tbuckley/cabot-search huggingface dataset:
Avelumab (MSB0010718C; anti-PD-L1) in patients with metastatic Merkel cell carcinoma previously treated with chemotherapy: Results of the phase 2 JAVELIN Merkel 200 trial.
Authors: Howard Kaufman, Jeffery Scott Russell, Omid Hamid, Shailender Bhatia, Patrick Terheyden, Sandra P. D'Angelo, Kent C. Shih, Celeste Lebbe, Gerald P Linette, Michele Milella, Isaac Brownell, Karl D. Lewis, Jochen H. Lorch, Kevin M. Chin, Lisa Mahnke, Anja von Heydebreck, Jean-Marie Cuillerot, Paul Nghiem
Journal: Journal of Clinical Oncology (2016)

9508 Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with Merkel cell polyomavirus. Therapeutic options are limited for metastatic MCC that has progressed after 1st-line chemotherapy. PD-L1 is frequently expressed in the MCC tumor microenvironment on tumor and immune cells. Avelumab* is a fully human anti-PD-L1 IgG1 mAb showing efficacy and an acceptable safety profile in multiple cancers. Avelumab received FDA breakthrough therapy and fast-track as well as FDA and EMA orphan drug designations in MCC. Methods: This phase 2 trial (NCT02155647) reports on single-agent avelumab in patients (pts) with metastatic MCC who had progressed on chemotherapy. Pts received avelumab 10 mg/kg IV Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks (RECIST 1.1 by independent review). Objective response rate (ORR; primary endpoint), duration of response, and PFS were evaluated. PD-L1 expression was assessed by IHC. Results: As of Nov 20, 2015, 88 pts with metastatic MCC were treated with avelumab. Median age was 72.5 y (range 33-88) and ECOG PS was 0 (55.7%) or 1 (44.3%). 65.9% of pts had received 1 prior therapy for metastatic disease; 34.1% had >1. For the subgroup followed ≥24 wks (61 pts), confirmed ORR was 29.5% (18/61 pts; 95% CI: 18.5, 42.6). Six pts (9.8%) had complete responses, 12 (19.7%) had partial responses, and 7 (11.5%) had stable disease. 15/18 (83.3%) responses were ongoing. Response duration was 2.8-14.6+ mos (median not reached). 14/18 responses occurred by week 7. Median PFS was 2.6 mos (95% CI: 1.4, 4.2) and PFS rate at 6 mos was 36% (95% CI: 23, 49). Treatment-related (TR) AEs occurred in 59 pts (67.0%); those occurring ≥10% were fatigue (21.6%) and infusion-related reaction (13.6%). Grade 3 TRAEs were reported in 3 pts (3.4%); there were no grade 4 TRAEs or treatment-related deaths. Conclusions: Avelumab showed a manageable safety profile with durable responses in pts with metastatic MCC who had progressed on chemotherapy. Additional clinical evaluation is warranted. *Proposed INN. Clinical trial information: NCT02155647.
A Phase 2 Study from Spanish Geltamo Group Investigating the Efficacy and Safety of Bendamustine As Part of Conditioning Regimen for Autologous Stem-Cell Transplantation in Patients with Aggressive Lymphomas: Second Interim Analysis
Authors: Alejandro Martín, Alba María Redondo, David Valcárcel, Ana Pilar Gonzalez, Armando López-Guillermo, José Luis Bello, Miguel A. Canales, Jorge Gayoso, Eulogio Conde, Isidro Jarque, Raquel Del campo, Reyes Arranz, María-José Terol, Jose J. Rifon, María-José Rodríguez, María-José Ramírez, Carlos Grande, Andrés Sánchez, Javier López-Jiménez, Dolores Caballero
Journal: Blood (2014)
Measuring the Real Clinical Impact of Randomized Clinical Trials in Oncology—Reply
Authors: Joseph M. Unger, Willliam E. Barlow, Dawn L. Hershman
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Early outcome of phase II study of preoperative chemotherapy (CX) with S-1 plus cisplatin for stage IV gastric cancer (StIV GC).
Authors: S. Satoh, H. Okabe, S. Teramukai, S. Hasegawa, N. Ozaki, S. Ueda, A. Tsuji, S. Sakabayashi, Y. Sakai
Journal: Journal of Clinical Oncology (2010)

