tbuckley/cabot-search huggingface dataset:
Immunotherapy in Endometrial Cancer: In the Nick of Time
Authors: Josep Maria Piulats, Xavier Matias-Guiu
Journal: Clinical Cancer Research (2016)

Immunotherapy with checkpoint inhibitors is changing the face of oncology treatments for many tumors, and endometrial carcinoma may not be an exception. Several endometrial cancer groups from the molecular taxonomy are characterized by having an ultramutated/hypermutated genome, which could be the first Achilles' heel identified in this malignancy in decades. Clin Cancer Res; 22(23); 5623-5. ©2016 AACRSee related article by Santin et al., p. 5682.
Ventricular tachycardia.
Authors: 和秀 出雲, 由晶 徐, 一太 川村, 太郎 小島, 幹 斎藤, 賢太 熊谷, 通 高橋, 由利子 田中, 慶憲 板岡, 修 岡崎, 光夫 樫田, 宣治 赤塚, 義雄 矢崎
Journal: BMJ (1969)

Ventricular TachycardiaIt is important to distinguish ventricular tachycardia from the other causes of fast heart rate both because of its worse prognosis and because it is treated differently.Unfortunately, it can usually be reliably differentiated only by the electro- cardiogram.Ventricular tachycardia is less common than
Training volume and soft tissue injury in professional and non-professional rugby union players: a systematic review
Authors: Shane Ball, Mark Halaki, Rhonda Orr
Journal: British Journal of Sports Medicine (2016)

Aim To investigate the relationship between training volume and soft tissue injury incidence, and characterise soft tissue injury in rugby union players. Design A systematic search of electronic databases was performed. The search strategy combined terms covering: training volume and injury, and rugby union, and players of all levels. Data sources Medline, SPORTDiscus, Web of Science, Embase, PubMed. Eligibility criteria for selecting studies Studies were included if they reported: male rugby union players, a clear definition of a rugby union injury, the amount of training volume undertaken by participants, and epidemiological data for soft-tissue injuries including the number or incidence. Results 15 studies were eligible for inclusion. Overall match and training injury incidence ranged from 3.3 to 218.0 injuries/1000 player match hours and 0.1–6.1 injuries/1000 player training hours, respectively. Muscle and tendon as well as joint (non-bone) and ligament injuries were the most frequently occurring injuries. The lower limb was the most prevalent injury location. Injury incidence was higher in professional rugby union players than non-professional players. Contact events were responsible for the greatest injury incidence. For non-contact mechanisms, running was responsible for the highest injury incidence. Inconsistent injury definitions hindered reliable comparison of injury data. The lack of reporting training volumes in hours per player per week limited the ability to investigate associations between training volume and injury incidence. Conclusions A higher level of play may result in higher match injury incidence. Muscle and tendon injuries were the most common type of soft tissue injury, while the lower limb was the most common location of injury in rugby union players, and running was responsible for the highest injury incidence during non-contact events.
Incidence and Clinical Features of Idiopathic Pneumonia Syndrome and Diffuse Alveolar Hemorrhage After Unrelated Cord Blood Transplantation.
Authors: Aya Nishida, Atsushi Wake, Hisashi Yamamoto, Kazuya Ishiwata, Nobuaki Nakano, Masanori Tsuji, Yuki Asano-Mori, Naoyuki Uchida, Koji Izutsu, Kazuhiro Masuoka, Akiko Yoneyama, Shigeyoshi Makino, Shuichi Taniguchi
Journal: Blood (2010)
A randomized phase II trial of intra-arterial chemotherapy using a novel lipophilic platinum derivative (SM-11355) in comparison with zinostatin stimalamer in patients with hepatocellular carcinoma
Authors: T. Okusaka, H. Kasugai, H. Ishii
Journal: Journal of Clinical Oncology (2009)

