Sample records for cancer current molecular

  1. The current state of molecular cytogenetics in cancer diagnosis. (United States)

    Liehr, Thomas; Othman, Moneeb A K; Rittscher, Katharina; Alhourani, Eyad


    Cytogenetics and molecular cytogenetics are and will continue to be indispensable tools in cancer diagnostics. Leukemia and lymphoma diagnostics are still emphases of routine (molecular) cytogenetics and corresponding studies of solid tumors gain more and more prominence. Here, first a historical perspective of molecular tumor cytogenetics is provided, which is followed by the basic principles of the fluorescence in situ hybridization (FISH) approach. Finally the current state of molecular cytogenetics in cancer diagnostics is discussed. Nowadays routine diagnostics includes basic FISH approaches rather than multicolor-FISH. The latter together with modern high-throughput methods have their impact on research to identify new tumor-associated genomic regions.

  2. Molecular prostate cancer pathology: current issues and achievements.

    NARCIS (Netherlands)

    Schalken, J.A.; Bergh, A. von; Bono, A.V.; Foster, C.; Gospadarowicz, M.; Isaacs, W.B.; Rubin, M.; Schroder, F.H.; Tribukait, B.; Tsukamotot, T.; Wiklund, P.


    Recent developments in the field of molecular techniques have provided new tools that have led to the discovery of many new promising biomarkers for prostate cancer. These biomarkers may be instrumental in the development of new tests that will have a high specificity for the diagnosis and prognosis

  3. Current Molecular and Genetic Aspects of Pancreatic Cancer, the Role of Metastasis Associated Proteins (MTA): A Review. (United States)

    Pavlidis, Efstathios T; Pavlidis, Theodoros E


    Purpose/aim: To focus on current molecular and genetic aspects and MTA proteins, since pancreatic cancer is a lethal malignant with poor prognosis. Early diagnosis is essential step, contributing to potential curative resection.

  4. Current Advances in the Application of Raman Spectroscopy for Molecular Diagnosis of Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Inês Raquel Martins Ramos


    Full Text Available Raman spectroscopy provides a unique biochemical fingerprint capable of identifying and characterizing the structure of molecules, cells, and tissues. In cervical cancer, it is acknowledged as a promising biochemical tool due to its ability to detect premalignancy and early malignancy stages. This review summarizes the key research in the area and the evidence compiled is very encouraging for ongoing and further research. In addition to the diagnostic potential, promising results for HPV detection and monitoring treatment response suggest more than just a diagnosis prospective. A greater body of evidence is however necessary before Raman spectroscopy is fully validated for clinical use and larger comprehensive studies are required to fully establish the role of Raman spectroscopy in the molecular diagnostics of cervical cancer.

  5. PI3K and Akt as molecular targets for cancer therapy: current clinical outcomes

    Institute of Scientific and Technical Information of China (English)

    Ipsita PAL; Mahitosh MANDAL


    The PI3K-Akt pathway is a vital regulator of cell proliferation and survival.Alterations in the PIK3CA gene that lead to enhanced PI3K kinase activity have been reported in many human cancer types,including cancers of the colon,breast,brain,liver,stomach and lung.Deregulation of PI3K causes aberrant Akt activity.Therefore targeting this pathway could have implications for cancer treatment.The first generation PI3K-Akt inhibitors were proven to be highly effective with a low IC50,but later,they were shown to have toxic side effects and poor pharmacological properties and selectivity.Thus,these inhibitors were only effective in preclinical models.However,derivatives of these first generation inhibitors are much more selective and are quite effective in targeting the PI3K-Akt pathway,either alone or in combination.These second-generation inhibitors are essentially a specific chemical moiety that helps to form a strong hydrogen bond interaction with the PI3K/Akt molecule.The goal of this review is to delineate the current efforts that have been undertaken to inhibit the various components of the PI3K and Akt pathway in different types of cancer both in vitro and in vivo.Our focus here is on these novel therapies and their inhibitory effects that depend upon their chemical nature,as well as their development towards clinical trials.

  6. Current status of multimodal molecular imaging of prostate cancer; Multimodale molekulare Bildgebung des Prostatakarzinoms - aktueller Stand

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    Reske, S.N. [Universitaetsklinikum Ulm (Germany). Klinik fuer Nuklearmedizin


    Prostate carcinoma is the most common life-threatening cancer affecting men in the western world. In Germany about 40 600 new cases have to be expected each year. The mortality is around 10%. The major goals of pretherapeutic imaging are to determine the local extent of prostate carcinoma in terms of intraprostate localisation, extracapsular extension (ECE), seminal vesicle invasion (SVI), tumour infiltration into neurovascular bundles, and if this has taken place, into surrounding tissues and organs in the small pelvis, detection of loco-regional metastases via the lymph nodes and if this so, of distant metastases. Exact pretherapeutic diagnosis and staging are essential, because the tumour treatment must be selected in strict dependence on clinical tumour stage and risk profile. Both anatomic and functional molecular imaging of prostate carcinoma have advanced significantly in recent years. When there are problems with diagnosis, e.g. when prostate punch biopsies are negative while the suspicion of prostate carcinoma persists, C-11/F-18 choline PET/CT and MRI/MRS may be helpful in localising the carcinoma, revealing how the carcinoma relates to the surrounding intra- and extraprostatic structures and organs, and making a targeted repeat biopsy possible. Lymphotropic contrast agents are highly promising for accurate nodal staging of prostate carcinoma, but are not yet available for routine clinical use. In these circumstances, the sensitivity of nodal staging with the widely available imaging modalities remains difficult. There has been particularly substantial progress in the localisation of local relapse, which can be imaged with contrast-enhanced C-11-choline PET/CT and MRI in most cases when PSA is considerably below 1 ng/ml. F-18-fluoride PET/CT has proved accurate in the diagnosis of skeletal metastases from prostate carcinoma. (orig.)

  7. Targeted Therapy Database (TTD: a model to match patient's molecular profile with current knowledge on cancer biology.

    Directory of Open Access Journals (Sweden)

    Simone Mocellin

    Full Text Available BACKGROUND: The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. OBJECTIVE: To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. METHODS: To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. RESULTS AND CONCLUSIONS: We created a manually annotated database (Targeted Therapy Database, TTD where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method

  8. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

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    Kaichun Li


    Full Text Available Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2, can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab, VEGF targeting monoclonal antibodies (bevacizumab, mTOR inhibitor (everolimus, or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.

  9. The National Cancer Institute's PREVENT Cancer Preclinical Drug Development Program: overview, current projects, animal models, agent development strategies, and molecular targets. (United States)

    Shoemaker, Robert H; Suen, Chen S; Holmes, Cathy A; Fay, Judith R; Steele, Vernon E


    The PREVENT Cancer Preclinical Drug Development Program (PREVENT) is a National Cancer Institute, Division of Cancer Prevention (NCI, DCP)-supported program whose primary goal is to bring new cancer preventive interventions (small molecules and vaccines) and biomarkers through preclinical development towards clinical trials by creating partnerships between the public sector (eg, academia, industry) and DCP. PREVENT has a formalized structure for moving interventions forward in the prevention pipeline using a stage-gate process with go/no go decision points along the critical path for development. This review describes the structure of the program, its focus areas, and provides examples of projects currently in the pipeline.

  10. Molecular imaging in cancer treatment

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    Michalski, Mark H. [Stanford University School of Medicine, Stanford, CA (United States); Chen, Xiaoyuan [National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), Bethesda, MD (United States)


    The success of cancer therapy can be difficult to predict, as its efficacy is often predicated upon characteristics of the cancer, treatment, and individual that are not fully understood or are difficult to ascertain. Monitoring the response of disease to treatment is therefore essential and has traditionally been characterized by changes in tumor volume. However, in many instances, this singular measure is insufficient for predicting treatment effects on patient survival. Molecular imaging allows repeated in vivo measurement of many critical molecular features of neoplasm, such as metabolism, proliferation, angiogenesis, hypoxia, and apoptosis, which can be employed for monitoring therapeutic response. In this review, we examine the current methods for evaluating response to treatment and provide an overview of emerging PET molecular imaging methods that will help guide future cancer therapies. (orig.)

  11. Current applications of molecular cytogenetic technologies. (United States)

    Mark, H F; Jenkins, R; Miller, W A


    This review discusses select current applications of fluorescent in situ hybridization (FISH) which may be of utility for the average clinical cytogenetic laboratory. Owing to the large number of men and women affected, the applications chosen to illustrate the use of FISH technology in cancer focus on two diseases: breast cancer and prostate cancer. The applicability of FISH to detect common aneuploidies, such as trisomy 21, trisomy 18, trisomy 13 and the sex chromosome aneuploidies in prenatal diagnosis, is discussed, as well as FISH for the detection of microdeletions and microduplications. Quality assurance/quality control issues and standards and guidelines relating to laboratory practices in molecular cytogenetic testing are reviewed.

  12. [Current status of p53 tumor suppressor gene as a possible molecular marker of cancer of the prostate]. (United States)

    Peña González, J A; Morote Robles, J; de Torres Ramírez, I M; Martínez Cuenca, E


    Diagnosis of prostate cancer has increased over the last few years both in localized and in more advanced stages. At present, several groups are working in the search and evaluation of alternative tumoral markers as the current ones do not cover all the Urologist's needs. In this context, a number of studies on the mutation of the tumour suppressor gen p53 in both localized and metastatic prostate cancer are being carried out. When a noxa acts on the DNA, protein p53 inhibits the cell cycle allowing the repair systems to operate and, if the damage is significant enough, cell apoptosis. The loss of this control mechanism secondary to the synthesis of anomalous proteins can result in the proliferation of neoplastic cells. A revision of the most representative papers in the literature is presented here, addressing the surrounding controversy and the resulting future possibilities.

  13. Histopathological, Molecular, and Genetic Profile of Hereditary Diffuse Gastric Cancer: Current Knowledge and Challenges for the Future. (United States)

    van der Post, Rachel S; Gullo, Irene; Oliveira, Carla; Tang, Laura H; Grabsch, Heike I; O'Donovan, Maria; Fitzgerald, Rebecca C; van Krieken, Han; Carneiro, Fátima


    Familial clustering is seen in 10 % of gastric cancer cases and approximately 1-3 % of gastric cancer arises in the setting of hereditary diffuse gastric cancer (HDGC). In families with HDGC, gastric cancer presents at young age. HDGC is predominantly caused by germline mutations in CDH1 and in a minority by mutations in other genes, including CTNNA1. Early stage HDGC is characterized by a few, up to dozens of intramucosal foci of signet ring cell carcinoma and its precursor lesions. These include in situ signet ring cell carcinoma and pagetoid spread of signet ring cells. Advanced HDGC presents as poorly cohesive/diffuse type carcinoma, normally with very few typical signet ring cells, and has a poor prognosis. Currently, it is unknown which factors drive the progression towards aggressive disease, but it is clear that most intramucosal lesions will not have such progression.Immunohistochemical profile of early and advanced HDGC is often characterized by abnormal E-cadherin immunoexpression, including absent or reduced membranous expression, as well as "dotted" or cytoplasmic expression. However, membranous expression of E-cadherin does not exclude HDGC. Intramucosal HDGC (pT1a) presents with an "indolent" phenotype, characterized by typical signet ring cells without immunoexpression of Ki-67 and p53, while advanced carcinomas (pT > 1) display an "aggressive" phenotype with pleomorphic cells, that are immunoreactive for Ki-67 and p53. These features show that the IHC profile is different between intramucosal and more advanced HDGC, providing evidence of phenotypic heterogeneity, and may help to define predictive biomarkers of progression from indolent to aggressive, widely invasive carcinomas.

  14. Molecular approaches towards development of purified natural products and their structurally known derivatives as efficient anti-cancer drugs: current trends. (United States)

    Saha, Santu Kumar; Khuda-Bukhsh, Anisur Rahman


    Several natural products and their derivatives, either in purified or structurally identified form, exhibit immense pharmacological and biological properties, some of them showing considerable anticancer potential. Although the molecular mechanisms of action of some of these products are yet to be elucidated, extensive research in this area continues to generate new data that are clinically exploitable. Recent advancement in molecular biology, high throughput screening, biomarker identifications, target selection and genomic approaches have enabled us to understand salient interactions of natural products and their derivatives with cancer cells vis-à-vis normal cells. In this review we highlight the recent approaches and application of innovative technologies made to improve quality as well as efficiency of structurally identified natural products and their derivatives, particularly in small molecular forms capable of being used in "targeted therapies" in oncology. These products preferentially involve multiple mechanistic pathways and overcome chemo-resistance in tumor types with cumulative action. We also mention briefly a few physico-chemical features that compare natural products with drugs in recent natural product discovery approaches. We further report here a few purified natural products as examples that provide molecular interventions in cancer therapeutics to give the reader a glimpse of the current trends of approach for discovering useful anticancer drugs.

  15. Molecular biology of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Miroslav Zavoral; Petra Minarikova; Filip Zavada; Cyril Salek; Marek Minarik


    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  16. Current status of cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Kono K


    Full Text Available To prove clinical benefits of cancer vaccine is currently difficult, except for one phase III trial has documented improved overall survival with the vaccine, Sipuleucel‑T, although induction of anti-tumor immune responses through cancer vaccine is theoretically promising and would be straightforward. In contrast, immune checkpoint blockade with anti-CTLA4 mAb and anti-PD‑1 mAb has demonstrated clear evidence of objective responses including improved overall survival and tumor shrinkage, driving renewed enthusiasm for cancer immunotherapy in multi­ple cancer types. In addition, there is a promising novel cancer immunotherapy, CAR therapy—a personalized treatment that involves genetically modifying a patient’s T- cells to make them target tumor cells. We are now facing new era of cancer immunotherapy.

  17. Molecular and Clinical Markers of Pancreas Cancer


    James L Buxbaum; Eloubeidi, Mohamad A


    Pancreas cancer has the worst prognosis of any solid tumor but is potentially treatable if it is diagnosed at an early stage. Thus there is critical interest in delineating clinical and molecular markers of incipient disease. The currently available biomarker, CA 19-9, has an inadequate sensitivity and specificity to achieve this objective. Diabetes mellitus, tobacco use, and chronic pancreatitis are associated with pancreas cancer. However, screening is currently only recommended in those wi...

  18. Current Status of Biomarkers for Prostate Cancer

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    Vicki M. Velonas


    Full Text Available Prostate cancer (PCa is a leading cause of cancer-related death of men globally. Since its introduction, there has been intense debate as to the effectiveness of the prostate specific antigen (PSA test as a screening tool for PCa. It is now evident that the PSA test produces unacceptably high rates of false positive results and is not prognostic. Here we review the current status of molecular biomarkers that promise to be prognostic and that might inform individual patient management. It highlights current efforts to identify biomarkers obtained by minimally invasive methods and discusses current knowledge with regard to gene fusions, mRNA and microRNAs, immunology, and cancer-associated microparticles.

  19. Molecular imaging of prostate cancer with PET. (United States)

    Jadvar, Hossein


    Molecular imaging is paving the way for precision and personalized medicine. In view of the significant biologic and clinical heterogeneity of prostate cancer, molecular imaging is expected to play an important role in the evaluation of this prevalent disease. The natural history of prostate cancer spans from an indolent localized process to biochemical relapse after radical treatment with curative intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling of the complex tumor biology of prostate cancer uniquely positions molecular imaging with PET to contribute significantly to every clinical phase of prostate cancer evaluation. The purpose of this article was to provide a concise review of the current state of affairs and potential future developments in the diagnostic utility of PET in prostate cancer.

  20. Current management of oral cancer

    Institute of Scientific and Technical Information of China (English)

    Robert Ord


    @@ This presentation will summarize some of the current areas of interest in the management of oral cancer. The presentation will be divided into a brief review of epidemiology and diagnosis, with a more extensive discussion regarding the controversial areas in surgery and a review of the adjuvant roles of radiation and chemotherapy.

  1. Multidrug-resistant breast cancer: current perspectives

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    Martin HL


    Full Text Available Heather L Martin,1 Laura Smith,2 Darren C Tomlinson11BioScreening Technology Group, Leeds Institutes of Molecular Medicine, University of Leeds, Leeds, UK; 2Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UKAbstract: Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. By understanding the molecular mechanisms behind multidrug-resistant breast cancer, new treatments may be developed. Here we review the recent advances in this understanding, emphasizing the common mechanisms underlying resistance to both targeted therapies, notably tamoxifen and trastuzumab, and traditional chemotherapies. We focus primarily on three molecular mechanisms, the phosphatidylinositide 3-kinase/Akt pathway, the role of microRNAs in gene silencing, and epigenetic alterations affecting gene expression, and discuss how these mechanisms can interact in multidrug resistance. The development of therapeutics targeting these mechanisms is also addressed.Keywords: PI3K/Akt, epigenetics, miRNA, ER, HER2, triple negative

  2. Molecular and Clinical Markers of Pancreas Cancer

    Directory of Open Access Journals (Sweden)

    James L Buxbaum


    Full Text Available Pancreas cancer has the worst prognosis of any solid tumor but is potentially treatable if it is diagnosed at an early stage. Thus there is critical interest in delineating clinical and molecular markers of incipient disease. The currently available biomarker, CA 19-9, has an inadequate sensitivity and specificity to achieve this objective. Diabetes mellitus, tobacco use, and chronic pancreatitis are associated with pancreas cancer. However, screening is currently only recommended in those with hereditary pancreatitis and genetic syndromes which predispose to cancer. Ongoing work to identify early markers of pancreas cancer consists of high throughput discovery methods including gene arrays and proteomics as well as hypothesis driven methods. While several promising candidates have been identified none has yet been convincingly proven to be better than CA 19-9. New methods including endoscopic ultrasound are improving detection of pancreas cancer and are being used to acquire tissue for biomarker discovery.

  3. [Current Approaches in Cancer Immunotherapy]. (United States)

    Otáhal, P; Trněný, M


    Methods of cancer immunotherapy have finally entered clinical medicine after years of preclinical research. Currently, there are several methods, which have proven to be very effective even in cases of incurable cancer. Antitumor monoclonal antibodies are among major therapeutic anti-cancer drugs and have been successfully used for many ears. Novel group of antibodies are immunomodulatory antibodies which can break tumor -specific immune tolerance and induce regression of tumors by nonspecific activation of immune system. Bispecific antibodies represent a novel class of anticancer agents which can induce expansion of T cells in vivo, blinatumomab is an example of such agents and is currently available for the treatment of acute B -cell leukemia. Cellular immunotherapy is also very effective, especially the use of Chimeric receptor modified T-cells for the therapy of B- cell lymphoproliferative diseases. Although it is a very complicated and expensive method, it is highly effective approach which can induce remission even in previously hopeless conditions. The goal of this article is to explain the basic principles of cancer immunotherapy and summarize the newest findings in this field.

  4. Clinical Advances in Molecular Biomarkers for Cancer Diagnosis and Therapy


    Sarkar, Fazlul H.; Philip, Philip A.; Seema Sethi; Shadan Ali


    Cancer diagnosis is currently undergoing a paradigm shift with the incorporation of molecular biomarkers as part of routine diagnostic panel. The molecular alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs are recently discovered small non-coding endogenous single-stranded RNAs that critically regulates the development, invasion and metastasis of cancers. They are altered in cancers and have the potential to serve as diagnostic markers for cancer...


    Directory of Open Access Journals (Sweden)

    V. N. Pavlov


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

  6. Molecular mechanisms of metastasis in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Noel W.Clarke; Claire A.Hart; Mick D.Brown


    Prostate cancer (PCa) preferentially metastasizes to the bone marrow stroma of the axial skeleton.This activity is the principal cause of PCa morbidity and mortality.The exact mechanism of PCa metastasis is currently unknown,although considerable progress has been made in determining the key players in this process.In this review,we present the current understanding of the molecular processes driving PCa metastasis to the bone.

  7. Introduction of molecular HPV testing as the primary technology in cervical cancer screening: Acting on evidence to change the current paradigm. (United States)

    Tota, Joseph E; Bentley, James; Blake, Jennifer; Coutlée, François; Duggan, Máire A; Ferenczy, Alex; Franco, Eduardo L; Fung-Kee-Fung, Michael; Gotlieb, Walter; Mayrand, Marie-Hélène; McLachlin, Meg; Murphy, Joan; Ogilvie, Gina; Ratnam, Sam


    Since being introduced in the 1940s, cervical cytology - despite its limitations - has had unequivocal success in reducing cervical cancer burden in many countries. However, we now know that infection with human papillomavirus (HPV) is a necessary cause of cervical cancer and there is overwhelming evidence from large-scale clinical trials, feasibility studies and real-world experience that supports the introduction of molecular testing for HPV as the primary technology in cervical cancer screening (i.e., "HPV primary screening"). While questions remain about the most appropriate age groups for screening, screening interval and triage approach, these should not be considered barriers to implementation. Many countries are in various stages of adopting HPV primary screening, whereas others have not taken any major steps towards introduction of this approach. As a group of clinical experts and researchers in cervical cancer prevention from across Canada, we have jointly authored this comprehensive examination of the evidence to implement HPV primary screening. Our intention is to create a common understanding among policy makers, agencies, clinicians, researchers and other stakeholders about the evidence concerning HPV primary screening to catalyze the adoption of this improved approach to cervical cancer prevention. With the first cohort of vaccinated girls now turning 21, the age when routine screening typically begins, there is increased urgency to introduce HPV primary screening, whose performance may be less adversely affected compared with cervical cytology as a consequence of reduced lesion prevalence post-vaccination.

  8. Bladder cancer: molecular determinants of personalized therapy. (United States)

    Lopez-Beltran, Antonio; Santoni, Matteo; Massari, Francesco; Ciccarese, Chiara; Tortora, Giampaolo; Cheng, Liang; Moch, Holger; Scarpelli, Marina; Reymundo, Carlos; Montironi, Rodolfo


    Several molecular and genetic studies have provided new perspectives on the histologic classification of bladder tumors. Recent developments in the field of molecular mutational pathway analyses based on next generation sequencing technology together with classic data derived from the description of mutations in the FGFR3 (fibroblast growth factor receptor 3) gene, mutations on TP53 gene, and cDNA technology profiling data gives support to a differentiated taxonomy of bladder cancer. All these changes are behind the use of non-traditional approach to therapy of bladder cancer patients and are ready to change our daily practice of uro-oncology. The observed correlation of some molecular alterations with tumor behavior and the identification of their targets at cellular level might support the use of molecular changes together with morphological data to develop new clinical and biological strategies to manage patients with urothelial cancer. The current review provides comprehensive data to support personalized therapy for bladder cancer based on an integrated approach including pathologic and clinical features and molecular biology.

  9. Molecular imaging: current status and emerging strategies

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    Pysz, M.A. [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA (United States); Gambhir, S.S. [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA (United States); Departments of Bioengineering and Materials Science and Engineering, Stanford University, Stanford, CA (United States); Willmann, J.K., E-mail: willmann@stanford.ed [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA (United States)


    In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use positron-emission tomography (PET) or single photon-emission computed tomography (SPECT)-based techniques. In ongoing preclinical research, novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multi-modality molecular imaging. Contrast-enhanced molecular ultrasound (US) with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and US imaging with molecularly-targeted microbubbles are attractive strategies as they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and US techniques involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with US. Current preclinical findings and advances in instrumentation, such as endoscopes and microcatheters, suggest that these molecular imaging methods have numerous potential clinical applications and will be translated into clinical use in the near future.

  10. Molecular diagnosis of prostate cancer: Topical issues

    Directory of Open Access Journals (Sweden)

    E. N. Knyazev


    Full Text Available Prostate cancer (PC is the second most common cancer and the fifth highest malignancy mortality rate in men worldwide. Although PC is detectable in 15-20% of men during life, its death risk is only about 3%. This means that not all PC cases require the same management tactics. The given review analyzes the current investigations searching for molecular biological markers to predict the course of PC and to choose its treatment policy, including that in the development of resistance to androgen-deprivation therapy.

  11. Ovarian cancer: a molecularly insidious disease. (United States)

    Mezzanzanica, Delia


    In this issue of the Chinese Journal of Cancer, European, American, and Chinese experts review the current management and future perspectives of epithelial ovarian cancer (EOC), the leading cause of gynecological cancer deaths. Although major advances have been made in understanding the cellular and molecular biology of this highly heterogeneous malignancy, the survival rate of women with EOC has changed little since the introduction of platinum-based treatment as a front-line therapy. The papers describe the progress in deciphering the molecular complexity of this disease and the newly available molecular-driven therapies, which have been applied by shifting trial designs toward restricting eligibility to specific subgroups of patients rather than testing agents in unselected populations. These new trial designs provide potential opportunities for improved efficacy in targeted populations. Given the molecular complexity of this disease, patient survival may be increased by searching for new molecular prognostic/predictive signatures as well as by translating the recent insight of microRNA involvement in EOC progression into new, targeted therapies. Particular attention has been given to the issue of fertility sparing for women affected by curable diseases.

  12. Molecular Testing for Gastrointestinal Cancer (United States)

    Lee, Hye Seung; Kim, Woo Ho; Kwak, Yoonjin; Koh, Jiwon; Bae, Jeong Mo; Kim, Kyoung-Mee; Chang, Mee Soo; Han, Hye Seung; Kim, Joon Mee; Kim, Hwal Woong; Chang, Hee Kyung; Choi, Young Hee; Park, Ji Y.; Gu, Mi Jin; Lhee, Min Jin; Kim, Jung Yeon; Kim, Hee Sung; Cho, Mee-Yon


    With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians. PMID:28219002

  13. Controlling local currents in molecular junctions

    CERN Document Server

    Yadalam, Hari Kumar


    The effect of non-equilibrium constraints and dephasing on the circulating currents in molecular junctions are analyzed. Circulating currents are manifestations of quantum effects and can be induced either by externally applied bias or an external magnetic field through the molecular system. In symmetric Aharonov-Bohm ring, bond currents have two contributions, bias driven and magnetic field driven. We analyze the competition between these two contributions and show that, as a consequence, current through one of the branches can be completely suppressed. We then study the effect of asymmetry (as a result of chemical substitution) on the current pathways inside the molecule and study asymmetry induced circulating currents (without magnetic field) by tuning the coupling strength of the substituent (at finite bias).

  14. [Molecular diagnostics of lung cancer]. (United States)

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


    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. Current insights into the molecular systems pharmacology of lncRNA-miRNA regulatory interactions and implications in cancer translational medicine

    Directory of Open Access Journals (Sweden)

    Sujit Nair


    Full Text Available In recent times, the role(s of microRNAs (miRNAs and long noncoding RNAs (lncRNAs in the pathogenesis of various cancers has received great attention. Indeed, there is also a growing recognition of regulatory RNA cross-talk, i.e., lncRNA-miRNA interactions, that may modulate various events in carcinogenesis and progression to metastasis. This review summarizes current evidence in the literature of lncRNA-miRNA interactions in various cancers such as breast, liver, stomach, lung, prostate, bladder, colorectal, blood, brain, skin, kidney, cervical, laryngeal, gall bladder, and bone. Further, the potential prognostic and theragnostic clinical applications of lncRNA-miRNA interactions in cancer are discussed along with an overview of noncoding RNA (ncRNA-based studies that were presented at the American Society of Clinical Oncology (ASCO 2015. Interestingly, the last decade has seen tremendous innovation, as well as increase in complexity, of the cancer biological network(s from mRNA- to miRNA- and lncRNA-based networks. Thus, biological networks devoted to understanding regulatory interactions between these ncRNAs would be the next frontier in better elucidating the contributions of lncRNA-miRNA interactions in cancer. Herein, a cancer biological network of lncRNA-miRNA interactions is presented wherein “edges” connect interacting lncRNA-miRNA pairs, with each ncRNA serving as a discrete “node” of the network. In conclusion, the untapped potential of lncRNA-miRNA interactions in terms of its diagnostic, prognostic and therapeutic potential as targets for clinically actionable intervention as well as biomarker validation in discovery pipelines remains to be explored. Future research will likely harness this potential so as to take us closer to the goal of “precision” and “personalized medicine” which is tailor-made to the unique needs of each cancer patient, and is clearly the way forward going into the future.

  16. Current concepts in cancer research

    Directory of Open Access Journals (Sweden)

    Ivan Kok Seng Yap


    Full Text Available Cancer research is an extremely broadtopic covering many scientific disciplines includingbiology (e.g. biochemistry and signal transduction,chemistry (e.g. drug discover and development,physics (e.g. diagnostic devices and even computerscience (e.g. bioinformatics. Some would argue thatcancer research will continue in much the same wayas it is by adding further layers of complexity to thescientific knowledge that is already complex and almostbeyond measure. But we anticipate that cancer researchwill undergo a dramatic paradigm shift due to therecent explosion of new discoveries in cancer biology.This review article focuses on the latest horizons incancer research concerning cancer epigenetics, cancerstem cells, cancer immunology and cancer metabolism.

  17. The molecular biology of cancer. (United States)

    Bertram, J S


    identifies key genes directly involved in carcinogenesis and demonstrates how mutations in these genes allow cells to circumvent cellular controls. This detailed understanding of the process of carcinogenesis at the molecular level has only been possible because of the advent of modern molecular biology. This new discipline, by precisely identifying the molecular basis of the differences between normal and malignant cells, has created novel opportunities and provided the means to specifically target these modified genes. Whenever possible this review highlights these opportunities and the attempts being made to generate novel, molecular based therapies against cancer. Successful use of these new therapies will rely upon a detailed knowledge of the genetic defects in individual tumors. The review concludes with a discussion of how the use of high throughput molecular arrays will allow the molecular pathologist/therapist to identify these defects and direct specific therapies to specific mutations.

  18. Current Status on Cholangiocarcinoma and Gallbladder Cancer (United States)

    Ebata, Tomoki; Ercolani, Giorgio; Alvaro, Domenico; Ribero, Dario; Di Tommaso, Luca; Valle, Juan W.


    Background Cholangiocarcinomas (CC) as well as gallbladder cancers are relatively rare and intractable diseases. Clinical, pathological, and epidemiological studies on these tumors have been under investigation. The current status and/or topics on biliary tract cancers have been reported in the East West Association of Liver Tumor (EWALT), held in Milano, Italy in 2015. Summary All the authors, herein, specifcally reported the current status and leading-edge findings on biliary tract cancers as the following sequence: epidemiology of CC, surgical therapy for intrahepatic CC, surgical therapy for perihilar CC, surgical therapy for gallblad der cancer, chemotherapy for biliary tract cancers, and new histological features in CC. Key Message The present review article will update the knowledge on biliary tract cancers, en hancing the quality of daily clinical practice. However, many features about these cancers remain unknown; further studies are required to establish disease-specific optimal treatment strategies. PMID:27995089

  19. Genetics and molecular biology of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.


    This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

  20. [Constipation and cancer: Current strategies]. (United States)

    Gervais, Claire; Ducrotté, Philippe; Piche, Thierry; Di Palma, Mario; Jovenin, Nicolas; Scotté, Florian


    Digestive disorders, in particular constipation, are symptoms very often reported by cancer patients as having a major impact on their quality of life. An accurate diagnosis of bowel delayed transit and defecation disorders is required to best adapt therapeutic management. Constipation associated with cancer may be related to several causes, which can be placed in three nosological categories that sometimes overlap: chronic constipation prior to cancer and having its own evolution; constipation related to the cancer condition, in particular the occlusive syndrome, and constipation induced by cancer therapies. The stricter application of diet and lifestyle measures is often necessary and sometimes sufficient. Laxative drug treatments come under various galenic forms and administration routes and must be selected according to the clinical features of constipation. Surgical management can be indicated in case of ileus or pelvic static disorders. In the case of refractory constipation induced by opioids and within the framework of palliative care to treat an advanced pathology, a peripheral morphinic antagonist can offer fast symptom relief. A way forward to improve the patients' quality of life could be to identify the contributing factors (in particular, genetic factors) to determine which patients are the more at risk and anticipate their management.

  1. Cancer and molecular biomarkers of phase 2

    DEFF Research Database (Denmark)

    Dalhoff, Kim; Enghusen Poulsen, Henrik


    as molecular genetic biomarkers of risk. GSTM(my)1 has been associated with an increased risk of colorectal cancer, lung cancer, and bladder cancer and GSTP(pi)1 with prostate cancer. UGT1A1*28 and *37 are both associated with an increased risk of breast cancer as is SULT1A1*2. The presence of UGT1A1...

  2. Molecular Taxonomy and Tumourigenesis of Colorectal Cancer. (United States)

    Biswas, S; Holyoake, D; Maughan, T S


    Over the last 5 years there has been a surge in interest in the molecular classification of colorectal cancer. The effect of molecular subtyping on current treatment decisions is limited to avoidance of adjuvant 5-fluorouracil chemotherapy in stage II microsatellite unstable-high disease and avoidance of epidermal growth factor receptor-targeted antibodies in extended RAS mutant tumours. The emergence of specific novel combination therapy for the BRAF-mutant cohort and of the microsatellite unstable-high cohort as a responsive group to immune checkpoint inhibition shows the growing importance of a clinically relevant molecular taxonomy. Clinical trials such as the Medical Research Council FOCUS4 trial using biomarkers to select patients for specific therapies are currently open and testing such approaches. The integration of mutation, gene expression and pathological analyses is refining our understanding of the biological subtypes within colorectal cancer. Sharing of data sets of parallel sequencing and gene expression of thousands of cancers among independent groups has allowed the description of disease subsets and the need for a validated consensus classification has become apparent. This biological understanding of the disease is a key step forward in developing a stratified approach to patient management. The discovery of stratifiers that predict a response to existing and emerging therapies will enable better use of these treatments. Improved scientific understanding of the biological characteristics of poorly responsive subgroups will facilitate the design of novel biologically rational combinations. Novel treatment regimens, including the combination of new drugs with radiation, and the discovery and validation of their associated predictive biomarkers will gradually lead to improved outcomes from therapy.

  3. Molecular Diagnostic Applications in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Laura Huth


    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.

  4. Molecular therapeutics in pancreas cancer

    Institute of Scientific and Technical Information of China (English)

    Vignesh Narayanan; Colin D Weekes


    The emergence of the "precision-medicine" paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma(PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease.

  5. Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action

    Institute of Scientific and Technical Information of China (English)

    Hiroaki; Itamochi


    Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitinproteasome pathway, epigenetic modulators, poly(ADPribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.

  6. Molecular therapy of colorectal cancer: progress and future directions. (United States)

    Weng, Wenhao; Feng, Junlan; Qin, Huanlong; Ma, Yanlei


    Colorectal cancer (CRC) remains one of the most common types of cancer and leading causes of cancer death worldwide. Although the introduction of cytotoxic drugs such as oxaliplatin, irinotecan and fluorouracil has improved the treatment of advanced CRC, the individual response to chemoradiotherapy varies tremendously from one patient to another. However, recent progress in CRC molecular therapies may provide new insight into the treatment of this disease. Currently, components of the EGFR, VEGF, Wnt and NF-kB pathways are the most important targets for CRC therapy. This review chronicles the development of molecular CRC therapies over the past few decades. We also provide an update on the current progress of research concerning the molecular pathways leading to CRC and discuss the possible implications for CRC therapy.

  7. Molecular Biology of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    HuanXi; JanBrabender; RalfMetzger; PaulM.Schneider


    There have been many new developments in our understanding of esophageal carcinoma biology over the past several years. Information regarding both of the major forms of this disease, adenocarcinoma and squamous cell carcinoma, has accumulated in conjunction with data on precursor conditions such as Barrett's esophagus. Interesting and promising findings have included overexpression of proto-oncogenes,loss of heterozygosity at multiple chromosomal loci, tumor suppressor gene inactivation, epigenetic silencing by DNA methylation, and mutations and deletions involving the tumor suppressor gene p53. Important cancer pathways, the cyclin kinase inhibitor cascade and the DNA mismatch repair process, implicated in the genesis of multiple tumor types have also been inculpated in esophageal carcinogenesis. Alterations in the p16 and p15 cyclin kinase inhibitors including point mutations and homozygous deletions have been reported in primary esophageal tumors. Further developments in the field of molecular carcinogenesis of esophageal malignancies promise to yield improvements in prevention, early detection, prognostic categorization, and perhaps gene-based therapy of this deadly disease.

  8. Gastric Cancer: Current Status of Diagnosis and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Tsunehiro; Saikawa, Yoshiro, E-mail:; Kitagawa, Yuko [Department of Surgery, School of Medicine, Keio University, Shinjuku-ku, Tokyo 1608582 (Japan)


    Gastric cancer is the second leading cause of death from malignant disease worldwide and most frequently discovered in advanced stages. Because curative surgery is regarded as the only option for cure, early detection of resectable gastric cancer is extremely important for good patient outcomes. Therefore, noninvasive diagnostic modalities such as evolutionary endoscopy and positron emission tomography are utilized as screening tools for gastric cancer. To date, early gastric cancer is being treated using minimally invasive methods such as endoscopic treatment and laparoscopic surgery, while in advanced cancer it is necessary to consider multimodality treatment including chemotherapy, radiotherapy, and surgery. Because of the results of large clinical trials, surgery with extended lymphadenectomy could not be recommended as a standard therapy for advanced gastric cancer. Recent clinical trials had shown survival benefits of adjuvant chemotherapy after curative resection compared with surgery alone. In addition, recent advances of molecular targeted agents would play an important role as one of the modalities for advanced gastric cancer. In this review, we summarize the current status of diagnostic technology and treatment for gastric cancer.

  9. Genetic and molecular changes in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Robert L Hollis; Charlie Gourley


    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

  10. Current practice of gastric cancer treatment

    Institute of Scientific and Technical Information of China (English)

    Yoon Young Choi; Ji Yeong An; Hyung-Il Kim; Jae-Ho Cheong; Woo Jin Hyung; Sung Hoon Noh


    Objective The aim of this review was to overview the current practice of gastric cancer treatment including surgery and other adjuvant modalities.Data sources The review was based on data obtained from the published articles and main guidelines in the East and West.Study selection Articles with high level of evidence or current best evidence in each issue were selected to be reviewed.Results Although varied adjuvant modalities have been proved to be benefit for treating gastric cancer,surgery is still the most important treatment strategy against gastric cancer.Actively adapting to new technology is important but it should be balanced with an effort to establish sound scientific rationale that adheres to oncologic principles.Conclusions Future treatment of gastric cancer will be focused on tailored,personalized therapy.For achieving it,collaboration across disciplines is essential.Also the philosophy of caring for the patients with gastric cancer should be rooted in the realization of true patient benefit regardless of who is providing the care.With these philosophies,we can shift the scientific and technological advances toward triumph over gastric cancer.

  11. Exercise after breast cancer treatment: current perspectives

    Directory of Open Access Journals (Sweden)

    Dieli-Conwright CM


    Full Text Available Christina M Dieli-Conwright, Breanna Z Orozco Division of Biokinesiology and Physical Therapy, Women's Health and Exercise Laboratory, University of Southern California, Los Angeles, CA, USA Abstract: Over the past 2 decades, great strides have been made in the field of exercise-oncology research, particularly with breast cancer. This area of research is particularly important since there are >2.8 million breast cancer survivors who are in need of an intervention that can offset treatment-related side effects. Noticeable reductions in physical fitness (ie, cardiopulmonary fitness and muscular strength, negative changes in body composition (ie, increase in body mass, decrease in lean body mass, and increase in fat mass, increased fatigue, depression, or anxiety are some of the common side effects of cancer treatments that negatively impact overall quality of life and increase the risk for the development of comorbidities. Exercise plays a vital role in improving cardiopulmonary function, psychological events, muscular strength, and endurance in breast cancer survivors, and thus should be considered as a key factor of lifestyle intervention to reverse negative treatment-related side effects. The purpose of this review is to address current perspectives on the benefits of aerobic and resistance exercise after breast cancer treatments. This review is focused on the well-established benefits of exercise on physical and emotional well-being, bone health, lymphedema management, and the postulated benefits of exercise on risk reduction for recurrence of breast cancer. Keywords: breast cancer, exercise, physical well-being

  12. Molecular Diagnosis in Bladder Cancer

    NARCIS (Netherlands)

    T.C.M. Zuiverloon (Tahlita)


    textabstractEpidemiologyBladder cancer (BC) is the most prevalent type of urothelial cancer and is associated with thehighest costs of all cancer types due to intensive patient surveillance. Because bladder tumorsfrequently recur, patients need to be monitored extensively [1-4]. Incidence increases

  13. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Adams, A.L.L.


    Breast cancer is the most common type of cancer in women. Imaging techniques play a pivotal role in breast cancer management, especially in lesion detection, treatment planning and evaluation, and prognostication. These imaging techniques have however limitations such as the use of ionizing radiatio

  14. [Matrix metalloproteases as molecular markers in gastric cancer]. (United States)

    de la Peña, Sol; Sampieri, Clara L; León-Córdoba, Kenneth


    Gastric cancer is the second leading cause of cancer-associated mortality in the world. Prognosis in patients with gastric cancer is difficult to establish because it is commonly diagnosed when gastric wall invasion and metastasis have occurred. Currently, some members of the extracellular matrix metalloproteinases have been identified, whose expression in gastric tumor tissue is significantly elevated compared to healthy gastric tissue. Matrix metalloproteinases are 24 zinc-dependent endopeptidases that catalyze the proteolysis of the extracellular matrix. This degradation allows the cancer cells invade the surrounding stroma and trigger metastasis. Upregulation of certain matrix metalloproteinases in gastric cancer has been associated with a poor prognosis and elevated invasive capacity. This review compiles evidence about the genetic expression of matrix metalloproteinases in gastric cancer and their role in tumour invasion and metastasis, emphasizing their potential as molecular markers of prognosis.

  15. Genitourinary cancers: molecular determinants for personalized therapies. (United States)

    Mazzucchelli, Roberta; Gasparrini, Silvia; Galosi, Andrea B; Massari, Francesco; Raspollini, Maria Rosaria; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo


    Recent insights and emerging strategies for individualized therapeutic approaches in patients with genitourinary (GU) cancers are based on patient's genomic and cancer's molecular profiles. This depends on the significant advances made in molecular biology technologies, such as next-generation sequencing and whole-exome sequencing. The rise of such novel techniques has grayly increased our knowledge on cancer cell biology and development, thus allowing to identify complex abnormalities at the genomic level. These findings have paved the way toward what is called precision medicine, thus providing healthcare from an individual perspective in patients with GU tumors.

  16. Molecular and genetic bases of pancreatic cancer. (United States)

    Vaccaro, Vanja; Gelibter, Alain; Bria, Emilio; Iapicca, Pierluigi; Cappello, Paola; Di Modugno, Francesca; Pino, Maria Simona; Nuzzo, Carmen; Cognetti, Francesco; Novelli, Francesco; Nistico, Paola; Milella, Michele


    Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

  17. Exploiting novel molecular targets in gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)


    Novel molecular targets are being discovered as we learn more about the aberrant processes underlying various cancers. Efforts to translate this knowledge are starting to impact on the care of patients with gastrointestinal cancers. The epidermal growth factor receptor (EGFR) pathway and angiogenesis have been targeted successfully in colorectal cancer with cetuximab, panitunumab and bevacizumab. Similarly, EGFR-targeting with erlotinib yielded significant survival benefit in pancreatic cancer when combined with gemcitabine. The multi-targeting approach with sorafenib has made it the first agent to achieve significant survival benefit in hepatocellular carcinoma. Efforts to exploit the dysregulated Akt/mTOR pathway in GI cancer therapy are ongoing. These molecular targets can be disrupted by various approaches, including the use of monoclonal antibody to intercept extracellular ligands and disrupt receptor-ligand binding, and small molecule inhibitors that interrupt the activation of intracellular kinases.

  18. Molecular genetics and genomics progress in urothelial bladder cancer. (United States)

    Netto, George J


    The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers.

  19. Current and emerging breast cancer biomarkers

    Directory of Open Access Journals (Sweden)

    Maryam Sana


    Full Text Available Breast cancer treatment has experienced several advancements in the past few decades with the discovery of specific predictive and prognostic biomarkers that make possible the application of individualized therapies. In addition to traditional prognostic factors of breast carcinoma, molecular biomarkers have played a significant role in tumor prediction and treatment. The most frequent genetic alterations of breast cancer are gained along chromosome 1q, 8q, 17q, 20q, and 11q and losses along 8p, 13q, 16q, 18q, and 11q. Interestingly, many of these chromosomal fragments harbor known proto oncogenes or tumor suppressor genes such as BRCA1, BRCA2, p53, HER2-neu, cyclin D1, and cyclin E, which are briefly described in this review.

  20. Terahertz molecular resonance of cancer DNA (United States)

    Cheon, Hwayeong; Yang, Hee-Jin; Lee, Sang-Hun; Kim, Young A.; Son, Joo-Hiuk


    Carcinogenesis involves the chemical and structural alteration of biomolecules in cells. Aberrant methylation of DNA is a well-known carcinogenic mechanism and a common chemical modification of DNA. Terahertz waves can directly observe changes in DNA because the characteristic energies lie in the same frequency region. In addition, terahertz energy levels are not high enough to damage DNA by ionization. Here, we present terahertz molecular resonance fingerprints of DNA methylation in cancer DNA. Methylated cytidine, a nucleoside, has terahertz characteristic energies that give rise to the molecular resonance of methylation in DNA. Molecular resonance is monitored in aqueous solutions of genomic DNA from cancer cell lines using a terahertz time-domain spectroscopic technique. Resonance signals can be quantified to identify the types of cancer cells with a certain degree of DNA methylation. These measurements reveal the existence of molecular resonance fingerprints of cancer DNAs in the terahertz region, which can be utilized for the early diagnosis of cancer cells at the molecular level.

  1. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer (United States)


    and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular mechanisms controlling melanoma and breast carcinoma...Bowman Show, August 17 Molecular regulation of melanoma and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular...Institute, April 20, Pathology ofNeoplasia Cumberland Unit, American Cancer Society, April 19; Breast Cancer Research Ministerio de Sanidad y

  2. Acoustic and photoacoustic molecular imaging of cancer. (United States)

    Wilson, Katheryne E; Wang, Tzu Yin; Willmann, Jürgen K


    Ultrasound and combined optical and ultrasonic (photoacoustic) molecular imaging have shown great promise in the visualization and monitoring of cancer through imaging of vascular and extravascular molecular targets. Contrast-enhanced ultrasound with molecularly targeted microbubbles can detect early-stage cancer through the visualization of targets expressed on the angiogenic vasculature of tumors. Ultrasonic molecular imaging can be extended to the imaging of extravascular targets through use of nanoscale, phase-change droplets and photoacoustic imaging, which provides further molecular information on cancer given by the chemical composition of tissues and by targeted nanoparticles that can interact with extravascular tissues at the receptor level. A new generation of targeted contrast agents goes beyond merely increasing imaging signal at the site of target expression but shows activatable and differential contrast depending on their interactions with the tumor microenvironment. These innovations may further improve our ability to detect and characterize tumors. In this review, recent developments in acoustic and photoacoustic molecular imaging of cancer are discussed.

  3. Acoustic and Photoacoustic Molecular Imaging of Cancer (United States)

    Wilson, Katheryne E.; Wang, Tzu Yin; Willmann, Jürgen K.


    Ultrasound and combined optical and ultrasonic (photoacoustic) molecular imaging have shown great promise in the visualization and monitoring of cancer through imaging of vascular and extravascular molecular targets. Contrast-enhanced ultrasound with molecularly targeted microbubbles can detect early-stage cancer through the visualization of targets expressed on the angiogenic vasculature of tumors. Ultrasonic molecular imaging can be extended to the imaging of extravascular targets through use of nanoscale, phase-change droplets and photoacoustic imaging, which provides further molecular information on cancer given by the chemical composition of tissues and by targeted nanoparticles that can interact with extravascular tissues at the receptor level. A new generation of targeted contrast agents goes beyond merely increasing imaging signal at the site of target expression but shows activatable and differential contrast depending on their interactions with the tumor microenvironment. These innovations may further improve our ability to detect and characterize tumors. In this review, recent developments in acoustic and photoacoustic molecular imaging of cancer are discussed. PMID:24187042

  4. Current Status of the Molecular Clock Hypothesis (United States)

    Hermann, Gilbert


    Molecular genetics is a rapidly changing field with new developments almost from day to day. One interesting hypothesis that has come from everyone's ability to sequence proteins and/or genes is that of the molecular clock. This hypothesis postulates that homologous sequences of DNA and thus macro molecules evolve at a constant and invariable rate…

  5. [Colorectal cancer (CCR): genetic and molecular alterations]. (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra


    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  6. Current early diagnostic biomarkers of prostate cancer

    Directory of Open Access Journals (Sweden)

    Min Qu


    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.

  7. Molecular Mechanisms Underlying Psychological Stress and Cancer. (United States)

    Shin, Kyeong Jin; Lee, Yu Jin; Yang, Yong Ryoul; Park, Seorim; Suh, Pann-Ghill; Follo, Matilde Yung; Cocco, Lucio; Ryu, Sung Ho


    Psychological stress is an emotion experienced when people are under mental pressure or encounter unexpected problems. Extreme or repetitive stress increases the risk of developing human disease, including cardiovascular disease (CVD), immune diseases, mental disorders, and cancer. Several studies have shown an association between psychological stress and cancer growth and metastasis in animal models and case studies of cancer patients. Stress induces the secretion of stress-related mediators, such as catecholamine, cortisol, and oxytocin, via the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis or the sympathetic nervous system (SNS). These stress-related hormones and neurotransmitters adversely affect stress-induced tumor progression and cancer therapy. Catecholamine is the primary factor that influences tumor progression. It can regulate diverse cellular signaling pathways through adrenergic receptors (ADRs), which are expressed by several types of cancer cells. Activated ADRs enhance the proliferation and invasion abilities of cancer cells, alter cell activity in the tumor microenvironment, and regulate the interaction between cancer and its microenvironment to promote tumor progression. Additionally, other stress mediators, such as glucocorticoids and oxytocin, and their cognate receptors are involved in stress-induced cancer growth and metastasis. Here, we will review how each receptor-mediated signal cascade contributes to tumor initiation and progression and discuss how we can use these molecular mechanisms for cancer therapy.

  8. Molecular markers for prostate cancer.

    NARCIS (Netherlands)

    Reynolds, M.A.; Kastury, K.; Groskopf, J.; Schalken, J.A.; Rittenhouse, H.G.


    Serum PSA testing has been used for over 20 years as an aid in the diagnosis and management of prostate cancer. Although highly sensitive, it suffers from a lack of specificity, showing elevated serum levels in a variety of other conditions including prostatitis, benign prostate hyperplasia, and non

  9. Oligometastatic non-small-cell lung cancer: current treatment strategies

    Directory of Open Access Journals (Sweden)

    Richard PJ


    Full Text Available Patrick J Richard, Ramesh Rengan Department of Radiation Oncology, University of Washington, Seattle, WA, USA Abstract: The oligometastatic disease theory was initially described in 1995 by Hellman and Weichselbaum. Since then, much work has been performed to investigate its existence in many solid tumors. This has led to subclassifications of stage IV cancer, which could redefine our treatment approaches and the therapeutic outcomes for this historically “incurable” entity. With a high incidence of stage IV disease, non-small-cell lung cancer (NSCLC remains a difficult cancer to treat and cure. Recent work has proven the existence of an oligometastatic state in NSCLC in terms of properly selecting patients who may benefit from aggressive therapy and experience long-term overall survival. This review discusses the current treatment approaches used in oligometastatic NSCLC and provides the evidence and rationale for each approach. The prognostic factors of many trials are discussed, which can be used to properly select patients for aggressive treatment regimens. Future advances in both molecular profiling of NSCLC to find targetable mutations and investigating patient selection may increase the number of patients diagnosed with oligometastatic NSCLC. As this disease entity increases, it is of utmost importance for oncologists treating NSCLC to be aware of the current treatment strategies that exist and the potential advantages/disadvantages of each. Keywords: oligometastatic, non-small-cell lung cancer, oligoprogressive, treatment

  10. Molecular targeting of acid ceramidase: implications to cancer therapy. (United States)

    Zeidan, Youssef H; Jenkins, Russell W; Korman, John B; Liu, Xiang; Obeid, Lina M; Norris, James S; Hannun, Yusuf A


    Increasingly recognized as bioactive molecules, sphingolipids have been studied in a variety of disease models. The impact of sphingolipids on cancer research facilitated the entry of sphingolipid analogues and enzyme modulators into clinical trials. Owing to its ability to regulate two bioactive sphingolipids, ceramide and sphingosine-1-phosphate, acid ceramidase (AC) emerges as an attractive target for drug development within the sphingolipid metabolic pathway. Indeed, there is extensive evidence supporting a pivotal role for AC in lipid metabolism and cancer biology. In this article, we review the current knowledge of the biochemical properties of AC, its relevance to tumor promotion, and its molecular targeting approaches.

  11. Transient currents in a molecular photo-diode


    Petrov, E. G.; Leonov, V. O.; May, V.; Hänggi, P.


    Light-induced charge transmission through a molecular junction (molecular diode) is studied in the framework of a HOMO-LUMO model and in using a kinetic description. Expressions are presented for the sequential (hopping) and direct (tunneling) transient current components together with kinetic equations governing the time-dependent populations of the neutral and charged molecular states which participate in the current formation. Resonant and off-resonant charge transmission processes are ana...

