tbuckley/cabot-search huggingface dataset:
Poor Prognosis With Different Induction Rate Was Observed In Children With Acute Myeloid Leukemia and FLT3-ITD According To The ITD/WT Allelic Ratio: A Result From The Japanese Pediatric Leukemia/Lymphoma Study Group
Authors: Akira Shimada, Yuka Yamashita, Daisuke Tomizawa, Akio Tawa, Tomoyuki Watanabe, Toshiya Yokozawa, Kazuko Kudo, Takashi Taga, Shotaro Iwamoto, Kiminori Terui, Hiroshi Moritake, Akitoshi Kinoshita, Hiroyuki Takahashi, Hideki Nakayama, Katsuyoshi Koh, Hiroaki Goto, Yoshiyuki Kosaka, Akiko Moriya Saito, Junichiro Fujimoto, Keizo Horibe, Kentaro Oki, Yasuhide Hayashi, Souichi Adachi
Journal: Blood (2013)
Targeted deletion of Atg5 in chondrocytes promotes age-related osteoarthritis
Authors: Thibault Bouderlique, Karuna K Vuppalapati, Phillip T Newton, Lei Li, Björn Barenius, Andrei S Chagin
Journal: Annals of the Rheumatic Diseases (2015)

Objectives It has been suggested that the lysosomal recycling process called macro-autophagy plays a role in osteoarthritis development. We thus decided to genetically ablate the autophagy-indispensable Atg5 gene specifically in chondrocytes and analyse the development of osteoarthritis upon aging and in a post-traumatic model. Methods Mice lacking the Atg5 gene in their chondrocytes (Atg5cKO) were generated by crossing Atg5-floxed mice with transgenic mice that expressed cre recombinase driven by the collagen type 2 promoter. Animals were analysed at the age of 2, 6 and 12 months for age-related osteoarthritis or underwent mini-open partial medial meniscectomy at 2 months of age and were analysed 1 or 2 months after surgery. We evaluated osteoarthritis using the Osteoarthritis Research Society International (OARSI) scoring on safranin-O-stained samples. Cell death was evaluated by terminal deoxy-nucleotidyl-transferase-mediated deoxy-UTP nick end labelling (TUNEL) and by immunostaining of cleaved caspases. Results We observed the development of osteoarthritis in Atg5cKO mice with aging including fibrillation and loss of proteoglycans, which was particularly severe in males. The ablation of Atg5 was associated with an increased cell death as assessed by TUNEL, cleaved caspase 3 and cleaved caspase 9. Surprisingly, no difference in the development of post-traumatic osteoarthritis was observed between Atg5cKO and control mice. Conclusions Autophagy protects from age-related osteoarthritis by facilitating chondrocyte survival.
Synthesis, Pharmacology, and Clinical Trial of the Riboflavine Analogue, Sodium-6,7-Dimethyl-9-(2′-Hemisuccinoxyethyl)-Isoalloxazine, U-6538
Authors: Montague Lane, Harold G. Petering, Clyde O. Brindley
Journal: JNCI Journal of the National Cancer Institute (1959)

The synthesis of a riboflavine analogue, sodium-6,7-dimethyl-9-(2′-hemisuccinoxyethyl)-isoalloxazine, U-6538, is reported. Administered parenterally this compound produced inhibition of rat growth which could be reversed by riboflavine. The drug was capable of inhibiting the growth of a rat lymphosarcoma. Prolonged parenteral administration of 1-6538 was well tolerated by rats and dogs. A trial of U-6538 was conducted in 4 patients with malignant neoplasms. Drug dosage was limited by precipitation of a metabolite in the urinary tract. Some patients had signs of renal injury. No definite evidence was obtained of clinical riboflavine deficiency or antitumor effect. An explanation for this is based on the metabolism of the drug.
Development and Validation of a Disease‐Specific Questionnaire to Assess Patient‐Reported Symptoms in Polycystic Liver Disease
Authors: Myrte K. Neijenhuis, Tom J.G. Gevers, Marie C. Hogan, Patrick S. Kamath, Titus F.M. Wijnands, Ralf C.P.M. van den Ouweland, Marie E. Edwards, Jeff A. Sloan, Wietske Kievit, Joost P.H. Drenth
Journal: Hepatology (2016)

