tbuckley/cabot-search huggingface dataset:
First-in-human phase I study exploring three schedules of OSI-027, a novel small molecule TORC1/TORC2 inhibitor, in patients with advanced solid tumors and lymphoma.
Authors: D. S. Tan, H. Dumez, D. Olmos, S. K. Sandhu, A. Hoeben, A. W. Stephens, S. Poondru, R. Gedrich, S. B. Kaye, P. Schoffski
Journal: Journal of Clinical Oncology (2010)

3006 Background: The mTOR pathway regulates cell growth, proliferation and survival; and is a clinically validated target for cancer therapy. Current rapamycin analogs preferentially target TORC1, with therapeutic efficacy limited by compensatory feedback loops resulting in AKT and ERK activation. OSI-027 is an oral inhibitor of TORC1 and TORC2 kinase activity and may have additional clinical activity over TORC1 selective inhibitors. Methods: Patients (pts) with advanced solid tumors or lymphoma received escalating doses of OSI-027 in 3 schedules (S1: days (d) 1-3 q7d, S2: once weekly, and S3: continuous once daily) to determine safety, maximum tolerated dose, pharmacokinetics (PK) and preliminary antitumor activity. Pharmacodynamic (PD) effects on phosphorylation of 4E-BP1 at threonine 37/46, a rapamycin insensitive, mTOR-dependent phosphorylation site, were examined. Results: To date, 34 pts have been enrolled (13M/21F, median age 59 yrs) and 31 treated (S1 11 pts, S2 12 pts, S3 8 pts). S1 and S2 pts were dosed at 10, 15 and 20 mg, S3 pts at 5, 10 and 20 mg. Median number of weeks on study was 6 (range <1-34). Three DLTs have been reported: grade (G) 2 decreased LVEF (10mg S1), and 2 pts with G3 fatigue (15 mg S2 and 20 mg S3). Other drug-related toxicities included G3 nausea and vomiting (1), G3 pneumonia (1); G1/2 fatigue (4), nausea (2), diarrhea (1), anorexia (1), elevated creatinine (1), and reversible increase in QTc (1). Preliminary PK indicate exposure (AUC, Cmax) of OSI-027 increased with dose. The median Tmax and terminal T3/4 were 2-6 hrs and 6-17 hrs, respectively. Preliminary PD data indicate that substantial decreases in 4E-BP1 (T37/46) phosphorylation were observed in PBMCs from 13 of 23 pts following OSI-027 treatment. Eight pts have had SD lasting ≥ 12 wks (26% of pts treated, range 12-33 wks); tumor types were colorectal (3 pts), melanoma, neuroendocrine, endometrial, renal, and cervical cancer (1 pt each). Conclusions: OSI-027 is a potent TORC1/2 kinase inhibitor. Preliminary evidence of pharmacological activity has been observed. It is well tolerated at the doses and schedules tested to date. MTD has not been reached and dose escalation is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI OSI
Close To Clinics: Acute Gvhd In a Novel Chemotherapy Based Minor Mismatch Transplantation Model
Authors: Katarina Riesner, Martina Kalupa, Steffen Cordes, Sefer Elezkurtaj, Karen Grossmann, Sandra Rudloff, Yu Shi, Sabine Westphal, Andrea Wilke, Jörg Mengwasser, Olaf Penack
Journal: Blood (2013)
Abdominal pain in a 31 year old woman
Authors: Anuja Mitra, Nebil Behar
Journal: BMJ (2016)

A 31 year old white woman presented with recurrent abdominal pain and distention. A barium follow through examination was performed. What is the diagnosis?



Congenital small bowel non-rotation as indicated by loops of small bowel on the right side of the abdomen only.

### Discussion

Intestinal malrotation describes aberrations in rotation and fixation of the alimentary tract during intrauterine development. Small bowel non-rotation is characterised by rotational …
NHS services will be cut without more funds, finance directors predict
Authors: Z. Kmietowicz
Journal: BMJ (2015)

Most NHS finance directors (84% of 200) have said that plans for the NHS in England set out in the Five Year Forward View 1 cannot be achieved without extra funding on top of the £8bn (€11.4bn; $12bn) by 2020 promised by the government, a survey has found.2

The finance directors said that if the government could not put more money into the NHS they would have to cut services.

