tbuckley/cabot-search huggingface dataset:
Pregabalin for hot flashes in women: NCCTG trial N07C1
Authors: C. L. Loprinzi, R. Qin, P. J. Stella, K. M. Rowland, D. L. Graham, N. Erwin, S. R. Dakhil, D. J. Jurgens, K. N. Burger
Journal: Journal of Clinical Oncology (2009)

9513 Background: Hot flashes are a major problem in many women for which better treatment options are needed. Given the known efficacy of gabapentin for decreasing hot flashes, it was decided to evaluate pregabalin, with hopes that it would work better and/or with fewer toxicities. Methods: A three-arm, double-blinded, placebo-controlled randomized trial was developed. Women with bothersome hot flashes (at least 28/week) were randomized to receive either a placebo or target pregabalin oral doses of 75 mg bid or 150 mg bid (starting at 50 mg/d and then increasing the dose at weekly intervals to 50 mg bid, then 75 mg bid, and then, in the higher dose arm, 150 mg bid); patients were treated for 6 weeks. Hot flash numbers and scores (hot flash number times mean severity) were measured using a validated daily hot flash diary. A one-week baseline period preceded initiation of study tablets. The primary endpoint was the average intra-patient difference in hot flash score between baseline and week six, comparing the higher dose pregabalin arm and the placebo arm. With the planned sample size of 55 patients per arm, there was an 80% power and two-sided 5% Type I error rate to detect a difference of 0.54 standard deviations, or 1.08 hot flashes per day, or 2.7 units of hot flash score per day. Results: 207 patients were randomized between 6/20/2008 and 8/21/2008. The study arms were well balanced. Mean/median daily hot flash scores and frequencies for all pts at baseline were 15.7/13.4 and 8.3/7.7, respectively. The table shows the decreases in hot flashes from the baseline to the sixth treatment week. Larger numbers illustrate greater hot flash reductions. Toxicity information, quality of life information, and information regarding the effects of hot flashes on subjective symptoms will be available at the meeting time. Conclusions: Pregabalin reduces hot flashes in women. There appears to be similar effects with both studied doses. [Table: see text] No significant financial relationships to disclose.
Dual or Single Hepatitis B and C Virus Infections in Childhood Cancer Survivors: Long-Term Follow-Up and Effect of Interferon Treatment
Authors: Riccardo Utili, Rosa Zampino, Pasquale Bellopede, Marta Marracino, Enrico Ragone, Luigi Elio Adinolfi, Giuseppe Ruggiero, Maria Capasso, Paolo Indolfi, Fiorina Casale, Adele Martini, Maria Teresa Di Tullio
Journal: Blood (1999)
Restructured abstracts for research in<i>The BMJ</i>
Authors: Elizabeth Loder, Vivien Chen
Journal: BMJ (2015)

This issue marks a shift in the way research articles will be presented in the print edition of The BMJ . We will continue to publish the definitive, unabridged version of accepted research papers online, with open access and no word limits. These articles will then be summarised for print in a newly designed, streamlined abstract format.

It has been 17 years since we first abridged research papers for the print version of The BMJ . There is no definite agreed format for structured abstracts, although there is consensus about the key pieces of information that such abstracts should contain. Our first attempts to produce shortened print versions …
A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients
Authors: M. S. Tsao, C. Zhu, K. Ding, D. Strumpf, M. Pintilie, M. Meyerson, L. Seymour, I. Jurisica, F. A. Shepherd
Journal: Journal of Clinical Oncology (2008)

