tbuckley/cabot-search huggingface dataset:
Signal Transduction and Activator of Transcription-3 (STAT3) in Patients with Colorectal Cancer: Associations with the Phenotypic Features of the Tumor and Host
Authors: James H. Park, Hester van Wyk, Donald C. McMillan, Jean Quinn, Jennifer Clark, Campbell S.D. Roxburgh, Paul G. Horgan, Joanne Edwards
Journal: Clinical Cancer Research (2016)

Purpose: In patients with colorectal cancer, a high-density local inflammatory infiltrate response is associated with improved survival, whereas elevated systemic inflammatory responses are associated with poor survival. One potential unifying mechanism is the IL6/JAK/STAT3 pathway. The present study examines the relationship between tumor total STAT3 and phosphorylated STAT3Tyr705 (pSTAT3) expression, host inflammatory responses, and survival in patients undergoing resection of stage I-III colorectal cancer.Experimental Design: Immunohistochemical assessment of STAT3/pSTAT3 expression was performed using a tissue microarray and tumor cell expression divided into tertiles using the weighted histoscore. The relationship between STAT3/pSTAT3 expression and local inflammatory (CD3+, CD8+, CD45R0+, FOXP3+ T-cell density, and Klintrup-Mäkinen grade) and systemic inflammatory responses and cancer-specific survival were examined.Results: A total of 196 patients were included in the analysis. Cytoplasmic and nuclear STAT3 expression strongly correlated (r = 0.363; P < 0.001); nuclear STAT3 and pSTAT3 expression weakly correlated (r = 0.130; P = 0.068). Cytoplasmic STAT3 was inversely associated with the density of CD3+ (P = 0.012), CD8+ (P = 0.003), and FOXP3+ T lymphocytes (P = 0.002) within the cancer cell nests and was associated with an elevated systemic inflammatory response as measured by modified Glasgow Prognostic Score (mGPS2: 19% vs. 4%, P = 0.004).The combination of nuclear STAT3/pSTAT3 stratified 5-year survival from 81% to 62% (P = 0.012), however, was not associated with survival independent of venous invasion, tumor perforation, or tumor budding.Conclusions: In patients undergoing colorectal cancer resection, STAT3 expression was associated with adverse host inflammatory responses and reduced survival. Upregulation of tumor STAT3 may be an important mechanism whereby the tumor deregulates local and systemic inflammatory responses. Clin Cancer Res; 23(7); 1698-709. ©2016 AACR.
O070 : CX3CR1 is a gatekeeper for intestinal barrier integrity: Limiting steatohepatitis by promoting intestinal homeostasis
Authors: K.M. Schneider, V. Bieghs, F. Heymann, W. Hu, L. Liao, N. Gassler, O. Pabst, E. Latz, G. Sellge, J. Penders, F. Tacke, C. Trautwein
Journal: Journal of Hepatology (2015)
Public Health Stops at the School House Door
Authors: Jerome A. Paulson, Claire L. Barnett
Journal: Environmental Health Perspectives (2016)

Summary:In the United States, all children of appropriate age are required to attend school, and many parents send their children to child care. Many school and day care buildings have been found to have environmental health problems that impact children’s health and diminish their ability to learn. No federal agency has the capacity or authority to identify, track, or remediate these problems. A recent meeting, coordinated by Healthy Schools Network, Inc., has developed a set of recommendations to begin to deal with the issue of environmental health problems in schools.
Transplantation of autologous bone marrow-derived stem cells in patients with ST-segment elevation myocardial infarction
Authors: Stefan Janssens, CL Dubois, Jan Bogaert, Koen Theunissen, C Derooze, M Kalantzis, Walter Desmet, Peter Sinnaeve, Joseph Dens, J Maertens, Johan Van Cleemput, O Ghysens, Steven Dymarkowski, Lieven Herbots, Frank Rademakers, Johan Nuyts, Ann Belmans, Luc Mortelmans, Marc Boogaerts, Frans Van de Werf
Journal: Circulation (2005)
New gene editing technique CRISPR-Cas9 raises important ethical questions, says advisory body
Authors: Nigel Hawkes
Journal: BMJ (2016)

New techniques for editing genes could transform biological research, with almost unlimited potential, says a new report from the UK Nuffield Council on Bioethics.1 But the advent of a cheap, precise, and widely used technique, known as CRISPR-Cas9, also raises ethical and moral issues that need to be resolved, says the council.

