tbuckley/cabot-search huggingface dataset:
PTEN/p-AKT expression as predictive markers for cetuximab in colorectal cancer.
Authors: T. Yokota, N. Shibata, T. Ura, D. Takahari, K. Shitara, T. Shibata, K. Muro, Y. Yatabe
Journal: Journal of Clinical Oncology (2010)

e14031 Background: Alterations in the Ras/Raf/ERK and PTEN/PI3K/AKT signaling pathways frequently occur in colorectal cancer (CRC). KRAS or BRAF mutations preclude responsiveness to EGFR-targeted therapies for CRC patients (pts). However, the biologic impact of the PTEN/PI3K/AKT pathway on anti-EGFR treatment is still controversial. This study aims to validate whether PTEN/p-AKT expression status is predictive of response to the anti-EGFR monoclonal antibody, cetuximab. Methods: We retrospectively investigated the role of PTEN/p-AKT expression in predicting the activity of cetuximab in CRC pts by immunohistochemistry (IHC). Results: As of today, PTEN/p-AKT IHC was performed on specimens from 40 CRC pts with wild-type KRAS/BRAF. All patients received cetuximab-based regimens including cetuximab plus irinotecan combination therapy (n = 33; 82.5%) and cetuximab monotherapy (n = 5; 12.5%). High PTEN expression were associated with decreased progression-free survival (PFS) compared with low PTEN (4.1 months vs. 9.6 months, HR 2.742, 95% CI, 1.001-7.508; p = 0.050). The response rate (RR) in patients with high PTEN was lower than in those with low expression, but not significantly (20% vs. 40%, p = 0.1675). Furthermore, strong p-AKT expression were significantly associated with a poor PFS compared with weak p-AKT (2.9 months vs. 6.9 months, HR = 4.14, 95% CI 1.206-14.23, p = 0.024). The RR in patients with strong and weak p-AKT expression was 0% and 34%, respectively. There were significant correlation between high p-AKT and high PTEN expression (Fisher's exact test, p = 0.0168). Conclusions: Our analysis suggests that the level of PTEN/p-AKT expression may predict the activity of cetuximab treatment. However, our data regarding PTEN contradicts previous reports. One possible explanation could be negative feedback loop between p-AKT and PTEN gene expression. Further analyses on PTEN and p-AKT immunostaining are ongoing. No significant financial relationships to disclose.
Quality Improvement Intervention and Mortality of Critically Ill Patients
Authors: Ramiro Manzano Nunez, Herney Andrés García Perdomo, Isabel Cristina Muñoz Chavez
Journal: JAMA (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 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
Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Multicenter Open French Study In High-Risk pediatrics
Authors: Catherine Paillard, Patrick Lutz, Guy Leverger, Gerard Michel, Pierre Bordigoni, Jean-Hugues Dalle, Yves Bertrand, Anne Sirvent, Pierre Rohrlich, Jean-Pierre Vannier, Dominique Plantaz, Charlotte Jubert, Benedicte Bruno, Virginie Gandemer, Eric Dore, Florentina Isfan, Etienne Merlin, Emmanuelle Rochette, Pascale Halle, Francois Demeocq, Justyna Kanold
Journal: Blood (2010)
FEBio: History and Advances
Authors: Steve A. Maas, Gerard A. Ateshian, Jeffrey A. Weiss
Journal: Annual Review of Biomedical Engineering (2017)

