tbuckley/cabot-search huggingface dataset:
YAP suppresses gluconeogenic gene expression through PGC1α
Authors: Yue Hu, Dong‐Ju Shin, Hui Pan, Zhiqiang Lin, Jonathan M. Dreyfuss, Fernando D. Camargo, Ji Miao, Sudha B. Biddinger
Journal: Hepatology (2017)

Cell growth and proliferation are tightly coupled to metabolism, and dissecting the signaling molecules which link these processes is an important step toward understanding development, regeneration, and cancer. The transcriptional regulator Yes‐associated protein 1 (YAP) is a key regulator of liver size, development, and function. We now show that YAP can also suppress gluconeogenic gene expression. Yap deletion in primary hepatocytes potentiates the gluconeogenic gene response to glucagon and dexamethasone, whereas constitutively active YAP suppresses it. The effects of YAP are mediated by the transcriptional coactivator peroxisome proliferator–activated receptor‐gamma coactivator 1. YAP inhibits its ability to bind to and activate transcription from the promoters of its gluconeogenic targets, and the effects of YAP are blunted upon its knockdown. In vivo , constitutively active YAP lowers plasma glucose levels and increases liver size. Conclusion : YAP appears to reprogram cellular metabolism, diverting substrates away from the energy‐consuming process of gluconeogenesis and toward the anabolic process of growth. (H epatology 2017;66:2029–2041)
Association between Endothelin-1 Levels and Kidney Disease among Blacks
Authors: Casey M. Rebholz, Jane L. Harman, Morgan E. Grams, Adolfo Correa, Daichi Shimbo, Josef Coresh, Bessie A. Young
Journal: Journal of the American Society of Nephrology (2017)

Endothelin-1, a marker of endothelial dysfunction, is a potent vasoconstrictor released by endothelial cells and an important regulator of renal physiology. It is not known whether elevated serum levels of endothelin-1 indicate future risk of kidney disease in the general population. In participants in the Jackson Heart Study, a community-based observational study of cardiovascular risk in black adults, we measured serum endothelin-1 level at baseline (2000–2004; n =3538). We defined incident CKD as eGFR&lt;60 ml/min per 1.73 m 2 and ≥30% eGFR decline at the third visit (2009–2013) relative to baseline among those participants with baseline eGFR ≥60 ml/min per 1.73 m 2 . At baseline, mean age was 55 years old, 37% of participants were men, and mean eGFR was 94 ml/min per 1.73 m 2 . Over a median follow-up of 8 years, 228 (6.4%) cases of incident CKD occurred in participants. Participants with baseline endothelin-1 levels in higher quartiles had a greater incidence of CKD in the fully adjusted model (odds ratio for fourth versus first quartile, 1.81; 95% confidence interval, 1.11 to 2.96; P trend =0.04). Endothelin-1 positively associated with all-cause mortality (hazard ratio for fourth versus first quartile, 1.64; 95% confidence interval, 1.24 to 2.16; P trend &lt;0.001). In conclusion, higher baseline serum endothelin-1 levels associated with incident CKD and all-cause mortality during follow-up in this general population sample of blacks.
Genomic signature of prognosis for Stage II colorectal cancer from FFPE tissue
Authors: Peter Kerr, Julie Black, Juergen von Frese, Robert Holt, Steven Walker, Karl Mulligan, Patrick Johnston, Paul Harkin
Journal: Clinical Cancer Research (2007)

