tbuckley/cabot-search huggingface dataset:
A phase II study of gefitinib as first line treatment for good performance advanced or metastatic non-small cell lung cancer in East Asian patients
Authors: C. Yang, C. Yu, K. Chen, Z. Lin, S. Kuo, T. Hwang, A. Cheng, P. Yang
Journal: Journal of Clinical Oncology (2006)

7167 Background: Gefitinib is an effective treatment for chemotherapy-treated nonsmall cell lung cancer (NSCLC) in East Asian patients. There were only limited prospective studies on the use of gefitinib in chemonaive advanced or metastatic NSCLC patients. Methods: Eligibility included histological or cytological proven chemonaive stage IIIB/IV NSCLC, measurable disease, ECOG performance status of 0–2, good organ functions and candidate for platinum-based chemotherapy. Patients were treated with 250mg gefitinib per day. Tumor assessments were performed every two months by RECIST criteria. Responding patients were treated until progression. Patients with stable disease more than 2 months may continue treatment or shift to chemotherapy. The primary objective of this study was overall response rate of patients. Secondary objectives included 1-year progression-free survival, overall survival, and ancillary biomarker studies. Simon’s two-stage design was used to aim at a response rate more than 20%. Forty-four patients were planned in stage one and the study will be terminated if 5 or less patients responded to the treatment. A total of 106 patients are planned. Results: The planned interim analysis on the first 44 patients is reported here. There were 13 male and 31 female, median age was 63 (range 39–86), ECOG performance status of 0/1/2 were 0/40/4. 33 patients were nonsmokers. 39 patients had adenocarcinoma. The side effects of the treatment were mild and well accepted by patients. There were 24/9/10/1 patients with PR/SD/PD/NE. Overall response rate was 54.5% and disease control rate was 75%. The response rates for female / adenocarcinoma / nonsmoker were 58%/59%/61% respectively. The response rates for male / non-adenocarcinoma / smoker patients were 46%/20%/36%. The median time to progression for all patients was 6.3 months. Conclusions: Gefitinib is a very effective treatment for East Asian chemonaive advanced or metastatic NSCLC patients. Although the patients’ number was small, the response rates for patients with one unfavorable predictive factor were comparable to the response rates of patients receiving combination chemotherapy. The response rates and duration for 106 patients will be presented in the meeting. [Table: see text]
Salvage therapy with single agent bendamustine for recurrent anaplastic glioma.
Authors: S. K. Johnston, M. C. Chamberlain
Journal: Journal of Clinical Oncology (2011)

e12506 Background: A prospective Phase II study of the novel alkylator, bendamustine, in adult patients with recurrent temozolomide-refractory anaplastic gliomas (AG) with a primary objective of evaluating 6-month progression free survival (PFS). Methods: Seven patients (2 men; 5 women) ages 33-59 years (median 37), with recurrent AG were treated. All patients had previously been treated with surgery, involved-field radiotherapy and temozolomide chemotherapy. Two patients were treated at first recurrence (2 following re-operation) and five patients at second recurrence with bendamustine administered intravenously on 2 consecutive days (100mg/m2/day) every 4 weeks (operationally defined as a single cycle). Neurological evaluation was performed every 4 weeks; neuroradiographic evaluation was performed every 8 weeks; laboratory assessments on days 21 and 28 of each cycle. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support provided by Cephalon, Inc. Results: All patients were evaluable. A total of 28 cycles of bendamustine (median 4 cycles; range 2–6) was administered. Grade 3 or higher bendamustine-related toxicity included lymphopenia (5/7 patients, 71%) and thrombocytopenia (1, 14.3 %). One patient required a dose reduction to 75mg/m2/day due to prolonged grade 2 neutropenia. No patient required transfusion or developed neutropenic fever. No treatment-related deaths occurred. No radiographic responses were seen however 3 patients (43%) demonstrated stable disease. Time to tumor progression ranged from 2 – 11+ months (median: 7+ months). Survival ranged from 4 – 11+ months (median: 8+ months). Three patients are alive, off therapy and with continued radiographic stable patterns of disease. 6-month PFS was 43% and according to protocol permits secondary expansion of the study to 24 patients. Conclusions: Bendamustine demonstrated sufficient efficacy with acceptable toxicity in this initial cohort of adult patients with recurrent AG that pre-specified study expansion is planned and actively enrolling.
Cloning and characterization of squalene synthase and cycloartenol synthase from Siraitia grosvenorii
Authors: Huan Zhao, Qi Tang, Changming Mo, Longhua Bai, Dongping Tu, Xiaojun Ma
Journal: Acta Pharmaceutica Sinica B (2016)

