tbuckley/cabot-search huggingface dataset:
Abstract 541: The oral proteasome inhibitor ONX 0912 has bone anabolic effects in addition to anti-myeloma effects
Authors: Michelle A. Hurchla, Mary C. Hornick, Aixiao Li, Lynne Collins, Christopher J. Kirk, David Piwnica-Worms, Ravi Vij, Michael H. Tomasson, Katherine N. Weilbaecher
Journal: Cancer Research (2011)

Abstract Multiple Myeloma (MM) is a cancer of antibody producing plasma cells in which tumors largely reside in and destroy the bone microenvironment. Drugs that inhibit proteasomal degradation of intracellular proteins such as those crucial for cell growth, have demonstrated significant efficacy in the treatment of MM. ONX 0912, is a next generation proteasome inhibitor that acts irreversibly and has the significant advantage of oral delivery. Pharmacokinetic data suggest that the in vivo serum half life of ONX 0912 is approximately 4 hours. We found that a physiologic 4 hour pulse treatment with low nanomolar doses of ONX 0912 effectively decreased the viability of human MM cell lines through the inhibition of proliferation and induction of apoptosis with similar efficacy as continuous drug administration in vitro. Because MM induces significant bone loss through the tumoral production of factors involved in the recruitment of bone resorping osteoclasts (OC) and suppression of bone forming osteoblasts (OB), we also evaluated the effects of ONX 0912 on bone cell viability and function. Bortezomib, an intravenous proteasome inhibitor in clinical use with a serum half-life of one hour, has been reported to suppress OC viability and enhance OB function. We found that culturing of primary murine macrophages, preosteoclasts, and OC under continuous incubation with bortezomib and ONX 0912 decreased cell viability, although at doses greater than 100-fold higher than those affecting MM cells. However, when primary macrophages and OC were incubated with a physiologic 1 hour pulse of bortezomib or 4 hour pulse of ONX0912, these cells were resistant to killing with in vitro osteoclastogenesis being modestly inhibited. In contrast, physiologic 4 hour pulse exposure of ONX 0912 to primary OB cultures, resulted in enhanced in vitro differentiation and mineralization. Likewise, oral administration of ONX 0912 to non-tumor bearing C57BL/6 mice significantly increased trabecular bone volume and bone mineral density. We then evaluated the effect of ONX 0912 on MM tumor burden and tumor associated bone loss in vivo. Oral administration of ONX 0912 significantly reduced the growth of human RPMI8226 MM cells in long bones of NOD-SCID-IL-2Rγc-/- mice and protected mice from bone loss compared to vehicle treated mice. These data suggest that, in addition to its anti-tumor effects, ONX 0912 may also shift the bone microenvironment during MM from a catabolic state to an anabolic state, reducing osteolysis, promoting bone formation and decreasing skeletal complications of MM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 541. doi:10.1158/1538-7445.AM2011-541
DISECCIÓN SUBMUCOSA ENDOSCÓPICA EN NUESTRO MEDIO. ¿DIFIEREN LOS RESULTADOS EN NEOPLASIAS GÁSTRICAS Y EN EL ÁREA COLORRECTAL?
Authors: JC Marín-Gabriel, J Díaz Tasende, P Hernán-Ocaña, A González-Blanco, S Rodríguez Muñoz, AJ Del Pozo García, M Alonso-Riaño, F Colina-Ruizdelgado, M Pérez Carreras, A Domínguez-Rodríguez, G Castellano Tortajada
Journal: Endoscopy (2013)

