tbuckley/cabot-search huggingface dataset:
Abstract 1898: Regulation of cysteine supply for survival in hepatocellular carcinoma an breast cancer cell lines
Authors: Do Hyung Kim, Seung Jin Lee
Journal: Cancer Research (2018)

Abstract Several types of tumor highly rely on extracellular cystine to supply cysteine for essential biological processes, therefore, cystine transporter, system xc-, has been suggested as a potential target for cancer therapy. However, it has not been known about cellular heterogeneity and regulatory mechanisms for cystine-dependency. Cystine dependency of 9 hepatocellular carcinoma cell lines and 6 breast cancer cell lines was measured using cystine-deprived medium or sulfasalazine, an inhibitor of system xc-. Cultivation with cystine-deficient media significantly reduced the growth in 9 cell lines, moderately in 3 cell lines, but in 2 cell lines including SNU398 cells. Sulfasalazine dose-dependently decreased the growth of cystine-dependent cell lines, which was prevented by the addition of 2-mercaptoethanol which reduces cystine to be shuttled via L-type transporter system. To identify regulatory mechanisms to render cells to be less dependent on extracellular cystine, siRNA kinase library was screened in SNU387 cells. The siRNAs to decrease viability of SNU387 cells in cystine-deficient media were identified. These research suggest cellular heterogeneity for the dependency on extracellular L-cystine and the kinase which may support cysteine supply in the absence of extracellular cystine could be a potential candidate for targeting cysteine metabolism. Citation Format: Do Hyung Kim, Seung Jin Lee. Regulation of cysteine supply for survival in hepatocellular carcinoma an breast cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1898.
Echocardographic Findings in Different Types of Mitral Regurgitation
Authors: Judithburgess, Ralphclark, Masanobukamigaki, Keithcohn
Journal: Circulation (1973)

Forty-eight patients with mitral regurgitation were studied by echocardiography to establish differential diagnostic features. Six patients with rheumatic mitral insufficiency manifested broad and bright echoes from the anterior mitral leaflets and slowed EF slopes. In the majority of patients with prolapse of the mitral valve leaflets due to rupture or redundancy of the chordae tendineae, a posterior sagging of the CD portion of the thin mitral leaflet echoes was evident. Cases with anterior leaflet rupture revealed increased rate and amplitude of anterior cusp opening with a spiked E point. Eight patients with posterior ruptured chordae tendineae were noted to have a paradoxical diastolic anterior motion of the posterior mitral leaflet. Eight instances of mitral insufficiency due to papillary muscle dysfunction manifested a flat CD segment and characteristic double diamond-shaped pattern of the leaflets, lying within an enlarged left ventricular cavity. In two patients with mitral insufficiency associat...
Abstract 17009: Metformin Treatment Decreases the ER Stress-mediated Mitochondrial Injury
Authors: Qun Chen, Jeremy Thompson, Ying Hu, Edward Lesnefsky
Journal: Circulation (2016)

Introduction: Endoplasmic reticulum (ER) stress contributes to cardiovascular disease including heart failure. The ER and mitochondria (MITO) are closely connected. ER stress sensitizes mitochondri...
Changes in Health Care Costs and Mortality Associated With Transitional Care Management Services After a Discharge Among Medicare Beneficiaries
Authors: Andrew B. Bindman, Donald F. Cox
Journal: JAMA Internal Medicine (2018)

