tbuckley/cabot-search huggingface dataset:
Abstract 288: Atheroprotective Effect of Probucol Is Related to Its Heme Oxygenase 1 Activation and Subsequent Suppression of Oxidized Low-Density Lipoprotein--Induced Dendritic Cell Maturation
Authors: Aijun Sun, Xueting Jin, Jingjing Zhao, Keqiang Wang, Fang Xu, Wei Huang, George Liu, Yunzeng Zou, Kai Hu, Junbo Ge
Journal: Circulation Research (2012)

Aims: Probucol, an agent characterized by lipid-lowering and anti-oxidant property, retards atherosclerosis effectively. Our study aimed to test the hypothesis that probucol might act its anti-athersclerotic role by suppressing maturation of human monocyte-derived dendritic cells (h-monDC). Furthermore, we also used a LDLR-/- mice model fed a high-fat diet to detect whether probucol also perform its anti-atherosclerotic effect on suppressing DCs maturation in vivo. Methods: H-monDCs were derived by incubating purified human monocytes with GM-CSF and IL-4. H-monDCs were pre-incubated with or without probucol and stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of heme oxygenase (HO-1) siRNA. In vivo studies, streptozotocin (STZ) induced LDLR-/- mice were fed either a high-fat (HF) diet or added with 0.5% probucol for 4 months. Expression of h-monDC membrane molecules and mice splenic CD11c+DC membrane molecules were analyzed by FACS, cytokines were measured by ELISA and the STAT1/CIITA associated signaling pathway was determined by Western blotting. Mice aortic lesions were observed by En face staining and the expression of CD11c+DCs within atherosclerotic plaques were shown under confocal microscopy. Results: Ox-LDL promoted h-monDC maturation and TNF-a production; and up-regulated STAT1 701 phosphorylation by activating HO-1 in STAT1/CIITA signaling pathway. These effects were inhibited by probucol. Knocking down HO-1 with specific siRNA blocked these effects of probucol. In LDLR-/- mice fed a high-fat diet, probucol treatment significantly regressed aortic atherosclerotic lesions, suppressed splenic CD11c+DCs maturation and IL-12p70 production; and resulted in absence of CD11c+DCs within atherosclerotic lesions. Conclusions: Our study indicated that probucol effectively suppressed maturation of h-monDC induced by ox-LDL through HO-1 activation, and retarded atherosclerosis at least partly through inhibiting maturations of CD11c+DCs in LDLR-/- mice.
Long persistence of tumour necrosis factor‐α antagonist‐induced autoantibodies under subsequent treatment with ustekinumab but no adverse effects: a case study of 14 patients with psoriasis
Authors: J.H.O. Hoffmann, C. Knoop, A.H. Enk, E.N. Hadaschik
Journal: British Journal of Dermatology (2017)

Induction of antinuclear antibodies (ANA) is a well-documented side effect of treatment with the TNF-α antagonists Infliximab, Adalimumab, and Etanercept. In this context, occasional organ-specific and systemic autoimmune phenomena, and an association of autoantibodies with treatment response and anti-drug antibody formation were reported. In genuine autoimmune disease, the detection of autoantibodies can predate clinical manifestations by almost 6 years. However, little is known about the post-treatment dynamics of TNF-antagonist induced ANA, and, in particular, on their effects on the response to, and their dynamics under subsequent biologic treatment.

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Abstract 193: Regulation of Mitochondrial KATP Channels In Pressure Overloaded Mouse Hearts
Authors: Nian-Qing (Nan) Shi, Jianjiong Gao, Wen-Jie Ou, Grzegorz Sabat, Dong Xu
Journal: Circulation Research (2013)

