tbuckley/cabot-search huggingface dataset:
Abstract #1925: p53-derived peptide targets a novel death pathway inducing selective necrosis in cancer cells
Authors: Kelley Sookraj, Victor Adler, Ehsan Yazdi, Michael Zenilman, Josef Michl, Matthew Pincus, Wilbur Bowne
Journal: Cancer Research (2009)

Introduction: In our preliminary studies we describe p53-derived peptides from the MDM-2 binding domain that possess anti-cancer activity. These molecules appear to promote necrosis of cancer cells while sparing their untransformed counterparts. However, the anti-cancer mechanism remains undefined. To further elucidate this observation we tested PNC-27 which contains the p53 MDM-2 binding domain 12-26 attached to penetratin against different human cancer cell lines. The mechanism of selective cancer cell death was then determined. Methods: Humancancer cell lines (MiaPaCa-2, pancreatic; HT1080, fibrosarcoma; and MCF-7, breast) plus respective untransformed counterparts (HPNE, BJ, and MCF-10) were treated with PNC-27 and control peptide. Peptide mediated necrosis and apoptosis were measured by release of lactate dehydrogenase (LDH) and pro-apoptotic proteins, respectively. Treatment with fluorescent labeled peptide, immunoprecipitation (IP), and time -lapse electron microscopy (EM) were employed to further study the anti-cancer mechanism. Results: Treatment with PNC-27 does not cause elevation of pro-apoptotic proteins (caspases 3,7) but induces early, rapid release of LDH. Accordingly, near 100% tumor cell death was observed. This activity was dose-dependent; an effect not detected in either untransformed or control peptide treated groups. This specific anti-cancer activity, in part, may be due to the observed increased expression of MDM-2 found in cancer cells compared to their normal cellular counterparts which is consistent with the abrogation of MDM-2 and stabilization of p53 protein levels after PNC-27 treatment. Moreover, following IP of fluorescent labeled PNC-27 from treated cancer cells; labeled MDM-2 was also detected. Furthermore, EM revealed the presence of membrane-pore formation and subsequent plasma cell membrane disruption in cancer cells only.Conclusions: These results suggest a mechanism of PNC-27 binding to MDM-2 in the cancer cell/membrane, leading to pore formation and membrane disruption; a p53-independent pathway consistent with rapid selective cancer cell necrosis.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1925.
Lesion-Specific Ischemia With Noninvasive Computed Tomographic Angiography
Authors: Leslee J. Shaw, Ed Nicol
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Triple Therapy Versus Biologic Therapy for Active Rheumatoid Arthritis
Authors: Nick Bansback, Ciaran S. Phibbs, Huiying Sun, James R. O'Dell, Mary Brophy, Edward C. Keystone, Sarah Leatherman, Ted R. Mikuls, Aslam H. Anis
Journal: Annals of Internal Medicine (2017)

Background: The RACAT (Rheumatoid Arthritis Comparison of Active Therapies) trial found triple therapy to be noninferior to etanercept–methotrexate in patients with active rheumatoid arthritis (RA). Objective: To determine the cost-effectiveness of etanercept–methotrexate versus triple therapy as a first-line strategy. Design: A within-trial analysis based on the 353 participants in the RACAT trial and a lifetime analysis that extrapolated costs and outcomes by using a decision analytic cohort model. Data Sources: The RACAT trial and sources from the literature. Target Population: Patients with active RA despite at least 12 weeks of methotrexate therapy. Time Horizon: 24 weeks and lifetime. Perspective: Societal and Medicare. Intervention: Etanercept–methotrexate first versus triple therapy first. Outcome Measures: Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results of Base-Case Analysis: The within-trial analysis found that etanercept–methotrexate as first-line therapy provided marginally more QALYs but accumulated substantially higher drug costs. Differences in other costs between strategies were negligible. The ICERs for first-line etanercept–methotrexate and triple therapy were $2.7 million per QALY and $0.98 million per QALY over 24 and 48 weeks, respectively. The lifetime analysis suggested that first-line etanercept–methotrexate would result in 0.15 additional lifetime QALY, but this gain would cost an incremental $77 290, leading to an ICER of $521 520 per QALY per patient. Results of Sensitivity Analysis: Considering a long-term perspective, an initial strategy of etanercept–methotrexate and biologics with similar cost and efficacy is unlikely to be cost-effective compared with using triple therapy first, even under optimistic assumptions. Limitation: Data on the long-term benefit of triple therapy are uncertain. Conclusion: Initiating biologic therapy without trying triple therapy first increases costs while providing minimal incremental benefit. Primary Funding Source: The Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, Canadian Institutes for Health Research, and an interagency agreement with the National Institutes of Health–American Recovery and Reinvestment Act.
Head impact exposure and time to recovery in youth american football players diagnosed with a concussion
Authors: Verle D Valentine, Jason C Dorman, Thayne A Munce
Journal: British Journal of Sports Medicine (2017)

