tbuckley/cabot-search huggingface dataset:
Methotrexate, homocysteine, and seizures.
Authors: C T Quinn, J C Griener, T Bottiglieri, B A Kamen
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.1.393 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9440774 Methotrexate, homocysteine, and seizures. C T QuinnxC T QuinnSearch for articles by this author , J C GrienerxJ C GrienerSearch for articles by this author , T BottiglierixT BottiglieriSearch for articles by this author , B A KamenxB A KamenSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.1.393 PDF "Methotrexate, homocysteine, and seizures.." Journal of Clinical Oncology, 16(1), pp. 393–394© 1998 by American Society of Clinical Oncology
Identification of a novel glucokinase mutation in an Indian woman with GCK-MODY
Authors: Sujeet Jha, Samreen Siddiqui, Swati Waghdhare, Shweta Dubey, Shuba Krishna, Kalyanasundaram Subramanian, Jyoti Bajpai Dikshit, L Ravikiran, Amit Bhargava
Journal: The Lancet Diabetes & Endocrinology (2016)
Folfoxiri Plus Bevacizumab (Bev) As First-Line Treatment of Ras Wild-Type (Wt) Metastatic Colorectal Cancer (Mcrc) Patients (Pts)
Authors: C. Antoniotti, C. Cremolini, F. Loupakis, S. Lonardi, C. Boni, C. Carlomagno, L. Salvatore, G. Masi, F. Negri, C. Barone, F. Zoratto, V. Ricci, A. Bonetti, F. D'Argenio, S. Leo, S. Chiara, E. Dell'Aquila, G. Fontanini, L. Boni, A. Falcone
Journal: Annals of Oncology (2014)
Abstract 5536: KB-164, a novel and highly potent Src family kinase inhibitor, reduces cancer cell invasion and abrogates downstream oncogenic pathways in triple negative breast cancer
Authors: Rabia A. Gilani, Kristoffer R. Brandvold, Li Wei Bao, Sameer Phadke, Michael E. Steffey, Matthew B. Soellner, Sofia D. Merajver
Journal: Cancer Research (2015)

Abstract Src is a non-receptor tyrosine kinase, which acts as an integrator of diverse signaling pathways used by cancer cells for cell proliferation, migration and metastasis. Recent interest in developing target specific therapy for improved benefits with manageable toxic effects has sharply increased the interest in testing new Src family kinase inhibitors for their potential anticancer therapeutic properties. In this study, we sought to investigate the chemical characteristics and the biological effects of the novel Src family kinase inhibitor KB-164, in Src expressing triple negative breast cancer cells. We show that KB-164 acts as a potent Src kinase inhibitor (IC50 1.3 nmol/L) in MDA-MB 231 cells, 100-fold more potent than the most widely used Src family kinase inhibitor dasatinib. At concentrations of 50nmol/L, KB-164 led to complete inhibition of Src activation for 48 hours. Analysis of downstream effectors of Src revealed that treatment with KB-164 inhibits the phosphorylation of several oncogenic pathways i.e. EGFR, ERK1/2, P38MAPK and AKT. A dramatic decrease in cancer cell motility and invasion was observed on treatment with KB-164 in both SUM 149 and MDA-MB 231 triple negative breast cancer cell lines. We also show that triple negative breast cancer cells derived from the patients are equally sensitive to growth inhibition by KB-164 within an IC50 of 1.8-nmol range. No cytotoxicity was observed both in vitro (18 micro mol/L in normal human mammary epithelial cells) and in vivo (70mg/kg in mice). Our findings indicate that KB-164 inhibits signaling pathways involved in controlling tumor cell proliferation and survival, suggesting that KB-164 might prove to be a promising therapeutic agent for breast cancer. Citation Format: Rabia A. Gilani, Kristoffer R. Brandvold, Li Wei Bao, Sameer Phadke, Michael E. Steffey, Matthew B. Soellner, Sofia D. Merajver. KB-164, a novel and highly potent Src family kinase inhibitor, reduces cancer cell invasion and abrogates downstream oncogenic pathways in triple negative breast cancer. [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 5536. doi:10.1158/1538-7445.AM2015-5536
Healthy aging and male sexual function
Authors: R C Schiavi, P Schreiner-Engel, J Mandeli, H Schanzer, E Cohen
Journal: American Journal of Psychiatry (1990)