A39  We have developed a microarray with specific content that is focused around colorectal cancer, the Colorectal Cancer DSATM Research Tool. The DSA™ range of tools (patent pending) are the first microarrays based on the transcriptome of an individual disease delivering reliable and relevant information not available on other arrays. Designed to maximise the expression data obtained from the chosen disease setting, these arrays enable Almac Diagnostics to generate significantly more information relevant to the disease of interest than that obtained with generic arrays. These arrays are powered by the Affymetrix Genechip™ system. Using this tool we have developed an accurate prognostic signature using formalin-fixed paraffin-embedded (FFPE) tissues capable of predicting disease recurrence in patients with stage II CRC as the basis for an in vitro diagnostic (IVD) test.  Primary tumours (FFPE) from 143 patients with stage II CRC were collected from 7 different hospitals, in 3 countries (USA, UK, Ireland). Tumours were from patients treated with surgery alone. Within the study group we defined 2 prognostic cohorts: a “poor prognostic cohort” (n=56) that relapsed within 5 years post surgery and a “good prognostic cohort” (n=87) that were disease free with a minimum of 5 years follow up. Patient samples were randomly divided to generate a training set of 93 and an independent test set of 50 samples. RNA processing and microarray hybridisations were performed using standardised in-house protocols. RNA expression data was analysed using Partial Least Squares (PLS) discriminant analysis to identify transcripts that best discriminate between patients at high risk of relapse versus patients likely to remain disease free, post surgery.   Expression profiling based on the 93 FFPE samples in the training set, identified a 91-transcript signature capable of identifying the recurrent population. The ability of the signature to predict recurrence was then evaluated in the independent test set of 50 samples. The overall accuracy was 80%, with a sensitivity of 79%, specificity of 81% and associated positive predictive value (PPV) of 62% and relative risk of 6.7.  Using our Colorectal Cancer DSATM research tool we have derived and validated a prognostic signature that accurately stratifies stage II CRC patients according to their risk of recurrence post surgery. Using a 91-transcript signature, we were able to stratify an independent set of stage II colorectal cancer patients to identify a sub-population with an approximately 7-fold higher risk of developing recurrent disease within five years of surgery. This signature will now form the basis for the development of an IVD test using FFPE tissues in stage II CRC.
Extending the Social Justice Call to Treatment Outcomes
Authors: Julie M. Zito
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Phase I clinical, pharmacokinetic, and pharmacodynamic study of CG200745, a histone deacetylase (HDAC) inhibitor, in patients with advanced solid tumors.
Authors: Kyu-Pyo Kim, Yong Sang Hong, Jin-Hee Ahn, Jae-Lyun Lee, Kyun-Seop Bae, Tae Won Kim
Journal: Journal of Clinical Oncology (2012)

e13560 Background: The aim of this study was to assess the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and efficacy of single dose of intravenous CG200745, a novel histone deacetylase (HDAC) inhibitor, in patients with advanced solid malignancies. Methods: Two to six patients received Intravenous CG200745 every 3 weeks according to the single dose-escalating 2+4 method. Acetylated histone H4 (Acetyl-H4) was measured in peripheral blood mononuclear cells (PBMCs). Results: Ten patients were treated at one of five doses (1.8-24.0 mg/m 2 ) and received 3 (1-7) cycles of CG200745 (median, range). No dose-limiting toxic effects or QTc prolongations were noted. Dose proportionality was observed for both C max and AUC. The elimination half-life and mean residual time was 5.43±0.37(mean±SD) and 4.15±0.50 hrs. An increase in Acetyl-H4 was observed at hour 1 and correlated with dose and Cmax. Acetyl-H4 persisted for 8 hrs in 3 pts and 24 hrs in another 3 pts. Stable disease was seen in 2 pts with colorectal cancer at levels 7.2 and 24 mg/m 2 . Conclusions: CG200745 can be safely administered at the effective dose levels that inhibit HDAC in PBMCs. As MTD was not reached, this agent is under further investigation for multiple ascending doses.
Erratum: Proximal tubular cells promote fibrogenesis by TGF-β1-mediated induction of peritubular myofibroblasts (Kidney International (2002) 6 (2066-2077))
Authors: M. Abbate, C. Zoja, D. Rottoli, D. Corna, S. Tomasoni, G. Remuzzi
Journal: Kidney International (2002)
Age standardized pattern of cancers in Pakistani population from 2008 to 2014.
Authors: Binafsha Manzoor Syed, Fayaz Hussain Mangi, Jawaid Naeem Qureshi, Noshad Ahmed Shaikh, Ikram Uddin Ujjan, Naeem Ahmed Laghari
Journal: Journal of Clinical Oncology (2017)

