tbuckley/cabot-search huggingface dataset:
Abstract LB-121: Polymorphic variants in <i>PPARGC1A</i> and <i>PCMTD1</i> associate with earlier age of onset in ER-negative breast cancer
Authors: Joseph P. Terlizzi, Alexei Vazquez, Madhura Sreenath Mehta, Kim Hirshfield
Journal: Cancer Research (2011)

Abstract Background: Breast cancer is the most frequent cancer and leading cause of cancer death among women worldwide. As &amp;lt;10% of breast cancers are due to mutations in BRCA1 and BRCA2, other perturbations such as single nucleotide polymorphisms (SNPs) may be genetic contributors. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) enhances estrogen receptor (ER) and estrogen related receptor gamma (ERRγ) activity by acting as a coactivator. ERRγ has been demonstrated to regulate vascular endothelial growth factor mRNA expression in both ER-positive and ER-negative breast cancer cell lines, indicating that it may accelerate angiogenesis and metastasis. PCMTD1 encodes protein-L-isoaspartate O-methyltransferase domain-containing protein 1, a S-adenosylmethionine-dependent methyltransferase whose biological relevance is largely unknown to present. SNPs in PPARGC1A have been correlated with metabolic diseases, but within the three studies evaluating cancer phenotypes for this gene, only Thr612Met (76873 C→T) revealed a significant association with familial breast cancers. Experimental Procedure: SNPs in PPARGC1A and PCMTD1 were selected using a bioinformatics approach based on SNP associations with drug response in NCI-60 cell lines and evidence of selection bias for haplotype frequencies. Allelic discrimination assays were performed on genomic DNA isolated from whole blood from over 900 Caucasian breast cancer patients with ductal carcinomas. Clinical information was linked to genotypes to search for genotype-phenotype correlations, and statistical analyses were carried out. Results: Analysis of PPARGC1A rs4619879 revealed a mean age of diagnosis of ER-negative cases for CC and AA carriers at 50.1 and 43.8 years, respectively (p=0.019). The difference was less striking in ER-positive ductal carcinomas, with only a 2.7year earlier onset for AA carriers (p=0.013). For PCMTD1 rs9298462, the mean age at diagnosis of ER-negative cases for CC carriers was 41.2, compared to 48.8 for the TT carriers (p=0.004). No significant difference was seen in ER-positive ductal carcinomas (p=0.15). Conclusions: Our results indicate that polymorphisms in PPARGC1A and PCMTD1, two transcriptional regulators, may play a role in age at diagnosis in breast cancer, particularly ER-negative ductal carcinomas. We are performing functional studies to further evaluate these findings and to elucidate the molecular mechanisms underlying these observations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-121. doi:10.1158/1538-7445.AM2011-LB-121
Abstract 1120: Role and relevance of TrkB mutations and expression in non-small cell lung cancer
Authors: Taishi Harada, Yisong Wang, Yasushi Yatabe, Masafumi Takeshita, Takaomi Koga, Tokujiro Yano, Giuseppe Giaccone
Journal: Cancer Research (2011)

Abstract Purpose: TrkB oncogene has been involved in poor cancer outcome. TrkB mutations have been reported in non-small cell lung cancer. In this study, we aimed at characterizing the role of 3 potentially sensitizing mutations previously reported in TrkB in lung cancer. Experimental design: We characterized three activation loop mutants of TrkB (M713I, R715G and R734C) in terms of pathway activation/phosphorylation, migration, anchorage independent growth and sensitivity to a Trk inhibitor, using NIH3T3 cells and Baf3 cells. We also sequenced the tyrosine kinase domain of TrkB in a large number of lung cancer samples and cell lines. Results: None of the mutants were constitutively active in NIH3T3 transformation and migration assays. M713I and R734C mutants showed low levels of autophosphorylation in comparison with wild-type TrkB. Although R715G showed similar level of autophosphorylation to wild-type TrkB upon BDNF stimulation, the mutant was not as competent as wild-type TrkB in supporting IL-3 independent growth of Baf3 cells. In addition, the Trk inhibitor inhibited wild-type TrkB induced cell migration and cell growth, whereas the mutants were relatively resistant to the Trk inhibitor compared to wild-type TrkB. We could not confirm the presence of non-synonymous mutation in 78 lung cancer samples and 29 cell lines. Conclusions: Wild-type TrkB but not its activation loop mutations enhances cell migration and transformation. Our study suggests that TrkB mutations should not be used for selection of patients with lung cancer treated with Trk inhibitors. High expression of wild-type TrkB might be beneficial for studies of Trk inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1120. doi:10.1158/1538-7445.AM2011-1120
AI-02 * HYPOXIA AS A MEASURE OF FUNCTIONAL STATUS OF GLIOBLASTOMA VASCULATURE
Authors: A. Alamsahebpour, S. Jalali, S. Singh, K. Burrell, G. Zadeh
Journal: Neuro-Oncology (2014)

