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Author: Kjetil Søreide
Publisher:
ISBN: 9781604567144
Category : Colon (Anatomy)
Languages : en
Pages : 0
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Book Description
The understanding of the mechanisms that explain the initiation and early evolution of colorectal cancer is evolving. This should facilitate the development of new approaches to effective prevention and intervention. Over the past years, deficiencies in the current adenoma-carcinoma model for colorectal cancer, in which APC mutation is placed at the point of initiation, have been suggested. Several pathways through which cancer may develop seem to exist, such as 'chromosomal instability' (CIN), 'microsatellite instability' (MSI), and most recently the 'serrated pathway' involving epigenetic changes. Parallel to discoveries in molecular pathways are the increased awareness of early and precursor features of the colorectal mucosa detected and treated by endoscopic and minimal-invasive techniques. Thus, new staging and classification systems have been developed to guide the clinician in diagnosis and choice of treatment. This book sets focus on selected clinical and molecular aspects of colorectal precursor lesions; from the endoscopically detected colorectal polyp, major molecular mechanisms, and aspects of protease-systems in colorectal cancer development. Future research on colorectal cancer needs to be stratified according to the appropriate clinical features and their associated genetic pathways involved in order to further explore important molecular mechanisms and clinicopathological consequences of chromosomal, microsatellite and epigenetic mechanisms.
Author: Kjetil Søreide
Publisher:
ISBN: 9781604567144
Category : Colon (Anatomy)
Languages : en
Pages : 0
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Book Description
The understanding of the mechanisms that explain the initiation and early evolution of colorectal cancer is evolving. This should facilitate the development of new approaches to effective prevention and intervention. Over the past years, deficiencies in the current adenoma-carcinoma model for colorectal cancer, in which APC mutation is placed at the point of initiation, have been suggested. Several pathways through which cancer may develop seem to exist, such as 'chromosomal instability' (CIN), 'microsatellite instability' (MSI), and most recently the 'serrated pathway' involving epigenetic changes. Parallel to discoveries in molecular pathways are the increased awareness of early and precursor features of the colorectal mucosa detected and treated by endoscopic and minimal-invasive techniques. Thus, new staging and classification systems have been developed to guide the clinician in diagnosis and choice of treatment. This book sets focus on selected clinical and molecular aspects of colorectal precursor lesions; from the endoscopically detected colorectal polyp, major molecular mechanisms, and aspects of protease-systems in colorectal cancer development. Future research on colorectal cancer needs to be stratified according to the appropriate clinical features and their associated genetic pathways involved in order to further explore important molecular mechanisms and clinicopathological consequences of chromosomal, microsatellite and epigenetic mechanisms.
Author: James M. Church
Publisher: Springer Science & Business Media
ISBN: 144199310X
Category : Medical
Languages : en
Pages : 196
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Book Description
Molecular Genetics of Colorectal Neoplasia A Primer for the Clinician provides the latest information on the genetics of colorectal cancer within a context of basic genetics, describing the subject in understandable language and making it clinically relevant. In this way, clinicians can become familiar with genetic terms and techniques related to colorectal neoplasia, providing a background upon which to build an appreciation of future advances and an ability to include them in the practicalities of patient care. This edition is intended for the healthcare provider or industry concerned with colorectal neoplasia: including general and colorectal surgeons, pathologists, oncologists, gastroenterologists, internal medicine and family practice physicians, nurses, geneticists, counsellors, registry co-ordinators, epidemiologists, and statisticians.