e13060 Background: Cancer is a heterogeneous disease, influenced largely by gender, genetic makeup and environmental factors. This study was therefore aimed to assess age-standardized pattern in both males and females in Pakistani population. Methods: During the period of seven years (January 2008 to December 2014) prospectively collected institutional data was retrieved. All patients presented with primary cancers were included and pattern of top ten tumors was assessed. The data was analyzed using SPSS 21.0. Results: During the study period, a total of 15,906 patients with primary cancer were reported. Pattern of distribution is given in the table below. Conclusions: Among males and females there has been a different pattern of cancers. However among young males oral cancers remains at the top while lung at the older age and breast cancer among females remains at the high rate regardless of age. [Table: see text]
Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns)
Authors: Martin Stocker, Wendy van Herk, Salhab el Helou, Sourabh Dutta, Matteo S Fontana, Frank A B A Schuerman, Rita K van den Tooren-de Groot, Jantien W Wieringa, Jan Janota, Laura H van der Meer-Kappelle, Rob Moonen, Sintha D Sie, Esther de Vries, Albertine E Donker, Urs Zimmerman, Luregn J Schlapbach, Amerik C de Mol, Angelique Hoffman-Haringsma, Madan Roy, Maren Tomaske, René F Kornelisse, Juliette van Gijsel, Eline G Visser, Sten P Willemsen, Annemarie M C van Rossum, A Bakry, S Dutta, S el Helou, K Kalaniti, D Pogorzelski, S Alliston, M Roy, V Grey, K Hauff, S Hill, S Kittanakom, J Janota, M Visnovska, M Fontana, N Lanz, M Stocker, D Glauser, U Zimmerman, M Tomaske, M Nelle, LJ Schlapbach, FABA Schuerman, SD Sie, MM van Weissenbruch, FAM van den Dungen, M Strik, HK van den Tooren-de, Groot A van Rossum, M Batstra, LH van der Meer-Kappelle, E de Vries, AC de Mol, J Bolt-Wieringa, Daniel Stok, R Moonen, S Donker, J van Gijsel, IPE Gondriet, W van Herk, S Hoekstein, M Hofhuis, W Hop, L de Ligt, B Manai, R Kornelisse, Y de Rijke, A van Rossum, S Siiskonen, J van der Velden, EG Visser, J Asch van Wijk, S Willemsen, GJ van der Geijn, A Haringsma, PA Andriessen, MAC Broeren, A Donker
Journal: The Lancet (2017)
Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an Increased Risk of Alzheimer Disease: Taiwan Diabetes Study
Authors: Tsai-Chung Li, Chun-Pai Yang, Shih-Ting Tseng, Chia-Ing Li, Chiu-Shong Liu, Wen-Yuan Lin, Kai-Lin Hwang, Sing-Yu Yang, Jen-Huai Chiang, Cheng-Chieh Lin
Journal: Diabetes Care (2017)

OBJECTIVE The relationship between glycemic variability and the incidence of Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to examine visit-to-visit variations in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) represented by the coefficient of variation (CV) and to determine whether they were independently associated with AD, irrespective of HbA1c and other traditional risk factors in such patients. RESEARCH DESIGN AND METHODS Patients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD (n = 16,706) were included in the study. Potential risk factors were analyzed using extended Cox proportional hazards regression models for competing risk of mortality on AD incidence. RESULTS During a median follow-up of 8.88 years, 831 incident cases of AD were identified, with a crude incidence rate of 3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle behaviors, diabetes-related variables, FPG and HbA1c, drug-related variables, and comorbidities, both FPG CV and HbA1c CV were found to be significant predictors of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06–1.52) for the third tertile in FPG CV and 1.32 (95% CI 1.11–1.58) for the third tertile in HbA1c CV. CONCLUSIONS FPG CV and HbA1c CV are independently associated with AD. The associations between glycemic variability and AD demonstrated in this study suggest a linked pathophysiological mechanism, which is worthy of further investigation. Further research is required to confirm our results and to evaluate whether FPG CV and HbA1c CV can be valuable therapeutic targets for patients with T2DM at risk.
Recreational Physical Activity in Relation to Prostate Cancer–specific Mortality Among Men with Nonmetastatic Prostate Cancer
Authors: Ying Wang, Eric J. Jacobs, Susan M. Gapstur, Maret L. Maliniak, Ted Gansler, Marjorie L. McCullough, Victoria L. Stevens, Alpa V. Patel
Journal: European Urology (2017)
Crenolanib, a Type I FLT3 TKI, Can be Safely Combined with Cytarabine and Anthracycline Induction Chemotherapy and Results in High Response Rates in Patients with Newly Diagnosed FLT3 Mutant Acute Myeloid Leukemia (AML)
Authors: Eunice S. Wang, Richard M. Stone, Martin S. Tallman, Roland B. Walter, John R. Eckardt, Robert Collins
Journal: Blood (2016)
Randomized phase II trial of weekly paclitaxel, carboplatin, cetuximab (PCC) versus cetuximab, docetaxel, cisplatin, and fluorouracil (C-TPF) in previously untreated patients with locally advanced head and neck squamous cell carcinoma.
Authors: Erminia Massarelli, Robert I. Haddad, J. Jack Lee, Adam S. Garden, George R. Blumenschein, William N. William, Roy B. Tishler, Bonnie S. Glisson, Kathryn A. Gold, Faye M. Johnson, Lawrence E. Ginsberg, Michelle D. Williams, Jeffrey Myers, Merrill S. Kies, Vassiliki Papadimitrakopoulou
Journal: Journal of Clinical Oncology (2014)