  12. Molecular pathogenesis ofsporadic colorectal cancers

    Institute of Scientific and Technical Information of China (English)

    HidetsuguYamagishi; HajimeKuroda; YasuoImai; HideyukiHiraishi


    Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classiifed into three major groups according to frequently altered/mutated genes. These genes have been identiifed by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the ifrst half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a lim-ited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research ifeld and discuss its prospects.

  13. Evolving molecularly targeted therapies for advanced-stage thyroid cancers. (United States)

    Bible, Keith C; Ryder, Mabel


    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research.

  14. [Molecular bases of cancer immunology]. (United States)

    Barrera-Rodríguez, R; Peralta-Zaragoza, O; Madrid-Marina, V


    The immune system is a tight network of different types of cells and molecules. The coordinated action of these elements mounts a precise immune response against tumor cells. However, these cells present several escape mechanisms, leading to tumor progression. This paper shows several cellular and molecular events involved in the regulation of the immune response against tumor cells. The interaction of several molecules such as MHC, TcR, adhesins, tumor antigens and cytokines are discussed, as well as the most recent knowledge about escape mechanisms and immunotherapy.

  15. Cancer screening in the United States, 2016: A review of current American Cancer Society guidelines and current issues in cancer screening. (United States)

    Smith, Robert A; Andrews, Kimberly; Brooks, Durado; DeSantis, Carol E; Fedewa, Stacey A; Lortet-Tieulent, Joannie; Manassaram-Baptiste, Deana; Brawley, Otis W; Wender, Richard C


    Each year the American Cancer Society (ACS) publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, we summarize current ACS cancer screening guidelines, including the update of the breast cancer screening guideline, discuss quality issues in colorectal cancer screening and new developments in lung cancer screening, and provide the latest data on utilization of cancer screening from the National Health Interview Survey.

  16. Current role of surgical therapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ryan Swan; Thomas J Miner


    Surgery is currently the only potentially curative treatment for gastric cancer. Since the inception of the gastrectomy for cancer of the stomach, there has been debate over the bounds of surgical therapy, balancing potential long-term survival with perioperative morbidity and mortality. This review delineates the current role of surgery in preoperative staging, curative resection, and palliative treatment for gastric cancer.

  17. Current trends in staging rectal cancer

    Institute of Scientific and Technical Information of China (English)

    Abdus Samee; Chelliah Ramachandran Selvasekar


    Management of rectal cancer has evolved over the years.In this condition preoperative investigations assist in deciding the optimal treatment.The relation of the tumor edge to the circumferential margin (CRM) is an important factor in deciding the need for neoadjuvant treatment and determines the prognosis.Those with threatened or involved margins are offered long course chemoradiation to enable R0 surgical resection.Endoanal ultrasound (EUS) is useful for tumor (T) staging;hence EUS is a useful imaging modality for early rectal cancer.Magnetic resonance imaging (MRI) is useful for assessing the mesorectum and the mesorectal fascia which has useful prognostic significance and for early identification of local recurrence.Computerized tomography (CT) of the chest,abdomen and pelvis is used to rule out distant metastasis.Identification of the malignant nodes using EUS,CT and MRI is based on the size,morphology and internal characteristics but has drawbacks.Most of the common imaging techniques are suboptimal for imaging following chemoradiation as they struggle to differentiate fibrotic changes and tumor.In this situation,EUS and MRI may provide complementary information to decide further treatment.Functional imaging using positron emission tomography (PET) is useful,particularly PET/CT fusion scans to identify areas of the functionally hot spots.In the current state,imaging has enabled the multidisciplinary team of surgeons,oncologists,radiologists and pathologists to decide on the patient centered management of rectal cancer.In future,functional imaging may play an active role in identifying patients with lymph node metastasis and those with residual and recurrent disease following neoadjuvant chemoradiotherapy.

  18. [New molecular classification of colorectal cancer, pancreatic cancer and stomach cancer: Towards "à la carte" treatment?]. (United States)

    Dreyer, Chantal; Afchain, Pauline; Trouilloud, Isabelle; André, Thierry


    This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion). In gastric adenocarcinoma, 4 groups were established: subtype "EBV" (9%, high frequency of PIK3CA mutations, hypermetylation and amplification of JAK2, PD-L1 and PD-L2), subtype "MSI" (22%, high rate of mutation), subtype "genomically stable tumor" (20%, diffuse histology type and mutations of RAS and genes encoding integrins and adhesion proteins including CDH1) and subtype "tumors with chromosomal instability" (50%, intestinal type, aneuploidy and receptor tyrosine kinase amplification). In pancreatic adenocarcinomas, a classification in four sub-groups has been proposed, stable subtype (20%, aneuploidy), locally rearranged subtype (30%, focal event on one or two chromosoms), scattered subtype (36%,200 structural variation events, defects in DNA maintenance). Although currently away from the care of patients, these classifications open the way to "à la carte" treatment depending on molecular biology.

  19. Clinical implications of the intrinsic molecular subtypes of breast cancer. (United States)

    Prat, Aleix; Pineda, Estela; Adamo, Barbara; Galván, Patricia; Fernández, Aranzazu; Gaba, Lydia; Díez, Marc; Viladot, Margarita; Arance, Ana; Muñoz, Montserrat


    Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo)adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications.

  20. Cellular and molecular aspects of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Malcolm G Smith; Georgina L Hold; Eiichi Tahara; Emad M El-Omar


    Gastric cancer remains a global killer with a shifting burden from the developed to the developing world.The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori (H pylori) as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie H pyloriinduced gastric cancer.

  1. Too Few Current, Former Smokers Screened for Lung Cancer (United States)

    ... html Too Few Current, Former Smokers Screened for Lung Cancer Such testing could cut death rate by 20 ... the United States don't get screened for lung cancer even though they're at increased risk for ...

  2. Molecular Pathogenesis and Current Therapy in Intrahepatic Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Høgdall, Dan Taksony Solyom; O'Rourke, Colm J; Taranta, Andrzej;


    approaches. Depending on the cellular target of malignant transformation, a large spectrum of molecular and morphological patterns is observed. As such, it is crucial to advance our existing understanding of the molecular pathogenesis of iCCA, particularly its genomic heterogeneity, to improve current...

  3. Status and Advances of RGD Molecular Imaging in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ning YUE


    Full Text Available Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD peptides could combine with integrins specifically, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to reflect its changes. The lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

  4. Molecular ultrasound imaging: current status and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Deshpande, N. [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California (United States); Needles, A. [Visualsonics, Toronto (Canada); Willmann, J.K., E-mail: willmann@stanford.ed [Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California (United States)


    Targeted contrast-enhanced ultrasound (molecular ultrasound) is an emerging imaging strategy that combines ultrasound technology with novel molecularly-targeted ultrasound contrast agents for assessing biological processes at the molecular level. Molecular ultrasound contrast agents are nano- or micro-sized particles that are targeted to specific molecular markers by adding high-affinity binding ligands onto the surface of the particles. Following intravenous administration, these targeted ultrasound contrast agents accumulate at tissue sites overexpressing specific molecular markers, thereby enhancing the ultrasound imaging signal. High spatial and temporal resolution, real-time imaging, non-invasiveness, relatively low costs, lack of ionising irradiation and wide availability of ultrasound systems are advantages compared to other molecular imaging modalities. In this article we review current concepts and future directions of molecular ultrasound imaging, including different classes of molecular ultrasound contrast agents, ongoing technical developments of pre-clinical and clinical ultrasound systems, the potential of molecular ultrasound for imaging different diseases at the molecular level, and the translation of molecular ultrasound into the clinic.

  5. Molecular aspects of prostate cancer: implications for future directions

    Directory of Open Access Journals (Sweden)

    Etel R. P. Gimba


    Full Text Available Many studies have been developed trying to understand the complex molecular mechanisms involved in oncogenesis and progression of prostate cancer (PCa. Current biotechnological methodologies, especially genomic studies, are adding important aspects to this area. The construction of extensive DNA sequence data and gene expression profiles have been intensively explored to search for candidate biomarkers to evaluate PCa. The use of DNA micro-array robotic systems constitutes a powerful approach to simultaneously monitor the expression of a great number of genes. The resulting gene expressing profiles can be used to specifically describe tumor staging and response to cancer therapies. Also, it is possible to follow PCa pathological properties and to identify genes that anticipate the behavior of clinical disease. The molecular pathogenesis of PCa involves many contributing factors, such as alterations in signal transduction pathways, angiogenesis, adhesion molecules expression and cell cycle control. Also, molecular studies are making clear that many genes, scattered through several different chromosomal regions probably cause predisposition to PCa. The discovery of new molecular markers for PCa is another relevant advance resulting from molecular biology studies of prostate tumors. Interesting tissue and serum markers have been reported, resulting in many cases in useful novelties to diagnostic and prognostic approaches to follow-up PCa. Finally, gene therapy comes as an important approach for therapeutic intervention in PCa. Clinical trials for PCa have been demonstrating that gene therapy is relatively safe and well tolerated, although some improvements are yet to be developed.

  6. Current perspectives between metabolic syndrome and cancer. (United States)

    Micucci, Carla; Valli, Debora; Matacchione, Giulia; Catalano, Alfonso


    Metabolic syndrome is a cluster of risk factors that lead to cardiovascular morbidity and mortality. Recent studies linked metabolic syndrome and several types of cancer. Although metabolic syndrome may not necessarily cause cancer, it is linked to poorer cancer outcomes including increased risk of recurrence and overall mortality. This review tends to discuss the major biological and physiological alterations involved in the increase of incidence and mortality of cancer patients affected by metabolic syndrome. We focus on metabolic syndrome-associated visceral adiposity, hyperinsulinemia, hyperglycemia, insulin-like growth factor (IGF-I) pathway as well as estrogen signaling and inflammation. Several of these factors are also involved in carcinogenesis and cancer progression. A better understanding of the link between metabolic syndrome and cancer may provide new insight about oncogenesis. Moreover, prevention of metabolic syndrome - related alterations may be an important aspect in the management of cancer patients during simultaneous palliative care.

  7. Controlling charge current through a DNA based molecular transistor (United States)

    Behnia, S.; Fathizadeh, S.; Ziaei, J.


    Molecular electronics is complementary to silicon-based electronics and may induce electronic functions which are difficult to obtain with conventional technology. We have considered a DNA based molecular transistor and study its transport properties. The appropriate DNA sequence as a central chain in molecular transistor and the functional interval for applied voltages is obtained. I-V characteristic diagram shows the rectifier behavior as well as the negative differential resistance phenomenon of DNA transistor. We have observed the nearly periodic behavior in the current flowing through DNA. It is reported that there is a critical gate voltage for each applied bias which above it, the electrical current is always positive.

  8. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail:; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)


    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  9. Current progress in immunotherapy for pancreatic cancer. (United States)

    Foley, Kelly; Kim, Victoria; Jaffee, Elizabeth; Zheng, Lei


    Pancreatic cancer remains one of the most lethal cancers with few treatment options. Immune-based strategies to treat pancreatic cancer, such as immune checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies, are showing promise where other approaches have failed. Immune checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, are effective as single agents in immune sensitive cancers like melanoma, but lack efficacy in immune insensitive cancers including pancreatic cancer. However, these inhibitors are showing clinical activity, even in traditionally non-immunogenic cancers, when combined with other interventions, including chemotherapy, radiation therapy, and therapeutic vaccines. Therapeutic vaccines given together with immune modulating agents are of particular interest because vaccines are the most efficient way to induce effective anti-tumor T cell responses, which is required for immunotherapies to be effective. In pancreatic cancer, early studies suggest that vaccines can induce T cells that have the potential to recognize and kill pancreatic cancer cells, but the tumor microenvironment inhibits effective T cell trafficking and function. While progress has been made in the development of immunotherapies for pancreatic cancer over the last several years, additional trials are needed to better understand the signals within the tumor microenvironment that are formidable barriers to T cell infiltration and function. Additionally, as more pancreatic specific antigens are identified, immunotherapies will continue to be refined to provide the most significant clinical benefit.

  10. [Update on current care guidelines: ovarian cancer]. (United States)

    Leminen, Arto; Auranen, Annika; Bützow, Ralf; Hietanen, Sakari; Komulainen, Marja; Kuoppala, Tapio; Mäenpää, Johanna; Puistola, Ulla; Vuento, Maarit; Vuorela, Piia; Yliskoski, Merja


    Ovarian cancer is the most lethal gynaecological cancer. It appears that seemingly ovarian or primary peritoneal carcinomas, in fact, originate from fimbriae. BRCA1/2 mutation carriers are recommended for the removal of ovaries and fimbriae, to reduce the risk of cancer. Treatment of epithelial ovarian cancer is based on the combination of surgery and chemotherapy. The residual tumour volume at the primary operation is the most important predictive factor of survival. The best response at the primary treatment is observed with combination chemotherapy with taxane and platinum. Adding bevacitzumab to first line chemotherapy may improve survival.

  11. Current issues in gastric cancer epidemiology. (United States)

    Patru, C L; Surlin, V; Georgescu, I; Patru, Emilia


    Gastric cancer, one of the most common malignant tumors of digestive tract continues to be a major health problem by frequency, aggressiveness and low rate of cure in symptomatic stage. Although its incidence is decreasing (especially in the West), globally the gastric cancer is ranked fourth in incidence among cancers at various sites. Despite these developments, the gastric cancer mortality, overall declining globally, is high. especially in the West where even if diagnosed fewer cases of gastric cancer, TNM stages are advanced and have a poor prognosis. In contrast, in Japan, where the incidence is still high, the percentage of cases diagnosed at the stage of "early gastric cancer" has greatly increased, thus improving prognosis. Gastric neoplasia affects more men, age range 50-70 years, disadvantaged social classes and black race. In Romania the gastric cancer incidence is increasing over recent years, presenting variations across the country being more common in men compared with women, reaching a peak of incidence around age 60. Gastric cancer mortality in the world places Romania among the countries with average mortality. Gastric cancer prognosis remains extremely reserved, in close correlation with tumor stage at diagnosis, surgical treatment being the only possibility to provide improved survival, especially in the early stages. Improvement of survival rate in recent years is due to increased gastric resectability result of an earlier diagnosis, a more complex treatment and a closer monitoring of the population at risk.

  12. Oral cancer: molecular technologies for risk assessment and diagnosis

    Institute of Scientific and Technical Information of China (English)

    Wan Tao Chen


    @@ Purpose: The effective biomarkers related to diagnosis, metastasis, drug resistance and irradiation sensitivity of oral cancers will help the pathologist and oncologist to determine the molecular taxonomy diagnosis and design the individualization treatment for the patients with oral cancers.

  13. Molecular diagnosis of lung cancer: an overview of recent developments. (United States)

    Mutti, Antonio


    Health surveillance of workers occupationally exposed to lung carcinogens calls for screening procedures which may not be fully justified, owing to current uncertainties about the outcome of early detection. Indeed, bias-free designs are difficult to set up, and the effects of lead time, length and screening biases can all result in an overestimation of the benefits of screenings, which certainly increase survival, but without any actual reduction of mortality. A major issue with modern imaging techniques is the very high incidence of discovery of lung nodules, usually false positive, but still calling for additional and sometimes painful examinations. Currently, the differential diagnosis is mainly based on additional imaging approaches, particularly positron emission tomography, which is very expensive and also shows limitations in terms of sensitivity and specificity. Therefore, purely morphological criteria seem to be insufficient to distinguish lung cancer at early stages from benign nodules with sufficient confidence. A molecular approach to the diagnosis of lung cancer through biomarkers measured by non-invasive means could greatly improve the specificity of imaging procedures. Extremely sensitive mass spectrometric techniques and polymerase chain reaction-based methods are available to detect, in accessible media, molecular alterations which characterise lung cancer at an early stage, thereby reducing the rate of false positives. The lessons learnt from decades of screening programmes based on imaging and the future prospects possibly enhanced by using biomarkers are briefly discussed in this overview. (

  14. Nanomedicines as cancer therapeutics: Current status

    NARCIS (Netherlands)

    Akhter, S.; Ahmad, M; Ramzani, F.; Singh, A..; Ahmad, I.; Rahman, Z.; Ahmad, F.J.; Storm, G.; Kok, R.J.


    As of 21st century, cancer is arguably the most complex and challenging disease known to mankind and an inevitable public health concern of this millennium. Nanotechnology, suitably amalgamated with cancer research, has ushered an era of highly personalized and safer medicines which can improve canc

  15. Current surgical treatment for bile duct cancer

    Institute of Scientific and Technical Information of China (English)

    Yasuji Seyama; Masatoshi Makuuchi


    Since extrahepatic bile duct cancer is difficult to diagnose and to cure, a safe and radical surgical strategy is needed. In this review, the modes of infiltration and spread of extrahepatic bile duct cancer and surgical strategy are discussed. Extended hemihepatectomy, with or without pancreatoduodenectomy (PD), plus extrahepatic bile duct resection and regional lymphadenectomy has recently been recognized as the standard curative treatment for hilar bile duct cancer. On the other hand, PD is the choice of treatment for middle and distal bile duct cancer. Major hepatectomy concomitant with PD (hepatopancreatoduodenectomy) has been applied to selected patients with widespread tumors. Preoperative biliary drainage (BD) followed by portal vein embolization (PVE) enables major hepatectomy in patients with hilar bile duct cancer without mortality. BD should be performed considering the surgical procedure, especially, in patients with separated intrahepatic bile ducts caused by hilar bile duct cancer. Right or left trisectoriectomy are indicated according to the tumor spread and biliary anatomy. As a result, extended radical resection offers a chance for cure of hilar bile duct cancer with improved resectability, curability, and a 5-year survival rate of 40%. A 5-year survival rate has ranged from 24% to 39% after PD for middle and distal bile duct cancer.

  16. Current Research and Management of Ovarian Cancer in China

    Institute of Scientific and Technical Information of China (English)

    GUMeijiao; SHIWei


    Ovarian cancer is ne of the most lethal malignant tumors in China,represents the third most common cancer after cervical cancer and endometrial cancer,and the first leading cause of death from hynaecological cancers.Due to the lack of effective screening strategies and the absence of symptoms in early-stage of disease,over 70% of patients present at an advanced stage.Despite the advances in surgical techniques and conventional chemotheraphy,the prognosis of ovarian cancer has not been improved significantly,and indeed the long-term survival for patients with advanced disease does not exceed 20%.The aetiology of ovarian cancer temains poorly understood.In China,the major focus of research is to clarify the mechanism underlying ovarian cancer,develop more effective life-saving diagnostic and therapeutic measures,and undertake more population-based studies.This article summarizes current research,diagnosis and management of ovarian cancer in China.

  17. Predictive and prognostic molecular markers for cancer medicine. (United States)

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


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

  18. Molecular markers for thyroid cancer diagnosis, prognosis, and targeted therapy. (United States)

    Yip, Linwah


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

  19. Current molecular methods in epidemiological typing of Acinetobacter baumannii. (United States)

    Rafei, Rayane; Kempf, Marie; Eveillard, Matthieu; Dabboussi, Fouad; Hamze, Monzer; Joly-Guillou, Marie-Laure


    The emergence of Acinetobacter baumannii during recent decades as an important nosocomial pathogen responsible of worldwide, intensively documented, outbreaks has resulted in a need for effective epidemiological typing methods. Throughout the years, many typing methods for A. baumannii epidemiological studies have been proposed from phenotypic to molecular methods. Currently, the use of phenotypic typing methods have declined considerably and been progressively replaced by molecular methods. In this review, we introduce the current molecular methods available for A. baumannii typing. Each method has its own advantages and disadvantages, and the selection of an appropriate genotyping method depends on studied objectives. This review sheds light on questions in different epidemiological settings and most molecular methods used to fit these objectives.

  20. Molecular profiling of childhood cancer: Biomarkers and novel therapies

    Directory of Open Access Journals (Sweden)

    Federica Saletta


    General significance: The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

  1. Chemoprevention of gastric cancer: current status

    Institute of Scientific and Technical Information of China (English)


    The development of gastric cancer is a multi-factor process. In addition to genetic factors, environmental factors including smoking, low gastric acidity, excessive intake of salt or salty food and low consumption of fresh fruits and vegetables all contribute to the development of gastric cancer. Of particular interest, epidemiological and experimental studies have demonstrated that Helicobacter pylori (H. pylori) infection is causally linked to gastric cancer. Most studies using micronutrient supplementation have failed to demonstrate any preventive effect against the development of gastric cancer. The use of non-steroidal anti-inflammatory drugs has been consistently observed to protect against the development of gastric cancer. Recently, eradication of H. pylori infection by a chemopreventative approach is being studied in a number of trials. Studies using precancerous lesions as an end point of the treatment have produced conflicting and mostly negative results. Trials using cancer as an end point are being cautiously carried out in high-risk populations, and will provide the definitive answer to this important question. In the end, vaccination may be proven to be the optimal strategy in human for the management of H. pylori infection and prevention of gastric cancer.

  2. Molecular targets of cancer chemoprevention by garlic-derived organosulfides

    Institute of Scientific and Technical Information of China (English)



    The medicinal benefits of Allium vegetables, especially garlic, have been noted throughout recorded history. The known health benefits of Allium vegetables and their constituents include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, radioprotection, improvement of memory loss, protection against microbial, viral and fungal infections, as well as anticancer effects. Population-based case control studies have suggested an inverse correlation between dietary intake of Allium vegetables and the risk of different types of cancers. The anticarcinogenic effect of Allium vegetables in-eluding garlic is attributed to organosulfur compounds (OSC), which are highly effective in affording protection against cancer in animal models induced by a variety of chemical carcinogens. More recent studies have shown that certain naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and in vivo. The OSC-induced changes in the proliferation of cancer Cellsare frequently associated with perturbations in cell cycle progression and induc-tion of G2/M phase arrest. The OSC have also been demonstrated to induce apoptosis via the intrinsic pathway by altering the ratio of the Bc1-2 family of proteins both in cell culture and in in vivo models. Anti-angiogenic activity for garlic-derived OSC has also been documented. This article summarizes current knowledge on molecular targets of cancer chemoprevention by OSC.

  3. The Current State of Targeted Agents in Rectal Cancer



    Targeted biologic agents have an established role in treating metastatic colorectal cancer (CRC), and the integration of targeted therapies into the treatment of CRC has resulted in significant improvements in outcomes. Rapidly growing insight into the molecular biology of CRC, as well as recent developments in gene sequencing and molecular diagnostics, has led to high expectations for the identification of molecular markers to be used in personalized treatment regimens. The mechanisms of act...

  4. Fecal Molecular Markers for Colorectal Cancer Screening

    Directory of Open Access Journals (Sweden)

    Rani Kanthan


    Full Text Available Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.

  5. [Cervical cancer screening in Switzerland - current practice and future challenges]. (United States)

    Untiet, Sarah; Schmidt, Nicole; Low, Nicola; Petignat, Patrick


    At the beginning of the 20th Century, cervical cancer was the leading cause of death from cancer in women. A marked decline in cervical cancer has been observed since the 1960s, in parallel with the introduction of the Papanicolau (Pap) test as a cytological screening method. Today, Pap smear screening is still the most widely used tool for cervical cancer prevention. Testing for human papillomavirus (HPV) in cervical specimens or a combination of Pap and HPV testing are also now available. In this article we compare current guidelines for cervical cancer screening in Switzerland with those in other European countries. In view of the opportunities offered by HPV testing and, since 2008, HPV vaccination, current guidelines for cervical cancer screening should be updated. Both the choice of screening tests and general organization of cervical cancer screening should be reviewed.

  6. Current status of oral cancer chemoprevention

    Institute of Scientific and Technical Information of China (English)

    Moni Abraham Kuriakose


    @@ Chemoprevention is the administration of agents to block or reverse carcinogenesis. Chemoprevention in oral cancer has been directed towards reversal of premalignant lesion and prevention of second primary tumor.

  7. Collaborative Research in Childhood Cancer Survivorship: The Current Landscape. (United States)

    Bhatia, Smita; Armenian, Saro H; Armstrong, Gregory T; van Dulmen-den Broeder, Eline; Hawkins, Michael M; Kremer, Leontien C M; Kuehni, Claudia E; Olsen, Jørgen H; Robison, Leslie L; Hudson, Melissa M


    Survivors of childhood cancer carry a substantial burden of morbidity and are at increased risk for premature death. Furthermore, clear associations exist between specific therapeutic exposures and the risk for a variety of long-term complications. The entire landscape of health issues encountered for decades after successful completion of treatment is currently being explored in various collaborative research settings. These settings include large population-based or multi-institutional cohorts and single-institution studies. The ascertainment of outcomes has depended on self-reporting, linkage to registries, or clinical assessments. Survivorship research in the cooperative group setting, such as the Children's Oncology Group, has leveraged the clinical trials infrastructure to explore the molecular underpinnings of treatment-related adverse events, and to understand specific complications in the setting of randomized risk-reduction strategies. This review highlights the salient findings from these large collaborative initiatives, emphasizing the need for life-long follow-up of survivors of childhood cancer, and describing the development of several guidelines and efforts toward harmonization. Finally, the review reinforces the need to identify populations at highest risk, facilitating the development of risk prediction models that would allow for targeted interventions across the entire trajectory of survivorship.

  8. Breast cancer molecular subtypes: from TNBC to QNBC (United States)

    Hon, Jane Date C; Singh, Baljit; Sahin, Aysegul; Du, Gang; Wang, Jinhua; Wang, Vincent Y; Deng, Fang-Ming; Zhang, David Y; Monaco, Marie E; Lee, Peng


    Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy. In an effort to develop targeted therapies for TNBC, it will be necessary to differentiate among specific TNBC subtypes. The subset of TNBC that expresses androgen receptor (AR) has been determined to express genes consistent with a luminal subtype and therefore may be amenable to therapies targeting either AR, itself, or other pathways typical of a luminal subtype. Recent investigations of the AR signal pathway within breast cancer lead to AR as a significant target for breast cancer therapy with several clinical trials currently in progress. The subclass of TNBC that lacks AR, which we have termed quadruple negative breast cancer (QNBC) currently lacks a defined targetable pathway. Unlike AR-positive TNBC, QNBC predominantly exhibits a basal-like molecular subtype. Several subtypes and related pathway proteins are preferentially expressed in QNBC that may serve as effective targets for treatment, such as ACSL4, SKP2 and EGFR. ACSL4 expression has been demonstrated to be inversely correlated with expression of hormone/growth factor receptors and may thus serve as a biomarker for QNBC as well as a target for therapy. In the following review we summarize some of the current efforts to develop alternatives to chemotherapy for TNBC and QNBC.

  9. Aromatic and antiaromatic ring currents in a molecular nanoring (United States)

    Peeks, Martin D.; Claridge, Timothy D. W.; Anderson, Harry L.


    Aromatic and antiaromatic molecules—which have delocalized circuits of [4n + 2] or [4n] electrons, respectively—exhibit ring currents around their perimeters. The direction of the ring current in an aromatic molecule is such as to generate a magnetic field that opposes the external field inside the ring (a ‘diatropic’ current), while the ring current in an antiaromatic molecule flows in the reverse direction (‘paratropic’). Similar persistent currents occur in metal or semiconductor rings, when the phase coherence of the electronic wavefunction is preserved around the ring. Persistent currents in non-molecular rings switch direction as a function of the magnetic flux passing through the ring, so that they can be changed from diatropic (‘aromatic’) to paratropic (‘antiaromatic’) simply by changing the external magnetic field. As in molecular systems, the direction of the persistent current also depends on the number of electrons. The relationship between ring currents in molecular and non-molecular rings is poorly understood, partly because they are studied in different size regimes: the largest aromatic molecules have diameters of about one nanometre, whereas persistent currents are observed in microfabricated rings with diameters of 20-1,000 nanometres. Understanding the connection between aromaticity and quantum-coherence effects in mesoscopic rings provides a motivation for investigating ring currents in molecules of an intermediate size. Here we show, using nuclear magnetic resonance spectroscopy and density functional theory, that a six-porphyrin nanoring template complex, with a diameter of 2.4 nanometres, is antiaromatic in its 4+ oxidation state (80 π electrons) and aromatic in its 6+ oxidation state (78 π electrons). The antiaromatic state has a huge paramagnetic susceptibility, despite having no unpaired electrons. This work demonstrates that a global ring current can be promoted in a macrocycle by adjusting its oxidation state

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Directory of Open Access Journals (Sweden)

    John Schofield


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

  12. Emerging Molecularly Targeted Therapies in Castration Refractory Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jesal C. Patel


    Full Text Available Androgen deprivation therapy (ADT with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration refractory metastatic prostate cancer (CRPC and die of their disease. Over the last decade, it has been recognized that despite the failure of ADT, most prostate cancers maintain some dependence on androgen and/or androgen receptor (AR signaling for proliferation. Furthermore, androgen independent molecular pathways have been identified as drivers of continued progression of CRPC. Subsequently, drugs have been developed targeting these pathways, many of which have received regulatory approval. Agents such as abiraterone, enzalutamide, orteronel (TAK-700, and ARN-509 target androgen signaling. Sipuleucel-T, ipilimumab, and tasquinimod augment immune-mediated tumor killing. Agents targeting classic tumorogenesis pathways including vascular endothelial growth factor, hepatocyte growth factor, insulin like growth factor-1, tumor suppressor, and those which regulate apoptosis and cell cycles are currently being developed. This paper aims to focus on emerging molecular pathways underlying progression of CRPC, and the drugs targeting these pathways, which have recently been approved or have reached advanced stages of development in either phase II or phase III clinical trials.

  13. Molecular Imaging of Prostate Cancer: A Concise Synopsis

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar


    Full Text Available Prostate cancer is the most common malignancy in men and continues to be a major public health problem. Imaging of prostate cancer remains particularly challenging owing to disease heterogeneity. Molecular imaging can provide unprecedented opportunities for deciphering the molecular mechanisms that are involved in the development and natural progression of prostate cancer from a localized process to the hormone-refractory metastatic disease. Such understanding will be the key for targeted imaging and therapy and for predicting and evaluating treatment response and prognosis. In this article, we review briefly the contribution of multimodality molecular imaging methods for the in vivo characterization of the pathophysiology of prostate cancer.

  14. Current therapy of small cell lung cancer

    DEFF Research Database (Denmark)

    Sorensen, M; Lassen, U; Hansen, H H


    This article reviews the most important recent clinical trials on the treatment of small cell lung cancer (SCLC). Two randomized studies addressing the timing of thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the two studies (n = 103), a survival benefit was associated...

  15. Current management of locally recurrent rectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Mette Bak; Laurberg, Søren; Holm, Thorbjörn


    ABSTRACT Objective: A review of the literature was undertaken to provide an overview of the surgical management of locally recurrent rectal cancer (LRRC) after the introduction of total mesorectal excision (TME). Method: A systematic literature search was undertaken using PubMed, Embase, Web...

  16. Current vaccination strategies for prostate cancer.

    NARCIS (Netherlands)

    Joniau, S.; Abrahamsson, P.A.; Bellmunt, J.; Figdor, C.G.; Hamdy, F.; Verhagen, P.; Vogelzang, N.J.; Wirth, M.; Poppel, H. van; Osanto, S.


    CONTEXT: The first therapeutic cancer vaccine demonstrating effectiveness in a phase 3 study was approved by the US Food and Drug Administration on 29 April 2010. The pivotal trial demonstrated overall survival (OS) benefit in patients treated with antigen-loaded leukapheresis cells compared with a

  17. Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers

    NARCIS (Netherlands)

    A.N.A. Milne; R. Carvalho; F.M. Morsink; A.R. Musler; W.W.J. de Leng; A. Ristimaki; G.J.A. Offerhaus


    Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (<= 45 years old) and conventional gastric cancers. Expression of cycloxygenase-2 (COX-2) is elevated in g

  18. Hormonal and molecular aspects of endometrioid endometrial cancer

    NARCIS (Netherlands)

    Jongen, Vincentius Hubertus Willibrordus Maria


    This thesis concerns the expression and prognostic value of various hormones and molecular markers playing a role n endometrioid endometrial cancer. Especially we were interested in the enzyme aromatase, its expression and (prognostic) role in endometrioid endometrial cancer. Endometrial cancer is t

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

    Directory of Open Access Journals (Sweden)

    Alphy Rose-James


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

  20. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)


    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

  1. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer. (United States)

    Kamel, Azza M; Teama, Salwa; Fawzy, Amal; El Deftar, Mervat


    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.

  2. Appraisal of progenitor markers in the context of molecular classification of breast cancers. (United States)

    Haviv, Izhak


    Clinical management of breast cancer relies on case stratification, which increasingly employs molecular markers. The motivation behind delineating breast epithelial differentiation is to better target cancer cases through innate sensitivities bequeathed to the cancer from its normal progenitor state. A combination of histopathological and molecular classification of breast cancer cases suggests a role for progenitors in particular breast cancer cases. Although a remarkable fraction of the real tissue repertoire is maintained within a population of independent cell line cultures, some steps that are closer to the terminal differentiation state and that form a majority of primary human breast tissues are missing in the cell line cultures. This raises concerns about current breast cancer models.

  3. Animal models and therapeutic molecular targets of cancer: utility and limitations

    Directory of Open Access Journals (Sweden)

    Cekanova M


    Full Text Available Maria Cekanova, Kusum Rathore Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients. Keywords: mouse cancer model, companion animal cancer model, dogs, cats, molecular targets

  4. Current therapeutic strategies for invasive and metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Vishnu P


    Full Text Available Prakash Vishnu, Jacob Mathew, Winston W TanDivision of Hematology Oncology, Mayo Clinic, Jacksonville, FL, USABackground: Bladder cancer is one of the most common cancers in Europe, the United States, and Northern African countries. Muscle-invasive bladder cancer is an aggressive epithelial tumor, with a high rate of early systemic dissemination. Superficial, noninvasive bladder cancer can most often be cured; a good proportion of invasive cases can also be cured by a combined modality approach of surgery, chemotherapy, and radiation. Recurrences are common and mostly manifest as metastatic disease. Those with distant metastatic disease can sometime achieve partial or complete remission with combination chemotherapy.Recent developments: Better understanding of the biology of the disease has led to the incorporation of molecular and genetic features along with factors such as tumor grade, lympho-vascular invasion, and aberrant histology, thereby allowing identification of ‘favorable’ and ‘unfavorable’ cancers which helps a more accurate informed and objective selection of patients who would benefit from neoadjuvant and adjuvant chemotherapy. Gene expression profiling has been used to find molecular signature patterns that can potentially be predictive of drug sensitivity and metastasis. Understanding the molecular pathways of invasive bladder cancer has led to clinical investigation of several targeted therapeutics such as anti-angiogenics, mTOR inhibitors, and anti-EGFR agents.Conclusion: With improvements in the understanding of the biology of bladder cancer, clinical trials studying novel and targeted agents alone or in combination with chemotherapy have increased the armamentarium for the treatment of bladder cancer. Although the novel biomarkers and gene expression profiles have been shown to provide important predictive and prognostic information and are anticipated to be incorporated in clinical decision-making, their exact utility

  5. Molecular aspects of carcinogenesis in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Alexandros Koliopanos; Constantinos Avgerinos; Constantina Paraskeva; Zisis Touloumis; Dionisisa Kelgiorgi; Christos Dervenis


    BACKGROUND: Pancreatic cancer (PCa) is one of the most aggressive human solid tumors, with rapid growth and metastatic spread as well as resistance to chemotherapeutic drugs, leading rapidly to virtually incurable disease. Over the last 20 years, however, signiifcant advances have been made in our understanding of the molecular biology of PCa, with a focus on the cytogenetic abnormalities in PCa cell growth and differentiation. DATA SOURCES: A MEDLINE search and manual cross-referencing were utilized to identify published data for PCa molecular biology studies between 1986 and 2008, with emphasis on genetic alterations and developmental oncology. RESULTS: Activation of oncogenes, deregulation of tumor suppressor and genome maintenance genes, upregulation of growth factors/growth factor receptor signaling cascade systems, and alterations in cytokine expression, have been reported to play important roles in the process of pancreatic carcinogenesis. Alterations in the K-ras proto-oncogene and the p16INK4a, p53, FHIT, and DPC4 tumor suppressor genes occur in a high percentage of tumors. Furthermore, a variety of growth factors are expressed at increased levels. In addition, PCa often exhibits alterations in growth inhibitory pathways and evades apoptosis through p53 mutations and aberrant expression of apoptosis-regulating genes, such as members of the Bcl family. Additional pathways in the development of an aggressive phenotype, local inifltration and metastasis are still under ongoing genetic research. The present paper reviews recent studies on the pathogenesis of PCa, and includes a brief reference to alterations reported for other types of pancreatic tumor. CONCLUSIONS: Advances in molecular genetics and biology have improved our perception of the pathogenesis of PCa. However, further studies are needed to better understand the fundamental changes that occur in PCa, thus leading to better diagnostic and therapeutic management.

  6. Current treatment options for colon cancer peritoneal carcinomatosis. (United States)

    Aoyagi, Tomoyoshi; Terracina, Krista P; Raza, Ali; Takabe, Kazuaki


    Peritoneal carcinomatosis (PC), the dissemination of cancer cells throughout the lining of the abdominal cavity, is the second most common presentation of colon cancer distant metastasis. Despite remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years, it has been repeatedly shown that these therapies remain ineffective for colon cancer PC. Recently, there has been a rapid accumulation of reports that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) prolongs the life of colon cancer PC patients. Here, we will review the clinical presentation, the mechanisms of disease progression, and current treatment options for colon cancer PC, with a focus on the benefits and limitations of CRS-HIPEC.

  7. The Molecular Biology of Soft-Tissue Sarcomas and Current Trends in Therapy

    Directory of Open Access Journals (Sweden)

    Jorge Quesada


    Full Text Available Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.

  8. Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Qingqing Meng


    Full Text Available Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.

  9. Staging Lung Cancer: Current Controversies and Strategies

    Directory of Open Access Journals (Sweden)

    Riyad Karmy-Jones


    Full Text Available A consistent approach to staging is required for the rational management of lung cancer. This paper was prepared at the request of the Standards Committee of the Canadian Thoracic Society, and reviews and discusses the relative merits of the available methods of staging. Whichever methods are chosen by a particular institution, the following points must be stressed. No patient can be considered automatically "unresectable" when chest radiography and/ or computed tomography demonstrate adenopathy or only suggest local invasion. Clinical and/or radiographical evidence suggesting extensive local or metastatic disease should be evaluated as completely as possible before subjecting the patient to a possible "nontherapeutic" thoracotomy. Finally, in some cases thoracotomy is required to decide whether the lesion is "completely" resectable.

  10. Molecular cytogenetics: an indispensable tool for cancer diagnosis. (United States)

    Wan, Thomas Sk; Ma, Edmond Sk


    Cytogenetic aberrations may escape detection or recognition in traditional karyotyping. The past decade has seen an explosion of methodological advances in molecular cytogenetics technology. These cytogenetics techniques add color to the black and white world of conventional banding. Fluorescence in-situ hybridization (FISH) study has emerged as an indispensable tool for both basic and clinical research, as well as diagnostics, in leukemia and cancers. FISH can be used to identify chromosomal abnormalities through fluorescent labeled DNA probes that target specific DNA sequences. Subsequently, FISH-based tests such as multicolor karyotyping, comparative genomic hybridization (CGH) and array CGH have been used in emerging clinical applications as they enable resolution of complex karyotypic aberrations and whole global scanning of genomic imbalances. More recently, crossspecies array CGH analysis has also been employed in cancer gene identification. The clinical impact of FISH is pivotal, especially in the diagnosis, prognosis and treatment decisions for hematological diseases, all of which facilitate the practice of personalized medicine. This review summarizes the methodology and current utilization of these FISH techniques in unraveling chromosomal changes and highlights how the field is moving away from conventional methods towards molecular cytogenetics approaches. In addition, the potential of the more recently developed FISH tests in contributing information to genetic abnormalities is illustrated.

  11. Pathological examination of breast cancer biomarkers: current status in Japan. (United States)

    Masuda, Shinobu


    This article reviews the current status of pathological evaluation for biomarkers in Japan. The introduced issues are the international trends for estimation of biomarkers considering diagnosis and treatment decision, and pathological issues under discussion, and how Japanese Breast Cancer Society (JBCS) members have addressed issues related to pathology and biomarkers evaluation. As topics of immunohistochemical study, (1) ASCO/CAP guidelines, (2) Ki67 and other markers, (3) quantification and image analysis, (4) application of cytologic samples, (5) pre-analytical process, and (6) Japan Pathology Quality Assurance System are introduced. Various phases of concepts, guidelines, and methodologies are co-existed in today's clinical practice. It is expected in near future that conventional methods and molecular procedures will be emerged, and Japanese Quality assurance/Quality control (QA/QC) system will work practically. What we have to do in the next generation are to validate novel procedures, to evaluate the relationship between traditional concepts and newly proposed ideas, to establish a well organized QA/QC system, and to standardize pre-analytical process that are the basis of all procedures using pathological tissues.

  12. Gastric cancer:current and evolving treatment landscape

    Institute of Scientific and Technical Information of China (English)

    Weijing Sun; Li Yan


    Gastric (including gastroesophageal junction) cancer is the third leading cause of cancer-related death in the world. In China, an estimated 420,000 patients were diagnosed with gastric cancer in 2011, ranking this malignancy the second most prevalent cancer type and resulting in near 300,000 deaths. The treatment landscape of gastric cancer has evolved in recent years. Although systemic chemotherapy is still the mainstay treatment of metastatic disease, the introduction of agents targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor/vascular endothelia growth factor receptor has brought this disease into the molecular and personalized medicine era. The preliminary yet encouraging clinical effcacy observed with immune checkpoint inhibitors, e.g., anti-pro-grammed cell death protein 1/programmed death-ligand 1, will further shape the treatment landscape for gastric cancer. Molecular characterization of patients will play a critical role in developing new agents, as well as in imple-menting new treatment options for this disease.

  13. A current global view of environmental and occupational cancers. (United States)

    Yang, Mihi


    This review is focused on current information of avoidable environmental pollution and occupational exposure as causes of cancer. Approximately 2% to 8% of all cancers are thought to be due to occupation. In addition, occupational and environmental cancers have their own characteristics, e.g., specific chemicals and cancers, multiple factors, multiple causation and interaction, or latency period. Concerning carcinogens, asbestos/silica/wood dust, soot/polycyclic aromatic hydrocarbons [benzo(a) pyrene], heavy metals (arsenic, chromium, nickel), aromatic amines (4-aminobiphenyl, benzidine), organic solvents (benzene or vinyl chloride), radiation/radon, or indoor pollutants (formaldehyde, tobacco smoking) are mentioned with their specific cancers, e.g., lung, skin, and bladder cancers, mesothelioma or leukemia, and exposure routes, rubber or pigment manufacturing, textile, painting, insulation, mining, and so on. In addition, nanoparticles, electromagnetic waves, and climate changes are suspected as future carcinogenic sources. Moreover, the aspects of environmental and occupational cancers are quite different between developing and developed countries. The recent follow-up of occupational cancers in Nordic countries shows a good example for developed countries. On the other hand, newly industrializing countries face an increased burden of occupational and environmental cancers. Developing countries are particularly suffering from preventable cancers in mining, agriculture, or industries without proper implication of safety regulations. Therefore, industrialized countries are expected to educate and provide support for developing countries. In addition, citizens can encounter new environmental and occupational carcinogen nominators such as nanomaterials, electromagnetic wave, and climate exchanges. As their carcinogenicity or involvement in carcinogenesis is not clearly unknown, proper consideration for them should be taken into account. For these purposes, new

  14. Applicability of RNA interference in cancer therapy: Current status

    Directory of Open Access Journals (Sweden)

    S Maduri


    Full Text Available Cancer is a manifestation of dysregulated gene function arising from a complex interplay of oncogenes and tumor suppressor genes present in our body. Cancer has been constantly chased using various therapies but all in vain as most of them are highly effective only in the early stages of cancer. Recently, RNA interference (RNAi therapy, a comparatively new entrant is evolving as a promising player in the battle against cancer due to its post-transcriptional gene silencing ability. The most alluring feature of this non-invasive technology lies in its utility in the cancer detection and the cancer treatment at any stage. Once this technology is fully exploited it can bring a whole new era of therapeutics capable of curing cancer at any stage mainly due to its ability to target the vital processes required for cell proliferation such as response to growth factors, nutrient uptake/synthesis, and energy generation. This therapy can also be used to treat stage IV cancer, the most difficult to treat till date, by virtue of its metastasis inhibiting capability. Recent research has also proved that cancer can even be prevented by proper modulation of physiological RNAi pathways and researchers have found that many nutrients, which are a part of routine diet, can effectively modulate these pathways and prevent cancer. Even after having all these advantages the potential of RNAi therapy could not be fully tapped earlier, due to many limitations associated with the administration of RNAi based therapeutics. However, recent advancements in this direction, such as the development of small interfering RNA (siRNA tolerant to nucleases and the development of non-viral vectors such as cationic liposomes and nanoparticles, can overcome this obstacle and facilitate the clinical use of RNAi based therapeutics in the treatment of cancer. The present review focuses on the current status of RNAi therapeutics and explores their potential as future diagnostics and

  15. Molecular cytogenetics: recent developments and applications in cancer. (United States)

    Das, K; Tan, P


    Aneuploidy or alteration in chromosome numbers is a characteristic feature in cancer that is generally a consequence of defective chromosome segregation during cell division. Molecular cytogenetic analyses have conferred substantial evidence with regards to the chromosomal architectures in cancer. Most importantly, the fluorescence in situ hybridization (FISH) technique that plays a leading role in diagnostic pathology for its single-cell analysis has provided crucial information regarding genomic variations in malignant cells. Further development of molecular cytogenetic methodologies such as chromosome specific FISH karyotyping and comparative genomic hybridization have also helped in the detection of cryptic genetic changes in cancer. But, the recent advancement of high throughput sequencing technologies have provided a more comprehensive genomic analyses resulting in novel chromosome rearrangements, somatic mutations as well as identification of fusion genes leading to new therapeutic targets. This review highlights the application of early molecular cytogenetics and the recent high throughput genomic approaches in characterizing various cancers and their invaluable support in cancer therapeutics.

  16. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Directory of Open Access Journals (Sweden)

    Maria Victoria Maliandi


    Full Text Available The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  17. Therapies targeting cancer stem cells: Current trends and future challenges

    Institute of Scientific and Technical Information of China (English)

    Denisa; L; Dragu; Laura; G; Necula; Coralia; Bleotu; Carmen; C; Diaconu; Mihaela; Chivu-Economescu


    Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers.

  18. Current Trends in the Molecular Classification of Renal Neoplasms

    Directory of Open Access Journals (Sweden)

    Andrew N. Young


    Full Text Available Renal cell carcinoma (RCC is the most common form of kidney cancer in adults. RCC is a significant challenge for pathologic diagnosis and clinical management. The primary approach to diagnosis is by light microscopy, using the World Health Organization (WHO classification system, which defines histopathologic tumor subtypes with distinct clinical behavior and underlying genetic mutations. However, light microscopic diagnosis of RCC subtypes is often difficult due to variable histology. In addition, the clinical behavior of RCC is highly variable and therapeutic response rates are poor. Few clinical assays are available to predict outcome in RCC or correlate behavior with histology. Therefore, novel RCC classification systems based on gene expression should be useful for diagnosis, prognosis, and treatment. Recent microarray studies have shown that renal tumors are characterized by distinct gene expression profiles, which can be used to discover novel diagnostic and prognostic biomarkers. Here, we review clinical features of kidney cancer, the WHO classification system, and the growing role of molecular classification for diagnosis, prognosis, and therapy of this disease.

  19. Cancer screening in the United States, 2015: a review of current American cancer society guidelines and current issues in cancer screening. (United States)

    Smith, Robert A; Manassaram-Baptiste, Deana; Brooks, Durado; Doroshenk, Mary; Fedewa, Stacey; Saslow, Debbie; Brawley, Otis W; Wender, Richard


    Each year, the American Cancer Society (ACS) publishes a summary of its guidelines for early cancer detection along with a report on data and trends in cancer screening rates and select issues related to cancer screening. In this issue of the journal, we summarize current ACS cancer screening guidelines. The latest data on utilization of cancer screening from the National Health Interview Survey (NHIS) also is described, as are several issues related to screening coverage under the Affordable Care Act, including the expansion of the Medicaid program.

  20. Molecular Imaging of Breast Cancer: Role of RGD Peptides. (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh


    Breast cancer is the leading cause of cancer deaths among women of all ages worldwide. With advances in molecular imaging procedures, it has been possible to detect breast cancer in its early stage, determine the extent of the disease to administer appropriate therapeutic protocol and also monitor the effects of treatment. By accurately characterizing the tumor properties and biological processes involved, molecular imaging can play a crucial role in minimizing the morbidity and mortality associated with breast cancer. The integrin αvβ3 plays an important role in breast cancer angiogenesis and is expressed on tumor endothelial cells as well as on some tumor cells. It is a receptor for the extracellular matrix proteins with the exposed arginine-glycine-aspartic acid (RGD) tripeptide sequence and therefore RGD peptides can preferentially bind to integrin αvβ3. In this context, targeting tumor vasculature or tumor cells by RGD-based probes is a promising strategy for molecular imaging of breast cancer. Using RGD-based probes, several preclinical studies have employed different imaging modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound and optical imaging for visualization of integrin αvβ3 expression in breast cancer models. Limited clinical trials using (18)F-labeled RGD peptides have also been initiated for non-invasive detection and staging of breast cancer. Herein, we provide a comprehensive overview of the latest advances in molecular imaging of breast cancer using RGD peptide-based probes and discuss the challenges and opportunities for advancement of the field. The reported strategies for molecular imaging of breast cancer using RGD peptide-based probes holds promise for making clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in improved quality of life for breast cancer patients.

  1. Basic evidence of molecular targeted therapy for oral cancer and salivary gland cancer.

    NARCIS (Netherlands)

    Hamakawa, H.; Nakashiro, K.; Sumida, T.; Shintani, S.; Myers, J.N.; Takes, R.P.; Rinaldo, A.; Ferlito, A.


    BACKGROUND: Recently, attention has been focused on molecular targeted cancer therapy in various tumors. Although there is no single consistent molecular target specific for oral squamous cell carcinoma (OSCC) and salivary gland cancer (SGC), there are a number of promising candidate proteins. The a

  2. Phytochemicals for breast cancer therapy: current status and future implications. (United States)

    Siddiqui, Jawed Akhtar; Singh, Aru; Chagtoo, Megha; Singh, Nidhi; Godbole, Madan Madhav; Chakravarti, Bandana


    Breast cancer is one of the most common malignancies among women, representing nearly 30% of newly diagnosed cancers every year. Till date, various therapeutic interventions, including surgery, chemotherapy, hormonal therapy, and radiotherapy are available and are known to cause a significant decline in the overall mortality rate. However, therapeutic resistance, recurrence and lack of treatment in metastasis are the major challenges that need to be addressed. Increasing evidence suggests the presence of cancer stem cells (CSCs) in heterogeneous population of breast tumors capable of selfrenewal and differentiation and is considered to be responsible for drug resistance and recurrence. Therefore, compound that can target both differentiated cancer cells, as well as CSCs, may provide a better treatment strategy. Due to safe nature of dietary agents and health products, investigators are introducing them into clinical trials in place of chemotherapeutic agents.This current review focuses on phytochemicals, mainly flavonoids that are in use for breast cancer therapy in preclinical phase. As phytochemicals have several advantages in breast cancer and cancer stem cells, new synthetic series for breast cancer therapy from analogues of most potent natural molecule can be developed via rational drug design approach.

  3. Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo. (United States)

    Luker, Gary D


    The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

  4. A Molecular Epidemiologic Case-Case Study of Prostate Cancer (United States)


    Receptor Polymorphism and Prostate Cancer Risk 1 Sara S. Strom 2, Qiang Zhang, Yun Gu, Margaret R. Spitz, Peter T. Scardino 3, Christopher J. Logothetis...Taylor, J. A. Vitamin D receptor polymorphisms and prostate cancer. Molecular Carcinogenesis, 27: 18-23, 2000. 6. Ma, J., Stampfer , M. J., Gann, P. H...Margaret R. Spitz, Richard J. Babaian, Christopher Logothetis, Sara S. Strom, University of Texas M.D. Anderson Cancer Center, Houston, TX; The University

  5. Current-Voltage Characteristics of Molecular Devices at Low Bias

    Institute of Scientific and Technical Information of China (English)

    LIAO Yun-Xing; CHEN Hao; R.Note; H.Mizuseki; Y.Kawazoe


    We use density functional theory and the Green function formalism with charge energy effect included in the self-consistent calculation of the Ⅰ- Ⅴ characteristics of a single benzene ring with an appendage of cf3, and identify some interesting properties of the Ⅰ-Ⅴ characteristics at low bias. The molecule picks up a fractional charge at zero bias, then the additional fractional charge produces a barrier on the junction of the molecule and contacts to perturb current flow on the molecule. This phenomenon may be useful for the design of future molecular devices.

  6. Molecular Basis and Current Treatment for Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Juan Armendariz-Borunda


    Full Text Available Alcohol use disorders and alcohol dependency affect millions of individuals worldwide. The impact of these facts lies in the elevated social and economic costs. Alcoholic liver disease is caused by acute and chronic exposure to ethanol which promotes oxidative stress and inflammatory response. Chronic consumption of ethanol implies liver steatosis, which is the first morphological change in the liver, followed by liver fibrosis and cirrhosis. This review comprises a broad approach of alcohol use disorders, and a more specific assessment of the pathophysiologic molecular basis, and genetics, as well as clinical presentation and current modalities of treatment for alcoholic liver disease.

