tbuckley/cabot-search huggingface dataset:
Regulation of IL-4 Gene Expression By SIRT1 in Human Mast Cell
Authors: Yuji Nakamaru, Dai Takagi, Satoshi Fukuda
Journal: Journal of Allergy and Clinical Immunology (2016)

Histone protein modification control gene transcription via chromatin remodeling. Because a differentiation from naïve T cell to Th2 cell was induced by the chromatin remodeling, it may regulate allergic diseases. SIRT1 is an NAD-dependent deacetylase that regulate stress response and modulates inflammation and cell survival. This study was to investigate whether SIRT1 control IL-4 production in human mast cells. The HMC-1 (human mast cell line) was cultured with or without SIRT1 activator and inhibitor and stimulated with calcium ionophore and PMA. Four hours after the stimulation, mRNA was extracted from these cells for IL-4 real time PCR. Quantitative measurement of IL-4 in cell supernatant was performed using the human IL-4 ELISA kit. To clarify the direct function of SIRT1, we used small interference RNA against SIRT1. Two kinds of SIRT1 siRNA and negative control siRNA were transfected into HMC-1 cells by electroporation. HMC-1 cells were expressing IL-4 mRNA in unstimulated state. Stimulation with A23187 and PMA increased the expression of IL-4 mRNA at basal level. Expressions of IL-4 mRNA were enhanced in the presence of splitomysin with dose dependent manner. On the other hand, the resveratrol suppressed IL-4 mRNA expression in dose dependent manner. Quantitative measurement of IL-4 in cell supernatant revealed that IL-4 protein production was enhanced in the presence of splitomysin and suppressed in the presence of resveratrol. SIRT1 knock down up regulates IL-4 mRNA expression. SIRT1 may play some role in developing allergic diseases via control IL-4 gene expression.
Randomized phase II, three-arm trial of lenvatinib (LEN), everolimus (EVE), and LEN+EVE in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Robert Motzer, Thomas Hutson, Hilary Glen, Dror Michaelson, Ana M. Molina, Timothy Eisen, Jacek Jassem, Jakub Zolnierek, Pablo Maroto, Begona Mellado, Bohuslav Melichar, Jiri Tomasek, Han-Joo Kim, Karen Wood, Corina Dutcus, James M. G. Larkin
Journal: Journal of Clinical Oncology (2015)

4506 Background: Lenvatinib (LEN), an oral tyrosine kinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT, in combination with EVE had manageable toxicity and antitumor activity in a phase 1 mRCC trial (CCP 2013;73:181). This phase II, open-label, multicenter study compared LEN, EVE, and LEN+EVE in pts with mRCC. Methods: Pts with progressive clear cell mRCC following 1 VEGF-targeted therapy were randomized 1:1:1 to LEN (24 mg/d), EVE (10 mg/d), or LEN+EVE (18+5 mg/d) in 28d cycles. The primary objective was progression-free survival (PFS) of LEN+EVE or LEN vs EVE. Secondary objectives included overall survival (OS), objective response rate (ORR), and safety. Primary analysis data cutoff was June 13, 2014. Results: One hundred and fifty-three pts were enrolled: 99% had one prior VEGF-targeted therapy, 1% had two; 18% had prior immunotherapy. LEN+EVE prolonged PFS vs EVE (Table; hazard ratio [HR] 0.40; 95% confidence interval [CI] 0.24–0.68; P < 0.001). LEN alone also prolonged PFS vs EVE (HR 0.61; 95% CI 0.38–0.98; P = 0.048). LEN+EVE and LEN improved ORR vs EVE (P < 0.001 and P = 0.007, respectively). Median duration of response (months) was longest in LEN+EVE, 13.1; LEN, 7.5; EVE, 8.5. OS analysis showed a trend favoring LEN+EVE vs EVE (HR 0.55; 95% CI 0.30–1.01; P = 0.062); this reached significance (HR 0.51; 95% CI 0.30–0.88; P = 0.024) in an updated analysis on Dec 10, 2014. For LEN+EVE, most common any-grade treatment-emergent adverse events (TEAEs) were diarrhea (84%), decreased appetite (51%), and fatigue (47%). Most common grade ≥ 3 TEAEs were diarrhea (20%), hypertension (14%), and fatigue (10%). Conclusions: LEN+EVE improved PFS and ORR versus EVE alone in this phase II trial of pts with mRCC following prior VEGF-targeted therapy. Updated OS also showed improvement with LEN+EVE. A phase III randomized trial of the combination in mRCC is planned. Clinical trial information: NCT01136733. Primary analysis LEN+EVE n = 51 LEN n = 52 EVE n = 50 Median survival, months (95% CI) PFS 14.6 (5.9–20.1) 7.4 (5.6–10.2) 5.5 (3.5–7.1) OS 25.5 (20.8–25.5) 18.4 (13.3–NE) 17.5 (11.8–NE) ORR, n (%) 22 (43) 14 (27) 3 (6) Median duration of response, months (95% CI) 13.1 (3.8–NE) 7.5 (3.8–NE) 8.5 (7.5–9.4) Median # of cycles, (range) 9.0 (1–25) 8.5 (1–25) 5.0 (1–22) NE, not evaluable
Abstract P2-09-03: Breast cancer prevention: Is it time for population-based mutation screening of high risk genes?
Authors: IG Campbell, AH Trainer, L Devereux, M-A Young, G Mitchell, S Rowley, N Li, PA James, E Thompson
Journal: Cancer Research (2016)

