tbuckley/cabot-search huggingface dataset:
The molecular basis of chemosensitivity to cytotoxic agents in primary cell cultures from human tumors
Authors: Ian Cree, Francis Gabriel, Penny Johnson, Marta Polak, Louise Knight, Katharine Parker, Sharon Glaysher, Matthew Poole, Ajit Narayanan
Journal: Clinical Cancer Research (2007)

B21  Background: Most cancers exhibit considerable heterogeneity in their sensitivity to chemotherapy. This study has tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients’ tumors.  Methods: The chemosensitivity of a series of 192 lung, breast, ovarian and colorectal tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA) and correlated with quantitative expression of resistance and target genes measured by RT-PCR in a Taqman Low Density Array (TLDA) following extraction of mRNA from formalin-fixed paraffin-processed tissue. The results for each tumor type were standardised against the least variable housekeeping gene (PBGD) of those tested, and assessed by multiple linear regression, resulting in a series of gene signatures.  Results: Predictive multiple linear regression models were derived for single agents and for combinations commonly used in NSCLC, colorectal, breast and ovarian cancers. Analysis of all of the genes entered into the resulting multiple linear regression models by SPSS shows that several were commonly entered, while others were observed to explain some of the variation of chemosensitivity within the ATP-TCA for different anti-drugs/tumor types. The genes most commonly associated were FPGS, Ki67, MLH1, MDR1, MRP5, and OPRT. However, 86 of the 96 genes on the array were present in at least one of the statistical models, each of which contained 12-20 genes.  Conclusion: The genes found to be most commonly associated with chemosensitivity in the ATP-TCA reflect the mechanisms involved, including cell proliferation (e.g. Ki67), DNA repair (e.g. MLH1) and the expression of xenobiotic pump molecules (e.g. MDR1 and MRP5). The models identified by the study are in line with previously published data and suggest that a limited number of genes are important in anti-cancer drug resistance.
Association of Antidepressant Medication Use During Pregnancy With Intellectual Disability in Offspring
Authors: Alexander Viktorin, Rudolf Uher, Alexander Kolevzon, Abraham Reichenberg, Stephen Z. Levine, Sven Sandin
Journal: JAMA Psychiatry (2017)

Maternal antidepressant medication use during pregnancy has previously been associated with adverse outcomes in offspring, but to our knowledge, the association with intellectual disability (ID) has not been investigated.To examine the association of maternal antidepressant medication use during pregnancy with ID in offspring and investigate the importance of parental mental illness for such an association.A population-based cohort study of 179 007 children born from January 1, 2006, through December 31, 2007, with complete parental information from national registers who were followed up from birth throughout 2014.We estimated relative risks (RRs) and 95% CIs of ID in children exposed during pregnancy to any antidepressant medication or specifically to selective serotonin reuptake inhibitor (SSRI) antidepressants, all other non-SSRI antidepressants, or other nonantidepressant psychotropic medications. Analyses were adjusted for potential confounders. In addition to full population analyses, we used a subsample to compare mothers who used antidepressants during pregnancy with mothers who had at least one diagnosis of depression or anxiety before childbirth but did not use antidepressants during pregnancy.Of the 179 007 children included in the study (mean [SD] age at end of follow-up, 7.9 [0.6] years; 92 133 [51.5%] male and 86 874 [48.5%] female), ID was diagnosed in 37 children (0.9%) exposed to antidepressants and in 819 children (0.5%) unexposed to antidepressants. With adjustment for potential confounders, the RR of ID after antidepressant exposure was estimated at 1.33 (95% CI, 0.90-1.98) in the full population sample and 1.64 (95% CI, 0.95-2.83) in the subsample of women with depression. Results from analyses of SSRI antidepressants, non-SSRI antidepressants, and nonantidepressant psychotropic medications and analyses in the clinically relevant subsample did not deviate from the full-sample results.The unadjusted RR of ID was increased in offspring born to mothers treated with antidepressants during pregnancy. After adjustment for confounding factors, however, the current study did not find evidence of an association between ID and maternal antidepressant medication use during pregnancy. Instead, the association may be attributable to a mechanism integral to other factors, such as parental age and mother's psychiatric disorder.
Outcomes of Allogeneic Stem Cell Transplant (Allo-SCT) for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) in Patients Older Than 75 Years: A Single Center Analysis
Authors: Rajneesh Nath, Jan Cerny, Muthalagu Ramanathan, Zheng Zhou, Neng Yu, Glen D Raffel, Jayde Bednarik
Journal: Blood (2016)
The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids
Authors: Puneet Puri, Kalyani Daita, Andrew Joyce, Faridoddin Mirshahi, Prasanna K. Santhekadur, Sophie Cazanave, Velimir A Luketic, Mohammad S. Siddiqui, Sherry Boyett, Hae‐Ki Min, Divya P. Kumar, Rohit Kohli, Huiping Zhou, Phillip B. Hylemon, Melissa J. Contos, Michael Idowu, Arun J. Sanyal
Journal: Hepatology (2017)

