tbuckley/cabot-search huggingface dataset:
Concurrent chemoradiation therapy for advanced head and neck squamous cell carcinoma (HNSCC) in a community hospital
Authors: M. A. Levine, J. R. Saunders, E. Zinreich, D. Kunar, J. Price, R. M. Hirata, M. Williams
Journal: Journal of Clinical Oncology (2004)

5558 Background: Concurrent chemotherapy and radiation therapy have made organ preservation feasible in patients with advanced head and neck squamous cell carcinoma. This study evaluates the use of chemotherapy with hyperfractionated radiation therapy in a community hospital and the importance of elective lymph node dissection for N2 and N3 patients. Methods: Forty-six patients with HNSCC stage III and IV (42/46 male, 35/46 oropharynx, 4 hypopharynx, 7 larynx, 25 N0–1, 21 N2–3) were treated. Median follow-up is 18.7 months (1–46 months). Hyperfractionated radiation therapy was administered twice daily with an interval of at least six hours and a total dose of 7000cGy to the primary site and 5–6000cGy to the adjacent lymph node bearing areas. Chemotherapy was administered during weeks 1 and 6 of radiation therapy and consisted of cis-platin 12mg/M2 IVPB days 1–5 and 5-fluorouracil 600mg/M2 continuous IV infusion over 20 hours days 1–5. Twenty of twenty-one patients with N2–3 disease underwent neck dissection 6–8 weeks following completion of XRT. All pts had insertion of indwelling venous access devices and percutaneous endoscopic gastrostomy tubes. Results: Complete response (CR) at the primary site following chemo-XRT occurred in 45/46 (98%). All pts with N1 achieved CR. 20 of 21 N2–3 underwent neck dissection. Fourteen were downstaged to N0 and six to N1. Two pts died in remission from intercurrent illnesses more than 11 months after completion of therapy. Of the remaining 44 pts, 38 remain NED (86%) (3 pts died from recurrent disease, 2 pts recurred locally and were salvaged surgically, one is alive with metastatic disease). Toxicity: short term, all pts developed confluent mucositis but hospitalization for dehydration or infection was rare; long term, mouth dryness was common but manageable and most pts were PEG independent within three months of completion of therapy. Conclusions:Aggressive chemo-XRT is feasible in a community hospital and affords advanced HNSCC pts the opportunity for organ preservation. Pts with N2 or N3 disease should undergo neck dissection following chemo-XRT since thirty percent of these pts will have node metastases. No significant financial relationships to disclose.
IOIBD technical review on endoscopic indices for Crohn's disease clinical trials
Authors: L Vuitton, P Marteau, W J Sandborn, B G Levesque, B Feagan, S Vermeire, S Danese, G D'Haens, M Lowenberg, R Khanna, G Fiorino, S Travis, J Y Mary, L Peyrin-Biroulet
Journal: Gut (2015)

<h3>Background</h3> Crohn9s disease (CD) is a chronic disabling and progressive IBD. Only strategies looking beyond symptoms and based on tight monitoring of objective signs of inflammation such as mucosal lesions may have the potential for disease modification. Endoscopic evaluation is currently the gold standard to assess mucosal lesions and has become a major therapeutic endpoint in clinical trials. Several endoscopic indices have been proposed to evaluate disease activity; unvalidated and arbitrary definitions have been used in clinical trials for defining endoscopic response and endoscopic remission in CD. <h3>Methods</h3> In these recommendations from the International Organization for the Study of Inflammatory Bowel Disease, we first reviewed all technical aspects of available endoscopic scoring systems in the literature. Second, in order to achieve consensus on endoscopic definitions of remission and response in trials, a two-round vote based on a Delphi method was performed among 14 specialists in the field of IBDs. <h3>Results</h3> At the end of the voting process, the investigators ranked first a &gt;50% decrease in Simple Endoscopic Score for Crohn9s Disease (SES-CD) or Crohn9s Disease Endoscopic Index of Severity for the definition of endoscopic response, and an SES-CD 0–2 for the definition of endoscopic remission in CD. All experts agreed on a Rutgeerts’ score i0–i1 for the definition of endoscopic remission after surgery.
Maintenance with either gemcitabine or erlotinib versus observation with predefined second-line treatment after cisplatin-gemcitabine induction chemotherapy in advanced NSCLC: IFCT-GFPC 0502 phase III study.
Authors: M. Perol, C. Chouaid, B. J. Milleron, R. Gervais, F. Barlesi, V. Westeel, J. Crequit, H. Lena, A. Vergnenegre, D. Pérol
Journal: Journal of Clinical Oncology (2010)

