tbuckley/cabot-search huggingface dataset:
Abstract 1155: Regulation of glutamine metabolism: Allosteric activation and inhibition of mitochondrial glutaminase
Authors: Clint Stalnecker, Scott Ulrich, Jon Erickson, Sekar Ramachandran, Ralph DeBerardinis, Rick Cerione
Journal: Cancer Research (2015)

Abstract The hydrolysis of glutamine to glutamate plus ammonia, catalyzed in the mitochondria by the enzyme glutaminase (Gls), plays a crucial role in the metabolism of glutamine by cancer cells. Recently, we discovered a novel class of allosteric inhibitors of a splice variant of Gls, known as glutaminase C (GAC), which inhibits the growth of Rho-GTPase transformed cells without affecting their normal cellular counterparts, with the lead compound being the bromo-benzophenanthridinone 968. Here, we took advantage of mouse embryonic fibroblasts (MEFs) transformed by the induced expression of an oncogenic guanine nucleotide exchange factor (GEF) named Dbl, which hyper-activates the Rho GTPases Rac, Rho, and CDC42, together with 13C-labeled glutamine and stable-isotope tracing methods, to establish that 968 selectively blocks the enhancement in glutaminolysis. We then determined how 968 inhibits the catalytic activity of GAC using biophysical approaches on purified GAC enzyme. First, we developed a FRET assay to examine the effects of 968 on the ability of GAC to undergo the dimer-to-tetramer transition necessary for enzyme activation. We next demonstrated how the fluorescence of a reporter group attached to GAC provides a direct read-out of the binding of 968 and related compounds to the enzyme. By combining these fluorescence assays, together with novel GAC mutants trapped in either the monomeric or dimeric state, we show that 968 has the highest affinity for monomeric GAC, and that the dose-dependent binding directly matches its dose-dependent inhibition of enzyme activity and cellular transformation. We then investigated the 968 structure-activity relationship, and to this end, characterized a robust real-time direct binding and inhibition assay for testing a panel of 968 derivatives. Additionally, we have developed novel 968-derivatives with unique functional moieties, such as fluorescent and photo-cross linking groups, to further elucidate the mechanism of GAC inhibition using recombinant GAC in vitro as well as in cancer cells. Together, these findings represent recent advances in our understanding of the regulation of GAC activity both in vitro and in cells, and highlight the potential future of targeting glutamine metabolism with novel small molecule therapeutics. Citation Format: Clint Stalnecker, Scott Ulrich, Jon Erickson, Sekar Ramachandran, Ralph DeBerardinis, Rick Cerione. Regulation of glutamine metabolism: Allosteric activation and inhibition of mitochondrial glutaminase. [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 1155. doi:10.1158/1538-7445.AM2015-1155
Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization
Authors: Joanne H. Reed, Jennifer Jackson, Daniel Christ, Christopher C. Goodnow
Journal: The Journal of Experimental Medicine (2016)

Clonal anergy is an enigmatic self-tolerance mechanism because no apparent purpose is served by retaining functionally silenced B cells bearing autoantibodies. Human autoantibodies with IGHV4-34*01 heavy chains bind to poly-N-acetyllactosamine carbohydrates (I/i antigen) on erythrocytes and B lymphocytes, cause cold agglutinin disease, and are carried by 5% of naive B cells that are anergic. We analyzed the specificity of three IGHV4-34*01 IgG antibodies isolated from healthy donors immunized against foreign rhesus D alloantigen or vaccinia virus. Each IgG was expressed and analyzed either in a hypermutated immune state or after reverting each antibody to its unmutated preimmune ancestor. In each case, the preimmune ancestor IgG bound intensely to normal human B cells bearing I/i antigen. Self-reactivity was removed by a single somatic mutation that paradoxically decreased binding to the foreign immunogen, whereas other mutations conferred increased foreign binding. These data demonstrate the existence of a mechanism for mutation away from self-reactivity in humans. Because 2.5% of switched memory B cells use IGHV4-34*01 and &amp;gt;43% of these have mutations that remove I/i binding, clonal redemption of anergic cells appears efficient during physiological human antibody responses.
FDA warns on antidepressant use
Authors: Annabel Ferriman
Journal: BMJ (2004)

The Food and Drug Administration has requested a warning statement on the labels of certain antidepressants to encourage close observation of adult and paediatric patients who are being treated with these agents for worsening depression or the emergence of suicidal thoughts.