Objective To compare head impact exposure (HIE) sustained by youth American football players on days of concussion with prior sessions, and to evaluate concussion resolution with objective assessments. Design Prospective,observational study. Setting Youth American football. Participants Youth American football players (11-14 yr, n=57) who had head impact sensors embedded in their helmets; six were diagnosed with a concussion. Interventions Over four consecutive seasons, baseline and post-injury concussion assessments were performed and HIE was monitored (Head Impact Telemetry system) for all practice/game sessions. Outcome measures Baseline/Post-concussion assessments – symptoms, balance, reaction time, neurocognitive function (ImPACT), and oculomotor performance (King-Devick). HIE – location, frequency, and magnitude (linear acceleration [LA] and rotational acceleration [RA]). Main results For concussive impacts, the average peak LA was 85.9 g (39.7-156.8 g ) and average peak RA was 6918rad·sec -2 (4508-8433rad·sec -2 ). On average, players sustained 21.3 impacts/session on days of concussion vs. 10.2 in previous sessions. Median LA and RA did not differ on days of concussion when compared to prior sessions (21.9 vs. 20.7 g ; 1480 vs. 1485 rad·sec -2 ). Average duration for a concussed player to have his assessment values return to baseline and be cleared for play was 32 days (17-53). Conclusions Considerable variation in magnitude existed between impacts that lead to concussion in this population. Players sustained more head impacts in sessions with a concussion compared to prior sessions. Frequency and magnitude of head impacts on the day of concussion did not correlate with time to recovery. Continued observation of a larger cohort is warranted. Competing interests None.
PERCEPTION OF HEALTH PROBLEMS AMONG COMPETITIVE RUNNERS: QUALITATIVE STUDY OF COGNITIVE APPRAISALS AND BEHAVIOURAL RESPONSES
Authors: Sara Jelvegård, Toomas Timpka, Victor Bargoria, Håkan Gauffin, Jenny Jacobsson
Journal: British Journal of Sports Medicine (2017)

Background About 2 out of 3 competitive runners sustain at least one health problem every season; most of these problems are non-traumatic injuries with gradual onset. The main known risk indicator for sustaining a new running-related injury episode is a history of a previous injury, suggesting that behavioural habits are part of the causal mechanisms. Objective To explore competitive runners' cognitive appraisals of perceived symptoms on injury and illness and how these appraisals are transformed into behaviour. Design Qualitative study using semi-structured interviews for data collection. Setting Swedish competitive middle- and long-distance runners. Participants 14 runners from the national top 15 list. Assessment of Risk Factors Qualitative research methods were used to categorize interview data and perform a thematic analysis. Main Outcome Measurements Categories resulting from the analysis were used to construct an explanatory model. Results Symptoms interpreted to be caused by illness or injury with a sudden onset were found to lead to immediate responses and changes to training and competition programs (activity pacing). In contrast, perceptions interpreted to be due to injuries with gradual onset led to varied behavioural reactions. These behavioural responses were planned with regard to short-term effects and were characterized by indifference and neglect of long-term implications, consistent with an overactivity behavioural pattern. The latter pattern was consistent with a psychological adaptation to stimuli that is presented progressively to the athlete. Conclusions Competitive runners appraise whether a health problem requires immediate withdrawal from training based on whether the problem is interpreted as an illness and/or has a sudden onset. The ensuing behaviours follow 2 distinct patterns that can be termed activity pacing and overactivity. Recurrent health problems among competitive runners can be addressed through the premise that overactivity behaviours are balanced by support of health literacy and psychological flexibility.
Clinical course and perinatal transmission of chronic hepatitis B during pregnancy: A real-world prospective cohort study
Authors: Zhi-Xian Chen, Gui-Fang Gu, Zhao-Lian Bian, Wei-Hua Cai, Yi Shen, Yan-Li Hao, Sheng Zhang, Jian-Guo Shao, Gang Qin
Journal: Journal of Infection (2017)