7507 Background: NSCLC patients (pts) whose tumors have not progressed following platinum-based chemotherapy (CT) obtain PFS and OS benefits with maintenance CT or erlotinib (E). We investigated maintenance gemcitabine (G) or E vs observation (O), following induction CT. Unlike previous maintenance trials, we included a predefined second-line therapy in all arms (pemetrexed [P]). Methods: Stage IIIB/IV pts with an ECOG PS of 0-1 whose tumors did not progress following four cycles of cisplatin-gemcitabine were randomized (stratified by center, gender, histology, response to induction CT and smoking status) to O, or to receive as maintenance therapy either G (1,250 mg/m2, days 1 and 8 of a 3 week cycle) or E 150 mg/day until disease progression. The primary endpoint was PFS by independent review with an 80% power to detect a 50% improvement in the median PFS (HR 0.66) for each comparison (G vs O and E vs O) at a two-sided 5% alpha level. Results: Of the 834 pts who received induction CT, 464 were randomized from November 06-September 09 to either O (155), G (154) or E (155). Baseline characteristics were well balanced between arms (overall 27% female, 91% stage IV, 50% ECOG PS 0, 65/20/15% adenocarcinoma/squamous/other, 38% non-smokers and 53% responders to induction CT). Median PFS by investigator assessment was 2.1, 3.7 and 2.8 months for O, G and E respectively. PFS by independent review (83% pts assessed) was significantly prolonged by G (HR [95% CI] 0.51 [0.39-0.66]) and E (HR 0.83 [0.73-0.94]) vs O. Second--line P was received by 72/55/60% of pts, respectively. Grade 3-4 treatment-related AEs were more common with G (27%) and E (14%) than with O (2%). Final results of the independent review will be available for the meeting, and will include mature OS data, subgroup analyses by stratification factors and EGFR mutation status. Conclusions: Maintenance with G or E significantly delays disease progression after cisplatin-gemcitabine induction. The impact on OS with a predefined second-line therapy will be discussed in the May 2010 update. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, GlaxoSmithKline, Lilly, Merck Serono, Pfizer, Roche Amgen, AstraZeneca, GlaxoSmithKline, Lilly, Merck, Merck Serono, Novartis, Roche Amgen, Lilly, Pfizer, Roche Lilly, Roche
Pembrolizumab (MK-3475) in combination with lenalidomide and low-dose dexamethasone for relapsed/refractory multiple myeloma (RRMM): KEYNOTE-023
Authors: Maria-Victoria Mateos, David Siegel, Jatin J Shah, Donna Reece, David Avigan, Robert Orlowski, Yang Ge, Arun Balakumaran, Patricia Marinello, Jesus San Miguel
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The immunomodulatory drug (IMiD) lenalidomide has single-agent activity against RRMM, and synergistic effects when combined with dexamethasone. Overexpression of PD-L1 is associated with tumor invasiveness in MM cells and may be a mechanism of immune evasion. Pembrolizumab, a
Eradication of Large Solid Tumors by Gene Therapy with a T-Cell Receptor Targeting a Single Cancer-Specific Point Mutation
Authors: Matthias Leisegang, Boris Engels, Karin Schreiber, Poh Yin Yew, Kazuma Kiyotani, Christian Idel, Ainhoa Arina, Jaikumar Duraiswamy, Ralph R. Weichselbaum, Wolfgang Uckert, Yusuke Nakamura, Hans Schreiber
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded by somatic nonsynonymous single nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a single type of T-cell receptor (TCR) that is specific for a single AAS. Experimental Design: By exome and RNA sequencing of an UV-induced tumor, we identified an AAS in p68 (mp68), a co-activator of p53. This AAS seemed to be an ideal tumor-specific neoepitope because it is encoded by a trunk mutation in the primary autochthonous cancer and binds with highest affinity to the MHC. A high-avidity mp68-specific TCR was used to genetically engineer T cells as well as to generate TCR-transgenic mice for adoptive therapy. Results: When the neoepitope was expressed at high levels and by all cancer cells, their direct recognition sufficed to destroy intratumor vessels and eradicate large, long-established solid tumors. When the neoepitope was targeted as autochthonous antigen, T cells caused cancer regression followed by escape of antigen-negative variants. Escape could be thwarted by expressing the antigen at increased levels in all cancer cells or by combining T-cell therapy with local irradiation. Therapeutic efficacies of TCR-transduced and TCR-transgenic T cells were similar. Conclusions: Gene therapy with a single TCR targeting a single AAS can eradicate large established cancer, but a uniform expression and/or sufficient levels of the targeted neoepitope or additional therapy are required to overcome tumor escape. Clin Cancer Res; 22(11); 2734–43. ©2015 AACR. See related commentary by Liu, p. 2602
A Comparative Effectiveness Trial of Alternate Formats for Presenting Benefits and Harms Information for Low-Value Screening Services
Authors: Stacey L. Sheridan, Anne Sutkowi-Hemstreet, Colleen Barclay, Noel T. Brewer, Rowena J. Dolor, Ziya Gizlice, Carmen L. Lewis, Daniel S. Reuland, Carol E. Golin, Christine E. Kistler, Maihan Vu, Russell Harris
Journal: JAMA Internal Medicine (2015)