Background: ATP-sensitive potassium channels (KATP), existing in both sarcolemmal and mitochondrial inner membranes, are thought to serve as metabolic sensors of the cell. In pathological hypertrophy, the heart requires increased workload to pump blood to meet the body’s needs. However, roles of KATP in hypertrophy stress signaling are not fully understood. Methods &amp; Results: We aimed at investigating regulation of SUR2, the regulatory subunit of KATP, via a systems biology approach. We hypothesized that mitochondrial KATP mediates the protective response in hypertrophied hearts. A pressure-overload model by transverse aortic constriction (TAC) was employed to induce hypertrophy in SUR2 knockout (SUR2KO) males. These mice had enlarged left ventricles at baseline and developed further hypertrophy post TAC. Hypertrophied KO hearts exhibited significantly higher mortality, cardiac dysfunction, reduced mitochondrial DNA content and elevated ROS formation, which were associated with the altered SUR2 (mitoSUR2) variant expression. Among the mitoSUR2 variants, a 55-kDa mitoSUR2A variant was significantly up-regulated 4-fold in both TAC and SHAM treated KO hearts. We then analyzed whether the mitoSUR2 variants were associated with a key ROS regulator ShcP66 variant, ShcP52, using quantitative BRET assays. Our data showed that ShcP52 could directly bind to the mitoSUR2 variants. Our data indicates that these mitoSUR2 variants are involved in mediating ROS signaling. Comparative proteomic profiling and subsequent canonical pathway enrichment analyses revealed that mitochondrial function was the top affected system among the 41 identified pathways in SUR2KO hearts. Semi-quantitative comparisons between KO and WT data showed that the ETC activity was severely disturbed in SUR2KO-TAC mitochondria. Further data mining identified compromised cardiac parameters, affected molecular functions and possible diseases in hypertrophied SUR2KO hearts. Conclusions: Our novel findings reveal that altered mitochondrial SUR2-based KATP activities likely contribute to the hypertrophic phenotype and abnormal mitochondrial function in SUR2KO hearts, suggesting that these channels play an essential role in mitochondrial remodeling and energy sensing.
Influences of environmental bacteria and their metabolites on allergies, asthma, and host microbiota
Authors: G. Jatzlauk, S. Bartel, H. Heine, M. Schloter, S. Krauss‐Etschmann
Journal: Allergy (2017)

The prevalence of allergic diseases and asthma has dramatically increased over the last decades, resulting in a high burden for patients and healthcare systems. Thus, there is an unmet need to develop preventative strategies for these diseases. Epidemiological studies show that reduced exposure to environmental bacteria in early life (eg, birth by cesarean section, being formula-fed, growing up in an urban environment or with less contact to various persons) is associated with an increased risk to develop allergies and asthma later in life. Conversely, a reduced risk for asthma is consistently found in children growing up on traditional farms, thereby being exposed to a wide spectrum of microbes. However, clinical studies with bacteria to prevent allergic diseases are still rare and to some extent contradicting. A detailed mechanistic understanding of how environmental microbes influence the development of the human microbiome and the immune system is important to enable the development of novel preventative approaches that are based on the early modulation of the host microbiota and immunity. In this mini-review, we summarize current knowledge and experimental evidence for the potential of bacteria and their metabolites to be used for the prevention of asthma and allergic diseases.
Double-blind, randomized phase III study to compare the efficacy and safety of CT-P6, trastuzumab biosimilar candidate versus trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC).
Authors: Justin Stebbing, Yauheni Valerievich Baranau, Valery Baryash, Alexey Manikhas, Vladimir Moiseyenko, Giorgi Dzagnidze, Edvard Javrid, Dmytro Boliukh, Daniil Stroyakovskiy, Joanna Pikiel, Alexandru E. Eniu, Dmitry Komov, Zakaria Zautashvili, Gabriela Morar-Bolba, Rubi Khaw Li, Igor Lifirenko, Andriy V. Rusyn, Sang Joon Lee, Sung Young Lee, Francisco J. Esteva
Journal: Journal of Clinical Oncology (2017)

510 Background: CT-P6 (C) is a proposed biosimilar to trastuzumab. This trial (NCT02162667) evaluated the similarity of C and trastuzumab in efficacy and safety for HER2+ EBC. Methods: 549 patients with HER2+ EBC were randomized to receive C (n=271) or trastuzumab (n=278) in combination with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (Cycles 5-8). C or trastuzumab was administered at 8 mg/kg (Cycle 1 only) followed by 6 mg/kg every 3 weeks. The primary endpoint was pathological complete response (pCR) rate at surgery. Secondary endpoints were overall response rate (ORR), PK, PD and safety. After surgery, patients received adjuvant C or trastuzumab to complete a total of 1-year treatment. Results: The pCR rate was 46.8% for C and 50.4% for trastuzumab. The 95% CIs for the risk ratio estimate were within the equivalence margin (0.74, 1.35) in PPS and ITT analyses. Other efficacy endpoints were similar between C and trastuzumab. The proportion of patients with at least 1 treatment-emergent SAE was 6.6% for C and 7.6% for trastuzumab. Only 1 patient in each group withdrew treatment due to significant LVEF decrease. Infusion-related reaction was reported for 8.5% of patients in C and 9.0% of patients in trastuzumab. Conclusions: This study demonstrated the similarity of efficacy in terms of pCR between CT-P6 and trastuzumab in EBC patients. Secondary efficacy endpoints also supported the similarity between CT-P6 and trastuzumab. CT-P6 was well tolerated with a similar safety profile to that of trastuzumab during the neoadjuvant period. Clinical trial information: NCT02162667. [Table: see text]
Standard vs Expanded Indications for Esophageal Magnetic Sphincter Augmentation for Reflux Disease
Authors: John P. Kuckelman, Cody J. Phillips, Mark O. Hardin, Matthew J. Martin
Journal: JAMA Surgery (2017)

