tbuckley/cabot-search huggingface dataset:
Investigation of the HDAC inhibitor resminostat in patients with sorafenib-resistant hepatocellular carcinoma (HCC): Clinical data from the phase I/II SHELTER study.
Authors: Michael Bitzer, Marius Horger, Tom M Ganten, Jens T Siveke, Marcus A Woerns, Matthias M. Dollinger, Guido Gerken, Max E. Scheulen, Henning Wege, Edoardo G Giannini, Vincenzo Montesarchio, Anna Mais, Rüdiger Jankowsky, Bernhard Hauns, Bernd Hentsch, Ulrich Lauer
Journal: Journal of Clinical Oncology (2012)

262 Background: Resminostat (4SC-201), an oral pan-HDAC inhibitor, is in clinical development in a variety of cancer indications. The SHELTER study aims to evaluate safety, tolerability and efficacy in HCC patients (pts) exhibiting progressive disease under sorafenib first-line therapy. Methods: Pts with advanced HCC, (BCLC B or C) are included in a multi-center, open-label, two-arm parallel group trial. Radiologic progression under sorafenib is determined acc. to RECIST by central review prior to study entry. For Arm A, dose escalation of resminostat and sorafenib is performed to determine the MTD. Resminostat is administered orally once-daily in a “5+9” schedule, consisting of 5 consecutive treatment days followed by a 9-day rest period resulting in 14 day cycles on dose levels of 200 (DL1), 400 (DL2) and 600 mg (DL3+4), either combined with continuously taken sorafenib at 400 (DL1-3) or 800 mg (DL4) (Arm A), or as resminostat monotherapy (600 mg, Arm B). Primary objective is to determine progression-free survival after 12 weeks (w) (6 cycles). Secondary objectives include safety, tolerability, tumor response, TTP, OS, PK, biomarkers. Results: To date, 39 pts were treated with 600 mg resminostat alone or on DL1-4 in combination with sorafenib. Up to now, no DLT occurred in 5 pts treated on DL4. Most frequently AE observed include CTC grade 1-2 gastrointestinal complaints such as nausea and vomiting and skin disorders like rash, pruritus and HFSR. CTC Grade 3-4 toxicity documented in SAE reports consisted mainly of no-hematological events and was mostly related to the tumor disease. Interim results revealed that 15 out of 27 pts (56%) assessed after 6 w of treatment, and 11 out of 24 pts after 12 w displayed SD. In one patient treated on DL2, SD persisted for more than 1 year along with good long-term tolerability. Conclusions: Preliminary clinical data show a favorable drug profile of resminostat either in mono or in combination treatment with sorafenib. No DLT was observed on the highest DL of the combination therapy up to now. Initial data on toxicity and therapeutic activity to overcome resistance to sorafenib are promising and will be updated for the meeting.
Safety and Efficacy of Abbreviated Induction with Oral Fludarabine (F) and Cyclophosphamide (C) Combined with Dose-Dense IV Rituximab (R) in Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL) Aged &gt; 65 years : Results of a Multicenter Trial (LLC 2007 SA) On Behalf of the French Goelams/Fcgcll-WM Intergroup
Authors: Caroline Dartigeas, Eric Van Den Neste, Christian Berthou, Herve Maisonneuve, Stéphane Leprêtre, Marie-Sarah Dilhuydy, Marie-Christine Bene, Florence Nguyen-Khac, Remi Letestu, Florence Cymbalista, Sophie De Guibert, Thérèse Aurran, Kamel Laribi, Jean Pierre Vilque, Olivier Tournilhac, Alain Delmer, Pierre Feugier, Bruno Cazin, Anne-Sophie Michallet, Vincent Levy, Xavier Troussard, Roselyne Delepine, Bruno Giraudeau, Philippe Colombat, Véronique Leblond
Journal: Blood (2012)
Bone marrow fibrosis grade is an independent risk factor for overall survival in patients with primary myelofibrosis
Authors: B Li, P Zhang, G Feng, Z Xu, T Qin, Y Zhang, Z Sha, D Dong, H Zhang, L Fang, L Pan, N Hu, S Qu, W Cai, G Huang, Z Xiao
Journal: Blood Cancer Journal (2016)

Bone marrow fibrosis grade is an independent risk factor for overall survival in patients with primary myelofibrosis
Incidence, Predictors, and Significance of Severe Toxicity in Patients with HIV-Associated Hodgkin Lymphoma
Authors: Hatoon Ezzat, Matthew C Cheung, Lisa K Hicks, Kevin C Murphy, Chantal S Leger, Linda R Taggart, Jordana Boro, Julio SG Montaner, Marianne Harris, Linda M Vickars, Heather A Leitch
Journal: Blood (2008)
Association Between Learning Environment Interventions and Medical Student Well-being
Authors: Lauren T. Wasson, Amberle Cusmano, Laura Meli, Irene Louh, Louise Falzon, Meghan Hampsey, Geoffrey Young, Jonathan Shaffer, Karina W. Davidson
Journal: JAMA (2016)