  7. Cancer survivorship research: a review of the literature and summary of current NCI-designated cancer center projects. (United States)

    Harrop, J Phil; Dean, Julie A; Paskett, Electra D


    The number of cancer survivors and the amount of cancer survivorship research have grown substantially during the past three decades. This article provides a review of interventional and observational cancer survivorship research efforts as well as a summary of current cancer survivorship research projects being conducted by National Cancer Institute-designated cancer centers in an effort to identify areas that need further attention.

  8. New generation of breast cancer clinical trials implementing molecular profiling

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Zardavas; Martine Piccart-Gebhart


    The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as pre-screening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i) longitudinal cohort studies that implement (or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.

  9. Cancer screening in the United States, 2013: a review of current American Cancer Society guidelines, current issues in cancer screening, and new guidance on cervical cancer screening and lung cancer screening. (United States)

    Smith, Robert A; Brooks, Durado; Cokkinides, Vilma; Saslow, Debbie; Brawley, Otis W


    Each year the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, a report on data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, current ACS cancer screening guidelines are summarized, as are updated guidelines on cervical cancer screening and lung cancer screening with low-dose helical computed tomography. The latest data on the use of cancer screening from the National Health Interview Survey also are described, as are several issues related to screening coverage under the Patient Protection and Affordable Care Act of 2010.

  10. Current strategies for the prevention of breast cancer

    Directory of Open Access Journals (Sweden)

    Advani P


    Full Text Available Pooja Advani, Alvaro Moreno-AspitiaDepartment of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USAAbstract: Due to the high incidence of breast cancer in the United States, optimal strategies for its prevention are imperative. This entails identification of women who are at an increased risk for breast cancer and an integrative approach that includes effective screening methods as well as nutritional, pharmacologic, and surgical management. Several breast cancer risk-assessment tools, such as the Gail and Claus models, can help clinicians determine the quantitative risk of breast cancer. The role of selective estrogen receptor modulators, such as tamoxifen and raloxifene, for the prevention of breast cancer has been well established. Several other agents, such as aromatase inhibitors, are currently being investigated. The potential adverse effects of these chemopreventive agents, which include an impact on the quality of life, must be discussed with the patient before deciding on this approach. Additionally, breast cancer risk factors have been identified over the years; some of them are modifiable, but others are not. Although there is no conclusive evidence to suggest the protective role of specific dietary components, alcohol consumption and obesity are associated with an increased breast cancer risk; thus lifestyle changes can lead to a lower risk of developing breast cancer. Surgical approaches, including bilateral risk-reduction mastectomy and salpingo-oophorectomy, are usually limited to women with a hereditary predisposition to development of breast cancer. The objective of this review is to summarize the various approaches directed at reducing the incidence of breast cancer.Keywords: chemoprevention, tamoxifen, raloxifene, prophylactic surgery

  11. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme



    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cel...

  12. Targeted therapy for advanced gastric cancer: A review of current status and future prospects

    Institute of Scientific and Technical Information of China (English)

    Ozkan; Kanat; Bert; O’Neil; Safi; Shahda


    In the West in particular, the vast majority of gastric cancer(GC) patients present with advanced-stage disease. Although combination chemotherapy is stillthe most important component of treatment for these patients, it confers a modest survival advantage. Recently, increased knowledge of the key molecular signaling pathways involved in gastric carcinogenesis has led to the discovery of specific molecular-targeted therapeutic agents. Some of these agents such as trastuzumab and ramucirumab have changed the treatment paradigm for this disease. In this paper, we will summarize the current clinical status of targeted drug therapy in the management of GC.

  13. Novel approaches for the molecular classification of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Robert H. Getzenberg


    @@ Among the urologic cancers, prostate cancer is by far the most common, and it appears to have the potential to affect almost all men throughout the world as they age. A number of studies have shown that many men with prostate cancer will not die from their disease, but rather with the disease but from other causes. These men have a form of prostate cancer that is de-scribed as "very low risk" and has often been called indolent. There are however a group of men that have a form of prostate cancer that is much more aggressive and life threatening. Unlike other cancer types, we have few tools to provide for the molecular classification of prostate cancer.

  14. Molecular and neuroendocrine mechanisms of cancer cachexia. (United States)

    Mendes, Maria Carolina S; Pimentel, Gustavo D; Costa, Felipe O; Carvalheira, José B C


    Cancer and its morbidities, such as cancer cachexia, constitute a major public health problem. Although cancer cachexia has afflicted humanity for centuries, its underlying multifactorial and complex physiopathology has hindered the understanding of its mechanism. During the last few decades we have witnessed a dramatic increase in the understanding of cancer cachexia pathophysiology. Anorexia and muscle and adipose tissue wasting are the main features of cancer cachexia. These apparently independent symptoms have humoral factors secreted by the tumor as a common cause. Importantly, the hypothalamus has emerged as an organ that senses the peripheral signals emanating from the tumoral environment, and not only elicits anorexia but also contributes to the development of muscle and adipose tissue loss. Herein, we review the roles of factors secreted by the tumor and its effects on the hypothalamus, muscle and adipose tissue, as well as highlighting the key targets that are being exploited for cancer cachexia treatment.

  15. Breast cancer stem cells: current advances and clinical implications. (United States)

    Luo, Ming; Clouthier, Shawn G; Deol, Yadwinder; Liu, Suling; Nagrath, Sunitha; Azizi, Ebrahim; Wicha, Max S


    There is substantial evidence that many cancers, including breast cancer, are driven by a population of cells that display stem cell properties. These cells, termed cancer stem cells (CSCs) or tumor initiating cells, not only drive tumor initiation and growth but also mediate tumor metastasis and therapeutic resistance. In this chapter, we summarize current advances in CSC research with a major focus on breast CSCs (BCSCs). We review the prevailing methods to isolate and characterize BCSCs and recent evidence documenting their cellular origins and phenotypic plasticity that enables them to transition between mesenchymal and epithelial-like states. We describe in vitro and clinical evidence that these cells mediate metastasis and treatment resistance in breast cancer, the development of novel strategies to isolate circulating tumor cells (CTCs) that contain CSCs and the use of patient-derived xenograft (PDX) models in preclinical breast cancer research. Lastly, we highlight several signaling pathways that regulate BCSC self-renewal and describe clinical implications of targeting these cells for breast cancer treatment. The development of strategies to effectively target BCSCs has the potential to significantly improve the outcomes for patients with breast cancer.

  16. Ultrasound for molecular imaging and therapy in cancer


    Kaneko, Osamu F; Willmann, Jürgen K.


    Over the past decade, molecularly-targeted contrast enhanced ultrasound (ultrasound molecular imaging) has attracted significant attention in preclinical research of cancer diagnostic and therapy. Potential applications for ultrasound molecular imaging run the gamut from early detection and characterization of malignancies to monitoring treatment responses and guiding therapies. There may also be a role for ultrasound contrast agents for improved delivery of chemotherapeutic drugs and gene th...

  17. Molecular Concordance Between Primary Breast Cancer and Matched Metastases

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Thomassen, Mads;


    . The purpose of this review is to illuminate the extent of cancer genome evolution through disease progression and the degree of molecular concordance between primary breast cancers and matched metastases. We present an overview of the most prominent studies investigating the expression of endocrine receptors......Clinical management of breast cancer is increasingly personalized and based on molecular profiling. Often, primary tumors are used as proxies for systemic disease at the time of recurrence. However, recent studies have revealed substantial discordances between primary tumors and metastases, both......, transcriptomics, and genome aberrations in primary tumors and metastases. In conclusion, biopsy of metastatic lesions at recurrence of breast cancer is encouraged to provide optimal treatment of the disease. Furthermore, molecular profiling of metastatic tissue provides invaluable mechanistic insight...

  18. Deciphering the Molecular Mechanisms of Breast Cancer (United States)


    BRCA1 and BRCA2, by a Signalosome-like Subunit and its Role in DNA Repair. Molecular Cell 12; 1087-1099 (2003). Presentations/Abstracts...BRCA1 and BRCA2, by a Signalosome-like Subunit and its Role in DNA Repair. Molecular Cell 12; 1087-1099. APPENDICIES: CURRICULUM VITAE...Oncogenesis Program Member, Faculty Recruitment Committee Periodic Manuscript Reviews: Cell, Science, Molecular Cell , Molecular and Cellular

  19. Anatomical and molecular imaging of skin cancer


    Cai, Weibo


    Hao Hong1, Jiangtao Sun1, Weibo Cai1,21Departments of Radiology and Medical Physics, School of Medicine and Public Health, University of Wisconsin – Madison, Madison, Wisconsin, USA; 2University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin, USAAbstract: Skin cancer is the most common form of cancer types. It is generally divided into two categories: melanoma (∼5%) and nonmelanoma (∼95%), which can be further categorized into basal cell...

  20. Current status of bevacizumab in advanced ovarian cancer

    Directory of Open Access Journals (Sweden)

    Tomao F


    Full Text Available Federica Tomao,1,* Anselmo Papa,2,* Luigi Rossi,2 Davide Caruso,2 Pierluigi Benedetti Panici,1 Martina Venezia,2 Silverio Tomao21Department of Gynaecology and Obstetrics, "Sapienza" University of Rome, Policlinico "Umberto I," Rome, Italy; 2Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Oncology Unit, "ICOT," Latina, Italy*Authors contributed equally to this workAbstract: Ovarian cancer is the most lethal gynecological cancer, mainly because of the delay in diagnosis. Recently, much effort has been put into investigating and introducing novel targeted agents into clinical practice, with the aim of improving prognosis and quality of life. Angiogenesis is a possible target. The aim of this review is to investigate the most common molecular pathways of angiogenesis, which have provided novel targets for tailored therapy in patients with ovarian cancer. These therapeutic strategies include monoclonal antibodies and tyrosine-kinase inhibitors. These drugs have as molecular targets vascular endothelial growth factor, vascular endothelial growth factor receptors, platelet-derived growth factor, fibroblast growth factor, and angiopoietin. Bevacizumab was investigated in several Phase III studies, with interesting results. Today, there is strong evidence for introducing bevacizumab in the treatment of patients with advanced and recurrent ovarian cancer. Nevertheless, further investigations and large clinical trials are needed to understand the safety and effectiveness of bevacizumab, the optimal duration and timing of treatment, and activity in association with other chemotherapeutic and targeted agents. It also is necessary to identify biologic factors predictive of efficacy to choose the most appropriate antiangiogenic agent in the integrated treatment of epithelial ovarian cancer.Keywords: epithelial ovarian cancer, angiogenesis, bevacizumab, vascular endothelial growth factor, chemotherapy

  1. Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

    Directory of Open Access Journals (Sweden)

    Bishnu P. Joshi


    Full Text Available Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research.

  2. Molecular advances to treat cancer of the brain. (United States)

    Fathallah-Shaykh, H M; Zhao, L J; Mickey, B; Kafrouni, A I


    Malignant primary and metastatic brain tumours continue to be associated with poor prognosis. Nevertheless, recent advances in molecular medicine, specifically in the strategies of gene therapy, targeting tumour cells, anti-angiogenesis and immunotherapy, have created novel tools that may be of therapeutic value. To date, gene therapy trials have not yet demonstrated clinical efficacy because of inherent defects in vector design. Despite this, advances in adenoviral technology, namely the helper-dependent adenoviral constructs (gutless) and the uncovering of brain parenchymal cells as effective and necessary targets for antitumour benefits of adenoviral-mediated gene transfer, suggest that developments in vector design may be approaching the point of clinical utility. Targeting tumour cells refers to strategies that destroy malignant but spare normal cells. A new assortment of oncolytic viruses have emerged, capable of specific lysis of cancer tissue while sparing normal cells and propagating until they reach the tumour borders. Furthermore, peptides have been transformed into bullets that specifically seek and destroy cancer cells. The concept of tumour angiogenesis has been challenged by new but still very controversial findings that tumour cells themselves may form blood channels. These results may lead to the redirecting of the molecular targets toward anti-angiogenesis in some tumours including glioblastoma multiform. Unfortunately, our knowledge regarding the immunological ignorance of the tumour is still limited. Even so, newly discovered molecules have shed light on novel pathways leading to the escape of the tumour from the immune system. Finally, significant limitations in our current experimental tumour models may soon be overcome by firstly, the development of models of reproducible organ-specific tumours in non-inbred animals and secondly applying genomics to individualize therapy for a particular tumour in a specific patient.

  3. Genistein and cancer: current status, challenges, and future directions. (United States)

    Spagnuolo, Carmela; Russo, Gian Luigi; Orhan, Ilkay Erdogan; Habtemariam, Solomon; Daglia, Maria; Sureda, Antoni; Nabavi, Seyed Fazel; Devi, Kasi Pandima; Loizzo, Monica Rosa; Tundis, Rosa; Nabavi, Seyed Mohammad


    Primary prevention through lifestyle interventions is a cost-effective alternative for preventing a large burden of chronic and degenerative diseases, including cancer, which is one of the leading causes of morbidity and mortality worldwide. In the past decade, epidemiologic and preclinical evidence suggested that polyphenolic phytochemicals present in many plant foods possess chemopreventive properties against several cancer forms. Thus, there has been increasing interest in the potential cancer chemopreventive agents obtained from natural sources, such as polyphenols, that may represent a new, affordable approach to curb the increasing burden of cancer throughout the world. Several epidemiologic studies showed a relation between a soy-rich diet and cancer prevention, which was attributed to the presence of a phenolic compound, genistein, present in soy-based foods. Genistein acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. Targeting caspases, B cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2, kinesin-like protein 20A (KIF20A), extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear transcription factor κB (NF-κB), mitogen-activated protein kinase (MAPK), inhibitor of NF-κB (IκB), Wingless and integration 1 β-catenin (Wnt/β-catenin), and phosphoinositide 3 kinase/Akt (PI3K/Akt) signaling pathways may act as the molecular mechanisms of the anticancer, therapeutic effects of genistein. Genistein also shows synergistic behavior with well-known anticancer drugs, such as adriamycin, docetaxel, and tamoxifen, suggesting a potential role in combination therapy. This review critically analyzes the available literature on the therapeutic role of genistein on different types of cancer, focusing on its chemical features, plant food sources, bioavailability, and safety.


    Directory of Open Access Journals (Sweden)

    A. Yu. Babayan


    Full Text Available A system of clinical and morphological criteria is currently used to determine the pattern of superficial bladder cancer (SBC. However, this system does not completely reflect the clinical potential of SBC and needs additional markers. The purpose of this study was to search for and evaluate molecular genetic disorders as additional markers of the course of SBC. The diagnostic panel included the deletion of the loci 3р14, 9р21, 9q34, 17р13 (ТР53, mutations of exon 7 of the FGFR3 gene, and hypermethylation of the promoter regions of the RASSF1, RARB, p16, p14, CDH1 genes. The study was made on 108 matched samples (tumor/peripheral blood obtained from patients with SBC. The deletions of the loci 3р14, 9р21 and anomalous methylation of the RARb and p16 genes are markers of the worse course of SBC while FGFR3 gene mutation is a marker of better prognosis. In the context of estimation of the relapsing potential of a primary tumor, the 9p21 locus deletion is a marker associated with recurrence within the first year after malignancy resection. The group of molecular genetic markers determined by the authors for poor prognosis in combination with classical clinical and morphological criteria will specify the pattern of the course of the disease and its prognosis.

  5. Breast cancer pain management - A review of current & novel therapies

    Directory of Open Access Journals (Sweden)

    Aanchal Satija


    Full Text Available Breast cancer is one of the most prevalent cancers amongst women in the world. Unfortunately, even after adequate treatment, some patients experience severe pain either due to disease progression or due to treatment related side effects. The persistent pain causes a negative physical and psychosocial impact on patients′ lives. Current rational pain management is patient-centred and requires a thorough psychological assessment. Usually adequate analgesia is achieved by adopting the WHO′s three step analgesic ladder. As the disease progresses, the pain experienced by the patient also increases. This necessitates the administration of opioids and adjuvant analgesics to the breast cancer patients experiencing severe pain. However, opioid use is associated with intolerable side effects like constipation, nausea, vomiting, fear of dependence, and tolerance. Concomitant medications are required to combat these unacceptable side effects. Adjuvant analgesics need to be added to provide adequate and satisfactory analgesia. These factors worsen the psychological state of patients and deteriorate their quality of life. Hence, there is a need to develop therapeutic modalities to provide adequate analgesia with minimum side effects. This review article focuses on the current treatments available for cancer pain management, their limitations, and novel targets and non-pharmacological measures under investigation which have the potential to produce a radical change in pain management measures for the breast cancer patients.

  6. Exploiting molecular methods to explore endodontic infections: Part 1--current molecular technologies for microbiological diagnosis. (United States)

    Siqueira, J F; Rôças, I N


    Endodontic infections have been traditionally studied by culture-dependent methods. However, as with other areas of clinical microbiology, culture-based investigations are plagued by significant problems, including the probable involvement of viable but uncultivable micro-organisms with disease causation and inaccurate microbial identification. Innumerous molecular technologies have been used for microbiological diagnosis in clinical microbiology, but only recently some of these techniques have been applied in endodontic microbiology research. This paper intended to review the main molecular methods that have been used or have the potential to be used in the study of endodontic infections. Moreover, advantages and limitations of current molecular techniques when compared to conventional methods for microbial identification are also discussed.

  7. Gallic acid: molecular rival of cancer. (United States)

    Verma, Sharad; Singh, Amit; Mishra, Abha


    Gallic acid, a predominant polyphenol, has been shown to inhibit carcinogenesis in animal models and in vitro cancerous cell lines. The inhibitory effect of gallic acid on cancer cell growth is mediated via the modulation of genes which encodes for cell cycle, metastasis, angiogenesis and apoptosis. Gallic acid inhibits activation of NF-κB and Akt signaling pathways along with the activity of COX, ribonucleotide reductase and GSH. Moreover, gallic acid activates ATM kinase signaling pathways to prevent the processes of carcinogenesis. The data so far available, both from in vivo and in vitro studies, indicate that this dietary polyphenol could be promising agent in the field of cancer chemoprevention.

  8. Targets for molecular therapy of skin cancer. (United States)

    Green, Cheryl L; Khavari, Paul A


    Cancers of the skin encompass the first and second most common neoplasms in the United States, epidermal basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), respectively, as well as the melanocytic malignancy, malignant melanoma (MM). Recently identified alterations in the function of specific genes in these cancers provide new potential therapeutic targets. These alterations affect conserved regulators of cellular proliferation and viability, including the Sonic Hedgehog, Ras/Raf, ARF/p53, p16(INK4A)/CDK4/Rb and NF-kappaB pathways. New modalities designed to target these specific proteins may represent promising approaches to therapy of human skin cancers.

  9. [Overview of current modalities of colorectal cancer screening]. (United States)

    Kajzrlíková, Ivana Mikoviny; Vítek, Petr


    There are one-step and two-steps programs for colorectal cancer screening. The aim of all screening examinations is to detect early stage of the disease in asymptomatic patient. The aim of this article is actual review of current screening modalities such as fecal occult blood test, flexible sigmoideoscopy, colonoscopy, CT colonography, capsule endoscopy, blood-based tests and stool DNA tests. Colonoscopy still remains the gold standard for detection of colorectal neoplasias. In majority of countries worldwide programs for colorectal cancer screening are based on immunochemical fecal occult blood test followed by colonoscopy when positive.

  10. Precursor lesions in pancreatic cancer: morphological and molecular pathology. (United States)

    Scarlett, Christopher J; Salisbury, Elizabeth L; Biankin, Andrew V; Kench, James


    Pancreatic cancer has a dismal prognosis and is the fourth most common cause of cancer related death in Western societies. In large part this is due to its typically late presentation, usually as locally advanced or metastatic disease. Identification of the non-invasive precursor lesions to pancreatic cancer raises the possibility of surgical treatment or chemoprevention at an early stage in the evolution of this disease, when more amenable to therapeutic interventions. Precursor lesions to pancreatic ductal adenocarcinoma, in particular pancreatic intraepithelial neoplasia (PanIN), have been recognised under a variety of synonyms for over 50 years. Over the past decade our understanding of the morphology, biological significance and molecular aberrations of these lesions has grown rapidly and there is now a widely accepted progression model integrating the accumulated morphological and molecular observations. Further progress is likely to be accelerated by improved mouse models of pancreatic cancer and by insight into the cancer genome gained by the International Cancer Genome Consortium (ICGC), in which an Australian consortium is leading the pancreatic cancer initiative. This review also outlines the morphological and molecular features of the other two precursors of pancreatic ductal adenocarcinoma, i.e., intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.

  11. 2. Molecular Biology as a Tool in Cancer Epidemiology

    Institute of Scientific and Technical Information of China (English)


    @@There can be little doubt that we are entering a new era in our understanding of the origins of human cancer. Unfortunately from the point of view of the cancer epidemiology community, some of the more recent advances in the molecular biology of cancer (once fully assimilated) will tend to make the talk of the up-to-date cancer epidemiologist a great deal less straightforward than many of us had previously envisaged it to be, There may still be a few cancers that will prove to result from only a few distinctive types of mutation in a relatively small number of genes, but I strongly suspect that the great majority of human cancers that we wish to study will prove to have their origins in a complex set of DNA changes whose precise

  12. Targeted therapies with companion diagnostics in the management of breast cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    Myers MB


    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

  13. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes (United States)

    de Anda-Jáuregui, Guillermo; Velázquez-Caldelas, Tadeo E.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique


    Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer. PMID:27920729

  14. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes

    Directory of Open Access Journals (Sweden)

    Guillermo de Anda-Jáuregui


    Full Text Available Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes.In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples is also inferred and analyzed.Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e. CNR2 or to a particular subtype (such as LCK. Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance.With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer.

  15. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes. (United States)

    de Anda-Jáuregui, Guillermo; Velázquez-Caldelas, Tadeo E; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique


    Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer.

  16. Molecular Cell Biology of Apoptosis and Necroptosis in Cancer. (United States)

    Dillon, Christopher P; Green, Douglas R


    Cell death is a major mechanism to eliminate cells in which DNA is damaged, organelles are stressed, or oncogenes are overexpressed, all events that would otherwise predispose cells to oncogenic transformation. The pathways that initiate and execute cell death are complex, genetically encoded, and subject to significant regulation. Consequently, while these pathways are often mutated in malignancy, there is considerable interest in inducing cell death in tumor cells as therapy. This chapter addresses our current understanding of molecular mechanisms contributing to two cell death pathways, apoptotic cell death and necroptosis, a regulated form of necrotic cell death. Apoptosis can be induced by a wide variety of signals, leading to protease activation that dismantles the cell. We discuss the physiological importance of each apoptosis pathway and summarize their known roles in cancer suppression and the current efforts at targeting each pathway therapeutically. The intricate mechanistic link between death receptor-mediated apoptosis and necroptosis is described, as well as the potential opportunities for utilizing necroptosis in the treatment of malignancy.

  17. Molecular targeted agents for gastric and gastroesophageal junction cancer. (United States)

    Oshima, Takashi; Masuda, Munetaka


    Despite recent improvements in surgical techniques and chemotherapy, advanced cancers of the stomach and gastroesophageal junction (GEJ) continue to have poor clinical outcomes. However, molecules intimately related to cancer cell proliferation, invasion, and metastasis have been studied as candidates for molecular targeted agents. Target molecules, such as the epidermal growth factor receptor, vascular endothelial growth factor receptor, and P13k/Akt/mTor pathway, as well as the insulin-like growth factor receptor, c-Met pathways, fibroblast growth factor receptor, and other pathways are considered to be promising candidates for molecular targeted therapy for gastric and GEJ cancer. In this review we focus on the recent developments in targeting relevant pathways in these types of cancer.

  18. Current Status of Methods to Assess Cancer Drug Resistance

    Directory of Open Access Journals (Sweden)

    Theodor H. Lippert, Hans-Jörg Ruoff, Manfred Volm


    Full Text Available Drug resistance is the main cause of the failure of chemotherapy of malignant tumors, resistance being either preexisting (intrinsic resistance or induced by the drugs (acquired resistance. At present, resistance is usually diagnosed during treatment after a long period of drug administration.In the present paper, methods for a rapid assessment of drug resistance are described. Three main classes of test procedures can be found in the literature, i.e. fresh tumor cell culture tests, cancer biomarker tests and positron emission tomography (PET tests. The methods are based on the evaluation of molecular processes, i.e. metabolic activities of cancer cells. Drug resistance can be diagnosed before treatment in-vitro with fresh tumor cell culture tests, and after a short time of treatment in-vivo with PET tests. Cancer biomarker tests, for which great potential has been predicted, are largely still in the development stage. Individual resistance surveillance with tests delivering rapid results signifies progress in cancer therapy management, by providing the possibility to avoid drug therapies that are ineffective and only harmful.

  19. Molecular Mechanism by Which Retinoids Prevent Breast Cancer Development (United States)


    clinicians to conquer this disease is to prevent the incidence, detect early and treat breast cancer with effective therapy resulting in long overall... biological functions such as embryogenesis, growth, differentiation, vision and reproduction (3-6). Retinoids also contain anti- proliferative...and are currently available to treat psoriasis , acne, photoaging, actinic keratosis or cancers such as acute promelocytic leukemia, cutaneous T-cell

  20. Radiotherapy in prostate cancer. Innovative techniques and current controversies

    Energy Technology Data Exchange (ETDEWEB)

    Geinitz, Hans [Krankenhaus der Barmherzigen Schwestern, Linz (Austria). Dept. of Radiation Oncology; Linz Univ. (Austria). Medical Faculty; Roach, Mack III [California Univ., San Francisco, CA (United States). Dept. of Radiation Oncology; Van As, Nicholas (ed.) [The Institute of Cancer Research, Sutton Surrey (United Kingdom)


    Examines in detail the role of innovative radiation techniques in the management of prostate cancer, including IMRT, IGRT, BART, and modern brachytherapy. Explores a range of current controversies in patient treatment. Intended for both radiation oncologists and urologists. Radiation treatment is rapidly evolving owing to the coordinated research of physicists, engineers, computer and imaging specialists, and physicians. Today, the arsenal of ''high-precision'' or ''targeted'' radiotherapy includes multimodal imaging, in vivo dosimetry, Monte Carlo techniques for dose planning, patient immobilization techniques, intensity-modulated radiotherapy (IMRT), image-guided radiotherapy (IGRT), biologically adapted radiotherapy (BART), quality assurance methods, novel methods of brachytherapy, and, at the far end of the scale, particle beam radiotherapy using protons and carbon ions. These approaches are like pieces of a puzzle that need to be put together to provide the prostate cancer patient with high-level optimized radiation treatment. This book examines in detail the role of the above-mentioned innovative radiation techniques in the management of prostate cancer. In addition, a variety of current controversies regarding treatment are carefully explored, including whether prophylactic treatment of the pelvic lymphatics is essential, the magnitude of the effect of dose escalation, whether a benefit accrues from hypofractionation, and what evidence exists for the superiority of protons or heavy ions. Radiotherapy in Prostate Cancer: Innovative Techniques and Current Controversies is intended for both radiation oncologists and urologists with an interest in the up-to-date capabilities of modern radiation oncology for the treatment of prostate cancer.

  1. Molecular mechanisms of TRAIL-induced apoptosis of cancer cells

    Institute of Scientific and Technical Information of China (English)


    @@Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) is a recently identified member of the tumor necrosis factor (TNF) family[1]. Numerous studies indicate that TRAIL can induce apoptosis of cancer cells but not of normal cells, pointing to the possibility of de-veloping TRAIL into a cancer drug[2-4]. This review will summary the molecular mechanisms of TRAIL-induced apoptosis and discuss the questions to be resolved in this field.

  2. DNA aptamers as molecular probes for colorectal cancer study.

    Directory of Open Access Journals (Sweden)

    Kwame Sefah

    Full Text Available BACKGROUND: Understanding the molecular features of specific tumors can increase our knowledge about the mechanism(s underlying disease development and progression. This is particularly significant for colorectal cancer, which is a heterogeneous complex of diseases developed in a sequential manner through a multistep carcinogenic process. As such, it is likely that tumors with similar characteristics might originate in the same manner and have a similar molecular behavior. Therefore, specific mapping of the molecular features can be potentially useful for both tumor classification and the development of appropriate therapeutic regimens. However, this can only be accomplished by developing high-affinity molecular probes with the ability to recognize specific markers associated with different tumors. Aptamers can most easily meet this challenge based on their target diversity, flexible manipulation and ease of development. METHODOLOGY AND RESULTS: Using a method known as cell-based Systematic Evolution of Ligands by Exponential enrichment (cell-SELEX and colorectal cancer cultured cell lines DLD-1 and HCT 116, we selected a panel of target-specific aptamers. Binding studies by flow cytometry and confocal microscopy showed that these aptamers have high affinity and selectivity. Our data further show that these aptamers neither recognize normal colon cells (cultured and fresh, nor do they recognize most other cancer cell lines tested. CONCLUSION/SIGNIFICANCE: The selected aptamers can identify specific biomarkers associated with colorectal cancers. We believe that these probes could be further developed for early disease detection, as well as prognostic markers, of colorectal cancers.

  3. Transcriptional networks inferred from molecular signatures of breast cancer. (United States)

    Tongbai, Ron; Idelman, Gila; Nordgard, Silje H; Cui, Wenwu; Jacobs, Jonathan L; Haggerty, Cynthia M; Chanock, Stephen J; Børresen-Dale, Anne-Lise; Livingston, Gary; Shaunessy, Patrick; Chiang, Chih-Hung; Kristensen, Vessela N; Bilke, Sven; Gardner, Kevin


    Global genomic approaches in cancer research have provided new and innovative strategies for the identification of signatures that differentiate various types of human cancers. Computational analysis of the promoter composition of the genes within these signatures may provide a powerful method for deducing the regulatory transcriptional networks that mediate their collective function. In this study we have systematically analyzed the promoter composition of gene classes derived from previously established genetic signatures that recently have been shown to reliably and reproducibly distinguish five molecular subtypes of breast cancer associated with distinct clinical outcomes. Inferences made from the trends of transcription factor binding site enrichment in the promoters of these gene groups led to the identification of regulatory pathways that implicate discrete transcriptional networks associated with specific molecular subtypes of breast cancer. One of these inferred pathways predicted a role for nuclear factor-kappaB in a novel feed-forward, self-amplifying, autoregulatory module regulated by the ERBB family of growth factor receptors. The existence of this pathway was verified in vivo by chromatin immunoprecipitation and shown to be deregulated in breast cancer cells overexpressing ERBB2. This analysis indicates that approaches of this type can provide unique insights into the differential regulatory molecular programs associated with breast cancer and will aid in identifying specific transcriptional networks and pathways as potential targets for tumor subtype-specific therapeutic intervention.

  4. Colorectal Cancer & Molecular Mutations and Polymorphism

    Directory of Open Access Journals (Sweden)

    Aga Syed Sameer


    Full Text Available Colorectal cancer (CRC is one of the major causes of mortality and morbidity, and is the third most common cancer in men and the second most common cancer in women worldwide. The incidence of CRC shows considerable variation among racially or ethnically defined populations in multiracial/ethnic countries. The tumorigenesis of CRC is either because of the chromosomal instability (CIN or microsatellite instability (MIN or involving various proto-oncogenes, tumor suppressor genes and also epigenetic changes in the DNA. In this review I have focused on the mutations and polymorphisms of various important genes of the CIN and MIN pathways which have been implicated in the development of CRC.

  5. Correlation of morphological and molecular parameters for colon cancer (United States)

    Yuan, Shuai; Roney, Celeste A.; Li, Qian; Jiang, James; Cable, Alex; Summers, Ronald M.; Chen, Yu


    Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. There is great interest in studying the relationship among microstructures and molecular processes of colorectal cancer during its progression at early stages. In this study, we use our multi-modality optical system that could obtain co-registered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) images simultaneously to study CRC. The overexpressed carbohydrate α-L-fucose on the surfaces of polyps facilitates the bond of adenomatous polyps with UEA-1 and is used as biomarker. Tissue scattering coefficient derived from OCT axial scan is used as quantitative value of structural information. Both structural images from OCT and molecular images show spatial heterogeneity of tumors. Correlations between those values are analyzed and demonstrate that scattering coefficients are positively correlated with FMI signals in conjugated. In UEA-1 conjugated samples (8 polyps and 8 control regions), the correlation coefficient is ranged from 0.45 to 0.99. These findings indicate that the microstructure of polyps is changed gradually during cancer progression and the change is well correlated with certain molecular process. Our study demonstrated that multi-parametric imaging is able to simultaneously detect morphology and molecular information and it can enable spatially and temporally correlated studies of structure-function relationships during tumor progression.

  6. Advanced imaging of colorectal cancer: From anatomy to molecular imaging


    García-Figueiras, Roberto; Baleato-González, Sandra; Padhani, Anwar R.; Marhuenda, Ana; Luna, Antonio; Alcalá, Lidia; Carballo-Castro, Ana; Álvarez-Castro, Ana


    Abstract Imaging techniques play a key role in the management of patients with colorectal cancer. The introduction of new advanced anatomical, functional, and molecular imaging techniques may improve the assessment of diagnosis, prognosis, planning therapy, and assessment of response to treatment of these patients. Functional and molecular imaging techniques in clinical practice may allow the assessment of tumour-specific characteristics and tumour heterogeneity. This paper will review recent...

  7. Molecular markers as therapeutic targets in lung cancer

    Institute of Scientific and Technical Information of China (English)

    Hsin-Hui Tseng; Biao He


    Lung cancer is responsible for 29% of cancer deaths in the United States and has very low 5-year survival rates of approximately 11% in men and 15% in women.Although the early diagnosis of lung cancer may increase the survival rate with adequate treatment,advanced lung cancers are often metastasized and receive limited benefit from therapeutic regimens.As conventional treatments for lung cancer reach their limitations,researchers have attempted to discover novel drug therapies aimed at specific targets contributing to the progression of tumorigenesis.Recent advances in systems biology have enabled the molecular biology of lung carcinogenesis to be elucidated.Our understanding of the physiologic processes of tumor development provide a means to design more effective and specific drugs with less toxicity,thereby accelerating the delivery of new drug therapies to the patient's bedside.

  8. Clinical variability and molecular heterogeneity in prostate cancer

    Directory of Open Access Journals (Sweden)

    Jonathan Shoag


    Full Text Available Prostate cancer is a clinically heterogeneous disease, with some men having indolent disease that can safely be observed, while others have aggressive, lethal disease. Over the past decade, researchers have begun to unravel some of the genomic heterogeneity that contributes to these varying clinical phenotypes. Distinct molecular sub-classes of prostate cancer have been identified, and the uniqueness of these sub-classes has been leveraged to predict clinical outcomes, design novel biomarkers for prostate cancer diagnosis, and develop novel therapeutics. Recent work has also elucidated the temporal and spatial heterogeneity of prostate cancer, helping us understand disease pathogenesis, response to therapy, and progression. New genomic techniques have provided us with a window into the remarkable clinical and genomic heterogeneity of prostate cancer, and this new perspective will increasingly impact patient care.

  9. [Advances of molecular targeted therapy in squamous cell lung cancer]. (United States)

    Ma, Li; Zhang, Shucai


    Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

  10. Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

    Directory of Open Access Journals (Sweden)

    Bruna Karina Banin Hirata


    Full Text Available Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity.

  11. Molecular-Genetic Aspects of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Krasteva M.


    Full Text Available Breast cancer is the most frequent malignancy among women. Advances in breast cancer knowledge have deciphered the involvement of a number of tumor suppressor genes and proto-oncogenes in disease pathogenesis. These genes are part of the complex biochemical pathways, which enable cell cycle control and maintenance of genome integrity. Their function may be disrupted as a result of alterations in gene sequence or misregulation of gene expression including alterations in DNA methylation pattern. The present review summarizes the main findings on major breast cancer related genes BRCA1/2, p53, ATM, CHEK2, HER2, PIK3CA and their tumorigenic inactivation/activation. The potential clinical importance of these genes with respect to patients’ prognosis and therapy are also discussed. The possible implication of other putative breast cancer related genes is also outlined. The first elaborate data on the genetic and epigenetic status of the above mentioned genes concerning Bulgarian patients with the sporadic form of the disease are presented. The studies indicate for a characteristic mutational spectrum in some of the genes for the Bulgarian patients and specific correlation between the status of different genes and clinicopathological characteristics.

  12. TCGA divides gastric cancer into four molecular subtypes:implications for individualized therapeutics

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang


    Gastric cancer is a leading cause of cancer deaths in the world. The treatment of gastric cancer is chalenging because of its highly heterogeneous etiology and clinical characteristics. Recent genomic and molecular characterization of gastric cancer, especialy the findings reported by the Cancer Genome Atlas (TCGA), have shed light on the heterogeneity and potential targeted therapeutics for four different subtypes of gastric cancer.

  13. Multi-modality molecular imaging for gastric cancer research (United States)

    Liang, Jimin; Chen, Xueli; Liu, Junting; Hu, Hao; Qu, Xiaochao; Wang, Fu; Nie, Yongzhan


    Because of the ability of integrating the strengths of different modalities and providing fully integrated information, multi-modality molecular imaging techniques provide an excellent solution to detecting and diagnosing earlier cancer, which remains difficult to achieve by using the existing techniques. In this paper, we present an overview of our research efforts on the development of the optical imaging-centric multi-modality molecular imaging platform, including the development of the imaging system, reconstruction algorithms and preclinical biomedical applications. Primary biomedical results show that the developed optical imaging-centric multi-modality molecular imaging platform may provide great potential in the preclinical biomedical applications and future clinical translation.

  14. Molecular imaging of cancer using PET and SPECT

    DEFF Research Database (Denmark)

    Kjaer, Andreas


    for molecular imaging of cancer. Especially the possibility of a quick transfer of methods developed in animals to patients (translational research) is an important strength. This article will briefly discuss the newest applications and their importance and perspective in relation to the shift in paradigm......Molecular imaging allows for the study of molecular and cellular events in the living intact organism. The nuclear medicine methodologies of positron emission tomography (PET) and single photon emission computer tomography (SPECT) posses several advantages, which make them particularly suited...


    Directory of Open Access Journals (Sweden)

    Sabrina Daniela Silva


    Full Text Available Oral cancer cavity (OCC is associated with high incidence of loco-regional recurrences, which account for the majority of treatment failures post-surgery and radiotherapy. The time-course of relapse manifestation and metastasis are unpredictable. Relapsed OCC represents a major clinical challenge in part due to their aggressive and invasive behaviors. Chemotherapy remains the only option for advanced OCC whenever salvage surgery or re-irradiation is not feasible, but its efficacy is limited as a result of the drug resistance development. Alternatives to use of different permutations of standard cytotoxic drugs or combinations with modulators of drug resistance have led to incremental therapeutic benefits. The introduction of targeted agents and biologics against selective targets that drive cancer progression has opened-up optimism to achieve superior therapeutic activity and overcome drug resistance because, unlike the non-selective cytotoxic, the target can be monitored at molecular levels to identify patients who can benefit from the drug. This review discusses the multifactorial aspects of clinical drug resistance and emerging therapeutic approaches in recurrent OCC, emphasizing recent advances in targeted therapies, immunotherapy, and potential relevance of new concepts such as epithelial-mesenchymal transition and cancer stem cell hypothesis to drug resistance.

  16. Biology of cancer: current issues and future prospects. (United States)

    Jenkins, J


    The future of cancer treatment is limited only by the rate of progress made in understanding the biology of cancer. The future will present a considerable challenge to health care professionals to learn new theories, understand new terms, and expect different toxicities. The explosion of information and technology is exciting, yet frightening. The willingness of scientists, health care professionals, and consumers to deal with the ethical, financial, and political issues generated by this progress is gratifying. Because science has created such advances, the effort to deal with the outcomes is worthwhile but still difficult. The challenge to rapidly facilitate the sharing of the scientific and clinical advances has been recognized by the nation. A legislative mandate to create a way to store and analyze the vast data related to molecular biology, biochemistry, and genetics resulted in the National Center for Biotechnology Information. The development of automated systems to analyze genetic, environmental, biological, and chemistry information can only enhance future progress in the management of cancer.

  17. Current status of radiation therapy for prostate cancer

    Institute of Scientific and Technical Information of China (English)


    Radiotherapy for the treatment of prostate cancer has been extensively explored in the past. Along with the comprehensive understanding of the biology of prostate cancer and rapid advances in terms of technology, the outcome of treatment for the patients with prostate cancer has improved. The authors review radiotherapy as the primary treatment for the disease, with particular emphasis on the technological advances from both the radiobiological and radiophysics aspects. Nonconventional fractionated irradiation like hyper- or hypo-fractionation has been implemented in the clinic, the final results still need to be confirmed in the future. Technological advances like IMRT, IGRT,in the last two decades have significantly improved the delivery of external radiotherapy to the prostate. This has resulted in an overall increase in the total dose that can be safely delivered to the prostate, which has led to modest improvements in the biochemical outcome. However, establishing the standard therapy for prostate cancer remains controversial. It is hoped that the next decades will bring continued advances in the development of biologicals that will further improve current clinical outcomes.

  18. Current imaging strategies for the evaluation of uterine cervical cancer. (United States)

    Bourgioti, Charis; Chatoupis, Konstantinos; Moulopoulos, Lia Angela


    Uterine cervical cancer still remains an important socioeconomic issue because it largely affects women of reproductive age. Prognosis is highly depended on extent of the disease at diagnosis and, therefore, accurate staging is crucial for optimal management. Cervical cancer is clinically staged, according to International Federation of Gynecology and Obstetrics guidelines, but, currently, there is increased use of cross sectional imaging modalities [computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT)] for the study of important prognostic factors like tumor size, parametrial invasion, endocervical extension, pelvic side wall or adjacent/distal organs involvement and lymph node status. Imaging indications also include cervical cancer follow-up, evaluation of tumor response to treatment and selection of suitable candidates for less radical surgeries like radical trachelectomy for fertility preservation. The preferred imaging method for local cervical cancer evaluation is MRI; CT is equally effective for evaluation of extrauterine spread of the disease. PET-CT shows high diagnostic performance for the detection of tumor relapse and metastatic lymph nodes. The aim of this review is to familiarize radiologists with the MRI appearance of cervical carcinoma and to discuss the indications of cross sectional imaging during the course of the disease in patients with cervical carcinoma.

  19. Preventing skin cancer through reduction of indoor tanning: current evidence. (United States)

    Watson, Meg; Holman, Dawn M; Fox, Kathleen A; Guy, Gery P; Seidenberg, Andrew B; Sampson, Blake P; Sinclair, Craig; Lazovich, DeAnn


    Exposure to ultraviolet radiation from indoor tanning devices (tanning beds, booths, and sun lamps) or from the sun contributes to the risk of skin cancer, including melanoma, which is the type of skin cancer responsible for most deaths. Indoor tanning is common among certain groups, especially among older adolescents and young adults, adolescent girls and young women, and non-Hispanic whites. Increased understanding of the health risks associated with indoor tanning has led to many efforts to reduce use. Most environmental and systems efforts in the U.S. (e.g., age limits or requiring parental consent/accompaniment) have occurred at the state level. At the national level, the U.S. Food and Drug Administration and the Federal Trade Commission regulate indoor tanning devices and advertising, respectively. The current paper provides a brief review of (1) the evidence on indoor tanning as a risk factor for skin cancer; (2) factors that may influence use of indoor tanning devices at the population level; and (3) various environmental and systems options available for consideration when developing strategies to reduce indoor tanning. This information provides the context and background for the companion paper in this issue of the American Journal of Preventive Medicine, which summarizes highlights from an informal expert meeting convened by the CDC in August 2012 to identify opportunities to prevent skin cancer by reducing use of indoor tanning devices.

  20. Current imaging strategies for the evaluation of uterine cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Charis Bourgioti; Konstantinos Chatoupis; Lia Angela Moulopoulos


    Uterine cervical cancer still remains an important socioeconomic issue because it largely affects women of reproductive age.Prognosis is highly depended on extent of the disease at diagnosis and,therefore,accurate staging is crucial for optimal management.Cervical cancer is clinically staged,according to International Federation of Gynecology and Obstetrics guidelines,but,currently,there is increased use of cross sectional imaging modalities [computed tomography(CT),magnetic resonance imaging(MRI),positron emission tomography-CT(PET-CT)] for the study of important prognostic factors like tumor size,parametrial invasion,endocervical extension,pelvic side wall or adjacent/distal organs involvement and lymph node status.Imaging indications also include cervical cancer follow-up,evaluation of tumor response to treatment and selection of suitable candidates for less radical surgeries like radical trachelectomy for fertility preservation.The preferred imaging method for local cervical cancer evaluation is MRI;CT is equally effective for evaluation of extrauterine spread of the disease.PETCT shows high diagnostic performance for the detection of tumor relapse and metastatic lymph nodes.The aim of this review is to familiarize radiologists with the MRI appearance of cervical carcinoma and to discuss the indications of cross sectional imaging during the course of the disease in patients with cervical carcinoma.

  1. Molecular Imaging of Breast Cancer: Present and future directions

    Directory of Open Access Journals (Sweden)

    David eAlcantara


    Full Text Available Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases and biological processes (e.g. apoptosis, angiogenesis, and metastasis that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

  2. Molecular Characterization of Indolent Prostate Cancer (United States)


    Luo, Ph.D. CONTRACTING ORGANIZATION: Johns Hopkins University Baltimore, MD 21218-2680 REPORT DATE: October 2015 TYPE OF REPORT: Annual...DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE Annual Report 3. DATES COVERED 15 Sep 2014- 14 Sep 2015...detected at biopsy , leading to the contemporary problem of prostate cancer over-diagnosis and over-treatment. The objective of the project is to

  3. Miniature and Molecularly Specific Optical Screening Technologies for Breast Cancer (United States)


    and molecular contrast in breast cancer V. Millon SR, Provenzano PP, Elicieri, KW, Brown, JQ, Keely, PJ, Ramanujam, N. "Imaging of ALA-induced PpIX...calculating tissue optical properties. Part I: Theory and validation on synthetic phantoms. Appl Opt, 2006. 45(5): p. 1062-71. 4. Baumann, M., C

  4. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    NARCIS (Netherlands)

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van


    ABSTRACT: BACKGROUND: Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers m

  5. Molecular Biology and Prevention of Endometrial Cancer (United States)


    of the oral contraceptive pill (OCP). Project 1: Objectives completed and data previously submitted with 2004 report. Data published this past year...molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC...not been altered appreciably. Despite the known protective effect of oral contraceptives , little has been learned regarding the underlying mechanism

  6. Methodologies in cancer cytogenetics and molecular cytogenetics. (United States)

    Wang, Nancy


    Various types of cytogenetic and molecular cytogenetic approaches, including conventional banding, fluorescence in situ hybridization (FISH), fiber-FISH, comparative genomic hybridization (CGH), matrix array CGH, chromosome microdissection, and microcell-mediated chromosome transfer are summarized. The rationale, advantage, and limitations of each approach are discussed with respect to research and clinical applications in human neoplasia.

  7. Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer. (United States)

    Clark, Owen; Yen, Katharine; Mellinghoff, Ingo K


    IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) and concomitantly produce reduced NADPH from NADP(+) Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. The mutant protein loses its normal enzymatic activity and gains a new ability to produce the "oncometabolite" R(-)-2-hydroxyglutarate (R-2-HG). R-2-HG competitively inhibits α-KG-dependent enzymes which play crucial roles in gene regulation and tissue homeostasis. Expression of mutant IDH impairs cellular differentiation in various cell lineages and promotes tumor development in cooperation with other cancer genes. First-generation inhibitors of mutant IDH have entered clinical trials, and have shown encouraging results in patients with IDH-mutant AML. This article summarizes recent progress in our understanding of the role of mutant IDH in tumorigenesis.Clin Cancer Res; 22(8); 1837-42. ©2016 AACR.

  8. Current status and progress in gastric cancer with liver metastasis

    Institute of Scientific and Technical Information of China (English)

    LIU Jing; CHEN Lin


    Objective This review discusses the current status and progress in studies on gastric cancer with liver metastasis (GCLM), involving the routes, subtypes, and prognosis of GCLM; the genes and molecules associated with metastasis;the feasibility and value of each imaging modality; and current treatment options.Data sources The data used in this review were mainly from Medline and PubMed published in English from 2005 to August 2010. The search terms were "gastric cancer" and "liver metastasis".Study selection Articles regarding the characteristics, diagnostic modalities, and vadous therapeutic options of GCLM were selected.Results The prognosis of GCLM is influenced by the clinicopathological characteristics of primary tumors, as well as the presence of liver metastases. Improved understanding of related genes and molecules will lead to the development of methods of early detection and targeted therapies. For the diagnosis of GCLM, each imaging modality has its relative benefits. There remains no consensus regarding therapeutic options.Conclusions Early detection and characterization of liver metastases is crucial for the prognosis of gastric cancer patients. Multidisciplinary team discussions are required to design optimal treatment strategies, which should be based on the clinicopathological characteristics of each patient.

  9. Molecular mechanisms linking adipokines to obesity-related colon cancer: focus on leptin. (United States)

    Drew, Janice E


    Obesity is linked to increased risk of colon cancer, currently the third most common cancer. Consequently rising levels of obesity worldwide are likely to significantly impact on obesity-related colon cancers in the decades to come. Understanding the molecular mechanisms whereby obesity increases colon cancer risk is thus a focus for research to inform strategies to prevent the increasing trend in obesity-related cancers. This review will consider research on deregulation of adipokine signalling, a consequence of altered adipokine hormone secretion from excess adipose tissue, with a focus on leptin, which has been studied extensively as a potential mediator of obesity-related colon cancer. Numerous investigations using colon cell lines in vitro, in vivo studies in rodents and investigations of colon cancer patients illuminate the complexity of the interactions of leptin with colon tissues via leptin receptors expressed by the colon epithelium. Although evidence indicates a role for leptin in proliferation of colon epithelial cells in vitro, this has been contradicted by studies in rodent models. However, recent studies have indicated that leptin may influence inflammatory mediators linked with colon cancer and also promote cell growth dependent on genotype and is implicated in growth promotion of colon cancer cells. Studies in human cancer patients indicate that there may be different tumour sub-types with varying levels of leptin receptor expression, indicating the potential for leptin to induce variable responses in the different tumour types. These studies have provided insights into the complex interplay of adipokines with responsive tissues prone to obesity-related colon cancer. Deregulation of adipokine signalling via adipokine receptors located in the colon appears to be a significant factor in obesity-related colon cancer. Molecular profiling of colon tumours will be a useful tool in future strategies to characterise the influence that adipokines may have

  10. Molecular imaging of cell-mediated cancer immunotherapy. (United States)

    Lucignani, Giovanni; Ottobrini, Luisa; Martelli, Cristina; Rescigno, Maria; Clerici, Mario


    New strategies based on the activation of a patient's immune response are being sought to complement present conventional exogenous cancer therapies. Elucidating the trafficking pathways of immune cells in vivo, together with their migratory properties in relation to their differentiation and activation status, is useful for understanding how the immune system interacts with cancer. Methods based on tissue sampling to monitor immune responses are inadequate for repeatedly characterizing the responses of the immune system in different organs. A solution to this problem might come from molecular and cellular imaging - a branch of biomedical sciences that combines biotechnology and imaging methods to characterize, in vivo, the molecular and cellular processes involved in normal and pathologic states. The general concepts of noninvasive imaging of targeted cells as well as the technology and probes applied to cell-mediated cancer immunotherapy imaging are outlined in this review.

  11. Epigenetic Markers for Molecular Detection of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Vera L. Costa


    Full Text Available Prostate cancer is a highly prevalent malignancy, which is clinically silent but curable while organ-confined. Because available screening methods show poor sensitivity and specificity, the development of new molecular markers is warranted. Epigenetic alterations, mainly promoter hypermethylation of cancer-related genes, are common events in prostate cancer and might be used as cancer biomarkers. Moreover, the development of quantitative, high-throughput techniques to assess promoter methylation enabled the simultaneous screening of multiple clinical samples. From the numerous cancer-related genes hypermethylated in prostate cancer only a few proved to be strong candidates to become routine biomarkers. This small set of genes includes GSTP1, APC, RARβ2, Cyclin D2, MDR1, and PTGS2. Single and/or multigene analyses demonstrated the feasibility of detecting early prostate cancer, with high sensitivity and specificity, in body fluids (serum, plasma, urine, and ejaculates and tissue samples. In addition, quantitative hypermethylation of several genes has been associated with clinicopathologic features of tumor aggressiveness, and also reported as independent prognostic factor for relapse. The identification of age-related methylation at specific loci and the differential frequency of methylation among ethnical groups, also provided interesting data linking methylation and prostate cancer risk. Although large trials are needed to validate these findings, the clinical use of these markers might be envisaged for the near future.

  12. Pathological Bases for a Robust Application of Cancer Molecular Classification

    Directory of Open Access Journals (Sweden)

    Salvador J. Diaz-Cano


    Full Text Available Any robust classification system depends on its purpose and must refer to accepted standards, its strength relying on predictive values and a careful consideration of known factors that can affect its reliability. In this context, a molecular classification of human cancer must refer to the current gold standard (histological classification and try to improve it with key prognosticators for metastatic potential, staging and grading. Although organ-specific examples have been published based on proteomics, transcriptomics and genomics evaluations, the most popular approach uses gene expression analysis as a direct correlate of cellular differentiation, which represents the key feature of the histological classification. RNA is a labile molecule that varies significantly according with the preservation protocol, its transcription reflect the adaptation of the tumor cells to the microenvironment, it can be passed through mechanisms of intercellular transference of genetic information (exosomes, and it is exposed to epigenetic modifications. More robust classifications should be based on stable molecules, at the genetic level represented by DNA to improve reliability, and its analysis must deal with the concept of intratumoral heterogeneity, which is at the origin of tumor progression and is the byproduct of the selection process during the clonal expansion and progression of neoplasms. The simultaneous analysis of multiple DNA targets and next generation sequencing offer the best practical approach for an analytical genomic classification of tumors.