INTRODUCTION: Glioblastoma (GBMs) exhibit distinct histopathological features including microvascular hyperplasia and heterogenous hypoxia within the tumor microenvironment. Newly formed vessels are often leaky/dysfunctional with intravascular thrombosis and potentially contribute to the hypoxic/necrotic foci seen throughout GBMs. By analyzing orthotopic xenograft models of GBM, we have established the correlation between tumor blood vessel and oxygen diffusion gradient. Additionally, we have established the effect of anti-angiogenic therapies (AATx) such as VEGF-Trap on this correlation. METHOD: Patient derived GSCs and established GBM cell line (U87) with or without VEGF-Trap were injected orthotopically in forebrains of NOD/SCID mice. Following 3-4 weeks of cell implantation, the mice were sacrificed and brains were harvested and imbedded in paraffin blocks. The sections were then stained for CD31 (endothelial marker) and CAIX (hypoxia marker). Images were scanned and quantified; using ImageJ (http://imagej.nih.gov/ij/), measurements include distance from tumor blood vessels to nearest hypoxic foci, total percent hypoxia, and cell proliferation. RESULTS: In literature it has been shown that any functional micro-vessel in normal tissue allows oxygen diffusion up to 100 µm radius. Using this as a guideline, we have defined the functional state of microvessels in our orthoptic tumor. We found that approximately 13% of the tumor blood vessels were dysfunctional, as their distance from immediate hypoxic cells was less than 20 µm. Upon treatment with AATx, we observed significant decrease in numbers of functional tumor blood vessels and cell prolliferation with concomitant increase in hypoxic areas within the tumor. CONCLUSIONS: AATx results in a significant decrease in the number of functional blood vessels - as measured by their proximity to the nearest hypoxic cells - and cell proliferation. We have provided a quantitative measure - distinct histopathological features including hypoxic and necrotic foci, microvascular hyperplasia and increased cell proliferation - for what was previously describe in qualitive terms in literature.
Life-Threatening Cache Valley Virus Infection
Authors: Daniel J. Sexton, Pierre E. Rollin, Edward B. Breitschwerdt, G. Ralph Corey, Sarah A. Myers, Mark R. Dumais, Michael D. Bowen, Cynthia S. Goldsmith, Sherif R. Zaki, Stuart T. Nichol, Clarence J. Peters, Thomas G. Ksiazek
Journal: New England Journal of Medicine (1997)

The Bunyamwera serogroup (family Bunyaviridae, genus bunyavirus) contains more than 20 serologically cross-reactive viruses, 7 of which have been isolated in North America.1 Cache Valley virus, first isolated in Utah in 1956,2 has been recovered mainly from mosquitoes (genera culiseta, aedes, and anopheles) and occasionally from vertebrates and has the widest apparent distribution among this serogroup of viruses. Antibodies against Cache Valley virus and other viruses of the Bunyamwera serogroup are prevalent in livestock, large wild mammals, and humans from Alaska to Argentina.3 An association between Cache Valley virus infections and congenital malformations (various musculoskeletal and central nervous system defects) . . .
Cancer Pain in the Elderly Needs Special Attention
Authors: Julie A. Steele
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Cancer Pain in the Elderly Needs Special Attention Get access Julie A. Steele Julie A. Steele Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 15, 5 August 1992, Page 1153, https://doi.org/10.1093/jnci/84.15.1153 Published: 05 August 1992
Abstract 1174: Genetic variations in microRNA biogenesis pathway genes as susceptibility loci for lung cancer risk
Authors: Yuanqing Ye, Margaret R. Spitz, Hushan Yang, Xifeng Wu
Journal: Cancer Research (2011)