7510 Background: The JBR.10 trial demonstrated a significant survival benefit from adjuvant chemotherapy in stage IB-II NSCLC patients (HR 0.69, p=0.04). However, a significant interaction with stage was seen, with benefit limited to stage II patients. Gene expression profiling may identify patient groups with significantly different prognosis, with potential for improved selection of patients to receive adjuvant chemotherapy. Methods: Gene expression profiling by Affymetrix U133A was performed on RNA isolated from snap-frozen banked tumor tissues of 133 (62 on observation and 71 on chemotherapy) JBR.10 patients. A minimal prognostic gene set was identified based on goodness-of-fit (R square) of the Cox proportional hazard model and leave one out cross-validation in the observation patients. Results: A 15-gene expression signature was identified that separated the 62 observation patients into groups with high (n=33) and low risk (n=29) for death (HR 60.1, p< 0.0001). This prognostic signature was validated in five independent public gene expression datasets (stage I-II patients, total n=372). Chemotherapy significantly reduced the risk of death in high-risk patients (HR 0.27, C.I. 0.14–0.51, p<0.0001). The benefit of chemotherapy was seen both in high-risk stage IB (HR 0.28, p=0.007) and stage II (HR 0.26, p=0.0059) patients, but not in low-risk patients (HR 15.49, p=0.008). Interaction of chemotherapy and expression signature was highly significant (p=0.0001). Conclusions: We have identified a 15-gene signature that is an independent prognostic marker in early stage NSCLC for identifying more selectively than stage, patients who may benefit from adjuvant chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pierre Fabre
Phase I study of safety and immunogenicity of ADU-623, a live-attenuated listeria monocytogenes vaccine (ΔactA/ΔinlB) expressing EGFRVIII and NY-ESO-1, in patients with who grade III/IV astrocytomas
Authors: Marka Crittenden, Keith S Bahjat, Rui Li, Pankaj Gore, Chris Fountain, Bill Hanson, Justin Skoble, Peter Lauer, Aimee L Murphy, Thomas Dubensky, Dirk G Brockstedt, Walter Urba
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The neo-antigen EGFRvIII is expressed in multiple tumor types, including high-grade astrocytomas. It is associated with a poor prognosis and resistance to conventional therapies such as chemotherapy and radiation that are part of the standard treatment. We propose that
Abstract 10844: Pitavastatin Reduces Inflammation in Atherosclerotic Plaques in Hyperlipidemic Mice with Chronic Renal Disease
Authors: Manabu Shibasaki, Jose-Luiz Figueiredo, Sophie E New, Thibaut Quillard, Goettsch Claudia, Hiroyuki Sonoki, Jiro Matsumoto, Masanori Aikawa, Elena Aikawa
Journal: Circulation (2012)

Background:  Chronic renal disease (CRD) accelerates atherosclerosis and cardiovascular calcification. Statins lower LDL-cholesterol levels in patients with CRD, however, the benefits of statins on cardiovascular disease in CRD remain unclear. We therefore investigated the effects of pitavastatin treatment on arterial inflammation and calcification in atherogenic mice with CRD induced by 5/6 nephrectomy.   Methods:  High-cholesterol-fed apolipoprotein E-deficient (apoE-/-) mice at 21 weeks of age were randomized to control mice (n=10) and CRD mice treated or untreated with pitavastatin (n=20 each). Pitavastatin (0.01% wt/wt) was administered as a food admixture for 10 weeks after surgery. Development of luminal stenosis in innominate artery was monitored by ultrasonography before nephrectomy and at the end of the study. Tissue harvesting for ex vivo near infrared (NIR) molecular imaging and histological analyses was performed at 32 weeks.   Results:  CRD mice had significantly higher levels of plasma phosphate (P   Conclusions:  This study provides in vivo evidence that pitavastatin reduces stenosis and inflammation within atherosclerotic lesions in CRD through the mechanisms independent of its lipid lowering effects.
Abstract 12140: Prognostic Value of Multiple Biomarkers on Mortality in Adults Congenital Heart Disease: Comparison of Single- and Two-Ventricle Physiology
Authors: Kenji Miyamoto, Daiji Takeuchi, Kei Inai, Tokuko Shinohara, Toshio Nakanishi
Journal: Circulation (2014)