Mogrosides and steroid saponins are tetracyclic triterpenoids found in Siraitia grosvenorii. Squalene synthase (SQS) and cycloartenol synthase (CAS) are key enzymes in triterpenoid and steroid biosynthesis. In this study, full-length cDNAs of SgSQS and SgCAS were cloned by a rapid amplification of cDNA-ends with polymerase chain reaction (RACE-PCR) approach. The SgSQS cDNA has a 1254 bp open reading frame (ORF) encoding 417 amino acids, and the SgCAS cDNA contains a 2298 bp ORF encoding 765 amino acids. Bioinformatic analysis showed that the deduced SgSQS protein has two transmembrane regions in the C-terminal. Both SgSQS and SgCAS have significantly higher levels in fruits than in other tissues, suggesting that steroids and mogrosides are competitors for the same precursors in fruits. Combined in silico prediction and subcellular localization, experiments in tobacco indicated that SgSQS was probably in the cytoplasm or on the cytoskeleton, and SgCAS was likely located in the nucleus or cytosol. These results will provide a foundation for further study of SgSQS and SgCAS gene functions in S. grosvenorii, and may facilitate improvements in mogroside content in fruit by regulating gene expression.
Abstract 4018: The role of c-MET/HGF signaling as a critical mediator of an invasive and resistant phenotype in colorectal cancer
Authors: Conor A. Bradley, Philip Dunne, Darragh McArt, Ken Arthur, Stephen McQuaid, Manuel Salto-Tellez, Patrick Johnston, Sandra Van Schaeybroeck
Journal: Cancer Research (2015)

Abstract The c-MET proto-oncogene is frequently overexpressed (50-60%), amplified (5-10%), and mutated (5%) in colorectal cancer (CRC). Hepatocyte growth factor (HGF)-induced c-MET activation has been linked with migration, survival, invasion, and resistance to targeted therapy, and has been suggested as a possible prognostic biomarker for CRC. We are currently investigating the role of c-MET and microenvironment derived HGF in the acquisition of an invasive and migratory phenotype, and resistance to targeted therapy in CRC. In order to model CRC tumour cell invasion and metastasis, we have generated invasive subpopulations from CRC cells using Boyden Invasion chambers. Invasive cell lines were characterised for protein expression/activity by Western blotting, and analysed for migratory and invasive potential using the xCELLigence System (Roche). To model the CRC microenvironment, we have utilised a range of co-culture techniques with CRC cell lines and colon fibroblasts. c-MET expression in FFPE tissues was measured using IHC in a tissue microarray (TMA) derived from early stage CRC patients. HCT116 and LoVo invasive subpopulations showed an EMT-like, mesenchymal, migratory/invasive phenotype. In addition, increased expression and activation levels of c-MET were found in these sublines, which was determined to be ligand independent. Inhibition of c-MET using RNAi abrogated both basal and HGF-induced migration and invasion in CRC cell lines. Co-culture of CRC cells with HGF-expressing colon-derived fibroblasts leads to activation of c-MET, inducing CRC migration, invasion, and resistance to MEK inhibition, and this phenotype could be diminished using a HGF neutralising antibody. Significant increased expression levels of c-MET were also found in a CRC TMA compared to matched normal tissues, and also at the invasive edge of some CRC tumours, where it may be driving invasive biology. The identification of key pathways driving metastasis has a huge potential to change treatment strategies in CRC. We intend to further investigate the role of c-MET in regulation of migration, invasion, and resistance to therapy in CRC. We hypothesise that patients with high tumoural c-MET at the invasive front may benefit in particular from anti- c-MET therapies. Citation Format: Conor A. Bradley, Philip Dunne, Darragh McArt, Ken Arthur, Stephen McQuaid, Manuel Salto-Tellez, Patrick Johnston, Sandra Van Schaeybroeck. The role of c-MET/HGF signaling as a critical mediator of an invasive and resistant phenotype in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4018. doi:10.1158/1538-7445.AM2015-4018
Abstract 22: CXCR4 Expression on Endogenous Bone Marrow Stem/Progenitor Cells is Crucial for Preservation of Myocardial Function After MI
Authors: Marcin Wysoczynski, Mitesh Solanki, Rakesh Ponnapureddy, Rakesh Gadde, Roberto Bolli, Gregg Rokosh
Journal: Circulation Research (2014)