4583 Background: SM-11355 (Miriplatin Hydrate) is a platinum complex developed to treat HCC via administration into the hepatic artery as a sustained-release formulation suspended in lipiodol. We conducted a phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355 using zinostatin stimalamer as a control. Methods: Patients with unresectable HCC were randomized 2:1 to receive an injection of SM-11355 or zinostatin stimalamer suspended in lipiodol into the hepatic artery at doses of up to 6 mL (SM-11355: 120 mg; zinostatin stimalamer: 6 mg) according to the tumor size. A second injection was given 4–12 weeks after the first injection. Efficacy was evaluated by CT 3 months after treatment and categorized as therapeutic effect (TE) V to I. The primary endpoint was achievement of TE V, which was defined as disappearance or 100% necrosis of all treated tumors. Lipiodol accumulation in tumors was regarded as indicating necrosis. Results: The study included 126 patients, of whom 122 were evaluable for efficacy and toxicity (SM-11355, n=83; zinostatin stimalamer, n=39). Baseline characteristics were similar in the two groups. The TE V rates were 26.5% (22/83) and 17.9% (7/39) in the SM-11355 and zinostatin stimalamer groups, respectively. The most frequent drug-related adverse events (AEs) of ≥ grade 3 (shown as SM-11355 vs. zinostatin stimalamer) were elevated AST (26.5 vs. 33.3%), elevated ALT (22.9 vs. 20.5%), thrombocytopenia (12.0 vs. 7.7%), and hyperbilirubinemia (9.6 vs. 5.1%). Serious AEs occurred in 9 (10.8%) and 3 (7.7%) patients in the SM-11355 and zinostatin stimalamer groups, respectively. The AEs with the largest difference in frequency between the two groups (SM-11355 vs. zinostatin stimalamer) were hepatic vascular injury (0 vs. 48.4%) and eosinophilia (84.3 vs. 41.0%). The 2-year survival rates were 75.9 and 70.3% in the SM-11355 and zinostatin stimalamer groups, respectively, and the 3-year survival rates were 58.4 vs. 48.7%, respectively. Conclusions: Our results suggest that SM-11355 in lipiodol has similar efficacy to that of zinostatin stimalamer, and that repeated dosing is possible without hepatic vascular injury in cases of relapse. No significant financial relationships to disclose.
A New Scoring System To Predict the Prognosis of Patients with Acute Myeloid Leukemia. -Study from the Japan Adult Leukemia Study Group.
Authors: Yasushi Miyazaki, Kazuhiro Nishida, Kazutaka Kuriyama, Masafumi Taniwaki, Hisashi Sakamaki, Shuichi Miyawaki, Shigeki Ohtake, Sumihisa Honda, Masao Tomonaga, Ryuzo Ohno
Journal: Blood (2005)
Primary Care “Provider” and Professional Identity
Authors: Martin Mayer, Dale Newton
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
FAST: An international, multicenter, randomized, phase II trial of epirubicin, oxaliplatin, and capecitabine (EOX) with or without IMAB362, a first-in-class anti-CLDN18.2 antibody, as first-line therapy in patients with advanced CLDN18.2+ gastric and gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Salah-Eddin Al-Batran, Martin H. Schuler, Zanete Zvirbule, Georgiy Manikhas, Florian Lordick, Andriy Rusyn, Yuriy Vynnyk, Ihor Vynnychenko, Natalia Fadeeva, Marina Nechaeva, Assen Dudov, Evgeny Gotovkin, Alexander Pecheniy, Igor Bazin, Igor Bondarenko, Bohuslav Melichar, Christian Mueller, Christoph Huber, Oezlem Tureci, Ugur Sahin
Journal: Journal of Clinical Oncology (2016)

LBA4001 Background: Claudin18.2 (CLDN18.2) is a tight junction protein expressed by several cancers including gastric and GEJ adenocarcinoma. IMAB362 is a chimeric monoclonal antibody that mediates specific killing of CLDN18.2-positive cancer cells by activation of immune effector mechanisms. IMAB362 has demonstrated single-agent activity and was safe and tolerable in patients (pts) with pretreated gastric cancer. Methods: Pts with advanced/recurrent gastric and GEJ cancer were centrally evaluated for CLDN18.2 expression by IHC (validated CLAUDETECT18.2 Kit). Eligible pts had a CLDN18.2 expression of ≥ 2+ in ≥ 40% tumor cells, an ECOG PS of 0–1 and were not eligible for trastuzumab. Pts were randomized 1:1 to first-line EOX (epirubicin 50 mg/m 2 and oxaliplatin 130 mg/m 2 d1, and capecitabine 625 mg/m 2 bid, d1–21; qd22) with or without IMAB362 (loading dose 800 mg/m 2 , then 600 mg/m 2 d1, qd21). The study was extended by an exploratory Arm3 (N = 85) to investigate a high dose IMAB362 (1000 mg/m 2 ) plus EOX, (not subject here). The primary study endpoint was PFS (Arm 1 v 2, 70% power, HR 0.72, 1-sided p = 0.1). Results: 730 pts were consented, of whom 352 pts (48%) were tested CLDN18.2+ per protocol criteria. Of those, 161 pts (median age, 58 yrs; male 64%; gastric, 80%; GEJ, 16%; esophageal, 4%) were randomized into Arms1 and 2. The study met its endpoints. IMAB362 plus EOX improved PFS (median 5.7 v 7.9 mon; HR 0.5; 95% CI 0.35–0.78, 1-sided p = 0.001) and OS (median 8.7 v 12.5 mon; HR 0.5, 95% CI 0.28–0.73) compared to EOX alone. In the subpopulation with very high CLDN18.2 expression ( ≥ 2+ intensity in ≥ 70% tumor cells), efficacy was more pronounced (PFS, 6.1 vs 9.1 mon; HR 0.46; OS, 9.3 v 16.6 mon; HR 0.44). Most common IMAB362-related adverse events included vomiting, neutropenia, and anemia, which were mostly of NCI-CTC grade 1/2. Grade 3/4 events were not significantly increased by IMAB362. Conclusions: IMAB362 combined with first-line chemotherapy exhibited a clinically relevant benefit in PFS and OS and a favorable risk/benefit profile. Clinical trial information: NCT01630083.
Abstract POSTER-BIOL-1351: Molecular characterization of cyclin-dependent kinase 1 pathway in newly established epithelial ovarian cancer cell lines
Authors: Wookyeom Yang, Hanbyoul Cho, Kim Sol, Jae-Hoon Kim
Journal: Clinical Cancer Research (2015)

