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Over the past 50 years many in vitro and in vivo drug response assay systems have been developed to determine the potential - tivity of chemotherapy agents. The idea was to eliminate ineffective agents and unnecessary toxic treatment while selecting drugs active in vitro or in the mouse model that might increase the probability of response in the patient. None of these test models, however, achieved routine clinical application in the past. This might be at least in part - lated to large discrepancies that were described between the s- cess rate of the assay systems and the clinical benefit in cancer - tients. The heterogeneity of chemosensitivity that exists between different tumors as well as between individual tumor lesions may be one explanation for these findings. Furthermore, different assay end points such as proliferation, metabolism, and vitality were - veloped to evaluate the effects of cytostatic drugs on tumor cells, and these might be related to the differing results. However, knowledge about procedures for assay-assisted treatment selection has increased rapidly within the past few years, and several studies suggest that test-directed chemotherapy selection now may - prove response rates and survival in various types of tumors. The International Society for Chemosensitivity Testing in - cology (ISCO) was founded to promote, coordinate, and improve clinical and laboratory research in the field of predictive drug te- ing in human tumor cells.
A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity, Volume 1: In Vitro Assays provides a panel of 16 in vitro measures of chemosensitivity in adherent and non-adherent cells for single agents and combinations of agents. In addition to immunohistochemical and imaging approaches, these assays include clonogenic, colorimetric, fluorometric, and physiological assays. Highlights include image analysis to assess drug sensitivity, high throughput approaches using green fluorescent protein, DIMSCAN (a microcomputer fluorescence-based assay), and the ChemoFx assay used in biotechnology. A companion volume, Volume 2: In Vivo Models, Imaging, and Molecular Regulators, provides protocols for classifying tumors into response categories and customizing chemotherapy regimens to individual patients.
Over the past 50 years many in vitro and in vivo drug response assay systems have been developed to determine the potential - tivity of chemotherapy agents. The idea was to eliminate ineffective agents and unnecessary toxic treatment while selecting drugs active in vitro or in the mouse model that might increase the probability of response in the patient. None of these test models, however, achieved routine clinical application in the past. This might be at least in part - lated to large discrepancies that were described between the s- cess rate of the assay systems and the clinical benefit in cancer - tients. The heterogeneity of chemosensitivity that exists between different tumors as well as between individual tumor lesions may be one explanation for these findings. Furthermore, different assay end points such as proliferation, metabolism, and vitality were - veloped to evaluate the effects of cytostatic drugs on tumor cells, and these might be related to the differing results. However, knowledge about procedures for assay-assisted treatment selection has increased rapidly within the past few years, and several studies suggest that test-directed chemotherapy selection now may - prove response rates and survival in various types of tumors. The International Society for Chemosensitivity Testing in - cology (ISCO) was founded to promote, coordinate, and improve clinical and laboratory research in the field of predictive drug te- ing in human tumor cells.
The carotid body initiates reflexes aimed principally at the homeostatic maintenance of blood gas tensions. This thesis tested the hypothesis that the carotid body is also a physiological glucosensor, with a role in mediating exercise hyperpnoea. In anaesthetised rats, insulin-induced hypoglycaemia (from ca. 6.5 to 2.8 mmol L-1) caused an ca. two-fold increase of oxygen consumption that was associated with a significant, carotid body-dependent increase in ventilation (from ca. 420 to 640 ml min-1 kg-1) without change in blood gas tensions. This hypoglycaemic hyperpnoea was associated with hypokalaemia and no alterations of ventilation or metabolism were observed in euglycaemic, control studies, thus excluding any role for [K+] or insulin. During hypermetabolism, a proportional augmentation of peripheral CO2 gain, measured from the phrenic electroneurogram during artificial ventilation, was shown to maintain the arterial blood gas status. In vitro, measurements of single-fibre chemoafferent discharge showed that low [glucose], over a physiological range and during normoxia, increased neither the carotid baseline discharge nor the CO2 sensitivity. Taken together, these results demonstrate that the carotid body is not a physiological sensor of glucose but augmentation of the carotid body chemosensitivity via an undetermined yet, hypermetabolism-related factor(s) is most likely to be involved in exercise hyperpnoea.
In Breast Cancer Chemosensitivity, a group of world leading experts review critical aspects of resistance to systemic therapy in breast cancer patients. Beginning with a clinical overview of the problem, the book then focuses on the latest findings of molecular mechanisms of drug resistance. Coverage provides an example of using novel approaches for chemosensitization of breast cancer cells that gives readers an idea about the future direction in breast cancer treatment. It allows those who are interested in breast cancer therapy to get a jump-start on critical issues in breast cancer therapeutic resistance.
'It will form an important addition to a scientific library and a useful addition to the (contributions series) which should be part of any obstetrics and gynaecology library.' New Zealand Journal of Obstetrics and Gynaecology
A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity,Volume 2: In Vivo Models, Imaging, and Molecular Regulators contains cutting-edge protocols for classifying tumors into response categories and for customizing therapy to individuals. These readily reproducible techniques allow measurements of DNA damage, apoptotic cell death, and the molecular and cellular regulators of cytotoxicity, as well as in vivo animal modeling of chemosensitivity. A companion volume, Volume 1: In Vitro Assays contains in vitro and in vivo techniques to identify which new agents or combination of agents are effective for each type of tumor.
DNA Repair and Cancer Therapy: Molecular Targets and Clinical Applications, Second Edition provides a comprehensive and timely reference that focuses on the translational and clinical use of DNA repair as a target area for the development of diagnostic biomarkers and the enhancement of cancer treatment. Experts on DNA repair proteins from all areas of cancer biology research take readers from bench research to new therapeutic approaches. This book provides a detailed discussion of combination therapies, in other words, how the inhibition of repair pathways can be coupled with chemotherapy, radiation, or DNA damaging drugs. Newer areas in this edition include the role of DNA repair in chemotherapy induced peripheral neuropathy, radiation DNA damage, Fanconi anemia cross-link repair, translesion DNA polymerases, BRCA1-BRCA2 pathway for HR and synthetic lethality, and mechanisms of resistance to clinical PARP inhibitors. - Provides a comprehensive overview of the basic and translational research in DNA repair as a cancer therapeutic target - Includes timely updates from the earlier edition, including Fanconi Anemia cross-link repair, translesion DNA polymerases, chemotherapy induced peripheral neuropathy, and many other new areas within DNA repair and cancer therapy - Saves academic, medical, and pharma researchers time by allowing them to quickly access the very latest details on DNA repair and cancer therapy - Assists researchers and research clinicians in understanding the importance of the breakthroughs that are contributing to advances in disease-specific research
The Fifth World Congress of the International Society for Diseases of the Esophagus was held in the historic city of Kyoto, Japan, from August 5 through 8, 1992. Approximately 40 countries throughout the world participated and roughly 500 presentations were made. Excellent authors were selected and they were requested to send in their manuscripts for publication of this book. It is our ardent hope that this book will prove to be beneficial to the doctor interested in the esophagus and that it will provide the reader with first-hand information from leading scientists and clinicians in this field. The incidence of esophageal diseases vary greatly from country to country and in recent years, worldwide interest in these diseases has resulted in various international studies. The International Society for Diseases of the Esophagus was inaugurated by Professor Komei Nakayama in 1979 and since that time it has actively contributed to the exchange of information regarding these diseases and has made endeavors in bringing about advancement in the struggle against diseases of the esophagus in every way possible.