tbuckley/cabot-search huggingface dataset:
Abstract P1-02-08: Reprogramming glucose metabolism and energy production in breast cancer cells
Authors: H Kim, J Dong, J Xu, D Li, Z Zheng, N Ye, Z Zhang, H Chen, J Zhou, Q Shen
Journal: Cancer Research (2018)

Abstract Most mammalian cells use glucose as a main fuel source. Glucose is metabolized via glycolysis to pyruvate, which enters the mitochondria and then generates ATP through Krebs cycle in normal condition. However, metabolism is characteristically reprogrammed and cancer cells or highly proliferative cells preferably generate ATP through lactate production by lactate dehydrogenase (LDH/LDHA), referred to as the Warburg effect or metabolic reprogramming toward aerobic glycolysis. Efficient control of energy metabolism is the key to maintaining metabolic homeostasis, and disturbance in energy balance provokes diseases such as obesity, diabetes and cancer. However, the mechanisms underlying efficient energy metabolic homeostasis and breast cancer development are poorly understood. HJC0152, a novel small molecule glucose metabolism modulator, was developed using structure- and fragment-based drug design strategies and molecular modeling techniques. Aggressively growing and metastatic breast cancer cells of triple-negative subtype (MDA-MB-231) treated with HJC0152 showed decreased activity and protein level of LDHA, which resulted in a decrease lactate production. In addition, these cells also exhibited decreased glucose uptake and HK2 protein level. Furthermore, the amount of intracellular ATP in MDA-MB-231 cells was significantly reduced. Our findings suggest that HJC0152 is capable of reprogramming caner metabolism by modulating glucose metabolism and ATP production. These results may provide a rationale to develop HJC0152 as an effective therapeutic for cancer and other metabolic diseases with aberrant glucose metabolism. In addition, HJC0152 can serve as a molecular probing tool for elucidating the key factors responsible for developing breast cancer and other metabolic diseases.This work was supported by Grants P50 CA097007, and P30DA028821 (JZ) from the NIH, CPRIT (JZ), John Sealy Memorial Endowment Fund (JZ), DFI Grants from MD Anderson Cancer Center (QS), Holden Family Research Grant in BC Prevention (QS), and NCI PREVENT Program HHSN26100002 (QS). Citation Format: Kim H, Dong J, Xu J, Li D, Zheng Z, Ye N, Zhang Z, Chen H, Zhou J, Shen Q. Reprogramming glucose metabolism and energy production in breast cancer cells [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-02-08.
Cabozantinib for metastatic castration-resistant prostate cancer (mCRPC) following docetaxel: Combined analysis of two phase III trials.
Authors: Gregory Russell Pond, Guru Sonpavde, Karim Fizazi, Johann S. De Bono, Ethan M Basch, Howard I. Scher, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2018)

225 Background: Two phase III trials, COMET-1 and COMET-2, have reported that cabozantinib did not extend overall survival (OS) outcomes compared to prednisone and prednisone plus mitoxantrone respectively, in unselected post-docetaxel patients with mCRPC. We conducted a retrospective analysis of a combined dataset of these trials in an attempt to identify a benefit in subsets of patients based on prognostic risk factors. Methods: Baseline characteristics and survival data were combined for COMET-1 and COMET-2. Prognostic ability of baseline factors on survival was evaluated using Cox proportional hazards regression models, which incorporated the factors in the modern post-docetaxel nomogram and overall bone scan lesion area (BSLA) by computer-assisted analysis. Regression models included trial as a stratification factor. Evaluation of potentially benefited subsets was performed by the use of interaction terms between the factors and cabozantinib. The hazard ratio between cabozantinib and comparator arms was evaluated after adjusting for baseline prognostic factors. All tests were 2-sided and a p-value ≤0.05 was considered statistically significant. Results: A total of 1147 post-docetaxel patients with mCRPC were available (1028 from COMET-1 and 119 from COMET-2). Age, albumin, LDH and BSLA were statistically significant prognostic factors in addition to variables from the Halabi model (site of metastases, pain, docetaxel-free interval, ECOG-PS, hemoglobin, alkaline phosphatase, PSA). There was no consistent interaction effect on survival between cabozantinib vs. comparator arms for any prognostic group. After adjusting for multiple potential prognostic factors, treatment with cabozantinib vs. comparator was associated with an observed hazard ratio of 0.77 (95% CI = 0.65 to 0.92, p = 0.003) for survival. Conclusions: After combining data from both COMET-1 and COMET-2 trials, no differential effect of cabozantinib on survival was observed for any prognostic risk factor. A modest treatment effect of cabozantinib on OS was observed after controlling for multiple potential prognostic factors.
UK pilot scheme to sell off specialty training places to Saudi Arabia
Authors: Helen Jaques
Journal: BMJ (2013)