Introduction: Although many biomarkers are associated with heart failure, limited data is available on their prognostic predictive value in adults with congenital heart disease (ACHD). We investigate the potential of various biomarkers to predict ACHD mortality. Methods and Results: This is a single-center, retrospective cohort study. Blood levels of neurohormones (endothelin-1 [ET1], norepinephrine [NE], aldosterone, and plasma renin activity [PRA]); inflammatory biomarkers (high sensitivity C-reactive protein [hs-CRP], high sensitivity tumor necrosis factor [hs-TNF]-α, soluble TNF receptor type I and II [sTNF-RI and sTNF-RII], and interleukin-6 [IL-6]); and brain natriuretic peptide (BNP) were measured in 115 ACHD (mean age, 30 ± 10 years). NYHA class was I/ II in 86% and III/IV in 14%. The subjects were divided into two groups: patients with single-ventricle (SV group, n = 65) and with two-ventricle physiology (TV group, n = 50). We retrospectively analyzed the relationship between levels of biomarkers and cardiovascular death. During a mean follow-up period of 4.6 years, 17 (14%) cardiovascular deaths occurred, including 7 in the SV group. Univariate cox regression analysis in all subjects showed strong association between elevated levels of ET1, NE, RPA, hs-CRP, sTNF-RI and II, IL-6, and BNP and cardiovascular death (p&lt; 0.05). In the SV group, using multivariate cox regression model, BNP and sTNF-RI were the most powerful predictors in these biomarkers (adjusted hazard ratio [aHR] of BNP: 14.84; 95%CI: 2.21-99.36 per 1 SD increase, p = 0.005) (aHR of sTNF-RI: 2.30; 95%CI: 1.91-4.55 per 1 SD increase, p = 0.017). The optimal cut-off values of BNP and sTNF-RI for mortality were 196 pg/mL and 1.26 ng/mL, respectively. Conversely, in the TV group, only IL-6 was an independent predictor of mortality (aHR: 3.24; 95%CI: 1.57-6.68 per 1 SD increase, p = 0.001), while BNP was not strongly associated with outcomes. The optimal cut-off value of IL-6 for mortality was 2.3 pg/mL. Conclusion: Various biomarkers, including sTNF-R, BNP, and IL-6, are associated with prognosis in overall ACHD. The most prominent mortality predictors might differ, due to differences in SV or TV physiology.
Doctors are prejudiced against transgender patients, MPs say
Authors: Jacqui Wise
Journal: BMJ (2016)

Transgender patients encounter prejudice and a lack of knowledge when they use NHS services in England, the first report on transgender equality produced by a UK parliamentary committee has found.1

The cross party parliamentary inquiry found that the NHS was letting down transgender people and failing in its legal duty under the Equality Act to ensure equal access to services. As an employer and a commissioner the NHS was failing to ensure zero tolerance of “transphobic” behaviour among staff and contractors. The committee also called for a root and branch review …
Candidate locus for familial abdominal aortic aneurysms by genome-wide DNA linkage analysis
Authors: H. Shibamura, S. Buxbaum, J. M. Olson, G. Tromp, M. Skunca, C. Arthur, R. Berguer, C. W. Cole, Raymond Limet, G. MacKean, G. Pals, Natzi Sakalihasan, C. van Vlijmen-van Keulen, Alain Verloes, H. Kuivaniemi
Journal: Circulation (2002)
Abstract 2939: Induction of apoptosis in prostate cancer cells by altering cell metabolism
Authors: Gonzalo Torga, Steven Mooney, Jelani C. Zarif, Kenneth J. Pienta
Journal: Cancer Research (2015)