Almost all (94%) of the directors in the Healthcare Financial Management Association’s twice a year survey of 200 NHS finance directors said that they believed that the £8bn already pledged will be needed in the next 18 months. …
Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function
Authors: David H. Hackos, Patrick J. Lupardus, Teddy Grand, Yelin Chen, Tzu-Ming Wang, Paul Reynen, Amy Gustafson, Heidi J.A. Wallweber, Matthew Volgraf, Benjamin D. Sellers, Jacob B. Schwarz, Pierre Paoletti, Morgan Sheng, Qiang Zhou, Jesse E. Hanson
Journal: Neuron (2016)
The Power of a Simple Intervention to Improve Student Health
Authors: Lindsey Turner, Erin Hager
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Diffuse Large B-Cell Lymphoma Version 1.2016
Authors: Andrew D. Zelenetz, Leo I. Gordon, William G. Wierda, Jeremy S. Abramson, Ranjana H. Advani, C. Babis Andreadis, Nancy Bartlett, John C. Byrd, Luis E. Fayad, Richard I. Fisher, Martha J. Glenn, Thomas M. Habermann, Nancy Lee Harris, Francisco Hernandez-Ilizaliturri, Richard T. Hoppe, Steven M. Horwitz, Mark S. Kaminski, Christopher R. Kelsey, Youn H. Kim, Susan Krivacic, Ann S. LaCasce, Matthew Lunning, Auayporn Nademanee, Pierluigi Porcu, Oliver Press, Rachel Rabinovitch, Nishitha Reddy, Erin Reid, Kenneth Roberts, Ayman A. Saad, Lubomir Sokol, Lode J. Swinnen, Julie M. Vose, Joachim Yahalom, Nadeem Zafar, Mary Dwyer, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2016)

Diffuse large B-cell lymphomas (DLBCL) are now considered a heterogeneous group of distinct molecular subtypes (germinal center B-cell DLBCL, activated B-cell DLBCL, and primary mediastinal large B-cell lymphoma (PMBL) with varied natural history and response to therapy. In addition, a subset of patients with DLBCL have concurrent MYC and/or BCL2 gene rearrangements (double-hit lymphomas; DHL) and others have a dual expression of both MYC and BCL2 proteins (double-expressing DLBCL; DEL). The standard of care for the treatment of patients with PMBL, DHL, or DEL has not been established. Adequate immunophenotyping and molecular testing (in selected circumstances) are necessary for the accurate diagnosis of different subtypes of DLBCL. The NCCN Guidelines included in this issue, part of the NCCN Guidelines for non-Hodgkin's lymphomas, address the diagnosis and management of DLBCL and its subtypes.
Anti-apoptosis and pro-apoptosis gene expressions in Barrett’s epithelial tumorigenesis
Authors: S. J. Park, J. H. Peters, D. Vallboehmer, D. Shimizu, H. Kuramochi, K. D. Danenberg, P. T. Chandrasoma, S. R. Demeester, T. R. Demeester, P. V. Danenberg
Journal: Journal of Clinical Oncology (2005)