The histologic spectrum of nonalcoholic fatty liver disease (NAFLD) includes fatty liver (NAFL) and steatohepatitis (NASH), which can progress to cirrhosis in up to 20% of NASH patients. Bile acids (BA) are linked to the pathogenesis and therapy of NASH. We (1) characterized the plasma BA profile in biopsy‐proven NAFL and NASH and compared to controls and (2) related the plasma BA profile to liver histologic features, disease activity, and fibrosis. Liquid chromatography/mass spectrometry quantified BAs. Descriptive statistics, paired and multiple group comparisons, and regression analyses were performed. Of 86 patients (24 controls, 25 NAFL, and 37 NASH; mean age 51.8 years and body mass index 31.9 kg/m 2 ), 66% were women. Increased total primary BAs and decreased secondary BAs (both P &lt; 0.05) characterized NASH. Total conjugated primary BAs were significantly higher in NASH versus NAFL ( P = 0.047) and versus controls ( P &lt; 0.0001). NASH had higher conjugated to unconjugated chenodeoxycholate ( P = 0.04), cholate ( P = 0.0004), and total primary BAs ( P &lt; 0.0001). The total cholate to chenodeoxycholate ratio was significantly higher in NAFLD without ( P = 0.005) and with ( P = 0.02) diabetes. Increased key BAs were associated with higher grades of steatosis (taurocholate), lobular (glycocholate) and portal inflammation (taurolithocholate), and hepatocyte ballooning (taurocholate). Conjugated cholate and taurocholate directly and secondary to primary BA ratio inversely correlated to NAFLD activity score. A higher ratio of total secondary to primary BA decreased (odds ratio, 0.57; P = 0.004) and higher conjugated cholate increased the likelihood of significant fibrosis (F≥2) ( P = 0.007). Conclusion : NAFLD is associated with significantly altered circulating BA composition, likely unaffected by type 2 diabetes, and correlated with histological features of NASH; these observations provide the foundation for future hypothesis‐driven studies of specific effects of BAs on specific aspects of NASH. (H epatology 2018;67:534‐548).
Snails and Skin Care—An Uncovered Combination
Authors: Lucy Liu, Anshum Sood, Stephanie Steinweg
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Leveraging peer-based support to facilitate HIV care in Kenya
Authors: Rakhi Karwa, Mercy Maina, Timothy Mercer, Benson Njuguna, Juddy Wachira, Celia Ngetich, Fatma Some, Beatrice Jakait, Regina K. Owino, Adrian Gardner, Sonak Pastakia
Journal: PLoS Medicine (2017)

Rakhi Karwa and colleagues discuss a program in which peer navigators support care for people with HIV at a Kenyan hospital.
Abstract 250: Elucidating the Role of Platelet Derived Growth Factor Receptor Alpha Signaling in Cardiac Fibroblasts
Authors: Malina J Ivey, Michelle Tallquist
Journal: Circulation Research (2015)