The technique, involving clustered regularly interspaced short palindromic repeats (CRISPR) of DNA and CRISPR associated protein 9 (Cas9), allows an individual gene to be targeted and cut precisely. CRISPR-Cas9 comprises a set of generic “scissors” to cut DNA and a guide in the form of a length of RNA that takes the scissors to the exact point where the cut is desired. Once cut, the DNA repairs itself, incorporating another section of DNA introduced at the same time.

In principle, it could …
Pharmacogenomic analysis of HER2 amplified breast cancer treated with preoperative trastuzumab and paclitaxel, 5-fluorouracil, epirubicin, cyclophosphamide (T/FEC) chemotherapy
Authors: F. J. Esteva, K. Anderson, F. Lin, R. Nahta, J. Mejia, K. Altundag, A. U. Buzdar, G. N. Hortobagyi, W. F. Symmans, L. Pusztai
Journal: Journal of Clinical Oncology (2006)

545 Background: We performed gene expression analysis to identify molecular predictors of resistance to preoperative concomitant trastuzumab and T/FEC chemotherapy. Methods: Pretreatment fine needle aspirations from 21 patients with HER2 amplified, stages II-III breast cancer were available for transcriptional profiling with Affymetrix U133 A chips. Results: Overall pathologic complete response (pCR) rate was 71%. Age, nuclear grade, tumor size, nodal status or quantitative estrogen and HER2 receptor mRNA expression showed no association with response in univariate and multivariate logistic regression. We tested the accuracy of a 30-gene pCR predictor that was previously developed from patients who received T/FEC only preoperative chemotherapy. This predictor was accurate in validation in T/FEC treated patients (n=51) but showed low sensitivity in patients who also received trastuzumab (sensitivity 53% versus 92%). We could not identify any differentially expressed genes between pCR (n=15) and residual disease (RD, n=6) at a false discovery rate (FDR) &lt;90% in the HER2 amplified trastuzumab-treated cases. Hierarchical clustering using the “Perou intrinsic gene set” also failed to separate pCR from RD. Gene Set Enrichment Analysis with 22 genes from trastuzumab-resistant cell lines showed a modest association with RD (FDR=9%). Conclusions: Clinical variables and pharmacogenomic predictors that predict pCR in the absence of trastuzumab are no longer accurate when trastuzumab is included in the treatment. Trastuzumab-resistance associated genes identified in vitro are also associated with resistance in vivo. Support: Ellence Foundation. No significant financial relationships to disclose.
Rebound Syndrome in Multiple Sclerosis After Fingolimod Cessation—Reply
Authors: Stacy Ellen Hatcher, Emmanuelle Waubant, Jennifer S. Graves
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Phase I/II study of low-dose cytarabine (LDAC) with sorafenib as first-line therapy of elderly patients with AML or high-risk myelodysplastic syndrome (MDS).
Authors: D. A. Macdonald, S. E. Assouline, J. Brandwein, S. Kamel-Reid, E. A. Eisenhauer, S. Couban, A. Foo, B. Leber
Journal: Journal of Clinical Oncology (2010)