The Department of Health is piloting a scheme that allows the Saudi Arabian government to buy specialty training places in the United Kingdom for their doctors.

The Saudi Ministry of Health has lined up 20 Saudi Arabian doctors to come to the UK in August 2013 to train in specially created places for specialty or core training in year 1. 

Under the International Postgraduate Medical Training Scheme, the Saudi doctors will train in ophthalmology, emergency medicine, cardiothoracic surgery, and anaesthesia. These specialties have been identified as areas of considerable demand by the Saudi government and where the UK system has additional training capacity, the Department of Health said.

The two governments have not yet …
Prevalence of Cognitive Impairment and Association With Survival Among Older Patients With Hematologic Cancers
Authors: Tammy T. Hshieh, Wooram F. Jung, Laura J. Grande, Jiaying Chen, Richard M. Stone, Robert J. Soiffer, Jane A. Driver, Gregory A. Abel
Journal: JAMA Oncology (2018)

As the population ages, cognitive impairment has promised to become increasingly common among patients with cancer. Little is known about how specific domains of cognitive impairment may be associated with survival among older patients with hematologic cancers.To determine the prevalence of domain-specific cognitive impairment and its association with overall survival among older patients with blood cancer.This prospective observational cohort study included all patients 75 years and older who presented for initial consultation in the leukemia, myeloma, or lymphoma clinics of a large tertiary hospital in Boston, Massachusetts, from February 1, 2015, to March 31, 2017. Patients underwent screening for frailty and cognitive dysfunction and were followed up for survival.The Clock-in-the-Box (CIB) test was used to screen for executive dysfunction. A 5-word delayed recall test was used to screen for impairment in working memory. The Fried frailty phenotype and Rockwood cumulative deficit model of frailty were also assessed to characterize participants as robust, prefrail, or frail.Among 420 consecutive patients approached, 360 (85.7%) agreed to undergo frailty assessment (232 men [64.4%] and 128 women [35.6%]; mean [SD] age, 79.8 [3.9] years), and 341 of those (94.7%) completed both cognitive screening tests. One hundred twenty-seven patients (35.3%) had probable executive dysfunction on the CIB, and 62 (17.2%) had probable impairment in working memory on the 5-word delayed recall. Impairment in either domain was modestly correlated with the Fried frailty phenotype (CIB, ρ = 0.177; delayed recall, ρ = 0.170; P = .01 for both), and many phenotypically robust patients also had probable cognitive impairment (24 of 104 [23.1%] on CIB and 9 of 104 [8.7%] on delayed recall). Patients with impaired working memory had worse median survival (10.9 [SD, 12.9] vs 12.2 [SD, 14.7] months; log-rank P < .001), including when stratified by indolent cancer (log-rank P = .01) and aggressive cancer (P < .001) and in multivariate analysis when adjusting for age, comorbidities, and disease aggressiveness (odds ratio, 0.26; 95% CI, 0.13-0.50). Impaired working memory was also associated with worse survival for those undergoing intensive treatment (log-rank P < .001). Executive dysfunction was associated with worse survival only among patients who underwent intensive treatment (log-rank P = .03).These data suggest that domains of cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival. Targeted interventions are needed for this vulnerable patient population.
GP workforce numbers will not meet demand until 2030
Authors: Helen Jaques
Journal: BMJ (2013)

England will not have enough GPs to meet patient demand in primary care until 2030, a preliminary analysis by the Centre for Workforce Intelligence has found.