Abstract The traditional model of familial breast cancer practice involves ascertaining high-risk individuals based on family history. However, most individuals who carry a BRCA1 or BRCA2 mutation will not have a family history of breast or other cancer in a close relative. Moving germline testing from the familial cancer center to the population will result in many essentially unanticipated findings of great significance in regards to the risk of breast cancer in healthy relatives. To date there have been no large studies that have directly measured the frequency of BRCA1 and BRCA2 mutations in a cancer-free general population. As a first step toward population based BRCA1 or BRCA2 screening, we sequenced the entire coding region of these genes in 1,997 cancer-free Australian women recruited from the lifepool study (www.lifepool.org) which is a cohort of women attending the Australian population based mammographic screening program. Sequencing data were filtered for known pathogenic or novel loss of function mutations. Twelve individuals were identified with pathogenic mutations in either BRCA1 (4 mutations) or BRCA2 (8 mutations), which is consistent with previous indirect estimates for Caucasian populations but to our knowledge this is the largest direct assessment of their prevalence. Interestingly, the self-reported cancer family history of the majority of the 12 mutation positive women was unremarkable. All 12 women subsequently accepted an invitation to attend a Familial Cancer Centre for advice on whether to proceed with formal clinical genetic testing. A population carrier frequency of 0.6% for mutations in BRCA1 and BRCA2, coupled with the rapidly declining costs of gene panel sequencing, suggests that population-based screening for these genes will be a highly cost effective way of reducing the incidence of breast and ovarian cancer through preventative strategies. Citation Format: Campbell IG, Trainer AH, Devereux L, Young M-A, Mitchell G, Rowley S, Li N, James PA, Thompson E. Breast cancer prevention: Is it time for population-based mutation screening of high risk genes?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-03.
Acetylcarnitine Is a Candidate Diagnostic and Prognostic Biomarker of Hepatocellular Carcinoma
Authors: Yonghai Lu, Ning Li, Liang Gao, Yong-Jiang Xu, Chong Huang, Kangkang Yu, Qingxia Ling, Qi Cheng, Shengsen Chen, Mengqi Zhu, Jinling Fang, Mingquan Chen, Choon Nam Ong
Journal: Cancer Research (2016)

Abstract The identification of serum biomarkers to improve the diagnosis and prognosis of hepatocellular carcinoma has been elusive to date. In this study, we took a mass spectroscopic approach to characterize metabolic features of the liver in hepatocellular carcinoma patients to discover more sensitive and specific biomarkers for diagnosis and progression. Global metabolic profiling of 50 pairs of matched liver tissue samples from hepatocellular carcinoma patients was performed. A series of 62 metabolites were found to be altered significantly in liver tumors; however, levels of acetylcarnitine correlated most strongly with tumor grade and could discriminate between hepatocellular carcinoma tumors and matched normal tissues. Post hoc analysis to evaluate serum diagnosis and progression potential further confirmed the diagnostic capability of serum acetylcarnitine. Finally, an external validation in an independent batch of 58 serum samples (18 hepatocellular carcinoma patients, 20 liver cirrhosis patients, and 20 healthy individuals) verified that serum acetylcarnitine was a meaningful biomarker reflecting hepatocellular carcinoma diagnosis and progression. These findings present a strong new candidate biomarker for hepatocellular carcinoma with potentially significant diagnostic and prognostic capabilities. Cancer Res; 76(10); 2912–20. ©2016 AACR.
Abstract 5: Secular Trends in Community Cardiac Arrest Survival: Results From the Resuscitation Outcomes Consortium (ROC)
Authors: Mohamud R Daya, Robert Schmicker, Dana Zive, Thomas Rea, James Christenson, Graham Nichol, Susanne May, Renee MacPhee, Jon Rittenberger, Jason E Buick, Steven Brooks, Alan Craig, Dan P Davis, Jane Wigginton, Henry E Wang
Journal: Circulation (2013)