6564 Background: Elderly patients (pts) with acute myeloid leukemia (AML) may not be suitable for intensive chemotherapy. Low-dose cytarabine (LDAC) is superior to supportive care in these pts (Burnett, 2007). In a phase I study of sorafenib, a multi-targeted kinase inhibitor with FLT-3 inhibitory activity, in AML/myelodysplastic syndrome (MDS) pts we observed modest activity (Crump, 2004) which seemed more prominent in AML pts with FLT3 mutations. The NCIC Clinical Trials Group initiated a multicentre phase I/II study of the combination of LDAC with sorafenib in elderly pts with AML or high risk MDS. Methods: Eligible pts were age > = 60 yrs and unsuitable for intensive chemotherapy regimens. Phase I dose escalation proceeded in cohorts of 3 pts based on toxicity in cycle 1. Phase II was a Simon 2-stage design; 2/15 complete remissions were required in stage 1 to accrue an additional 17 pts in stage 2. FLT3 mutational status was determined in all pts. Results: 21 pts were enrolled: 4 MDS, 17 AML (9 with prior MDS). Median age was 77 (range 63-83). The recommended phase II dose (RP2D) was LDAC 10 mg bid days 1-10 and sorafenib 300 mg bid days 2-28. Further escalation was not possible due to fatigue, sepsis, diarrhea and skin rash at this dose. In 15 evaluable pts at the RP2D, 1 CR, 1 PR, 2 SD, 2 PD, 9 treatment failures were seen. Duration of response in CR, PR, and SD pts was 2.8, 3.9, 2.5, and 8.7 mos. FLT3 internal tandem duplication (FLT3- ITD) was found in 1 pt (this pt had the PR), and tyrosine kinase domain mutation (FLT3-TKD) in 2 pts. The CR was seen in a pt without FLT3 mutation. Conclusions: The study did not meet the prespecified criteria to complete the second stage of phase II accrual. The response rate might have been affected by: (i) the low frequency of FLT3 mutation in the study population compared to historical estimates; (ii) the dose of LDAC achievable in combination; (iii) the response criteria requirement for platelet recovery: a challenge with continuous dosing of sorafenib plus intermittent LDAC. We conclude that this combination of sorafenib and LDAC has limited activity in an unselected cohort of elderly pts in which pts with FLT-3 mutations seem underrepresented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer
Evolution de la résistance aux antibiotiques chez les salmonelles non typhiques en Grèce de 1990 à 1997
Authors: E N Velonakis, A Markogiannakis, L Kondili, E Varjioti, Z Mahera, N Vakalis, E Dedouli, A Karaitianou, K Bethimouti
Journal: Eurosurveillance (2001)

La sensibilite de 1548 souches de salmonella paratyphi a 15 antibiotiques a ete determinee en Grece de 1990 a 1997. La prevalence globale de la resistance chez deux serotypes Salmonella enterica serotype Enteritidis et Salmonella enterica serotype Typhimurium a augmente au cours des dernieres annees de l’etude. Une baisse a ete observee a partir de 1996, en particulier pour S. Enteritidis, qui a montre les taux de resistance aux antibiotiques les plus eleves. S. Typhimurium s’est revele etre le serotype le plus multi-resistant. Les autres serotypes presentaient une prevalence de resistance tres faible compares a S. Enteritidis et S. Typhimurium.
Outcome of Allogeneic Hematopoietic Stem-Cell Transplantation for Acute Myeloid Leukemia (AML) with 11q23 (MLL) Rearrangement (MLL-r AML). A Retrospective Analysis From the Acute Leukemia Working Party of EBMT
Authors: Arnaud Pigneux, Myriam Labopin, Johann Maertens, Ulrike Bacher, Gérard Socié, Catherine Cordonnier, Noel-Jean Milpied, Jean-Pierre Jouet, Bernard Rio, Didier Blaise, Jordi Esteve, Mohamad Mohty
Journal: Blood (2011)
Prevention of progression from small to large varices: are we there yet? An updated meta-analysis
Authors: Mattias Mandorfer, Markus Peck-Radosavljevic, Thomas Reiberger
Journal: Gut (2016)

We read the article by Bhardwaj and coworkers1 with great interest. With their elegantly designed, randomised, single-blind, placebo-controlled study, Dr. Sarin and his research group have turned over a new leaf in the controversy on the effectiveness of non-selective beta blockers (NSBBs) in preventing the progression from small to large varices in patients who have not bled (table 1).

