Current Issue : October - December Volume : 2012 Issue Number : 4 Articles : 7 Articles
Disease biomarkers are used widely in medicine. But very few biomarkers are useful for cancer diagnosis and monitoring. Over the past 15 years, major investments have been made to discover and validate cancer biomarkers. The knowledge about cancer biomarkers has increased tremendously providing great opportunities for improving the management of cancer patients by enhancing the efficiency of detection and efficacy of treatment. Recent technological advancement has enabled the examination of many potential biomarkers and renewed interest in developing new biomarkers. Biomarkers of cancer could include a broad range of biochemical entities, such as nucleic acids, proteins, sugars, lipids, and small metabolites, cytogenetic and cytokinetic parameters as well as whole tumour cells found in the body fluid. A comprehensive understanding of the relevance of each biomarker will be very important not only for diagnosing the disease reliably, but also help in the choice of multiple therapeutic alternatives currently available that is likely to benefit the patients. This review provides an account on various biomarkers for diagnosis, prognosis and therapeutic purposes, which include markers already in clinical practice as well as various upcoming biomarkers as per disease. Review also provide the list of biomarkers in various types of cancer like breast cancer, lung cancer....
Apoptosis, or programmed cell death, is an essential physiological process that plays a critical role in development and tissue homeostasis. The progress of apoptosis is regulated in an orderly way by series of signal cascades under certain circumstances. The caspase-cascade system plays vital roles in the induction, transduction and amplification of intracellular apoptotic signals. Caspases, closely associated with apoptosis, are aspartate-specific cysteine proteases and members of the interleukin-1β-converting enzyme family. The activation and function of caspases, involved in the delicate caspase-cascade system, are regulated by various kinds of molecules, such as the inhibitor of apoptosis protein, Bcl-2 family proteins, calpain, and Ca2+The caspases are not the only executors of apoptotic change. Various pathways that result in apoptosis without the action of the caspase fraternity have been described. One involves a protein termed AIF (apoptotic initiating factor) that is released from the mitochondria, enters the nucleus and triggers cell suicide. Note that not all caspases are death-mediating enzymes; some have a role in the processing and activating of cytokines (e.g. caspase 8 is active in processing the inflammatory cytokines IL-1 and IL-18). In apoptosis the cardinal morphological features are cell shrinkage, accompanied by trisient but violent bubbling and blebbing from the surface, and culminating in separation of cell in cluster of membrane bounded bodies. Change in several cell surface molecule also ensure that, in tissues, apoptotic cell are immediately recognised and phagocytosed by their neighbours. The result is that many cells can be deleted from tissues in relatively short time. Apoptosis is clinically implicated in various body systems like cardiovascular system, central nervous system, gastrointestinal system, reproductive system, immune system and various pathological conditions like cardiovascular diseases, neurodegenerative disorder, cancer, sepsis, renal diseases Deficient apoptosis is associated with cancer, auto-immunity and viral infections. Excessive apoptosis is associated with ischaemic heart disease, stroke, neurodegenerative disease, sepsis and multiple organ dysfunction syndrome....
In 1976, Sporn has defined chemoprevention as ââ?¬Å?the use of pharmacologic or natural agents that inhibit the development of\r\ninvasive breast cancer either by blocking the DNA damage that initiates carcinogenesis, or by arresting or reversing the progression\r\nof premalignant cells in which such damage has already occurred.ââ?¬Â Although the precise mechanism or mechanisms that promote\r\na breast cancer are not completely established, the success of several recent clinical trials in preventive settings in selected highrisk\r\npopulations suggests that chemoprevention is a rational and an appealing strategy. Breast cancer chemoprevention has focused\r\nheavily on endocrine intervention using selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). Achieving\r\nmuch success in this particular setting and new approaches as low-dose administration are actually under investigations in several\r\ntopics. Unfortunately, these drugs are active in prevention of endocrine responsive lesions only and have no effect in reducing\r\nthe risk of estrogen-negative breast cancer. Thus, recently new pathways, biomarkers, and agents likely are to be effective in this\r\nsubgroup of cancers and were put under investigation. Moreover, the identification of new potential molecular targets and the\r\ndevelopment of agents aimed at these targets within cancer have already had a significant impact on advanced cancer therapy\r\nand provide a wealth of opportunities for chemoprevention. This paper will highlight current clinical research in both ERpositive\r\nand ER-negative breast cancer chemoprevention, explaining the biologic effect of the various agents on carcinogenesis and\r\nprecancerous lesions, and finally presenting an excursus on the state-of-the-art about new molecular targets under investigations\r\nin breast cancer settings....