Abstract Many studies have demonstrated that genetic susceptibility played an important role in lung cancer etiology. It has been estimated that microRNAs (miRNAs) may regulate the expression of one third of all human genes and are related to carcinogenesis through their function as oncogenes or tumor suppressors. To test the hypothesis that common sequence variants in microRNA pathways may affect individuals’ lung cancer susceptibility, we assessed the association of 75 haplotype tagging and potential functional single nucleotide polymorphisms (SNPs) in 8 miRNA biogenesis pathway genes with lung cancer risk in a case control study of 1135 lung cancer cases and 803 healthy controls among Caucasians. Overall, SNP rs2302905 from RNASEN exhibited the strongest association and remained significant after adjusting for multiple comparisons using q value at 10% level. Individuals carrying the variant allele of rs2302905 showed a 1.40-fold increased risk of lung cancer (95% CI = 1.11- 1.77; P = 0.0042). Interestingly, similar to rs2302905, two additional SNPs (rs10805564 and rs639174) from RNASEN also showed increased risk of lung cancer (OR = 1.29, 95% CI = 1.04- 1.60; and OR = 1.24, 95% CI = 1.00- 1.53). Two SNPs (rs197412 and rs85276) from DDX20 had significantly reduced lung cancer risk (OR = 0.80, 95% CI = 0.65- 1.00; and OR = 0.78, 95% CI = 0.61- 1.00). Stratified analyses by age, gender, and smoking status identified several additional SNPs that were associated with lung cancer risks in sub-populations. We also counted the number of unfavorable genotypes in each individual to assess the cumulative effect of the top 5 SNPs on lung cancer risk and found a significant gene-dosage effect (P for trend = 0.00028). Compared to the individuals with ≤ 3 unfavorable genotypes in the low risk group, carriers of 4 and 5 unfavorable genotypes had increased risk of lung cancer (OR = 1.30, 95% CI = 0.96 to 1.77; and OR = 2.09, 95% CI = 1.47 to 2.98, respectively). In conclusion, genetic variants in miRNA biogenesis pathway genes may affect the risk of lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1174. doi:10.1158/1538-7445.AM2011-1174
A Novel Approach to Global Benchmarking of Risk-Adjusted Surgical Outcomes
Authors: Richard T. Spence, Jessica L. Mueller, David C. Chang
Journal: JAMA Surgery (2016)

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 Surgery 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 Surgery journal
THU0440 Effectiveneeffectiveness of ultrasound guided corticosteroids injections in interdigital morton’s neuroma a survey of 23 patients
Authors: R. Ghozlan, F. Zeitoun
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Morton's Neuroma (interdigital Neuroma), first described in 1876, is a perineural fibrosis and nerve degeneration of the common interdigital nerve The most frequent location is between the 3 and 4 metatarsals (third webspace). Clinical symptoms combine pain on walking, burning sensation, paresthesiae. Neuromas are visualised by sonography as hypoechoic nodules or by MRI which showed hyposignal in T1and T2. <h3>Objectives</h3> The goal of the study was to demonstrate the effectiveness of ultrasound guided corticosteroids injections <h3>Methods</h3> 23 patients (3 males, 20 females), (mean age 64,7; age range 49 to 85 years) underwent ultrasound corticosteroid guided injections The neuroma was unilateral 11 times and bilateral 10 times Location: 2th intermetatarsal webspace: 16 3th intermetatarsal webspace: 23 The injection was performed 1 time in 17 cases and 2 times in 6 cases. The injection of 1cc Cortivazol with 1cc of 1% lidocaïne was performed in the symptomatic intermetatarsal webspace. The efficacy of the injection was evaluated clinically (improvement of symptoms by the Johnson grading scale) and by imaging: reduction of size of the neuromas <h3>Results</h3> 60% of the neuromas showed complete satisfaction 6 months after the treatment and a very important reduction of size of the neuroma. 20% showed significant improvement of the pain and significant reduction of size of the neuroma. 20% showed no improvement and 10% required surgery. <h3>Conclusions</h3> Ultrasound guided corticosteroid injections are a simple, safe and efficace procedure in the treatment of Morton's Neuroma. <h3>References</h3> Sofka C.M., Adler R.S., Ciavarra G.A. and Pavlov H. Ultrasound guided interdigital neuromas injections: short term clinical outcomes after a single percutaneous injection. Preliminary results HSS J 2007, 3(1), 44-49 Markovic M, Crichton K., Read J.W., Lam P. Stater H.K., Foot Ankle 2008, 29(5), 483-7 <h3>Disclosure of Interest</h3> None Declared
Concurrent disruption of cell cycle associated genes in mantle cell lymphoma: a genotypic and phenotypic study of cyclin D1, p16, p15, p53 and pRb
Authors: K Grønbæk, T Nedergaard, MK Andersen, P thor Straten, P Guldberg, P Møller, J Zeuthen, N Ebbe Hansen, K Hou-Jensen, E Ralfkiaer
Journal: Leukemia (1998)
Abstract 645: Preclinical efficacy of AZD8055, an ATP-competitive mammalian target of rapamycin (mTOR) kinase inhibitor, <i>in vitro</i> in clear cell renal cell carcinoma (RCC)
Authors: Gopal N. Gupta, Kelly Y. Lin, Carole Sourbier, Masaya Baba, Sylvie Guichard, W. Marston Linehan, Ramaprasad Srinivasan
Journal: Cancer Research (2011)