IMPORTANCE Healthcare overuse, the delivery of low-value services, is increasingly recognized as a critical problem.However, little is known about the comparative effectiveness of alternate formats for presenting benefits and harms information to patients as a strategy to reduce overuse.OBJECTIVE To examine the effect of different benefits and harms presentations on patients' intentions to accept low-value or potentially low-value screening services (prostate cancer screening in men ages 50-69 years; osteoporosis screening in low-risk women ages 50-64 years; or colorectal cancer screening in men and women ages 76-85 years).DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 775 individuals eligible to receive information about any 1 of the 3 screening services and scheduled for a visit with their clinician.Participants were randomized to 1 of 4 intervention arms that differed in terms of presentation format: words, numbers, numbers plus narrative, and numbers plus framed presentation.The trial was conducted from September 2012 to June 2014 at 2 family medicine and 2 internal medicine practices affiliated with the Duke Primary Care Research Consortium.The data were analyzed between May and September of 2015.INTERVENTIONS One-page evidence-based decision support sheets on each of the 3 screening services, with benefits and harms information presented in 1 of 4 formats: words, numbers, numbers plus narratives, or numbers plus a framed presentation. MAIN OUTCOMES AND MEASURESThe primary outcome was change in intention to accept screening (on a response scale from 1 to 5).Our secondary outcomes included general and disease-specific knowledge, perceived risk and consequences of disease, screening attitudes, perceived net benefit of screening, values clarity, and self-efficacy for screening. RESULTSWe enrolled and randomly allocated 775 individuals, aged 50 to 85 years, to 1 of 4 intervention arms: 195 to words, 192 to numbers, 196 to narrative, and 192 to framed formats.Intentions to accept screening were high before the intervention and change in intentions did not differ across intervention arms (words, -0.07; numbers, -0.05; numbers plus narrative, -0.12; numbers plus framed presentation, -0.02; P = .57for all comparisons).Change in other outcomes also showed no difference across intervention arms.Results were similar when stratified by screening service.CONCLUSIONS AND RELEVANCE Single, brief, written decision support interventions, such as the ones in this study, are unlikely to be sufficient to change intentions for screening.Alternate and additional interventions are needed to reduce overused screening services.
Dimethyl Fumarate Induces Cytoprotection and Inhibits Inflammation and Vaso-Occlusion in Transgenic Sickle Mice
Authors: John D. Belcher, Julia Nguyen, Chunsheng Chen, Fuad Abdulla, Phong Nguyen, Minh Nguyen, Ping Zhang, Pauline Xu, Nicholas J. Slipek, Gregory M. Vercellotti
Journal: Blood (2014)
ACE Inhibitors of Little Benefit to Kidney Transplant Patients
Authors: Anita Slomski
Journal: JAMA (2015)