At a minimum the government will need to take on 3250 new GP specialty trainees a year from 2015 onwards to meet this goal, 22% more than it took on in 2012 (2669 trainees).

This target should be supplemented by other measures to boost workforce supply, the centre added, such as changing medical training and increasing the supply of practice nurses.

The …
CLINICAL PREDICTORS OF CULPRIT LESION LIPID QUANTIFIED BY NEAR INFRARED SPECTROSCOPY: INSIGHTS FROM THE COLOR REGISTRY
Authors: Akiko Fujino, Akiko Maehara, Myong Hwa Yamamoto, Mitsuaki Matsumura, Jordan Andrews, Annapoorna Subhash Kini, Emmanouil Brilakis, David Gerard Rizik, Kendrick Shunk, Eric Powers, Priti Shah, Aaron Crowley, Gregg Stone, Gary Mintz, Stephen Nicholls, James Muller, Giora Weisz
Journal: Journal of the American College of Cardiology (2018)
Impact and effectiveness of ioMRI and awake surgery in glioma surgery
Authors: Angelo Pichierri, Venkat Iyer
Journal: Neuro-Oncology (2018)

Despite all ours “technological bubbles”, surgical removal of infiltrating brain tumours remains limited to 65%-76% in the recent large series published in the Literature. Fuzzy tumour/brain margins are the main cause of failure in reaching “complete” removals. Aggressive attempts at “supramarginal” resection often carry a risk of functional cortical and subcortical structures’ damage with an unacceptable decrease in quality of life and post-operative functional status and an increase in post-operative psychological, human and financial costs for the patient, his/her carers and the NHS.Awake surgery and ioMRI (intra-operative MRI) proved to be the most effective individual aids in preventing damage to functional brain while maximizing the extent of resection.We present our series of 22 patients operated on at Southmead Hospital (North Brstol NHS Trust) in between July 2014 and Dec 2016 using both ioMRI and awake surgery (MAC, monitored anaesthesia care). Setting, patients’ features, indications, type and size of tumours, and surgical times will be analysed and discussed.Using ioMRI together with awake surgery is demanding for the anaesthetic team, stuff nurse and for the patient. Theatre times are about 2 hours longer than the standard awakes, with an average stay of 10 hours. Nevertheless, post-operative patient’s satisfaction together with very low morbidity and higher total resections rates (well above the average of the current published data) wipe the aforementioned concerns about ioMRI+awake feasibility in challenging neuro-oncology cases.
Colleges work to improve the “med reg” role
Authors: Abi Rimmer
Journal: BMJ (2018)

The three UK colleges of physicians have introduced a set of criteria to improve the working lives of medical registrars.

The medical registrar role has long been perceived as one of the most difficult jobs in hospitals because of the level of responsibility for managing acute patients, especially at nights and weekends.

In light of these concerns, as well as concerns about rota gaps and falling recruitment, the Joint Royal Colleges …
IMPACT OF ACUTE KIDNEY INJURY ON SHORT- AND LONG-TERM MORTALITY IN ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION AND NON-ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION PATIENTS: THE J-MINUET SUBSTUDY
Authors: Shotaro Kuji, Masami Kosuge, Kazuo Kimura, Koichi Nakao, Yukio Ozaki, Junya Ako, Teruo Noguchi, Satoshi Yasuda, Satoru Suwa, Kazuteru Fujimoto, Yasuharu Nakama, Takashi Morita, Wataru Shimizu, Yoshihiko Saito, Atsushi Hirohata, Yasuhiro Morita, Teruo Inoue, Atsunori Okamura, Toshiaki Mano, Kazuhito Hirata, Kunihiro Nishimura, Yoshihiro Miyamoto, Hisao Ogawa, Masaharu Ishihara
Journal: Journal of the American College of Cardiology (2018)
Abstract P2-04-03: Epigenomic analysis of cancer stem cell (CSC)-enriched triple-negative breast cancer (TNBC) populations reveals gene regulatory circuitry and novel tumor cell vulnerabilities
Authors: MG Guenther, AW Lambert, MW Chen, C Fiore, M Eaton, D Orlando, B Bierie, RA Weinberg, CC Fritz, ER Olson
Journal: Cancer Research (2018)

