tbuckley/cabot-search huggingface dataset:
<i>CREBBP</i>Inactivation Promotes the Development of HDAC3-Dependent Lymphomas
Authors: Yanwen Jiang, Ana Ortega-Molina, Huimin Geng, Hsia-Yuan Ying, Katerina Hatzi, Sara Parsa, Dylan McNally, Ling Wang, Ashley S. Doane, Xabier Agirre, Matt Teater, Cem Meydan, Zhuoning Li, David Poloway, Shenqiu Wang, Daisuke Ennishi, David W. Scott, Kristy R. Stengel, Janice E. Kranz, Edward Holson, Sneh Sharma, James W. Young, Chi-Shuen Chu, Robert G. Roeder, Rita Shaknovich, Scott W. Hiebert, Randy D. Gascoyne, Wayne Tam, Olivier Elemento, Hans-Guido Wendel, Ari M. Melnick
Journal: Cancer Discovery (2016)

Abstract Somatic mutations in CREBBP occur frequently in B-cell lymphoma. Here, we show that loss of CREBBP facilitates the development of germinal center (GC)–derived lymphomas in mice. In both human and murine lymphomas, CREBBP loss-of-function resulted in focal depletion of enhancer H3K27 acetylation and aberrant transcriptional silencing of genes that regulate B-cell signaling and immune responses, including class II MHC. Mechanistically, CREBBP-regulated enhancers are counter-regulated by the BCL6 transcriptional repressor in a complex with SMRT and HDAC3, which we found to bind extensively to MHC class II loci. HDAC3 loss-of-function rescued repression of these enhancers and corresponding genes, including MHC class II, and more profoundly suppressed CREBBP-mutant lymphomas in vitro and in vivo. Hence, CREBBP loss-of-function contributes to lymphomagenesis by enabling unopposed suppression of enhancers by BCL6/SMRT/HDAC3 complexes, suggesting HDAC3-targeted therapy as a precision approach for CREBBP-mutant lymphomas. Significance: Our findings establish the tumor suppressor function of CREBBP in GC lymphomas in which CREBBP mutations disable acetylation and result in unopposed deacetylation by BCL6/SMRT/HDAC3 complexes at enhancers of B-cell signaling and immune response genes. Hence, inhibition of HDAC3 can restore the enhancer histone acetylation and may serve as a targeted therapy for CREBBP-mutant lymphomas. Cancer Discov; 7(1); 38–53. ©2016 AACR. See related commentary by Höpken, p. 14. This article is highlighted in the In This Issue feature, p. 1
Protective effects of <i>Aloe barbadensis</i> and <i>Myracrodruon urundeuva</i> on 5-fluorouracil-induced oral mucositis in hamsters
Authors: R. O. Sant'ana, S. G. Fonseca, C. B. Diogenes, R. N. Macedo, A. Alexandre, G. C. Brito, R. A. Ribeiro
Journal: Journal of Clinical Oncology (2007)

19606 Introduction: Oral mucositis (OM) is a frequent dose-limiting and costly complication of antineoplastic chemotherapy. It's caractherized by ulcerative lesions and cause pain, restrict food and fluids oral intake and substancial risk for sepsis. In severe cases, hospitalization, parenteral nutrition and opiode analgesics are required. Objectives: Evaluate the effects of extracts of two herbal medicines, Aloe barbadensis Miller (Ab) and Myracrodruon urundeuva Allemão (Mu) on 5-fluorouracil-induced OM in hamsters. To evaluate the possible mecanisms by the extracts act, it was performed analysis of intensity of activity of myeloperoxidase (MPO) and analysis of immunohistochemistry for TNFa e iNOS in the mucosa specimes. Methods: Golden siriam hamsters were submitted to intra- peritoneal 60 and 40 mg/Kg injections of 5-fluorouracil (5-FU) in day 1 and 2, respectively. On day 4, animals were submitted to anaesthesia, followed by mecanic trauma with needle to potenciate the effect of 5-FU. After that, the mucosas were treated with topical gel containing Mu extract at 5, 10 or 20%, Ab extract at 25, 50 or 100% (experimental groups) or carbapol gel (control group). The treatments above were mantained twice daily until day 9. On day 10 the animals were sacrified. Diferent parameters were evaluated: macroscopic and microscopic scores of OM, body mass variation and immunohistochemistry for TNFa e iNOS. Results: Mu significantly inhibited macroscopic oral mucositis at 5 and 10% concentrations (5% Mu - Md 2; 10% Mu - Md 3; control - Md 4, p &lt; 0,01). Ab also inhibited OM (25% Ab - Md 1; 50% Ab - Md 1,5; 100% Ab - Md 1; control - Md 4, p &lt; 0,001). These results were confirmed by histological analysis (5% Mu - Md 1,5; 10% Mu - Md 1; 25% Ab - Md 1; 50% Ab - Md 1,5; 100% Ab - Md 1; control - Md 2, p &lt; 0,01). MPO activity was significantly decreased by Mu and Ab compared to control animals. Both Mu and Ab decreased expression of TNFa e iNOS on tissue. It was observed a decrease on ponderal lost in experimental groups. Conclusions: Myracrodruon urundeuva and Aloe barbadensis cause important inhbitory effects in oral mucositis 5-FU induced probably by their antiinflamatory properties. No significant financial relationships to disclose.
An AS04-containing human papillomavirus (HPV) 16/18 vaccine for prevention of cervical cancer is immunogenic and well-tolerated in women 15–55 years old
Authors: T. F. Schwarz
Journal: Journal of Clinical Oncology (2006)