<h3>Importance</h3> Concerns exist about the current quality of undergraduate medical education and its effect on students' well-being. <h3>Objective</h3> To identify best practices for undergraduate medical education learning environment interventions that are associated with improved emotional well-being of students. <h3>Data Sources</h3> Learning environment interventions were identified by searching the biomedical electronic databases Ovid MEDLINE, EMBASE, the Cochrane Library, and ERIC from database inception dates to October 2016. Studies examined any intervention designed to promote medical students' emotional well-being in the setting of a US academic medical school, with an outcome defined as students' reports of well-being as assessed by surveys, semistructured interviews, or other quantitative methods. <h3>Data Extraction and Synthesis</h3> Two investigators independently reviewed abstracts and full-text articles. Data were extracted into tables to summarize results. Study quality was assessed by the Medical Education Research Study Quality Instrument (MERQSI), which has a possible range of 5 to 18; higher scores indicate higher design and methods quality and a score of 14 or higher indicates a high-quality study. <h3>Findings</h3> Twenty-eight articles including at least 8224 participants met eligibility criteria. Study designs included single-group cross-sectional or posttest only (n = 10), single-group pretest/posttest (n = 2), nonrandomized 2-group (n = 13), and randomized clinical trial (n = 3); 89.2% were conducted at a single site, and the mean MERSQI score for all studies was 10.3 (SD, 2.11; range, 5-13). Studies encompassed a variety of interventions, including those focused on pass/fail grading systems (n = 3; mean MERSQI score, 12.0), mental health programs (n = 4; mean MERSQI score, 11.9), mind-body skills programs (n = 7; mean MERSQI score, 11.3), curriculum structure (n = 3; mean MERSQI score, 9.5), multicomponent program reform (n = 5; mean MERSQI score, 9.4), wellness programs (n = 4; mean MERSQI score, 9.0), and advising/mentoring programs (n = 3; mean MERSQI score, 8.2). <h3>Conclusions and Relevance</h3> In this systematic review, limited evidence suggested that some specific learning environment interventions were associated with improved emotional well-being among medical students. However, the overall quality of the evidence was low, highlighting the need for high-quality medical education research.
Post-Translational Modification and Differential Protein Binding Partners of CCAAT Enhancer Binding Protein Alpha (C/EBPα) p42 Versus p30 May Contribute to Aberrant C/EBPα Activity in Acute Leukemia
Authors: Matthew Silver, Nirmalee Abayasekara, Dylan Perry, Hong Sun, Nancy Berliner, Arati Khanna-Gupta
Journal: Blood (2008)
Measurement of Free Circulating Bcr-Abl Fusion Protein and Its Phosphorylation in Patients with Chronic Myeloid Leukemia.
Authors: I. Jilani, H. Kantarjian, H. Faraji, M. Gorre, J. Cortes, O. Ottmann, K. Bhalla, S. O’Brien, F. Giles, M. Albitar
Journal: Blood (2005)
Factors associated with vertebral fractures in men treated with androgen-deprivation therapy (ADT) for prostate cancer.
Authors: P. J. Saylor, M. L. Hancock, G. Barnette, M. S. Steiner, R. A. Morton, M. R. Smith
Journal: Journal of Clinical Oncology (2011)