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
Should Patients Choose Their Care?
Authors: Diana Lee Farmer, Rebecca Anne Stark
Journal: JAMA Surgery (2015)

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
A BCMA-specific CAR T cell produced with clinically scalable lentiviral and T cell manufacturing processes has potent anti-multiple myeloma activity
Authors: Tracy E Garrett, Alena A Chekmasova, John W Evans, Stacie L Seidel, Holly M Horton, Howard J Latimer, Johanna A Griecci, Christopher J Horvath, Byoung Y Ryu, Kevin M Friedman, Richard A Morgan
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Chimeric antigen receptors (CARs) operably link T cell activation domains to the antigen recognition properties of an antibody, thereby redirecting T lymphocytes to cells expressing the antigen. B cell maturation antigen (BCMA) is an attractive CAR T cell target to treat patients
Combined resection, intraperitoneal chemotherapy, and whole abdominal radiation for malignant peritoneal mesothelioma (MPM)
Authors: R. N. Taub, M. E. Hesdorffer, M. L. Keohan, J. A. Chabot, K. S. Fountain, S. Talbot, M. Gabay, S. Lee
Journal: Journal of Clinical Oncology (2005)

7175 Background: We have carried out a prospective single-institution Phase I-II trial of surgical debulking, intraperitoneal chemotherapy and immunotherapy followed by whole abdominal radiotherapy in patients with malignant peritoneal mesothelioma. (MPM). Methods: Between 1997 and 2000 27 patients with malignant peritoneal mesothelioma were enrolled, 23 with the epithelial subtype, and 4 with a sarcomatoid or mixed subtype. The treatment regimen consisted of: initial exploratory laparotomy with surgical debulking and placement of indwelling intraperitoneal (ip) catheters; four ip courses of doxorubicin alternating with four ip courses of cisplatin; 4 ip doses of gamma interferon; a second laparotomy with biopsy verification of complete response or attempted resection of residual disease; intraoperative hyperthermic (41 degrees centigrade) ip perfusion with mitomycin plus cisplatin; and finally whole abdominal radiotherapy. Results: The median overall survival was 68 months with a 3 year survival of 67% (95% CI: 46–81%). Thirteen patients died from their disease at a mean of 37.2 (range 8–68) months after initiation of treatment. Ten patients are alive with a laparotomy-verified complete pathologic response and without further evidence of disease at a mean of 58.5 (range 39–78) months. Four patients are alive with disease at a mean of 62 (range 54–81) months. The entire regimen was well tolerated; there were no patients with Grade III or IV hematological toxicities, 2 patients with Grade III ototoxicity, and 3 patients with Grade III gastrointestinal toxicity. Conclusions: Based on the results of this study intensive multimodality therapy appears feasible and effective in this group of MPM patients. No significant financial relationships to disclose.
Multiparameter evaluation of in vivo gene delivery using ultrasound-guided, microbubble-enhanced sonoporation
Authors: Galina Shapiro, Andrew W. Wong, Maxim Bez, Fang Yang, Sarah Tam, Lisa Even, Dmitriy Sheyn, Shiran Ben-David, Wafa Tawackoli, Gadi Pelled, Katherine W. Ferrara, Dan Gazit
Journal: Journal of Controlled Release (2015)
CD126 and Targeted Therapy with Tocilizumab in Chronic Lymphocytic Leukemia
Authors: Feng-Ting Liu, Li Jia, Ping Wang, Timothy Farren, Hong Li, Xishan Hao, Samir G. Agrawal
Journal: Clinical Cancer Research (2015)

