals their importance. A variety of these techniques, including Artificial Neural Networks (ANNs), Bayesian Networks (BNs), Support Vector Machines (SVMs) and Decision Trees (DTs) have been widely applied in cancer research for the development of predictive models, resulting in effective and accurate decision making. Even though it is evident that the use of ML methods can improve our understanding of cancer progression, an appropriate level of validation is needed in order for these methods to be considered in the everyday clinical practice. In this work, we present a review of recent ML approaches employed in the modeling of cancer progression. The predictive models discussed here are based on various supervised ML techniques as well as on different input features and data samples. Given the growing trend on the application of ML methods in cancer research, we present here the most recent publications that employ these techniques as an aim to model cancer risk or patient outcomes.

  2. PBK/TOPK Expression Predicts Prognosis in Oral Cancer

    Directory of Open Access Journals (Sweden)

    Chin-Fang Chang

    2016-06-01

    Full Text Available Oral cancer is a common cancer with poor prognosis. We evaluated the expression of PBK/TOPK (PDZ-binding kinase/T-LAK cell-originated protein kinase and its prognostic significance in oral cancer. PBK/TOPK expression was measured by immunohistochemical staining of samples from 287 patients with oral cancer. The association between PBK/TOPK expression and clinicopathological features was analyzed. The prognostic value of PBK/TOPK for overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. A high PBK/TOPK expression level was correlated with long overall survival. The prognostic role of PBK/TOPK expression was significant in young patients (p < 0.05, patients with smoking habits (p < 0.05, and late stage disease (p < 0.05. Our results suggest that PBK/TOPK expression is enhanced in oral cancer. High PBK/TOPK expression, either alone or in subgroups according to clinicopathological features, may serve as a favorable prognostic marker for patients with oral cancer.

  3. Using data mining techniques for diagnosis and prognosis of cancer disease

    CERN Document Server

    Kharya, Shweta

    2012-01-01

    Breast cancer is one of the leading cancers for women in developed countries including India. It is the second most common cause of cancer death in women. The high incidence of breast cancer in women has increased significantly in the last years. In this paper we have discussed various data mining approaches that have been utilized for breast cancer diagnosis and prognosis. Breast Cancer Diagnosis is distinguishing of benign from malignant breast lumps and Breast Cancer Prognosis predicts when Breast Cancer is to recur in patients that have had their cancers excised. This study paper summarizes various review and technical articles on breast cancer diagnosis and prognosis also we focus on current research being carried out using the data mining techniques to enhance the breast cancer diagnosis and prognosis.

  4. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Science.gov (United States)

    2010-04-01

    ... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Tumor... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer...

  5. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer

    NARCIS (Netherlands)

    Bergman, L; Beelen, MLR; Gallee, MPW; Hollema, H; Benraadt, J; van Leeuwen, FE

    2000-01-01

    Background Tamoxifen increases the risk of endometrial cancer. However, few studies have produced reliable risk estimates by duration, dose, and recency of use, or addressed the prognosis of endometrial cancers in tamoxifen-treated women. Methods We did a nationwide case-control study on the risk an

  6. Inflammation-based factors and prognosis in patients withcolorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Several parameters for predicting survival in patientswith colorectal cancer have been identified, includingthe performance status, age, gender and tumor-nodemetastasis(TNM) stage. Although the TNM stage isimportant and useful for predicting the prognosis anddetermining the appropriate treatment, it is well knownthat the survival time varies widely, even in patients withthe same stage of disease. Therefore, the identificationof new parameters capable of more precisely predictingpatient survival is needed to help select the optimaltreatment, especially in patients in the advanced stageof disease. Although the TNM stage reflects the tumorcharacteristics, cancer progression and survival are notdetermined solely based on the local characteristics ofthe tumor, but also the host systemic immune/inflammatoryresponse. Therefore, using a combination ofparameters that reflect both tumor characteristics andthe host systemic inflammatory status is thought to beimportant for accurately predicting patient survival.

  7. PROGNOSIS OF EPITHELIAL OVARIAN CANCER RELATED TO ITS ASCITES

    Institute of Scientific and Technical Information of China (English)

    宋水勤; 张国楠; 吴艳丽; 周红; 赵素兰; 谢方; 陈毅男

    2001-01-01

    Objective: To investigate the relationship between the prognosis of Epithelial Ovarian Cancer (EOC) and its ascites. Methods: Retrospectively analysis is performed for the clinical, pathological and followed up data of 101 in-patients suffering from epithelial ovarian cancer and operated with tumor debulking surgery in our hospital from January 1986 to December 1993. The patients was divided into two groups based upon the first laparotomy finding with ascites(62) or without(39). Age average, cell type, advanced proportion and survival rate of the patients are evaluated by a c2 test. Results: For age average and cell type, no statistical difference was noted. However, there were more advanced cases in ascites group than in the other (P<0.01). The 3-, 4- and 5-year survival in the no-ascites group were 87.02%, 73.42%, 57.10% respectively compared with 65.02%, 38.66%, 28.12% in the ascites group. The 5-year survival rate of stage I, II,III, IV patients in no-ascites group are 77%, 70%, 41.1%, 0 respectively, compared with that of 60%, 56.8%, 15.46%, 0 respectively in the ascites group. The results shows that 3-, 4-, and 5-year survival in no-ascites group were significantly higher than those in ascites group(P<0.01). Conclusion: Presence of ascites is a factor of poor prognosis for EOC.

  8. 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.

  9. Oct-4 is associated with gastric cancer progression and prognosis

    Directory of Open Access Journals (Sweden)

    Jiang WL

    2016-01-01

    Full Text Available Wen-Li Jiang,1 Peng-Fei Zhang,2 Guo-Feng Li,1 Jian-Hua Dong,1 Xue-Song Wang,1 Yuan-Yu Wang3 1Department of Surgery, Juxian People’s Hospital, 2Department of Surgery, Rizhao People’s Hospital of Traditional Chinese Medicine, Rizhao, 3Department of Gastrointestinal Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, People’s Republic of China Aim: To investigate the clinical significance of Oct-4 in the development and progression of gastric cancer.Methods: Immunohistochemistry was used to analyze Oct-4 expression in 412 gastric cancer cases. Oct-4 protein levels were upregulated in gastric cancer tissues compared with adjacent noncancerous tissues.Results: Positive expression of Oct-4 correlated with age, depth of invasion, Lauren classification, lymph node metastasis, distant metastasis, and TNM stage. In stages I, II, and III, the 5-year survival rate of patients with high expression of Oct-4 was significantly lower than that in patients with low expression of Oct-4. In stage IV, Oct-4 expression did not correlate with the 5-year survival rate. Furthermore, multivariate analysis suggested that the depth of invasion, lymph node metastasis, distant metastasis, TNM stage, and upregulation of Oct-4 were independent prognostic factors of gastric cancer.Conclusion: Oct-4 protein is a useful marker in predicting tumor progression and prognosis. Keywords: gastric carcinoma, invasion, metastasis, survival rate

  10. 上皮性卵巢癌患者 LDL 与 ox-LDL 的诊价值及与预后的关系%Diagnostic values of LDL and ox-LDL in patients with epithelial ovarian cancer and their relationship with prognosis

    Institute of Scientific and Technical Information of China (English)

    周晅; 周彦杰; 李新春

    2015-01-01

    目的:研究血清中低密度脂蛋白(LDL)和氧化型低密度脂蛋白(ox‐LDL )在临床诊断的价值,同时分析其与上皮性卵巢癌患者预后的相关性。方法选取2010年4月至2014年5月入院治疗的40例良性上皮性卵巢肿瘤患者、28例上皮性卵巢癌患者,以及同期来体检的30例健康体检者,比较各组标本血清中高密度脂蛋白、三酰甘油、LDL 和总胆固醇水平,分析血脂水平变化与上皮性卵巢癌分化的关系,同时对 LDL 及 ox‐LDL 水平与患者远期生存预测相关性进行分析。结果上皮性卵巢癌患者血清中 ox‐LDL 、LDL 水平显著高于健康体检者,差异有统计学意义(P<0.05);高分化型上皮性卵巢癌患者 ox‐LDL 和 LDL 水平显著高于其低、中分化型患者,差异有统计学意义(P<0.05);LDL 及 ox‐LDL 水平与患者远期生存预测有相关性。结论 LDL 及 ox‐LDL 水平改变是上皮性卵巢癌患者远期临床预后的重要预测因素,具有重要临床意义。%Objective To study the diagnostic values of serum low density lipoprotein (LDL) and oxidation of serum lipoprotein (ox‐LDL ) in patients with epithelial ovarian cancer and their relationship with prognosis . Methods 40 cases of patients with ovarian tumor ,28 cases of patients with epithelial ovarian cancer ,and 30 cases of healthy people were enrolled in the study from April 2010 to May 2014 .The serum levels of high density lipoprotein in serum (HDL) ,three glycerol (TG) ,LDL and ox‐LDL of each group were detected and compared .The relationship between the changes of lipid levels and the differentiation of epithelial ovarian cancer was analyzed ,and the correlation between the levels of LDL and ox‐LDL and the long‐term survival prediction was also analyzed .Results The serum levels of ox‐LDL and LDL in patients with epithelial ovarian cancer were significantly higher than healthy people (P< 0 .05

  11. Classification of breast cancer stroma as a tool for prognosis

    Science.gov (United States)

    Reis, Sara; Gazinska, Patrycja; Hipwell, John H.; Mertzanidou, Thomy; Naidoo, Kalnisha; Pinder, Sarah; Hawkes, David J.

    2016-03-01

    It has been shown that the tumour microenvironment plays a crucial role in regulating tumour progression by a number of different mechanisms, including the remodeling of collagen fibres in tumour-associated stroma. It is still unclear, however, if these stromal changes are of benefit to the host or the tumour. We hypothesise that stromal maturity is an important reflection of tumour biology, and thus can be used to predict prognosis. The aim of this study is to develop a texture analysis methodology which will automatically classify stromal regions from images of hematoxylin and eosin-stained (H and E) sections into two categories: mature and immature. Subsequently we will investigate whether stromal maturity could be used as a predictor of survival and also as a means to better understand the relationship between the radiological imaging signal and the underlying tissue microstructure. We present initial results for 118 regions-of-interest from a dataset of 39 patients diagnosed with invasive breast cancer.

  12. Genetic susceptibility variants associated with colorectal cancer prognosis.

    Science.gov (United States)

    Abulí, Anna; Lozano, Juan José; Rodríguez-Soler, María; Jover, Rodrigo; Bessa, Xavier; Muñoz, Jenifer; Esteban-Jurado, Clara; Fernández-Rozadilla, Ceres; Carracedo, Angel; Ruiz-Ponte, Clara; Cubiella, Joaquín; Balaguer, Francesc; Bujanda, Luis; Reñé, Josep M; Clofent, Juan; Morillas, Juan Diego; Nicolás-Pérez, David; Xicola, Rosa M; Llor, Xavier; Piqué, Josep M; Andreu, Montserrat; Castells, Antoni; Castellví-Bel, Sergi

    2013-10-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death among men and women in Western countries. Once a tumour develops, a differentiated prognosis could be determined by lifestyle habits or inherited and somatic genetic factors. Finding such prognostic factors will be helpful in order to identify cases with a shorter survival or at a higher risk of recurrence that may benefit from more intensive treatment and follow-up surveillance. Sixteen CRC genetic susceptibility variants were directly genotyped in a cohort of 1235 CRC patients recruited by the EPICOLON Spanish consortium. Univariate Cox and multivariate regression analyses were performed taking as primary outcomes overall survival (OS), disease-free survival and recurrence-free interval. Genetic variants rs9929218 at 16q22.1 and rs10795668 at 10p14 may have an effect on OS. The G allele of rs9929218 was linked with a better OS [GG genotype, genotypic model: hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.45-0.93, P = 0.0179; GG/GA genotypes, dominant model: HR = 0.66, 95% CI 0.47-0.94, P = 0.0202]. Likewise, the G allele of rs10795668 was associated with better clinical outcome (GG genotype, genotypic model: HR = 0.73, 95% CI 0.53-1.01, P = 0.0570; GA genotype, genotypic model: HR = 0.66, 95% CI 0.47-0.92, P = 0.0137; GG/GA genotypes, dominant model: HR = 0.68, 95% CI 0.50-0.94, P = 0.0194). In conclusion, CRC susceptibility variants rs9929218 and rs10795668 may exert some influence in modulating patient's survival and they deserve to be further tested in additional CRC cohorts in order to confirm their potential as prognosis or predictive biomarkers.

  13. Clinicopathological characteristics and prognosis of early gastric cancer after gastrectomy

    Institute of Scientific and Technical Information of China (English)

    WANG Yong-xiang; SHAO Qin-shu; YANG Qiong; WANG Yuan-yu; YANG Jin; ZHAO Zhong-kuo; XU Ji; YE Zai-yuan

    2012-01-01

    Background Assessment of lymph node metastasis (LNM) is important in early gastric cancer (EGC) and affects treatment decisions.However,the relationship between clinicopathological characteristics and LNM in EGC remains unclear.This study therefore explored favorable predictors of LNM in EGC.Methods A total of 716 specimens from gastric cancer patients who underwent curative gastrectomy between 1996 and 2003 at Zhejiang Provincial People's Hospital were reviewed.Forty-five cases were EGC,and clinicopathological characteristics such as gender,age,tumor size,location,gross type,differentiation,invasion depth,and vessel involvement were assessed to identify predictive factors for LNM and survival time.Results The overall cumulative 5-year survival rate of EGC patients was 88.92%.Among these,22.4% developed LNM,which was associated with a poor 5-year survival rate of only 72.7%.Patients with tumors larger than 2 cm in diameters,with depth of tumor invasion to the submucosa,and with positive lymphatic or nerve involvement were also inclined to have poorer survival performances.EGC limited to the mucosa but poorly differentiated also had a high risk for LNM.Multivariate analysis identified lymphatic invasion and tumor size as independent prognosis factors related to survival in EGC patients.Conclusions Careful planning is required in EGC patients at high risk of lymph node metastases.Endoscopic mucosal resection or endoscopic submucosal dissection and laparoscopic partial gastrectomy should be cautiously used in EGC,and curative gastrectomy including lymphatic dissection and postoperative adjuvant therapy might be considered to improve the prognosis.

  14. Adjusting breast cancer patient prognosis with non-HER2-gene patterns on chromosome 17.

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    Vassiliki Kotoula

    Full Text Available BACKGROUND: HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization (FISH. However, FISH probes do not target only the annotated gene, while chromosome 17 (chr17 is among the most unstable chromosomes in breast cancer. Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients. METHODS: Copy numbers (CN for 14 genes on chr17, 4 of which were within and 10 outside the core HER2 amplicon (HER2- and non-HER2-genes, respectively were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials. PRINCIPAL FINDINGS: HER2-genes CN strongly correlated to each other (Spearman's rho >0.6 and were concordant with FISH HER2 status (Kappa 0.6697 for ERBB2 CN. TOP2A CN were not concordant with TOP2A FISH status (Kappa 0.1154. CN hierarchical clustering revealed distinct patterns of gains, losses and complex alterations in HER2- and non-HER2-genes associated with IHC4 breast cancer subtypes. Upon multivariate analysis, non-HER2-gene gains independently predicted for shorter disease-free survival (DFS and overall survival (OS in patients with triple-negative cancer, as compared to luminal and HER2-positive tumors (interaction p = 0.007 for DFS and p = 0.011 for OS. Similarly, non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy (p = 0.004 for both DFS and OS. Non-HER2-gene losses were unfavorable prognosticators in patients with 1-3 metastatic nodes, as compared to those with 4 or more nodes (p = 0.017 for DFS and p = 0.001 for OS. CONCLUSIONS: TOP2A FISH and qPCR may not identify the same pathology on chr17q. Non-HER2 chr17 CN patterns may further predict outcome in breast cancer

  15. Predicting cancer prognosis using interactive online tools: a systematic review and implications for cancer care providers.

    Science.gov (United States)

    Rabin, Borsika A; Gaglio, Bridget; Sanders, Tristan; Nekhlyudov, Larissa; Dearing, James W; Bull, Sheana; Glasgow, Russell E; Marcus, Alfred

    2013-10-01

    Cancer prognosis is of keen interest for patients with cancer, their caregivers, and providers. Prognostic tools have been developed to guide patient-physician communication and decision-making. Given the proliferation of prognostic tools, it is timely to review existing online cancer prognostic tools and discuss implications for their use in clinical settings. Using a systematic approach, we searched the Internet, Medline, and consulted with experts to identify existing online prognostic tools. Each was reviewed for content and format. Twenty-two prognostic tools addressing 89 different cancers were identified. Tools primarily focused on prostate (n = 11), colorectal (n = 10), breast (n = 8), and melanoma (n = 6), although at least one tool was identified for most malignancies. The input variables for the tools included cancer characteristics (n = 22), patient characteristics (n = 18), and comorbidities (n = 9). Effect of therapy on prognosis was included in 15 tools. The most common predicted outcome was cancer-specific survival/mortality (n = 17). Only a few tools (n = 4) suggested patients as potential target users. A comprehensive repository of online prognostic tools was created to understand the state-of-the-art in prognostic tool availability and characteristics. Use of these tools may support communication and understanding about cancer prognosis. Dissemination, testing, refinement of existing, and development of new tools under different conditions are needed.

  16. Breast cancer after hormone replacement therapy--does prognosis differ in perimenopausal and postmenopausal women?

    Science.gov (United States)

    Baumgärtner, A K; Häusler, A; Seifert-Klauss, V; Schuster, T; Schwarz-Boeger, U; Kiechle, M

    2011-10-01

    Hormone replacement therapy (HRT) has been associated with higher incidence of breast cancer in postmenopausal women, but it is unclear if breast cancers developing after HRT use have different prognosis. 1053 women with hormone receptor positive non-metastasized breast cancer were analyzed in a retrospective trial, stratifying by HRT use before diagnosis. Postmenopausal HRT users had significantly more early tumor stages (pprognosis in perimenopausal women only (TTP: HR=1.16; OS: HR=1.31). In this retrospective analysis postmenopausal HRT users seemed to have a better breast cancer prognosis. For perimenopausal HRT users however, a trend towards worse prognosis was found.

  17. 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.

  18. 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

  19. Acute Escherichia coli mastitis in dairy cattle: diagnostic parameters associated with poor prognosis.

    Science.gov (United States)

    Hagiwara, Seiichi; Mori, Kouichiro; Okada, Hiroyuki; Oikawa, Shin; Nagahata, Hajime

    2014-11-01

    This study aimed to identify the diagnostic characteristics associated with poor prognosis and mortality in dairy cows with acute clinical Escherichia coli mastitis. On 17 dairy farms, 24 dairy cows with acute E. coli mastitis that had received therapeutic treatment were categorized into 2 groups by outcome: 17 cows that recovered (survivors) and 7 cows that died or were euthanized (non-survivors). Two days after onset of acute E. coli mastitis, dysstasia was observed in non-survivors, but not in survivors. Compared with survivors, significantly increased hematocrit (HCT) values and non-esterified fatty acid (NEFA) concentrations, and significantly decreased antithrombin activity and platelet counts were found in non-survivors on days 2 and 3 after therapy. Dysstasia, associated with decreased antithrombin activity and platelet counts, and with increased HCT and NEFA concentrations, was considered to be the major prognostic indicator associated with high mortality after therapeutic treatment in acute E. coli mastitis.

  20. Low expression of a few genes indicates good prognosis in estrogen receptor positive breast cancer

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    Buechler Steven

    2009-07-01

    Full Text Available Abstract Background Many breast cancer patients remain free of distant metastasis even without adjuvant chemotherapy. While standard histopathological tests fail to identify these good prognosis patients with adequate precision, analyses of gene expression patterns in primary tumors have resulted in more successful diagnostic tests. These tests use continuous measurements of the mRNA concentrations of numerous genes to determine a risk of metastasis in lymph node negative breast cancer patients with other clinical traits. Methods A survival model is constructed from genes that are both connected with relapse and have expression patterns that define distinct subtypes, suggestive of different cellular states. This in silico study uses publicly available microarray databases generated with Affymetrix GeneChip technology. The genes in our model, as represented by array probes, have distinctive distributions in a patient cohort, consisting of a large normal component of low expression values; and a long right tail of high expression values. The cutoff between low and high expression of a probe is determined from the distribution using the theory of mixture models. The good prognosis group in our model consists of the samples in the low expression component of multiple genes. Results Here, we define a novel test for risk of metastasis in estrogen receptor positive (ER+ breast cancer patients, using four probes that determine distinct subtypes. The good prognosis group in this test, denoted AP4-, consists of the samples with low expression of each of the four probes. Two probes target MKI67, antigen identified by monoclonal antibody Ki-67, one targets CDC6, cell division cycle 6 homolog (S. cerevisiae, and a fourth targets SPAG5, sperm associated antigen 5. The long-term metastasis-free survival probability for samples in AP4- is sufficiently high to render chemotherapy of questionable benefit. Conclusion A breast cancer subtype defined by low

  1. Pan-Cancer Analyses Reveal Long Intergenic Non-Coding RNAs Relevant to Tumor Diagnosis, Subtyping and Prognosis.

    Science.gov (United States)

    Ching, Travers; Peplowska, Karolina; Huang, Sijia; Zhu, Xun; Shen, Yi; Molnar, Janos; Yu, Herbert; Tiirikainen, Maarit; Fogelgren, Ben; Fan, Rong; Garmire, Lana X

    2016-05-01

    Long intergenic noncoding RNAs (lincRNAs) are a relatively new class of non-coding RNAs that have the potential as cancer biomarkers. To seek a panel of lincRNAs as pan-cancer biomarkers, we have analyzed transcriptomes from over 3300 cancer samples with clinical information. Compared to mRNA, lincRNAs exhibit significantly higher tissue specificities that are then diminished in cancer tissues. Moreover, lincRNA clustering results accurately classify tumor subtypes. Using RNA-Seq data from thousands of paired tumor and adjacent normal samples in The Cancer Genome Atlas (TCGA), we identify six lincRNAs as potential pan-cancer diagnostic biomarkers (PCAN-1 to PCAN-6). These lincRNAs are robustly validated using cancer samples from four independent RNA-Seq data sets, and are verified by qPCR in both primary breast cancers and MCF-7 cell line. Interestingly, the expression levels of these six lincRNAs are also associated with prognosis in various cancers. We further experimentally explored the growth and migration dependence of breast and colon cancer cell lines on two of the identified lncRNAs. In summary, our study highlights the emerging role of lincRNAs as potentially powerful and biologically functional pan-cancer biomarkers and represents a significant leap forward in understanding the biological and clinical functions of lincRNAs in cancers.

  2. 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...

  3. 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....

  4. Assessment of performance of survival prediction models for cancer prognosis

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    Chen Hung-Chia

    2012-07-01

    Full Text Available Abstract Background Cancer survival studies are commonly analyzed using survival-time prediction models for cancer prognosis. A number of different performance metrics are used to ascertain the concordance between the predicted risk score of each patient and the actual survival time, but these metrics can sometimes conflict. Alternatively, patients are sometimes divided into two classes according to a survival-time threshold, and binary classifiers are applied to predict each patient’s class. Although this approach has several drawbacks, it does provide natural performance metrics such as positive and negative predictive values to enable unambiguous assessments. Methods We compare the survival-time prediction and survival-time threshold approaches to analyzing cancer survival studies. We review and compare common performance metrics for the two approaches. We present new randomization tests and cross-validation methods to enable unambiguous statistical inferences for several performance metrics used with the survival-time prediction approach. We consider five survival prediction models consisting of one clinical model, two gene expression models, and two models from combinations of clinical and gene expression models. Results A public breast cancer dataset was used to compare several performance metrics using five prediction models. 1 For some prediction models, the hazard ratio from fitting a Cox proportional hazards model was significant, but the two-group comparison was insignificant, and vice versa. 2 The randomization test and cross-validation were generally consistent with the p-values obtained from the standard performance metrics. 3 Binary classifiers highly depended on how the risk groups were defined; a slight change of the survival threshold for assignment of classes led to very different prediction results. Conclusions 1 Different performance metrics for evaluation of a survival prediction model may give different conclusions in

  5. Abnormal expression of calcyphosine is associated with poor prognosis and cell biology function in colorectal cancer

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    Shao W

    2016-01-01

    Full Text Available Weiwei Shao,* Quhui Wang,* Feiran Wang, Yasu Jiang, Meirong Xu, Junfei XuDepartment of General Surgery, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workAbstract: The aim of this study was to investigate the calcyphosine (CAPS expression in human colorectal cancer (CRC and to explore its clinical and prognostic significances. CAPS expression was measured by Western blot, real-time polymerase chain reaction analysis, and immunohistochemistry. The relationships between the CAPS expression levels and the clinicopathological factors were investigated. The Kaplan–Meier method and log-rank test were used to investigate the overall survival of the patients. Moreover, the effects of CAPS on biological roles of CRC cells were also evaluated by MTT assay, colony formation assay, and transwell assay. CAPS was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent nontumor tissue and a normal human intestinal epithelial cell line. Overexpression of CAPS was significantly associated with histological grade (P=0.004, invasive depth (P<0.001, lymph node metastasis (P=0.003, tumor node metastasis stage (P=0.017, and distant metastasis (P=0.042. Furthermore, silencing of CAPS expression in CRC cells inhibited their proliferation, colony formation, migration, and invasion. Kaplan–Meier survival analysis showed that high CAPS expression might demonstrate poor prognosis in CRC patients. Cox regression analysis revealed that CAPS expression was an independent prognostic factor of CRC. Our data suggested that the upregulation of CAPS might play a role in the carcinogenesis and progression of CRC. CAPS could be used as a potential diagnostic factor and be an independent good prognostic indicator for CRC patients.Keywords: calcyphosine, colorectal cancer, prognosis

  6. Convergence of mutation and epigenetic alterations identifies common genes in cancer that predict for poor prognosis.

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    Timothy A Chan

    2008-05-01

    Full Text Available BACKGROUND: The identification and characterization of tumor suppressor genes has enhanced our understanding of the biology of cancer and enabled the development of new diagnostic and therapeutic modalities. Whereas in past decades, a handful of tumor suppressors have been slowly identified using techniques such as linkage analysis, large-scale sequencing of the cancer genome has enabled the rapid identification of a large number of genes that are mutated in cancer. However, determining which of these many genes play key roles in cancer development has proven challenging. Specifically, recent sequencing of human breast and colon cancers has revealed a large number of somatic gene mutations, but virtually all are heterozygous, occur at low frequency, and are tumor-type specific. We hypothesize that key tumor suppressor genes in cancer may be subject to mutation or hypermethylation. METHODS AND FINDINGS: Here, we show that combined genetic and epigenetic analysis of these genes reveals many with a higher putative tumor suppressor status than would otherwise be appreciated. At least 36 of the 189 genes newly recognized to be mutated are targets of promoter CpG island hypermethylation, often in both colon and breast cancer cell lines. Analyses of primary tumors show that 18 of these genes are hypermethylated strictly in primary cancers and often with an incidence that is much higher than for the mutations and which is not restricted to a single tumor-type. In the identical breast cancer cell lines in which the mutations were identified, hypermethylation is usually, but not always, mutually exclusive from genetic changes for a given tumor, and there is a high incidence of concomitant loss of expression. Sixteen out of 18 (89% of these genes map to loci deleted in human cancers. Lastly, and most importantly, the reduced expression of a subset of these genes strongly correlates with poor clinical outcome. CONCLUSIONS: Using an unbiased genome

  7. Prognosis of synchronous bilateral breast cancer: a review and meta-analysis of observational studies.

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    Holm, Marianne; Tjønneland, Anne; Balslev, Eva; Kroman, Niels

    2014-08-01

    Currently, no consistent evidence-based guidelines for the management of synchronous bilateral breast cancer (SBBC) exist and it is uncertain how presenting with SBBC affects patients' prognosis. We conducted a review of studies analyzing the association between SBBC and prognosis. The studies that reported adjusted effect measures were included in meta-analyses of effect of bilaterality on breast cancer mortality. From 57 initially identified records 17 studies from 11 different countries including 8,050 SBBC patients were included. The quality of the studies varied but was generally low with small sample sizes, and lack of consistent, detailed histo-pathological information. When doing meta-analysis on the subgroup of studies that provided adjusted effect estimates on breast cancer mortality (nine studies including 3,631 SBBC cases), we found that bilaterality in itself had a negative impact on prognosis after adjustment for known prognostic factors (pooled HR 1.37, 95 % CI 1.24-1.50, p prognosis. The previously accepted convention that appropriate adjuvant treatment can be determined by considering the higher risk cancer was not confirmed in this review; rather it seems that being diagnosed with two tumors simultaneously entails a worse prognosis above and beyond that of the unilateral cancers of the same stage. To determine the true association between SBBC and breast cancer prognosis, studies of large and updated samples of SBBC should be done and include thorough histo-pathologic information.

  8. Diagnostic and prognostic epigenetic biomarkers in cancer.

    Science.gov (United States)

    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.

  9. Clinicopathologic and gene expression parameters predict liver cancer prognosis

    Directory of Open Access Journals (Sweden)

    Hao Ke

    2011-11-01

    Full Text Available Abstract Background The prognosis of hepatocellular carcinoma (HCC varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model. Methods Tumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction. Results HCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis. Conclusion When applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome.

  10. MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer.

    Science.gov (United States)

    Bertoli, Gloria; Cava, Claudia; Castiglioni, Isabella

    2015-01-01

    Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, prognosis, and therapy of BC. Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs are of interest as new, easily accessible, affordable, non-invasive tools for the personalized management of patients with BC because they are circulating in body fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).

  11. Abnormal expression of calcyphosine is associated with poor prognosis and cell biology function in colorectal cancer

    Science.gov (United States)

    Shao, Weiwei; Wang, Quhui; Wang, Feiran; Jiang, Yasu; Xu, Meirong; Xu, Junfei

    2016-01-01

    The aim of this study was to investigate the calcyphosine (CAPS) expression in human colorectal cancer (CRC) and to explore its clinical and prognostic significances. CAPS expression was measured by Western blot, real-time polymerase chain reaction analysis, and immunohistochemistry. The relationships between the CAPS expression levels and the clinicopathological factors were investigated. The Kaplan–Meier method and log-rank test were used to investigate the overall survival of the patients. Moreover, the effects of CAPS on biological roles of CRC cells were also evaluated by MTT assay, colony formation assay, and transwell assay. CAPS was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent nontumor tissue and a normal human intestinal epithelial cell line. Overexpression of CAPS was significantly associated with histological grade (P=0.004), invasive depth (P<0.001), lymph node metastasis (P=0.003), tumor node metastasis stage (P=0.017), and distant metastasis (P=0.042). Furthermore, silencing of CAPS expression in CRC cells inhibited their proliferation, colony formation, migration, and invasion. Kaplan–Meier survival analysis showed that high CAPS expression might demonstrate poor prognosis in CRC patients. Cox regression analysis revealed that CAPS expression was an independent prognostic factor of CRC. Our data suggested that the upregulation of CAPS might play a role in the carcinogenesis and progression of CRC. CAPS could be used as a potential diagnostic factor and be an independent good prognostic indicator for CRC patients. PMID:26889086

  12. Surgical Treatment and Prognosis of Synchronous Double Primary Lung Cancer: a Report of 31 Cases

    Institute of Scientific and Technical Information of China (English)

    Feiyue Feng; Dechao Zhang; Xiangyang Liu; Yonggang Wang; Yousheng Mao

    2005-01-01

    OBJECTIVE The concept of double primary lung cancer (DPLC) has been generally accepted. Recently, an increasing incidence of synchronous DPLC has been reported, while the diagnostic standard and treatment strategies remain to be improved. This study was conducted to investigate effective surgical treatment and prognosis of synchronous DPLC.METHODS From January 1983 to April 2004, 31 patients with synchronous DPLC were operated in our department. Clinical data, such as surgical pattern, postoperative complications, and survival status, of all these patients were reviewed retrospectively.RESULTS The 31 patients with synchronous DPLC accounted for 0.67% of all the 4,649 patients operated for primary lung cancer in our department during the same period. Both tumors of the synchronous DPLC were resected with Iobectomy or pneumonectomy in 12 patients, while among the other 19 patients at least 1 tumor was treated with partial pulmonary resection. The postoperative morbidity was 29%(9/31), including 1 case of respiratory insufficiency, 3 cases of atelectasis, 2 cases of atrial fibrillation, 1 case of haemoptysis, 1 case of pleural effusion, and 1 case of wound fat necrosis.No deaths occurred during the operations or within 30 days postoperatively.The postoperative 1 -, 3-, and 5-year survival rates were 52%, 29%, and 20%, respectively.CONCLUSION The incidence of synchronous DPLC is low. An aggressive and reasonable surgical approach can achieve a satisfactory outcome in patients with synchronous DPLC. The postoperative morbidity is low. Some patients might achieve long-term survival.

  13. Use of a Novel Embryonic Mammary Stem Cell Gene Signature to Improve Human Breast Cancer Diagnostics and Therapeutic Decision Making

    Science.gov (United States)

    2014-10-01

    SUBTITLE Use of a Novel Embryonic Mammary Stem Cell Gene Signature to Improve Human Breast Cancer Diagnostics and Therapeutic Decision Making Improve...to determine whether Fetal Mammary Stem Cell (fMaSC) signatures correlate with response to chemotherapy and metastasis in different breast cancer...positioned to achieve its aims. 15. SUBJECT TERMS Breast Cancer Prognosis, Mammary Stem Cells, Embryonic Development, Single Cell Transcriptomics 16

  14. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer

    DEFF Research Database (Denmark)

    Allin, Kristine H; Nordestgaard, Børge G

    2011-01-01

    -phase response, chronic inflammation, the molecular biology, function and measurement of CRP, circulating levels of CRP in health and disease, the principle of Mendelian randomization, the association between circulating levels of CRP and cancer prognosis, and cancer biomarkers. In the Copenhagen General...

  15. Elevated plasma vitamin B12 levels and cancer prognosis: A population-based cohort study

    DEFF Research Database (Denmark)

    Arendt, Johan Frederik Håkonsen; Farkas, Dora Kormendine; Pedersen, Lars;

    2015-01-01

    BACKGROUND: Elevated plasma vitamin B12 levels (cobalamin, Cbl) are associated with increased short-term cancer risk among patients referred for this laboratory measurement. We aimed to assess prognosis in cancer patients with elevated plasma Cbl. METHODS: We conducted a population-based cohort...

  16. Loss of partner and breast cancer prognosis - a population-based study, Denmark, 1994-2010

    DEFF Research Database (Denmark)

    Olsen, M H; Bidstrup, P E; Frederiksen, K;

    2012-01-01

    The extent to which experiencing a stressful life event influences breast cancer prognosis remains unknown, as the findings of the few previous epidemiological studies are inconsistent. This large population-based study examines the association between a common major life event, loss of a partner...... and breast cancer recurrence and all-cause mortality....

  17. Tumor-infiltrating immune cells and prognosis: the potential link between conventional cancer therapy and immunity.

    Science.gov (United States)

    Jochems, Caroline; Schlom, Jeffrey

    2011-05-01

    Numerous studies have now documented a link between the immune infiltrate in several human carcinoma types and prognosis and response to therapy. The most comprehensive of these studies were in colorectal cancer with similar conclusions by numerous groups. Analyses of immune infiltrate of several other carcinoma types also showed general correlations between immune infiltrate and prognosis, but with some conflicting results. This review will attempt to summarize the current state of this field and point out what factors may be responsible for some of the conflicting findings. Nonetheless, the breadth of reports drawing similar conclusions for some cancer cell types leads one to more seriously consider the link between immune cell infiltrate and tumor prognosis and/or response to therapy, and the potential for combining conventional cancer therapy with active immunotherapy employing therapeutic cancer vaccines.

  18. Prognosis and Diagnostics of Water-absorbing Capacity of Polydisperse Materials by pH-metry Data

    OpenAIRE

    Ikonnikova, Ksenia Vladimirovna; Ikonnikova, Liubov Fedorovna; Koltunova, Ekaterina

    2015-01-01

    The work focuses on the solution of the problem concerning the diagnostics and prognosis of water-absorbing capacity of polydisperse materials. The relation of water absorption and acid-base properties of the surface is considered. The advantages of the research of acid-base properties of the surface by the pH-metry method are illustrated. The algorithm of the processing and interpretation of pH metric results to diagnose water absorption of powdery substances is suggested. The diagnostics is...

  19. OPTIMIZATION OF DIAGNOSTIC IMAGING IN BREAST CANCER

    Directory of Open Access Journals (Sweden)

    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.  

  20. Lgr5 Methylation in Cancer Stem Cell Differentiation and Prognosis-Prediction in Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Shasha Su

    Full Text Available Leucine-rich-repeat-containing G-protein-coupled receptor 5 (lgr5 is a candidate marker for colorectal cancer stem cells (CSC. In the current study, we investigated the methylation status within thelgr5 promoter and evaluated its relationship with CSC differentiation, prognosis for colorectal cancer, and its clinicopathological features.The methylation status within Lgr5 promoter was detected with a methylation-specific PCR in six colorectal cancer cell lines as well as 169 primary colorectal tumor tissues. Differentiation of CSC was examined with immunofluorescence and immunocytochemistry. Down-regulation of lgr5 was achieved with gene-specific siRNA. The associations between lgr5 methylation and the clinicopathological features as well as survival of patients were analyzed with statistical methods.The lgr5 promoter was methylated to different degrees for the six colorectal cell lines examined, with complete methylation observed in HCT116 cells in which the lgr5 expression was partially recovered following DAC treatment. The stem-cell sphere formation from HCT116 cells was accompanied by increasing methylation within the lgr5 promoter and decreasing expression of lgr5. Knocking down lgr5 by siRNA also led to stem-cell spheres formation. Among primary colorectal tumors, 40% (67/169 were positive for lgr5 methylation, while none of the normal colon tissues were positive for lgr5 methylation. Furthermore, lgr5 methylation significantly associated with higher tumor grade, and negative distant metastasis (p < 0.05, as well as better prognosis (p = 0.001 in patients with colorectal cancer.Our data suggests that lgr5 methylation, through the regulation of lgr5 expression and colorectal CSC differentiation, may constitute a novel prognostic marker for colorectal cancer patients.

  1. 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.

  2. Effect of ALDH1 on prognosis and chemoresistance by breast cancer subtype.

    Science.gov (United States)

    Kida, Kumiko; Ishikawa, Takashi; Yamada, Akimitsu; Shimada, Kazuhiro; Narui, Kazutaka; Sugae, Sadatoshi; Shimizu, Daisuke; Tanabe, Mikiko; Sasaki, Takeshi; Ichikawa, Yasushi; Endo, Itaru

    2016-04-01

    Aldehyde dehydrogenase 1 (ALDH1) has been identified as a breast cancer stem cell marker, but its value as a predictor of prognosis and chemoresistance is controversial. This study investigated the effect of ALDH1 on prognosis and chemoresponse by breast cancer subtype. We immunohistochemically analyzed 653 invasive breast cancer specimens and evaluated correlations among clinicopathological factors, survival status, response to neoadjuvant chemotherapy, and ALDH1 expression. Of 653 specimens, 139 (21.3 %) expressed ALDH1 in tumor cells. ALDH1 expression was correlated significantly with larger tumor size, node metastasis, higher nuclear grade, and with HER2(+) and progesterone/estrogen receptor (HR)(-) subtypes. ALDH1 expression was significantly observed in HER2 type and triple-negative breast cancer (TNBC). Patients with ALDH1(+) cancers had significantly shorter disease-free survival (P prognosis of luminal types, but not TNBC and HER2-enriched types. For the 234 patients treated with neoadjuvant chemotherapy, pathological complete response (pCR) rate was significantly lower in ALDH1(+) cases (13.5 vs. 30.3 %, P = 0.003). pCR and ALDH1 expression were significantly correlated in TNBC patients (P = 0.003). ALDH1(+) breast cancers tended to be aggressive, with poor prognoses. Although ALDH1(+) TNBC showed higher chemoresistance, ALDH1 had significant impact on prognosis in the luminal type but not in TNBC.

  3. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer

    DEFF Research Database (Denmark)

    Allin, Kristine H; Nordestgaard, Børge G

    2011-01-01

    -phase response, chronic inflammation, the molecular biology, function and measurement of CRP, circulating levels of CRP in health and disease, the principle of Mendelian randomization, the association between circulating levels of CRP and cancer prognosis, and cancer biomarkers. In the Copenhagen General...... increased risk of death from breast cancer compared to patients with CRP levels......The aim of this review is to summarize present evidence of an association between circulating levels of C-reactive protein (CRP) and cancer risk, and to evaluate whether elevated circulating CRP levels cause cancer. Additionally, the review provides background information on the acute...

  4. Timing of surgery during the menstrual cycle and prognosis of breast cancer

    Indian Academy of Sciences (India)

    R A Badwe; I Mittra; R Havaldar

    2000-03-01

    There are conflicting reports on the differential effect of surgery performed during the two phases of the menstrual cycle, namely, follicular and luteal, and prognosis of operable breast cancer. A statistical meta-analysis of the published evidence suggests a modest survival benefit of 15 ± 4% when the operation is performed during the lueteal phase. Further research in this area might provide a novel avenue to understand the natural history of breast cancer. A spin off from these studies might be the understanding of the importance of events that occur at the time of surgery in determining long term prognosis.

  5. A MicroRNA Expression Signature for Cervical Cancer Prognosis

    Science.gov (United States)

    Hu, Xiaoxia; Schwarz, Julie K.; Lewis, James S.; Huettner, Phyllis C.; Rader, Janet S.; Deasy, Joseph O.; Grigsby, Perry W.; Wang, Xiaowei

    2010-01-01

    Invasive cervical cancer is a leading cause of cancer death in women worldwide, resulting in about 300,000 deaths each year. The clinical outcomes of cervical cancer vary significantly and are difficult to predict. Thus, a method to reliably predict disease outcome would be important for individualized therapy by identifying patients with high-risk of treatment failures prior to therapy. In this study, we have identified a microRNA-based signature for the prediction of cervical cancer survival. MicroRNAs (miRNAs) are a newly identified family of small non-coding RNAs that are extensively involved in human cancers. Using our recently established PCR-based miRNA assays, we have analyzed 102 cervical cancers and identified two miRNAs (miR-200a and miR-9) that are likely to predict patient survival. A logistic regression model was developed based on these two miRNAs and the prognostic value of the model was subsequently validated with 42 independent cervical cancers. Furthermore, functional studies were performed to characterize the effect of miRNAs in cervical cancer cells. Our results suggest that both miR-200a and miR-9 could play important regulatory roles in cervical cancer control. In particular, miR-200a is likely to affect the metastatic potential of cervical cancer cells by simultaneously suppressing the expression of multiple genes that are important to cell motility. PMID:20124485

  6. p16 upregulation is linked to poor prognosis in ERG negative prostate cancer.

    Science.gov (United States)

    Burdelski, Christoph; Dieckmann, Tatsiana; Heumann, Asmus; Hube-Magg, Claudia; Kluth, Martina; Beyer, Burkhard; Steuber, Thomas; Pompe, Raisa; Graefen, Markus; Simon, Ronald; Minner, Sarah; Tsourlakis, Maria Christina; Koop, Christina; Izbicki, Jakob; Sauter, Guido; Krech, Till; Schlomm, Thorsten; Wilczak, Waldemar; Lebok, Patrick

    2016-09-01

    Altered expression of the p16 tumor suppressor is frequently found in prostate cancer, but its role for tumor development and patient prognosis is disputed. In order to clarify the prognostic role of p16 and to draw conclusions on interactions with key molecular features of prostate cancer, we studied p16 expression in a tissue microarray (TMA) with more than 12,400 prostate cancers and attached clinical, pathological, and molecular data such as ERG status and deletions of 3p13, 5q21, 6q15, and PTEN. p16 immunostaining was absent in non-neoplastic prostate cells but was found in 37 % of 9627 interpretable prostate cancers. Finding p16 expression in 58 % of ERG positive but in only 22 % of ERG negative cancers (p p16 upregulation and tumor phenotype or patient prognosis were strictly limited to the subset of ERG negative cancers. For example, p16 positivity increased from 15 % in Gleason ≤3 + 3 to 38 % in Gleason ≥4 + 4 cancers (p p16 upregulation was strongly linked to deletions of PTEN (p p16 upregulation is a strong prognostic factor in ERG negative cancers. The strict limitation of its prognostic impact to a molecularly defined subgroup challenges the concept of molecular prognosis testing without considering molecular subtypes.

  7. 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.

  8. Evaluation of ceruloplasmin concentration in prognosis of human cancer.

    Directory of Open Access Journals (Sweden)

    Chakravarty,Prabir Kishore

    1986-04-01

    Full Text Available The serum ceruloplasmin concentration was determined in cancer patients before and after radiotherapy, and after relapse of cancer, The ceruloplasmin concentration in patients who responded to therapy, decreased to the range of normal controls. In patients who did not respond to treatment, the ceruloplasmin concentration was more or less elevated. In patients with relapse of cancer, the ceruloplasmin concentration was higher than before treatment.

  9. Sixteen-kinase gene expression identifies luminal breast cancers with poor prognosis.

    Science.gov (United States)

    Finetti, Pascal; Cervera, Nathalie; Charafe-Jauffret, Emmanuelle; Chabannon, Christian; Charpin, Colette; Chaffanet, Max; Jacquemier, Jocelyne; Viens, Patrice; Birnbaum, Daniel; Bertucci, François

    2008-02-01

    Breast cancer is a heterogeneous disease made of various molecular subtypes with different prognosis. However, evolution remains difficult to predict within some subtypes, such as luminal A, and treatment is not as adapted as it should be. Refinement of prognostic classification and identification of new therapeutic targets are needed. Using oligonucleotide microarrays, we profiled 227 breast cancers. We focused our analysis on two major breast cancer subtypes with opposite prognosis, luminal A (n = 80) and basal (n = 58), and on genes encoding protein kinases. Whole-kinome expression separated luminal A and basal tumors. The expression (measured by a kinase score) of 16 genes encoding serine/threonine kinases involved in mitosis distinguished two subgroups of luminal A tumors: Aa, of good prognosis and Ab, of poor prognosis. This classification and its prognostic effect were validated in 276 luminal A cases from three independent series profiled across different microarray platforms. The classification outperformed the current prognostic factors in univariate and multivariate analyses in both training and validation sets. The luminal Ab subgroup, characterized by high mitotic activity compared with luminal Aa tumors, displayed clinical characteristics and a kinase score intermediate between the luminal Aa subgroup and the luminal B subtype, suggesting a continuum in luminal tumors. Some of the mitotic kinases of the signature represent therapeutic targets under investigation. The identification of luminal A cases of poor prognosis should help select appropriate treatment, whereas the identification of a relevant kinase set provides potential targets.

  10. Human breast cancer: its genetics, biology and prognosis

    NARCIS (Netherlands)

    M. Riaz (Muhammad)

    2013-01-01

    textabstractCancer is a major public health problem, being the second leading cause of death, after cardiovascular diseases1. Among women, breast cancer is the first neoplasm for incidence and the second for mortality all over the world. World-wide, an incidence of 1.4 million new cases and a mortal

  11. HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

    LENUS (Irish Health Repository)

    2012-02-01

    p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.

  12. HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

    LENUS (Irish Health Repository)

    2011-06-01

    p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.

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

    Science.gov (United States)

    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.

  14. Global histone post-translational modifications and cancer:Biomarkers for diagnosis,prognosis and treatment?

    Institute of Scientific and Technical Information of China (English)

    Shafqat; Ali; Khan; Divya; Reddy; Sanjay; Gupta

    2015-01-01

    Global alterations in epigenetic landscape are now recognized as a hallmark of cancer. Epigenetic mechanismssuch as DNA methylation,histone modifications,nucleosome positioning and non-coding RNAs are proven to have strong association with cancer. In particular,covalent post-translational modifications of histone proteins are known to play an important role in chromatin remodeling and thereby in regulation of gene expression. Further,histone modifications have also been associated with different aspects of carcinogenesis and have been studied for their role in the better management of cancer patients. In this review,we will explore and discuss how histone modifications are involved in cancer diagnosis,prognosis and treatment.

  15. Preoperative mannan-binding lectin pathway and prognosis in colorectal cancer

    DEFF Research Database (Denmark)

    Ytting, Henriette; Christensen, Ib Jarle; Jensenius, Jens Christian

    2005-01-01

    PURPOSE: Deficiency of the mannan-binding lectin (MBL) pathway of innate immunity is associated with increased susceptibility to infections. In patients with colorectal cancer (CRC), postoperative infection is associated with poor prognosis. The aim of the present study was to evaluate (1...

  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. Mining novel biomarkers for prognosis of gastric cancer with serum proteomics

    Directory of Open Access Journals (Sweden)

    Sui Mei-Hua

    2009-09-01

    Full Text Available Abstract Background Although gastric caner (GC remains the second cause of cancer-related death, useful biomarkers for prognosis are still unavailable. We present here the attempt of mining novel biomarkers for GC prognosis by using serum proteomics. Methods Sera from 43 GC patients and 41 controls with gastritis as Group 1 and 11 GC patients as Group 2 was successively detected by Surface Enhanced Laser Desorption/ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS with Q10 chip. Peaks were acquired by Ciphergen ProteinChip Software 3.2.0 and analyzed by Zhejiang University-ProteinChip Data Analysis System (ZJU-PDAS. CEA level were evaluated by chemiluminescence immunoassay. Results After median follow-up periods of 33 months, Group 1 with 4 GC patients lost was divided into 20 good-prognosis GC patients (overall survival more than 24 months and 19 poor-prognosis GC patients (no more than 24 months. The established prognosis pattern consisted of 5 novel prognosis biomarkers with 84.2% sensitivity and 85.0% specificity, which were significantly higher than those of carcinoembryonic antigen (CEA and TNM stage. We also tested prognosis pattern blindly in Group 2 with 66.7% sensitivity and 80.0% specificity. Moreover, we found that 4474-Da peak elevated significantly in GC and was associated with advanced stage (III+IV and short survival (p Conclusion We have identified a number of novel biomarkers for prognosis prediction of GC by using SELDI-TOF-MS combined with sophisticated bioinformatics. Particularly, elevated expression of 4474-Da peak showed very promising to be developed into a novel biomarker associated with biologically aggressive features of GC.

  18. The performance of the Nottingham Prognosis Index and the adjuvant online decision making tool for prognosis in early-stage breast cancer patients

    Directory of Open Access Journals (Sweden)

    Mehri Rejali

    2015-01-01

    Full Text Available Background: Prognostic tools are widely used in the practice of Oncology and have been developed to help stratify patients into specific risk-related grouping. We sought to apply of two such tools used for patients with early-stage breast cancer and to correlate them with actual outcomes. Methods: A retrospective study was designed to include early-stage breast cancer cases seen from 1994 to 2014 at the Seyedoshohada Hospital in Isfahan, Iran. Information was derived from the patients′ records, and indices were derived from prognostic tools. Information was analyzed using descriptive statistics and one sample t-test. Results: In 233 patients, the difference between the predicted overall survival (OS by the Adjuvant Online (AO prognosis tools (69.28 and the observed OS (71.2 was not statistically significant (P = 0.52, and the AO prognosis tools had predicted the patients′ OS correctly. In the Nottingham prognosis index (NPI, this difference in all groups except the very poor prognosis group was not statistically significant. Conclusions: Adjuvant Online prognosis tools were capable of predicting the 10-year OS rate although not in all of the subgroups. The NPI was capable of distinguishing good, moderate, and poor survival rates, but this ability was not visible in more specific groups with moderate and poor prognosis.

  19. 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.

  20. [Peripheral artery disease as supplemental diagnosis in coronary heart disease--influence on diagnostics, treatment and prognosis].

    Science.gov (United States)

    Espinola-Klein, C; Savvidis, S; Kopp, H

    2014-01-01

    Peripheral arterial disease (PAD) increases cardiovascular event rate in patients with coronary artery disease (CAD). Therefore PAD should be considered in patients with CAD with regard to diagnostic and therapeutic strategies. PAD may difficult diagnostic tests in CAD patients. Patients with PAD and CAD may be limited in stress testing by decreased leg perfusion. In addition, arterial puncture can be more difficult in sclerotic femoral arteries. Cardiovascular risk factors should be treated carefully in all manifestations of atherosclerosis. Target values from current guidelines are similar for PAD and CAD. Inhibitors of platelet aggregation are indication in both CAD and PAD. Exercise not only improves walking distance in patients with intermittent claudication but also improves cardiovascular prognosis in patients with atherosclerosis.

  1. Sex hormones and breast cancer risk and prognosis.

    Science.gov (United States)

    Folkerd, Elizabeth; Dowsett, Mitch

    2013-08-01

    The study of large prospective collections of plasma samples from women prior to the development of breast cancer has firmly established certain sex steroids as being significantly associated with risk. The strongest associations have been found in postmenopausal women in whom the within person variability of most hormones is markedly reduced but some positive associations have also been seen in premenopausal women. Plasma estrogens show the strongest correlations with risk and these are strengthened by measurement or calculation of the proportion of estradiol that circulates free of sex hormone binding globulin (SHBG), consistent with this being the most active fraction. The relationships have been reported to potentially explain virtually all of the association of breast cancer with body mass index in postmenopausal women; this is likely to be due to non-ovarian estrogen synthesis being prominent in subcutaneous fat. These strong relationships have led to plasma and urine estrogen levels being used as intermediate end-points in the search for genes that affect breast cancer risk via their role in steroid disposition. Plasma androgen levels also show a relationship with breast cancer risk that is weakened but not eliminated by 'correction' for estrogen levels. This has been argued to be evidence of the local production of estrogens being important in the etiology of breast cancer. Given that plasma steroid levels do not correlate closely with mammographic density, which is strongly associated with risk, the opportunity exists to combine the two factors in assessing breast cancer risk but the low availability of suitable estrogen assays is a major impediment to this. In established breast cancer, plasma estrogens have been found to correlate with gene expression of estrogen dependent genes and the expression of these varies across the menstrual cycle of premenopausal women. There is infrequently a need for routine measurement of plasma estrogen levels but it has

  2. High expression of FOXR2 in breast cancer correlates with poor prognosis.

    Science.gov (United States)

    Song, Haiping; He, Wenshan; Huang, Xiaoqing; Zhang, Huiqiong; Huang, Tao

    2016-05-01

    Forkhead box protein R2 (FOXR2) is associated with human central nervous system neoplasms. However, the expression level of FOXR2 in breast cancer specimens remains largely unknown. To identify whether FOXR2 can serve as a biomarker for the diagnosis and prognosis of breast cancer, real-time PCR and immunohistochemistry (IHC) staining were utilized to detect the expression of FOXR2. The messenger RNA (mRNA) and protein levels of FOXR2 in breast cancer samples were novelty higher compared to non-tumorous breast tissues. IHC results revealed FOXR2 expression was significantly correlated to classifications tumor size (p = 0.007) and Ki-67 (p = 0.019). The patients with high expression of FOXR2 had a significantly poor prognosis compared to those of low expression (p = 0.003), especially in the patients with tumor size ≥2 cm (p = 0.006) and lymph node metastasis status (p = 0.004). Furthermore, multivariate analysis indicated that FOXR2 expression was an independent prognostic factor for breast cancer patients (p = 0.035). This study first identifies that FOXR2 may be an important molecular marker for diagnosis and prognosis of breast cancer.

  3. Implications of microRNAs in Colorectal Cancer Development, Diagnosis, Prognosis and Therapeutics

    Directory of Open Access Journals (Sweden)

    Haiyan eZhai

    2011-11-01

    Full Text Available MicroRNAs (miRNAs are a class of non-coding small RNAs with critical regulatory functions as post-transcriptional regulators. Due to the fundamental importance and broad impact of miRNAs on multiple genes and pathways, dysregulated miRNAs have been associated with human diseases, including cancer. Colorectal cancer (CRC is among the most deadly diseases, and miRNAs offer a new frontier for target discovery and novel biomarkers for both diagnosis and prognosis. In this review, we summarize the recent advancement of miRNA research in CRC, in particular, the roles of miRNAs in colorectal cancer stem cells, EMT, chemoresistance, therapeutics, diagnosis and prognosis.

  4. A network medicine approach to build a comprehensive atlas for the prognosis of human cancer.

    Science.gov (United States)

    Zhang, Fan; Ren, Chunyan; Lau, Kwun Kit; Zheng, Zihan; Lu, Geming; Yi, Zhengzi; Zhao, Yongzhong; Su, Fei; Zhang, Shaojun; Zhang, Bin; Sobie, Eric A; Zhang, Weijia; Walsh, Martin J

    2016-11-01

    The Cancer Genome Atlas project has generated multi-dimensional and highly integrated genomic data from a large number of patient samples with detailed clinical records across many cancer types, but it remains unclear how to best integrate the massive amount of genomic data into clinical practice. We report here our methodology to build a multi-dimensional subnetwork atlas for cancer prognosis to better investigate the potential impact of multiple genetic and epigenetic (gene expression, copy number variation, microRNA expression and DNA methylation) changes on the molecular states of networks that in turn affects complex cancer survivorship. We uncover an average of 38 novel subnetworks in the protein-protein interaction network that correlate with prognosis across four prominent cancer types. The clinical utility of these subnetwork biomarkers was further evaluated by prognostic impact evaluation, functional enrichment analysis, drug target annotation, tumor stratification and independent validation. Some pathways including the dynactin, cohesion and pyruvate dehydrogenase-related subnetworks are identified as promising new targets for therapy in specific cancer types. In conclusion, this integrative analysis of existing protein interactome and cancer genomics data allows us to systematically dissect the molecular mechanisms that underlie unexpected outcomes for cancer, which could be used to better understand and predict clinical outcomes, optimize treatment and to provide new opportunities for developing therapeutics related to the subnetworks identified.