1008 Background: Genital HPV infections can be acquired shortly after sexual debut, and the risk remains throughout a sexually active woman’s lifetime. In women 15–25 years of age, the AS04-containing HPV vaccine was highly immunogenic and conferred 100% protection against HPV-16/18 persistent infection and associated cervical lesions up to 27 months. In the long-term follow-up of this study, sustained vaccine efficacy has been observed up to 48 months. The present phase III study (580299/014) assessed immune responses to the AS04-containing HPV-16/18 vaccine in women 26–55 years old compared with women 15–25 years old. Methods: Healthy women in Germany and Poland between 15 and 55 years of age received 3 doses of HPV-16/18 AS04-containing vaccine at months 0, 1, and 6. The groups were age stratified: 15–25 (n=229), 26–45 (n=226), and 46–55 (n=211). Anti-HPV-16/18 antibody titers were assessed at months 0, 2, 7, and 12 by ELISA (EU/mL). Seropositivity rates and geometric mean antibody titers (GMTs) were calculated for all groups. Safety was assessed after each dose in all participants. Results: All initially seronegative women became seropositive for both HPV 16 and 18 at Month 2. At Month 7, HPV-16 GMTs (95% CI) were 7908.4 (6874.0–9098.5) in 15–25 year olds, 4029.2 (3402.7–4771.0) in 26–45 year olds, and 2566.8 (2181.2–3020.6) in 46–55 year olds. For HPV-18, GMTs were 3499.3 (3098.7–3951.6) in 15–25 year olds, 1837.3 (1602.1–2107.0) in 26–45 year olds, and 1313.0 (1145.6–1504.9) in 46–55 year olds. Overall the vaccine was well-tolerated, and the incidence of local symptoms (within 30 days) tended to be lower in the 46–55 year-old group (69.2% versus 81.6% [26–45] and 85.7% [15–25]). Conclusions: An AS04-containing HPV-16/18 vaccine was immunogenic and generally safe in 15–55 year-old females. As observed with other vaccines, GMTs decreased with age, however, the Month 7 postvaccination antibody levels in the oldest age group (46–55) were still 3–4 times higher than those observed during a separate long-term follow-up study where sustained efficacy has been observed up to 48 months. [Table: see text]
Radiotherapy followed by temozolomide in the treatment of patients with melanoma metastatic to the brain: An Italian multicentre study
Authors: L. Serrone, A. Freschi, V. Chiarion-Sileni, R. Ridolfi, S. Toma, M. Guida, F. Cognetti
Journal: Journal of Clinical Oncology (2004)