Abstract The levels of ceramides, sphingosine and their related metabolites have been reported to play an important role in cell fate by determining the balance between apoptosis and cell survival signaling through what has been called the sphingolipid rheostat. One of sphingosine metabolic product, sphingosine-1-phosphate, has been widely proven to be related with tumor growth, resistance to apoptosis, angiogenesis, metastasis and invasiveness in several tumors. In prostate cancer, sphingosine-1-phosphate levels correlate with risk of progression to castration-resistant prostate cancer (CRPC), PSA levels, Gleason score, positive surgical margins, lymph node extension, metastatic extension and mortality. Hypoxia-inducible factors (HIFs) act as pleiotropic transcription factors which serve as major components for cancer progression, upregulation of HIFs are essential for metastasis and tumor growth once hypoxia has ensued. Several relations between HIFs and ceramides/sphingosine metabolism have been reported recently, suggesting that both mechanisms might be somehow interconnected. Despite decades of research inhibitors to HIF have been few and far between. The DNA-intercalating agent doxorubicin was identified one such inhibitor by a mechanism not yet understood. The major mechanism of doxorubicin-mediated apoptosis has been established to be induced by the transcription factor, p53. The p53 cell cycle arrest is usually through p21 which has been shown to have enhanced expression in response to sphingosine kinase 2, one of the enzymes that mediate the conversion of sphingosine to sphingosine-1-phosphate. Several studies associating chemotherapy with different drugs that attempt to modify sphingosine and ceramides metabolism have been published with some remarkable results, although never complete responses. We hypothesize that the incomplete responses may be due to an incomplete blockade of the conversion of ceramides and sphingosine towards their phosphorylated metabolites, sphingosine-1-phosphate and ceramide-1-phospate respectively. Previous work has focused on single agents to enhance chemotherapy. In this work we are interested in studying the combination of different modifiers in the metabolism of ceramides/sphingosine with doxorubicin in order to achieve a total metabolic blockade in an effort to elicit a complete clinical response for prostate cancer. Citation Format: Gonzalo Torga, Steven Mooney, Jelani C. Zarif, Kenneth J. Pienta. Induction of apoptosis in prostate cancer cells by altering cell metabolism. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2939. doi:10.1158/1538-7445.AM2015-2939
Radiation therapy and vaccination against tumor-specific EGFRvIII effectively clears tumors in a murine model of head and neck squamous cell carcinoma
Authors: Lauren Uhde, Shelly Bambina, Alejandro Alice, Peter Lauer, Marka Crittenden, Keith S Bahjat, Michael Gough
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts EGFRvIII is a constitutively active and tumor-specific deletional mutant of EGFR found in multiple tumor types including glioblastoma multiforme, and has been reported in head and neck squamous cell carcinomas (HNSCC). The deletion of EGFR exons 2-7 results in a novel glycine at
NHS trust first to face trial for corporate manslaughter after “wholly avoidable” death of patient
Authors: Clare Dyer
Journal: BMJ (2016)

Two anaesthetists and the NHS trust that employed them were responsible for the “wholly avoidable” death of a 30 year old teacher, a jury at Inner London Crown Court heard this week.

At the start of the first trial of an NHS trust for corporate manslaughter, John Price QC told the jury that the death of Frances Cappuccini, a healthy young woman whose second baby had been delivered only hours before by emergency caesarean, was “wholly exceptional” and “wholly avoidable.”

Cappuccini’s baby was delivered at 8 28 am on 9 October 2012 at Pembury Hospital in Tunbridge Wells, Kent.1 She had a significant postpartum haemorrhage and …
Hypoacetylation, hypomethylation, and dephosphorylation of H2B histones and excessive histone deacetylase activity in DU-145 prostate cancer cells
Authors: Shundong Cang, Xiaobin Xu, Yuehua Ma, Delong Liu, J. W. Chiao
Journal: Journal of Hematology & Oncology (2016)