TPS6102 Background: The use of induction chemotherapy in patients (pts) with locally advanced head and neck squamous cell carcinoma (HNSCC) remains controversial. The induction strategy has shown to reduce risk of distant metastases but also represents a vehicle for the evaluation of other clinical and molecular endpoints. The development of increasingly effective induction chemotherapy may eventually affect the efficacy of radiotherapy with an improvement in local disease control. To determine the efficacy of combining cetuximab with induction chemotherapy, we designed a randomized phase II trial in previously untreated pts with locally advanced HNSCC using two induction chemotherapy regimens that had previously demonstrated efficacy and acceptable toxicity, followed by definitive risk-appropriate local therapy, taking into consideration both tumor (T) stage at presentation as well as human papillomavirus (HPV) status. Methods: Pts with stage IV T0-4 N2b-2c/3 M0 measurable disease in either the T or nodal (N) site by RECIST criteria were included in the trial. Pts were randomized to receive 6-weekly cycles of paclitaxel 135 mg/m2, carboplatin AUC 2 and cetuximab 400 mg/m2 week 1 then 250 mg/m2 weekly (PCC) or 3 cycles of every 3 weeks docetaxel 75 mg/m2 on day 1, cisplatin 100 mg/m2 on day 1, 5-fluorouracile (5-FU) 700 mg/m2/day continuous infusion days 1-4 and cetuximab 400 mg/m2 week 1 then 250 mg/m2 weeks 2, 4, 5, 7, 8 (C-TPF). HPV status was required at study entrance. Primary objective was progression free survival of both regimens followed by definitive local therapy selected on the basis of stage and HPV status, compared to historical control docetaxel/cisplatin/5-FU (TPF). Secondary objectives were: overall survival, response rate, duration of locoregional control, patterns of tumor recurrence, toxicity and biomarker analysis by HPV status and outcome. The trial has accrued a total of 135 pts as of January 2014. Planned analyses beyond primary and secondary objectives include evaluation of tumor genotype and immune phenotype in correlation with HPV-status and outcome. Clinical trial information: NCT01154920.
Ecology of Helicobacter pylori in Peru: infection rates in coastal, high altitude, and jungle communities. The Gastrointestinal Physiology Working Group of the Cayetano Heredia and the Johns Hopkins University.
Authors: Cayetano Heredia, Robert Gilman, A Ramirez-Ramos, W Spira, S Recavarren, J Watanabe, R Leon-Barua, C Rodriguez, C Guevara, G Gago, J Bonilla, J Cok, Huidobro Ruiz, E Gomez, E Olivares, Garrido Klinge, G Vargas, M Astete, M Valdivia, R Berendson
Journal: Gut (1992)