Abstract Background: Epithelial ovarian cancer (EOC) is a heterogeneous gynecologic tumor. To better understand the biological pathways involved in the development of EOC, we performed mRNA expression profiling on newly established EOC cell lines. Methods: Five newly established EOC cell lines were characterized by transcript profiling. Microarray analyses were validated using quantitative real-time PCR (RT-PCT) and immunoblotting. Furthermore, biological networks of the differentially expressed genes were predicted using the STRING database and literature review. Results: A total of 239 genes represented by 24,957 probes were identified from microarray analysis, of which 98 and 141 genes are up- (&amp;gt; 2 fold, p &amp;lt; 0.05) or down-regulated (&amp;lt; 3 fold, p &amp;lt; 0.05), respectively, in EOC cell line compare to human ovarian surface epithelial cell lines. We identified a subset of EOC characterized by the numerous genes related to cell cycle and apoptosis, along with cyclin-dependent kinase 1 (CDK1). A total of 24 genes were validated by quantitative RT-PCR, and expressional reliabilities of 4 CDK1 pathway-related genes were confirmed by immunoblotting. Further biological network analysis revealed that the CDK1 pathway might be essential for EOC tumorigenesis. Conclusions: These data reveal that the CDK1 pathway is important to EOC development and progression, providing new insight into the biology of EOC. Citation Format: Wookyeom Yang, Hanbyoul Cho, Kim Sol, Jae-Hoon Kim. Molecular characterization of cyclin-dependent kinase 1 pathway in newly established epithelial ovarian cancer cell lines [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1351.
Emphysematous Prostatitis
Authors: Hsun-Shuan Wang, Ming-Chen Shih
Journal: New England Journal of Medicine (2016)

A 42-year-old man with diabetes presented to the ED with severe dysuria and incontinence. Laboratory studies were notable for pyuria, leukocytosis, elevated C-reactive protein, and hyperglycemia. Radiography showed an atypical focus of gas accumulation behind the right pubic ramus.
FEB study: Efficacy treatment evaluation in metastatic colorectal cancer (mCRC) patients (pts) changing monoclonal antibody (MA) after progression with chemotherapy.
Authors: R. Grande, G. Cianci, I. Sperduti, D. Gemma, A. Gelibter, M. Giampaolo, L. Mentuccia, F. Narducci, E. Magnolfi, T. Gamucci
Journal: Journal of Clinical Oncology (2010)

