tbuckley/cabot-search huggingface dataset:
Low-Dose Desmopressin Nasal Spray and FDA Approval—Reply
Authors: Michael Fralick, Aaron S. Kesselheim
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
A biomarker-guided approach to combining PARP inhibitors with radiotherapy in pediatric solid tumors.
Authors: Anang Shelat, Christopher Tinkle, Elizabeth Stewart, Sara Michele Federico, Brandon Bianski, Marcia Mellado-Lagarde
Journal: Journal of Clinical Oncology (2017)

10556 Background: Ewing sarcoma (EWS) expresses high levels of Schlafen-11 (SLFN11). SLFN11 disrupts checkpoint maintenance and may serve as a biomarker to assess sensitivity to Poly (ADP-ribose) polymerase 1 and 2 inhibitors (PARPi). The goal of this study is to evaluate SLFN11 protein expression in a panel of pediatric solid tumors and correlate levels of protein with sensitivity to PARP inhibition combined with ionizing radiation (IR), a component of therapy for many pediatric solid tumors and a potent inducer of DNA damage. Methods: SLFN11 mRNA and protein levels were assessed by quantitative RT-PCR, and immunohistochemistry, Western blot, and immunofluorescence microscopy, respectively. PARPi included: talazoparib (TAL), niraparib (NIR), veliparib (VEL), and olaparib (OLA). Approximately 30 minutes after addition of systemic therapy, graded doses of radiation were delivered and viability across a panel of pediatric solid tumor cell lines was measured using the ATP-based Cell TiterGlo assay and confirmed with the colony formation assay. Results: We found that SLFN11 mRNA and protein is expressed at high levels in EWS, and SLFN11 is also variably present in a subset of other pediatric solid tumor lines, including desmoplastic small round cell tumor, osteosarcoma, and rhabdomyosarcoma. In all tumor cells with detectable SLFN11 expression, viability was reduced by greater than 90% when exposed to 2Gy IR and 1-10nM TAL, whereas cells with undetectable levels of SLFN11 were 5-10 times less sensitive. Intriguingly, variation in the potentiation between specific PARPi and IR correlated with the ability to form drug-induced PARP-DNA adducts, with the strong PARP trapper TAL showing ~10-fold higher potency compared to the moderate trapper NIR, and ~300-fold more potency relative to the weak trapper VEL. Consistent with our PARPi findings, the toposiomerase 1 inhibitor irinotecan, which also forms DNA adducts, potentiated with IR similarly to TAL at concentrations &lt; 10nM in tumor cells expressing detectable levels of SLFN11. Conclusions: SLFN11 is present in select pediatric solid tumors and may induce a DNA repair defect that is best exploited by combining low-doses of TAL and irinotecan with IR.
Abstract 15882: Intramyocardial Therapy: a Novel Accurate and Fast Method to Target the Infarct Border Zone
Authors: René van Es, Hans T van den Broek, Mira van der Naald, Leon de Jong, Eliane Nieuwenhuis, Adriaan O Kraaijeveld, Pieter A Doevendans, S A Chamuleau, Frebus J van Slochteren
Journal: Circulation (2016)

Introduction: For the optimal application of cardiac regenerative therapy in ischemic heart disease, targeting of the correct location to perform intramyocardial injections is of the utmost importa...
Worsening of quality of life (QoL), cognitive functions (CF) and psychological status (PSY) can predict radiologic progressive disease (RPD) in glioblastoma (GBM) patients (PTS) treated with radiation therapy (RT) and temozolomide (TMZ): A mono-institutional prospective study
Authors: E. Bergo, G. Lombardi, P. Del Bianco, S. Dal Pos, F. Berti, L. Bellu, A. Pambuku, V. Zagonel
Journal: Annals of Oncology (2017)
Investigating the feasibility of tumour molecular profiling in gastrointestinal malignancies in routine clinical practice
Authors: S.Y. Moorcraft, D. Gonzalez de Castro, D. Cunningham, T. Jones, B.A. Walker, C. Peckitt, L.C. Yuan, M. Frampton, R. Begum, Z. Eltahir, A. Wotherspoon, L.S. Teixeira Mendes, S. Hulkki Wilson, A. Gillbanks, C. Baratelli, N. Fotiadis, A. Patel, C. Braconi, N. Valeri, M. Gerlinger, S. Rao, D. Watkins, I. Chau, N. Starling
Journal: Annals of Oncology (2017)
Enhancer profiling identifies critical cancer genes and characterizes cell identity in adult T-cell leukemia
Authors: Regina Wan Ju Wong, Phuong Cao Thi Ngoc, Wei Zhong Leong, Alice Wei Yee Yam, Tinghu Zhang, Kaori Asamitsu, Shinsuke Iida, Takashi Okamoto, Ryuzo Ueda, Nathanael S. Gray, Takashi Ishida, Takaomi Sanda
Journal: Blood (2017)
Prevalence and Predictors of Sperm Banking in Adolescents Newly Diagnosed With Cancer: Examination of Adolescent, Parent, and Provider Factors Influencing Fertility Preservation Outcomes
Authors: James L. Klosky, Fang Wang, Kathryn M. Russell, Hui Zhang, Jessica S. Flynn, Lu Huang, Karen Wasilewski-Masker, Wendy Landier, Marcia Leonard, Karen H. Albritton, Abha A. Gupta, Jacqueline Casillas, Paul Colte, William H. Kutteh, Leslie R. Schover
Journal: Journal of Clinical Oncology (2017)