  13. Advances of Molecular Targeted Therapy in Squamous Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li MA


    Full Text Available Squamous cell lung cancer (SQCLC is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR inhibitors or anaplastic lymphoma kinase (ALK inhibitors that show exquisite activity in lungadenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1 gene, the discoidin domain receptor 2 (DDR2 gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lungcancer assessing the value of novel therapeutics addressing these targets.

  14. Using large-scale genome variation cohorts to decipher the molecular mechanism of cancer. (United States)

    Habermann, Nina; Mardin, Balca R; Yakneen, Sergei; Korbel, Jan O


    Characterizing genomic structural variations (SVs) in the human genome remains challenging, and there is a growing interest to understand somatic SVs occurring in cancer, a disease of the genome. A havoc-causing SV process known as chromothripsis scars the genome when localized chromosome shattering and repair occur in a one-off catastrophe. Recent efforts led to the development of a set of conceptual criteria for the inference of chromothripsis events in cancer genomes and to the development of experimental model systems for studying this striking DNA alteration process in vitro. We discuss these approaches, and additionally touch upon current "Big Data" efforts that employ hybrid cloud computing to enable studies of numerous cancer genomes in an effort to search for commonalities and differences in molecular DNA alteration processes in cancer.

  15. Application of Proteomics to Cancer Molecular Diagnostics

    Institute of Scientific and Technical Information of China (English)

    Sam HANASH


    @@ Strategies to achieve personalized medicine and improve public health encompass assessment of an individual's risk for disease, early detection and molecular classification of disease resulting in an informed choice of the most appropriate treatment instituted at an early stage of disease develop- ment. A major contribution of proteomics in this field is the development of blood based tests to achieve the goals of personalized medicine.

  16. Molecular Determinants of Hormone Refractory Prostate Cancer (United States)


    to known prostate cancer oncogenes, Never In Mitosis A (NIMA) related kinase 6 (NEK6) reproducibly yielded androgen-independent tumors in female...constitutively active MEK, RAF1, ERBB2, AKT1, PIM1 and PIM2), overexpression of the Never In Mitosis A (NIMA) related kinase 6 (NEK6) reproducibly yielded...Never In Mitosis A (NIMA) related kinase 6 (NEK6), and nemo-like kinase (NLK). Aim 1. Elucidating the role of NIMA-related kinase 6 (NEK6) and nemo

  17. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Moira Ragazzi


    Full Text Available Anaplastic thyroid carcinoma (ATC is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features.

  18. BRCA-Associated Ovarian Cancer: From Molecular Genetics to Risk Management


    Giulia Girolimetti; Anna Myriam Perrone; Donatella Santini; Elena Barbieri; Flora Guerra; Simona Ferrari; Claudio Zamagni; Pierandrea De Iaco; Giuseppe Gasparre; Daniela Turchetti


    Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposit...

  19. Alcohol and breast cancer: reconciling epidemiological and molecular data. (United States)

    Zakhari, Samir; Hoek, Jan B


    Breast cancer is the most diagnosed cancer in women worldwide. Epidemiological studies have suggested a possible causative role of alcohol consumption as a risk factor for breast cancer. However, such conclusions should be interpreted with considerable caution for several reasons. While epidemiological studies can help identify the roots of health problems and disease incidence in a community, they are by necessity associative and cannot determine cause and effect relationships. In addition, all these studies rely on self-reporting to determine the amount and type of alcoholic beverage consumed, which introduces recall bias. This is documented in a recent study which stated that the apparent increased risk of cancer among light-moderate drinkers may be "substantially due to underreporting of intake." Another meta-analysis about alcohol and breast cancer declared "the modest size of the association and variation in results across studies leave the causal role of alcohol in question." Furthermore, breast cancer develops over decades; thus, correlations between alcohol consumption and breast cancer cannot be determined in epidemiological studies with windows of alcohol exposure that captures current or recent alcohol intake, after clinical diagnosis. Numerous risk factors are involved in breast carcinogenesis; some are genetic and beyond the control of a woman; others are influenced by lifestyle factors. Breast cancer is a heterogeneous and polygenic disease which is further influenced by epigenetic mechanisms that affect the transciptomes, proteomes and metabolomes, and ultimately breast cancer evolution. Environmental factors add another layer of complexity by their interactions with the susceptibility genes for breast cancer and metabolic diseases. The current state-of-knowledge about alcohol and breast cancer association is ambiguous and confusing to both a woman and her physician. Confronting the huge global breast cancer issue should be addressed by sound

  20. The molecular mechanisms between metabolic syndrome and breast cancer. (United States)

    Chen, Yi; Wen, Ya-yuan; Li, Zhi-rong; Luo, Dong-lin; Zhang, Xiao-hua


    Metabolic syndrome, which is extremely common in developed and some developing countries, is a clustering of at least three of five of the following medical conditions: abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein levels. It has been proved that there is a strong association between metabolic syndrome and breast cancer. Metabolic syndrome could increase the risk of breast cancer and influence the prognosis of the breast cancer patients. Some characteristic of metabolic syndrome such as obesity and lack of physical exercise are all risk factors for developing breast cancer. The metabolic syndrome mainly include obesity, type 2 diabetes, hypercholesterolemia and nonalcoholic fatty liver disease, and each of them impacts the risk of breast cancer and the prognosis of the breast cancer patients in different ways. In this Review, we focus on recently uncovered aspects of the immunological and molecular mechanisms that are responsible for the development of this highly prevalent and serious disease. These studies bring new insight into the complex associations between metabolic syndrome and breast cancer and have led to the development of novel therapeutic strategies that might enable a personalized approach in the management of this disease.

  1. Molecular biology of breast cancer stem cells: potential clinical applications. (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent


    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy.

  2. Molecular markers and targets for colorectal cancer prevention

    Institute of Scientific and Technical Information of China (English)

    Naveena B JANAKIRAM; Chinthalapally V RAO


    Colorectal cancer is the third most prevalent cancer in the world. If detected at an early stage, treatment often might lead to cure. As prevention is better than cure, epidemiological studies reveal that having a healthy diet often protects from pro-moting/developing cancer. An important consideration in evaluating new drugs and devices is determining whether a product can effectively treat a targeted disease. There are quite a number of biomarkers making their way into clinical trials and few are awaiting the preclinical efficacy and safety results to enter into clinical trials. Researchers are facing challenges in modifying trial design and defining the right control population, validating biomarker assays from the bio-logical and analytical perspective and using biomarker data as a guideline for decision making. In spite of following all guidelines, the results are disappointing from many of the large clinical trials. To avoid these disappointments, selection of biomarkers and its target drug needs to be evaluated in appropriate animal models for its toxicities and efficacies. The focus of this review is on the few of the potential molecular targets and their biomarkers in colorectal cancers. Strengths and limitations of biomarkers/surrogate endpoints are also discussed. Various pathways involved in tumor cells and the specific agents to target the altered molecular biomarkerin biomolecular pathwayare elucidated. Importance of emerging new platforms siRNAs and miRNAs technology for colorectal cancer therapeutics is reviewed.

  3. Molecular damage in cancer: an argument for mTOR-driven aging. (United States)

    Blagosklonny, Mikhail V


    Despite common belief, accumulation of molecular damage does not play a key role in aging. Still, cancer (an age-related disease) is initiated by molecular damage. Cancer and aging share a lot in common including the activation of the TOR pathway. But the role of molecular damage distinguishes cancer and aging. Furthermore, an analysis of the role of both damage and aging in cancer argues against "a decline, caused by accumulation of molecular damage" as a cause of aging. I also discuss how random molecular damage, via rounds of multiplication and selection, brings about non-random hallmarks of cancer.

  4. Molecular markers in prostate cancer.Part II:potential roles in management

    Institute of Scientific and Technical Information of China (English)

    Sachin Agrawal; Krishnaji P.Patil; William D.Dunsmuir


    Predicting treatment responses in advanced prostate cancer (PCa) currently centres on prostate-specific antigen (PSA) kinetics and on being able to visualize measurable changes in imaging modalities.New molecular markers have emerged as potential diagnostic and prognostic indicators;these were summarized in Part I of this review in the Asian Journal of Andrology.A number of molecular markers are now being used to enhance PCa imaging and staging.However,management options for advanced and hormone-resistant PCa (HRPC) are limited and additional therapeutic options are needed.Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation.Additionally,markers identified in early PCa and precursor lesions may offer novel targets for chemoprevention and vaccine development.This review summarizes the current advances regarding the roles of these markers in the management of PCa.

  5. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F


    Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  6. MicroRNAs as molecular markers in lung cancer

    Directory of Open Access Journals (Sweden)

    Javier Silva


    Full Text Available Lung cancer is the most common cause of cancer death in the western world for both men and women. Lung cancer appears to be a perfect candidate for a screening program, since it is the number one cancer killer, it has a long preclinical phase, curative treatment for the minority of patients who are diagnosed early and a target population at risk (smokers and it is also a major economic burden. The earliest approaches to identifying cancer markers were based on preliminary clinical or pathological observations, although molecular biology is a strong candidate for occupying a place among the set of methods. In search of markers, several alterations, such as mutations, loss of heterozygosity, microsatellite instability, DNA methylation, mitochondrial DNA mutations, viral DNA, modified expression of mRNA, miRNA and proteins, and structurally altered proteins have all been analysed. MicroRNAs (miRNA are small RNA molecules, about 19-25 nucleotides long and encoded in genomes of plants, animals, fungi and viruses. It has been reported that miRNAs may have multiple functions in lung development and that aberrant expression of miRNAs could induce lung tumorigenesis. We review here the role of miRNAs in lung tumorigenesis and also as a novel type of biomarker.-----------------------------------Cite this article as:Silva J, Garcia V, Lopez-Gonzalez A, Provencio M. MicroRNAs as molecular markers in lung cancer. Int J Cancer Ther Oncol 2013;1(1:010111. DOI:

  7. Current principles of effective therapy for ovarian cancer

    Directory of Open Access Journals (Sweden)

    L. A. Ashrafyan


    Full Text Available In spite of all of modern medicine»s advances, ovarian cancer (OC mortality remains to be incommensurably high and to hold the lead among gynecological cancers. The initial cause of this deplorable statistics is the absence of a clear concept of the pathogenesis of OC and hence the justified prevention and methodology of early diagnosis of the disease; in this connection, therapy that proves to be ineffective is frequently used by medical oncologists in their daily practice. As a consequence, there is a high proportion of its further progression: the rates of early and late recurrences were about 30 and 60–65 %, respectively; most of which are drug resistant to further chemotherapy cycles. By taking into account these strikingly modest statistics, it becomes apparent that oncologists desire to make changes in the existing treatment regimen to achieve meaningful results. To use target drugs is one of these promising areas owing to new views on the concept of the pathogenesis of OC.Nevertheless, considering a wide variety of the signaling cascades and molecules, which are involved in the process of carcinogenesis, even target compounds, if they have only one point of application, cannot always produce their desirable therapeutic effect and their co-administration is responsible for high toxicity. In this light, the most effective drugs are indole-3-carbinol and epigallocathechin-3-gallate, which virtually cause no adverse reactions and can block various molecular targets at different levels of the mechanism of malignant transformation. Based on L. A. Ashrafyan, s concept of two pathogenetic variants of sporadic OC (2009 and on the recent findings in molecular biology and epigenetics, the incorporation of the above medications into the standard treatment regimen for OC should increase survival rates and change the nature of recurrence by that of more locally advanced forms. On this basis, a clinical trial was carried out to study

  8. Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC). (United States)

    Kumarakulasinghe, Nesaretnam Barr; van Zanwijk, Nico; Soo, Ross A


    Historically, patients with advanced stage non-small cell lung cancer (NSCLC) were treated with chemotherapy alone, but a therapeutic plateau has been reached. Advances in the understanding of molecular genetics have led to the recognition of multiple molecularly distinct subsets of NSCLC. This in turn has led to the development of rationally directed molecular targeted therapy, leading to improved clinical outcomes. Tumour genotyping for EGFR mutations and ALK rearrangement has meant chemotherapy is no longer given automatically as first-line treatment but reserved for when patients do not have a 'druggable' driver oncogene. In this review, we will address the current status of clinically relevant driver mutations and emerging new molecular subsets in lung adenocarcinoma and squamous cell carcinoma, and the role of targeted therapy and mechanisms of acquired resistance to targeted therapy.

  9. Intraoperative Assessment of Breast Cancer Margins ex vivo using Aqueous Quantum Dot-Functionalized Molecular Probes (United States)

    Au, Giang Hoang Thuy

    Breast cancer is increasingly diagnosed at an early stage, allowing the diseased breast to be removed only partially or breast conserving surgery (BCS). Current BCS procedures have no rapid methods during surgery to assess if the surgical margin is clear of cancer, often resulting in re-excision. The current breast cancer re-excision rate is estimated to be 15% to as high as 60%. It would be desirable if there is a rapid and reliable breast cancer margin assessment tool in the operating room to help assess if the surgical margin is clean to minimize unnecessary re-excisions. In this research, we seek to develop an intraoperative, molecular probe-based breast cancer surgical margin assessment tool using aqueous quantum dots (AQDs) coupled with cancer specific biomarkers. Quantum dots (QDs) are photoluminescent semiconductor nanoparticles that do not photobleach and are brighter than organic fluorescent dyes. Aqueous quantum dots (AQDs) such as CdSe and near infrared (NIR) CdPbS developed in Shih's lab emit light longer than 600 nm. We have examined conjugating AQDs with antibodies to cancer specific biomarkers such as Tn antigen, a cancer-associated glycan antigen for epithelial cancers. We showed that AQDs could achieve ~80% antibody conjugation efficiency, i.e., 100 times less antibodies than required by commercial, making such AQD molecular probe surgical margin evaluation economically feasible. By conjugating AQDs with anti-Tn-antigen antibody, the AQDs molecular probe exhibited 94% sensitivity and 92% specificity in identifying breast cancer against normal breast tissues as well as benign breast tumors in 480 tissue blocks from 126 patients. Furthermore, mice model and clinical human studies indicated that AQDs imaging did not interfere with the following pathological staining. More interestingly, we showed that it it possible to directly conjugate one antibody to multiple AQDs, further reduces the required amount of antibodies needed, a feat that could not be

  10. Molecular epidemiology, cancer-related symptoms, and cytokines pathway. (United States)

    Reyes-Gibby, Cielito C; Wu, Xifeng; Spitz, Margaret; Kurzrock, Razelle; Fisch, Michael; Bruera, Eduardo; Shete, Sanjay


    The Human Genome Project and HapMap have led to a better appreciation of the importance of common genetic variation in determining cancer risk, created potential for predicting response to therapy, and made possible the development of targeted prevention and therapeutic interventions. Advances in molecular epidemiology can be used to explore the role of genetic variation in modulating the risk for severe and persistent symptoms, such as pain, depression, and fatigue, in patients with cancer. The same genes that are implicated in cancer risk might also be involved in the modulation of therapeutic outcomes. For example, polymorphisms in several cytokine genes are potential markers for genetic susceptibility both for cancer risk and for cancer-related symptoms. These genetic polymorphisms are stable markers and easily and reliably assayed to explore the extent to which genetic variation might prove useful in identifying patients with cancer at high-risk of symptom development. Likewise, they could identify subgroups who might benefit most from symptom intervention, and contribute to developing personalized and more effective therapies for persistent symptoms.

  11. Cellular and molecular effects of yeast probiotics on cancer. (United States)

    Saber, Amir; Alipour, Beitollah; Faghfoori, Zeinab; Yari Khosroushahi, Ahmad


    The cancer is one of the main causes of human deaths worldwide. The exact mechanisms of initiation and progression of malignancies are not clear yet, but there is a common agreement about the role of colonic microbiota in the etiology of different cancers. Probiotics have been examined for their anti-cancer effects, and different mechanisms have been suggested about their antitumor functions. Nonpathogenic yeasts, as members of probiotics family, can be effective on gut microbiota dysbiosis. Generally safe yeasts have shown so many beneficial effects on human health. Probiotic yeasts influence physiology, metabolism, and immune homeostasis in the colon and contribute to cancer treatment due to possessing anti-inflammatory, anti-proliferative and anti-cancer properties. This study reviews some of the health-beneficial effects of probiotic yeasts and their biological substances like folic acid and β-glucan on cancer and focuses on the possible cellular and molecular mechanisms of probiotic yeasts such as influencing pathogenic bacteria, inactivation of carcinogenic compounds, especially those derived from food, improvement of intestinal barrier function, modulation of immune responses, antitoxic function, apoptosis, and anti-proliferative effects.


    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征


    Objectives. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-based case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel art and Falconer methods were used to analyze the segregation ratio and heritability. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significartly, OR is 3.905 ( 95 % CI = 1.079 ~ 14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blood relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LOH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome aberrations were observed. Conclusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.


    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征


    Obieaites. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-besed case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel-Gart and Falconer methods were used to analyze the segregation ratio and heritability. Polymemse chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significantly, OR is 3.905(95% CI = 1.079—14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blnod relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LDH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome abermtions were observed.Condusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  14. Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Donavon Hiss


    Full Text Available The hallmarks of ovarian cancer encompass the development of resistance, disease recurrence and poor prognosis. Ovarian cancer cells express gene signatures which pose significant challenges for cancer drug development, therapeutics, prevention and management. Despite enhancements in contemporary tumor debulking surgery, tentative combination regimens and abdominal radiation which can achieve beneficial response rates, the majority of ovarian cancer patients not only experience adverse effects, but also eventually relapse. Therefore, additional therapeutic possibilities need to be explored to minimize adverse events and prolong progression-free and overall response rates in ovarian cancer patients. Currently, a revival in cancer drug discovery is devoted to identifying diagnostic and prognostic ovarian cancer biomarkers. However, the sensitivity and reliability of such biomarkers may be complicated by mutations in the BRCA1 or BRCA2 genes, diverse genetic risk factors, unidentified initiation and progression elements, molecular tumor heterogeneity and disease staging. There is thus a dire need to expand existing ovarian cancer therapies with broad-spectrum and individualized molecular targeted approaches. The aim of this review is to profile recent developments in our understanding of the interrelationships among selected ovarian tumor biomarkers, heterogeneous expression signatures and related molecular signal transduction pathways, and their translation into more efficacious targeted treatment rationales.

  15. Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones


    Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S; Zhang, Yan-Bing; Zi, Xiaolin


    There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reacti...

  16. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy (United States)

    Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan


    Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL) and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

  17. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yang eLiu


    Full Text Available Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT, magnetic resonance imaging (MRI, positron emission tomography (PET, as well as nanoprobes for photoacoustic tomography (PAT, two-photon photoluminescence (TPL and surface-enhanced Raman spectroscopy (SERS. Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

  18. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao


    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  19. Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes (United States)

    Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan


    Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual

  20. Lymph node-positive prostate cancer: current issues, emerging technology and impact on clinical outcome. (United States)

    Adams, Julia; Cheng, Liang


    Lymph node metastasis in patients with prostate cancer indicates a poorer prognosis compared with patients without lymph node metastasis; however, some patients with node-positive disease have long-term survival. Many studies have attempted to discern what characteristics of lymph node metastasis are prognostically significant. These characteristics include nodal tumor volume, number of positive lymph nodes, lymph node density, extranodal extension, lymphovascular invasion and tumor dedifferentiation. Favorable characteristics of regional lymph node involvement included a smaller tumor size and smaller tumor volume. However, the current staging system for prostate cancer does not provide different subclassifications for patients with node-positive prostate cancer. In recent years numerous advanced technologies for the detection of lymph node metastasis have been developed, including molecular imaging techniques and the CellSearch Circulating Tumor Cell System. With the increased detection of patients with prostate cancer, emergence of new technology to identify lymph node metastasis and the number of radical prostatectomies being performed on the rise, subclassifying patients with lymph node-positive disease is imperative. Subclassification would provide a better picture of patient prognosis and allow for a better understanding of targeted therapies to treat patients with lymph node metastasis.

  1. Research Status on Molecular Targeted Therapy for Squamous-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yanan LI


    Full Text Available Lung cancer is one of the world's highest morbidity and mortality disease in malignant tumors currently. Squamous-cell lung cancer (SQCLC is one of the most prevalent subtypes of lung cancer worldwide, after surgery, radiotherapy, chemotherapy and other comprehensive treatment, its 5-year survival rate is still below 15%. The current molecular targeted therapy plays an important role in the treatment of SQCLC, an urgent need to be more in-depth study. SQCLC molecular targeted therapy mainly epidermal growth factor receptor (EGFR, phosphoin-3-kinase catalytic alpha polypeptide (PIK3CA, fibroblast growth factor receptor 1 (FGFR1, discoidin domain receptor 2 (DDR2, phosphatase and tensin homolog deleted on chromosome ten (PTEN, BRAF, MET, insulin-like growth factor 1 receptor (IGF-1R and other as the target of the drug, some targeted drugs are being developed, and some targeted drugs have entered clinical trials. In recent years, with studies molecular targeted therapy in SQCLC, analysis of the development and trgeted therapy achieved substantial progress in improving the survival rate of SQCLC, and other research to improve the quality of life, make is possible to individualized targeted therapy of SQCLC.

  2. Molecular Classification of Gastric Cancer: A new paradigm (United States)

    Shah, Manish A.; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y.; Klimstra, David S.; Gerdes, Hans; Kelsen, David P.


    Purpose Gastric cancer may be subdivided into three distinct subtypes –proximal, diffuse, and distal gastric cancer– based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Experimental Design Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (NCI 5917) underwent endoscopic biopsy for fresh tumor procurement. 4–6 targeted biopsies of the primary tumor were obtained. Macrodissection was performed to ensure >80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Results Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the three gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross validation error was 0.14, suggesting that >85% of samples were classified correctly. Gene set analysis with the False Discovery Rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Conclusions Subtypes of gastric cancer that have epidemiologic and histologic distinction are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. PMID:21430069

  3. Chitosan in Molecularly-Imprinted Polymers: Current and Future Prospects

    Directory of Open Access Journals (Sweden)

    Long Xu


    Full Text Available Chitosan is widely used in molecular imprinting technology (MIT as a functional monomer or supporting matrix because of its low cost and high contents of amino and hydroxyl functional groups. The various excellent properties of chitosan, which include nontoxicity, biodegradability, biocompatibility, and attractive physical and mechanical performances, make chitosan a promising alternative to conventional functional monomers. Recently, chitosan molecularly-imprinted polymers have gained considerable attention and showed significant potential in many fields, such as curbing environmental pollution, medicine, protein separation and identification, and chiral-compound separation. These extensive applications are due to the polymers’ desired selectivity, physical robustness, and thermal stability, as well as their low cost and easy preparation. Cross-linkers, which fix the functional groups of chitosan around imprinted molecules, play an important role in chitosan molecularly-imprinted polymers. This review summarizes the important cross-linkers of chitosan molecularly-imprinted polymers and illustrates the cross-linking mechanism of chitosan and cross-linkers based on the two glucosamine units. Finally, some significant attempts to further develop the application of chitosan in MIT are proposed.

  4. Josephson current through a molecular transistor in a dissipative environment

    DEFF Research Database (Denmark)

    Novotny, T; Rossini, Gianpaolo; Flensberg, Karsten


    We study the Josephson coupling between two superconductors through a single correlated molecular level, including Coulomb interaction on the level and coupling to a bosonic environment. All calculations are done to the lowest, i.e., the fourth, order in the tunneling coupling and we find a suppr...

  5. Pavlovian Conditioning of "Hermissenda": Current Cellular, Molecular, and Circuit Perspectives (United States)

    Crow, Terry


    The less-complex central nervous system of many invertebrates make them attractive for not only the molecular analysis of the associative learning and memory, but also in determining how neural circuits are modified by learning to generate changes in behavior. The nudibranch mollusk "Hermissenda crassicornis" is a preparation that has contributed…

  6. Chitosan in Molecularly-Imprinted Polymers: Current and Future Prospects. (United States)

    Xu, Long; Huang, Yun-An; Zhu, Qiu-Jin; Ye, Chun


    Chitosan is widely used in molecular imprinting technology (MIT) as a functional monomer or supporting matrix because of its low cost and high contents of amino and hydroxyl functional groups. The various excellent properties of chitosan, which include nontoxicity, biodegradability, biocompatibility, and attractive physical and mechanical performances, make chitosan a promising alternative to conventional functional monomers. Recently, chitosan molecularly-imprinted polymers have gained considerable attention and showed significant potential in many fields, such as curbing environmental pollution, medicine, protein separation and identification, and chiral-compound separation. These extensive applications are due to the polymers' desired selectivity, physical robustness, and thermal stability, as well as their low cost and easy preparation. Cross-linkers, which fix the functional groups of chitosan around imprinted molecules, play an important role in chitosan molecularly-imprinted polymers. This review summarizes the important cross-linkers of chitosan molecularly-imprinted polymers and illustrates the cross-linking mechanism of chitosan and cross-linkers based on the two glucosamine units. Finally, some significant attempts to further develop the application of chitosan in MIT are proposed.

  7. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, Hebert Alberto; Sala, Evis; Hricak, Hedvig [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Grimm, Jan [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York (United States); Donati, Olivio F. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)


    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. (orig.)

  8. The current role of radiotherapy in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aleman, B.M.P.; Bartelink, H. [Nederlands Kanker Inst. `Antoni van Leeuwenhoekhuis`, Amsterdam (Netherlands); Gunderson, L.L. [Mayo Clinic, Rochester, MN (United States)


    During the last two decades, radiotherapy has become an integral part of the multidisciplinary approach in the treatment of patients with colorectal cancer. Currently, radiotherapy is seen mainly as an adjuvant therapy, sometimes in combination with chemotherapy, in a pre- or post-operative setting. Adjuvant radiotherapy alone leads to a significant reduction of local recurrence rates, but an impact on survival is seen only in subset analyses. Combined modality treatment can reduce local recurrence rates even further, and can also reduce the rate of distant relapses and increase survival. The acute toxicity of combined modality is considerably higher. Local radiation can also be used as a component of organ conserving local treatment for selected early lesions. Radiotherapy has been an important palliative treatment modality, diminishing symptoms in cases of inoperable primary rectal cancers or pelvic recurrences. The timing of radiation, surgery and chemotherapy has been under evaluation for years. For patients with locally advanced primary or recurrent malignancies (unresectable due to fixation), the preferred sequence is pre-operative irradiation with or without chemotherapy, followed by surgical resection. For mobile resectable lesions, sequencing issues are being tested in phase III randomised trials. (author).

  9. Immunotherapy and lung cancer: current developments and novel targeted therapies. (United States)

    Domingues, Duarte; Turner, Alice; Silva, Maria Dília; Marques, Dânia Sofia; Mellidez, Juan Carlos; Wannesson, Luciano; Mountzios, Giannis; de Mello, Ramon Andrade


    Non-small-cell lung cancer (NSCLC) is a highly prevalent and aggressive disease. In the metastatic setting, major advances include the incorporation of immunotherapy and targeted therapies into the clinician's therapeutic armamentarium. Standard chemotherapeutic regimens have long been reported to interfere with the immune response to the tumor; conversely, antitumor immunity may add to the effects of those therapies. The aim of immunotherapy is to specifically enhance the immune response directed to the tumor. Recently, many trials addressed the role of such therapies for metastatic NSCLC treatment: ipilimumab, tremelimumab, nivolumab and lambrolizumab are immunotherapeutic agents of main interest in this field. In addition, anti-tumor vaccines, such as MAGE-A3, Tecetomide, TG4010, CIMAvax, ganglioside vaccines, tumor cell vaccines and dendritic cell vaccines, emerged as potent inducers of immune response against the tumor. The current work aims to address the most recent developments regarding these innovative immunotherapies and their implementation in the treatment of metastatic NSCLC.

  10. Molecular subtypes and imaging phenotypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nariya [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)


    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  11. [Molecular-targeted therapy for hormone-refractory prostate cancer]. (United States)

    Nishimura, Kazuo; Takayama, Hitoshi; Nakayama, Masashi; Nonomura, Norio; Okuyama, Akihiko


    Molecular-targeted therapy is to treat pathologic pathways specifically in tumor cell or tumor microenvironment. Specific molecular-targeted therapeutic agents for hormone-refractory prostate cancer (HRPC) include endothelin-A receptor antagonist, EGF receptor (EGFR) inhibitor, platelet derived growth factor receptor (PDGFR) inhibitor, nuclear factor of kappaB (NF-kappaB) inhibitor, cyclooxygenase-2 (COX2) inhibitor, and active form of Vitamin D. These agents have been investigated in clinical trials. So far, none of the above-mentioned agent has shown a sufficient clinical efficacy alone. However, docetaxel-based combinations with thalidomide or calcitriol have promising clinical activities. Further investigations are needed to optimize the molecular-targeted agents in the combinations with chemotherapeutic agents for the treatment of HRPC.

  12. Current concepts in cancer: effects of cancer and cancer treatment on the nutrition of the host

    Energy Technology Data Exchange (ETDEWEB)

    Costa, G.; Donaldson, S.S.


    The growth of cancer in man leads to destruction of tissues and alterations of functions. The consequences of this process, culminating in overt cachexia and death, are so varied that cancer has replaced syphilis as the great imitator. Many of the manifestations of cachexia (weakness, anorexia, depletion and translocation of host component, and loss of immunocompetence) resemble malnutrition and are accountable for, in many patients, by poor nutritional intake, neoplastic invasion of the gastrointestinal tract or creation by the tumor of abnormal routes through which nutrients can be lost. The development of cachexia, nevertheless, bears no simple relation to caloric intake, tumor burden, tumor cell type or anatomic site of involvement. Indeed, it has long been apparent that, in many patients succumbing to cancer, if the same lesions were composed of scar tissue rather than neoplastic cells, the affected individuals might not only be alive but in reasonably good health. Distant metabolic effects of cancers have therefore come into focus, are well documented and are known collectively as paraneoplastic syndromes. They imply release by the tumor of chemically identifiable toxic mediators. Recently, a third mechanism has been recognized as an important determinant of cachexia and malnutrition: cancer treatment. As our tools have become more powerful and our philosophies more agressive,the effects of therapy on normal cell populations have become visible. The present paper discusses the most important manifestations of cachexia that resemble malnutrition. Technics of nutritional assessment and intervention that have proved successful in patients with cancer are also briefly discussed.

  13. Immunotherapy in prostate cancer: review of the current evidence. (United States)

    Fernández-García, E M; Vera-Badillo, F E; Perez-Valderrama, B; Matos-Pita, A S; Duran, I


    Prostate cancer is the most common male malignancy in the Western world. Once it metastasizes, it is incurable. The current gold standard for metastatic disease is the combined docetaxel/prednisone regimen. Prostate cancer shows several characteristics that make it a suitable candidate for immunotherapy, as recently exemplified by the approval of sipuleucel-T, the first vaccine to treat any malignancy. Here, we review different tumor-associated antigen immunotherapy strategies currently being investigated, from a humanized radiolabeled monoclonal antibody (J-591) that targets radiation into tumor cells, moving on to vaccines and through to immunomodulator agents such as anti-CPLA-4 and anti-PD-1 monoclonal antibodies that activate T-cell responses via immune checkpoint inhibition. We explore different opinions on the best approach to integrate immunotherapy into existing standard therapies, such as androgen-deprivation therapy, radiotherapy or chemotherapy, and review different combination sequences, patient types and time points during the course of the disease to achieve a lasting immune response. We present data from recent phase III clinical trials that call for a change in trial endpoint design with immunotherapy agents, from the traditional tumor progression to overall survival and how such trials should include immune response measurements as secondary or intermediate endpoints to help identify patient clinical benefit in the earlier phases of treatment. Finally, we join in the recent questioning on the validity of RECIST criteria to measure response to immunotherapeutic agents, as initial increases in the size of tumors/lymph nodes, which are part of a normal immune response, could be categorized as disease progression under RECIST.

  14. Single-band upconversion nanoprobes for multiplexed simultaneous in situ molecular mapping of cancer biomarkers (United States)

    Zhou, Lei; Wang, Rui; Yao, Chi; Li, Xiaomin; Wang, Chengli; Zhang, Xiaoyan; Xu, Congjian; Zeng, Aijun; Zhao, Dongyuan; Zhang, Fan


    The identification of potential diagnostic markers and target molecules among the plethora of tumour oncoproteins for cancer diagnosis requires facile technology that is capable of quantitatively analysing multiple biomarkers in tumour cells and tissues. Diagnostic and prognostic classifications of human tumours are currently based on the western blotting and single-colour immunohistochemical methods that are not suitable for multiplexed detection. Herein, we report a general and novel method to prepare single-band upconversion nanoparticles with different colours. The expression levels of three biomarkers in breast cancer cells were determined using single-band upconversion nanoparticles, western blotting and immunohistochemical technologies with excellent correlation. Significantly, the application of antibody-conjugated single-band upconversion nanoparticle molecular profiling technology can achieve the multiplexed simultaneous in situ biodetection of biomarkers in breast cancer cells and tissue specimens and produce more accurate results for the simultaneous quantification of proteins present at low levels compared with classical immunohistochemical technology.

  15. [Current status and perspectives of radiotherapy for esophageal cancer]. (United States)

    Wu, S X; Wang, L H


    Esophageal cancer is one of the most common cancers in China. More than 80% of esophageal cancer patients are diagnosed at a late stage and are not eligible for surgery. Radiotherapy is one of the most important modalities in esophageal cancer treatment. Here we reviewed the advances in esophageal cancer radiotherapy and radiotherapy-based combined-modality therapy, such as optimization of radiation dose and target volume, application of precise radiotherapy technique and the integration of radiotherapy with chemotherapy and targeted therapy.

  16. Epigenetic: a molecular link between testicular cancer and environmental exposures?

    Directory of Open Access Journals (Sweden)

    Aurelie eVega


    Full Text Available In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters (EDs exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the Testicular Dysgenesis Syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Futhermore, infertility has been stated as a risk factor for testicular cancer. The incidence of testicular cancer has been increasing over the past decades. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS from fetal germ cells (primordial germ cell or gonocyte. During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications plays an important role in normal development as well as in various diseases, including testicular cancer.Here we will review chromatin modifications which can affect testicular physiology leading to the development of testicular cancer; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

  17. Xenogeneic homologous genes, molecular evolution and cancer therapy

    Institute of Scientific and Technical Information of China (English)

    田聆; 魏于全


    Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.

  18. Molecular cytogenetic applications in analysis of the cancer genome. (United States)

    Rao, Pulivarthi H; Nandula, Subhadra V; Murty, Vundavalli V


    Cancer cells exhibit nonrandom and complex chromosome abnormalities. The role of genomic changes in cancer is well established. However, the identification of complex and cryptic chromosomal changes is beyond the resolution of conventional banding methods. The fluorescence microscopy afforded by imaging technologies, developed recently, facilitates a precise identification of these chromosome alterations in cancer. The three most commonly utilized molecular cytogenetics methods comparative genomic hybridization, spectral karyotype, and fluorescence in situ hybridization, that have already become benchmark tools in cancer cytogenetics, are described in this chapter. Comparative genomic hybridization is a powerful tool for screening copy-number changes in tumor genomes without the need for preparation of metaphases from tumor cells. Multicolor spectral karyotype permits visualization of all chromosomes in one experiment permitting identification of precise chromosomal changes on metaphases derived from tumor cells. The uses of fluorescence in situ hybridization are diverse, including mapping of alteration in single copy genes, chromosomal regions, or entire chromosomes. The opportunities to detect genetic alterations in cancer cells continue to evolve with the use of these methodologies both in diagnosis and research.

  19. Multi-study integration of brain cancer transcriptomes reveals organ-level molecular signatures.

    Directory of Open Access Journals (Sweden)

    Jaeyun Sung

    Full Text Available We utilized abundant transcriptomic data for the primary classes of brain cancers to study the feasibility of separating all of these diseases simultaneously based on molecular data alone. These signatures were based on a new method reported herein--Identification of Structured Signatures and Classifiers (ISSAC--that resulted in a brain cancer marker panel of 44 unique genes. Many of these genes have established relevance to the brain cancers examined herein, with others having known roles in cancer biology. Analyses on large-scale data from multiple sources must deal with significant challenges associated with heterogeneity between different published studies, for it was observed that the variation among individual studies often had a larger effect on the transcriptome than did phenotype differences, as is typical. For this reason, we restricted ourselves to studying only cases where we had at least two independent studies performed for each phenotype, and also reprocessed all the raw data from the studies using a unified pre-processing pipeline. We found that learning signatures across multiple datasets greatly enhanced reproducibility and accuracy in predictive performance on truly independent validation sets, even when keeping the size of the training set the same. This was most likely due to the meta-signature encompassing more of the heterogeneity across different sources and conditions, while amplifying signal from the repeated global characteristics of the phenotype. When molecular signatures of brain cancers were constructed from all currently available microarray data, 90% phenotype prediction accuracy, or the accuracy of identifying a particular brain cancer from the background of all phenotypes, was found. Looking forward, we discuss our approach in the context of the eventual development of organ-specific molecular signatures from peripheral fluids such as the blood.

  20. Identifying molecular targets of lifestyle modifications in colon cancer prevention

    Directory of Open Access Journals (Sweden)

    Molly Marie Derry


    Full Text Available One in four deaths in the United States is cancer-related, and colorectal cancer (CRC is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; ~20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological and behavioral processes that could positively influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

  1. Molecular analysis of precursor lesions in familial pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Tatjana Crnogorac-Jurcevic

    Full Text Available BACKGROUND: With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical. METHODS AND FINDINGS: We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses. CONCLUSIONS: Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive

  2. Translating clinical research of Molecular Biology into a personalized, multidisciplinary approach of colorectal cancer patients. (United States)

    Strambu, V; Garofil, D; Pop, F; Radu, P; Bratucu, M; Popa, F


    Although multimodal treatment has brought important benefit, there is still great heterogeneity regarding the indication and response to chemotherapy in Stage II and III, and individual variations related to both overall survival and toxicity of new therapies in metastatic disease or tumor relapse. Recent research in molecular biology led to the development of a large scale of genetic biomarkers, but their clinical use is not concordant with the high expectations. The Aim of this review is to identify and discuss the molecular markers with proven clinical applicability as prognostic and/or predictive factors in CRC and also to establish a feasible algorithm of molecular testing, as routine practice, in the personalized, multidisciplinary approach of colorectal cancer patients in our country. Despite the revolution that occurred in the field of molecular marker research, only Serum CEA, Immunohistochemical analysis of mismatch repair proteins and PCR testing for KRAS and BRAF mutations have confirmed their clinical utility in the management of colorectal cancer. Their implementation in the current practice should partially resolve some of the controversies related to this heterogenic pathology, in matters of prognosis in different TNM stages, stage II patient risk stratification, diagnosis of hereditary CRC and likelihood of benefit from anti EGFR therapy in metastatic disease. The proposed algorithms of molecular testing are very useful but still imperfect and require further validation and constant optimization.

  3. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics


    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping


    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment...

  4. Current molecular blood group technology:availability and practical applications

    Institute of Scientific and Technical Information of China (English)

    Willy A.Flegel


    @@ Almost all clinically important RBC antigens are defined at the molecular level.The expression of protein-and sugar-based antigens on the RBC surface can be predicted by determining the blood group gene variants(alleles).Most of the time,a single nucleotide polymorphism(sNP)distinguishes the allele,which determines an antigen and hence allows predicting the antigen.PCR with sequence specific priming(PCR-SSP)followed by gel electrophoresis was the original technique widely applied for blood group genotyping.Realtime PCR obviated the need for gels.

  5. Women at high risk of breast cancer: Molecular characteristics, clinical presentation and management. (United States)

    Kleibl, Zdenek; Kristensen, Vessela N


    The presence of breast cancer in any first-degree female relative in general nearly doubles the risk for a proband and the risk gradually increases with the number of affected relatives. Current advances in molecular oncology and oncogenetics may enable the identification of high-risk individuals with breast-cancer predisposition. The best-known forms of hereditary breast cancer (HBC) are caused by mutations in the high-penetrance genes BRCA1 and BRCA2. Other genes, including PTEN, TP53, STK11/LKB1, CDH1, PALB2, CHEK2, ATM, MRE11, RAD50, NBS1, BRIP1, FANCA, FANCC, FANCM, RAD51, RAD51B, RAD51C, RAD51D, and XRCC2 have been described as high- or moderate-penetrance breast cancer-susceptibility genes. The majority of breast cancer-susceptibility genes code for tumor suppressor proteins that are involved in critical processes of DNA repair pathways. This is of particular importance for those women who, due to their increased risk of breast cancer, may be subjected to more frequent screening but due to their repair deficiency might be at the risk of developing radiation-induced malignancies. It has been proven that cancers arising from the most frequent BRCA1 gene mutation carriers differ significantly from the sporadic disease of age-matched controls in their histopathological appearances and molecular characteristics. The increased depth of mutation detection brought by next-generation sequencing and a better understanding of the mechanisms through which these mutations cause the disease will bring novel insights in terms of oncological prevention, diagnostics, and therapeutic options for HBC patients.

  6. Current trends in molecular diagnostics of chronic myeloid leukemia. (United States)

    Vinhas, Raquel; Cordeiro, Milton; Pedrosa, Pedro; Fernandes, Alexandra R; Baptista, Pedro V


    Nearly 1.5 million people worldwide suffer from chronic myeloid leukemia (CML), characterized by the genetic translocation t(9;22)(q34;q11.2), involving the fusion of the Abelson oncogene (ABL1) with the breakpoint cluster region (BCR) gene. Early onset diagnosis coupled to current therapeutics allow for a treatment success rate of 90, which has focused research on the development of novel diagnostics approaches. In this review, we present a critical perspective on current strategies for CML diagnostics, comparing to gold standard methodologies and with an eye on the future trends on nanotheranostics.

  7. Optical contrast agents to visualize molecular expression in breast cancer (United States)

    Langsner, Robert James

    Breast cancer is the second leading cause of death of women in the United States. Improvements in screening technology have increased the breast cancer incidence rate, as smaller lesions are being detected. Due to the small size of lesions, patients can choose to receive breast conservation therapy (BCT) rather than a modified radical mastectomy. Even though the breast retains cosmesis after BCT, there is an increased risk of the patient having residual microscopic disease, known as positive margins. Patients with positive margins receive increased radiation and have an increased chance of second surgery. Pathology with hematoxylin and eosin (H&E) remains the gold standard for diagnosing margin status in patients. Intraoperative pathology has been shown to reduce the rate of positive margins in BCT. However, a minority of surgery centers have intraoperative pathology centers, limiting the number of patients that receive this standard of care. The expression profiles of surface receptors such as ErbB2 (HER2-positive) and epidermal growth factor receptor (EGFR) provide information about the aggressiveness of a particular tumor. Recent research has shown that there was elevated EGFR expression in patients with a local recurrence even though the biopsies were assessed to be disease free using standard H&E. If the physicians had known the molecular expression of these biopsies, a different treatment regimen or excision of more tissue might have prevented the recurrence. This thesis investigates targeted molecular contrast agents that enhance the visualization of molecular markers such as glucose transporters (GLUTs) and growth factor receptors in tissue specimens. First, application of 2-NBDG, a fluorescent deoxyglucose, enhances signal in cancerous tissue with a 20-minute incubation. Then, antibody functionalized silica-gold nanoshells enhance the visualization of ErbB2 overexpression in specimens with a 5-minute incubation. To image these contrast agents in cancerous

  8. Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early (United States)


    10-1-0422 TITLE: Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early PRINCIPAL...DATES COVERED 1 July 2010 - 30 June 2013 4. TITLE AND SUBTITLE Targeting Cell Surface Proteins in Molecular 5a. CONTRACT NUMBER Photoacoustic ...upon request). Aim 2) Prioritize ovarian cancer-associated surface proteins for their utility as molecular photoacoustic imaging targets and

  9. Guidance for laboratories performing molecular pathology for cancer patients. (United States)

    Cree, Ian A; Deans, Zandra; Ligtenberg, Marjolijn J L; Normanno, Nicola; Edsjö, Anders; Rouleau, Etienne; Solé, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J Han


    Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here.

  10. Current medical treatment of estrogen receptor-positive breast cancer

    Institute of Scientific and Technical Information of China (English)

    Franco; Lumachi; Davide; A; Santeufemia; Stefano; MM; Basso


    Approximately 80% of breast cancers(BC) are estrogen receptor(ER)-positive and thus endocrine therapy(ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of(1) ovarian function suppression(OFS), usually obtained using gonadotropinreleasing hormone agonists(Gn RHa);(2) selective estrogen receptor modulators or down-regulators(SERMs or SERDs); and(3) aromatase inhibitors(AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs(i.e., tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ, especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs(i.e., fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type Ⅰ are permanent steroidal inhibitors of aromatase, while type Ⅱ are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs(i.e., anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors(palbociclib) and mammalian target of rapamycin(m TOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness.

  11. Current treatment options for colon cancer peritoneal carcinomatosis


    Aoyagi, Tomoyoshi; Terracina, Krista P; Raza, Ali; Takabe, Kazuaki


    Peritoneal carcinomatosis (PC), the dissemination of cancer cells throughout the lining of the abdominal cavity, is the second most common presentation of colon cancer distant metastasis. Despite remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years, it has been repeatedly shown that these therapies remain ineffective for colon cancer PC. Recently, there has been a rapid accumulation of reports that cytoreductive surgery combined with hyper...

  12. The molecular genetics of the corneal dystrophies--current status. (United States)

    Klintworth, Gordon K


    The pertinent literature on inherited corneal diseases is reviewed in terms of the chromosomal localization and identification of the responsible genes. Disorders affecting the cornea have been mapped to human chromosome 1 (central crystalline corneal dystrophy, familial subepithelial corneal amyloidosis, early onset Fuchs dystrophy, posterior polymorphous corneal dystrophy), chromosome 4 (Bietti marginal crystalline dystrophy), chromosome 5 (lattice dystrophy types 1 and IIIA, granular corneal dystrophy types 1, 2 and 3, Thiel-Behnke corneal dystrophy), chromosome 9 (lattice dystrophy type II), chromosome 10 (Thiel-Behnke corneal dystrophy), chromosome 12 (Meesmann dystrophy), chromosome 16 (macular corneal dystrophy, fish eye disease, LCAT disease, tyrosinemia type II), chromosome 17 (Meesmann dystrophy, Stocker-Holt dystrophy), chromosome 20 (congenital hereditary endothelial corneal dystrophy types I and II, posterior polymorphous corneal dystrophy), chromosome 21 (autosomal dominant keratoconus) and the X chromosome (cornea verticillata, cornea farinata, deep filiform corneal dystrophy, keratosis follicularis spinulosa decalvans, Lisch corneal dystrophy). Mutations in nine genes (ARSC1, CHST6, COL8A2, GLA, GSN, KRT3, KRT12, M1S1and TGFBI [BIGH3]) account for some of the corneal diseases and three of them are associated with amyloid deposition in the cornea (GSN, M1S1, TGFBI) including most of the lattice corneal dystrophies (LCDs) [LCD types I, IA, II, IIIA, IIIB, IV, V, VI and VII] recognized by their lattice pattern of linear opacities. Genetic studies on inherited diseases affecting the cornea have provided insight into some of these disorders at a basic molecular level and it has become recognized that distinct clinicopathologic phenotypes can result from specific mutations in a particular gene, as well as some different mutations in the same gene. A molecular genetic understanding of inherited corneal diseases is leading to a better appreciation of the

  13. Challenges and opportunities in international molecular cancer prevention research: An ASPO Molecular Epidemiology and the Environment and International Cancer Prevention Interest Groups Report. (United States)

    Epplein, Meira; Bostick, Roberd M; Mu, Lina; Ogino, Shuji; Braithwaite, Dejana; Kanetsky, Peter A


    The International Agency for Research on Cancer estimates that over half of the new cancer cases and almost two-thirds of the cancer deaths in 2012 occurred in low and middle income countries. To discuss the challenges and opportunities to reducing the burden of cancer worldwide, the Molecular Epidemiology and the Environment and the International Issues in Cancer Special Interest Groups joined forces to hold a session during the 38th Annual Meeting of the American Society of Preventive Oncology (March 2014, Arlington, Virginia). The session highlighted three topics of particular interest to molecular cancer prevention researchers working internationally, specifically: 1) biomarkers in cancer research; 2) environmental exposures and cancer; and 3) molecular pathological epidemiology. A major factor for successful collaboration illuminated during the discussion was the need for strong, committed, and reliable international partners. A key element of establishing such relationships is to thoroughly involve individual international collaborators in the development of the research question; engaged international collaborators are particularly motivated to champion and shepherd the project through all necessary steps, including issues relating to institutional review boards, political sensitivity, laboratory-based assays, and tumor subtyping. Also essential is allotting time for the building, maintaining, and investing in such relationships so that successful international collaborations may take root and bloom. While there are many challenges inherent to international molecular cancer research, the opportunities for furthering the science and prevention of cancer worldwide are great, particularly at this time of increasing cancer incidence and prevalence in low and middle income countries.

  14. Targeting PD-1/PD-L1 in lung cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    González-Cao M


    Full Text Available María González-Cao,1 Niki Karachaliou,1 Santiago Viteri,1 Daniela Morales-Espinosa,1 Cristina Teixidó,2 Jesús Sánchez Ruiz,3 Miquel Ángel Molina-Vila,2 Mariacarmela Santarpia,4 Rafael Rosell1,2,5,61Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona, Spain; 2Pangaea Biotech SL, Barcelona, Spain; 3Centro Nacional de Investigación Oncología (CNIO, Madrid, Spain; 4Medical Oncology Unit, Human Pathology Department, University of Messina, Messina, Italy; 5Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Badalona, Barcelona, Spain; 6Fundación Molecular Oncology Research, Barcelona, SpainAbstract: Increased understanding of tumor immunology has led to the development of effective immunotherapy treatments. One of the most important advances in this field has been due to pharmacological design of antibodies against immune checkpoint inhibitors. Anti-PD-1/PD-L1 antibodies are currently in advanced phases of clinical development for several tumors, including lung cancer. Results from Phase I–III trials with anti-PD-1/PD-L1 antibodies in non-small-cell lung cancer have demonstrated response rates of around 20% (range, 16%–50%. More importantly, responses are long-lasting (median duration of response, 18 months and fast (50% of responses are detected at time of first tumor evaluation with very low grade 3–4 toxicity (less than 5%. Recently, the anti-PD-1 antibody pembrolizumab received US Food and Drug Administration (FDA breakthrough therapy designation for treatment of non-small-cell lung cancer, supported by data from a Phase Ib trial. Another anti-PD-1 antibody, nivolumab, has also been approved for lung cancer based on survival advantage demonstrated in recently released data from a Phase III trial in squamous cell lung cancer.Keywords: immunotherapy, immunoncology

  15. Molecular Characterization of ERα-positive and Triple Negative Breast Cancer

    NARCIS (Netherlands)

    Severson, T.M.


    Breast cancer, one of the most common of all cancers, is diagnosed in over 1.5 million people world-wide each year. Overall, treatments for breast cancer are considered relatively successful, however recurrence is a clinical problem of paramount importance. Molecular subtypes of breast cancer, defin

  16. Molecular Link between Vitamin D and Cancer Prevention

    Directory of Open Access Journals (Sweden)

    William B. Grant


    Full Text Available The metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (also known as calcitriol, is a biologically active molecule required to maintain the physiological functions of several target tissues in the human body from conception to adulthood. Its molecular mode of action ranges from immediate nongenomic responses to longer term mechanisms that exert persistent genomic effects. The genomic mechanisms of vitamin D action rely on cross talk between 1α,25-dihydroxyvitamin D3 signaling pathways and that of other growth factors or hormones that collectively regulate cell proliferation, differentiation and cell survival. In vitro and in vivo studies demonstrate a role for vitamin D (calcitriol in modulating cellular growth and development. Vitamin D (calcitriol acts as an antiproliferative agent in many tissues and significantly slows malignant cellular growth. Moreover, epidemiological studies have suggested that ultraviolet-B exposure can help reduce cancer risk and prevalence, indicating a potential role for vitamin D as a feasible agent to prevent cancer incidence and recurrence. With the preventive potential of this biologically active agent, we suggest that countries where cancer is on the rise—yet where sunlight and, hence, vitamin D may be easily acquired—adopt awareness, education and implementation strategies to increase supplementation with vitamin D in all age groups as a preventive measure to reduce cancer risk and prevalence.