7558 Background: Whole Brain Radiotherapy (WBRT) and systemic chemotherapy remain the mainstays of therapy for metastatic brain melanoma not amenable to surgical resection. The proven efficacy of Temozolomide (TMZ) on both primary and metastatic brain tumors prompted us to conduct this phase II study to determine the activity of TMZ treatment following WBRT in patients (pts) with untreated brain metastases from melanoma. Methods: Single CNS metastases eligible to surgery and/or stereotactic radiosurgery, prior treatment for CNS metastases, severe medical conditions interfering with oral intake were the main exclusion criteria. Treatment plan included : WBRT at 6 Gy/day administered over a two-week period (on wks 1–2) for 4 fractions (total dose 24 Gy), followed, on wk 7, by orally TMZ at a dose of 150 mg/m2/day × 5 days every 4 wks, for up to 6 cycles. Pts who received at least one cycle of TMZ were assessable for response. Results: Twenty-seven pts (15 M and 12 F, ages 26 to 72) entered the study. Number of CNS metastases was 1 (6 pts), ≥ 2 (21 pts, range 2–6). In most of the pts (85%), extracerebral disease sites were detected (range, 1–5). Ten pts (37%), after received RT as initial management, dropped out due to death or general physical impairment. Among 17 pts who started TMZ chemotherapy, 2 pts lost to follow-up, 6 pts prematurely withdrew from study due to cerebral progression, 9 pts received ≥ 3 cycles, and 5 pts completed treatment plan. The median number of TMZ cycles/pt was 3 (range, 1–6). Among 15 evaluable pts, 5 stabilization of disease and 3 partial responses on cerebral sites were achieved. The median survivals of pts who received RT alone or RT plus TMZ, were 35 days (range, 5–80 days) and 180 days (range, 56–360 days), respectively. Treatment related toxicity was minimal with only two dose-modifications required due to thrombocytopenia and vomiting. Conclusions: Compared with historical data, these preliminary results show that some of the pts who received complete treatment plan could achieve prolonged disease control and survival. Final data analysis will be presented. No significant financial relationships to disclose.
Aspirin for Primary Cardiovascular Risk Prevention and Beyond in Diabetes Mellitus
Authors: Davide Capodanno, Dominick J. Angiolillo
Journal: Circulation (2016)

Daily administration of low-dose aspirin has proved to be beneficial in preventing recurrent cardiovascular events. However, the role of aspirin for primary prevention in patients with no overt cardiovascular disease is more controversial. In fact, in lower risk patients, the modest benefit in reducing serious vascular events can be offset by the increased risk of bleeding, including intracranial and gastrointestinal hemorrhage. Diabetes mellitus has been associated with a substantially increased risk of both first and recurrent atherothrombotic events, which makes aspirin therapy of potential value in these subjects. Moving from general aspects of aspirin pharmacology and specific issues in diabetes mellitus, this article reviews the literature on the topic of aspirin for primary prevention in general, and in subjects with diabetes mellitus in particular, to culminate with arguments pro and con and a practical risk-based algorithm for aspirin initiation in daily practice.
Survival in previously treated advanced NSCLC: Pemetrexed versus best supportive care (BSC)
Authors: F. V. Fossella, D. A. Berry, S. Adachi, P. McAndrews, P. Peterson
Journal: Journal of Clinical Oncology (2006)

17015 Background: Patients with advanced NSCLC who progress following initial treatment have several approved secondary treatment options including single agent intravenous chemotherapy (docetaxel or pemetrexed) and an oral EGFR tyrosine kinase inhibitor (erlotinib). Docetaxel and erlotinib were shown in randomized trials to have an overall survival (OS) advantage over BSC. On the other hand, pemetrexed was approved based on a randomized trial (JMEI) in which it showed clinically equivalent survival to docetaxel. Investigators felt that it was not ethical to compare pemetrexed to BSC because docetaxel was approved in that setting. However, indirect comparisons of pemetrexed with BSC are possible and are legitimate statistically. Methods: We used summary data from JMEI and TAX317(b) in the analysis. Studies BR21 and ISEL provide relevant data from recent trials with a BSC arm. We based comparisons on the logarithms of these HRs and their variances in proportional hazards models, accounting for interstudy variability. Results: Patients in these studies had similar prognostic characteristics. Docetaxel in TAX317(b) showed a significant survival benefit over BSC (HR = 0.56, 95% CI 0.35–0.88). In JMEI, the pemetrexed over docetaxel HR was 0.99 (95% CI 0.82–1.20). The HR of pemetrexed over BSC for survival was 0.55 (95% CI 0.33–0.90). The similarity of median OS for the placebo (or BSC) arms of studies TAX317(b), BR21 and ISEL supports the above analysis. Conclusions: In comparison with BSC pemetrexed lowers the hazard of mortality in previously treated advanced NSCLC by an estimated 45% (95% CI 10%-67%). [Table: see text] [Table: see text]
Prognostic Significance of Weight Loss and BMI during Induction Chemotherapy of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients
Authors: Zachary Smith, Gabriel Vidal, Michael Machiorlatti, Sara K. Vesely, Summer Frank, Adam S. Asch, Jennifer L Holter-Chakrabarty, Mohamad Khawandanah, Mohamad Cherry
Journal: Blood (2015)
GW27-e0690 Endovascular versus open surgical repair for the treatment of ruptured abdominal aortic aneurysm in a single Chinese tertiary vascular referral centre
Authors: Zheng Ziyu, Yan Xiong, Ruibin Cai, Jinli Liao, Jieyu Luo, Henghui Yin
Journal: Journal of the American College of Cardiology (2016)
Neoadjuvant bevacizumab treatment for colorectal liver metastasis: A retrospective study.
Authors: P. García, S. Alvarez, A. Muñoz, P. Lopez, M. Riesco, J. Adeva Alfonso, M. Martin
Journal: Journal of Clinical Oncology (2011)