The drugs that are the focus of this new warning statement include fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, bupropion, venlafaxine, nefazodone, and mirtazapine.

More information is at www.fda.gov/cder/drug/antidepressants/default.htm
Case 39-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Claude E. Welch, Austin L. Vickery
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 64-year-old woman was admitted to the hospital because of hematemesis.She was well until 10 years previously, when she began to experience intermittent postprandial epigastric pain, without radiation to the back or the shoulder; the pain was often provoked by ingestion of fatty foods and was not relieved by antacids. She passed clay-colored stools on several occasions, but there was no history of jaundice, chills or fever. Two years before admission she was seen in the Medical Clinic, where examination revealed a blood pressure of 180/100 and marked obesity. The abdominal examination was negative. An oral . . .
Transcriptome sequencing reveals a profile that corresponds to genomic variants in Waldenström macroglobulinemia
Authors: Zachary R. Hunter, Lian Xu, Guang Yang, Nicholas Tsakmaklis, Josephine M. Vos, Xia Liu, Jie Chen, Robert J. Manning, Jiaji G. Chen, Philip Brodsky, Christopher J. Patterson, Joshua Gustine, Toni Dubeau, Jorge J. Castillo, Kenneth C. Anderson, Nikhil M. Munshi, Steven P. Treon
Journal: Blood (2016)
Challenges in Surgical Quality at Safety-Net Hospitals
Authors: Ryan Macht, David McAneny, Gerard Doherty
Journal: JAMA Surgery (2016)

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 Surgery 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 Surgery journal
Inhibiting DX2-p14/ARF Interaction Exerts Antitumor Effects in Lung Cancer and Delays Tumor Progression
Authors: Ah-Young Oh, Youn Sang Jung, Jiseon Kim, Jee-Hyun Lee, Jung-Hyun Cho, Ho-Young Chun, Soyoung Park, Hyunchul Park, Sikeun Lim, Nam-Chul Ha, Jong Sook Park, Choon-Sik Park, Gyu-Yong Song, Bum-Joon Park
Journal: Cancer Research (2016)

The aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) splice variant designated DX2 is induced by cigarette smoke carcinogens and is often detected in human lung cancer specimens. However, the function of DX2 in lung carcinogenesis is obscure. In this study, we found that DX2 expression was induced by oncogenes in human lung cancer tissues and cells. DX2 prevented oncogene-induced apoptosis and senescence and promoted drug resistance by directly binding to and inhibiting p14/ARF. Through chemical screening, we identified SLCB050, a novel compound that blocks the interaction between DX2 and p14/ARF in vitro and in vivo SLCB050 reduced the viability of human lung cancer cells, especially small cell lung cancer cells, in a p14/ARF-dependent manner. Moreover, in a mouse model of K-Ras-driven lung tumorigenesis, ectopic expression of DX2 induced small cell and non-small cell lung cancers, both of which could be suppressed by SLCB050 treatment. Taken together, our findings show how DX2 promotes lung cancer progression and how its activity may be thwarted as a strategy to treat patients with lung cancers exhibiting elevated DX2 levels. Cancer Res; 76(16); 4791-804. ©2016 AACR.
Liver Tumors Induced in Rats by &lt;italic&gt;p&lt;/italic&gt;-Dimethylaminobenzene-1-Azo-1-Naphthalene Compared With Tumors Induced by &lt;italic&gt;p&lt;/italic&gt;-Dimethylaminoazobenzene
Authors: Ambadas S. Mulay, Harlan I. Firminger
Journal: JNCI Journal of the National Cancer Institute (1952)

Liver Tumors Induced in Rats by p-Dimethylaminobenzene-1-Azo-1-Naphthalene Compared With Tumors Induced by p-Dimethylaminoazobenzene Get access Ambadas S. Mulay, Ambadas S. Mulay Laboratory of Pathology, National Cancer Institute3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Harlan I. Firminger Harlan I. Firminger Laboratory of Pathology, National Cancer Institute3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 13, Issue 1, August 1952, Pages 35–55, https://doi.org/10.1093/jnci/13.1.35 Published: 01 August 1952 Article history Received: 11 March 1952 Published: 01 August 1952
ERADICATION OF TUBERCULOSIS: A PROBLEM IN EPIDEMIOLOGICOPEDICS
Authors: M B COVENTRY
Journal: JAMA (1965)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
QOL-23ASSOCIATION BETWEEN QUALITY OF LIFE AND VESTIBULAR SCHWANNOMA VOLUME, WORD RECOGNITION SCORES, AND PATIENT- AND PHYSICIAN-REPORTED DISEASE SEVERITY IN A US POPULATION OF NF2 PATIENTS
Authors: Roy Strowd, Shannon Langmead, Yao Lu, Jaishri Blakeley
Journal: Neuro-Oncology (2015)