Introducción: Los expertos nipones recomiendan iniciar el aprendizaje de la DSE en lesiones gástricas y, paulatinamente, pasar al colon. Objetivo: Evaluar si se detectan diferencias en la duración del procedimiento y otros parámetros relacionados con la técnica o las complicaciones en las lesiones gástricas (G) comparadas con el área colorrectal (CR). Material y Métodos: Se recogieron de forma prospectiva los datos de neoplasias G y CR resecadas mediante DSE. Resultados: Se llevaron a cabo 51 D.S.E.s entre septiembre de 2008 y junio de 2013 (15 G y 31 CR en el Hospital Universitario 12 de Octubre de Madrid así como 1 G y 4 CR en el Hospital Sanitas La Moraleja). El ratio G vs. CR fue 1: 2,2. No se detectaron diferencias estadísticamente significativas en la distribución por edad (mediana 75,5 años G vs. 67 años CR; p = 0,3) ni sexo (hombres 50% G vs. 57,1% CR; p = 0,63). La mediana de tamaño de las lesiones fue superior de manera estadísticamente significativa en las CR (24 mm G vs. 31 mm CR; p = 0,01) así como la duración del procedimiento (132,5 min. G vs. 185 min. CR; p = 0,04). No se detectaron diferencias significativas en la incidencia de perforaciones o sangrados (18,8% G vs. 27,3% CR; p = 0,73), la conversión a DSE híbrida (37,5% G vs. 45,7% CR; p = 0,58), el empleo de > 1 endoknife (50% G vs. 57,1% CR; p = 0,63) ni en el porcentaje de lesiones extirpadas en bloc (62,5% G vs. 40% CR; p = 0,13). Las resecciones R0 se lograron más frecuentemente en las lesiones gástricas (56,2% G vs. 20% CR; p = 0,01), con significación estadística (OR: 5,14; IC95%: 1,42 – 18,66). Conclusión: La DSE en el área CR presenta mayor dificultad técnica: mayor tamaño de las lesiones y superior duración del procedimiento con menor proporción de resecciones R0.
Abstract 1477: Tumor cell-leukocyte fusion in human cancer: A melanoma brain metastasis with a donor-patient hybrid genome following allogeneic BMT
Authors: Rossitza Lazova, Greggory S. Laberge, Eric Duvall, Nicole Spoelstra, Mario Sznol, Dennis Cooper, Richard Spritz, John M. Pawelek
Journal: Cancer Research (2011)

Abstract Tumor cell fusion with motile bone marrow-derived cells (BMDCs) has long been proposed as a mechanism for metastasis, but while such fusion has been demonstrated in animal models little is known of this in human cancer. Here we report the first genetic evidence for BMDC-tumor fusion and genomic hybridization in a human melanoma brain metastasis from a patient with a prior allogeneic bone marrow transplant (male-male, sibling). STR analyses of DNA from melanoma cells throughout the tumor revealed the presence of both donor and patient alleles, with common aberrant allelic patterns at multiple chromosomal loci indicating a clonal origin of the tumor. Methods. All procedures were in accordance with HIPAA regulations and approved by the Yale HIC. Donor and patient DNAs were obtained from frozen lymphocytes and from a patient buccal swab. Formalin-fixed, paraffin-embedded tumor specimens were stained by immuniohistochemistry with common leucocyte antigen (CLA) in order to avoid leucocytes during microdissection of tumor cells. LCA-negative tumor cells were isolated with an Arturus XT laser dissection microscope system. DNA was extracted and analyzed for donor and patient alleles using forensic STR analyses at 13 chromosomal loci and amelogenin for the X and Y. Tissue sections were analyzed from 14 areas throughout the tumor. Results. DNA from donor and patient lymphocytes showed balanced diploidy at all loci and the allelic patterns were consistent with the sibling relationship. On the other hand, DNA from tumor cells contained a mixture of donor and host alleles at some loci, only donor or patient alleles at others, and numerous allelic imbalances throughout–particularly for the X and Y (X:Y = 2.8:1) that pointed to a probable tumor genotype of XXXY. With few exceptions, aberrant genetic profiles seen in one tumor section were seen in all, demonstrating a clonal origin of the tumor. Conclusions. The results provide the first genetic proof of leucocyte-tumor fusion and genomic hybridization in human cancer and indicate that the tumor was generated from a single fusion event. While this report concerns only one case, we demonstrate that forensic genetic analyses of tumors arising as secondary malignancies represents a fruitful area for research in tumor cell fusion in human cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1477. doi:10.1158/1538-7445.AM2011-1477
BMA urges government to return to junior contract negotiations
Authors: Abi Rimmer
Journal: BMJ (2016)

The BMA has urged the government to return to negotiations on a new junior doctor contract in England, ahead of a fourth round of industrial action.