613 Background: Patients with colorectal cancer (CRC) and liver metastases have a poor prognosis and may benefit from perioperative chemotherapy and disease resection. Bevacizumab is proven to improve outcomes in patients with metastatic CRC. Methods: This is a retrospective chart review performed in colorectal patients with liver metastases. All the patients were &gt; 18 years old and have undergone bevacizumab therapy as neoadjuvant treatment. Results: 20 patients were analyzed. Baseline characteristics: median age 54.8 (49.2-65.8) years; male 45%; ECOG 0/1 40%/60%, 13 patients had metastatic disease at the time of their initial diagnosis. Median time from diagnosis of metastasis to surgery was 7.1 (5.4-9.6) months. Primary tumour locations were rectum (21.4%), colon (64.3%) and colon and rectum (14.3%). 80% and 20% of the patients received one and two lines of treatment before surgery, respectively. Mean cycles were 7.3±3.4 and 3.5±1.8 in first and second line, respectively. In 95% of the patients resection was curative. Mean number of resected metastasis was 3.4±2.8. 90%·of the patients achieved complete resection (R0) and 10% incomplete resection (R1). All the synchronous primary tumours (15) were resected. Among 16 valuable patients for pathological response, 1 (6.3%) experienced a pCR, 11 (68.8%) major response and 4 (25%) minor response. The median DFS was 12.2 months. The median OS was 48.9 months. Only one patient experienced grade 3-4 toxicity (rectal haemorraghe). Most frequent surgical complications were anastomotic filtration (8.7%) and wound infection (8.7%). Most frequent hepatic toxicities after surgery were steatohepatitis (25%) and sinusoidal dilatation (20%). Conclusions: These data provide evidence that neoadjuvant chemotherapy including bevacizumab can be safely administered in patients with mCRC. No significant financial relationships to disclose.
DNMT3A Mutations Independently Predict Poor Outcome in Older AML Patients: A SWOG Report,
Authors: Fabiana Ostronoff, Megan Othus, Phoenix A. Ho, Stephen H. Petersdorf, Jeanne E. Anderson, John E. Godwin, Cheryl L Willman, Jerald P. Radich, Frederick R. Appelbaum, Derek L. Stirewalt, Soheil Meshinchi
Journal: Blood (2011)
Nilotinib Combined with Multi-Agents Chemotherapy for Adult Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Results of a Prospective Study from a Single Center
Authors: Bingcheng Liu, Ying Wang, Chunlin Zhou, Hui Wei, Dong Lin, Wei Li, Kaiqi Liu, Guangji Zhang, Shuning Wei, Yan Li, Benfa Gong, Yuntao Liu, Yingchang Mi, Jianxiang Wang
Journal: Blood (2015)
Multi-level selection, social signaling, and the evolution of human suffering gestures: The example of pain behaviors
Authors: Jacob M Vigil, Eric Kruger
Journal: Behavioral and Brain Sciences (2016)

Abstract Pain suffering has been naturally selected to be experienced and expressed within a wider social system. The communication of pain improves group coordination and decision-making about engaging in resource dependent and potentially risky endeavors. Recent findings warrant the development of a cohesive framework for understanding the reciprocal nature of pain expression and individual and group-level outcomes that can generate novel predictions on the heuristical expression of human suffering in naturalistic and clinical settings.
Attempting to Classify Prolonged Graft-Versus-Host-Disease According to Monocyte Activation Status in Addition to T-Cell
Authors: Rie Kuroda, Hideaki Maeba, Shintaro Mase, Raita Araki, Toshihiro Fujiki, Shoichi Koizumi, Akihiro Yachie, Ryosei Nishimura
Journal: Blood (2011)
Case 31-2016
Authors: Thomas N. Byrne, John H. Stone, Shiv S. Pillai, Otto Rapalino, Vikram Deshpande
Journal: New England Journal of Medicine (2016)