Medicare adopted transitional care management (TCM) payment codes in 2013 to encourage clinicians to furnish TCM services after beneficiaries were discharged to the community from medical facilities. To bill for the 30-day service, a care team member must communicate with the beneficiary or the caregiver within 2 business days after the discharge and the clinician must provide an office visit within 14 days.To investigate whether the receipt of TCM services was associated with the subsequent health care costs and mortality of the beneficiaries in the month after the service was provided.Retrospective cohort analysis of all Medicare fee-for-service claims for the period of January 1, 2013, through December 31, 2015, for 18 756 707 Medicare fee-for-service beneficiaries with discharges eligible for subsequent TCM services. Discharges from a hospital, an inpatient psychiatric facility, a long-term care hospital, a skilled nursing facility, an inpatient rehabilitation facility, or an outpatient facility for an observational stay were included. Data analysis was performed from July 2016 to March 2018.Furnishing of TCM services for the 30 days following an eligible discharge for Medicare beneficiaries as reflected in Medicare fee-for-service claims.Total Medicare (Parts A, B, and D) health care costs and mortality in the 31 to 60 days after discharge, which is 30 days beyond the potential period for which the beneficiary could receive TCM services. Health care costs and mortality were adjusted for beneficiary age, sex, risk score, dual eligibility for Medicare and Medicaid, type of eligible discharge, year of discharge, and whether the eligible discharge to the community included home health care.Of 18 756 707 eligible Medicare beneficiaries during the study period, 43.9% were male and had a mean (SD) age of 72.5 (13.8) years. Transitional care management services were billed following eligible discharges in 3.1% of cases in 2013, 5.5% in 2014, and 7.0% in 2015. The adjusted total Medicare costs ($3358; 95% CI, $3324-$3392 vs $3033; 95% CI, $3001-$3065; P < .001) and mortality (1.6%; 95% CI, 1.6%-1.6% vs 1.0%; 95% CI, 1.0%-1.1%; P < .001) were higher among those beneficiaries who did not receive TCM services compared with those who did receive TCM services in the 31 to 60 days following an eligible discharge.Despite the apparent benefits of TCM services for Medicare beneficiaries, the use of this service remains low. An assessment should be made of interventions that can increase the appropriate use of this service.
Abstract 4450: Integrative genomic and transcriptomic analysis of CHD family chromatin remodelers in human cancers: Initial evidence of an oncogenic role for CHD7
Authors: Zeng-Quan Yang, Xiaofang Chu, hui Guo, Yuanyuan Jiang, Huimei Yu, Lanxin Liu, Wenqi Shan
Journal: Cancer Research (2018)

Abstract Chromodomain helicase DNA binding proteins (CHDs) are characterized by N-terminal tandem chromodomains and a central adenosine triphosphate-dependent helicase domain. CHDs govern the cellular machinery's access to DNA, thereby playing critical roles in various cellular processes including transcription, proliferation, and DNA damage repair. Accumulating evidence demonstrates that mutation and dysregulation of CHDs are implicated in the pathogenesis of developmental disorders and cancer. However, we know little about genomic and transcriptomic alterations and the clinical significance of most CHDs in human cancer. We used TCGA and METABRIC datasets to perform integrated genomic and transcriptomic analyses of nine CHD genes in more than 10 000 primary cancer specimens from 32 tumor types, focusing on breast cancers. We identified associations among recurrent copy number alteration, gene expression, clinicopathological features, and patient survival. We found that CHD7 was the most commonly gained/amplified and mutated, whereas CHD3 was the most deleted across the majority of tumor types, including breast cancer. Overexpression of CHD7 was more prevalent in aggressive subtypes of breast cancer and was significantly correlated with high tumor grade and poor prognosis. CHD7 is required to maintain open, accessible chromatin, thus providing fine-tuning of transcriptional regulation of certain classes of genes. We found that CHD7 expression was positively correlated with a small subset of classical oncogenes, notably NRAS, in breast cancer. Knockdown of CHD7 inhibits cell proliferation and decreases gene expression of several CHD7 targets, including NRAS, in breast cancer cell lines. Thus, our results demonstrate the oncogenic potential of CHD7 and its association with poor prognostic parameters in human cancer. Citation Format: Zeng-Quan Yang, Xiaofang Chu, hui Guo, Yuanyuan Jiang, Huimei Yu, Lanxin Liu, Wenqi Shan,. Integrative genomic and transcriptomic analysis of CHD family chromatin remodelers in human cancers: Initial evidence of an oncogenic role for CHD7 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4450.
Duvelisib, an oral dual PI3K‐δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study
Authors: Susan O'Brien, Manish Patel, Brad S. Kahl, Steven M. Horwitz, Francine M. Foss, Pierluigi Porcu, Jeffrey Jones, Jan Burger, Nitin Jain, Kerstin Allen, Kerrie Faia, Mark Douglas, Howard M. Stern, Jennifer Sweeney, Patrick Kelly, Virginia Kelly, Ian Flinn
Journal: American Journal of Hematology (2018)