The principal goal of the FEBio project is to provide an advanced finite element tool for the biomechanics and biophysics communities that allows researchers to model mechanics, transport, and electrokinetic phenomena for biological systems accurately and efficiently. In addition, because FEBio is geared toward the research community, the code is designed such that new features can be added easily, thus making it an ideal tool for testing novel computational methods. Finally, because the success of a code is determined by its user base, integral goals of the FEBio project have been to offer support and outreach to our community; to provide mechanisms for dissemination of results, models, and data; and to encourage interaction between users. This review presents the history of the FEBio project, from its initial developments through its current funding period. We also present a glimpse into the future of FEBio.
<i>A Lady at the Virginal With a Gentleman</i>
Authors: Thomas B. Cole
Journal: JAMA (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 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
Human<i>TERT</i>promoter mutation enables survival advantage from<i>MGMT</i>promoter methylation in<i>IDH1</i>wild-type primary glioblastoma treated by standard chemoradiotherapy
Authors: HuyTram N. Nguyen, Amy Lie, Tie Li, Reshmi Chowdhury, Fei Liu, Byram Ozer, Bowen Wei, Richard M. Green, Benjamin M. Ellingson, He-jing Wang, Robert Elashoff, Linda M. Liau, William H. Yong, Phioanh L. Nghiemphu, Timothy Cloughesy, Albert Lai
Journal: Neuro-Oncology (2016)

Promoter mutation in the human telomerase reverse transcriptase gene (hTERT) occurs in ~75% of primary glioblastoma (GBM). Although the mutation appears to upregulate telomerase expression and contributes to the maintenance of telomere length, its clinical significance remains unclear.We performed hTERT promoter genotyping on 303 isocitrate dehydrogenase 1 wild-type GBM tumors treated with standard chemoradiotherapy. We also stratified 190 GBM patients from the database of The Cancer Genome Atlas (TCGA) by hTERT gene expression. We analyzed overall and progression-free survival by Kaplan-Meier and Cox regression.We detected hTERT promoter mutation in 75% of the patients. When included as the only biomarker, hTERT mutation was not prognostic in our patient cohort by Cox regression analysis. However, when hTERT and O6-DNA methylguanine-methyltransferase (MGMT) were included together, we observed an interaction between these 2 factors. To further investigate this interaction, we performed pairwise comparison of the 4 patient subcohorts grouped by hTERT-MGMT status (MUT-M, WT-M, MUT-U, and WT-U). MGMT methylated patients showed improved survival only in the presence of hTERT promoter mutation: MUT-M versus MUT-U (overall survival of 28.3 vs 15.9 mos, log-rank P < .0001 and progression-free survival of 15.4 vs 7.86 mo, log-rank P < .0001). These results were confirmed by Cox analyses. Analogously, the cohort from TCGA demonstrated survival benefit of MGMT promoter methylation only in patients with high hTERT expression. In addition, hTERT mutation was negatively prognostic in our MGMT unmethylated patients, while the analogous association with high expression was not observed in the cohort from TCGA.The prognostic influence of MGMT promoter methylation depends on hTERT promoter mutation. This interaction warrants further mechanistic investigation.
Addressing Administrative and Regulatory Burden in Cancer Clinical Trials: Summary of a Stakeholder Survey and Workshop Hosted by the American Society of Clinical Oncology and the Association of American Cancer Institutes
Authors: Julie M. Vose, Laura A. Levit, Patricia Hurley, Carrie Lee, Michael A. Thompson, Teresa Stewart, Janie Hofacker, Suanna S. Bruinooge, Daniel F. Hayes
Journal: Journal of Clinical Oncology (2016)
Frontline Treatment of CD30+ Peripheral T-Cell Lymphomas with Brentuximab Vedotin in Combination with CHP: 3-Year Durability and Survival Follow-up
Authors: Steven M Horwitz, Andrei R. Shustov, Andres Forero-Torres, Nancy L Bartlett, Ranjana Advani, Barbara Pro, Robert Chen, Andrew J Davies, Tim Illidge, Dirk Huebner, Dana A. Kennedy, Michelle A. Fanale
Journal: Blood (2015)
Coexistence of gastrointestinal stromal tumor (GIST) with desmoid tumor (DT): Case series of 22 patients.
Authors: A. G. Dumont, L. Rink, M. Miettinen, H. Joensuu, J. R. Strosberg, A. Gronchi, C. L. Corless, A. J. Lazar, D. Lev, M. von Mehren
Journal: Journal of Clinical Oncology (2010)