Treatment of polycystic liver disease (PLD) focuses on symptom improvement. Generic questionnaires lack sensitivity to capture PLD‐related symptoms, a prerequisite to determine effectiveness of therapy. We developed and validated a disease‐specific questionnaire that assesses symptoms in PLD (PLD‐Q). We identified 16 PLD‐related symptoms (total score 0‐100 points) by literature review and interviews with patients and clinicians. The developed PLD‐Q was validated in Dutch (n = 200) and United States (US; n = 203) PLD patients. We assessed the correlation of PLD‐Q total score with European Organization for Research and Treatment of Cancer (EORTC) symptom scale, global health visual analogue scale (VAS) of EQ‐5D, and liver volume. To test discriminative validity, we compared PLD‐Q total scores of patients with different PLD severity stages (Gigot classification) and PLD‐Q total scores of PLD patients with general controls and polycystic kidney disease patients without PLD. Reproducibility was tested by comparing original test scores with 2‐week retest scores. In total, 167 Dutch and 124 US patients returned the questionnaire. Correlation between PLD‐Q total score and EORTC symptom scale (The Netherlands [NL], r = 0.788; US, r = 0.811) and global health VAS (NL, r = −0.517; US, r = −0.593) was good. There was no correlation of PLD‐Q total score with liver volume (NL, r = 0.138; P = 0.236; US, r = 0.254; P = 0.052). Gigot type III individuals scored numerically higher than type II patients (NL, 46 vs. 40; P = 0.089; US, 48 vs. 36; P = 0.055). PLD patients scored higher on the PLD‐Q total score than general controls (NL, 42 vs. 17; US, 40 vs. 13 points) and polycystic kidney disease patients without PLD (22 points). Reproducibility of PLD‐Q was excellent (NL, r = 0.94; US, 0.96). Conclusion: PLD‐Q is a valid, reproducible, and sensitive disease‐specific questionnaire that can be used to assess PLD‐related symptoms in clinical care and future research. (H epatology 2016;64:151–160)
RTOG 0625: A phase II study of bevacizumab with irinotecan in recurrent glioblastoma (GBM)
Authors: M. R. Gilbert, M. Wang, K. Aldape, A. Lassman, A. G. Sorensen, T. Mikkelson, M. Groves, M. Werner-Wasik, W. Regine, M. Mehta
Journal: Journal of Clinical Oncology (2009)

2011 Background: Angiogenesis is a hallmark of GBM, making the tumor vasculature an attractive therapeutic target. In gliomas, vascular endothelial growth factor (VEGF) promotes both angiogenesis and invasion of tumor cells. Bevacizumab is a humanized monoclonal antibody against VEGF-A that rapidly reduces the concentration of VEGF in the circulation. Irinotecan may enhance efficacy by synergistic tumor endothelial cell death or improved tumor delivery of the chemotherapy via “normalized” tumor vasculature. Prior studies of this combination demonstrated high radiographic response and 6-month progression free (6-mPFS) rates. This study was designed to determine the efficacy and safety of this regimen in the cooperative group setting. Methods: Eligibility included age ≥ 18, centrally confirmed GBM or gliosarcoma, progressive or recurrent disease. Enzyme-inducing anticonvulsants were not allowed. Treatment was intravenous bevacizumab 10 mg/kg and irinotecan 200 mg/m 2 every 2 weeks. Accrual goal was 57 eligible patients. Primary endpoint was 6-mPFS rate where an estimate of ≥ 35% would define efficacy (15% improvement over historical data). Results: Full enrollment (57) was achieved, median age was 57, median KPS was 80; all had prior radiation and temozolomide treatment. The 6m-PFS rate was 37% (95% CI: 24–50%), with 21 of 57 patients progression-free at 6 months. Moderate toxicity was noted with 21(37%) grade 3, seven (12%) grade 4, and one (&lt;2%) treatment-related death (intracranial hemorrhage). There were six episodes of venous thrombosis, 14 episodes of grade 3 or 4 hematologic toxicity, predominantly lymphopenia (7), and neutropenia (4), no opportunistic infections or febrile neutropenia were noted. Other toxicities included fatigue (9), diarrhea (2), and hypertension (2). Conclusions: These results, in the cooperative group context, corroborate the efficacy of the bevacizumab and irinotecan combination for recurrent GBM with the 6m-PFS surpassing the predetermined efficacy threshold. Previously described toxicities were confirmed with a moderately high rate of venous thrombosis, one intracranial hemorrhage, and moderate hypertension. Studies to determine the contribution of the cytotoxic agent to efficacy and the role of bevacizumab in newly diagnosed GBM are planned. [Table: see text]
Effect of microscopic residual tumor (MRT) at surgical margin of resection (SMR) in ductal carcinoma in-situ (DCIS) on survival of non-Hispanic white women in central Pennsylvania (PA)
Authors: P. Kumar, A. M. Ingle, B. Baney, K. Day, T. Dagen, A. S. Galley, R. H. Dixon
Journal: Journal of Clinical Oncology (2006)

