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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.
This book examines in depth the evidence, clinical applications and potential cancer signatures in the circulation and discusses alterations in circulating cell-free nucleic acids, and circulating tumor DNA, as well as the epigenome, genome, transcriptome (coding and noncoding), proteome (both traditional serum proteins and proteomic profiles) and metabolome. Further, it highlights the clinical applications of circulating tumor cells for each cancer type and addresses the emerging importance of extracellular vesicular contents, including miRNA, oncogenes and drug resistant factors. As such, it offers a valuable reference guide for cancer researchers, oncologists, clinicians, surgeons, medical students, oncology nurses, diagnostic laboratories, and the pharmaceutical industry.
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.
This book examines in depth the evidence, clinical applications and potential cancer signatures in the circulation and discusses alterations in circulating cell-free nucleic acids, and circulating tumor DNA, as well as the epigenome, genome, transcriptome (coding and noncoding), proteome (both traditional serum proteins and proteomic profiles) and metabolome. Further, it highlights the clinical applications of circulating tumor cells for each cancer type and addresses the emerging importance of extracellular vesicular contents, including miRNA, oncogenes and drug resistant factors. As such, it offers a valuable reference guide for cancer researchers, oncologists, clinicians, surgeons, medical students, oncology nurses, diagnostic laboratories, and the pharmaceutical industry.
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.
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.
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