The authors examined the effect of age on sexual function and behavior and on nocturnal penile tumescence in 65 healthy married men aged 45 to 74 years. There was a significant negative relation between age and sexual desire, arousal, and activity and an increasing prevalence of sexual dysfunction with age but no age difference in sexual enjoyment and satisfaction. Significant age-related decreases in frequency, duration, and degree of nocturnal penile tumescence were found. Sexual desire, arousal, coital frequency, and prevalence of erectile problems correlated with nocturnal penile tumescence measures. The authors discuss the relevance of these findings for the understanding of sexual function in aging men.
Validation of a screening test for elderly patients in oncology
Authors: P. Soubeyran, C. A. Bellera, F. Gregoire, J. Blanc, J. Ceccaldi, C. Blanc-Bisson, C. Mertens, S. Mathoulin-Pélissier, M. Fonck, M. Rainfray
Journal: Journal of Clinical Oncology (2008)

20568 Background: Treatment-related toxicity risk increases with age and may even lead to toxic death. Detailed evaluation of patient's status becomes mandatory. Comprehensive Geriatric assessment (CGA) is an adequate method to evaluate these patients but it is probably not necessary to all patients so that a screening tool should be developed. Methods: In a prospective multicentric cohort, we studied patients older than 70 with cancer and first-line chemotherapy. 364 patients were evaluated with the following CGA tools: MMS, ADL, IADL, MNA, Get up and go, GDS15, CIRSG, QLQ-C30. The data collected allowed us to perform an exploratory study in order to design a screening tool. Results: Analysis of this cohort allowed us to propose a new screening tool (generic name : G8), which included 7 MNA items (A, B, C, E, F, H, P) and age (<80, 80–85, >85), for a total score ranging from 0 (poor score) to 17 (good score). First, geriatrists and oncologists selected these specific items since they were expected to correlate with different dimensions of CGA. Indeed, we observed the following correlations: A (appetite), B (weight loss) and F (BMI) with total MNA score; E (cognition and depression) with MMS; C (motricity) and P (self-related health) with ADL; C with Get up and go; E and P with GDS15; H (medications) with CIRS-G. Next, we applied this new tool to our population of 364 patients. Results suggested that the area under the curve was maximized when the threshold was 14, equivalent to a 90% sensitivity, and a 60% specificity. Conclusions: This exploratory study allowed us to propose the G8 questionnaire as a screening tool for CGA. In collaboration with 15 geriatric French cancer units, we are now conducting a large prospective study (1500 patients) sponsored by the French National Cancer Institute in order to validate the G8 screening tool, as well as the VES-13 questionnaire, using the CGA as the gold- standard. Sponsored by PHRC, sanofi-aventis, AMGEN, Pfizer Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Pfizer Oncology, sanofi-aventis
Hepatitis C Disease Burden in the United States in the era of oral direct‐acting antivirals
Authors: Jagpreet Chhatwal, Xiaojie Wang, Turgay Ayer, Mina Kabiri, Raymond T. Chung, Chin Hur, Julie M. Donohue, Mark S. Roberts, Fasiha Kanwal
Journal: Hepatology (2016)