To determine the clinical course and perinatal transmission of chronic hepatitis B during pregnancy in a real life setting.A total of 221 singleton pregnant women with detectable HBV-DNA levels (≥103 copies/mL) were enrolled during January 2011 to June 2015. Forty-three high viraemic patients (≥106 copies/mL) received telbivudine in the 2nd or 3rd trimester according to their intention, while 89 high viraemic and 79 low viraemic (≥103 and <106 copies/mL) patients were the control cohorts. Primary endpoint was the pregnancy outcomes and secondary endpoint the perinatal transmission including intrauterine infection, immunoprophylaxis failure and occult infection.In all, 209 patients completed pregnancy with 209 infants, while 2 in telbivudine-treated cohort had unexplained late stillbirths. Twenty-nine (70.7%) of telbivudine-treated patients and 3 (3.4%) of untreated high viraemic controls achieved undetectable HBV-DNA levels prior delivery. At 7 months postpartum, immunoprophylaxis failure was significantly lower (2.4%) in telbivudine-treated cohort, compared with 16.9% and 10.1% in untreated high and low viraemic cohorts, respectively.Low viraemic patients may also need antiviral therapy since they bear moderate risk for perinatal transmission of HBV. However, more multicenter, large-scale studies are required before antepartum antiviral therapy is routinely recommended in patients with detectable viral loads.
Intra and Interspecific Variations of Gene Expression Levels in Yeast Are Largely Neutral: (Nei Lecture, SMBE 2016, Gold Coast)
Authors: Jian-Rong Yang, Calum J. Maclean, Chungoo Park, Huabin Zhao, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2017)

It is commonly, although not universally, accepted that most intra and interspecific genome sequence variations are more or less neutral, whereas a large fraction of organism-level phenotypic variations are adaptive. Gene expression levels are molecular phenotypes that bridge the gap between genotypes and corresponding organism-level phenotypes. Yet, it is unknown whether natural variations in gene expression levels are mostly neutral or adaptive. Here we address this fundamental question by genome-wide profiling and comparison of gene expression levels in nine yeast strains belonging to three closely related Saccharomyces species and originating from five different ecological environments. We find that the transcriptome-based clustering of the nine strains approximates the genome sequence-based phylogeny irrespective of their ecological environments. Remarkably, only ∼0.5% of genes exhibit similar expression levels among strains from a common ecological environment, no greater than that among strains with comparable phylogenetic relationships but different environments. These and other observations strongly suggest that most intra and interspecific variations in yeast gene expression levels result from the accumulation of random mutations rather than environmental adaptations. This finding has profound implications for understanding the driving force of gene expression evolution, genetic basis of phenotypic adaptation, and general role of stochasticity in evolution.
Effects of AG-348, a Pyruvate Kinase Activator, on Anemia and Hemolysis in Patients with Pyruvate Kinase Deficiency: Data from the DRIVE PK Study
Authors: Rachael F Grace, Christian Rose, D Mark Layton, Hassan M Yaish, Wilma Barcellini, Frédéric Galactéros, D Holmes Morton, Yaddanapudi Ravindranath, Kevin H.M. Kuo, Eduard J van Beers, Janet L Kwiatkowski, Bruce A Silver, Elizabeth Merica, Charles Kung, Marvin Cohen, Hua Yang, Jeffrey Hixon, Penelope A Kosinski, Lee Silverman, Lenny Dang, Zheng (Jason) Yuan, Ann J Barbier, Bertil Glader
Journal: Blood (2016)
4EGI-1 represses cap-dependent translation in malignant pleural mesothelioma
Authors: Arpita De, Blake Jacobson, Mark Peterson, Marian Kratzke, Robert Kratzke
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