  17. Mangiferin in cancer chemoprevention and treatment: pharmacokinetics and molecular targets. (United States)

    Rajendran, Peramaiyan; Rengarajan, Thamaraiselvan; Nandakumar, Natarajan; Divya, H; Nishigaki, Ikuo


    A variety of bioactive food components have been shown to modulate inflammatory responses and to attenuate carcinogenesis. Polyphenols isolated several years ago from various medicinal plants now seem to have a prominent role in the prevention and therapy of a variety of ailments. Mangiferin, a unique, important, and highly investigated polyphenol, has attracted much attention of late for its potential as a chemopreventive and chemotherapeutic agent against various types of cancer. Mangiferin has been shown to target multiple proinflammatory transcription factors, cell- cycle proteins, growth factors, kinases, cytokines, chemokines, adhesion molecules, and inflammatory enzymes. These targets can potentially mediate the chemopreventive and therapeutic effects of mangiferin by inhibiting the initiation, promotion, and metastasis of cancer. This review not only summarizes the diverse molecular targets of mangiferin, but also gives the results of various preclinical studies that have been performed in the last decade with this promising polyphenol.

  18. Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities (United States)

    Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

  19. Lobular breast cancer: Clinical, molecular and morphological characteristics. (United States)

    Christgen, Matthias; Steinemann, Doris; Kühnle, Elna; Länger, Florian; Gluz, Oleg; Harbeck, Nadia; Kreipe, Hans


    Infiltrating lobular breast cancer (ILBC) is the most common special breast cancer subtype. This review provides a comprehensive description of ILBC characteristics, including epidemiology, clinical features, molecular genetics and histomorphology. Twenty detailed supplemental data tables guide through primary data of more than 200 original studies. Meta-analyses indicate that ILBC is at least twice as common in the Western world as it is in other geographic regions. ILBC is over-represented in so-called interval carcinomas and in primary metastatic breast cancer. ILBC is also associated higher age, higher pT stage and hormone receptor (ER/PR) positivity. Pathological complete response rates after neoadjuvant chemotherapy are low, ranging between 0% and 11%. Positive resection margins after breast-conserving surgery are comparatively frequent and 17% to 65% of patients undergo a second surgical intervention. Depending on the morphological stringency in the diagnosis of ILBC, lack of E-cadherin expression is observed in 55% to 100% of cases. CDH1/E-cadherin mutation detection rates vary between 12% and 83%. Various additional molecular factors, including PIK3CA, TP53, FOXA1, FGFR1, ZNF703 and BCAR4, have been implicated in ILBC or progression of lobular carcinoma in situ (LCIS) to invasive cancer and are discussed in detail. Eight instructive figure plates recapitulate the histomorphology of ILBC and its variants. Furthermore, we draw attention to rarely addressed histological details, such as two-sided nuclear compression and fat-avoiding growth at the invasion front. Last but not least, we discuss future translational research directions and emphasize the concept of synthetic lethality, which promises new options for targeted ILBC therapy.

  20. Use of multivariate analysis to suggest a new molecular classification of colorectal cancer (United States)

    Domingo, Enric; Ramamoorthy, Rajarajan; Oukrif, Dahmane; Rosmarin, Daniel; Presz, Michal; Wang, Haitao; Pulker, Hannah; Lockstone, Helen; Hveem, Tarjei; Cranston, Treena; Danielsen, Havard; Novelli, Marco; Davidson, Brian; Xu, Zheng-Zhou; Molloy, Peter; Johnstone, Elaine; Holmes, Christopher; Midgley, Rachel; Kerr, David; Sieber, Oliver; Tomlinson, Ian


    Abstract Molecular classification of colorectal cancer (CRC) is currently based on microsatellite instability (MSI), KRAS or BRAF mutation and, occasionally, chromosomal instability (CIN). Whilst useful, these categories may not fully represent the underlying molecular subgroups. We screened 906 stage II/III CRCs from the VICTOR clinical trial for somatic mutations. Multivariate analyses (logistic regression, clustering, Bayesian networks) identified the primary molecular associations. Positive associations occurred between: CIN and TP53 mutation; MSI and BRAF mutation; and KRAS and PIK3CA mutations. Negative associations occurred between: MSI and CIN; MSI and NRAS mutation; and KRAS mutation, and each of NRAS, TP53 and BRAF mutations. Some complex relationships were elucidated: KRAS and TP53 mutations had both a direct negative association and a weaker, confounding, positive association via TP53–CIN–MSI–BRAF–KRAS. Our results suggested a new molecular classification of CRCs: (1) MSI+ and/or BRAF-mutant; (2) CIN+ and/or TP53– mutant, with wild-type KRAS and PIK3CA; (3) KRAS- and/or PIK3CA-mutant, CIN+, TP53-wild-type; (4) KRAS– and/or PIK3CA-mutant, CIN–, TP53-wild-type; (5) NRAS-mutant; (6) no mutations; (7) others. As expected, group 1 cancers were mostly proximal and poorly differentiated, usually occurring in women. Unexpectedly, two different types of CIN+ CRC were found: group 2 cancers were usually distal and occurred in men, whereas group 3 showed neither of these associations but were of higher stage. CIN+ cancers have conventionally been associated with all three of these variables, because they have been tested en masse. Our classification also showed potentially improved prognostic capabilities, with group 3, and possibly group 1, independently predicting disease-free survival. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:23165447

  1. Current advances in T-cell-based cancer immunotherapy. (United States)

    Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu


    Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

  2. Clinical and Molecular Characteristics of Post-Colonoscopy Colorectal Cancer

    DEFF Research Database (Denmark)

    Stoffel, Elena M; Erichsen, Rune; Frøslev, Trine;


    BACKGROUND AND AIMS: Colonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy....... METHODS: We performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (d...

  3. Current state of prostate cancer treatment in Jamaica. (United States)

    Morrison, Belinda F; Aiken, William D; Mayhew, Richard


    Prostate cancer is the commonest cancer in Jamaica as well as the leading cause of cancer-related deaths. One report suggested that Jamaica has the highest incidence rate of prostate cancer in the world, with an age-standardised rate of 304/100,000 per year. The Caribbean region is reported to have the highest mortality rate of prostate cancer worldwide. Prostate cancer accounts for a large portion of the clinical practice for health-care practitioners in Jamaica. The Jamaica Urological Society is a professional body comprising 19 urologists in Jamaica who provide most of the care for men with prostate cancer in collaboration with medical oncologists, radiation oncologists, and a palliative care physician. The health-care system is structured in two tiers in Jamaica: public and private. The urologist-to-patient ratio is high, and this limits adequate urological care. Screening for prostate cancer is not a national policy in Jamaica. However, the Jamaica Urological Society and the Jamaica Cancer Society work synergistically to promote screening as well as to provide patient education for prostate cancer. Adequate treatment for localised prostate cancer is available in Jamaica in the forms of active surveillance, nerve-sparing radical retropubic prostatectomy, external beam radiation, and brachytherapy. However, there is a geographic maldistribution of centres that provide prostate cancer treatment, which leads to treatment delays. Also, there is difficulty in affording some treatment options in the private health-care sectors. Androgen deprivation therapy is available for treatment of locally advanced and metastatic prostate cancer and is subsidised through a programme called the National Health Fund. Second-line hormonal agents and chemotherapeutic agents are available but are costly to most of the population. The infrastructure for treatment of prostate cancer in Jamaica is good, but it requires additional technological advances as well as additional specialist

  4. Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer


    Antonelli,Giovanna; Libra, Massimo; PANEBIANCO, VINCENZO; Russo,Alessia Erika; Vitale, Felice Vito; COLINA, PAOLO; D'Angelo,Alessandro; ROSSELLO, ROSALBA; Ferraù, Francesco


    Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared wit...

  5. Molecular profiling in the treatment of colorectal cancer: focus on regorafenib

    Directory of Open Access Journals (Sweden)

    Yan Y


    Full Text Available Yiyi Yan, Axel Grothey Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA Abstract: Metastatic colorectal cancer (mCRC is a highly heterogeneous disease. Its treatment outcome has been significantly improved over the last decade with the incorporation of biological targeted therapies, including anti-EGFR antibodies, cetuximab and panitumumab, and VEGF inhibitors, bevacizumab, ramucirumab, and aflibercept. The identification of predictive biomarkers has further improved the survival by accurately selecting patients who are most likely to benefit from these treatments, such as RAS mutation profiling for EGFR antibodies. Regorafenib is a multikinase inhibitor currently used as late line therapy for mCRC. The molecular and genetic markers associated with regorafenib treatment response are yet to be characterized. Here, we review currently available clinical evidence of mCRC molecular profiling, such as RAS, BRAF, and MMR testing, and its role in targeted therapies with special focus on regorafenib treatment. Keywords: metastatic colon cancer, targeted therapy, molecular profiling, regorafenib 

  6. Molecular complexity of primary open angle glaucoma: current concepts

    Indian Academy of Sciences (India)

    Kunal Ray; Suddhasil Mookherjee


    Glaucoma is a group of heterogeneous optic neuropathies with complex genetic basis. Among the three principle subtypes of glaucoma, primary open angle glaucoma (POAG) occurs most frequently. Till date, 25 loci have been found to be linked to POAG. However, only three underlying genes (Myocilin, Optineurin and WDR36) have been identified. In addition, at least 30 other genes have been reported to be associated with POAG. Despite strong genetic influence in POAG pathogenesis, only a small part of the disease can be explained in terms of genetic aberration. Current concepts of glaucoma pathogenesis suggest it to be a neurodegenerative disorder which is triggered by different factors including mechanical stress due to intra-ocular pressure, reduced blood flow to retina, reperfusion injury, oxidative stress, glutamate excitotoxicity, and aberrant immune response. Here we present a mechanistic overview of potential pathways and crosstalk between them operating in POAG pathogenesis.

  7. Influence of Random Potentials on the Current of the Molecular Motor Model

    Institute of Scientific and Technical Information of China (English)

    贾亚; 李家荣


    The current of the molecular motor model disturbed by random potentials, which involve the dichotomous and Ornstein-Uhlenbeck potentials, is studied using a finite-space correlation function. It is found that: (i) the amplitude and the correlation length of random potentials play opposing roles in the transport of the molecular motor model; (ii) a random potential with small amplitude and large correlation length is very useful in the molecular motor system.

  8. Current Status of Cryotherapy for Prostate and Kidney Cancer (United States)

    Cho, Seok


    In terms of treating diseases, minimally invasive treatment has become a key element in reducing perioperative complications. Among the various minimally invasive treatments, cryotherapy is often used in urology to treat various types of cancers, especially prostate cancer and renal cancer. In prostate cancer, the increased incidence of low-risk, localized prostate cancer has made minimally invasive treatment modalities an attractive option. Focal cryotherapy for localized unilateral disease offers the added benefit of minimal morbidities. In renal cancer, owing to the increasing utilization of cross-sectional imaging, nearly 70% of newly detected renal masses are stage T1a, making them more susceptible to minimally invasive nephron-sparing therapies including laparoscopic and robotic partial nephrectomy and ablative therapies. This article reviews the various outcomes of cryotherapy compared with other treatments and the possible uses of cryotherapy in surgery. PMID:25512811

  9. Molecular Mechanisms and Translational Therapies for Human Epidermal Receptor 2 Positive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Quanxia Lv


    Full Text Available Breast cancer is the second leading cause of cancer death among women. Human epidermal receptor 2 (HER2 positive breast cancer (HER2+ BC is the most aggressive subtype of breast cancer, with poor prognosis and a high rate of recurrence. About one third of breast cancer is HER2+ BC with significantly high expression level of HER2 protein compared to other subtypes. Therefore, HER2 is an important biomarker and an ideal target for developing therapeutic strategies for the treatment HER2+ BC. In this review, HER2 structure and physiological and pathological roles in HER2+ BC are discussed. Two diagnostic tests, immunohistochemistry (IHC and fluorescent in situ hybridization (FISH, for evaluating HER2 expression levels are briefly introduced. The current mainstay targeted therapies for HER2+ BC include monoclonal antibodies, small molecule tyrosine kinase inhibitors, antibody–drug conjugates (ADC and other emerging anti-HER2 agents. In clinical practice, combination therapies are commonly adopted in order to achieve synergistic drug response. This review will help to better understand the molecular mechanism of HER2+ BC and further facilitate the development of more effective therapeutic strategies against HER2+ BC.

  10. BRCA-Associated Ovarian Cancer: From Molecular Genetics to Risk Management

    Directory of Open Access Journals (Sweden)

    Giulia Girolimetti


    Full Text Available Ovarian cancer (OC mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposition, on pathology and clinical behavior of OC occurring in BRCA mutation carriers, and on the available options for managing asymptomatic carriers.

  11. BRCA-associated ovarian cancer: from molecular genetics to risk management. (United States)

    Girolimetti, Giulia; Perrone, Anna Myriam; Santini, Donatella; Barbieri, Elena; Guerra, Flora; Ferrari, Simona; Zamagni, Claudio; De Iaco, Pierandrea; Gasparre, Giuseppe; Turchetti, Daniela


    Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposition, on pathology and clinical behavior of OC occurring in BRCA mutation carriers, and on the available options for managing asymptomatic carriers.

  12. Molecular basis of the potential of mesalazine to prevent colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Carmine Stolfi; Roberto Pellegrini; Eleonora Franzè; Francesco Pallone; Giovanni Monteleone


    Patients with ulcerative colitis (UC) and Crohn's disease (CD) are at increased risk for developing colorectal cancer (CRC), and this is believed to be a result of chronic inflammation. Although conclusive evidence is still missing, both epidemiological and experimental observations suggest that certain drugs used to treat inflammation, such as mesalazine,can reduce the incidence of colitis-associated CRC.Therefore, in recent years, several studies have been conducted to dissect the mechanisms by which mesalazine interferes with CRC cell growth and survival. This review summarizes the current information on the molecular mechanisms that underlie the antineoplastic action of mesalazine.

  13. Current perspectives and emerging issues on cancer rehabilitation. (United States)

    Stubblefield, Michael D; Hubbard, Gill; Cheville, Andrea; Koch, Uwe; Schmitz, Kathryn H; Dalton, Susanne Oksbjerg


    Cancer rehabilitation is a rapidly emerging and evolving medical field in both Europe and the United States, in large part because of increases in the number of cancer survivors. Although few argue with the need to restore function and quality of life to patients affected by cancer and its treatments, differences exist between European countries with regard to the funding, accessibility, and even the definition of cancer rehabilitation services. In the United States, there is tremendous variability in the provision of rehabilitation services resulting from a variety of factors, including a lack of highly trained cancer rehabilitation physicians and therapists as well as a lack of comprehensive cancer rehabilitation programs, even at the majority of top cancer centers. Although studies evaluating the effectiveness of rehabilitation programs in the cancer setting, particularly exercise, have influenced clinical decision-making in both Europe and the United States for some time, this emerging evidence base also is now starting to influence guideline and policy making. Coordinated research efforts are essential to establish a robust framework to support future investigation and establish shared initiatives. Determining the best way forward for cancer survivors will require investment in large-scale prospective cohort studies that sufficiently describe their rehabilitation needs through the continuum of the survivorship experience.

  14. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer. (United States)

    Ciriello, Giovanni; Gatza, Michael L; Beck, Andrew H; Wilkerson, Matthew D; Rhie, Suhn K; Pastore, Alessandro; Zhang, Hailei; McLellan, Michael; Yau, Christina; Kandoth, Cyriac; Bowlby, Reanne; Shen, Hui; Hayat, Sikander; Fieldhouse, Robert; Lester, Susan C; Tse, Gary M K; Factor, Rachel E; Collins, Laura C; Allison, Kimberly H; Chen, Yunn-Yi; Jensen, Kristin; Johnson, Nicole B; Oesterreich, Steffi; Mills, Gordon B; Cherniack, Andrew D; Robertson, Gordon; Benz, Christopher; Sander, Chris; Laird, Peter W; Hoadley, Katherine A; King, Tari A; Perou, Charles M


    Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

  15. Anti-cancer chalcones: Structural and molecular target perspectives. (United States)

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar; Asati, Vivek


    Chalcone or (E)-1,3-diphenyl-2-propene-1-one scaffold remained a fascination among researchers in the 21st century due to its simple chemistry, ease of synthesis and a wide variety of promising biological activities. Several natural and (semi) synthetic chalcones have shown anti-cancer activity due to their inhibitory potential against various targets namely ABCG2/P-gp/BCRP, 5α-reductase, aromatase, 17-β-hydroxysteroid dehydrogenase, HDAC/Situin-1, proteasome, VEGF, VEGFR-2 kinase, MMP-2/9, JAK/STAT signaling pathways, CDC25B, tubulin, cathepsin-K, topoisomerase-II, Wnt, NF-κB, B-Raf and mTOR etc. In this review, a comprehensive study on molecular targets/pathways involved in carcinogenesis, mechanism of actions (MOAs), structure activity relationships (SARs) and patents granted have been highlighted. With the knowledge of molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective anti-cancer chalcones.

  16. Molecular profiling of multiple human cancers defines an inflammatory cancer-associated molecular pattern and uncovers KPNA2 as a uniform poor prognostic cancer marker.

    Directory of Open Access Journals (Sweden)

    Saleh M Rachidi

    Full Text Available BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An "Inflammatory Gene Integrated Score" was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2 is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only

  17. Molecular targeted treatment and radiation therapy for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Marquardt, Friederike; Roedel, Franz; Capalbo, Gianni; Weiss, Christian; Roedel, Claus [Dept. of Radiation Therapy, Univ. of Frankfurt/Main (Germany)


    Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have been noted in several phase II studies. The K-ras mutation status and the gene copy number of EGFR may predict tumor response. The toxicity pattern (radiation-induced enteritis, perforations) and surgical complications (wound healing, fistula, bleeding) observed in at least some of the clinical studies with bevacizumab and CRT warrant further investigations. Conclusion: longer follow-up (and, finally, randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates, and toxicity associated with these novel treatment approaches. (orig.)

  18. Influence of low molecular weight heparin on cancer patients’ survival

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin


    Full Text Available There is an evidence of interaction between the hemostasis system and tumor progression factors. It is known that in addition to the fibrin formation and platelets activation, thrombin can influence many cells function interacting with protease-activating receptors including tumor cells. These receptors are involved in the malignant cell phenotype formation (adhesion, proliferation, proteolysis. Thrombin can also affect angiogenesis by stimulating endothelial cells penetration through basal membrane and its migration with new vessels formation. Furthermore, it can cause the release of main neoangiogenesis promoter – vascular endothelial growth factor. All of the above and many other linkages of coagulation and tumor create a theoretical background of possible affecting tumor by regulation of the coagulation activity. Thepromise of this approach is controversial, but there is some clinical and experimental evidence of their effectiveness. The most used group ofdrugs for this purpose was heparins. Several retrospective studies have shown a benefit of low molecular weight heparins (LMWH over unfractionated heparin in cancer patient survival. The appearance of a new heparins group – ultra LMWH are of interest from this point ofview and their possible use in cancer patients. To date bemiparin and semuloparin are used in clinic. Both (bemiparin about 3600 kDa,semuloparin 3000 kDa have substancially reduced molecular weight as compared with the smallest of LMWH – enoxaparin (4600 kDa.Use of bemiparin in patients with small cell lung cancer receiving chemotherapy resulted in increased of 2-year survival rate compared to the control group (68.6 % vs. 29.4 %, p = 0.0042.

  19. Nuclear EGFR as a molecular target in cancer. (United States)

    Brand, Toni M; Iida, Mari; Luthar, Neha; Starr, Megan M; Huppert, Evan J; Wheeler, Deric L


    The epidermal growth factor receptor (EGFR) has been one of the most targeted receptors in the field of oncology. While anti-EGFR inhibitors have demonstrated clinical success in specific cancers, most patients demonstrate either intrinsic or acquired resistance within one year of treatment. Many mechanisms of resistance to EGFR inhibitors have been identified, one of these being attributed to alternatively localized EGFR from the cell membrane into the cell's nucleus. Inside the nucleus, EGFR functions as a co-transcription factor for several genes involved in cell proliferation and angiogenesis, and as a tyrosine kinase to activate and stabilize proliferating cell nuclear antigen and DNA dependent protein kinase. Nuclear localized EGFR is highly associated with disease progression, worse overall survival in numerous cancers, and enhanced resistance to radiation, chemotherapy, and the anti-EGFR therapies gefitinib and cetuximab. In this review the current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to target nuclear EGFR as an anti-cancer strategy in the future.

  20. Nano Delivers Big: Designing Molecular Missiles for Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    J. Silvio Gutkind


    Full Text Available Current first-line treatments for most cancers feature a short-list of highly potent and often target-blind interventions, including chemotherapy, radiation, and surgical excision. These treatments wreak considerable havoc upon non-cancerous tissue and organs, resulting in deleterious and sometimes fatal side effects for the patient. In response, this past decade has witnessed the robust emergence of nanoparticles and, more relevantly, nanoparticle drug delivery systems (DDS, widely touted as the panacea of cancer therapeutics. While not a cure, nanoparticle DDS can successfully negotiate the clinical payoff between drug dosage and side effects by encompassing target-specific drug delivery strategies. The expanding library of nanoparticles includes lipoproteins, liposomes, dendrimers, polymers, metal and metal oxide nano-spheres and -rods, and carbon nanotubes, so do the modes of delivery. Importantly, however, the pharmaco-dynamics and –kinetics of these nano-complexes remain an urgent issue and a serious bottleneck in the transition from bench to bedside. This review addresses the rise of nanoparticle DDS platforms for cancer and explores concepts of gene/drug delivery and cytotoxicity in pre-clinical and clinical contexts.

  1. Research on cancer diagnosis in Malaysia: current status. (United States)

    Looi, L M; Zubaidah, Z; Cheah, P L; Cheong, S K; Gudum, H R; Iekhsan, O; Ikram, S I; Jamal, R; Mak, J W; Othman, N H; Puteri, J N; Rosline, H; Sabariah, A R; Seow, H F; Sharifah, N A


    Cancer is a major morbidity and mortality concern in Malaysia. Based on National Cancer Registry data, the Malaysian population is estimated to bear a cancer burden of about 40,000 new cases per year, and a cumulative lifetime risk of about 1:4. Cancer research in Malaysia has to consider needs relevant to our population, and resources constraints. Hence, funding bodies prioritise cancers of high prevalence, unique to our community and posing specific clinical problems. Cancer diagnosis is crucial to cancer management. While cancer diagnosis research largely aims at improvements in diagnostic information towards more appropriate therapy, it also impacts upon policy development and other areas of cancer management. The scope of cancer diagnosis upon which this paper is based, and their possible impact on other R&D areas, has been broadly categorized into: (1) identification of aetiological agents and their linkages to the development of precancer and cancer (impact on policy development, cancer prevention and treatment), (2) cancer biology and pathogenesis (impact on cancer prevention, treatment strategies and product development), (3) improvements in accuracy, sensitivity and specificity in cancer detection, monitoring and classification (impact on technology development) and (4) prognostic and predictive parameters (impact on treatment strategies). This paper is based on data collected by the Working Group on Cancer Diagnosis Research for the First National Conference on Cancer Research Coordination in April 2004. Data was collated from the databases of Institutions/Universities where the authors are employed, the Ministry of Science, Technology and Innovation (MOSTI) and targeted survey feedback from key cancer researchers. Under the 7th Malaysia Plan, 76 cancer projects were funded through the Intensified Research in Priority Areas (IRPA) scheme of MOSTI, amounting to almost RM15 million of grant money. 47(61.8%) of these projects were substantially in cancer

  2. Cancer and Radiation Therapy: Current Advances and Future Directions

    Directory of Open Access Journals (Sweden)

    Rajamanickam Baskar, Kuo Ann Lee, Richard Yeo, Kheng-Wei Yeoh


    Full Text Available In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed.

  3. [Current topics in mutations in the cancer genome]. (United States)

    Iwaya, Takeshi; Mimori, Koshi; Wakabayashi, Go


    Several oncogenes and tumor suppressor genes are involved in the multistep process of carcinogenesis in many cancer types. Recently, global mutational analyses have revealed that the cancer genome has far greater numbers of mutations than previously thought. Furthermore, the next-generation sequencing method, which has a different principle from conventional Sanger sequencing, has provided more information on the cancer genome such as new cancer-related genes and the existence of many rearrangements in solid cancers. Somatic mutations occurring in cancer cells are divided into "driver" and "passenger" mutations. Driver mutations confer a growth advantage upon the neoplastic clone and are crucial for carcinogenesis. The remaining large majority of mutations are passengers, which, by definition, do not confer a growth advantage. Driver genes with low-frequency mutation rates (less than 10%) are also involved in carcinogenesis along with well-known drivers with high-frequency mutations. There are now several celebrated examples of anticancer drugs of which the efficacy in cancer patients can be predicted based on the genotype of several driver genes, such as EGFR, KRAS, and BRAF on the EGFR signaling pathway. The complete catalogs of somatic mutations provided by the sequencing of the cancer genome are expected to prompt new approaches to diagnosis, therapy, and potentially prevention.

  4. Current treatment options for the management of esophageal cancer

    Directory of Open Access Journals (Sweden)

    Mawhinney MR


    Full Text Available Mark R Mawhinney, Robert E GlasgowDepartment of Surgery, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USAAbstract: In recent years, esophageal cancer characteristics and management options have evolved significantly. There has been a sharp increase in the frequency of esophageal adenocarcinoma and a decline in the frequency of squamous cell carcinoma. A more comprehensive understanding of prognostic factors influencing outcome has also been developed. This has led to more management options for esophageal cancer at all stages than ever before. A multidisciplinary, team approach to management in a high volume center is the preferred approach. Each patient should be individually assessed based on type of cancer, local or regional involvement, and his or her own functional status to determine an appropriate treatment regimen. This review will discuss management of esophageal cancer relative to disease progression and patient functional status.Keywords: esophageal adenocarcinoma, squamous cell carcinoma, treatment regimen, disease progression, patient functional status

  5. Transvaginal ultrasonography in ovarian cancer screening: current perspectives

    Directory of Open Access Journals (Sweden)

    van Nagell Jr JR


    Full Text Available John R van Nagell Jr, John T HoffDepartment of Obstetrics and Gynecology, University of Kentucky Chandler Medical Center/Markey Cancer Center, Lexington, KY, USAAbstract: Transvaginal ultrasonography (TVS is an integral part of all major ovarian cancer screening trials. TVS is accurate in detecting abnormalities in ovarian volume and morphology, but is less reliable in differentiating benign from malignant ovarian tumors. When used as the only screening test, TVS is sensitive, but has a low positive predictive value. Therefore, serum biomarkers and tumor morphology indexing are used together with TVS to identify ovarian tumors at high risk for malignancy. This allows preoperative triage of high-risk cases to major cancer centers for therapy while decreasing unnecessary surgery for benign disease. Ovarian cancer screening has been associated with a decrease in stage at detection in most trials, thereby allowing treatment to be initiated when the disease is most curable.Keywords: ovarian cancer, ultrasound, screening, serum Ca-125

  6. Communicating the molecular basis of cancer cell-by-cell: an interview with Tatsushi Igaki

    Directory of Open Access Journals (Sweden)


    Full Text Available Tatsushi Igaki is currently based at the Kyoto University Graduate School of Biostudies, where he leads a research group dedicated to using Drosophila genetics to build a picture of the cell-cell communications underlying the establishment and maintenance of multicellular systems. His work has provided insight into the molecular bases of cell competition in the context of development and tumorigenesis, including the landmark discovery that oncogenic cells communicate with normal cells in the tumor microenvironment to induce tumor progression in a non-autonomous fashion. In this interview, he describes his career path, highlighting the shift in his research focus from the basic principles of apoptosis to clonal evolution in cancer, and also explains why Drosophila provides a powerful model system for studying cancer biology.

  7. Common molecular pathways involved in human CD133+/CD34+ progenitor cell expansion and cancer

    Directory of Open Access Journals (Sweden)

    Vêncio Ricardo Z


    Full Text Available Abstract Background Uncovering the molecular mechanism underlying expansion of hematopoietic stem and progenitor cells is critical to extend current therapeutic applications and to understand how its deregulation relates to leukemia. The characterization of genes commonly relevant to stem/progenitor cell expansion and tumor development should facilitate the identification of novel therapeutic targets in cancer. Methods CD34+/CD133+ progenitor cells were purified from human umbilical cord blood and expanded in vitro. Correlated molecular changes were analyzed by gene expression profiling using microarrays covering up to 55,000 transcripts. Genes regulated during progenitor cell expansion were identified and functionally classified. Aberrant expression of such genes in cancer was indicated by in silico SAGE. Differential expression of selected genes was assessed by real-time PCR in hematopoietic cells from chronic myeloid leukemia patients and healthy individuals. Results Several genes and signaling pathways not previously associated with ex vivo expansion of CD133+/CD34+ cells were identified, most of which associated with cancer. Regulation of MEK/ERK and Hedgehog signaling genes in addition to numerous proto-oncogenes was detected during conditions of enhanced progenitor cell expansion. Quantitative real-time PCR analysis confirmed down-regulation of several newly described cancer-associated genes in CD133+/CD34+ cells, including DOCK4 and SPARCL1 tumor suppressors, and parallel results were verified when comparing their expression in cells from chronic myeloid leukemia patients Conclusion Our findings reveal potential molecular targets for oncogenic transformation in CD133+/CD34+ cells and strengthen the link between deregulation of stem/progenitor cell expansion and the malignant process.

  8. Current cancer incidence and trends in Yaounde, Cameroon

    Directory of Open Access Journals (Sweden)

    Enow Orock GE


    Full Text Available Background: Except for some information on relative frequencies of different cancers in selected areas, the epidemiology of cancer in Cameroon is relatively unknown. Though there is no reliable data on its incidence and pattern, with an estimated 15,000 new cases diagnosed annually and a prevalence of about 25.000 cases throughout the country, cancer is being increasingly recognized as a public health problem in Cameroon. The Yaounde Cancer Registry is a population registry physically located at the General Hospital Yaounde that has been operating since 2004. It collects data from about 20 sources that cover the entire population of Yaounde estimated in 2010 at about 1,299,369. Objectives: The objective of this study was to find out the incidence and trends of cancer in the Yaounde population in the period 2004 – 2006/2010 – 2011. It is hoped that this will enable policy makers, health providers and other stake holders plan appropriate health management policy in this population. Materials and Methods: This report presents the cancer incidence for 5 years, 2004 – 2006/2010 – 2011 in the Yaounde population estimated at 1,299,369. Data of the Yaounde Cancer Registry was reviewed for the period under study using Canreg5 software. Only malignant cases registered during the period under study were used in the analysis while benign and other uncertain tumours were excluded. The 2010 census estimates by the National Institute of Statistics was employed to calculate the incidence, age-standardized and crude rates. Other software like excel, epi info were also used for analysis. Survival studies were not carried out in this study. Results: A total of 4,689 new malignant cases were reported, of which 2,901 (68% were females and 1,788 (32% were males. The incidence showed an average of 358 for men and 580 for women. The average age of cancer patients in Yaounde is 44.8 years. Morphologically confirmed cases accounted for 89% .The annual number of

  9. Colorectal cancer management in Poland: current improvements and future challenges. (United States)

    Ruszkowski, Jacek


    Colorectal cancer (CRC) is the second most commonly identified malignant neoplasm diagnosed in men (12% of total cancers) and women (11%) in Poland, while CRC mortality is second in men (10.1%) and third in women (11.2%). The main reasons for increasing incidence and mortality are an aging population and an increase in environmental and lifestyle factors which may lead to cancer. In Poland there is a lack of historical (regularly published and accessible) data on cancer morbidity and survival rates. The Oncology Centre published cancer data for the first time in February 2009 the 2006, which, also for the first time, embraced the entire country. Oncology data collection in Poland is based on a network of 16 Regional Cancer Registries reporting to the Polish National Cancer Registry in Warsaw. An additional source of oncology data is the National Health Fund and the Central Statistical Office. The National Cancer Programme (2005) provides funding at ca 780 million euro, which includes amongst others the Early CRC Detection Programme to promote a free screening colonoscopy. Oncology services in Poland are funded almost entirely by public resources--the national budget as sustained by tax revenues (Ministry of Health) and the National Health Fund as sustained by the obligatory public health insurance contribution. Oncology expenditure covered by the national budget (Ministry of Health) and the National Cancer Programme in 2006 amounted to 44.8 million euro and 105.2 million euro, respectively. All these preventive, curative and organizational efforts have significantly improved access to efficient therapies (including radiotherapy) and diagnostic procedures in recent years in Poland, although, clearly, a lot remains to be done.

  10. The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing

    Institute of Scientific and Technical Information of China (English)

    Alexander W Wyatt; Fan Mo; Yuzhuo Wang; Colin C Collins


    Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity.In recent years,the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression.It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity,where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity.This review dissects our current understanding of prostate cancer ‘omics',including the sentinel role of copy number variation,the growing spectrum of oncogenic fusion genes,the potential influence of chromothripsis,and breakthroughs in defining mutation-associated subtypes.Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways,yet recurrent gene aberration appears rare.Therefore,it is critical that we continue to define individual tumour genomes,especially in the context of their expressed transcriptome.Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.

  11. Mouse Low-Grade Gliomas Contain Cancer Stem Cells with Unique Molecular and Functional Properties

    Directory of Open Access Journals (Sweden)

    Yi-Hsien Chen


    Full Text Available The availability of adult malignant glioma stem cells (GSCs has provided unprecedented opportunities to identify the mechanisms underlying treatment resistance. Unfortunately, there is a lack of comparable reagents for the study of pediatric low-grade glioma (LGG. Leveraging a neurofibromatosis 1 (Nf1 genetically engineered mouse LGG model, we report the isolation of CD133+ multi-potent low-grade glioma stem cells (LG-GSCs, which generate glioma-like lesions histologically similar to the parent tumor following injection into immunocompetent hosts. In addition, we demonstrate that these LG-GSCs harbor selective resistance to currently employed conventional and biologically targeted anti-cancer agents, which reflect the acquisition of new targetable signaling pathway abnormalities. Using transcriptomic analysis to identify additional molecular properties, we discovered that mouse and human LG-GSCs harbor high levels of Abcg1 expression critical for protecting against ER-stress-induced mouse LG-GSC apoptosis. Collectively, these findings establish that LGG cancer stem cells have unique molecular and functional properties relevant to brain cancer treatment.

  12. Antitumor effects and molecular mechanisms of ponatinib on endometrial cancer cells harboring activating FGFR2 mutations. (United States)

    Kim, Do-Hee; Kwak, Yeonui; Kim, Nam Doo; Sim, Taebo


    Aberrant mutational activation of FGFR2 is associated with endometrial cancers (ECs). AP24534 (ponatinib) currently undergoing clinical trials has been known to be an orally available multi-targeted tyrosine kinase inhibitor. Our biochemical kinase assay showed that AP24534 is potent against wild-type FGFR1-4 and 5 mutant FGFRs (V561M-FGFR1, N549H-FGFR2, K650E-FGFR3, G697C-FGFR3, N535K-FGFR4) and possesses the strongest kinase-inhibitory activity on N549H-FGFR2 (IC50 of 0.5 nM) among all FGFRs tested. We therefore investigated the effects of AP24534 on endometrial cancer cells harboring activating FGFR2 mutations and explored the underlying molecular mechanisms. AP24534 significantly inhibited the proliferation of endometrial cancer cells bearing activating FGFR2 mutations (N549K, K310R/N549K, S252W) and mainly induced G1/S cell cycle arrest leading to apoptosis. AP24534 also diminished the kinase activity of immunoprecipitated FGFR2 derived from MFE-296 and MFE-280 cells and reduced the phosphorylation of FGFR2 and FRS2 on MFE-296 and AN3CA cells. AP24534 caused substantial reductions in ERK phosphorylation, PLCγ signaling and STAT5 signal transduction on ECs bearing FGFR2 activating mutations. Akt signaling pathway was also deactivated by AP24534. AP24534 causes the chemotherapeutic effect through mainly the blockade of ERK, PLCγ and STAT5 signal transduction on ECs. Moreover, AP24534 inhibited migration and invasion of endometrial cancer cells with FGFR2 mutations. In addition, AP24534 significantly blocked anchorage-independent growth of endometrial cancer cells. We, for the first time, report the molecular mechanisms by which AP24534 exerts antitumor effects on ECs with FGFR2 activating mutations, which would provide mechanistic insight into ongoing clinical investigations of AP24534 for ECs.

  13. Molecular pathways: the role of NR4A orphan nuclear receptors in cancer.

    LENUS (Irish Health Repository)

    Mohan, Helen M


    Nuclear receptors are of integral importance in carcinogenesis. Manipulation of classic ligand-activated nuclear receptors, such as estrogen receptor blockade in breast cancer, is an important established cancer therapy. Orphan nuclear receptors, such as nuclear family 4 subgroup A (NR4A) receptors, have no known natural ligand(s). These elusive receptors are increasingly recognized as molecular switches in cell survival and a molecular link between inflammation and cancer. NR4A receptors act as transcription factors, altering expression of downstream genes in apoptosis (Fas-ligand, TRAIL), proliferation, DNA repair, metabolism, cell migration, inflammation (interleukin-8), and angiogenesis (VEGF). NR4A receptors are modulated by multiple cell-signaling pathways, including protein kinase A\\/CREB, NF-κB, phosphoinositide 3-kinase\\/AKT, c-jun-NH(2)-kinase, Wnt, and mitogen-activated protein kinase pathways. NR4A receptor effects are context and tissue specific, influenced by their levels of expression, posttranslational modification, and interaction with other transcription factors (RXR, PPAR-Υ). The subcellular location of NR4A "nuclear receptors" is also important functionally; novel roles have been described in the cytoplasm where NR4A proteins act both indirectly and directly on the mitochondria to promote apoptosis via Bcl-2. NR4A receptors are implicated in a wide variety of malignancies, including breast, lung, colon, bladder, and prostate cancer; glioblastoma multiforme; sarcoma; and acute and\\/or chronic myeloid leukemia. NR4A receptors modulate response to conventional chemotherapy and represent an exciting frontier for chemotherapeutic intervention, as novel agents targeting NR4A receptors have now been developed. This review provides a concise clinical overview of current knowledge of NR4A signaling in cancer and the potential for therapeutic manipulation.

  14. Molecular Basis of the Anti-Cancer Effects of Genistein Isoflavone in LNCaP Prostate Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Hartmann J


    Full Text Available Background: Prostate cancer is the most common form of non-skin cancer within the United States and the second leading cause of cancer deaths. Survival rates for the advanced disease remain relatively low, and conventional treatments may be accompanied by significant side effects. As a result, current research is aimed at alternative or adjuvant treatments that will target components of the signal transduction, cell-cycle and apoptosis pathways, to induce cell death with little or no toxic side effects to the patient. In this study, we investigated the effect of genistein isoflavone, a soy derivative, on expression levels of genes involved in these pathways. The mechanism of genistein-induced cell death was also investigated. The chemosensitivity of the LNCaP prostate cancer cells to genistein was investigated using ATP and MTS assays, and a caspase binding assay was used to determine apoptosis induction. Several molecular targets were determined using cDNA microarray and RT-PCR analysis.Results: The overall data revealed that genistein induces cell death in a time- and dose-dependent manner, and regulates expression levels of several genes involved in carcinogenesis and immunity. Several cell-cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin-dependent kinases. Various members of the Bcl-2 family of apoptotic proteins were also affected. The DefB1 and the HLA membrane receptor genes involved in immunogenicity were also up-regulated.Conclusion: The results indicate that genistein inhibits growth of the hormone-dependent prostate cancer cells, LNCaP, via apoptosis induction through regulation of some of the genes involved in carcinogenesis of many tumors, and immunogenicity. This study augments the potential phytotherapeutic and immunotherapeutic significance of genistein isoflavone.

  15. [Prostate cancer stem cells: advances in current research]. (United States)

    Wu, Gang; Wu, Deng-long


    Prostate cancer is one of the most common malignancies threatening men's health, and the mechanisms underlying its initiation and progression are poorly understood. Last decade has witnessed encouraging progress in the studies of prostate cancer stem cells (PCSCs), which are considered to play important roles in tumor initiation, recurrence and metastasis, castration resistance, and drug resistance. Therefore, a deeper insight into PCSCs is of great significance for the successful management of prostate cancer. This article presents an overview on the location, origin, and markers of PCSCs as well as their potential correlation with tumor metastasis and castration resistance.

  16. Book Review of "The Molecular Biology of Cancer" by Stella Pelengaris, Michael Khan (Editors

    Directory of Open Access Journals (Sweden)

    Schmidt Christian


    Full Text Available Abstract Here, a review of "The Molecular Biology of Cancer" (Stella Pelengaris and Michael Khan [Editors] is given. The detailed description of the book is provided here: Pelengaris S, Khan M (Eds: The Molecular Biology of Cancer; Blackwell Publishing, Oxford (U.K.; 2006. 531 pages, 214 illustrations, ISBN 9-78140-511-814-9, £31.99.

  17. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics. (United States)

    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping


    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment of cancer metastasis. Numerous types of photothermal nanotherapeutics (PTN) have been developed with encouraging therapeutic efficacy on metastatic cancer in many preclinical animal experiments. We summarize the design and performance of various PTN in PTT alone and their combinational therapy. We also point out the lacking area and the most promising approaches in this challenging field. In conclusion, PTT or their combinational therapy can provide an essential promising therapeutic modality against cancer metastasis.

  18. Angiogenesis Inhibition in Prostate Cancer: Current Uses and Future Promises

    Directory of Open Access Journals (Sweden)

    Jeanny B. Aragon-Ching


    Full Text Available Angiogenesis has been well recognized as a fundamental part of a multistep process in the evolution of cancer progression, invasion, and metastasis. Strategies for inhibiting angiogenesis have been one of the most robust fields of cancer investigation, focusing on the vascular endothelial growth factor (VEGF family and its receptors. There are numerous regulatory drug approvals to date for the use of these agents in treating a variety of solid tumors. While therapeutic efficacy has been established, challenges remain with regards to overcoming resistance and assessing response to antiangiogenic therapies. Prostate cancer is the most common noncutaneous malignancy among American men and angiogenesis plays a role in disease progression. The use of antiangiogenesis agents in prostate cancer has been promising and is hereby explored.

  19. SPARCoC: a new framework for molecular pattern discovery and cancer gene identification.

    Directory of Open Access Journals (Sweden)

    Shiqian Ma

    Full Text Available It is challenging to cluster cancer patients of a certain histopathological type into molecular subtypes of clinical importance and identify gene signatures directly relevant to the subtypes. Current clustering approaches have inherent limitations, which prevent them from gauging the subtle heterogeneity of the molecular subtypes. In this paper we present a new framework: SPARCoC (Sparse-CoClust, which is based on a novel Common-background and Sparse-foreground Decomposition (CSD model and the Maximum Block Improvement (MBI co-clustering technique. SPARCoC has clear advantages compared with widely-used alternative approaches: hierarchical clustering (Hclust and nonnegative matrix factorization (NMF. We apply SPARCoC to the study of lung adenocarcinoma (ADCA, an extremely heterogeneous histological type, and a significant challenge for molecular subtyping. For testing and verification, we use high quality gene expression profiling data of lung ADCA patients, and identify prognostic gene signatures which could cluster patients into subgroups that are significantly different in their overall survival (with p-values < 0.05. Our results are only based on gene expression profiling data analysis, without incorporating any other feature selection or clinical information; we are able to replicate our findings with completely independent datasets. SPARCoC is broadly applicable to large-scale genomic data to empower pattern discovery and cancer gene identification.

  20. KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative to Molecular Biology in Colorectal Cancer?

    Directory of Open Access Journals (Sweden)

    Nicolas Piton


    Full Text Available KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to undertaking antiepidermal growth factor receptor (EGFR monoclonal antibody therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG island methylator phenotype and microsatellite instability. Currently, KRAS and BRAF evaluation is based on molecular biology techniques such as SNaPshot or Sanger sequencing. As molecular testing is performed on formalin-fixed paraffin-embedded (FFPE samples, immunodetection would appear to be an attractive alternative for detecting mutations. Thus, our objective was to assess the validity of KRAS and BRAF immunodetection of mutations compared with the genotyping reference method in colorectal adenocarcinoma. KRAS and BRAF genotyping was assessed by SNaPshot. A rabbit anti-human KRAS polyclonal antibody was tested on 33 FFPE colorectal tumor samples with known KRAS status. Additionally, a mouse anti-human BRAF monoclonal antibody was tested on 30 FFPE tumor samples with known BRAF status. KRAS immunostaining demonstrated both poor sensitivity (27% and specificity (64% in detecting KRAS mutation. Conversely, BRAF immunohistochemistry showed perfect sensitivity (100% and specificity (100% in detecting V600E mutation. Although molecular biology remains the reference method for detecting KRAS mutation, immunohistochemistry could be an attractive method for detecting BRAF V600E mutation in colorectal cancer.

  1. KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative to Molecular Biology in Colorectal Cancer? (United States)

    Piton, Nicolas; Borrini, Francesco; Bolognese, Antonio; Lamy, Aude; Sabourin, Jean-Christophe


    KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to undertaking antiepidermal growth factor receptor (EGFR) monoclonal antibody therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG island methylator phenotype and microsatellite instability. Currently, KRAS and BRAF evaluation is based on molecular biology techniques such as SNaPshot or Sanger sequencing. As molecular testing is performed on formalin-fixed paraffin-embedded (FFPE) samples, immunodetection would appear to be an attractive alternative for detecting mutations. Thus, our objective was to assess the validity of KRAS and BRAF immunodetection of mutations compared with the genotyping reference method in colorectal adenocarcinoma. KRAS and BRAF genotyping was assessed by SNaPshot. A rabbit anti-human KRAS polyclonal antibody was tested on 33 FFPE colorectal tumor samples with known KRAS status. Additionally, a mouse anti-human BRAF monoclonal antibody was tested on 30 FFPE tumor samples with known BRAF status. KRAS immunostaining demonstrated both poor sensitivity (27%) and specificity (64%) in detecting KRAS mutation. Conversely, BRAF immunohistochemistry showed perfect sensitivity (100%) and specificity (100%) in detecting V600E mutation. Although molecular biology remains the reference method for detecting KRAS mutation, immunohistochemistry could be an attractive method for detecting BRAF V600E mutation in colorectal cancer.

  2. Cancer immunotherapy in veterinary medicine: Current options and new developments. (United States)

    Regan, Daniel; Guth, Amanda; Coy, Jonathan; Dow, Steven


    Excitement in the field of tumor immunotherapy is being driven by several remarkable breakthroughs in recent years. This review will cover recent advances in cancer immunotherapy, including the use of T cell checkpoint inhibitors, engineered T cells, cancer vaccines, and anti-B cell and T cell antibodies. Inhibition of T cell checkpoint molecules such as PD-1 and CTLA-4 using monoclonal antibodies has achieved notable success against advanced tumors in humans, including melanoma, renal cell carcinoma, and non-small cell lung cancer. Therapy with engineered T cells has also demonstrated remarkable tumor control and regression in human trials. Autologous cancer vaccines have recently demonstrated impressive prolongation of disease-free intervals and survival times in dogs with lymphoma. In addition, caninized monoclonal antibodies targeting CD20 and CD52 just recently received either full (CD20) or conditional (CD52) licensing by the United States Department of Agriculture for clinical use in the treatment of canine B-cell and T-cell lymphomas, respectively. Thus, immunotherapy for cancer is rapidly moving to the forefront of cancer treatment options in veterinary medicine as well as human medicine.

  3. TOPICAL REVIEW: Current-driven dynamics in molecular-scale devices (United States)

    Seideman, Tamar


    We review recent theoretical work on current-triggered processes in molecular-scale devices - a field at the interface between solid state physics and chemical dynamics with potential applications in diverse areas, including artificial molecular machines, unimolecular transport, surface nanochemistry and nanolithography. The qualitative physics underlying current-triggered dynamics is first discussed and placed in context with several well-studied phenomena with which it shares aspects. A theory for modelling these dynamics is next formulated within a time-dependent scattering approach. Our end result provides useful insight into the system properties that determine the reaction outcome as well as a computationally convenient framework for numerical realization. The theory is applied to study single-molecule surface reactions induced by a scanning tunnelling microscope and current-triggered dynamics in single-molecule transistors. We close with a discussion of several potential applications of current-induced dynamics in molecular devices and several opportunities for future research.

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

    NARCIS (Netherlands)

    Vermeulen, J.F.


    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

  5. Prostate cancer heterogeneity: Discovering novel molecular targets for therapy. (United States)

    Ciccarese, Chiara; Massari, Francesco; Iacovelli, Roberto; Fiorentino, Michelangelo; Montironi, Rodolfo; Di Nunno, Vincenzo; Giunchi, Francesca; Brunelli, Matteo; Tortora, Giampaolo


    Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity. Recent genomic profiling studies have deeply improved the knowledge of the genomic landscape of localized and metastatic PCa. The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy. Moreover, somatic or germline aberrations of DNA repair genes (DRGs) have been observed at high frequency, supporting the potential role of platinum derivatives and PARP inhibitors as effective therapeutic strategies. In the future, the identification of driver mutations present at a specific stage of the disease, the classification PCa based on specific molecular alterations, and the selection of the most appropriate therapy based on biomarkers predictors of response represent the foundations for an increasingly more accurate personalized medicine.

  6. Molecular Basis of Triple Negative Breast Cancer and Implications for Therapy

    Directory of Open Access Journals (Sweden)

    Parvin F. Peddi


    Full Text Available Triple negative breast cancer is an aggressive form of breast cancer with limited treatment options and is without proven targeted therapy. Understanding the molecular basis of triple negative breast cancer is crucial for effective new drug development. Recent genomewide gene expression and DNA sequencing studies indicate that this cancer type is composed of a molecularly heterogeneous group of diseases that carry multiple somatic mutations and genomic structural changes. These findings have implications for therapeutic target identification and the design of future clinical trials for this aggressive group of breast cancer.

  7. The Morphological and Molecular Changes of Brain Cells Exposed to Direct Current Electric Field Stimulation


    Pelletier, Simon J.; Lagacé, Marie; St-Amour, Isabelle; Arsenault, Dany; Cisbani, Giulia; Chabrat, Audrey; Fecteau, Shirley; Lévesque, Martin; Cicchetti, Francesca


    Background: The application of low-intensity direct current electric fields has been experimentally used in the clinic to treat a number of brain disorders, predominantly using transcranial direct current stimulation approaches. However, the cellular and molecular changes induced by such treatment remain largely unknown. Methods: Here, we tested various intensities of direct current electric fields (0, 25, 50, and 100V/m) in a well-controlled in vitro environment in order to investigate the r...

  8. Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach (United States)


    Bethesda, MD, USA2014. Available from: csr /1975_2011/. 4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer...Bioinformatics 2015. Available from: http:// 35. Brandes JC, Carraway H, Herman JG. Optimal primer design using the novel primer design...Cancer Statistics Review, 1975-2011. csr /1975_2011/. 2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J

  9. Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology. (United States)

    Ogino, S; Lochhead, P; Giovannucci, E; Meyerhardt, J A; Fuchs, C S; Chan, A T


    Regular use of aspirin reduces incidence and mortality of various cancers, including colorectal cancer. Anticancer effect of aspirin represents one of the 'Provocative Questions' in cancer research. Experimental and clinical studies support a carcinogenic role for PTGS2 (cyclooxygenase-2), which is an important enzymatic mediator of inflammation, and a target of aspirin. Recent 'molecular pathological epidemiology' (MPE) research has shown that aspirin use is associated with better prognosis and clinical outcome in PIK3CA-mutated colorectal carcinoma, suggesting somatic PIK3CA mutation as a molecular biomarker that predicts response to aspirin therapy. The PI3K (phosphatidylinositol-4,5-bisphosphonate 3-kinase) enzyme has a pivotal role in the PI3K-AKT signaling pathway. Activating PIK3CA oncogene mutations are observed in various malignancies including breast cancer, ovarian cancer, brain tumor, hepatocellular carcinoma, lung cancer and colon cancer. The prevalence of PIK3CA mutations increases continuously from rectal to cecal cancers, supporting the 'colorectal continuum' paradigm, and an important interplay of gut microbiota and host immune/inflammatory reaction. MPE represents an interdisciplinary integrative science, conceptually defined as 'epidemiology of molecular heterogeneity of disease'. As exposome and interactome vary from person to person and influence disease process, each disease process is unique (the unique disease principle). Therefore, MPE concept and paradigm can extend to non-neoplastic diseases including diabetes mellitus, cardiovascular diseases, metabolic diseases, and so on. MPE research opportunities are currently limited by paucity of tumor molecular data in the existing large-scale population-based studies. However, genomic, epigenomic and molecular pathology testings (for example, analyses for microsatellite instability, MLH1 promoter CpG island methylation, and KRAS and BRAF mutations in colorectal tumors) are becoming routine

  10. Current and future care of patients with the cancer anorexia-cachexia syndrome. (United States)

    Del Fabbro, Egidio


    Many important advances have occurred in the field of cancer cachexia over the past decade, including progress in understanding the mechanisms of the cancer anorexia-cachexia syndrome (CACS) and the development of promising pharmacologic and supportive care interventions. However, no approved agents for cancer cachexia currently exist, emphasizing the unmet need for an effective pharmacologic therapy. This article reviews the key elements of CACS assessment in daily practice, the contribution of nutritional impact symptoms (NIS), the evidence for current pharmacologic options, and promising anticachexia agents in perclinical and clinical trials. It also proposes a model for multimodality therapy and highlights issues pertinent to CACS in patients with pancreatic, gastric, and esophageal cancer.