BACKGROUND: Neurofibromatosis type 2 (NF2) is associated with histologically benign but morbid tumors. Patient-reported outcomes (PROs) are important measures of patient function for this neuro-oncologic syndrome which impacts quality of life (QOL) due to multiple chronic tumors. Hence, NF2 serves as a model for developing PROs in neuro-oncology trials. The NFTI-QOL is a validated disease-specific QOL-instrument developed in the United Kingdom which has not been compared against historical clinical trial endpoints in NF2 including total vestibular schwannoma (VS) volume and best word recognition score (WRS). METHODS: An IRB-approved prospective observational study was conducted enrolling adult NF2 patients at Johns Hopkins. Measures included: NFTI-QOL, SF-36; total volume of bilateral VS, best WRS, provider- and patient-reported disease severity (ProvSev, PatSev) by institutionally-derived multi-item (e.g. symptom burden, age-of-onset, fatality-risk) and single-item Likert (mild, moderate, severe) scales. RESULTS: Twenty patients were enrolled; mean age at testing 46 + 21 years and age at diagnosis 32 + 18 years; 35% male. Prior treatment included surgery (50%), radiotherapy (25%), and systemic therapy (40%). Mean best WRS was 71.8 + 37% (n = 20). Two patients had no functional hearing and 10 had unilateral hearing. Mean total VS volume was 5.8 + 7.4 cc (n = 15). Additional lesions included meningioma (75%) and ependymoma (20%). Mean NFTI-QOL score was 8.5 + 5.1 and correlated well with all physical dimensions of the SF-36 (all p < 0.002). NFTI-QOL correlated well with PatSev (r = 0.60, 95%CI 0.21-0.82, p < 0.005) and multi-item ProvSev (r = 0.66, 0.31-0.85, p = 0.002) but not single-item ProvSev (r = 0.33, -0.13-0.68, p = 0.15). A trend toward positive correlation was observed between PatSev and multi-item ProvSev (r = 0.41, -0.04-0.72, p = 0.07). NFTI-QOL scores did not correlate with VS volume (r = 0.10, -0.44-0.58, p = 0.73), or best WRS (r = -0.40, -0.71-0.05, p-0.08). CONCLUSION: NFTI-QOL scores did not correlate with hearing function or tumor volume, but did correlate with patient and provider-reported disease severity underscoring the importance of patient-focused measures in therapeutic outcome assessment in NF2.
Abstract P246: Influence of Latin Dance on Physical Activity Among Community Dwelling Older Latino Adults
Authors: Priscilla Vasquez, Susan Aguinaga, Robert S Wilson, Louis F Fogg, JoEllen Wilbur, Susan L Hughes, David X Marquez
Journal: Circulation (2016)

Background: The American Heart Association’s 2020 goals target seven key risk factors including physical activity (PA) which can reduce risk for cardiovascular disease. Older Hispanic/Latino individuals are usually not physically active at recommended levels. Dance is a culturally appropriate form of PA for older Latinos and physically challenges individuals to engage in this activity. Objective: To test the impact of a dance program, BAILAMOS©, on lifestyle PA. Methods: Participants from a pilot clinical trial (N=57) were randomly assigned to a 4-month twice-weekly dance program or a weekly health education (control group). They completed the CHAMPS PA questionnaire to assess leisure activity and also engaged in a 400 meter walk test pre- and post-program. Results: Participants were low active, older [ M ( SD ) age= 64.9 (5.9)], Spanish-speaking [81.8% Mexican, years in US= 31.2 (16.8), years of education = 7.0 (4.3)], majority were female [81.8%], and there were no statistically significant differences between groups. There was a main effect for time in minutes of light, moderate, and vigorous leisure physical activity (LMVLPA) per week F(5.2)= p&lt;.05. The dance group reported 650.56 (472.54) minutes of LMVLPA at baseline and reported 817.78 (529.37) minutes of LMVLPA at post-testing. The health education group reported 522.78 (368.57) minutes of LMVLPA at baseline and reported 628.89 (387.46) minutes of LMVLPA at post-testing. A repeated measures ANOVA revealed a main effect for time F(9.25) = p&lt;.05 for the 400 meter walk test. Dance participants completed the walk in 429.90 (66.28) seconds at baseline and 391.83 (58.80) seconds at post-testing. Health education participants completed the walk in 419.25 (93.78) seconds at baseline and 409.10 (74.31) seconds at post-testing. Conclusion: A culturally appropriate dance intervention is a viable approach for older Hispanic/Latino individuals to engage and increase PA, and it is possible that participation in regular dancing can improve physical function, such as walking.
Case 44-1969
Authors: John F. Burke, Robert E. Scully
Journal: New England Journal of Medicine (1969)