Abstract Duvelisib (IPI‐145), an oral, dual inhibitor of phosphoinositide‐3‐kinase (PI3K)‐δ and ‐γ, was evaluated in a Phase 1 study in advanced hematologic malignancies, which included expansion cohorts in relapsed/refractory (RR) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and treatment‐naïve (TN) CLL. Per protocol, TN patients were at least 65 years old or had a del(17p)/ TP53 mutation. Duvelisib was administered twice daily (BID) in 28‐day cycles at doses of 8‐75 mg in RR patients ( n = 55) and 25 mg in TN patients ( n = 18.) Diarrhea was the most common nonhematologic AE (TN 78%, RR 47%); transaminase elevations the most frequent lab‐abnormality AE (TN 33.3%, RR 30.9%); and neutropenia the most common ≥grade 3 AE (RR 44%, TN 33%). The overall response rates were 56.4% for RR patients (1.8% CR, 54.5% PR) and 83.3% for TN patients (all PRs); median response duration was 21.0 months in RR patients but was not reached for TN patients. Based upon phase 1 efficacy, pharmacodynamics, and safety, duvelisib 25 mg BID was selected for further investigation in a phase 3 study in RR CLL/SLL.
DETECT III: A multicenter, randomized, phase III study to compare standard therapy alone versus standard therapy plus lapatinib in patients (pts) with initially HER2-negative metastatic breast cancer but with HER2-positive circulating tumor cells (CTC).
Authors: Carsten Hagenbeck, Carola Anna Melcher, Johann Wolfgang Janni, Andreas Schneeweiss, Peter A. Fasching, Bahriye Aktas, Klaus Pantel, Erich-Franz Solomayer, Uta Ortmann, Bernadette Anna Sophia Jaeger, Volkmar Mueller, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2012)

TPS1146 Background: HER2 status may change over the course of disease in breast cancer pts. Approx. 20-30% of pts with initially HER2-negative breast cancer have HER2-positive metastasis (Zidan et al. 2005; Tewes et al. 2009). Determining HER2 status on CTC is one option to re-evaluate HER2 status at the time metastasis is diagnosed. Currently it is unclear if HER2-targeted therapy based on the assessment of HER2 status of CTC reveals a clinical benefit. Methods: This is a randomized, open-label, two arm phase III study to investigate the clinical efficacy of lapatinib, as a HER2-targeted therapy in initially HER2-negative metastatic breast cancer pts with HER2-positive CTC at the time of distant disease. As only half of the pts with HER2-negative metastatic breast cancer show CTC-positivity and of those approx. 32% will exhibit HER2-positive CTC (Fehm et al. 2010), screening of about 1420 pts is required to enroll 228 pts. Main inclusion criteria: metastatic breast cancer with HER2-negative primary tumor tissue and/or biopsies from metastatic sites or locoregional recurrences, evidence of ≥1 HER2-positive CTC and ≥1 measurable metastatic lesion according to RECIST. Eligible pts will be randomized 1:1 to receive standard treatment vs. standard treatment plus lapatinib. Standard chemo- or endocrine therapy must be approved in combination with lapatinib or been investigated in prior clinical trials. Primary endpoint is progression free survival. Secondary endpoints include overall response rate, clinical benefit rate, overall survival and dynamic of CTC. The DETECT III trial is one of the first trials where treatment is based on phenotypic characteristics of CTC. If this trial succeeds in proving efficacy of lapatinib in pts with initially HER2-negative metastatic breast cancer but HER2-positive CTC, this will establish a new strategy in the treatment of metastatic breast cancer.
Abstract 4583: Combined analysis of circulating tumor cells, fecal occult blood test and serum carcinoembryonic antigen for early detection and monitoring recurrence of patients with colorectal cancer
Authors: Wei-Shan Hung, Wen-Sy Tsai, Tzu-Min Wang, Hsueh-Ling Hsu, Hsuan Liu, Chia-Yu Yang, Ching-Ping Tseng, Ju-Chien Cheng
Journal: Cancer Research (2018)