Background: The Resuscitation Outcomes Consortium (ROC) is a research network evaluating interventions in out-of-hospital cardiac arrest (OHCA) which maintains an epidemiologic registry of consecutive cases of OHCA assessed by emergency medical services (EMS) agencies. ROC has completed 3 cardiac arrest clinical trials with no significant survival differences. However, we hypothesize that OHCA survival may have changed over time due to participation in ROC. Objectives: To evaluate changes in OHCA survival to hospital discharge over time in ROC sites. Methods: We included OHCA cases treated by 139 participating EMS agencies between 1/1/06-12/31/10. We excluded cases with definite non-cardiac etiology and months with incomplete case capture. The association between survival and year was assessed using multi-level mixed effects logistic regression with agency nested in region and region nested in site. Covariates included: age; sex; EMS response interval; witness status; bystander CPR; location of arrest and first rhythm. We used an independent covariance structure with random intercepts. Results: Mean EMS response interval, median age and male gender proportion were similar over time. Survival to hospital discharge increased over time for treated cases between 2006 and 2010, as well as for the subgroups of VT/VF and witnessed VT/VF (Table). Survival increase compared to 2006 remained significant for each subsequent year after covariate adjustment with OR’s (95% CI) for survival in 2010 of 1.73 (1.52, 1.95) for all cases, 1.66 (1.42, 1.95) for VT/VF and 1.59 (1.33, 1.89) for witnessed VT/VF. Test for trend according to year was significant for all cases and among the VT/VF subgroups (p=&lt;0.001). Conclusion: Survival from OHCA increased over time within the ROC research network despite a lack of survival differences in the clinical trials. Further research is required to identify the specific factors associated with this improvement.
Long-Term Propagation of the Rauscher Murine Leukemia Virus in Tissue Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Bruce S. Wright, Jennie C. Lasfargues
Journal: JNCI Journal of the National Cancer Institute (1965)

An established cell line, derived from cells of the spleen and thymus of normal weanling BALB/c mice, propagated the Rauscher murine leukemia virus. The sixth passage of this culture was infected with a mouse spleen virus preparation. The infected culture has since been through 135 successive transfers, with tissue culture fluids sampled frequently. Infectivity bioassays of these fluids showed that virus collected after 194 days was as active as that taken after 21 days. Both newborn and weanling BALB/c mice responded not only to concentrated but also to unprocessed cell-free tissue culture fluids. These mice developed the typical leukemia symptoms described by Rauscher. Continued virus multiplication was evaluated by electron microscopy and assays in vivo of cell-free tissue culture fluids. The virus was identified by serum neutralization, gross pathology of infected mice, electron microscopy, and the fluorescent-antibody technique. No cytopathogenic effects of the virus have been seen in the infected cell line.
Inpact of a ten week mind-body medicine intervention on peristent fatigue following breast cancer treatment: 6 month follow- up
Authors: K. J. Helzlsouer, S. E. Appling, S. Scarvalone, M. McBeth, L. Gallicchio, S. Hoffman
Journal: Journal of Clinical Oncology (2007)

9062 Background: Persistent fatigue following breast cancer treatment, which affects up to 40% of breast cancer patients, is the result of diverse patient and treatment factors. The multi-dimensional underlying etiology of fatigue calls for broad based interventions aimed at managing stress, improving diet and exercise patterns and short term cognitive therapy supporting attitudinal and behavioral changes. A pilot study was conducted to obtain preliminary efficacy information for a ten week group-based mind body intervention to treat persistent fatigue among breast cancer survivors. Methods: The quasi-experimental study design used a before/after evaluation of fatigue scores. Subjects were women who were between six months and five years post-completion of adjuvant chemotherapy and/or radiation therapy for breast cancer and who had a baseline fatigue score of ≤ 50 as measured by the vitality subscale of the SF-36 Health Survey. Twenty- one women entered the study. Three participants dropped out after attending only two of the ten weekly sessions and are excluded from the analysis. Main outcome measures were change in severity of fatigue as measured by the Piper Fatigue Scale and vitality subscale score of the SF-36. Results: At baseline, the mean age of participants was 52.7 years; 66.7% were Caucasian and 23.7% were African-American. Median time since breast cancer diagnosis was 2.9 years. The mean Piper fatigue score improved from 6.0 (SD 1.5) at baseline to 4.0 (SD 2.1) at the end of the ten week intervention (p&lt; 0.001). Fatigue scores at two and six months post-intervention were 3.2 (SD 2.9; p= 0.001) and 4.1 (SD 2.1; p= 0.02), respectively. Similarly the SF-36 vitality subscale score improved following the intervention with persistent improvement at 6 months (p=0.02). Conclusion: A holistic integrated mind body medicine intervention holds promise for long-term impact on reducing fatigue following breast cancer treatment. Sponsored by Susan G. Komen Breast Cancer Foundation No significant financial relationships to disclose.
Marijuana Tourism and Emergency Department Visits in Colorado
Authors: Howard S Kim, Katelyn E Hall, Emma K Genco, Mike Van Dyke, Elizabeth Barker, Andrew A Monte
Journal: New England Journal of Medicine (2016)