Abstract Inhibitors of the mTORC1 complex such as the rapamycin analogues temsirolimus and everolimus are approved by the FDA for treatment of advanced renal cell carcinoma. However, objective responses with these agents are infrequent and clinical benefits transient, with the majority of patients eventually developing progressive disease and dying from metastatic disease. Dual mTORC1/2 inhibitors may overcome some of the limitations of rapamycin analogues by suppressing the feedback activation of AKT induced by mTORC1 inhibition. In this study, we investigated the in vitro efficacy of AZD8055, a potent inhibitor of both mTORC1 and mTORC2, in clear cell RCC utilizing 2 von Hippel Lindau (VHL) null clear cell kidney cancer cell lines, UOK139 and UOK140. AZD8055 strongly suppressed mTORC2 signaling in RCC and at concentrations ranging from 50nM-250nM, downregulated pAKTs473 and pmTORs2481 in a concentration-dependent fashion. Phosphorylation of AKTt308 was also diminished in both cell lines at these concentrations. In contrast, rapamycin did not significantly inhibit either mTORC2 signaling or AKTt308 phosphorylation. Both AZD8055 and rapamycin were able to downregulate the mTORC1 substrate pS6; however, only AZD8055 was effective in downregulating p4E-BP1, a critical component of cap-dependent translation that is regulated by mTORC1. The vast majority of clear cell renal tumors are characterized by inactivation of the VHL tumor suppressor gene due to mutation or promoter hypermethylation. One well characterized consequence of VHL inactivation is upregulation of hypoxia inducible factor-2α (HIF-2α), an important mediator of both tumorigenesis and neo-angiogenesis in clear cell RCC. While HIF expression is dependent on mTOR activity, it has been reported that mTORC1 inhibition does not reliably suppress HIF-2α expression; we show that treatment with AZD8055 resulted in significant downregulation of HIF-2α levels in both UOK139 and UOK140, an effect that may be mediated by mTORC2 inhibition. AZD8055 exhibited potent in vitro antitumor activity against clear cell RCC, with an IC50 of 100-150nM in the MTT assay; rapamycin had minimal antitumor activity at these concentrations (IC50 not reached at 10uM). These data demonstrate that AZD8055 is a potent inhibitor of mTORC2 and a more effective inhibitor of downstream mTORC1 targets than rapamycin. Simultaneous mTORC1/2 kinase inhibition may be superior to selective mTORC1 inhibition, and is worthy of clinical evaluation in clear cell RCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 645. doi:10.1158/1538-7445.AM2011-645
AB0039 TH17 cells are effective in defining the severity of HSP nephritis
Authors: B. Gülhan, D. Orhan, N. Beşbaş, F. Özaltın, S. Özen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Henoch-Schönlein Purpura (HSP) is the most frequent vasculitis of childhood and mainly affects vessels of the skin, gastrointestinal system and kidneys. Kidney involvement is an important factor for morbidity and affects about 1/3 of the patients. Recently the role of Th1 on autoimmune diseases was challenged by the discovery of another subgroup of CD<sub>4</sub>+ T cells, namely Th17 cells. There has been increasing evidence for the role of Th17 cells in a number of rheumatic and autoimmune diseases. <h3>Objectives</h3> The aim of the study is to investigate the role of Th17 cells in the pathogenesis of HSP nephritis. <h3>Methods</h3> We retrospectively studied the renal biopsies of 23 HSP patients with nephritis; who were admitted to our university hospital and biopsied in the last 30 years. Patient files were retrospectively analysed for clinical and laboratory data. On kidney biopsy sections, crescent formation was investigated. The glomeruler and tubuler frequency and intensity of IL-17 were determined by immunohistochemical analyses of kidney sections. <h3>Results</h3> Out of 23 HSP patients, 13 patients were female and 10 patients were male. Mean age of diagnosis was 10.0±3.4 years (minimum 4, maximum 15.8). Proteinuria at the time of kidney biopsy correlated with the glomerular extent and intensity of IL-17 (r<sub>s</sub>:0.62, p: &lt;0.05 and 0.67, p: &lt;0.05, respectively). Furthermore the glomerular intensity and extent of IL17 correlated with crescent formation (r<sub>s</sub>: 0,52, p: 0.018; r<sub>s</sub>: 0,69, p: 0.001, respectively). <h3>Conclusions</h3> This is the first study suggesting that IL17 participates in the glomerular injury and that is maybe important in determining the severity of kidney disease in HSP. <h3>References</h3> Turner JE, Paust HJ, Steinmetz OM, Panzer U. The Th17 immune response in renal inflammation. Kidney Int 2010; 77: 1070-1075 Ooi JD, Kitching AR, Holdsworth SR. Review: T helper 17 cells: their role in glomerulonephritis. Nephrology (Carlton) 2010; 15: 513-521 <h3>Disclosure of Interest</h3> None Declared
Variable Loss of Lung Function in COPD
Authors: Peter Burney
Journal: New England Journal of Medicine (2011)