Abstract Purpose: IL6 promotes tumor growth and signal transduction via both its membrane-bound (CD126) and soluble receptors (sCD126). We aimed to study whether the levels of CD126 expression in chronic lymphocytic leukemic (CLL) cells can predict in vitro and in vivo treatment response. Experimental Design: The levels of membrane-bound CD126 expression were determined on freshly isolated CLL B cells (n = 58) using flow cytometry. These CLL cells were treated with chlorambucil or fludarabine with or without anti-CD126 antibody tocilizumab for 24 hours and IL6-mediated STAT3 transcriptional activity and cell-cycle alteration were evaluated. Results: CD126 surface expression was found in all cases and positively correlated with the levels of in vivo constitutive STAT3 activity. The levels of CD126 expression were significantly and positively correlated with the resistance of CLL cells to in vitro treatment with chlorambucil or fludarabine and poor in vivo treatment response of CLL patients. Blocking IL6 signaling with the anti-CD126 antibody, tocilizumab, had profound effects on STAT3-mediated survival and growth signals: decreased Mcl-1 and Bcl-xL, favoring an apoptotic profile; and decreased p27 with increased cyclin E and CDK2 expression, leading to cell-cycle shift from G0–G1. These tocilizumab-mediated changes induced chemosensitization in resistant CLL cells, with the greatest effect seen in cells with higher CD126 expression (P &amp;lt; 0.001). Conclusions: CLL cells with higher CD126 expression are more resistant to treatment in vivo and in vitro via IL6–CD126–STAT3 axis. Blocking CD126 using tocilizumab sensitizes CLL cells to chemotherapy. Clin Cancer Res; 22(10); 2462–9. ©2015 AACR.
ScaleS: an optical clearing palette for biological imaging
Authors: Hiroshi Hama, Hiroyuki Hioki, Kana Namiki, Tetsushi Hoshida, Hiroshi Kurokawa, Fumiyoshi Ishidate, Takeshi Kaneko, Takumi Akagi, Takashi Saito, Takaomi Saido, Atsushi Miyawaki
Journal: Nature Neuroscience (2015)
Emotional and behavioral problems in adolescents and young adults with food allergy
Authors: M. A. Ferro, R. J. Van Lieshout, J. Ohayon, J. G. Scott
Journal: Allergy (2015)

Adolescents with food allergy have poorer psychosocial outcomes compared with their nonallergic counterparts; however, few studies have prospectively examined the mental health of adolescents and young adults in this vulnerable population. Our objectives were to estimate the prevalence of emotional and behavioral problems in an epidemiological sample of adolescents and young adults with food allergy; determine whether food allergy is associated with adolescent and maternal reports of such problems; and examine the patterns of change in emotional and behavioral problems from adolescence to young adulthood among individuals with and without food allergy.Data came from 1303 participants at 14 and 21 years of age in the Mater University Study of Pregnancy. Emotional and behavioral problems were measured using self- and maternal-reported symptoms of depression, anxiety, attention/deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder.Maternal, but not self-reports suggested that emotional and behavioral problems were higher among adolescents with food allergy. Food allergy was associated with increased odds of elevated levels of maternal-reported symptoms of depression [OR = 4.50 (1.83, 11.07)], anxiety [OR = 2.68 (1.12, 6.44)], and ADHD [OR = 3.14 (1.07, 9.19)] in adolescence. Food allergy was also associated with depressive symptoms that persisted from adolescence to young adulthood [OR = 2.05 (1.04, 4.03)].Emotional and behavioral problems, particularly symptoms of depression, anxiety, and ADHD, are common among adolescents with food allergy in the general population and, in the case of elevated levels of depressive symptoms, persist into young adulthood. Healthcare professionals should seek adolescent and parental perspectives when assessing emotional and behavioral problems and monitor mental health during the transition to adulthood.