9652 Background: Apoptosis-related genes are known to modulate apoptosis and various studies have implicated the dysregulation of these genes in tumorigenesis. COX2 is thought to decrease apoptosis frequency in the development of gastrointestinal cancer, bax is identified as an apoptosis accelerator in the mitochondrial pathway and DR-5 is a receptor of TRAIL which activates apoptosis via the death receptor pathway. We investigated the expression of these genes at each stage of the Barrett’s esophagus-dysplasia-adenocarcinoma sequence to study their relationship to the process of esophageal carcinogenesis. Methods: Tissue samples (17 non-dysplastic Barrett’s, 13 dysplastic Barrett’s, 42 adenocarcinoma) were obtained by biopsy or operation and immediately frozen. No samples were taken from the same patient. COX2, bax, and DR-5 mRNA expressions were measured utilizing laser capture microdissection and real-time quantitative RT-PCR. The relationship between each gene expression and histologic parameter was evaluated using the Wilcoxon test. The Benjamini and Hochberg correction was applied to each p value. Strength of correlation among these gene expressions was tested by Spearman’s rank test. Results: No significant differences in bax or DR-5 expressions were observed among the histologic stages. However, COX2 gene expression was significantly higher in adenocarcinoma than non-dysplastic Barrett’s (p=0.0246). A significant positive correlation was found between bax and DR-5 (rs=0.167, p=0.0245). Conclusions: COX2 gene activation is more closely associated with Barrett’s epithelial malignant transformation than either bax or DR-5. The positive correlation between bax and DR-5 supports the cross talk model between the mitochondrial and the death receptor apoptosis pathways during Barrett’s epithelial tumorigenesis. No significant financial relationships to disclose.
Perioperative blood transfusion does not influence recurrence-free and overall survivals after curative resection for hepatocellular carcinoma
Authors: Tian Yang, Jun-Hua Lu, Wan Yee Lau, Tian-Yi Zhang, Han Zhang, Yi-Nan Shen, Kutaiba Alshebeeb, Meng-Chao Wu, Myron Schwartz, Feng Shen
Journal: Journal of Hepatology (2015)
Poorly differentiated neuroendocrine carcinoma-small cell of the gastrointestinal tract. Institutional experience
Authors: J. M. O′connor, J. P. Sade, A. Pairola, E. Domenichini, A. Cabanne, F. Marmisole, G. Mendez, C. Bestani, M. Chacón, E. Roca
Journal: Journal of Clinical Oncology (2006)

14142 Background: PDNEC-Small cell (OMS Clasification, grade III)of the GI tract are rare diseases. Small cel represent 0,1% to 1% of all GI malignancies, and are included in the group of PDNEC but: Do these group behave biologically and respond to treatment in the same way? Trying to elucidate this matter, we performed a retrospective analysis of our group of pts. with PDNEC. Methods: A database search was done. from 1997 to 2005 we found 31 pts. with PDNEC/Small cell from the GI Tract treated in our Centers. A review of the clinical records was performed with special interest in response rate and overall survival. interest. Results: 14 pts. were informed by the pathologist at diagnosis PDNEC and 17 pts. as small cell. Median age: 50 years (r 19–84). The most common primary site was Esophagus-Stomach (29%), followed by pancreas 9 pts. (29%. 9 pts.(29%) presented with metastatic disease with unknown orimary Sistemic symptoms were common. A majority of our pts. (61%) presented with overt metastases. The liver was involved in 14 pts. (61%) follow by lymph nodes in 5 (16%). The most common chemotherapy used was a combination Platinum based. Overall response rate was 43%. TTP for all pts were 7 months (95% IC 0.34–0.69). Overall survival was 12 months (95% IC 0,31–0,70). We observed differences in term of overall survival and TTP in favor of PDNEC (15 months vs 10 months and 8 vs 4 months respectively) pNS. Conclusions: PDNEC-Small cell had bad prognosis. In our Serie we found differences between both groups, although not statiscally significant (due to a low number of patients). Definitive data of treatment for the management of this group of pts. still lacks. No significant financial relationships to disclose.
Phospho-Kinase Expression and Anti-Tumoral Activity of the Novel Multikinase Inhibitor Ec-70124 in Colon Cancer
Authors: A. Ocana, M. Cuenca, G. Serrano, J.C. Montero, V. Corrales, F. Morís, L.E. Nuñez, A. Pandiella
Journal: Annals of Oncology (2014)
IMMUNOLOGIC ASPECTS OF ULCERATIVE COLITIS
Authors: J M Herrerias, M A Pérez Ruilópez, F J Pellicer, J Olivan, J A Sanchez Cousteau, M Garrido
Journal: JAMA (1966)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Two ascomycete classes based on fruiting-body characters and ribosomal DNA sequence.
Authors: M L Berbee, J W Taylor
Journal: Molecular Biology and Evolution (1992)