Junior doctors are set to take industrial action, providing emergency care only for 48 hours, between 8am on Wednesday 6 April and 8am on Friday 8 April.

Johann Malawana, chair of the BMA’s Junior Doctors Committee, said that junior doctors were taking action because …
Abstract 955: n-3 polyunsaturated fatty acids promote apoptosis in oxidatively stressed transgenic mouse models
Authors: Yang-Yi Fan, Shinya Toyokuni, Evelyn S. Callaway, Qitao Ran, Joanne R. Lupton, Robert S. Chapkin
Journal: Cancer Research (2010)

Abstract Colorectal cancer is the second most common cause of cancer death in the United States. An increase in reactive oxygen species (ROS) generated from oxidative stress is generally associated with abnormal cancer cell growth and reflects a disruption of redox homeostasis. Manganese superoxide dismutase (SOD2) and glutathione peroxidase 4 (Gpx4) are two of the most important antioxidant defense enzymes that protect cells against oxidative stress. Interestingly, we have recently demonstrated that n-3 polyunsaturated fatty acids (PUFA) enhance apoptosis, a useful marker of colorectal cancer risk, in colonocytes by enhancing phospholipid oxidation. In order to elucidate the mechanisms regulating oxidative stress-induced apoptosis in vivo, we fed SOD2het, Gpx4het and Gpx4 over-expressing (Gpx4TG) transgenic mouse models diets containing either n-3 or n-6 PUFA (control). Animals were fed diets containing either 15% corn oil by weight (CO, enriched in n-6 PUFA) or 3.5% CO + 11.5% fish oil (FO, enriched in n-3 PUFA) for 4 wk. Apoptotic cells in the distal colon were enumerated in situ. Relative to their respective wild type siblings, Gpx4het and SOD2het mice had significantly (P&amp;lt;0.05) enhanced levels of colonocyte apoptosis, 63% and 20%, respectively. In contrast, apoptosis in Gpx4TG mice was significantly (P&amp;lt;0.05) reduced by 16% compared to wild type siblings. FO vs CO feeding further increased (P&amp;lt;0.05) apoptosis in Gpx4het and SOD2het mice by 42% and 18%, respectively. In addition, n-3 PUFA elevated apoptosis in Gpx4TG mice back to a level comparable with wild type (control) siblings. These data indicate that dietary and/or genetic pre-deposition to oxidative stress facilitates apoptosis in the colon, thereby reducing colon cancer risk. Supported in part by NIH grants CA59034, CA129444, P30ES09106, and USDA 2008-34402-19195, “Designing Foods for Health” through the Vegetable &amp; Fruit Improvement Center. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 955.
O5.02 * CORTICAL AND SUBCORTICAL LANGUAGE MAPPING WITH HIGHFREQUENCY (HF) STIMULATION: FEASIBILITY AND CLINICAL RESULTS
Authors: M. Riva, A. Comi, E. Fava, T. Alfiero, A. Casarotti, F. Pessina, L. Bello
Journal: Neuro-Oncology (2014)