View this table:

Table 1 
Randomised controlled trials investigating the effect of NSBB treatment on the development of large varices



Carvedilol has been shown to be more potent in decreasing portal pressure due to its additional anti-α1-adrenergic activity,2 and thus, achieves hemodynamic response even in non-responders to propranolol.3 Based on the stage-dependent pathophysiology of portal hypertension (PH), the anti-α1-mediated decrease in intrahepatic resistance might be particularly beneficial in patients with less pronounced clinically significant PH, when intrahepatic resistance is still a major determinant of portal …
Achievement of Red Blood Cell (RBC) Transfusion Independence with Azacitidine (AZA) Leads to Improved Survival In Patients with Higher-Risk Myelodysplasias Regardless of Baseline Transfusion Needs
Authors: John F Seymour, Valeria Santini, Pierre Fenaux, Aristoteles A.N. Giagounidis, Guillermo F. Sanz, Carlo Finelli, Lela M. Lucy, Jay Backstrom, CL Beach
Journal: Blood (2010)
Metabolic and hepatic effects of bloodletting in dysmetabolic iron overload syndrome: A randomized controlled study in 274 patients
Authors: Fabrice Lainé, Marc Ruivard, Véronique Loustaud‐Ratti, Fabrice Bonnet, Paul Calès, Edouard Bardou‐Jacquet, Sylvie Sacher‐Huvelin, Xavier Causse, Christine Beusnel, Alain Renault, Eric Bellissant, Yves Deugnier
Journal: Hepatology (2016)

Dysmetabolic iron overload syndrome (DIOS) is a common cause of hyperferritinemia, accounting for a mild increase of iron stores in insulin‐resistant subjects. Iron removal could improve insulin sensitivity. We performed a prospective, randomized, controlled trial (NCT01015525) in nondiabetic DIOS patients with hepatic iron &gt;50 μmol/g at magnetic resonance imaging to compare the metabolic and hepatic outcomes of 1‐year maintenance of serum ferritin levels &lt;50 μg/L by bloodletting associated with lifestyle and diet advice (LFDA) to those of LFDA only. Patients were randomly assigned (1:1) with stratification by center (n = 8) and hyperglycemia (&gt;5.6 mmol/L). Sample size was calculated to provide 90% power and a difference in fasting glycemia of 0.25 mmol/L. Analysis was done in an intention‐to‐treat population. In 2010‐2014, 146 patients were randomly assigned to receive venesections with LFDA and 128 to LFDA only. At the end of the study, comparison of iron‐depleted patients and controls showed ferritin levels 71 ± 48 μg/L after removal of 4.9 ± 1.6 L of blood versus 733 ± 277 μg/L ( P &lt; 0.0001), glycemia 5.44 ± 0.7 versus 5.49 ± 0.7 mmol/L ( P = 0.57), body weight +0.5 ± 4.3% versus ‐0.6 ± 3.3% ( P = 0.03), homeostasis model of assessment of insulin resistance 3.39 versus 2.40 ( P = 0.002), alanine aminotransaminase 33 ± 22 versus 37 ± 21 IU/L ( P = 0.10), aspartate aminotransaminase 27 ± 13 versus 27 ± 10 IU/L ( P = 0.81), gamma‐glutamyl transferase 54 ± 138 versus 49 ± 35 IU/L ( P = 0.72), Fatty Liver Index 58.9 ± 24.6 versus 61.2 ± 22.9 ( P = 0.37), and Fibrosis‐4 score 1.5 ± 0.6 versus 1.30 ± 0.6 ( P = 0.51). Fatigue occurred in 25.3% of venesected patients versus 2.3% of controls ( P &lt; 0.0001). In the subgroup of patients who lost weight, glycemia, homeostasis model of assessment of insulin resistance, serum ferritin, lipid profile, and liver function tests improved irrespective of bloodletting. Conclusion : In DIOS patients, iron depletion by bloodletting does not improve metabolic and hepatic features, is associated with weight gain, and is not as well tolerated as expected; sustained modification of diet and lifestyle habits remains the first therapeutic intervention in DIOS. (H epatology 2017;65:465‐474).
Recombinant human adenovirus p53 injection enhanced sensitivity of chemotherapeutics through DNA damage response pathway in advanced papillary thyroid cancer in vitro and in vivo.
Authors: Jingqiang Zhu, Zhimian Huang, Wenshuang Wu
Journal: Journal of Clinical Oncology (2016)