10052 Background: Both gastrointestinal stromal tumor (GIST) and desmoid tumors (DT) are mesenchymal tumors. Anecdotal reports of individuals with both diseases led us to evaluate a larger cohort of patients with both tumors including clinical, molecular and histopathologic features. Methods: We identified 22 patients with GIST associated with DT between 1985 and 2008 at 9 institutions in U.S., Australia and Europe. Standardized Incidence Ratio (SIR) and its 95% confidence intervals were calculated comparing the incidence of DT in GIST patients for 2000 through 2008 in U.S. population. Results: We found 13 men and 9 women aged from 39-88 yrs. In 15 cases, the GIST was diagnosed prior to the DT, 6 cases had both tumors synchronous at presentation, and 1 patient had DT prior to GIST. The primary site of the GIST was gastric in 14 cases, small intestine in 8 cases, and 1 was mesenteric. Imatinib mesylate was administered to 11 patients, all with partial response. In 17/22 cases KIT expression was observed immunohistochemically for GIST but 0/22 for DT. Additionally, 15/22 cases of DT but 0/22 cases of GIST had to have B-Catenin expression by immunohistochemistry. When tissues were available KIT, PDGFRA and CTNNB1 were genotyped for both tumors. KIT mutations were observed in 7 of 10 GIST, all in exon 11. CTNNB1 mutations were observed in 4 of 9 DT, all in exon 3 (T41A and S45P). In GIST patients, the estimated risk of DT was significantly higher (SIR of 43; 95% CI, 19-74) than that expected in the general population. Conclusions: Preliminary evidence suggests that the relationship between the development of GIST and DT is not coincidental. The precise relationship between these tumors remains unknown. No significant financial relationships to disclose.
Brief Report: Estimating Disease Activity Using Multi‐Biomarker Disease Activity Scores in Rheumatoid Arthritis Patients Treated With Abatacept or Adalimumab
Authors: Roy Fleischmann, Sean E. Connolly, Michael A. Maldonado, Michael Schiff
Journal: Arthritis & Rheumatology (2016)

To assess the ability of a multi-biomarker disease activity (MBDA) test (Vectra DA) to reflect clinical measures of disease activity in patients enrolled in the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) trial.In the AMPLE trial, patients with active rheumatoid arthritis (RA) who were naive to biologic agents and had an inadequate response to methotrexate were randomized (1:1) to receive subcutaneous abatacept (125 mg every week) or subcutaneous adalimumab (40 mg every 2 weeks), with background methotrexate, for 2 years. The MBDA score was determined using serum samples collected at baseline, month 3, and years 1 and 2. The adjusted mean change from baseline in the MBDA score was compared between the abatacept and adalimumab treatment groups. Cross-tabulation was used to compare the MBDA score with the following clinical measures of disease activity: Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), and Routine Assessment of Patient Index Data 3 (RAPID-3).In total, 318 patients were randomized to receive abatacept, and 328 were randomized to receive adalimumab; MBDA data were available for 259 and 265 patients, respectively. No association between the MBDA score and disease activity defined by the CDAI, SDAI, DAS28-CRP, or RAPID-3 in the abatacept and adalimumab treatment groups was observed.The MBDA score did not reflect clinical disease activity in patients enrolled in AMPLE and should not be used to guide decision-making in the management of RA, particularly for patients who receive abatacept or adalimumab as the first biologic agent.
INTRAPERITONEAL FAT IS ASSOCIATED WITH THICKENING OF THE THORACIC AORTA IN INDIVIDUALS AT HIGH RISK FOR CARDIOVASCULAR EVENTS
Authors: Haroon Chughtai, Timothy M. Morgan, Craig A. Hamilton, Charaslak Charoenpanichkit, Jingzhong Ding, Tina E. Brinkley, William G. Hundley
Journal: Journal of the American College of Cardiology (2011)
Incidental detection of a urinary Escherichia coli isolate harbouring mcr-1 of a patient with no history of colistin treatment
Authors: M. Fritzenwanker, C. Imirzalioglu, K. Gentil, L. Falgenhauer, F.M. Wagenlehner, T. Chakraborty
Journal: Clinical Microbiology and Infection (2016)
Pharmacogenomic analysis for prediction of individual response to mFOLFOX6 in colorectal cancer.
Authors: H. Takemoto, K. Murata, N. Tomita, M. Fukunaga, M. Watanabe, M. Ohue, R. Ikeda, K. Tanimoto, K. Hiyama, M. Nishiyama
Journal: Journal of Clinical Oncology (2010)