  11. Pharmacogenomics and Pancreatic Cancer Treatment. Optimizing Current Therapy and Individualizing Future Therapy

    Directory of Open Access Journals (Sweden)

    Soonmo Peter Kang


    Full Text Available Each year, more than 30,000 Americans are diagnosed with pancreatic cancer. We have only made incremental advancements in treatment of pancreatic cancer despite our best efforts. Research has revealed that pancreatic cancer is a genetic disease which is associated with various forms of cancer associated genetic alterations. Identification and understanding of these carcinogenic gene alterations is the base upon which we can overcome drug resistance and develop novel treatment approaches. In this paper, we review current understanding of pharmacogenomics of pancreatic cancer treatment and address future direction of the field.

  12. Sentinel Lymph Node Mapping In Gastric Cancer Surgery: Current Status

    Directory of Open Access Journals (Sweden)

    Bara Tivadar


    Full Text Available Lymphonodular metastases remain an important predictive and prognostic factor in gastric cancer development. The precise determination of the lymphonodular invasion stage can be made only by extended intraoperative lymphadenectomy and histopathological examination. But the main controversy is the usefulness of extended lymph dissection in early gastric cancer. This increases the duration of the surgery and the complications rate, and it is unnecessary without lymphonodular invasion. The identification of the sentinel lymph nodes has been successfully applied for some time in the precise detection of lymph nodes status in breast cancer, malignant melanoma and the use for gastric cancer patients has been a controversial issue. The good prognosis in early gastric cancer had been a surgery challenge, which led to the establishment of minimally invasive individualized treatment and acceptance of sentinel lymph node mapping. The dual-tracer method, submucosally administered endoscopically is also recommended in sentinel lymph node biopsy by laparoscopic approach. There are new sophisticated technologies for detecting sentinel lymph node such as: infrared ray endoscopy, florescence imaging and near-infrared technology, carbon nanoparticles, which will open new perspectives in sentinel lymph nodes mapping.

  13. Molecular Biomarkers of Colorectal Cancer: A Review of Published Articles From Iran

    Directory of Open Access Journals (Sweden)



    Full Text Available Context Colorectal cancer is one of the most common cancers worldwide (the third most common cancer in the world and is especially more common in Western countries; however, its incidence has been increased significantly during the last few years in Eastern countries such as Iran and considered as one of the five common cancers in this country. According to molecular pathways, numerous biomarkers have been identified for colorectal cancers which help patients’ management. Evidence aquisition In this study, we tried to review published articles about the molecular biomarkers of colorectal cancer from Iran. We searched medical databases such as google scholar, Scopus, PubMed, Magiran, SID and Iran Medex for keywords of “colon cancer, KRAS, BRAF, mismatch repair gene, Microsatellite instability, molecular genetics, molecular pathogenesis, biomarker and Iran” to find studies published about colorectal cancers from Iran regarding molecular biomarkers. Conclusion This study showed that molecular biomarkers in colorectal cancer of Iranian patients are not so different from Western population.

  14. [Medicinal plants in cancer patients: current practices and evaluation data]. (United States)

    Huet, Matthieu


    Many complementary and alternatives medicines are offered to patients with cancer. Among them, herbal medicines have a substantial place. These plants are mainly used to reduce adverse effects of anticancer treatments and for specific anticancer properties. Our review shows that only few clinical data support medicinal plants effectiveness in cancer patients. Arguments rely mainly on usual indications and pharmacological data for minimization of treatments toxicity while for the anticancer properties, on epidemiological and preclinical data. To inform and counsel patients and people around, healthcare professionals need to evaluate benefit-risk balance on evidence-based information. Because the medical decision should be shared with the patient, his beliefs and preferences have to be considered. When no adverse effect or drug interaction is associated with herbal medicine, we state that their use is acceptable. This paper discuss of potential risk and benefit of the most used medicinal plants by cancer patients.

  15. RNA profiling reveals familial aggregation of molecular subtypes in non-BRCA1/2 breast cancer families

    DEFF Research Database (Denmark)

    Larsen, Martin J; Thomassen, Mads; Tan, Qihua


    BACKGROUND: In more than 70% of families with a strong history of breast and ovarian cancers, pathogenic mutation in BRCA1 or BRCA2 cannot be identified, even though hereditary factors are expected to be involved. It has been proposed that tumors with similar molecular phenotypes also share similar...... underlying pathophysiological mechanisms. In the current study, the aim was to investigate if global RNA profiling can be used to identify functional subgroups within breast tumors from families tested negative for BRCA1/2 germline mutations and how these subgroupings relate to different breast cancer...... patients within the same family. METHODS: In the current study we analyzed a collection of 70 frozen breast tumor biopsies from a total of 58 families by global RNA profiling and promoter methylation analysis. RESULTS: We show that distinct functional subgroupings, similar to the intrinsic molecular breast...

  16. [Cancer-related Cognitive Impairment: Current Knowledge and Future Challenges]. (United States)

    Tanimukai, Hitoshi


    Cancer patients often suffer from various distresses, including cognitive impairment. Cognitive impairment during and after cancer diagnosis and treatment are collectively called "Cancer-related cognitive impairment (CRCI)". The number of publications about cognitive impairment due to cancer therapy, especially chemotherapy, hormonal therapy, and radiotherapy, has been growing. Patients often worry not only about their disease condition and therapies, but also experience concerns regarding their memory, attention, and ability to concentrate. Even subtle CRCI can have a significant impact on social relationships, the ability to work, undergo treatment, accomplish meaningful goals, and the quality of life. Longitudinal studies of cancer patients indicated that up to 75% experience CRCI during treatment. Furthermore, CRCI may persist for many years following treatment. However, it is not well understood by most physicians and medical staff. CRCI can be mediated through increased inflammatory cytokines and hormonal changes. In addition, the biology of the cancer, stress, and attentional fatigue can also contribute to CRCI. Genetic factors and co-occurring symptoms may explain some of the inter-individual variability in CRCI. Researchers and patients are actively trying to identify effective interventional methods and useful coping strategies. Many patients are willing to discuss their disease condition and future treatment with medical staff and/or their families. Some patients also hope to discuss their end-of-life care. However, it is difficult to express their will after developing cognitive impairment. Advance care planning (ACP) can help in such situations. This process involves discussion between a patient, their family, and clinicians to clarify and reflect on values, treatment preferences, and goals to develop a shared understanding of how end-of-life care should proceed. The number of cancer patients with cognitive impairment has been increasing owing to the

  17. Current approaches in treatment of triple-negative breast cancer

    Institute of Scientific and Technical Information of China (English)

    Hanan Ahmed Wahba; Hend Ahmed El-Hadaad


    Triple-negative breast cancer (TNBC) is diagnosed more frequently in younger and premenopausal women and is highly prevalent in African American women. TNBC is a term derived from tumors that are characterized by the absence of ER, PgR, and HER2. So patients with TNBC do not beneift from hormonal or trastuzumab-based therapies. TNBCs are biologically aggressive, although some reports suggest that they respond to chemotherapy better than other types of breast cancer, prognosis remains poor. hTis is due to:shortened disease-free interval in the adjuvant and neoadjuvant setting and a more aggressive course in the metastatic setting.

  18. Application of Quantum Dots-Based Biotechnology in Cancer Diagnosis: Current Status and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Chun-Wei Peng


    Full Text Available The semiconductor nanocrystal quantum dots (QDs have excellent photo-physical properties, and the QDs-based probes have achieved encouraging developments in cellular and in vivo molecular imaging. More and more researches showed that QDs-based technology may become a promising approach in cancer research. In this review, we focus on recent application of QDs in cancer diagnosis and treatment, including early detection of primary tumor such as ovarian cancer, breast cancer, prostate cancer and pancreatic cancer, as well as regional lymph nodes and distant metastases. With the development of QDs synthesis and modification, the effect of QDs on tumor metastasis investigation will become more and more important in the future.

  19. Clinical impact of extensive molecular profiling in advanced cancer patients. (United States)

    Cousin, Sophie; Grellety, Thomas; Toulmonde, Maud; Auzanneau, Céline; Khalifa, Emmanuel; Laizet, Yec'han; Tran, Kevin; Le Moulec, Sylvestre; Floquet, Anne; Garbay, Delphine; Robert, Jacques; Hostein, Isabelle; Soubeyran, Isabelle; Italiano, Antoine


    Previous precision medicine studies have investigated conventional molecular techniques and/or limited sets of gene alterations. The aim of this study was to describe the impact of the next-generation sequencing of the largest panel of genes used to date in tumour tissue and blood in the context of institutional molecular screening programmes. DNA analysis was performed by next-generation sequencing using a panel of 426 cancer-related genes and by comparative genomic hybridization from formalin-fixed and paraffin-embedded archived tumour samples when available or from fresh tumour samples. Five hundred sixty-eight patients were enrolled. The median number of prior lines of treatment was 2 (range 0-9). The most common primary tumour types were lung (16.9%), colorectal (14.4%), breast (10.6%), ovarian (10.2%) and sarcoma (10.2%). The median patient age was 63 years (range 19-88). A total of 292 patients (51.4%) presented with at least one actionable genetic alteration. The 20 genes most frequently altered were TP53, CDKN2A, KRAS, PTEN, PI3KCA, RB1, APC, ERBB2, MYC, EGFR, CDKN2B, ARID1A, SMAD4, FGFR1, MDM2, BRAF, ATM, CCNE1, FGFR3 and FRS2. One hundred fifty-nine patients (28%) were included in early phase trials. The treatment was matched with a tumour profile in 86 cases (15%). The two main reasons for non-inclusion were non-progressive disease (31.5%) and general status deterioration (25%). Twenty-eight percent of patients presented with a growth modulation index (time to progression under the early phase trial treatment/time to progression of the previous line of treatment) >1.3.Extensive molecular profiling using high-throughput techniques allows for the identification of actionable mutations in the majority of cases and is associated with substantial clinical benefit in up to one in four patients.

  20. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Abdollahi, H


    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.

  1. Molecular profiling of patients with colorectal cancer and matched targeted therapy in phase I clinical trials. (United States)

    Dienstmann, Rodrigo; Serpico, Danila; Rodon, Jordi; Saura, Cristina; Macarulla, Teresa; Elez, Elena; Alsina, Maria; Capdevila, Jaume; Perez-Garcia, Jose; Sánchez-Ollé, Gessamí; Aura, Claudia; Prudkin, Ludmila; Landolfi, Stefania; Hernández-Losa, Javier; Vivancos, Ana; Tabernero, Josep


    Clinical experience increasingly suggests that molecular prescreening and biomarker enrichment strategies in phase I trials with targeted therapies will improve the outcomes of patients with cancer. In keeping with the exigencies of a personalized oncology program, tumors from patients with advanced chemorefractory colorectal cancer were analyzed for specific aberrations (KRAS/BRAF/PIK3CA mutations, PTEN and pMET expression). Patients were subsequently offered phase I trials with matched targeted agents (MTA) directed at the identified anomalies. During 2010 and 2011, tumor molecular analysis was conducted in 254 patients: KRAS mutations (80 of 254, 31.5%), BRAF mutations (24 of 196, 12.2%), PIK3CA mutations (15 of 114, 13.2%), KRAS and PIK3CA mutations (9 of 114, 7.9%), low PTEN expression (97 of 183, 53.0%), and high pMET expression (38 of 64, 59.4%). In total, 68 patients received 82 different MTAs: phosphoinositide 3-kinase (PI3K) pathway inhibitor (if PIK3CA mutation, n = 10; or low PTEN, n = 32), PI3K pathway inhibitor plus MEK inhibitor (if KRAS mutation, n = 10; or BRAF mutation, n = 1), second-generation anti-EGF receptor monoclonal antibodies (if wild-type KRAS, n = 11), anti-hepatocyte growth factor monoclonal antibody (if high pMET, n = 10), mTOR inhibitor plus anti-insulin-like growth factor-1 receptor monoclonal antibody (if low PTEN, n = 5), and BRAF inhibitor (if BRAF mutation, n = 3). Median time-to-treatment failure on MTA was 7.9 versus 16.3 weeks for their prior systemic antitumor therapy (P 16 weeks in 10 cases (12.2%). These results suggest that matching chemorefractory patients with colorectal cancer with targeted agents in phase I trials based on the current molecular profile does not confer a significant clinical benefit.

  2. Current Surgical Aspects of Palliative Treatment for Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Karapanos, Konstantinos, E-mail:; Nomikos, Iakovos N. [Department of Surgery (B' Unit), METAXA Cancer Memorial Hospital, Piraeus (Greece)


    Despite all improvements in both surgical and other conservative therapies, pancreatic cancer is steadily associated with a poor overall prognosis and remains a major cause of cancer mortality. Radical surgical resection has been established as the best chance these patients have for long-term survival. However, in most cases the disease has reached an incurable state at the time of diagnosis, mainly due to the silent clinical course at its early stages. The role of palliative surgery in locally advanced pancreatic cancer mainly involves patients who are found unresectable during open surgical exploration and consists of combined biliary and duodenal bypass procedures. Chemical splanchnicectomy is another modality that should also be applied intraoperatively with good results. There are no randomized controlled trials evaluating the outcomes of palliative pancreatic resection. Nevertheless, data from retrospective reports suggest that this practice, compared with bypass procedures, may lead to improved survival without increasing perioperative morbidity and mortality. All efforts at developing a more effective treatment for unresectable pancreatic cancer have been directed towards neoadjuvant and targeted therapies. The scenario of downstaging tumors in anticipation of a future oncological surgical resection has been advocated by trials combining gemcitabine with radiation therapy or with the tyrosine kinase inhibitor erlotinib, with promising early results.

  3. Diabetes and Cancer: a Review of Current Knowledge. (United States)

    Wojciechowska, J; Krajewski, W; Bolanowski, M; Kręcicki, T; Zatoński, T


    Diabetes mellitus (DM), one of the most common life-threatening illnesses worldwide, is a group of metabolic diseases, characterized by sustained hyperglycemia. The global prevalence of diabetes mellitus among adults reached 387 millions in 2014 and is still rising. It is suggested there is a strong association between diabetes mellitus (especially type 2 diabetes mellitus) and carcinogenesis. The possible biological links between diabetes mellitus and cancer comprise hyperinsulinemia, hyperglycemia and fat-induced chronic inflammation. Although, the strongest association refers to pancreas and liver, there are many other organs involved in carcinogenesis in diabetic patients including breast, endometrium, bladder and kidney.Recent studies suggest that there is also association between cancer incidence and anti-diabetic medications. It was observed that some medications decrease the risk of carcinogenesis and some increase that risk. The majority of studies concern metformin, a drug of choice in type 2 diabetes mellitus, and its anti-neoplastic and tumor-suppressing activity. The positive effect of metformin was found in numerous researches investigating breast, pancreas, liver, colon, ovaries and prostate tumors.Because a variety of studies have suggested that diabetes mellitus and cancer are frequently coexisting diseases, recently published studies try to explain the influence of diabetes mellitus and anti-diabetic medications on carcinogenesis in different organs.We present the review of the latest studies investigating the association between both diabetes mellitus and anti-diabetic medications and cancer incidence and prognosis.Particularly we highlight the problem of concomitant head and neck cancers in diabetics, rarely analysed and often omitted in studies.

  4. Molecular genetics of colorectal cancer Genética molecular del cáncer colorrectal

    Directory of Open Access Journals (Sweden)

    D. Cruz-Bustillo Clarens


    Full Text Available Colorectal tumours constitute an excellent system to study carcinogenesis and the molecular events implicated in the development of cancer. Attending to the way it is transmitted, colorectal cancer may appear in one of three forms: sporadic, familial, and hereditary. The sporadic form is most common and has no familial or hereditary associated factor thus far, while familial and hereditary forms show the same inheritance pattern. Hereditary colorectal cancers develop by means of defined stages that go from lesions in the crypt of the colon through adenomas to manifest cancer. They are characterised by the accumulation of multiple mutations in tumour suppressor genes and oncogenes that affect the balance between cell proliferation and apoptosis. The colorectal carcinogenesis pathway is not unique and there are probably several ways for the initiation, development and progression of colorectal tumours.Los tumores colorrectales constituyen un excelente sistema para estudiar la carcinogénesis y los eventos moleculares involucrados en el desarrollo de un tumor. El cáncer colorrectal puede presentarse en tres formas, según su forma de transmisión: esporádico, familiar y hereditario. La forma esporádica que es la mayoritaria, no tiene hasta el momento ningún factor familiar o hereditario asociado, mientras que las formas familiares y hereditarias siguen un patrón de herencia en la propensión familiar a padecerlo. Los cánceres colorrectales hereditarios se desarrollan mediante etapas definidas que van desde lesiones en la cripta del colon a través de adenomas hasta manifestar el cáncer y se caracterizan por la acumulación de múltiples mutaciones en genes supresores de tumor y oncogenes que afectan el balance entre la proliferación celular y la apoptosis. La vía de carcinogénesis colorrectal no es una sola y probablemente existan varios caminos para el inicio, desarrollo y progresión de un tumor colorrectal.

  5. Current practices in cancer spatial data analysis: a call for guidance

    Directory of Open Access Journals (Sweden)

    Lawson Andrew B


    Full Text Available Abstract There has long been a recognition that place matters in health, from recognition of clusters of yellow fever and cholera in the 1800s to modern day analyses of regional and neighborhood effects on cancer patterns. Here we provide a summary of discussions about current practices in the spatial analysis of georeferenced cancer data by a panel of experts recently convened at the National Cancer Institute.

  6. Prostate-specific antigen: does the current evidence support its use in prostate cancer screening?

    LENUS (Irish Health Repository)

    Duffy, Michael J


    Although widely used, the value of prostate-specific antigen (PSA) in screening asymptomatic men for prostate cancer is controversial. Reasons for the controversy relate to PSA being less than an ideal marker in detecting early prostate cancer, the possibility that screening for prostate cancer may result in the overdetection and thus overtreatment of indolent disease and the lack of clarity as to the definitive or best treatment for men diagnosed with localized prostate cancer. Although the results from some randomized prospective trials suggest that screening with PSA reduces mortality from prostate cancer, the overall benefit was modest. It is thus currently unclear as to whether the modest benefit of reduced mortality outweighs the harms of overdetection and overtreatment. Thus, prior to undergoing screening for prostate cancer, men should be informed of the risks and benefits of early detection. Newly emerging markers that may complement PSA in the early detection of prostate cancer include specific isoforms of PSA and PCA3.

  7. An Overview of Current Screening and Management Approaches for Prostate Cancer. (United States)

    Akram, Omar N; Mushtaq, Gohar; Kamal, Mohammad Amjad


    Prostate cancer is the fourth leading cause of mortality in Australian men. The prevalence and incidence is increasing in both developed and developing nations, thus there is a need for better screening and management of this disorder. While there is no direct known cause of prostate cancer, management is largely focused on early detection and treatment strategies. Of particular concern is advanced prostate cancer which can manifest as castrate resistant prostate cancer characterized by therapy resistance. This short review outlines the global epidemiology of prostate cancer, clinical manifestations, risk factors, current screening strategies including first line clinical screening as well as the use of circulating biomarkers, and treatment of prostate cancer through mainstream therapeutics as well as the cutting edge peptide and nano-technology based therapeutics that are being implemented or in the process of development to overcome therapeutic obstacles in the treatment of prostate cancer.

  8. [Current status and future prospect of internal medicine treatment for advanced esophageal cancer]. (United States)

    Wang, F; Fan, Q X


    Esophageal cancer (EC) is one of common malignant tumors, and the incidence and mortality of EC in China rank the first place in the world. Because of the occult onset, the early atypical symptoms, and the lack of effective early diagnostic methods, most of patients are diagnosed at an advanced stage of the disease and lost the chance of surgery. Comprehensive treatment including palliative medical treatment, molecular targeted therapy, immunotherapy and so on is appropriate for these patients. How to choose the chemotherapy regimen and formulate reasonable treatment plan has become a hot spot in clinical research. Molecular targeted drugs have become a new developmental direction in cancer treatment because of their high specificity and antitumor activity, but the effects on esophageal cancer remain controversial. With the development of immune check point blockade treatment, breakthrough has been made in tumor immunotherapy, which has become an important means in cancer comprehensive treatment and shown a good prospect of treatment.

  9. Current trends in cancer vaccines--a bioinformatics perspective. (United States)

    Sankar, Shanju; Nayanar, Sangeetha K; Balasubramanian, Satheesan


    Cancer vaccine development is in the process of becoming reality in future, due to successful phase II/III clinical trials. However, there are still problems due to the specificity of tumor antigens and weakness of tumor associated antigens in eliciting an effective immune response. Computational models to assess the vaccine efficacy have helped to improve and understand what is necessary for personalized treatment. Further research is needed to elucidate the mechanisms of activation of antigen specific cytotoxic T lymphocytes, decreased TREG number functionality and antigen cascade, so that overall improvement in vaccine efficacy and disease free survival can be attained. T cell epitomic based in sillico approaches might be very effective for the design and development of novel cancer vaccines.

  10. Current treatment for liver metastases from colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Lian-Xin Liu; Wei-Hui Zhang; Hong-Chi Jiang


    The liver is the commonest site of distant metastasis ofcolorectal cancer and nearly half of the patients withcolorectal cancer ultimately develop liver involved duringthe course of their diseases. Surgery is the only therapythat offers the possibility of cure for patients with hepaticmetastatic diseases. Five-year survival rates after resectionof all detectable liver metastases can be up to 40 %.Unfortunately, only 25 % of patients with colorectal livermetastases are candidates for liver resection, while the othersare not amenable to surgical resection. Regional therapiessuch as radiofrequency ablation and cryotherapy may beoffered to patients with isolated unresectable metastasesbut no extrahepatic diseases. Hepatic artery catheterchemotherapy and chemoembolization and portal veinembolization are often used for the patients with extensiveliver metastases but without extrahepatic diseases, whichare not suitable for regional ablation. For the patients withmetastatic colorectal cancer beyond the liver, systemicchemotherapy is a more appropriate choice. Immunotherapyis also a good option when other therapies are used incombination to enhance the efficacy. Selective internalradiation therapy is a new radiation method which can beused in patients given other routine therapies Without effects.

  11. Imaging in primary penile cancer: current status and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Kochhar, Rohit; Taylor, Ben [Christie, NHS Foundation Trust, Department of Radiology, Manchester (United Kingdom); Sangar, Vijay [Christie, NHS Foundation Trust, Department of Urology, Manchester (United Kingdom)


    Penile cancer is a rare neoplasm in the developed world. Clinical assessment often results in inaccurate staging and radiological techniques have a key role in staging and postoperative assessment. Magnetic resonance imaging (MRI) depicts penile anatomy in detail and is the most accurate technique for local staging and postoperative follow-up. MRI and ultrasound (US), although helpful for assessment of lymph nodes, are not reliable enough for accurate nodal staging. US-guided fine needle aspiration cytology (FNAC), however, remains a valuable tool to confirm metastases in suspicious inguinal nodes. Lymphoscintigraphy with dynamic sentinel node biopsy (DSNB) is a promising technique used to predict occult lymph node metastases. Novel imaging techniques such as positron emission tomography/computed tomography (PET-CT) and nanoparticle enhanced MRI have high sensitivity and specificity for lymph node metastases but their availability is limited and clinical utility is not fully established. The radiologist needs to be familiar with the normal penile anatomy, imaging appearances of pre- and post-treatment penile cancer, and the advantages and limitations of the available imaging techniques. This review highlights the above points and presents a systematic approach to make the best use of imaging in the management of patients with penile cancer. (orig.)

  12. Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions. (United States)

    Lee, Dae-Won; Lee, Kyung-Hun; Kim, Jin Wook; Keam, Bhumsuk


    Leptomeningeal carcinomatosis (LMC) is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR)-targeted therapy or an anaplastic lymphoma kinase (ALK) inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2)-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma). Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC.

  13. Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions

    Directory of Open Access Journals (Sweden)

    Dae-Won Lee


    Full Text Available Leptomeningeal carcinomatosis (LMC is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR-targeted therapy or an anaplastic lymphoma kinase (ALK inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma. Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC.

  14. Molecular targets of selenium in prostate cancer prevention (Review). (United States)

    Abdulah, Rizky; Kobayashi, Kenji; Yamazaki, Chiho; Koyama, Hiroshi


    Prostate cancer is one of the leading causes of cancer-related deaths among males. Although use of the micro-nutrient selenium in prostate cancer clinical trials is limited, the outcomes indicate that selenium is a promising treatment. Furthermore, selenium inhibits prostate cancer through multiple mechanisms, and it is beneficial in controlling the development of this disease. This review highlights the latest epidemiological and biomolecular research on selenium in prostate cancer, as well as its prospects for future clinical use.

  15. The lectin-like oxidized LDL receptor-1: a new potential molecular target in colorectal cancer. (United States)

    Murdocca, Michela; Mango, Ruggiero; Pucci, Sabina; Biocca, Silvia; Testa, Barbara; Capuano, Rosamaria; Paolesse, Roberto; Sanchez, Massimo; Orlandi, Augusto; di Natale, Corrado; Novelli, Giuseppe; Sangiuolo, Federica


    The identification of new biomarkers and targets for tailored therapy in human colorectal cancer (CRC) onset and progression is an interesting challenge. CRC tissue produces an excess of ox-LDL, suggesting a close correlation between lipid dysfunction and malignant transformation. Lectin-like oxidized LDL receptor-1 (LOX-1) is involved in several mechanisms closely linked to tumorigenesis. Here we report a tumor specific LOX-1 overexpression in human colon cancers: LOX-1 results strongly increased in the 72% of carcinomas (Pcancer cells by siRNA and anti-LOX-1 antibody triggers to an impaired proliferation rate and affects the maintenance of cell growth and tumorigenicity. The wound-healing assay reveals an evident impairment in closing the scratch. Lastly knockdown of LOX-1 delineates a specific pattern of volatile compounds characterized by the presence of a butyrate derivative, suggesting a potential role of LOX-1 in tumor-specific epigenetic regulation in neoplastic cells. The role of LOX-1 as a novel biomarker and molecular target represents a concrete opportunity to improve current therapeutic strategies for CRC. In addition, the innovative application of a technology focused to the identification of LOX-1 driven volatiles specific to colorectal cancer provides a promising diagnostic tool for CRC screening and for monitoring the response to therapy.

  16. Molecular Targeted Agents for Gastric Cancer: A Step Forward Towards Personalized Therapy

    Directory of Open Access Journals (Sweden)

    Tom Geldart


    Full Text Available Gastric cancer (GC represents a major cancer burden worldwide, and remains the second leading cause of cancer-related death. Due to its insidious nature, presentation is usually late and often carries a poor prognosis. Despite having improved treatment modalities over the last decade, for most patients only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and its signaling pathways, offers the hope of clinically significant promising advances for selected groups of patients. Patients with Her-2 overexpression or amplification have experienced benefit from the integration of monoclonal antibodies such as trastuzumab to the standard chemotherapy. Additionally, drugs targeting angiogenesis (bevacizumab, sorafenib, sunitinib are under investigation and other targeted agents such as mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors are in preclinical or early clinical development. Patient selection and the development of reliable biomarkers to accurately select patients most likely to benefit from these tailored therapies is now key. Future trials should focus on these advances to optimize the treatment for GC patients. This article will review recent progress and current status of targeted agents in GC.

  17. Molecular and cellular functions of the FANCJ DNA helicase defective in cancer and in Fanconi Anemia

    Directory of Open Access Journals (Sweden)

    Robert M. Brosh


    Full Text Available The FANCJ DNA helicase is mutated in hereditary breast and ovarian cancer as well as the progressive bone marrow failure disorder Fanconi anemia (FA. FANCJ is linked to cancer suppression and DNA double strand break (DSB repair through its direct interaction with the hereditary breast cancer associated gene product, BRCA1. FANCJ also operates in the FA pathway of interstrand cross-link (ICL repair and contributes to homologous recombination (HR. FANCJ collaborates with a number of DNA metabolizing proteins implicated in DNA damage detection and repair, and plays an important role in cell cycle checkpoint control. In addition to its role in the classical FA pathway, FANCJ is believed to have other functions that are centered on alleviating replication stress. FANCJ resolves G-quadruplex (G4 DNA structures that are known to affect cellular replication and transcription, and potentially plays a role in the preservation and functionality of chromosomal structures such as telomeres. Recent studies suggest that FANCJ helps to maintain chromatin structure and preserve epigenetic stability by facilitating smooth progression of the replication fork when it encounters DNA damage or an alternate DNA structure such as a G4. Ongoing studies suggest a prominent but still not well-understood role of FANCJ in transcriptional regulation, chromosomal structure and function, and DNA damage repair to maintain genomic stability. This review will synthesize our current understanding of the molecular and cellular functions of FANCJ that are critical for chromosomal integrity.

  18. High risk bladder cancer: current management and survival

    Directory of Open Access Journals (Sweden)

    Anna M. Leliveld


    Full Text Available PURPOSE: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC in the Comprehensive Cancer Center North-Netherlands (CCCN and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. MATERIALS AND METHODS: Retrospective analysis of 412 patients with newly diagnosed high risk NMIBC. Clinical, demographic and follow-up data were obtained from the CCCN Cancer Registry and a detailed medical record review. Uni and multivariate analysis was performed to identify factors related to choice of treatment and 5 year recurrence and progression free survival. RESULTS: 74/412 (18% patients with high risk NMIBC underwent a transurethral resection (TUR as single treatment. Adjuvant treatment after TUR was performed in 90.7% of the patients treated in teaching hospitals versus 71.8 % in non-teaching hospitals (p 80 years OR 0.1 p = 0.001 and treatment in non-teaching hospitals (OR 0.25; p < 0.001 were associated with less adjuvant treatment after TUR. Tumor recurrence occurred in 191/392 (49% and progression in 84 /392 (21.4% patients. The mean 5-years progression free survival was 71.6% (95% CI 65.5-76.8. CONCLUSION: In this pattern of care study in high risk NMIBC, 18% of the patients were treated with TUR as single treatment. Age and treatment in non-teaching hospitals were associated with less adjuvant treatment after TUR. None of the variables sex, age, comorbidity, hospital type, stage and year of treatment was associated with 5 year recurrence or progression rates.

  19. Bases moleculares de la cancerización de cavidad oral Molecular basis on oral cavity cancerization

    Directory of Open Access Journals (Sweden)

    M.A. González-Moles


    Full Text Available Se presenta una revisión bibliográfica breve sobre los principales aspectos moleculares de interés en la cancerización de cavidad oral. Se hace referencia a los conocimientos más recientes sobre las aberraciones cromosómicas más comunes y las alteraciones de los oncogenes y genes supresores tumorales que están implicados en la carcinogénesis oral. Así mismo, se resume la teoría molecular actual que explica el proceso de cancerización de campo.A review about the main molecular aspects on oral cavity cancerization is presented, with special reference to the common chromosomal aberration, oncogenes and tumour suppressor genes implied in oral carcinogenesis. A summary about molecular theory explaining the field cancerization process is also presented.

  20. Current opportunities and challenges of magnetic resonance spectroscopy, positron emission tomography, and mass spectrometry imaging for mapping cancer metabolism in vivo. (United States)

    Lin, Gigin; Chung, Yuen-Li


    Cancer is known to have unique metabolic features such as Warburg effect. Current cancer therapy has moved forward from cytotoxic treatment to personalized, targeted therapies, with some that could lead to specific metabolic changes, potentially monitored by imaging methods. In this paper we addressed the important aspects to study cancer metabolism by using image techniques, focusing on opportunities and challenges of magnetic resonance spectroscopy (MRS), dynamic nuclear polarization (DNP)-MRS, positron emission tomography (PET), and mass spectrometry imaging (MSI) for mapping cancer metabolism. Finally, we highlighted the future possibilities of an integrated in vivo PET/MR imaging systems, together with an in situ MSI tissue analytical platform, may become the ultimate technologies for unraveling and understanding the molecular complexities in some aspects of cancer metabolism. Such comprehensive imaging investigations might provide information on pharmacometabolomics, biomarker discovery, and disease diagnosis, prognosis, and treatment response monitoring for clinical medicine.

  1. The Morphological and Molecular Changes of Brain Cells Exposed to Direct Current Electric Field Stimulation (United States)

    Pelletier, Simon J.; Lagacé, Marie; St-Amour, Isabelle; Arsenault, Dany; Cisbani, Giulia; Chabrat, Audrey; Fecteau, Shirley; Lévesque, Martin


    Background: The application of low-intensity direct current electric fields has been experimentally used in the clinic to treat a number of brain disorders, predominantly using transcranial direct current stimulation approaches. However, the cellular and molecular changes induced by such treatment remain largely unknown. Methods: Here, we tested various intensities of direct current electric fields (0, 25, 50, and 100V/m) in a well-controlled in vitro environment in order to investigate the responses of neurons, microglia, and astrocytes to this type of stimulation. This included morphological assessments of the cells, viability, as well as shape and fiber outgrowth relative to the orientation of the direct current electric field. We also undertook enzyme-linked immunosorbent assays and western immunoblotting to identify which molecular pathways were affected by direct current electric fields. Results: In response to direct current electric field, neurons developed an elongated cell body shape with neurite outgrowth that was associated with a significant increase in growth associated protein-43. Fetal midbrain dopaminergic explants grown in a collagen gel matrix also showed a reorientation of their neurites towards the cathode. BV2 microglial cells adopted distinct morphological changes with an increase in cyclooxygenase-2 expression, but these were dependent on whether they had already been activated with lipopolysaccharide. Finally, astrocytes displayed elongated cell bodies with cellular filopodia that were oriented perpendicularly to the direct current electric field. Conclusion: We show that cells of the central nervous system can respond to direct current electric fields both in terms of their morphological shape and molecular expression of certain proteins, and this in turn can help us to begin understand the mechanisms underlying the clinical benefits of direct current electric field. PMID:25522422

  2. Molecular basis of colorectal cancer: Towards an individualized management?

    Directory of Open Access Journals (Sweden)

    J. Perea

    Full Text Available Colorectal cancer (CRC has become a highly relevant condition nowadays. In this respect, advances in the understanding of its molecular basis are key for an adequate management. From the time when the adenoma-carcinoma sequence was formulated as a carcinogenesis model to this day, when, among other things, three major carcinogenic pathways have been identified, the CRC concept has evolved from that of a single disease to the notion that each CRC is a differentiated condition in itself. The suppressor or chromosome instability pathway, the mutator or microsatellite instability pathway, and the methylator or CpG island methylation pathway allow various phenotypes to be identified within CRC. Similarly, the presence of different changes in certain genes confers several behaviors on CRC from both the prognostic and responsive standpoints to specific therapies. However, this apparent complexity does help develop the clinical management of this disease through the identification of novel, more specific therapy targets, and also markers for various behaviors within the condition, which will most likely lead us to an individualized management for these patients.

  3. Molecular basis of colorrectal cancer: towards an individualized management? (United States)

    Perea, J; Lomas, M; Hidalgo, M


    Colorectal cancer (CRC) has become a highly relevant condition nowadays. In this respect, advances in the understanding of its molecular basis are key for an adequate management. From the time when the adenoma-carcinoma sequence was formulated as a carcinogenesis model to this day, when -among other things- three major carcinogenic pathways have been identified, the CRC concept has evolved from that of a single disease to the notion that each CRC is a differentiated condition in itself. The suppressor or chromosome instability pathway, the mutator or microsatellite instability pathway, and the methylator or CpG island methylation pathway allow various phenotypes to be identified within CRC. Similarly, the presence of different changes in certain genes confers several behaviors on CRC from both the prognostic and responsive standpoints to specific therapies. However, this apparent complexity does help develop the clinical management of this disease through the identification of novel, more specific therapy targets, and also markers for various behaviors within the condition, which will most likely lead us to an individualized management for these patients.

  4. Nuclear Molecular and Theranostic Imaging for Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Arif Sheikh


    Full Text Available Traditional nuclear medicine is rapidly being transformed by the evolving concepts in molecular imaging and theranostics. The utility of new approaches in differentiated thyroid cancer (DTC diagnostics and therapy has not been fully appreciated. The clinical information, relevant to disease management and patient care, obtained by scintigraphy is still being underestimated. There has been a trend towards moving away from the use of radioactive iodine (RAI imaging in the management of the disease. This paradigm shift is supported by the 2015 American Thyroid Association Guidelines (1. A more systematic and comprehensive understanding of disease pathophysiology and imaging methodologies is needed for optimal utilization of different imaging modalities in the management of DTC. There have been significant developments in radiotracer and imaging technology, clinically proven to contribute to the understanding of tumor biology and the clinical assessment of patients with DTC. The research and development in the field continues to evolve, with expected emergence of many novel diagnostic and therapeutic techniques. The role for nuclear imaging applications will continue to evolve and be reconfigured in the changing paradigm. This article aims to review the clinical uses and controversies surrounding the use of scintigraphy, and the information it can provide in assisting in the management and treatment of DTC.

  5. Advances in understanding the molecular mechanism of pancreatic cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Yong-Xing Du; Zi-Wen Liu; Lei You; Wen-Ming Wu; Yu-Pei Zhao


    BACKGROUND: Pancreatic cancer (PC) is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identiifed groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecu-lar mechanisms of PC metastasis. DATA SOURCES: Relevant articles on PC metastasis were searched in MEDLINE via PubMed prior to April 2015. The search was limited in English publications. RESULTS: PC metastatic cascades are multi-factorial events including both intrinsic and extrinsic elements. This review highlights the most important genetic alterations and other mechanisms that account for PC invasion and metastasis, with particular regard to epithelial-mesenchymal transition, inlfammation, stress response, and circulating tumor cells. CONCLUSIONS: Analyses of relevant gene functions and signaling pathways are needed to establish the gene regula-tory network and to deifne the pivotal modulators. Another promising area of study is the genotyping and phenotyping of circulating tumor cells, which could lead to a new era of per-sonalized therapy by identifying speciifc markers and targets.

  6. Genomic analyses identify molecular subtypes of pancreatic cancer. (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M


    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  7. Understanding the molecular pathogenesis and prognostics of bladder cancer: an overview. (United States)

    Zhao, Ming; He, Xiang-Lei; Teng, Xiao-Dong


    The knowledge of cellular mechanisms in malignances of the bladder has grown exponentially. Molecular technologies have led to the discovery of the molecular pathways distinguishing low-and high-grade urothelial neoplasms. This trend portends the future in which the classification and diagnosis of the bladder tumors through morphologic analysis will be supported by molecular information correlating with prognosis and targeted therapy. This article outlines tumor molecular pathology of bladder cancer with an emphasis on several promising candidate biomarkers that may soon make their transition to the realm of clinical management of bladder cancer.

  8. Current debate in the oncologic management of rectal cancer. (United States)

    Millard, Trish; Kunk, Paul R; Ramsdale, Erika; Rahma, Osama E


    Despite the considerable amount of research in the field, the management of locally advanced rectal cancer remains a subject to debate. To date, effective treatment centers on surgical resection with the standard approach of total mesorectal resection. Radiation therapy and chemotherapy have been incorporated in order to decrease local and systemic recurrence. While it is accepted that a multimodality treatment regimen is indicated, there remains significant debate for how best to accomplish this in regards to order, dosing, and choice of agents. Preoperative radiation is the standard of care, yet remains debated with the option for chemoradiation, short course radiation, and even ongoing studies looking at the possibility of leaving radiation out altogether. Chemotherapy was traditionally incorporated in the adjuvant setting, but recent reports suggest the possibility of improved efficacy and tolerance when given upfront. In this review, the major studies in the management of locally advanced rectal cancer will be discussed. In addition, future directions will be considered such as the role of immunotherapy and ongoing trials looking at timing of chemotherapy, inclusion of radiation, and non-operative management.

  9. Molecular genetic, diagnosis, prevention and gene therapy in prostatic cancer: review article

    Directory of Open Access Journals (Sweden)

    Noori Daloii MR


    Full Text Available "nThe prostate is a small gland located below the bladder and upper part of the urethra. In developed countries prostate cancer is the second common cancer (after skin cancer, and also the second leading cause of cancer death (after lung cancer among men. The several studies have been shown prostate cancer familial aggregation. The main reason for this aggregation is inheritance included genes. The family history is an important risk factor for developing the disease. The genes AR, CYP17, SRD5A2, HSD3B1 and HSD3B2 are all intimately involved in androgen metabolism and cell proliferation in the prostate. Each shows intraspecific polymorphism and variation among racial-ethnic groups that is associated with the risk of prostate cancer. Some of genes expressed in the prostate are in association with the production of seminal fluid and also with prostate cancer. Epigenetic modifications, specifically DNA hypermethylation, are believed to play an important role in the down-regulation of genes important for protection against prostate cancer. In prostate cancer numerous molecular and genetic aberrations have been described. It is now well established that cancer cells exhibit a number of genetic defects in apoptotic pathways. In this review article, the most recent data in molecular genetic, prevention and especially gene therapy in prostate cancer are introduced.

  10. Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

    Institute of Scientific and Technical Information of China (English)

    Anil; Suri; Nirmala; Jagadish; Shikha; Saini; Namita; Gupta


    Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.

  11. [Current progress in functions of axon guidance molecule Robo and underlying molecular mechanism]. (United States)

    Li, Xiao-Tong; Zhou, Qi-Sheng; Yu, Qi; Zhao, Xiao; Liu, Qing-Xin


    The axon guidance molecule Robo is a transmembrane protein which is conserved during evolution. Robo and its ligand, Slit, have been implicated in regulating many developmental processes, such as axon guidance, neuronal migration, tumor metastasis, angiogenesis, lung morphogenesis, kidney morphogenesis, heart morphogenesis, ovary development and gonad development. Robo function mainly depends on the binding of its Ig1 domain to the LRR-2 domain of Slit ligand. Meanwhile, Robo function is also mediated by binding to some signaling molecules, including the heparan sulfate proteoglycans (HSPGs), GTPase-activating proteins (GAPs) and tyrosine kinase Abelson. Several transcription factors, including Hox, Midline and Nkx2.9, were shown to regulate robo expression. In addition, alternative splicing and transport regulation also affect Robo function. In this review, we summarized the studies on the molecular structure, functions and molecular mechanism of Robo, which would propose a novel strategy for the research of neural development, as well as prevention and treatment of nervous system diseases and cancers.

  12. Preserving fertility in young patients with endometrial cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    Kalogera E


    Full Text Available Eleftheria Kalogera, Sean C Dowdy, Jamie N Bakkum-Gamez Division of Gynecologic Surgery, Mayo Clinic, Rochester, MN, USA Abstract: Endometrial cancer (EC is the most common gynecologic malignancy in developed countries and affects predominantly postmenopausal women. It is estimated, however, that 15%–25% of women will be diagnosed before menopause. As more women choose to defer childbearing until later in life, the feasibility and safety of fertility-sparing EC management have been increasingly studied. Definitive treatment of total hysterectomy and bilateral salpingo-oophorectomy precludes future fertility and may thus be undesirable by women who wish to maintain their reproductive potential. However, the consideration of conservative management carries the oncologic risks of unstaged EC and the risk of missing a synchronous ovarian cancer. It is further complicated by the lack of consensus regarding the initial assessment, treatment, and surveillance. Conservative treatment with progestins has been shown to be a feasible and safe fertility-sparing approach for women with low grade, early stage EC with no myometrial invasion. The two most commonly adopted regimens are medroxyprogesterone acetate at 500–600 mg daily and megestrol acetate at 160 mg daily for a minimum of 6–9 months, with initial response rates commonly reported between 60% and 80% and recurrence rates between 25% and 40%. Photodynamic therapy and hysteroscopic EC excision have recently been reported as alternative approaches to progestin therapy alone. However, limited efficacy and safety data exist. Live birth rates after progestin therapy have typically been reported around 30%; however, when focusing only on those who do pursue fertility after successful treatment, the live birth rates were found to be higher than 60%. Assisted reproductive technology has been associated with a higher live birth rate compared with spontaneous conception, most likely reflecting the

  13. Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Norihisa; Uemura; Tadashi; Kondo


    Neoadjuvant therapy has been proven to be extremely valuable and is widely used for advanced esophageal cancer. However, a significant proportion of treated patients(60%-70%) does not respond well to neoadjuvant treatments and develop severe adverse effects. Therefore, predictive markers for individualization of multimodality treatments are urgently needed in esophageal cancer. Recently, molecular biomarkers that predict the response to neoadjuvant therapy have been explored in multimodal approaches in esophageal cancer and successful examples of biomarker identification have been reported. In this review, promising candidates for predictive molecular biomarkers developed by using multiple molecular approaches are reviewed. Moreover, treatment strategies based on the status of predicted biomarkers are discussed, while considering the international differences in the clinical background. However, in the absence of adequate treatment options related to the results of the biomarker test, the usefulness of these diagnostic tools is limited and new effective therapies for biomarker-identified nonresponders to cancer treatment should be concurrent with the progress of predictive technologies. Further improvement in the prognosis of esophageal cancer patients can be achieved through the introduction of novel therapeutic approaches in clinical practice.

  14. Molecular approach to genetic and epigenetic pathogenesisof early-onset colorectal cancer

    Institute of Scientific and Technical Information of China (English)


    Colorectal cancer (CRC) is the third most frequent cancertype and the incidence of this disease is increasinggradually per year in individuals younger than 50 yearsold. The current knowledge is that early-onset CRC(EOCRC) cases are heterogeneous population thatincludes both hereditary and sporadic forms of theCRC. Although EOCRC cases have some distinguishingclinical and pathological features than elder age CRC,the molecular mechanism underlying the EOCRC ispoorly clarified. Given the significance of CRC in theworld of medicine, the present review will focus on therecent knowledge in the molecular basis of genetic andepigenetic mechanism of the hereditary forms of EOCRC,which includes Lynch syndrome, Familial CRC type X,Familial adenomatous polyposis, MutYH-associatedpolyposis, Juvenile polyposis syndrome, Peutz-JeghersSyndrome and sporadic forms of EOCRC. Recent findingsabout molecular genetics and epigenetic basis of EOCRCgave rise to new alternative therapy protocols. Althoughexact diagnosis of these cases still remains complicated,the present review paves way for better predictions andcontributes to more accurate diagnostic and therapeuticstrategies into clinical approach.

  15. A good molecular target for prostate cancer chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Sidney R Grimes


    @@ An exciting new basic medical research study shows that inhibition of the activity of the kinesin spindle protein Eg5 effectively blocks cell division and induces cell death in prostate cancer cells.1 The potent anticancer drug S-(methoxytrityl)-L-cysteine(S(MeO)TLC)spe-cifically blocks activity of Eg5 in prostate cancer cells, arrests cell division, induces cell death during mitosis and inhibits prostate cancer cells in a mouse model of prostate cancer.

  16. Molecular biomarker set for early detection of ovarian cancer

    KAUST Repository

    Bajic, Vladimir B.


    Embodiments of the present invention concern methods and compositions related to detection of ovarian cancer, including detection of the stage of ovarian cancer, in some cases. In particular, the invention encompasses use of expression of TFAP2A and in some embodiments CA125 and/or E2F5 to identify ovarian cancer, including detecting mRNA and/or protein levels of the respective gene products. Kits for detection of ovarian cancer are also described.

  17. 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


    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.

  18. Advances in the Development of Molecularly Targeted Agents in Non-Small-Cell Lung Cancer. (United States)

    Dolly, Saoirse O; Collins, Dearbhaile C; Sundar, Raghav; Popat, Sanjay; Yap, Timothy A


    Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that involves personalized strategies based on histological and molecular subtypes. The molecular era has revolutionized the treatment of patients harboring epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and ROS1 gene aberrations. In the appropriately selected population, anti-tumor agents against these molecular targets can significantly improve progression-free survival. However, the emergence of acquired resistance is inevitable. Novel potent compounds with much improved and rational selectivity profiles, such as third-generation EGFR T790M resistance mutation-specific inhibitors, have been developed and added to the NSCLC armamentarium. To date, attempts to overcome resistance bypass pathways through downstream signaling blockade has had limited success. Furthermore, the majority of patients still do not harbor known driver genetic or epigenetic alterations and/or have no new available treatment options, with chemotherapy remaining their standard of care. Several potentially actionable driver aberrations have recently been identified, with the early clinical development of multiple inhibitors against these promising targets currently in progress. The advent of immune checkpoint inhibitors has led to significant benefit for advanced NSCLC patients with durable responses observed. Further interrogation of the underlying biology of NSCLC, coupled with modern clinical trial designs, is now required to develop novel targeted therapeutics rationally matched with predictive biomarkers of response, so as to further advance NSCLC therapeutics through the next decade.

  19. Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

    Directory of Open Access Journals (Sweden)

    Alexandre Andrade dos Anjos Jácome


    Full Text Available Abstract: Approximately 90% of the world population is infected by Epstein-Barr virus (EBV. Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

  20. From bench to bedside: current and future applications of molecular profiling in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yousef George M


    Full Text Available Abstract Among the adult population, renal cell carcinoma (RCC constitutes the most prevalent form of kidney neoplasm. Unfortunately, RCC is relatively asymptomatic and there are no tumor markers available for diagnostic, prognostic or predictive purposes. Molecular profiling, the global analysis of gene and protein expression profiles, is an emerging promising tool for new biomarker identification in RCC. In this review, we summarize the existing knowledge on RCC regarding clinical presentation, treatment options, and tumor marker status. We present a general overview of the more commonly used approaches for molecular profiling at the genomic, transcriptomic and proteomic levels. We also highlight the emerging role of molecular profiling as not only revolutionizing the process of new tumor marker discovery, but also for providing a better understanding of the pathogenesis of RCC that will pave the way towards new targeted therapy discovery. Furthermore, we discuss the spectrum of clinical applications of molecular profiling in RCC in the current literature. Finally, we highlight some of the potential challenging that faces the era of molecular profiling and its transition into clinical practice, and provide an insight about the future perspectives of molecular profiling in RCC.

  1. Molecular and Clinical Predictors of Aggressive Prostate Cancer (United States)


    Trichomonas vaginalis and subsequent risk of prostate cancer. Cancer Epidemiology Biomarkers and Prevention 2006;15: 939-45. 12. Urisman A, Molinaro...combined with the findings of serologic evidence of T vaginalis and prostate cancer mortality provide supportive evidence for the study hypothesis

  2. Three interrelated themes in current breast cancer research: gene addiction, phenotypic plasticity, and cancer stem cells. (United States)

    Cardiff, Robert D; Couto, Suzana; Bolon, Brad


    Recent efforts to understand breast cancer biology involve three interrelated themes that are founded on a combination of clinical and experimental observations. The central concept is gene addiction. The clinical dilemma is the escape from gene addiction, which is mediated, in part, by phenotypic plasticity as exemplified by epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition. Finally, cancer stem cells are now recognized as the basis for minimal residual disease and malignant progression over time. These themes cooperate in breast cancer, as induction of epithelial-to-mesenchymal transition enhances self-renewal and expression of cancer stem cells, which are believed to facilitate tumor resistance.

  3. KRAS oncogene in lung cancer: focus on molecularly driven clinical trials

    Directory of Open Access Journals (Sweden)

    Emmanuelle Kempf


    Full Text Available KRAS mutations are the most frequent molecular abnormalities found in one out of four nonsmall cell lung cancers (NSCLC. Their incidence increases in cases of adenocarcinoma, smokers and Caucasian patients. Their negative value in terms of prognosis and responsiveness to both standard chemotherapy and targeted therapies remains under debate. Many drugs have been developed specifically for KRAS-mutated NSCLC patients. Direct inhibition of RAS activation failed to show any clinical efficacy. Inhibition of downstream targets of the mitogen-activated protein kinase (MEK pathway is a promising strategy: phase II combinations of MEK 1/2 kinase inhibitors with chemotherapy doubled patients’ clinical outcomes. One phase III trial in such a setting is ongoing. Double inhibition of MEK and epidermal growth factor receptor proteins is currently being assessed in early-phase trials. The association with mammalian target of rapamycin pathway inhibition leads to non-manageable toxicity. Other strategies, such as inhibition of molecular heat-shock proteins 90 or focal adhesion kinase are currently assessed. Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, showed promising results in a phase I trial, with a 54% disease control rate. Results of an ongoing phase III trial are warranted. Immunotherapy might be the next relevant step in KRAS-mutated NSCLC management due to the high burden of associated mutations and neo-antigens.

  4. Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers | Division of Cancer Prevention (United States)

    This randomized phase II trial studies the effects of aspirin and zileuton on genes related to tobacco use in current smokers. Aspirin and zileuton may interfere with genes related to tobacco use and may be useful in preventing lung cancer in current smokers. |

  5. Rationale and design of the Japan molecular epidemiology for lung cancer study. (United States)

    Kawaguchi, Tomoya; Ando, Masahiko; Ito, Norimasa; Isa, Shun-Ichi; Tamiya, Akihiro; Shimizu, Shigeki; Saka, Hideo; Kubo, Akihito; Koh, Yasuhiro; Matsumura, Akihide


    We present the rationale for the Japan Molecular Epidemiology for Lung Cancer study designed to elucidate molecular mechanisms of carcinogenesis in smokers and never-smokers with non-small-cell lung cancer. This prospective, ongoing, multicenter study is being conducted nationwide in Japan. Although there is no doubt that active smoking is the major cause of lung cancer, the contribution of other possible factors, including environmental tobacco or wood smoke, human papilloma virus, radon, occupational exposures, and genetic susceptibility, is highly likely, based on studies of never-smokers with non-small-cell lung cancer. Because of the predominance of women in the never-smoker subgroup, the role of female hormones in lung cancer development has also been considered. We hypothesize that driver mutations, which are critical for the development of lung cancer, are triggered by the environmental factors with or without the influence of the hormone. The SWOG-led intergroup molecular epidemiology study S0424 was conducted to focus on these issues by using a detailed questionnaire and specimen collection in statistically significant cohorts of smokers and never-smokers from both sexes. The Japan Molecular Epidemiology for Lung Cancer study follows and extends the S0424 molecular epidemiology concept in principle by using a similar approach that will facilitate future comparisons between the studies but with a greater focus on more recently defined driver mutations and broad genomic sequencing.