Traditional fruiting body-based classification of ascomycetes has been under attack for 2 decades. Fruiting-body types can converge, and few researchers now assume that either the closed fruiting bodies (cleistothecia) characterizing the class Plectomycetes or the flask-shaped fruiting bodies (perithecia) characterizing the class Pyrenomycetes are stable, unifying characters. Unless we identify characters uniting major ascomycete groups, orders of ascomycetes remain narrowly defined, and supraordinal classification is impossible. We sequenced both strands of 18s rDNA from nine ascomycete fungi, adding three sequences from GenBank into our analysis. The phylogeny, inferred from 162 informative sites in 1,700 bp of DNA sequence data and using yeast as an outgroup, divided the fungi into two groups correlating well both with fruiting-body type and with the traditional classes Plectomycetes and Pyrenomycetes. Each group received strong statistical support. Genera producing cleistothecia, such as Talaromyces (with a Penicillium asexual state) and the human pathogen Ajellomyces capsulatus (causing histoplasmosis), fall within the plectomycete group. Plectomycetes also includes Eremascus albus and the bee pathogen Ascosphaera apis, although both lack typical fruiting bodies. The Dutch elm disease fungus groups with pyrenomycetes such as Neurospora, in spite of its confusing mixture of class-level characters.
Implantation of healthy matrix-embedded endothelial cells rescues dysfunctional endothelium and ischaemic tissue in liver engraftment
Authors: Pedro Melgar-Lesmes, Mercedes Balcells, Elazer R Edelman
Journal: Gut (2016)

Liver transplantation is limited by ischaemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recovery after hepatectomy and engraftment.Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomised recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analysed 7 days post-op.Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischaemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts and syngeneic engraftment.Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischaemic injury after major hepatectomy and engraftment. This study highlights endothelial-hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation.
Elevated beta-2-microglobulin in Epstein-Barr virus lymphoproliferative disease after bone marrow transplantation.
Authors: D Przepiorka
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.7.1202 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3292715 Elevated beta-2-microglobulin in Epstein-Barr virus lymphoproliferative disease after bone marrow transplantation. D PrzepiorkaxD PrzepiorkaSearch for articles by this author https://doi.org/10.1200/JCO.1988.6.7.1202 First Page PDF © 1988 by American Society of Clinical Oncology
Lapatinib in combination with ECF/x in EGFR1 or HER2-overexpressing first-line metastatic gastric cancer (GC): A phase II randomized placebo controlled trial (EORTC 40071).
Authors: A. Roth, M. H. Moehler, M. Mauer, A. Schad, M. Karrasch, M. Praet, M. L. Lim, A. Das-Gupta, M. P. Lutz
Journal: Journal of Clinical Oncology (2010)