  5. Overexpression of stathmin 1 is associated with poor prognosis of patients with gastric cancer.

    Science.gov (United States)

    Ke, Bin; Wu, Liang-Liang; Liu, Ning; Zhang, Ru-Peng; Wang, Chang-Li; Liang, Han

    2013-10-01

    Recently, stathmin 1 has been proposed to function as an oncogene based on some relevant studies in multiple types of human cancers. However, the role of stathmin 1 in gastric cancer carcinogenesis has not been elucidated yet. The aim of this study was to investigate the expression of stathmin 1 as well as its association with overall survival of gastric cancer patients. The expression of stathmin 1 was detected by real-time quantitative reverse transcription polymerase chain reaction and Western blotting in gastric cancer and adjacent nontumor tissues. In addition, stathmin 1 expression was analyzed by immunohistochemistry in paraffin samples from 210 primary gastric cancer patients. The expression levels of stathmin 1 mRNA and protein in gastric cancer tissues were both significantly higher than those in adjacent nontumor tissues. In addition, the expression of stathmin 1 is correlated with Lauren's classification, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (all P stathmin 1 expression was associated with poor prognosis in gastric cancer patients (P = 0.040). Multivariate analysis demonstrated that only lymph node metastasis and TNM stage were the independent prognostic indicators for gastric cancer. Stathmin 1 expression status is not an independent prognostic factor for patients with gastric cancer. Further subgroup analysis revealed that stathmin 1 expression was significantly correlated with prognosis in diffuse type gastric cancer. This research showed that the stathmin 1 overexpression might play an important role in the pathogenesis and subsequent progression of gastric cancer. Stathmin 1 could also be a potential therapeutic target in gastric cancer, especially for diffuse type gastric cancer.

  6. Survivin: Potential role in diagnosis, prognosis and targeted therapy of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Wang; Xiao-Ping Qian; Bao-Rui Liu

    2007-01-01

    Survivin is a protein that is highly expressed in a vast number of malignancies, but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells, thus facilitating the growth of these cells.Tn the case of gastric cancer, survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells,it has been described as an "ideal target" for cancer therapy. Currently, several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis, prognosis and treatment of gastric tumors.

  7. Adjuvant androgen deprivation therapy augments cure and long-term cancer control in men with poor prognosis, nonmetastatic prostate cancer.

    NARCIS (Netherlands)

    Fleshner, N.; Keane, T.E.; Lawton, C.A.; Mulders, P.F.A.; Payne, H.; Taneja, S.S.; Morris, T.

    2008-01-01

    Historically, adjuvant androgen deprivation therapy has been viewed as a palliative treatment option for patients with poor-prognosis non-metastatic prostate cancer. In addition, guidelines from bodies such as the European Association of Urology and American Society for Clinical Oncology do not spec

  8. 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

  9. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment

    Directory of Open Access Journals (Sweden)

    Fasching Peter A

    2011-11-01

    Full Text Available Abstract Background The pathological complete response (pCR after neoadjuvant chemotherapy is a surrogate marker for a favorable prognosis in breast cancer patients. Factors capable of predicting a pCR, such as the proliferation marker Ki67, may therefore help improve our understanding of the drug response and its effect on the prognosis. This study investigated the predictive and prognostic value of Ki67 in patients with invasive breast cancer receiving neoadjuvant treatment for breast cancer. Methods Ki67 was stained routinely from core biopsies in 552 patients directly after the fixation and embedding process. HER2/neu, estrogen and progesterone receptors, and grading were also assessed before treatment. These data were used to construct univariate and multivariate models for predicting pCR and prognosis. The tumors were also classified by molecular phenotype to identify subgroups in which predicting pCR and prognosis with Ki67 might be feasible. Results Using a cut-off value of > 13% positively stained cancer cells, Ki67 was found to be an independent predictor for pCR (OR 3.5; 95% CI, 1.4, 10.1 and for overall survival (HR 8.1; 95% CI, 3.3 to 20.4 and distant disease-free survival (HR 3.2; 95% CI, 1.8 to 5.9. The mean Ki67 value was 50.6 ± 23.4% in patients with pCR. Patients without a pCR had an average of 26.7 ± 22.9% positively stained cancer cells. Conclusions Ki67 has predictive and prognostic value and is a feasible marker for clinical practice. It independently improved the prediction of treatment response and prognosis in a group of breast cancer patients receiving neoadjuvant treatment. As mean Ki67 values in patients with a pCR were very high, cut-off values in a high range above which the prognosis may be better than in patients with lower Ki67 values may be hypothesized. Larger studies will be needed in order to investigate these findings further.

  10. Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer.

    Directory of Open Access Journals (Sweden)

    Peter Arner

    Full Text Available Cancer cachexia (CC is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia.Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32 or without (n = 27 cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer.Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1 was confirmed by sandwich immunoassay to be lower in CC (p = 0.008. In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results.In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.

  11. High expression of REGγ is associated with metastasis and poor prognosis of patients with breast cancer.

    Science.gov (United States)

    Chai, Fan; Liang, Yan; Bi, Jiong; Chen, Li; Zhang, Fan; Cui, Youhong; Bian, Xiuwu; Jiang, Jun

    2014-01-01

    REGgamma (REGγ) has been recently found in several types of human cancer, however, its clinical significance in metastasis and prognosis of breast cancer remains unknown. In this study, immunohistochemical staining and western blot analysis were performed to evaluate REGγ expression in both mouse and human breast cancer specimens. We found that in MMTV-PyMT mice, 14 out of 20 (70%) mouse mammary carcinomas were REGγ positive, which was significantly higher than control (0/20, 0%, P breast cancer tissues with the paired peritumoural normal breast tissues and 140 breast benign disease tissue samples showed that REGγ was undetectable in normal breast tissues and nonmetastatic axillary lymph nodes (ALNs), whereas 111 out of 136 (81.6%) breast cancer tissue samples were REGγ positive, which was significantly higher than breast benign disease tissues (9/140, 6.4%, P breast cancer (OR = 4.369, P = 0.008). Our results suggest that the high expression of REGγ might predict metastasis and poor prognosis in breast cancer.

  12. Incorporating gene co-expression network in identification of cancer prognosis markers

    Directory of Open Access Journals (Sweden)

    Li Yang

    2010-05-01

    Full Text Available Abstract Background Extensive biomedical studies have shown that clinical and environmental risk factors may not have sufficient predictive power for cancer prognosis. The development of high-throughput profiling technologies makes it possible to survey the whole genome and search for genomic markers with predictive power. Many existing studies assume the interchangeability of gene effects and ignore the coordination among them. Results We adopt the weighted co-expression network to describe the interplay among genes. Although there are several different ways of defining gene networks, the weighted co-expression network may be preferred because of its computational simplicity, satisfactory empirical performance, and because it does not demand additional biological experiments. For cancer prognosis studies with gene expression measurements, we propose a new marker selection method that can properly incorporate the network connectivity of genes. We analyze six prognosis studies on breast cancer and lymphoma. We find that the proposed approach can identify genes that are significantly different from those using alternatives. We search published literature and find that genes identified using the proposed approach are biologically meaningful. In addition, they have better prediction performance and reproducibility than genes identified using alternatives. Conclusions The network contains important information on the functionality of genes. Incorporating the network structure can improve cancer marker identification.

  13. Circulating Tumor Cells in Breast Cancer Patients: An Evolving Role in Patient Prognosis and Disease Progression

    Directory of Open Access Journals (Sweden)

    Holly Graves

    2011-01-01

    Full Text Available In this paper, we examine the role of circulating tumor cells (CTCs in breast cancer. CTCs are tumor cells present in the peripheral blood. They are found in many different carcinomas but are not present in patients with benign disease. Recent advances in theories regarding metastasis support the role of early release of tumor cells in the neoplastic process. Furthermore, it has been found that phenotypic variation exists between the primary tumor and CTCs. Of particular interest is the incongruency found between primary tumor and CTC HER2 status in both metastatic and early breast cancer. Overall, CTCs have been shown to be a poor prognostic marker in metastatic breast cancer. CTCs in early breast cancer are not as well studied, however, several studies suggest that the presence of CTCs in early breast cancer may also suggest a poorer prognosis. Studies are currently underway looking at the use of CTC level monitoring in order to guide changes in therapy.

  14. Chalkley estimates of angiogenesis in early breast cancer--relevance to prognosis

    DEFF Research Database (Denmark)

    Offersen, Birgitte V; Sørensen, Flemming Brandt; Yilmaz, Mette;

    2002-01-01

    The aim of this study was to investigate whether Chalkley estimates of angiogenesis add new knowledge regarding prediction of prognosis in 455 consecutive early breast carcinomas, both node-positive (52%) and node-negative (48%). Median follow-up was 101 months. Intense vascularization indicated...... poor disease-specific (p = 0.003) and overall (p = 0.004) survival. In node-negative patients, Chalkley counts were not associated with prognosis, whereas in node-positive patients, high Chalkley scores indicated poor disease-specific (p = 0.0006) and overall (p = 0.0008) survival. A multivariate...... analysis showed that positive lymph nodes, high histopathological grades, and negative oestrogen receptors were independent markers of cancer-related death. A high histopathological grade was associated with cancer-related death in node-negative patients, whereas in node-positive patients, many lymph nodes...

  15. Elevated Aurora B expression contributes to chemoresistance and poor prognosis in breast cancer.

    Science.gov (United States)

    Zhang, Yiqian; Jiang, Chunling; Li, Huilan; Lv, Feng; Li, Xiaoyan; Qian, Xiaolong; Fu, Li; Xu, Bo; Guo, Xiaojing

    2015-01-01

    Aurora-B is a major kinase responsible for appropriate mitotic progression. Elevated expression of Aurora-B has been frequently associated with several types of cancer, including breast cancer. However, it is not clear whether the alteration contributes to tumor responses to therapies and prognosis. In this study, we conducted immunohistochemistry using antibodies against Aurora-B, S1981p-ATM, Ki67, and p53 in paraffin-embedded tumor tissues from 312 invasive breast cancer patients. The correlation between disease-free-survival (DFS) and Aurora-B expression was analyzed using the Kaplan-Meier method and log-rank test. A Cox proportional hazards regression analysis was used to determine whether Aurora-B was an independent prognostic factor for breast cancer. We found that Aurora-B expression was correlated with the proliferation index (P breast cancer tissues. Further we found that Aurora-B expression was associated with lymph node metastasis (P = 0.002) and histological grade (P = 0.001). Multivariate analyses indicated that elevated Aurora-B expression predicted a poor survival. In a subgroup of patients that received neoadjuvant chemotherapy, we found that elevated Aurora-B contributed to chemoresistance (P = 0.011). In conclusion, elevated Aurora-B expression in breast cancer patients contributes to chemoresistance and predicts poor prognosis.

  16. Identifying subgroups among poor prognosis patients with nonseminomatous germ cell cancer by tree modelling: a validation study.

    NARCIS (Netherlands)

    M.R. van Dijk (Merel); E.W. Steyerberg (Ewout); S.P. Stenning; J.D.F. Habbema (Dik)

    2004-01-01

    textabstractBACKGROUND: In order to target intensive treatment strategies for poor prognosis patients with non-seminomatous germ cell cancer, those with the poorest prognosis should be identified. These patients might profit most from more intensive treatment strategies. For this p

  17. Identification of inherited genetic variations influencing prognosis in early-onset breast cancer.

    Science.gov (United States)

    Rafiq, Sajjad; Tapper, William; Collins, Andrew; Khan, Sofia; Politopoulos, Ioannis; Gerty, Sue; Blomqvist, Carl; Couch, Fergus J; Nevanlinna, Heli; Liu, Jianjun; Eccles, Diana

    2013-03-15

    Genome-Wide Association Studies (GWAS) have begun to investigate associations between inherited genetic variations and breast cancer prognosis. Here, we report our findings from a GWAS conducted in 536 patients with early-onset breast cancer aged 40 or less at diagnosis and with a mean follow-up period of 4.1 years (SD = 1.96). Patients were selected from the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer. A Bonferroni correction for multiple testing determined that a P value of 1.0 × 10(-7) was a statistically significant association signal. Following quality control, we identified 487,496 single nucleotide polymorphisms (SNP) for association tests in stage 1. In stage 2, 35 SNPs with the most significant associations were genotyped in 1,516 independent cases from the same early-onset cohort. In stage 2, 11 SNPs remained associated in the same direction (P ≤ 0.05). Fixed effects meta-analysis models identified one SNP associated at close to genome wide level of significance 556 kb upstream of the ARRDC3 locus [HR = 1.61; 95% confidence interval (CI), 1.33-1.96; P = 9.5 × 10(-7)]. Four further associations at or close to the PBX1, RORα, NTN1, and SYT6 loci also came close to genome-wide significance levels (P = 10(-6)). In the first ever GWAS for the identification of SNPs associated with prognosis in patients with early-onset breast cancer, we report a SNP upstream of the ARRDC3 locus as potentially associated with prognosis (median follow-up time for genotypes: CC = 4 years, CT = 3 years, and TT = 2.7 years; Wilcoxon rank-sum test CC vs. CT, P = 4 × 10(-4) and CT vs. TT, P = 0.76). Four further loci may also be associated with prognosis.

  18. Guanine nucleotide binding protein-like 3 is a potential prognosis indicator of gastric cancer.

    Science.gov (United States)

    Chen, Jing; Dong, Shuang; Hu, Jiangfeng; Duan, Bensong; Yao, Jian; Zhang, Ruiyun; Zhou, Hongmei; Sheng, Haihui; Gao, Hengjun; Li, Shunlong; Zhang, Xianwen

    2015-01-01

    Guanine nucleotide binding protein-like 3 (GNL3) is a GIP-binding nuclear protein that has been reported to be involved in various biological processes, including cell proliferation, cellular senescence and tumorigenesis. This study aimed to investigate the expression level of GNL3 in gastric cancer and to evaluate the relationship between its expression and clinical variables and overall survival of gastric cancer patients. The expression level of GNL3 was examined in 89 human gastric cancer samples using immunohistochemistry (IHC) staining. GNL3 in gastric cancer tissues was significantly upregulated compared with paracancerous tissues. GNL3 expression in adjacent non-cancerous tissues was associated with sex and tumor size. Survival analyses showed that GNL3 expression in both gastric cancer and adjacent non-cancerous tissues were not related to overall survival. However, in the subgroup of patients with larger tumor size (≥ 6 cm), a close association was found between GNL3 expression in gastric cancer tissues and overall survival. GNL3-positive patients had a shorter survival than GNL3-negative patients. Our study suggests that GNL3 might play an important role in the progression of gastric cancer and serve as a biomarker for poor prognosis in gastric cancer patients.

  19. Characteristics of fatty acid distribution is associated with colorectal cancer prognosis.

    Science.gov (United States)

    Zhang, Junjie; Zhang, Lijian; Ye, Xiaoxia; Chen, Liyu; Zhang, Liangtao; Gao, Yihua; Kang, Jing X; Cai, Chun

    2013-05-01

    To investigate tissue fatty acid distribution in relation to the incidence of colorectal cancer prognosis, adjacent normal tissue and cancerous tissue from 35 samples of clinically incident colorectal cancer were obtained. Fatty acids were measured in the colorectal mucosa phospholipid fraction by gas chromatography mass spectrometry. Palmitoleic acid and oleic acid were significantly lower in colorectal cancerous tissue, ranging from 20% to 50% less than the adjacent normal tissue. The omega-6 (n-6) fatty acid family members (20:2, 20:3, 20:4 and 22:4) were higher by 1-3 fold in cancerous colorectal tissue. Contrary with the high level of n-6 fatty acids, about a 37% to 87% reduction in EPA and DHA was observed in colorectal cancerous tissue. A higher level of linoleic acid and arachidonic acid was detected in the C cancer stage than in the B cancer stage (pdistribution of colorectal tissue is strongly linked to the incidence of colorectal cancer. This study also provides scientific basis for identifying novel biomarkers for the diagnosis and treatment of cancer.

  20. Assessing the role of IL-35 in colorectal cancer progression and prognosis.

    Science.gov (United States)

    Zeng, Jin-Cheng; Zhang, Zhi; Li, Tian-Yu; Liang, Yan-Fang; Wang, Hong-Mei; Bao, Jing-Jing; Zhang, Jun-Ai; Wang, Wan-Dang; Xiang, Wen-Yu; Kong, Bin; Wang, Zhi-Yong; Wu, Bin-Hua; Chen, Xiao-Dong; He, Long; Zhang, Shu; Wang, Cong-Yi; Xu, Jun-Fa

    2013-01-01

    Despite the recent realization of Interleukin (IL)-35 in tumorigenesis, its exact impact on colorectal cancer (CRC) progression and prognosis, however, is yet to be elucidated clearly. We thus in the present report conducted comparative analysis of IL-35 levels between CRC patients and matched control subjects. IL-35 is highly expressed in all CRC tissues, which can be detected in vast majority of colorectal cancer cells. IL-35 levels in CRC lysates and serum samples are highly correlated to the severity of malignancy and the clinical stage of tumor. Particularly, a significant reduction for serum IL-35 was noted in patients after surgical resection, indicating that IL-35 promotes CRC progression associated with poor prognosis. Mechanistic study demonstrated a significant correlation between serum IL-35 levels and the number of peripheral regulatory T (Treg) cells in CRC patients, suggesting that IL-35 implicates in CRC pathogenesis probably by inducing Treg cells, while cancer cell-derived IL-35 may also recruit Treg cells into the tumor microenvironment in favor of tumor growth. Together, our data support that IL-35 could be a valuable biomarker for assessing CRC progression and prognosis in clinical settings.

  1. MicroRNAs in the diagnosis, prognosis and treatment of cancer

    Directory of Open Access Journals (Sweden)

    Violaine Havelange

    2011-12-01

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs that regulate critical cell processes such as cell proliferation, apoptosis and differentiation by modulating gene expression. MiRNAs deregulation has been observed extensively in cancer. Elegant studies have demonstrated that miRNAs are involved in the initiation and progression of several malignancies. In this review we will address the role of miRNAs in the diagnosis and prognosis of cancer. The development of new drugs mimicking or blocking miRNAs will be discussed.

  2. Soluble and nuclear oestrogen receptor status in human breast cancer in relation to prognosis.

    Science.gov (United States)

    Leake, R E; Laing, L; McArdle, C; Smith, D C

    1981-01-01

    The relationship between oestrogen receptor (RE) content of primary breast cancer and subsequent prognosis was examined with regard to nodal status. It was found that, within a particular nodal group, patients with tumours containing fully functional RE experienced a longer disease-free interval than those with RE- disease. An earlier observation that RE- primary disease gave rise to distant metastases as first site of recurrence more frequently than did RE+ disease, was not sustained. However, patients with RE+ primary disease had a much reduced chance of dying from cancer within a 3-year period.

  3. The basic mechanisms the influence of metabolic syndrome on the risk and prognosis of breast cancer (review

    Directory of Open Access Journals (Sweden)

    I. B. Schepotin

    2013-01-01

    Full Text Available Breast cancer and metabolic syndrome remains one of the most urgent problems of modern medicine worldwide. In this review, highlights the molecular pathways that underlie the negative impact of metabolic syndrome on the risk and prognosis of breast cancer. A better understanding of these pathways will help to optimize prevention and treatment of breast cancer in patients with metabolic syndrome.

  4. DISSECTING AORTIC ANEURYSM IN REAL–LIFE CLINICAL PRACTICE: DIAGNOSTICS, TREATMENT AND PROGNOSIS

    Directory of Open Access Journals (Sweden)

    S. V. Seleznev

    2016-01-01

    Full Text Available Objective: analysis of clinical features of the dissecting aortic aneurysm (DAA and factors affecting prognosis in a group of 40 patients, hospitalized in Ryazan Regional Cardiology Dispensary during 2008–2012.Material and methods. We have analyzed clinical data of 40 patients with DAA, assessed their survival and identified factors affecting prognosis.Results. The mean age of the patients was 61.1 ± 15.6 years; 82 % of them were males. 80 % of the patients were hospitalized in the acute period of the disease, 60 % – during the first 24 hours. 4 2 % of the patients had DAA as a referral diagnosis. The main clinical manifestations of DAA included: chest pain and abdominal pain (92 %, weakness (51 %, shortness of breath (28 %, heart disruptions (8 %, dizziness (5 %, and cough (3 %. Pain syndrome was absent in 8 % of the DAA patients. At physical examination 49 % of the patients demonstrated pale skin, 1 patient (3 % had cyanotic skin. Low blood pressure was observed in 33 % of the cases, tachycardia – in 31 %, and tachypnea – in 13 % of the cases. 26 % of the patients were found to have murmur over the aorta, 10 % – abnormal heart rhythm. 44 % showed tenderness on palpation of the abdomen.Electrocardiography was carried out for 97 % of the study population, chest X-ray for 33 %, transthoracic echocardiography for 4 4 %, and computed tomography (CT for 42 %, including contrast-enhanced computed tomography scanning for 38 %. 31 % of the patients received antiplatelet agents and anticoagulants. 24 % of the patients underwent surgical treatment in Ryazan» Regional Cardiology Dispensary, 36 % were referred to Federal centers of cardiovascular surgery. In-hospital mortality rate was 52 %, 24-hour mortality rate was 30 %. The following factors were found to be statistically significant in terms of the disease prognosis: systolic and diastolic blood pressure, left ventricular ejection fraction, levels of hemoglobin, blood urea and creatinine

  5. Peritoneal lavage cytology and carcinoembryonic antigen determination in predicting peritoneal metastasis and prognosis of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ji-Kun Li; Miao Zheng; Chuan-Wen Miao; Jian-Hai Zhang; Guang-Han Ding; Wen-Shen Wu

    2005-01-01

    AIM: To evaluate the role of peritoneal lavage cytology (PLC) and carcinoembryonic antigen (CEA) determination of peritoneal washes (pCEA) in predicting the peritoneal metastasis and prognosis after curative resection of gastric cancer.METHODS: PLC and radioimmunoassay of CEA were performed in peritoneal washes from 64 patients with gastric cancer and 8 patients with benign diseases.RESULTS: The positive rate of pCEA (40.6%) was significantly higher than that of PLC (23.4%) (P<0.05).The positive rates of PLC and pCEA correlated with the depth of tumor invasion and lymph node metastasis (P<0.05). pCEA was found to have a higher sensitivity and a lower false-positive rate in predicting peritoneal metastasis after curative resection of gastric cancer as compared to PLC. The 1-, 3-, and 5-year survival rates of patients with positive cytologic findings or positive pCEA results were significantly lower than those of patients with negative cytologic findings or negative pCEA results (P<0.05). Multivariate analysis indicated that pCEA was an independent prognostic factor for the survival of patients with gastric cancer.CONCLUSION: Intraoperative pCEA is a more sensitive and reliable predictor of peritoneal metastasis as well as prognosis in patients with gastric cancer as compared to PLC method.

  6. MicroRNAs in Pancreatic Cancer: Involvement in Carcinogenesis and Potential Use for Diagnosis and Prognosis

    Directory of Open Access Journals (Sweden)

    Tereza Halkova

    2015-01-01

    Full Text Available Pancreatic cancer is one of the most fatal malignancies with increasing incidence and high mortality. Possibilities for early diagnosis are limited and there is currently no efficient therapy. Molecular markers that have been introduced into diagnosis and treatment of other solid tumors remain unreciprocated in this disease. Recent discoveries have shown that certain microRNAs (miRNAs take part in fundamental molecular processes associated with pancreatic cancer initiation and progression including cell cycle, DNA repair, apoptosis, invasivity, and metastasis. The mechanism involves both positive and negative regulation of expression of protooncogenes and tumor suppressor genes. Various miRNAs are expressed at different levels among normal pancreatic tissue, chronic pancreatitis, and pancreatic cancer and may therefore serve as a tool to differentiate chronic pancreatitis from early stages of cancer. Other miRNAs can indicate the probable course of the disease or determine the survival prognosis. In addition, there is a growing interest directed at the understanding of miRNA-induced molecular mechanisms. The possibility of intervention in the molecular mechanisms of miRNAs regulation could begin a new generation of pancreatic cancer therapies. This review summarizes the recent reports describing functions of miRNAs in cellular processes underlying pancreatic cancerogenesis and their utility in diagnosis, survival prognosis, and therapy.

  7. 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...

  8. 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...

  9. Not telling the truth: circumstances leading to concealment of diagnosis and prognosis from cancer patients.

    Science.gov (United States)

    Shahidi, J

    2010-09-01

    While autonomy has gradually become a key concept in the doctor-patient relationship, truth-telling is far from being the norm in many countries in the world. Despite the general agreement on the benefits of open communication between physicians and cancer patients, there is still strong resistance against disclosure of cancer diagnosis and prognosis in many cultures. Although fear of causing psychological morbidity to patients and their reluctance to find out the truth are two main justifications of non-disclosure attitudes, there are other important contributing factors that need to be further explored and better understood including those related to the relatives, doctors and healthcare systems. Cultural disparities in attitudes towards truth-telling persist; however, these differences should not be used as excuses not to respect the rights and individual preferences of cancer patients by making assumptions based on their age, sex, type of cancer, language and/or cultural background.

  10. Prognosis of invasive breast cancer after adjuvant therapy evaluated with VEGF microvessel density and microvascular imaging.

    Science.gov (United States)

    Li, Ying; Wei, Xi; Zhang, Sheng; Zhang, Jin

    2015-11-01

    The aim of this study was to investigate the role of ultrasonographic microvascular imaging in the evaluation of prognosis of patients with invasive breast cancer treated by adjuvant therapies. A total of 121 patients with invasive breast cancer underwent ultrasonographic contrast-enhanced imaging, vascular endothelial growth factor (VEGF) staining, and microvessel density (MVD) counts. The parameters of microvascular imaging and the expression of VEGF and MVD in primary breast cancer were calculated. The correlation between these factors and the overall and progression-free survival rate were analyzed using the Kaplan-Meier method. Among 121 cases, the positive VEGF cases were 75 and negative ones were 46. The cut point of 52.3 was calculated by the regressive curve for MVD counts. The data showed the mean intensity (MI) was positively associated with both the MVD counts (r = .51, p prognosis of patients, high VEGF expression and MVD counts were associated with reduced progressive and survival times (PFS, p = .032 and p = .034; OS, p = .041 and p = .038, respectively). The correlation between parameters of microvascular imaging, VEGF expressive status, and the MVD counts were established. The cut point of mean intensity (MI = 40) was used to investigate as an independent predictor for PFS (p = .021) and OS (p = .025), respectively, due to a strong correlation between MVD counts and VEGF expression in patients with invasive breast cancer. The microvascular imaging could be a visual and helpful tool to predict the prognosis of patients with invasive breast cancer treated by adjuvant therapies.

  11. The associations between immunity-related genes and breast cancer prognosis in Korean women.

    Directory of Open Access Journals (Sweden)

    Jaesung Choi

    Full Text Available We investigated the role of common genetic variation in immune-related genes on breast cancer disease-free survival (DFS in Korean women. 107 breast cancer patients of the Seoul Breast Cancer Study (SEBCS were selected for this study. A total of 2,432 tag single nucleotide polymorphisms (SNPs in 283 immune-related genes were genotyped with the GoldenGate Oligonucleotide pool assay (OPA. A multivariate Cox-proportional hazard model and polygenic risk score model were used to estimate the effects of SNPs on breast cancer prognosis. Harrell's C index was calculated to estimate the predictive accuracy of polygenic risk score model. Subsequently, an extended gene set enrichment analysis (GSEA-SNP was conducted to approximate the biological pathway. In addition, to confirm our results with current evidence, previous studies were systematically reviewed. Sixty-two SNPs were statistically significant at p-value less than 0.05. The most significant SNPs were rs1952438 in SOCS4 gene (hazard ratio (HR = 11.99, 95% CI = 3.62-39.72, P = 4.84E-05, rs2289278 in TSLP gene (HR = 4.25, 95% CI = 2.10-8.62, P = 5.99E-05 and rs2074724 in HGF gene (HR = 4.63, 95% CI = 2.18-9.87, P = 7.04E-05. In the polygenic risk score model, the HR of women in the 3rd tertile was 6.78 (95% CI = 1.48-31.06 compared to patients in the 1st tertile of polygenic risk score. Harrell's C index was 0.813 with total patients and 0.924 in 4-fold cross validation. In the pathway analysis, 18 pathways were significantly associated with breast cancer prognosis (P<0.1. The IL-6R, IL-8, IL-10RB, IL-12A, and IL-12B was associated with the prognosis of cancer in data of both our study and a previous study. Therefore, our results suggest that genetic polymorphisms in immune-related genes have relevance to breast cancer prognosis among Korean women.

  12. JAM-A expression positively correlates with poor prognosis in breast cancer patients.

    Science.gov (United States)

    McSherry, Elaine A; McGee, Sharon F; Jirstrom, Karin; Doyle, Emma M; Brennan, Donal J; Landberg, Goran; Dervan, Peter A; Hopkins, Ann M; Gallagher, William M

    2009-09-15

    The cell-cell adhesion protein junctional adhesion molecule-A (JAM-A) influences epithelial cell morphology and migration. As migration is required for tumor cell invasion and metastasis, we sought to elucidate the role of JAM-A in invasive breast cancer. A breast cancer tissue microarray was analyzed for JAM-A protein expression, in parallel with analysis of JAM-A gene expression data from a breast cancer clinical dataset. Our data demonstrate a novel association between JAM-A gene and protein upregulation and poor prognosis in breast cancer. To mechanistically dissect this process, we used lentiviral technology to stably knock down JAM-A gene expression by shRNA in MCF7 breast cancer cells, which express high-endogenous levels of JAM-A. We also antagonized JAM-A function in wild-type MCF7 cells using an inhibitory antibody that blocks JAM-A dimerization. Knockdown or functional antagonism of JAM-A decreased breast cancer cell migration in scratch-wound assays. Reductions in beta1-integrin protein levels were observed after JAM-A-knockdown in MCF7 cells, suggesting a mechanism for reduced motility after loss of JAM-A. Consistent with this hypothesis, tissue microarray analysis of beta1-integrin protein expression in invasive breast cancer tissues revealed a trend toward high beta1-integrin protein levels being indicative of poor prognosis. Twenty-two percent of patients were observed to coexpress high levels of JAM-A and beta1-integrin protein, and MDA-MB-231 breast cells stably overexpressing JAM-A showed an increase in beta1-integrin protein expression. Our results are consistent with a previously unreported role for JAM-A overexpression as a possible mechanism contributing to progression in primary breast cancer; and a potential therapeutic target.

  13. Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer.

    Science.gov (United States)

    Yan, Shushan; Wang, Zengfang; Wang, Zengyan; Duan, Quanhong; Wang, Xiaochen; Li, Jun; Sun, Beicheng

    2016-08-01

    Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta-analysis relating OS (I (2) = 0 %) and DFS (I (2) = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07-1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03-1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer.

  14. Is the lymph node ratio superior to the Union for International Cancer Control (UICC) TNM system in prognosis of colon cancer?

    OpenAIRE

    2013-01-01

    Background Decision making for adjuvant chemotherapy in stage III colon cancer is based on the TNM system. It is well known that prognosis worsens with higher pN classification, and several recent studies propose superiority of the lymph node ratio (ln ratio) to the TNM system. Therefore, we compared the prognosis of ln ratio to TNM system in our stage III colon cancer patients. Methods A total of 939 patients underwent radical surgery for colorectal cancer between January 2000 and December 2...

  15. Myofibrillogenesis regulator-1 overexpression is associated with poor prognosis of gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    Jing Guo; Bin Dong; Jia-Fu Ji; Ai-Wen Wu

    2012-01-01

    AIM:To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer.METHODS:In our previous study of human wholegenome gene expression profiling,the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa.We found that MR-1 was associated with the location and differentiation of tumors.In this study,MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients.A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized,fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA.The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients.A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records.RESULTS:MR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues.MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238,P < 0.001) and protein levels (34.2% vs 13.2%,P =0.003) in gastric cancer tissues.Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P =0.034).Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group,and the difference was statistically significant (P =0.002).Among all the patients with stage Ⅰ-Ⅳ carcinoma,the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%,respectively,with respective median survival times of 64.27 mo (95

  16. Decreased expression of SOX17 is associated with tumor progression and poor prognosis in breast cancer.

    Science.gov (United States)

    Fu, De-Yuan; Tan, Hao-Sheng; Wei, Jin-Li; Zhu, Chang-Ren; Jiang, Ji-Xin; Zhu, Yu-Xiang; Cai, Feng-Lin; Chong, Mei-Hong; Ren, Chuan-Li

    2015-09-01

    The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of biological processes and is related to the tumorigenesis and progression of multiple tumors. However, the clinical application of SOX17 for breast cancer prognosis is currently limited. The aim of this study was to investigate the clinicopathologic and prognostic significance of SOX17 expression in human breast cancer. qPCR and western blot assays were performed to measure the expression of SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and corresponding noncancerous tissues. A SOX17 overexpression cell model was used to examine changes in cell growth in vitro. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of SOX17 expression in 187 additional breast cancer patients. Our results showed that SOX17 expression was decreased at both the messenger RNA (mRNA) and protein levels in the breast cancer cell lines and tissues, and that SOX17 overexpression could strongly suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression was strongly correlated with higher tumor grade (P = 0.002), lymph node metastasis (P breast cancer. Our findings indicate that SOX17 expression is a useful prognostic biomarker for breast cancer.

  17. Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy

    Science.gov (United States)

    Peng, Peike; Min, Lingqiang; Song, Shushu; Zhao, Junjie; Li, Lili; Yang, Caiting; Shao, Miaomiao; Zhang, Mingming; Wu, Hao; Zhang, Jie; Li, Can; Wang, Xuefei; Wang, Hongshan; Qin, Jing; Ruan, Yuanyuan; Gu, Jianxin

    2016-01-01

    Calpain-4 belongs to the calpain family of calcium-dependent cysteine proteases, and functions as a small regulatory subunit of the calpains. Recent evidence indicates that calpain-4 plays critical roles in tumor migration and invasion. However, the roles of calpain-4 in gastric tumorigenesis remain poorly understood. Herein, we examined calpain-4 expression by immunohistochemical staining on tissue microarrays containing tumor samples of 174 gastric cancer patients between 2004 and 2008 at a single center. The Kaplan-Meier method was used to compare survival curves, and expression levels were correlated to clinicopathological factors and overall survival. Our data demonstrated that calpain-4 was generally increased in gastric cancer cell lines and primary tumor tissues. High expression of calpain-4 was positively associated with vessel invasion, lymph node metastasis, and advanced TNM (Tumor Node Metastasis) stage. Multivariate analysis identified calpain-4 as an independent prognostic factor for poor prognosis. A predictive nomogram integrating calpain-4 expression with other independent prognosticators was constructed, which generated a better prognostic value for overall survival of gastric cancer patients than a TNM staging system. In conclusion, calpain-4 could be regarded as a potential prognosis indicator for clinical outcomes in gastric cancer. PMID:27689993

  18. Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy

    Directory of Open Access Journals (Sweden)

    Peike Peng

    2016-09-01

    Full Text Available Calpain-4 belongs to the calpain family of calcium-dependent cysteine proteases, and functions as a small regulatory subunit of the calpains. Recent evidence indicates that calpain-4 plays critical roles in tumor migration and invasion. However, the roles of calpain-4 in gastric tumorigenesis remain poorly understood. Herein, we examined calpain-4 expression by immunohistochemical staining on tissue microarrays containing tumor samples of 174 gastric cancer patients between 2004 and 2008 at a single center. The Kaplan-Meier method was used to compare survival curves, and expression levels were correlated to clinicopathological factors and overall survival. Our data demonstrated that calpain-4 was generally increased in gastric cancer cell lines and primary tumor tissues. High expression of calpain-4 was positively associated with vessel invasion, lymph node metastasis, and advanced TNM (Tumor Node Metastasis stage. Multivariate analysis identified calpain-4 as an independent prognostic factor for poor prognosis. A predictive nomogram integrating calpain-4 expression with other independent prognosticators was constructed, which generated a better prognostic value for overall survival of gastric cancer patients than a TNM staging system. In conclusion, calpain-4 could be regarded as a potential prognosis indicator for clinical outcomes in gastric cancer.

  19. Pregnancy after treatment of breast cancer in young women does not adversely affect the prognosis.

    Science.gov (United States)

    Córdoba, Octavi; Bellet, Meritxell; Vidal, Xavier; Cortés, Javier; Llurba, Elisa; Rubio, Isabel T; Xercavins, Jordi

    2012-06-01

    We assessed whether pregnancy after breast cancer in patients younger than 36 years of age affects the prognosis. Of 115 women with breast cancer followed for a mean of 6 years, 18 became pregnant (median time between diagnosis and the first pregnancy 44.5 months). Voluntary interruption of pregnancy was decided by 8 (44.4%) women. Significant differences in prognostic factors between pregnant and non-pregnant women were not observed. Pregnant women showed a lower frequency of positive estrogen receptors (41%) than non-pregnant (64%) (P=0.06). At 5 years of follow-up, 100% of women in the pregnant group and 80% in the non-pregnant group were alive. The percentages of disease-free women were 94% and 64%, respectively (P=0.009). Breast cancer patients presented a high number of unwanted pregnancies. Pregnancy after breast cancer not only did not adversely affect prognosis of the neoplasm but also may have a protective effect.

  20. Testing breast cancer serum biomarkers for early detection and prognosis in pre-diagnosis samples

    Science.gov (United States)

    Kazarian, Anna; Blyuss, Oleg; Metodieva, Gergana; Gentry-Maharaj, Aleksandra; Ryan, Andy; Kiseleva, Elena M; Prytomanova, Olga M; Jacobs, Ian J; Widschwendter, Martin; Menon, Usha; Timms, John F

    2017-01-01

    Background: Breast cancer is a leading cause of morbidity and mortality worldwide. Although mammography screening is available, there is an ongoing interest in improved early detection and prognosis. Herein, we have analysed a combination of serological biomarkers in a case–control cohort of sera taken before diagnosis. Methods: This nested case–control study within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) used serum samples from 239 women who subsequently developed breast cancer and 239 matched cancer-free controls. Sera were screened by ELISA for 9 candidate markers. Univariate and multivariate analyses were performed to examine associations with clinico-pathological features and between case controls in different time groups before diagnosis. Results: Significant associations with clinico-pathological features related to prognosis were found for several candidates (CA15-3, HSP90A and PAI-1). However, there were no consistent differences between cases and controls for any candidate in the lead up to diagnosis. Whilst combination models outperformed single markers, there was no increase in performance towards diagnosis. Conclusions: This study using unique pre-diagnosis samples shows that CA15-3, HSP90A and PAI-1 have potential as early prognostic markers and warrant further investigation. However, none of the candidates or combinations would be useful for screening. PMID:28081538

  1. Stem cell-like gene expression in ovarian cancer predicts type II subtype and prognosis.

    Directory of Open Access Journals (Sweden)

    Matthew Schwede

    Full Text Available Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age, the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further

  2. Tumor markers for diagnosis, monitoring of recurrence and prognosis in patients with upper gastrointestinal tract cancer.

    Science.gov (United States)

    Jing, Jie-Xian; Wang, Yan; Xu, Xiao-Qin; Sun, Ting; Tian, Bao-Guo; Du, Li-Li; Zhao, Xian-Wen; Han, Cun-Zhi

    2014-01-01

    To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (pdiagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.

  3. Analysis of the Clinicopathologic Features and Prognosis in Triple-Negative Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Dehong Yang; Hong Liu; Jing Zhao

    2008-01-01

    OBJECTIVE To investigate the clinical and pathological features,as well as prognosis in triple-negative breast cancer patients.METHODS A total of 509 cases of operable breast cancer from January,2002 to June,2002 treated in the Cancer Hospital of Tianjin Medical University were analyzed.The Her-2,ER and PR status was determined using immunohistochemistry.Of the total cases,one group was identified as triple negative breast cancer,ie defined as ER,PR and Her-2 negative.The other group was nontriple-negative breast cancer.Clinicopathologic features of the groups were compared and 5-year disease-free survival (DFS)analyzed by the Kaplan-Meier method.RESULTS Of the total cases,21.4% (109/509) of cases were found to be triple- negative while 78.6% (400/509) were non-triplenegative.The triple negative group had higher incidence rates than the non-triple-negative group of the medullary type and Grade Ⅲ tumors (P < 0.05).There was no other difference in the clinicopathologic features between the 2 groups.From follow-up to June,2007,21.1% (23/109) of the triple-negative group and 12.7%(51/400) of the non-triple negative group had a local recurrence or distant metastasis,resulting in a significant difference (P < 0.05).In the triple-negative group and non-triple-negative group,5-year DFS were 78.9% and 87.3% respectively.There was a statistically significant difference between the 2 groups (P = 0.031).CONCLUSION Compared with non-triple-negative breast cancer,triple-negative breast cancer patients have an increased likehood of a local recurrence or distant metastasis and a poorer prognosis.

  4. Status and prognosis of lymph node metastasis in patients with cardia cancer - a systematic review

    DEFF Research Database (Denmark)

    Okholm, Cecilie; Svendsen, Lars Bo; Achiam, Michael P

    2014-01-01

    BACKGROUND: Adenocarcinoma of the gastroesophageal junction (GEJ) has a poor prognosis and survival rates significantly decreases if lymph node metastasis is present. An extensive lymphadenectomy may increase chances of cure, but may also lead to further postoperative morbidity and mortality...... identifying relevant studies describing lymph node metastasis and the associated prognosis. Lymph node stations were classified according to the Japanese Gastric Cancer Association guidelines. RESULTS: The highest incidence of metastasis is seen in the nearest regional lymph nodes, station no. 1......-3 and additionally in no. 7, 9 and 11. Correspondingly the best survival is seen when metastasis remain in the most locoregional nodes and survival equally tends to decrease as the metastasis become more distant. Furthermore, the presence of lymph node metastasis significantly correlates to the TNM-stage. Incidences...

  5. Relationship between H.Pylori infection and clinicopathological features and prognosis of gastric cancer

    Directory of Open Access Journals (Sweden)

    Wang Guo-Qiang

    2010-07-01

    Full Text Available Abstract Background Aimed to assess the relationship between H.Pylori and the clinicopathological features and prognosis of gastric cancer by quantitative detection of H.Pylori. Methods 157 patients were enrolled, all patients had a record of clinicopathological parameters. Specimens including the tumor and non-neoplastic were detected for H.Pylori by Real-Time PCR and analyzed clinical data retrospectively. Variables independently affecting prognosis were investigated by means of multivariate analysis using the Cox proportional hazards model. Results H.Pylori infection was greater in non-neoplastic tissue than the tumor tissue (p Conclusions H.Pylori infection status and its copies were related to N staging. The OS and RFS in patients with positive H.Pylori status has no significant difference from the patients with negative H.Pylori status.

  6. Malignant Melanoma of the Urethra: A Rare Histologic Subdivision of Vulvar Cancer with a Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Veronika Günther

    2012-01-01

    Full Text Available Malignant melanoma of the urethra is a rare tumour that is difficult to diagnose and treat, resulting in a poor prognosis. In this paper, we present the case of a 65-year-old woman who was referred to a gynaecologist because of a urethral mass that mimicked a caruncle. The tumour was removed by local excision, and a pathological analysis revealed a malignant melanoma. Distal urethrectomy was performed after three months with no evidence of residual tumour. There was no evidence of disease at a six-year followup. In this paper, we compare the epidemiology, treatment, staging, and prognosis of vulvar cancer in general to malignant melanoma of the vulva in particular.

  7. 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.

  8. Clinical value of prognosis gene expression signatures in colorectal cancer: a systematic review.

    Directory of Open Access Journals (Sweden)

    Rebeca Sanz-Pamplona

    Full Text Available INTRODUCTION: The traditional staging system is inadequate to identify those patients with stage II colorectal cancer (CRC at high risk of recurrence or with stage III CRC at low risk. A number of gene expression signatures to predict CRC prognosis have been proposed, but none is routinely used in the clinic. The aim of this work was to assess the prediction ability and potential clinical usefulness of these signatures in a series of independent datasets. METHODS: A literature review identified 31 gene expression signatures that used gene expression data to predict prognosis in CRC tissue. The search was based on the PubMed database and was restricted to papers published from January 2004 to December 2011. Eleven CRC gene expression datasets with outcome information were identified and downloaded from public repositories. Random Forest classifier was used to build predictors from the gene lists. Matthews correlation coefficient was chosen as a measure of classification accuracy and its associated p-value was used to assess association with prognosis. For clinical usefulness evaluation, positive and negative post-tests probabilities were computed in stage II and III samples. RESULTS: Five gene signatures showed significant association with prognosis and provided reasonable prediction accuracy in their own training datasets. Nevertheless, all signatures showed low reproducibility in independent data. Stratified analyses by stage or microsatellite instability status showed significant association but limited discrimination ability, especially in stage II tumors. From a clinical perspective, the most predictive signatures showed a minor but significant improvement over the classical staging system. CONCLUSIONS: The published signatures show low prediction accuracy but moderate clinical usefulness. Although gene expression data may inform prognosis, better strategies for signature validation are needed to encourage their widespread use in the clinic.

  9. Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?

    Science.gov (United States)

    Bigley, Austin B; Spielmann, Guillaume; LaVoy, Emily C P; Simpson, Richard J

    2013-09-01

    Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients.

  10. Colorectal cancers with aneuploids show high CD133 expression and poor prognosis

    Institute of Scientific and Technical Information of China (English)

    Dongdong Yu; Yonghong Zhang; You Zou; Ming Tian; Deding Tao; Junbo Hu; Jianping Gong

    2010-01-01

    Objective:The aim of the study was to investigate the relationship of DNA ploidy status in colorectal cancers with patients' prognosis and also the relationship of DNA ploidy status with expression of the colorectal cancer stem cell marker CD133.Methods:The DNA ploidy status and CD133 expression in colorectal cancers were detected by flow cytometry.The clinicopathological characteristics and progression-free survival analysis of patients was evaluated based on the clinical data.Results:DNA ploidy pattern did not correlated with gender,age,lesion diameter,histological type,depth of tumor invasion,lymphatic invasion and Dukes stage.Only primary lesion cite showed significant correlation with DNA ploidy pattern,more aneuploids were observed in colonic cancer than rectal cancer,P < 0.05.The 2-year progression-free survival rate and total progression-free time in patients with aneuploids were lower than that with diploids,P < 0.05.Tumors contained aneuploids showed higher expression of CD133 than tumors of only diploids,P < 0.05.Conclusion:Tumor DNA ploidy status is a significant prognostic factor in patients with colorectal cancer and also associated with the existence of CD133 positive colorectal cancer stem cells.

  11. CD147 expression in human gastric cancer is associated with tumor recurrence and prognosis.

    Directory of Open Access Journals (Sweden)

    Dake Chu

    Full Text Available CD147 is correlated with tumor aggressiveness in various human malignancies. Here, we investigated CD147 protein expression in 223 patients with gastric cancer by immunohistochemistry and analyzed its association with disease-free and overall survival. CD147 was increased in gastric cancer compared to normal tissues. Additionally, CD147 expression was associated with gastric cancer invasion, metastasis and TNM stage, whereas it was not related to age, sex, differentiation status, tumor site or Lauren classification. Kaplan-Meier analysis confirmed that CD147 was associated with disease-free and overall survival in patients with gastric cancer; i.e., patients with positive CD147 staining tend to have worse disease-free and overall survival. Moreover, Cox's proportional hazards analysis demonstrated that CD147 was an independent marker of disease-free and overall survival for patients with gastric cancer. These results confirm the association of CD147 with gastric cancer invasion and metastasis and prove that CD147 might be an indicator of tumor recurrence and prognosis in gastric cancer.

  12. CD147 expression in human gastric cancer is associated with tumor recurrence and prognosis.

    Science.gov (United States)

    Chu, Dake; Zhu, Shaojun; Li, Jipeng; Ji, Gang; Wang, Weizhong; Wu, Guosheng; Zheng, Jianyong

    2014-01-01

    CD147 is correlated with tumor aggressiveness in various human malignancies. Here, we investigated CD147 protein expression in 223 patients with gastric cancer by immunohistochemistry and analyzed its association with disease-free and overall survival. CD147 was increased in gastric cancer compared to normal tissues. Additionally, CD147 expression was associated with gastric cancer invasion, metastasis and TNM stage, whereas it was not related to age, sex, differentiation status, tumor site or Lauren classification. Kaplan-Meier analysis confirmed that CD147 was associated with disease-free and overall survival in patients with gastric cancer; i.e., patients with positive CD147 staining tend to have worse disease-free and overall survival. Moreover, Cox's proportional hazards analysis demonstrated that CD147 was an independent marker of disease-free and overall survival for patients with gastric cancer. These results confirm the association of CD147 with gastric cancer invasion and metastasis and prove that CD147 might be an indicator of tumor recurrence and prognosis in gastric cancer.

  13. Growth Factor Receptors and Apoptosis Regulators: Signaling Pathways, Prognosis, Chemosensitivity and Treatment Outcomes of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Siddik Sarkar

    2009-01-01

    Full Text Available Biomarkers of breast cancer are necessary for prognosis and prediction to chemotherapy. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancers are growth factor receptors, steroid receptors, Ki-67, cyclins, urokinase plasminogen activator, p53, p21, pro- and anti-apoptotic factors, BRCA1 and BRCA2. But currently, the predictive markers are Estrogen and Progesterone receptors responding to endocrine therapy, and HER-2 responding to herceptin. But there are numerous breast cancer cases, where tamoxifen is ineffective even after estrogen receptor positivity. This lead to search of new prognostic and predictive markers and the number of potential markers is constantly increasing due to proteomics and genomics studies. However, most biomarkers individually have poor sensitivity or specificity, or other clinical value. It can be resolved by studying various biomarkers simultaneously, which will help in better prognosis and increasing sensitivity for chemotherapeutic agents. This review is focusing on growth factor receptors, apoptosis markers, signaling cascades, and their correlation with other associated biomarkers in breast cancers. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors. Rigorous comparison of these existing as well as emerging markers with current treatment selection is likely to see an escalation in an era of personalized medicines to ensure the breast cancer patients receive optimal treatment. This will also solve the treatment modalities and complications related to chemotherapeutic regimens.

  14. Menopausal symptoms among breast cancer patients: a potential indicator of favorable prognosis.

    Directory of Open Access Journals (Sweden)

    Yong Chen

    Full Text Available Menopausal symptoms have been suggested to be an indicator of better prognosis among patients treated for breast cancer, because women who experience these symptoms usually have a lower level of estrogen. We tested this hypothesis in a population-based, prospective cohort study involving 4,842 women with stage 0 to III primary breast cancer who were enrolled in the Shanghai Breast Cancer Survival Study between March 2002 and April 2006, were aged 20 to 75 years, and were recruited 6 months post-diagnosis. They were followed-up by in-person surveys and record linkages with the vital statistics registry. Cox regression analysis was used to evaluate the association of menopausal symptoms at baseline with breast cancer recurrence. Approximately 56% of patients experienced at least one menopausal symptom, including hot flashes, night sweats, and/or vaginal dryness at baseline. During a median follow-up period of 5.3 years, 720 women had a recurrence. Experiencing hot flashes or having ≥2 menopausal symptoms was associated with lower risk of recurrence among premenopausal women (hazard ratio [HR]=0.77, 95% confidence interval [CI]: 0.62-0.96 for hot flashes; 0.73, 0.56-0.96 for ≥2 menopausal symptoms. Lower recurrence risk in relation to hot flashes was also observed among women who were not overweight/obese (HR=0.78, 95% CI: 0.64-0.99, those with relatively low waist-to-hip ratio (WHR (HR=0.77, 95% CI: 0.61-0.97, and those who used tamoxifen (HR=0.75, 95% CI: 0.58-0.98. Consistently experiencing multiple menopausal symptoms was associated with lower recurrence risk among women with low WHR or who used tamoxifen. This large, population-based cohort study of women with breast cancer confirms that experiencing menopausal symptoms is an indicator of favorable breast cancer prognosis.

  15. Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

    Science.gov (United States)

    Lan, Xiuwen; Li, Sen; Gao, Hongyu; Nanding, Abiyasi; Quan, Lina; Yang, Chunyan; Ding, Shaohua; Xue, Yingwei

    2017-01-01

    Purpose Deregulation of immune checkpoint molecules by tumor cells is related to immune escape. This study was conducted to investigate the relationship between the appearance of B- and T-lymphocyte attenuator (BTLA) and its ligand herpesvirus entry mediator (HVEM) with the prognosis in gastric cancer patients. Patients and methods A total of 136 patients with curative gastrectomy were included. The expression of BTLA and HVEM was detected by immunohistochemistry, and its correlation with the clinical significance of gastric cancer was further analyzed. Results The positivity of BTLA and HVEM was detected in 74.3% (101/136) and 89.0% (121/136) of the gastric cancer specimens, respectively. A high expression of BTLA and HVEM was detected, respectively, in 28.7% (39/136) and 44.9% (61/136) of the specimens. Characteristics analysis showed that the high expression of BTLA was significantly associated with lymph node metastasis (P=0.030). Similarly, the high expression of HVEM was also significantly correlated with lymph node metastasis (P=0.007) and depth of invasion (P=0.011). In addition, there was a positive correlation between the expression of BTLA and HVEM in gastric cancer specimens (r=0.245, P=0.004). Univariate analysis revealed that the high expression of BTLA and HVEM was associated with overall survival of patients along with tumor size, Borrmann type, depth of invasion, lymph node metastasis, and histological grade (Pcancer. Conclusion The increased BTLA and HVEM levels correlate with the development and poor prognosis of gastric cancer. HVEM is an important prognostic indicator, and BTLA/HVEM pathway is considered to be a promising candidate for immunotherapy of gastric cancer.

  16. PROGNOSIS OF PATIENTS WITH BREAST CANCER RELATED TO THE TIMING OF OPERATION DURING MENSTRUAL CYCLE

    Institute of Scientific and Technical Information of China (English)

    Zhang Baoning

    1998-01-01

    Objective: To evaluate the effect of operation timing during menstrual cycle on the prognosis of patients with breast cancer. Methods: 218 operated premenopausal patients with breast cancer had been followed-up for more than 10 years. Prognostic factors related to these patients had been selected to be underwent univariate analysis and multivariate analysis by Cox regression model. Results: Univariage analysis showed that the menstrual timing of operation, as other Known prognostic factors (tumor size, node status,histological grade, TNM classification, adjuvent systemic therapy, etc), had an influence on the patients' outcome.Multivariate analysis by Cox regression model indicated that disease-free rate and overall survival rate of patients operated during the periovulatory phase (123 cases) were significantly superior to those operated during the premenstrual phase (95 cases) (P<0.01). There were no significant differences in prognosis between patients who received operations during the follicular phase (96 cases)and those during the luteal phase (122 cases) (P>0.01).Conclusion: Probably there is an optimal timing of operation for premenopausal breast cancer patients. Any prospective, randomized clinical study should be carried out to make this problem clear.

  17. Upregulation of CENP-H in tongue cancer correlates with poor prognosis and progression

    Directory of Open Access Journals (Sweden)

    Weng Gui-Xiang

    2009-06-01

    Full Text Available Abstract Background Centromere protein H (CENP-H is one of the fundamental components of the human active kinetochore. Recently, CENP-H was identified to be associated with tumorigenesis. This study was aimed to investigate the clinicopathologic significance of CENP-H in tongue cancer. Methods RT-PCR, real time RT-PCR and Western blot were used to examine the expression of CENP-H in tongue cancer cell lines and biopsies. CENP-H protein level in paraffin-embedded tongue cancer tissues were tested by immunohistochemical staining and undergone statistical analysis. CENP-H-knockdown stable cell line was established by infecting cells with a retroviral vector pSuper-retro-CENP-H-siRNA. The biological function of CENP-H was tested by MTT assay, colony formation assay, and Bromodeoxyuridine (BrdU incorporation assay. Results CENP-H expression was higher in tongue cancer cell lines and cancer tissues (T than that in normal cell and adjacent noncancerous tongue tissues (N, respectively. It was overexpressed in 55.95% (94/168 of the paraffin-embedded tongue cancer tissues, and there was a strong correlation between CENP-H expression and clinical stage, as well as T classification. CENP-H can predict the prognosis of tongue cancer patients especially those in early stage. Depletion of CENP-H can inhibit the proliferation of tongue cancer cells (Tca8113 and downregulate the expression of Survivin. Conclusion These findings suggested that CENP-H involves in the development and progression of tongue cancer. CENP-H might be a valuable prognostic indicator for tongue cancer patients within early stage.