Author: James M. Church
Publisher: Igaku-Shoin Medical Publishers
ISBN:
Category : Medical
Languages : en
Pages : 134
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Book Description
Author: Jennifer Liang
Publisher:
ISBN:
Category : Adenoma
Languages : en
Pages : 484
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Book Description
Summary: Colorectal cancer (CRC) affects approximately 150,000 Americans and 2716 New Zealanders annually, and approximately one third of Americans and 45 percent of New Zealanders will eventually succumb to the condition. In the past, CRC has been one of the best understood malignancies in terms of its molecular alterations. The first step of carcinogenesis involves the development of pre-malignant lesions (polyps) in the colonic mucosa. Certain histological features of the polyp determine its malignant potential, and the risk of cancer will be significantly reduced if all the precursor lesions are removed endoscopically. However, despite close surveillance, many studies have shown that a significant number of CRCs will still develop. This could be because some cancers are missed on prior endoscopy, their precursor lesions are not easily recognised at the time of colonoscopy, or they may be a result of rapid development of cancer. There are two major polyp subtypes which serve as precursors to colorectal cancers (adenoma and serrated polyps). Colorectal cancers mostly arise from adenomas but a lesser proportion can arise from serrated polyps. Once thought to be harmless, the spectrum of serrated colorectal polyps includes some potentially dangerous lesions, such as the sessile serrated adenoma/polyp (SSA/P) and the traditional serrated adenoma (TSA). SSA/Ps develop through a distinct molecular pathway featuring proto-oncogene B-Raf or v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations, hypermethylation of CpG sites in gene promoters, and loss of expression of mismatch repair gene MLH1. The first part of this thesis focuses on determining the natural history of serrated neoplasms, and the endoscopic detection and treatment of these lesions in Cleveland Clinic, Ohio. The main body of the thesis is based on the hypothesis that hypermethylation of CpG islands results in epigenetic silencing of specific microRNAs (miRNAs) that function as tumour suppressors, and this silencing results in increased cell growth and development of serrated neoplasia. Methods and Results: In the first part of thesis I have determeined the natural history of the serrated polyps, compared their detection rate with the adenoma detection rate, and have demonstrated that endoscopic removal of these precursor lesions is feasible. microRNAs are post-transcriptional regulators that may function as tumor suppressors. Previously, with global DNA methylation screening, miR-1247 is found to be hypermethylated in three methylated tumors when compared with three non-methylated tumors and normal colonic mucosa. By TaqMan® quantitative polymerase chain reaction (PCR), this was further confirmed in 20 tumours of each group. Treatment with the DNA de-methylation reagent, 5-Aza-2'-deoxycytidine (5'-Aza), has resulted in upregulation of miR-1247 expression in CRC cell lines. Transiently transfected miR-1247 cells have shown reduced cell growth and less cell migration in vitro. Moreover, stable transfected miR-1247 cells have significantly impaired tumour development when implanted into immunocompromised mice. These results strongly suggest that miR-1247 is a tumor suppressor. Demethylation with 5'-Aza has significantly decreased tumor growth in nude mice. The predicted gene target of miR-1247 is E3 ubiquitin-protein ligase MYCBP2 also known as myc-binding protein 2 or protein associates with myc (PAM), a significant decrease in MYCBP2 protein levels has been seen in cells transfected with miR-1247. Moreover, inhibition of endogenous miR-1247 by a miR inhibitor significantly has increased MYCBP2 expression. Direct targeting of MYCBP2 3'UTR by miR-1247 is confirmed with luciferase assays. Most importantly, with immunohistochemistry staining, a reciprocal relationship between MYCBP2 expression and miR-1247 level in seven methylated versus non-methylated cancers has been demonstrated. Conclusion: This thesis has demonstrated that epigenetic regulation plays an important part in the tumorigenesis of serrated CRC. DNA hypermethylation is a key feature in this subtype of colorectal CRC, which in turn suppresses miR-1247 expression and causes an increase in MYCBP2 and its downstream MYC protein. The findings of this thesis open up a whole new area for therapeutic approaches in the treatment of serrated colorectal cancer.
Author: Kevin M. Haigis, Ph.D.