4124 Background: Prognosis of StIV GC is poor due to unresectability and high frequency of peritoneal dissemination. S-1 plus cisplatin now becomes one of the Japanese standards for unresectable or recurrent GC. Therefore, we conducted a multicenter phase II study of preoperative S-1 plus cisplatin for StIV GC confirmed by helical CT and staging laparoscopy (KYUH-UHA- GC03-01, NCT00088816). Methods: Eligibility criteria included histologically proven StIV GC according to Japanese staging system; no prior therapy; PS 0,1; 20- 80 years old. Helical CT and staging laparoscopy were mandatory in all cases. Patients (pts) received oral S-1 (80-120 mg/body, b.i.d., day 1-21) and intravenous cisplatin (60 mg/m2 on day 8) every 5 weeks for 2 courses. After CX, gastrectomy with D2 lymph node dissection was performed. S-1 (80-120 mg/body, b.i.d., day 1-14) was administered every 3 weeks for one year postoperatively. The primary endpoint was %2-year overall survival, and the secondary endpoints were time to progression, %response, %pathologic response, %R0 resection, surgical complication, the first recurrence sites and toxicities. Sample size of 46 was required to show significant improvement of this therapy compared with our historical control (one-sided alpha: 0.025, power: 0.80). Results: 51 pts were enrolled in this study. The median age was 63 (range 35-79); male/female: 29/22; PS0/1: 44/7. CX was accomplished in 44 cases (ave. 1.80 cycles). Grade 3/4 neutropenia was observed 25%. In 20 cases with the measurable lesions, response was CR in 2, PR in 8, %response was 50% (95%CI 27.2-72.8%). 44 (86.3%) pts underwent surgery and R0 resection was done in 26 pts (51%). %R0 in GC with single StIV factor (n = 24) was 79.2% and that in GC with multiple StIV factors (n = 27) was 25.9%, respectively. No treatment related death was observed. Operative morbidity was 18.2%. Conclusions: The combination of S-1 and cisplatin was feasible and promising as preoperative chemotherapy regimen for patients with St.IV GC. No significant financial relationships to disclose.
<i>Ogg1</i> -Dependent DNA Repair Regulates NLRP3 Inflammasome and Prevents Atherosclerosis
Authors: Gantsetseg Tumurkhuu, Kenichi Shimada, Jargalsaikhan Dagvadorj, Timothy R. Crother, Wenxuan Zhang, Daniel Luthringer, Roberta A. Gottlieb, Shuang Chen, Moshe Arditi
Journal: Circulation Research (2016)

Rationale: Activation of NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome-mediating interleukin (IL)-1β secretion has emerged as an important component of inflammatory processes in atherosclerosis. Mitochondrial DNA (mtDNA) damage is detrimental in atherosclerosis, and mitochondria are central regulators of the nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 inflammasome. Human atherosclerotic plaques express increased mtDNA damage. The major DNA glycosylase, 8-oxoguanine glycosylase (OGG1), is responsible for removing the most abundant form of oxidative DNA damage. Objective: To test the role of OGG1 in the development of atherosclerosis in mouse. Methods and Results: We observed that Ogg1 expression decreases over time in atherosclerotic lesion macrophages of low-density lipoprotein receptor ( Ldlr ) knockout mice fed a Western diet. Ogg1 −/− Ldlr −/− mice fed a Western diet resulted in an increase in plaque size and lipid content. We found increased oxidized mtDNA, inflammasome activation, and apoptosis in atherosclerotic lesions and also higher serum IL-1β and IL-18 in Ogg1 −/− Ldlr −/− mice than in Ldlr −/− . Transplantation with Ogg1 −/− bone marrow into Ldlr −/− mice led to larger atherosclerotic lesions and increased IL-1β production. However, transplantation of Ogg1 −/− Nlrp3 −/− bone marrow reversed the Ogg1 −/− phenotype of increased plaque size. Ogg1 −/− macrophages showed increased oxidized mtDNA and had greater amounts of cytosolic mtDNA and cytochrome c , increased apoptosis, and more IL-1β secretion. Finally, we found that proatherogenic miR-33 can directly inhibit human OGG1 expression and indirectly suppress both mouse and human OGG1 via AMP-activated protein kinase. Conclusions: OGG1 plays a protective role in atherogenesis by preventing excessive inflammasome activation. Our study provides insight into a new target for therapeutic intervention based on a link between oxidative mtDNA damage, OGG1, and atherosclerosis via NLRP3 inflammasome.
Assessment of vincristine safe preparation and administration in Riyadh hospitals.
Authors: Nagwa Abdel Rahman Ibrahim, Mariyam Alfaqih, Razan AlGhunaim, Nahla Alaqeel
Journal: Journal of Clinical Oncology (2016)