Chronic obstructive pulmonary disease (COPD) is a large and increasing global health problem.1 Although cigarette smoking is the most common preventable cause of COPD, not all cases of COPD are associated with smoking.2,3 Most of the clinical limitations stem from the accelerated loss of lung function that characterizes COPD, but few data speak to the factors that cause, aggravate, and determine this loss.The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study4 was undertaken to fill some of the gaps in our knowledge of these factors. The study recruited patients with what the Global Initiative on . . .
Abstract 2797: Breast cancer methylomes establish an epigenomic foundation for metastasis
Authors: Timothy A. Chan, Fang Fang, Sevin Turcan, Andreas Rimner
Journal: Cancer Research (2011)

Abstract Cancer-specific alterations in DNA methylation are hallmarks of human malignancies. The nature of the breast cancer epigenome and its effects on metastatic behavior remain obscure. To address this issue, we used genome-wide analysis to characterize the methylomes of breast cancers with diverse metastatic behavior. Here, we describe the identification of novel groups of breast tumors characterized by the presence or absence of coordinate hypermethylation at a large number of genes, demonstrating the existence of a breast-CpG island methylator phenotype (B-CIMP). B-CIMP imparts a distinct epigenomic profile and is a strong determinant of metastatic potential. Specifically, the presence of B-CIMP in tumors is associated with low metastatic risk and survival, and the absence of B-CIMP is associated with high metastatic risk and death. B-CIMP loci are highly enriched for genes comprising the metastasis transcriptome. Importantly, methylation at B-CIMP genes accounts for much of the transcriptomal diversity between breast cancers of varying prognosis, indicating a fundamental epigenomic contribution to metastasis. Comparison of the loci affected by B-CIMP with those affected by the hypermethylator phenotype in glioma and colon cancer reveals the presence of a CIMP signature shared by multiple human malignancies. These data provide a unifying epigenomic framework linking breast cancers with varying outcome and transcriptomic changes underlying metastasis. Our findings have significant implications for the understanding of breast cancer oncogenesis and for the development of new diagnostic and therapeutic modalities for this common malignancy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2797. doi:10.1158/1538-7445.AM2011-2797