tbuckley/cabot-search huggingface dataset:
Abstract 3596: The role of PIM1 kinase in the prostate tumor microenvironment
Authors: Marina Zemskova, Andrew S. Kraft
Journal: Cancer Research (2014)

Abstract Prostate cancer (PCa) remains the second leading cause of cancer-related deaths in men. The prostate is a tubulo-alveolar gland composed of epithelial tissues embedded in stromal components. PCa includes reactive stroma which consists of myofibroblasts and extracellular matrix (ECM) remodeling. Increasing evidence suggests that myofibroblasts may refine the prognostic assessment of tumors. The PIM1 serine/threonine protein kinase is a true oncogene and has been implicated in the initiation and progression of multiple cancer types including PCa. The level of PIM1 correlates with the disease state and Gleason grade and has been shown to stimulate growth of murine prostate cancer. The role of PIM1 in prostate stromal cells has never been investigated. Using human prostate tissue microarray analysis we now demonstrate that (1) the PIM1 protein is detected in human stroma adjacent to cancer tissue; (2) stromal cells isolated from PIM1 knockout mice contain a decreased number of myofibroblasts and expose slow growth rate when compared with wild type control, suggesting that kinase expression can alter stromal cell composition and proliferation; (3) elevated level of PIM1 kinase in human benign prostate stromal cells increases migration and growth of prostate epithelial cells and this effect can be reversed by PIM inhibitors; (4) PIM1 over-expressing stromal cells increase epithelial cell growth in tissue regeneration model; (5) stromal cells with elevated level of PIM1 expose increased number of myofibroblasts when co-cultivated with prostate epithelial cells. These data suggest that PIM1 kinase may contribute in formation of a “reactive stroma” phenotype. We used the conditioning media analysis to decipher the PIM1 specific signal transduction pathways that may lead to stroma activation and drive prostate cancer growth. Using cytokine/chemokine arrays and ECM protein analysis we found that overexpression of PIM1 kinase in stromal cells is associated with elevated level of CCL5 chemokine and increased secretion of collagen1. Examination of the pathways involved in formation of myofibroblasts revealed that PIM1 can modulate activation of PDGFRβ leading to the increased CCL5 expression. We are suggesting that PIM1 is a modulator of stromal cells response to the stimuli produced by prostate epithelial cells through increase of matrix stiffness, receptor activation and accumulation of myofibroblasts which induce further ECM remodeling and expression of the growth factors leading to epithelial cells transformation and cancer propagation. Citation Format: Marina Zemskova, Andrew S. Kraft. The role of PIM1 kinase in the prostate tumor microenvironment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3596. doi:10.1158/1538-7445.AM2014-3596
Science, medicine, and the future: Helicobacter pylori and gastric diseases
Authors: M. J Blaser
Journal: BMJ (1998)

The isolation of Helicobacter pylori from clinical specimens by Marshall and Warren 15 years ago1 launched revolutions in gastroenterology and microbiology. 2 3 Like other revolutions in history, the original directions of the H pylori story have changed in response to conflicting ideologies, observation, and practices. Currently, enthusiasts, drug companies, and the lay press are putting pressure on physicians to eliminate H pylori from all patients, symptomatic or not, in whom it is detected. There is little evidence that this is appropriate, and management will continue to change as new knowledge emerges and socioeconomic environments change in ways that are relevant to H pylori and clinical medicine. This article looks at past and current trends to anticipate the future of these common bacteria and the disorders associated with them.

H pylori is one of a large family of related bacteria that are well adapted to persist in the stomachs of vertebrates for the life span of their hosts. It is likely that H pylori has colonised our stomachs since well before we became humans.4 Studies of primates and human populations in developing countries suggest that, until the last century, nearly all humans carried H pylori or closely related bacteria in their stomachs. H pylori can thus be regarded as indigenous or “normal” flora, which most humans acquire within the first few years of childhood and then carry for life.