Purpose To estimate the prevalence of sperm banking among adolescent males newly diagnosed with cancer and to identify factors associated with banking outcomes. Patients and Methods A prospective, single-group, observational study design was used to test the contribution of sociodemographic, medical, psychological/health belief, communication, and developmental factors to fertility preservation outcomes. At-risk adolescent males (N = 146; age 13.00 to 21.99 years; Tanner stage ≥ 3), their parents, and medical providers from eight leading pediatric oncology centers across the United States and Canada completed self-report questionnaires within 1 week of treatment initiation. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs for specified banking outcomes (collection attempt v no attempt and successful completion of banking v no banking). Results Among adolescents (mean age, 16.49 years; standard deviation, 2.02 years), 53.4% (78 of 146) made a collection attempt, with 43.8% (64 of 146) successfully banking sperm (82.1% of attempters). The overall attempt model revealed adolescent consultation with a fertility specialist (OR, 29.96; 95% CI, 2.48 to 361.41; P = .007), parent recommendation to bank (OR, 12.30; 95% CI, 2.01 to 75.94; P = .007), and higher Tanner stage (OR, 5.42; 95% CI, 1.75 to 16.78; P = .003) were associated with an increased likelihood of a collection attempt. Adolescent history of masturbation (OR, 5.99; 95% CI, 1.25 to 28.50; P = .025), banking self-efficacy (OR, 1.23; 95% CI, 1.05 to 1.45; P = .012), and parent (OR, 4.62; 95% CI, 1.46 to 14.73; P = .010) or medical team (OR, 4.26; 95% CI, 1.45 to 12.43; P = .008) recommendation to bank were associated with increased likelihood of sperm banking completion. Conclusion Although findings suggest that banking is underutilized, modifiable adolescent, parent, and provider factors associated with banking outcomes were identified and should be targeted in future intervention efforts.
A Comparison of Staging Systems for Hepatocellular Carcinoma in a Multicenter US Cohort
Authors: Neehar D. Parikh, Steve Scaglione, Yumeng Li, Corey Powell, Olutola A. Yerokun, Pauline Devlin, Shaham Mumtaz, Sahil Mittal, Amit G. Singal
Journal: Clinical Gastroenterology and Hepatology (2017)
In silico analysis of DNA damage repair variants in advanced NSCLC patients (pts) to predict response to platinum-based chemotherapy (PBC).
Authors: Saradasri Karri, Matthew K Stein, Kruti Patel, Melissa Crawley, Namratha Reddy Vontela, Taylor Alloway, Lindsay Kaye Morris, John Mays, Felicia Hare, Philippe Prouet, Kenneth P Byrd, Eric Wiedower, Jason Claud Chandler, Moon Jung Fenton, Benny Weksler, Lee Steven Schwartzberg, Michael Gary Martin
Journal: Journal of Clinical Oncology (2017)