205 Background: Fragility fractures are common among men and have the potential to cause considerable morbidity and mortality. Androgen deprivation therapy (ADT) for prostate cancer causes accelerated loss of bone mineral density (BMD) and is associated with increased risk for fractures. We evaluated clinical risk factors associated with fracture among men receiving ADT and at elevated risk for fracture due to age and/or BMD. Methods: Analysis included men receiving ongoing ADT for prostate cancer and enrolled in a phase III fracture prevention trial. All men were either age ≥ 70 years or had low BMD (T-score &lt; −1.5 for the lumbar spine or total hip). We analyzed baseline demographic and laboratory characteristics of those with and without vertebral fractures at the time of study entry. Given that the trial enrolled patients who were age &lt; 70 only if BMD was low, we conducted additional analyses confined to the portion of the cohort that was age ≥ 70. Results: A total of 162 of the 1,244 subjects (13.0%) had a vertebral fracture at baseline. Two factors were significantly associated with prevalent fractures: white race (p = 0.028 when compared with non-white race) and osteoporosis (p = 0.002 for osteoporosis at any site; p = 0.053 for osteoporosis at the spine; p = 0.002 for osteoporosis at the hip). Lower BMD was also significantly associated with fractures when analyzed as a continuous variable. Factors not associated with fractures included age, country of residence, ADT duration at baseline, ADT mode, body mass index, testosterone, estradiol, C-terminal telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase, and osteocalcin. Results were similar in analyses limited to men ≥ 70 years old (n = 1,002). Conclusions: Vertebral fractures cause substantial morbidity and mortality among men treated with ADT for prostate cancer. In this study of men receiving ADT, white race and low BMD were significantly associated with vertebral fractures. These observations should inform the assessment of fracture risk in this vulnerable population. [Table: see text]
Prognosis and non-sentinel lymph node status of the breast cancer patients with micrometastatic sentinel lymph nodes.
Authors: M. Takahashi, H. Jinno, T. Hayashida, S. Hirose, M. Mukai, Y. Kitagawa
Journal: Journal of Clinical Oncology (2011)

140 Background: Sentinel lymph node biopsy (SLNB) is a more sensitive and accurate nodal staging procedure than axillary lymph node dissection (ALND). Because of detailed pathologic evaluation in SLNs, more nodal micrometastases have been identified. However, it remains controversial whether to perform ALND for patients with micrometastases in SLNs and their prognostic significance is also a matter of debate. The purpose of this study is to determine the non-sentinel lymph node (NSLN) status and prognosis of the patients with micrometastatic SLNs. Methods: A prospective database of 1,012 clinically node-negative, T1-T2 breast cancer patients, who underwent SLNB from January 2002 to Dec 2010 at Keio University Hospital was analyzed. SLNs were detected using a combined method of isosulfun blue dye and small-sized technetium-99m-labeled tin colloid. Intraoperative frozen examination was performed with hematoxylin and eosin (HE) staining. SLNs, fixed and embedded in paraffin, were additionally diagnosed with HE staining and immunohistochemical (IHC) analysis. Results: Micrometastases in SLNs were found in 69 (6.8%) of 1,012 patients. Thirty eight (55.1%) of 69 patients with micrometastatic SLNs underwent immediate or delayed ALND and revealed no NSLN metastasis. Among 31 (44.9%) patients with micrometastatic SLNs who omitted ALND and axillary radiation therapy, no axillary lymph node recurrence has been observed after a median follow-up of 50 months, although 29 patients (93.5%) in these 31 patients received adjuvant systemic therapy. There is no significant difference in recurrence free survival between the patients with micrometastatic and negative SLNs (98.0% vs. 95.7%, respectively). Conclusions: These date suggested that it may not be necessary to perform ALND for the patients with micrometastatic SLNs and the presence of micrometastases in SLNs may not worsen prognosis with proper systemic therapy.
Role of detection of metastatic disease as a leading cause of screening failure in an ongoing phase III trial of zibotentan versus placebo in patients with nonmetastatic castration-resistant prostate cancer (CRPC).
Authors: E. Y. Yu, F. E. Nathan, C. S. Higano
Journal: Journal of Clinical Oncology (2011)

135 Background: Many patients with biochemical relapse after definitive therapy for prostate cancer receive androgen deprivation therapy. Although most patients experience a decline in PSA, PSA eventually rises despite a castrate level of testosterone. Many of these patients have non-metastatic disease and do not develop metastases for a median of 30 mos (Smith MR. JCO, 2005). However, there is no standard therapy for asymptomatic patients with non-metastatic CRPC. ENTHUSE M0 (Study 15) is an ongoing global phase III study comparing zibotentan 10 mg (an oral specific endothelin A receptor antagonist) vs placebo in non-metastatic CRPC patients. Co-primary endpoints are overall survival and progression-free survival; secondary endpoints are safety, PSA, quality of life, and time to symptomatic progression. Eligible patients are screened for metastases by bone and CT/MRI scan and other parameters. An unexpectedly high number of patients failed screening, prompting this analysis. Methods: All patients who were screened were included in the analysis. Reasons for exclusion were recorded. Results: As of June 3, 2010, 1,756 patients completed screening. Of these patients, 960 (55%) were randomized and 796 (45%) failed screening. The leading causes of screen failures are listed in the table. Exclusion rates by investigator specialty and country will be reported. Conclusions: As 30% of patients had metastatic disease on screening and were excluded, these data suggest that the frequency of asymptomatic metastases is high in men thought to have non-metastatic CRPC. These findings stress the value of periodic staging studies in men progressing from hormone sensitive to non-metastatic CRPC as metastatic CRPC patients may benefit from standard treatments or research treatments on other protocols. [Table: see text] [Table: see text]
Indirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysis
Authors: Tinevimbo Shiri, Samik Datta, Jason Madan, Alexander Tsertsvadze, Pamela Royle, Matt J Keeling, Noel D McCarthy, Stavros Petrou
Journal: The Lancet Global Health (2016)