With socioeconomic development, fewer children are acquiring H pylori .5 This is a worldwide phenomenon that seems to have preceded the introduction of antibiotics, although it may have been accelerated by their widespread use. The reasons for the decline in the prevalence of H pylori colonisation are unknown. Improved nutrition and clean water have been proposed. An alternative hypothesis is that most transmission is from child to child …
HIV/AIDS Guidelines
Authors: Joan Stephenson
Journal: JAMA (1999)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study Pre-eclampsia and cardiovascular disease later in life: who is at risk?
Authors: H. U Irgens, L. Reisater, L. M Irgens, R. T Lie, J. M Roberts
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To assess whether mothers and fathers have a higher long term risk of death, particularly from cardiovascular disease and cancer, after the mother has had pre-eclampsia. <b>Design:</b> Population based cohort study of registry data. <b>Subjects:</b> Mothers and fathers of all 626 272 births that were the mothers9 first deliveries, recorded in the Norwegian medical birth registry from 1967 to 1992. Parents were divided into two cohorts based on whether the mother had pre-eclampsia during the pregnancy. Subjects were also stratified by whether the birth was term or preterm, given that pre-eclampsia might be more severe in preterm pregnancies. <b>Main outcome measures:</b> Total mortality and mortality from cardiovascular causes, cancer, and stroke from 1967 to 1992, from data from the Norwegian registry of causes of death. <b>Results:</b> Women who had pre-eclampsia had a 1.2-fold higher long term risk of death (95% confidence interval 1.02 to 1.37) than women who did not have pre-eclampsia. The risk in women with pre-eclampsia and a preterm delivery was 2.71-fold higher (1.99 to 3.68) than in women who did not have pre-eclampsia and whose pregnancies went to term. In particular, the risk of death from cardiovascular causes among women with pre-eclampsia and a preterm delivery was 8.12-fold higher (4.31 to 15.33). However, these women had a 0.36-fold (not significant) decreased risk of cancer. The long term risk of death was no higher among the fathers of the pre-eclamptic pregnancies than the fathers of pregnancies in which pre-eclampsia did not occur. <b>Conclusions:</b> Genetic factors that increase the risk of cardiovascular disease may also be linked to pre-eclampsia. A possible genetic contribution from fathers to the risk of pre-eclampsia was not reflected in increased risks of death from cardiovascular causes or cancer among fathers. <h3>What is already known on this topic</h3> Maternal and fetal genes (including those inherited from the father) may contribute to pre-eclampsia, which occurs in 3-5% of pregnancies One set of candidate genes for pre-eclampsia is the maternal genes for thrombophilia, which may increase the mother9s risk of death from cardiovascular disease <h3>What this study adds</h3> Women who have pre-eclampsia during a pregnancy that ends in a preterm delivery have an eightfold higher risk of death from cardiovascular disease compared with women who do not have pre-eclampsia and whose pregnancy goes to term Fathers of pregnancies in which pre-eclampsia occurred have no increased risk of death from cardiovascular disease These results are compatible with maternal genes for thrombophilia having an effect on the risk of pre-eclampsia and of death from cardiovascular disease
THE CURRENT STATUS OF THE PREGNANT CARDIAC
Authors: JACK M. KAUFMAN, M.D., PAUL E. RUBLE, M.D.
Journal: Annals of Internal Medicine (1958)

ExcerptAs with every endeavor in medicine, we should stop frequently to re-evaluate the old, add the new, and discard tenets which are no longer applicable. The pregnant cardiac who formerly was said to be a candidate for abortion is now able to continue through pregnancy with safety to both mother and child. This recent change in prognosis is due to a better understanding of the physiology of pregnancy, improved medical management and modern heart surgery. We feel that, when indicated, operation should be done even during pregnancy. This may be done without fear of subsequent miscarriage or excessive risk to...
Peripheral-blood cell-free Epstein-Barr viral DNA load complements clinical staging in nasopharyngeal carcinoma prognostication
Authors: Sing F. Leung, Benny Zee, Brigette B. Ma, Edwin P. Hui, Frankie Mo, Maria Lai, K. C. Allen Chan, Lisa Ys Chan, Wing Hong Kwan, Y. M. Lo, Anthony Tc Chan
Journal: Clinical Cancer Research (2006)

A57   Purpose: To evaluate the effect of combining plasma/serum Epstein-Barr viral (EBV) DNA load data with clinical staging information in prognostication of nasopharyngeal carcinoma (NPC).Patients and Methods: 376 patients of all stages of NPC, but excluding those with distant metastases on presentation, were studied. The histology of the tumors was World Health Organisation Type II or III in all except two patients. Clinical stage designation (Stages I-IV) was according to the 5 th  edition of the UICC-AJCC on staging. Pre-treatment plasma/serum EBV DNA concentrations were quantified by a real-time PCR assay that amplified a DNA segment in the  Bam HI-W fragment region of the EBV genome. A cutoff level of 4000 copies/mL was used to define low and high EBV-DNA load. All patients received radiation therapy and 41 patients also received chemotherapy. Kaplan-Meier plots of overall survival were established for patient groups of clinical stages I to IV, and for patients sub-groups with high, and low EBV DNA loads within early (Stages I-II), and advanced (Stages III-IV) UICC stages. Differences in survival probabilities were analysed by the log-rank test. P values of
IL-12/Th1 and IL-23/Th17 biliary microenvironment in primary biliary cirrhosis: Implications for therapy
Authors: Chen-Yen Yang, Xiong Ma, Koichi Tsuneyama, Shanshan Huang, Toru Takahashi, Naga P. Chalasani, Christopher L. Bowlus, Guo-Xiang Yang, Patrick S.C. Leung, Aftab A. Ansari, Linda Wu, Ross L. Coppel, Eric M. Gershwin
Journal: Hepatology (2013)