Hypoacetylation on histone H3 of human prostate cancer cells has been described. Little is known about the modifications of other histones from prostate cancer cells.Histones were isolated from the prostate cancer cell line DU-145 and the non-malignant prostatic cell line RC170N/h. Post-translational modifications of histone H2B were determined by liquid chromatography-mass spectrometry (LC-MS)/MS.The histone H2B of the prostate cancer cell line DU-145 was found to have hypoacetylation, hypomethylation, and dephosphorylation as compared to the non-malignant prostatic cell line RC170N/h. H2B regained acetylation on multiple lysine residues, phosphorylation on Thr19, and methylation on Lys23 and Lys43 in the DU-145 cells after sodium butyrate treatment.The histone H2B of DU-145 prostate cancer cells are hypoacetylated, hypomethylated, and dephosphorylated. Histone deacetylase inhibitor reversed this phenotype. Epigenetic agent may therefore be useful for prostate cancer therapy and worth further investigation.
Discontinuation of oral antivirals in chronic hepatitis B: A systematic review
Authors: George Papatheodoridis, Ioannis Vlachogiannakos, Evangelos Cholongitas, Karsten Wursthorn, Christos Thomadakis, Giota Touloumi, Jörg Petersen
Journal: Hepatology (2016)

The possibility of safe discontinuation of therapy with nucleos(t)ide analogues (NAs) remains one of the most controversial topics in the management of chronic hepatitis B. Therefore, we systematically reviewed the existing data on NA discontinuation in this setting and tried to identify factors affecting the probability of posttherapy remission. A literature search was performed in order to identify all published studies including patients who discontinued NAs in virological remission (VR) and were followed for ≥12 months thereafter. Twenty-five studies with 1716 patients were included. The pooled rates of durable VR remission were 51.4%, 39.3%, and 38.2% at 12, 24, and 36 months, respectively, after NA discontinuation, being relatively higher in initially hepatitis B e antigen (HBeAg)-positive patients (62.5%, 53.4%, 51.5%) than HBeAg-negative patients (43.7%, 31.3%, 30.1%) (P = 0.064). The weighted probability of durable biochemical remission was 65.4%, being numerically higher in HBeAg-positive than HBeAg-negative patients (76.2% versus 56.7%, P = 0.130). The weighted probability of hepatitis B surface antigen loss was 2.0%. The rates of durable VR did not significantly differ according to the VR definition (hepatitis B virus DNA <200, < 2000, < 20,000 IU/mL) or duration of on-therapy VR in HBeAg-positive patients, but they were significantly higher in studies with HBeAg-negative patients and on-therapy VR > 24 than ≤ 24 months (VR at 12 months off-NAs: 75.0% versus 35.6%, P = 0.005). The weighted probability of durable HBeAg seroconversion was 91.9% and 88.0% at 12 and 24 months, respectively, after NA discontinuation without being affected by the duration of on-therapy VR or consolidation therapy (>6 months in all studies).Durable VR seems to be feasible in a substantial proportion of patients who discontinue long-term NA therapy; on-therapy VR > 24 months offers higher chances of off-NA VR in patients with HBeAg-negative chronic hepatitis B.
Incorporation of Next-Generation Sequencing into Routine Clinical Care to Direct Treatment of Head and Neck Squamous Cell Carcinoma
Authors: Nicole G. Chau, Yvonne Y. Li, Vickie Y. Jo, Guilherme Rabinowits, Jochen H. Lorch, Roy B. Tishler, Danielle N. Margalit, Jonathan D. Schoenfeld, Don J. Annino, Laura A. Goguen, Tom Thomas, Hailey Becker, Tyler Haddad, Jeffrey F. Krane, Neal I. Lindeman, Geoffrey I. Shapiro, Robert I. Haddad, Peter S. Hammerman
Journal: Clinical Cancer Research (2016)