Oral direct‐acting antivirals (DAAs) represent a major advance in hepatitis C virus (HCV) treatment. Along with recent updates in HCV screening policy and expansions in insurance coverage, treatment demand in the United States is changing rapidly. Our objective was to project the characteristics and number of people needing antiviral treatment and HCV‐associated disease burden in the era of oral DAAs. We used a previously developed and validated Hepatitis C Disease Burden Simulation model (HEP‐SIM). HEP‐SIM simulated the actual clinical management of HCV from 2001 onward, which included antiviral treatment with pegylated interferon (Peg‐IFN)‐based therapies as well as the recent oral DAAs, risk‐based and birth‐cohort HCV screening, and the impact of the Affordable Care Act. We also simulated two hypothetical scenarios—no treatment and treatment with Peg‐IFN‐based therapies only. We estimated that in 2010, 2.5 (95% confidence interval [CI], 1.9‐3.1) million noninstitutionalized people were viremic, which dropped to 1.9 (95% CI, 1.4‐2.6) million in 2015, and projected to drop below 1 million by 2020. A total of 1.8 million HCV patients will receive HCV treatment from the launch of oral DAAs in 2014 until 2030. Based on current HCV management practices, it will take 4‐6 years to treat the majority of patients aware of their disease. However, 560,000 patients would still remain unaware by 2020. Even in the oral DAA era, 320,000 patients will die, 157,000 will develop hepatocellular carcinoma, and 203,000 will develop decompensated cirrhosis in the next 35 years. Conclusions: HCV‐associated disease burden will still remain substantial in the era of oral DAAs. Increasing HCV screening and treatment capacity is essential to further decreasing HCV burden in the United States. (H epatology 2016;64:1442‐1450)
Evaluating new surgical procedures
Authors: D. J Pegg
Journal: BMJ (1996)

and two related to relief.Firstly, good information should be given to parents, schools, and children and should include the dangers of cannabis (memory impairment, the fact that it contains more carcinogens than tobacco, etc).Secondly, drugs should be eliminated.The police are on the right track in the way that they tackle big dealers, but they should be allowed to tackle street dealing as well, because it is difficult to find drugs when petty sales are reduced.'Thirdly, users should be able to gain admission to drug free institutions where they are treated with respect and encouragement so that they can regain their self respect.
IMCT-12A PHASE 1 TRIAL OF VACCINATION WITH AUTOLOGOUS DENDRITIC CELLS PULSED WITH LYSATE DERIVED FROM AN ALLOGENEIC GLIOBLASTOMA STEM-LIKE CELL LINE FOR PATIENTS WITH NEWLY DIAGNOSED OR RECURRENT GLIOBLASTOMA
Authors: Jethro Hu, Surasak Phuphanich, Jeremy Rudnick, Mia Mazer, HongQiang Wang, Christopher Wheeler, Keith Black, John Yu
Journal: Neuro-Oncology (2015)

BACKGROUND: Dendritic cell vaccines are a promising treatment for glioblastoma. The glioblastoma stem-like cell subpopulation is refractory to standard chemotherapy and radiation treatment, but may be susceptible to immunotherapeutic targeting. METHODS: This single-institution phase I trial is designed to assess the safety, tolerability, and potential efficacy of an autologous dendritic cell vaccine pulsed with lysate derived from a glioblastoma stem-like cell line. Patients with newly diagnosed glioblastoma (Cohort A) receive standard radiation and temozolomide in addition to vaccine. Patients with up to third glioblastoma recurrence (Cohort B) receive vaccine alone, although patients previously treated with bevacizumab are allowed to continue bevacizumab on study. Prior to enrollment, patients must undergo a qualifying gross total or near-gross total resection. Treatment consists of a Vaccine Induction Phase (weekly vaccines x 4 – for Cohort A, given upon completion of radiation), followed by a Vaccine Maintenance Phase (vaccine every 8 weeks until supply depleted). Imaging is performed during Week 4 of the Induction phase and every 8 weeks thereafter until progression. The primary objective of safety and tolerability includes adverse event grading per NCI CTC. Clinical assessment includes progression-free survival at 6 months and overall survival. Immunological testing to assess cytotoxic T-lymphocyte response will be performed at predetermined intervals. Goal enrollment is 20 patients in each cohort. Stopping rules for safety and efficacy using Bayesian sequential design will be followed. RESULTS: To date, 18 patients (7 new GBM, 11 recurrent GBM) have enrolled in this trial. No adverse events related to vaccine have been noted. CONCLUSION: This single-institution phase I dendritic cell vaccine trial builds upon our previous research efforts by specifically targeting the glioblastoma stem-like cell subpopulation that is resistant to standard radiation and chemotherapy. Accrual is proceeding rapidly, and results will be published when available.
Angiographic and Intracoronary Manifestations of Coronary Fibromuscular Dysplasia
Authors: Jacqueline Saw, Hiram Bezerra, Heather L. Gornik, Lindsay Machan, G.B. John Mancini
Journal: Circulation (2016)