Presentation of Case First admission. A forty-six-year-old man was admitted to the hospital because of an abdominal mass.One month previously fever, night sweats, malaise and pain in the chest developed, and he was told by a physician that he had pneumonia. He was treated at home with antibiotic therapy, with subsidence of the symptoms in a week, but he then complained of epigastric discomfort, heartburn and occasional nausea. An upper gastrointestinal series (Fig. 1) revealed displacement of the stomach to the left by an extrinsic mass compressing the lesser curvature. An oral cholecystographic study with two doses of contrast . . .
A Novel Tumor-Specific Agent for Intraoperative Near-Infrared Fluorescence Imaging: A Translational Study in Healthy Volunteers and Patients with Ovarian Cancer
Authors: Charlotte E.S. Hoogstins, Quirijn R.J.G. Tummers, Katja N. Gaarenstroom, Cor D. de Kroon, J. Baptist M.Z. Trimbos, Tjalling Bosse, Vincent T.H.B.M. Smit, Jaap Vuyk, Cornelis J.H. van de Velde, Adam F. Cohen, Philip S. Low, Jacobus Burggraaf, Alexander L. Vahrmeijer
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Completeness of cytoreductive surgery is a key prognostic factor for survival in patients with ovarian cancer. The ability to differentiate clearly between malignant and healthy tissue is essential for achieving complete cytoreduction. Using current approaches, this differentiation is often difficult and can lead to incomplete tumor removal. Near-infrared fluorescence imaging has the potential to improve the detection of malignant tissue during surgery, significantly improving outcome. Here, we report the use of OTL38, a near-infrared (796 nm) fluorescent agent, that binds folate receptor alpha, which is expressed in &amp;gt;90% of epithelial ovarian cancers. Experimental Design: We first performed a randomized, placebo-controlled study in 30 healthy volunteers. Four single increasing doses of OTL38 were delivered intravenously. At fixed times following drug delivery, tolerability and blood/skin pharmacokinetics were assessed. Next, using the results of the first study, three doses were selected and administered to 12 patients who had epithelial ovarian cancer and were scheduled for cytoreductive surgery. We measured tolerability and blood pharmacokinetics, as well as the ability to detect the tumor using intraoperative fluorescence imaging. Results: Intravenous infusion of OTL38 in 30 healthy volunteers yielded an optimal dosage range and time window for intraoperative imaging. In 12 patients with ovarian cancer, OTL38 accumulated in folate receptor alpha–positive tumors and metastases, enabling the surgeon to resect an additional 29% of malignant lesions that were not identified previously using inspection and/or palpation. Conclusions: This study demonstrates that performing real-time intraoperative near-infrared fluorescence imaging using a tumor-specific agent is feasible and potentially clinically beneficial. Clin Cancer Res; 22(12); 2929–38. ©2016 AACR.
PCM-15SOMATIC CRISPR/Cas9-MEDIATED TUMOR SUPPRESSOR DISRUPTION ENABLES VERSATILE BRAIN TUMOR MODELING
Authors: Marc Zuckermann, Volker Hovestadt, Christiane B. Knobbe-Thomsen, Marc Zapatka, Paul A. Northcott, Kathrin Schramm, Jelena Belic, David T.W. Jones, Barbara Tschida, Branden Moriarity, David Largaespada, Martine F. Roussel, Andrey Korshunov, Guido Reifenberger, Stefan M. Pfister, Peter Lichter, Daisuke Kawauchi, Jan Gronych
Journal: Neuro-Oncology (2016)
Twice-Weekly Trimethoprim-Sulfamethoxazole for the Prevention of Pneumocystis Jiroveci Pneumonia in Non-Hodgkin Lymphoma Patients
Authors: Keiko Ono, Hideki Tsujimura, Takeaki Sugawara, Mikiko Ise, Akiyasu Satou, Xiaofei Wang, Kyoya Kumagai
Journal: Blood (2015)
Studies of a Plasma-Cell Neoplasm of the Mouse. I. Characterization of Neoplasm 70429, Including Its Sensitivity to Various Antimetabolites with the Rapid Development of Resistance to Azaserine, DON, and <italic>N</italic>-Methylformamide
Authors: Michael Potter, L. W. Law
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Studies of a Plasma-Cell Neoplasm of the Mouse. I. Characterization of Neoplasm 70429, Including Its Sensitivity to Various Antimetabolites with the Rapid Development of Resistance to Azaserine, DON, and N-Methylformamide Get access Michael Potter, Michael Potter National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar L. W. Law L. W. Law National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 18, Issue 3, March 1957, Pages 413–441, https://doi.org/10.1093/jnci/18.3.413 Published: 01 March 1957 Article history Received: 26 October 1956 Published: 01 March 1957
Whole Grain Intake and Mortality From All Causes, Cardiovascular Disease, and Cancer
Authors: Geng Zong, Alisa Gao, Frank B. Hu, Qi Sun
Journal: Circulation (2016)