163 

Purpose of the study: Malignant pleural mesothelioma is a disease with a poor prognosis and a median survival time of only 1 year. Thus, it is very essential to find potential new therapies for mesothelioma and thereby identify new targets regulated by cap-dependent translation in this cancer. 4EGI-1 inhibits the interaction between translation initiation factors eIF4E and eIF4G and thus inhibits cap-dependent translation in other cancers. Here, we study the effect of 4EGI-1 on cap-dependent translation in mesothelioma.    Methods: Human mesothelioma cell lines H2596 and H2461 and the non-transformed human mesothelial cell line LP9 were used for these studies. Proliferation studies using the Cell Counting Kit-8 were performed. Cap-binding assay using the 7-methyl-GTP-Sepharose resin was done to study the inhibition of the formation of the cap-dependent translation initiation complex. Western blot analysis was used to evaluate the levels of various proteins on treatment of cells with [4EGI][1]-1 . Polysome analysis is presently being carried out in order to identify preferentially translated transcripts in cancerous cells compared to cells treated with 4EGI-1.    Results: Compared to LP9, 4EGI-1 preferentially inhibited the growth of H2596 and H2461. 4EGI-1 also disrupted cap-binding in these cell lines both invitro and in cells. Besides, 4EGI-1 treatment in these cancer cells also lead to a decrease in the protein levels of osteopontin (a known biomarker for mesothelioma) and survivin (an inhibitor of apoptosis). Surprisingly, we also observed that treatment with 4EGI-1 caused an increase in the hypophosphorylated form (active form) of the translational repressor 4EBP-1 in the cancer cells.    Conclusions: Our studies show that 4EGI-1 can be a possible new strategy for treating mesothelioma. Also, this drug might help to identify new targets preferentially translated by cap-dependent translation in mesothelioma and validate their potential efficacy in treating this disease.

 [1]: /lookup/external-ref?link_type=PDB&access_num=4EGI&atom=%2Fcanres%2F68%2F9_Supplement%2F163.atom
Cigarette Filter Ventilation and its Relationship to Increasing Rates of Lung Adenocarcinoma
Authors: Min-Ae Song, Neal L Benowitz, Micah Berman, Theodore M Brasky, K Michael Cummings, Dorothy K Hatsukami, Catalin Marian, Richard O’Connor, Vaughan W Rees, Casper Woroszylo, Peter G Shields
Journal: JNCI Journal of the National Cancer Institute (2017)

The 2014 Surgeon General's Report on smoking and health concluded that changing cigarette designs have caused an increase in lung adenocarcinomas, implicating cigarette filter ventilation that lowers smoking machine tar yields. The Food and Drug Administration (FDA) now has the authority to regulate cigarette design if doing so would improve public health. To support a potential regulatory action, two weight-of-evidence reviews were applied for causally relating filter ventilation to lung adenocarcinoma. Published scientific literature (3284 citations) and internal tobacco company documents contributed to causation analysis evidence blocks and the identification of research gaps. Filter ventilation was adopted in the mid-1960s and was initially equated with making a cigarette safer. Since then, lung adenocarcinoma rates paradoxically increased relative to other lung cancer subtypes. Filter ventilation 1) alters tobacco combustion, increasing smoke toxicants; 2) allows for elasticity of use so that smokers inhale more smoke to maintain their nicotine intake; and 3) causes a false perception of lower health risk from "lighter" smoke. Seemingly not supportive of a causal relationship is that human exposure biomarker studies indicate no reduction in exposure, but these do not measure exposure in the lung or utilize known biomarkers of harm. Altered puffing and inhalation may make smoke available to lung cells prone to adenocarcinomas. The analysis strongly suggests that filter ventilation has contributed to the rise in lung adenocarcinomas among smokers. Thus, the FDA should consider regulating its use, up to and including a ban. Herein, we propose a research agenda to support such an effort.
Incidence of head impacts at elite-level male and female cricket in australia
Authors: Alex Kountouris, John Orchard
Journal: British Journal of Sports Medicine (2017)