We previously described a strong association between fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection. Angiographic manifestations of coronary FMD aside from dissection were considered rare. However, we observed several coronary FMD angiographic abnormalities with corresponding optical coherence tomography abnormalities.Baseline demographics and imaging of patients with suspected coronary FMD at Vancouver General Hospital were reviewed. Presence of multifocal (string-of-beads) extracoronary FMD was confirmed by 2 specialists. In these patients, coronary angiographic findings (excluding dissected segments) were reviewed and classified by 2 experienced angiographers for irregular stenosis, that is, stenosis with irregular borders in a focal or diffuse pattern with/without systolic accentuation; smooth stenosis, diffuse or focal; segmental dilatation/ectasia; and tortuosity. Optical coherence tomography was performed in a subset of patients. Of 32 patients with extracoronary FMD and suspected coronary involvement, 28 were women (88%), and their mean age was 59.4±9.9 years. Nineteen presented with myocardial infarction (13 caused by spontaneous coronary artery dissection), and 13 had stable symptoms. The observed coronary angiographic abnormalities included tortuosity in all cases (91% were moderate to severe), irregular stenosis in 59%, smooth stenosis in 19%, and segmental dilatation/ectasia in 56%. Fifteen patients had optical coherence tomography of the abnormal segments showing abnormalities, including multiple areas of patchy or diffuse intimal, medial or adventitial abnormalities with thickening/accumulation of varied reflectivities, macrophage infiltration, loss/duplication of elastic membranes, and cavitation.This is the first case series describing findings suggestive of angiographic and intracoronary manifestations of coronary FMD. Future studies should prospectively review these features in patients with extracoronary FMD.
Economic Analysis of Prostate-Specific Antigen Screening and Selective Treatment Strategies
Authors: Joshua A. Roth, Roman Gulati, John L. Gore, Matthew R. Cooperberg, Ruth Etzioni
Journal: JAMA Oncology (2016)

Prostate-specific antigen (PSA) screening for prostate cancer is controversial. Experts have suggested more personalized or more conservative strategies to improve benefit-risk tradeoffs, but the value of these strategies-particularly when combined with increased conservative management for low-risk cases-is uncertain.To evaluate the potential cost-effectiveness of plausible PSA screening strategies and to assess the value added by increased use of conservative management among low-risk, screen-detected cases.A microsimulation model of prostate cancer incidence and mortality was created. A simulated contemporary cohort of US men beginning at 40 years of age underwent 18 strategies for PSA screening. Treatment strategies included (1) contemporary treatment practices based on age and cancer stage and grade observed in the Surveillance, Epidemiology, and End Results program in 2010 or (2) selective treatment practices whereby cases with a Gleason score lower than 7 and clinical T2a stage cancer or lower are treated only after clinical progression, and all other cases undergo contemporary treatment practices. National and trial data on PSA growth, screening and biopsy patterns, incidence of prostate cancer, treatment distributions, treatment efficacy, mortality, health-related quality of life, and direct medical expenditure were analyzed. Data were collected from March 18, 2009, to August 15, 2014, and analyzed from November 20, 2012, to December 11, 2015.Eighteen screening strategies that vary by start and stop age, screening interval, and criteria for biopsy referral and contemporary or selective treatment practices.Life-years (LYs), quality-adjusted life-years (QALYs), direct medical expenditure, and cost per LY and QALY gained.All 18 screening strategies were associated with increased LYs (range, 0.03-0.06) and costs ($263-$1371) compared with no screening, with the cost ranging from $7335 to $21 649 per LY. With contemporary treatment, only strategies with biopsy referral for PSA levels higher than 10.0 ng/mL or age-dependent thresholds were associated with increased QALYs (0.002-0.004), and only quadrennial screening of patients aged 55 to 69 years was potentially cost-effective in terms of cost per QALY (incremental cost-effectiveness ratio, $92 446). With selective treatment, all strategies were associated with increased QALYs (0.002-0.004), and several strategies were potentially cost-effective in terms of cost per QALY (incremental cost-effectiveness ratio, $70 831-$136 332).For PSA screening to be cost-effective, it needs to be used conservatively and ideally in combination with a conservative management approach for low-risk disease.
Characterization of neuroendocrine prostate cancer (NEPC) in patients with metastatic castration resistant prostate cancer (mCRPC) resistant to abiraterone (Abi) or enzalutamide (Enz): Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).
Authors: Eric Jay Small, Jiaoti Huang, Jack Youngren, Artem Sokolov, Rahul Raj Aggarwal, George Thomas, Lawrence D. True, Li Zhang, Adam Foye, Joshi J. Alumkal, Charles J. Ryan, Matthew Rettig, Christopher P. Evans, Martin Edwin Gleave, Robert Baertsch, Josh Stuart, Robert Evan Reiter, Primo Lara, Kim N. Chi, Tomasz M. Beer
Journal: Journal of Clinical Oncology (2015)