The interleukin (IL)-12/IL-23-mediated Th1/Th17 signaling pathway has been associated with the etiopathogenesis of primary biliary cirrhosis (PBC). To address the cytokine microenvironment specifically in the liver, we examined the localized expression of cytokine subunits and their corresponding receptors using previously optimized immunohistochemistry with an extensive panel of antibodies directed at IL-12p70, IL-12p35, interferon-gamma (IFN-γ), IL-12RB2, IL-23p40, IL-23p19, IL-17, and IL-23R using liver from PBC (n = 51) and non-PBC (n = 80) control liver disease patients. Multiple portal tracts in each patient were blindly evaluated and individually scored. We report herein that although IL-12/Th1 and IL-23/Th17 staining was detected in all of the liver sections, they were primarily localized around the damaged interlobular bile ducts in PBC. Most important, Th17 skewing was prominent in advanced PBC patients with intensive secretion of IL-23p19 by inflamed hepatocytes around IL-23R, IL-12RB2, and IFN-γ expressing degenerated cholangiocytes. Our novel finding on the direct association of Th17 skewing and disease severity illustrates the significance of the IL-23/Th17 pathway in the perpetuation of IL-12/Th1-mediated immunopathology in PBC. Furthermore, localized IL-23p19 production by hepatocytes may enhance profibrotic Th17 signaling and proinflammatory IFN-γ production that contribute to PBC pathology. Conclusion : Our data emphasize the pathogenic relevance of IL-12/Th1 and IL-23/Th17 in the evolution of PBC. Of significance, however, the shift from a Th1 to a Th17 imbalance at advanced stages of the disease suggests the necessity to consider modulation of the IL-23/Th17 pathway as a potential target for therapeutic intervention. (Hepatology 2014;59:1944–1953)
Nickel dermatitis hazards from prostheses.
Authors: M.H. SAMITZ, S.A. KATZ
Journal: British Journal of Dermatology (1975)

This report reviews data relating to the nickel hazard from implanted prostheses. It is shown that nickel is released from stainless steel prostheses by the action of sweat, blood and physiological saline solution. In laboratory animals, solubilized nickel is localized in the tissue near the implant.
Nutrition and Metabolism of Animal Tissue Cultures&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Charity Waymouth
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Nutrition and Metabolism of Animal Tissue Cultures Get access Charity Waymouth Charity Waymouth Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 4, October 1957, Pages 495–510, https://doi.org/10.1093/jnci/19.4.495 Published: 01 October 1957 Article history Received: 28 May 1957 Published: 01 October 1957
The 44 kDa Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug resistant activity in human prostate cancer cells
Authors: Yingqiu Xie, Kexin Xu, Douglas Linn, Zhiyong Guo, Takeo Nakanishi, Douglas Ross, Yun Qiu
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3244 

We previously showed that the 44 kDa serine/threonine kinase Pim-1 (Pim-1L) can protect prostate cancer cells from apoptosis induced by chemotherapeutic drugs (Oncogene, 25: 70-78, 2006). To further explore the mechanisms of Pim-1L mediated resistance to chemotherapeutic drugs in prostate cancer cells, we employed a yeast two-hybrid screening to identify cellular proteins that are associated with Pim-1L and we found the ABC transporter BCRP/ABCG2 as one of the potential interacting partners of Pim-1L. We also showed that the expression level of Pim-1L and BCRP are up-regulated in mitoxantrone and docetaxel-resistant prostate cancer cell lines. Pim-1L is colocalized with BCRP on the plasma membrane and induces phosphorylation of BCRP at Threonine 362. Knocking-down Pim-1L expression in the drug resistant prostate cancer cells abolished multimer formation of endogenous BCRP and resensitized the resistant cells to chemotherapeutic drugs, suggesting that BCRP phosphorylation induced by Pim-1L is essential for its functionality. This is further corroborated by our finding that the plasma membrane localization and drug resistant activity of BCRP was compromised by T362A mutation. Our data suggest that Pim-1L may protect prostate cancer cells from apoptosis, at least in part, through regulation of transmembrane drug efflux pump. These findings may provide a potential therapeutic approach by disrupting Pim-1 signaling to reverse BCRP-mediated multidrug resistance.
Gonorrhea in the Male and Female: A Book for Practitioners.
Authors: P. S. Pelouze
Journal: JAMA (1933)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 4272: Applying TCGA data for breast cancer diagnostics and pathway analysis
Authors: Jannik Andersen, Parantu Shah, Konstanty Korski, Matthew Ibbs, Violetta Filas, Michal Kosiedowski, Juliusz Pukacki, Cezary Mazurek, Yuanqing Wu, Edward Chang, Carlo Toniatti, Giulio Draetta, Maciej Wiznerowicz
Journal: Cancer Research (2014)