  18. Diagnostic features of lung metastases differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    T. M. Geliashvili

    2015-01-01

    Full Text Available Background. The worldwide increasing incidence of thyroid cancer (TC is mainly due to a rise in its major form of differentiated TC (DTC: papillary. Most patients with DTC have a good prognosis; 10-year survival overall rates are as high as 85 %, but not greater than 40 % in a group of patients with distant metastases. At the same time, the lung is the most frequent target for distant metastases, accounting for 70 % of all sites.Objective: to estimate and compare the capabilities of different diagnostic techniques to detect lung metastases of DTC. Materials and methods. The results of diagnosing lung metastases were retrospectively analyzed in 36 patients (33 women and 3 men; mean age 53 years with DTC (29 patients with papillary TC and 7 with follicular TC treated at the department of radiotherapy with systemic therapy, Chelyabinsk Regional Clinical Oncology Center from 2011 to 2014.Results. Chest X-ray could reveal pulmonary metastases in 13 (36 % patients; lung pathology foci were absent in 23 (64 % patients. 131I whole-body scintigraphy (WBS proved to be of informative value in 24 (66.7 % patients, it displayed no increased accumulation of the radiopharmaceutical in the lung of 12 (33.3 % cases. Multislice spiral computed tomography (MSCT of the chest was carried out in 22 (61 % patients; out of them 21 (95.5 % were found to have 1.4-to-20-mm lung cancer foci. 18Fluorodeoxyglucose (18FDG positron emission tomography / computed tomography (PET / CT was performed in 18 (50 % patients, which showed 3–26-mm lung pathology foci in all the patents; out of them 16 (88.9 % were detected to have metastases owing to the CT component of this method. Thus, the highest sensitivity was exhibited by MSCT (95.5 %, 18FDG PET / CT (100 % due to its CT component, and 131I WBS (66.7 %.Conclusion. When lung metastases of DTC are suspected, 1 chest X-ray should be used as a screening test; 2 131I WBS should be performed in all patients; 3 MSCT of the chest is

  19. Clinical features and prognosis of obese breast cancer patients:a retrospective study*

    Institute of Scientific and Technical Information of China (English)

    Zhendong Zheng; Heng Cao; Shuxian Qu; Yongye Liu; Ying Piao; Xiaodong Xie

    2013-01-01

    Objective:The aim of our study was to investigate the prognosis of obese breast cancer patients. Methods:This study was conducted on a total of 317 breast cancer patients who were histopathological y and clinical y diagnosed at the General Hospital of Shenyang Military Region (China) from 2004 to 2006. Clinical data including height, weight, age at diagnosis, tumor size, lymph node status, menopausal status, family history of cancer and hormone receptor status were col-lected. Log-rank test was performed to compare the disease free survival (DFS) and overal survival (OS). Cox proportional hazards regression analysis was conducted to make multivariate analysis. The Chi square test was used to compare the clinical features among normal weight group, overweight group, and obese group. Results:Obesity was an independent prognostic factor for DFS (P=0.022) and OS (P=0.032) in breast cancer patients. In the stratified analysis based on the hormone receptor status, obesity was independently associated with OS in patients with negative ER/PR (P=0.002), but such association was not observed in patients with positive hormone receptors. Obesity was also associated with lymph node status (P=0.001) and smoking (P=0.009). Conclusion:Obesity is associated with poor DFS and OS in patients with breast cancer. Therefore, maintaining normal weight may benefit breast cancer patients.

  20. Dietary fiber, carbohydrates, glycemic index, and glycemic load in relation to breast cancer prognosis in the HEAL cohort

    NARCIS (Netherlands)

    Belle, F.N.; Kampman, E.; McTiernan, A.; Bernstein, L.; Baumgartner, K.; Baumgartner, R.; Ambs, A.; Ballard-Barbash, R.; Neuhouser, M.L.

    2011-01-01

    BACKGROUND: Dietary intake of fiber, carbohydrate, glycemic index (GI), and glycemic load (GL) may influence breast cancer survival, but consistent and convincing evidence is lacking. METHODS: We investigated associations of dietary fiber, carbohydrates, GI, and GL with breast cancer prognosis among

  1. Dietary Fiber, Carbohydrates, Glycemic Index, and Glycemic Load in Relation to Breast Cancer Prognosis in the HEAL Cohort

    NARCIS (Netherlands)

    Belle, F.N.; Kampman, E.; McTiernan, A.; Bernstein, L.; Baumgartner, K.; Baumgartner, R.; Ambs, A.; Ballard-Barbash, R.; Neuhouser, M.L.

    2011-01-01

    Background: Dietary intake of fiber, carbohydrate, glycemic index (GI), and glycemic load (GL) may influence breast cancer survival, but consistent and convincing evidence is lacking. Methods: We investigated associations of dietary fiber, carbohydrates, GI, and GL with breast cancer prognosis among

  2. 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    J. Li (Jingmei); L.S. Lindström (Linda); J.N. Foo (Jia); M. Rafiq (Meena); M.K. Schmidt (Marjanka); P.D.P. Pharoah (Paul); K. Michailidou (Kyriaki); J. Dennis (Joe); M.K. Bolla (Manjeet); Q. Wang (Qing); L.J. van 't Veer (Laura); S. Cornelissen (Sten); E.J.T. Rutgers (Emiel); M.C. Southey (Melissa); C. Apicella (Carmel); G.S. Dite (Gillian); J.L. Hopper (John); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias); C. Blomqvist (Carl); T.A. Muranen (Taru); K. Aittomäki (Kristiina); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V-M. Kosma (Veli-Matti); J. Hartikainen (Jaana); V. Kataja (Vesa); G. Chenevix-Trench (Georgia); K. Investigators (Kconfab); K.-A. Phillips (Kelly-Anne); S.-A. McLachlan (Sue-Anne); D. Lambrechts (Diether); B. Thienpont (Bernard); A. Smeets (Ann); H. Wildiers (Hans); J. Chang-Claude (Jenny); D. Flesch-Janys (Dieter); P. Seibold (Petra); A. Rudolph (Anja); G.G. Giles (Graham); L. Baglietto (Laura); G. Severi (Gianluca); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); V. Kristensen (Vessela); G.G. Alnæs (Grethe); A.-L. Borresen-Dale (Anne-Lise); S. Nord (Silje); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); M.J. Hooning (Maartje); M. Kriege (Mieke); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); Y. Li (Yi); U. Hamann (Ute); D. Torres (Diana); H.U. Ulmer (Hans); T. Rüdiger (Thomas); C-Y. Shen (Chen-Yang); C.-N. Hsiung (Chia-Ni); P.-E. Wu (Pei-Ei); S.-T. Chen (Shou-Tung); S.-H. Teo; N.A.M. Taib (Nur Aishah Mohd); C. Har Yip (Cheng); G. Fuang Ho (Gwo); K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hisato); K. Tajima (Kazuo); D. Kang (Daehee); J.-Y. Choi (Ji-Yeob); S.K. Park (Sue); K-Y. Yoo (Keun-Young); T. Maishman (Tom); W. Tapper (William); A.M. Dunning (Alison); M. Shah (Mitul); R.N. Luben (Robert); J. Brown (Judith); C. Chuen Khor (Chiea); D. Eccles (Diana); H. Nevanlinna (Heli); D.F. Easton (Douglas); M.K. Humphreys (Manjeet); J. Liu (Jianjun); P. Hall (Per); K. Czene (Kamila)

    2014-01-01

    textabstractLarge population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oes

  3. Loss of Bad expression confers poor prognosis in non-small cell lung cancer.

    Science.gov (United States)

    Huang, Yi; Liu, Dan; Chen, Bojiang; Zeng, Jing; Wang, Lei; Zhang, Shangfu; Mo, Xianming; Li, Weimin

    2012-09-01

    Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.

  4. Expression of Cyclin E and Its Relationship with the Prognosis of Patients with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    HE Wenshan; HUANG Tao; WANG Haijiu

    2006-01-01

    Objective: To investigate the expression of cyclin E in breast cancer tissues and its relationship with prognosis of the patients with breast cancer. Methods: The expression of cyclin E, HER-2/neu,nm23-H1 and actin was detected in 80 breast cancer tissues and 18 benign breast tumor tissues by immunohistochemical methods. The relationship between cyclin E and the remaining genes or the clinical data of the patients with breast cancer was analyzed. Results: The over expression rate of cyclin E in malignant tissues was obviously higher than that in benign tumor tissues (P<0.01). The over expression of cyclin E in later stage of disease was higher than that in early stage of disease (P<0.05). The expression of cyclin E in ER positive tissues was lower than that in ER negative tissues (P<0.05). The expression of cyclin E in PR positive tissues and PR negative tissues had no significant difference (P>0.05). The expression of cyclin E in HER-2/neu positive tissues was higher than that in HER-2/neu negative tissues (P<0.05). And the expression of cyclin E in ER, PR and HER-2/neu all positive tissues was much higher (P<0.01). There was no significant difference in the expression of cyclin E between nm23-H1 positive tissues and nm23-H1 negative tissues (P>0.05). The expression of cyclin E in actin positive and continuous distribution tissues was lower than that in actin negative or discontinuous distribution tissues (P<0.05). Conclusion: The expression of cyclin E has a strong correlation to the prognosis of the patients with breast cancer.

  5. Radiation exposure from diagnostic imaging in young patients with testicular cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, C.J.; Twomey, M.; O' Regan, K.N. [Cork and Mercy University Hospitals, Department of Radiology, Cork (Ireland); Murphy, K.P.; Maher, M.M.; O' Connor, O.J. [Cork and Mercy University Hospitals, Department of Radiology, Cork (Ireland); University College Cork, Department of Radiology, Cork (Ireland); McLaughlin, P.D. [Cork and Mercy University Hospitals, Department of Radiology, Cork (Ireland); Vancouver General Hospital, Department of Emergency and Trauma Radiology, Vancouver, British Columbia (Canada); Power, D.G. [Cork and Mercy University Hospitals, Department of Medical Oncology, Cork (Ireland)

    2015-04-01

    Risks associated with high cumulative effective dose (CED) from radiation are greater when imaging is performed on younger patients. Testicular cancer affects young patients and has a good prognosis. Regular imaging is standard for follow-up. This study quantifies CED from diagnostic imaging in these patients. Radiological imaging of patients aged 18-39 years, diagnosed with testicular cancer between 2001 and 2011 in two tertiary care centres was examined. Age at diagnosis, cancer type, dose-length product (DLP), imaging type, and frequency were recorded. CED was calculated from DLP using conversion factors. Statistical analysis was performed with SPSS. In total, 120 patients with a mean age of 30.7 ± 5.2 years at diagnosis had 1,410 radiological investigations. Median (IQR) surveillance was 4.37 years (2.0-5.5). Median (IQR) CED was 125.1 mSv (81.3-177.5). Computed tomography accounted for 65.3 % of imaging studies and 98.3 % of CED. We found that 77.5 % (93/120) of patients received high CED (>75 mSv). Surveillance time was associated with high CED (OR 2.1, CI 1.5-2.8). Survivors of testicular cancer frequently receive high CED from diagnostic imaging, mainly CT. Dose management software for accurate real-time monitoring of CED and low-dose CT protocols with maintained image quality should be used by specialist centres for surveillance imaging. (orig.)

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

    Science.gov (United States)

    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.

  7. Discovery of dachshund 2 protein as a novel biomarker of poor prognosis in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Nodin Björn

    2012-01-01

    Full Text Available Abstract Background The Dachshund homolog 2 (DACH2 gene has been implicated in development of the female genital tract in mouse models and premature ovarian failure syndrome, but to date, its expression in human normal and cancerous tissue remains unexplored. Using the Human Protein Atlas as a tool for cancer biomarker discovery, DACH2 protein was found to be differentially expressed in epithelial ovarian cancer (EOC. Here, the expression and prognostic significance of DACH2 was further evaluated in ovarian cancer cell lines and human EOC samples. Methods Immunohistochemical expression of DACH2 was examined in tissue microarrays with 143 incident EOC cases from two prospective, population-based cohorts, including a subset of benign-appearing fallopian tubes (n = 32. A nuclear score (NS, i.e. multiplier of staining fraction and intensity, was calculated. For survival analyses, cases were dichotomized into low (NS 3 using classification and regression tree analysis. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the impact of DACH2 expression on survival. DACH2 expression was analysed in the cisplatin sensitive ovarian cancer cell line A2780 and its cisplatin resistant derivative A2780-Cp70. The specificity of the DACH2 antibody was tested using siRNA-mediated silencing of DACH2 in A2780-Cp70 cells. Results DACH2 expression was considerably higher in the cisplatin resistant A2780-Cp70 cells compared to the cisplatin-sensitive A2780 cells. While present in all sampled fallopian tubes, DACH2 expression ranged from negative to strong in EOC. In EOC, DACH2 expression correlated with several proteins involved in DNA integrity and repair, and proliferation. DACH2 expression was significantly higher in carcinoma of the serous subtype compared to non-serous carcinoma. In the full cohort, high DACH2 expression was significantly associated with poor prognosis in univariable analysis, and in carcinoma of the serous subtype

  8. Identification and targeting of a TACE-dependent autocrine loopwhich predicts poor prognosis in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, Paraic A.; Bissell, Mina J.

    2005-06-15

    The ability to proliferate independently of signals from other cell types is a fundamental characteristic of tumor cells. Using a 3D culture model of human breast cancer progression, we have delineated a protease-dependent autocrine loop which provides an oncogenic stimulus in the absence of proto-oncogene mutation. Inhibition of this protease, TACE/ADAM17, reverts the malignant phenotype by preventing mobilization of two crucial growth factors, Amphiregulin and TGF{alpha}. We show further that the efficacy of EGFR inhibitors is overcome by physiological levels of growth factors and that successful EGFR inhibition is dependent on reducing ligand bioavailability. Using existing patient outcome data, we demonstrate a strong correlation between TACE and TGF{alpha} expression in human breast cancers that is predictive of poor prognosis.

  9. G388R mutation of the FGFR4 gene is not relevant to breast cancer prognosis.

    Science.gov (United States)

    Jézéquel, P; Campion, L; Joalland, M-P; Millour, M; Dravet, F; Classe, J-M; Delecroix, V; Deporte, R; Fumoleau, P; Ricolleau, G

    2004-01-12

    This study screened large cohorts of node-positive and node-negative breast cancer patients to determine whether the G388R mutation of the FGFR4 gene is a useful prognostic marker for breast cancer as reported by Bange et al in 2002. Node-positive (n=139) and node-negative (n=95) breast cancer cohorts selected for mutation screening were followed up for median periods of 89 and 87 months, respectively. PCR - RFLP analysis was modified to facilitate molecular screening. Curves for disease-free survival were plotted according to the Kaplan - Meier method, and a log-rank test was used for comparisons between groups. Three other nonparametric linear rank-tests particularly suitable for investigating possible relations between G388R mutation and early cancer progression were also used. Kaplan - Meier analysis based on any of the four nonparametric linear rank tests performed for node-positive and node-negative patients was not indicative of disease-free survival time. G388R mutation of the FGFR4 gene is not relevant for breast cancer prognosis.

  10. Does Pregnancy-Associated Breast Cancer Imply a Worse Prognosis? A Matched Case-Case Study

    Science.gov (United States)

    Dimitrakakis, Constantine; Zagouri, Flora; Tsigginou, Alexandra; Marinopoulos, Spyros; Sergentanis, Theodoros N.; Keramopoulos, Antonis; Zografos, George C.; Ampela, Konstantina; Mpaltas, Dimosthenis; Papadimitriou, Christos; Dimopoulos, Meletios-Athanassios; Antsaklis, Aris

    2013-01-01

    Summary Background Significant controversy exists in the literature regarding the role of pregnancy in the prognosis of breast cancer. We designed a matched case-case study, matching pregnancy-associated breast cancer (PABC) cases with breast cancer cases for stage, age, and year of diagnosis. Patients and Methods 39 consecutive cases of PABC were matched with 39 premenopausal cases of breast cancer. Univariate and multivariate survival analyses followed by adjustment for stage, grade, estrogen receptor status, and age at diagnosis, were performed. Results Regarding overall survival (OS), univariate analysis pointed to longer OS in non-PABC cases vs. PABC cases. Accordingly, a more advanced stage predicted shorter survival. In the multivariate analysis, the independent aggravating effect mediated by pregnancy persisted. Interestingly, a post hoc nested analysis within PABC cases indicated that the 3rd trimester pointed to shorter OS. The aforementioned results on OS were also replicated during the examination of relapse-free survival. Conclusion Implementing a matched case-case design, the present study points to pregnancy as a poor prognostic factor for breast cancer. PMID:24415971

  11. Polymorphisms of interleukin-10 promoter are not associated with prognosis of advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Jie Liu; Bao Song; Jia-Lin Wang; Zeng-Jun Li; Wan-Hu Li; Zhe-Hai Wang

    2011-01-01

    AIM: To evaluate the association between of the interleukin- 10 (IL-10) promoter polymorphisms and survival of advanced gastric cancer (GC) patients. METHODS: The IL-10 (-1082, rs1800896; -819, rs1800871; and-592, rs1800896) genotypes in 234 patients with advanced gastric cancer and in 243 healthy controls were determined by polymerase chain reactionrestriction fragment length polymorphism assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression for the associations between IL-10 genotypes and the risk of GC. The Kaplan-Meier method with log-rank testing was used to evaluate the association between genotype and survival of the patients. RESULTS: The IL-10 -1082 G allele and GCC (-1082, -819 and -592) haplotype were associated with increased gastric cancer risks (OR 1.2, 95% CI 0.6-3.2, P = 0.007, for -1082 G allele, OR = 2.3, 95% CI, 1.2-4.1, P = 0.005, for GCC haplotype, respectively). However, none of the three IL-10 gene polymorphisms (-1082, -819 and -592) was correlated with gastric cancer survival (P > 0.05), and none of the genotypes of the three IL-10 sites was found as independent prognostic risk factors in the multivariate test. CONCLUSION: IL-10 gene promoter polymorphisms may not be associated with the prognosis of advanced gastric cancer.

  12. Type 2 diabetes mellitus and prognosis in early stage breast cancer women.

    Science.gov (United States)

    Kaplan, Muhammet Ali; Pekkolay, Zafer; Kucukoner, Mehmet; Inal, Ali; Urakci, Zuhat; Ertugrul, Hamza; Akdogan, Recai; Firat, Ugur; Yildiz, Ismail; Isikdogan, Abdurrahman

    2012-09-01

    It has been suggested that type 2 diabetes mellitus may affect breast cancer prognosis, possibly due to increased diabetes-related comorbidity, or direct effects of insulin resistance and/or hyperinsulinemia. The aim of this study was to determine the impact of diabetes on disease-free survival (DFS) following mastectomy for breast cancer patients. The cases included in this retrospective study were selected from breast cancer women who had undergone mastectomy and completed adjuvant chemotherapy from 1998 to 2010. Patients were classified into two groups: diabetic and non-diabetic. Patients' age, sex, menopausal status, body mass index (BMI), histopathological features, tumor size, lymph node involvement, hormone receptor and HER2-neu status, and treatment types were recorded. There were 483 breast cancer patients included in the study. Postmenopausal patients' rate (53.7% vs. 36.8%, P = 0.016) and mean BMI levels were statistically higher (32.2 vs. 27.9, P = 0.007) in diabetic patients. There was no statistical difference for histological subgroup, grade, ER and PR positivity, HER2-neu overexpression rate, and tumor size between the diabetic and non-diabetic group. Lymph node involvements were statistically higher in diabetic patients compared with non-diabetic patients (P = 0.013). Median disease-free survival is 81 months (95% CI, 61.6-100.4) in non-diabetic patients and 36 months (95% CI, 13.6-58.4) in diabetic patients (P breast cancer.

  13. Endosomal gene expression: a new indicator for prostate cancer patient prognosis?

    LENUS (Irish Health Repository)

    Johnson, Ian R D

    2015-11-10

    Prostate cancer continues to be a major cause of morbidity and mortality in men, but a method for accurate prognosis in these patients is yet to be developed. The recent discovery of altered endosomal biogenesis in prostate cancer has identified a fundamental change in the cell biology of this cancer, which holds great promise for the identification of novel biomarkers that can predict disease outcomes. Here we have identified significantly altered expression of endosomal genes in prostate cancer compared to non-malignant tissue in mRNA microarrays and confirmed these findings by qRT-PCR on fresh-frozen tissue. Importantly, we identified endosomal gene expression patterns that were predictive of patient outcomes. Two endosomal tri-gene signatures were identified from a previously published microarray cohort and had a significant capacity to stratify patient outcomes. The expression of APPL1, RAB5A, EEA1, PDCD6IP, NOX4 and SORT1 were altered in malignant patient tissue, when compared to indolent and normal prostate tissue. These findings support the initiation of a case-control study using larger cohorts of prostate tissue, with documented patient outcomes, to determine if different combinations of these new biomarkers can accurately predict disease status and clinical progression in prostate cancer patients.

  14. Use of immunohistochemical markers can refine prognosis in triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Cheang Maggie CU

    2007-07-01

    Full Text Available Abstract Background Basal-like breast cancer has been extensively characterized on the basis of gene expression profiles, but it is becoming increasingly common for these tumors to be defined on the basis of immunohistochemical (IHC staining patterns, particularly in retrospective studies where material for expression profiling may not be available. The IHC pattern that best defines basal-like tumors is under investigation and various combinations of ER, PR, HER2-, CK5/6+ and EGFR+ have been tested. Methods Using datasets from two different hospitals we describe how using different combinations of immunohistochemical patterns has different effects on estimating prognosis at different time intervals after diagnosis. As our baseline, we used two IHC patterns ER-/PR-/HER2-("triple negative phenotype", TNP and ER-/HER2-/CK5/6+ and/or EGFR+ ("core basal phenotype", CBP. Results There was no overall difference in survival between the two hospital-based series, but there was a difference between the TNP and non-TNP groups which was most marked at 3 years (76.8% vs 93.5%, p Conclusion Our findings suggests that CK5/6 and/or EGFR expressing tumor types have a persistently poorer prognosis over the longer term, an observation that may have important therapeutic implications as drugs that target the EGFR are currently being evaluated in breast cancer.

  15. CD147/EMMPRIN overexpression and prognosis in cancer: A systematic review and meta-analysis

    Science.gov (United States)

    Xin, Xiaoyan; Zeng, Xianqin; Gu, Huajian; Li, Min; Tan, Huaming; Jin, Zhishan; Hua, Teng; Shi, Rui; Wang, Hongbo

    2016-01-01

    CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) plays an important role in tumor progression and a number of studies have suggested that it is an indicator of tumor prognosis. This current meta-analysis systematically reevaluated the predictive potential of CD147/EMMPRIN in various cancers. We searched PubMed and Embase databases to screen the literature. Fixed-effect and random-effect meta-analytical techniques were used to correlate CD147 expression with outcome measures. A total of 53 studies that included 68 datasets were eligible for inclusion in the final analysis. We found a significant association between CD147/EMMPRIN overexpression and adverse tumor outcomes, such as overall survival, disease-specific survival, progression-free survival, metastasis-free survival or recurrence-free survival, irrespective of the model analysis. In addition, CD147/EMMPRIN overexpression predicted a high risk for chemotherapy drugs resistance. CD147/EMMPRIN is a central player in tumor progression and predicts a poor prognosis, including in patients who have received chemo-radiotherapy. Our results provide the evidence that CD147/EMMPRIN could be a potential therapeutic target for cancers. PMID:27608940

  16. HER-2,P53 and Hormonal Receptors Protein Expression as Predictive Factors in Breast Cancer Prognosis

    Institute of Scientific and Technical Information of China (English)

    seyed Mohanmmad Rabiee Hashemi; Somayeh Rabiee Hashemi

    2008-01-01

    Breast cancer is a heterogeneous disease with vari-able biological and clinical characteristics. We conducted a study to evaluate P53,HER-2/neu and hormonal receptor expression as predictors of prognosis in breast cancer. METHODS In a prospective study, we recruited 81 consecutive patients with primary operable breast cancer who were treated with mastectomy followed by locoregional radiotherapy or che-motherapy and studied the presence of P53,HER-2/neu and hormonal receptors(ER/PR) expression in tumor tissues by im-munohistochemical staining. Associations between these markers expression and clinical outcomes, including local and regional recurrence and metastasis were evaluated. Statistical analysis was performed with the SPSS software. RESUITS The mean time of follow-up was (47.3±4.6)months. Expression of P53, HER-2/neu, Estrogen receptors and progester-one receptors were observed in 31.1%, 38.5%, 31.8%and 51.7%ofthe patients, respectively. P53,HER-2/neu and Negative ER status were potent predictors of local-regional recurrence(P=0.034,0.038,0.044,respectively).Also HER-2/neu,Negative ER and Negative PR status were strong predictors of metastasis(P=0.001,0.042,0.054,respectively).CONCLUSION OP53 and HER-2/neu expression and also steroid receptors status(ER/PR status)have an important role in predict-ing the outcome of breast cancer and thus may be of value in se-lecting suitable therapeutic strategy and determining prognosis in these patients.

  17. Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma.

    Science.gov (United States)

    Iura, Kunio; Kohashi, Kenichi; Hotokebuchi, Yuka; Ishii, Takeaki; Maekawa, Akira; Yamada, Yuichi; Yamamoto, Hidetaka; Iwamoto, Yukihide; Oda, Yoshinao

    2015-07-01

    Myxoid liposarcoma is the second most common liposarcoma. Although myxoid liposarcoma is relatively chemosensitive and thus a good candidate for chemotherapy, cases with relapsed or metastatic disease still have poor outcome. Here, we performed a gene microarray analysis to compare the gene expression profiles in six clinical myxoid liposarcoma samples and three normal adipose tissue samples, and to identify molecular biomarkers that would be useful as diagnostic markers or treatment targets in myxoid liposarcoma. This showed that the cancer-testis antigen PRAME was up-regulated in myxoid liposarcoma. We then performed immunohistochemical, western blotting and real-time polymerase chain reaction analyses to quantify the expression of PRAME and another cancer-testis antigen, NY-ESO-1, in clinical samples of myxoid liposarcoma (n = 93), dedifferentiated (n = 46), well-differentiated (n = 32) and pleomorphic liposarcomas (n = 14). Immunohistochemically, positivity for PRAME and NY-ESO-1 was observed in 84/93 (90%) and 83/93 (89%) of the myxoid liposarcomas, and in 20/46 (43%) and 3/46 (7%) of the dedifferentiated, 3/32 (9%) and 1/32 (3%) of the well-differentiated and 7/14 (50%) and 3/21 (21%) of the pleomorphic liposarcomas, respectively. High immunohistochemical expression of PRAME and/or NY-ESO-1 was significantly correlated with tumour diameter, the existence of tumour necrosis, a round-cell component of >5%, higher histological grade and advanced clinical stage. High PRAME and NY-ESO-1 expression correlated significantly with poor prognosis in a univariate analysis. The myxoid liposarcomas showed significantly higher protein and mRNA expression levels of PRAME and NY-ESO-1 (CTAG1B) than the other liposarcomas. In conclusion, PRAME and NY-ESO-1 (CTAG1B) were expressed in the vast majority of myxoid liposarcomas, and their high-level expression correlated with tumour grade and poor prognosis. Our results support the potential use of PRAME and NY

  18. Diagnostic utility of DTI in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Lung cancer associated hypercalcemia: An analysis of factors influencing survival and prognosis in 34 cases

    Directory of Open Access Journals (Sweden)

    Su-jie ZHANG

    2012-06-01

    Full Text Available Objectives  To explore the factors influencing survival time in lung cancer associated hypercalcemia patients. Methods  Thirty-four patients with pathologically confirmed lung cancer complicated with hypercalcemia, who were treated at the Department of Oncology in General Hospital of PLA from Jan. 2001 to Dec. 2010, were enrolled in this study. The clinical data analyzed included sex, age, pathological type of the malignancies, organ metastasis (bone, lung, liver, kidney, brain, number of distal metastatic site, mental status, interval between final diagnosis of lung cancer and of hypercalcemia, peak value of blood calcium during the disease course, treatment methods and so on. Survival analysis was performed with the Kaplan-Meier method and Cox analysis with statistic software SPSS 18.0 to identify the potential prognostic factors. Results  The highest blood calcium level ranged from 2.77 to 4.87mmol/L, and the median value was 2.94mmol/L. The patients' survival time after diagnosis of hypercalcemia varied from 1 day to 1067 days, and the median survival time was 92 days. With the log-rank test, age above 50 years old, hypercalcemia occurring over 90 days after diagnosis of cancer, central nervous system symptoms and renal metastasis were predictors for poor survival (P=0.048, P=0.001, P=0.000, P=0.003. In the COX proportional hazard model analysis, age above 50 years old, hypercalcemia occurring over 90 days after cancer diagnosis, central nervous system symptoms and renal metastasis were significant prognostic factors for poor survival (HR=11.483, P=0.006; HR=4.371, P=0.002; HR=6.064, P=0.026; HR=8.502, P=0.011. Conclusions  Patients with lung cancer associated hypercalcemia have a shorter survival time and poor prognosis. Age above 50 years old, hypercalcemia occurring over 90 days after cancer diagnosis, central nervous system symptoms and renal metastasis are significant factors of poor prognosis.

  20. BRCA2 promoter polymorphism is associated with breast cancer prognosis in Chinese women

    Institute of Scientific and Technical Information of China (English)

    Liu Lu; Fang Yi; Fan Jianlin; Hu Jianming; Xu Xiaoting; Jin Xiaohong; Wang Xiuzhen

    2014-01-01

    Background Breast cancer 2 (BRCA2) is an important breast cancer-susceptibility gene.Promoter polymorphisms in BRCA2 may affect its transcription and be associated with cancer prognosis.Methods We identified five polymorphisms of the BRCA2 promoter region by in silico searching and direct sequencing:-254A/G (rs3092989),-908A/G (rs206117),-1134A/G (rs206115),-1144C/T (rs206116),and-1260CTTAGA/-(rs3072036).The-908A/G,-1134A/G,-1144C/T,and-1260CTTAGA/-polymorphisms were genotyped by direct sequencing in 491 breast cancer patients,and the-254A/G polymorphism was genotyped by Sequenom.Results The-1144C/T polymorphism was associated with clinical outcome.Carriers of the TT genotype had longer disease-free intervals (DFIs,P=0.029),especially among patients with sporadic unilateral breast cancer (P=0.010).Linkage disequilibrium (LD) analysis showed that all the five single nucleotide polymorphisms (SNPs) were in LD (D'>0.8).Carriers of haplotypes containing the-1144T allele showed longer DFIs (P=0.049),and the result was more significant in patients with sporadic unilateral cancer (P=0.018).There were no significant associations between the other polymorphisms and DFI.Conclusions The results of this study suggest that homozygosity for the BRCA2 T(-1144) allele is associated with a longer DFI in Chinese women with breast cancer.Further functional studies are warranted to clarify this relationship.

  1. Evaluation of Androgen Receptor Function in Prostate Cancer Prognosis and Therapeutic Stratification

    Science.gov (United States)

    2014-10-01

    Bethesda, MD 20817 REPORT DATE: October 2014 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick...October 2014 2. REPORT TYPE : Annual 3. DATES COVERED (From - To) 30 SEP 2013 - 29 SEP 2014 4. TITLE AND SUBTITLE: Evaluation of Androgen Receptor...examined human prostate cancer tissues (surgery or diagnostic biopsy specimens) at early stages of the disease and matched with longitudinal follow up data

  2. Papillary Thyroid Cancer, Macrofollicular Variant: The Follow-Up and Analysis of Prognosis of 5 Patients

    Directory of Open Access Journals (Sweden)

    Varlık Erol

    2014-01-01

    Full Text Available Objective. The main aim of this study was to comparatively analyze the recurrence and prognosis of this rare variant with the literature by analyzing the follow-up data of 5 patients diagnosed with papillary cancer macrofollicular variant. Methods. The demographic data, radiological and pathological data, and prognostic data of 5 patients who underwent surgery for thyroid cancer and were diagnosed with papillary cancer macrofollicular variant pathologically were retrospectively analyzed. Results. The mean age of patients whose mean follow-up period was determined as 7.2 years was 41, and the male/female ratio was 4/1. All patients underwent total thyroidectomy. The pathology report of 2 patients (40% revealed macrofollicular variant of papillary microcancer, and 3 patients papillary cancer macrofollicular variant. Central dissection was performed in one patient (20% due to macroscopic pathologic lymph node and 4 metastatic lymph nodes were reported. Also, locoregional recurrence was present in 3 out of 5 patients (60%. Conclusions. Although an impression of earlier and increased risk of recurrence in papillary carcinoma with macrofollicular variant has been documented, more studies with extensive follow-up times and large populations are required.

  3. Tumour-infiltrating lymphocytes in melanoma prognosis and cancer immunotherapy.

    Science.gov (United States)

    Lee, Nayoung; Zakka, Labib R; Mihm, Martin C; Schatton, Tobias

    2016-02-01

    The field of systemic cancer therapy for metastatic disease has entered an exciting era with the advent of novel immunomodulatory strategies targeting immune checkpoints. At the heart of these promising efforts are the tumour-infiltrating lymphocytes (TILs). As the reports demonstrating efficacy of modulating TIL effector function in patients with advanced stage cancer continue to accrue, it has become essential to better understand TIL immunobiology in order to further improve clinical outcome. In addition to providing an overview of the current immunotherapies available for metastatic melanoma, this review will briefly introduce the history and classification of TILs. Moreover, we will dissect the multifaceted roles of TILs in tumour-specific immunity and melanoma immune escape. The significance of TILs in melanoma prognosis and cancer immunotherapy will also be discussed, with a particular focus on their potential utility as biomarkers of patient response. The goal of personalised medicine appears to be in realistic sight, as new immunomodulatory techniques and technological innovations continue to advance the field of cancer immunotherapy. In light of recent studies highlighting the possible utility of TILs in determining therapeutic outcome, further characterisation of TIL phenotype and function has the potential to help translate individualised care into current medical practice.

  4. Human papilloma virus (HPV) status associated with prognosis of cervical cancer after radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Harima, Yoko; Miyazaki, Yuki; Imamura, Masahiro; Sougawa, Mitsuharu; Sawada, Satoshi [Kansai Medical Univ., Moriguchi, Osaka (Japan)

    2002-06-01

    Our study explored whether the HPV status of tumors is associated with the outcome of radiotherapy in patients with cervical cancer. A total of 84 patients with cervical cancer (6 stage I, 10 stage II, 49 stage III, and 19 stage IV) who underwent definitive radiotherapy between January 1995 and June 2000 were included in this study. Tumor samples were obtained from all patients by punch biopsy prior to radiotherapy. The presence of HPV and its type were analyzed by PCR-based assay using the consensus primers for E6 and L1 regions. Actuarial methods were used to calculate overall survival, and disease-free survival. A total of 42 patients (50%) had cancer recurrence after radiotherapy. HPV-positive tumors were found in 76.2% (64 cases) of the patients. HPV-negative patients survived significantly shorter compared to the HPV-positive patients in the overall survival (p=0.007) and the disease-free survival (p=0.005). According to multivariate analysis, HPV status is a significant predictor of both overall (p=0.02) and disease-free survival time (p=0.005). These results of this study suggest that HPV-negative patients with cervical carcinoma are have a significantly poorer prognosis after radiotherapy, and may be used as a marker in order to optimize the treatment of patients with this type of cancer. (author)

  5. Circulating miRNAs: roles in cancer diagnosis, prognosis and therapy.

    Science.gov (United States)

    Cheng, Guofeng

    2015-01-01

    MicroRNAs (miRNAs) belong to a class of small non-coding RNAs that regulate numerous biological processes by targeting a broad set of messenger RNAs. Recently, miRNAs have been detected in remarkably stable forms in many types of body fluids. A comparison between cancer patients and healthy individuals has clearly shown that certain types of circulating miRNAs are associated with cancer initiation and progression. Research on miRNA-based biomarkers has witnessed phenomenal growth, owing to the non-invasive nature of miRNA-based screening assays and their sensitivity and specificity in detecting cancers. Consequently, a considerable effort has been devoted to identify suitable miRNAs for cancer diagnosis and also decode the information carried by circulating miRNAs. This review highlights the current studies that focus on the identification of circulating miRNA-based diagnostic and prognostic markers, for the most prevalent types of cancer. Additionally, the review also provides an insight into the putative functions of miRNAs, and attempts to delineate the mechanisms through which they are released into the bloodstream. Moreover, methodologies and strategies for identification of circulating miRNAs in cancers are summarized. Finally, potential strategies for circulating miRNA-based cancer therapies are proposed.

  6. Clinicopathological features and prognosis of pregnancy associated breast cancer - a matched case control study.

    Science.gov (United States)

    Madaras, Lilla; Kovács, Kristóf Attila; Szász, Attila Marcell; Kenessey, István; Tőkés, Anna-Mária; Székely, Borbála; Baranyák, Zsuzsanna; Kiss, Orsolya; Dank, Magdolna; Kulka, Janina

    2014-07-01

    Pregnancy Associated Breast Cancer (PABC) manifests during pregnancy or within a year following delivery. We sought to investigate differences in management, outcome, clinical, histopathology and immunohistochemistry (IHC) characteristics of PABC and matched controls in a retrospective case control study. PABC and control patients were selected from breast cancer cases of women ≤45 years, diagnosed in the 2nd Department of Pathology, Semmelweis University, Budapest, Hungary between 1998 and 2012. Histopathology information on tumor type, grade, size, T, N, lympho-vascular invasion (LVI), Nottingham Prognostic Index (NPI), associated in situ lesions and IHC charcteristics: ER, PgR, HER2, Ki67, p53 were recorded, IHC-based subtype was assessed, clinical, management and outcome data were analysed. Thirty-one breast cancer cases were pregnancy related. Clinical management data did not differ in cases and controls. Histopathology of disease at presentation was not significantly different, but NPI assessed the PABC group as having poor, whereas controls as having intermediate prognosis. Associated in situ lesion was more often high grade Extensive Intraductal Carcinoma Component (EIC) in PABC. Triple negative and LuminalB prol tumors predominated in PABC. Disease-free and overall survival was inferior compared to controls. PABC patients with LuminalB prol and Triple negative tumors had inferior outcomes. On multivariate analysis inferior prognosis of PABC was associated with pregnancy. Our study has demonstrated inferior outcome of PABC. Difference in tumor biology is reflected by the predominance of triple negative and LuminalB tumors in PABC. The strength of the study is the analysis of complete pathology and IHC data.

  7. Impact of Sulfatase-2 on cancer progression and prognosis in patients with renal cell carcinoma.

    Science.gov (United States)

    Kumagai, Shin; Ishibashi, Kei; Kataoka, Masao; Oguro, Toshiki; Kiko, Yuichirou; Yanagida, Tomohiko; Aikawa, Ken; Kojima, Yoshiyuki

    2016-11-01

    Heparan sulfate-specific endosulfatase-2 (SULF-2) can modulate the signaling of heparan sulfate proteoglycan-binding proteins. The involvement of SULF-2 in cancer growth varies by cancer type. The roles of SULF-2 expression in the progression and prognosis of renal cell carcinomas (RCC) have not yet been fully clarified. In the present study, the expression levels of SULF-2 mRNA and protein in 49 clinical RCC samples were determined by RT-PCR and immunostaining. The existence of RCC with higher SULF-2 expression and lower SULF-2 expression compared to the adjacent normal kidney tissues was suggested. High SULF-2 expression was correlated with an early clinical stage and less invasive pathological factors. Low SULF-2 expression was correlated with an advanced stage and higher invasive factors. Three-year cancer-specific survival (CSS) for high SULF-2 RCC and low SULF-2 RCC were 100% and 71.4%, respectively (log-rank P = 0.0019), with a significantly shorter CSS observed in low SULF-2 RCC patients. The influence of SULF-2 expression level on Wnt/VEGF/FGF signaling, cell viability and invasive properties was examined in three RCC cell lines, Caki-2, ACHN and 786-O, using a SULF-2 suppression model involving siRNA or a SULF-2 overexpression model involving a plasmid vector. High SULF-2 expression enhanced Wnt signaling and Wnt-induced cell viability, but not cell invasion. In contrast, low levels of SULF-2 expression significantly enhanced both cell invasion and viability through the activation of VEGF/FGF pathways. RCC with lower SULF-2 expression might have a higher potential for cell invasion and proliferation, leading to a poorer prognosis via the activation of VEGF and/or FGF signaling.

  8. Integrated proteo-genomic approach for early diagnosis and prognosis of cancer.

    Science.gov (United States)

    Shukla, Hem D; Mahmood, Javed; Vujaskovic, Zeljko

    2015-12-01

    Cancer is the leading cause of mortality among men and women worldwide. Despite the availability of numerous diagnostic techniques for various cancers, the overall survival rate remains low and the majority of patients die due to late diagnosis and advanced stage of the disease. Diagnosing and treating cancer at its early stages ideally during the precancerous phase could significantly increase survival rate with the possibility of cure and prolong survival. Cancer is a genetic disease and it is illicitly activated by the acquisition of somatic DNA lesions and aberrations in genome structure and defects in maintenance and repair. These somatic DNA mutations known as driver mutations seem to be the prime cause in initiating tumorigenesis. The advances in genomic technologies have immensely facilitated the understanding of cancer progression and metastasis, and the discovery of novel biomarkers. However, changes in somatic mutational landscape of the oncogenome are translated into aberrantly regulated oncoproteome which drives the cancer initiation. Thus, combination of proteomic and genomic technologies is urgently required to discover biomarkers for early diagnosis. The recent advances in human genome based detection of cancer using advanced genomic technologies like NextGen Sequencing, digital PCR, cfDNA technology have shown promise; for example oncogenic somatic mutation variants, transcriptomic analysis, copy number variant, and methylation data from the Cancer Genome Atlas. Similarly, oncoproteomics has the potential to revolutionize clinical management of the disease, including cancer diagnosis and screening based on new proteomic database which embodies somatic variants and post translational modifications, thus devising proteomic technologies as a complement to histopathology. Further, the use of multiple proteomic and genomic biomarkers rather than a single gene or protein could greatly improve diagnostic accuracy and enhance the predictive power for

  9. Targeting SR-BI for cancer diagnostics, imaging and therapy

    Directory of Open Access Journals (Sweden)

    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.

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

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    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

  11. Distinct Clinicopathological Features and Prognosis of Helicobacter pylori Negative Gastric Cancer

    Science.gov (United States)

    Chen, Mei-Jyh; Chen, Chien-Chuan; Kuo, Sung-Hsin; Lai, I-Rue; Yeh, Kun-Huei; Lin, Ming-Tsan; Wang, Hsiu-Po; Cheng, Ann-Lii; Lin, Jaw-Town; Shun, Chia-Tung; Wu, Ming-Shiang

    2017-01-01

    Background Whether the characteristics and prognosis of gastric cancer (GC) are different in patients with and without Helicobacter pylori (HP) remains controversial. The definitions of HP status in patients with atrophic gastritis but negative tests for HP are heterogeneous. We aimed to assess the impact of HP on the prognosis of GC using different definitions. Methods From 1998 Nov to 2011 Jul, five hundred and sixty-seven consecutive patients with GC were included. HP status was determined by serology and histology. Patients with any positive test were defined as HP infection. Patients without HP infection whose serum pepsinogen (PG) I gastritis and they were categorized into model 1: HP positive; model 2: HP negative; and model 3: exclusion of these patients. Results We found four characteristics of HP negative GC in comparison to HP positive GC: (1) higher proportion of the proximal tumor location (24.0%, P = 0.004), (2) more diffuse histologic type (56.1%, p = 0.008), (3) younger disease onset (58.02 years, p = 0.008) and (4) more stage IV disease (40.6%, p = 0.03). Patients with negative HP had worse overall survival (24.0% vs. 35.8%, p = 0.035). In Cox regression models, the negative HP status is an independent poor prognostic factor (HR: 1.34, CI:1.04–1.71, p = 0.019) in model 1, especially in stage I, II and III patients (HR: 1.62; CI:1.05–2.51,p = 0.026). Conclusion We found the distinct characteristics of HP negative GC. The prognosis of HP negative GC was poor. PMID:28152027

  12. CpG Island Methylator Phenotype and Prognosis of Colorectal Cancer in Northeast China

    Directory of Open Access Journals (Sweden)

    Xia Li

    2014-01-01

    Full Text Available Purpose. To investigate the association between CpG island methylator phenotype (CIMP and the overall survival of sporadic colorectal cancer (CRC in Northeast China. Methods. 282 sporadic CRC patients were recruited in this study. We selected MLH1, MGMT, p16, APC, MINT1, MINT31, and RUNX3 as the CIMP panel markers. The promoter methylation was assessed by methylation sensitive high resolution melting (MS-HRM. Proportional hazards-regression models were fitted with computing hazard ratios (HR and the corresponding 95% confidence intervals (95% CI. Results. 12.77% (36/282 of patients were CIMP-0, 74.1% (209/282 of patients were CIMP-L, and 13.12% (37/282 of patients were CIMP-H. The five-year survival of the 282 CRC patients was 58%. There was significant association between APC gene promoter methylation and CRC overall survival (HR = 1.61; 95% CI: 1.05–2.46; P=0.03. CIMP-H was significantly associated with worse prognosis compared to CIMP-0 (HR = 3.06; 95% CI: 1.19–7.89; P=0.02 and CIMP-L (HR = 1.97; 95% CI: 1.11–3.48; P=0.02, respectively. While comparing with the combine of CIMP-L and CIMP-0 (CIMP-L/0, CIMP-H also presented a worse prognosis (HR = 2.31; 95% CI: 1.02–5.24; P=0.04. Conclusion. CIMP-H may be a predictor of a poor prognosis of CRC in Northeast China patients.

  13. Pregnancy-associated breast cancer in women from Shanghai: risk and prognosis.

    Science.gov (United States)

    Strasser-Weippl, Kathrin; Ramchandani, Ritesh; Fan, Lei; Li, Junjie; Hurlbert, Marc; Finkelstein, Dianne; Shao, Zhi-Ming; Goss, Paul E

    2015-01-01

    Breast cancer (BC) has been associated with pregnancy if diagnosed within 5-10 years after delivery (pregnancy-associated BC, PABC). PABC carries a poor prognosis compared to sporadic BC in Western populations. Data are limited regarding PABC in Asian populations, where longer periods of breastfeeding, higher birth rates and a lower median age of BC at diagnosis have been noted, all of which are known to influence prognosis. We used two datasets of women treated for early BC in Shanghai 1990-2012 (n = 10,161 and n = 7,411). For the analysis of BC risk after pregnancy we compared the distribution of pregnancy in our dataset to that in Shanghai using age-specific fertility rates. For disease-free survival (DFS) evaluation, we restricted our data to women ≤45 years. Women pregnancy compared to women who had not been pregnant in the previous 5 years. In women aged 20-24 the relative risk (RR) was 3.33 (P = 0.012), and for women aged 25-29 the RR was 1.76 (P = 0.0074). For women >30, the RR was decreased. Patients with PABC had a higher risk of recurrence or death (hazard ratio (HR) for DFS 1.72, P = 0.019) compared to women with non-PABC by univariable analysis. Age was eliminated from the multivariable model by backward selection, resulting in tumor stage (3 versus 1, HR 3.08, P pregnancy (HR 1.62, P pregnancy in the previous 5 years was associated with a 62 % increased risk of recurrence. We show that recent full-term pregnancy significantly elevates BC risk in women <30 in Shanghai, and that women diagnosed with PABC have a particularly adverse prognosis. Health care providers and women in Asian populations should be made aware of these results.

  14. Expression of XPG protein in the development, progression and prognosis of gastric cancer.

    Directory of Open Access Journals (Sweden)

    Na Deng

    Full Text Available BACKGROUND: Xeroderma pigmentosum group G (XPG plays a critical role in preventing cells from oxidative DNA damage. This study aimed to investigate XPG protein expression in different gastric tissues and in patients with diverse prognoses, thus providing insights into its role in the development, progression and prognosis of gastric cancer (GC. METHODS: A total of 176 GC, 131 adjacent non-tumour tissues, 53 atrophic gastritis (AG and 49 superficial gastritis (SG samples were included. Immunohistochemical staining was used to detect XPG protein expression. RESULTS: XPG expression was significantly higher in GC tissues compared with adjacent non-tumour tissues. In the progressive disease sequence SG→AG→GC, XPG expression was significantly higher in AG and GC compared with SG. Analysis of clinicopathological parameters and survival in GC patients demonstrated a significant association between XPG expression level and depth of tumour invasion, macroscopic type, Lauren's classification, smoking, Helicobacter pylori infection and family history. Cox multivariate survival analysis indicated that patients with positive XPG expression had significantly longer overall survival (P = 0.020, HR = 0.394, 95%CI 0.179-0.866, especially in aged younger than 60 years (P = 0.027, HR = 0.361, 95%CI 0.147-0.888 and male patients (P = 0.002, HR = 0.209, 95%CI 0.077-0.571. CONCLUSIONS: This study demonstrated that XPG protein expression was related to the development, progression and prognosis of GC, and might thus serve as a potential biomarker for its diagnosis and prognosis.

  15. 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...

  16. 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.

  17. 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.)

  18. Regulator of G protein signaling 20 correlates with clinicopathological features and prognosis in triple-negative breast cancer.

    Science.gov (United States)

    Li, Quan; Jin, Wenxu; Cai, Yefeng; Yang, Fang; Chen, Endong; Ye, Danrong; Wang, Qingxuan; Guan, Xiaoxiang

    2017-04-08

    Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype lacking effective prognostic indicators or therapeutic targets. Therefore, finding a novel molecular biomarker for TNBC to achieve target therapy and predict its prognosis is crucial in preventing inappropriate treatment. Regulator of G-protein signaling (RGS) families of protein can negatively regulate signaling of heterotrimeric G proteins and are known to be upregulated in various tumors. In this study, we demonstrated that RGS20 was more highly expressed in TNBC tumor tissue than in adjacent normal tissue by analyzing the cancer genome atlas (TCGA) database. However, RGS20 expression was low in all breast cancer and luminal breast cancer patients. Validated by the TCGA cohort, RGS20 was upregulated in lymph node-positive TNBC compared with that in lymph node-negative breast cancer. High expression of RGS20 had a risk of lymph node metastasis, ki-67 > 14%, poor N stage, and poor clinical stage in the immunohistochemistry of tissue microarrays. Moreover, K-M plot analysis showed that TNBC patients with high RGS20 expression had poor relapse-free survival. In summary, the findings revealed that RGS20 was a special TNBC oncogene that promoted tumor progression and influenced TNBC prognosis. This study is the first to show that RGS20 was a special oncogene, and its high expression was significantly associated with the progression and prognosis of TNBC. RGS20 may be a novel molecular biomarker for the targeted therapy and prognosis of TNBC.

  19. A novel model to combine clinical and pathway-based transcriptomic information for the prognosis prediction of breast cancer.

    Directory of Open Access Journals (Sweden)

    Sijia Huang

    2014-09-01

    Full Text Available Breast cancer is the most common malignancy in women worldwide. With the increasing awareness of heterogeneity in breast cancers, better prediction of breast cancer prognosis is much needed for more personalized treatment and disease management. Towards this goal, we have developed a novel computational model for breast cancer prognosis by combining the Pathway Deregulation Score (PDS based pathifier algorithm, Cox regression and L1-LASSO penalization method. We trained the model on a set of 236 patients with gene expression data and clinical information, and validated the performance on three diversified testing data sets of 606 patients. To evaluate the performance of the model, we conducted survival analysis of the dichotomized groups, and compared the areas under the curve based on the binary classification. The resulting prognosis genomic model is composed of fifteen pathways (e.g., P53 pathway that had previously reported cancer relevance, and it successfully differentiated relapse in the training set (log rank p-value = 6.25e-12 and three testing data sets (log rank p-value < 0.0005. Moreover, the pathway-based genomic models consistently performed better than gene-based models on all four data sets. We also find strong evidence that combining genomic information with clinical information improved the p-values of prognosis prediction by at least three orders of magnitude in comparison to using either genomic or clinical information alone. In summary, we propose a novel prognosis model that harnesses the pathway-based dysregulation as well as valuable clinical information. The selected pathways in our prognosis model are promising targets for therapeutic intervention.

  20. 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

  1. 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

  2. Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures

    Directory of Open Access Journals (Sweden)

    Dharanija eMadhavan

    2013-06-01

    Full Text Available In the recent years, circulating microRNAs (miRNAs have garnered a lot of attention and interest in the field of disease biomarkers. With characteristics such as high stability, low cost, possibility of repeated sampling and minimal invasiveness, circulating miRNAs are ideal for development into diagnostic tests. There have been many studies reported on the potential of circulating miRNAs as early detection, prognostic and predictive biomarkers in cancer. Here, we have reviewed the use of plasma and serum miRNAs as biomarkers for cancer focusing on epithelial carcinomas (prostate, breast, lung, colorectal and gastric cancer and haematological malignancies (leukaemia and lymphoma. We have also addressed the common challenges that need to be overcome to achieve a successful bench to bedside transition.

  3. FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Leandra Fiori Lopes

    2014-01-01

    Full Text Available Triple negative breast cancer (TNBC is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2. FOXP3 (forkhead transcription factor 3 is a marker of regulatory T cells (Tregs, whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548 and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction. Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06 in relation to TNBC susceptibility. Most of the patients (83% showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026. In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Intrathecal trastuzumab: immunotherapy improves the prognosis of leptomeningeal metastases in HER-2+ breast cancer patient.

    Science.gov (United States)

    Lu, Nu T; Raizer, Jeffrey; Gabor, Erwin P; Liu, Natalie M; Vu, James Q; Slamon, Dennis J; Barstis, John L

    2015-01-01

    We describe the clinical and therapeutic course of a 51-year-old woman with HER-2+ breast cancer who developed leptomeningeal (LM) and spinal cord metastases after 8 years of stable disease on combination therapy with intravenous (IV) trastuzumab. Due to progressive CNS disease, intrathecal (IT) trastuzumab was introduced to enhance HER-2+ therapy into the CSF space. A combination HER-2+ targeted approach achieved clinical remission with stable disease in our patient 46 months after she was diagnosed with LM metastases. However, spinal cord C-1 metastasis was not fully controlled with IT trastuzumab, ultimately leading to the patient's respiratory compromise. In our patient, IT trastuzumab immunotherapy improved prognosis and was an effective strategy to manage HER-2+ LM disease. Given alone or alongside other anti-HER-2+ therapeutics with sufficient CNS penetration, IT trastuzumab could extend the lifespan of patients with leptomeningeal and CNS metastases.

  6. Preoperative mannan-binding lectin pathway and prognosis in colorectal cancer

    DEFF Research Database (Denmark)

    Ytting, Henriette; Christensen, Ib Jarle; Jensenius, Jens Christian

    2005-01-01

    PURPOSE: Deficiency of the mannan-binding lectin (MBL) pathway of innate immunity is associated with increased susceptibility to infections. In patients with colorectal cancer (CRC), postoperative infection is associated with poor prognosis. The aim of the present study was to evaluate (1......) the relation between the MBL pathway and postoperative infectious complications and survival of patients resected for CRC, and (2) the role of MBL in acute phase response compared to C-reactive protein (CRP). METHODS: Preoperative MBL concentration, MBL-associated serine protease (MBL/MASP) activity and CRP...... were determined in serum from 611 patients and 150 healthy controls. The patients were observed for 8 years. Postoperative infections, recurrence and survival were recorded. RESULTS: The MBL pathway components were increased in the patients compared with the healthy controls (p

  7. Influence of Perioperative Blood Transfusion on Prognosis in Patients with Colon Cancer

    Institute of Scientific and Technical Information of China (English)

    LIANG Han; WANG Xiaona; WANG Baogui; PAN Yuan; LIU Ning; WANG Dianchang; HAO Xishan

    2006-01-01

    Objective: To explore the influence of perioperative blood transfusion on the postoperative survival of patients with colon cancer. Methods: Univariate and multivariate retrospective analyses were performed on the survival in a total of 723 colon cancer patients which were treated surgically during a period of 10 years. Results: Kaplan-Meicr estimates showed that more than 800 mL perioperative blood transfusion was the survival predictor. Blood transfusion influenced significantly the prognosis of patients 40 years old and younger, those undergoing helicoloectomy left side, those with papillary adenocarcinoma,those with big tumors (diameter ≥8 em), those with stage I tumors, those with lymphatic node metastases and those without liver metastases. In multivariate analysis only the tumor location, radicality of operation, lymphatic invasion, liver metastasis, depth of tumor invasion and TNM stage retained their significance. Conclusion: Perioperative blood transfusion is the prognostic factor for patients with colon cancer to some extent. The indication of blood transfusion must be restricted strictly, specially in patients younger than 40 years old, with right side lesion, papillary adenocarcinoma, big tumors (diameter ≥8 em), stage I tumors and lymphatic node metastases or without liver metastases. But perioperative blood transfusion may not be deleterious for patients with staging Ⅳ disease and with distant metastases.