Abstract Current methods for clinical early detection and disease monitoring of patients with colorectal cancer (CRC) are immunochemical fecal occult blood test (iFOBT) and serum levels of carcinoembryonic antigen (CEA), which are known with low sensitivity. There is an unmet need to seek for additional molecular tools for early detection and disease monitoring of patients with CRC. Whether enumeration of circulating tumor cells (CTCs) supplements current clinical tests and facilitates early detection and monitoring disease progression was investigated. A total of 109 pre-operative patients with CRC (including early and advanced stages) and 65 non-cancerous controls were enrolled in this study. CTCs were enriched from the peripheral blood of these individuals by using the PowerMag negative selection system. Immunofluorescence staining of epithelial cell adhesion molecule (EpCAM), and podoplanin (PDPN, a marker related to poor cancer progression) was performed to define the two distinct subtypes of CTCs. Heterogeneous CTCs expressing PDPN or EpCAM are defined in the peripheral blood of patients with CRC. Regardless clinical stages in patients, the number of both EpCAM+-CTCs and PDPN+-CTCs explicitly differentiated non-cancerous controls and patients with CRC, and were also correlated with clinicopathological diagnosis. Receiver operating characteristic analysis demonstrated that the sensitivity and specificity of EpCAM+-CTCs was 86.32% and 78.46%, respectively, when the cutoff value was 23 EpCAM+-CTCs/mL. Using 7 PDPN+-CTCs/mL as the cutoff value, the sensitivity and specificity of PDPN+-CTCs was 77.98% and 75.38%, respectively. 84.2% and 80.3% of patients with serum CEA &amp;lt; 5 ng/mL were found to have higher EpCAM+-CTCs and PDPN+-CTCs counts, respectively. In addition, simultaneous measurements of iFOBT and CTCs could compromise the false-positive rate of iFOBT, while measurements of CEA and CTCs are applicable to monitor cancer recurrence after surgery. This study implicates that CTC testing supplements the current clinical methods to facilitate early detection and disease monitoring in CRC. Citation Format: Wei-Shan Hung, Wen-Sy Tsai, Tzu-Min Wang, Hsueh-Ling Hsu, Hsuan Liu, Chia-Yu Yang, Ching-Ping Tseng, Ju-Chien Cheng. Combined analysis of circulating tumor cells, fecal occult blood test and serum carcinoembryonic antigen for early detection and monitoring recurrence of patients with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4583.
Gene Supplementation Therapy for CNGA3-Linked Achromatopsia
Authors: Stylianos Michalakis, M. Dominik Fischer, Christian Schön, Barbara Wilhelm, Ditta Zobor, Regine Muhlfriedel, Vithiyanjali Sothilingam, Susanne Kohl, Tobias Peters, Eberhart Zrenner, Karl Ulrich Bartz-Schmidt, Marius Üffing, Bernd Wissinger, Mathias Seeliger, Martin Biel
Journal: Molecular Therapy (2017)
Abstract 4479: Protein arginine methyltransferase PRMT6 regulates cancer stemness through CRAF methylation in hepatocellular carcinoma
Authors: LH Chan, L Zhou, Kai Yu Ng, TL Wong, TK Lee, YP Ching, YF Yuan, D Xie, S Richard, MS Huen, XY Guan, S Ma
Journal: Cancer Research (2018)