3550 Background: Monoclonal antibodies bevacizumab (B) and cetuximab (C) both improve overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) when combined with irinotecan-containing regimens. The optimal sequence of these monoclonal antibodies in combination with chemotherapy (CT) is controversial. This study analyzed the efficacy of C associated with irinotecan- based CT (FOLFIRI) after progression with the same regimen plus B in pts with mCRC. Methods: Eligibility criteria: progressive disease (PD) after CT with Folfiri-B (FB)->B; ECOG PS 0-1. Primary endpoints: ORR and disease control rate (DCR:ORR plus stable disease > 6 months); secondary endpoints: PFS, duration of response, OS and toxicity. ORR and DCR were reported with their confidence interval at 95%. Kaplan-Meier method was used for PFS and OS evaluation. Results: 50 pts were enrolled to receive Folfiri-C (FC)->C after PD to FB->B. Four pts were not evaluable for response rate. Median age was 67 (43-80), M/F 29/21, ECOG PS 0/1 was 18/ 32, WT Kras 40 (80%). Median cycles of first line FB->B was 12 (range 4- 16)/8 (range 1-23) and median cycles of second line FC->C was 7 (range 1-14)/6 (range 2-15). The ORR was 24% (CI 95% 12-36), DCR was 54% (CI 95% 40-69). In the group of patients responders to FB->B 37% of pts continued to be responsive to FC->C; in the group of non responders 15% obtained a response. Median duration of response was 5 months (range 1-9) and clinical benefit 8 months (CI 95% 4-12). PFS and OS are shown in the Table. Acne-like rash occurred in 76% of pts (42% grade ≥ 2). No grade 4 toxicity was observed. Conclusions: Efficacy in response and survival is maintained in pts with mCRC treated with the same CT regimen changing monoclonal antibodies. Data collection is ongoing and update results will be presented. Endpoints 6 months (%) 12 months(%) 24 months (%) Median (CI95%) PFS 51 23 — 7 (6-8) OS 80 61 22 17 (10-24) No significant financial relationships to disclose.
Importance of rare gene copy number alterations for personalized tumor characterization and survival analysis
Authors: Michael Seifert, Betty Friedrich, Andreas Beyer
Journal: Genome biology (2016)

It has proven exceedingly difficult to ascertain rare copy number alterations (CNAs) that may have strong effects in individual tumors. We show that a regulatory network inferred from gene expression and gene copy number data of 768 human cancer cell lines can be used to quantify the impact of patient-specific CNAs on survival signature genes. A focused analysis of tumors from six tissues reveals that rare patient-specific gene CNAs often have stronger effects on signature genes than frequent gene CNAs. Further comparison to a related network-based approach shows that the integration of indirectly acting gene CNAs significantly improves the survival analysis.
Clonal evolution of resistance to imatinib (IM) in patients (pts) with gastrointestinal stromal tumor (GIST): molecular and radiologic evaluation of new lesions
Authors: J. Desai, S. Shankar, M. C. Heinrich, J. A. Fletcher, C. D. M. Fletcher, K. Tuncali, S. G. Silverman, A. D. Van Den Abbeele, E. Vansonnenberg, G. D. Demetri
Journal: Journal of Clinical Oncology (2004)

3010 Background: Resistance to IM is emerging as a clinical challenge in pts with metastatic GIST following durable benefit and response. Novel patterns of progression have been noted in GIST pts, and we have explored the molecular and radiologic patterns of IM-refractory disease to supplement existing conventional criteria. Methods: Pts with metastatic GIST treated with IM were followed with serial CT/MRI and 18FDG-PET scans. Where feasible, biopsies were performed to document disease progression. Results: 89 pts were followed for a median of 39 months (m). 42/89 pts eventually developed progressive disease (PD, SWOG criteria) following partial (n=34) or minor (n=8) response (25–49% bidimensional decrease). A unique “nodule within a mass” pattern was seen in 22/42 pts, thought to represent emergence of a clone resistant to IM. This was defined as a new enhancing nodular focus enclosed within a pre-existing, non- or hypo-enhancing tumor mass that previously responded to IM. Nodules arose prior to development of PD defined by “tumor size” criteria by median of 5m (range 0–13m) and were the first sign of progression in 17/22 pts. Development of nodules was independent of IM starting dose (400–800mg/d). 9 pts had IM dose increased, with no effect on nodule growth. 5 pts were treated with radiofrequency ablation and continuation of IM, with overall disease control for a further 4–12m. Comparative tumor biopsies were performed in 9 pts at baseline and with appearance of progressing nodules. Genotypic analyses of KITand PDGFRAkinases were performed, revealing new activating kinase mutations in 7/9 (78%) pts. Conclusions: The “nodule within a mass” is a unique pattern of disease progression seen in pts with GIST after an initial response to IM and reflects the emergence of IM-resistant clones, supported by the appearance of secondary mutations in tumor genotype. Conventional tumor measurements (SWOG/RECIST) do not adequately account for this subtle finding. A new enhancing nodule growing within a pre-existing tumor mass should be classified as a “new lesion” and should define at least partial progression of GIST. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis
Dual Characteristics of Novel HER2 Kinase Domain Mutations in Response to HER2-Targeted Therapies in Human Breast Cancer
Authors: Wen-Jia Zuo, Yi-Zhou Jiang, Yu-Jie Wang, Xiao-En Xu, Xin Hu, Guang-Yu Liu, Jiong Wu, Gen-Hong Di, Ke-Da Yu, Zhi-Ming Shao
Journal: Clinical Cancer Research (2016)