e18212 Background: Vincristine is an antineoplastic agent that should be given by IV route only. Unintentional IT administration of vincristine may lead to death. The risk of this medication error is recurrent and well documented. The purpose of this study is to assess the awareness of healthcare practitioners about the safe handling of vincristine and to verify the approaches followed in Riyadh city governmental hospitals to prevent this fatal error. Methods: A descriptive survey consisting of 41 questions was designed based on recommendations from world health organization, joint commission international and the institute of safe medication practices. It was distributed to nurses, pharmacy technicians and pharmacists in 6 main governmental hospitals in Riyadh city. Results: Surveys were completed by 266 participants. About 63.9% practitioners in these hospitals stated that vincristine was prepared in a minibag while only 16.9% respondents said that the syringe was employed in preparation of vincristine, the main reasons for that were shorter administration time and lower risk of extravasation. In four hospitals, most of the staff answered that they are educated about the risks associated with intrathecal administration in a range of 53%- 81%. Surprisingly, when practitioners were asked about the consequence of giving vincristine intrathecally, only 65% in all hospitals answered that it will lead to death. Conclusions: The participants answers indicates that there is a policy in each hospital but in general there are deficiencies in implementing important safety practices as recommended by international bodies. Further regulations and education are needed to improve awareness and eradicate the possibility of this fatal medication error.
The modulation of tumor vessel permeability by thalidomide and its impacts on different types of targeted drug delivery systems in a sarcoma mouse model
Authors: Dan Wang, Jijun Fu, Yujie Shi, Dong Peng, Lan Yuan, Bing He, Wenbing Dai, Hua Zhang, Xueqing Wang, Jie Tian, Qiang Zhang
Journal: Journal of Controlled Release (2016)
Erythropoietin Resistant Anemia Following Burn Trauma Is in Part Due to Defective Terminal Maturation of Orthochromatic Erythroblasts Influenced By Erythroblast Island Macrophages
Authors: Shirin Hasan, Ameet R Kini, Andrea Szilagyi, Peggie Conrad, Richard L Gamelli, Kuzhali Muthumalaiappan
Journal: Blood (2015)
‘Acute myeloid leukemia: a comprehensive review and 2016 update’
Authors: I De Kouchkovsky, M Abdul-Hay
Journal: Blood Cancer Journal (2016)

Abstract Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with an incidence of over 20 000 cases per year in the United States alone. Large chromosomal translocations as well as mutations in the genes involved in hematopoietic proliferation and differentiation result in the accumulation of poorly differentiated myeloid cells. AML is a highly heterogeneous disease; although cases can be stratified into favorable, intermediate and adverse-risk groups based on their cytogenetic profile, prognosis within these categories varies widely. The identification of recurrent genetic mutations, such as FLT3-ITD, NMP1 and CEBPA, has helped refine individual prognosis and guide management. Despite advances in supportive care, the backbone of therapy remains a combination of cytarabine- and anthracycline-based regimens with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens, and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of AML.
P13 Allo- and auto-antibody responses in alcoholic liver disease as biomarkers of prognosis
Authors: I Patanwala, J Palmer, E Henderson, C Day, D Jones
Journal: Gut (2010)