e13500 Background: Despite recent encouraging data, the clinical efficacy and toxicity of mFOLFOX6 in most patients with colorectal cancer remain unpredictable. We conducted this prospective study to determine potent predictive markers of individual response to the regimen, in terms of efficacy and toxicity, for the following large scale validation study. Methods: Chemonaive patients with stage IV colorectal cancer were eligible for this trial after palliative operation, and received mFLOFOX6 therapy: oxaliplatin 85 mg/m2 and l-LV 175 mg/body (2h infusion) followed by a 5-FU bolus 400 mg/m2 on day 1 and 5- FU 2400 mg/m2 day (46-h infusion) on days 1 to 2 every 2 weeks. Tumor response and toxicity were evaluated by RECIST and CTCAE, respectively. Tumor and blood samples collected at surgery were subjected into expression analysis and genotyping for 10 genes-DPYD, TYMS, ERCC1, ERCC2, XRCC1, GSTP1, EGFR, VEGF, TYMP and TNFRSF1B-, along with KRAS mutation analysis. Results: Fifty pts received a total of 424 treatment cycles (median: 8, range: 1 to 31). Overall response rate was 60.4% (1 CR and 28 PRs). Median OS (overall survival) was 930 days (95% CI, 569 to NC) and median PFS (progression-free survival) was 234 days (95% CI, 185 to 294 days). The most common grade 3/4 toxicities were neutropenia (40%), vomiting (6%), anemia (4%), leucopenia (4%), and neuropathy: sensory (DEB-NTC; 4%). Although there was no correlative genotype with the toxicities and no association between KRAS mutational status and tumor response, overexpression of 3 genes -ERCC1, ERCC2, and TYMS- in tumor tissues was significantly associated with an absence of tumor response to mFOLFOX6 (ERCC1, p=0.0171; ERCC2, p= 0.0283; TYMS, p=0.0316). OS was significantly better in patients with low ERCC2 expression (p=0.0117), and PFS was significantly longer in patients with low expression of all of the 3 genes (p=0.0029). Furthermore, TYMS expression levels were highly correlative with the best tumor response (ratio of tumor size from post- to pre-treatment) (r=0.414, p=0.0039). Conclusions: Overexpression of ERCC1, ERCC2, and TYMS would be of predictive value for individual response to mFOLFOX6. Further investigation in prospective validation studies is warranted. No significant financial relationships to disclose.
Physical Medicine and Rehabilitation
Authors: Joel M. Press
Journal: JAMA (1999)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Textbook of Family Practice
Authors: Scott J. Tilleson
Journal: JAMA (1996)

The fifth edition of Rakel's bible of family practice updates a classic text to keep pace with the ever-changing field of medicine. Dr Rakel has succeeded again in providing a valuable resource for primary care that keeps current with recent medical advances. The text is also intended as a resource for non-primary care physicians, who are increasingly called upon to provide primary care services to their patients. Despite the breadth of family practice, efforts have been made to keep the material concise, practical, and clinically relevant. The first edition policy of co-authored chapters, pairing an authority in the field with an experienced family physician, has been continued. There are also 60 new authors among the 118 contributors. New chapters expand on psychiatric disorders and condense material on domestic abuse. Another new chapter deals with biopsychosocial medicine. All other chapters have been revised and updated or rewritten to contain fresh information.
Trends in hepatocellular carcinoma among people with HBV or HCV notification in Australia (2000–2014)
Authors: Reem Waziry, Jason Grebely, Janaki Amin, Maryam Alavi, Behzad Hajarizadeh, Jacob George, Gail V. Matthews, Matthew Law, Gregory J. Dore
Journal: Journal of Hepatology (2016)
India’s NEET exam poses problems in its current form
Authors: Vagish Kumar L Shanbhag
Journal: BMJ (2016)