Somatic mutations in the tyrosine kinase domain of human epidermal growth factor receptor 2 (HER2) may be an alternative mechanism to HER2 activation and can affect the sensitivity toward HER2-targeted therapies. We aimed to investigate the prevalence, clinicopathologic characteristics, and functional relevance of novel HER2 mutations in breast cancer.We performed Sanger sequencing of all exons of the HER2 gene in 1,248 primary tumors and 18 paired metastatic samples. Novel HER2 mutations were functionally characterized.The total HER2 somatic mutation rate was 2.24% (28/1,248). Of the seven novel HER2 mutations, L768S and V773L were only detected in HER2-negative tumors, whereas K753E was found in HER2-positive disease. L768S and V773L mutations exhibited a significant increase in tyrosine kinase-specific activity and strongly increased the phosphorylation of signaling proteins in various cell lines. Xenograft experiments showed that NIH3T3 cells bearing the L768S and V773L mutations displayed more rapid growth. MCF10A, BT474, and MDA-MB-231 cells bearing the K753E mutation were resistant to lapatinib, but could be inhibited by neratinib. Finally, comparison of HER2 mutations in 18 pairs of primary and metastatic lesions revealed that the drug-resistant HER2 mutations (K753E and L755S) were enriched in metastatic lesions.HER2-negative breast cancer with activating mutations can benefit from HER2-targeted therapies. Meanwhile, mutations in the HER2 kinase domain might be a key mechanism of resistance to HER2-targeted therapy, and irreversible tyrosine kinase inhibitors such as neratinib may offer alternative treatment options. Clin Cancer Res; 22(19); 4859-69. ©2016 AACR.
Oldest people are most likely to experience care abuse, shows report
Authors: Adrian O’Dowd
Journal: BMJ (2016)

People aged 85 and over are the group most at risk of abuse and neglect, official figures published by the NHS in England have shown.

Its Safeguarding Adults Annual Report for 2015-16 gives information on numbers of cases of abuse investigated by councils in that period.1 This is the first time that such information has been published since local authorities were given new duties under the Care Act 2014, which came into force last year.

The report showed that 102 970 people had inquiries opened under section 42 of the act (the equivalent of referrals under the previous system) in 2015-16.

Most section 42 inquiries (63% (65 085)) were undertaken for adults aged 65 and over. Of this …
Quality of life (QOL) and pain in advanced stage prostate cancer: impact of missing data on evaluating palliation in SWOG 9916
Authors: D. L. Berry, C. M. Moinpour, C. Jiang, L. V. Vinson, P. N. Lara, S. Lanier, M. E. Taplin, P. A. Burch, D. P. Petrylak, E. D. Crawford
Journal: Journal of Clinical Oncology (2004)

4579 Background: Both regimens, estramustine plus docetaxel (Arm 1) and mitoxantrone plus prednisone (Arm 2), are known to palliate pain in hormone refractory metastatic prostate cancer. In SWOG 9916, Arm 1 was hypothesized to have greater clinical efficacy as well as equivalent or better palliation of disease-related symptoms. Methods: Men with stage D1 or D2 prostate cancer were randomized to one of the two regimens. We report preliminary data for the Present Pain Intensity (PPI) scale of the McGill Pain Questionnaire and the Global QOL (GQOL) scale score from the EORTC QLQ-C30 at baseline, week 10, months 6, and 12. Results: 333 eligible patients were registered to each arm. Arm 1 had statistically better survival (72% vs. 62% at year 1). The table presents cross-sectional means and sample size for patients by treatment arm and time point. Arm 1 has better submission rates than Arm 2, consistent with Arm 1's longer survival. Data not shown suggest that patients who submitted fewer forms over time had worse scores at baseline and worsening QOL at time of drop-out. Across time and treatment arms, standard errors were on the order of .08 for the PPI but ranged from 1.38 to 2.58 for GQOL. Conclusions: QOL/pain data are particularly important given superior Arm 1 clinical efficacy. However, since reliance on cross-sectional comparisons can be misleading, we will compare treatment arms using 1) pattern mixture model sensitivity analyses for the GQOL outcome and 2) a composite measure (pain reduction and duration, analgesic use) to identify pain palliation responders to examine the influence of informative missing data. Mean QOL Scores by Assessment Time (n) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Response to High Dose Cytarabine (HIDAC) As First Salvage for Relapsed Acute Lymphocytic Leukemia in Patients Receiving HIDAC As Initial Therapy
Authors: Anjali S. Advani, Holly Gundacker, Nolyn Nyatanga, Paul Elson, Peter J. Rosen, Jennifer Bates, Mikkael A. Sekeres, Matt Kalaycio, Ronald Sobecks, Edward Copelan, Frederick R. Appelbaum
Journal: Blood (2011)