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  • 1
    ISSN: 1432-0843
    Keywords: Key words Hormone-resistant prostate carcinoma ; CI-958 ; Chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To assess the antitumor activity of the benzothiopyranoindazole CI-958 {5-[(2-aminomethyl)amino]-2-[2-(diethylamino)ethyl]-2H-[l]benzothi- opyrano[4,3,2-cd]-indazol-8-ol trihydrochloride} in hormone-resistant prostate carcinoma, using an intravenous dose of 700 mg/m2 every 3 weeks. Patients and methods: Patients eligible for this study had advanced prostate carcinoma that had failed hormonal treatment. Changes in an initially elevated prostate-specific antigen (PSA) level and regression of objectively measurable disease were used as response criteria. Results: All 33 patients enrolled were evaluated. Of 30 with elevated PSA levels, 6 had a 〉50% decline maintained for 〉30 days; response durations ranged from 105 to 623 days. Eleven patients had objectively measurable disease; two had partial responses (lasting 316 and 461 days) consisting of shrinkage of retroperitoneal nodes and of masses surrounding the rectum and bladder. The survival of all responding patients ranged from 366 days to 709 days and the median survival of all patients was 12 months (range 1–23 + months). Neutropenia was common, but thrombocytopenia was not. Nonhematologic side effects included nausea, vomiting, anorexia, asthenia, and chills, but were usually mild. The drug caused phlebitis when given into peripheral veins and central venous administration is recommended. No consistent reductions in cardiac function were documented by sequential assessment of left ventricular ejection fractions. Conclusions: CI-958 has modest but definite antitumor activity in hormone-resistant prostate carcinoma. Its toxicities include neutropenia, nausea, vomiting, anorexia, asthenia, chills and phlebitis.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2022-10-26
    Description: © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Vuillemin, A., Vargas, S., Coskun, O. K., Pockalny, R., Murray, R. W., Smith, D. C., D'Hondt, S., & Orsi, W. D. Atribacteria reproducing over millions of years in the Atlantic abyssal subseafloor. Mbio, 11(5), (2020): e01937-20, doi:10.1128/mBio.01937-20.
    Description: How microbial metabolism is translated into cellular reproduction under energy-limited settings below the seafloor over long timescales is poorly understood. Here, we show that microbial abundance increases an order of magnitude over a 5 million-year-long sequence in anoxic subseafloor clay of the abyssal North Atlantic Ocean. This increase in biomass correlated with an increased number of transcribed protein-encoding genes that included those involved in cytokinesis, demonstrating that active microbial reproduction outpaces cell death in these ancient sediments. Metagenomes, metatranscriptomes, and 16S rRNA gene sequencing all show that the actively reproducing community was dominated by the candidate phylum “Candidatus Atribacteria,” which exhibited patterns of gene expression consistent with fermentative, and potentially acetogenic, metabolism. “Ca. Atribacteria” dominated throughout the 8 million-year-old cored sequence, despite the detection limit for gene expression being reached in 5 million-year-old sediments. The subseafloor reproducing “Ca. Atribacteria” also expressed genes encoding a bacterial microcompartment that has potential to assist in secondary fermentation by recycling aldehydes and, thereby, harness additional power to reduce ferredoxin and NAD+. Expression of genes encoding the Rnf complex for generation of chemiosmotic ATP synthesis were also detected from the subseafloor “Ca. Atribacteria,” as well as the Wood-Ljungdahl pathway that could potentially have an anabolic or catabolic function. The correlation of this metabolism with cytokinesis gene expression and a net increase in biomass over the million-year-old sampled interval indicates that the “Ca. Atribacteria” can perform the necessary catabolic and anabolic functions necessary for cellular reproduction, even under energy limitation in millions-of-years-old anoxic sediments.
    Description: This work was supported primarily by the Deutsche Forschungsgemeinschaft (DFG) project OR 417/1-1 granted to W.D.O. Preliminary work was supported by the Center for Dark Energy Biosphere Investigations project OCE-0939564 also granted to W.D.O. The expedition was funded by the US National Science Foundation through grant NSF-OCE-1433150 to S.D. and R.P. R.W.M. led the expedition. Shipboard microbiology efforts were supported by the Center for Dark Energy Biosphere Investigations (C-DEBI grant NSF-OCE-0939564). This is C-DEBI publication 545. This is a contribution of the Deep Carbon Observatory (DCO).
    Keywords: Deep biosphere ; Energy limit to life ; Atribacteria ; Acetogenesis ; Metagenomics ; Transcriptomics ; Fermentation ; Bacterial microcompartment ; Clade JS1 ; Metatranscriptomics ; Subseafloor life
    Repository Name: Woods Hole Open Access Server
    Type: Article
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