  6. Molecular targeted therapy in gastrointestinal cancer%胃肠癌分子靶向治疗

    Institute of Scientific and Technical Information of China (English)

    Miao Xiang; Ximing Xu


    Gastrointestinal cancer is one of the highly prevalent malignant diseases worldwide which is a major cause of morbidity and mortality. Gastric cancer is the second leading cause of cancer mortality in the world and its management,especially in advanced stages, has evolved relatively little [1]. Colorectal cancer (CRC) remains the third most common malignancy and the third leading cause of cancer death worldwide [2]. The surgical treatment is still the most effective therapy for the gastrointestinal cancer. However, the majority of the patients had lost the opporunity of surgical therapy when it was detected at advanced stage, so to seek means other than surgical treatment of gastrointestinal cancer metastasis and recurrence also has an important significance. With the deeping research of the molecular biology, molecular targeted therapy has become the hotspot and focus of comprehensive treatment of gastrointestinal cancer which is proposed against the molecular biological targets such as tumor cell growth, apoptosis, cell cycle, invasion and angiogenesis. Molecular targeted therapy can be grouped into six main areas: the epidermal growth factor receptor (EGFR) inhibitors, anti-angiogenic factors, cell cycle inhibitors, apoptosis promoters and matrix metalloproteinase innhibitors, cyclooxygenase inhibitors. The review of the progress are as follows.

  7. Research data supporting "Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer"



    Complete data set for the manuscript "Crowdsourcing the general public for large scale molecular pathology studies in cancer". Published at: This work was supported by the Cancer Research UK [C490/A10124, C490/A16561

  8. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.

    Directory of Open Access Journals (Sweden)

    Laetitia Marisa

    -free survival, even after adjusting for age, sex, stage, and the emerging prognostic classifier Oncotype DX Colon Cancer Assay recurrence score (hazard ratio 1.5, 95% CI 1.1-2.1, p = 0.0097. However, a limitation of this study is that information on tumor grade and number of nodes examined was not available. CONCLUSIONS: We describe the first, to our knowledge, robust transcriptome-based classification of CC that improves the current disease stratification based on clinicopathological variables and common DNA markers. The biological relevance of these subtypes is illustrated by significant differences in prognosis. This analysis provides possibilities for improving prognostic models and therapeutic strategies. In conclusion, we report a new classification of CC into six molecular subtypes that arise through distinct biological pathways.

  9. Molecular biology and riddle of cancer: the ‘Tom & Jerry’ show

    Directory of Open Access Journals (Sweden)

    Md. Al Mamun


    Full Text Available From the conventional Bird’s eye, cancer initiation and metastasis are generally intended to be understood beneath the light of classical clonal genetic, epigenetic and cancer stem cell model. But inspite decades of investigation, molecular biology has shown hard success to give Eagle’s eye in unraveling the riddle of cancer. And it seems, tiring Tom runs in vague behind naughty Jerry.

  10. [Progress of the micronucleus test in the field of molecular cancer epidemiology]. (United States)

    Xu, Huadong; Jia, Guang


    The micronucleus test (MNT) can be used to detect multiple genetic end points simultaneously, including chromosome aberration, mis-repaired DNA damage, apoptosis, parts of mutation and so on, which MNT has been an important part of the study of cancer epidemiology.Here, we reviewed the progress of MNT in the field of molecular cancer epidemiology in recent years, including early detection and diagnosis of cancer, evaluation of carcinogenic substances, genetic susceptibility biomarkers, micronutrient and cohort studies.

  11. Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. (United States)

    Polivka, Jiri; Janku, Filip


    Aberrations in various cellular signaling pathways are instrumental in regulating cellular metabolism, tumor development, growth, proliferation, metastasis and cytoskeletal reorganization. The fundamental cellular signaling cascade involved in these processes, the phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR), closely related to the mitogen-activated protein kinase (MAPK) pathway, is a crucial and intensively explored intracellular signaling pathway in tumorigenesis. Various activating mutations in oncogenes together with the inactivation of tumor suppressor genes are found in diverse malignancies across almost all members of the pathway. Substantial progress in uncovering PI3K/AKT/mTOR alterations and their roles in tumorigenesis has enabled the development of novel targeted molecules with potential for developing efficacious anticancer treatment. Two approved anticancer drugs, everolimus and temsirolimus, exemplify targeted inhibition of PI3K/AKT/mTOR in the clinic and many others are in preclinical development as well as being tested in early clinical trials for many different types of cancer. This review focuses on targeted PI3K/AKT/mTOR signaling from the perspective of novel molecular targets for cancer therapy found in key pathway members and their corresponding experimental therapeutic agents. Various aberrant prognostic and predictive biomarkers are also discussed and examples are given. Novel approaches to PI3K/AKT/mTOR pathway inhibition together with a better understanding of prognostic and predictive markers have the potential to significantly improve the future care of cancer patients in the current era of personalized cancer medicine.

  12. Organizing the Cellular and Molecular Heterogeneity in High Grade Serous Ovarian Cancer by Mass Cytometry (United States)


    or CyTOF (Cytometry by Time-Of-Flight), largely developed in our laboratory, for immunologic and cancer cell studies6-9. CyTOF uses antibodies...infiltrate of each individual sample (Figure 3). The choice of antibodies was from an extensive review of the literature, focused on ovarian and cancer ...Structured Immune System & Cancer Hierarchies, San Diego, CA 4. Nolan: StandUp2Cancer – Google [X] Immunology Summit, January 6, 2015, Current and Imminent

  13. Redox regulation of cancer metastasis: molecular signaling and therapeutic opportunities. (United States)

    Yang, Wenyong; Zou, Linzhi; Huang, Canhua; Lei, Yunlong


    Cancer metastasis is the major cause of cancer-related mortality. Accumulated evidence has shown that high-metastasis potential cancer cells have more reactive oxygen species (ROS) accumulation compared with low-metastasis potential cancer cells. ROS can function as second messengers to regulate multiple cancer metastasis-related signaling pathways via reversible oxidative posttranslational modifications of cysteine in key redox-sensitive proteins, which leads to the structural and functional change of these proteins. Because ROS can promote cancer metastasis, therapeutic strategies aiming at inducing/reducing cellular ROS level or targeting redox sensors involved in metastasis hold great potential in developing new efficient approaches for anticancer therapy. In this review, we summarize recent findings on regulation of tumor metastasis by key redox sensors and describe the potential of targeting redox signaling pathways for cancer therapy.

  14. Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development. (United States)

    Chung, Min-Yu; Lim, Tae Gyu; Lee, Ki Won


    Cancer is one of the leading causes of death worldwide. Commonly used cancer treatments, including chemotherapy and radiation therapy, often have side effects and a complete cure is sometimes impossible. Therefore, prevention, suppression, and/or delaying the onset of the disease are important. The onset of gastroenterological cancers is closely associated with an individual's lifestyle. Thus, changing lifestyle, specifically the consumption of fruits and vegetables, can help to protect against the development of gastroenterological cancers. In particular, naturally occurring bioactive compounds, including curcumin, resveratrol, isothiocyanates, (-)-epigallocatechin gallate and sulforaphane, are regarded as promising chemopreventive agents. Hence, regular consumption of these natural bioactive compounds found in foods can contribute to prevention, suppression, and/or delay of gastroenterological cancer development. In this review, we will summarize natural phytochemicals possessing potential antioxidant and/or anti-inflammatory and anti-carcinogenic activities, which are exerted by regulating or targeting specific molecules against gastroenterological cancers, including esophageal, gastric and colon cancers.

  15. Anesthesia and cancer recurrences: The current knowledge and evidence

    Directory of Open Access Journals (Sweden)

    Sukhminder Jit Singh Bajwa


    Full Text Available Surgical removal of solid tumors is of utmost importance as total resection can be curative. The surgical insult however itself may result in tumor micrometastasis coupled with depression of cell-mediated immunity culminating in tumor recurrence. Recent research suggests that few anesthetic agents or procedures can influence pathophysiology of metastasis in the postoperative period. Whereas opioids and volatile anesthetics have been implicated in angiogenesis and immunosuppression, evidences accumulated over the recent years have undoubtedly highlighted the attenuation of immunosuppression by regional anesthetic agents thereby making it superior over general anesthesia in preventing cancer recurrence. As anesthetic drugs are given at that time when patient is at the maximum risk of spread of metastasis, thus an understanding of the effect of anesthesia drugs and their impact on tumor metastasis is important so that appropriate anesthetic strategy can be made to improve long term survival in these patients. The purpose of the present review is therefore to emphasize the pivotal role of various anesthetic agents and anesthesia techniques in preventing tumor recurrence after surgery.

  16. Current opinion on lymphadenectomy in pancreatic cancer surgery

    Institute of Scientific and Technical Information of China (English)

    Theodoros E Pavlidis; Efstathios T Pavlidis; Athanasios K Sakantamis


    BACKGROUND: Adenocarcinoma of the pancreas exhibits aggressive behavior in growth, inducing an extremely poor prognosis with an overall median 5-year survival rate of only 1%-4%. Curative resection is the only potential therapeutic opportunity. DATA  SOURCES: A PubMed search of relevant articles published up to 2009 was performed to identify information about the value of lymphadenectomy and its extent in curative resection of pancreatic adenocarcinoma. RESULTS: Despite recent advances in chemotherapy, radio-therapy or even immunotherapy, surgery still remains the major factor that affects the outcome. The initial promising performance in Japan gave conflicting results in Western countries for the extended and more radical pancreatectomy;it has failed to prove beneficial. Four prospective, randomized trials on extended versus standard lymphadenectomy during pancreatic cancer surgery have shown no improvement in long-term survival by the extended resection. The exact lymph node status, including malignant spread and the total number retrieved as well as the lymph node ratio, is the most important prognostic factor. Positive lymph nodes after pancreatectomy are present in 70%. Paraaortic lymph node spread indicates poor prognosis. CONCLUSIONS: Undoubtedly, a standard lymphadenectomy including >15 lymph nodes must be no longer preferred in patients with the usual head location. The extended lymphadenectomy does not have any place, unless in randomized trials. In cases with body or tail location, the radical antegrade modular pancreatosplenectomy gives promising results. Nevertheless, accurate localization and detailed examination of the resected specimen are required for better staging.

  17. Immunotherapy of Head and Neck Cancer: Current and Future Considerations

    Directory of Open Access Journals (Sweden)

    Alexander D. Rapidis


    Full Text Available Patients with head and neck squamous cell carcinoma (HNSCC are at considerable risk for death, with 5-year relative survival rates of approximately 60%. The profound multifaceted deficiencies in cell-mediated immunity that persist in most patients after treatment may be related to the high rates of treatment failure and second primary malignancies. Radiotherapy and chemoradiotherapy commonly have severe acute and long-term side effects on immune responses. The development of immunotherapies reflects growing awareness that certain immune system deficiencies specific to HNSCC and some other cancers may contribute to the poor long-term outcomes. Systemic cell-mediated immunotherapy is intended to activate the entire immune system and mount a systemic and/or locoregional antitumor response. The delivery of cytokines, either by single cytokines, for example, interleukin-2, interleukin-12, interferon-, interferon-, or by a biologic mix of multiple cytokines, such as IRX-2, may result in tumor rejection and durable immune responses. Targeted immunotherapy makes use of monoclonal antibodies or vaccines. All immunotherapies for HNSCC except cetuximab remain investigational, but a number of agents whose efficacy and tolerability are promising have entered phase 2 or phase 3 development.

  18. Robotic Radical Cystectomy for Bladder Cancer: Current Perspectives

    Directory of Open Access Journals (Sweden)

    Abdullah Erdem Canda


    Full Text Available The most effective local treatment of muscle invasive bladder cancer and non-invasive, high-grade bladder tumours that recur or progress despite intravesical therapies, is open radical cystectomy (RC, extended pelvic lymph node (LN dissection with urinary diversion. Performing these complex procedures using pure laparoscopy is extremely difficult. On the other hand, the surgical robot has the advantage of enabling the console surgeon to perform complex procedures more easily, providing three-dimensional (3D and magnified views, higher grades of wristed hand movements, and decreased hand tremor, while the fourth robotic arm offers additional assistance and tissue retraction which facilitates the learning curve. The number of centres performing robot-assisted radical cystectomy (RARC is increasing. Although most of the centres perform extracorporeal urinary diversion following RARC, very few centres – including ours – have reported their outcomes on RARC with total intracorporeal urinary diversion. Some of the articles, comparing open RC versus RARC, have suggested similar outcomes in terms of operative time, mean LN yield, positive surgical margin (PSM rates, and complication rates, whereas others have suggested decreased estimated blood loss, transfusion rate, complications, length of hospital stay, wound problems, time to flatus, and time to regular diet in the postoperative period in RARC patients. The surgical technique of total intracorporeal RARC with urinary diversions is still evolving, and these complex robotic procedures seem to be technically feasible with good intermediate-term oncologic results, acceptable morbidities, excellent short-term surgical and pathological outcomes, and satisfactory functional results.

  19. Intensity modulated radiation therapy for breast cancer: current perspectives (United States)

    Buwenge, Milly; Cammelli, Silvia; Ammendolia, Ilario; Tolento, Giorgio; Zamagni, Alice; Arcelli, Alessandra; Macchia, Gabriella; Deodato, Francesco; Cilla, Savino; Morganti, Alessio G


    Background Owing to highly conformed dose distribution, intensity modulated radiation therapy (IMRT) has the potential to improve treatment results of radiotherapy (RT). Postoperative RT is a standard adjuvant treatment in conservative treatment of breast cancer (BC). The aim of this review is to analyze available evidence from randomized controlled trials (RCTs) on IMRT in BC, particularly in terms of reduction of side effects. Methods A literature search of the bibliographic database PubMed, from January 1990 through November 2016, was performed. Only RCTs published in English were included. Results Ten articles reporting data from 5 RCTs fulfilled the selection criteria and were included in our review. Three out of 5 studies enrolled only selected patients in terms of increased risk of toxicity. Three studies compared IMRT with standard tangential RT. One study compared the results of IMRT in the supine versus the prone position, and one study compared standard treatment with accelerated partial breast IMRT. Three studies reported reduced acute and/or late toxicity using IMRT compared with standard RT. No study reported improved quality of life. Conclusion IMRT seems able to reduce toxicity in selected patients treated with postoperative RT for BC. Further analyses are needed to better define patients who are candidates for this treatment modality. PMID:28293119

  20. Recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, Karsten; Ørntoft, Torben Falck


    individually contributed to the management of the disease. However, the development of high-throughput techniques for simultaneous assessment of a large number of markers has allowed classification of tumors into clinically relevant molecular subgroups beyond those possible by pathological classification. Here......, we review the recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers....

  1. The current pattern of reconstructive surgery for breast cancer

    Directory of Open Access Journals (Sweden)

    A. Kh. Ismagilov


    Full Text Available In Russia, breast cancer (BC occupies a leading place in the pattern of cancers, the incidence of which is 20.9 %, among the female population; in 2013 there were 60,717 new cases, including women under the age of 40 years (15 %. While considering the history of the development of breast surgery from the operation performed by W. S. Halsted to its technique modified by J. L. Madden and the identification of sentinel lymph nodes, we can observe improved quality of life in patients in reference to the lower rate of the manifestation of lymphedemas. However, patients who have undergone this or that mastectomy are observed to have lower self-appraisal scores, a change in their professional sphere, irritability and apprehensiveness Thus, the decreased rate of the manifestation of lymphedema and obvious postoperative traumatization are not the only components of quality of life in patients with BC. According to the data obtained by E. Frank et al. (1978, G.P. Maguire et al. (1978, and F. Meerwein (1981, removal of the breast itself leads to a woman’s loss of femininity, attractiveness, and sexiness, which was also confirmed and reported by L. Aerts et al. (2014. In this connection, classical radical mastectomy begins to give way to organ-sparing treatment. Taking into account that psychotherapy and external prosthetics do not alleviate the above problems and that there are always women with established BC who have contraindications to organ-sparing treatment, breast reconstructive plastic operations arouse more and more interest. Reconstruction of the breast implies restoration of both its shape and contours to be maximally brought closer to its preoperative level. However, with regard to cancer alertness to breast reconstructive surgery, not only aesthetic requirements are imposed. The next step in improving quality of life in patients with BC was the emergence and development of breast-sparing mastectomies, the first point of these

  2. Induction chemotherapy for oral cavity cancer patients: Current status and future perspectives. (United States)

    Marta, Gustavo Nader; William, William N; Feher, Olavo; Carvalho, André Lopes; Kowalski, Luiz Paulo


    There is a lack of data from phase III randomized studies to support an ideal approach for locally advanced oral cavity cancer patients. In general, surgery, radiotherapy and chemotherapy are valid treatment options, and combined approach is usually indicated given poor clinical outcomes with single modality therapy. The aim of this study is to review the current status and future perspectives of induction chemotherapy for locally advanced oral cavity cancer patients.


    Directory of Open Access Journals (Sweden)

    Orlin Savov


    Full Text Available The aim of this publication includes the try to act as intermediary to the readers, which should be able to understand: - The description of the cancer immunotherapy mechanisms in the context of current therapy decisions for the treatment of cancer - The including criteria for those patients with cancer who could be appropriate candidates for immunotherapy - And to optimize patient outcomes by using best practices to manage the adverse events associated with immunotherapy treatment More than 15 promising immunotherapy approaches being tested in clinical trials with appropriate patients and colleagues for enrollment and peer-to-peer education purposes, respectively.

  4. Current Challenges in Prostate Cancer Management and the Rationale behind Targeted Focal Therapy

    Directory of Open Access Journals (Sweden)

    Al B. Barqawi


    Full Text Available Among men, prostate cancer has a high prevalence, with relatively lower cancer-specific mortality risk compared to lung and colon cancer. Prostate-specific antigen (PSA screening has increased prostate cancer awareness since its implementation as a screening tool almost 25 years ago, but, due to the largely indolent course of this disease and the unspecific nature of the PSA test, increased incidence has largely been associated with cancers that would not go on to cause death (clinically insignificant, leading to an overdiagnosis challenge and an ensuing overtreatment consequences. The overtreatment problem is exacerbated by the high risk of side effects that current treatment techniques have, putting patients’ quality of life at risk with little or no survival benefit. The goals of this paper are to evaluate the rise, prevalence, and impact of the overdiagnosis and ensuing overtreatment problems, as well as highlight potential solutions. In this effort, a review of major epidemiological and screening studies, cancer statistics from the advent of prostate-specific antigen screening to the present, and reports on patient concerns and treatment outcomes was conducted to present the dominant factors that underlie current challenges in prostate cancer treatment and illuminate potential solutions.

  5. Biologia molecular do câncer cervical Molecular biology of cervical cancer

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    Waldemar Augusto Rivoire


    Full Text Available A carcinogênese é um processo de múltiplas etapas. Alterações no equilíbrio citogenético ocorrem na transformação do epitélio normal a câncer cervical. Numerosos estudos apoiam a hipótese de que a infecção por HPV está associada com o desenvolvimento de alterações malignas e pré-malignas do trato genital inferior. Neste trabalho são apresentadas as bases para a compreensão da oncogênese cervical. O ciclo celular é controlado por proto-oncogenes e genes supressores. Quando ocorrem mutações, proto-oncogenes tornam-se oncogenes, que são carcinogênicos e causam multiplicação celular excessiva. A perda da ação de genes supressores funcionais pode levar a célula ao crescimento inadequado. O ciclo celular também pode ser alterado pela ação de vírus, entre eles o HPV (Human Papiloma Virus, de especial interesse na oncogênese cervical. Os tipos de HPV 16 e 18 são os de maior interesse, freqüentemente associados a câncer cervical e anal. O conhecimento das bases moleculares que estão envolvidas na oncogênese cervical tem sido possível devido a utilização de técnicas avançadas de biologia molecular. A associação destas técnicas aos métodos diagnósticos clássicos, poderão levar a uma melhor avaliação das neoplasias cervicais e auxiliar no desenvolvimento de novas terapias, talvez menos invasivas e mais efetivas.Carcinogenesis involves several steps. Disorders of the cytogenetic balance occur during the evolution from normal epithelium to cervical cancer. Several studies support the hypothesis that the Human Papiloma Virus (HPV infection is associated to development of premalignant and malignant lesions of cervical cancer. In this review we show the basis to understand cervical oncogenesis. The cell cycle is controlled by protooncogenes and supressive genes. This orchestrated cell cycle can be affected by virus such as HPV. Of special interest in the cervical carcinogenesis are the HPV subtypes 16 and 18

  6. Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer (United States)


    will use a recombinant molecular biology platform to produce a series of molecular grenades, each based upon the bacterial toxin proaerolysin, but...Engineer enzymatically cleavable linker for the release and activation of PA from HSA with lead peptides. Using standard molecular biology techniques to...mouse models. Other avenues of training enrichment include attending the biannual Prostate Cancer United Kingdom meeting which arranged PCa

  7. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease]. (United States)

    Maroto Rey, José Pablo; Cillán Narvaez, Elena


    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  8. Definition of molecular determinants of prostate cancer cell bone extravasation. (United States)

    Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J


    Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

  9. Molecular Epidemiology Investigation of Obesity and Lethal Prostate Cancer (United States)


    unmethylated and active, a cryptic promoter located within the 5ʹ end of IAP’s long terminal repeat hijacks the transcriptional control of the agouti gene...methyl donors.88 Alternatively, peri-conceptional feeding of a methyl- deficient diet to female sheep resulted in adult offspring with CpG islands that...and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin 2012; 62

  10. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Frolich, Camilla; Albrechtsen, Reidar; Andersen, Lars Dyrskjøt


    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...

  11. What are the current barriers to effective cancer care coordination? A qualitative study

    Directory of Open Access Journals (Sweden)

    Solomon Michael J


    Full Text Available Abstract Background National cancer policies identify the improvement of care coordination as a priority to improve the delivery of health services for people with cancer. Identification of the current barriers to effective cancer care coordination is needed to drive service improvement. Methods A qualitative study was undertaken in which semi-structured individual interviews and focus groups were conducted with those best placed to identify issues; patients who had been treated for a range of cancers and their carers as well as health professionals involved in providing cancer care. Data collection continued until saturation of concepts was reached. A grounded theory influenced approach was used to explore the participants' experiences and views of cancer care coordination. Results Overall, 20 patients, four carers and 29 health professionals participated. Barriers to cancer care coordination related to six aspects of care namely, recognising health professional roles and responsibilities, implementing comprehensive multidisciplinary team meetings, transitioning of care: falling through the cracks, inadequate communication between specialist and primary care, inequitable access to health services and managing scarce resources. Conclusions This study has identified a number of barriers to coordination of cancer care. Development and evaluation of interventions based on these findings is now required.

  12. Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives

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    McClung EC


    Full Text Available E Clair McClung, Robert M WenhamDepartment of Gynecologic Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USAAbstract: Patients with platinum-resistant ovarian cancer have progression of disease within 6 months of completing platinum-based chemotherapy. While several chemotherapeutic options exist for the treatment of platinum-resistant ovarian cancer, the overall response to any of these therapies is ~10%, with a median progression-free survival of 3–4 months and a median overall survival of 9–12 months. Bevacizumab (Avastin, a humanized, monoclonal antivascular endothelial growth factor antibody, has demonstrated antitumor activity in the platinum-resistant setting and was recently approved by US Food and Drug Administration for combination therapy with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. This review summarizes key clinical trials investigating bevacizumab for recurrent, platinum-resistant ovarian cancer and provides an overview of efficacy, safety, and quality of life data relevant in this setting. While bevacizumab is currently the most studied and clinically available antiangiogenic therapy, we summarize recent studies highlighting novel alternatives, including vascular endothelial growth factor-trap, tyrosine kinase inhibitors, and angiopoietin inhibitor trebananib, and discuss their application for the treatment of platinum-resistant ovarian cancer.Keywords: bevacizumab, angiogenesis, ovarian cancer, platinum-resistant ovarian cancer, recurrent ovarian cancer

  13. Meta-analysis of cancer transcriptomes: A new approach to uncover molecular pathological events in different cancer tissues

    Directory of Open Access Journals (Sweden)

    Sundus Iqbal


    Full Text Available To explore secrets of metastatic cancers, individual expression of true sets of respective genes must spread across the tissue. In this study, meta-analysis for transcriptional profiles of oncogenes was carried out to hunt critical genes or networks helping in metastasizing cancers. For this, transcriptomic analysis of different cancerous tissues causing leukemia, lung, liver, spleen, colorectal, colon, breast, bladder, and kidney cancers was performed by extracting microarray expression data from online resource; Gene Expression Omnibus. A newly developed bioinformatics technique; Dynamic Impact Approach (DIA was applied for enrichment analysis of transcriptional profiles using Database for Annotation Visualization and Integrated Discovery (DAVID. Furthermore, oPOSSUM (v. 2.0 and Cytoscape (v. 2.8.2 were used for in-depth analysis of transcription factors and regulatory gene networks respectively. DAVID analysis uncovered the most significantly enriched pathways in molecular functions that were 'Ubiquitin thiolesterase activity' up regulated in blood, breast, bladder, colorectal, lung, spleen, prostrate cancer. 'Transforming growth factor beta receptor activity' was inhibited in all cancers except leukemia, colon and liver cancer. oPOSSUM further revealed highly over-represented Transcription Factors (TFs; Broad-complex_3, Broad-complex_4, and Foxd3 except for leukemia and bladder cancer. From these findings, it is possible to target genes and networks, play a crucial role in the development of cancer. In the future, these transcription factors can serve as potential candidates for the therapeutic drug targets which can impede the deadly spread.

  14. Three interrelated themes in current breast cancer research: gene addiction, phenotypic plasticity, and cancer stem cells



    Recent efforts to understand breast cancer biology involve three interrelated themes that are founded on a combination of clinical and experimental observations. The central concept is gene addiction. The clinical dilemma is the escape from gene addiction, which is mediated, in part, by phenotypic plasticity as exemplified by epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition. Finally, cancer stem cells are now recognized as the basis for minimal residual disease an...

  15. Earlier Detection of Breast Cancer with Ultrasound Molecular Imaging in a Transgenic Mouse Model (United States)

    Bachawal, Sunitha V.; Jensen, Kristin C.; Lutz, Amelie M.; Gambhir, Sanjiv S.; Tranquart, Francois; Tian, Lu; Willmann, Jürgen K.


    While there is an increasing role of ultrasound for breast cancer screening in patients with dense breast, conventional anatomical-ultrasound lacks sensitivity and specificity for early breast cancer detection. In this study we assessed the potential of molecular-ultrasound imaging, using clinically-translatable vascular endothelial growth factor receptor (VEGFR2)-targeted microbubbles (MBVEGFR2), to improve the diagnostic accuracy of ultrasound in earlier detection of breast cancer and ductal carcinoma in situ (DCIS) in a transgenic mouse model (FVB/N-Tg(MMTV-PyMT)634Mul). In vivo binding specificity studies (n=26 tumors) showed that ultrasound imaging signal was significantly higher (P95% of cases and highly agreed between each other (ICC=0.98; 95% CI, 97, 99). These results suggest that VEGFR2-targeted ultrasound molecular imaging allows highly accurate detection of DCIS and breast cancer in transgenic mice and may be a promising approach for early breast cancer detection in women. PMID:23328585

  16. Clinical Distribution and Molecular Basis of Traditional Chinese Medicine ZHENG in Cancer

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    Zhen Chen


    Full Text Available In traditional Chinese medicine (TCM clinical practice, ZHENG (also known as syndrome helps to guide design of individualized treatment strategies. In this study, we investigated the clinical use of ZHENG in TCM-treated cancer patients by systematically analyzing data from all relevant reports in the Chinese-language scientific literature. We aimed to determine the clinical ZHENG distributions in six common cancers (lung, liver, gastric, breast, colorectal, and pancreatic with the expectation of uncovering a theoretical basis for TCM ZHENG as a clinical cancer treatment. In addition, we also reviewed the molecular basis underlying Xue-Yu (blood stasis, Shi-Re (dampness-heat, Yin-Xu (Yin deficiency, and Pi-Xu (spleen deficiency ZHENG that are commonly found in cancer patients. The results from our summary study provide insights into the potential utility of TCM ZHENG and may contribute to a better understanding of the molecular basis of TCM ZHENG in cancer.

  17. Accurate molecular classification of cancer using simple rules

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    Gotoh Osamu


    Full Text Available Abstract Background One intractable problem with using microarray data analysis for cancer classification is how to reduce the extremely high-dimensionality gene feature data to remove the effects of noise. Feature selection is often used to address this problem by selecting informative genes from among thousands or tens of thousands of genes. However, most of the existing methods of microarray-based cancer classification utilize too many genes to achieve accurate classification, which often hampers the interpretability of the models. For a better understanding of the classification results, it is desirable to develop simpler rule-based models with as few marker genes as possible. Methods We screened a small number of informative single genes and gene pairs on the basis of their depended degrees proposed in rough sets. Applying the decision rules induced by the selected genes or gene pairs, we constructed cancer classifiers. We tested the efficacy of the classifiers by leave-one-out cross-validation (LOOCV of training sets and classification of independent test sets. Results We applied our methods to five cancerous gene expression datasets: leukemia (acute lymphoblastic leukemia [ALL] vs. acute myeloid leukemia [AML], lung cancer, prostate cancer, breast cancer, and leukemia (ALL vs. mixed-lineage leukemia [MLL] vs. AML. Accurate classification outcomes were obtained by utilizing just one or two genes. Some genes that correlated closely with the pathogenesis of relevant cancers were identified. In terms of both classification performance and algorithm simplicity, our approach outperformed or at least matched existing methods. Conclusion In cancerous gene expression datasets, a small number of genes, even one or two if selected correctly, is capable of achieving an ideal cancer classification effect. This finding also means that very simple rules may perform well for cancerous class prediction.

  18. Sentinel Node Mapping for Breast Cancer: Current Situation

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    Sergi Vidal-Sicart


    Full Text Available Axillary node status is a major prognostic factor in early-stage disease. Traditional staging needs levels I and II axillary lymph node dissection. Axillary involvement is found in 10%–30% of patients with T1 (<2 cm tumours. Sentinel lymph node biopsy is a minimal invasive method of checking the potential nodal involvement. It is based on the assumption of an orderly progression of lymph node invasion by metastatic cells from tumour site. Thus, when sentinel node is free of metastases the remaining nodes are free, too (with a false negative rate lesser than 5%. Moreover, Randomized trials demonstrated a marked reduction of complications associated with the sentinel lymph node biopsy when compared with axillary lymph node dissection. Currently, the sentinel node biopsy procedure is recognized as the standard treatment for stages I and II. In these stages, this approach has a positive node rate similar to those observed after lymphadenectomy, a significant decrease in morbidity and similar nodal relapse rates at 5 years. In this review, the indications and contraindications of the sentinel node biopsy are summarized and the methodological aspects discussed. Finally, the new technologic and histologic developments allow to develop a more accurate and refinate technique that can achieve virtually the identification of 100% of sentinel nodes and reduce the false negative rate.

  19. Current and Potential Uses of Immunocytokines as Cancer Immunotherapy

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    Paul M. Sondel


    Full Text Available Immunocytokines (ICs are a class of molecules created by linking tumor-reactive monoclonal antibodies to cytokines that are able to activate immune cells. Tumor selective localization is provided by the ability of the mAb component to bind to molecules found on the tumor cell surface or molecules found selectively in the tumor microenvronment. In this way the cytokine component of the immunocytokine is selectively localized to sites of tumor and can activate immune cells with appropriate receptors for the cytokine. Immunocytokines have been made and tested by us, and others, using a variety of tumor-reactive mAbs linked to distinct cytokines. To date, the majority of clinical progress has been made with ICs that have linked human interleukin-2 (IL2 to a select number of tumor reactive mAbs that had already been in prior clinical testing as non-modified mAbs. Here we briefly review the background for the creation of ICs, summarize current clinical progress, emphasize mechanisms of action for ICs that are distinct from those of their constituent components, and present some directions for future development and testing.

  20. Is diabetes a causal agent for colorectal cancer? Pathophysiological and molecular mechanisms

    Institute of Scientific and Technical Information of China (English)

    Olga Giouleme; Michael D Diamantidis; Marios G Katsaros


    The possible relationship between diabetes mellitus (DM) and colorectal cancer (CRC), concerning pathophysiological and molecular mechanisms is highlighted in this review. The most recent and complete articles and developments in this particular field were thoroughly reviewed. Common risk factors, such as obesity, sedentary lifestyle, and Western diet between DM and CRC, led to the theory that DM might be a causal agent for CRC development. Various studies have connected type 2 DM and CRC, either proximal or distal, in both sexes. Additionally, chronic insulin treatment has been linked with increased colorectal tumor risk among type 2 diabetic patients. Interestingly, elevated hemoglobin A1c has been proven to be an independent predictor of aggressive clinical behavior in CRC patients. These mechanisms include the insulin-like growth factor-hyperinsulinemia theory and the participation of oncogenic intracellular signaling pathways. Furthermore, it has been proposed that Cox-2 inhibitors might have a role in decreasing the incidence of CRC. Finally, the use of statins to reduce the risk for colon cancer in patients with diabetes has remained controversial. Diabetic patients over 50 should receive counseling regarding their elevated risk for CRC, and screening colonoscopy should be recommended before initiating insulin therapy. However, there are no current guidelines, and this strategy is not yet applicable to some countries, as the corresponding risk would not allow screening colonoscopy to be adopted. There is strong evidence to indicate that DM is a causal agent for CRC development. This conclusion provides new impetus for re-evaluating CRC screening worldwide.

  1. Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis. (United States)

    Yeung, Tsz-Lun; Leung, Cecilia S; Yip, Kay-Pong; Au Yeung, Chi Lam; Wong, Stephen T C; Mok, Samuel C


    Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the "seed-and-soil" hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

  2. Progresses in molecular imaging of prostate cancer%前列腺癌的分子影像学进展

    Institute of Scientific and Technical Information of China (English)

    范校周; 郭燕丽


    前列腺癌是严重威胁男性健康的疾病.分子影像学的出现,从一个全新角度为前列腺癌的早期诊断与治疗提供了可能,新的前列腺癌标志物也不断出现.本文对当前分子影像学技术,包括核素显像、MRI、超声和光学技术在前列腺癌诊治中的应用进展进行回顾.%Prostate cancer is a serious threat to male health, and the development of molecular imaging provides the possibility for early diagnosis and treatment of prostate cancer from a new perspective. With the emerging markers of prostate cancer, the current modalities of molecular imaging, including radionuclide imaging, MRI, ultrasound and optical imaging in diagnosis and treatment of prostate cancer were reviewed in this article.

  3. Excerpts from the 1st international NTNU symposium on current and future clinical biomarkers of cancer

    DEFF Research Database (Denmark)

    Robles, Ana I; Olsen, Karina Standahl; Tsui, Dana W T;


    The goal of biomarker research is to identify clinically valid markers. Despite decades of research there has been disappointingly few molecules or techniques that are in use today. The "1st International NTNU Symposium on Current and Future Clinical Biomarkers of Cancer: Innovation and Implement......The goal of biomarker research is to identify clinically valid markers. Despite decades of research there has been disappointingly few molecules or techniques that are in use today. The "1st International NTNU Symposium on Current and Future Clinical Biomarkers of Cancer: Innovation...

  4. The origin, dynamics, and molecular evolution of transmissible cancers

    Directory of Open Access Journals (Sweden)

    Jones EA


    Full Text Available Elizabeth A Jones, Yuanyuan Cheng, Katherine BelovFaculty of Veterinary Science, University of Sydney, NSW, AustraliaAbstract: Three transmissible cancers are known to have emerged naturally in the wild: canine transmissible venereal tumor (CTVT; Tasmanian devil facial tumor disease (DFTD; and a recently discovered leukemia-like cancer in soft-shell clams (Mya arenaria. These cancers have all acquired the ability to pass between individuals. DFTD emerged approximately 20 years ago and has decimated the Tasmanian devil population. CTVT arose over 10,000 years ago in an ancient breed of dog. The clam cancer is believed to have evolved at least 40 years ago. In this manuscript, we review CTVT and DFTD, the two transmissible mammalian cancers, and provide an overview of the leukemia-like cancer of clams. We showcase how genetics and genomics have enhanced our understanding of the unique biology, origins, and evolutionary histories of these rare cancers.Keywords: transmissible cancer, devil facial tumor disease, DFTD, canine transmissible venereal tumor, origin, evolution

  5. Molecular epidemiology of and genetic susceptibility to esophageal cancer. (United States)

    Bajpai, Manisha; Das, Kiron M; Lefferts, Joel; Lisovsky, Mikhail; Mashimo, Hiroshi; Phillips, Wayne A; Srivastava, Amitabh; To, Henry


    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on clonal evolution in Barrett's carcinogenesis; biomarkers for early detection of esophageal cancer; the role of the methylguanine methyl transferase biomarker in the management of adenocarcinoma; and the discovery of high-risk genes in families.

  6. Molecular genetics of cancer and tumorigenesis: Drosophila models

    Institute of Scientific and Technical Information of China (English)

    Wu-Min Deng


    Why do some cells not respond to normal control of cell division and become tumorous? Which signals trigger some tumor cells to migrate and colonize other tissues? What genetic factors are responsible for tumorigenesis and cancer development? What environmental factors play a role in cancer formation and progression? In how many ways can our bodies prevent and restrict the growth of cancerous cells?How can we identify and deliver effective drugs to fight cancer? In the fight against cancer,which kills more people than any other disease,these and other questions have long interested researchers from a diverse range of fields.To answer these questions and to fight cancer more effectively,we must increase our understanding of basic cancer biology.Model organisms,including the fruit fly Drosophila melanogaster,have played instrumental roles in our understanding of this devastating disease and the search for effective cures.Drosophila and its highly effective,easy-touse,and ever-expanding genetic tools have contributed toand enriched our knowledge of cancer and tumor formation tremendously.

  7. Molecular Indicators of Castration-Resistant Prostate Cancer (United States)


    two components /kits. Briefly, the ProstateCancerSelect (Product No. T-1-520) kit was used to enrich CTC from 5ml blood using magnetic particles PatientsWithMetastatic Castration-Resistant Prostate Cancer Emmanuel S. Antonarakis, MD; Changxue Lu, PhD; Brandon Luber, ScM ; HaoWang, PhD; Yan

  8. The Genetics and Molecular Alterations of Pancreatic Cancer

    NARCIS (Netherlands)

    Wilde, R.F. de


    The prospect that pancreatic cancer will be the second most common cause of cancer death by 2030 is worrisome. Considering that the approximate 6% overall 5-year survival has not merely changed in the past decades illustrates the need to revert the bleak prognosis. Centralization of surgery (pancr

  9. NIH scientists identify molecular link between metabolism and breast cancer (United States)

    A protein associated with conditions of metabolic imbalance, such as diabetes and obesity, may play a role in the development of aggressive forms of breast cancer, according to new findings by researchers at the National Cancer Institute (NCI), part of th

  10. In search of molecular approaches to improving cancer therapy efficacy. (United States)

    Cherepenko, E; Telegeev, G


    The study of genome rearrangement sites using full genome sequences is an important approach to revealing the nature of cancer and finding effective ways for cancer treatment. The progress in DNA sequencing could make the procedure of whole genome reading close to routine procedure of lower cost. The personal analysis of rearranged ends (PARE) method used for rearrangement study is reviewed. PARE allows identifying of individual cancer biomarkers making personal medicine possible. Also, the progress in "liquid biopsy" technology based on detection of circulating tumor cells in the patient's blood is shortly summarized. Another important approach is the discovered phenomenon of synthetic lethality causing cancer cell death due to appropriate combination of mutations in different genes or inhibitors of their protein products. Studies of genome rearrangements and synthetic lethality are considered promising for the development of effective cancer treatment approaches.

  11. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise;


    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined...... by microarray analysis, and the level of ADAM12 mRNA correlated with disease stage. Reverse transcription-PCR, quantitative PCR, and in situ hybridization validated the gene expression results. Using immunohistochemistry, we found ADAM12 protein expression correlated with tumor stage and grade. Finally, ADAM12...

  12. Ab initio theory for current-induced molecular switching: Melamine on Cu(001)

    KAUST Repository

    Ohto, Tatsuhiko


    Melamine on Cu(001) is mechanically unstable under the current of a scanning tunneling microscope tip and can switch among configurations. However, these are not equally accessible, and the switching critical current depends on the bias polarity. In order to explain such rich phenomenology, we have developed a scheme to evaluate the evolution of the reaction paths and activation barriers as a function of bias, which is rooted in the nonequilibrium Green\\'s function method implemented within density functional theory. This, combined with the calculation of the inelastic electron tunneling spectroscopy signal, allows us to identify the vibrational modes promoting the observed molecular conformational changes. Finally, once our ab initio results are used within a resonance model, we are able to explain the details of the switching behavior, such as its dependence on the bias polarity, and the noninteger power relation between the reaction rate constants and both the bias voltage and the electric current. © 2013 American Physical Society.

  13. Lung cancer in never smokers: change of a mindset in the molecular era. (United States)

    Lee, Young Joo; Kim, Joo-Hang; Kim, Se Kyu; Ha, Sang-Jun; Mok, Tony S; Mitsudomi, Tetsuya; Cho, Byoung Chul


    Lung cancer is a leading cause of cancer-related mortality across the world. Although the majority of lung cancer is attributed to tobacco smoke, approximately 25% of lung cancers worldwide occur in lifelong never smokers. Over the past decades, the bulk of research on this disease suggested that several genetic, environmental, hormonal, and viral factors might increase the risk of lung cancer among never smokers. However, there has been no dominant risk factor whose significance has been validated across racial and ethnic groups. However, this subset of lung cancers has received renewed attention due to the introduction of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors showing the dramatic therapeutic response on selected patients with activating EGFR mutations which occur more commonly in never smokers. The treatment strategy blocking EGFR pathway in EGFR-mutant lung cancer represents a remarkable example of molecular targeted therapies which completely repress tumor by inhibition of driving oncogenes. More recently, a surprising positive effect of an ALK inhibitor on EML4-ALK-positive lung cancer has been suggested that lung cancer in never smokers is likely to be an assemblage of molecularly defined subsets which would be a good candidate for personalized diagnostic and therapeutic approaches.

  14. Correlative Study on MRI Morphologic Features,Pathology, and Molecular Biology of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Rong Chen; Shuigen Gong; Weiguo Zhang; Jinhua Chen; Shuangwu He; Baohua Liu; Zengpeng Li


    OBJECTIVE To investigate the correlation among MRI morphologic features,pathology, and molecular biology of breast cancer.METHORDS MRI was used to analyze the morphologic features of breast cancers of 78 patients before operation. The mastectomy specimens of the breast neoplasms were immunohistochemically stained, and the expression of the estrogen (ER), progesterone receptor (PR), C-erbB-2, P53, and the distribution of microvessel density (MVD) measured. The pathologic results were compared with the MRI features.RESULTS Among the 80 breast cancers, ER positive expression was positively correlated with the spicular contour of breast cancers (P<0.01),while showing a significant inverse correlation with the T-stage (P<0.05). CerbB-2 and P53 positive expression were positively correlated with the necrotic center of the cancers (P<0.05). The expression of PR was not significantly correlated with the spicular contour, obscure margin, necrotic center, and T-stage of these cancers (P>0.05). Among 41 breast cancers examined with dynamic contrast enhanced MR, there was a positive correlation between the spatial distribution of the contrast agent and MVD(P<0.01).CONCLUSION To a certain extent there is some correlation among the MRI morphologic features, pathology, and molecular biological factors in breast cancer. The biological behavior and prognosis of breast cancer can be assessed based on MRI features.

  15. Current status of molecular biological techniques for plant breeding in the Republic of Korea

    Energy Technology Data Exchange (ETDEWEB)

    Sohn, Seong-Han; Lee, Si-Myung; Park, Bum-Seok; Yun, In-Sun; Goo, Doe-Hoe; Kim, Seok-Dong [Rural Development Administration, National Institute of Agricultural Science and Technology, Suwon (Korea)


    Classical plant breeding has played an important role in developing new varieties in current agriculture. For decades, the technique of cross-pollination has been popular for breeding in cereal and horticultural crops to introduce special traits. However, recently the molecular techniques get widely accepted as an alternative tool in both introducing a useful trait for developing the new cultivars and investigating the characteristics of a trait in plant, like the identification of a gene. Using the advanced molecular technique, several genetically modified (GM) crops (e.g., Roundup Ready Soybean, YieldGard, LibertyLink etc.) became commercially cultivated and appeared in the global market since 1996. The GM crops, commercially available at the moment, could be regarded as successful achievements in history of crop breeding conferring the specific gene into economically valuable crops to make them better. Along with such achievements, on the other hand these new crops have also caused the controversial debate on the safety of GM crops as human consumption and environmental release as well. Nevertheless, molecular techniques are widespread and popular in both investigating the basic science of plant biology and breeding new varieties compared to their conventional counterparts. Thus, the Department of Bioresources at the National Institute of Agricultural Science and Technology (NIAST) has been using the molecular biological techniques as a complimentary tool for the improvement of crop varieties for almost two decades. (author)

  16. Molecular mobility of hydroxyethyl cellulose (HEC) films characterised by thermally stimulated currents (TSC) spectroscopy. (United States)

    Owusu-Ware, Samuel K; Boateng, Joshua; Jordan, Daniel; Portefaix, Sara; Tasseto, Renata; Ramano, Camila D; Antonijević, Milan D


    Molecular mobility has long been established to relate to textural properties and stability of polymer films and is therefore an important property to characterise to better understand pharmaceutical film formulations. The molecular mobility of solvent cast hydroxyethyl cellulose (HEC) films has been investigated by means of thermally stimulated current (TSC) below the temperature at which the film was formed. Preliminary physical characterisation of the films was performed using XRPD, TGA, DSC and texture analysis (tensile properties). XRPD results showed the films to be completely amorphous with Tg determined by DSC to be 127 ± 1°C. TGA analysis showed the films to contain 8 ± 1% water and film was dried to only 0.06 ± 0.01% water content when heated to 160°C. Application of TSC detected molecular mobility in HEC films at sub-zero temperatures. Two motional transitions with average relaxation time of 50 ± 3s were identified; a β-relaxation at -57 ± 2°C, attributed to localised non-cooperative orientation of HEC polymer chain ends and the hydroxyethyl side groups and an α-relaxation, originating from cooperative segmental mobility, at -20 ± 2°C. The tensile properties i.e., elongation, tensile strength and elastic modulus of the HEC film have been related to the molecular relaxation processes detected by TSC.

  17. Telomerase promoter mutations in cancer: an emerging molecular biomarker? (United States)

    Vinagre, João; Pinto, Vasco; Celestino, Ricardo; Reis, Marta; Pópulo, Helena; Boaventura, Paula; Melo, Miguel; Catarino, Telmo; Lima, Jorge; Lopes, José Manuel; Máximo, Valdemar; Sobrinho-Simões, Manuel; Soares, Paula


    Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the "alternative mechanism of telomere lengthening" (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target.

  18. Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

    Directory of Open Access Journals (Sweden)

    Paola Ulivi


    Full Text Available In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC. A great deal of effort has been focused on identifying specific markers that predict treatment response, given that a tailored approach would maximize both the therapeutic index and the cost-effectiveness. The epidermal growth factor receptor (EGFR pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Gefitinib and erlotinib are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs, demonstrating good results in selected cases both in terms of objective response rate and of overall survival. At present, EGFR gene mutations are the best positive predictive factors for TKI therapy, and a number of other potential biomarkers are being investigated as additional positive or negative predictors of response. The correct selection of patients that could benefit from these innovative therapies, based on an accurate molecular characterization, is mandatory to provide the best clinical management. Currently, the main factor limiting the characterization of metastatic NSCLC patients is the small quantity of tumor cells available for molecular analysis. In this paper we provide an overview of the most important molecular predictive markers for EGFR-TKIs therapy in NSCLC patients, and focus attention on biological samples suitable for analysis and alternative sampling approaches such as plasma- or serum-derived DNA.

  19. Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer (United States)

    Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei


    Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

  20. STAT3 as an emerging molecular target in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Sharma NK


    Full Text Available Narinder Kumar Sharma,1 Sharmila Shankar,2 Rakesh K Srivastava1 1Department of Pharmacology, Toxicology and Therapeutics, and Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 2Kansas City VA Medical Center, Kansas City, MO, USA Abstract: Pancreatic cancer is the fourth leading cause of cancer related deaths. Although, surgical resection of pancreatic cancer may provide the best chance for cure and long-term survival, due to the late onset of symptoms only 15% to 20% of patients have resectable tumors. Most of the pancreatic tumors have mutations in the K-ras gene, followed by mutations in tumor suppressor genes such as p53 and SMAD4. In addition, there is growing evidence for the potential involvement of signal transducer and activator of transcription 3 (STAT3 in malignant transformation of pancreatic cancer. STAT3 plays critical roles in regulating many physiological functions in normal and malignant tissues, such as inflammation, survival, proliferation, differentiation, and angiogenesis. STAT3 is activated by a wide variety of cytokines, growth factors, and other stimuli. Unlike other members of the STAT family, ablation of STAT3 leads to embryonic lethality and conditional loss of STAT3 protein in adult tissues, leading to a variety of abnormalities, confirming that STAT3 participates in a wide variety of physiological processes. Constitutive activation of STAT3 is implicated in a wide range of human cancers; therefore, STAT3 has been identified as a novel target to treat and prevent cancers. Several STAT3 inhibitors display antitumor effectiveness, and data supporting the use of STAT3 inhibitors are emerging. Different approaches used for the inhibition of activated STAT3 include modulating upstream positive or negative regulators or directly targeting its different domains. These approaches have been used in the inhibition of STAT3 in different cancers, but in this review, we will focus specifically on the inhibition

  1. Molecular target based combinational therapeutic approaches in thyroid cancer

    Directory of Open Access Journals (Sweden)

    Rajoria Shilpi


    Full Text Available Abstract Background Thyroid cancer, as with other types of cancer, is dependent on angiogenesis for its continued growth and development. Interestingly, estrogen has been shown to contribute to thyroid cancer aggressiveness in vitro, which is in full support of the observed increased incidence of thyroid cancer in women over men. Provided that estrogen has been observed to contribute to increased angiogenesis of estrogen responsive breast cancer, it is conceivable to speculate that estrogen also contributes to angiogenesis of estrogen responsive thyroid cancer. Methods In this study, three human thyroid cancer cells (B-CPAP, CGTH-W-1, ML-1 were treated with estrogen alone or estrogen and anti-estrogens (fulvestrant and 3,3′-diindolylmethane, a natural dietary compound for 24 hours. The cell culture media was then added to human umbilical vein endothelial cell (HUVECs and assayed for angiogenesis associated events. Vascular endothelial growth factor (VEGF levels were also quantified in the conditioned media so as to evaluate if it is a key player involved in these observations. Results Conditioned medium from estrogen treated thyroid cancer cells enhanced phenotypical changes (proliferation, migration and tubulogenesis of endothelial cells typically observed during angiogenesis. These phenotypic changes observed in HUVECs were determined to be modulated by estrogen induced secretion of VEGF by the cancer cells. Lastly, we show that VEGF secretion was inhibited by the anti-estrogens, fulvestrant and 3,3′-diindolylmethane, which resulted in diminished angiogenesis associated events in HUVECs. Conclusion Our data establishes estrogen as being a key regulator of VEGF secretion/expression in thyroid cells which enhances the process of angiogenesis in thyroid cancer. These findings also suggest the clinical utility of anti-estrogens as anti-angiogenic compounds to be used as a therapeutic means to treat thyroid cancer. We also observed that 3,3

  2. Investigation of the molecular relationship between breast cancer and obesity by candidate gene prioritization methods

    Directory of Open Access Journals (Sweden)

    Saba Garshasbi


    Full Text Available Background: Cancer and obesity are two major public health concerns. More than 12 million cases of cancer are reported annually. Many reports confirmed obesity as a risk factor for cancer. The molecular relationship between obesity and breast cancer has not been clear yet. The purpose of this study was to investigate priorities of effective genes in the molecular relationship between obesity and breast cancer. Methods: In this study, computer simulation method was used for prioritizing the genes that involved in the molecular links between obesity and breast cancer in laboratory of systems biology and bioinformatics (LBB, Tehran University, Tehran, Iran, from March to July 2014. In this study, ENDEAVOUR software was used for prioritizing the genes and integrating multiple data sources was used for data analysis. Training genes were selected from effective genes in obesity and/or breast cancer. Two groups of candidate genes were selected. The first group was included the existential genes in 5 common region chromosomes (between obesity and breast cancer and the second group was included the results of genes microarray data analysis of research Creighton, et al (In 2012 on patients with breast cancer. The microarray data were analyzed with GER2 software (R online software on GEO website. Finally, both training and candidate genes were entered in ENDEAVOUR software package. Results: The candidate genes were prioritized to four style and five genes in ten of the first priorities were repeated twice. In other word, the outcome of prioritizing of 72 genes (Product of microarray data analysis and genes of 5 common chromosome regions (Between obesity and breast cancer showed, 5 genes (TNFRSF10B, F2, IGFALS, NTRK3 and HSP90B1 were the priorities in the molecular connection between obesity and breast cancer. Conclusion: There are some common genes between breast cancer and obesity. So, molecular relationship is confirmed. In this study the possible effect

  3. Current Management of Low Risk Differentiated Thyroid Cancer and Papillary Microcarcinoma. (United States)

    Tarasova, V D; Tuttle, R M


    Each year, the proportion of thyroid cancer patients presenting with low risk disease is increasing. Moreover, the definition of low risk thyroid cancer is expanding and several histological subtypes beyond papillary microcarcinomas are now classified as low risk disease. This shift in the landscape of thyroid cancer presentation is forcing clinicians to critically re-evaluate whether or not traditional management paradigms that were effective in treating intermediate and high risk disease are applicable to these low risk patients. Here we review the definition of low risk disease, examine the various histological subtypes that are considered low risk in the 2015 American Thyroid Association guidelines for the management of thyroid nodules and thyroid cancer, and review our current approach to the management of these low risk tumours.

