mitochondrial genetics and cancer

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Mitochondrial Genetics And Cancer

Author : Gabriel D. Dakubo
ISBN : 3642114164
Genre : Medical
File Size : 58. 4 MB
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With very few exceptions, eukaryotic cells possess two interdependent genomes, chromosomal and extra-chromosomal. Over the past several decades, cancer - search has focused primarily on deciphering the intricate alterations in the chro- somal genome, with until recently, very little attention to its cytoplasmic counterpart. In spite of the enormous complexity of the nuclear genome, which we now fully appreciate after completion of the human genome project, the efforts of cancer researchers are commendable in terms of the tremendous gains made in unraveling the numerous genetic changes in cancer. These changes include d- coveries of tumor suppressor genes, oncogenes, and caretaker genes that are often mutated in cancer. Recent studies of genomic pro?les are uncovering even more altered and mutated genes in cancer. Besides these ?ndings, several therapeutic targets for chemotherapy are currently made from studies of altered nuclear genetic pathways. Inspite of all these positive efforts, the war on cancer, declared in 1971 by Richard Nixon, is far from being worn. Indeed, the failure of chemotherapy is obvious to clinicians, oncologists, and their patients alike. Moreover, the global incidence and prevalence of cancer continue to rise. What are we missing? Which direction should we be taking? Of course, modern integrated nuclear genomics, proteomics, and metabolomics should provide important clues to carcinogenesis, but the contribution of cytoplasmic genetic alterations to carcinogenesis cannot be neglected.

Mitochondrial Genetics And Cancer

Author : Gabriel D. Dakubo
ISBN : 3642114164
Genre : Medical
File Size : 78. 38 MB
Format : PDF, ePub
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With very few exceptions, eukaryotic cells possess two interdependent genomes, chromosomal and extra-chromosomal. Over the past several decades, cancer - search has focused primarily on deciphering the intricate alterations in the chro- somal genome, with until recently, very little attention to its cytoplasmic counterpart. In spite of the enormous complexity of the nuclear genome, which we now fully appreciate after completion of the human genome project, the efforts of cancer researchers are commendable in terms of the tremendous gains made in unraveling the numerous genetic changes in cancer. These changes include d- coveries of tumor suppressor genes, oncogenes, and caretaker genes that are often mutated in cancer. Recent studies of genomic pro?les are uncovering even more altered and mutated genes in cancer. Besides these ?ndings, several therapeutic targets for chemotherapy are currently made from studies of altered nuclear genetic pathways. Inspite of all these positive efforts, the war on cancer, declared in 1971 by Richard Nixon, is far from being worn. Indeed, the failure of chemotherapy is obvious to clinicians, oncologists, and their patients alike. Moreover, the global incidence and prevalence of cancer continue to rise. What are we missing? Which direction should we be taking? Of course, modern integrated nuclear genomics, proteomics, and metabolomics should provide important clues to carcinogenesis, but the contribution of cytoplasmic genetic alterations to carcinogenesis cannot be neglected.

Mitochondria And Cancer

Author : Keshav Singh
ISBN : 0387848355
Genre : Medical
File Size : 44. 4 MB
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An exhaustive analysis of the role of mitochondria in cancer, this book surveys the Warburg Hypothesis, mitochondrial structure and function, and then outlines the metabolic and molecular alterations in mitochondria that are associated with human cancer.

Mitochondrial Genetics And Function Among Men Screened For Prostate Cancer

Author : Marc L. Sprouse
ISBN : OCLC:1035214802
Genre :
File Size : 36. 53 MB
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Genetic alterations are associated with sporadic cancer development, progression and metastasis. Until now, more was known about nuclear DNA (nDNA) mutations and their role in cancer than the types of genetic changes that occur in the mitochondrial genome (mtGenome). Changes to mitochondrial DNA (mtDNA) are frequent in prostate cancer (PCa). Further, these changes have been associated with enhanced tumorigenesis and progression to an aggressive phenotype. However, it is unclear whether changes to the mtGenome can delineate PCa progression from indolent cancer to an advanced metastatic disease. An exhaustive characterization of the mtGenome of men screened for PCa was performed to determine if genetic differences between varying PCa disease states can be measured. Two genetic techniques (copy number and genome sequencing) were used to perform a comprehensive characterization of the changes to mtDNA in whole blood extracts from three groups of men screened for prostate cancer: normal control (NC), no evidence of disease (NED), and, biochemical recurrence/metastasis (BCR/MET). Mitochondrial DNA copies per cell and mtGenome deletion ratio (whole mtGenomes:truncated mtGenomes) were measured using a multiplex real-time quantitative PCR (qPCR) assay. Whole mtGenome sequence data were generated using a massively parallel sequencing platform, the Ion Torrent Personal Genome Machine (PGM). Real-time qPCR revealed a higher dispersion of mtDNA copies per cell and mtGenomes harboring a large scale deletion in samples from men with advanced stages of PCa when compared to normal controls and indolent PCa. Whole mtGenome sequencing showed a higher number of genetic variants in men with PCa, some of which are predicted to be pathological. A significant positive correlation was observed between mutational load and PCa disease status. Further, three-dimensional comparative modeling evidenced the negative effect of a single mtDNA missense mutation on a protein’s structural integrity. Overall, the presented data suggest there are differences in the mtGenome between men with and without PCa that are measurable in peripheral blood and may be used as a potential risk assessment tool. Future analyses with a larger sample size may lead to more compelling evidence that supports the role of changes to the mtGenome with PCa progression.