e20582 Background: There are no biomarkers that reliably predict benefit from PBC in NSCLC. We hypothesize cancers with DNA damage repair pathway nsSNPs may be more sensitive to PBC. Methods: Pts with advanced NSCLC that received first-line PBC and next-generation sequencing (NGS) with Caris (2013-2015) were retrospectively identified. The total pathogenic burden (SUM) was defined as test-determined pathogenic mutations (Pmut) plus nsSNPs predicted-damaging (pnsSNPs) by in silico analysis with PolyPhen-2 (Harvard). 13 DNA damage repair genes were also selectively analyzed. All p-values were two-tailed. Results: 84 pts were found; 35% female; 58% white, 37% black; median age was 64 (range 26-81); 82% had ≥20 pack-years (py), 12% with &lt; 20 and 6% never-smokers; 27% received immunotherapy (IT) and 5% tyrosine kinase inhibitors (TKI) subsequently. 49 pts had primary progressive disease (58%), 9 stable disease (11%), 16 partial response (19%) and 10 complete response (12%). Median overall survival (OS) was 11 months (1-18). Median SUM was 5 (0-14) with median pnsSNPs 3 (0-11) and Pmut 1 (0-4). For all genes, no link was found between SUM and response (p = 0.95, ANOVA) or OS (p = 0.48, log-rank test). 26 pts (31%) had DNA damage repair lesions (range 1-3) with 33 nsSNPs (23/33 pnsSNPs) and 4 Pmut; genes commonly-mutated were ATM (16), BRCA2 (10) and BRCA1 (5). Race and smoking status did not predict mutation frequency. A trend towards better OS was seen for pts more heavily-mutated in DNA damage repair ( p= 0.01, log-rank test for trend) as &gt; 60% pts with 1-3 nsSNPs survived &gt; 300 days versus &lt; 50% pts with 0. OS was longer for pts with 1+ DNA damage repair lesions (455 days) versus 0 (252 days) [HR 1.81; CI 1.19-3.89; p = 0.01]; no difference in response rate ( p= 0.59, Fisher’s exact) was found. Similar proportions of pts without (16/58; 28%) and with (7/26; 27%) DNA damage repair variants received IT; 4/4 pts TKI-treated had no such lesions. Conclusions: Advanced NSCLC tumors with ≥1 DNA damage repair nsSNP had a superior OS of &gt; 200 days; however, no link with response was found. Further studies are indicated to determine the extent to which DNA damage repair burden can predict benefit in platinum-treated NSCLC pts.
Analysis of programmed death-ligand 1 (PD-L1) expression, transforming growth factor (TGF)-β gene expression signatures (GES) and tumor-infiltrating immune cells (IC) in hepatocellular carcinoma (HCC): Rationale for targeting PD-L1- and TGF-β
Authors: Y. Zhang, B.J. Naughton, P.A. Rolfe, E. Frick-Krieger, I. Dussault, L. Terracciano, C. Ihling
Journal: Annals of Oncology (2017)
Soils and Seeds That Initiate Pancreatic Cancer Metastasis
Authors: Christopher R. Vakoc, David A. Tuveson
Journal: Cancer Discovery (2017)

Abstract Summary: Pathways that stimulate metastasis of pancreatic cancer cells are critical for understanding tumor evolution and can serve as potential therapeutic targets. The microenvironment produces a host of metabolic perturbations and tropic factors that may play a formative role in this process. Cancer Discov; 7(10); 1067–8. ©2017 AACR. See related article by Chiou et al., p. 1184.
Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody–drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study
Authors: Toshihiko Doi, Kohei Shitara, Yoichi Naito, Akihiko Shimomura, Yasuhiro Fujiwara, Kan Yonemori, Chikako Shimizu, Tatsunori Shimoi, Yasutoshi Kuboki, Nobuaki Matsubara, Atsuko Kitano, Takahiro Jikoh, Caleb Lee, Yoshihiko Fujisaki, Yusuke Ogitani, Antoine Yver, Kenji Tamura
Journal: The Lancet Oncology (2017)
CCND2 Overexpression Enhances the Regenerative Potency of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes
Authors: Wuqiang Zhu, Meng Zhao, Saidulu Mattapally, Sifeng Chen, Jianyi Zhang
Journal: Circulation Research (2017)