  8. Molecular Biomarkers in Bladder Cancer: Novel Potential Indicators of Prognosis and Treatment Outcomes

    Directory of Open Access Journals (Sweden)

    Masayoshi Nagata

    2016-01-01

    Full Text Available Although many clinical and molecular markers for predicting outcomes in bladder cancer (BC have been reported, their application in clinical practice remains unclear. Bladder carcinogenesis has two distinct molecular pathways that direct the development of BC. FGFR3 mutations are common in low-grade BC, while TP53 mutation or loss of RB1 is associated with muscle-invasive BC. However, no tissue-based gene markers confirmed by prospective large-scale trials in BC have been used in clinical practice. Micro-RNA analyses of BC tissue revealed that miR-145 and miR-29c⁎ function as tumor suppressors, whereas miR-183 and miR-17-5p function as oncogenic miRNAs. In liquid biopsy, circulating tumor cells (CTC, exosomes, or cell-free RNA is extracted from the peripheral blood samples of cancer patients to analyze cancer prognosis. It was reported that detection of CTC was associated with poor prognostic factors. However, application of liquid biopsy in BC treatment is yet to be explored. Although several cell-free RNAs, such as miR-497 in plasma or miR-214 in urine, could be promising novel circulating biomarkers, they are used only for diagnosing BC as the case that now stands. Here, we discuss the application of novel biomarkers in evaluating and measuring BC outcomes.

  9. The Trend of Age-Group Effect on Prognosis in Differentiated Thyroid Cancer

    Science.gov (United States)

    Shi, Rong-liang; Qu, Ning; Liao, Tian; Wei, Wen-jun; Wang, Yu-Long; Ji, Qing-hai

    2016-01-01

    Age has been included in various prognostic scoring systems for differentiated thyroid cancer (DTC). The aim of this study is to re-examine the relationship between age and prognosis by using Surveillance, Epidemiology, and End Results (SEER) population-based database. We identified 51,061 DTC patients between 2004 and 2012. Patients were separated into 10-year age groups. Cancer cause-specific survival (CSS) and overall survival (OS) data were obtained. Kaplan-Meier and multivariable Cox models were built to analyze the outcomes and risk factors. Increasing age gradient with a 10-year interval was associated with the trend of higher proportions for male gender, grade III/IV and summary stage of distant metastases. Both CSS and OS continued to worsen with increasing age, being poorest in in the oldest age group (≥71); multivariate analysis confirmed that CSS continued to fall with each age decade, significantly starting at 60 years (HR = 7.5, 95% 1.0–54.1, p = 0.047) compared to the young group (≤20). Similarly, multivariate analysis suggested that OS continued worsening with increasing age, but starting at 40 years (HR = 3.7, 95% 1.4–10.1, p = 0.009) compared to the young group. The current study suggests that an age exceeding 60 years itself represents an unfavorable prognostic factor and high risk for cancer-specific death in DTC. PMID:27272218

  10. Differential involvement of RASSF2 hypermethylation in breast cancer subtypes and their prognosis

    Science.gov (United States)

    Perez-Janices, Noemi; Blanco-Luquin, Idoia; Torrea, Natalia; Liechtenstein, Therese; Escors, David; Cordoba, Alicia; Vicente-Garcia, Francisco; Jauregui, Isabel; De La Cruz, Susana; Illarramendi, José Juan; Coca, Valle; Berdasco, Maria; Kochan, Grazyna; Ibañez, Berta; Lera, José Miguel; Guerrero-Setas, David

    2015-01-01

    Breast cancer is a heterogeneous disease that can be subdivided into clinical, histopathological and molecular subtypes (luminal A-like, luminal B-like/HER2-negative, luminal B-like/HER2-positive, HER2-positive, and triple-negative). The study of new molecular factors is essential to obtain further insights into the mechanisms involved in the tumorigenesis of each tumor subtype. RASSF2 is a gene that is hypermethylated in breast cancer and whose clinical value has not been previously studied. The hypermethylation of RASSF1 and RASSF2 genes was analyzed in 198 breast tumors of different subtypes. The effect of the demethylating agent 5-aza-2′-deoxycytidine in the re-expression of these genes was examined in triple-negative (BT-549), HER2 (SK-BR-3), and luminal cells (T-47D). Different patterns of RASSF2 expression for distinct tumor subtypes were detected by immunohistochemistry. RASSF2 hypermethylation was much more frequent in luminal subtypes than in non-luminal tumors (p = 0.001). The re-expression of this gene by lentiviral transduction contributed to the differential cell proliferation and response to antineoplastic drugs observed in luminal compared with triple-negative cell lines. RASSF2 hypermethylation is associated with better prognosis in multivariate statistical analysis (P = 0.039). In conclusion, RASSF2 gene is differently methylated in luminal and non-luminal tumors and is a promising suppressor gene with clinical involvement in breast cancer. PMID:26284587

  11. Early prognosis of metastasis risk in inflammatory breast cancer by texture analysis of tumour microscopic images.

    Science.gov (United States)

    Kolarevic, Daniela; Tomasevic, Zorica; Dzodic, Radan; Kanjer, Ksenija; Vukosavljevic, Dragica Nikolic; Radulovic, Marko

    2015-10-01

    Inflammatory breast cancer (IBC) is a rare and aggressive type of locally advanced breast cancer. The purpose of this study was to determine the value of microscopic tumour histomorphology texture for prognosis of local and systemic recurrence at the time of initial IBC diagnosis. This retrospective study included a group of 52 patients selected on the basis of non-metastatic IBC diagnosis, stage IIIB. Gray-Level-Co-Occurrence-Matrix (GLCM) texture analysis was performed on digital images of primary tumour tissue sections stained with haematoxylin/eosin. Obtained values were categorized by use of both data- and outcome-based methods. All five acquired GLCM texture features significantly associated with metastasis outcome. By accuracies of 69-81% and AUCs of 0.71-0.81, prognostic performance of GLCM parameters exceeded that of standard major IBC clinical prognosticators such as tumour grade and response to induction chemotherapy. Furthermore, a composite score consisting of tumour grade, contrast and correlation as independent features resulted in further enhancement of prognostic performance by accuracy of 89%, discrimination efficiency by AUC of 0.93 and an outstanding hazard ratio of 71.6 (95%CI, 41.7-148.4). Internal validation was successfully performed by bootstrap and split-sample cross-validation, suggesting that the model is generalizable. This study indicates for the first time the potential use of primary breast tumour histology texture as a highly accurate, simple and cost-effective prognostic indicator of metastasis risk in IBC. Clinical relevance of the obtained results rests on the role of prognosis in decisions on induction chemotherapy and the resulting impact on quality of life and survival.

  12. Increased red blood cell distribution width associates with cancer stage and prognosis in patients with lung cancer.

    Directory of Open Access Journals (Sweden)

    Yasuko Koma

    Full Text Available BACKGROUND: Red cell distribution width (RDW, one of many routinely examined parameters, shows the heterogeneity in erythrocyte size. We investigated the association of RDW levels with clinical parameters and prognosis of lung cancer patients. METHODS: Clinical and laboratory data from 332 patients with lung cancer in a single institution were retrospectively studied by univariate analysis. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. RESULTS: THE RDW LEVELS WERE DIVIDED INTO TWO GROUPS: high RDW (>=15%, n=73 vs. low RDW, n=259 (<15%. Univariate analysis showed that there were significant associations of high RDW values with cancer stage, performance status, presence of other disease, white blood cell count, hemoglobin, mean corpuscular volume, platelet count, albumin level, C-reactive protein level, and cytokeratin 19 fragment level. Kruskal-Wallis tests revealed an association of RDW values with cancer stage in patients irrespective of comorbidity (patient with/without comorbidity: p<0.0001, patient without comorbidity: p<0.0001. Stages I-IV lung cancer patients with higher RDW values had poorer prognoses than those with lower RDW values (Wilcoxon test: p=0.002. In particular, the survival rates of stage I and II patients (n=141 were lower in the high RDW group (n=19 than in the low RDW group (n=122 (Wilcoxon test: p<0.001. Moreover, multivariate analysis showed higher RDW is a significant prognostic factor (p=0.040. CONCLUSION: RDW is associated with several factors that reflect inflammation and malnutrition in lung cancer patients. Moreover, high levels of RDW are associated with poor survival. RDW might be used as a new and convenient marker to determine a patient's general condition and to predict the mortality risk of lung cancer patients.

  13. Trends in incidence and prognosis of the histological subtypes of lung cancer in North America, Australia, New Zealand and Europe

    NARCIS (Netherlands)

    M.L.G. Janssen-Heijnen (Maryska); J.W.W. Coebergh (Jan Willem)

    2001-01-01

    textabstractBackground: Since the incidence of the histological subtypes of lung cancer in industrialised countries has changed dramatically over the last two decades, we reviewed trends in the incidence and prognosis in North America, Australia, New Zealand and Europe, according to period of diagno

  14. Long-term prognosis of breast cancer: An analysis of 462 patients in a general hospital in south east Netherlands

    NARCIS (Netherlands)

    H.W. Nab (Henk); N. Kluck (Nadine); E.J.T. Rutgers (Emiel); J.W.W. Coebergh (Jan Willem); W.C.J. Hop (Wim)

    1995-01-01

    textabstractIn this study the long-term prognosis was analysed of all 462 consecutive female breast cancer patients who were diagnosed and carefully staged between 1970 and 1980 in a 600-bed community hospital in Eindhoven, south east Netherlands. Follow-up of recurrence and causes of death was obta

  15. Long-term prognosis of patients with local recurrence after conservative surgery and radiotherapy for early breast cancer

    NARCIS (Netherlands)

    A.C. Voogd (Adri); F.J. van Oost (F.); E.J.T. Rutgers (Emiel); S. Elkhuizen (Sylvia); A.N. van Geel (Albert); L.J.E.E. Scheijmans (L. J E E); M.J.C. van der Sangen (Maurice); G. Botke (G.); C.J.M. Hoekstra (C. J M); J.J. Jobsen (Jan); C.J.H. van de Velde (Cornelis); M.F. von Meyenfeldt (Maarten); J.M. Tabak (J.); J.L. Peterse (J.); M.J. Vijver (Marc ); J.W.W. Coebergh (Jan Willem); G. van Tienhoven (Geertjan)

    2005-01-01

    textabstractWe have studied the long-term prognosis of 266 patients considered to have isolated local recurrence in the breast following conservative surgery and radiotherapy for early breast cancer. The median follow-up of the patients still alive after diagnosis of local relapse was 11.2 years. At

  16. TRIB3 protein denotes a good prognosis in breast cancer patients and is associated with hypoxia sensitivity

    NARCIS (Netherlands)

    Wennemers, M.; Bussink, J.; Grebenchtchikov, N.J.; Sweep, F.C.; Span, P.N.

    2011-01-01

    BACKGROUND: Tribbles homolog 3 (TRIB3) is a pseudokinase involved in the regulation of several signaling pathways involved in cell survival and/or cell stress. Here, we determined the correlation between breast cancer prognosis and TRIB3 protein levels and established the role of TRIB3 in cell survi

  17. Determinants of prognosis in breast cancer patients with tumor involvement of the skin (pT4b).

    NARCIS (Netherlands)

    Wieland, A.W.; Louwman, M.W.; Voogd, A.C.; Beek, M.W. van; Vreugdenhil, G.R.; Roumen, R.M.H.

    2004-01-01

    Determinants of prognosis were studied in patients with breast cancer with histologically proven tumor extension to the skin without clinical evidence of distant metastases (i.e., pT4b N0-3 M0). Data were collected retrospectively on 77 consecutive patients diagnosed in one community teaching hospit

  18. MicroRNAs as biomarkers for early breast cancer diagnosis, prognosis and therapy prediction.

    Science.gov (United States)

    Nassar, Farah J; Nasr, Rihab; Talhouk, Rabih

    2016-12-01

    Breast cancer is a major health problem that affects one in eight women worldwide. As such, detecting breast cancer at an early stage anticipates better disease outcome and prolonged patient survival. Extensive research has shown that microRNA (miRNA) are dysregulated at all stages of breast cancer. miRNA are a class of small noncoding RNA molecules that can modulate gene expression and are easily accessible and quantifiable. This review highlights miRNA as diagnostic, prognostic and therapy predictive biomarkers for early breast cancer with an emphasis on the latter. It also examines the challenges that lie ahead in their use as biomarkers. Noteworthy, this review addresses miRNAs reported in patients with early breast cancer prior to chemotherapy, radiotherapy, surgical procedures or distant metastasis (unless indicated otherwise). In this context, miRNA that are mentioned in this review were significantly modulated using more than one statistical test and/or validated by at least two studies. A standardized protocol for miRNA assessment is proposed starting from sample collection to data analysis that ensures comparative analysis of data and reproducibility of results.

  19. Downregulation of the long noncoding RNA EGOT correlates with malignant status and poor prognosis in breast cancer.

    Science.gov (United States)

    Xu, Shou-Ping; Zhang, Jin-Feng; Sui, Shi-Yao; Bai, Nan-Xia; Gao, Song; Zhang, Guang-Wen; Shi, Qing-Yu; You, Zi-Long; Zhan, Chao; Pang, Da

    2015-12-01

    Eosinophil granule ontogeny transcript (EGOT) is a long noncoding RNA involved in the regulation of eosinophil granule protein transcript expression. However, little is known about the role of EGOT in malignant disease. This study aimed to assess the potential role of EGOT in the pathogenesis of breast cancer. Quantitative real-time polymerase chain reaction was performed to detect the expression levels of EGOT in 250 breast cancerous tissues and 50 adjacent noncancerous tissues. The correlation of EGOT expression with clinicopathological features and prognosis was also analyzed. EGOT expression was lower in breast cancer compared with the adjacent noncancerous tissues (P prognosis for overall survival (P = 0.040), and this result was further validated in a larger cohort from a public database. Multivariate analysis suggested that low levels of EGOT were a poor independent prognostic predictor for breast cancer patients (HR = 1.857, 95 % CI = 1.032-3.340, P = 0.039). In conclusion, EGOT may play an important role in breast cancer progression and prognosis and may serve as a new potential prognostic target in breast cancer patients.

  20. Plasma testosterone in the general population, cancer prognosis and cancer risk

    DEFF Research Database (Denmark)

    Orsted, D D; Nordestgaard, B G; Bojesen, S E

    2014-01-01

    BACKGROUND: Testosterone is an important anabolic hormone in humans and in vitro testosterone stimulates growth of lung and colon cancer cells. We tested the hypothesis that plasma testosterone associate with increased risk of cancer and with increased risk of early death after cancer. MATERIALS...... AND METHODS: Plasma testosterone was measured in 8771 20- to 94-year-old men and women who participated in a prospective study of the general population. Participants were included in 1981-1983 and followed for a median of 22 years (range: 0-30 years). RESULTS: During follow-up, 1140 men and 809 women...

  1. NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

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    Chunhao Niu

    2016-10-01

    Full Text Available Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6 in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC. NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO stage (p = 0.006, squamous cell carcinoma antigen (p = 0.006, vital status (p < 0.001, tumor recurrence (p = 0.001, chemotherapy (p = 0.039, and lymph node metastasis (p < 0.001. Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer.

  2. The Role of Epigenomics in the Study of Cancer Biomarkers and in the Development of Diagnostic Tools.

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    Verma, Mukesh

    2015-01-01

    Epigenetics plays a key role in cancer development. Genetics alone cannot explain sporadic cancer and cancer development in individuals with no family history or a weak family history of cancer. Epigenetics provides a mechanism to explain the development of cancer in such situations. Alterations in epigenetic profiling may provide important insights into the etiology and natural history of cancer. Because several epigenetic changes occur before histopathological changes, they can serve as biomarkers for cancer diagnosis and risk assessment. Many cancers may remain asymptomatic until relatively late stages; in managing the disease, efforts should be focused on early detection, accurate prediction of disease progression, and frequent monitoring. This chapter describes epigenetic biomarkers as they are expressed during cancer development and their potential use in cancer diagnosis and prognosis. Based on epigenomic information, biomarkers have been identified that may serve as diagnostic tools; some such biomarkers also may be useful in identifying individuals who will respond to therapy and survive longer. The importance of analytical and clinical validation of biomarkers is discussed, along with challenges and opportunities in this field.

  3. Potential uses of microRNA in lung cancer diagnosis, prognosis, and therapy.

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    Wang, Qi Zhao; Xu, William; Habib, Nagy; Xu, Ruian

    2009-06-01

    Lung cancer is the leading cause of death from cancer in the world. Although the molecular network of lung carcinogenesis has been partly known at the levels of genes and proteins, and personalized therapy based on the genetic changes has made considerable progress in the last decade, the high mortality rate is not markedly changed. MicroRNAs (miRNAs), a class of short endogenous RNAs, acting as post-transcriptional regulators of gene expression, are similar with siRNAs in both the biosynthesis and the function steps. While, miRNAs mostly silence gene expression by binding imperfectly matched sequences in the 3' UTR of target mRNA, which is different with siRNAs by targeting ORF of mRNA with a perfectly complementary manner. miRNAs have multiple functions in lung development, and abnormal expression of miRNAs could lead to lung tumorigenesis. The different expression profiles of miRNAs in lung cancer, and the stability of miRNAs in serum, all together make them as new potentially clinical biomarkers for diagnosis and prognosis. Moreover, miRNAs may serve as either novel potential targets acting directly as oncogenes (e.g. miR-17-92 cluster) or directly therapeutic molecules working as tumor suppressor genes (e.g. let-7 family). RNAi technology based on miRNAs has many advantages over siRNAs, such as in vivo stability, highly RNA promoter-compatibility and no overt toxicity. Eventually, it might overcome the present disadvantages and become a good candidate for lung cancer therapy.

  4. Phosphoglycerate dehydrogenase is a novel predictor for poor prognosis in gastric cancer

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    Xian Y

    2016-09-01

    Full Text Available Yun Xian,1,* Shu Zhang,2,* Xudong Wang,3 Jin Qin,2 Wei Wang,2 Han Wu4 1School of Public Health, Nantong University, 2Department of Pathology, 3Department of Laboratory Medicine, 4Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China *These authors contributed equally to this work Purpose: Phosphoglycerate dehydrogenase (PHGDH acts as a key metabolic enzyme in the rate-limiting step in serine biosynthesis and plays an important role in metastasis of several cancers. The aim of this study was to investigate the prognostic value of PHGDH in gastric cancer (GC. Methods: The messenger RNA expression of PHGDH was determined in 20 pairs of cancerous and adjacent nontumor tissues by real-time polymerase chain reaction. Immunohistochemistry of PHGDH was performed on tissue microarray, composed of 482 GC and 64 matched adjacent nontumor tissues acquired from surgery, 20 chronic gastritis, 18 intestinal metaplasia, and 31 low-grade and 66 high-grade intraepithelial neoplasias acquired through gastric endoscopic biopsy. Univariate and multivariate Cox proportional hazard models were used to perform survival analyses. Results: Both PHGDH messenger RNA and protein product exhibited GC tissue-preferred expression, when compared with benign tissues. The high PHGDH expression was significantly correlated with histological type (P=0.011, tumor stage (P=0.014, and preoperative carcinoembryonic antigen (P<0.001. A negative correlation was found between PHGDH expression and the 5-year survival rate of patients with GC. Furthermore, multivariate analysis indicated that PHGDH was an independent prognostic factor for outcome in GC. Conclusion: PHGDH is important in predicting patient outcomes and is a potential target for the development of therapeutic approaches to GC. Keywords: metabolism, gastric cancer, prognosis, serine biosynthesis

  5. The prognosis of patients less than 40 years with bladder cancer

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    Seong Woong Na

    2014-01-01

    Full Text Available Aims: Natural history of young patients with bladder cancer has not yet been known. So this study aimed to understand characteristics and prognosis of patients less than 40 years with bladder cancer. Materials and Methods: We retrospectively analyzed 42 patients (group 1 less than 40 years with bladder cancer followed up for 6 months at least from October 1998 to January 2010. As controlled group (group 2 consisted 44 patients of 60 years or more who had same condition as above mentioned from January to December 2009 was set. Tumor size and number, pathological results, urine cytology results and recurrence rate were reviewed. Results: The mean ages and the gender distribution in the two groups showed no difference. Tumor size (P = 0.021 and number (P = 0.016 in group 1 was smaller than control. The proportion of muscle invasive type was not significant, but pTa in group 1 was occupied larger portion than group 2 (P = 0.01. Group 1 had more low grade cancer (P = 0.013, and lower recurrence rate (7.1% than group 2 (38.6% (P = 0.001. In addition, the mean recurrence free duration of group 1 and 2 were 37.7 ± 6.3 and 9.9 ± 2.5 months, respectively. Group 1 showed later relapse than group 2 (P = 0.002. No progression in stage at recurrence was in group 1, but 1 case had progression in group 2. In grade, 1 case was worsen in group 1 and 3 cases were worsen in group 2.

  6. Relationship Between HER2 Status and Prognosis in Women With Brain Metastases From Breast Cancer

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    Xu Zhiyuan [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Marko, Nicholas F. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Chao, Sam T. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Angelov, Lilyana; Vogelbaum, Michael A. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Suh, John H. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Barnett, Gene H. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Weil, Robert J., E-mail: weilr@ccf.org [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States)

    2012-04-01

    Purpose: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. Methods and Materials: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. Results: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2- breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. Conclusions: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2- lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2- and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions.

  7. Evaluation of correlation between CT image features and ERCC1 protein expression in assessing lung cancer prognosis

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    Tan, Maxine; Emaminejad, Nastaran; Qian, Wei; Sun, Shenshen; Kang, Yan; Guan, Yubao; Lure, Fleming; Zheng, Bin

    2014-03-01

    Stage I non-small-cell lung cancers (NSCLC) usually have favorable prognosis. However, high percentage of NSCLC patients have cancer relapse after surgery. Accurately predicting cancer prognosis is important to optimally treat and manage the patients to minimize the risk of cancer relapse. Studies have shown that an excision repair crosscomplementing 1 (ERCC1) gene was a potentially useful genetic biomarker to predict prognosis of NSCLC patients. Meanwhile, studies also found that chronic obstructive pulmonary disease (COPD) was highly associated with lung cancer prognosis. In this study, we investigated and evaluated the correlations between COPD image features and ERCC1 gene expression. A database involving 106 NSCLC patients was used. Each patient had a thoracic CT examination and ERCC1 genetic test. We applied a computer-aided detection scheme to segment and quantify COPD image features. A logistic regression method and a multilayer perceptron network were applied to analyze the correlation between the computed COPD image features and ERCC1 protein expression. A multilayer perceptron network (MPN) was also developed to test performance of using COPD-related image features to predict ERCC1 protein expression. A nine feature based logistic regression analysis showed the average COPD feature values in the low and high ERCC1 protein expression groups are significantly different (p < 0.01). Using a five-fold cross validation method, the MPN yielded an area under ROC curve (AUC = 0.669±0.053) in classifying between the low and high ERCC1 expression cases. The study indicates that CT phenotype features are associated with the genetic tests, which may provide supplementary information to help improve accuracy in assessing prognosis of NSCLC patients.

  8. Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis

    Science.gov (United States)

    Bria, E.; Pilotto, S.; Simbolo, M.; Fassan, M.; de Manzoni, G.; Carbognin, L.; Sperduti, I.; Brunelli, M.; Cataldo, I.; Tomezzoli, A.; Mafficini, A.; Turri, G.; Karachaliou, N.; Rosell, R.; Tortora, G.; Scarpa, A.

    2016-01-01

    In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29.4%), KRAS (26.5%), TP53 (26.5%) MET (8.8%), SMAD4 (8.8%) and STK11 (8.8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9.5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82.4%), followed by E-Cadherin (76.5%) and FHIT (52.9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC. PMID:26961069

  9. Downregulated Ku70 and ATM associated to poor prognosis in colorectal cancer among Chinese patients

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    Lu YF

    2014-10-01

    Full Text Available Yuanfang Lu,1,2 Jingyan Gao,1,3 Yuanming Lu,1 1Department of Toxicology, School of Public Health, Guilin Medical University, Guangxi, People's Republic of China; 2Department of Clinical Research Center, Affiliated 2nd Hospital of Nanjing Medical University, Nanjing, People's Republic of China; 3Department of Human Anatomy and Histo-Embryology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Background: Double-strand DNA breaks (DSBs are a key factor in carcinogenesis. The necessary repair of DSBs is pivotal in maintaining normal cell division. To address the relationship between altered expression of DSB repair of proteins Ku70 and ataxia-telangiectasia mutated (ATM in colorectal cancer (CRC, we examined the expression levels and patterns of Ku70 and ATM in CRC samples. Methods: Expression and coexpression of Ku70 and ATM were investigated by using real-time quantitative polymerase chain reaction assays and confirmed further with fluorescent immunohistochemistry in CRC and pericancerous samples from 112 Chinese patients. Results: Downexpression patterns for both Ku70 and ATM were found in the CRC samples and were significantly associated with advanced tumor node metastasis stage and decreased 5-year overall survival rate. Conclusion: Downregulated Ku70 and ATM were associated with poor disease-free survival. Loss of Ku70 and ATM expression might act as a biomarker to predict poor prognosis in patients with CRC. Keywords: DNA double-strand breaks, ataxia-telangiectasia mutated, Ku70, colorectal cancer

  10. Identification of CEACAM5 as a Biomarker for Prewarning and Prognosis in Gastric Cancer.

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    Zhou, Jinfeng; Fan, Xing; Chen, Ning; Zhou, Fenli; Dong, Jiaqiang; Nie, Yongzhan; Fan, Daiming

    2015-12-01

    MGd1, a monoclonal antibody raised against gastric cancer cells, possesses a high degree of specificity for gastric cancer (GC). Here we identified that the antigen of MGd1 is CEACAM5, and used MGd1 to investigate the expression of CEACAM5 in non-GC and GC tissues (N=643), as a biomarker for prewarning and prognosis. The expression of CEACAM5 was detected by immunohistochemistry in numerous tissues; its clinicopathological correlation was statistically analyzed. CEACAM5 expression was increased progressively from normal gastric mucosa to chronic atrophic gastritis, intestinal metaplasia, dysplasia and finally to GC (pgastric precancerous lesions (intestinal metaplasia and dysplasia), CEACAM5-positive patients had a higher risk of developing GC as compared with CEACAM5-negative patients (OR = 12.68, pgastric adenocarcinoma (p<0.001). In survival analysis, CEACAM5 was demonstrated to be an independent prognostic predictor for patients with GC of clinical stage IIIA/IV (p=0.033). Our results demonstrate that CEACAM5 is a promising biomarker for GC prewarning and prognostic evaluation.

  11. Stroma-associated master regulators of molecular subtypes predict patient prognosis in ovarian cancer

    Science.gov (United States)

    Zhang, Shengzhe; Jing, Ying; Zhang, Meiying; Zhang, Zhenfeng; Ma, Pengfei; Peng, Huixin; Shi, Kaixuan; Gao, Wei-Qiang; Zhuang, Guanglei

    2015-01-01

    High-grade serous ovarian carcinoma (HGS-OvCa) has the lowest survival rate among all gynecologic cancers and is hallmarked by a high degree of heterogeneity. The Cancer Genome Atlas network has described a gene expression-based molecular classification of HGS-OvCa into Differentiated, Mesenchymal, Immunoreactive and Proliferative subtypes. However, the biological underpinnings and regulatory mechanisms underlying the distinct molecular subtypes are largely unknown. Here we showed that tumor-infiltrating stromal cells significantly contributed to the assignments of Mesenchymal and Immunoreactive clusters. Using reverse engineering and an unbiased interrogation of subtype regulatory networks, we identified the transcriptional modules containing master regulators that drive gene expression of Mesenchymal and Immunoreactive HGS-OvCa. Mesenchymal master regulators were associated with poor prognosis, while Immunoreactive master regulators positively correlated with overall survival. Meta-analysis of 749 HGS-OvCa expression profiles confirmed that master regulators as a prognostic signature were able to predict patient outcome. Our data unraveled master regulatory programs of HGS-OvCa subtypes with prognostic and potentially therapeutic relevance, and suggested that the unique transcriptional and clinical characteristics of ovarian Mesenchymal and Immunoreactive subtypes could be, at least partially, ascribed to tumor microenvironment. PMID:26530441

  12. EpCAM nuclear localization identifies aggressive Thyroid Cancer and is a marker for poor prognosis

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    MacMillan Christina

    2010-06-01

    Full Text Available Abstract Background Proteolytic cleavage of the extracellular domain (EpEx of Epithelial cell adhesion molecule (EpCAM and nuclear signaling by its intracellular oncogenic domain Ep-ICD has recently been implicated in increased proliferation of cancer cells. The clinical significance of Ep-ICD in human tumors remains an enigma. Methods EpEx, Ep-ICD and β-catenin immunohistochemistry using specific antibodies was conducted on 58 archived thyroid cancer (TC tissue blocks from 34 patients and correlated with survival analysis of these patients for up to 17 years. Results The anaplastic (ATC and aggressive thyroid cancers showed loss of EpEx and increased nuclear and cytoplasmic accumulation of Ep-ICD. In contrast, the low grade papillary thyroid cancers (PTC showed membranous EpEx and no detectable nuclear Ep-ICD. The ATC also showed concomitant nuclear expression of Ep-ICD and β-catenin. Kaplan-Meier Survival analysis revealed reduced overall survival (OS for TC patients showing nuclear Ep-ICD expression or loss of membranous EpEx (p Conclusion We report reciprocal loss of membrane EpEx but increased nuclear and cytoplasmic accumulation of Ep-ICD in aggressive TC; nuclear Ep-ICD correlated with poor OS of TC patients. Thus nuclear Ep-ICD localization may serve as a useful biomarker for aggressive TC and may represent a novel diagnostic, prognostic and therapeutic target for aggressive TC.

  13. Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis

    Institute of Scientific and Technical Information of China (English)

    Meng-Meng Tian; Yu Sun; Zhong-Wu Li; Ying Wu; Ai-Lian Zhao; Ji-You Li

    2012-01-01

    AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 (ICAM-1) and the risk, biological behavior and prognosis of gastric cancer (GC) in Chinese population. METHODS: The study group consisted of 332 GC patients and 380 healthy controls. Genotyping was performed using polymerase chain reaction and the results were confirmed by sequencing. The association of ICAM-1 K469E polymorphisms and the risk of GC were studied, and the correlation of ICAM-1 K469E polymorphisms with the clinicopathological parameters and prognosis of the patients with complete clinical and follow-up data was analyzed.RESULTS: Carriers of AA genotype had a significantly increased risk of GC compared with carriers of AG and GG genotypes [odds ratios: 1.36; 95% confidence interval (CI): 1.01-1.84; P = 0.041]. GC patients with AA genotype were more prone to distant metastasis than those carrying AG and GG genotypes (18.9% vs 7.0%, respectively; P = 0.002). In addition, patients at stage Ⅳ had significantly more carriers of AA genotype than those of AG and GG genotype (27.4% vs 16.9%, respectively; P = 0.046). Follow-up study showed that the overall cumulative survival rate was 23.7% in AA genotype group and 42.9% in AG and GG genotypes group. In univariate analysis, AA genotype was correlated with the overall cumulative survival (P = 0.034). But in multivariate analysis, ICAM-1 polymorphism was not an independent prognostic factor for the overall survival (relative risk, 1.145; 95% CI: 0.851-1.540; P = 0.370). CONCLUSION: Polymorphisms of ICAM-1 K469E can be a useful biomarker for identifying individuals with higher risk of GC, predicting disease progression, and guiding individualized treatment.

  14. Aurora-A identifies early recurrence and poor prognosis and promises a potential therapeutic target in triple negative breast cancer.

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    Xu, Jie; Wu, Xing; Zhou, Wei-hua; Liu, An-wen; Wu, Jian-bing; Deng, Jin-yun; Yue, Cai-feng; Yang, Shao-bing; Wang, Jing; Yuan, Zhong-yu; Liu, Quentin

    2013-01-01

    Triple negative breast cancer (TNBC) acquires an unfavorable prognosis, emerging as a major challenge for the treatment of breast cancer. In the present study, 122 TNBC patients were subjected to analysis of Aurora-A (Aur-A) expression and survival prognosis. We found that Aur-A high expression was positively associated with initial clinical stage (P = 0.025), the proliferation marker Ki-67 (P = 0.001), and the recurrence rate of TNBC patients (Pprognosis compared with low expression of both Aur-A and Ki-67. Importantly, we further found that Aur-A was overexpressed in TNBC cells, and inhibition of this kinase inhibited cell proliferation and prevented cell migration in TNBC. Our findings demonstrated that Aur-A was a potential therapeutic target for TNBC and inhibition of Aur-A kinase was a promising regimen for TNBC cancer therapy.

  15. Predictive gene lists for breast cancer prognosis: A topographic visualisation study

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    Lowe David

    2008-04-01

    Full Text Available Abstract Background The controversy surrounding the non-uniqueness of predictive gene lists (PGL of small selected subsets of genes from very large potential candidates as available in DNA microarray experiments is now widely acknowledged 1. Many of these studies have focused on constructing discriminative semi-parametric models and as such are also subject to the issue of random correlations of sparse model selection in high dimensional spaces. In this work we outline a different approach based around an unsupervised patient-specific nonlinear topographic projection in predictive gene lists. Methods We construct nonlinear topographic projection maps based on inter-patient gene-list relative dissimilarities. The Neuroscale, the Stochastic Neighbor Embedding(SNE and the Locally Linear Embedding(LLE techniques have been used to construct two-dimensional projective visualisation plots of 70 dimensional PGLs per patient, classifiers are also constructed to identify the prognosis indicator of each patient using the resulting projections from those visualisation techniques and investigate whether a-posteriori two prognosis groups are separable on the evidence of the gene lists. A literature-proposed predictive gene list for breast cancer is benchmarked against a separate gene list using the above methods. Generalisation ability is investigated by using the mapping capability of Neuroscale to visualise the follow-up study, but based on the projections derived from the original dataset. Results The results indicate that small subsets of patient-specific PGLs have insufficient prognostic dissimilarity to permit a distinction between two prognosis patients. Uncertainty and diversity across multiple gene expressions prevents unambiguous or even confident patient grouping. Comparative projections across different PGLs provide similar results. Conclusion The random correlation effect to an arbitrary outcome induced by small subset selection from very high

  16. Molecular Targeted Enhanced Ultrasound Imaging of Flk1 Reveals Diagnosis and Prognosis Potential in a Genetically Engineered Mouse Prostate Cancer Model

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    Jim W. Xuan

    2009-07-01

    Full Text Available Molecular imaging techniques used to detect the initiation of disease have the potential to provide the best opportunity for early treatment and cure. This report aimed at testing the possibility that Flk1+ (vascular endothelial growth factor receptor 2, a crucial angiogenesis factor of most tumor cells, could be a molecular targeted imaging marker for the diagnosis and prognosis of cancer. We performed Flk1-targeted microbubble-enhanced ultrasound (US imaging of prostate cancer in a genetically engineered mouse model with normal-appearing intact US (negative prostates and with three different tumor sizes (small, medium, and large. Higher levels of Flk1+ molecular signals were identified in the intact US (negative prostate group by US-targeted imaging and immunohistochemical analysis. The increase in Flk1+ expression occurred prior to the angiogenesis switch-on phase and vascularity peak. After this peak accumulation stage of Flk1+ molecules, lower and stabilized levels of Flk1+ signals were maintained together with tumor growth from small, to medium, to large size. In a longitudinal observation in a subset (n = 5 of mice with established tumors, elevated Flk1+ signals were observed in tissues surrounding the prostate cancer, for example, the ipsilateral boundary zones between two developing tumor lobes, new tumor blood vessel recruits, the urethra border, and the pelvic node basin. The potential of Flk1-targeted US imaging as a predictive imaging tool was confirmed by correlation studies of three-dimensional US B-mode imaging, gross pathology, and histology analyses. The results of the application in a genetically engineered mouse model with prostate cancer of molecular Flk1-targeted US imaging support the contention that Flk1 can be used as a molecular imaging marker for small tumors undetectable by microimaging and as a molecular diagnostic and prognosis marker for tumor metastasis and progression.

  17. Vascular endothelial growth factor C (VEGF-C in esophageal cancer correlates with lymph node metastasis and poor patient prognosis

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    Naganawa Yasuhiro

    2010-06-01

    VEGF-C expression group survived. Conclusions The expression of VEGF-C correlates with lymph node metastasis and poor prognosis. In patients with Tis and T1 esophageal tumors, the expression of VEGF-C may be a good diagnostic factor for determining metastasis of the lymph node.

  18. Prognosis for patients diagnosed with pregnancy-associated breast cancer: a paired case-control study

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    Wagner Brant Moreira

    Full Text Available CONTEXT AND OBJECTIVE: Previous studies have suggested that the occurrence of pregnancy concomitantly with a diagnosis of breast cancer may affect the evolution of the neoplasia. The present study aimed to compare pregnancy-associated breast cancer (PABC patients with non-pregnant cancer patients (controls in relation to the time taken to diagnose the disease, tumor characteristics and mortality. DESIGN AND SETTING: A retrospective, paired case-control study was conducted at the Hospital da Santa Casa de Misericórdia and Centro de Quimioterapia Antiblástica e Imunoterapia in Belo Horizonte, Brazil. METHODS: The study involved 87 PABC and 252 control patients. The influence of covariables (interval between first symptoms and diagnosis, tumor histology, size of primary tumor, distant metastasis, grade of malignancy, hormone receptor status and axillary lymph node involvement and the pregnancy variable on overall survival was investigated using univariate and multivariate analyses. RESULTS: The median overall survival for PABC patients of 30.1 months (95% confidence interval, CI: 19.4-40.9 months was significantly different (P = 0.005 from that of the control group (53.1 months; 95% CI: 35.1-71.0 months. The cumulative overall survivals after five and ten years were, respectively, 29.7 and 19.2% for PABC patients, and 47.3 and 34.8% for control patients (P = 0.005. Tumor size, grade of malignancy, distant metastasis and pregnancy were independent factors that significantly modified disease prognosis. CONCLUSIONS: Pregnancy was an independent prognostic factor. The overall survival of PABC patients was shorter than that of non-pregnant patients.

  19. Effect of retroperitoneal lymphadenectomy on prognosis of patients with epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    王泽华; 熊宙芳; 王世宣

    2003-01-01

    Objective To evaluate prognostic factors which have an influence on overall survival and to assess the rational application of retroperitoneal lymphadenectomy in patients with epithelial ovarian cancer. Methods The data of 131 patients treated between January 1990 and December 1998 in Union Hospital and Tongji Hospital were analyzed retrospectively. Survival was calculated using the Kaplan-Meier method and comparisons were performed using Log-rank test. Independent prognostic factors were identified by the Cox proportional hazards regression model. Results Univariate analysis showed that age, general conditions, menopausal status, stage, pathological types, location of the tumor, residual tumor and retroperitoneal lymphadenectomy were prognostic factors. Multivariate analysis showed that age, stage, residual tumor, retroperitoneal lymphadenectomy and the number of courses of chemotherapy were the most important prognostic factors. The survival rate could not be improved through retroperitoneal lymphadenectomy in the patients in early stage, advanced stage with residual tumor >2 cm or those with mucinous adenocarcinoma (P>0.05). Among patients in advanced stage cancer with a residual tumor ≤2 cm, 5-year survival was 65% and 30% for patients who did and did not undergo lymphadenectomy, respectively (P<0.01). Among patients with serous adenocarcinoma, 5-year survival was 61% and 31% for patients who did and did not undergo lymphadenectomy, respectively (P<0.01). Conclusions The prognosis of the patients with epithelial ovarian cancer may be influenced by age, stage, residual tumor, retroperitoneal lymphadenectomy and the number of courses of chemotherapy. Although retroperitoneal lymphadenectomy could improve the survival rate, it should be carried out selectively.

  20. An Apta-Biosensor for Colon Cancer Diagnostics.

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    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.

  1. 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.

  2. The molecular biology of cancer and its diagnostic implications.

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    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.

  3. Ovarian cancer patients at high risk of BRCA mutation: the constitutional genetic characterization does not change prognosis.

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    Sabatier, Renaud; Lavit, Elise; Moretta, Jessica; Lambaudie, Eric; Noguchi, Tetsuro; Eisinger, François; Cherau, Elisabeth; Provansal, Magali; Livon, Doriane; Rabayrol, Laetitia; Popovici, Cornel; Charaffe-Jauffret, Emmanuelle; Sobol, Hagay; Viens, Patrice

    2016-10-01

    Ovarian neoplasms secondary to germline BRCA mutations had been described to have a more favourable survival. There is only few data concerning the prognosis of non mutated patients presenting clinical features evocative of BRCA alterations. We retrospectively collected data from patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. Patients considered at high risk of BRCA mutation were tested for BRCA1/2 germline mutations. We described clinical, pathological and therapeutic features and compared prognosis of BRCA mutation carriers and non-mutated patients. Out of 617 ovarian cancer patients, we identified 104 patients who were considered at high risk of mutation. The 33 mutated patients were more likely to present a personal (33 vs. 10 %, p = 0.003) or a family (42 vs. 24 %, p = 0.06) history of breast/ovarian cancers. BRCA1/2 mutation carriers and wild type patients displayed similar prognosis: median progression-free survival (PFS) of 20.9 versus 37.7 months (p = 0.21); median overall survival (OS) of 151.2 versus 122.5 months (p = 0.52). Personal history of breast cancer increased both PFS [HR = 0.45 (95CI 0.25-0.81)] and OS [HR = 0.35 (95CI 0.16-0.75)]. In multivariate analysis, this parameter was an independent prognostic feature, whereas the identification of a BRCA1/2 mutation was not. In our cohort, all patients at high risk of BRCA mutation share a similar prognosis, whatever is their germline mutation status. Prognosis seems to be more influenced by clinical history than by germline mutations identification. If it is confirmed in larger and independent series, this result suggests that the hypothesis of other BRCA pathway alterations (BRCAness phenotype) deserves to be deeply explored.

  4. Downregulation of ALDOB is associated with poor prognosis of patients with gastric cancer

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    He, Jun; Jin, Yi; Chen, Yuan; Yao, Hai-Bo; Xia, Ying-Jie; Ma, Ying-Yu; Wang, Wei; Shao, Qin-Shu

    2016-01-01

    Objectives To examine the expression of ALDOB in gastric cancer (GC) tissue and to reveal its potential clinicopathological and prognostic significance. Materials and methods We screened for genes that were differentially expressed between GC and nontumor tissues using a microarray, specifically the Affymetrix U133 Plus 2.0 Array platform. We then verified the transcriptional and translational levels of ALDOB by performing quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). In addition, a merged data set based on the Gene Expression Omnibus was generated and a survival analysis performed. Results The microarray analysis revealed that ALDOB was downregulated (more than sevenfold) in GC compared with nontumor tissue. Both qRT-PCR and IHC validated the decrease of ALDOB in GC tissue. Moreover, we found that the expression of ALDOB was significantly related to tumor-invasion depth, lymph-node metastasis, distant metastasis, and TNM stage. The survival analysis, based on the IHC and merged data set, indicated that the overall survival was better in patients with high ALDOB expression. The Cox regression analysis showed that ALDOB expression was an independent prognostic factor for GC. Conclusion The expression of ALDOB in GC tissue was significantly related to the clinicopathological features and prognosis of the disease, thus suggesting that ALDOB could act as a novel molecular marker for GC.

  5. Prognosis value of MGMT promoter methylation for patients with lung cancer: a meta-analysis.

    Science.gov (United States)

    Chen, Chao; Hua, Haiqing; Han, Chenglong; Cheng, Yuan; Cheng, Yin; Wang, Zhen; Bao, Jutao

    2015-01-01

    The role of MGMT promoter methylation in lung cancer (LC) remains controversial. To clarify the association of MGMT promoter methylation with survival in LC, we performed a meta-analysis of the literature with meta-analysis. Trials were selected for further analysis if they provided an independent assessment of MGMT promoter methylation in LC and reported the survival data in the context of MGMT promoter methylation status. Subgroup analyses were conducted according to the study characteristic. A total of 9 trials, which comprised 859 patients, were included in the meta-analysis. The combined hazard ratio (HR) of 1.27 [95% CI 0.88-1.82; test for heterogeneity P = 0.027] suggests that MGMT promoter methylation has none impact on patient survival. In Stage I-III or younger populations, a significant association was found for MGMT promoter methylation in the prognosis of LC. In addition, the heterogeneity disappeared when the analysis was restricted to Stage I-III LC. Our analysis indicates that MGMT promoter methylation in stage I-III or younger patients was significantly correlated with wore survival. Further study is needed to determine these specific subgroups of LC patients.

  6. Downregulation of ALDOB is associated with poor prognosis of patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    He J

    2016-10-01

    Full Text Available Jun He,1 Yi Jin,1 Yuan Chen,2 Hai-Bo Yao,1 Ying-Jie Xia,3 Ying-Yu Ma,4 Wei Wang,2 Qin-Shu Shao1 1Department of Gastroenterology and Pancreatic Surgery, 2Department of Pathology, 3Key Laboratory of Gastroenterology of Zhejiang Province, 4Clinic Research Institute, Zhejiang Provincial People’s Hospital, Hangzhou, People’s Republic of China Objectives: To examine the expression of ALDOB in gastric cancer (GC tissue and to reveal its potential clinicopathological and prognostic significance.Materials and methods: We screened for genes that were differentially expressed between GC and nontumor tissues using a microarray, specifically the Affymetrix U133 Plus 2.0 Array platform. We then verified the transcriptional and translational levels of ALDOB by performing quantitative real-time polymerase chain reaction (qRT-PCR and immunohistochemistry (IHC. In addition, a merged data set based on the Gene Expression Omnibus was generated and a survival analysis performed.Results: The microarray analysis revealed that ALDOB was downregulated (more than sevenfold in GC compared with nontumor tissue. Both qRT-PCR and IHC validated the decrease of ALDOB in GC tissue. Moreover, we found that the expression of ALDOB was significantly related to tumor-invasion depth, lymph-node metastasis, distant metastasis, and TNM stage. The survival analysis, based on the IHC and merged data set, indicated that the overall survival was better in patients with high ALDOB expression. The Cox regression analysis showed that ALDOB expression was an independent prognostic factor for GC.Conclusion: The expression of ALDOB in GC tissue was significantly related to the clinicopathological features and prognosis of the disease, thus suggesting that ALDOB could act as a novel molecular marker for GC. Keywords: ALDOB, gastric cancer, microarray analysis, molecular marker

  7. The impact of the Polish mass breast cancer screening program on prognosis in the Pomeranian Province

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    Skokowski, Jarosław; Bartoszek, Krzystof; Kosowska, Anna; Kalinowski, Leszek; Jaśkiewicz, Janusz

    2016-01-01

    Introduction Mammographic screening results in diagnosis of less advanced breast cancer (BC). A meta-analysis of randomized clinical trials confirmed that BC screening reduces mortality. In 2007, the National Breast Cancer Screening Program (NBCSP) was established in Poland with the crucial aim of reducing mortality from BC. The purpose of this study was to assess the impact of participation in the NBCSP on prognosis. Material and methods A single institution, non-randomized retrospective study was undertaken. The study population comprised 643 patients with BC treated in the Department of Surgical Oncology (DSO) at the Medical University of Gdansk over a 4-year period, from 01.01.2007 until 31.12.2010. Patients were divided into two groups: group A – patients who participated in the NBCSP (n = 238, 37.0%); and group B – patients who did not participate in the NBCSP (n = 405, 63.0%). Results Statistical analysis revealed that group A displayed a less advanced AJCC stage (more patients in AJCC stage I, p = 0.002), lower tumor diameter (more patients with pT1, p = 0.006, and pT pNO, p = 0.01). From 2009 to 2010 the NBCSP revealed a statistically significant benefit – significantly more patients in stage 0 + I (60.7% vs. 48.8%, p = 0.018) and with tumors pT < 15 mm (48.8% vs. 35.1%, p = 0.011) were observed in group A. Conclusions The study results revealed the beneficial impact of the NBCSP. Superior prognostic factors and favorable staging were observed in women who participated in the NBCSP. PMID:28261300

  8. Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

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    Reis Sabrina

    2012-06-01

    Full Text Available Abstract Background Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC. Methods MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003. Invasive tumors (pT1-pT2 had higher expression levels of MMP-9 than superficial tumors (pTa (p = 0.026. The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048. Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003 and IL-8 (p = 0.005. Conclusion We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

  9. Mitochondrial DNA content in breast cancer: Impact on in vitro and in vivo phenotype and patient prognosis

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    Weerts, Marjolein J.A.; Sieuwerts, Anieta M.; Smid, Marcel; Look, Maxime P.; Foekens, John A.; Sleijfer, Stefan; Martens, John W.M.

    2016-01-01

    Reduced mitochondrial DNA (mtDNA) content in breast cancer cell lines has been associated with transition towards a mesenchymal phenotype, but its clinical consequences concerning breast cancer dissemination remain unidentified. Here, we aimed to clarify the link between mtDNA content and a mesenchymal phenotype and its relation to prognosis of breast cancer patients. We analyzed mtDNA content in 42 breast cancer cell lines and 207 primary breast tumor specimens using a combination of quantitative PCR and array-based copy number analysis. By associating mtDNA content with expression levels of genes involved in epithelial-to-mesenchymal transition (EMT) and with the intrinsic breast cancer subtypes, we could not identify a relation between low mtDNA content and mesenchymal properties in the breast cancer cell lines or in the primary breast tumors. In addition, we explored the relation between mtDNA content and prognosis in our cohort of primary breast tumor specimens that originated from patients with lymph node-negative disease who did not receive any (neo)adjuvant systemic therapy. When patients were divided based on the tumor quartile levels of mtDNA content, those in the lowest quarter (≤ 350 mtDNA molecules per cell) showed a poorer 10-year distant metastasis-free survival than patients with > 350 mtDNA molecules per cell (HR 0.50 [95% CI 0.29–0.87], P = 0.015). The poor prognosis was independent of established clinicopathological markers (HR 0.54 [95% CI 0.30–0.97], P = 0.038). We conclude that, despite a lack of evidence between mtDNA content and EMT, low mtDNA content might provide meaningful prognostic value for distant metastasis in breast cancer. PMID:27081694

  10. Effects of the combination of blood transfusion and postoperative infectious complications on prognosis after surgery for colorectal cancer. Danish RANX05 Colorectal Cancer Study Group

    DEFF Research Database (Denmark)

    Mynster, T; Christensen, Ib Jarle; Moesgaard, F

    2000-01-01

    BACKGROUND: The frequency of postoperative infectious complications is significantly increased in patients with colorectal cancer receiving perioperative blood transfusion. It is still debated, however, whether perioperative blood transfusion alters the incidence of disease recurrence or otherwise...... affects the prognosis. METHODS: Patient risk variables, variables related to operation technique, blood transfusion and the development of infectious complications were recorded prospectively in 740 patients undergoing elective resection for primary colorectal cancer. Endpoints were overall survival (n.......13-2.82)), localization of cancer in the rectum and Dukes classification were independent risk factors. CONCLUSION: Blood transfusion per se may not be a risk factor for poor prognosis after colorectal cancer surgery. However, the combination of perioperative blood transfusion and subsequent development of postoperative...

  11. Role of immunohistochemical overexpression of matrix metalloproteinases MMP-2 and MMP-11 in the prognosis of death by ovarian cancer.

    Science.gov (United States)

    Périgny, Martine; Bairati, Isabelle; Harvey, Isabelle; Beauchemin, Michel; Harel, François; Plante, Marie; Têtu, Bernard

    2008-02-01

    Matrix metalloproteinases (MMPs) are enzymes thought to be involved in tumor invasion. We hypothesized that MMP-2 and MMP-11 overexpression was associated with the aggressiveness of ovarian carcinoma. This study was performed on samples from 100 patients with stage III ovarian carcinomas treated surgically between 1990 and 2000. Immunohistochemical staining was performed on ovarian tumors and peritoneal implants using monoclonal antibodies. Overexpression was defined as more than 10% of cells expressing the marker. Multivariate analyses showed that only MMP-2 overexpression by cancer cells in peritoneal implants was associated with a significant risk of death by disease (hazard ratio, 2.65; 95% confidence interval, 1.41-4.97; P =.003). MMP-11 overexpression was not predictive of survival. These results suggest that MMP-2 overexpression by cancer cells in peritoneal implants and not in the primary ovarian cancer is predictive of ovarian cancer prognosis and more likely reflects the presence of particularly aggressive clones of cancer cells.

  12. Prediction of the prognosis of breast cancer in routine histologic specimens using a simplified, low-cost gene expression signature

    DEFF Research Database (Denmark)

    Marcell, S.A.; Balazs, A.; Emese, A.;

    2013-01-01

    Prediction of the prognosis of breast cancer in routine histologic specimens using a simplified, low-cost gene expression signature Background: Grade 2 breast carcinomas do not form a uniform prognostic group. Aim: To extend the number of patients and the investigated genes of a previously...... identified prognostic signature described by the authors that reflect chromosomal instability in order to refine characterization of grade 2 breast cancers and identify driver genes. Methods: Using publicly available databases, the authors selected 9 target and 3 housekeeping genes that are capable to divide...... prognosis groups. Centroid-based ranking showed that 3 genes, FOXM1, TOP2A and CLDN4 were able to separate the good and poor prognostic groups of grade 2 breast carcinomas. Conclusion: Using appropriately selected control genes, a limited set of genes is able to split prognostic groups of breast carcinomas...

  13. Prostate cancer: towards the standardization and synthesis of morphology, genetics, and prognosis.

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    Berney, Dan; Cheng, Liang

    2012-01-01

    Prostate cancer research and diagnosis is undergoing a revolution in our understanding of the disease process and standardization of diagnostic criteria. Although great progress has been made, there remain many areas of uncertainty and debate. The revolution towards a synthesis of pathology with genetic changes and prognostic models is only just beginning. This supplement presents the opinions and findings of leading international experts in histopathology and prostate research dealing with subjects ranging from aetiology, basic anatomy and morphology to prognostic models, genetic changes and new drug treatments. We hope that this exciting and rapidly changing field will capture the imagination of both experienced and trainee pathologists to advance the field in both research and diagnosis.

  14. A decision-analytic approach to define poor prognosis patients: A case study for non-seminomatous germ cell cancer patients

    NARCIS (Netherlands)

    M.R. van Dijk (Merel); E.W. Steyerberg (Ewout); J.D.F. Habbema (Dik)

    2008-01-01

    textabstractBackground. Classification systems may be useful to direct more aggressive treatment to cancer patients with a relatively poor prognosis. The definition of 'poor prognosis' often lacks a formal basis. We propose a decision analytic approach to weigh benefits and harms explicitly to defin

  15. MicroRNA-183 correlates cancer prognosis, regulates cancer proliferation and bufalin sensitivity in epithelial ovarian caner.

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    Chen, Huixiao; Zhang, Ling; Zhang, Lili; Du, Jing; Wang, Hongying; Wang, Bin

    2016-01-01

    Background we intended to explore the functional implication of microRNA-183 (miR-183) in predicting clinical prognosis and regulating cancer proliferation and bufalin sensitivity in epithelial ovarian cancer (EOC). Methods In 75 EOC patients, miR-183 expression was examined, by quantitative RT-PCR (qRT-PCR), between paired EOC tumors and adjacent normal tissues, and between tumor samples from patients at early clinical stages and those at advanced clinical stages. The association of serum miR-183 and patients' clinicopathological variables were examined. The overall survival (OS) was estimated by Kaplan-Meier model. And the possibility of miR-183 as a prognostic biomarker for EOC was examined by cox proportional hazard regression model. In EOC cell lines SKOV3 and ES-2 cells, lentiviral transduction was conducted to genetically suppress miR-183. The effect of miR-183 downregulation on EOC in vitro growth, bufalin sensitivity and in vivo tumorigenicity were examined. Results MiR-183 was highly expressed in EOC tumors, as well ass in patients at advanced clinical stages. Serum miR-183 was significantly associated with major clinicopathological variables in EOC patients, such as clinical stage and lymph node metastases. High level of serum miR-183 was associated with poor OS in EOC patients, and proved to be a potential biomarker for EOC. In EOC cell lines, functional assays demonstrated that miR-183 downregulation inhibited cancer proliferation, enhanced bufalin sensitivity and reduced tumorigenicity in vivo. Conclusion MiR-183 may be a prognostic biomarker for EOC, and inhibiting miR-183 may have therapeutic effect to inhibit tumor growth in EOC.

  16. Low expression of BMPRIB indicates poor prognosis of breast cancer and is insensitive to taxane-anthracycline chemotherapy.

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    Dai, Kun; Qin, Fengxia; Zhang, Huikun; Liu, Xiaoli; Guo, Caixia; Zhang, Ming; Gu, Feng; Fu, Li; Ma, Yongjie

    2016-01-26

    Bone morphogenetic protein receptor type IB (BMPRIB) is one osteogenesis factor, which function in breast cancer has been rarely explored until recently. In the clinical study presented here, involving a cohort of 368 invasive ductal carcinoma (IDC) patients, we identified that patients with low expression of BMPRIB exhibited poor prognosis, especially in the luminal B subtype. We also provided the first piece of evidence that low level of BMPRIB was a promoting factor for breast cancer patients to develop bone metastasis, but not lung, liver or brain. The first of its kind, we reported that patients with high expression of BMPRIB exhibited favorable prognosis by a retrospective analysis consisting of 168 patients treated with TE (taxane and anthracycline) regimens. And the patients with high expression of BMPRIB were more sensitive to TE regimens in the detection of 32 paired pre-neoadjuvant and post-neoadjuvant specimens. Overall, our study concluded that low expression of BMPRIB indicated poor prognosis of breast cancer and was insensitive to taxane-anthracycline chemotherapy. Our findings also lay a foundation to help clinicians improve identification of patients for TE regimens by BMPRIB in the era of precision medicine.