Background— Current findings on associations between whole grain (WG) intake and mortality are inconsistent and have not been summarized by meta-analysis. Methods and Results— We searched for prospective cohort studies reporting associations between WG intake and mortality from all causes, cardiovascular disease (CVD), and cancer through February 2016 in Medline, Embase, and clinicaltrials.gov, and we further included unpublished results from National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999 to 2004. Fourteen studies were eligible for analysis, which included 786 076 participants, 97 867 total deaths, 23 957 CVD deaths, and 37 492 cancer deaths. Pooled relative risks comparing extreme WG categories (high versus low) were 0.84 (95% confidence interval [CI], 0.80–0.88; P &lt;0.001; I 2 =74%; P heterogeneity &lt;0.001) for total mortality, 0.82 (95% CI, 0.79–0.85; P &lt;0.001; I 2 =0%; P heterogeneity =0.53) for CVD mortality, and 0.88 (95% CI, 0.83–0.94; P &lt;0.001; I 2 =54%; P heterogeneity =0.02) for cancer mortality. Intakes of WG ingredients in dry weight were estimated among studies reporting relative risks for ≥3 quantitative WG categories, and they were &lt;50 g/d among most study populations. The 2-stage dose-response random-effects meta-analysis showed monotonic associations between WG intake and mortality ( P nonlinearity &gt;0.05). For each 16-g/d increase in WG (≈1 serving per d), relative risks of total, CVD, and cancer mortality were 0.93 (95% CI, 0.92–0.94; P &lt;0.001), 0.91 (95% CI, 0.90–0.93; P &lt;0.001), and 0.95 (95% CI, 0.94–0.96; P &lt;0.001), respectively. Conclusions— Our meta-analysis demonstrated inverse associations of WG intake with total and cause-specific mortality, and findings were particularly strong and robust for CVD mortality. These findings further support current Dietary Guidelines for Americans, which recommends at least 3 servings per day of WG intake.
Ongoing African measles virus genotype outbreak in Tel Aviv district since April, Israel, 2012
Authors: E Kopel, Z Amitai, M Savion, Y Aboudy, E Mendelson, R Sheffer
Journal: Eurosurveillance (2012)

A measles outbreak is affecting the Tel Aviv district, Israel, since April 2012. As of 10 September, 99 cases were confirmed, including 63 (64%) migrants of Eritrean and Sudanese origin. All genotyped cases had the African B3 genotype*. The mean age of migrant and non-migrant cases was 6.0±9.6 and 30.2±24.2 years, respectively (p<0.001). The majority of both migrant and non-migrant cases was unvaccinated. This is the second African measles B3 genotype outbreak within the World Health Organization European region in 2012.