5003 Background: Mechanisms of resistance to androgen signaling inhibitors such as Abi or Enz are poorly understood. An increasing % of these pts develop NEPC. Pathologic (path), clinical, and genomic characterization of pts with NEPC was undertaken in the context of the WCDT project, which seeks to identify genetic pathways underlying primary and acquired resistance to Abi and Enz. Methods: Eligible mCRPC pts underwent a metastasis (met) biopsy (bx) at one of 5 WCDT centers, using a standardized bx protocol, and were uniformly followed for clinical outcomes. Tissue was both frozen, and formalin fixed/paraffin embedded. Independent path review was undertaken by 3 pathologists. Frozen specimens underwent laser capture micro-dissection, RNA isolation, library preparation and RNA sequencing (seq). Machine learning was used to derive a NEPC expression signature. Results: 150 of 300 planned mCRPC pts have undergone bx. Path review has been undertaken in 101. Classic small cell cancer (SmCC) was identified in 12%, adenocarcinoma (adenoca) in 33%. An intermediate histology distinct from SmCC or adenoca was seen in 27%. The remaining 28% were mixed histologies or were not classifiable. Anatomic site of bx (node, bone, liver) did not appear to enrich for a particular histology. Median overall survival was: not reached at 22 mos of follow-up in pts with adenoca, 8.9 mos in pts with intermediate histology, and 6.6 mos in pts with SmCC (log rank p = 0.027). RNAseq data are available on 45 biopsies. A 50 gene signature with 97% accuracy for NEPC (defined as SmCC or intermediate histology) was developed. Conclusions: RNAseq and expression analysis can be accomplished in small bone and soft tissue mCRPC biopsies. A distinct histology, intermediate to SmCC and adeno, was observed in 27% of pts. The development of NEPC in mCRPC resistant to Abi or Enz is far more common than previously appreciated and appears to result in poor survival. A 50 gene NEPC expression signature was derived which provides insight into the biology and potential treatment of NEPC.
Abstract 6089: Myocardial Blush Predicts Outcomes in Patients with Acute Coronary Syndromes: An Analysis of the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial
Authors: Kenji Goto, Alexandra Lansky, Halil Mutlu, Ecatarina Cristea, Roxana Mehran, David Cox, Micheal Bertrand, Frederick Feit, Stuckey Hamon, Steven V. Manoukian, George Dangas, Magnus Ohman, Bernard Gersh, Jeffery W Moses, Gregg W Stone
Journal: Circulation (2008)
Handgun Politics
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1979)

Legislation to control handguns is not usually included in the lists of health-related matters before the Congress. But that's where it belongs, because handguns now annually kill nearly 10,000 people in this country, seriously injure scores of thousands, and greatly contribute to making homicide the leading cause of death among teen-agers and young adults. If some rogue bacillus produced this damage, it would easily, and rationally, come under the jurisdiction of an institute at Bethesda; meanwhile, legislators and presidents would proffer their support for a medical victory, rather than indulge in rhetorical acrobatics to explain mixed feelings about the offending . . .