Introduction  Alcoholic liver disease (ALD) frequently has a poor prognosis and in many populations, including in the UK, its impact is growing as a result of alcohol consumption patterns. Whereas abstinence from alcohol is clearly the optimum approach to treatment, patients need to survive the initial episode of liver disease in order to benefit. Although the trigger for ALD is self-evident, the process by which alcohol gives rise to liver injury remains unclear, precluding the informed targeting of interventions based on ameliorating pathogenic processes. Furthermore, we lack reliable biomarkers to identify patients at particular risk of poor outcome at the outset of a liver disease episode in order to target therapy. Several studies have identified the presence, in sub-sets of ALD patients, of antibodies reactive with adduct-modified self-proteins such as malondialdehyde (MDA)-adducted albumin (MDA-HSA) and self-antigens such as cytochrome P450 2E1 (Cyp2E1, arising, it is thought as a consequence of an “altered-self” mechanism). To date, however, the biological significance of these antibodies and the implications that they hold for prognosis and treatment are unclear.  Aim  In this study we set out, in a serial cohort of 38 ALD patients (all cirrhotic and all continuing to consume alcohol), to address the biological significance of auto- and allo-antibody responses.  Method  Patients were fully phenotyped with regard to their antibody, clinical, biochemical and histological status. Clinical follow-up was then undertaken for 5 years.  Results  The presence of both MDA-HSA and Cyp2E1 reactive antibody was significantly associated with risk of death during follow-up (Cyp2E1 AUC for prediction of death during follow-up 0.78 (95% CI 0.64 to 0.93), p=0.01; MDA 0.73 (0.55–0.92, p=0.05). An optimal composite measure based on reactivity to both antigens was highly predictive of risk of death during follow-up (auc 0.83 (0.7–0.96, p=0.005)). Interestingly amongst baseline biochemical parameters only bilirubin was (weakly) predictive of death during follow-up (auc 0.74 (0.62–0.92), all other biochemical parameters p=ns). Individual histological parameters were similarly not predictive of death during follow-up.  Conclusion  Antibody reactivity with allo- and auto-antigens in ALD is a predictor of poor outcome and the optimal composite risk measure warrants prospective validation in outcome series. It is unclear at present whether the association with antibody reactivity results from a pathogenetic process (immune-mediated damage driving liver injury) or occurs as a consequence of enhanced injury (increased liver damage enhancing reactivity to these antigens). Further work in this area is warranted.
Antithymocyte Rabbit Globulin Is Safe and Effective in Children with Severe Aplastic Anemia Report Polish Pediatric Hematology Group (Warszawa, Krakow, Wroclaw, Bydgoszcz, Poznan, Lodz, Bialystok, Szczecin, Gdansk).
Authors: Katarzyna Pawelec, Michal Matysiak, Malgorzata Salamonowicz, Walentyna Balwierz, Ewa Zaleska-Czepko, Alicja Chybicka, Krzysztof Szmyd, Danuta Sonta-Jakimczyk, Halina Bubala, Mariusz Wysocki, Andrzej Kurylak, Jacek Wachowiak, Grzegorz Grund, Wojciech Mlynarski, Monika Bulas, Maryna Krawczuk-Rybak, Elzbieta Leszczynska, Tomasz Urasinski, Jaroslaw Peregud-Pogorzelski, Barbara Kaczorowska, Anna Balcerska
Journal: Blood (2009)
Racial/ethnic difference in initiation and timing of adjuvant endocrine therapy among older women with hormone receptor-positive breast cancer.
Authors: Albert Farias, Xianglin L. Du
Journal: Journal of Clinical Oncology (2016)

e18076 Background: Adjuvant endocrine therapy (AET) effectively reduces breast cancer recurrence and mortality, however, a substantial proportion of breast cancer patients indicated for AET treatment do not take AET altogether or do not initiate in a timely manner. Therefore, we determine whether there are racial/ethnic differences in initiation and timing of AET among women enrolled in Medicare Part D. Methods: We conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results Medicare-linked data to assess racial/ethnic, socio-demographic, and tumor characteristic variations in the initiation of AET among patients over the age of 65 with hormone receptor-positive breast cancer enrolled in Medicare Part D from 2007-2009. We used logistic regression models to assess the association between race/ethnicity and the initiation of tamoxifen, aromatase inhibitors (AIs), and overall AET within the first 12 months of diagnosis. Results: Of the 12,198 women with hormone receptor-positive breast cancer, 74.8% received AET within 12 months of diagnosis of which 17.3% received tamoxifen, and 82.8% received AIs. After controlling for all variables, Asian women were found to have a greater odds of initiation of overall AET compared to non-Hispanic white women (OR 1.28, 95% CI 1.03-1.58). Hispanic Mexicans and non-Hispanic black patients had a significantly lower odds of tamoxifen initiation compared to non-Hispanic white patients (OR 0.70, 95% CI 0.54-0.91; OR 0.25, 95% CI 0.10-0.62). For AI initiation, Hispanic Mexicans and Asians had a higher odds compared to non-Hispanic white women (OR 2.06, 95% CI 1.34-3.10; OR 1.33, 95% CI 1.11-1.61). Black patients had a significantly lower odds of early initiation within the first 6 months of diagnosis compared to Non-Hispanic white patients (OR 0.85, 95% CI 0.72-1.00). Conclusions: A suboptimal proportion of women did not initiate AET within 12 months of diagnosis and therefore do not receive the full benefits of treatment. Racial/ethnic differences in the initiation of tamoxifen and AIs has important implications on cost, adherence to treatment, and side-effects that require further investigation.
STEM-24miR-340 ACTS AS A TUMOR SUPPRESSOR IN TUMORIGENESIS OF HUMAN GLIOMA-INITIATING CELLS BY TARGETING TISSUE PLASMINOGEN ACTIVATOR
Authors: Daisuke Yamashita, Toru Kondo, Hisaaki Takahashi, Satoshi Suehiro, Shohei Kohno, Shiro Ohue, Takanori Ohnishi
Journal: Neuro-Oncology (2015)
Tracking: an answer to psychiatry's recruitment problem?
Authors: W Weintraub, G U Balis, L Donner
Journal: American Journal of Psychiatry (1982)