Cardiac fibrosis is a major component of heart disease and is a hallmark of decreased cardiac function. Currently, there are no treatments that attenuate fibrosis directly. This major hurdle can be overcome by targeting the resident fibroblast. Preliminary data demonstrates that loss of PDGFRα expression in the adult cardiac fibroblast lineage results in loss of over half of resident fibroblasts. A time course experiment revealed that in as little as 4 days after PDGFRα gene deletion fibroblast loss can observed. Based on the basal level of fibroblast proliferation (0.8%+/-0.9, i.e. 4 of 398 cells), we hypothesize that PDGFRα signaling is essential for fibroblast maintenance and that fibroblasts undergo rapid turnover. We have begun to elucidate which downstream signals of PDGFRα are involved the different roles of the fibroblast. Using a PDGFRα-dependent-PI3K-deficient mouse model, preliminary data indicates that PDGFRα-dependent PI3K signaling is involved in this cell survival response. Future studies will investigate cardiac fibroblast maintenance signals by determining which cell types secrete PDGF ligands. We will also investigate the role of PDGFRα signaling after myocardial infarction. Our lab has genetic tools that enable us to follow fibroblasts after injury, and we have determined both the number of proliferating fibroblasts at different time points, as well as the fraction of fibroblasts that make up the total population of proliferating cells after LAD ligation. Our preliminary data in control hearts shows that fibroblasts reach their peak of proliferation within a week after infarction, although they remain one of the most proliferative cell types as long as three weeks after induction. Our studies will illuminate the role of the fibroblast in tissue homeostasis and after infarction and identify how these cells contribute to overall cardiovascular function and delineate the fine balance between the essential and detrimental functions of the fibroblast.
Copy number variation of the drug-associated genes
Authors: Shumpei Ishikawa, Hiroyuki Aburatani
Journal: Clinical Cancer Research (2007)

A56   During the Structural Variation Consortium project, over 3000 genes have been found to be overlapped with copy number variations (CNVs), which covers as much as 12% of the human genome. Particularly, drug-associated genes are enriched within CNV regions, as well as olfactory receptors and immunoglobulin superfamilies. They include drug metabolizing genes such as CYP and UGT families, and drug transporters like ABCs.  This implies that human genomes have been dynamically changing local copy number according to environmental stress including xenobiotics. Some of them are frequent in particular populations, potentially generating common response variation to drugs like chemotherapeutics, antibiotics, hormones, and alkaloids.  Importantly, the HapMap SNPs are significantly under-represented in CNV regions. This is because some SNPs in these regions are not-called due to unusual signal, and others are deleted due to H-W and Mendelian inheritance errors. This indicates that any pharmacogenetic approach based on current public SNP data potentially loses these large scale polymorphisms, and more dense genotyping around CNVs and/or next generation platform will be needed for direct detection of copy numbers.
Validated antibody arrays for cancer biomarker profiling
Authors: Bryce Nelson, Tamara Zielinski
Journal: Clinical Cancer Research (2007)