Abstract The main objective of our project is to obtain a comprehensive insight into oncogenic signaling in order to develop novel diagnostic tools for molecular subtypes of breast cancer (BRCA). We have provided about 100 BRCA samples along with full pathology and clinical annotations to the TCGA program. These cancer samples have been extensively characterized using all available genomics platforms and the obtained molecular data contributed to the molecular characterization of BRCA. This integrated effort identified four major molecular subtypes of breast cancer that can be identified across five profiling platform including genomics, transcriptomics and proteomics (Nature, 490 (7418):61-70). Building upon these datasets we aim to translate these genomics profiles into diagnostic tools that can be used in every day medical practice. In the first step, we have generated tissue microarrays (TMAs) from FFPE BRCA samples obtained from the patients enrolled into the TCGA project. Next, the TMA slides were used for immunohistochemistry (IHC) using about 100 antibodies specific for major cancer markers, including oncogenic kinases frequently activated or overexpressed in BRCA. The obtained IHC results have been scored and verified independently for each marker by two board-certified pathologists. To identify markers that correlate with or are specific to the molecular subtypes of BRCA, the TMA/IHC read-outs from each tumor sample were correlated with all TCGA genomic data. In addition, we integrate the pathology and genomics results with clinical data obtained from the TCGA-enrolled patients, including up to 4 years follow-up. Finally, we apply system biology tools to integrate the genomic data from TCGA with the proteomic analysis to understand causalities between changes in DNA, transcriptome and signal transduction pathways. Our long-term goal is to identify novel diagnostic biomarkers that will precisely identify each molecular subtype of BRCA and which may be predictive of patient response to therapy thus paving the way for novel personalized therapies for cancer. Citation Format: Jannik Andersen, Parantu Shah, Konstanty Korski, Matthew Ibbs, Violetta Filas, Michal Kosiedowski, Juliusz Pukacki, Cezary Mazurek, Yuanqing Wu, Edward Chang, Carlo Toniatti, Giulio Draetta, Maciej Wiznerowicz. Applying TCGA data for breast cancer diagnostics and pathway analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4272. doi:10.1158/1538-7445.AM2014-4272
Abstract 17047: Role of Mitochondrial Function and Mitochondrial DNA Integrity in Coronary Metabolic Dilation
Authors: Giacinta Guarini, Christopher Kolz, Vahagn A Ohanyan, Ian N Bratz, Liya Yin, Inna Shokolenko, Glenn L Wilson, William M Chilian
Journal: Circulation (2010)

Alterations in mitochondrial function are observed in a variety of animal models with impaired cardiac pump function. Often these models have coronary insufficiency and show blunted metabolic regul...
Abstract 1720: MSK1 mediates PI3K inhibition resistance by induction of β-catenin phosphorylation in glioblastoma
Authors: Shaofang Wu, Jun Fu, Siyuan Zheng, Roel G. Verhaak, W. K Yung, Dimpy Koul
Journal: Cancer Research (2014)

Abstract Glioblastoma (GBM), the most common malignant brain tumor in adults, represents a compelling disease for kinase inhibitor therapy because majority of these tumors harbor genetic alterations that result in aberrant activation of growth factor signaling pathways. PI3K/mTOR-pathway is dysregulated in over 50% of human glioblastomas (GBM) and represents an attractive target for therapy. One major challenge for single pathway PI3K inhibition targeting therapy is intrinsic resistance. To study the mechanism of intrinsic resistance to PI3K inhibition, we analyzed the pre- and post-treatment reverse phase protein arrays (RPPA) data of both giloma cells and giloma initiating cells (GIC). Mitogen- and stress-activated protein kinase 1 (MSK1) was markedly induced after PI3K inhibitor treatment and it was linked with increase expression of β-catenin. We further found that MSK1 directly interacts with β-catenin and stabilizes β-catenin protein level. MSK1 also regulates β-catenin nuclear translocation and β-catenin transcriptional activity. More interestingly, using in vitro kinase assay, we identified MSK1 is a kinase that phosphorylates β-catenin. Finally, we showed that depletion of β-catenin potentiates PI3K inhibitors induced cytotoxity in a series of GICs. Taken together, our results suggest that MSK1/β-catenin signaling may serve as an escape survival signaling upon PI3K inhibition, and combination of PI3K inhibition and MSK1/β-catenin inhibition is required to induce lethal growth inhibition in human glioblastoma cells. Citation Format: Shaofang Wu, Jun Fu, Siyuan Zheng, Roel G. Verhaak, W. K Yung, Dimpy Koul. MSK1 mediates PI3K inhibition resistance by induction of β-catenin phosphorylation in glioblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1720. doi:10.1158/1538-7445.AM2014-1720