At a large hospital in Colorado, the rate of ED visits related to cannabis use doubled for out-of-state patients, with little change for in-state patients, from 2013 through 2014, the first year of retail marijuana sales. Statewide data confirmed these differential trends.
IL-36R signalling activates intestinal epithelial cells and fibroblasts and promotes mucosal healing in vivo
Authors: Kristina Scheibe, Ingo Backert, Stefan Wirtz, Axel Hueber, Georg Schett, Michael Vieth, Hans Christian Probst, Tobias Bopp, Markus F Neurath, Clemens Neufert
Journal: Gut (2016)

<h3>Objective</h3> Interleukin (IL)-36R signalling plays a proinflammatory role in different organs including the skin, but the expression of IL-36R ligands and their molecular function in intestinal inflammation are largely unknown. <h3>Design</h3> We studied the characteristics of IL-36R ligand expression in IBDs and experimental colitis. The functional role of IL-36R signalling in the intestine was addressed in experimental colitis and wound healing models in vivo by using mice with defective IL-36R signalling (<i>IL-36R</i>−/−) or Myd88, neutralising anti-IL-36R antibodies, recombinant IL-36R ligands and RNA-seq genome expression analysis. <h3>Results</h3> Expression of IL-36α and IL-36γ was significantly elevated in active human IBD and experimental colitis. While IL-36γ was predominantly detected in nuclei of the intestinal epithelium, IL-36α was mainly found in the cytoplasm of CD14<sup>+</sup> inflammatory macrophages. Functional studies showed that defective IL-36R signalling causes high susceptibility to acute dextran sodium sulfate colitis and impairs wound healing. Mechanistically, IL-36R ligands released upon mucosal damage activated IL-36R<sup>+</sup> colonic fibroblasts via Myd88 thereby inducing expression of chemokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-6. Moreover, they induced proliferation of intestinal epithelial cells (IECs) and expression of the antimicrobial protein lipocalin 2. Finally, treatment of experimental intestinal wounds with IL-36R ligands significantly accelerated mucosal healing in vivo. <h3>Conclusions</h3> IL-36R signalling is activated upon intestinal damage, stimulates IECs and fibroblasts and drives mucosal healing. Modulation of the IL-36R pathway emerges as a potential therapeutic strategy for induction of mucosal healing in IBD.
The lipid interaction capacity of Sin a 2 and Ara h 1, major mustard and peanut allergens of the cupin superfamily, endorses allergenicity
Authors: A. Angelina, S. Sirvent, C. Palladino, A. Vereda, J. Cuesta‐Herranz, T. Eiwegger, R. Rodríguez, H. Breiteneder, M. Villalba, O. Palomares
Journal: Allergy (2016)