  17. Aurora-A identifies early recurrence and poor prognosis and promises a potential therapeutic target in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Jie Xu

    Full Text Available Triple negative breast cancer (TNBC acquires an unfavorable prognosis, emerging as a major challenge for the treatment of breast cancer. In the present study, 122 TNBC patients were subjected to analysis of Aurora-A (Aur-A expression and survival prognosis. We found that Aur-A high expression was positively associated with initial clinical stage (P = 0.025, the proliferation marker Ki-67 (P = 0.001, and the recurrence rate of TNBC patients (P<0.001. In TNBC patients with Aur-A high expression, the risk of distant recurrence peaked at the first 3 years and declined rapidly thereafter, whereas patients with Aur-A low expression showed a relatively constant risk of recurrence during the entire follow-up period. Univariate and multivariate analysis showed that overexpression of Aur-A predicted poor overall survival (P = 0.002 and progression-free survival (P = 0.012 in TNBC. Furthermore, overexpression of Aur-A, associated with high Ki-67, predicted an inferior prognosis compared with low expression of both Aur-A and Ki-67. Importantly, we further found that Aur-A was overexpressed in TNBC cells, and inhibition of this kinase inhibited cell proliferation and prevented cell migration in TNBC. Our findings demonstrated that Aur-A was a potential therapeutic target for TNBC and inhibition of Aur-A kinase was a promising regimen for TNBC cancer therapy.

  18. Multiphoton microscopy as a diagnostic imaging modality for lung cancer

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    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Peters, Rachel M.; Weiss, Robert S.; Webb, Watt W.

    2010-02-01

    Lung cancer is the leading killer among all cancers for both men and women in the US, and is associated with one of the lowest 5-year survival rates. Current diagnostic techniques, such as histopathological assessment of tissue obtained by computed tomography guided biopsies, have limited accuracy, especially for small lesions. Early diagnosis of lung cancer can be improved by introducing a real-time, optical guidance method based on the in vivo application of multiphoton microscopy (MPM). In particular, we hypothesize that MPM imaging of living lung tissue based on twophoton excited intrinsic fluorescence and second harmonic generation can provide sufficient morphologic and spectroscopic information to distinguish between normal and diseased lung tissue. Here, we used an experimental approach based on MPM with multichannel fluorescence detection for initial discovery that MPM spectral imaging could differentiate between normal and neoplastic lung in ex vivo samples from a murine model of lung cancer. Current results indicate that MPM imaging can directly distinguish normal and neoplastic lung tissues based on their distinct morphologies and fluorescence emission properties in non-processed lung tissue. Moreover, we found initial indication that MPM imaging differentiates between normal alveolar tissue, inflammatory foci, and lung neoplasms. Our long-term goal is to apply results from ex vivo lung specimens to aid in the development of multiphoton endoscopy for in vivo imaging of lung abnormalities in various animal models, and ultimately for the diagnosis of human lung cancer.

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

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    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.

  20. Dephosphorylated cofilin expression is associated with poor prognosis in cases of human breast cancer: a tissue microarray analysis

    Directory of Open Access Journals (Sweden)

    Maimaiti Y

    2016-10-01

    Full Text Available Yusufu Maimaiti,1,2,* Zeming Liu,1,* Jie Tan,1 Kelimu Abudureyimu,2 Bangxing Huang,3 Chunping Liu,1 Yawen Guo,1 Changwen Wang,1 Xiu Nie,3 Jing Zhou,1 Tao Huang1 1Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of General Surgery, Research Institute of Minimally Invasive, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 3Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Background: Proteins in the cofilin pathway regulate actin dynamics and may be involved in cancer cell migration and invasion. However, there are no direct data that suggest that dephosphorylated cofilin can affect breast cancer prognosis.Methods: We assessed the expressions of cofilin and phosphorylated cofilin (P-cofilin in breast cancer tissue microarrays (290 patients, mean follow-up: 95.7±2.49 months to evaluate dephosphorylated cofilin and its relationship with breast cancer prognosis. The associations of pathological characteristics with cumulative survival were evaluated using Kaplan–Meier analysis.Results: Univariate analyses revealed that overall survival was associated with cofilin levels, N category, TNM stage, estrogen receptor status, progesterone receptor status, and molecular subtypes. Cofilin status and TNM stage independently affected overall survival, although P-cofilin expression was not associated with patient survival. In the P-cofilin-negative subgroup, cofilin expression was significantly associated with patient survival, although cofilin expression was not significantly associated with patient survival in the P-cofilin-positive subgroup. We further analyzed the P-cofilin-negative cases and found that Ki-67 expression was significantly elevated in the subgroup that was strongly positive for

  1. Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy

    NARCIS (Netherlands)

    J. Lei (Jieping); A. Rudolph (Anja); K.B. Moysich (Kirsten); M. Rafiq (Meena); T.W. Behrens (Timothy); E.L. Goode (Ellen); P.D.P. Pharoah (Paul); P. Seibold (Petra); P.A. Fasching (Peter); I.L. Andrulis (Irene); V. Kristensen (Vessela); F.J. Couch (Fergus); U. Hamann (Ute); M.J. Hooning (Maartje); H. Nevanlinna (Heli); U. Eilber (Ursula); M.K. Bolla (Manjeet); J. Dennis (Joe); Q. Wang (Qing); A. Lindblom (Annika); A. Mannermaa (Arto); D. Lambrechts (Diether); M. García-Closas (Montserrat); P. Hall (Per); G. Chenevix-Trench (Georgia); M. Shah (Mitul); R.N. Luben (Robert); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); G.G. Alnæs (Grethe Grenaker); A.-L. Borresen-Dale (Anne-Lise); S. Nord (Silje); J.E. Olson (Janet); B. Hallberg (Boubou); C. Vachon (Celine); D. Torres (Diana); H.U. Ulmer (Hans); T. Rud̈iger (Thomas); A. Jager (Agnes); C.H.M. van Deurzen (Carolien); M.M.A. Tilanus-Linthorst (Madeleine); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); S. Margolin (Sara); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); V. Kataja (Vesa); S. Hatse (Sigrid); H. Wildiers (Hans); A. Smeets (Ann); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); J. Li (Jingmei); M.K. Humphreys (Manjeet); K.-A. Phillips (Kelly-Anne); S.C. Linn (Sabine); S. Cornelissen (Sten); S.A.J. van den Broek (Sandra Alexandra); D. Kang (Daehee); J.-Y. Choi (J.); S.K. Park (Sue); K.Y. Yoo; C.-N. Hsiung (Chia-Ni); P.-E. Wu (Pei-Ei); M.-F. Hou (Ming-Feng); C-Y. Shen (Chen-Yang); S.-H. Teo; N.A.M. Taib (Nur Aishah Mohd); C.-H. Yip (Cheng-Har); G.F. Ho (Gwo Fuang); K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hisato); K. Tajima (Kazuo); A.M. Dunning (Alison); J. Benítez (Javier); K. Czene (Kamila); L. Sucheston (Lara); T. Maishman (Tom); W. Tapper (William); D. Eccles (Diana); D.F. Easton (Douglas); M.K. Schmidt (Marjanka); J. Chang-Claude (Jenny)

    2015-01-01

    textabstractIntroduction: Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we st

  2. Effect of chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy on patients’ prognosis

    Institute of Scientific and Technical Information of China (English)

    Xin-Cheng Shu; Ping Gao; Xin-Jua Zuo

    2016-01-01

    Objective:To study the effect of chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy on patients' prognosis.Methods:A total of78 cases of patients with colon cancer who received radical surgery of colon cancer assisted by postoperative chemotherapy in our hospital from May 2012 to December 2014 were selected for treatment and randomly divided into two groups, combined treatment group received chemotherapy combined with cascade primed immune cell therapy, simple chemotherapy group received FOLFOX chemotherapy, and then serum tumor marker contents and angiogenesis molecule contents as well as red blood cell immune function indicators in peripheral blood were detected.Results:Serum tumor markers CCSA-2, CCSA-3, CCSA-4, PTN, NGAL and sMICA as well as angiogenesis molecules VEGF, FGF10, sICAM-1, sVCAM-1, Musashi1 and Dkk1 contents of combined treatment group were lower than those of conventional chemotherapy group; the proportion of CR1, CR3, CD58 and CD59 as well as the rosette formation rates of red blood cell C3b receptor and immune complex in peripheral blood of combined treatment group were significantly higher than those of conventional chemotherapy group.Conclusions:Chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy helps to kill tumor cells and inhibit angiogenesis while enhance red blood cell immune function, and it can improve the prognosis of radical surgery of colon cancer.

  3. Impact of young age on the prognosis for oral cancer: a population-based study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Ting-Shou Chang

    Full Text Available BACKGROUND: Oral cancer leads to a considerable use of health care resources. Wide resection of the tumor and reconstruction with a pedicle flap/ free flap is widely used. This study was conducted to investigate if young age at the time of diagnosis of oral cancer requiring this treatment confers a worse prognosis. METHODS: A total of 2339 patients who underwent resections for oral cancer from 2004 to 2005 were identified from The Taiwan National Health Insurance Research Database. Survival analysis, Cox proportional regression model, propensity scores, and sensitivity test were used to evaluate the association between 5-year survival rates and age. RESULTS: In the Cox proportional regression model, the older age group (>65 years had the worst survival rate (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.45-2.22; P65 years, compared to those with younger age (<45 years (P<0.001. In sensitivity test, the adjusted hazard ratio remained no statistically elevated in the younger age group (<45 years. CONCLUSIONS: For those oral cancer patients who underwent wide excision and reconstruction, young age did not confer a worse prognosis using a Cox proportional regression model, propensity scores or sensitivity test. Young oral cancer patients may be treated using general guidelines and do not require more aggressive treatment.

  4. Nestin expression associates with poor prognosis and triple negative phenotype in locally advanced (T4 breast cancer

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    F. Piras

    2011-11-01

    Full Text Available Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients’ outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02 and with borderline significance at 10-years of survival (P=0.05 in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers.

  5. Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer

    DEFF Research Database (Denmark)

    de Wit, Ronald; Skoneczna, Iwona; Daugaard, Gedske

    2012-01-01

    To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC).......To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC)....

  6. 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.

  7. CCL7 and CCL21 overexpression in gastric cancer is associated with lymph node metastasis and poor prognosis

    Institute of Scientific and Technical Information of China (English)

    Tsann-Long Hwang; Li-Yu Lee; Chee-Chan Wang; Ying Liang; Shu-Fang Huang; Chi-Ming Wu

    2012-01-01

    AIM:TO investigate how a complex network of CC chemokine ligands (CCLs) and their receptors influence the progression of tumor and metastasis.METHODS:In the present study,we used immunohistochemistry to examine the expression of CCL7,CCL8 and CCL21 in 194 gastric cancer samples and adjacent normal tissues.We analyzed their correlation with tumor metastasis,clinicopathologic parameters and clinical outcome.RESULTS:We found that the higher expression of CCL7 and CCL21 in cancer tissues than in normal tissues was significantly correlated with advanced depth of wall invasion,lymph node metastasis and higher tumor node metastasis stage.Moreover,Kaplan-Meier survival analysis revealed that CCL7 and CCL21 overexpression in cancer tissues was correlated with poor prognosis.CONCLUSION:These results suggest that overexpression of these two CC chemokine ligands is associated with tumor metastasis and serves as a prognostic factor in patients with gastric cancer.

  8. Sphingosine 1-phosphate receptors and sphingosine kinase 1: novel biomarkers for clinical prognosis in breast, prostate, and hematological cancers

    Directory of Open Access Journals (Sweden)

    Susan ePyne

    2012-12-01

    Full Text Available There is substantial evidence for a role in cancer of the bioactive lipid sphingosine 1-phosphate (S1P, the enzyme sphingosine kinase 1 (that catalyses S1P formation and S1P-specific G protein coupled receptors. This perspective highlights recent findings demonstrating that sphingosine kinase 1 and S1P receptors are new important biomarkers for detection of early cancer and progression to aggressive cancer. The impact of the sub-cellular distribution of S1P metabolising enzymes and S1P receptors and their spatial functional interaction with oncogenes is considered with respect to prognostic outcome. These findings suggest that S1P, in addition to being a biomarker of clinical prognosis, might also be a new therapeutic target for intervention in cancer.

  9. Applications of FT-IR spectrophotometry in cancer diagnostics.

    Science.gov (United States)

    Bunaciu, Andrei A; Hoang, Vu Dang; Aboul-Enein, Hassan Y

    2015-01-01

    This review provides a brief background to the application of infrared spectroscopy, including Fourier transform-infrared spectroscopy, in biological fluids. It is not meant to be complete or exhaustive but to provide the reader with sufficient background for selected applications in cancer diagnostics. Fourier transform-infrared spectroscopy (FT-IR) is a fast and nondestructive analytical method. The infrared spectrum of a mixture serves as the basis to quantitate its constituents, and a number of common clinical chemistry tests have proven to be feasible using this approach. This review focuses on biomedical FT-IR applications, published in the period 2009-2013, used for early detection of cancer through qualitative and quantitative analysis.

  10. Millimeter Wave Spectroscopy for Breast Cancer Diagnostics and Detection

    Science.gov (United States)

    Korolev, Konstantin; Chen, Shu; Afsar, Mohammed; Naber, Stephen

    2009-03-01

    Broad-band millimeter wave transmittance measurements of normal and tumorous (cancerous) human breast tissue samples have been acquired in--vitro by employing a free-space, quasi-optical spectrometer. Freshly excised breast tissues were prepared and preserved in 10% neutral-buffered formalin solution before testing. Significant differences in the transmittance profiles have been found between the normal and tumorous tissues. It has been found that despite the inhomogeneity and variable structure and composition of each single tissue, the tumorous specimens consistently manifest much higher absorption level of millimeter wave radiation than the normal ones. It has been shown that free space, quasi-optical spectrometer is capable of contributing valuable insights into the dielectric properties of normal and tumorous human breast tissues and aiding in further developments of millimeter wave spectroscopy and mammography for the breast cancer diagnostics and detection.

  11. Gold Nanoconstructs for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

    Science.gov (United States)

    Coughlin, Andrew James

    Cancer accounts for nearly 1 out of every 4 deaths in the United States, and because conventional treatments are limited by morbidity and off-target toxicities, improvements in cancer management are needed. This thesis further develops nanoparticle-assisted photothermal therapy (NAPT) as a viable treatment option for cancer patients. NAPT enables localized ablation of disease because heat generation only occurs where tissue permissive near-infrared (NIR) light and absorbing nanoparticles are combined, leaving surrounding normal tissue unharmed. Two principle approaches were investigated to improve the specificity of this technique: multimodal imaging and molecular targeting. Multimodal imaging affords the ability to guide NIR laser application for site-specific NAPT and more holistic characterization of disease by combining the advantages of several diagnostic technologies. Towards the goal of image-guided NAPT, gadolinium-conjugated gold-silica nanoshells were engineered and demonstrated to enhance imaging contrast across a range of diagnostic modes, including T1-weighted magnetic resonance imaging, X-Ray, optical coherence tomography, reflective confocal microscopy, and two-photon luminescence in vitro as well as within an animal tumor model. Additionally, the nanoparticle conjugates were shown to effectively convert NIR light to heat for applications in photothermal therapy. Therefore, the broad utility of gadolinium-nanoshells for anatomic localization of tissue lesions, molecular characterization of malignancy, and mediators of ablation was established. Molecular targeting strategies may also improve NAPT by promoting nanoparticle uptake and retention within tumors and enhancing specificity when malignant and normal tissue interdigitate. Here, ephrinA1 protein ligands were conjugated to nanoshell surfaces for particle homing to overexpressed EphA2 receptors on prostate cancer cells. In vitro, successful targeting and subsequent photothermal ablation of

  12. Radiation dose is associated with prognosis of small cell lung cancer with superior vena cava syndrome

    Science.gov (United States)

    Wang, Zhen-Bo; Ning, Fang-Ling; Wang, Xiao-Le; Cheng, Yu-Feng; Dong, Xin-Jun; Liu, Chang-Min; Chen, Shao-Shui

    2015-01-01

    Approximately 10% of small cell lung cancer (SCLC) cases develop superior vena cava syndrome (SVCS). Many SCLC patients with SVCS have relatively limited disease, requiring curative rather than palliative treatment. Besides chemotherapy, radiotherapy is important for treating SCLC with SVCS. We retrospectively evaluated the influence of radiotherapy dose on the prognosis of 57 patients with SCLC with SVCS treated with concurrent chemoradiotherapy. The mean biological equivalent radiation dose was 71.5 Gy. We administered etoposide/cisplatin as sequential and concurrent chemotherapy. All patients received at least one cycle of concurrent chemotherapy. All patients had partial or complete response; SVCS-associated symptoms were reduced in 87.7% (50/57) of patients within 3-10 days after treatment. Radiation dose did not affect 2-year local control (74.2% vs. 80.8%). Patients who received high-dose radiation had a lower 2-year overall survival rate than those who received low-dose radiation (11.6 vs. 33%; P = 0.024). The high dose group median survival was 15.0 months (95% confidence interval [CI]: 11.2-19.0) compared with 18.7 months (95% CI: 13.9-23.6) in the low dose group. Grade 3/4 neutropenia occurred in 22/26 high dose patients (84.6%) and 21/31 low dose patients (67.7%). In the high dose group, 30.8% of patients had grade 3/4 esophagitis compared with 19.4% of low dose patients. Only 29.0% of low dose patients received < 4 cycles of chemotherapy in the first 12 weeks after treatment began compared with 46.2% of high dose patients. Concurrent chemoradiotherapy is a tolerable modality for treating stage IIIA/IIIB SCLC with SVCS. Moderate-dose radiotherapy is preferable. PMID:26064339

  13. BRIEF REVIEW ON DIAGNOSTIC TECHNIQUE AND NOVEL MOLECULES IN CLINICAL TRIALS FOR TREATMENT OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    VISHAL KUMAR S. MODI

    2015-01-01

    Full Text Available Breast cancer is the most common cancer in women in both developed and undeveloped countries, and the second most frequent cause of cancer deaths after lung cancer. Although there have been many chemotherapeutic agents like 5-fluorouracil, taxol, tamoxifen, doxorubicin, cisplatin, and camptothecin and hormones are used to treat breast cancer. This review focuses on the causes of breast cancer, latest diagnostic techniques and various molecules under clinical trials for the treatment of breast cancer.

  14. Low levels of serum miR-99a is a predictor of poor prognosis in breast cancer.

    Science.gov (United States)

    Li, J; Song, Z J; Wang, Y Y; Yin, Y; Liu, Y; Nan, X

    2016-08-26

    MicroRNA (miRNA) deregulation has been previously linked to the initiation and development of breast cancer. Although miR-99a is aberrantly expressed in many types of cancers, including breast cancer, the serum miR-99a expression level in breast cancer and its clinical significance remains unknown. Blood samples were obtained from 72 patients with breast cancer and 40 healthy volunteers, and subjected to real-time polymerase chain reaction to evaluate the level of expression of serum miR-99a in the study participants. Furthermore, we investigated the association between serum miR-99a and the clinical outcome of breast cancer. Serum miR-99a expression was significantly downregulated in patients with breast cancer, compared to that in healthy controls (P breast cancer, including lymph node metastasis (P = 0.0194), distant metastasis (P = 0.0037), Ki67 intensity (P = 0.0164), TNM stage (P = 0.0096), and histological grade (P = 0.0051) of cancer. Additionally, breast cancer patients displaying lower miR-99a levels showed poorer overall survival rates (P = 0.0411). The serum miR-99a level was also found to be an independent risk factor for breast cancer (hazard ratio = 3.176, 95% confidence interval = 1.543-7.360, P = 0.023). Our data indicated that serum miR-99a expression was downregulated in breast cancer patients; moreover, this downregulation was associated with poor prognosis, suggesting that serum miR-99a could function as a tumor suppressor in breast cancer.

  15. Microfluidic optoelectronic sensor for salivary diagnostics of stomach cancer.

    Science.gov (United States)

    Zilberman, Yael; Sonkusale, Sameer R

    2015-05-15

    We present a microfluidic optoelectronic sensor for saliva diagnostics with a potential application for non-invasive early diagnosis of stomach cancer. Stomach cancer is the second most common cause of cancer-related deaths in the world. The primary identified cause is infection by a gram-negative bacterium Helicobacter pylori. These bacteria secrete the enzyme urease that converts urea into carbon dioxide (CO2) and ammonia (NH3), leading to their elevated levels in breath and body fluids. The proposed optoelectronic sensor will detect clinically relevant levels of CO2 and NH3 in saliva that can potentially be used for early diagnosis of stomach cancer. The sensor is composed of the embedded in a microfluidic device array of microwells filled with ion-exchange polymer microbeads doped with various organic dyes. The optical response of this unique highly diverse sensor is monitored over a broad spectrum, which provides a platform for cross-reactive sensitivity and allows detection of CO2 and NH3 in saliva at ppm levels.

  16. Effect of β-catenin alterations in the prognosis of patients with sporadic colorectal cancer

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    Sara Rafael

    2014-01-01

    Conclusion: Frequency of point mutations in exon 3 β-catenin gene is low in our population. It would be interesting to increase the population size to test the clinically relevant influence in the prognosis found, and to test the relation of these events with Microsatellite Instabillity (MSI pathway. If these findings were confirmed, β-catenin determination would help in the selection of patients with different prognosis.

  17. Overexpression of the long non-coding RNA, linc-UBC1, is associated with poor prognosis and facilitates cell proliferation, migration, and invasion in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Gao X

    2017-02-01

    the present study suggest that overexpression of linc-UBC1 promotes proliferation and metastasis in CRC, and may be considered as a novel diagnostic marker of CRC. Keywords: linc-UBC1, long non-coding RNA, colorectal cancer, diagnosis, prognosis, gene function

  18. Differential Proteomic Analysis of Nuclear Matrix in Muscle-Invasive Bladder Cancer: Potential to Improve Diagnosis and Prognosis

    Directory of Open Access Journals (Sweden)

    Paola Barboro

    2008-01-01

    Full Text Available Introduction: Although several molecular markers for bladder cancer have been identified, at present little information on prognostic biomarkers is available in the literature. Prognostication of this tumor is largely based on clinicopathological characteristics. Our aim was to identify nuclear matrix (NM proteins that might serve to better characterize the phenotype of the invasive bladder cancer and to investigate their diagnostic and prognostic roles.

  19. MiRNAs Predict the Prognosis of Patients with Triple Negative Breast Cancer: A Meta-Analysis

    Science.gov (United States)

    Liu, Yanli; Zhang, Yuchao; Li, Qingfu; Li, Junfang; Ma, Xiaotian; Xing, Jinfang; Rong, Shouhua; Wu, Zhong; Tian, Yuan; Li, Jing; Jia, Liting

    2017-01-01

    Purpose miRNAs are stable and can be extracted from tissues, blood and other body fluid without degradation. miRNAs are abnormally expressed in the presence of a pathological status, including cancer. Therefore, miRNAs are ideal biomarkers for cancer diagnosis and prognosis. Patients with triple negative breast cancer (TNBC) suffer the worst prognosis, although great efforts have been made. Many studies have investigated the role of miRNAs in predicting the outcomes of TNBC patients for better adjustment of treatment. However, results were inconsistent. Thus, we performed a meta-analysis to summarize the published studies for conclusive results. Methods Eligible studies from different database were retrieved from the online databases, and we used STSTA 12.0 to analysis the prognostic role of miRNAs in triple negative breast cancer. Results Overall high miRNA expression indicated a worse survival with HR value of 1.78 (95% CI: 0.97–3.25). However, subtotal HRs of oncogenic miRNAs and tumor suppressive miRNAs were 2.73 (95% CI: 2.08–3.57; P<0.001) and 0.44 (95% CI: 0.21–0.90; P = 0.024), respectively, and no heterogeneity was observed within the subgroups. Conclusions The miRNAs showed a slightly stronger prognostic value for disease-free survival, relapse-free survival and distant metastasis-free survival compared to the overall survival of TNBC patients. Circulating miRNAs could serve as potential biomarkers for the prognosis of TNBC patients and need further investigation. PMID:28085956

  20. Prognosis of HER2 over-expressing gastric cancer patients with liver metastasis

    Institute of Scientific and Technical Information of China (English)

    Hai-Zhen Dang; Yang Yu; Shun-Chang Jiao

    2012-01-01

    AIM:To study the risk factors for liver metastasis and the prognosis in patients with human epidermal growth factor receptor 2 (HER2) over-expressing gastric cancer (GC).METHODS:A total of 84 GC patients recruited from the General Hospital of the People's Liberation Army (PLA) between 2003 and 2010 were randomly enrolled in this study.HER2 expression was detected by immunohistochemistry in 84 GC patients with liver metastases.The study group consisted of 66 men and 18 women,with an average age of 54 years (range:19-74years).Liver metastasis was diagnosed by magnetic resonance imaging or computed tomography.Patients were followed-up and predictive factors of liver metastasis were evaluated.RESULTS:The median follow-up period was 47 mo (range:6-85 mo).The characteristics of 35 (25.7%)patients with HER2 over-expression of liver metastatic GC are presented.HER2 over-expression was detected in 23 out of 49 (46.9%) patients with intestinal GC,and 9 out of 35 (25.7%) patients with diffuse GC.29 out of 59 (49.2%) patients aged < 60 years were HER2-positive,while 8 out of 25 (32%) patients aged ≥ 60were HER2-positive; a significant difference (P < 0.05).Univariate analysis (log-rank test) showed that HER2 over-expression,sex,Lauren classification,differentiation and disease-free interval were correlated with poor survival (P < 0.05).Survival analysis with a survival curve showed that HER2 over-expression was significantly relevant,with a reduced survival time in GC patients with liver metastases (P < 0.01).2-year survival was not associated with the patient's age.A diseasefree survival longer than 12 mo has a significant association with extended overall survival (OS) in GC patients with liver metastases.The median survival time after the diagnosis of liver metastases was 18 mo [95% confidence interval (CI):9.07-26.94] among HER2 positive GC patients with liver metastases.In comparison,for 49 (69.4%) out of 84 HER2 negative patients with liver

  1. Final Report - DOE Center for Laser Imaging and Cancer Diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Alfano, Robert R.; Koutcher, Jason A.

    2002-10-31

    This Final Report summarizes the significant progress made by the researchers, students and staff of the Center for Laser Imaging and Cancer Diagnostics (CLICD) from January 1998 through May 2002. During this period, the Center supported several projects. Most projects were proposed initially, some were added subsequently as their relevance and importance to the DOE mission became evident. DOE support has been leveraged to obtain continuing funding for some projects. Leveraged funds come from various sources, including NIH, Army, NSF and the Air Force. The goal of the Center was to develop laser-based instruments for use in the detection and diagnosis of major diseases, with an emphasis on detection and diagnosis of various cancers. Each of the supported projects is a collaborative effort between physicists and laser scientists and the City College of New York and noted physicians, surgeons, pathologists, and biologists located at medical centers in the Metropolitan area. The participating institutions were: City College of New York Institute for Ultrafast Lasers and Spectroscopy, Hackensack University Medical Center, Lawrence Livermore National Laboratory, Memorial Sloan Kettering Cancer Center, and New York Eye and Ear Institute. Each of the projects funded by the Center is grouped into one of four research categories: a) Disease Detection, b) Non-Disease Applications, c) New Diagnostic Tools, and, d) Education, Training, Outreach and Dissemination. The progress achieved by the multidisciplinary teams was reported in 51 publications and 32 presentations at major national conferences. Also, one U.S. patent was obtained and six U.S. patent applications have been filed for innovations resulting from the projects sponsored by the Center.

  2. Time trends in incidence and prognosis of primary liver cancer and liver metastases of unknown origin in a Danish region, 1985-2004

    DEFF Research Database (Denmark)

    Erichsen, Rune; Jepsen, Peter; Jacobsen, Jacob;

    2008-01-01

    OBJECTIVES: Changes, over the last 20 years, in the diagnostic procedures and treatment of primary liver cancer (PLC) and liver metastases of unknown origin (LMUO) may have affected the clinical course of both cancers. Few longitudinal studies examined this issue. In a population-based setting, we...... studied changes in the incidence and prognosis of PLC and LMUO over time. METHODS: Between 1985 and 2004, we identified 2675 patients with PLC and LMUO in three Danish counties, with a population of 1.4 million. We computed the standardized incidence rate (SIR), ratio of PLC to LMUO diagnoses, median...... survival, and estimated mortality rate ratio adjusted for age, sex, and comorbidity. RESULTS: The SIR of PLC increased from 3.2 in 1985 to 5.0 in 2003, and the SIR of LMUO increased from 3.7 to 6.4. No increase was noted in the PLC-to-LMUO ratio over time (P=0.1 for trend). From 1985 to 2004, the median...

  3. Co-expression of HER3 and MUC1 is associated with a favourable prognosis in patients with bladder cancer

    DEFF Research Database (Denmark)

    Nielsen, Trine O; Borre, Michael; Nexo, Ebba;

    2015-01-01

    OBJECTIVES: To investigate the functional impact of the interaction of MUC1 with the epidermal growth factor receptors HER3 and HER4 in patients with bladder cancer. PATIENTS AND METHODS: Using reverse transcription quantitative polymerase chain reaction, we examined MUC1 expression in 82 bladder...... cancer biopsies previously examined for the expression of HER3. RESULTS: Patients expressing high MUC1 had a favourable survival when the expression of HER3 was also high compared with when the expression of HER3 was low (P = 0.004). When MUC1 expression was low, HER3 co-expression did not influence...... the prognostic value of MUC1 (P = 0.488). MUC1 expression had no correlation with survival, tumour stage or grade, or to the prognostic value of HER4. CONCLUSIONS: A high MUC1 expression was associated with a favourable prognosis in patients with bladder cancer when the expression of HER3 was also high...

  4. Relation of nm23 gene expression to CT sign and prognosis in peripheral nonsmall cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    MA Shu-hua; XU Ke; HUANG Tao; HUANG Bao-jun; ZHU Yu-sen; LI Jun; LI Shu; SUN Li-hua

    2005-01-01

    @@ CT observations and the cellular factors of molecular biology each enable one to recognize macro/micro changes in lung cancer. Growing pattern, characteristic shapes, degree of malignancy, relapse and metastasis of lung cancer are mainly determined by their molecular biology. Change of tumour shape, determined by the tumour's biological behaviour, is the basis of CT observations. That is, the pathological change acts as a bridge which links the CT observation to molecular biology and makes the investigation of internal relationship between CT sign and molecular biology behaviour possible. As a tumour suppressor gene, nm23 gene is located in chromosome 17q21.3, encoding a nucleoside diphosphate kinase.1,2 We studied the expression of nm23 in peripheral nonsmall cell lung cancer (NSCLC) using the streptavidin peroxidase (SP) immunohistochemical method and investigated retrospectively the relationship between nm23 gene, CT observation, biological behaviour and prognosis of NSCLC.

  5. Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer.

    Science.gov (United States)

    Rosenberger, I; Strauss, A; Dobiasch, S; Weis, C; Szanyi, S; Gil-Iceta, L; Alonso, E; González Esparza, M; Gómez-Vallejo, V; Szczupak, B; Plaza-García, S; Mirzaei, S; Israel, L L; Bianchessi, S; Scanziani, E; Lellouche, J-P; Knoll, P; Werner, J; Felix, K; Grenacher, L; Reese, T; Kreuter, J; Jiménez-González, M

    2015-09-28

    Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).

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

    Directory of Open Access Journals (Sweden)

    Raquel Marques

    2015-12-01

    electrodes (SPCEs were used as the transducers. These SPCEs (working volume: ~40 μL are widely employed in the construction of electrochemical (biosensors because of several reasons: simplicity and low cost, versatility of design, small dimensions and possibility of incorporation in portable systems, as well as adequate electroanalytical characteristics. These SPCEs were modified with gold nanoparticles (nAu through the electrochemical deposition of ionic gold from a solution. The developed sensors were applied to the analysis of the selected biomarkers in spiked human serum samples.Besides these immunosensors, a molecularly imprinted polymer (MIP sensor was developed for the analysis of HER2-ECD. In this case a gold electrode was used as the transducer. The MIP was formed by surface imprinting and electrochemical impedance spectroscopy and voltammetry were used for detection purposes.Results: For the immunoassays the following parameters were optimized: capture and detection antibody concentration, surface blocking, reaction mixtures and incubation times. The best limits of detection obtained were below the established cut-off values (25 U/mL and 15 ng/mL for CA15-3 and HER2-ECD, respectively. For the MIP sensor the most adequate polymer was chosen and the electropolymerization, template removal, and incubation conditions were optimized. The lowest HER2-ECD concentration that was analyzed was 50 µg/mL.Conclusion: The obtained results indicate that the developed sensors could be promising tools in breast cancer diagnostics and follow-up. However, further studies should be conducted using patients' samples and the results of these assays should be validated with the established analysis procedures for these cancer biomarkers.-----------------------------------------Cite this article as:  Marques R, Pacheco J, Rama EC, Viswanathan S, Nouws H, Delerue-Matos C. Electrochemical sensors in breast cancer diagnostics and follow-up. Int J Cancer Ther Oncol 2015; 3(4:34012.[This

  7. Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT

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    Zhen-Yu He

    2017-02-01

    Full Text Available Triple-negative breast cancer (TNBC was regarded as the most aggressive and mortal subtype of breast cancer (BC since the molecular subtype system has been established. Abundant studies have revealed that epithelial-mesenchymal transition (EMT played a pivotal role during breast cancer metastasis and progression, especially in TNBC. Herein, we showed that inhibition the expression of replication factor C subunit 3 (RFC3 significantly attenuated TNBC metastasis and progression, which was associated with EMT signal pathway. In TNBC cells, knockdown of RFC3 can down-regulate mesenchymal markers and up-regulate epithelial markers, significantly attenuated cell proliferation, migration and invasion. Additionally, silencing RFC3 expression can decrease nude mice tumor volume, weight and relieve lung metastasis in vivo. Furthermore, we also demonstrated that overexpression of RFC3 in TNBC showed increased metastasis, progression and poor prognosis. We confirmed all of these results by immunohistochemistry analysis in 127 human TNBC tissues and found that RFC3 expression was significantly associated with poor prognosis in TNBC. Taken all these findings into consideration, we can conclude that up-regulation of RFC3 promotes TNBC progression through EMT signal pathway. Therefore, RFC3 could be an independent prognostic factor and therapeutic target for TNBC.

  8. Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.

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    Yifan Wang

    Full Text Available Solid tumors exist in a hypoxic microenvironment, and possess high-glycolytic metabolites. To avoid the acidosis, tumor cells must exhibit a dynamic cytosolic pH regulation mechanism(s. The voltage-gated proton channel Hv1 mediates NADPH oxidase function by compensating cellular loss of electrons with protons. Here, we showed for the first time, that Hv1 expression is increased in colorectal tumor tissues and cell lines, associated with poor prognosis. Immunohistochemistry showed that Hv1 is strongly expressed in adenocarcinomas but not or lowly expressed in normal colorectal or hyperplastic polyps. Hv1 expression in colorectal cancer is significantly associated with the tumor size, tumor classification, lymph node status, clinical stage and p53 status. High Hv1 expression is associated significantly with shorter overall and recurrence-free survival. Furthermore, real-time RT-PCR and immunocytochemistry showed that Hv1 is highly expressed in colorectal cancer cell lines, SW620, HT29, LS174T and Colo205, but not in SW480. Inhibitions of Hv1 expression and activity in the highly metastatic SW620 cells by small interfering RNA (siRNA and Zn(2+ respectively, markedly decrease the cell invasion and migration, restraint proton extrusion and the intracellular pH recovery. Our results suggest that Hv1 may be used as a potential biomarker for diagnosis and prognosis of colorectal carcinoma, and a potential target for anticancer drugs in colorectal cancer therapy.

  9. Thermoacoustic imaging and spectroscopy for enhanced cancer diagnostics

    Science.gov (United States)

    Bauer, Daniel Ryan

    Early detection of cancer is paramount for improved patient survival. This dissertation presents work developing imaging techniques to improve cancer diagnostics and detection utilizing light and microwave induced thermoacoustic imaging. In the second chapter, the well-established pre-clinical mouse window chamber model is interfaced with simultaneously acquired high-resolution pulse echo (PE) ultrasound and photoacoustic (PA) imaging. Co-registered PE and PA imaging, coupled with developed image segmentation algorithms, are used to quantitatively track and monitor the size, shape, heterogeneity, and neovasculature of the tumor microenvironment during a month long study. Average volumetric growth was 5.35 mm3/day, which correlated well with two dimensional results from fluorescent imaging (R = 0.97, p imaging is also employed to probe the assumed oxygenation status of the tumor vasculature. The window chamber model combined with high-resolution PE and PA imaging could form a powerful testbed for characterizing cancers and evaluating new contrast and therapeutic agents. The third chapter utilizes a clinical ultrasound array to facilitate fast volumetric spectroscopic PA imaging to detect and discriminate endogenous absorbers (i.e. oxy/deoxygenated hemoglobin) as well as exogenous PA contrast agents (i.e. gold nanorods, fluorophores). In vivo spatiotemporal tracking of administered gold nanorods is presented, with the contrast agent augmenting the PA signal 18 dB. Furthermore, through the use of spectral unmixing algorithms, the relative concentrations of multiple endogenous and exogenous co-localized absorbers were reconstructed in tumor bearing mice. The concentration of Alexaflour647 was calculated to increase nearly 20 dB in the center of a prostate tumor after a tail-vein injection of the contrast agent. Additionally, after direct subcutaneous injections of two different gold nanorods into a breast tumor, the concentration of each nanoparticle was discriminated

  10. Utility of 18FDG-PET/CT in breast cancer diagnostics--a systematic review

    DEFF Research Database (Denmark)

    Warning, Karina; Hildebrandt, Malene Grubbe; Kristensen, Bent;

    2011-01-01

    as a primary diagnostic procedure in breast cancer; but it has the potential to be useful for the detection of distant metastases and for monitoring response to chemotherapy in breast cancer patients. PET/CT should still be regarded as a supplement to conventional diagnostic procedures such as CT and MRI....

  11. RNA quantification using gold nanoprobes - application to cancer diagnostics

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    Baptista Pedro V

    2010-02-01

    Full Text Available Abstract Molecular nanodiagnostics applied to cancer may provide rapid and sensitive detection of cancer related molecular alterations, which would enable early detection even when those alterations occur only in a small percentage of cells. The use of gold nanoparticles derivatized with thiol modified oligonucleotides (Au-nanoprobes for the detection of specific nucleic acid targets has been gaining momentum as an alternative to more traditional methodologies. Here, we present an Au-nanoparticles based approach for the molecular recognition and quantification of the BCR-ABL fusion transcript (mRNA, which is responsible for chronic myeloid leukemia (CML, and to the best of our knowledge it is the first time quantification of a specific mRNA directly in cancer cells is reported. This inexpensive and very easy to perform Au-nanoprobe based method allows quantification of unamplified total human RNA and specific detection of the oncogene transcript. The sensitivity settled by the Au-nanoprobes allows differential gene expression from 10 ng/μl of total RNA and takes less than 30 min to complete after total RNA extraction, minimizing RNA degradation. Also, at later stages, accumulation of malignant mutations may lead to resistance to chemotherapy and consequently poor outcome. Such a method, allowing for fast and direct detection and quantification of the chimeric BCR-ABL mRNA, could speed up diagnostics and, if appropriate, revision of therapy. This assay may constitute a promising tool in early diagnosis of CML and could easily be extended to further target genes with proven involvement in cancer development.

  12. Stratification of Prognosis of Triple-Negative Breast Cancer Patients Using Combinatorial Biomarkers.

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    Yong Yue

    Full Text Available Triple-negative breast cancer (TNBC is highly diverse group of cancers, and generally considered an aggressive disease associated with poor survival. Stratification of TNBC is highly desired for both prognosis and treatment decisions to identify patients who may benefit from less aggressive therapy.This study retrieved 192 consecutive non-metastasis TNBC patients who had undergone a resection of a primary tumor from 2008 to 2012. All samples were negative for ER, PR, and HER2/neu. Disease-free-survival (DFS and overall-survival (OS were evaluated for expression of immunohistochemical biomarkers (P53, Ki-67, CK5/6 and EGFR, as well as clinicopathological variables including age, tumor size, grade, lymph node status, pathologic tumor and nodal stages. The cutoff values of the basal biomarkers, EGFR and CK5/6, were estimated by time-dependent ROC curves. The prognostic values of combinatorial variables were identified by univariate and multivariate Cox analysis. Patients were stratified into different risk groups based on expression status of identified prognostic variables.Median age was 57 years (range, 28-92 years. Patients' tumor stage and nodal stage were significantly associated with OS and DFS. EGFR and CK5/6 were significant prognostic variables at cutoff points of 15% (p = 0.001, AUC = 0.723, and 50% (p = 0.006, AUC = 0.675, respectively. Multivariate Cox analysis identified five significant variables: EGFR (p = 0.016, CK5/6 (p = 0.018, Ki-67 (p = 0.048, tumor stage (p = 0.010, and nodal stage (p = 0.003. Patients were stratified into low basal (EGFR≤15% and CK5/6≤50% and high basal (EGFR>15% and/or CK5/6>50% expression groups. In the low basal expression group, patients with low expressions of Ki-67, low tumor and nodal stage had significantly better survival than those with high expressions/stages of three variables, log-rank p = 0.015 (100% vs 68% at 50 months. In the high basal expression group, patient with high basal expression

  13. A study on the effect of IL-6 gene polymorphism on the prognosis of non-small-cell lung cancer

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    Jia W

    2015-09-01

    Full Text Available Wei Jia, Guang-He Fei, Jie-Gui Hu, Xian-Wei Hu Pulmonary Department, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China Background: Lung cancer is one of the most commonly diagnosed clinical diseases. IL-6 is a multifunctional cytokine that is related to chemotactic factors and tumor biological regulation. -174G/C polymorphism in the promoter region of the IL-6 gene single-nucleotide polymorphism is the -174 position change from G to C. However, the relationship between the IL-6 gene polymorphism and prognosis of lung cancer is elusive. Therefore, the aim of this study was to evaluate the effect of -174G/C polymorphism on the prognosis of patients with non-small-cell lung cancer (NSCLC.Methods: DNA was extracted from the peripheral blood of 434 cases diagnosed with NSCLC by cytologic or histologic examination. Polymerase chain reaction–restriction fragment length polymorphism (NlaIII was used to detect the genotype of -174G/C. Based on the functional activity of the IL-6 gene polymorphism, genotypes were divided into G vector (CG/GG (high yield and CC genotype (low yield. Prognosis of patients was analyzed and independent risk factors evaluated. A quantitative analysis of the degree of pain after diagnosis was performed to evaluate the correlations between gene polymorphisms and the degree of pain and use of analgesics.Results: Survival analysis showed that survival of the patients carrying the G allele (CG/GG was significantly lower than that of patients with CC genotype (42.31 versus 62.79 months; P=0.032. The IL-6 gene promoter region revealed the presence of polymorphic variants, which may be associated with changes in the gene transcription process that affect the level of serum cytokines. IL-6 -174G/C gene polymorphism is associated with a significant morphine equivalent daily dose (IL-6 GG, 69.61; GC, 73.17; CC, 181.67; P=0.004. Homozygous IL-6 -174C/C genotype carriers required higher doses of

  14. New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

    Science.gov (United States)

    Cortinas, Inés Vidal; Beretta, Mario; Alonso, Omar; Mut, Fernando

    2015-01-01

    Background Myocardial perfusion scintigraphy (MPS) in patients not reaching 85% of the maximum predicted heart rate (MPHR) has reduced sensitivity. Objectives In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP) was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols. Methods In patients not reaching a sufficient exercise (SE) test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection. Results Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR) and 67 underwent the dipyridamole alone test (DIP). They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43). For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35). Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001). Conclusions The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP. PMID:26039661

  15. New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

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    Inés Vidal Cortinas

    2015-08-01

    Full Text Available AbstractBackground:Myocardial perfusion scintigraphy (MPS in patients not reaching 85% of the maximum predicted heart rate (MPHR has reduced sensitivity.Objectives:In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols.Methods:In patients not reaching a sufficient exercise (SE test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection.Results:Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR and 67 underwent the dipyridamole alone test (DIP. They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43. For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35. Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001.Conclusions:The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP.

  16. New Exercise-Dipyridamole Combined Test for Nuclear Cardiology in Insufficient Effort: Appropriate Diagnostic Sensitivity Keeping Exercise Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Cortinas, Inés Vidal, E-mail: invi@montevideo.com.uy; Beretta, Mario; Alonso, Omar; Mut, Fernando [Departamento de Medicina Nuclear do Hospital ‘Asociación Española’, Br. Artigas 1515, Montevideo (Uruguay)

    2015-08-15

    Myocardial perfusion scintigraphy (MPS) in patients not reaching 85% of the maximum predicted heart rate (MPHR) has reduced sensitivity. In an attempt to maintain diagnostic sensitivity without losing functional exercise data, a new exercise and dipyridamole combined protocol (EDCP) was developed. Our aim was to evaluate the feasibility and safety of this protocol and to compare its diagnostic sensitivity against standard exercise and dipyridamole protocols. In patients not reaching a sufficient exercise (SE) test and with no contraindications, 0.56 mg/kg of dipyridamole were IV administered over 1 minute simultaneously with exercise, followed by 99mTc-MIBI injection. Of 155 patients, 41 had MPS with EDCP, 47 had a SE test (≥ 85% MPHR) and 67 underwent the dipyridamole alone test (DIP). They all underwent coronary angiography within 3 months. The three stress methods for diagnosis of coronary lesions had their sensitivity compared. For stenosis ≥ 70%, EDCP yielded 97% sensitivity, SE 90% and DIP 95% (p = 0.43). For lesions ≥ 50%, the sensitivities were 94%, 88% and 95%, respectively (p = 0.35). Side effects of EDCP were present in only 12% of the patients, significantly less than with DIP (p < 0.001). The proposed combined protocol is a valid and safe method that yields adequate diagnostic sensitivity, keeping exercise prognostic information in patients unable to reach target heart rate, with fewer side effects than the DIP.

  17. Decreased expression of miR-204 is associated with poor prognosis in patients with breast cancer.

    Science.gov (United States)

    Li, Weidong; Jin, Xuejun; Zhang, Qianbing; Zhang, Gong; Deng, Xubin; Ma, Lei

    2014-01-01

    The identification of biomarkers in breast cancer diagnosis and therapy is important in achieving early cancer diagnosis and improving patient outcomes. The aim of this study was to examine clinical significance of miR-204 expression in tissues from breast cancer patients. The relationship between miR-204 expression and clinicopathological characteristics was investigated. MiR-204 expression was significantly associated with TNM stage and metastasis. Patients with low miR-204 expression had poorer overall survival time and disease free survival time than those with high miR-204 expression. Furthermore, miR-204 expression was correlated with chemotherapeutic resistance of breast cancer patients. In conclusion, the miR-204 may be a potential diagnostic and prognostic biomarker of breast cancer.

  18. Overexpression of Notch3 and pS6 Is Associated with Poor Prognosis in Human Ovarian Epithelial Cancer

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    Zhaoxia Liu

    2016-01-01

    Full Text Available Notch3 and pS6 play important roles in tumor angiogenesis. To assess the expression of Notch3 and pS6 in Chinese ovarian epithelial cancer patients, a ten-year follow-up study was performed in ovarian epithelial cancer tissues from 120 specimens of human ovarian epithelial cancer, 30 specimens from benign ovarian tumors, and 30 samples from healthy ovaries by immunohistochemistry. The results indicate that the expression of Notch3 and pS6 was higher in ovarian epithelial cancer than in normal ovary tissues and in benign ovarian tumor tissues (p0.05 but positively associated with clinical stage, pathological grading, histologic type, lymph node metastasis, and ascites (p<0.05 or p<0.01. A follow-up survey of 64 patients with ovarian epithelial cancer showed that patients with high Notch3 and pS6 expression had a shorter survival time (p<0.01, in which the clinical stage (p<0.05 and Notch3 expression (p<0.01 played important roles. In conclusion, Notch3 and pS6 are significantly related to ovarian epithelial cancer development and prognosis, and their combination represents a potential biomarker and therapeutic target in ovarian tumor angiogenesis.

  19. Lectin-histochemical reactivity of sialic acid in breast cancer and its relationship to prognosis using limulus polyphemus agglutinin.

    Science.gov (United States)

    Ding, K; Yamaguchi, A; Goi, T; Maehara, M; Nakagawara, G

    1997-04-01

    Studies of circulating sialic acid have revealed its relationship with a variety of malignant tumors. It is not vet clear whether sialic acid could be used as a prognostic marker of breast cancer, and few studies have examined sialic acid expression in the cell membrane and cytoplasm of breast cancer cells by means of the lectin-histochemical technique. In the present study, we used biotinylated limulus polyphemus agglutinin (LPA), a special binding lectin of sialic acid, to stain sialic acid in breast cancer cells. Of the 104 cases of breast cancer examined, 59 (56.7%) positive cases were observed. There was a significant correlation between the LPA staining and the clinicopathologic features of all patients, including pathological stage and lymph node metastasis. Among the 100 patients who underwent curative operation, the mean disease-free survival rate of the 45 patients who were LPA-negative was significantly higher than that of the 55 LPA-positive patients (psialic acid in breast cancer could be used as a marker of malignancy potential, as well as a poor survival factor, and the biotinylated LPA assay may provide a convenient and useful method to predict the prognosis of breast cancer.

  20. Integration of Breast Cancer Secretomes with Clinical Data Elucidates Potential Serum Markers for Disease Detection, Diagnosis, and Prognosis.

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    Yvonne S Ziegler

    Full Text Available Cancer cells secrete factors that influence adjacent cell behavior and can lead to enhanced proliferation and metastasis. To better understand the role of these factors in oncogenesis and disease progression, estrogen and progesterone receptor positive MCF-7 cells, triple negative breast cancer MDA-MB-231, DT22, and DT28 cells, and MCF-10A non-transformed mammary epithelial cells were grown in 3D cultures. A special emphasis was placed on triple negative breast cancer since these tumors are highly aggressive and no targeted treatments are currently available. The breast cancer cells secreted factors of variable potency that stimulated proliferation of the relatively quiescent MCF-10A cells. The conditioned medium from each cell line was subjected to mass spectrometry analysis and a variety of secreted proteins were identified including glycolytic enzymes, proteases, protease inhibitors, extracellular matrix proteins, and insulin-like growth factor binding proteins. An investigation of the secretome from each cell line yielded clues about strategies used for breast cancer proliferation and metastasis. Some of the proteins we identified may be useful in the development of a serum-based test for breast cancer detection, diagnosis, prognosis, and monitoring.

  1. LED-based near infrared sensor for cancer diagnostics

    Science.gov (United States)

    Bogomolov, Andrey; Ageev, Vladimir; Zabarylo, Urszula; Usenov, Iskander; Schulte, Franziska; Kirsanov, Dmitry; Belikova, Valeria; Minet, Olaf; Feliksberger, E.; Meshkovsky, I.; Artyushenko, Viacheslav

    2016-03-01

    Optical spectroscopic technologies are increasingly used for cancer diagnostics. Feasibility of differentiation between malignant and healthy samples of human kidney using Fluorescence, Raman, MIR and NIR spectroscopy has been recently reported . In the present work, a simplification of NIR spectroscopy method has been studied. Traditional high-resolution NIR spectrometry was replaced by an optical sensor based on a set of light-emitting diodes at selected wavelengths as light sources and a photodiode. Two prototypes of the sensor have been developed and tested using 14 in-vitro samples of seven kidney tumor patients. Statistical evaluation of results using principal component analysis and partial least-squares discriminant analysis has been performed. Despite only partial discrimination between tumor and healthy tissue achieved by the presented new technique, the results evidence benefits of LED-based near-infrared sensing used for oncological diagnostics. Publisher's Note: This paper, originally published on 4 March, 2016, was replaced with a corrected/revised version on 7 April, 2016. If you downloaded the original PDF but are unable to access the revision, please contact SPIE Digital Library Customer Service for assistance.

  2. ALDH1A1 mRNA expression in association with prognosis of triple-negative breast cancer.

    Science.gov (United States)

    Liu, Yan; Baglia, Michelle; Zheng, Ying; Blot, William; Bao, Ping-Ping; Cai, Hui; Nechuta, Sarah; Zheng, Wei; Cai, Qiuyin; Shu, Xiao Ou

    2015-12-01

    ALDH1 is a crucial element in the retinoic acid signaling pathway regulating the self-renewal and differentiation of normal stem cells, and may play an important role in cancer progression. However, research on ALDH1 gene expression and breast cancer prognosis has yielded conflicting results. We evaluated the association between tumor tissue ALDH1A1/ALDH1A3 mRNA expression and triple-negative breast cancer (TNBC) prognosis in the Shanghai Breast Cancer Survival Study (SBCSS, N=463), Nashville Breast Health Study (NBHS, N=86), and Southern Community Cohort Study (SCCS, N=47). Gene expression was measured in RNA isolated from breast cancer tissues. In the SBCSS, higher ALDH1A1 mRNA level was associated with improved disease-free (HR=0.87, 95% CI: 0.80-0.95, per log unit change) and overall survival (HR=0.85, 95% CI: 0.78-0.93 per log unit change) independent of age at diagnosis, TNM stage and treatment. We replicated the findings for overall survival in the NBHS and SCCS (HR = 0.27, 95% CI: 0.10-0.73) and for disease-free survival by a meta-analysis of four publicly-available gene expression datasets (HR = 0.86, 95% CI: 0.76-0.97). No significant association was found for ALDH1A3.Our study suggests high expression of ALDH1A1 mRNA in tumor tissues may be an independent predictor of a favorable TNBC outcome.

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

    Science.gov (United States)

    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.

  4. Circulating plasma MiR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis.

    Directory of Open Access Journals (Sweden)

    Hanyin Cheng

    Full Text Available BACKGROUND: Colorectal cancer (CRC remains one of the major cancer types and cancer related death worldwide. Sensitive, non-invasive biomarkers that can facilitate disease detection, staging and prediction of therapeutic outcome are highly desirable to improve survival rate and help to determine optimized treatment for CRC. The small non-coding RNAs, microRNAs (miRNAs, have recently been identified as critical regulators for various diseases including cancer and may represent a novel class of cancer biomarkers. The purpose of this study was to identify and validate circulating microRNAs in human plasma for use as such biomarkers in colon cancer. METHODOLOGY/PRINCIPAL FINDINGS: By using quantitative reverse transcription-polymerase chain reaction, we found that circulating miR-141 was significantly associated with stage IV colon cancer in a cohort of 102 plasma samples. Receiver operating characteristic (ROC analysis was used to evaluate the sensitivity and specificity of candidate plasma microRNA markers. We observed that combination of miR-141 and carcinoembryonic antigen (CEA, a widely used marker for CRC, further improved the accuracy of detection. These findings were validated in an independent cohort of 156 plasma samples collected at Tianjin, China. Furthermore, our analysis showed that high levels of plasma miR-141 predicted poor survival in both cohorts and that miR-141 was an independent prognostic factor for advanced colon cancer. CONCLUSIONS/SIGNIFICANCE: We propose that plasma miR-141 may represent a novel biomarker that complements CEA in detecting colon cancer with distant metastasis and that high levels of miR-141 in plasma were associated with poor prognosis.

  5. Circulating Plasma MiR-141 Is a Novel Biomarker for Metastatic Colon Cancer and Predicts Poor Prognosis

    Science.gov (United States)

    Cogdell, David E.; Zheng, Hong; Schetter, Aaron J.; Nykter, Matti; Harris, Curtis C.; Chen, Kexin; Hamilton, Stanley R.; Zhang, Wei

    2011-01-01

    Background Colorectal cancer (CRC) remains one of the major cancer types and cancer related death worldwide. Sensitive, non-invasive biomarkers that can facilitate disease detection, staging and prediction of therapeutic outcome are highly desirable to improve survival rate and help to determine optimized treatment for CRC. The small non-coding RNAs, microRNAs (miRNAs), have recently been identified as critical regulators for various diseases including cancer and may represent a novel class of cancer biomarkers. The purpose of this study was to identify and validate circulating microRNAs in human plasma for use as such biomarkers in colon cancer. Methodology/Principal Findings By using quantitative reverse transcription-polymerase chain reaction, we found that circulating miR-141 was significantly associated with stage IV colon cancer in a cohort of 102 plasma samples. Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of candidate plasma microRNA markers. We observed that combination of miR-141 and carcinoembryonic antigen (CEA), a widely used marker for CRC, further improved the accuracy of detection. These findings were validated in an independent cohort of 156 plasma samples collected at Tianjin, China. Furthermore, our analysis showed that high levels of plasma miR-141 predicted poor survival in both cohorts and that miR-141 was an independent prognostic factor for advanced colon cancer. Conclusions/Significance We propose that plasma miR-141 may represent a novel biomarker that complements CEA in detecting colon cancer with distant metastasis and that high levels of miR-141 in plasma were associated with poor prognosis. PMID:21445232

  6. Blood levels of vitamin D and early stage breast cancer prognosis: a systematic review and meta-analysis.

    Science.gov (United States)

    Rose, April A N; Elser, Christine; Ennis, Marguerite; Goodwin, Pamela J

    2013-10-01

    Vitamin D regulates expression of genes important in development and progression of breast cancer. The association of vitamin D with breast cancer outcomes among breast cancer patients is controversial. We conducted a systematic review and meta-analysis of this association in early stage breast cancer outcome. We searched MEDLINE (1982-May 1, 2013), the American Society of Clinical Oncology (2009-2012), and the San Antonio Breast Cancer Symposium (2010-2012) for abstracts, using the following keywords: "breast cancer" and "prognosis" or "survival", and "vitamin D" or" calcitriol" to identify studies reporting the associations of blood vitamin D levels (drawn close to diagnosis) with breast cancer outcomes. Meta-analyses were performed using an inverse-variance weighted fixed-effects model with Stata Version 12. Eight studies including 5,691 patients were identified. Vitamin D deficiency was variably categorized across studies; a median of 36.8 % of patients were classified as deficient. Low vitamin D levels were associated with a pooled hazard ratio of 2.13 (95 % CI 1.64-2.78) and 1.76 (95 % CIs 1.35-2.30) for recurrence (six studies) and death (four studies), respectively, with no evidence of significant heterogeneity across studies. There was potential evidence of a publication bias in studies examining associations with death (but not in those examining associations with recurrence). These findings support an association of low levels of vitamin D with increased risk of recurrence and death in early stage breast cancer patients. Given the observational nature of the included studies, it cannot be concluded that this association is causal. Further research is warranted to investigate the potential beneficial effects of vitamin D in breast cancer.