Rationale: The effectiveness of transplanted, human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) for treatment of ischemic myocardial injury is limited by the exceptionally low engraftment rate. Objective: To determine whether overexpression of the cell cycle activator CCND2 (cyclin D2) in hiPSC-CMs can increase the graft size and improve myocardial recovery in a mouse model of myocardial infarction by increasing the proliferation of grafted cells. Methods and Results: Human CCND2 was delivered to hiPSCs via lentiviral-mediated gene transfection. In cultured cells, markers for cell cycle activation and proliferation were ≈3- to 7-folds higher in CCND2-overexpressing hiPSC-CMs (hiPSC-CCND2 OE CMs) than in hiPSC-CMs with normal levels of CCND2 (hiPSC-CCND2 WT CMs; P &lt;0.01). The pluripotent genes (Oct 4, Sox2, and Nanog) decrease to minimal levels and undetectable levels at day 1 and 10 after differentiating to CMs. In the mouse myocardial infarction model, cardiac function, infarct size, and the number of engrafted cells were similar at week 1 after treatment with hiPSC-CCND2 OE CMs or hiPSC-CCND2 WT CMs but was about tripled in hiPSC-CCND2 OE CM–treated than in hiPSC-CCND2 WT CM–treated animals at week 4 ( P &lt;0.01). The cardiac function and infarct size were significantly better in both cell treatment groups’ hearts than in control hearts, which was most prominent in hiPSC-CCND2 OE CM–treated animals ( P &lt;0.05, each). No tumor formation was observed in any hearts. Conclusions: CCND2 overexpression activates cell cycle progression in hiPSC-CMs that results in a significant enhanced potency for myocardial repair as evidenced by remuscularization of injured myocardium. This left ventricular muscle regeneration and increased angiogenesis in border zone are accompanied by a significant improvement of left ventricular chamber function.
Improving the Efficiency of Psychotherapy for Depression: Computer-Assisted Versus Standard CBT
Authors: Michael E. Thase, Jesse H. Wright, Tracy D. Eells, Marna S. Barrett, Stephen R. Wisniewski, G.K. Balasubramani, Paul McCrone, Gregory K. Brown
Journal: American Journal of Psychiatry (2017)

Objective: The authors evaluated the efficacy and durability of a therapist-supported method for computer-assisted cognitive-behavioral therapy (CCBT) in comparison to standard cognitive-behavioral therapy (CBT). Method: A total of 154 medication-free patients with major depressive disorder seeking treatment at two university clinics were randomly assigned to either 16 weeks of standard CBT (up to 20 sessions of 50 minutes each) or CCBT using the “Good Days Ahead” program. The amount of therapist time in CCBT was planned to be about one-third that in CBT. Outcomes were assessed by independent raters and self-report at baseline, at weeks 8 and 16, and at posttreatment months 3 and 6. The primary test of efficacy was noninferiority on the Hamilton Depression Rating Scale at week 16. Results: Approximately 80% of the participants completed the 16-week protocol (79% in the CBT group and 82% in the CCBT group). CCBT met a priori criteria for noninferiority to conventional CBT at week 16. The groups did not differ significantly on any measure of psychopathology. Remission rates were similar for the two groups (intent-to-treat rates, 41.6% for the CBT group and 42.9% for the CCBT group). Both groups maintained improvements throughout the follow-up. Conclusions: The study findings indicate that a method of CCBT that blends Internet-delivered skill-building modules with about 5 hours of therapeutic contact was noninferior to a conventional course of CBT that provided over 8 additional hours of therapist contact. Future studies should focus on dissemination and optimizing therapist support methods to maximize the public health significance of CCBT.
Vaccination Challenges in Confronting the Resurgent Threat From Yellow Fever
Authors: Lin H. Chen, Davidson H. Hamer
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
Pembrolizumab and nanoparticle albumin bound paclitaxel (nab-paclitaxel) for metastatic urothelial carcinoma (UC) after chemotherapy failure: the open-label, single-arm, phase 2 PEANUT study
Authors: A. Necchi, L. Mariani, A. Anichini, P. Giannatempo, D. Raggi, G. Calareso, R. Salvioni
Journal: Annals of Oncology (2017)
Prognostic impact of hepatitis B virus (HBV) infection in advanced intrahepatic cholangiocarcinoma (iCCA) patients (pts) treated with first-line gemcitabine plus cisplatin (GEMCIS)
Authors: E.J. Kim, H. Cho, C. Yoo, K-P. Kim, H-M. Chang, B-Y. Ryoo
Journal: Annals of Oncology (2017)
Neurocognitive function (NCF) outcomes in patients with glioblastoma (GBM) enrolled in RTOG 0825.
Authors: Jeffrey Scott Wefel, Stephanie L. Pugh, Terri S. Armstrong, Mark R. Gilbert, Minhee Won, Merideth M Wendland, David Brachman, Ritsuko Komaki, Ian R. Crocker, H. Ian Robins, R. Jeffrey Lee, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2013)

