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121.
Hasmik Keshishian E Robert McDonald III Filip Mundt Randy Melanson Karsten Krug Dale A Porter Luke Wallace Dominique Forestier Bokang Rabasha Sara E Marlow Judit JaneValbuena Ellen Todres Harrison Specht Margaret Lea Robinson Pierre M Jean Beltran Ozgun Babur Meagan E Olive Javad Golji Eric Kuhn Michael Burgess Melanie A MacMullan Tomas Rejtar Karen Wang DR Mani Shankha Satpathy Michael A Gillette William R Sellers Steven A Carr 《Molecular systems biology》2021,17(9)
Reliable methods to quantify dynamic signaling changes across diverse pathways are needed to better understand the effects of disease and drug treatment in cells and tissues but are presently lacking. Here, we present SigPath, a targeted mass spectrometry (MS) assay that measures 284 phosphosites in 200 phosphoproteins of biological interest. SigPath probes a broad swath of signaling biology with high throughput and quantitative precision. We applied the assay to investigate changes in phospho‐signaling in drug‐treated cancer cell lines, breast cancer preclinical models, and human medulloblastoma tumors. In addition to validating previous findings, SigPath detected and quantified a large number of differentially regulated phosphosites newly associated with disease models and human tumors at baseline or with drug perturbation. Our results highlight the potential of SigPath to monitor phosphoproteomic signaling events and to nominate mechanistic hypotheses regarding oncogenesis, response, and resistance to therapy. 相似文献
122.
Lihong?BuEmail author Kenneth?DR?Setchell Edwin?D?Lephart 《Reproductive biology and endocrinology : RB&E》2005,3(1):58
Background
Isoflavones, the most abundant phytoestrogens in soy foods, are structurally similar to 17beta-estradiol. Few studies have examined the nociception and stress hormone responses after consumption of soy isoflavones. 相似文献123.
124.
Apoptosis is also known as programmed cell death. Apoptosis plays an essential role in maintaining normal tissue and cell physiology in multicellular organisms. Clearance of aberrant or pre-cancerous cells occurs through the induction of apoptosis. It has been reported that many tumors and tumor cell lines have dysfunctional apoptosis signaling, causing these tumors to escape immune monitoring and internal cellular control mechanisms. One potential cause of this dysfunctional apoptosis is the tumor suppressor p53, an important regulator of growth arrest and apoptosis that is mutated in over 50% of all cancers. Retinoids have great potential in the areas of cancer therapy and chemoprevention. While some tumor cells are sensitive to the growth inhibitory effects of natural retinoids such as all-trans-retinoic acid (ATRA), many ovarian tumor cells are not. 6-[3-(1-Admantyl)]-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and fenretinide N-[4-hydroxyphenyl] retinamide (4-HPR) are conformationally restricted synthetic retinoids that induce growth arrest and apoptosis in both ATRA-sensitive and ATRA-resistant ovarian tumor cell lines. Recently, we have identified the molecular pathways of apoptosis induced by treatment of ovarian carcinoma cells with mutated p53 by CD437 and 4-HPR. 相似文献
125.
Retinoids in biological control and cancer 总被引:1,自引:0,他引:1
More than 80 years ago, Wolbach and Howe provided the first evidence suggesting a link between alterations within human cells that lead to malignancies and vitamin A deficiencies (Wolbach and Howe 1925 Nutr. Rev. 36: 16-19). Since that time, epidemiological, preclinical and clinical studies have established a causative relationship between vitamin A deficiency and cancer. Laboratory research has provided insight into the intracellular targets, various signaling cascades and physiological effects of the biologically-active natural and synthetic derivatives of vitamin A, known as retinoids. Collectively, this body of research supports the concept of retinoids as chemopreventive and chemotherapeutic agents that can prevent epithelial cell tumorigenesis by directing the cells to either differentiate, growth arrest, or undergo apoptosis, thus preventing or reversing neoplasia. Continued refinement of the retinoid signaling pathway is essential to establishing their use as effective therapeutics for tumor subtypes whose oncogenic intracellular signaling pathways can be blocked or reversed by treatment with retinoids. 相似文献
126.