Part of psychiatry's recruitment problem stems from large-scale defections among students who were planning careers in psychiatry when they entered medical school. The authors present data indicating that University of Maryland freshmen who preferred psychiatry were more than four times as likely to enter psychiatric residency training if they participated in the Combined Accelerated Program in Psychiatry, a continuous 4-year medical school track, than if they pursued the regular undergraduate psychiatry program. The authors believe that an enthusiastic psychiatric faculty intimately involved with students over an extended period of time was the crucial factor neutralizing antipsychiatric socialization experiences in medical school.
PD3-3-2: A randomized double-blind Phase IIa dose-finding study of vandetanib in Japanese patients with NSCLC
Authors: Yuichiro Ohe, Katsuyuki Kiura, Kazuhiko Nakagawa, Tetsu Shinkai, Kenji Eguchi, Nobuyuki Yamamoto, Masahiro Tsuboi, Soichiro Yokota, Haiyi Jiang, Kazuto Nishio
Journal: Journal of Thoracic Oncology (2007)
Case 49-1963
Authors: Lloyd H. Smith, Austin L. Vickery
Journal: New England Journal of Medicine (1963)

Presentation of Case* First admission. A fifty-nine-year-old woman was admitted to the hospital because of a persistent cough.Six weeks previously she had the onset of a dry, hacking cough accompanied by anorexia, profuse nocturnal sweating and an intermittent fever, with occasional elevation of the temperature to 102°F. She experienced tight sensations in the chest and weakness, but there was no hemoptysis, chest pain or dyspnea. Shortly before admission her physician told her that she was anemic. Mild pain in the right ear developed three weeks before entry.The patient had not been exposed to tuberculosis, animals or noxious fumes . . .
Antileukemic HLA-Restricted T-Cell Clones Generated With Naturally Processed Peptides Eluted From Acute Myeloblastic Leukemia Blasts
Authors: Marina Ostankovitch, Agnès Buzyn, Delphine Bonhomme, Francine Connan, Didier Bouscary, Fahrad Heshmati, François Dreyfus, Jeannine Choppin, Jean-Gérard Guillet
Journal: Blood (1998)
Hypermethylation of N33 (TUSC3) as independent molecular predictor for ovarian cancer
Authors: Dietmar Pils, Peter Horak, Andreas Kirisits, Andreas Gleiss, Markus Omann, Alexander Pinter, Christoph Zielinski, Alexander Mustea, Dominique Koensgen, Robert Zeillinger, Michael Krainer
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3224 

Purpose: In ovarian cancer routinely used clinical markers include tumor stage, grading and residual tumor after primary debulking surgery. Molecular biomarkers add little information to date and need to be explored. Methods: TUSC3 (formerly N33 ) expression - shown previously to correlate with disease progression [Pils et al., Cancer, 2005] - was evaluated by quantitative real-time RT-PCR in a large ovarian cancer population. Consequently, hypermethylation of the TUSC3 promoter was studied by methylation specific PCR. Both factors and clinical variables were analyzed as prognostic markers for ovarian cancer by statistical methods. Results: TUSC3 expression was significantly downregulated in ovarian cancer samples compared to controls ( P < 0.001). Epigenetic mechanisms were the responsible cause in most but not all cases. Additionally, in 8 of 38 ovarian cancer cell lines expression of TUSC3 was missing, seven of them were hypermethylated. A concentration-dependent reconstitution of TUSC3 expression with a DNA-demethylating agent in two hypermethylated cell lines was shown. At primary diagnosis 29.4% (30/102) of ovarian cancer patients showed hypermethylation of the TUSC3 promoter versus none of the controls. TUSC3 expression and hypermethylation at the time of diagnosis had a strong influence on progression free (relative risk 2.07 (CI 1.06-4.02), P = 0.03) and overall survival (relative risk 4.08 (CI 1.41-11.81), P = 0.01) which was independent from other prognostic factors (histology, FIGO, grade, age at diagnosis, residual tumor, and response to chemotherapy). Conclusion: In about one third of ovarian cancer patients downregulation of expression of TUSC3 is primarily caused by promoter hypermethylation. Whereas the functional relevance is unclear to date this phenomenon has a considerable impact on prognosis in ovarian cancer patients, and could provide new treatment decision guidance, particularly given the development of DNA-demethylating chemotherapeutics.