  7. Toward development of a surface-enhanced Raman scattering (SERS)-based cancer diagnostic immunoassay panel.

    Science.gov (United States)

    Granger, Jennifer H; Granger, Michael C; Firpo, Matthew A; Mulvihill, Sean J; Porter, Marc D

    2013-01-21

    Proteomic analyses of readily obtained human fluids (e.g., serum, urine, and saliva) indicate that the diagnosis of complex diseases will be enhanced by the simultaneous measurement of multiple biomarkers from such samples. This paper describes the development of a nanoparticle-based multiplexed platform that has the potential for simultaneous read-out of large numbers of biomolecules. For this purpose, we have chosen pancreatic adenocarcinoma (PA) as a test bed for diagnosis and prognosis. PA is a devastating form of cancer in which an estimated 86% of diagnoses resulted in death in the United States in 2010. The high mortality rate is due, in part, to the asymptomatic development of the disease and the dearth of sensitive diagnostics available for early detection. One promising route lies in the development of a serum biomarker panel that can generate a signature unique to early stage PA. We describe the design and development of a proof-of-concept PA biomarker immunoassay array coupled with surface-enhanced Raman scattering (SERS) as a sensitive readout method.

  8. Diagnostic delay experienced among gynecological cancer patients: a nationwide survey in Denmark

    DEFF Research Database (Denmark)

    Robinson, Kirstine Magtengaard; Ottesen, Bent; Christensen, Karl Bang;

    2009-01-01

    OBJECTIVE: To examine diagnostic delay among gynecological cancer patients. DESIGN: Nationwide study. SETTING: The cohort comprised all women receiving their first treatment for cervical, endometrial, or ovarian cancer between 1 October 2006 and 1 December 2007 in four of the five centers...... for gynecological cancer surgery in Denmark. SAMPLE: Of the 911 women alive, 648 participated, resulting in a response rate of 71.1%; of these, 30.1% were diagnosed with cervical cancer, 31.0% with endometrial cancer, and 38.9% with ovarian cancer. METHODS: Questionnaire survey. MAIN OUTCOME MEASURES: Diagnostic...... experiencing very long delays. Ovarian cancer patients experienced significantly shorter delays compared with other gynecological cancer patients in all parts of the health care system. CONCLUSIONS: Delays occur in all parts of the diagnostic process, suggesting that a multifaceted approach should be adopted...

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

    Science.gov (United States)

    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.

  10. Multiplexed electrochemical protein detection and translation to personalized cancer diagnostics.

    Science.gov (United States)

    Rusling, James F

    2013-06-04

    Measuring diagnostic panels of multiple proteins promises a new, personalized approach to early detection and therapy of diseases like cancer. Levels of biomarker proteins in patient serum can provide a continually updated record of disease status. Research in electrochemical detection of proteins has produced exquisitely sensitive approaches. Most utilize ELISA-like sandwich immunoassays incorporating various aspects of nanotechnology. Several of these ultrasensitive methodologies have been extended to microfluidic multiplexed protein detection, but engineered solutions are needed to measure more proteins in a single device from a small patient sample such as a drop of blood or tissue lysate. To achieve clinical or point-of-care (POC) use, simplicity and low cost are essential. In multiplexed microfluidic immunoassays, required reagent additions and washing steps pose a significant problem calling for creative engineering. A grand challenge is to develop a general cancer screening device to accurately measure 50-100 proteins in a simple, cost-effective fashion. This will require creative solutions to simplified reagent addition and multiplexing.

  11. Epidemiology, diagnostics and long-term overall survival of patients with non-small cell lung cancer in the Brest Region

    Directory of Open Access Journals (Sweden)

    Siarhei Panko

    2013-10-01

    Full Text Available Introduction: Lung cancer has been the most common cancer in the world and in Belarus. Aim of the research: To evaluate the epidemiology of non-small cell lung cancer and improvements in diagnostics and treatment for the past 11 years in the Brest Region of Belarus. Material and methods: We conducted a retrospective analysis of statistical data (incidence rate, mortality in the regional cancer registry of the Brest oncological clinic since 2000 and assessed survival for 652 adult patients with different stages of non-small-cell lung cancer (NSCLC who underwent surgery in the Thoracic Surgery Department of Brest Regional Hospital in 2002–2010. Results: Lung cancer continues to have the highest incidence rate among malignant neoplasms and because of its high fatality rate is a leading cause of cancer-related mortality in the Brest Region and Belarus. The chest radiography screening programme of lung cancer since 2000 and the implementation of computed tomography (CT- and ultrasonography (USG-guided needle biopsy and VATS LigaSure pulmonary wedge resection for the evaluation of solitary pulmonary nodules has allowed an increase of diagnostic rates and improved the histological confirmation rate of lung cancer in the Brest Region. Multivariate analysis indicates that male sex, age older than seventy and incomplete surgical resection are independent predictors of poor prognosis for postoperative long-term overall survival. Conclusions : Today it is necessary to carry out low-dose spiral computerized diagnostics in the Brest Region, which would detect a greater proportion of asymptomatic lung cancers. Surgical resection remains the only consistent and successful option of a cure for patients with lung cancer.

  12. [DNA microarray-based gene expression profiling in diagnosis, assessing prognosis and predicting response to therapy in colorectal cancer].

    Science.gov (United States)

    Kwiatkowski, Przemysław; Wierzbicki, Piotr; Kmieć, Andrzej; Godlewski, Janusz

    2012-06-11

     Colorectal cancer is the most common cancer of the gastrointestinal tract. It is considered as a biological model of a certain type of cancerogenesis process in which progression from an early to late stage adenoma and cancer is accompanied by distinct genetic alterations. Clinical and pathological parameters commonly used in clinical practice are often insufficient to determine groups of patients suitable for personalized treatment. Moreover, reliable molecular markers with high prognostic value have not yet been determined. Molecular studies using DNA-based microarrays have identified numerous genes involved in cell proliferation and differentiation during the process of cancerogenesis. Assessment of the genetic profile of colorectal cancer using the microarray technique might be a useful tool in determining the groups of patients with different clinical outcomes who would benefit from additional personalized treatment. The main objective of this study was to present the current state of knowledge on the practical application of gene profiling techniques using microarrays for determining diagnosis, prognosis and response to treatment in colorectal cancer.

  13. Expression of dickkopf-1 and beta-catenin related to the prognosis of breast cancer patients with triple negative phenotype.

    Directory of Open Access Journals (Sweden)

    Wen-Huan Xu

    Full Text Available BACKGROUND AND AIM: We investigated the prognostic importance of dickkopf-1(DKK1 and beta-catenin expression in triple negative breast cancers. METHODS: The expression of DKK1 and beta-catenin was evaluated in breast cell lines using RT-PCR and western blot. Immunohistochemistry was used to characterize the expression pattern of DKK1 and beta-catenin in 85 triple negative breast cancers and prognostic significance was assessed by Kaplan-Meier analysis and Cox proportional hazards regression modeling. RESULTS: The expression of DKK1 was confirmed in hormone-resistant breast cell lines MDA-MB-231, MDA-MB-231-HM and MDA-MB-435. Expression of DKK1 in triple negative breast cancers correlated with cytoplasmic/nuclear beta-catenin (p = 0.000. Elevated expression of DKK1 and cytoplasmic/nuclear beta-catenin in triple negative cancers indicate poor outcome of patients. DKK1 was also a prognostic factor for patients with earlier stage or no lymph node metastasis. CONCLUSION: DKK1 together with beta-catenin might be important prognostic factors in triple negative breast carcinoma. DKK1 might be a valuable biomarker in predicting the prognosis of patients with earlier stage or no lymph node metastasis. It is possible that through further understanding of the role of Wnt/beta-catenin pathway activation, beta-catenin would be a potential therapeutic target for the triple negative breast cancer.

  14. Up-regulation of 91H promotes tumor metastasis and predicts poor prognosis for patients with colorectal cancer.

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    Qiwen Deng

    Full Text Available Long noncoding RNAs (lncRNAs play widespread roles in gene regulation and cellular processes. However, the functional roles of lncRNAs in colorectal cancer (CRC are not yet well elucidated. The aim of the present study was to measure the levels of lncRNA 91H expression in CRC and evaluate its clinical significance and biological roles in the development and progression of CRC.91H expression and copy number variation (CNV were measured in 72 CRC tumor tissues and adjacent normal tissues by real-time PCR. The biological roles of 91H were evaluated by MTT, scratch wound assay, migration and invasion assays, and flow cytometry.91H was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Moreover, 91H overexpression was closely associated with distant metastasis and poor prognosis in patients with CRC, except for CNV of 91H. Multivariate analysis indicated that 91H expression was an independent prognostic indicator, as well as distant metastasis. Our in vitro data indicated that knockdown of 91H inhibited the proliferation, migration, and invasiveness of CRC cells.91H played an important role in the molecular etiology of CRC and might be regarded as a novel prognosis indicator in patients with CRC.

  15. Expression of Glut-1 and HK-II in Pancreatic Cancer and Their Impact on Prognosis and FDG Accumulation

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    Hai-Jing Yang

    2016-12-01

    Full Text Available OBJECTIVE: The purpose of this article is to analyze the expression of Glut-1 and HK-II, the association between their expression and 18F-FDG accumulation in pancreatic cancer. METHODS: Fifty patients with histologically proven pancreatic cancer were included in this preliminary study, all of whom received 18F-FDG PET/CT performance before surgery. Immunohistochemical staining of tumor tissue and adjacent normal tissue was performed for Glut-1 and HK-II. By combining proportions and intensity of immunochemical staining, we obtained the modified immunohistological scores for Glut-1 and HK-II respectively. The relationship between expression of Glut-1, HK-II and series of parameters was analyzed, i.e. clinicopathological characteristics, prognosis of patients and SUVmax of PET-CT. RESULTS: Compared with normal tissue, the Glut-1 and HK-II expression in pancreatic cancer tissue was significantly increased (P  .05. During the follow-up period, the survival curves of low Glut-1 group and high Glut-1 group were statistically different (P = .049. Multivariate analysis (Cox regression revealed that Glut-1 expression was not associated with mortality (P > .05. No statistical difference was found in the survival curves of negative HK-II group and positive HK-II group (P = .545. There was no correlation between 18F-FDG uptake and expression of Glut-1 and HK-II(P > .05. CONCLUSION: The Glut-1 and HK-II expression in pancreatic cancer tissue was significantly increased. There was no correlation between expression of Glut-1, HK-II and clinicopathological characteristics, prognosis and 18F-FDG uptake.

  16. Physical Inactivity And Low Fitness Deserve More Attention To Alter Cancer Risk And Prognosis

    Science.gov (United States)

    Sanchis-Gomar, Fabian; Lucia, Alejandro; Yvert, Thomas; Ruiz-Casado, Ana; Pareja-Galeano, Helios; Santos-Lozano, Alejandro; Fiuza-Luces, Carmen; Garatachea, Nuria; Lippi, Giuseppe; Bouchard, Claude; Berger, Nathan A.

    2015-01-01

    Sedentary lifestyle is associated with elevated cancer risk whereas regular physical activity (PA) and high cardiorespiratory fitness (CRF) have the opposite effect, with several biological mechanisms mediating such associations. There is a need for lifestyle interventions aimed at increasing the PA levels and CRF of the general population and particularly cancer survivors. Further, provocative data suggest a dose-dependent benefit of increasing levels of PA and/or CRF against cancer risk or mortality. Thus, current PA guidelines (≥150 min/week of moderate-to-vigorous PA) may not be sufficiently rigorous for preventing cancer nor for extending cancer survivorship. Research targeting this issue is urgently needed. Promoting regular PA along with monitoring indicators of CRF and adiposity may provide powerful strategies to prevent cancer in populations, help cancer patients more effectively deal with their disease and enhance secondary prevention programs in those who are affected by cancer. PMID:25416409

  17. Molecular markers in breast cancer: new tools in imaging and prognosis

    NARCIS (Netherlands)

    Vermeulen, J.F.

    2012-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared fluoresc

  18. Long-term prognosis of patients with lung cancer detected on low-dose chest computed tomography screening.

    Science.gov (United States)

    Nawa, Takeshi; Nakagawa, Tohru; Mizoue, Tetsuya; Kusano, Suzushi; Chonan, Tatsuya; Fukai, Shimao; Endo, Katsuyuki

    2012-02-01

    The effectiveness of lung cancer screening using low-dose chest computed tomography (CT) remains elusive. The present study examined the prognosis of patients with lung cancer detected on CT screening in Japanese men and women. Subjects were 210 patients with primary lung cancer identified on CT screening at two medical facilities in Hitachi, Japan, where a total of 61,914 CT screenings were performed among 25,385 screenees between 1998 and 2006. Prognostic status of these patients was sought by examining medical records at local hospitals, supplemented by vital status information from local government. The 5-year survival rate was estimated according to the characteristics of patients and lung nodule. A total of 203 (97%) patients underwent surgery. During a 5.7-year mean follow-up period, 19 patients died from lung cancer and 6 died from other causes. The estimated 5-year survival rate for all patients and for those on stage IA was 90% and 97%, respectively. Besides cancer stage, smoking and nodule appearance were independent predictors of a poor survival; multivariable-adjusted hazard ratio (95% confidence interval) was 4.7 (1.3, 16.5) for current and past smokers versus nonsmokers and 4.6 (1.6, 13.9) for solid nodule versus others. Even patients with solid shadow had a 5-year survival of 82% if the lesion was 20mm or less in size. Results suggest that lung cancers detected on CT screening are mostly curative. The impact of CT screening on mortality at community level needs to be clarified by monitoring lung cancer deaths.

  19. Histological Image Feature Mining Reveals Emergent Diagnostic Properties for Renal Cancer.

    Science.gov (United States)

    Kothari, Sonal; Phan, John H; Young, Andrew N; Wang, May D

    2011-11-01

    Computer-aided histological image classification systems are important for making objective and timely cancer diagnostic decisions. These systems use combinations of image features that quantify a variety of image properties. Because researchers tend to validate their diagnostic systems on specific cancer endpoints, it is difficult to predict which image features will perform well given a new cancer endpoint. In this paper, we define a comprehensive set of common image features (consisting of 12 distinct feature subsets) that quantify a variety of image properties. We use a data-mining approach to determine which feature subsets and image properties emerge as part of an "optimal" diagnostic model when applied to specific cancer endpoints. Our goal is to assess the performance of such comprehensive image feature sets for application to a wide variety of diagnostic problems. We perform this study on 12 endpoints including 6 renal tumor subtype endpoints and 6 renal cancer grade endpoints. Keywords-histology, image mining, computer-aided diagnosis.

  20. Hierarchy of Gene Expression as a Biomarker for Breast Cancer Prognosis

    Science.gov (United States)

    Chen, Man

    2013-03-01

    Cancer is a dedifferentiation of healthy cellular and genetic processes. At the same time, specific oncological pathways are activated in the cancer state. Cancer metastasis exposes cancer cells to a variety of microenvironments, in which physics of evolution suggests modularity is a relevant order parameter. We were thus motivated to examine the structure in gene and tissue networks of breast cancer patients. We studied the relation between metastasis and breast cancer network structure. We found that hierarchy of cancer networks distinguishes non-metastatic from metastatic patient populations. We also found that for cancer-associated genes, likelihood of metastasis is correlated with increased network hierarchy. Conversely for tissue networks using all gene data, reduced network structure is correlated with likelihood of metastasis. We suggest hierarchy of gene expression may be useful as a biomarker for breast cancer breast cancer metastasis and recurrence. For those patients with reduced structure, which is at least 5% of the patient population, this biomarker provides a strong signal for likelihood of cancer metastasis.

  1. A prognosis classifier for breast cancer based on conserved gene regulation between mammary gland development and tumorigenesis: a multiscale statistical model.

    Science.gov (United States)

    Tian, Yingpu; Chen, Baozhen; Guan, Pengfei; Kang, Yujia; Lu, Zhongxian

    2013-01-01

    Identification of novel cancer genes for molecular therapy and diagnosis is a current focus of breast cancer research. Although a few small gene sets were identified as prognosis classifiers, more powerful models are still needed for the definition of effective gene sets for the diagnosis and treatment guidance in breast cancer. In the present study, we have developed a novel statistical approach for systematic analysis of intrinsic correlations of gene expression between development and tumorigenesis in mammary gland. Based on this analysis, we constructed a predictive model for prognosis in breast cancer that may be useful for therapy decisions. We first defined developmentally associated genes from a mouse mammary gland epithelial gene expression database. Then, we found that the cancer modulated genes were enriched in this developmentally associated genes list. Furthermore, the developmentally associated genes had a specific expression profile, which associated with the molecular characteristics and histological grade of the tumor. These result suggested that the processes of mammary gland development and tumorigenesis share gene regulatory mechanisms. Then, the list of regulatory genes both on the developmental and tumorigenesis process was defined an 835-member prognosis classifier, which showed an exciting ability to predict clinical outcome of three groups of breast cancer patients (the predictive accuracy 64∼72%) with a robust prognosis prediction (hazard ratio 3.3∼3.8, higher than that of other clinical risk factors (around 2.0-2.8)). In conclusion, our results identified the conserved molecular mechanisms between mammary gland development and neoplasia, and provided a unique potential model for mining unknown cancer genes and predicting the clinical status of breast tumors. These findings also suggested that developmental roles of genes may be important criteria for selecting genes for prognosis prediction in breast cancer.

  2. miR-21 Expression in Pregnancy-Associated Breast Cancer: A Possible Marker of Poor Prognosis

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    Beatriz A. Walter, Gabriela Gómez-Macias, Vladimir A. Valera, Mark Sobel, Maria J. Merino

    2011-01-01

    Full Text Available Aims: microRNAs (miRNAs are a class of small noncoding RNAs that can act as key modulators in tumorigenesis-related genes. Specifically, it has been suggested that miR-21 overexpression plays a role in the development and progression of breast cancer. So far, the role of miRNAs in pregnancy-associated breast cancer (PABC has not been investigated.Methods and Results: We evaluated miR-21 expression by quantitative RT-PCR in 35 patients, 25 with PABC and 10 control breast cancer cases not pregnancy-associated with similar clinicopathological features. We then analyzed protein expression for PTEN, BCL2 and PDCD4 as miR-21 target genes by IHC, and finally correlated the results with patients' clinicopathological features.Significant overexpression of miR-21 in PABC tumors compared to normal adjacent tissue was found. Overexpression of miR-21 was frequently found in high grade tumors with loss of hormone receptor expression and was significantly associated with positive lymph nodes (p=0.025. In PABC patients, PTEN, BCL2 and PDCD4 target protein expression was decreased in 80%, 76% and 40% respectively.Conclusion: Our study supports the involvement of miR-21 in breast cancer progression and metastasis formation in PABC implying a role of this miRNA as a marker for poor prognosis in PABC patients.

  3. Analysis of the Relationship between Expressions of TF and MMP-9 and Prognosis of Breast Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    Jianxin Zhao; Zengmao Lin; Hongwei Yao; Yuanlian Wan

    2008-01-01

    OBJECTIVE To investigate expression of the tissue factor(TF) and matrix metalloproteinase-9 (MMP-9) in breast cancers,and to assess their expression in relation to possible prognostic significance.METHODS The expression of TF and MMP-9 in 71 breast cancer specimens were determined by EnVision immunohistochemistry,and the positive expressions related to the patient clinical outcome.RESULTS Positive rates of TF and MMP-9 staining were respectively 43.7% and 42.3%. K-M monofactorial analysis showed that the 5-year survival rate of the patients with a positive expression of TF and MMP-9 was lower than those with negative expression (P < 0.05). However, the COX multifactorial analysis indicated that TNM staging and lymph node metastasis were the prognostic factors for breast cancer patients, and that TF and MMP-9 could not be used as the independent prognostic factors (P> 0.05).CONCLUSION The positive rates of TF and MMP-9 were considerably high in breast cancers, which could provide useful information for patient prognosis.

  4. Monocarboxylate transporter 4 (MCT4 and CD147 overexpression is associated with poor prognosis in prostate cancer

    Directory of Open Access Journals (Sweden)

    Pereira Helena

    2011-07-01

    Full Text Available Abstract Background Monocarboxylate transporters (MCTs are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown. The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma. Methods Prostate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n = 171, adjacent non-neoplastic tissues (n = 135, PIN lesions (n = 40 and normal prostatic tissue (n = 14. Protein expression was correlated with patients' clinicopathologic characteristics. Results In the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence. Conclusions Our data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and

  5. Prognosis and treatment of brain metastases in breast cancer%乳腺癌脑转移的预后及治疗的研究进展

    Institute of Scientific and Technical Information of China (English)

    钟颖

    2012-01-01

    This paper reviews the recent advances in the clinical research on breast cancer brain metastases. The main contents include the morbidity, risk factors, prognosis and treatment of this condition, among which the prognosis assessment system for breast cancer brain metastases is highlighted.%笔者就近年来乳腺癌脑转移的临床研究状况进行综述.主要包括乳腺癌脑转移的发病率、危险因素、预后及治疗.其中重点介绍乳腺癌脑转移的预后评价体系.

  6. 76 FR 65518 - Prospective Grant of Exclusive License: The Development of a Companion Diagnostic Kit for...

    Science.gov (United States)

    2011-10-21

    ... effect of an anti- cancer agent in the treatment of kidney, lung, and breast cancers that includes at...: This invention concerns methods for the prognosis for a subject with cancer and to evaluate therapeutic... a Companion Diagnostic Kit for Predicting Therapeutic Efficacy of Anti- Cancer Agents...

  7. Over-expression of Metastasis-associated in Colon Cancer-1 (MACC1)Associates with Better Prognosis of Gastric Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    Shao-hua Ge; Jia-fu Ji; Xiao-jiang Wu; Xiao-hong Wang; Xiao-fang Xing; Lian-hai Zhang; Yu-bing Zhu; Hong Du; Bin Dong; Ying Hu

    2011-01-01

    Objective: The aim of this study was to detect metastasis-associated in colon cancer-1 (MACC1) expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods: The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results: The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa (P<0.001). MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage Ⅲ carcinoma (P=0.032). Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 (P=0.057). Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer (P=0.002), but P53 expression was not associated with MACC1 expression. Conclusion: MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.

  8. Association of FGFR4 genetic polymorphisms with prostate cancer risk and prognosis.

    Science.gov (United States)

    FitzGerald, L M; Karlins, E; Karyadi, D M; Kwon, E M; Koopmeiners, J S; Stanford, J L; Ostrander, E A

    2009-01-01

    The fibroblast growth factor receptor 4 (FGFR4) is thought to be involved in many critical cellular processes and has been associated with prostate cancer risk. Four single nucleotide polymorphisms (SNPs) within or near FGFR4 were analyzed in a population-based study of 1458 prostate cancer patients and 1352 age-matched controls. We found no evidence to suggest that any of the FGFR4 SNP genotypes were associated with prostate cancer risk or with disease aggressiveness, Gleason score or stage. A weak association was seen between rs351855 and prostate cancer-specific mortality. Subset analysis of cases that had undergone radical prostatectomy revealed an association between rs351855 and prostate cancer risk. Although our results confirm an association between FGFR4 and prostate cancer risk in radical prostatectomy cases, they suggest that the role of FGFR4 in disease risk and outcomes at a population-based level appears to be minor.

  9. Association of telomerase reverse transcriptase promoter mutations with clinicopathological features and prognosis of thyroid cancer: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Su X

    2016-11-01

    Full Text Available Xingyun Su,1 Xiaoxia Jiang,1 Weibin Wang,1 Haiyong Wang,1 Xin Xu,2 Aihui Lin,1 Xiaodong Teng,3 Huiling Wu,4 Lisong Teng1 1Department of Surgical Oncology, 2Department of Medical Oncology, 3Department of Pathology, 4Department of Plastic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: The clinicopathological and prognostic significance of telomerase reverse transcriptase (TERT promoter mutations have been widely investigated in thyroid cancer; however, the results are still discrepant. Systematic searches were performed in PubMed, Web of Science, Scopus, Ovid, and the Cochran Library databases for relevant articles prior to April 2016. Mutation rates were synthesized by R statistical software. The odds ratio or standardized mean difference with 95% confidence interval was pooled by Stata. A total of 22 studies with 4,907 cases were included in this meta-analysis. TERT promoter mutations tended to present in aggressive histological types including poorly differentiated thyroid cancer (33.37%, anaplastic thyroid cancer (38.69%, and tall-cell variant papillary thyroid cancer (30.23%. These promoter mutations were likely to exist in older patients and males and were well associated with larger tumor size, extrathyroidal extension, vascular invasion, lymph node metastasis, distant metastasis, advanced tumor stage, disease recurrence/persistence, and mortality. In addition, TERT promoter mutations (especially C228T tended to coexist with BRAFV600E mutation, which indicated more aggressive tumor behavior. Therefore, TERT promoter mutations may be promising biomarkers for early diagnosis, risk stratification, prognostic prediction, and management of thyroid cancer. Keywords: TERT promoter mutations, thyroid cancer, clinicopathological features, prognosis, BRAFV600E mutation

  10. Correlation between Protein Expression of PTEN in Human Pancreatic Cancer and the Proliferation, Infiltration, Metastasis and Prognosis

    Institute of Scientific and Technical Information of China (English)

    TAO Jing; XIONG Jiongxin; LI Tao; YANG Zhiyong; LI Xiaohui; LI Kai; WU Heshui; WANG Chunyou

    2006-01-01

    In order to investigate the correlation between protein expression of PTEN and the proliferation, infiltration, metastasis and prognosis in pancreatic cancer, immunohistochemical SP method was used to examine the protein expression of PTEN, PCNA, MVD, MMP-2, MMP-9 and TUNEL method to detect the levels of apoptosis of pancreatic cells in 41 pancreatic head cancers from regional pancreatectomy (RP) and 10 normal pancreatic tissues. The results showed that among 41 cases of pancreatic cancers, the positive staining of PTNE (39.02 %) was significantly weaker than that in normal pancreatic tissues (P<0.05). The levels of PCNA labeling index (LI), apoptotic index(AI), microvessel density (MVD), MMP-2 LI and MMP-9 LI were decreased gradually with the increase of the expression intensity of PTEN, and there was a significant difference in the above parameters among the patients having different expression levels of PTEN (P<0.01 or P<0.05). There was a negative correlation between the expression of PTEN and PCNA LI, MVD, MMP-2 LI,MMP-9 LI, and a positive correlation between AI and the expression of PTEN. The expression intensity of PTEN was correlated with the postoperative survival of the patients with pancreatic cancer(x2=22.3400, P<0.0001, RR=2.030). It was suggested that the expression levels of PTEN protein were closely related with proliferation, infiltration and metastasis in human pancreatic cancer, and the expression of PTEN protein was one of the prognostic factors for pancreatic cancer following RP.

  11. Transcriptional coactivator CBP upregulates hTERT expression and tumor growth and predicts poor prognosis in human lung cancers.

    Science.gov (United States)

    Guo, Wei; Lu, Jianjun; Dai, Meng; Wu, Taihua; Yu, Zhenlong; Wang, Jingshu; Chen, Wangbing; Shi, Dingbo; Yu, Wendan; Xiao, Yao; Yi, Canhui; Tang, Zhipeng; Xu, Tingting; Xiao, Xiangsheng; Yuan, Yuhui; Liu, Quentin; Du, Guangwei; Deng, Wuguo

    2014-10-15

    Upregulated expression and activation of human telomerase reverse transcriptase (hTERT) is a hallmarker of lung tumorigenesis. However, the mechanism underlying the aberrant hTERT activity in lung cancer cells remains poorly understood. In this study, we found the transcriptional co-activator CBP as a new hTERT promoter-binding protein that regulated hTERT expression and tumor growth in lung adenocarcinoma cells using a biotin-streptavidin-bead pulldown technique. Chromatin immunoprecipitation assay verified the immortalized cell and tumor cell-specific binding of CBP on hTERT promoter. Overexpression of exogenous CBP upregulated the expression of the hTERT promoter-driven luciferase and endogenous hTERT protein in lung cancer cells. Conversely, inhibition of CBP by CBP-specific siRNA or its chemical inhibitor repressed the expression of hTERT promoter-driven luciferase and endogenous hTERT protein as well as telomerase activity. Moreover, inhibition of CBP expression or activity also significantly reduced the proliferation of lung cancer cells in vitro and tumor growth in an xenograft mouse model in vivo. Immunohistochemical analysis of tissue microarrays of lung cancers revealed a positive correlation between CBP and hTERT. Importantly, the patients with high CBP and hTERT expression had a significantly shorter overall survival. Furthermore, CBP was found to interact with and acetylate transactivator Sp1 in lung cancer cells. Inhibition of CBP by CBP-specific siRNA or its chemical inhibitor significantly inhibited Sp1 acetylation and its binding to the hTERT promoter. Collectively, our results indicate that CBP contributes to the upregulation of hTERT expression and tumor growth, and overexpression of CBP predicts poor prognosis in human lung cancers.

  12. CSNK1E/CTNNB1 Are Synthetic Lethal To TP53 in Colorectal Cancer and Are Markers for Prognosis

    Directory of Open Access Journals (Sweden)

    Khong-Loon Tiong

    2014-05-01

    Full Text Available Two genes are called synthetic lethal (SL if their simultaneous mutations lead to cell death, but each individual mutation does not. Targeting SL partners of mutated cancer genes can kill cancer cells specifically, but leave normal cells intact. We present an integrated approach to uncovering SL pairs in colorectal cancer (CRC. Screening verified SL pairs using microarray gene expression data of cancerous and normal tissues, we first identified potential functionally relevant (simultaneously differentially expressed gene pairs. From the top-ranked pairs, ~20 genes were chosen for immunohistochemistry (IHC staining in 171 CRC patients. To find novel SL pairs, all 169 combined pairs from the individual IHC were synergistically correlated to five clinicopathological features, e.g. overall survival. Of the 11 predicted SL pairs, MSH2-POLB and CSNK1E-MYC were consistent with literature, and we validated the top two pairs, CSNK1E-TP53 and CTNNB1-TP53 using RNAi knockdown and small molecule inhibitors of CSNK1E in isogenic HCT-116 and RKO cells. Furthermore, synthetic lethality of CSNK1E and TP53 was verified in mouse model. Importantly, multivariate analysis revealed that CSNK1E-P53, CTNNB1-P53, MSH2-RB1, and BRCA1-WNT5A were independent prognosis markers from stage, with CSNK1E-P53 applicable to early-stage and the remaining three throughout all stages. Our findings suggest that CSNK1E is a promising target for TP53-mutant CRC patients which constitute ~40% to 50% of patients, while to date safety regarding inhibition of TP53 is controversial. Thus the integrated approach is useful in finding novel SL pairs for cancer therapeutics, and it is readily accessible and applicable to other cancers.

  13. Treatment and prognosis of cervical cancer associated with pregnancy: analysis of 20 cases from a Chinese tumor institution.

    Science.gov (United States)

    Zhang, Xiang; Gao, Yong-liang; Yang, Yue

    2015-05-01

    This study was designed to investigate the therapeutic approaches and prognosis for cervical cancer associated with pregnancy. Clinical information, therapeutic strategies, and follow-up results of 20 patients with cervical cancer associated with pregnancy from Jan. 2000 to June 2009 in the Zhejiang Cancer Hospital were retrospectively analyzed. The International Federation of Gynecology and Obstetrics (FIGO) stages were: in situ (n=1), stage IA1 (n=1), stage IB1 (n=5), stage IB2 (n=1), stage IIA (n=8), stage IIB (n=3), and stage IIIB (n=1). Eight patients were in the first trimester of pregnancy, four in the second, two in the third, and six at postpartum when diagnosed. The therapeutic strategies were either single or combined modalities, including surgery, radiotherapy, and chemotherapy. Fourteen patients survived, five patients died (four of remote metastasis and one of uremia), and one patient was lost to follow-up. One newborn from a patient at stage IIA carcinoma in the third trimester with postponed therapy six weeks after diagnosis survived. Retarded fetal growth was observed in one patient receiving neoadjuvant chemotherapy and cesarean section. Out of the six postpartum patients, three underwent cesarean section and survived, whereas only one out of the three who underwent vaginal delivery survived. The remaining two died of remote metastasis. Therefore, personalized treatment is necessary for cervical cancer associated with pregnancy. Cervical cancer patients in the third trimester of pregnancy can continue the pregnancy for a short period of time. There may be potential risk for the fetus by chemotherapy during pregnancy. Cesarean section is the preferred mode of delivery for pregnant cervical cancer patients.

  14. CD147 Expression in Human Gastric Cancer Is Associated with Tumor Recurrence and Prognosis

    OpenAIRE

    Dake Chu; Shaojun Zhu; Jipeng Li; Gang Ji; Weizhong Wang; Guosheng Wu; Jianyong Zheng

    2014-01-01

    CD147 is correlated with tumor aggressiveness in various human malignancies. Here, we investigated CD147 protein expression in 223 patients with gastric cancer by immunohistochemistry and analyzed its association with disease-free and overall survival. CD147 was increased in gastric cancer compared to normal tissues. Additionally, CD147 expression was associated with gastric cancer invasion, metastasis and TNM stage, whereas it was not related to age, sex, differentiation status, tumor site o...

  15. Transient Fourier holography with bacteriorhodopsin films for breast cancer diagnostics

    Science.gov (United States)

    Rao, Devulapalli; Kothapalli, Sri-Rajasekar; Wu, Pengfei; Yelleswarapu, Chandra

    X-ray mammography is the current gold standard for breast cancer screening. Microcalcifications and other features which are helpful to the radiologist for early diagnostics are often buried in the noise generated by the surrounding dense tissue. So image processing techniques are required to enhance these important features to improve the sensitivity of detection. An innovative technique is demonstrated for recording a hologram of the mammogram. It is recorded on a thin polymer film of Bacteriorhodopsin (bR) as photo induced isomerization grating containing the interference pattern between the object beam containing the Fourier spatial frequency components of the mammogram and a reference beam. The hologram contains all the enhanced features of the mammogram. A significant innovation of the technique is that the enhanced components in the processed image can be viewed by the radiologist in time scale. A technician can record the movie and when the radiologist looks at the movie at his convenience, freezing the frame as and when desired, he would see the microcalcifications as the brightest and last long in time. He would also observe lesions with intensity decreasing as their size increases. The same bR film can be used repeatedly for recording holograms with different mammograms. The technique is versatile and a different frequency band can be chosen to be optimized by changing the reference beam intensity. The experimental arrangement can be used for mammograms in screen film or digital format.

  16. Nuclear physics applications in diagnostics and cancer therapy

    CERN Document Server

    Amaldi, Ugo

    2005-01-01

    Only 1% of the 18,000 world accelerators are devoted to the production of radioisotopes for medical diagnostics. In fact at present about 85% of all the medical examinations use /sup 99m/Tc produced in nuclear reactors. But the development of Positron Emission Tomography and of its combination with Computer Tomography will boost the hospital use of cyclotrons. Much more general is the use of electron linacs in cancer therapy about 40% of the world accelerators are used for this so called "conventional" radiotherapy. In the developed countries every 10 million inhabitants about 20,000 oncological patients are irradiated every year with high-energy photons (called X-rays by radiotherapists) produced by electron linacs. Much less used is "hadrontherapy", the radiotherapy technique that employs protons, neutrons or carbon ions. Protons and ions are 'heavy' charged particles: they assure a more 'conformal' treatment than X-rays and thus spare better the surrounding healthy tissues allowing a larger dose and thus a...

  17. Overexpression of Mcl-1L Splice Variant Is Associated with Poor Prognosis and Chemoresistance in Oral Cancers

    Science.gov (United States)

    Palve, Vinayak; Mallick, Sanchita; Ghaisas, Gauri; Kannan, Sadhana; Teni, Tanuja

    2014-01-01

    Background Altered expression of Mcl-1, an anti-apoptotic member of the Bcl-2 family, has been linked to the progression and outcome of a variety of malignancies. We have previously reported the overexpression of Mcl-1 protein in human oral cancers. The present study aimed to evaluate the clinicopathological significance of the expression of three known Mcl-1 isoforms in oral tumors and the effect of targeting Mcl-1L isoform on chemosensitivity of oral cancer cells. Methods The expression of Mcl-1 isoforms- Mcl-1L, Mcl-1S & Mcl-1ES was analyzed in 130 paired oral tumors and 9 oral cell lines using quantitative real-time PCR & protein by western blotting. The Mcl-1 mRNA levels were correlated with clinicopathological parameters and outcome of oral cancer patients. The effect of Mcl-1L shRNA or Obatoclax (a small molecule Mcl-1 inhibitor), in combination with Cisplatin on chemosensitivity of oral cancer cells was also assessed. Results Anti-apoptotic Mcl-1L was predominantly expressed, over low or undetectable pro-apoptotic Mcl-1S and Mcl-1ES isoforms. The Mcl-1L transcripts were significantly overexpressed in all cancer cell lines and in 64% oral tumors versus adjacent normals (P<0.02). In oral cancer patients, high Mcl-1L expression was significantly associated with node positivity (P = 0.021), advanced tumor size (P = 0.013) and poor overall survival (P = 0.002). Multivariate analysis indicated Mcl-1L to be an independent prognostic factor for oral cancers (P = 0.037). Mcl-1L shRNA knockdown or its inhibition by Obatoclax in combination with Cisplatin synergistically reduced viability and growth of oral cancer cells than either treatment alone. Conclusion Our studies suggest that overexpression of Mcl-1L is associated with poor prognosis and chemoresistance in oral cancers. Mcl-1L is an independent prognostic factor and a potential therapeutic target in oral cancers. PMID:25409302

  18. Altered glycometabolism affects both clinical features and prognosis of triple-negative and neoadjuvant chemotherapy-treated breast cancer.

    Science.gov (United States)

    Dong, Tieying; Kang, Xinmei; Liu, Zhaoliang; Zhao, Shu; Ma, Wenjie; Xuan, Qijia; Liu, Hang; Wang, Zhipeng; Zhang, Qingyuan

    2016-06-01

    Glycometabolism is a distinctive aspect of energy metabolism in breast cancer, and key glycometabolism enzymes/pathways (glycolysis, hexosamine biosynthetic pathway, and pentose phosphate pathway) may directly or indirectly affect the clinical features. In this study, we analyzed the particular correlation between the altered glycometabolism and clinical features of breast cancer to instruct research and clinical treatment. Tissue microarrays containing 189 hollow needle aspiration samples and 295 triple-negative breast cancer tissues were used to test the expression of M2 isoform of pyruvate kinase (PKM2), glutamine-fructose-6-phosphate transaminase 1 (GFPT1), glucose-6-phosphate dehydrogenase (G6PD), and p53 by immunohistochemistry and the intensity of these glycometabolism-related protein was evaluated. Chi-square test, Kaplan-Meier estimates, and Cox proportional hazards model were used to analyze the relationship between the expression of these factors and major clinical features. PKM2, GFPT1, and G6PD affect the pathologic complete response rate of neoadjuvant chemotherapy patients in different ways; pyruvate kinase muscle isozyme 2 (PKM2) and G6PD are closely associated with the molecular subtypes, whereas GFPT1 is correlated with cancer size. All these three factors as well as p53 have impacts on the progression-free survival and overall survival of triple-negative breast cancer patients. Cancer size shows significant association with PKM2 and GFPT1 expression, while the pN stage and grade are associated with PKM2 and G6PD expression. Our study support that clinical characteristics are reflections of specific glycometabolism pathways, so their relationships may shed light on the orientation of research or clinical treatment. The expression of PKM2, GFPT1, and G6PD are hazardous factors for prognosis: high expression of these proteins predict worse progression-free survival and overall survival in triple-negative breast cancer, as well as worse pathologic

  19. Decreased expression of the ARID1A gene is associated with poor prognosis in primary gastric cancer.

    Directory of Open Access Journals (Sweden)

    Dan-dan Wang

    Full Text Available BACKGROUND: The ARID1A gene encodes adenine-thymine (AT-rich interactive domain-containing protein 1A, which participates in chromatin remodeling. ARID1A has been showed to function as a tumor suppressor in various cancer types. In the current study, we investigated the expression and prognosis value of ARID1A in primary gastric cancer. Meanwhile, the biological role of ARID1A was further investigated using cell model in vitro. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of ARID1A gene in primary gastric cancer pathogenesis, real-time quantitative PCR and western blotting were used to examine the ARID1A expression in paired cancerous and noncancerous tissues. Results revealed decreased ARID1A mRNA (P = 0.0029 and protein (P = 0.0015 expression in most tumor-bearing tissues compared with the matched adjacent non-tumor tissues, and in gastric cancer cell lines. To further investigate the clinicopathological and prognostic roles of ARID1A expression, we performed immunohistochemical analyses of the 224 paraffin-embedded gastric cancer tissue blocks. Data revealed that the loss of ARID1A expression was significantly correlated with T stage (P = 0.001 and grade (P = 0.006. Consistent with these results, we found that loss of ARID1A expression was significantly correlated with poor survival in gastric cancer patients (P = 0.003. Cox regression analyses showed that ARID1A expression was an independent predictor of overall survival (P = 0.029. Furthermore, the functions of ARID1A in the proliferation and colony formation of gastric cell lines were analyzed by transfecting cells with full-length ARID1A expression vector or siRNA targeting ARID1A. Restoring ARID1A expression in gastric cancer cells significantly inhibited cell proliferation and colony formation. Silencing ARID1A expression in gastric epithelial cell line significantly enhanced cell growth rate. CONCLUSIONS/SIGNIFICANCE: Our data suggest that ARID1A may play an important role

  20. Prognosis and staging of superficial endobronchial lung cancer: the impact of invasion depth, tumor diameter, and coexistent pneumonitis or atelectasis

    Institute of Scientific and Technical Information of China (English)

    CHEN Chang; ZHENG Hui; GAO Wen; ZHOU Ying; JIANG Sen; SUEN Hon-chi

    2010-01-01

    Background There are few reports discussing the surgical pathological characteristics of superficial endobronchial lung cancer (SELC) defined as cancer growth limited to the bronchial wall. Its prognosis and corresponding TNM staging have not been fully clarified. Little is known as to whether T status is impacted by the existence of associated atelectasis or pneumonia (which might be controversial, indicating either T1 or T2), and circumstantial invasion depth.Methods Between 1988 and 2007, 81 out of 8817 surgically treated patients met SELC criteria; there was no detectable invasion beyond the bronchial wall. A retrospective review was performed and follow-up information was collected.Results The overall five-year survival rate of 81 patients was 85.6%; for NOM0 (n=67), N1M0 (n=7) and N2M0 (n=7)patients, they were 89.3%, 75.0% and 60.0%, respectively. Intraluminal tumor size measured from 0.4 to 3.0 cm;obstructive atelectasis or pneumonia was noted in 14 patients. The presence of tumor-associated obstructive atelectasis or pneumonia did not have a significant impact upon prognosis (P=0.96), nor did the greatest diameter of the tumor (P=0.70). Histology showed carcinoma in situ (level one) in 13 cases; invasion of the submucosal layer (level two) in 12,involvement of the muscular layer (level three) in 20, invasion into the space between the muscular layer and cartilage (level four) in 21, and bronchial cartilage infiltration in 15 (level five). In cases without lymphnode metastases, five-year survival was 100% for the first three levels and 84.0% and 61.3% for the level four and level five.Conclusions Relative to TNM-based prognostic data, superficial endobronchial lung cancer exhibits increased five-year survival rates, and therefore should be placed at the forefront among tumors in the T1 class, regardless of tumor size or the presence of secondary obstructive atelectasis or pneumonia. Lymphnode metastasis is associated with a worse prognosis. Survival is

  1. Malignant melanoma of the urethra: a rare histologic subdivision of vulvar cancer with a poor prognosis

    OpenAIRE

    Veronika Günther; I. Alkatout; C. Lez; Altarac, S.; Fures, R.; Cupic, H.; Persec, Z.; Hrgovic, Z.; Mundhenke, C

    2012-01-01

    Malignant melanoma of the urethra is a rare tumour that is difficult to diagnose and treat, resulting in a poor prognosis. In this paper, we present the case of a 65-year-old woman who was referred to a gynaecologist because of a urethral mass that mimicked a caruncle. The tumour was removed by local excision, and a pathological analysis revealed a malignant melanoma. Distal urethrectomy was performed after three months with no evidence of residual tumour. There was no evidence of disease at ...

  2. Macrophage Inhibitory Cytokine-1 (MIC-1 as A Biomarker for Diagnosis 
and Prognosis of Stage I-II Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuning LIU

    2016-04-01

    Full Text Available Background and objective Increased macrophage inhibitory cytokine-1 (MIC-1, member of transforming growth factor-β (TGF-β superfamily, was found in patients serum with epithelial tumors. Therefore, our aim was to delineate the diagnostic and prognostic value of serum MIC-1 in patients with stage I-II non-small cell lung cancer (NSCLC. Methods A total of 152 consecutive patients with stage I–II NSCLC were prospectively enrolled and underwent follow up after total resection of tumor. Serum MIC-1 level was detected in lung cancer patients by ELISA, 48 benign pulmonary disease patients and 105 healthy controls, and was correlated with clinical features and prognosis of patients. Results The level of MIC-1 of NSCLC patients was significantly higher than that of controls (P<0.001 and benign pulmonary disease patients (P<0.001. A threshold of 1,000 pg/mL could be used to diagnose early-stage NSCLC with 70.4% sensitivity and 99.0% specificity. The level of MIC-1 was associated with elder age (P=0.001, female (P=0.03 and T2 (P=0.022. A threshold of 1,465 pg/mL could identify patients with early poor outcome with 72.2% sensitivity and 66.1% specificity. The overall 3-year survival rate in patients with high level of MIC-1 (≥1,465 pg/mL was significantly lower than that of patients with low MIC-1 level (77.6% vs 94.8%. Multivariable Cox regression revealed that a high level of MIC-1 was an independent risk factor for compromised overall survival (HR=3.37, 95%CI: 1.09-10.42, P=0.035. Conclusion High level of serum MIC-1 could be served as a potential biomarker for diagnosis and poorer outcome in patients with early-stage NSCLC.

  3. Nasal metastases from renal cell carcinoma are associated with Memorial Sloan-Kettering Cancer Center poor-prognosis classification

    Institute of Scientific and Technical Information of China (English)

    Caroline Victoria Choong; Tiffany Tang; Wen Yee Chay; Christopher Goh; Miah Hiang Tay; Nor Azhari Mohd Zam; Puay Hoon Tan; Min-Han Tan

    2011-01-01

    Unusual sites of metastases are recognized in patients with renai cell carcinoma (RCC). However, the prognostic implications of these sites are not well understood. We used the Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification for metastatic RCC to evaluate 912 consecutive patients with RCC managed at the Singapore General Hospital between 1990 and 2009. Among these patients, 301 had metastases either at diagnosis or during the course of illness. Nasal metastases, all arising from clear cell RCC, were identified histologically in 4 patients (1.3% of those with metastasis). All 4 patients were classified as MSKCC poor prognosis by current risk criteria. Nasal metastases were significantly associated with lung and bone metastases. The frequency of nasal metastases in patients with metastatic RCC is about 1%, occurring predominantly in patients with clear cell RCC. Nasal metastases are associated with poor prognosis as estimated by the MSKCC risk classification, with attendant implications for selection of targeted therapy, and are usually associated with multi-organ dissemination, including concurrent lung and bone involvement.

  4. Genomic gain of the PRL-3 gene may represent poor prognosis of primary colorectal cancer, and associate with liver metastasis.

    Science.gov (United States)

    Nakayama, N; Yamashita, K; Tanaka, T; Kawamata, H; Ooki, A; Sato, T; Nakamura, T; Watanabe, M

    2016-01-01

    PRL-3 genomic copy number is increased in colorectal cancer (CRC), and PRL-3 expression is closely associated with lymph node and liver metastasis of CRC. However, the clinical significance of PRL-3 genomic gain for CRC remains obscure. Here, PRL-3 genomic status in 109 primary CRC tumors and in 44 CRC tumors that had metastasized to the liver, was quantified using real time PCR. Association of PRL-3 genomic status with clinicopathological factors and prognosis was assessed in detail. PRL-3 genomic gain was identified in 31 primary CRC (27.4 %) and was more frequently seen in stage III than in stage II (p = 0.025). Among the clinicopathological factors assessed, PRL-3 genomic gain was significantly associated with poorly differentiated histology (p = 0.0039). Moreover, CRC patients with PRL-3 genomic gain exhibited poorer prognosis than those with no gain in stage II-IV CRC (p = 0.017). PRL-3 genomic gain was identified in 18 (41 %) of the liver metastasis tumors, and this frequency of gain was significantly increased as compared to that of the corresponding primary CRCs (11 %) (p = 0.001). Our findings suggested that PRL-3 genomic gain may represent an aggressive phenotype of primary CRC, and may associate with liver metastasis.

  5. Malignant mesothelioma and asbestos-related lung cancer: diagnosis, prognosis and burden

    NARCIS (Netherlands)

    van der Bij, S.

    2012-01-01

    The negative health-related consequences of the use of asbestos have become very clear and widely recognized. This thesis focused on the most frequent asbestos induced cancers: mesothelioma and lung cancer. Mesothelioma A confirmed diagnosis of malignant mesothelioma is important to ensure proper me

  6. The role of depression and neuroimmune axis in the prognosis of cancer patients.

    Science.gov (United States)

    Aldea, Mihaela; Craciun, Lucian; Tomuleasa, Ciprian; Crivii, Carmen

    2014-01-01

    New exciting research in psycho-oncology has shed light on the mechanisms by which biobehavioral signaling in cancer interplays with the neuroimmune axis, as well as on the progression and mortality of cancer patients. Cancer and cancer therapy can collectively result in inflammation and cytokine production, which have been associated with occurrence of depression. Conversely, depression supports a chronic activated hypothalamopituitary-adrenal axis (HPA) and further determines cortisol and adrenal disturbances, as well as immune dysfunction and increased cytokine production. Through these processes, depression is associated with a worse cancer outcome. New treatment strategies which counter the aberrant pathways between depression and cancer, such as drugs that target cytokines, pro-inflammatory signaling, neuroendocrine, metabolic pathways and sympathetic activation, might disrupt important vehicles for cancer progression. In this review, we emphasize the major pathways that link inflammation, depression and immunity, in order to highlight potential therapeutic strategies which may become of paramount importance to those depressed individuals with cancer that have a higher risk for developing a more aggressive disease.

  7. Metformin Impacts the Prognosis of Cancer Patients with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Aldea Mihaela

    2014-06-01

    Full Text Available A long term complication of diabetes is the increased susceptibility to develop various malignancies and also to negatively impact the progression of cancer. However, metformin, widely used in the treatment of type II diabetes, seems to impact the outcome of several types of cancer, in terms of overall survival, disease-free survival or rates of recurrences. Metformin might impact cancer through various mechanisms, including reduced insulin and insulin-like growth factor-mediated signaling as well as modulation of inflammation and adipokine activity. This review presents the clinical studies that deal with the prognostic impact of metformin on cancer and discuss the possible reasons for why certain types of cancer are affected by anti-diabetic therapy. In addition, it tries to integrate the preclinical and clinical evidence into guidelines for future prospective clinical studies

  8. Acid ceramidase (AC)--a key enzyme of sphingolipid metabolism--correlates with better prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Hanker, Lars Christian; Karn, Thomas; Holtrich, Uwe; Gätje, Regine; Rody, Achim; Heinrich, Tomas; Ruckhäberle, Eugen; Engels, Knut

    2013-05-01

    Acid ceramidase (AC), a key enzyme of sphingolipid metabolism, seems to play an important role in cancer progression. The objective of this study was to explore the expression of AC in ovarian cancer and its impact on prognosis. Expression analysis of AC in n=112 ovarian cancer patients was performed by immunohistochemical analysis of primary paraffin-embedded tumor samples. The results were scored on the basis of the staining intensity and percentage of positive tumor cells, resulting in an immunoreactive score from 0 to 12. These results were correlated to clinical and pathologic characteristics and survival. AC expression correlated significantly only with FIGO stage (0.047). In serous carcinoma, low level of AC was independently associated with reduced progression-free survival and overall survival of 12.0 mo [95% confidence interval (CI), 5.78-18.23] versus 18.1 mo (95% CI, 11.61-24.59; P=0.008) and 35.7 mo (95% CI, 22.24-47.16) versus 58.7 mo (95% CI, 36.48-80.91; P=0.032), respectively. In multivariate analysis, AC presents as an independent prognostic factor for progression-free survival (hazard ratio 1.88; 95% CI, 1.13-3.11; P=0.015). AC is a prognostic factor in epithelial ovarian cancer. Low AC expression can be associated with tumor progression in carcinoma of the ovaries. These results are in contrast to the concept of AC as a promoter for cancer progression. Nevertheless, they are supported by the lately discovered tumor-suppressing function of sphingosine, the enzymatic product of AC.

  9. Overexpression of RBBP6, alone or combined with mutant TP53, is predictive of poor prognosis in colon cancer.

    Directory of Open Access Journals (Sweden)

    Jian Chen

    Full Text Available Retinoblastoma binding protein 6 (RBBP6 plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of RBBP6 expression in colon cancer is unknown; in particular, the prognostic value of RBBP6 combined with TP53 expression has not been explored. Therefore, quantitative real-time PCR and western blot analyses were performed to detect RBBP6 expression in colon cancer tissues. RBBP6 and TP53 expression were assessed by immunohistochemistry in a tissue microarray format, in which the primary colon cancer tissue was paired with noncancerous tissue. Tissue specimens were obtained from 203 patients. We found that RBBP6 was overexpressed in colon tumorous tissues and was significantly associated with clinical stage, depth of tumor invasion, lymph node metastasis (LNM, distant metastasis, and histologic grade. Further studies revealed that a corresponding correlation between RBBP6 overexpression and mutant TP53 was evident in colon cancer (r = 0.450; P<0.001. RBBP6 expression was an independent prognostic factor for overall survival (OS and disease free survival (DFS. Interestingly, patients with tumors that had both RBBP6 overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P<0.001. Multivariate analysis showed that patients with LNM and patients with both RBBP6- and TP53-positive tumors had extremely poor OS (HR 6.75; 95% CI 2.63-17.35; P<0.001 and DFS (HR 8.08; 95% CI 2.80-23.30; P<0.001. These clinical findings indicate that the assessment of both RBBP6 and mutant TP53 expression will be helpful in predicting colon cancer prognosis.

  10. Heterogeneous nuclear ribonucleoprotein K is overexpressed and associated with poor prognosis in gastric cancer.

    Science.gov (United States)

    Yang, Ruirui; Zeng, Ying; Xu, Haifan; Chen, Zhuo; Xiang, Mengqin; Fu, Yun; Yin, Yufang; Zhong, Jing; Zeng, Min; Wang, Peihua; You, Qin; Zeng, Xi

    2016-08-01

    Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is one of the major pre-mRNA-binding proteins, that is involved in translational modifications. In our previous studies, we found that hnRNP K is associated with human gastric cancer. The protein levels of hnRNP K were detected in cell lines and tissue microarrays. The correlation between hnRNP K expression and patient survival rate was evaluated by Kaplan-Meier survival analysis. In addition, we also detected hnRNP K expression in preoperative and postoperative serum samples from patients with gastric cancer, and serum samples from healthy volunteers. We found that hnRNP K was overexpressed in the gastric cancer cell lines. The levels of hnRNP K were significantly elevated in the gastric cancer tissues compared with that noted in the tumor-adjacent gastric mucosal and normal gastric mucosal sampes, and hnRNP K expression was found to correlate with tumor stage and lymph node metastasis. However, the level of serum hnRNP K did not differ significantly between gastric cancer patients and healthy volunteers. We also found that patients whose tumors showed elevated expression of hnRNP K had poor survival. The present study suggests that hnRNP K is a promising tissue biomarker for diagnosing gastric cancer and is a prognostic indicator for patients with gastric cancer.

