Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Jan 2000
ReviewPreclinical and clinical trials of topoisomerase inhibitors.
CPT-11, developed by Yakult Honsha, has achieved the position of standard chemotherapy for colorectal cancer in the United States and in Western countries because CPT-11 + 5FU + LV showed survival benefit compared with 5FU-LV in two randomized controlled trials. CPT-11 has been distributed to almost all countries. In Japan, combination therapy of CDDP + CPT-11 was significantly superior to CDDP-VP-16 in the treatment of extensive disease small cell lung cancer. ⋯ The new topoisomerase I inhibitors of indolocarbazol derivatives, NB-506 and J107088, developed by Banyu Co., have strong antitumor activity and a wide therapeutic ratio. The phase I trial of J107088 is currently ongoing in the United States and Japan. These do not show any cross-resistance to MDR drugs.
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Ann. N. Y. Acad. Sci. · Nov 1999
ReviewSelective loss of inner hair cells and type-I ganglion neurons in carboplatin-treated chinchillas. Mechanisms of damage and protection.
Carboplatin preferentially destroys inner hair cells (IHCs) and type-I spiral ganglion neurons while sparing outer hair cells (OHCs). Loss of IHCs and type-I ganglion cells is associated with a significant reduction of the compound action potential (CAP). However, the cochlear microphonic (CM) potential and distortion product otoacoustic emissions (DPOAEs) remain normal, indicating that the OHCs are functionally intact. ⋯ Intracochlear infusion of L-buthionine-[S,R]-sulfoximine (BSO), which depletes intracellular glutathione (GSH), increases IHC and OHC loss. Previous in vitro studies have shown that neurotrophin 4/5 (NT-4/5) promotes the survival of spiral ganglion neurons from cisplatin ototoxicity. In vivo perfusion of NT-4/5 promoted the survival of spiral ganglion neurons, but did not protect the hair cells.
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A variety of different isoforms of mammalian voltage-gated sodium channels have been identified. These channels can be classified into three different types. Eight type 1 isoforms have been identified in the CNS, PNS, skeletal muscle, and heart. ⋯ These channels diverge from the type 1 channels in critical regions, and have not been functionally expressed, so their significance is unknown. A single isoform identified in the PNS may represent a third class of channels, in that it diverges from both type 1 and 2 channels. The type 3 channel has not been functionally expressed.
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Ann. N. Y. Acad. Sci. · Apr 1999
ReviewMolecular and functional diversity of voltage-gated calcium channels.
The contributing roles of voltage-gated calcium channels (VGCC) to the generation of electrical signaling are well documented. VGCCs open in response to depolarization of the plasma membrane and mediate the flux of calcium into excitable cells, which further depolarizes the membrane. ⋯ The functional consequences of such interactions as well as other molecular aspects of VGCC will be discussed. Finally, although far from a final conclusion, what is currently known about the molecular composition of native calcium channels will be summarized.
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Ann. N. Y. Acad. Sci. · Jan 1999
ReviewSocioeconomic status and health. Policy implications in research, public health, and medical care.
The role of public policy in research, public health, and medical care is discussed as well as the extent to which public policy has been informed by increased knowledge about the relationship between SES and health and to what extent policy has affected SES-related health disparities. Observations on current healthcare policy and recommendations for the future are offered.