10706 Background: Few studies that have investigated the long-term effect of MRT in DCIS, have demonstrated conflicting results. Mount Nittany Medical Center (MNMC) is located in an agricultural, ethnically-homogenous (Non-Hispanic White) county in PA. To the best of our knowledge, there have been no similar studies conducted on such populations. Our study has investigated the effect of MRT at SMR on overall survival (OS) and event-free survival (EFS) of patients with DCIS. Methods: All women diagnosed with DCIS from 04/1992 to 06/2005 at MNMC were deemed eligible. Log-rank statistics and Cox proportional hazard models (CPHM) were used for obtaining survival rates. Results: Of the 266 eligible women analysis were performed on 167 women (age range 33–89 years; median 56 years) with complete data on diagnosis, surgical margins and treatment modalities. With median follow-up time of 4.6 years (range 0.03–11.6years), 148 (88.6%) patients had no residual tumor at SMR. 78 (46.7%) patients received radiation therapy (RT) ± hormonal therapy (HT), 42 (25.2%) received HT ± RT. The CPHM demonstrated no statistical significance of MRT on OS (hazard ratio 2.9, p = 0.19), and EFS (hazard ratio = 1.9, p = 0.43) after adjusting for treatment and age. Univariate 5-year OS rate in patients with no MRT was 93.9% (95% confidence interval (CI) 87.6% to 97.1%), versus 89.2% (95% CI 63.1% to 97.2%) in patients with MRT (p-value = 0.38). Five-year EFS was observed to be 92.6% (95% CI 85.6% to 96.3%) in patients with no MRT, versus 89.2% (95% CI 63.1% to 97.2%) in patients with MRT (p-value = 0.49). Conclusions: In our study, patients with DCIS who have MRT at surgical margin of resection have a 2.9 times the risk of death and 1.9 times the risk of recurrence as compared to patients with no MRT. However, this difference is statistically not significant over time. No significant financial relationships to disclose.
Usefulness of interim FDG-PET after induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck receiving induction chemotherapy and definitive chemoradiotherapy.
Authors: S. Kim, D. Yoon, Y. Cho, S. Nam, S. Choi, S. Lee, J. Lee, J. Kim, K. Cho
Journal: Journal of Clinical Oncology (2010)

5524 Background: Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Still, the clinical outcomes of locally advanced SCCHN patients who showed response to ICT are heterogenous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of locally advanced SCCHN patients who achieved partial response (PR) or complete response (CR) to ICT to predict clinical outcome following concurrent chemoradiotherapy (CCRT). Methods: Twenty one patients with locally advanced SCCHN who showed at least PR to ICT by RECIST prior to definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2 to 4 weeks after ICT to assess the extent of the disease at baseline and metabolic response to ICT, respectively. We examined the correlation of metabolic response by the percent decrease in maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or specific threshold of SUVmax on interim FDG-PET with clinical outcome including CR rate to CCRT, progression-free survival (PFS) and overall survival (OS). Results: SUVmax of 4.8 on interim FDG-PET could predict clinical CR following CCRT (100% vs. 20%, p=0.001), PFS (median, not reached vs. 8.5 mo, p<0.001), and OS (median, not reached vs. 12.0 mo, p=0.001) with a median follow-up of 20.3 mo in surviving patients. Sixty five percent decrease in SUVmax after ICT from baseline also could predict clinical CR following CCRT (100% vs. 33.3%, p=0.003), PFS (median, not reached vs. 8.9 mo, p<0.001) and OS (median, not reached vs. 24.4 mo, p=0.001) of the patients. Conclusions: These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcome in patients with locally advanced SCCHN receiving sequential ICT followed by CCRT. No significant financial relationships to disclose.
Providing Medical Services Through School-Based Health Programs
Journal: JAMA (1989)

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
Bit1 knockdown contributes to growth suppression as well as the decreases of migration and invasion abilities in esophageal squamous cell carcinoma via suppressing FAK-paxillin pathway
Authors: Tianli Fan, Jing Chen, Lirong Zhang, Pan Gao, Yiran Hui, Peirong Xu, Xiaqing Zhang, Hongtao Liu
Journal: Molecular Cancer (2016)