Abstract Tumor-initiating cells (TICs), also termed cancer stem cells (CSCs) are involved in breast cancer chemoresistance, metastasis and disease progression. To pinpoint tumor cell vulnerabilities and transcriptional drivers of therapeutic relevance, we have characterized the triple negative breast cancer (TNBC) CSC transcriptional landscape using epigenome mapping and nucleosome occupancy determination. We identify a set of transcriptional regulators and signaling mediators that enforce the cancer stem cell state and instruct potential therapeutic strategies. The basal epithelial marker, integrin-β4 (ITGB4), can be used to stratify mesenchymal-like triple-negative breast cancer (TNBC) cells into populations of low and high tumor-initiating ability in vivo. We used ChIP-seq to measure H3K27ac occupancy and map the transcriptional enhancers in SUM159 cells segregated into ITGB4HI (High tumor initiating ability) and ITGB4LOW (Low tumor initiating ability) populations. Gene-enhancer linking and comparative analysis of enhancer usage revealed an epigenomically defined set of genes that are candidate drivers of the CSC cell state, including GSK3β, DNA-binding transcription factors and cellular adhesion proteins. To further define the chromatin architecture and transcriptional regulatory circuitry that underlies CSC state, we deployed ATAC-seq (Assay for Transposase-Accessible Chromatin with high throughput sequencing) within ITGB4HI and ITGB4LOW populations. By pairing nucleosome occupancy and transcription factor kinetics, we created enhancer-linked transcriptional regulatory circuitry of these tumor-initiating cells. Together, the isolation of partially mesenchymal ITGB4HI CSCs, coupled with enhancer mapping and distillation of transcriptional regulatory circuitry from these cells enable the identification of cancer vulnerabilities and therapeutic opportunities for high-risk patients with TNBC. Citation Format: Guenther MG, Lambert AW, Chen MW, Fiore C, Eaton M, Orlando D, Bierie B, Weinberg RA, Fritz CC, Olson ER. Epigenomic analysis of cancer stem cell (CSC)-enriched triple-negative breast cancer (TNBC) populations reveals gene regulatory circuitry and novel tumor cell vulnerabilities [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-04-03.
Long Coat Doctor
Authors: Phillip D. Bertram
Journal: Annals of Internal Medicine (2018)

On Being a Doctor6 February 2018Long Coat DoctorPhillip D. Bertram, MDPhillip D. Bertram, MDCookeville Regional Medical Center, Cookeville, Tennessee (P.D.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-2238 Audio Reading - “Long Coat Doctor” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Long Coat Author," by P.D. Bertram. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The letter was on my desk when I returned from lunch. Though its plain envelope was unremarkable, the name on the return address caught my attention and unlocked a distant memory. Smiling, I leaned back and read the contents. …He had arrived at my office with six other second-year students, fresh out of basic sciences, excited to see real patients, camouflaging their uncertainty behind their short white coats, clutching their black bags and stethoscopes for security. Over the next 10 weeks they would begin to learn the subtleties of history taking, weaving patients' symptoms into a flowing narrative, a ... Author, Article, and Disclosure InformationAffiliations: Cookeville Regional Medical Center, Cookeville, Tennessee (P.D.B.)Corresponding Author: Phillip D. Bertram, MD, Cookeville Regional Medical Center, 438 North Whitney Avenue, Cookeville, TN 38501; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Long Coat Doctor” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Long Coat Author," by P.D. Bertram. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 6 February 2018Volume 168, Issue 3Page: 227KeywordsHeartHerniaHipIschemiaLiverMemoryPainPostural controlReasoningThorax ePublished: 6 February 2018 Issue Published: 6 February 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Accountability for Underuse and Overuse of Cancer Screening
Authors: Allison Lipitz-Snyderman
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
All foundation trainees should undertake a GP attachment
Authors: An T Ngo
Journal: BMJ (2009)

With my sights firmly set on a career in cardiology, I had never seriously thought of myself as a general practitioner. In the days leading up to the start of my four month attachment to general practice, I admit to a feeling of trepidation. After all, I would be far removed from the beloved buzz and all the “hardcore” medicine the hospital has to offer. Instead, I would be taking my place in the less glamorous world of “GP land,” where my daily dilemmas would include whether to give an antibiotic to the next patient with a cough, or how best to manage the patient complaining of being tired all the time. What could four months in general practice possibly have to offer a budding hospital doctor? 