Background: Studies examining the role of bone marrow CXCR4 in the response to myocardial infarction (MI) using the CXCR4 antagonist AMD3100 in animal myocardial infarction (MI) models are inconclusive. Chronic AMD3100 administration exacerbated injury and myocardial dysfunction while bolus injection immediately post-MI reduced size of the injury with improvement of systolic function. Aims: As MI mobilizes bone marrow stem/progenitor cells and immune cells into peripheral blood which then home to injured myocardium to facilitate and impair, respectively, regeneration and healing we were interested in the role of bone marrow CXCR4 on functional recovery, angiogenesis, and cardiomyogenesis. Experimental Approach: To define the role of CXCR4 in the bone marrow we generated chimeras with bone marrow from CXCR4 flox/flox mice. Wild type mice were transplanted with CXCR4 flox/flox or CXCR4 flox/flox UBQ Cre bone marrow cells after a lethal dose of irradiation. CXCR4 deletion was induced 5 weeks after transplant with Tamoxifen. The coronary artery was ligated after another two weeks. Function was evaluated five weeks post MI function by echo and pathology analysis was performed to measure scar size, collagen content, hypertrophy, capillary counts, CSCs counts, angiogenesis and cardiomyogenesis. Results: compared to wild type, mice with CXCR4 KO bone marrow had impaired LV systolic function evaluated 5 weeks post-MI by echocardiography. Morphometric analysis of Masson’s Trichrome stained sections confirmed LV exacerbated chamber enlargement (expansion index), larger scar and decreased infarcted wall thickness in mice with bone marrow cells deficient for CXCR4. More detailed analysis revealed c-kit positive CSC numbers were decreased as were proliferating c-kit CSC indicated by Ki67 staining. Decreased proliferation also correlated with reduced numbers of newly formed myocytes (αsarcomeric actin pos /BrdU pos ). Capillary and arteriole counts were also reduced in infarcted hearts of mice with CXCR4 KO bone marrow compared to wild type. Conclusion: based on these findings we can conclude that CXCR4 is necessary for bone marrow cell homing to infarcted myocardium to preserve LV function, regenerate lost myocardium, and promote angiogenesis.
Differential Effects of Fructose and Glucose on Cerebral Blood Flow
Authors: Steve Hertzler
Journal: JAMA (2013)

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
Elotuzumab Plus Bortezomib and Dexamethasone Versus Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: 2-Year Follow-up
Authors: Antonio Palumbo, Massimo Offidani, Brigitte Pégourie, Javier De La Rubia, Laurent Garderet, Kamel Laribi, Alberto Bosi, Roberto Marasca, Jacob P. Laubach, Ann Mohrbacher, Angelo Michele Carella, Anil K. Singhal, Mark Lynch, Ying-Ming Jou, Andrzej Jakubowiak
Journal: Blood (2015)
Decisive Steps Toward Patient-Reported Outcomes for Claudication—Tread Lightly or Full Steam Ahead?
Authors: Philip P. Goodney, Matthew A. Corriere
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Measuring the Quality of Care for Patients With Traumatic Brain Injury—Reply
Authors: Aaron J. Dawes, H. Gill Cryer
Journal: JAMA Surgery (2015)

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 Surgery 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 Surgery journal
Panobinostat-Augmented Cytarabine and Daunorubicin (7+3) Induction for Older Patients with AML or High-Risk MDS Is Well Tolerated and Results in Favorable Clinical Outcomes: The Panda Trial
Authors: Matthew J. Wieduwilt, Scott Thomas, Rebecca L. Olin, Aaron C. Logan, Lloyd E. Damon, Thomas G. Martin, McNancy Kang, Peter H. Sayre, Wanda Boyer, Karin ML Gaensler, Kirsten Anderson, Pamela Munster, Charalambos Andreadis
Journal: Blood (2015)
Primary Prevention of Cardiovascular Disease Endpoints Using β-Blockers-Reply
Authors: Bruce M. Psaty
Journal: JAMA (1997)

<h3>In Reply.</h3> —In our meta-analysis,<sup>1</sup>we classified trials according to the "primary treatment strategy used in the active group." "While most studies," we stated, "used more than 1 drug in the treated group, the agents were usually applied in a stepped-care approach that was clearly identified." In other words, treatment strategies were defined by the first-line drug, and a variety of other drugs might also be used in the active group. Even the 2 MRC trials described by Dr Michalewicz and colleagues as "β-blocker studies" used supplemental drugs in 11% to 34% of subjects. Indeed, we drew attention to the ambiguous position of the STOP-H study, which "was classified as a β-blocker trial since the first-line agent for 68% in the active group was β-blocker therapy".<sup>1</sup>This approach to classifying trials in terms of primary treatment strategies corresponds to the intention-to-treat principle and simply acknowledges the typical design features of
Sirtuin 2 aggravates postischemic liver injury by deacetylating mitogen‐activated protein kinase phosphatase‐1
Authors: Jie Wang, Hyoung‐Won Koh, Lu Zhou, Ui‐Jin Bae, Hwa‐Suk Lee, In Hyuk Bang, Sun‐O Ka, Seon‐Hee Oh, Eun Ju Bae, Byung‐Hyun Park
Journal: Hepatology (2016)