  4. Cellular and Molecular Mechanisms of 3,3′-Diindolylmethane in Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Soo Mi Kim


    Full Text Available Studies in humans have shown that 3,3′-diindolylmethane (DIM, which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers.

  5. Current and upcoming approaches to exploit the reversibility of epigenetic mutations in breast cancer. (United States)

    Falahi, Fahimeh; van Kruchten, Michel; Martinet, Nadine; Hospers, Geke A P; Rots, Marianne G


    DNA methylation and histone modifications are important epigenetic modifications associated with gene (dys)regulation. The epigenetic modifications are balanced by epigenetic enzymes, so-called writers and erasers, such as DNA (de)methylases and histone (de)acetylases. Aberrant epigenetic alterations have been associated with various diseases, including breast cancer. Since aberrant epigenetic modifications are potentially reversible, they might represent targets for breast cancer therapy. Indeed, several drugs have been designed to inhibit epigenetic enzymes (epi-drugs), thereby reversing epigenetic modifications. US Food and Drug Administration approval has been obtained for some epi-drugs for hematological malignancies. However, these drugs have had very modest anti-tumor efficacy in phase I and II clinical trials in breast cancer patients as monotherapy. Therefore, current clinical trials focus on the combination of epi-drugs with other therapies to enhance or restore the sensitivity to such therapies. This approach has yielded some promising results in early phase II trials. The disadvantage of epi-drugs, however, is genome-wide effects, which may cause unwanted upregulation of, for example, pro-metastatic genes. Development of gene-targeted epigenetic modifications (epigenetic editing) in breast cancer can provide a novel approach to prevent such unwanted events. In this context, identification of crucial epigenetic modifications regulating key genes in breast cancer is of critical importance. In this review, we first describe aberrant DNA methylation and histone modifications as two important classes of epigenetic mutations in breast cancer. Then we focus on the preclinical and clinical epigenetic-based therapies currently being explored for breast cancer. Finally, we describe epigenetic editing as a promising new approach for possible applications towards more targeted breast cancer treatment.

  6. Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor with Activity in Multiple Molecularly Defined Cancer Indications. (United States)

    Ardini, Elena; Menichincheri, Maria; Banfi, Patrizia; Bosotti, Roberta; De Ponti, Cristina; Pulci, Romana; Ballinari, Dario; Ciomei, Marina; Texido, Gemma; Degrassi, Anna; Avanzi, Nilla; Amboldi, Nadia; Saccardo, Maria Beatrice; Casero, Daniele; Orsini, Paolo; Bandiera, Tiziano; Mologni, Luca; Anderson, David; Wei, Ge; Harris, Jason; Vernier, Jean-Michel; Li, Gang; Felder, Eduard; Donati, Daniele; Isacchi, Antonella; Pesenti, Enrico; Magnaghi, Paola; Galvani, Arturo


    Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non-small cell lung cancers (NSCLC) as well as other tumor types and their oncogenic relevance as actionable targets has been demonstrated by the efficacy of selective kinase inhibitors such as crizotinib, ceritinib, and alectinib. More recently, low-frequency rearrangements of TRK kinases have been described in NSCLC, colorectal carcinoma, glioblastoma, and Spitzoid melanoma. Entrectinib, whose discovery and preclinical characterization are reported herein, is a novel, potent inhibitor of ALK, ROS1, and, importantly, of TRK family kinases, which shows promise for therapy of tumors bearing oncogenic forms of these proteins. Proliferation profiling against over 200 human tumor cell lines revealed that entrectinib is exquisitely potent in vitro against lines that are dependent on the drug's pharmacologic targets. Oral administration of entrectinib to tumor-bearing mice induced regression in relevant human xenograft tumors, including the TRKA-dependent colorectal carcinoma KM12, ROS1-driven tumors, and several ALK-dependent models of different tissue origins, including a model of brain-localized lung cancer metastasis. Entrectinib is currently showing great promise in phase I/II clinical trials, including the first documented objective responses to a TRK inhibitor in colorectal carcinoma and in NSCLC. The drug is, thus, potentially suited to the therapy of several molecularly defined cancer settings, especially that of TRK-dependent tumors, for which no approved drugs are currently available. Mol Cancer Ther; 15(4); 628-39. ©2016 AACR.

  7. Alcohol consumption and distinct molecular pathways to colorectal cancer

    NARCIS (Netherlands)

    Bongaerts, B.W.C.; Goeij, A.F.P.M. de; Vogel, S. de; Brandt, P.A. van den; Goldbohm, R.A.; Weijenberg, M.P.


    High alcohol consumption is related to colorectal cancer (CRC). Our objective was to study associations between alcohol consumption and risk of CRC according to characteristics of aetiological pathways: the chromosomal instability (CIN) and the microsatellite instability (MIN) pathway. We classified

  8. Implications and applications of current-induced dynamics in molecular junctions. (United States)

    Jorn, Ryan; Seideman, Tamar


    Instances of strongly nonadiabatic electronic-vibrational energy transfer have been studied since the early days of quantum mechanics and remain a topic of fundamental interest. Often such transfers are associated with electronic resonances, temporary states where transient localization of charge on the molecule provides a mechanism for channeling electronic energy into vibrational excitation. Extensively studied in the gas phase, electron resonance scattering also occurs with surface adsorbed molecules, where it manifests itself in broadened cross sections and desorption of adsorbates from metal surfaces. In this Account, we focus on a related topic: the implications of nonadiabatic, resonance-mediated scattering to the exciting field of molecular electronics. In this context, researchers can induce directed nuclear dynamics and control these processes in single molecules in contact with metallic and semiconducting electrodes. We discuss a variety of consequences and applications of current-driven nuclear excitation in molecular devices, ranging from the design of new forms of molecular machines to surface chemistry at the single-molecule level and atom-resolved lithography. We highlight two specific examples of molecular nanomachines. In the first, a Au-C(60)-Au transistor, the current induces the oscillatory motion of the center-of-mass coordinate of the C(60). The second, a zwitterion-based rattle, demonstrates excitation of intramolecular motion as the positively charged moiety is threaded back and forth through the negatively charged carbon ring. Finally, we discuss the current-induced desorption of organic molecules from Si(100) both to suggest the potential for controlled surface nanochemistry and to develop guidelines for the design of stable molecular junctions. Modeling the exchange of energy between tunneling electrons and the vibrational degrees of freedom of a target molecule subject to bias voltage, open boundary conditions in the electronic subspace

  9. Helicobacter pylori and gastric cancer: current status of the Austrian-Czech-German gastric cancer prevention trial (PRISMA-Study)

    Institute of Scientific and Technical Information of China (English)

    S. Miehlke; A. Leodolter; P. Malfertheiner; A. Neubauer; G. Ehninger; M. Stolte; E, Bayerdorffer; C. Kirsch; B. Dragosics; M. Gschwantler; G. Oberhuber; D. Antos; P. Dite; J. Lauter; J. Labenz


    AIM To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease.METHODS It is a prospective, randomized,double-blind, placebo-controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacterpylori gastritis are randomized to receive a 7-day course of omeprazole 2 × 20 mg,clarithromycin 2 × 500 mg, and amoxicillin 2 ×lg for 7 days, or omeprazole2 × 20mg plusplacebo. Follow - up endoscopy is scheduled 3months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, anddeath.RESULTS Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus-dominant type of H.pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (n -- 86), H. pylori infection infection was cured in 88.9% of patients. Currently, thecumulative follow-up time is 3046 months (253.8patient-years, median follow-up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three(1.8%) patients reached study endpoints other than gastric cancer.CONCLUSION Among men between 55 and 65years of age, the gastric cancer phenotype of H.pylori gastritis appears to be more common than expected. Further follow- up and continuing recruitment are necessary to fulfil the main aim of the study.

  10. Oral mucosal injury caused by cancer therapies: current management and new frontiers in research

    DEFF Research Database (Denmark)

    Jensen, Siri Beier; Peterson, Douglas E.


    This invited update is designed to provide a summary of the state-of-the-science regarding oral mucosal injury (oral mucositis) caused by conventional and emerging cancer therapies. Current modeling of oral mucositis pathobiology as well as evidence-based clinical practice guidelines for prevention...

  11. Relationship satisfaction in couples confronted with colorectal cancer : the interplay of past and current spousal support

    NARCIS (Netherlands)

    Hagedoorn, Mariet; Dagan, Meirav; Puterman, Eli; Hoff, Christiaan; Meijerink, W. J. H. Jeroen; DeLongis, Anita; Sanderman, Robbert


    Based on attribution theory, this study hypthesized that past spousal supportiveness may act as a moderator of the link between one partner's current support behavior and the other partner's relationship satisfaction. A sample of 88 patients with colorectal cancer and their partners completed questi


    Directory of Open Access Journals (Sweden)

    R. I. Tamrazov


    Full Text Available The article describes the main stages of the development of sphincter-saving surgery for rectal cancer. An historical look at this issue from the standpoint of research of past years in our country and abroad, as well as analysis of current sphincter-preserving surgery and future directions in this area.

  13. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer (United States)


    mammary epithelial cells ( Stampfer , 1985). Protein from 184 cell lysate was kindly supplied by Dr. Bruce Lessey, University of North Carolina, Chapel...characterization of a spontaneously immortalized human breast epithelial cell line, MCF- 10. Cancer Res. 50, 6075-6086. Stampfer , M.R. (1985). Isolation and...Exp Cell Neri, Satya Murthy, Christopher Stackpole and Res, 204, 171-80. Janet Price who provided unpublished data, 15. Liotta LA, 1992, Cancer cell

  14. Molecular complexities of patched signaling in cancer development



    Basal Cell Cancer (BCC) is the most common cancer in the Western world. Although BCCs hardly ever metastasize, invasive growth may cause considerable local tissue destruction. BCCs mainly occur as sporadic tumors but can also be found in a hereditary form in the Nevoid Basal Cell Carcinoma Syndrome (NBCCS). The gene underlying the NBCCS is Patched1 (PTCH1), a tumor suppressor gene that is mutated or deleted in these patients. This thesis is focusing in deciphering complex...

  15. Molecular imaging of HER2-positive breast cancer

    DEFF Research Database (Denmark)

    Capala, Jacek; Bouchelouche, Kirsten


    HER2 overexpression is correlated with aggressive tumor behavior and poor clinical outcome. Therefore, HER2 has become an important prognostic and predictive factor, as well as a target for molecular therapies. The article reviews recent advances in molecular imaging of HER2 that could facilitate...

  16. Molecular Genetics Techniques to Develop New Treatments for Brain Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Jacob; Fathallan-Shaykh, Hassan


    The objectives of this report are: (1) to devise novel molecular gene therapies for malignant brain tumors, (2) advance our understanding of the immune system in the central nervous system; and (3) apply genomics to find molecular probes to diagnose brain tumors, predict prognosis, biological behavior and their response to treatment.

  17. Molecular Adsorption Bond Lengths at Metal Oxide Surfaces: Failure of Current Theoretical Methods

    Energy Technology Data Exchange (ETDEWEB)

    Hoeft, J.-T.; Kittel, M.; Polcik, M.; Bao, S.; Toomes, R. L.; Kang, J.-H.; Woodruff, D. P.; Pascal, M.; Lamont, C. L. A.


    New experimental structure determinations for molecular adsorbates on NiO(100) reveal much shorter Ni-C and Ni-N bond lengths for adsorbed CO and NH{sub 3} as well as NO (2.07, 1.88, 2.07{angstrom}) than previously computed theoretical values, with discrepancies up to 0.79{angstrom}, highlighting a major weakness of current theoretical descriptions of oxide-molecule bonding. Comparisons with experimentally determined bond lengths of the same species adsorbed atop Ni on metallic Ni(111) show values on the oxide surface that are consistently larger (0.1--0.3{angstrom}) than on the metal, indicating somewhat weaker bonding.

  18. Non-perturbative calculation of molecular magnetic properties within current-density functional theory. (United States)

    Tellgren, E I; Teale, A M; Furness, J W; Lange, K K; Ekström, U; Helgaker, T


    We present a novel implementation of Kohn-Sham density-functional theory utilizing London atomic orbitals as basis functions. External magnetic fields are treated non-perturbatively, which enable the study of both magnetic response properties and the effects of strong fields, using either standard density functionals or current-density functionals-the implementation is the first fully self-consistent implementation of the latter for molecules. Pilot applications are presented for the finite-field calculation of molecular magnetizabilities, hypermagnetizabilities, and nuclear magnetic resonance shielding constants, focusing on the impact of current-density functionals on the accuracy of the results. Existing current-density functionals based on the gauge-invariant vorticity are tested and found to be sensitive to numerical details of their implementation. Furthermore, when appropriately regularized, the resulting magnetic properties show no improvement over standard density-functional results. An advantage of the present implementation is the ability to apply density-functional theory to molecules in very strong magnetic fields, where the perturbative approach breaks down. Comparison with high accuracy full-configuration-interaction results show that the inadequacies of current-density approximations are exacerbated with increasing magnetic field strength. Standard density-functionals remain well behaved but fail to deliver high accuracy. The need for improved current-dependent density-functionals, and how they may be tested using the presented implementation, is discussed in light of our findings.

  19. Non-perturbative calculation of molecular magnetic properties within current-density functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Tellgren, E. I., E-mail:; Lange, K. K.; Ekström, U.; Helgaker, T. [Centre for Theoretical and Computational Chemistry, Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, N-0315 Oslo (Norway); Teale, A. M., E-mail: [Centre for Theoretical and Computational Chemistry, Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, N-0315 Oslo (Norway); School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom); Furness, J. W. [School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)


    We present a novel implementation of Kohn–Sham density-functional theory utilizing London atomic orbitals as basis functions. External magnetic fields are treated non-perturbatively, which enable the study of both magnetic response properties and the effects of strong fields, using either standard density functionals or current-density functionals—the implementation is the first fully self-consistent implementation of the latter for molecules. Pilot applications are presented for the finite-field calculation of molecular magnetizabilities, hypermagnetizabilities, and nuclear magnetic resonance shielding constants, focusing on the impact of current-density functionals on the accuracy of the results. Existing current-density functionals based on the gauge-invariant vorticity are tested and found to be sensitive to numerical details of their implementation. Furthermore, when appropriately regularized, the resulting magnetic properties show no improvement over standard density-functional results. An advantage of the present implementation is the ability to apply density-functional theory to molecules in very strong magnetic fields, where the perturbative approach breaks down. Comparison with high accuracy full-configuration-interaction results show that the inadequacies of current-density approximations are exacerbated with increasing magnetic field strength. Standard density-functionals remain well behaved but fail to deliver high accuracy. The need for improved current-dependent density-functionals, and how they may be tested using the presented implementation, is discussed in light of our findings.

  20. Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment. (United States)

    Teoh, Seong Lin; Das, Srijit


    Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.

  1. Molecular biology of cancer-associated fibroblasts: can these cells be targeted in anti-cancer therapy? (United States)

    Gonda, Tamas A; Varro, Andrea; Wang, Timothy C; Tycko, Benjamin


    It is increasingly recognized that the non-neoplastic stromal compartment in most solid cancers plays an active role in tumor proliferation, invasion and metastasis. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types in the tumor stroma, and these cells are pro-tumorigenic. Evidence that CAFs are epigenetically and possibly also genetically distinct from normal fibroblasts is beginning to define these cells as potential targets of anti-cancer therapy. Here, we review the cell-of-origin and molecular biology of CAFs, arguing that such knowledge provides a rational basis for designing therapeutic strategies to coordinately and synergistically target both the stromal and malignant epithelial component of human cancers.

  2. Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment. (United States)

    Langer, Corey J; Obasaju, Coleman; Bunn, Paul; Bonomi, Philip; Gandara, David; Hirsch, Fred R; Kim, Edward S; Natale, Ronald B; Novello, Silvia; Paz-Ares, Luis; Pérol, Maurice; Reck, Martin; Ramalingam, Suresh S; Reynolds, Craig H; Socinski, Mark A; Spigel, David R; Wakelee, Heather; Mayo, Carlos; Thatcher, Nick


    Squamous cell lung cancer (sqCLC) is an aggressive form of cancer that poses many therapeutic challenges. Patients tend to be older, present at a later stage, and have a high incidence of comorbidities, which can compromise treatment delivery and exacerbate toxicity. In addition, certain agents routinely available for nonsquamous cell histologic subtypes, such as bevacizumab and pemetrexed, are contraindicated or lack efficacy in sqCLC. Therapeutic progress has been much slower for advanced sqCLC, with median survival times of approximately 9 to 11 months in most studies. Herein, we discuss the current therapeutic landscape for patients with sqCLC versus with nonsquamous NSCLC. Current evidence indicates that new targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab can provide survival prolongation, although the benefits are still relatively modest. These incremental improvements, all realized since 2012, in aggregate, will very likely have a clinically meaningful impact for patients with sqCLC. We also discuss recent genomic studies of sqCLC that have identified potentially actionable molecular targets, as well as the relevant targeted agents in clinical development. Finally, we discuss the magnitude of survival benefit and the risk-to-benefit ratio that would prove clinically meaningful in this underserved patient population with unmet needs.

  3. Molecular epidemiology, and possible real-world applications in breast cancer. (United States)

    Ito, Hidemi; Matsuo, Keitaro


    Gene-environment interaction, a key idea in molecular epidemiology, has enabled the development of personalized medicine. This concept includes personalized prevention. While genome-wide association studies have identified a number of genetic susceptibility loci in breast cancer risk, however, the application of this knowledge to practical prevention is still underway. Here, we briefly review the history of molecular epidemiology and its progress in breast cancer epidemiology. We then introduce our experience with the trial combination of GWAS-identified loci and well-established lifestyle and reproductive risk factors in the risk prediction of breast cancer. Finally, we report our exploration of the cumulative risk of breast cancer based on this risk prediction model as a potential tool for individual risk communication, including genetic risk factors and gene-environment interaction with obesity.

  4. Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer. (United States)

    Haque, Absarul; Alam, Qamre; Alam, Mohammad Zubair; Azhar, Esam I; Sait, Khalid Hussain Wali; Anfinan, Nisrin; Mushtaq, Gohar; Kamal, Mohammad Amjad; Rasool, Mahmood


    Heat Shock Protein 90 (HSP90) is a ubiquitous molecular chaperone that is considered to be the most abundantly expressed protein in various human cancers such as breast, lung, colon, prostate, leukemia and skin. The master regulator, HSP90 plays a pivotal role in the conformational stabilization, maturation and activity of its various labile oncogenic client proteins such as p53, ErbB2, Bcr-Abl, Akt, Her-2, Cdk4, Cdk6, Raf-1 and v-Src in altered cells. Hence, making a guaranteed attempt to inhibit such a master regulator for cancer therapy appears to be a potential approach for combinatorial inhibition of numerous oncogenic signaling pathways simultaneously. Considerable efforts are being under way to develop novel molecular targets and its inhibitors that may block key signaling pathways involved in the process of tumorigenesis and metastasis. In this regards, HSP90 has acquired immense interest as a potent anticancer drug-target due to its key functional link with multiple signaling pathways involved in the process of cell proliferation and cell survival. Notably, geldanamycin and its derivatives (17-AAG, 17-DMAG) have shown quite encouraging results in inhibiting HSP90 function in several cancers and currently almost 17 drug candidates known to be target HSP90 are being under clinical trials either as single agents or combinatorial therapy. Hence, this review is an attempt to get new insight into novel drug target therapy by focusing on recent advances made in understanding HSP90 chaperone structure-function relationships, identification of new HSP90 client proteins and, more importantly, on the advancements of HSP90 targeted therapy based on various existing and emerging classical inhibitors.

  5. Effects of hydrogen bonding on current-voltage characteristics of molecular junctions (United States)

    Kula, Mathias; Jiang, Jun; Lu, Wei; Luo, Yi


    We present a first-principles study of hydrogen bonding effect on current-voltage characteristics of molecular junctions. Three model charge-transfer molecules, 2'-amino-4,4'-di(ethynylphenyl)-1-benzenethiolate (DEPBT-D), 4,4'-di(ethynylphenyl)-2'-nitro-1-benzenethiolate (DEPBT-A), and 2'-amino-4,4'-di(ethynylphenyl)-5'-nitro-1-benzenethiolate (DEPBT-DA), have been examined and compared with the corresponding hydrogen bonded complexes formed with different water molecules. Large differences in current-voltage characteristics are observed for DEPBT-D and DEPBT-A molecules with or without hydrogen bonded waters, while relatively small differences are found for DEPBT-DA. It is predicted that the presence of water clusters can drastically reduce the conductivities of the charge-transfer molecules. The underlying microscopic mechanism has been discussed.

  6. Electrostatic potential profile and nonlinear current in an interacting one-dimensional molecular wire

    Indian Academy of Sciences (India)

    S Lakshmi; Swapan K Pati


    We consider an interacting one-dimensional molecular wire attached to two metal electrodes on either side of it. The electrostatic potential profile across the wire-electrode interface has been deduced solving the Schrodinger and Poisson equations self-consistently. Since the Poisson distribution crucially depends on charge densities, we have considered different Hamiltonian parameters to model the nanoscale wire. We find that for very weak electron correlations, the potential gradient is almost zero in the middle of the wire but are large near the chain ends. However, for strong correlations, the potential is essentially a ramp function. The nonlinear current, obtained from the scattering formalism, is found to be less with the ramp potential than for weak correlations. Some of the interesting features in current-voltage characteristics have been explained using one-electron formalism and instabilities in the system.

  7. Transcriptional networks controlling breast cancer metastasis : molecular mechanisms shaping the SOX4 response

    NARCIS (Netherlands)

    Vervoort, S.J.


    Breast cancer is the most commonly diagnosed cancer in women. Despite great improvements in diagnosis and treatment of this disease, mortality remains high due to the development of metastatic disease resulting in clinical relapse. The majority of current treatment options primarily target the prima

  8. Molecular alterations in gastric cancer with special reference to the early-onset subtype

    NARCIS (Netherlands)

    Skierucha, Małgorzata; Milne, Anya Na; Offerhaus, G Johan A; Polkowski, Wojciech P; Maciejewski, Ryszard; Sitarz, Robert


    Currently, gastric cancer (GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the pro-carcinogenic activity of important genes. These

  9. Human Papillomavirus: Current and Future RNAi Therapeutic Strategies for Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Hun Soon Jung


    Full Text Available Human papillomaviruses (HPVs are small DNA viruses; some oncogenic ones can cause different types of cancer, in particular cervical cancer. HPV-associated carcinogenesis provides a classical model system for RNA interference (RNAi based cancer therapies, because the viral oncogenes E6 and E7 that cause cervical cancer are expressed only in cancerous cells. Previous studies on the development of therapeutic RNAi facilitated the advancement of therapeutic siRNAs and demonstrated its versatility by siRNA-mediated depletion of single or multiple cellular/viral targets. Sequence-specific gene silencing using RNAi shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, siRNA-based targeting requires further validation of its efficacy in vitro and in vivo, for its potential off-target effects, and of the design of conventional therapies to be used in combination with siRNAs and their drug delivery vehicles. In this review we discuss what is currently known about HPV-associated carcinogenesis and the potential for combining siRNA with other treatment strategies for the development of future therapies. Finally, we present our assessment of the most promising path to the development of RNAi therapeutic strategies for clinical settings.

  10. Current status and prospects of clinical proteomics studies on detection of colorectal cancer: Hopes and fears

    Institute of Scientific and Technical Information of China (English)

    ME de Noo; RAEM Tollenaar; AM Deelder; LH Bouwman


    Colorectal adenocarcinoma (CRC) is the third most common type of cancer and the fourth most frequent cause of death due to cancer worldwide. Given the natural history of CRC, early diagnosis appears to be the most appropriate tool to reduce disease-related mortality. A field of recent interest is clinical proteomics, which was reported to lead to high sensitivity and specificities for early detection of several solid tumors. This emerging field uses mass spectrometry-based protein profiles/patterns of easy accessible body fluids to distinguish cancer from non-cancer patients. These discrepancies may be a result of: (1) proteins being abnormally produced or shed and added to the serum proteome, (2) proteins clipped or modified as a consequence of the disease process, or (3) proteins subtracted from the proteome owing to disease-related proteolytic degradation pathways. Therefore, protein pattern diagnostics would provide easy and reliable tools for detection of cancer. This paper focuses on the current status of clinical proteomics research in oncology and in colorectal cancer especially,and will reflect on pitfalls and fears in this relatively new area of clinical medicine, which are reproducibility issues and pre-analytical factors, statistical issues, and identification and nature of discriminating proteins/peptides.

  11. Current Challenges in Volatile Organic Compounds Analysis as Potential Biomarkers of Cancer

    Directory of Open Access Journals (Sweden)

    Kamila Schmidt


    Full Text Available An early diagnosis and appropriate treatment are crucial in reducing mortality among people suffering from cancer. There is a lack of characteristic early clinical symptoms in most forms of cancer, which highlights the importance of investigating new methods for its early detection. One of the most promising methods is the analysis of volatile organic compounds (VOCs. VOCs are a diverse group of carbon-based chemicals that are present in exhaled breath and biofluids and may be collected from the headspace of these matrices. Different patterns of VOCs have been correlated with various diseases, cancer among them. Studies have also shown that cancer cells in vitro produce or consume specific VOCs that can serve as potential biomarkers that differentiate them from noncancerous cells. This review identifies the current challenges in the investigation of VOCs as potential cancer biomarkers, by the critical evaluation of available matrices for the in vivo and in vitro approaches in this field and by comparison of the main extraction and detection techniques that have been applied to date in this area of study. It also summarises complementary in vivo, ex vivo, and in vitro studies conducted to date in order to try to identify volatile biomarkers of cancer.

  12. Drug resistance in cancer: molecular evolution and compensatory proliferation. (United States)

    Friedman, Ran


    Targeted therapies have revolutionized cancer treatment. Unfortunately, their success is limited due to the development of drug resistance within the tumor, which is an evolutionary process. Understanding how drug resistance evolves is a prerequisite to a better success of targeted therapies. Resistance is usually explained as a response to evolutionary pressure imposed by treatment. Thus, evolutionary understanding can and should be used in the design and treatment of cancer. In this article, drug-resistance to targeted therapies is reviewed from an evolutionary standpoint. The concept of apoptosis-induced compensatory proliferation (AICP) is developed. It is shown that AICP helps to explain some of the phenomena that are observed experimentally in cancers. Finally, potential drug targets are suggested in light of AICP.

  13. MicroRNAs and cancer resistance: A new molecular plot. (United States)

    Fanini, F; Fabbri, M


    The most common cause of cancer relapse is drug resistance, acquired or intrinsic, which strongly limits the efficacy of both conventional and new targeted chemotherapy. MicroRNAs (miRNAs) are a growing, large family of short noncoding RNAs frequently dysregulated in malignancies. Although the mechanism of miRNA-mediated drug resistance is not fully understood, an increasing amount of evidence suggests their involvement in the acquisition of tumor cell drug resistance, pointing towards the need for novel and more innovative therapeutic approaches. Use of antagomiRs or mimics can modulate specific miRNAs in order to restore gene networks and signaling pathways, perhaps optimizing chemotherapies by increasing cancer cell sensitivity to drugs. The aim of this review is to provide a state-of-the-art scenario with regard to the most recent discoveries in the field of miRNAs involved in the process of resistance to cancer therapy.

  14. The molecular biology of cancer and its diagnostic implications. (United States)

    Aw, S E


    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.

  15. The molecular and cellular origin of human prostate cancer. (United States)

    Packer, John R; Maitland, Norman J


    Prostate cancer is the most commonly diagnosed male malignancy. Despite compelling epidemiology, there are no definitive aetiological clues linking development to frequency. Pre-malignancies such as proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) yield insights into the initiating events of prostate cancer, as they supply a background "field" for further transformation. An inflammatory aetiology, linked to recurrent prostatitis, and heterologous signalling from reactive stroma and infiltrating immune cells may result in cytokine addiction of cancer cells, including a tumour-initiating population also known as cancer stem cells (CSCs). In prostate tumours, the background mutational rate is rarely exceeded, but genetic change via profound sporadic chromosomal rearrangements results in copy number variations and aberrant gene expression. In cancer, dysfunctional differentiation is imposed upon the normal epithelial lineage, with disruption/disappearance of the basement membrane, loss of the contiguous basal cell layer and expansion of the luminal population. An initiating role for androgen receptor (AR) is attractive, due to the luminal phenotype of the tumours, but alternatively a pool of CSCs, which express little or no AR, has also been demonstrated. Indolent and aggressive tumours may also arise from different stem or progenitor cells. Castrate resistant prostate cancer (CRPC) remains the inevitable final stage of disease following treatment. Time-limited effectiveness of second-generation anti-androgens, and the appearance of an AR-neuroendocrine phenotype imply that metastatic disease is reliant upon the plasticity of the CSC population, and indeed CSC gene expression profiles are most closely related to those identified in CRPCs.

  16. Theranostic liposomes for cancer diagnosis and treatment: current development and pre-clinical success. (United States)

    Muthu, Madaswamy S; Feng, Si-Shen


    Liposomes are one of the effective drug delivery systems that are developed based on the nanotechnology concept. Liposomal formulation is the first nanomedicine approved by the US FDA for clinical application. Recently, the marketed liposomes and stealth liposomes have made impact for cancer therapy. In addition, a few receptor-targeted liposome products have been in different phases of clinical trials, which are yet to be marketed. In the present editorial, the advantages of vitamin E TPGS-coated liposomes over the currently available PEG-coated liposomes will be described and their great potentials for nanotheranostics for cancer imaging and therapy will be covered.

  17. [Current problems and challenges in the diagnosis and treatment of colorectal cancer in China]. (United States)

    Wang, Jianping; Wang, Lei


    In the past 20 years, researches regarding colorectal cancer have experienced unprecedented boom in China. However, a seris problems have been exposed, including a rapid increase in morbility, the geographical limitations of tumor screening, nonstandard diagnosis and treatment, very limited mechanism researches, and lack of randomized controlled clinical trials with Chinese characteristics. This article puts forward some main emphases of the current work, based on the above problems and challenges, in order to improve the overall level of the diagnosis and treatment of colorectal cancer in China.

  18. Molecular Pathways: Reactive Oxygen Species Homeostasis in Cancer Cells and Implications for Cancer Therapy


    Nogueira, Veronique; Hay, Nissim


    Reactive oxygen species (ROS) are important in regulating normal cellular processes, but deregulated ROS contribute to the development of various human diseases including cancers. Cancer cells have increased ROS levels compared to normal cells, because of their accelerated metabolism. The high ROS levels in cancer cells, which distinguish them from normal cells, could be pro-tumorigenic, but are also their Achilles’ heel. The high ROS content in cancer cells renders them more susceptible to o...

  19. Genetic and epigenetic heterogeneity of epithelial ovarian cancer and the clinical implications for molecular targeted therapy. (United States)

    Bai, Huimin; Cao, Dongyan; Yang, Jiaxin; Li, Menghui; Zhang, Zhenyu; Shen, Keng


    Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and tumoural heterogeneity (TH) has been blamed for treatment failure. The genomic and epigenomic atlas of EOC varies significantly with tumour histotype, grade, stage, sensitivity to chemotherapy and prognosis. Rapidly accumulating knowledge about the genetic and epigenetic events that control TH in EOC has facilitated the development of molecular-targeted therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors, designed to target homologous recombination, are poised to change how breast cancer susceptibility gene (BRCA)-related ovarian cancer is treated. Epigenetic treatment regimens being tested in clinical or preclinical studies could provide promising novel treatment approaches and hope for improving patient survival.

  20. Xmrk, kras and myc transgenic zebrafish liver cancer models share molecular signatures with subsets of human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Weiling Zheng

    Full Text Available Previously three oncogene transgenic zebrafish lines with inducible expression of xmrk, kras or Myc in the liver have been generated and these transgenic lines develop oncogene-addicted liver tumors upon chemical induction. In the current study, comparative transcriptomic approaches were used to examine the correlation of the three induced transgenic liver cancers with human liver cancers. RNA profiles from the three zebrafish tumors indicated relatively small overlaps of significantly deregulated genes and biological pathways. Nevertheless, the three transgenic tumor signatures all showed significant correlation with advanced or very advanced human hepatocellular carcinoma (HCC. Interestingly, molecular signature from each oncogene-induced zebrafish liver tumor correlated with only a small subset of human HCC samples (24-29% and there were conserved up-regulated pathways between the zebrafish and correlated human HCC subgroup. The three zebrafish liver cancer models together represented nearly half (47.2% of human HCCs while some human HCCs showed significant correlation with more than one signature defined from the three oncogene-addicted zebrafish tumors. In contrast, commonly deregulated genes (21 up and 16 down in the three zebrafish tumor models generally showed accordant deregulation in the majority of human HCCs, suggesting that these genes might be more consistently deregulated in a broad range of human HCCs with different molecular mechanisms and thus serve as common diagnosis markers and therapeutic targets. Thus, these transgenic zebrafish models with well-defined oncogene-induced tumors are valuable tools for molecular classification of human HCCs and for understanding of molecular drivers in hepatocarcinogenesis in each human HCC subgroup.

  1. Lung Cancer and Human Papilloma Viruses (HPVs: Examining the Molecular Evidence

    Directory of Open Access Journals (Sweden)

    Priya R. Prabhu


    Full Text Available Human papilloma virus (HPV, known to be an etiological agent for genital cancers, has been suggested also to be a possible contributory agent for lung cancer. Alternatively, lung cancer, formerly considered to be solely a smoker's disease, may now be more appropriately categorised into never smoker's and smoker's lung cancer. Through this paper we attempt to bring forth the current knowledge regarding mechanisms of HPV gaining access into the lung tissue, various strategies involved in HPV-associated tumorigenesis in lung tissue.

  2. Sphingosine kinase 1 is a relevant molecular target in gastric cancer

    DEFF Research Database (Denmark)

    Fuereder, Thorsten; Hoeflmayer, Doris; Jaeger-Lansky, Agnes


    Sphingosine kinase 1 (Sphk1), a lipid kinase implicated in cell transformation and tumor growth, is overexpressed in gastric cancer and is linked with a poor prognosis. The biological relevance of Sphk1 expression in gastric cancer is unclear. Here, we studied the functional significance of Sphk1...... as a novel molecular target for gastric cancer by using an antisense oligonucleotide approach in vitro and in vivo. Gastric cancer cell lines (MKN28 and N87) were treated with Sphk1 with locked nucleic acid-antisense oligonucleotides (LNA-ASO). Sphk1 target regulation, cell growth, and apoptosis were...... assessed for single-agent Sphk1 LNA-ASO and for combinations with doxorubicin. Athymic nude mice xenografted with gastric cancer cells were treated with Sphk1 LNA and assessed for tumor growth and Sphk1 target regulation, in vivo. In vitro, nanomolar concentrations of Sphk1 LNA-ASO induced an approximately...

  3. Molecular Cancer Imaging with Polymeric Nanoassemblies: From Tumor Detection to Theranostics. (United States)

    Mi, Peng; Wang, Fang; Nishiyama, Nobuhiro; Cabral, Horacio


    Several imaging modalities have been widely applied for the detection of cancer and its pathological activity in combination with probes capable of improving the contrast between healthy and cancerous tissues. Biocompatible polymeric nanoassemblies have been developed for precise detection of malignant tumors by enhancing the selectivity and sensitivity of the imaging. Exploiting the compartmentalized structure of the nanoassemblies advantageously allows delivering both imaging and therapeutic agents for cancer multifunctional imaging and theranostics, i.e., the combination of therapy and diagnosis tool on a single platform. Thus, nanoassemblies have high potential not only for cancer molecular imaging but also for tracing nanoparticles in biological systems, studying their biological pathways, gathering pathological information, monitoring therapeutic effects, and guiding pinpoint therapies. In this review, polymeric nanoassemblies for optical imaging, magnetic resonance imaging, multifunctional imaging, and image-guided therapy, emphasizing their role in cancer diagnosis and theranostics are highlighted.

  4. CD24 as a Molecular Marker in Ovarian Cancer: A Literature Review

    Directory of Open Access Journals (Sweden)

    Lu Huang


    Full Text Available Ovarian cancer is the most lethal gynecologic cancer, with a mortality rate of > 60%. Cancer stem cell (CSC hypothesis offers an attractive explanation of chemoresistance, metastasis, etc., associated with the disease. However, there are still controversy and limitation in defining the CSC markers. CD24 is a mucin-type glycosyl-phosphatidylinositol-linked glycoprotein, expressed on the surface of cells, which serves as a normal receptor for P-selectin and is found involved in molecular adhesion and metastatic tumor spread. Expression rate of CD24 has been associated with progression of various cancers and poor survival rates. In this review, the function of CD24 in ovarian cancer, especially in ovarian CSC system, was discussed in an effort to broaden the interpretation of potential mechanism.

  5. Androgen receptor- and PIAS1-regulated gene programs in molecular apocrine breast cancer cells. (United States)

    Malinen, Marjo; Toropainen, Sari; Jääskeläinen, Tiina; Sahu, Biswajyoti; Jänne, Olli A; Palvimo, Jorma J


    We have analyzed androgen receptor (AR) chromatin binding sites (ARBs) and androgen-regulated transcriptome in estrogen receptor negative molecular apocrine breast cancer cells. These analyses revealed that 42% of ARBs and 39% androgen-regulated transcripts in MDA-MB453 cells have counterparts in VCaP prostate cancer cells. Pathway analyses showed a similar enrichment of molecular and cellular functions among AR targets in both breast and prostate cancer cells, with cellular growth and proliferation being among the most enriched functions. Silencing of the coregulator SUMO ligase PIAS1 in MDA-MB453 cells influenced AR function in a target-selective fashion. An anti-apoptotic effect of the silencing suggests involvement of the PIAS1 in the regulation of cell death and survival pathways. In sum, apocrine breast cancer and prostate cancer cells share a core AR cistrome and target gene signature linked to cancer cell growth, and PIAS1 plays a similar coregulatory role for AR in both cancer cell types.

  6. Molecular Biology and Prevention of Endometrial Cancer. Addendum (United States)


    gain insight into the biologic mechanism underlying the chemopreventive effect of the oral contraceptive pill (OCP). Project 1: Objectives completed...oral contraceptive pill and hormone replacement therapy on reproductive organs. This objective has been completed and the results were submitted...protective effect of oral contraceptive (OC) therapy. Methods: 1) Oligonucleotide microarray analysis was performed on a panel of endometrial cancers

  7. [New strategies in the clinical evaluation of patients with colon cancer based on molecular studies]. (United States)

    Panduro, A; Morales, L; Santos, A; Valdés, L; Lima, G; Meléndez, J; Cabrera, G; Maldonado, V; Villalobos, J J


    During the last five years molecular studies allowed important advances in the knowledge of cancer colon with important clinical implications. The main finding was the identification and sequence analysis of the APC gen. Structural alterations of this gene have been detected in patients with Familial Adenomatous Polyposis and Gardner syndrome, which suggest a common disease. Furthermore, alterations of the APC gen appears to be also altered in cases of cancer of colon sporadic. Indicating that structural alteration of the APC gen can be inherited and/or acquired. Restriction fragment-length polymorphisms in the chromosome 5q21-22 can now be used clinically for premorbid diagnosis and counseling in familial adenomatous polyposis. The molecular studies allow the clinician to have a new approach in the management and screening of families with familial adenomatous polyposis. The sequence analysis and specific identification of the structural alteration of the APC gene is a more expensive and sophisticated study, although represent a more direct approach. In the Department of Gastroenterology of the INNSZ we are performing such molecular studies. The main purpose of our group is to proportionate integral clinical-molecular studies for families with hereditary colon cancer, create a national register of these diseases and investigate the molecular bases in order to generate new molecular diagnosis tools.

  8. Molecular subtypes of breast cancer and amplification of topoisomerase II alpha : predictive role in dose intensive adjuvant chemotherapy

    NARCIS (Netherlands)

    Hannemann, J.; Kristel, P.; van Tinteren, H.; Bontenbal, M.; van Hoesel, Q. G. C. M.; Smit, W. M.; Nooij, M. A.; Voest, E. E.; van der Wall, E.; Hupperets, P.; de Vries, E. G. E.; Rodenhuis, S.; van de Vijver, M. J.


    Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour. In a retrospective analysis, we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took

  9. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon. (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag


    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs.

  10. Evolving Paradigm of Radiotherapy for High-Risk Prostate Cancer: Current Consensus and Continuing Controversies

    Directory of Open Access Journals (Sweden)

    Aditya Juloori


    Full Text Available High-risk prostate cancer is an aggressive form of the disease with an increased risk of distant metastasis and subsequent mortality. Multiple randomized trials have established that the combination of radiation therapy and long-term androgen deprivation therapy improves overall survival compared to either treatment alone. Standard of care for men with high-risk prostate cancer in the modern setting is dose-escalated radiotherapy along with 2-3 years of androgen deprivation therapy (ADT. There are research efforts directed towards assessing the efficacy of shorter ADT duration. Current research has been focused on assessing hypofractionated and stereotactic body radiation therapy (SBRT techniques. Ongoing randomized trials will help assess the utility of pelvic lymph node irradiation. Research is also focused on multimodality therapy with addition of a brachytherapy boost to external beam radiation to help improve outcomes in men with high-risk prostate cancer.

  11. Bisphenol A and Hormone-Associated Cancers: Current Progress and Perspectives (United States)

    Gao, Hui; Yang, Bao-Jun; Li, Nan; Feng, Li-Min; Shi, Xiao-Yu; Zhao, Wei-Hong; Liu, Si-Jin


    Abstract Bisphenol A (BPA), a carbon-based synthetic compound, exhibits hormone-like properties and is present ubiquitously in the environment and in human tissues due to its widespread use and biological accumulation. BPA can mimic estrogen to interact with estrogen receptors α and β, leading to changes in cell proliferation, apoptosis, or migration and thereby, contributing to cancer development and progression. At the genetic level, BPA has been shown to be involved in multiple oncogenic signaling pathways, such as the STAT3, MAPK, and PI3K/AKT pathways. Moreover, BPA may also interact with other steroid receptors (such as androgen receptor) and plays a role in prostate cancer development. This review summarizes the current literature regarding human exposure to BPA, the endocrine-disrupting effects of BPA, and the role of BPA in hormone-associated cancers of the breast, ovary, and prostate. PMID:25569640

  12. Raf kinase inhibitory protein role in the molecular subtyping of breast cancer. (United States)

    Al-Mulla, Fahd; Marafie, Makia; Zea Tan, Tuan; Paul Thiery, Jean


    In this study, we examined the association between the RKIP expression and the molecular subtypes of breast cancer. Microarray gene expression data of 2,333 human breast cancer from 26 different cohorts performed on Affymetrix U133A or U133Plus2 platforms were downloaded from Array Express and Gene Expression Omnibus and the molecular subtype of breast cancer for the samples was determined by single sample Gene Set Enrichment Analysis. Differences in recurrence-free survival (RFS) were tested using the Log-rank test in univariate analysis and displayed using Kaplan-Meier curves. Cox proportional-hazards model was used to calculate the hazard ratio using univariate and multivariate analysis. Loss or reduced RKIP expression was associated with reduced RFS in breast cancer using univariate and multivariate analyses, which was independent of lymph node (LN) metastasis status. Basal-like, Claudin-low, and Her-2-enriched tumors had significantly lower RKIP levels compared to other subclasses (P < 0.0001). Conversely, the Luminal subclass exhibited the highest expression levels of RKIP (P < 0.0001 for Luminal A and P = 0.0005 for Luminal B subtype), while in normal-like breast cancer subtype, RKIP expression was not informative. RKIP expression was prognostic in ER+ and ER- subgroups. RKIP expression had no significant prognostic power within Basal-like, Claudine-low, Luminal B, or Her-2-enriched breast cancer subtypes. However, its expression pinpointed excellent from intermediate-poor Luminal A survivors, in both ER+ (P = 0.035) and ER- (P = 0.012) subgroups, especially in LN negative breast cancers. In conclusion, RKIP expression adds significant value to the molecular subclassification of breast cancer especially for the Luminal A subtype.

  13. Study Points to Genetic Subtypes of Esophageal Cancer (United States)

    A Cancer Currents blog post about a study by The Cancer Genome Atlas Research Network that identified distinct genetic and molecular changes in esophageal cancers that could improve their classification and identify potential new treatments.

  14. Current Understanding of Molecular Pathology and Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Tirsa L. E. van Westering


    Full Text Available Duchenne muscular dystrophy (DMD is a genetic muscle disorder caused by mutations in the Dmd gene resulting in the loss of the protein dystrophin. Patients do not only experience skeletal muscle degeneration, but also develop severe cardiomyopathy by their second decade, one of the main causes of death. The absence of dystrophin in the heart renders cardiomyocytes more sensitive to stretch-induced damage. Moreover, it pathologically alters intracellular calcium (Ca2+ concentration, neuronal nitric oxide synthase (nNOS localization and mitochondrial function and leads to inflammation and necrosis, all contributing to the development of cardiomyopathy. Current therapies only treat symptoms and therefore the need for targeting the genetic defect is immense. Several preclinical therapies are undergoing development, including utrophin up-regulation, stop codon read-through therapy, viral gene therapy, cell-based therapy and exon skipping. Some of these therapies are undergoing clinical trials, but these have predominantly focused on skeletal muscle correction. However, improving skeletal muscle function without addressing cardiac aspects of the disease may aggravate cardiomyopathy and therefore it is essential that preclinical and clinical focus include improving heart function. This review consolidates what is known regarding molecular pathology of the DMD heart, specifically focusing on intracellular Ca2+, nNOS and mitochondrial dysregulation. It briefly discusses the current treatment options and then elaborates on the preclinical therapeutic approaches currently under development to restore dystrophin thereby improving pathology, with a focus on the heart.

  15. The Role of Ovarian Sex Steroids in Metabolic Homeostasis, Obesity, and Postmenopausal Breast Cancer: Molecular Mechanisms and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Viroj Boonyaratanakornkit


    Full Text Available Obese postmenopausal women have an increased risk of breast cancer and are likely to have a worse prognosis than nonobese postmenopausal women. The cessation of ovarian function after menopause results in withdrawal of ovarian sex steroid hormones, estrogen, and progesterone. Accumulating evidence suggests that the withdrawal of estrogen and progesterone causes homeostasis imbalances, including decreases in insulin sensitivity and leptin secretion and changes in glucose and lipid metabolism, resulting in a total reduction in energy expenditure. Together with a decrease in physical activity and consumption of a high fat diet, these factors significantly contribute to obesity in postmenopausal women. Obesity may contribute to breast cancer development through several mechanisms. Obesity causes localized inflammation, an increase in local estrogen production, and changes in cellular metabolism. In addition, obese women have a higher risk of insulin insensitivity, and an increase in insulin and other growth factor secretion. In this review, we describe our current understanding of the molecular actions of estrogen and progesterone and their contributions to cellular metabolism, obesity, inflammation, and postmenopausal breast cancer. We also discuss how modifications of estrogen and progesterone actions might be used as a therapeutic approach for obesity and postmenopausal breast cancer.

  16. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells

    DEFF Research Database (Denmark)

    Llorente, A.; Skotland, T.; Sylvanne, T.


    The molecular lipid composition of exosomes is largely unknown. In this study, sophisticated shotgun and targeted molecular lipidomic assays were performed for in-depth analysis of the lipidomes of the metastatic prostate cancer cell line, PC-3, and their released exosomes. This study, based...... in the quantification of approximately 280 molecular lipid species, provides the most extensive lipid analysis of cells and exosomes to date. Interestingly, major differences were found in the lipid composition of exosomes compared to parent cells. Exosomes show a remarkable enrichment of distinct lipids, demonstrating...

  17. Concurrent chemo-radiotherapy in the treatment of early breast cancer: Current status

    Directory of Open Access Journals (Sweden)

    Nabil Ismaili


    Full Text Available Concurrent chemo-radiotherapy (CCRT in early breast cancer was investigated by few authors and remains controversial. This treatment is more commonly used for locally advanced breast cancer and showed high rate of complete pathological response. A search of articles published in English literature, between 1980 and November 2012, was conducted on Medline using the following terms: "breast cancer", "chemotherapy", "concurrent radiotherapy", and "Trastuzumab". We identified five phase I/II trials and three randomized phase three trials evaluating concurrent chemoradiotherapy in the adjuvant of breast cancer. In patients with early breast cancer having positive lymph nodes, phases III clinical trials showed that CCRT improved local control after conservative breast surgery. However, these randomized trials used non-standard regimen: Cyclophosphamide, methotrexate and fluorouracil (CMF or fluorouracil, mitoxantrone and cyclophosphamide (FNC. In addition, in phases II clinical trials, concurrent use of taxanes and anthracycline with standard whole-breast irradiation showed high rate of toxicity: Pulmonary toxicity with taxane; and cardiac and skin toxicity with anthracycline. Consequentely, CCRT is not be used in practice because of concerns of toxicity with the standard drugs (anthracyclines and taxanes and radiation. Anthracyclines with partial breast irradiation (PBI was feasible according to one phase I clinical trial, and should be investigated in randomized clinical trials. Concurrent Trastuzumab plus radiotherapy is safe and can be used in HER2-positive breast cancer; in this case, cardiac volume sparing and patient selections for internal mammary chain irradiation are highly recommended. The present paper aimed to review the current data evaluating the efficacy and safety of CCRT in early breast cancer.

  18. Current innovations in sentinel lymph node mapping for the staging and treatment of resectable lung cancer. (United States)

    Hachey, Krista J; Colson, Yolonda L


    Despite surgical resectability, early-stage lung cancer remains a challenge to cure. Survival outcomes are hindered by variable performance of adequate lymphadenectomy and the limitations of current pathologic nodal staging. Sentinel lymph node (SLN) mapping, a mainstay in the management of breast cancer and melanoma, permits targeted nodal sampling for efficient and accurate staging that can influence both intraoperative and adjuvant treatment decisions. Unfortunately, standard SLN identification techniques with blue dye and radiocolloid tracers have not been shown to be reproducible in lung cancer. In more recent years, intraoperative near-infrared image-guided lung SLN mapping has emerged as promising technology for the identification of the tumor-associated lymph nodes most likely to contain metastatic disease. Additionally, the clinical relevance of SLN mapping for lung cancer remains pressing, as the ability to identify micrometastatic disease in SLNs could facilitate trials to assess chemotherapeutic response and the clinical effect of occult nodal disease. This review outlines the status of lung cancer lymphatic mapping and techniques in development that may help close the gap between translational research in this field and routine clinical practice.

  19. Molecular pathways: targeting ETS gene fusions in cancer. (United States)

    Feng, Felix Y; Brenner, J Chad; Hussain, Maha; Chinnaiyan, Arul M


    Rearrangements, or gene fusions, involving the ETS family of transcription factors are common driving events in both prostate cancer and Ewing sarcoma. These rearrangements result in pathogenic expression of the ETS genes and trigger activation of transcriptional programs enriched for invasion and other oncogenic features. Although ETS gene fusions represent intriguing therapeutic targets, transcription factors, such as those comprising the ETS family, have been notoriously difficult to target. Recently, preclinical studies have demonstrated an association between ETS gene fusions and components of the DNA damage response pathway, such as PARP1, the catalytic subunit of DNA protein kinase (DNAPK), and histone deactylase 1 (HDAC1), and have suggested that ETS fusions may confer sensitivity to inhibitors of these DNA repair proteins. In this review, we discuss the role of ETS fusions in cancer, the preclinical rationale for targeting ETS fusions with inhibitors of PARP1, DNAPK, and HDAC1, as well as ongoing clinical trials targeting ETS gene fusions.

  20. Curcumin: a Polyphenol with Molecular Targets for Cancer Control. (United States)

    Qadir, Muhammad Imran; Naqvi, Syeda Tahira Qousain; Muhammad, Syed Aun


    Curcumin, is a polyphenol from Curcuma longa (turmeric plant), is a polyphenol that belongs to the ginger family which has long been used in Ayurveda medicines to treat various diseases such as asthma, anorexia, coughing, hepatic diseases, diabetes, heart diseases, wound healing and Alzheimer's. Various studies have shown that curcumin has anti-infectious, anti-inflammatory, anti-oxidant, hepatoprotective, thrombosuppressive, cardio protective, anti-arthritic, chemo preventive and anti-carcinogenic activities. It may suppress both initiation and progression stages of cancer. Anticancer activity of curcumin is due to negative regulation of inflammatory cytokines, transcription factors, protein kinases, reactive oxygen species (ROS) and oncogenes. This review focuses on the different targets of curcumin to treat cancer.