Background: Activation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell\r\nproliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5) expression in human\r\ncolorectal cancer (CRC) tissues and correlated it with clinicopathologic data.\r\nMethods: pMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA) containing 335\r\nclinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19\r\ncases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship\r\nbetween pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression\r\nwith CRC survival were analyzed respectively.\r\nResults: pMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2%) than in normal tissues\r\n(6 out of 80, 7.5%; P < 0.001). Western blotting demonstrated that pMEK5 expression was upregulated in 12 of 19\r\nCRC tissues (62.1%) compared to the corresponding adjacent nontumor colorectal tissues. Overexpression of\r\npMEK5 in CRC tissues was significantly correlated to the depth of invasion (P = 0.001), lymph node metastasis (P <\r\n0.001), distant metastasis (P < 0.001) and high preoperative CEA level (P < 0.001). Consistently, the pMEK5 level in\r\nCRC tissues was increased following stage progression of the disease (P < 0.001). Analysis of the survival curves\r\nshowed a significantly worse 5-year disease-free (P = 0.002) and 5-year overall survival rate (P < 0.001) for patients\r\nwhose tumors overexpressed pMEK5. However, in multivariate analysis, pMEK5 was not an independent prognostic\r\nfactor for CRC (DFS: P = 0.139; OS: P = 0.071).\r\nConclusions: pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the\r\nTNM staging system of CRC....
Tissue markers may be helpful in enhancing prediction of radiation therapy (RT) failure of prostate cancer (PCa). Among the\r\nvarious biomarkers tested in Phase III randomized trials conducted by the Radiation Therapy Oncology Group, p16, Ki-67,\r\nMDM2, COX-2, and PKA yielded the most robust data in predicting RT failure. Other pathways involved in RT failure are also\r\nimplicated in the development of castration-resistant PCa, including the hypersensitive androgen receptor, EGFR, VEGF-R, and\r\nPI3K/Akt. Most of them are detectable in PCa tissue even at the time of initial diagnosis. Emerging evidence suggests that RT\r\nfailure of PCa results from a multifactorial and heterogeneous disease process. A number of tissue markers are available to identify\r\npatients at high risk to fail RT. Some of these markers have the promise to be targeted by drugs currently available to enhance the\r\nefficacy of RT and delay disease progression....
Background: Cutaneous squamous cell carcinoma (SCC) is associated with underlying immunosuppression, so it\r\nmay be a prognostic marker in patients with subsequent cancer. We therefore conducted a nationwide\r\npopulation-based Danish cohort study to evaluate whether a history of cutaneuos SCC has prognostic impact in\r\npatients with one of the following index cancers: non-Hodgkin�s lymphoma (NHL), or cancer of the lung, colon,\r\nrectum, breast, or prostate.\r\nMethods: We used Danish medical databases, which cover the entire Danish population of 5.6 million inhabitants\r\nand linked them using the unique personal identification number assigned to all Danish residents. From 1982\r\nthrough 2003, we identified 745 index cancer patients with and 79,143 without previous cutaneous SCC. Using Cox\r\nproportional hazards regression, we calculated adjusted mortality rate ratios (MRRs) with 95% confidence intervals\r\n(CIs).\r\nResults: Overall, previous SCC was associated with an increased mortality of cancer (MRR 1.13, 95% CI: 1.04-1.23).\r\nWhen examining index cancers separately, increased MRRs were found for cancer of the lung (MRR 1.23, 95% CI:\r\n1.05-1.43), colon (MRR 1.13, 95% CI: 0.92-1.40), rectum (MRR 1.29, 95% CI: 1.00-1.67), breast (MRR 1.09, 95% CI: 0.82-\r\n1.43), and NHL (MRR 1.09, 95% CI: 0.81-1.47), but not for prostate cancer (MRR 0.99, 95% CI: 0.83-1.18).\r\nConclusions: Our results suggest that previous cutaneous SCC is associated with poor prognosis of some cancers.\r\nThis finding stresses the importance of adherence to the existing recommendations of screening, diagnosis, and\r\ntreatment of cancer in patients with a history of SCC....
Background: Population-based studies on endometrial cancer providing survival estimates by age, histology, and\r\nstage have been sparse. We aimed to derive most up-to-date and detailed survival estimates for endometrial\r\ncancer patients in Germany.\r\nMethods: We used a pooled German national dataset including data from 11 cancer registries covering a\r\npopulation of 33 million people. 30,906 patients diagnosed with endometrial cancer in 1997-2006 were included.\r\nPeriod analysis was performed to calculate 5-year relative survival (RS) in 2002-2006. Trends in survival between\r\n2002 and 2006 were examined using model-based period analysis. Age-adjustment was performed using five age\r\ngroups (15-44, 45-54, 55-64, 65-74, and 75+ years).\r\nResults: Overall, age-adjusted 5-year relative survival in 2002-2006 was 81%. A moderate age gradient was\r\nobserved, with 5-year RS decreasing from 90% in the age group 15-49 years to 75% in the age group 70+ years.\r\nFurthermore prognosis varied strongly by histologic subtypes and stage, with age-adjusted 5-year RS ranging from\r\n43% (for sarcoma) to 94% (for squamous metaplasia), and reaching 91% for localized, 51% for regional, and 20% for\r\ndistant stage. Except for age group 65-74 years, no significant improvement in survival was seen during the recent\r\n5-year period under investigation.\r\nConclusion: In this comprehensive population-based survival analysis of patients with endometrial cancer from\r\nGermany, prognosis of endometrial cancer moderately varied by age, and strongly varied by histology and stage.\r\nWhile prognosis is rather good overall, further improvement in 5-year relative survival of endometrial cancer\r\npatients has been stagnating in the early 21st century...
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