Sirtuin 2 (Sirt2) is known to negatively regulate anoxia-reoxygenation injury in myoblasts. Because protein levels of Sirt2 are increased in ischemia-reperfusion (I/R)-injured liver tissues, we examined whether Sirt2 is protective or detrimental against hepatic I/R injury. We overexpressed Sirt2 in the liver of C57BL/6 mice using a Sirt2 adenovirus. Wild-type and Sirt2 knockout mice were subjected to a partial (70%) hepatic ischemia for 45 minutes, followed by various periods of reperfusion. In another set of experiments, wild-type mice were pretreated intraperitoneally with AGK2, a Sirt2 inhibitor. Isolated hepatocytes and Kupffer cells from wild-type and Sirt2 knockout mice were subjected to hypoxia-reoxygenation injury to determine the in vitro effects of Sirt2. Mice subjected to I/R injury showed typical patterns of hepatocellular damage. Prior injection with Sirt2 adenovirus aggravated liver injury, as demonstrated by increases in serum aminotransferases, prothrombin time, proinflammatory cytokines, hepatocellular necrosis and apoptosis, and neutrophil infiltration relative to control virus-injected mice. Pretreatment with AGK2 resulted in significant improvements in serum aminotransferase levels and histopathologic findings. Similarly, experiments with Sirt2 knockout mice also revealed reduced hepatocellular injury. The molecular mechanism of Sirt2's involvement in this aggravation of hepatic I/R injury includes the deacetylation and inhibition of mitogen-activated protein kinase phosphatase-1 and consequent activation of mitogen-activated protein kinases. Conclusion: Sirt2 is an aggravating factor during hepatic I/R injury. (Hepatology 2017;65:225-236).
Clinical update on a phase I/II trial of HDAC inhibitor resminostat in patients with sorafenib-resistant hepatocellular carcinoma (HCC): The SHELTER study.
Authors: M. Bitzer, M. Horger, T. M. Ganten, M. P. Ebert, J. T. Siveke, M. A. Woerns, M. M. Dollinger, G. Gerken, M. E. Scheulen, A. Mais, R. Jankowsky, B. Hauns, B. Hentsch, U. M. Lauer
Journal: Journal of Clinical Oncology (2011)

e13603 Background: Resminostat (4SC-201) is a novel oral pan-HDAC inhibitor in clinical development in a variety of cancer indications. The aim of the SHELTER study is to evaluate safety, tolerability and efficacy in HCC patients (pts) exhibiting progressive disease under sorafenib first-line therapy. Methods: Pts with sorafenib-refractory HCC, BCLC B or C, are included in a multi-center, open-label, two-arm parallel group trial. Resminostat is administered orally once-daily on dose levels of 200 (DL1), 400 (DL2) and 600 mg (DL3, 4), either combined with sorafenib to overcome resistance at 400 mg (DL1-3) or 800 mg (DL4) (arm A) or as mono therapy (600 mg, arm B). For arm A, a dose escalation of resminostat and sorafenib is performed to determine the MTD for which sorafenib is given twice daily continuously. Resminostat is administered in a “5+9” dosing schedule, with 5 consecutive treatment days (D1-5) followed by a 9-day resting period, resulting in 14 day cycles. Primary objective is to determine progression-free survival after 12 weeks (w) (6 cycles). Secondary objectives include safety and tolerability, tumor response, TTP, OS, PK, and biomarkers. Results: To date, 18 pts were treated with 600 mg resminostat alone or on DL1-3 in combination with 400 mg sorafenib. The majority of AE observed so far include gastrointestinal disorders such as nausea and vomiting. Plasma exposure to resminostat increased dose-dependently on Day 1 (cycle 1) with mean AUC 0-6 h values of 10.5 h*mg/L (600 mg mono) and 9.01 h*mg/L (DL3). No major changes in PK characteristics of resminostat were found with or without co-administration of sorafenib. A considerable portion of pts showed stabilization of their disease (SD): 9 out of 14 pts examined after 6 w, and 7 out of 13 pts after 12 w displayed SD. In one patient treated on DL2, SD persisted for 36 w along with good long-term tolerability. Conclusions: Preliminary clinical data showed a favorable drug profile of resminostat either in mono or in combination treatment with sorafenib. Initial data on therapeutic activity to overcome resistance to sorafenib are promising and will be updated for the meeting, including results of the dose-escalation.
Safety and Efficacy of the Novel Combination of Panobinostat (LBH589) and Everolimus (RAD001) in Relapsed/Refractory Hodgkin and Non-Hodgkin Lymphoma,
Authors: Anas Younes, Amanda Copeland, Michelle A. Fanale, Luis Fayad, Jorge E Romaguera, Larry W Kwak, Sattva S. Neelapu, Fredrick Hagemeister, Barbara Pro, Silvana de Castro Faria, Yuan Ji, Donald Berry, Daniela Buglio, L. Jeffrey Medeiros
Journal: Blood (2011)