Supe’s article on India’s National Eligibility-cum-Entrance Test (NEET) was interesting.1 In reality, however, some disadvantages arise from conducting the test in its present form.

States in India have different state syllabuses and eligibility criteria, with a diverse medium of languages in pre-university exams. NEET is currently conducted only in English and Hindi.2 A sudden change from …
Radioimmunotherapy (RIT) with <sup>131</sup>l-L19SIP in solid cancers (SC) and lymphoproliferative diseases: Final results of the first human trial.
Authors: G. Del Conte, P. A. Erba, A. Fasolo, C. Chiesa, C. Grana, H. Menssen, D. Neri, G. Mariani, E. Bombardieri, L. Gianni
Journal: Journal of Clinical Oncology (2010)

2523 Background: The extradomain B of fibronectin (EDBF) is a promising target for cancer therapies due to its selective expression in newly formed blood vessels of SC and lymphomas. L19 is a human recombinant antibody that selectively binds EDBF. This phase I study investigated the whole-body distribution, tumor localization, and RIT potential of 131I-L19SIP, which is the L19-small immunoprotein (SIP, variable regions of L19) linked to 131I. Methods: Patients (pts) underwent RIT after dosimetry, based on dual-head gamma-camera planar imaging, only with lesion/red marrow absorbed dose ratio ≥10. 131I-L19SIP doses were diagnostic 5 mCi or RIT 3.7 GBq (100 mCi; n=16) or 5.5 GBq (150 mCi; n=10). Response and toxicity were assessed by RECIST and CTC-AE. Results: Fifty-one pts have been treated: 39 SC, 12 hematologic malignancies (HEM), median age 59 yrs (range 23-82), ECOG PS 0/1 74.5%/23.5%, ≥3 prior regimens in 35% of SC pts, 92% of HEM pts; peripheral blood stem cell transplant in 75% of HEM pts. The mono-exponential blood elimination profile of 131I-L19SIP gave a T1/2 ∼ 10 h, with low inter-patient variability. Median absorbed doses to healthy organs were within the safety threshold TD5/5 with maximum doses 50/5 in all pts. Approximately half of pts received RIT (20 SC, 6 HEM). Only hematologic toxicities were observed: grade 3-4 thrombocytopenia in 30% and 66% of SC and HEM pts, respectively (median duration 12 d; range 1- 56); platelet transfusion required in 4 pts; grade 4 neutropenia in 4 pts (>7 d, 2 pts). Imaging showed 131I-L19SIP selectively localized to tumor lesions and revealed lesions undetected by MRI or CT in some patients. In pts with Hodgkin's lymphoma (HL), 3/6 maintained partial responses for 5.3, >5.5, and 14 m, with complete disappearance of 21/25 and 6/11 lesions after repeated RIT in 2 pts, 1 of whom with a completely negative FDG-PET-CT. Also, 6 SC pts experienced disease stabilization sustained in 3 cases by repeated RIT (mesothelioma in 2 pts, thymoma in 1 pt). Conclusions: RIT with up to 5.5 GBq 131I-L19SIP is feasible and safe in SC and HEM, inducing sustained responses in 50% of treated HL pts and confirming EDBF as a promising neoangiogenic target for antibody-based therapies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Shering Pharma, Philogen Bayer Onix, Philogen Bayer Schering Pharma, Philogen Philogen SpA