A 53-year-old man was seen in outpatient clinics of this hospital because of a 1-year history of diplopia, polydipsia, and polyuria. Imaging studies showed mucosal thickening of the sphenoid sinus and enlargement of the pituitary gland. A diagnostic procedure was performed.
Phase II trial of karenitecin (BNP1350) in malignant: Clinical and translational study
Authors: F. H. Hausheer, E. Berghorn, Z. Liu, D. Sullivan, B. Centeno, J. Derderian, R. Deconti, A. Daud, P. Sullivan, S. Andrews
Journal: Journal of Clinical Oncology (2004)

7554 Background: To determine the efficacy and safety of the novel camptothecin, karenitecin (BNP1350), in patients with metastatic melanoma and to measure the level of expression of topoisomerase I, IIα and IIβ through directed patient biopsy. Methods: Eligible patients had a histopathological diagnosis of metastatic melanoma with up to 3 prior chemotherapy regimens and any prior immunotherapy regimens. Treatment consisted of a 60-minute intravenous infusion of 1 mg/m2 of karenitecin daily for 5 consecutive days with cycles repeated every 3 weeks. Patients were evaluated for progression every 2 cycles and continued on treatment ifthey experienced clinical benefit as evidenced by stable disease or objective response to therapy. Fine needle aspiration biopsies were performed pre-treatment and on Day 3 to determine the topoisomerase expression from patients' tumors. Results: Forty-three patients were evaluable for tumor response and toxicity. The majority of patients (72%) had stage M1C disease and was previously exposed to chemotherapy (56%). This investigational new drug was well tolerated with limited GI side effects or fatigue. The major dose-limiting toxicity observed was reversible non-cumulative myelosuppression. One patient had a complete response after 11 months of therapy. No partial responses were noted, but 33% of the patients had disease stabilization lasting 3 months or longer. Topoisomerase I, IIα and IIβ expression and localization were determined prior to and on Day 3 of chemotherapy in 13 paired tumor samples, and pre- in an additional 7 patients. Topoisomerase I expression was highest, followed by topoisomerase IIβ and topoisomerase IIα. Conclusions: Karenitecin was a well-tolerated investigational agent in this Phase 2 study; side effects were generally mild and mostly hematological in this population with largely adverse prognostic factors. Karenitecin has moderate activity in metastatic melanoma. While melanoma metastases express high levels of topoisomerase I, there appears to be no correlation between topoisomerase expression with response in the subset of patients that underwent biopsies. Further studies are planned with this agent. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration BioNumerik Pharmaceuticals, Inc. BioNumerik Pharmaceuticals, Inc. BioNumerik Pharmaceuticals, Inc.
Pre-emptive pharmacogenetic testing implementation for chemotherapy dosage optimization: the translational experience at CRO of Aviano
Authors: E. Cecchin, L. Giodini, A. Buonadonna, M. Berretta, A. De Paoli, S. Scalone, G. Miolo, E. Mini, S. Nobili, T. Mazzei, S. Lonardi, V. Zagonel, N. Pella, G. Fasola, U. Tirelli, M. Montico, R. Roncato, G. Toffoli
Journal: Annals of Oncology (2015)
TCT-169 Increased troponin concentrations in patients with stable coronary artery disease are associated with thin-cap fibroatheroma and future major adverse cardiovascular events
Authors: Adam J. Brown, Anoop S. Shah, Mateusz Orzalkiewicz, Nick E. West, David E. Newby, Nicholas Mills, Martin R. Bennett, Patrick A. Calvert
Journal: Journal of the American College of Cardiology (2015)
TCT-360 Impact of Tissue Protrusion Assessed by Optical Coherence Tomography on Early Stent Thrombosis in Patients with ST Elevation Myocardial Infarction
Authors: Yasushi Ino, Takashi Kubo, Yoshiki Matsuo, Hironori Kitabata, Yasutsugu Shiono, Takeyoshi Kameyama, Shigetoshi Hikimoto, Makoto Orii, Yamano Takashi, Tomoyuki Yamaguchi, Akio Kuroi, Hiroshi Aoki, Ikuko Teraguchi, Keishi Ookochi, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2015)
TCT-181 Uric acid is neither the risk factor nor prognostic factor for clinical outcomes during 3-year follow-up period in coronary vasospastic angina
Authors: Sang-Ho Park, Seung-Woon Rha, Ung Jun, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Jin oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2015)
Impact of Socioeconomic Status and Distance from Treatment Center on Survival in Patients Receiving Remission Induction Therapy for Newly Diagnosed Acute Myelogenous Leukemia (AML).
Authors: Cristina Rodriguez, Rachid Baz, Rony Abou Jawde, Lisa Rybicki, Christopher Lowe, Matt Kalaycio, Anjali Advani, Ronald Sobecks, Mikkael A. Sekeres
Journal: Blood (2006)