Abstract Background Sin a 2 (11S globulin) and Ara h 1 (7S globulin) are major allergens from yellow mustard seeds and peanut, respectively. The ability of these two allergens to interact with lipid components remains unknown. Objective To study the capacity of Sin a 2 and Ara h 1 to interact with lipid components and the potential effects of such interaction in their allergenic capacity. Methods Spectroscopic and SDS ‐ PAGE binding assays of Sin a 2 and Ara h 1 with different phospholipid vesicles and gastrointestinal and endolysosomal digestions in the presence or absence of lipids were performed. The capacity of human monocyte‐derived dendritic cells (hmo DC s) to capture food allergens in the presence or absence of lipids, the induced cytokine signature, and the effect of allergens and lipids to regulate TLR 2‐L‐induced NF ‐ kB / AP ‐1 activation in THP 1 cells were analyzed. Results Sin a 2 and Ara h 1 bind phosphatidylglycerol ( PG ) acid but not phosphatidylcholine ( PC ) vesicles in a pH ‐dependent manner. The interaction of these two allergens with lipid components confers resistance to gastrointestinal digestion, reduces their uptake by hmo DC s, and enhances their stability to microsomal degradation. Mustard and peanut lipids favor a proinflammatory environment by increasing the IL ‐4/ IL ‐10 ratio and IL ‐1β production by hmo DC s. The presence of mustard lipids and PG vesicles inhibits TLR 2‐L‐induced NF ‐ kB / AP ‐1 activation in THP 1 cells. Conclusion Sin a 2 and Ara h 1 interact with lipid components, which might well contribute to explain the potent allergenic capacity of these two clinically relevant allergens belonging to the cupin superfamily.
Heroin-Induced Rhabdomyolysis as a Cause of Reflex Sympathetic Dystrophy
Authors: BI-FANG LEE, NAN-TSING CHIU, WEI-HSI CHEN, GIN-CHUNG LIU, HSIN-SU YU
Journal: Clinical Nuclear Medicine (2001)

Reflex sympathetic dystrophy is an excessive or abnormal response of the sympathetic nervous system in an extremity to an injury or other condition. The authors describe a 37-year-old man who experienced constant pain and vasomotor instability in both feet after nontraumatic rhabdomyolysis secondary to smoking heroin. Three-phase bone scintigraphy was performed and revealed significantly increased blood-flow, blood-pool, and delayed-phase radioactivity. The follow-up three-phase bone scinitigram showed less radiotracer uptake that was consistent with a good response to calcitonin therapy. Heroin-induced rhabdomyolysis should be added to the list of precipitating conditions that can induce this syndrome.
Effect of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor priming (CAG regimen) on the outcome of elderly patients with acute myeloid leukemia
Authors: S. Qian, J. Li, S. Zhang
Journal: Journal of Clinical Oncology (2007)

7067 Background: To evaluate the efficacy and toxicity of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) protocol in elderly patients with acute myeloid leukemia (AML). Methods: A total of fifty-two elderly patients were enrolled. Twenty-eight patients were male, and 24 were female, with ages ranging from 60 to 81 years (median, 65 years). Complete remission (CR) had not been achieved in five patients after 2 courses of a standard induction regimen including daunorubicin and cytarabine or an equivalent anthracycline-based regimen. Cytogenetic analysis was performed in 40 patients, and unfavourable cytogenetic aberrations were showed in 10 patients. All patients were treated with CAG regimen including low-dose cytarabine (10 mg/m 2 per 12 hours, days 1 to 14), aclarubicin (10 mg per day, days 1 to 8), and G-CSF priming (200 μg/m 2 per day, days 1 to 14). Results: The overall response rate was 69.2%, and 29 of 52 (55.8%) patients achieved CR, including 23 of 35 (65.8%) patients with previously untreated AML, 6 of 17 (35.2% ) patients with refractory, relapsed and secondary AML, 4 of 9 (44.4%) patients aged over 70 years, 4 of 10 (40.0%) patients with unfavourable cytogenetic aberrations. The early death rate was 7.6%. The median overall survival duration 14 months. Myelosuppression was mild to moderate, severe nonhematologic toxicity was not observed. Conclusions: CAG priming regimen as the induction therapy is well tolerable and effective in elderly patients with AML. No significant financial relationships to disclose.
Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease
Authors: HT Yee, M Ponzoni, A Merson, M Goldstein, A Scarpa, M Chilosi, F Menestrina, S Pittaluga, C de Wolf-Peeters, M Shiota, S Mori, G Frizzera, G Inghirami
Journal: Blood (1996)
Rate of Cell Division of Malignant Mouse Melanoma B16&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Felix D. Bertalanffy, Cheryl McAskill
Journal: JNCI Journal of the National Cancer Institute (1964)

The mitotic rate of transplantable malignant B16 melanoma was investigated in C57BL/6J mice at 10 and 14 days after transplantation, with the use of the colchicine technique. No significant difference in mitotic rate was observed. The B16 melanoma apparently grew at a constant rate by a daily addition of 34 to 36 percent of new cells to its population, which implied a doubling time of 2.8 days. Further, the mitotic rate of metastases in spleen and liver was similar to that of the transplanted primary tumors. Moreover, diurnal fluctuations of mitotic activity did not occur in the B16 melanoma. In many respects, the cell population of this tumor behaved like other neoplastic cell populations whose mitotic rates have been ascertained. The histology of the B16 melanoma is described.