How my perspectives have changed. I write to share my overwhelmingly positive experience of my attachment and to explain why I believe all foundation trainees should do a general practice rotation, regardless of their career aspirations.

Foundation training aims to build on the skills, knowledge, and competencies we cultivated as medical undergraduates. Over the course of two years, we are expected to become competent in several practical procedures. Work based assessments constantly review our …
Circulating tumor DNA (ctDNA) landscape and prognostic implications in advanced gastroesophageal adenocarcinoma (GEC).
Authors: Steven Brad Maron, Smita Suhas Joshi, S Lomnicki, Tomasz Oliwa, Stacie Landron, Julie Johnson, Lesli Ann Kiedrowski, Rebecca J Nagy, Richard B. Lanman, Yelena Yuriy Janjigian, Kaitlyn J. Kelly, Seung Tae Kim, Jeeyun Lee, Daniel V.T. Catenacci
Journal: Journal of Clinical Oncology (2018)

45 Background: Esophagogastric junction (EGJ) and gastric (GC) cancer, together GEA, have a poor prognosis, high molecular heterogeneity, and few targeted therapeutic options. Guardant360 is a clinical gene panel test for next generation sequencing (NGS) of plasma circulating tumor (ct) DNA. Methods: We evaluated a large cohort of ctDNA-derived genomic results (Guardant Health, Inc.), including a subset of pts from the University of Chicago (UC) with clinical data. GEA pts in these 2 cohorts were assessed for genomic alteration (GA) distribution: mutations (mt), indels, amplifications (amp) and fusions. UC survival analyses were performed using log-rank test and select gene-by-gene alteration frequency by pt with chi-square comparisons. Results: The overall ctDNA cohort comprised 1128 pts with median age 64 yrs (range 19-98) and 73% males. At least 1 detectable GA (median 4, range 0-102) was observed in 870 pts (77%). The UC subset of pts (n=171), median age 63 yrs (range 19-87), included 2/10/27/61% stage I/II/III/IV, 77/13/5/5% Caucasian/African American/Asian/Hispanic, 74% male and 63% EGJ. At least 1 detectable GA (median 4, range 1-102) was observed in 157 pts; median GAs per test by stage I vs II/III vs IV was 1.5/3.5/4.5. GA distributions were similar to the larger cohort (Table 1). Stage IV pts tested within 6 weeks of diagnosis/recurrence (n=34) had a median survival of 8.7 months. In these pts, BRAF/ FGFR2 amps and ARAF mts were each prognostic for worse survival ( p&lt;0.05), and MET and KRAS amps trended towards significance. Mt allele frequency (MAF) ctDNA burden inversely correlated with survival ( p=0.01) . In 138 pts with ≥2 serial tests, non-synonymous GAs in MET, PIK3CA, and FGFR1 were more commonly late events (all p&lt;0.05 ). Conclusions: GAs in plasma ctDNA were detected in 77% of GEA pts including numerous actionable targets. ctDNA analysis merits further evaluation as a prognostic biomarker assessing specific genes, overall ctDNA burden, and molecular heterogeneity at baseline and serially. [Table: see text]
GPs still face rising demand and falling resources despite contract changes, says BMA
Authors: Abi Rimmer
Journal: BMJ (2014)

GPs will continue to have to deal with rising demand and falling resources despite the introduction of the 2014-15 GP contract, the chairman of the BMA’s General Practitioners Committee has said.

The 2014-15 contract came into effect on 1 April after an agreement between the committee and NHS Employers was reached last November.1

In England the agreed changes included a shift of £450m worth of funding from the Quality and Outcomes Framework …
I have done three years of psychiatry as a senior house officer: how can I become “section 12 approved”?
Authors: Jim Bolton
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>