The full extent to which childhood pneumococcal conjugate vaccines (PCV) can indirectly reduce illness in unvaccinated populations is not known. We aimed to estimate the magnitude and timing of indirect effects of PCVs on invasive pneumococcal disease.In this systematic review and meta-analysis, we searched bibliographic databases for non-randomised quasi-experimental or observational studies reporting invasive pneumococcal disease changes following PCV introduction in unvaccinated populations (studies published Sept 1, 2010, to Jan 6, 2016), updating the previous systematic review of the same topic (studies published Jan 1, 1994, to Sept 30, 2010). Two reviewers extracted summary data by consensus. We used a Bayesian mixed-effects model to account for between-study heterogeneity to estimate temporal indirect effects by pooling of invasive pneumococcal disease changes by serotype and serogroup.Data were extracted from 70 studies included in the previous review and 172 additional studies, covering 27 high-income and seven middle-income countries. The predicted mean times to attaining a 90% reduction in invasive pneumococcal disease were 8·9 years (95% credible interval [CrI] 7·8-10·3) for grouped serotypes contained in the seven-valent PCV (PCV7), and 9·5 years (6·1-16·6) for the grouped six additional serotypes contained in the 13-valent PCV (PCV13) but not in PCV7. Disease due to grouped serotypes contained in the 23-valent pneumococcal polysaccharide vaccine (PPV23) decreased at similar rates per year in adults aged 19-64 years (relative risk [RR] 0·85, 95% CrI 0·75-0·95) and 65 years and older (0·87, 0·84-0·90). However, we noted no changes in either group in invasive pneumococcal disease caused by the additional 11 serotypes covered by PPV23 but not PCV13.Population childhood PCV programmes will lead, on average, to substantial protection across the whole population within a decade. This large indirect protection should be considered when assessing vaccination of older age groups.Policy Research Programme of the Department of Health, England.
Learning from the lowest incidence rates in breast cancer: Health information from men, young women, and Native American/Alaskan native women.
Authors: V. Dedousi-Huebner, A. Chakravarti, T. Lautenschlaeger
Journal: Journal of Clinical Oncology (2011)

185 Background: Breast cancer rates by the NCI show the lowest incidence for young women under 30, Native American/Alaskan Native women and males overall. Using the National Health Interview Survey we set out to investigate what these three very heterogeneous appearing groups seem to have in common in order to possibly detect preventive factors for breast cancer. Methods: The NHIS is a continuous national survey of the US civilian population. The data are collected yearly through in-person computer assisted household interviews. All members of the household 17 years of age and over who are at home at the time of the interview were invited to participate and respond for themselves. Using the data from this survey provided by the Office of Analysis and Epidemiology, National Center for Health Statistics, Centers for Disease Control and Prevention, we controlled for gender, race/ethnicity, poverty level and age. Results: Over 29.5% of all questioned Native American/Alaskan Native women responded to be in good health while only 17.8% of all white women responded the same. The difference in reported health status between white women and white men was not statistically different. For the health status of women in different age groups we found a picture that is reverse to the incidence trend of breast cancer. The older the women, the more likely they were to respond that they were in good health. Conclusions: As can be expected from such heterogeneous groups they did not have one variable in common that might have a preventive effect on breast cancer. The higher estimate of positively reported health status in association with the low incidence of breast cancer of Native American/Alaskan Native women certainly makes it worth investigating the positive attributes associated with this group’s health behavior. Another more unsettling interpretation of the low incidence rate in this population may be attributed to health insurance coverage, 32.5%—more than double the rate of the population of Caucasian females—do not have health insurance coverage which might lead to a lower rate of reported cancer cases.
Causes of Death in Anticoagulated Patients With Atrial Fibrillation
Authors: Antonio Gómez-Outes, Julián Lagunar-Ruíz, Ana-Isabel Terleira-Fernández, Gonzalo Calvo-Rojas, Maria Luisa Suárez-Gea, Emilio Vargas-Castrillón
Journal: Journal of the American College of Cardiology (2016)
Purinergic mechanisms in breast cancer metastasis.
Authors: I. L. Buxton
Journal: Journal of Clinical Oncology (2011)