Publisher: Springer Science & Business Media
ISBN: 146148412X
Category : Medical
Languages : en
Pages : 319
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Book Description
Colorectal cancer has for more than two decades served as the paradigm for the multi-step concept of cancer initiation and progression. Perhaps more than any other organ site, cancer of the colon is extensively characterized at the molecular level. We are now entering a time when molecular classification, rather than histologic classification, of cancer subtypes is driving the development of clinical trials with emerging targeted therapies. The book will focus on the progression from the identification of mutations that drive colorectal cancer initiation and progression to the search for novel therapies to treat the disease.
Author: Carlos M. Alvarez
Publisher: Nova Publishers
ISBN: 9781600217296
Category : Cancer
Languages : en
Pages : 218
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Book Description
Focus on Cancer Research
Author: Douglas B. Evans
Publisher: Springer Science & Business Media
ISBN: 0387951857
Category : Medical
Languages : en
Pages : 413
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Book Description
The MD Anderson Solid Tumor Oncology series presents cutting-edge surgical treatment and medical therapy for specific sites. This volume, Pancreatic Cancer, addresses epidemiology and molecular biology, inherited syndromes, staging, surgical techniques, multimodality therapy, and emerging therapies. The individual chapters focus on narrow, specific topics to produce a reference work of value to those interested in pancreatic cancer from a clinical and translational research perspective. A must-have for surgical oncologists and general surgeons.
Author: William B. Coleman
Publisher: Academic Press
ISBN: 0128132582
Category : Medical
Languages : en
Pages : 634
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Book Description
Essential Concepts in Molecular Pathology, Second Edition, offers an introduction to molecular genetics and the "molecular" aspects of human disease. The book illustrates how pathologists harness their understanding of these entities to develop new diagnostics and treatments for various human diseases. This new edition offers pathology, genetics residents, and molecular pathology fellows an advanced understanding of the molecular mechanisms of disease that goes beyond what they learned in medical and graduate school. By bridging molecular concepts of pathogenesis to the clinical expression of disease in cell, tissue and organ, this fully updated, introductory reference provides the background necessary for an understanding of today’s advances in pathology and medicine. Explains the practice of "molecular medicine" and the translational aspects of molecular pathology, including molecular diagnostics, molecular assessment and personalized medicine Orients non-pathologists on what pathologists look for and how they interpret their observational findings based on histopathology Provides the reader with what is missing from most targeted introductions to pathology—the cell biology behind pathophysiology
Author: Bruce Alberts
Publisher:
ISBN: 9780815332183
Category : Cytology
Languages : en
Pages : 0
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Book Description
Author: William B. Coleman
Publisher: Academic Press
ISBN: 0128027878
Category : Medical
Languages : en
Pages : 805
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Book Description
As the molecular basis of human disease becomes better characterized, and the implications for understanding the molecular basis of disease becomes realized through improved diagnostics and treatment, Molecular Pathology, Second Edition stands out as the most comprehensive textbook where molecular mechanisms represent the focus. It is uniquely concerned with the molecular basis of major human diseases and disease processes, presented in the context of traditional pathology, with implications for translational molecular medicine. The Second Edition of Molecular Pathology has been thoroughly updated to reflect seven years of exponential changes in the fields of genetics, molecular, and cell biology which molecular pathology translates in the practice of molecular medicine. The textbook is intended to serve as a multi-use textbook that would be appropriate as a classroom teaching tool for biomedical graduate students, medical students, allied health students, and others (such as advanced undergraduates). Further, this textbook will be valuable for pathology residents and other postdoctoral fellows that desire to advance their understanding of molecular mechanisms of disease beyond what they learned in medical/graduate school. In addition, this textbook is useful as a reference book for practicing basic scientists and physician scientists that perform disease-related basic science and translational research, who require a ready information resource on the molecular basis of various human diseases and disease states. Explores the principles and practice of molecular pathology: molecular pathogenesis, molecular mechanisms of disease, and how the molecular pathogenesis of disease parallels the evolution of the disease Explains the practice of “molecular medicine and the translational aspects of molecular pathology Teaches from the perspective of “integrative systems biology Enhanced digital version included with purchase