Objective To document the incidence of head impacts at the elite level in the sport of cricket, where there currently is very little epidemiological data regarding concussion. Design Prospective registry of head impacts reported by medical and physiotherapy staff and/or discovered by Chief Medical Officer from clinical record-keeping systems and media reports Setting Elite-level male and female cricket in Australia for one season (2015–16) Main results There were 64 head impacts on the registry for season 2015–16, with 20 of these occurring in List A/First Class men’s matches and 6 occurring in List A women’s matches. The match incidence rates were 3.9 head impacts/1000 player days in elite male cricket and 3.1 head impacts/1000 player days in elite female cricket. The vast majority were caused by ball-helmet(head) impact, with a majority in batters (strikers). The next most common players affected were wicketkeepers and close-in fielders. An incidence rate for concussion is not presented as there were a number of ambiguous head impact cases (clinically not diagnosed as concussion on the field but with symptoms or abnormal Cogsport tests after the match) Conclusions The rate of head impact in cricket is perhaps higher than previously appreciated (as it has been traditionally considered a low-risk sport for concussion), although lower than the football codes. Definition of concussion in this sport is quite subjective and problematic, perhaps as it is the only team sport in which injury substitution is not permitted, which may influence the reporting of symptoms by players during the match. Competing interests Chief Medical Officer, Cricket Australia.
Outcomes of triple-negative breast cancer (TNBC) versus non-TNBC patients: Does the survival vary for all stages?
Authors: Gaurav Agarwal, Gitika Nanda, Punita Lal, Sushma Agrawal, Narendra Krishnani, Niraj Kumari, Gyan Chand, Anjali Mishra, Amit Agarwal, Ashok Kumar Verma, Saroj Kanta Mishra
Journal: Journal of Clinical Oncology (2014)

e12034 Background: Triple-negative breast cancer (TNBC) poses a therapeutic challenge. In a cohort treated at a tertiary care North Indian center, outcomes of TNBC patients were compared with those with ER, PR &/or HER2neu expressing tumors (non-TNBC). Methods: Consecutive patients managed during 2004-2010, and with complete treatment and follow-up (1-147 months, median 36) data were grouped into TNBC and nonTNBC based on ER, PR and HER2neu status. OS and DFS were compared between the two groups, and further compared based on TNM stage. Results: TNBC (n=249) comprised 35.3% of 705 patients, and were younger than nonTNBC (mean age 49.1+11.2y TNBC vs 51.8+11.3 nonTNBC, p=0.02). TNM stage was similar in two groups (St I&II 37% vs 44.3%, St III 47.5% vs 39.5%, St IV 15.5% vs 16.2%, p=0.09). Tumor size (5.7+2.9 cm TNBC vs 5.4+2.8 nonTNBC, p=0.22) was similar but LN metastases was commoner in TNBC (77.3% vs 69.8%, p=0.03). 97.1% TNBC had histologic grade II / III as against 91.2% nonTNBC (p=0.01). Both groups received similar treatment (conservation vs mastectomy; anthracyclines, taxanes or combination chemotherapy). 104(41.7%) TNBC & 268 (38%) non-TNBC received NACT. More TNBC patients (27.5%) achieved pathological complete response (pCR) c.w. nonTNBC (17.1%; p=0.04). Kaplan-Meier survival analysis for whole cohort revealed OS (81.8+4.5 TNBC vs 97.9+3.9 months non-TNBC, p<0.001) and DFS (89.2+5.1 vs 113.8+4.3, p<0.001) were shorter in TNBC. In sub-group analysis, OS differed significantly only in stage III (47.4+5.3 months TNBC vs 74.5+4.4 nonTNBC, p<0.001). The survival in stages I/II (p=0.30) and IV (p=0.11) were similar. In patients who achieved pCR, OS (73.5 months TNBC vs 83.6 nonTNBC, p=0.15) and DFS (83.1 TNBC vs 73.6 nonTNBC, p=0.40) were similar. Univariate and multivariate analysis revealed TNM stage and IHC classification of TNBC vs nonTNBC as determinants of survival. Conclusions: TNBC patients are younger, and have more aggressive pathology. They have poorer OS and DFS than nonTNBC patients. However, DFS and OS of only stage III TNBC patients are significantly worse than the same stage nonTNBC patients. TNBC patients who achieve pCR with NACT have similar survival as nonTNBC complete responders.