229 Background: Breast cancers survive in patients in a dormant state only to grow as metastatic disease in the future. Surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. Many breast cancer deaths might be averted if we understand the cellular mechanisms underlying escape from dormancy. We have proposed that extracellular nucleotide signaling constitutes a pathological axis from the transformed tumor cell to the endothelium in the service of intravasation, dissemination, extravasation and angiogenesis. We demonstrate a role for the dinucleotide kinase NM23/NDPK in the generation of signals that stimulate angiogenesis and escape from latency. Methods: We have employed protein purification and identification by Western blot, tubulogenesis, migration and proliferation assays in human endothelial cells, signaling assays of receptor activation, nucleotide and receptor transactivation/phosphorylation assays and tumor growth and metastasis imaging in immunocompromized mice (SCID) to establish a role of r nucleotides in breast cancer metastasis. Results: A panel of breast cancer cell lines, but not normal breast cells, shed/secrete large amounts of NM23 that is active as an ADP transphosphorylase. NM23 stimulates tubulogenesis, proliferation and migration in cultures of human endothelial cells in a manner blocked by purinergic receptor antagonist, inhibitors of the nucleoside diphosphate kinase activity of NM23, or by VEGFR2 antagonists. In SCID mice carrying MDA-MB-231 luciferase over-expressing breast cancers, NM23 appears in the blood early in tumorigenesis. Treatment with the P2Y1 receptor antagonist MRS2179, or the NM23 antagonist ellagic acid slows the growth of primary breast tumors and prevents metastatic tumor formation. Conclusions: NM23 secretion leading to nucleotide generation activates endothelial P2Y1 receptors resulting in transactivation of VEGFR2 and angiogenesis in support of metastasis. Identification of Nm23 as a marker of early of breast cancer development and blockade of the extracellular actions of NM23 offer a new approach to breast cancer detection and treatment.
Macroscopic tumor size as an independent prognostic factor for patients with stage II/III gastric cancer who underwent D2 gastrectomy followed by adjuvant chemotherapy with S-1.
Authors: Toru Aoyama, Takaki Yoshikawa, Tsutomu Hayashi, Hiroshi Kuwabara, Yo Mikayama, Takashi Ogata, Haruhiko Cho, Akira Tsuburaya
Journal: Journal of Clinical Oncology (2012)

56 Background: In patients with stage II/III gastric cancer, tumors often recur even after curative D2 gastrectomy followed by adjuvant S-1 chemotherapy. The objective of this retrospective study was to clarify the prognostic factors in these patients that might be useful for future patients. Methods: Overall survival was examined in 82 gastric cancer patients who underwent curative D2 surgery, were diagnosed with stage IIA, II B, IIIA, IIIB, or IIIC pathologically, and received adjuvant S-1 after surgery between June of 2002 and March of 2010. Results: When overall survival was compared by the log-rank test, a significant difference was observed with regard to macroscopic tumor diameter and the depth of tumor invasion. A macroscopic tumor diameter greater than 70mm was regarded as a critical point of classification considering the survival. Uni- and muliti-variate Cox’s proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The five-year survival was 64.9% in patients with a macroscopic tumor diameter &lt;70mm, and 33.1% in patients with a macroscopic tumor diameter ≥70mm (P=0.022). Conclusions: The macroscopic tumor diameter was the most important prognostic factor for survival in patients with stage II/III gastric cancer who underwent D2 gastrectomy followed by adjuvant S-1 chemotherapy. Prognostic factors can be affected by adjuvant chemotherapy.
New Transgenic Mouse Lines for Selectively Targeting Astrocytes and Studying Calcium Signals in Astrocyte Processes In Situ and In Vivo
Authors: Rahul Srinivasan, Tsai-Yi Lu, Hua Chai, Ji Xu, Ben S. Huang, Peyman Golshani, Giovanni Coppola, Baljit S. Khakh
Journal: Neuron (2016)
Absolute Values of Serum Immunoglobulin Free Light Chains Predict for Survival in Patients with Primary Systemic Amyloidosis Undergoing Peripheral Blood Stem Cell Transplant.
Authors: Angela Dispenzieri, Martha Q. Lacy, Jerry A. Katzmann, S. Vincent Rajkumar, Roshini S. Abraham, Suzanne R. Hayman, Shaji K. Kumar, Raynell Clark, Robert A. Kyle, Mark R. Litzow, David J. Inwards, Michelle A. Elliott, Ivana M. Micallef, Steve M. Ansell, Luis F. Porrata, Patrick Johnston, Steve R. Zeldenrust, Thomas E. Witzig, Philip R. Greipp, John A. Lust, Steve R. Russell, Morie A. Gertz
Journal: Blood (2005)