We have examined endoscopic clinic patients in three widely different geographic regions of Peru (the coast, the Sierra of the Andes Mountains, and the Amazon jungle) for the presence of Helicobacter pylori infection associated with active gastritis. The overall rates of infection were high (80% or greater) in all three zones and rates for men were approximately 10% higher than for women in the same zone. Men and women in the Sierra and jungle areas had significantly higher rates of infection than did those on the coast. There was no significant difference between the three populations with respect to the relationship between infection and grade of gastritis.
Pharmacokinetic parameters of gefitinib predicts its progression-free survival and adverse events.
Authors: Kosuke Mizoguchi, Yoichi Nakamura, Kazumi Sano, Yoji Ikegami, Kohei Motoshima, Shinnosuke Takemoto, Daiki Ogawara, Takaya Ikeda, Nanae Tomonaga, Hiroyuki Yamaguchi, Katsumi Nakatomi, Minoru Fukuda, Seiji Nagashima, Shigeru Kohno
Journal: Journal of Clinical Oncology (2014)

e19038 Background: Previously, through measuring plasma trough levels of gefitinib on days 3(D3) and 8 (D8), we reported that a high D8/D3 ratio was independently associated with better PFS in patients with advanced non-small cell lung cancer (NSCLC) treated with gefitinib. In this time, we also assessed the relationship between the biological half-life of gefitinib and its efficacy in patients with advanced NSCLC harboring Epidermal growth factor receptor (EGFR) mutations treated with gefitinib. Methods: Plasma trough levels of gefitinib were measured on days 2 (D2) and 8 (D8) by high-performance liquid chromatography in 30 patients. Additionally, We measured plasma concentration of gefitinib in 10 hours (10H) after first administration in 22 out of 30 patients to calculate the biological half-life of gefitinib using the values of 10H and D2. All patients were diagnosed pathologically with advanced NSCLC harboring EGFR mutations and 22 cases with values of 10H had no prior chemotherapy. Results: The median plasma gefitinib values were 248.5 ng/ml on D2 and 704.0ng/ml on D8, respectively, and the D8/D2 ratio was 2.676. The median biological half-life was 15.7 hrs. The median progression-free survival (PFS) and overall survival(OS) were 273 days and 901 days, respectively. A High D8/D2 ratio was associated with better PFS(hazard ratio, 0.4141; 95%CI, 0.1580 to 0.9262; P=0.042), and a high biological half-life was correlated with high probability of grade3 or 4 adverse events(P<0.01, total seven patients; six liver damage, one urticaria, one paronychia). Conclusions: A high D8/D2 ratio and a high biological half-life were respectively associated with better PFS and high probability of grade 3 or 4 adverse events in patients with advanced NSCLC harboring EGFR mutations treated with gefitinib. This results suggest that pharmacokinetics of gefitinib may be involved in its antitumor activity and adverse events.
Sexual function, sexual activity, and quality of life in women with ovarian and endometrial cancer.
Authors: Philipp Harter, Inga Schrof, Karl M Lehmann, Rita Hils, Verena Kullmann, Alexander Traut, Herbert Scheller, Andreas Du Bois
Journal: Journal of Clinical Oncology (2012)

5051 Background: Gynecological cancer (GC) is generally assumed to have an impact on sexual function and activity. Although there are several studies addressing the issue, case control studies are currently limited. Methods: We performed a cross-sectional investigation of sexual function and activity utilizing the sexual activity questionnaire, the female sexual function index, and parts of the EORTC QLQ C30. Patients with gynecological cancer (GC) like ovarian and endometrial cancer were compared with a control group (C) of non-cancer patients. Inclusion of GC was only allowed if treatment was completed ≥12 months previously and patients were disease-free. Results: The questionnaires were sent out to 727 women (335 x GC and 392 x C), 22.8% of which responded. Response rates in both groups were equivalent (79 pts with GC [23.6%] and 87 control subjects [22.2%]). Median age was 57 years (C) and 62 years (GC), respectively (p=0.237). 51.5% (C) and 59.5% (GC) were not sexually active, mainly owing to lack of a partner (37%) or lack of interest (21%) in controls and lack of interest (40%, p&lt;0.05), self-reported physical problems (31.9%, p&lt;0.05), and physical problems of the partner (21%, p&lt;0.05). There were significant differences between both groups in the SAQ discomfort score (p&lt;0.05). We did not observe significant differences in quality of life or other scores regarding sexuality. Conclusions: About half of the women in both groups were not sexually active. However, reasons for non-activity differ. Quality of sexuality tends to be impaired in GC patients, but this seems not to influence quality of life. A shift of priority caused by substantial anxiety regarding cancer specific survival might explain our findings.