Resection of language pathways tumors requires intraoperative identification of cortical and subcortical language essential sites. Language mapping is traditionally performed with LowFrequency(60Hz) stimulation. In patients with previous treatment or long history of seizures, the use of LF may be problematic and results in inadequate mapping. HighFrequency(HF)(To5) stimulation represents an alternative strategy. We present our experience with HF stimulation for language mapping in patients with gliomas involving language pathways. Efficacy of mapping was compared with LF, and clinical impact (percentage of immediate and permanent deficits) and Extent-of-Resection(EOR)) was also reported. 80 patients were included (49 were frontal, 21 temporal). HF (repetition rate of 3Hz) identified language sites in all patients. In patients with long history of seizures, high doses of antiepileptic drugs (AEDs), previous treatments, in whom LF induced seizures and was inadequate for mapping, HF efficiently identified language sites at cortical and subcortical level. In patients (30 cases) in whom LF and HF were compared, HF induced positive language responses in the same sites as LF, in frontal and temporal lobes. Intraoperative seizures were 24% with LF, 2% with HF, also in patients with previous history of seizures, high doses of AEDs. Percentage of immediate and permanent deficits were 78% and 2%, also in patients in whom only HF was used. EOR was total in 82%. HF(To5, repetition rate of 3Hz) represents an efficient alternative stimulation strategy for language mapping, particularly in patients with long history of seizures and high AEDs, associated with a low risk of intraoperative seizures.
Cancer treatment and survivorship statistics, 2014
Authors: Carol E. DeSantis, Chun Chieh Lin, Angela B. Mariotto, Rebecca L. Siegel, Kevin D. Stein, Joan L. Kramer, Rick Alteri, Anthony S. Robbins, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2014)

The number of cancer survivors continues to increase due to the aging and growth of the population and improvements in early detection and treatment. In order for the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborated to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results (SEER) program registries. In addition, current treatment patterns for the most common cancer types are described based on information in the National Cancer Data Base and the SEER and SEER‐Medicare linked databases; treatment‐related side effects are also briefly described. Nearly 14.5 million Americans with a history of cancer were alive on January 1, 2014; by January 1, 2024, that number will increase to nearly 19 million. The 3 most common prevalent cancers among males are prostate cancer (43%), colorectal cancer (9%), and melanoma (8%), and those among females are cancers of the breast (41%), uterine corpus (8%), and colon and rectum (8%). The age distribution of survivors varies substantially by cancer type. For example, the majority of prostate cancer survivors (62%) are aged 70 years or older, whereas less than one‐third (32%) of melanoma survivors are in this older age group. It is important for clinicians to understand the unique medical and psychosocial needs of cancer survivors and to proactively assess and manage these issues. There are a growing number of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. CA Cancer J Clin 2014;64:252–271. © 2014 American Cancer Society.
Radiofrequency ablation for the treatment of gastric antral vascular ectasia
Authors: Xavier Dray, Alessandro Repici, Pedro Gonzalez, Claus Fristrup, Stéphane Lecleire, Sergey Kantsevoy, Dov Wengrower, Peter Elbe, Marine Camus, Alessandra Carlino, Francisco Pérez-Roldán, Tomer Adar, Philippe Marteau
Journal: Endoscopy (2014)

<b>Background and study aims:</b> The traditional endoscopic treatment for gastric antral vascular ectasia (GAVE) is argon plasma coagulation, but results are not always positive. Radiofrequency ablation (RFA) is a new endoscopic therapy that may be an attractive option for the treatment of GAVE. The aim of this study was to assess the efficacy and safety of RFA for the treatment of GAVE. <b>Patients and methods:</b> This was an open-label, retrospective, case series study. The main outcome measures were number of red blood cell (RBC) packs transfused (transfusion requirement) and hemoglobin concentrations (g/dL) in the 6 months prior to and after RFA. Success was defined as a decrease in transfusion requirement in the 6 months after RFA compared with before treatment. <b>Results:</b> A total of 24 patients underwent a mean of 1.8 ± 0.8 RFA sessions. No complications were reported. One patient was referred for additional argon plasma coagulation during follow-up. The mean number of RBC packs decreased in all 23 transfusion-dependent patients, from a mean of 10.6 ± 12.1 during the 6 months prior to RFA, to a mean of 2.5 ± 5.9 during the 6 months after RFA treatment (<i>P</i> < 0.001), and 15 patients (65.2 %) were weaned off transfusions completely. An increase in the hemoglobin concentration was reported in all patients after RFA (from 6.8 ± 1.4 g/dL to 9.8 ± 1.8 g/dL; <i>P</i> < 0.001). <b>Conclusion:</b> RFA for the treatment of GAVE seems feasible and safe, and significantly reduced the need for RBC transfusion and increased the hemoglobin level in this retrospective case series.
A phase I trial of a bi-weekly combination of capecitabine/irinotecan (XELIRI) in solid tumors
Authors: E. Assenat, A. Kramar, P. Senesse, E. Samalin, F. Portales, M. Ychou
Journal: Journal of Clinical Oncology (2008)