e17560 Background: investigate the activity and mechanism of rAd-p53 combined with chemotherapeutics in advanced PTC. Methods: PTC cells (TPC-1) were treated with vehicle, paclitaxel (5 μM), cisplatin (5 μM), rAd-P53 (1010 VP/mL), paclitaxel (5 μM) and cisplatin (5 μM), or rAd-P53 (1010 VP/mL) combined with paclitaxel (5 μM) and cisplatin (5 μM), respectively. MTT assay and TPC-1 cells xenograft model were employed to evaluate the effect of rAd-P53 combined with paclitaxel and cispaltin on the growth of PTC in vitro and in vivo. Furthermore, in vitro experiments discussed the underlying mechanism of anti-tumor activity of rAd-P53 combined with paclitaxel and cisplatin in detail. Results: MTT assay showed that rAd-P53 combined with paclitaxel and cisplatin showed the best anti-tumor effects on the proliferation of TPC-1 cells and rAd-P53 displayed an enhanced sensitivity to chemotherapeutics. The inhibitory rate of tumor weight proved that rAd-P53 enhanced sensitivity to chemotherapeutics to inhibit the tumor growth. Flow cytometry revealed the combined administration induced apoptosis in TPC-1 cells with 24 h treatment. Western blot and immunofluorescence showed the combined administration increased the protein levels of r-H2AX, Parp-1, Bax, Bad and caspase 3 and decreased the level of Bcl-2 preotein. Comet assay demonstrated combined administration induced DNA damage in PTC-1 cells. The results of rAd-P53 combined with paclitaxel and cisplatin to inhibit the growth of lamellipodia and the expression of VEGFR-3 in TPC-1 cells hinted that the combined administration inhibited the metastasis of TPC-1 cells. These results indicated that rAd-P53 combined with paclitaxel and cisplatin did not only inhibit the tumor growth via DNA damage response pathway but also inhibited metastasis in TPC-1 cells. Conclusions: Excellent in vitro and in vivo anti-tumor activity suggested the potential for rAd-P53 combined with chemotherapeutics in the treatment of advanced PTC.
Flow-Cytometry MRD Evaluation in Children with ALL; Can MRD Level on Day 33 Serve As a Surrogate Marker for Relapse?
Authors: Maria Ampatzidou, George Paterakis, Konstantinos Tsitsikas, Stephanos I. Papadhimitriou, Vassilios Papadakis, Vassilios Vasdekis, Loizos Petrikkos, Sophia Polychronopoulou
Journal: Blood (2014)
CPT-11 + CDDP in patients with metastatic and recurrent gastric cancer as a third-line chemotherapy
Authors: T. Yoshida, H. Murakami, A. Tsuburaya, O. Kobayashi, M. Sairenji, H. Motohashi
Journal: Journal of Clinical Oncology (2004)