There is growing evidence that Bit1 exerts different roles in the development and progression of human cancers. Although Bit1 was highly exhibited in ESCC tissues in our previous study, its roles and molecular mechanisms implicated in development and progression of ESCC remain unknown. Bit1 protein expression in ESCC cell lines and normal esophageal epithelial cell was detected by Western blotting. Bit1 protein expression mediated by Bit1 shRNA was investigated by Western blotting. MTT, migration assay, invasion experiment, ELISA and Flow cytometry were utilized to determine the effects of Bit1 knockdown on cell proliferation, migration, invasion and apoptosis, respectively. A xenograft model was used to examine in vivo tumourigenicity, and immunohistochemistry and TUNEL were utilized to evaluate the related protein expression and apoptosis. Gene microarray was determined by Agilent SurePrint G3 Human GE 8 × 60 K Microarray, the interaction of Bit1 and FAK proteins were detected by Immunoprecipitation and the key protein expressions of FAK-paxillin pathway were detected by Western blotting. We found Bit1 expression in all human ESCC cell lines tested was significantly higher than that in normal esophageal epithelial cell Het-1A (P < 0.05), in which EC9706 presented the highest Bit1 level. Bit1 protein level was significantly downregulated at day 1 after transfection with specific shRNA against Bit1 (P < 0.05). At days 2 and 3, Bit1 level reached the lowest value after transfection with Bit1 shRNA. Moreover, Bit1 depletion contributed to growth inhibition in vitro and in vivo, reduced cell migration and invasion abilities, and induced cell apoptosis in EC9706 and TE1 cells. More importantly, Bit1 downregulation significantly lowered Bcl-2 and MMP-2 levels in EC9706 xenografted tumor tissues, meanwhile triggered apoptosis after treatment with different doses of Bit1 shRNA. Further gene microarray revealed that 23 genes in Bit1-RNAi group were markedly downregulated, whereas 16 genes were obviously upregulated. Notably, Bit1 intrinsically interacted with FAK protein in EC9706 cells. Moreover, paxillin was downregulated at mRNA and protein levels in Bit1 shRNA group, coupled with the decreases of FAK mRNA and protein expressions. Bit1 may be an important regulator in cell growth, apoptosis, migration and invasion of ESCC via targeting FAK-paxillin pathway, and thereby combinative manipulation of Bit1 and FAK-paxillin pathway may be the novel and promising therapeutic targets for the patients with ESCC.
Abstract 3: Il-10 Regulated Mir-375 Enhances Endothelial Progenitor Cell Mediated Myocardial Repair And Survival After Myocardial Infarction.
Authors: Venkata N Garikipati, Prasanna Krishnamurthy, Suresh K Verma, Alexandra R Mackie, Erin E Vaughan, Mohsin Khan, Veronica Ramirez, Tatiana Abramowa, Kenneth L Ellingson, Sol Misener, Aiko I klingler, Gangjian Qin, Walter J Koch, Raj Kishore
Journal: Circulation Research (2014)

We hypothesized that IL-10 regulates miR-375 signaling in EPCs to enhance their survival and function in ischemic myocardium after MI. miR-375 knock down EPC were transplanted intramyocardially after induction of MI. Mice receiving EPC treated with miR-375 inhibitor showed increased number of GFP+EPCs retention that was associated with reduced EPC apoptosis in the myocardium. The engraftment of EPC into the vascular structures and the associated capillary density was significantly higher in miR-375-treated mice. The above findings further correlated with reduced infarct size, fibrosis and enhanced LV function (echocardiography) in miR-375 knock down EPC group as compared to scrambled EPC. Our in vitro studies revealed that the knockdown of miR-375 enhanced EPC proliferation, migration; tube formation ability and inhibited cell apoptosis, while the up-regulation of miR-375 with the mimic had the opposite effects. In addition, we found that miR-375 negatively regulates the expression of 3-phosphoinositide-dependent protein kinase 1 (PDK1) by directly targeting the 3'UTR of the PDK1 transcript. Interestingly, EPC isolated from IL-10-deficient mice has elevated basal levels of miR-375 and exhibited poor proliferation and tube formation ability where as miR-375 knock down in EPC isolated from IL-10 deficient mice attenuated these effects. Furthermore, transplantation of miR-375 knock down IL-10 deficient EPC after MI resulted in attenuated cardiac functions compared to scramble IL-10 deficient EPCs. Taken together, our studies suggest that IL-10 regulated miR-375 enhances EPC survival and function, associated with efficient myocardial repair via activation of PDK-1/AKT signaling cascades.
Different Th17 immunity in gut, liver, and adipose tissues during obesity: the role of diet, genetics, and microbes
Authors: Joseph F. Cavallari, Emmanuel Denou, Kevin P. Foley, Waliul I. Khan, Jonathan D. Schertzer
Journal: Gut Microbes (2016)