13556 Background: Oral fluoropyrimidines, notably capecitabine, are increasingly replacing IV 5-FU/LV as the backbone of therapy for metastatic colorectal cancer. The bi-weekly combination of capecitabine/irinotecan warrants further examination. Methods: We conducted an open-label phase I trial, in metastatic cancer patients treated for solid tumors, to determine the recommended dose of capecitabine administered orally bid from day 1 to 8 in combination with a bi-weekly fixed-dose of IV irinotecan 180 mg/m2 delivered on day 1. Five increasing dose levels (DL1–5) of capecitabine were planned: 1000, 1250, 1500, 1750, and 2000 mg/m2 bid. The continual reassessment method was used for the dose-escalation strategy. Results: A total of 17 patients were enrolled, with a median age of 60 (range 52–73) years. All patients had an ECOG performance status of either 0 (59%), 1 (35%), or 2 (6%). Primary tumor types were: pancreatic adenocarcinoma (n=6), endocrine tumors (n=5), cholangiocarcinoma (n=2), esophageal adenocarcinoma (n=1), anal carcinoma (n=1), and adenocarcinomas with unknown primary site (n=2). Patients received a total of 122 (range 3–12) cycles at 4 dose levels (3 patients at DL1, 4 at DL2, 6 at DL3, and 4 at DL4). Four patients experienced dose-limiting toxicity: 2 (12%) patients developed grade 4 neutropenia (at DL 1 and 4) and 2 others (12%) developed grade 4 febrile neutropenia (at DL 3 and 4). No toxicity-related deaths occurred. The maximal tolerated dose (MTD) was DL4, and the recommended dose regimen was bi-weekly irinotecan 180 mg/m2 combined with capecitabine 1500 mg/m2 bid (administered from days 1 to 8). At this dose level, the capecitabine/irinotecan dose intensity is greater than that previously reported in many studies using a tri- or bi-weekly XELIRI combination. Conclusions: This bi-weekly combination of capecitabine/irinotecan (XELIRI) is feasible and could be tested in patients with metastatic colorectal cancer in combination with a targeted therapy. This phase I trial will be continued into a second stage to define the MTD of capecitabine in bi-weekly combination with a fixed dose of irinotecan and oxaliplatin (XELIRINOX). No significant financial relationships to disclose.
Folate-Responsive Homocystinuria and “Schizophrenia”
Authors: John M. Freeman, James D. Finkelstein, S. Harvey Mudd
Journal: New England Journal of Medicine (1975)

Original Article from The New England Journal of Medicine — Folate-Responsive Homocystinuria and "Schizophrenia" — A Defect in Methylation Due to Deficient 5,10-Methylenetetrahydrofolate Reductase Activity
FDA Approval of Flibanserin — Treating Hypoactive Sexual Desire Disorder
Authors: Hylton V. Joffe, Christina Chang, Catherine Sewell, Olivia Easley, Christine Nguyen, Somya Dunn, Kimberly Lehrfeld, LaiMing Lee, Myong-Jin Kim, Ashley F. Slagle, Julie Beitz
Journal: New England Journal of Medicine (2015)