4204 Background: Among the patients with gastric cancer for whom two consecutive chemotherapy have failed, some still hold good performance status (PS) and organ function and may benefit from further cytotoxic therapy. The response rate (RR) and toxicity of CPT-11 + CDDP in patients treated with two regimens of prior chemotherapy is assessed retrospectively. Methods: 12 patients were treated with CPT-11 (60mg/m2) and CDDP (30mg/m2) on day 1 and 15, and the cycle repeated every 4 weeks. All had received TS-1 (80mg/m2, on day 1–28 every 6 weeks) as a first line, and weekly paclitaxel (80mg/m2, on day 1, 8, 15 every 28 days) as a second line chemotherapy. The median age was 56 yrs (range: 45–69); PS (0/1/2) was 8/3/1; male/female ratio was 10/2. In total, 47 courses were administrated with median of 3 courses (range: 1–9). Initial 4 patients were treated in the hospital, and the latter 8 patients in the outpatient. Results: Grade 3 toxicity occurred in 3 patients including pancytopenia, anemia, and elevation of AST/ALT. Other toxicities were mild. There were no treatment-related deaths. The overall RR was 25.0% (3 PR, 5 SD, 5 PD). RR of patients with metastases in the liver (n=5), lymph node (n=7), lung (n=2), and other (n=3: local, abdominal wall, spleen) were 20.0%, 42.9%, 0%, and 0%, respectively. Median survival time after initiation of CPT-11/CDDP was 214 days (range: 29–366). Conclusions: As a third line chemotherapy, CPT-11/CDDP may benefit patients with relatively good PS in terms of survival. No significant financial relationships to disclose.
P1267 : Retrieval of patients with chronic hepatitis B and C by intensifying regional collaboration, Arnhem region, the Netherlands
Authors: C. Richter, T. Waegemaeckers, I. Polling, L. de Graaf, C. Swanink, M. Roelofs, C. Poorterman, M. Spanier, J.M. Vrolijk, J. Gisolf, G. ter Beest
Journal: Journal of Hepatology (2015)
Dasatinib combined with gemcitabine (Gem) in patients (pts) with locally advanced pancreatic adenocarcinoma (PaCa): Design of CA180-375, a placebo-controlled, randomized, double-blind phase II trial.
Authors: T.R. Jeffry Evans, Eric Van Cutsem, Malcolm J. Moore, Joseph D. Purvis, Lewis C. Strauss, Edwin P. Rock, Jennifer Lee, Chihche Lin, Alexander Rosemurgy, Francis P. Arena, Michelle Gara, Elizabeth Armstrong, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2012)

TPS4134 Background: Dasatinib, a potent oral BCR-ABL and SRC family kinase (SFK) inhibitor, is approved for first- and second-line therapy of Philadelphia chromosome-positive chronic phase chronic myeloid leukemia (CML) in pts with newly diagnosed CML or CML resistant/intolerant to prior therapy. SRC expression and activity is upregulated in PaCa and correlates with reduced survival in resected high-grade PaCa (Morton, Gastroenterology 2010) and resistance to Gem, a PaCa standard of care (Duxbury, J Am Coll Surg 2004). In preclinical PaCa studies, inhibition of SFKs with dasatinib reduces tumor cell proliferation, migration, and invasion; increases apoptosis; sensitizes cells to Gem; and inhibits development of metastases in vivo either alone or in combination with Gem (Duxbury, Clin Cancer Res 2004; Duxbury, J Am Coll Surg 2004; Nagaraj, Mol Cancer Ther 2010; Morton, op cit). Phase I clinical studies of dasatinib and Gem therapy in PaCa have demonstrated feasibility and suggested efficacy of the combination (Uronis, ASCO 2009, abstract e15506). Methods: This double-blind phase II study tests whether addition of dasatinib to Gem is tolerable and improves efficacy in pts with histologically/cytologically confirmed unresectable locally advanced nonmetastatic PaCa. Eligible pts, aged ≥18 years with Eastern Cooperative Oncology Group performance status ≤1 and adequate organ function, are randomized 1:1 to Gem 1000 mg/m 2 IV once weekly (Weeks 1–3 of a 4-week cycle) plus either dasatinib 100 mg once daily or matched placebo. Pts are treated until progression, unacceptable toxicity, withdrawal of consent, or study termination. The primary endpoint is OS, and secondary endpoints are progression-free survival and safety. Exploratory endpoints include freedom from distant metastases, measures of pain and fatigue, overall response rate, and carbohydrate antigen 19-9. Final study analysis will be conducted after 135 deaths; all pts will be followed for survival. To date, 23/200 pts have enrolled; estimated primary completion date is March 2013. ClinicalTrials.gov identifier: NCT01395017.