  11. Diagnostic delay, quality of life and patient satisfaction among women diagnosed with endometrial or ovarian cancer

    DEFF Research Database (Denmark)

    Robinson, Kirstine M; Christensen, Karl Bang; Ottesen, Bent;

    2012-01-01

    This study investigates the association between diagnostic delay (total delay), quality of life (QoL) and patient satisfaction, and the associations between QoL and patient satisfaction scores and survival for women diagnosed with ovarian or endometrial cancer.......This study investigates the association between diagnostic delay (total delay), quality of life (QoL) and patient satisfaction, and the associations between QoL and patient satisfaction scores and survival for women diagnosed with ovarian or endometrial cancer....

  12. NDRG1 expression is related to the progression and prognosis of gastric cancer patients through modulating proliferation, invasion and cell cycle of gastric cancer cells.

    Science.gov (United States)

    Chang, Xiaojing; Xu, Xiaoyang; Ma, Jinguo; Xue, Xiaoying; Li, Zhenhua; Deng, Peng; Zhang, Shuanglong; Zhi, Yu; Chen, Jing; Dai, Dongqiu

    2014-09-01

    N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1-NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer.

  13. Seasonal and geographical variations in lung cancer prognosis in Norway. Does Vitamin D from the sun play a role?

    Science.gov (United States)

    Porojnicu, Alina Carmen; Robsahm, Trude Eid; Dahlback, Arne; Berg, Jens Petter; Christiani, David; Bruland, Oyvind Sverre; Moan, Johan

    2007-03-01

    hypothesised that the seasonal variation of calcidiol might be of prognostic significance for colon-, breast- prostate cancer as well as for Hodgkins lymphoma in Norway. Patients diagnosed during summer and autumn have a better survival after standard treatment than patients diagnosed during the winter season . This might be a consequence of a higher Vitamin D level. An American study investigated the effect of season of surgery and recent Vitamin D intake on the survival of non-small cell lung cancer patients. The authors reported a significant beneficial joint effect of summer season and high Vitamin D intake compared with winter season and low Vitamin D intake while Vitamin D intake alone did not affect prognosis. Similar results were recently reported from a large study in United Kingdom involving over a million cancer patients including over 190,000 patients diagnosed with lung cancer . Norway (58-71 degrees N) has a significant north-south variation in UV fluence. This makes the country suitable for studies relating cancer epidemiology to UV levels . We investigated whether variations in UV, and, consequently, in Vitamin D level, influence the prognosis of lung cancer, using season of diagnosis and residential regions as variables. Survival data obtained for patients diagnosed over a 40 years period were compared with variations in serum Vitamin D levels obtained from routine measurements performed in The Hormone Laboratory of Aker University Hospital during the period 1996-2001. Seasonal and gender variations in Vitamin D level have been estimated from the analyses.

  14. Distress in suspected lung cancer patients following rapid and standard diagnostic programs: a prospective observational study

    NARCIS (Netherlands)

    Brocken, P.; Heijden, E.H. van der; Oud, K.T.; Bootsma, G.; Groen, H.J.M.; Donders, A.R.T.; Dekhuijzen, P.N.R.; Prins, J.B.

    2015-01-01

    OBJECTIVE: Timeliness may influence emotional distress during the diagnostic phase of suspected lung cancer patients. We performed a prospective observational study to compare distress and quality of life (QoL) in two medical centres with a Rapid Outpatient Diagnostic Program (RODP) and two using co

  15. 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.

  16. Exosomal microRNA Signatures in the Diagnosis and Prognosis of Ovarian Cancer

    Science.gov (United States)

    2013-10-01

    regard to early stage cancer detection (sensitivity from 50–60%).8 CA125 quantitation is only approved for and consistently proven for remission ...general peptide patterns in patient serum to define the presence of cancer. SELDI-TOF-MS profiling has been successfully used to...sensitivity. While removal of prevalent proteins or peptides can greatly increase the informational content that can be acquired from particular

  17. The network of pluripotency, epithelial–mesenchymal transition, and prognosis of breast cancer

    Directory of Open Access Journals (Sweden)

    Voutsadakis IA

    2015-09-01

    Full Text Available Ioannis A Voutsadakis1,2 1Division of Medical Oncology, Department of Internal Medicine, Sault Area Hospital, Sault Ste Marie, ON, Canada; 2Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, ON, Canada Abstract: Breast cancer is the leading female cancer in terms of prevalence. Progress in molecular biology has brought forward a better understanding of its pathogenesis that has led to better prognostication and treatment. Subtypes of breast cancer have been identified at the genomic level and guide therapeutic decisions based on their biology and the expected benefit from various interventions. Despite this progress, a significant percentage of patients die from their disease and further improvements are needed. The cancer stem cell theory and the epithelial–mesenchymal transition are two comparatively novel concepts that have been introduced in the area of cancer research and are actively investigated. Both processes have their physiologic roots in normal development and common mediators have begun to surface. This review discusses the associations of these networks as a prognostic framework in breast cancer. Keywords: stem cells, epithelial-to-mesenchymal transition, mesenchymal-to-epithelial transition

  18. Chronic Activation of Innate Immunity Correlates With Poor Prognosis in Cancer Patients Treated With Oncolytic Adenovirus.

    Science.gov (United States)

    Taipale, Kristian; Liikanen, Ilkka; Juhila, Juuso; Turkki, Riku; Tähtinen, Siri; Kankainen, Matti; Vassilev, Lotta; Ristimäki, Ari; Koski, Anniina; Kanerva, Anna; Diaconu, Iulia; Cerullo, Vincenzo; Vähä-Koskela, Markus; Oksanen, Minna; Linder, Nina; Joensuu, Timo; Lundin, Johan; Hemminki, Akseli

    2016-02-01

    Despite many clinical trials conducted with oncolytic viruses, the exact tumor-level mechanisms affecting therapeutic efficacy have not been established. Currently there are no biomarkers available that would predict the clinical outcome to any oncolytic virus. To assess the baseline immunological phenotype and find potential prognostic biomarkers, we monitored mRNA expression levels in 31 tumor biopsy or fluid samples from 27 patients treated with oncolytic adenovirus. Additionally, protein expression was studied from 19 biopsies using immunohistochemical staining. We found highly significant changes in several signaling pathways and genes associated with immune responses, such as B-cell receptor signaling (P immunity before treatment is associated with inferior survival in patients treated with oncolytic adenovirus. Conversely, lack of chronic innate inflammation at baseline may predict improved treatment outcome, as suggested by good overall prognosis.

  19. Effects of the combination of blood transfusion and postoperative infectious complications on prognosis after surgery for colorectal cancer. Danish RANX05 Colorectal Cancer Study Group

    DEFF Research Database (Denmark)

    Mynster, T; Christensen, Ib Jarle; Moesgaard, F;

    2000-01-01

    = 740) and time to diagnosis of recurrent disease in the subgroup of patients operated on with curative intention (n = 532). The patients were analysed in four groups divided with respect to administration or not of perioperative blood transfusion and development or non-development of postoperative......BACKGROUND: The frequency of postoperative infectious complications is significantly increased in patients with colorectal cancer receiving perioperative blood transfusion. It is still debated, however, whether perioperative blood transfusion alters the incidence of disease recurrence or otherwise...... affects the prognosis. METHODS: Patient risk variables, variables related to operation technique, blood transfusion and the development of infectious complications were recorded prospectively in 740 patients undergoing elective resection for primary colorectal cancer. Endpoints were overall survival (n...

  20. Post-surgical highly sensitive C-reactive protein and prognosis in early-stage breast cancer.

    Science.gov (United States)

    Tibau, Ariadna; Ennis, Marguerite; Goodwin, Pamela J

    2013-10-01

    Obesity, associated with inflammation, has been linked to poor prognosis in breast cancer. Research investigating the potential role of C-reactive protein (CRP), an obesity-associated systemic marker of inflammation, as a mediator of adverse prognostic effects of obesity has yielded inconsistent results. We examined the association of highly sensitive CRP (hsCRP) with obesity-related factors and breast cancer outcome. A cohort of 535 non-diabetic women diagnosed with T1-3, N0-1, M0 breast cancer, was assembled between 1989 and 1996 and followed prospectively. Circulating levels of hsCRP were analyzed on blood obtained postoperatively, prior to systemic therapy, in 501 women. Correlations and prognostic associations were analyzed using one-way analysis of variance, Spearman's rank correlation coefficients (r) and Cox models. hsCRP was significantly correlated with body mass index (r = 0.60), insulin (r = 0.44), leptin (r = 0.54), and lipids, but not T or N stage, grade or estrogen receptor/progesterone receptor. At a median follow-up of 12 years, hsCRP was not associated with distant disease-free survival or overall survival in univariable [Q4 vs. Q1 hazard ratio (HR) 1.03, 95 % confidence interval (CI) 0.69-1.52, P = 0.9 and HR 1.27, 95 % CI 0.86-1.86, P = 0.24, respectively] or multivariable [Q4 vs Q1 HR 1.02, 95 % CI 0.66-1.59, P = 0.93 and HR 1.17, 95 % CI 0.76-1.81, P = 0.48 respectively] analyses. hsCRP was associated with age, comorbidities, and the insulin resistance syndrome but not with breast cancer outcome.

  1. A pooled analysis of post-diagnosis lifestyle factors in association with late estrogen-receptor-positive breast cancer prognosis.

    Science.gov (United States)

    Nechuta, Sarah; Chen, Wendy Y; Cai, Hui; Poole, Elizabeth M; Kwan, Marilyn L; Flatt, Shirley W; Patterson, Ruth E; Pierce, John P; Caan, Bette J; Ou Shu, Xiao

    2016-05-01

    Lifestyle factors have been well studied in relation to breast cancer prognosis overall; however, associations of lifestyle and late outcomes (>5 years after diagnosis) have been much less studied, and no studies have focused on estrogen receptor-positive (ER+) breast cancer survivors, who may have high risk of late recurrence and mortality. We utilized a large prospective pooling study to evaluate the associations of lifestyle factors with late recurrence and all-cause mortality among 6,295 5-year ER+ Stage I-III breast cancer survivors. Pooled and harmonized data were available on clinical factors and lifestyle factors (pre- to post-diagnosis weight change, body mass index (BMI) (kg/m(2)), recreational physical activity, alcohol intake and smoking history), measured on average 2.1 years after diagnosis. Updated information for weight only was available. Study heterogeneity was evaluated by the Q-statistic. Multivariable Cox regression models were stratified by study. Adjusting for clinical factors and potential confounders, ≥ 10% weight gain and obesity (BMI, 30-34.99 and ≥ 35) were associated with increased risk of late recurrence (hazard ratios (95% confidence intervals): 1.24 (1.00-1.53), 1.40 (1.05-1.86) and 1.41 (1.02-1.93), respectively). Daily alcohol intake was associated with late recurrence, 1.28 (1.01-1.62). Physical activity was inversely associated with late all-cause mortality (0.81 (0.71-0.93) and 0.71 (0.61-0.82) for 4.9 to factors were associated with late outcomes among long-term ER+ breast cancer survivors.

  2. Decreased expression of STING predicts poor prognosis in patients with gastric cancer

    Science.gov (United States)

    Song, Shushu; Peng, Peike; Tang, Zhaoqing; Zhao, Junjie; Wu, Weicheng; Li, Haojie; Shao, Miaomiao; Li, Lili; Yang, Caiting; Duan, Fangfang; Zhang, Mingming; Zhang, Jie; Wu, Hao; Li, Can; Wang, Xuefei; Wang, Hongshan; Ruan, Yuanyuan; Gu, Jianxin

    2017-01-01

    STING (stimulator of interferon genes) has recently been found to play an important role in host defenses against virus and intracellular bacteria via the regulation of type-I IFN signaling and innate immunity. Chronic infection with Helicobacter pylori is identified as the strongest risk factor for gastric cancer. Thus, we aim to explore the function of STING signaling in the development of gastric cancer. Immunohistochemistry was used to detect STING expression in 217 gastric cancer patients who underwent surgical resection. STING protein expression was remarkably decreased in tumor tissues compared to non-tumor tissues, and low STING staining intensity was positively correlated with tumor size, tumor invasion depth, lymph mode metastasis, TNM stage, and reduced patients’ survival. Multivariate analysis identified STING as an independent prognostic factor, which could improve the predictive accuracy for overall survival when incorporated into TNM staging system. In vitro studies revealed that knock-down of STING promoted colony formation, viability, migration and invasion of gastric cancer cells, and also led to a defect in cytosolic DNA sensing. Besides, chronic H. pylori infection up-regulated STING expression and activated STING signaling in mice. In conclusion, STING was proposed as a novel independent prognostic factor and potential immunotherapeutic target for gastric cancer. PMID:28176788

  3. Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis.

    Science.gov (United States)

    Yuan, Xun; Zhang, Mingsheng; Wu, Hua; Xu, Hanxiao; Han, Na; Chu, Qian; Yu, Shiying; Chen, Yuan; Wu, Kongming

    2015-01-01

    Various studies have evaluated the significance of Notch1 expression in breast cancer, but the results have ever been disputed. By using 21 studies involving 3867 patients, this meta-analysis revealed that the expression of Notch1 was significantly higher in breast cancer than in normal tissues (OR=7.21; 95%CI, 4.7-11.07) and that higher Notch1 expression was associated with transition from ductal carcinoma in situ (DCIS) to invasive cancer (OR=3.75; 95% CI, 1.8-7.78). Higher Notch1 activity was observed in the basal subtype of breast cancer (OR=2.53; 95% CI, 1.18-5.43). Moreover, patients with Notch1 overexpression exhibited significantly worse overall and recurrence-free survival. Our meta-analysis suggests that Notch inhibitors may be useful in blocking the early progression of DCIS and that the outcomes of clinical trials for Notch1-targeting therapeutics could be improved by the molecular stratification of breast cancer patients.

  4. Impact of estrogen receptor-β expression on breast cancer prognosis: a meta-analysis.

    Science.gov (United States)

    Liu, Jieqiong; Guo, Huishan; Mao, Kai; Zhang, Kan; Deng, Heran; Liu, Qiang

    2016-02-01

    Estrogen receptor (ER)-β has been discovered for decades; however, its prognostic value in breast cancer patients remains controversial. We aimed to evaluate the impact of ER-β expression on breast cancer survival. A systematic search of Medline, Embase, and Cochrane Library was performed to identify the association between ER-β expression and outcomes in early breast cancer patients. Random-effects meta-analysis was conducted to generate combined hazard ratios (HRs) with 95 % confidence intervals (CIs) for overall survival (OS) and disease-free survival (DFS). A total of 6769 patients for ER-β1, 2295 patients for ER-β2, and 2271 patients for ER-β5 from 21 studies were included. ER-β1 protein expression was correlated with both favorable 5-year DFS and OS (HR 0.690, 95 % CI 0.610-0.779; P early breast cancer patients. The prognostic significance of ER-β1 for DFS is independent of ER-α coexpression, whereas the impact on OS was only in ER-α positive breast cancer.

  5. Genomic Signatures in Breast Cancer: Limitations of Available Predictive Data and the Importance of Prognosis.

    Science.gov (United States)

    Esteva, Francisco J

    2015-06-01

    Several biomarkers and gene mutations in breast cancer have been shown to be predictive, in that they determine which treatments a patient should receive. Ideally, predictive markers would be available that could determine the most appropriate treatment plan based on a patient’s biology. This goal is becoming a reality in some treatment settings and cancer types, with the increasing use of targeted therapies directed against specific molecular abnormalities. Immunohistochemistry (IHC) testing is in standard use for guiding breast cancer therapy. Testing for the estrogen receptor (ER) and progesterone receptor (PR) guides the use of endocrine therapy, and human epidermal growth factor receptor 2 (HER2) testing guides the use of HER2-targeted therapies. Although IHC provides some discrimination among breast cancer subsets and helps identify appropriate therapy, more information can be gained through gene expression analyses. Contemporary multianalyte assays have demonstrated greater precision and reproducibility than seen with IHC-based assays. The most important contribution of multigene assays is the identification of women with ER/PR-positive, HER2-negative, early-stage breast cancer who are at low risk of recurrence and therefore will likely do well with endocrine therapy alone. These patients can be safely spared from the cytotoxic effects of chemotherapy.

  6. Expression of Notch1 Correlates with Breast Cancer Progression and Prognosis.

    Directory of Open Access Journals (Sweden)

    Xun Yuan

    Full Text Available Various studies have evaluated the significance of Notch1 expression in breast cancer, but the results have ever been disputed. By using 21 studies involving 3867 patients, this meta-analysis revealed that the expression of Notch1 was significantly higher in breast cancer than in normal tissues (OR=7.21; 95%CI, 4.7-11.07 and that higher Notch1 expression was associated with transition from ductal carcinoma in situ (DCIS to invasive cancer (OR=3.75; 95% CI, 1.8-7.78. Higher Notch1 activity was observed in the basal subtype of breast cancer (OR=2.53; 95% CI, 1.18-5.43. Moreover, patients with Notch1 overexpression exhibited significantly worse overall and recurrence-free survival. Our meta-analysis suggests that Notch inhibitors may be useful in blocking the early progression of DCIS and that the outcomes of clinical trials for Notch1-targeting therapeutics could be improved by the molecular stratification of breast cancer patients.

  7. Recurrence Incidence in Differentiated Thyroid Cancers and the Importance of Diagnostic Iodine-131 Scintigraphy in Clinical Follow-up

    Directory of Open Access Journals (Sweden)

    Filiz Hatipoğlu

    2016-06-01

    Full Text Available Objective: Differentiated thyroid cancers (DTC are tumors with good prognosis. However, local recurrence or distant metastasis can be observed. In our study, we aimed to investigate the incidence of recurrence and the importance of diagnostic iodine-131 whole body scan (WBS in clinical follow-up in patients with DTC. Methods: The clinical data of 217 patients with DTC who were followed-up more than 3 years were reviewed retrospectively. The incidence of recurrence was investigated in a group of patients who had radioactive iodine (RAI treatment and showed no sign of residual thyroid tissue or metastasis with diagnostic WBS that was performed at 6-12 months after therapy and had a thyroglobulin (Tg level lower than 2 ng/dl. Results: At the time of diagnosis, ten cases had thyroid capsule invasion, 25 cases had extra-thyroid soft tissue invasion, 11 patients showed lymph node metastasis and four patients had distant organ metastasis. One hundred forty-five patients had RAI treatment at ablation dose (75-100 mCi, whereas 35 patients had RAI treatment at metastasis dose (150-200 mCi. Thirty-seven patients with papillary microcarcinoma did not receive RAI treatment. In 12 (%7.5 of the 160 patients who were considered as “successful ablation”, a recurrence was identified. Recurrence was detected by diagnostic WBS in all cases and stimulated Tg level was <2 ng/dL with the exception of the two cases who had distant metastasis. Conclusion: Identification of pathological findings with WBS in patients who developed local recurrence in the absence of elevated Tg highlights the importance of diagnostic WBS in clinical follow-up.

  8. High Rab11-FIP4 expression predicts poor prognosis and exhibits tumor promotion in pancreatic cancer

    Science.gov (United States)

    He, Yun; Ye, Mengsi; Zhou, Lingling; Shan, Yunfeng; Lu, Guangrong; Zhou, Yuhui; Zhong, Jinwei; Zheng, Jihang; Xue, Zhanxiong; Cai, Zhenzhai

    2017-01-01

    Some studies have demonstrated that Rab11-family interacting proteins (Rab11-FIPs) are connected with the tumorigenesis, and they may act as tumor promoters in some cancers. The clinicopathological significance of Rab11-family interacting protein 4 (Rab11-FIP4) expression and its possible effects on pancreatic cancer (PC) are still undiscovered. In this study, Rab11-FIP4 protein expression level in 60 PC specimens and pair-matched non-cancerous samples were detected by immunohistochemistry analysis. The results were analysed and compared with each patients' clinical data. Rab11-FIP4 expression in PC tissues increased significantly more than that of adjacent non-cancerous tissues (P=0.0001). Overexpression of Rab11-FIP4 in the PC tissues was significantly related to tumor size (P=0.0001), histological grade (P=0.028), metastasis (P=0.001) and TNM stage (P=0.004) but not with age (P=0.832), gender (P=0.228) or tumor site (P=0.875). Kaplan-Meier survival analysis showed that overexpression of Rab11-FIP4 was significantly related to overall survival time (P=0.0036). In addition, Rab11-FIP4 in PANC-1 pancreatic cancer cells were successfully knocked-out using the CRISPR/Cas9 system. Rab11-FIP4 knockout in PANC-1 cells inhibited cell growth, invasion and metastasis, and arrested cell cycle progression, but did not alter apoptosis. Our findings suggest that overexpression of Rab11-FIP4 predicts poor clinical outcomes for pancreatic cancer and contributes to pancreatic tumor progression. PMID:28035375

  9. High Expression of Stromal Cell-Derived Factor 1 (SDF-1) and NF-κB Predicts Poor Prognosis in Cervical Cancer.

    Science.gov (United States)

    Song, Zhiwang; Zhang, Xia; Ye, Xiaojuan; Feng, Chan; Yang, Guang; Lu, Yonglin; Lin, Yun; Dong, Chunyan

    2017-01-11

    BACKGROUND SDF-1 and NF-κB are associated with the prognosis of a wide range of cancers, but their value in cervical cancer remains controversial. The aim of this study was to investigate the expression of SDF-1and NF-κB in cervical cancer and their significance in clinical prognosis. MATERIAL AND METHODS The expression of SDF-1and NF-κB in 105 formalin-fixed, paraffin-embedded cervical cancer tissues and the adjacent tissues was examined by immunohistochemistry (IHC). The results were semi-quantitatively scored and analyzed by chi-square test. The overall survival times (OS) were collected by follow-up and analyzed by Kaplan-Meier analysis. RESULTS The expression level of both SDF-1and NF-κB in cervical cancer are higher than that in the adjacent tissues (PSDF-1 expression are correlated with tumor size and FIGO histology grade (PSDF-1or NF-κB tended to have much shorter survival time than patients with negative expression. In addition, multivariate Cox regression analysis demonstrated that SDF-1 expression and lymph node metastasis are independent predictors of the OS in cervical cancer patients. CONCLUSIONS The expression of SDF-1 is significantly associated with tumor size and FIGO histology grade. The expression of NF-κB is significantly associated with tumor size, FIGO histology grade, and lymph node metastasis. The positive SDF-1or NF-κB expression is significantly correlated with poor prognosis. These may be valuable biomarkers for the prognosis and the potential therapeutic targets of cervical cancer.

  10. An Approach with Support Vector Machine using Variable Features Selection on Breast Cancer Prognosis

    Directory of Open Access Journals (Sweden)

    Sandeep Chaurasia

    2013-09-01

    Full Text Available Cancer diagnosis and clinical outcome prediction are among the most important emerging applications of machine learning. In this paper we have used an approach by using support vector machine classifier to construct a model that is useful for the breast cancer survivability prediction. We have used both 5 cross and 10 cross validation of variable selection on input feature vectors and the performance measurement through bio-learning class performance while measuring AUC, specificity and sensitivity. The performance of the SVM is much better than the other machine learning classifier.

  11. Prognosis of cancer with branch duct type IPMN of the pancreas

    Institute of Scientific and Technical Information of China (English)

    Nobuhito; Ikeuchi; Takao; Itoi; Atsushi; Sofuni; Fumihide; Itokawa; Takayoshi; Tsuchiya; Toshio; Kurihara; Kentaro; Ishii; Shujiro; Tsuji; Junko; Umeda; Fuminori; Moriyasu; Akihiko; Tsuchida; Kazuhiko; Kasuya

    2010-01-01

    AIM:To examine the coexistence of metachronous and synchronous cancer in branch duct intraductal papillary mucinous neoplasms of the pancreas (IPMN).METHODS: We reviewed the records of 145 patients with branch duct IPMN between January 1991 and April 2008 and assessed the relationship between IPMN and intraor extra-pancreatic carcinoma and the outcome of IPMN.RESULTS: The mean observation period was 55.9 ± 45.3 mo. Among the 145 patients, the frequency of extra-pancreatic cancer was 29.0%. The frequency of ...

  12. The diagnostic process of cervical cancer; areas of good practice, and windows of opportunity

    NARCIS (Netherlands)

    Zaal, A.; de Wilde, Marlieke; Duk, M.J.; Graziosi, G.C.M.; van Haaften, Maarten; von Mensdorff-Pouilly, S.; van Diest, Paul J.; Zweemer, RP; Peeters, Petra H.M.; Verheijen, RHM

    2015-01-01

    Objective Despite an extensive screening programme in The Netherlands, some cases of cervical cancer are still diagnosed in late stages of disease. The aim of the present study was to investigate which elements in the diagnostic process of cervical cancer may be improved. Methods This is a retrospec

  13. LAPTM4B Gene Expression And Polymorphism As Diagnostic Markers Of Breast Cancer In Egyptian Patients

    Directory of Open Access Journals (Sweden)

    Shaker Olfat

    2015-10-01

    Full Text Available Background: The aim of this study was to investigate the association between LAPTM4B gene polymorphism and the risk of breast cancer among Egyptian female patients. Also, measurement was done of its serum level to evaluate its significance as a diagnostic marker for breast cancer.

  14. Recent advances in salivary cancer diagnostics enabled by biosensors and bioelectronics.

    Science.gov (United States)

    Mishra, Saswat; Saadat, Darius; Kwon, Ohjin; Lee, Yongkuk; Choi, Woon-Seop; Kim, Jong-Hoon; Yeo, Woon-Hong

    2016-07-15

    There is a high demand for a non-invasive, rapid, and highly accurate tool for disease diagnostics. Recently, saliva based diagnostics for the detection of specific biomarkers has drawn significant attention since the sample extraction is simple, cost-effective, and precise. Compared to blood, saliva contains a similar variety of DNA, RNA, proteins, metabolites, and microbiota that can be compiled into a multiplex of cancer detection markers. The salivary diagnostic method holds great potential for early-stage cancer diagnostics without any complicated and expensive procedures. Here, we review various cancer biomarkers in saliva and compare the biomarkers efficacy with traditional diagnostics and state-of-the-art bioelectronics. We summarize biomarkers in four major groups: genomics, transcriptomics, proteomics, and metabolomics/microbiota. Representative bioelectronic systems for each group are summarized based on various stages of a cancer. Systematic study of oxidative stress establishes the relationship between macromolecules and cancer biomarkers in saliva. We also introduce the most recent examples of salivary diagnostic electronics based on nanotechnologies that can offer rapid, yet highly accurate detection of biomarkers. A concluding section highlights areas of opportunity in the further development and applications of these technologies.

  15. Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

    Science.gov (United States)

    Thirdborough, Steve; Mellows, Toby; Garcia, Edwin; Woo, Jeongmin; Tod, Joanne; Frampton, Steve; Jenei, Veronika; Moutasim, Karwan A.; Kabir, Tasnuva D.; Brennan, Peter A; Venturi, Giulia; Ford, Kirsty; Herranz, Nicolas; Lim, Kue Peng; Clarke, James; Lambert, Daniel W.; Prime, Stephen S.; Underwood, Timothy J.; Vijayanand, Pandurangan; Eliceiri, Kevin W.; Woelk, Christopher; King, Emma V.; Gil, Jesus; Ottensmeier, Christian H.; Thomas, Gareth J.

    2017-01-01

    Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes. PMID:27992856

  16. Effects of phenotype transformation of receptors of triple-negative breast cancer(TNBC on clinical prognosis of patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Xin ZHAO

    2012-04-01

    Full Text Available Objective To evaluate the expression of estrogen receptor (ER, progesterone receptor (PR and human epidermis growth-factor receptor 2(HER-2, to determine the phenotype transformation of these receptors before and after recurrence and/or metastasis, and to explore the effects of expression and phenotype transformation of receptors on the treatment efficacy and clinical prognosis of patients with breast cancer. Methods Based on the phenotype transformation of ER, PR, and HER-2 receptor, 211 breast cancer patients were assigned to 3 groups. Twenty patients of Group A were with primary triple-negative breast cancer (TNBC, defined as lacking expression of ER, PR and HER2 which transformed into non-TNBC after recurrence and/ or metastasis, 73 of Group B were with primary non-TNBC which transformed into TNBC after recurrence and/or metastasis, and 118 of Group C were with primary TNBC which was still TNBC after recurrence and/or metastasis. The phenotype transformation of receptors, recurrence/metastasis, and efficacy and clinical prognosis were analyzed following collection of general information of the patients. Results The median age of 211 recurrent patients was 52 years (range, 22 to 78 years. Most of the patients exhibited solitary metastasis. The most common locations of the initial metastasis were lymph node, bone and skin. The median disease-free survival for Groups A, B, and C was 34.0, 25.0, and 20.0 months, respectively. The clinical effect of Groups B and C was better than that of Group A for first-line, second-line, and third-line rescuing therapy (P=0.030, 0.003, 0.001. However, the clinical benefit rate of Group A was higher than those of Groups B and C for rescuing endocrine therapy. The median follow-up time of the 211 patients was 68 months (range, 20 to 127 months, and the median survival after recurrence for Groups A, B, and C was 63.1, 33.7, and 25.8 months respectively (P=0.000. The median overall survival for Groups A, B

  17. Downregulation of ZNF132 in prostate cancer is associated with aberrant promoter hypermethylation and poor prognosis

    DEFF Research Database (Denmark)

    Abildgaard, Mette Opstrup; Borre, Michael; Mørck Mortensen, Martin;

    2012-01-01

    immunoreactivity was significantly associated with high Gleason score and advanced T stage in both PC patient cohorts. By univariate analysis, no/weak ZNF132 staining was a significant adverse predictor of PSA recurrence after RP (p = 0.024) and cancer-specific death following conservative treatment (p = 0...

  18. Patient Preferences for the Disclosure of Prognosis After Esophagectomy for Cancer with Curative Intent

    NARCIS (Netherlands)

    Lagarde, Sjoerd M.; Franssen, Sanne J.; van Werven, Jochem R.; Smets, Ellen M. A.; Tran, T. C. Khe; Tilanus, Hugo W.; Plukker, John Th. M.; de Haes, Johanna C. J. M.; van Lanschot, J. Jan B.

    2008-01-01

    Introduction: The aim of this study was to determine the preferences for content, style, and format of prognostic information of patients after potentially curative esophagectomy for cancer and to explore predictors of these preferences. Patients and Methods: This multicenter study included a consec

  19. Clonal Evaluation of Prostate Cancer by ERG/SPINK1 Status to Improve Prognosis Prediction

    Science.gov (United States)

    2015-10-01

    SUBJECT TERMS Multiclonality, ERG, SPINK1, immunohistochemistry, active surveillance, prostate biopsy, prostatectomy 16. SECURITY CLASSIFICATION OF: 17...and in doing so, will increase the number of men eligible for active surveillance, enhancing the well-being of men with prostate cancer through...minimizing over- treatment and treatment-related side effects. KEYWORDS: Multiclonality, ERG, SPINK1, immunohistochemistry, active surveillance

  20. Annexin A1 expression in a pooled breast cancer series: Association with tumor subtypes and prognosis

    NARCIS (Netherlands)

    M. Sobral-Leite (Marcelo); J. Wesseling (Jelle); V.T.H.B.M. Smit (Vincent); H. Nevanlinna (Heli); M.H. van Miltenburg (Martine H.); J. Sanders (Joyce); I. Hofland (Ingrid); F. Blows (Fiona); P. Coulson (Penny); G. Patrycja (Gazinska); J.H.M. Schellens (Jan); R. Fagerholm (Rainer); P. Heikkilä (Päivi); K. Aittomäki (Kristiina); C. Blomqvist (Carl); E. Provenzano (Elena); H.R. Ali (Hamid Raza); J.D. Figueroa (Jonine); M.E. Sherman (Mark); J. Lissowska (Jolanta); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); K.-A. Phillips (Kelly-Anne); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); D. Visscher (Daniel); H. Brenner (Hermann); K. Butterbach (Katja); V. Arndt (Volker); B. Holleczek (B.); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John); C.H.M. van Deurzen (Carolien); B. Van de Water (Bob); A. Broeks (Annegien); J. Chang-Claude (Jenny); G. Chenevix-Trench (Georgia); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); M. García-Closas (Montserrat); M. de Graauw (Marjo); M.K. Schmidt (Marjanka)

    2015-01-01

    textabstractBackground: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, B

  1. Recurrent venous thromboembolism in anticoagulated patients with cancer : management and short-term prognosis

    NARCIS (Netherlands)

    Schulman, S.; Zondag, M.; Linkins, L.; Pasca, S.; Cheung, Y. W.; De Sancho, M.; Gallus, A.; Lecumberri, R.; Molnar, S.; Ageno, W.; Le Gal, G.; Falanga, A.; Hulegardh, E.; Ranta, S.; Kamphuisen, P.; Debourdeau, P.; Rigamonti, V.; Ortel, T. L.; Lee, A.

    2015-01-01

    BackgroundRecommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagul

  2. The prognosis of incurable cachectic cancer patients on home parenteral nutrition

    DEFF Research Database (Denmark)

    Bozzetti, F; Santarpia, L; Pironi, L

    2014-01-01

    BACKGROUND: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. PATIENTS AND METHODS: We studied prospectively 414 incurable cachectic (sub...

  3. RELATIONSHIP AMONG PS2 PROTEIN EXPRESSION, ESTROGEN AND PROGESTERONE RECEPTOR STATUS, AND PROGNOSIS OF BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    LIU Jingxian; LI Jiyou; HE Luowen; ZHAO Yajuan

    1999-01-01

    Objective: To study the relationship between the expression of PS2 protein and Estrogen (ER) and Progesterone Receptor (PR) status and their prognotic value in breast cancer. Methods: Using the immunohistochemical method, PS2 protein expressions were detected in 105 cases with breast cancer. Results:The positive rate of PS2 protein was 50.48% (53/105) in 105 cases. The positive rate of PS2 in the patients who survived five years or more was 56.96% (45/79), which was higher than that of those who lived less than five years (30.77%, 8/26). In the ER, PR (+) patients, the positive rate of PS2 was higher (76.74%, 33/34), than that of those with ER, PR (-) (22.5%, 9/40). Conclusions:Our results suggest that the expression of PS2 protein was positively correlated with the S-year-survival and that of ER and PR in breast cancer. It is considered that PS2 may be as a prognostic predictor, and detection of PS2 protein expression was useful for a guiding treatment of breast cancer.

  4. Carbonic anhydrase-9 expression levels and prognosis in human breast cancer: association with treatment outcome.

    NARCIS (Netherlands)

    Span, P.N.; Bussink, J.; Manders, P.; Beex, L.V.A.M.; Sweep, C.G.J.

    2003-01-01

    Here, we set out to assess CA9 expression levels by real-time quantitative RT-PCR in breast cancer tissue samples obtained from 253 patients, and correlated those with relapse-free (RFS) survival. The median follow-up time was 75 months (range 2-168 months). CA9 expression was mainly found in high-g

  5. Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen; Christensen, Ib Jarle; Højen, Helle

    2012-01-01

    of cancer development. Method:  Follow-up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included chi(2) test, actuarial method and Kaplan-Meier analysis. Results:  Among 304 patients, 261 (86%) had more than one endoscopy. The median follow-up was 14 years...

  6. Duodenal surveillance improves the prognosis after duodenal cancer in familial adenomatous polyposis

    DEFF Research Database (Denmark)

    Bülow, Steffen; Christensen, Ib Jarle; Højen, Helle

    2012-01-01

    of cancer development. Method: Follow-up of patients in a previous study with gastroduodenoscopy in 1990-2010. Statistical analysis included chi(2) test, actuarial method and Kaplan-Meier analysis. Results: Among 304 patients, 261 (86%) had more than one endoscopy. The median follow-up was 14 years...

  7. Impact of Triple-Negative Phenotype on Prognosis of Patients With Breast Cancer Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Xu Zhiyuan [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Schlesinger, David [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Toulmin, Sushila [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Rich, Tyvin [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Sheehan, Jason, E-mail: jps2f@virginia.edu [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States)

    2012-11-01

    Purpose: To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). Methods and Materials: A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. Results: The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. Conclusion: The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor.

  8. Annexin A1 expression in a pooled breast cancer series : Association with tumor subtypes and prognosis

    NARCIS (Netherlands)

    Sobral-Leite, Marcelo; Wesseling, Jelle; Smit, Vincent T H B M; Nevanlinna, Heli; van Miltenburg, Martine H.; Sanders, Joyce; Hofland, Ingrid; Blows, Fiona M.; Coulson, Penny; Patrycja, Gazinska; Schellens, Jan H M; Fagerholm, Rainer; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Provenzano, Elena; Ali, Hamid Raza; Figueroa, Jonine; Sherman, Mark; Lissowska, Jolanta; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Phillips, Kelly Anne; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Visscher, Daniel; Brenner, Hermann; Butterbach, Katja; Arndt, Volker; Holleczek, Bernd; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W M; van Deurzen, Carolien H M; van de Water, Bob; Broeks, Annegien; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Easton, Douglas F.; Pharoah, Paul D P; García-Closas, Montserrat; de Graauw, Marjo; Schmidt, Marjanka K.; Aghmesheh, Morteza; Amor, David; Andrews, Lesley; Antill, Yoland; Armitage, Shane; Arnold, Leanne; Balleine, Rosemary; Bankier, Agnes; Bastick, Patti; Beesley, Jonathan; Beilby, John; Bennett, Barbara; Bennett, Ian; Berry, Geoffrey; Blackburn, Anneke; Bogwitz, Michael; Brennan, Meagan; Brown, Melissa; Buckley, Michael; Burgess, Matthew; Burke, Jo; Butow, Phyllis; Byron, Keith; Callen, David; Campbell, Ian; Chauhan, Deepa; Chauhan, Manisha; Christian, Alice; Clarke, Christine; Colley, Alison; Cotton, Dick; Crook, Ashley; Cui, James; Culling, Bronwyn; Cummings, Margaret; Dawson, Sarah Jane; deFazio, Anna; Delatycki, Martin; Dickson, Rebecca; Dixon, Joanne; Dobrovic, Alexander; Dudding, Tracy; Edkins, Ted; Edwards, Stacey; Eisenbruch, Maurice; Farshid, Gelareh; Fawcett, Susan; Fellows, Andrew; Fenton, Georgina; Field, Michael; Firgaira, Frank; Flanagan, James; Fleming, Jean; Fong, Peter; Forbes, John; Fox, Stephen; French, Juliet; Friedlander, Michael; Gaff, Clara; Gardner, Mac; Gattas, Mike; George, Peter; Giles, Graham; Gill, Grantley; Goldblatt, Jack; Greening, Sian; Grist, Scott; Haan, Eric; Hardie, Kate; Harris, Marion; Hart, Stewart; Hayward, Nick; Healey, Sue; Heiniger, Louise; Hopper, John; Humphrey, Evelyn; Hunt, Clare; James, Paul; Jenkins, Mark; Jones, Alison; Kefford, Rick; Kidd, Alexa; Kiely, Belinda; Kirk, Judy; Koehler, Jessica; Kollias, James; Kovalenko, Serguei; Lakhani, Sunil; Leaming, Amanda; Leary, Jennifer; Lim, Jacqueline; Lindeman, Geoff; Lipton, Lara; Lobb, Liz; Mann, Graham; Marsh, Deborah; McLachlan, Sue Anne; Meiser, Bettina; Meldrum, Cliff; Milne, Roger; Mitchell, Gillian; Newman, Beth; Niedermayr, Eveline; Nightingale, Sophie; O'Connell, Shona; O'Loughlin, Imelda; Osborne, Richard; Pachter, Nick; Patterson, Briony; Peters, Lester; Phillips, Kelly; Price, Melanie; Purser, Lynne; Reeve, Tony; Reeve, Jeanne; Richards, Robert; Rickard, Edwina; Robinson, Bridget; Rudzki, Barney; Saleh, Mona; Salisbury, Elizabeth; Sambrook, Joe; Saunders, Christobel; Saunus, Jodi; Sayer, Robyn; Scott, Elizabeth; Scott, Rodney; Scott, Clare; Seshadri, Ram; Sexton, Adrienne; Sharma, Raghwa; Shelling, Andrew; Simpson, Peter; Southey, Melissa; Spurdle, Amanda; Suthers, Graeme; Sykes, Pamela; Tassell, Margaret; Taylor, Donna; Taylor, Jessica; Thierry, Benjamin; Thomas, Susan; Thompson, Ella; Thorne, Heather; Townshend, Sharron; Trainer, Alison; Tran, Lan; Tucker, Kathy; Tyler, Janet; Visvader, Jane; Walker, Logan; Walpole, Ian; Ward, Robin; Waring, Paul; Warner, Bev; Warren, Graham; Williams, Rachael; Wilson, Judy; Winship, Ingrid; Wu, Kathy; Young, Mary Ann; Bowtell, D.; Green, A.; Webb, P.; de Fazio, A.; Gertig, D.

    2015-01-01

    Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germl

  9. Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.

    Science.gov (United States)

    Zhao, Xiangshan; Mirza, Sameer; Alshareeda, Alaa; Zhang, Ying; Gurumurthy, Channabasavaiah Basavaraju; Bele, Aditya; Kim, Jun Hyun; Mohibi, Shakur; Goswami, Monica; Lele, Subodh M; West, William; Qiu, Fang; Ellis, Ian O; Rakha, Emad A; Green, Andrew R; Band, Hamid; Band, Vimla

    2012-07-01

    Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.

  10. Is overexpression of HER-2 a predictor of prognosis in colorectal cancer?

    LENUS (Irish Health Repository)

    Kavanagh, Dara O

    2012-01-31

    BACKGROUND: The development of novel chemotherapeutic agents in colorectal cancer has improved survival. Following initial response to chemotherapeutic strategies many patients develop refractory disease. This poses a significant challenge common to many cancer subtypes. Newer agents such as Bevacizumab have successfully targeted the tyrosine kinase receptor epidermal growth factor receptor in metastatic colorectal cancer. Human epidermal growth factor receptor-2 is another member of the tyrosine kinase receptor family which has been successfully targeted in breast cancer. This may play a role in colorectal cancer. We conducted a clinicopathological study to determine if overexpression of human epidermal growth factor receptor-2 is a predictor of outcome in a cohort of patients with colorectal cancer. METHODS: Clinicopathological data and paraffin-embedded specimens were collected on 132 consecutive patients who underwent colorectal resections over a 24-month period at Mayo General Hospital. Twenty-six contained non-malignant disease. Her-2\\/neu protein overexpression was detected using immunohistochemistry (IHC). The HER-2 4B5 Ventana monoclonal antibody was used. Fluorescent insitu hybridisation (FISH) was performed using INFORM HER-2\\/Neu Plus. Results were correlated with established clinical and pathological predictors of outcome including TNM stage. Statistical analysis was performed using SPSS version 11.5. RESULTS: 114 were HER-2\\/Neu negative using IHC, 7 showed barely perceptible positivity (1+), 9 showed moderate staining (2+) and 2 were strongly positive (3+). There was no correlation with gender, age, grade, Dukes\\' stage, TNM stage, time to recurrence and 5-year survival (p > 0.05). FISH was applied to all 2+ and 3+ cases as well as some negative cases selected at random. Three were amplified (2 were 3+ and 1 was 2+). Similarly, HER-2 gene overexpression did not correlate with established prognostic indicators. CONCLUSION: HER-2 protein is over

  11. Is overexpression of HER-2 a predictor of prognosis in colorectal cancer?

    Directory of Open Access Journals (Sweden)

    Bennani Fadel

    2009-01-01

    Full Text Available Abstract Background The development of novel chemotherapeutic agents in colorectal cancer has improved survival. Following initial response to chemotherapeutic strategies many patients develop refractory disease. This poses a significant challenge common to many cancer subtypes. Newer agents such as Bevacizumab have successfully targeted the tyrosine kinase receptor epidermal growth factor receptor in metastatic colorectal cancer. Human epidermal growth factor receptor-2 is another member of the tyrosine kinase receptor family which has been successfully targeted in breast cancer. This may play a role in colorectal cancer. We conducted a clinicopathological study to determine if overexpression of human epidermal growth factor receptor-2 is a predictor of outcome in a cohort of patients with colorectal cancer. Methods Clinicopathological data and paraffin-embedded specimens were collected on 132 consecutive patients who underwent colorectal resections over a 24-month period at Mayo General Hospital. Twenty-six contained non-malignant disease. Her-2/neu protein overexpression was detected using immunohistochemistry (IHC. The HER-2 4B5 Ventana monoclonal antibody was used. Fluorescent insitu hybridisation (FISH was performed using INFORM HER-2/Neu Plus. Results were correlated with established clinical and pathological predictors of outcome including TNM stage. Statistical analysis was performed using SPSS version 11.5. Results 114 were HER-2/Neu negative using IHC, 7 showed barely perceptible positivity (1+, 9 showed moderate staining (2+ and 2 were strongly positive (3+. There was no correlation with gender, age, grade, Dukes' stage, TNM stage, time to recurrence and 5-year survival (p > 0.05. FISH was applied to all 2+ and 3+ cases as well as some negative cases selected at random. Three were amplified (2 were 3+ and 1 was 2+. Similarly, HER-2 gene overexpression did not correlate with established prognostic indicators. Conclusion HER-2 protein

  12. Decreased galectin-9 and increased Tim-3 expression are related to poor prognosis in gastric cancer.

    Directory of Open Access Journals (Sweden)

    Jing Jiang

    Full Text Available INTRODUCTION: Galectin-9 (Gal-9 induces adhesion and aggregation of certain cell types and inhibits the metastasis of tumor cells. T-cell immunoglobulin-and mucin domain-3-containing molecule 3 (TIM-3 plays a pivotal role in immune regulation. The aim of this study is to investigate Gal-9 and TIM-3 alterations in gastric cancer and their prognostic values. METHODS: Gal-9 and Tim-3 expression was evaluated using a tissue microarray immunohistochemistry method in 305 gastric cancers, of which 84 had paired adjacent normal samples. Cell lines SGC-7901, BGC-823, MGC-803, MKN45 and GES-1 were also stained. Correlations were analyzed between expression levels of Gal-9 and Tim-3 protein and tumor parameters or clinical outcomes. RESULTS: Gal-9 and Tim-3 stained positive on tumor cells in 86.2% (263/305, and 60.0% (183/305 patients with gastric cancer, respectively. Gal-9 expression was significantly higher in cancer than in normal mucosa (P<0.001. Reduced Gal-9 expression was associated with lymph-vascular invasion, lymph node metastasis, distant metastasis and worse TNM staging (P = 0.034, P = 0.009, P = 0.002 and P = 0.043, respectively. In contrast, Tim-3 expression was significantly lower in cancer than in control mucosa (P<0.001. Patients with lymph-vascular invasion had higher expression levels of Tim-3 (P<0.001. Moreover, multivariate analysis shows that both high Gal-9 expression and low Tim-3 expression were significantly associated with long overall survival (P = 0.002, P = 0.010, respectively; the combination of Gal-9 and Tim-3 expression was an independent prognostic predictor for patients with gastric cancer (RR: 0.43; 95%CI: 0.20-0.93. H.pylori infection status was not associated with Gal-9 and Tim-3 expression (P = 0.102, P = 0.565. CONCLUSION: The results suggest that expression of Gal-9 and Tim-3 in tumor cells may be a potential, independent prognostic factor for patients with gastric cancer. Gal-9 and TIM-3 may play an important part

  13. Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer

    LENUS (Irish Health Repository)

    Rexhepaj, Elton

    2010-11-23

    validated survivin CNR as a marker of good prognosis in breast cancer in a large independent cohort. These findings provide robust evidence of the importance of survivin CNR as a breast cancer biomarker, and its potential to predict outcome in tamoxifen-treated patients.

  14. Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer

    Directory of Open Access Journals (Sweden)

    Duffy Michael J

    2010-11-01

    validated survivin CNR as a marker of good prognosis in breast cancer in a large independent cohort. These findings provide robust evidence of the importance of survivin CNR as a breast cancer biomarker, and its potential to predict outcome in tamoxifen-treated patients.

  15. The prognosis was poorer in colorectal cancers that expressed both VEGF and PROK1 (No correlation coefficient between VEGF and PROK1).

    Science.gov (United States)

    Goi, Takanori; Nakazawa, Toshiyuki; Hirono, Yasuo; Yamaguchi, Akio

    2015-10-06

    The angiogenic proteins vascular endothelial growth factor (VEGF) and prokineticin1 (PROK1) proteins are considered important in colorectal cancer, the relationship between their simultaneous expression and prognosis was investigated in the present study. VEGF and PROK1 expression in 620 primary human colorectal cancer lesions was confirmed via immunohistochemical staining with anti-VEGF and anti-PROK1 antibodies, and the correlation between the expression of these 2 proteins and recurrence/prognosis were investigated. VEGF protein was expressed in 329 (53.1%) and PROK1 protein was expressed in 223 (36.0%). PROK1 and VEGF were simultaneously expressed in 116 (18.7%) of the 620 cases. The correlation coefficient between VEGF expression and PROK1 expression was r = 0.11, and therefore correlation was not observed. Clinical pathology revealed that substantially lymphnode matastasis, hematogenous metastasis, or TMN advanced-stage IV was significantly more prevalent in cases that expressed both VEGF and PROK1 than in the cases negative for both proteins or those positive for only 1 of the proteins. Also the cases positive for both proteins exhibited the worst recurrence and prognosis. In the Cox proportional hazards model, VEGF and PROK1 expression was an independent prognostic factor. The prognosis was poorer in colorectal cancers that expressed both PROK1 and VEGF relative to the cases that expressed only 1 protein, and the expression of both proteins was found to be an independent prognostic factor.

  16. Elevated serum apolipoprotein E is associated with metastasis and poor prognosis of non-small cell lung cancer.

    Science.gov (United States)

    Luo, Jinmei; Song, Junli; Feng, Pinning; Wang, Yanhong; Long, Weiqing; Liu, Min; Li, Laisheng

    2016-08-01

    Apolipoprotein E (ApoE) is a factor involved in Alzheimer's disease, which recently attracted great attention as an important protein related to tumorigenesis and metastasis. However, serum ApoE levels and its diagnosis and prognosis value in non-small cell lung cancer (NSCLC) patients are still unknown. In 196 NSCLC patients and 203 healthy controls, serum ApoE was measured by turbidimetric immunoassay. The associations of serum ApoE levels with the clinicopathological characteristics and clinical outcomes of NSCLC patients were analyzed. Serum ApoE levels were obviously elevated in NSCLC patients compared with healthy controls (41.6 ± 11.63 vs. 33.8 ± 6.24 mg/L) and were associated with TNM stage, lymph node metastasis status, and distant metastasis status (all P metastasis predicting, the area under the ROC curve was 0.68 at a specificity of 0.56 and sensitivity of 0.73. From ROC/area under curve (AUC) analysis, we used 41.25 mg/L as the serum ApoE cut-off value, to divide NSCLC patients into two groups, the median survival was 11.0 weeks (95 % CI = 8.7 to 13.3) for patients in high serum ApoE group and 20.0 weeks (95 % CI = 15.0 to 25.0) in low serum ApoE group. Serum ApoE levels elevated in NSCLC patients, which also associated with TNM stages, lymph node metastasis, distant metastasis, and poor prognosis, suggest that serum ApoE may act as a useful clinical serological biomarkers for evaluating the progress of NSCLC.

  17. Importance of metabolic changes induced by chemotherapy on prognosis of early-stage breast cancer patients: a review of potential mechanisms.

    Science.gov (United States)

    Gadéa, E; Thivat, E; Planchat, E; Morio, B; Durando, X

    2012-04-01

    Weight variation has been reported as a side effect of chemotherapy treatment in early breast cancer patients and has been identified as a factor of poor prognosis. Causes of weight variation during chemotherapy and mechanisms involved in the poor prognosis have been little studied. Here is reviewed the current knowledge about the main causes and mechanisms involved in body weight change. Special emphasis is placed on factors associated with weight variation which could potentially be involved in the risk of relapse in breast cancer survivors. In recent decades, some studies have investigated the causes of weight variation by studying energy balance of breast cancer patients during chemotherapy. Weight gain or loss may be the consequence of energy imbalance through different factors linked with chemotherapy, such as poor treatment tolerance, decreased muscle mass and function, or hormonal alterations. This results in body composition modifications in favour of fat gain and/or lean body mass loss. Increased adipose tissue, especially in the abdominal region, could induce metabolic disturbances such as insulin resistance, through various pathways involving adipokines. These molecules have growth properties and could therefore play a role in cancer relapse. Understanding such mechanisms is key to developing preventive strategies for improving the prognosis of early-stage breast cancer patients.

  18. Search for potential markers for prostate cancer diagnosis, prognosis and treatment in clinical tissue specimens using amine-specific isobaric tagging (iTRAQ) with two-dimensional liquid chromatography and tandem mass spectrometry.

    Science.gov (United States)

    Garbis, Spiros D; Tyritzis, Stavros I; Roumeliotis, Theodoros; Zerefos, Panagiotis; Giannopoulou, Eugenia G; Vlahou, Antonia; Kossida, Sophia; Diaz, Jose; Vourekas, Stavros; Tamvakopoulos, Constantin; Pavlakis, Kitty; Sanoudou, Despina; Constantinides, Constantinos A

    2008-08-01

    This study aimed to identify candidate new diagnosis and prognosis markers and medicinal targets of prostate cancer (PCa), using state of the art proteomics. A total of 20 prostate tissue specimens from 10 patients with benign prostatic hyperplasia (BPH) and 10 with PCa (Tumour Node Metastasis [TNM] stage T1-T3) were analyzed by isobaric stable isotope labeling (iTRAQ) and two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS) approaches using a hybrid quadrupole time-of-flight system (QqTOF). The study resulted in the reproducible identification of 825 nonredundant gene products (p or =2-fold) and another 35 exhibited down-regulation (prostate tissue specimens. The proteins determined support existing knowledge and uncover novel and promising PCa biomarkers. The PCa proteome found can serve as a useful aid for the identification of improved diagnostic and prognostic markers and ultimately novel chemopreventive and therapeutic targets.

  19. Routine radiography does not have a role in the diagnostic evaluation of ambulatory adult febrile neutropenic cancer patients

    NARCIS (Netherlands)

    Nijhuis, CSMO; Gietema, JA; Vellenga, E; Daenen, SMGJ; De Bont, ESJM; Kamps, WA; Groen, HJM; van der Jagt, EJ; van der Graaf, WTA

    2003-01-01

    Cancer patients treated with chemotherapy are susceptible to bacterial infections. When an adult patient presents with febrile neutropenia. standard diagnostic care includes physical examination, laboratory diagnostics, chest X-ray (CXR) and sinus radiography. However, the yield of routine radiograp

  20. A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Amparo; Loizaga, Ana; Arceo, Raquel; Lacasa, Isabel; Rabade, Ainara [Urology Service, Basurto University Hospital, Bilbao 48013, Bizkaia (Spain); Zorroza, Kerman [Basque Foundation for Health Innovation and Research (BIOEF), DNA Laboratory, Basurto Hospital, Bilbao 48013, Bizkaia (Spain); Mosen-Ansorena, David [Genome Analysis Platform, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); Gonzalez, Esperanza [Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); Aransay, Ana M. [Genome Analysis Platform, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); Falcon-Perez, Juan M. [Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain); IKERBASQUE, Basque Foundation for Science, Bilbao 48011, Bizkaia (Spain); Unda-Urzaiz, Miguel [Urology Service, Basurto University Hospital, Bilbao 48013, Bizkaia (Spain); Royo, Felix, E-mail: froyo.ciberehd@cicbiogune.es [Metabolomics Unit, CIC bioGUNE, CIBERehd, Bizkaia Technology Park, Derio 48160, Bizkaia (Spain)

    2014-01-22

    Bladder cancer is one of the most common cancers and, together with prostate carcinoma, accounts for the majority of the malignancies of the genitourinary tract. Since prognosis ameliorates with early detection, it will be beneficial to have a repertoire of diagnostic markers that could complement the current diagnosis protocols. Recently, cell-secreted extracellular vesicles have received great interest as a source of low invasive disease biomarkers because they are found in many body fluids, including urine. The current work describes a pilot study to generate an array-based catalogue of mRNA associated to urinary vesicles, and also a comparison with samples obtained from bladder cancer patients. After an analysis of presence/absence of transcripts in bladder cancer EVs, a list of genes was selected for further validation using PCR technique. We found four genes differentially expressed in cancer samples. LASS2 and GALNT1 were present in cancer patients, while ARHGEF39 and FOXO3 were found only in non-cancer urinary vesicles. Previous studies have pointed to the involvement of those genes in tumour progression and metastasis.