After three reviews, the FDA approved flibanserin for hypoactive sexual desire disorder in premenopausal women, concluding that efficacy had been established but requiring a boxed warning, an alcohol contraindication, and a risk evaluation and mitigation strategy.
F-18 FDG Uptake Patterns and Disease Activity of Collagen Vascular Diseases-Associated Arthritis
Authors: Tetsuhiko Okabe, Hirofumi Shibata, Kazuya Shizukuishi, Tomohiro Yoneyama, Tomio Inoue, Ukihide Tateishi
Journal: Clinical Nuclear Medicine (2011)

Purpose: The purpose of the present study was to investigate F-18 FDG uptake patterns, and to see whether joint F-18 FDG uptake reflected disease activity in patients with collagen vascular diseases (CVD)-associated arthritis. Materials and Methods: A total of 72 patients with CVD-associated arthritis and 30 control subjects who underwent F-18 FDG PET or PET/CT were retrospectively investigated. PET images of 12 major joints, 7 minor joints, and extra-articular accumulation were assessed. We investigated F-18 FDG uptake patterns and the relationships between the degree of F-18 FDG uptake and distribution, clinical symptoms, and laboratory test results. Results: Remitting seronegative symmetric synovitis with pitting edema syndrome, mixed connective tissue disease, rheumatoid arthritis, and systemic sclerosis tended to show strong and multiple joint F-18 FDG uptake. F-18 FDG uptake was found in bone marrow (86%) and/or spleen (57%) in 7 patients with adult-onset Still disease. The maximum standardized uptake value (SUVmax) correlated with the counts of erythrocyte sedimentation rate, matrix metalloproteinase-3, IgG, and IgA. Joint swelling had a positive association with SUVmax. Multiple logistic regression analyses revealed that factor associated with increased SUVmax of the joint was joint swelling (P = 0.005). Conclusions: The degree of joint F-18 FDG uptake may contribute to predict active inflammatory process of the joint. In addition, F-18 FDG uptake patterns may have a potential which helps differential diagnosis of CVD-associated arthritis.
Immediate and Delayed Bronchoconstriction after Exercise in Patients with Asthma
Authors: Israel Rubinstein, Henry Levison, Arthur S. Slutsky, Hank Hak, Janet Wells, Noe Zamel, Anthony S. Rebuck
Journal: New England Journal of Medicine (1987)

Although an immediate asthmatic response after exercise is known to occur in some patients with asthma, the existence of a delayed asthmatic response after exercise is controversial. Accordingly, we studied 53 patients who had an immediate mean (±SD) decrease in forced expiratory volume at one second (FEV1) of 36±13 percent, which was maximal 13±12 minutes after the completion of treadmill exercise. Eight of these patients also had a delayed asthmatic response (a 32±5 percent decrease in FEV1 occurring 5.0±1.8 hours after exercise). During a control day, on which the FEV1 was measured serially but no exercise was performed, the same delayed asthmatic response was observed in all but one patient. This finding suggests that the delayed asthmatic response observed in these patients after exercise was not specifically related to the performance of exercise. We conclude that in patients who have bronchoconstriction immediately after exercise, a second asthmatic response occurring later after the exercise is uncommon. (N Engl J Med 1987; 317:482–5.)
Giant Mediastinal Parathyroid Adenoma in a Woman with Hypercalcemia
Authors: C Batsakis, C Kalkana, I Ilias, G Panoutsopoulos, I Christakopoulou
Journal: Clinical Nuclear Medicine (2001)

BATSAKIS, CHRISTOS M.D.*; KALKANA, CHRYSSOULA M.D.†; ILIAS, IOANNIS M.D.*; PANOUTSOPOULOS, GEORGIOS M.D.*; CHRISTAKOPOULOU, IOULIA M.D.* Author Information