DR Suresh Vamseedhar Annam K Pratibha BV Maruti Prasad 《Journal of biomedical science》2009,16(1):61-4
Background
Oxidative stress induced by the production of reactive oxygen species may play a critical role in the stimulation of HIV replication and the development of immunodeficiency. This study was conducted as there are limited and inconclusive studies on the significance of a novel early marker of oxidative stress which can reflect the total antioxidant capacity in HIV patients, 相似文献127.
Thirty-four cytochrome P-450 sequences from one bacterial and six
vertebrate species have been aligned with the aid of a computer alignment
algorithm. Phylogenetic trees were constructed using the
unweighted-pair-group and neighbor-joining methods. The two trees differed
at only a single branch point near the base of the tree. The cytochrome
P-450 superfamily of proteins clustered into eight families and contained
16 gene-duplication events. The first gene duplication occurred
approximately 1,360 Myr before the present (Mybp) and gave rise to
cytochrome P-450s found in two different cellular organelles, the
mitochondria and the endoplasmic reticulum. Both groups utilize cholesterol
or its metabolites as substrates, implying that cholesterol existed greater
than 1,360 Mybp. The fourth gene duplication (approximately 900 Mybp) gave
rise to the drug-metabolizing P-450s. These proteins aid in the
detoxification of foreign chemicals, as opposed to the metabolism of
endogenous compounds. The importance of the capacity to metabolize drugs is
reflected in 11 further gene duplications occurring in this lineage. The
first occurred approximately 800 Mybp and gave rise to the two major P-450
families, the phenobarbital and 3-methylcholanthrene families. An apparent
increase in the rate of cytochrome P-450 evolution is noted between the
bird-mammal divergence (300 Mybp) and the mammalian radiation (75 Mybp).
相似文献
128.
Localization of lipoprotein lipase mRNA in selected rat tissues 总被引:2,自引:0,他引:2
I J Goldberg D R Soprano M L Wyatt T M Vanni T G Kirchgessner M C Schotz 《Journal of lipid research》1989,30(10):1569-1577
Measurements of enzymatic activity have demonstrated that lipoprotein lipase (LPL), the principal enzyme responsible for hydrolysis of circulating triglyceride, is present in a number of tissues including brain, kidney, and adrenal gland. To determine the sites of synthesis of LPL in these tissues, in situ hybridization studies were performed using a non-sense 35S-labeled RNA probe produced from a 624-bp mouse LPL cDNA fragment. Control studies were performed with a sense RNA strand. Using 5-10-micron sections of 5-day-old rat brain, strong hybridization was found in pyramidal neurons of the hippocampus. Positive hybridization, indicating the presence of LPL mRNA, was also found in brain cortex and in the intermediate lobe of adult rat pituitary gland. Specific areas of adrenal and kidney medulla showed hybridization with the probe. LPL mRNA is, therefore, present in a number of specific regions of the body. LPL in these areas may not be important in regulating circulating levels of lipoproteins, but may be essential for cellular uptake, binding, and transfer of free fatty acids or other lipophilic substances. 相似文献
129.
130.
Maxuel de Oliveira Andrade Jaqueline Cristina da Silva Adriana Santos Soprano Hugo Massayoshi Shimo Adriana Franco Paes Leme Celso Eduardo Benedetti 《Molecular Plant Pathology》2023,24(4):331-345
Citrus cancer, caused by strains of Xanthomonas citri (Xc) and Xanthomonas aurantifolii (Xa), is one of the most economically important citrus diseases. Although our understanding of the molecular mechanisms underlying citrus canker development has advanced remarkably in recent years, exactly how citrus plants fight against these pathogens remains largely unclear. Using a Xa pathotype C strain that infects Mexican lime only and sweet oranges as a pathosystem to study the immune response triggered by this bacterium in these hosts, we herein report that the Xa flagellin C protein (XaFliC) acts as a potent defence elicitor in sweet oranges. Just as Xa blocked canker formation when coinfiltrated with Xc in sweet orange leaves, two polymorphic XaFliC peptides designated flgIII-20 and flgIII-27, not related to flg22 or flgII-28 but found in many Xanthomonas species, were sufficient to protect sweet orange plants from Xc infection. Accordingly, ectopic expression of XaFliC in a Xc FliC-defective mutant completely abolished the ability of this mutant to grow and cause canker in sweet orange but not Mexican lime plants. Because XaFliC and flgIII-27 also specifically induced the expression of several defence-related genes, our data suggest that XaFliC acts as a main immune response determinant in sweet orange plants. 相似文献