TPS205 Background: ECF/X (epirubicin + cisplatin + 5-FU or capecitabine (X)) is a preferred GC chemotherapy (CT) regimen. Survival of HER2+ metastatic GC is prolonged by trastuzumab when administered with CF/X (VanCutsem, ASCO 2009). Lapatinib inhibits both EGFR1 and HER2, is active in HER2+ gastric cell lines, and has shown clinical activity in uncontrolled phase II GC trials. A phase III trial of lapatinib with X + oxaliplatin in HER2+ (FISH) GC is ongoing. Additional unaddressed questions include the efficacy and safety of lapatinib with ECF/X and its activity in patients (pts) with discordant FISH or IHC HER2 status or EGFR1+, which are addressed in this phase II trial. Methods: This is a phase II, randomized, double- blind, placebo controlled, multicenter trial sponsored by the EORTC. About 350 pts with adenocarcinoma of the stomach or esophagogastric junction not amenable to curative surgery and without prior palliative CT will be screened centrally for HER2/EGFR1 by FISH and IHC. Pts will be enrolled into one of three strata: 1) HER2 FISH+ and IHC 2/3+, 2) HER2 FISH- and IHC 2/3+, or 3) HER2 IHC 0/+ and EGFR1 FISH+ or IHC 2/3+. Pts without HER2 and EGFR1 by FISH and IHC will be excluded. Within each stratum, pts will be randomized to oral lapatinib 1,250 mg continuously until progression or placebo, administered with six cycles of ECF or ECX (investigator-selected CT). Approximately 96 pts are anticipated to be randomized to lapatinib + ECF/X (35, 26, and 35 in stratum 1-3, respectively). A safety cohort analysis will be performed in the first 15 pts receiving lapatinib. The primary endpoint is progression -free survival (PFS) in stratum 1, estimating that 70 pts should be randomized to observe the 58 events needed to have 80% power to detect an increase in mPFS from 4 to 7 months with lapatinib (HR=0.571) using a one-sided alpha of 10%. Secondary endpoints include PFS in strata 2 and 3, toxicity, response rate, overall survival, HER2 concordance by FISH/IHC, and correlation of HER2/EGFR status with response. Conclusions: This is the first trial to analyze prospectively and separately the role of HER2 and EGFR1 by FISH and IHC for lapatinib combined with chemotherapy in GC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Hepatic Angiosarcomas in Dogs: An Excessive Frequency as Compared With Man
Authors: William A. Priester
Journal: JNCI Journal of the National Cancer Institute (1976)

A series of 18 angiosarcomas of the liver in dogs reported by veterinary schools in the United States and Canada suggested that certain breeds may have an excess of the tumor and that there is no marked predilection by sex. Histologic characteristics of hepatic angiosarcomas were similar in man and dog, but the relative frequency in dogs was about 25–100 times that of man.
A randomized phase II study of TSU-68 in patients (pts) with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE).
Authors: Y. Arai, Y. Inaba, T. Yamamoto, F. Kanai, T. Aramaki, T. Tanaka, K. Yamakado, M. Kudo, S. Kaneko, K. Imanaka
Journal: Journal of Clinical Oncology (2010)

4030 Background: HCC is well known for hypervascular tumors and currently clinical trials for many antiangiogenic drugs are conducted. TSU-68 is an oral compound which inhibits VEGFR, PDGFR and FGFR, and it showed promising efficacy with a high safety profile, even in heavily pretreated HCC pts with Child-Pugh B liver cirrhosis (Kanai et al., 4589, ASCO 2008). TACE is an internationally established standard treatment for pts with intermediate stage HCC. Most pts will have intrahepatic recurrence after TACE, and VEGF level has been reported to be associated with recurrence. We conducted a randomized phase II trial to assess the efficacy and safety of the TSU-68 after TACE. Methods: This study was an open-label, multicenter, randomized phase II trial. Pts who were not indicated to surgical treatment or local treatment such as radiofrequency ablation, absence of portal vein thrombosis and extrahepatic metastases, and had either Child-Pugh A or B liver function were randomly assigned to group A with TSU-68 400 mg/d or group B without antitumor therapy. The primary endpoint was progression free survival (PFS) and it was assessed with an independent review manner in the computed tomography images. Results: 101 eligible pts (male/female: 82/19; median age 71 years; Child-Pugh A/B: 77/24; HCV/HBV/other: 75/5/21) were enrolled (group A: 50 pts; group B: 51 pts). Median PFS was 5.2 months in group A and 4.0 months in group B (HR in group A, 0.699; p = 0.054). The most frequent grade 3/4 events were fatigue (6% vs. 0%), ALT elevation (26% vs. 8%), AST elevation (46% vs. 12%), T-Bil elevation (6% vs. 0%), hypokalemia (14% vs. 2%), r-GTP elevation (8% vs. 4%), Lymphopenia (12% vs. 4%), decreased platelets (12% vs. 2%) and ALP elevation (8% vs. 0%) for group A vs group B. Conclusions: TSU-68 was well tolerated after TACE, and marginally significant efficacy to prolong PFS compared to TACE alone. This result suggests that the combination of TSU- 68 may improve the overall survival of pts treated by TACE. No significant financial relationships to disclose.