Cancer As A Metabolic Disease

Author : Thomas Seyfried
ISBN : 9781118310304
Genre : Science
File Size : 31. 41 MB
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The book addresses controversies related to the origins of cancer and provides solutions to cancer management and prevention. It expands upon Otto Warburg's well-known theory that all cancer is a disease of energy metabolism. However, Warburg did not link his theory to the "hallmarks of cancer" and thus his theory was discredited. This book aims to provide evidence, through case studies, that cancer is primarily a metabolic disease requring metabolic solutions for its management and prevention. Support for this position is derived from critical assessment of current cancer theories. Brain cancer case studies are presented as a proof of principle for metabolic solutions to disease management, but similarities are drawn to other types of cancer, including breast and colon, due to the same cellular mutations that they demonstrate.

Mitochondrial Dna And Diseases

Author : Hongzhi Sun
ISBN : 9789811066740
Genre : Science
File Size : 37. 38 MB
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The book describes molecular principles and mechanisms by which mitochondrial DNA (mtDNA) can drive the occurrence of diseases and the latest understanding of mtDNA biology. The book explores roles of mtDNA mutation and genetic changes in cancer, with a special focus on lung cancer, and the significance of approach, application, and bioethics of mtDNA sequencing. Authors made a great effort to overview roles of mtDNA signaling pathways, base excision repair, methylation, USP30-mediated regulation, mitochondrial ribosome, autophagy pathways, or ROS-dependent signaling in the pathogenesis, diagnosis, prevention and treatment of diseases. It also demonstrates the importance of basic mitochondrial genetics and the relationship between mutations and disease phenotypes and ageing. This book covers not only the basic information of mtDNA, the relationship of mtDNA and disease, but also mtDNA in stem cell and mitochondria and metabolism etc. The book is written for biological and clinical students and researchers in the field of mtDNA–associated diseases.

Principles Of Cancer Genetics

Author : Fred Bunz
ISBN : 9789401774840
Genre : Medical
File Size : 61. 19 MB
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This is the second edition of a widely used textbook that consolidates the basic concepts of the cancer gene theory and provides a framework for understanding the genetic basis of cancer. Particular attention is devoted to the origins of the mutations that cause cancer, and the application of evolutionary theory to explain how the cell clones that harbor cancer genes tend to expand. Focused on the altered genes and pathways that cause the growth of the most common tumors, Principles of Cancer Genetics is aimed at advanced undergraduates who have completed introductory coursework in genetics, biology and biochemistry, medical students and medical house staff. For students with a general interest in cancer, this book provides a highly accessible and readable overview. For more advanced students contemplating future study in the field of oncology and cancer research, this concise book will be useful as a primer.

Mitochondrial Dna Mutations In Aging Disease And Cancer

Author : Keshav K. Singh
ISBN : 9783662125090
Genre : Science
File Size : 40. 27 MB
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Many human genetic diseases associated with blood, brain, colon, ear, eye, heart, kidney, liver, muscle, and pancreas are caused by mutations in mitochondrial DNA. Mutations in DNA can result in defects of the electron transport complexes, intermediates of the tricarboxylic acid cycle and substrate transport. The clinical manifestation of these diseases often involves muscle and the nervous system. Mitochondrial DNA mutations have now been associated with aging as well as age-related degenerative diseases such as Parkinson's, Alzheimer's, and Huntington's diseases. Changes in structure, function, and a number of mitochondria play an important role in carcinogenesis. Furthermore, the role of mitochondria in the execution of programmed cell death or apoptosis has been recognized recently.

Cancer Biomarkers In Body Fluids

Author : Gabriel D. Dakubo
ISBN : 9783319015804
Genre : Medical
File Size : 40. 44 MB
Format : PDF
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The molecular and genetic signatures of cancer are represented in the peripheral circulation and other body fluids, giving rise to the “liquid biopsy” concept. This new paradigm of molecular profiling of cancer cells offers several advantages over traditional tissue biopsy. It is convenient, noninvasive, conforms to current clinical practice, enables real time disease monitoring and the study of tumor evolution, can easily be sampled multiple times, and this sample is more representative of the heterogeneous cancer cells than biopsy sampling. Indeed, all aspects of cancer molecular genetic information, stemming from DNA (both nuclear and mitochondria), RNA (coding and noncoding), peptides and proteins, metabolites and lipids are present in body fluids as free, cell surface bound or enclosed in membrane vesicles, and are being harnessed for disease management. Additionally, circulating tumor, and tumor stem cells provide prognostic information, and also enable the study of the intricate molecular processes associated with metastasis and drug resistance. This treatise deals with the general principles of the molecular pathology of cancer, and its associated imprints in circulation. The transitional process from discovery, prototype development, translational research, to product development can be complex and costly. The critical path to biomarker development and qualification for successful use in drug development is detailed herein as well. This book is of interest to Cancer Researchers, Oncologists, Clinicians, Surgeons, Medical Students, Nurses, Diagnostic Laboratories, and Pharmaceutical Industries.​​

Mitochondria The Anti Cancer Target For The Third Millennium

Author : Jiri Neuzil
ISBN : 9789401789844
Genre : Medical
File Size : 41. 22 MB
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This book will be focused on mitochondria as very promising targets for anti-cancer drugs, yet to be fully exploited. It will contain chapters focused on aspects of basic research as well as on clinical relevance, which will be written by specialists in the field. That the role of mitochondria in human pathologies goes beyond the neoplastic diseases will be documented by a chapter of the role of mitochondria in Friedreich's ataxia.

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