Microbes modify immunometabolism responses linking obesity and type 2 diabetes. Immunity helps maintain a host-microbe symbiosis, but inflammation can promote insulin resistance in tissues that control blood glucose. We were interested in compartmentalization of immune responses during obesity and show here that feeding mice an obesity-causing high-fat diet (HFD) decreased a marker of neutrophil activation and cytokines related to Th17 responses in the gut. A HFD decreased IL-17 and IL-21/22 in the ileum and colon, respectively. A HFD increased IL-17, IL-21/22 and other related Th17 responses in the liver. At the whole tissue level, there is divergence in gut and metabolic tissue Th17 cytokines during diet-induced obesity. Deletion of the bacterial peptidoglycan sensor NOD2 had relatively minor effects on these immune responses. We propose a model where diet-induced obesity promotes a permissive gut immune environment and sets the stage for host genetics to contribute to dysbiosis-driven metabolic tissue inflammation.
HMGB1 Release and TLR4-Mediated Inflammation In Sickle Cell Disease At Baseline and During Acute Vaso-Occlusive Crisis
Authors: Hao Xu, Nancy J. Wandersee, YiHe H. Guo, Deron W. Jones, Sandra L. Holzhauer, Madelyn S. Hanson, Neil Hogg, John C. Densmore, Sushma Kaul, Cheryl A. Hillery, Kirkwood A. Pritchard
Journal: Blood (2013)
A Longitudinal, Prospective Study On Adherence To Medical Regimen Before and After Liver Transplantation
Authors: Giacomo Germani, Francesca Gnoato, V. Borella, Silvia Lazzaro, Egle Perissinotto, Marco Senzolo, Francesco Paolo Russo, Eleonora De Martin, Martina Gambato, Umberto Cillo, Giacomo Sturniolo, Patrizia Burra
Journal: Hepatology (2009)
Secretory IgA in complex with Lactobacillus rhamnosus potentiates mucosal dendritic cell-mediated Treg cell differentiation via TLR regulatory proteins, RALDH2 and secretion of IL-10 and TGF-β
Authors: Josip Mikulic, Stéphanie Longet, Laurent Favre, Jalil Benyacoub, Blaise Corthesy
Journal: Cellular and Molecular Immunology (2016)
Circulating tumor cells - not serum tumor markers - predict survival in metastatic breast cancer
Authors: A. Stopeck, M. Cristofanilli, G. T. Budd, M. J. Ellis, J. Matera, M. C. Miller, G. V. Doyle, W. J. Allard, L. W. Terstappen, D. F. Hayes
Journal: Journal of Clinical Oncology (2005)

9516 Background: The presence of ≥5 circulating tumor cells (CTCs) in 7.5mL of blood in women with metastatic breast cancer (MBC) is associated with poor outcome (NEJM 2004). Here we provide previously unreported data from this multi-center trial on the assessment of the serum tumor marker MUC-1 (CA27.29 and/or CA15–3). Methods: In 65 of 177 MBC patients CTCs were assessed at 1st follow-up and MUC-1 at baseline, 1st follow-up (n=65), and the first disease reassessment (V1) after initiation of therapy (n=54). Assessment of MUC-1 was not mandated by the protocol and was only available from investigators that performed the assay as part of their routine assessment. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch Kit. Only nucleated (DAPI+) cells with the phenotype EpCAM+, Cytokeratin 8, 18 and/or 19+, and CD45- were counted using the CellSpotter Analyzer. Patients were classified as positive when ≥5 CTCs/7.5mL were detected. Patients were classified as positive when MUC-1 increased by 25% over the two time points. Results: Twenty-four of 65 (37%) patients had ≥ 5CTCs, 19 of 65 (29%) and 18 of 54 (33%) had >25% increase in MUC-1 at 1st follow-up and V1 respectively. CTCs and change in MUC-1 did not significantly correlate at any time point. In a univariate Cox hazards regression analysis, significant parameters for Progression Free Survival (PFS) were type of therapy (p=0.0197), change in MUC-1 (p≤0.0008), and CTCs (p=0.0008). For Overall Survival (OS) significant parameters were ER/PR (p=0.0172), ECOG (p=0.0128), type of therapy (p=0.0314) and CTCs (p=0.0064). MUC-1 was not significant for OS at 1st follow-up or 1st disease reassessment (p≥0.2255). In multivariate analyses, CTCs remained the strongest and most significant independent predictor of poor outcome. Conclusions: A significant correlation between PFS and change in serum MUC-1 tumor marker and CTCs was found in MBC. MUC-1 however did not correlate with overall survival. The presence of CTCs after initiation of therapy strongly correlates with survival and may be a more appropriate surrogate measure of disease progression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunicon Immunicon