The clinical impact of next-generation sequencing (NGS) in patients with head and neck squamous cell carcinoma (HNSCC) has not been described. We aimed to evaluate the clinical impact of NGS in the routine care of patients with HNSCC and to correlate genomic alterations with clinical outcomes.Single-center study examining targeted NGS platform used to sequence tumor DNA obtained from 213 HNSCC patients evaluated in outpatient head and neck oncology clinic between August 2011 and December 2014. We correlated tumor genomic profiling results with clinical outcomes.PI3K/RTK pathway activation occurred frequently [activating PIK3CA mutation or amplification (13%), PTEN inactivation (3%), RAS activation (6%), EGFR or ERBB2 activation (9%)]. Alterations in pathways affecting cell-cycle regulation [CCND1 amplification (9%), CDKN2A inactivation (17%), BRCA2 inactivation (2%)] and squamous differentiation [NOTCH1 inactivation (8%) andEP300 inactivation (6%)] were identified. PIK3CA amplification (n = 43), not PIK3CA mutation, was associated with significantly poorer progression-free survival (P = 0.0006). Oncogenic RAS mutations (n = 13) were associated with significantly poorer progression-free survival (P = 0.0001) and lower overall survival (P = 0.003). Eight patients with advanced, treatment-refractory HNSCC enrolled on clinical trials matched to tumor profiling results, and 50% achieved a partial response.Incorporation of NGS clinical assays into the routine care of patients with HNSCC is feasible and may readily facilitate enrollment into clinical trials of targeted therapy with a higher likelihood of success. Data can be utilized for discovery of genomic biomarkers of outcome. PIK3CA amplification and RAS mutations were frequently identified and associated with poorer prognosis in this cohort. Clin Cancer Res; 22(12); 2939-49. ©2016 AACR.
Melanoma Thickness and Survival Trends in the United States, 1989–2009
Authors: Waqas R. Shaikh, Stephen W. Dusza, Martin A. Weinstock, Susan A. Oliveria, Alan C. Geller, Allan C. Halpern
Journal: JNCI Journal of the National Cancer Institute (2015)

With melanoma incidence rising and mortality stable, some question whether the melanoma epidemic is real. Melanoma thickness and survival trends may provide insights, but previous studies have been limited because of missing data on thickness. With a validated imputation method for missing thickness data, we characterized melanoma thickness and survival trends among men and women in the Surveillance, Epidemiology, and End Results (SEER)-9 registries between 1989 and 2009. A total of 98,498 cases of invasive melanoma were identified. All statistical tests were two-sided. Incidence per 100 000 person-years increased (13.94, 95% confidence interval [CI] = 13.65 to 14.23, to 21.87, 95% CI = 21.56 to 22.19, P < .001) between 1989 to 1991 and 2007 to 2009, fatal incidence remained stable (2.32, 95% CI = 2.2 to 2.4, to 2.08, 95% CI = 2.0 to 2.2, P = .20) between 1989 to 1991 and 1998 to 2000, and five-year survival increased (88.29%, 95% CI = 87.60% to 88.95%, to 91.68%, 95% CI = 91.22% to 92.12%, P < .001) between 1989 to 1991 and 2001 to 2003. Increase in incidence occurred across all thickness groups. Median thickness decreased (0.73 to 0.58mm). Geometric mean thickness decreased (0.77 to 0.65mm) 4.6% (95% CI = 4.2% to 5.0%) every three years in multivariable analysis. Thickness decreased among T1/T2 tumors (0.01-1.00 and 1.01-2.00mm) and among all age and sex groups, whites, non-Hispanics, and all body sites. However, thickness increased among T3/T4 tumors (2.01-4.00 and > 4.00mm) and nodular melanomas; acral lentiginous melanomas approached statistical significance. Thickness remained unchanged among some racial minorities. Melanoma-specific survival improved (hazard ratio [HR] = 0.89, 95% CI = 0.88 to 0.91) every three years in multivariable analysis. Improvements in survival occurred across all subgroups except nonblack minorities, and nodular and acral lentiginous subtypes. Increasing incidence across all thickness groups coupled with T3/T4 lesions becoming thicker suggests that the melanoma epidemic is real and not simply an artifact of increased detection pressure of earlier-stage T1/T2 lesions. Survival is generally improving independent of thickness, but improvements in survival have not been experienced by certain minorities, and nodular and acral lentiginous subtypes.