  1. UROKINASE-TYPE PLASMINOGEN ACTIVATOR, ITS RECEPTOR AND INHIBITOR EXPRESSION IN HEPATOCELLULAR CARCINOMA RELATION TO CANCER INVASIVENESS AND PROGNOSIS

    Institute of Scientific and Technical Information of China (English)

    Zheng Qi; Tang Zhaoyou; Wu Zhiquan; Shi Daren; Tang Huibin; Zhu Yunsong; Song Houyan

    1998-01-01

    Objective:To study the relevance of uPA, uPAR and PAI-1 to hepatocellular carcinoma (HCC). Methods:The expression at protein level of uPA, uPAR and PAI-1was determined in 48 cases of HCC and 12 cases of benign tumors of liver (as control) by immunohistochemistry.Results: When compared to cancer-adjacent liver tissue and the control, positive rate of immune staining for uPA,uPAR and PAI-1 on cell membrane were significantly higher in HCC cells (P<0.05). Positive staining of uPA and uPAR was seen in 16 of 22 and 19 of 22 cases of HCC with invasion, respectively (P<0.01 and P<0.001). In 8 of 8cases with cancer embolus, and in 6 of 6 cases with lymph node metastasis was the expression of positive uPAR.Compared with 2 of 17 cases without recurrence, uPAR was positive in 15 of 17 recurrent cases (P<0.01). In 36cases who survived, 17 was positive uPAR and 15 positive PAI-1, while in 12 cases who died 2 years after surgery, 12were positive for uPAR and 9 positive PAI-1, respectively (P<0.01 and P<0.05). In 15 positive cases for all three parameters, 11 had cancer invasion and 7 died within 2 years, while in negative cases, 2 had invasion and none died within 2 years (P<0.05). Conclusion: Expression of.uPA, uPAR and PAI-1 is increased in HCC, uPA and uPAR may contribute significantly to HCC invasion and metastasis. uPAR and PAI-1 are associated with poor prognosis of HCC.

  2. Composite Biomarkers For Non-invasive Screening, Diagnosis And Prognosis Of Colorectal Cancer

    KAUST Repository

    Mansour, Hicham

    2014-09-11

    The present invention concerns particular biomarkers for diagnosing and/or prognosticating colorectal cancer, in particular in a non-invasive manner. The methods and compositions concern analysis of methylation patterns of one or more genes from a set of 29 genes identified as described herein. In certain embodiments, the gene set includes at least P15.INK4b, SST, GAS7, CNRIP1, and PIK3CG.

  3. The Inflammatory-Nutritional Index: assessing nutritional status and prognosis in gastrointestinal and lung cancer patients

    OpenAIRE

    Carla Alberici Pastore; Silvana Paiva Orlandi; Maria Cristina Gonzalez

    2014-01-01

    Objective: To evaluate the prognostic capacity of the Inflammatory-Nutritional Index (INI) in gastrointestinal and lung cancer patients. Methods: Longitudinal study, including patients from a chemotherapy service in Brazil, between July 2008 and May 2010. INI (Albumin/CRP) and nutritional status (by Subjective Global Assessment - SGA) were evaluated. Risk INI was defined as lower than 0.35. The mean follow-up of survival was 1.6 year. Statistical analyses were performed using Stata 11.1™. Res...

  4. External validation of Adjuvant! Online breast cancer prognosis tool. Prioritising recommendations for improvement.

    Directory of Open Access Journals (Sweden)

    David Hajage

    Full Text Available BACKGROUND: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors. PATIENTS AND METHODS: The French data set is composed of 456 women with early breast cancer. The Dutch data set is composed of 295 women less than 52 years of age. Agreement between observation and Adjuvant! Online prediction was checked, and logistic models were performed to estimate the prognostic information added by risk factors to Adjuvant! Online prediction. RESULTS: Adjuvant! Online prediction was overall well-calibrated in the French data set but failed in some subgroups of such high grade and HER2 positive patients. HER2 status, Mitotic Index and Ki67 added significant information to Adjuvant! Online prediction. In the Dutch data set, the overall 10-year survival was overestimated by Adjuvant! Online, particularly in patients less than 40 years old. CONCLUSION: Adjuvant! Online needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider new predictors such as Ki67, HER2 and Mitotic Index.

  5. Oxidative Stress: A New Target for Pancreatic Cancer Prognosis and Treatment

    Science.gov (United States)

    Martinez-Useros, Javier; Li, Weiyao; Cabeza-Morales, Marticela; Garcia-Foncillas, Jesus

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumors, and its incidence is rising worldwide. Survival can be improved when tumors are detected at an early stage; however, this cancer is usually asymptomatic, and the disease only becomes apparent after metastasis. Several risk factors are associated to this disease. Chronic pancreatitis, diabetes, and some infectious disease are the most relevant risk factors. Incidence of PDAC has increased in the last decades. It is hypothesized it could be due to other acquired risk habits, like smoking, high alcohol intake, and obesity. Indeed, adipose tissue is a dynamic endocrine organ that secretes different pro-inflammatory cytokines, enzymes, and other factors that activate oxidative stress. Reactive oxygen species caused by oxidative stress, damage DNA, proteins, and lipids, and produce several toxic and high mutagenic metabolites that could modify tumor behavior, turning it into a malignant phenotype. Anti-oxidant compounds, like vitamins, are considered protective factors against cancer. Here, we review the literature on oxidative stress, the molecular pathways that activate or counteract oxidative stress, and potential treatment strategies that target reactive oxygen species suitable for this kind of cancer. PMID:28282928

  6. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer.

    Science.gov (United States)

    Kamel, Azza M; Teama, Salwa; Fawzy, Amal; El Deftar, Mervat

    2016-06-01

    Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions.

  7. Analysis of Clinicopathological Feature and Prognosis for 
Leptomeningeal Metastasis in Non-small Cell Lung Cancer

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    Min ZHU

    2016-08-01

    Full Text Available Background and objective Leptomeningeal metastases (LM is one of the most serious complications of advanced non-small cell lung cancer (NSCLC due to the lower quality of life and poor prognosis. The aim of this study is to analyze the clinicopathological features and prognosis of patients with LM from NSCLC (NSCLC-LM. Methods Clinical data of 3 patients with NSCLC-LM collected from January 2015 to June 2016 were analyzed with a brief review. Results All 3 patients had adenocarcinoma histology harboring epidermal growth factor receptor (EGFR exon 21 point mutations (m. Of the 3 cases, 1 was male, 2 were female. The mean age was 61.3 years (range, 59-64 years. The main clinical manifestations and positive physical examination included headache (3/3, dizziness (3/3, nausea (3/3 and vomiting (3/3, epilepsy (2/3, diplopia (1/3, hearing loss (1/3 and meningeal stimulation sign (3/3. The median time from symptom to diagnosis of LM was 2.3 months (range, 1 to 4 months. Except 1 patient with lung cancer and LM diagnosised at the same time, the other 2 cases received the diagnosis of LM after tyrosine kinase inhibitors (TKIs therapy or chemotherapy respectively, the median time from diagnosis of NSCLC to LC was 8.5 months. The brain enhanced magnetic resonance imaging (MRI manifestations of all 3 cases revealed linear meningeal enhancement. Cerebrospinal fluid in 3 cases were positive cytology in whom two cases had EGFR exon 21 L858R mutations, consistenting with the lung tissue. The symptom of the 2 cases improved after TKIs therapy, and temozolomide was used as supplement of 1 case of which the progression-free survival (PFS and overall survival (OS was 4.9 months and 13.9 months respectively. Conclusion Lung adenocarcinoma with sensitive EGFR mutations are likely to appear LM. Lacking of typical symptoms, NSCLC-LM was easily to be missed and misdiagnosed. TKIs therapy combined with temozolomide may be effective therapies for EGFRm-NSCLC-LM patients.

  8. Association of Polymorphisms in three pri-miRNAs that Target Pepsinogen C with the Risk and Prognosis of Gastric Cancer

    Science.gov (United States)

    Wu, Ye-feng; Xu, Qian; He, Cai-yun; Li, Ying; Liu, Jing-wei; Deng, Na; Sun, Li-ping; Yuan, Yuan

    2017-01-01

    We aimed to explore the associations of polymorphisms in three microRNAs (miRNAs) (let-7e rs8111742, miR-365b rs121224 and miR-4795 rs1002765) that target PGC with the risk and prognosis of gastric cancer/atrophic gastritis. Sequenom’s MassArray was used to genotype the miRNA polymorphisms in 724 gastric cancer cases, 862 atrophic gastritis cases and 862 controls in a Chinese population. We found that let-7e rs8111742 and miR-4795 rs1002765 were associated with the risk of gastric cancer in the H. pylori-positive subgroup. MiR-365b rs121224 was associated with the risk of intestinal-type gastric cancer in the alcohol consumption subgroup. Intestinal-type gastric cancer patients at Borrmann stages III-IV who carry the miR-365b rs121224 GG genotype had better prognosis compared with those who carry the CG or CC genotypes. MiR-365b rs121224 was associated with Lauren typing and TNM staging, in which the distribution of GG genotype carriers in intestinal-type gastric cancer and the TNM stage I-II subgroup was higher than that of CG or CC genotypes, which contrasted with the distribution in diffuse-type gastric cancer or TNM III-IV groups. These findings suggested that the polymorphisms in these miRNAs might be biomarkers for gastric cancer risk and prognosis, especially for populations infected with Helicobacter pylori or who consume alcohol. PMID:28067243

  9. Existential Anxiety in Diagnostic Process of Genital Cancer

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    Saliha Hallac

    2011-12-01

    Full Text Available Learning to have a cancer diagnosis is a concrete threat and a stressful life experience for individuals. Cancer is interpreted as fatal, painful, frightening and scary disease by the patients and makes them realize the presence of death and their own mortality. Facing the reality of death brings an existential questioning of self. This questioning is directly related to the interpretation and biopsychosocial characteristics of the individual and clearly influenced by the patients’ previous experiences and type of cancer involved. The occurrence of a genital organ cancer would lead patient to evaluate the meaning of being human and review his life, his values and his routine habits. This process has significant effect upon the patient’s response and coping mechanisms with cancer. Nurses have a unique position among medical team members for helping such patients to find a meaning in their life by providing necessary support at every stage of the cancer.

  10. Targeted therapies with companion diagnostics in the management of breast cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    Myers MB

    2016-01-01

    Full Text Available Meagan B Myers Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA Abstract: Breast cancer is a multifaceted disease exhibiting both intertumoral and intratumoral heterogeneity as well as variable disease course. Over 2 decades of research has advanced the understanding of the molecular substructure of breast cancer, directing the development of new therapeutic strategies against these actionable targets. In vitro diagnostics, and specifically companion diagnostics, have been integral in the successful development and implementation of these targeted therapies, such as those directed against the human epidermal growth factor receptor 2. Lately, there has been a surge in the development, commercialization, and marketing of diagnostic assays to assist in breast cancer patient care. More recently, multigene signature assays, such as Oncotype DX, MammaPrint, and Prosigna, have been integrated in the clinical setting in order to tailor decisions on adjuvant endocrine and chemotherapy treatment. This review provides an overview of the current state of breast cancer management and the use of companion diagnostics to direct personalized approaches in the treatment of breast cancer. Keywords: HER2, precision medicine, in vitro diagnostics, estrogen receptor, multigene assay

  11. Proliferating Cell Nuclear Antigen Has an Association with Prognosis and Risks Factors of Cancer Patients: a Systematic Review.

    Science.gov (United States)

    Lv, Qiongying; Zhang, Juan; Yi, Yuexiong; Huang, Yue; Wang, Yong; Wang, Yijun; Zhang, Wei

    2016-11-01

    Proliferating cell nuclear antigen (PCNA) is reported as a famous marker in various tumors. A couple of articles have been published about the clinical function of PCNA on cancer progression; however, these results are conflicting in some degree. Thus, it is crucial to perform a systematic review and meta-analysis to identify their real actions. Here, we took cervical cancer and glioma as example and then pooled hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (95 % CIs). In the present study, the PCNA expression in cervical cancer and gliomas patients was both correlated with 5-year-overall survival (OS) (HR = 4.41, 95 % CI 2.71-7.17, p = 0.000; HR = 4.40, 95 % CI 3.00-6.47, p = 0.000; respectively). In addition, a fixed effect model revealed a significant association between PCNA and FIGO stage (OR = 4.48, 95 % CI 3.48-5.77, p = 0.000) or WHO grade (OR = 5.64, 95 % CI 4.15-7.68, p = 0.000), rather than age (OR = 1.01, 95 % CI 0.71-1.43, p = 0.957; OR = 1.00, 95 % CI 0.80-1.24, p = 0.989; respectively). No heterogeneity was observed across all studies. According to funnel plot, no publication bias was reported. In conclusion, our systematic review suggests that PCNA expression is significantly associated with poor 5-year survival, advanced stage or higher WHO grade, which might be suggested as a useful prognostic and diagnostic biomarker, or an effective therapy target in cervical cancer, gliomas, or even more cancers.

  12. Overexpression of glucose transporter-1 (GLUT-1) predicts poor prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Cho, Hanbyoul; Lee, You Sun; Kim, Julie; Chung, Joon-Yong; Kim, Jae-Hoon

    2013-11-01

    Illumina microarray was used to identify differentially expressed genes in three epithelial ovarian cancer (EOC) cells. To validate the microarray data, mRNA and protein level of glucose transporter-1 (GLUT-1) was examined. GLUT-1 had an EOC/normal cells ratio of 5.51 based on microarray. Real-time PCR and immunohistochemistry demonstrated that GLUT-1 expression was significantly increased in EOC (p = .029 and p GLUT-1 overexpression (HR = 4.80, p = .027) and lymph node metastases (HR = 8.35, p = .016) conferred a significantly worse overall survival. In conclusion, GLUT-1 expression is remarkably upregulated in EOC and predicts a poor overall survival.

  13. Automated characterization and counting of Ki-67 protein for breast cancer prognosis: A quantitative immunohistochemistry approach.

    Science.gov (United States)

    Mungle, Tushar; Tewary, Suman; Arun, Indu; Basak, Bijan; Agarwal, Sanjit; Ahmed, Rosina; Chatterjee, Sanjoy; Maity, Asok Kumar; Chakraborty, Chandan

    2017-02-01

    Ki-67 protein expression plays an important role in predicting the proliferative status of tumour cells and deciding the future course of therapy in breast cancer. Immunohistochemical (IHC) determination of Ki-67 score or labelling index, by estimating the fraction of Ki67 positively stained tumour cells, is the most widely practiced method to assess tumour proliferation (Dowsett et al. 2011). Accurate manual counting of these cells (specifically nuclei) due to complex and dense distribution of cells, therefore, becomes critical and presents a major challenge to pathologists. In this paper, we suggest a hybrid clustering algorithm to quantify the proliferative index of breast cancer cells based on automated counting of Ki-67 nuclei. The proposed methodology initially pre-processes the IHC images of Ki-67 stained slides of breast cancer. The RGB images are converted to grey, L*a*b*, HSI, YCbCr, YIQ and XYZ colour space. All the stained cells are then characterized by two stage segmentation process. Fuzzy C-means quantifies all the stained cells as one cluster. The blue channel of the first stage output is given as input to k-means algorithm, which provides separate cluster for Ki-67 positive and negative cells. The count of positive and negative nuclei is used to calculate the F-measure for each colour space. A comparative study of our work with the expert opinion is studied to evaluate the error rate. The positive and negative nuclei detection results for all colour spaces are compared with the ground truth for validation and F-measure is calculated. The F-measure for L*a*b* colour space (0.8847) provides the best statistical result as compared to grey, HSI, YCbCr, YIQ and XYZ colour space. Further, a study is carried out to count nuclei manually and automatically from the proposed algorithm with an average error rate of 6.84% which is significant. The study provides an automated count of positive and negative nuclei using L*a*b*colour space and hybrid

  14. Gene Expression Signature TOPFOX Reflecting Chromosomal Instability Refines Prediction of Prognosis in Grade 2 Breast Cancer

    DEFF Research Database (Denmark)

    Szasz, A.; Li, Qiyuan; Sztupinszki, Z.

    2011-01-01

    were diagnosed between 1999–2002 at the Budai MA´ V Hospital. 187 formalinfixed, paraffin-embedded breast cancer samples were included in the qPCR-based measurement of expression of AURKA, FOXM1, TOP2A and TPX2 genes. The expression of the genes were correlated to recurrencefree survival (RFS......Purpose: To assess the ability of genes selected from those reflecting chromosomal instability to identify good and poor prognostic subsets of Grade 2 breast carcinomas. Methods: We selected genes for splitting grade 2 tumours into low and high grade type groups by using public databases. Patients...

  15. Applying a radiomics approach to predict prognosis of lung cancer patients

    Science.gov (United States)

    Emaminejad, Nastaran; Yan, Shiju; Wang, Yunzhi; Qian, Wei; Guan, Yubao; Zheng, Bin

    2016-03-01

    Radiomics is an emerging technology to decode tumor phenotype based on quantitative analysis of image features computed from radiographic images. In this study, we applied Radiomics concept to investigate the association among the CT image features of lung tumors, which are either quantitatively computed or subjectively rated by radiologists, and two genomic biomarkers namely, protein expression of the excision repair cross-complementing 1 (ERCC1) genes and a regulatory subunit of ribonucleotide reductase (RRM1), in predicting disease-free survival (DFS) of lung cancer patients after surgery. An image dataset involving 94 patients was used. Among them, 20 had cancer recurrence within 3 years, while 74 patients remained DFS. After tumor segmentation, 35 image features were computed from CT images. Using the Weka data mining software package, we selected 10 non-redundant image features. Applying a SMOTE algorithm to generate synthetic data to balance case numbers in two DFS ("yes" and "no") groups and a leave-one-case-out training/testing method, we optimized and compared a number of machine learning classifiers using (1) quantitative image (QI) features, (2) subjective rated (SR) features, and (3) genomic biomarkers (GB). Data analyses showed relatively lower correlation among the QI, SR and GB prediction results (with Pearson correlation coefficients 0.5). Among them, using QI yielded the highest performance.

  16. The role of macrophages polarization in predicting prognosis of radically resected gastric cancer patients

    Science.gov (United States)

    Pantano, Francesco; Berti, Pierpaolo; Guida, Francesco Maria; Perrone, Giuseppe; Vincenzi, Bruno; Amato, Michelina Maria Carla; Righi, Daniela; Dell'Aquila, Emanuela; Graziano, Francesco; Catalano, Vincenzo; Caricato, Marco; Rizzo, Sergio; Muda, Andrea Onetti; Russo, Antonio; Tonini, Giuseppe; Santini, Daniele

    2013-01-01

    Tumour-associated Macrophages (TAM) present two different polarizations: classical (M1) characterized by immunostimulation activity and tumour suppression; alternative (M2) characterized by tumour promotion and immune suppression. In this retrospective study, we evaluated the correlation between the two forms of TAM with survival time in radically resected gastric cancer patients. A total of 52 chemo- and radio-naive patients were included. Two slides were prepared for each patient and double-stained for CD68/NOS2 (M1) or CD68/CD163 (M2) and five representative high-power fields per slide were evaluated for TAM count. The median value of the two macrophage populations density and the median value of M1/M2 ratio were used as cut-off. Twenty-seven patients with M1 density above-the-median had a significantly higher survival compared to those below the median. Twenty-six patients with M1/M2 ratio above the median showed median OS of 27.2 months compared to 15.5 months of the patients below the median. No association between M2 macrophage density and patient's outcome was found. In multivariate analysis, M1/M2 was a positive independent predictor of survival. The M1 macrophage density and M1/M2 ratio, as confirmed in multivariate analysis, are factors that can help in predicting patients survival time after radical surgery for gastric cancer. PMID:24283947

  17. Correlation between cytological and histological grading of breast cancer and its role in prognosis

    Science.gov (United States)

    Pal, Shweta; Gupta, Mohan Lal

    2016-01-01

    Context: Assigning grade to breast cancer on FNAC provides prognostic information and guides optimal therapy. Aims: The present study was undertaken to grade breast carcinoma on cytology by Robinson's grading system and correlate it with Elstons modified Bloom Richardson histological grading system. Settings and Design: It is a prospective study done on fifty cases of breast cancer reported on cytology. Materials and Methods: Fifty patients who underwent FNAC and mastectomy for breast carcinoma were cytologically and histologically graded. Correlation between cytological and histological grading system was determined. Sensitivity and specificity of Robinson's cytological grading system was calculated in each grade. All cases evaluated for presence of metastasis to axillary lymph nodes. Statistical Analysis Used: Correlation between cytological and histological grading was established using the non parametric Spearman’ s correlation coefficient. Results: Concordance rate between cytological and histological grade was 78%. The coefficient of correlation between cytological grade and histological grade was 0.804 and P value was <0.001 which indicated a strong correlation and significant association between the cytological and histological grade. Sensitivity was maximum in cytological grade I tumors (100%) and least in cytological grade III tumors (45.45%). Specificity was maximum in cytological grade III tumors (94.87%) and least in cytological grade II tumors (72.72%). The incidence of axillary lymph node metastasis was maximum in cytological grade III tumors and grade I tumors. Conclusions: Cytological grade strongly predicts histological grade and is useful in selecting neoadjuvant chemotherapy. PMID:28028331

  18. ID2 predicts poor prognosis in breast cancer, especially in triple-negative breast cancer, and inhibits E-cadherin expression

    Directory of Open Access Journals (Sweden)

    Li K

    2014-06-01

    classified into four subgroups with different DFS (P=0.023. Conclusion: The overexpression of ID2 can be used as a prognostic marker in breast cancer patients, especially in triple-negative breast cancer patients. ID proteins were still, unexpectedly, revealed to inhibit E-cadherin abundance. Keywords: breast cancer, prognosis, biomarker

  19. A CLDN1-negative phenotype predicts poor prognosis in triple-negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Fei Ma

    Full Text Available INTRODUCTION: Triple-negative breast cancer (TNBC is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs. MATERIALS AND METHODS: The surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed. RESULTS: Positive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P = 0.014. The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P = 0.003. Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS in both lymph node positive (LN+ and negative (LN- cases (both P<0.001. Similarly it was also associated with shorter overall survival (OS(P = 0.003 in LN+ cases; P = 0.018 in LN- cases. In the LN+ subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P = 0.008. Multivariate analysis revealed that negative CLDN1 expression was an independent prognostic factor for high risk of both recurrence and death (HR 5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P = 0.002. However, neither CLDN4 nor CLDN7 expression was associated with survival. CONCLUSION: In TNBC, the CLDN1-negative phenotype predicts a high risk of recurrence and death. The absence of CLDN1 expression is strongly suggested to be an independent adverse prognostic factor

  20. Highly Sensitive Marker Panel for Guidance in Lung Cancer Rapid Diagnostic Units

    Science.gov (United States)

    Blanco-Prieto, Sonia; De Chiara, Loretta; Rodríguez-Girondo, Mar; Vázquez-Iglesias, Lorena; Rodríguez-Berrocal, Francisco Javier; Fernández-Villar, Alberto; Botana-Rial, María Isabel; de la Cadena, María Páez

    2017-01-01

    While evidence for lung cancer screening implementation in Europe is awaited, Rapid Diagnostic Units have been established in many hospitals to accelerate the early diagnosis of lung cancer. We seek to develop an algorithm to detect lung cancer in a symptomatic population attending such unit, based on a sensitive serum marker panel. Serum concentrations of Epidermal Growth Factor, sCD26, Calprotectin, Matrix Metalloproteinases −1, −7, −9, CEA and CYFRA 21.1 were determined in 140 patients with respiratory symptoms (lung cancer and controls with/without benign pathology). Logistic Lasso regression was performed to derive a lung cancer prediction model, and the resulting algorithm was tested in a validation set. A classification rule based on EGF, sCD26, Calprotectin and CEA was established, able to reasonably discriminate lung cancer with 97% sensitivity and 43% specificity in the training set, and 91.7% sensitivity and 45.4% specificity in the validation set. Overall, the panel identified with high sensitivity stage I non-small cell lung cancer (94.7%) and 100% small-cell lung cancers. Our study provides a sensitive 4-marker classification algorithm for lung cancer detection to aid in the management of suspicious lung cancer patients in the context of Rapid Diagnostic Units. PMID:28117344

  1. The influence of goal-directed fluid therapy on the prognosis of elderly patients with hypertension and gastric cancer surgery

    Directory of Open Access Journals (Sweden)

    Zeng K

    2014-10-01

    Full Text Available Kai Zeng,* Yanzhen Li,* Min Liang, Youguang Gao, Hongda Cai, Caizhu LinDepartment of Anesthesia, the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of China*These authors contributed equally to this workPurpose: We aimed to investigate the influence of perioperative goal-directed fluid therapy (GDFT on the prognosis of elderly patients with gastric cancer and hypertension. Methods: Sixty elderly patients (>60 years old with primary hypertension who received gastric cancer radical surgery and who were American Society of Anesthesiologists (ASA class II or III were enrolled in the current study. Selected patients were divided randomly into two arms, comprising a conventional intraoperative fluid management arm (arm C, n=30 and a GDFT arm (arm G, n=30. Patients in arm C were infused with crystalloids or colloids according to the methods of Miller’s Anesthesia (6th edition, while those in arm G were infused with 200 mL hydroxyethyl starch over 15 minutes under the FloTrac/Vigileo monitoring system, with stroke volume variation between 8% and 13%. Hemodynamics and tissue perfusion laboratory indicators in patients were recorded continuously from 30 minutes before the operation to 24 hours after the operation. Results: Compared with arm C, the average intraoperative intravenous infusion quantity in arm G was significantly reduced (2,732±488 mL versus 3,135±346 mL, P<0.05, whereas average colloid fluid volume was significantly increased (1,235±360 mL versus 760±280 mL, P<0.05. In addition, there were more patients exhibiting intraoperatively and postoperatively stable hemodynamics and less patients with low blood pressure in arm G. Postoperative complications were less frequent, and the time of postoperative hospital stay shorter, in arm G. No significant differences were observed in mortality between the two arms.Conclusion: Our research showed that GDFT stabilized perioperative hemodynamics and reduced the

  2. Differentiated Thyroid Cancer with Extrathyroidal Extension: Prognosis and the Role of External Beam Radiotherapy

    Directory of Open Access Journals (Sweden)

    Michael A. Sia

    2010-01-01

    Full Text Available A study was performed to identify variables that affected cause-specific survival (CSS and local relapse-free rate (LRFR in patients with differentiated thyroid cancer (DTC and extrathyroid extension (ETE and to examine the role of external beam radiotherapy (XRT. Prognostic factors were similar to those found in studies of all patients with DTC. In patients with postoperative gross residual disease treated with radiotherapy, 10-year CSS and LRFR were 48% and 90%. For patients with no residual or microscopic disease, 10-year CSS and LRFR were 92% and 93%. In patients older than 60 years with T3 ETE but no gross residual disease postoperatively there was an improved LRFR at 5 years of 96%, compared to 87.5% without XRT (P=.02. Patients with gross ETE benefit from XRT and there may be a potential benefit in reducing locoregional failure in patients over 60 years with minimal extrathyroidal extension (T3.

  3. Dipeptidyl-peptidase IV activity is correlated with colorectal cancer prognosis.

    Directory of Open Access Journals (Sweden)

    Gorka Larrinaga

    Full Text Available Dipeptidyl-peptidase IV (EC 3.4.14.5 (DPPIV is a serine peptidase involved in cell differentiation, adhesion, immune modulation and apoptosis, functions that control neoplastic transformation. Previous studies have demonstrated altered expression and activity of tissue and circulating DPPIV in several cancers and proposed its potential usefulness for early diagnosis in colorectal cancer (CRC.The activity and mRNA and protein expression of DPPIV was prospectively analyzed in adenocarcinomas, adenomas, uninvolved colorectal mucosa and plasma from 116 CRC patients by fluorimetric, quantitative RT-PCR and immunohistochemical methods. Results were correlated with the most important classic pathological data related to aggressiveness and with 5-year survival rates. Results showed that: 1 mRNA levels and activity of DPPIV increased in colorectal neoplasms (Kruskal-Wallis test, p<0.01; 2 Both adenomas and CRCs displayed positive cytoplasmic immunostaining with luminal membrane reinforcement; 3 Plasmatic DPPIV activity was lower in CRC patients than in healthy subjects (Mann-U test, p<0.01; 4 Plasmatic DPPIV activity was associated with worse overall and disease-free survivals (log-rank p<0.01, Cox analysis p<0.01.1 Up-regulation of DPPIV in colorectal tumors suggests a role for this enzyme in the neoplastic transformation of colorectal tissues. This finding opens the possibility for new therapeutic targets in these patients. 2 Plasmatic DPPIV is an independent prognostic factor in survival of CRC patients. The determination of DPPIV activity levels in the plasma may be a safe, minimally invasive and inexpensive way to define the aggressiveness of CRC in daily practice.

  4. Polymorphisms in the RANK/RANKL genes and their effect on bone specific prognosis in breast cancer patients.

    Science.gov (United States)

    Hein, Alexander; Bayer, Christian M; Schrauder, Michael G; Häberle, Lothar; Heusinger, Katharina; Strick, Reiner; Ruebner, Matthias; Lux, Michael P; Renner, Stefan P; Schulz-Wendtland, Rüdiger; Ekici, Arif B; Hartmann, Arndt; Beckmann, Matthias W; Fasching, Peter A

    2014-01-01

    The receptor activator of NF-κB (RANK) pathway is involved in bone health as well as breast cancer (BC) pathogenesis and progression. Whereas the therapeutic implication of this pathway is established for the treatment of osteoporosis and bone metastases, the application in adjuvant BC is currently investigated. As genetic variants in this pathway have been described to influence bone health, aim of this study was the prognostic relevance of genetic variants in RANK and RANKL. Single nucleotide polymorphisms in RANK(L) (rs1054016/rs1805034/rs35211496) were genotyped and analyzed with regard to bone metastasis-free survival (BMFS), disease-free survival, and overall survival for a retrospective cohort of 1251 patients. Cox proportional hazard models were built to examine the prognostic influence in addition to commonly established prognostic factors. The SNP rs1054016 seems to influence BMFS. Patients with two minor alleles had a more favorable prognosis than patients with at least one common allele (HR 0.37 (95% CI: 0.17, 0.84)), whereas other outcome parameters remained unaffected. rs1805034 and rs35211496 had no prognostic relevance. The effect of rs1054016(RANKL) adds to the evidence that the RANK pathway plays a role in BC pathogenesis and progression with respect to BMFS, emphasizing the connection between BC and bone health.

  5. Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy

    Directory of Open Access Journals (Sweden)

    Keck Bastian

    2013-02-01

    Full Text Available Abstract Background Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention. Methods We reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC and 9 micropapillary (MPC carcinomas of the bladder were identified. Kaplan Meier analysis and backward multivariate Cox’s proportional hazards regression analysis were performed to compare overall survival between the three histologic subtypes. Results Patients suffering from PUC have the worst clinical outcome regarding overall survival compared to conventional UC and MPC of the bladder that in turn seem have to best clinical outcome (27.4 months, 62.6 months, and 64.2 months, respectively; p=0.013 by Kaplan Meier analysis. Backward multivariate Cox´s proportional hazards regression analysis (adjusted to relevant clinicopathological parameters showed a hazard ratio of 3.2 (p=0.045 for PUC in contrast to patients suffering from MPC. Conclusions Histopathological diagnosis of rare variants of urothelial carcinoma can identify patients with poor prognosis.

  6. Polymorphisms in the RANK/RANKL Genes and Their Effect on Bone Specific Prognosis in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Alexander Hein

    2014-01-01

    Full Text Available The receptor activator of NF-κB (RANK pathway is involved in bone health as well as breast cancer (BC pathogenesis and progression. Whereas the therapeutic implication of this pathway is established for the treatment of osteoporosis and bone metastases, the application in adjuvant BC is currently investigated. As genetic variants in this pathway have been described to influence bone health, aim of this study was the prognostic relevance of genetic variants in RANK and RANKL. Single nucleotide polymorphisms in RANK(L (rs1054016/rs1805034/rs35211496 were genotyped and analyzed with regard to bone metastasis-free survival (BMFS, disease-free survival, and overall survival for a retrospective cohort of 1251 patients. Cox proportional hazard models were built to examine the prognostic influence in addition to commonly established prognostic factors. The SNP rs1054016 seems to influence BMFS. Patients with two minor alleles had a more favorable prognosis than patients with at least one common allele (HR 0.37 (95% CI: 0.17, 0.84, whereas other outcome parameters remained unaffected. rs1805034 and rs35211496 had no prognostic relevance. The effect of rs1054016(RANKL adds to the evidence that the RANK pathway plays a role in BC pathogenesis and progression with respect to BMFS, emphasizing the connection between BC and bone health.

  7. The Significance of Molecular Classification in Breast Cancer for Prognosis%乳腺癌分子分型对乳腺癌预后的意义

    Institute of Scientific and Technical Information of China (English)

    王会东

    2013-01-01

    Objective To investigate the molecular classification and prognosis of breast cancer and the relationship between . Methods Retrospective analysis of 316 cases of female primary breast cancer patients with the clinical pathological ,average age 54.5 years.According to estrogen receptor (ER),pregnancy hormone receptor (PR) and human epidermal growth factor receptor 2(HER2) immu-nohistochemical findings,breast cancer types as type Luminal A ,type Luminal B,triple-negative and HER2 positive type,differences in mo-lecular classification of breast cancer prognosis were observed ,various types of patients with postoperative disease -free survival were com-pared.Results The patients were followed up for 5~124 months,a median follow-up time of 58 months,32 patients had recurrence of metas-tasis or death,the single factor analysis showed that the breast cancer disease free survival and molecular types had relation .Conclusion The molecular classification of breast cancer accurately reflects the prognosis of breast cancer .Type Luminal has the best prognosis ,while triple-negative has the worst prognosis .%  目的 探讨乳腺癌分子分型与预后之间的关系。方法 回顾性分析316例原发性乳腺癌患者的临床病理资料,患者均为女性,平均年龄54.5岁。根据雌激素受体(ER)、孕激素受体(PR)及人类表皮生长因子受体2(HER2)的免疫组织化学结果,乳腺癌分型为Luminal A型、Luminal B型、三阴型及 HER2阳性型,观察不同分子分型乳腺癌的预后,比较各型患者术后的无病生存期。结果 随访5~124个月,中位随访时间58个月,32例患者复发转移或死亡,单因素分析示乳腺癌无病生存期与分子分型有关。结论 乳腺癌的分子分型能够准确反映乳腺癌的预后,Luminal型预后最好,而三阴型预后最差。

  8. Decreased FOXF2 mRNA expression indicates early-onset metastasis and poor prognosis for breast cancer patients with histological grade II tumor.

    Directory of Open Access Journals (Sweden)

    Peng-Zhou Kong

    Full Text Available The transcription factor, FOXF2, plays an important role in tissue development, extracellular matrix synthesis, and epithelial-mesenchymal interactions, implying that it may be associated with the metastatic capabilities of cancer cells. However, the relationship between FOXF2 expression and breast cancer progression, metastasis, and prognosis, remains to be elucidated. In this study, FOXF2 mRNA levels in 305 primary breast cancer tissues were examined using RT-QPCR. Results showed that FOXF2 mRNA levels in primary breast cancer were negatively associated with tumor progression, including tumor size, number of metastatic lymph nodes, and clinical stage. Patients with low FOXF2 mRNA levels had a high risk of relapse and metastasis within three years. Low FOXF2 mRNA levels could predict shorter disease-free survival for those patients with histological grade II and triple-negative breast cancer. Taken together, we conclude that decreased FOXF2 expression indicates the early-onset metastasis and poor prognosis for patients with histological grade II and triple-negative breast cancer.

  9. Decreased FOXF2 mRNA expression indicates early-onset metastasis and poor prognosis for breast cancer patients with histological grade II tumor.

    Science.gov (United States)

    Kong, Peng-Zhou; Yang, Fan; Li, Lin; Li, Xiao-Qing; Feng, Yu-Mei

    2013-01-01

    The transcription factor, FOXF2, plays an important role in tissue development, extracellular matrix synthesis, and epithelial-mesenchymal interactions, implying that it may be associated with the metastatic capabilities of cancer cells. However, the relationship between FOXF2 expression and breast cancer progression, metastasis, and prognosis, remains to be elucidated. In this study, FOXF2 mRNA levels in 305 primary breast cancer tissues were examined using RT-QPCR. Results showed that FOXF2 mRNA levels in primary breast cancer were negatively associated with tumor progression, including tumor size, number of metastatic lymph nodes, and clinical stage. Patients with low FOXF2 mRNA levels had a high risk of relapse and metastasis within three years. Low FOXF2 mRNA levels could predict shorter disease-free survival for those patients with histological grade II and triple-negative breast cancer. Taken together, we conclude that decreased FOXF2 expression indicates the early-onset metastasis and poor prognosis for patients with histological grade II and triple-negative breast cancer.

  10. In-vitro and in-vivo diagnostic techniques for prostate cancer: a review.

    Science.gov (United States)

    McClure, Patrick; Elnakib, Ahmed; Abou El-Ghar, Mohamed; Khalifa, Fahmi; Soliman, Ahmed; El-Diasty, Tarek; Suri, Jasjit S; Elmaghraby, Adel; El-Baz, Ayman

    2014-10-01

    This paper overviews one of the most important, interesting, and challenging problems in oncology, early diagnosis of prostate cancer. Developing effective diagnostic techniques for prostate cancer is of great clinical importance and can improve the effectiveness of treatment and increase the patient's chance of survival. The main focus of this study is to overview the different in-vitro and in-vivo technologies for diagnosing prostate cancer. This review discusses the current clinically used in-vitro cancer diagnostic tools, such as biomarker tests and needle biopsies and including their applications, advantages, and limitations. Moreover, the current in-vitro research tools that focus on the role of nanotechnology in prostate cancer diagnosis have been detailed. In addition to the in-vitro techniques, the current study discusses in detail developed in-vivo non-invasive state-of-the-art Computer-Aided Diagnosis (CAD) systems for prostate cancer based on analyzing Transrectal Ultrasound (TRUS) and different types of magnetic resonance imaging (MRI), e.g., T2-MRI, Diffusion Weighted Imaging (DWI), Dynamic Contrast Enhanced (DCE)-MRI, and multi-parametric MRI, focusing on their implementation, experimental procedures, and reported outcomes. Furthermore, the paper addresses the limitations of the current prostate cancer diagnostic techniques, outlines the challenges that these techniques face, and introduces the recent trends to solve these challenges, which include biomarkers used in in-vitro lab-on-a-chip nanotechnology-based methods.

  11. Decentral gene expression analysis: analytical validation of the Endopredict genomic multianalyte breast cancer prognosis test

    Directory of Open Access Journals (Sweden)

    Kronenwett Ralf

    2012-10-01

    Full Text Available Abstract Background EndoPredict (EP is a clinically validated multianalyte gene expression test to predict distant metastasis in ER-positive, HER2-negative breast cancer treated with endocrine therapy alone. The test is based on the combined analysis of 12 genes in formalin-fixed, paraffin-embedded (FFPE tissue by reverse transcription-quantitative real-time PCR (RT-qPCR. Recently, it was shown that EP is feasible for reliable decentralized assessment of gene expression. The aim of this study was the analytical validation of the performance characteristics of the assay and its verification in a molecular-pathological routine laboratory. Methods Gene expression values to calculate the EP score were assayed by one-step RT-qPCR using RNA from FFPE tumor tissue. Limit of blank, limit of detection, linear range, and PCR efficiency were assessed for each of the 12 PCR assays using serial samples dilutions. Different breast cancer samples were used to evaluate RNA input range, precision and inter-laboratory variability. Results PCR assays were linear up to Cq values between 35.1 and 37.2. Amplification efficiencies ranged from 75% to 101%. The RNA input range without considerable change of the EP score was between 0.16 and 18.5 ng/μl. Analysis of precision (variation of day, day time, instrument, operator, reagent lots resulted in a total noise (standard deviation of 0.16 EP score units on a scale from 0 to 15. The major part of the total noise (SD 0.14 was caused by the replicate-to-replicate noise of the PCR assays (repeatability and was not associated with different operating conditions (reproducibility. Performance characteristics established in the manufacturer’s laboratory were verified in a routine molecular pathology laboratory. Comparison of 10 tumor samples analyzed in two different laboratories showed a Pearson coefficient of 0.995 and a mean deviation of 0.15 score units. Conclusions The EP test showed reproducible performance

  12. True Local Recurrences after Breast Conserving Surgery have Poor Prognosis in Patients with Early Breast Cancer

    Science.gov (United States)

    Sarsenov, Dauren; Ilgun, Serkan; Ordu, Cetin; Alco, Gul; Bozdogan, Atilla; Elbuken, Filiz; Nur Pilanci, Kezban; Agacayak, Filiz; Erdogan, Zeynep; Eralp, Yesim; Dincer, Maktav

    2016-01-01

    Background: This study was aimed at investigating clinical and histopathologic features of ipsilateral breast tumor recurrences (IBTR) and their effects on survival after breast conservation therapy. Methods: 1,400 patients who were treated between 1998 and 2007 and had breast-conserving surgery (BCS) for early breast cancer (cT1-2/N0-1/M0) were evaluated. Demographic and pathologic parameters, radiologic data, treatment, and follow-up related features of the patients were recorded. Results: 53 patients (3.8%) had IBTR after BCS within a median follow-up of 70 months. The mean age was 45.7 years (range, 27-87 years), and 22 patients (41.5%) were younger than 40 years. 33 patients (62.3%) had true recurrence (TR) and 20 were classified as new primary (NP). The median time to recurrence was shorter in TR group than in NP group (37.0 (6-216) and 47.5 (11-192) months respectively; p = 0.338). Progesterone receptor positivity was significantly higher in the NP group (p = 0.005). The overall 5-year survival rate in the NP group (95.0%) was significantly higher than that of the TR group (74.7%, p 20 mm), high grade tumor and triple-negative molecular phenotype along with developing TR negatively affected overall survival (hazard ratios were 4.2 (CI 0.98-22.76), 4.6 (CI 1.07-13.03), 4.0 (CI 0.68-46.10), 6.5 (CI 0.03-0.68), and 6.5 (CI 0.02- 0.80) respectively, p 2 cm), high grade, triple negative phenotype, and having true recurrence were identified as independent prognostic factors with a negative impact on overall survival in this dataset of patients with recurrent breast cancer. In conjunction with a more intensive follow-up program, the role of adjuvant therapy strategies should be explored further in young patients with large and high-risk tumors to reduce the risk of TR. PMID:27158571

  13. Conformational SERS Classification of K-Ras Point Mutations for Cancer Diagnostics.

    Science.gov (United States)

    Morla-Folch, Judit; Gisbert-Quilis, Patricia; Masetti, Matteo; Garcia-Rico, Eduardo; Alvarez-Puebla, Ramon A; Guerrini, Luca

    2017-02-20

    Point mutations in Ras oncogenes are routinely screened for diagnostics and treatment of tumors (especially in colorectal cancer). Here, we develop an optical approach based on direct SERS coupled with chemometrics for the study of the specific conformations that single-point mutations impose on a relatively large fragment of the K-Ras gene (141 nucleobases). Results obtained offer the unambiguous classification of different mutations providing a potentially useful insight for diagnostics and treatment of cancer in a sensitive, fast, direct and inexpensive manner.

  14. Uptodate view on diagnostics and treatment of medullary thyroid cancer

    Directory of Open Access Journals (Sweden)

    D O Gazizova

    2013-09-01

    Full Text Available During last 4 years leading endocrine societies of the world published clinical recommendations on diag nostics and treatment of medullary thyroid cancer. The article covers most aspects of following patients with this pathology.

  15. Prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Lyu Jima; Hao Xuezhi; Hui Zhouguang; Liang Jun; Zhou Zongmei; Feng Qinfu; Xiao Zefen

    2014-01-01

    Background The prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer (NSCLC) remains unclear.This study intends to identify the prognostic factors and to optimize treatments for these patients under update conditions.Methods The data of 124 NSCLC patients who underwent R1-resection at the bronchial stump was reviewed.There were 41 patients in the surgery group (S),21 in the postoperative radiotherapy (PORT) group (S+R),30 in the postoperative chemotherapy (POCT) group (S+C),and 32 in the PORT plus POCT group (S+R+C).The constitute proportion in different groups was tested using the X2 method,univariate analysis was performed using the Kaplan-Meier and log-rank method,and multivariate analysis was done using the Cox hazard regression with entry factors including age,sex,pathological type and stage,classification of the residual disease,and treatment procedure.The process was performed stepwise backward with a maximum iteration of 20 and an entry possibility of 0.05 as well as an excluded possibility of 0.10 at each step.Results In univariate analysis,survival was more favorable for patients with squamous cell carcinoma,early pathological T or N stage,and chemotherapy or radiotherapy.There was no significant difference in the survival for patients with different types of the residual disease,except for the difference between patients with carcinoma in situ and lymphangiosis carcinomatosa (P=0.030).The survival for patients receiving chemoradiotherapy was superior to that for those undergoing surgery alone (P=0.016).In multivariate analysis,the pathological type (HR 2.51,95% CI 1.59 to 3.96,P=0.000),pathological T (HR 1.29,95% CI 1.04 to 1.60,P=-0.021) or N stage (HR 2.04,95% CI 1.40 to 2.98,P=0.000),and chemotherapy (HR 0.24,95% CI 0.13 to 0.43,P=0.000) were independent prognostic factors.Conclusion Patients with squamous cell carcinoma,early pathological T or N stage,or receiving chemotherapy had a more favorable

  16. Diagnostic competence of Swiss general practitioners in skin cancer

    OpenAIRE

    Badertscher, N; Braun, R P; Held, U; Kofmehl, R; Senn, O; Hofbauer, G.F.; Rossi, P O; Wensing, M.J.; Rosemann, T.; Tandjung, R

    2013-01-01

    QUESTIONS UNDER STUDY: In Switzerland, skin cancer is one of the most prevalent neoplasms. General practitioners (GPs) are often faced with suspicious skin lesions in their patients. The aim of our study was to assess GPs' competence to diagnose skin cancer and to examine whether this can be improved by a one-day dermatologic education programme. METHODS: Study design: Pre / post-intervention study. Study population: 78 GPs in the Canton of Zurich. Intervention: A one day dermatologic educ...

  17. The diagnostic value of transrectal ultrasonographic features in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoli Zou; Guang Yang; Hui Wang

    2012-01-01

    Objective: The aim of the study was to detect the valuable ultrasonographic features in diagnosing prostate cancer.Methods: The patients who underwent transrectal ultrasound in the period from May 2005 to October 2009 at the 1st Affiliated Hospital of Dalian Medical University, China, were included, with needle biopsy diagnosis for patients with the prostate cancer and prostatic hyperplasia.Seventy-four cases of prostate cancer were diagnosed as adenocarcinoma, compared with 51 cases diagnosed as prostatic hyperplasia.Retrospective analysis of patients with transrectal ultrasound were done, comparing the difference between the two groups in the echo level (hypoechogenic), outlines (ill-defined margin), posterior acoustic attenuation, periphery halo, microcalcification incidence, the blood supply level, peak systolic velocity (Vs) and resistance index (RI).Results: The ratios of hypoechogenic lesions in the prostate cancer group and prostatic hyperplasia group were 56.76% and 35.90%, respectively (P 0.05).Vs of the two groups were (44.00 ± 15.30) cm/s and (17.32 ± 4.65) cm/s, respectively (P < 0.05).RI of the two groups were 0.76 ± 0.10, and 0.51 ± 0.03 respectively (P < 0.05).The significant correlation was designated in the blood supply level between the prostate cancer group and prostatic hyperplasia group (r = -0.388, P < 0.01).Higher revascularization grade was seen in the prostate cancer group compared to benign prostatic hyperplasia group.Conclusion: (1) The significant roles for diagnosing prostate cancer are hypoechogenic, irregular outlines, spiculation, microcalcification, high revascularization grade, posterior acoustic attenuation, high Vs and high RI.(2) It could not help in diagnosing prostate cancer with ultrasonographic periphery halo or not.

  18. New Diagnostic and Therapeutic Approaches to Eradicating Recurrent Breast Cancer

    Science.gov (United States)

    2015-09-01

    international scientific conference, where they gave poster or oral presentations . For example, students attended the San Antonio Breast Cancer Conference...cancer research/patient advocates (Liz Frank and Ruth Fax. The retreat was held over a 2-day period in which investigators gave formal presentations ...of their work in progress and we had dedicated discussion time for feedback and exchange of ideas. C. What opportunities for training and

  19. A decision-analytic approach to define poor prognosis patients: a case study for non-seminomatous germ cell cancer patients

    Directory of Open Access Journals (Sweden)

    Steyerberg Ewout W

    2008-01-01

    Full Text Available Abstract Background Classification systems may be useful to direct more aggressive treatment to cancer patients with a relatively poor prognosis. The definition of 'poor prognosis' often lacks a formal basis. We propose a decision analytic approach to weigh benefits and harms explicitly to define the treatment threshold for more aggressive treatment. This approach is illustrated by a case study in advanced testicular cancer, where patients with a high risk of mortality under standard treatment may be eligible for high-dose chemotherapy with stem cell support, which is currently defined by the IGCC classification. Methods We used published literature to estimate the benefit and harm of high-dose chemotherapy (HD-CT versus standard-dose chemotherapy (SD-CT for patients with advanced non-seminomatous germ cell cancer. Benefit and harm were defined as the reduction and increase in absolute risk of mortality due to HD-CT respectively. Harm included early and late treatment related death, and treatment related morbidity (weighted by 'utility'. Results We considered a conservative and an optimistic benefit of 30 and 40% risk reduction respectively. We estimated the excess treatment related mortality at 2%. When treatment related morbidity was taken into account, the harm of HD-CT increased to 5%. With a relative benefit of 30% and harm of 2 or 5%, HD-CT might be beneficial for patients with over 7 or 17% risk of cancer specific mortality with SD chemotherapy, while with a relative benefit of 40% HD-CT was beneficial over 5 and 12.5% risk respectively. Compared to the IGCC classification 14% of the patients would receive more aggressive treatment, and 2% less intensive treatment. Conclusion Benefit and harm can be used to define 'poor prognosis' explicitly for non-seminomatous germ cell cancer patients who are considered for high-dose chemotherapy. This approach can readily be adapted to new results and extended to other cancers to define candidates for

  20. HER2 and β-catenin protein location: importance in the prognosis of breast cancer patients and their correlation when breast cancer cells suffer stressful situations.

    Science.gov (United States)

    Cuello-Carrión, F Darío; Shortrede, Jorge E; Alvarez-Olmedo, Daiana; Cayado-Gutiérrez, Niubys; Castro, Gisela N; Zoppino, Felipe C M; Guerrero, Martín; Martinis, Estefania; Wuilloud, Rodolfo; Gómez, Nidia N; Biaggio, Verónica; Orozco, Javier; Gago, Francisco E; Ciocca, Leonardo A; Fanelli, Mariel A; Ciocca, Daniel R

    2015-02-01

    In human breast cancer, β-catenin localization has been related with disease prognosis. Since HER2-positive patients are an important subgroup, and that in breast cancer cells a direct interaction of β-catenin/HER2 has been reported, in the present study we have explored whether β-catenin location is related with the disease survival. The study was performed in a tumor bank from patients (n = 140) that did not receive specific anti-HER2 therapy. The proteins were detected by immunohistochemistry in serial sections, 47 (33.5%) patients were HER2-positive with a long follow-up. HER2-positive patients that displayed β-catenin at the plasma membrane (completely surrounding the tumour cells) showed a significant better disease-free survival and overall survival than the patients showing the protein on other locations. Then we explored the dynamics of the co-expression of β-catenin and HER2 in human MCF-7 and SKBR3 cells exposed to different stressful situations. In untreated conditions MCF-7 and SKBR3 cells showed very different β-catenin localization. In MCF-7 cells, cadmium administration caused a striking change in β-catenin localization driving it from plasma membrane to cytoplasmic and perinuclear areas and HER2 showed a similar localization patterns. The changes induced by cadmium were compared with heat shock, H2O2 and tamoxifen treatments. In conclusion, this study shows the dynamical associations of HER2 and β-catenin and their changes in subcellular localizations driven by stressful situations. In addition, we report for the first time the correlation between plasma membrane associated β-catenin in HER2-positive breast cancer and survival outcome, and the importance of the protein localization in breast cancer samples.

  1. Methylene blue as an early diagnostic marker for oral precancer and cancer.

    Science.gov (United States)

    Riaz, Akhtar; Shreedhar, Balasundari; Kamboj, Mala; Natarajan, S

    2013-12-01

    Oral cancer is one of the most common neoplasm's and is ranked eighth in the cancer incidence worldwide. Early detection is of critical importance because survival rates markedly improve. In vivo staining is a simple, inexpensive, and fairly sensitive method. Involved 120 patients (50 with Premalignant Lesion, 50 with OSCC and 20 controls) stained by Methylene Blue (MB). The results of MB uptake were compared with a simultaneous biopsy of these lesions. Pathologically confirmed precancers and cancers were the positive targets of this screening, while hyperkeratosis without dysplasia and no evidence of malignancy were sorted as negative subjects of screening. The results revealed sensitivity of 91.4%, specificity of 66.6%, positive predictive value 97.7% and negative predictive value 33% leading to diagnostic accuracy of MB stain to 90%. We state that MB staining is useful diagnostic tool in community oral cancer screening programmes for high-risk individuals.

  2. Pre-diagnostic alcohol consumption and breast cancer recurrence and mortality

    DEFF Research Database (Denmark)

    Holm, Marianne; Olsen, Anja; Christensen, Jane Hvarregaard;

    2013-01-01

    The association between pre-diagnostic alcohol consumption and breast cancer recurrence and breast cancer specific mortality was investigated in 1,052 women diagnosed with early breast cancer in a prospective cohort of 29,875 women. Known clinical, lifestyle and socioeconomic risk factors were...... evaluated and adjusted for in multivariate analysis. We found a modest but significant association between pre-diagnostic alcohol consumption and breast cancer recurrence with a median follow-up of six years after date of diagnosis, both when using baseline measures of alcohol intake (HR, 1.65; 95% CI, 1.......02-2.67; >2 units/day vs. ≤1 unit/day) and cumulated alcohol intake (HR, 2.02; 95% CI, 1.06-3.85; >40 drinking years vs. 0...

  3. The impact of insurance coverage during insurance reform on diagnostic resolution of cancer screening abnormalities.

    Science.gov (United States)

    Kapoor, Alok; Battaglia, Tracy A; Isabelle, Alexis P; Hanchate, Amresh D; Kalish, Richard L; Bak, Sharon; Mishuris, Rebecca G; Shroff, Swati M; Freund, Karen M

    2014-02-01

    We examined the impact of Massachusetts insurance reform on the care of women at six community health centers with abnormal breast and cervical cancer screening to investigate whether stability of insurance coverage was associated with more timely diagnostic resolution. We conducted Cox proportional hazards models to predict time from cancer screening to diagnostic resolution, examining the impact of 1) insurance status at time of screening abnormality, 2) number of insurance switches over a three-year period, and 3) insurance history over a three-year period. We identified 1,165 women with breast and 781 with cervical cancer screening abnormalities. In the breast cohort, Medicaid insurance at baseline, continuous public insurance, and losing insurance predicted delayed resolution. We did not find these effects in the cervical cohort. These data provide evidence that stability of health insurance coverage with insurance reform nationally may improve timely care after abnormal cancer screening in historically underserved women.

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

    OpenAIRE

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

    2015-01-01

    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...

  5. Expression of Survivin, CyclinD1, p21WAF1, Caspase-3 in Cervical Cancer and Its Relation with Prognosis

    Institute of Scientific and Technical Information of China (English)

    LU Shi; ZHANG Baohua; WANG Zehua

    2005-01-01

    The implications of Survivin, CyclinD1, p21WAF1, Caspase-3 in the development, progression and prognosis in cervical cancer were investigated. By using immunohistochemical SP method, the expression of Survivin, CyclinD1, p21WAF1 , Caspase-3 was detected in 41 cases of cervical cancer, 17 cases of cervical intraepithelial neoplasia (CIN) and 10 cases of normal tissues, and their relation with pathological grade, clinical stage, metastasis and survival time was analyzed.The results showed that the positive expression rate of Survivin, CyclinD1 in cervical cancer was significantly higher than in CIN group and normal control group (P<0.05). The median survival time in the patients with cervical cancer positive for Survivin and CyclinD1 was significantly shorter than in those with negative expression (P<0.05). The expression of both Survivin and CyclinD1 was not related with tumor grade, clinical stage and metastasis (P>0. 05). The positive expression rate of p21WAF1 , Caspase-3 in cervical ca rcer was significantly lower than in CIN group and normal control group (P<0.05), and had a close relation with tumor grade (P<0.05). The expression of Survivin in cervical cancer in cervical cancer was negatively associated with that of Caspase-3 (P<0.01), but positively with that of CyclinD1 (P<0.01). Cox Multivariate analysis revealed that Survivin was the independent prognostic indicator influencing the survival time of the patients with cervical cancer (P<0.05). It was suggested that the high expression of Survivin or CyclinD1, and low expression of p21WAF1 or Caspase-3 was closely correlated with the development of cervical cancer. Survivin and CyclinD1 could be used as a useful indicator to predict the prognosis of cervical cancer.

  6. Liposomal delivery of radionuclides for cancer diagnostics and radiotherapy

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa

    , as the use of positron emission tomography (PET) scanners for molecular and diagnostic imaging has become more attractive. Furthermore, the importance of molecular and diagnostic imaging in nanotechnology has also been recognized, and significant research has been conducted on radiolabeled liposomes...... for scintigraphy and single photon emission computed tomography (SPECT) imaging. Preclinical as well as clinical SPECT studies on radiolabeled liposomes have contributed with valuable information on the pharmacokinetics of liposomes during several liposomal drug developments. SPECT has lower detection sensitivity......, an in vivo study is presented, where passive tumor accumulation of 64Cu loaded liposomes (64Cu-liposomes) in tumor-bearing mice was quantified directly by PET and computed tomography (CT) imaging. Furthermore, Article I present an evalu