B29  The search for protein biomarkers with predictive value for cancer diagnosis requires multiple protein assays and large sample sets. Microarrays are an attractive choice for performing parallel analysis of the abundance of multiple proteins in serum and plasma samples. Single-capture (also called high-density) antibody arrays, while not as sensitive as sandwich assays, are not limited by cross-reactivity between detector antibodies and analytes, and can therefore contain as many as several hundred antibody probes on a single chip. Single-capture antibody arrays capture proteins that have been directly labeled and incubated on the array and enable users to reproducibly screen for changes in protein abundance between samples. Several high-density antibody arrays are now commercially available; however, few if any of these arrays have been developed and fully validated for detectable and specific capture of the target protein in serum and plasma. As a result, many high-density arrays show significant cross-talk (low specificity) with regard to proteins contained in complex mixtures like serum.  In this presentation, we describe validation of a high-density, single-capture antibody microarray developed for highly specific capture of target proteins in serum and plasma. The array targets over fifty cancer-related serum proteins in sixteen patient sample wells using a single chip. Specific and linear capture of each targeted protein was demonstrated using either recombinant or purified proteins. Proteins were directly labeled using a platinum complex that forms a coordinative bond to sulphur and nitrogen containing side chains of methionine, cysteine and histidine. Detection was accomplished using fluor-labeled detector antibody.  Each immobilized antibody on the array showed linear capture of labeled proteins spiked into serum at approximate physiological concentrations over 2-3 logs and showed less than 5% cross-talk to other proteins in the panel. Additionally, several unlabeled proteins were spiked into serum and shown to cause a decrease in the binding of endogenous proteins through competition.  Data from clinical samples was obtained comparing results obtained from prostate cancer patient sera (Stage II, III and IV) with sera from patient diagnosed with benign prostatic hyperplasia. Data was also obtained using sera from breast, colon, rectal, and lung cancer patients. These experiments are designed to demonstrate the feasibility of an approach for the creation of high density arrays that could have wide-spread applicability to cancer research and help find better biomarkers for cancer diagnosis.
Abstract #5579: The inhibitory effects of organoselenium compounds on mTOR signaling in prostate cancer cells
Authors: Nicole Facompre, Indu Sinha, Karam El-Bayoumy, Raghu Sinha
Journal: Cancer Research (2009)

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer-related death in men in the United States. Androgen receptor signaling is critical for prostate cancer cell growth and thus anti-androgen therapies are commonly used to treat localized disease. However, the cancer eventually relapses into a hormone-resistant state. Currently there is a lack of effective treatments for advanced and hormone-resistant prostate cancers. We have previously shown that selenomethionine (SM), and 1,4-phenylenebis(methylene)selenocyanate (p-XSC) down-regulate androgen receptor expression and its phosphorylation in androgen responsive (AR) and androgen independent (AI) cells. Preclinical studies and proteomic analyses of human prostate tissues have implicated the mammalian target of rapamycin (mTOR) signaling pathway in the progression of prostate cancer and its transition to androgen independence, suggesting mTOR as a potential target for new therapies. Experimental studies further demonstrate a cross-talk between mTOR and androgen signaling in prostate cancer cells. We hypothesize that selenium inhibits prostate cancer cell growth by interfering with the mTOR signaling pathway and this inhibition may be linked to down-regulation of androgen receptor signaling in these cells. Here we showed, for the first time, that selenium compounds (SM, p-XSC, and methylseleninic acid) inhibit phosphorylation of mTOR and its downstream target p70S6 kinase in both LNCaP (AR) and LNCaP C4-2 (AI) human prostate cancer cells. Selenium-mediated inhibition of mTOR is attenuated by stimulation with androgens in AR but not in AI cells. Experiments are underway to determine if there is a link between mTOR inhibition by selenium and selenium-mediated modulation of androgen receptor signaling. In addition, the effects of different forms and doses of selenium on both mTOR complexes (mTORC1 and mTORC2) and their components are being examined. Validation of mTOR as a target of selenium in prostate cancer will provide evidence for its potential role against advanced and hormone refractory prostate disease either individually or in combination with anti-androgens. Support: DOD PC074101, NCI R01127729, Penn State Hershey Cancer Institute Funds   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5579.
Letter of response to Greenhawt et al. ‘LEAPing Through the Looking Glass: Secondary Analysis of the Effect of Skin Test Size and Age of Introduction on Peanut Tolerance after Early Peanut Introduction’
Authors: K. Lawson, H. T. Bahnson, E. Brittain, M. Sever, G. Du Toit, G. Lack, C. Keet, M. Greenhawt, D. Fleischer, E. S. Chan, C. Venter, D. Stukus, R. Gupta, J. Spergel
Journal: Allergy (2017)
Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus
Authors: Jason K Karimy, Jinwei Zhang, David B Kurland, Brianna Carusillo Theriault, Daniel Duran, Jesse A Stokum, Charuta Gavankar Furey, Xu Zhou, M Shahid Mansuri, Julio Montejo, Alberto Vera, Michael L DiLuna, Eric Delpire, Seth L Alper, Murat Gunel, Volodymyr Gerzanich, Ruslan Medzhitov, J Marc Simard, Kristopher T Kahle
Journal: Nature Medicine (2017)
The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer’s disease
Authors: Shuang-shuang Yang, Rui Zhang, Gang Wang, Yong-fang Zhang
Journal: Translational Neurodegeneration (2017)

Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is associated with learning and memory impairment in the elderly. Recent studies have found that treating AD in the way of chromatin remodeling via histone acetylation is a promising therapeutic regimen. In a number of recent studies, inhibitors of histone deacetylase (HDACs) have been found to be a novel promising therapeutic agents for neurological disorders, particularly for AD and other neurodegenerative diseases. Although HDAC inhibitors have the ability to ameliorate cognitive impairment, successful treatments in the classic AD animal model are rarely translated into clinical trials. As for the reduction of unwanted side effects, the development of HDAC inhibitors with increased isoform selectivity or seeking other directions is a key issue that needs to be addressed. The review focused on literatures on epigenetic mechanisms in recent years, especially on histone acetylation in terms of the enhancement of specificity, efficacy and avoiding side effects for treating AD.
Severe chest pain in an asthmatic patient
Authors: Michael Dromey, Chukwuemeka Nwaneri, David Wilson
Journal: BMJ (2017)

A 20 year old woman with a history of asthma presented to the emergency department complaining of shortness of breath and sharp pains in her chest and neck. The pain was worse on deep inspiration. She had a cough which produced small amounts of whitish sputum. The patient had had several previous exacerbations of asthma, and recently had not been using her inhalers regularly. On examination, her airway was patent and she had a generalised moderate wheeze in her chest, but no other obvious clinical signs. She could speak in full sentences and had normal oxygen saturations and temperature. She was mildly tachycardic and appeared slightly anxious. Her blood tests showed a mild neutrophilia and elevated C reactive protein.

She was given salbutamol and ipratropium nebulisers. These improved her wheezing, but she still complained of a severe central chest pain. In light of the unresolved chest pain and raised inflammatory markers, a chest radiograph was performed (fig 1⇓)



Fig 1  Chest radiograph
Effect of copper on the proliferation of testicular Leydig cells
Authors: James W. Dumond, Joycelynn Butler, Michele Walker-Brown
Journal: Cancer Research (2005)

1183  The toxic effect of copper on spermatozoa is well established. Copper is known to reduce the oxidative processes and glucose consumption in sperm, which reduces or abolishes its mobility. This property of copper has been exploited in intrauterine devices for birth control and is the focus for the development of for male contraceptives. The later has given rise to experimental implantations of particles covered with copper at various sites within the male reproductive system (lumen of the deferens, epididymis and seminal vesicle scrotum). These implantations have reportedly been successful in significantly decreasing the mobility of the spermatozoa. To date, these implantation studies have failed to report any systemic effects of the copper implants. However, copper has been shown to increase oxidative damage to DNA. This in itself indicates that copper exposure may increase the risk of carcinogenesis. In addition, copper ions have been reported to stimulate proliferation and migration of endothelial cells, which is the first stage in tumor angiogenesis. In this study we have examined the effect of low doses of copper on the proliferation of testicular Leydig cells. Cells were grown in DMEM/F12 culture media containing 5% horse serum and 2.5% fetal bovine serum. The cells were allowed to attach for 24 hrs, then switched to serum free media. Treatments consisted of 1pg, 10pg, 100pg, 1ng, 10ng, and 100ng per ml of copper along with a control (distilled water). Cell growth was measured at 72hrs via a hemacytometer. Copper treatment resulted in a significant (P