2004 Background: RTOG 0825 evaluated overall survival (OS) and progression-free survival (PFS) differences in patients with newly diagnosed GBM treated with standard chemoradiation, maintenance temozolomide and placebo (Arm 1) or bevacizumab (Arm 2). While OS was equivalent, PFS was longer in Arm 2. Longitudinal NCF testing was performed to evaluate clinical benefit. Methods: NCF was evaluatedat baseline and while on study and progression free with the Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT) and Controlled Oral Word Association (COWA). Change in NCF from baseline was categorized using the reliable change index. Differences between treatment arms were compared at follow-up evaluations. Additionally, baseline (B) and early changes (EC) (B to week 10) in NCF were examined as prognostic factors. Results: 542 patients consented and 507 randomized patients participated, with test completion rates at weeks 0 (B), 10, 22, and 34 of 94-97, 69-73, 59-64, and 53-58%, respectively. Mean test performance at B was equivalent between arms and ranged from -0.8 to -4.8 SDs below healthy population norms with global NCF on a composite variable at -2.0 SDs. There were no statistically significant between arm differences in frequency of improvement through week 34. Decline on COWA (verbal measure of executive function) at week 34 relative to baseline was more common (16.1 vs 5.7%) in patients in Arm 1 (p&lt;0.05); whereas, there were trends for more decline in Arm 2 on a visuomotor measure of executive function (TMT B, p&lt; 0.06; 22.2 vs 35.4%). B performance and EC in global NCF, memory, executive function and processing speed were prognostic for OS. At B, global NCF was prognostic for PFS. EC in global NCF, memory and executive function were prognostic for PFS. Conclusions: There was a statistically significant difference in the frequency of decline on a verbal test of executive function at week 34 favoring Arm 2. However, this was not found at earlier time points and was not found on a visuomotor test of executive function. B and EC in NCF were prognostic for OS and PFS. Longitudinal modeling is ongoing to further evaluate the impact of treatment on patients’ NCF. Support: U10 CA21661, U10 CA37422 and Genentech, Inc. Clinical trial information: NCI-2009-01670.
Phase II clinical trial of second-line weekly paclitaxel plus trastuzumab for patients with HER2-positive metastatic gastric cancer
Authors: Y. Horita, M. Nishino, S. Sugimoto, A. Kida, A. Mizukami, M. Yano, F. Arihara, K. Matsuda, M. Matsuda, A. Sakai
Journal: Annals of Oncology (2017)
Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes
Authors: Ophélie Rouxel, Jennifer Da silva, Lucie Beaudoin, Isabelle Nel, Céline Tard, Lucie Cagninacci, Badr Kiaf, Masaya Oshima, Marc Diedisheim, Marion Salou, Alexandra Corbett, Jamie Rossjohn, James McCluskey, Raphael Scharfmann, Manuela Battaglia, Michel Polak, Olivier Lantz, Jacques Beltrand, Agnès Lehuen
Journal: Nature Immunology (2017)
Relationship of PD-L1 and a T-cell inflamed gene expression profile (GEP) to clinical response in a multicohort trial of solid tumors (KEYNOTE [KN]028)
Authors: P.A. Ott, Y-J. Bang, A.R.A. Razak, J. Bennouna, J-C. Soria, H.S. Rugo, R.B. Cohen, B.H. O'Neil, J.M. Mehnert, J. Lopez, T. Doi, E. van Brummelen, D. Levitan, G. Zhao, K. Emancipator, K. Stein, A. Joe, M. Ayers, J. Lunceford, S.A. Piha-Paul
Journal: Annals of Oncology (2017)
Adolescents and Young Adults with Acute Myeloid Leukemia Are Associated with Higher Treatment-Related Mortality and Inferior Overall Survival after Allogeneic Hematopoietic Cell Transplantation Compared with Children
Authors: Daisuke Tomizawa, Shiro Tanaka, Tadakazu Kondo, Yoshiko Hashii, Yasuyuki Arai, Kazuko Kudo, Takashi Taga, Jiro Inagaki, Katsuyoshi Koh, Masami Inoue, Junji Tanaka, Koji Kato, Yoshiko Atsuta, Souichi Adachi, HIroyuki Ishida
Journal: Blood (2016)
Authors’ reply: Rabid puppy-dog imported into the Netherlands from Morocco via Spain, February 2012
Authors: G G van Rijckevorsel
Journal: Eurosurveillance (2012)

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