Abstract Arginine methylation is a post-translational modification that plays pivotal roles in signal transduction and gene transcription during cell fate determination. We found protein methyltransferase 6 (PRMT6) to be frequently down-regulated in hepatocellular carcinoma (HCC) cells and its expression to negatively correlate with aggressive cancer features in HCC patients. Silencing of PRMT6 promoted the tumor-initiating, metastasis and therapy resistance potential of HCC cells. Consistently, loss of PRMT6 expression aggravated liver tumorigenesis in a DEN+CCL4 HCC induced PRMT6-/- mouse model. Integrated transcriptome and protein-protein interaction studies revealed an enrichment of genes implicated in RAS signaling and that PRMT6 interacted with CRAF, and likely other RAF family members, and their methylation at conserved arginine 100, negatively regulating its activity, and as a consequence resulting in enhanced MEK/ERK signaling. Our work uncovered a critical repressive function for PRMT6 in maintenance of HCC cells by regulating the MEK/ERK pathway via arginine methylation of RAF, providing a new avenue of molecular mechanism by which ERK mediated stemness in HCC cells are developed. Citation Format: LH Chan, L Zhou, Kai Yu Ng, TL Wong, TK Lee, YP Ching, YF Yuan, D Xie, S Richard, MS Huen, XY Guan, S Ma. Protein arginine methyltransferase PRMT6 regulates cancer stemness through CRAF methylation in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4479.
Six-Year Incidence of and Risk Factors for Cataract Surgery in a Multi-ethnic Asian Population
Authors: Ava Grace Tan, Annette Kifley, Yih-Chung Tham, Yuan Shi, Miao Li Chee, Charumathi Sabanayagam, Nicholas Yi Qiang Tan, Kah Hie Wong, Paul Mitchell, Robert G. Cumming, Tien Yin Wong, Jie Jin Wang, Ching-Yu Cheng
Journal: Ophthalmology (2018)
Nonischemic Chest Pain Induced by Coronary Interventions
Authors: AllenJeremias, SvenKutscher, MichaelHaude, DagmarHeinen, GeraldHoltmann, WolfgangSenf, RaimundErbel
Journal: Circulation (1998)

Background—Chest pain frequently occurs without any signs of ischemia within the first 24 hours after coronary interventions. To test the hypothesis that this pain may be due to local vessel injury (“stretch pain”), we performed a prospective study enrolling patients after PTCA, stent implantation, or diagnostic coronary angiography alone. Methods and Results—A total of 145 patients after coronary angiography were evaluated by a validated questionnaire for quantifying postinterventional chest pain within 24 hours. To detect myocardial ischemia, all patients were evaluated with a 12-lead ECG and cardiac isoenzymes immediately after the procedure and the morning after. After stent implantation, 21 of the 51 patients (41.2%) developed chest pain, compared with 4 of the 33 patients (12.1%) undergoing PTCA and 6 of the 61 patients (9.8%) with a diagnostic angiography (P<0.001). Of these 31 patients who developed chest pain, only 3 (9.7%) felt that the pain was similar to previously experienced angina pectoris....
Family History of Breast or Prostate Cancer and Prostate Cancer Risk
Authors: Lauren Barber, Travis Gerke, Sarah C. Markt, Samuel F. Peisch, Kathryn M. Wilson, Thomas Ahearn, Edward Giovannucci, Giovanni Parmigiani, Lorelei A. Mucci
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Breast and prostate cancer co-occur in families, and women with a family history of prostate cancer are at increased breast cancer risk. Prostate cancer is among the most heritable cancers, but few studies have investigated its association with familial breast cancer. The objective of this study is to investigate the extent to which familial breast or prostate cancer in first-degree relatives increases prostate cancer risk. Experimental Design: A prospective study of 37,002 U.S. men in the Health Professionals Follow-up Study. During the 16-year follow-up to 2012, 4,208 total and 344 lethal cases were diagnosed. Using cause-specific hazards regression, we estimated the multivariable HRs and 95% confidence intervals (CI) for associations between familial breast or prostate cancer and total and lethal prostate cancer. Results: Those with familial breast cancer had a 21% greater risk of prostate cancer overall (95% CI, 1.10–1.34), and a 34% greater risk of lethal disease (HR 1.34; 95% CI, 0.96–1.89). Family history of prostate cancer alone was associated with a 68% increased risk of total disease (95% CI, 1.53–1.83) and a 72% increased risk of lethal disease (95% CI, 1.25–2.38). Men with a family history of both cancers were also at elevated risk. Conclusions: Our study found that men with a family history of breast or prostate cancer had elevated prostate cancer risks, including risk of lethal disease. These findings have translational relevance for cancer risk prediction in men.