Standard vs Expanded Indications for Esophageal Magnetic Sphincter Augmentation for Reflux DiseaseMagnetic sphincter augmentation (MSA) has proven to be safe and effective for appropriate candidates with gastroesophageal reflux disease (GERD). 1 Standard indications include patients with GERD, normal motility, body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) <35, no prior foregut surgery, and no or small (<3 cm) hiatal defect.Although many surgeons are now offering MSA to candidates with expanded criteria, there are scant data on outcomes in these patients.Our aim was to evaluate the postoperative outcomes associated with MSA for expanded indications.Methods | After receiving institutional review board approval including waiver of informed consent from Madigan Army Medical Center, we performed a retrospective medical review of patients undergoing MSA over 1 year at a single tertiary training facility.Patients included had GERD with normal esophageal motility and were categorized as standard indications (SI) or expanded indications (EI) including large hiatal hernia, BMI >35, or prior foregut surgery.Descriptive and comparison statistics (Fischer exact test, t test, Wilcoxon rank sum test) were completed for the cohort and between the SI and EI groups, including preoperative and postoperative GERD quality of life (G-QOL) scores.The G-QOL percentage of improvement was determined by dividing the difference between pre-and postoperative scores by the preoperative survey scores and multiplying by 100.The minimum follow-up was 3 months.
An NCDB analysis of trends in male breast cancer from 2004-2009 and 2010-2014.
Authors: Esther Dubrovsky, Shira Schwartz, Jennifer Chun, Amber Guth, Deborah M. Axelrod, Richard L. Shapiro, Freya Ruth Schnabel
Journal: Journal of Clinical Oncology (2017)

544 Background: To examine the trends in clinicopathologic features, treatment, and survival of male breast cancer (MBC), utilizing the National Cancer Data Base (NCDB). Methods: MBC patients entered in the NCDB from 2004-2009 were compared with those from 2010-2014 for demographics, stage at diagnosis, tumor characteristics, treatment type, and overall survival (OS). Male patients were also compared to female patients from the same time periods. Statistical analysis included Pearson’s chi-square test. Results: Of 2,047,868 breast cancer cases, a total of 19,409 (0.95%) men were available for analysis. The group of MBC patients from 2004 to 2009 included 9,790 men with a median age of 65. The group from 2010 to 2014 included 9,619 men with a median age of 66. In the later group there was a decreased rate of DCIS, increased rate of invasive ductal carcinoma, and increased rate of hormone positive tumors. Among the earlier and later MBC groups, 24% vs. 27% of patients underwent lumpectomy. Of these, 61% vs 68% received post-lumpectomy radiation, respectively. Patients in the later group (2010-2014) were more likely to receive adjuvant hormonal therapy (61% vs. 84%, p &lt; 0.0001). MBC patients were older than female patients (65 vs. 61 years, p &lt; 0.0001), had larger tumors (20mm vs. 16mm, p &lt; 0.0001), slightly later stage at diagnosis, and more likely to undergo mastectomy (74 vs. 42%, p &lt; 0.0001). MBC patients also had higher rates of hormone positive tumors, but lower rates of adjuvant hormonal therapy (55% vs. 58%, p &lt; 0.0001). The OS for male vs. female patients in the 2004-2009 groups was 66% vs. 77% (median follow-up 73.9m vs 80.4m) respectively. Similarly, in the 2010-2014 groups, survival was 84% vs. 90% (median follow-up 33.85m vs 35.91m), respectively. Conclusions: Although men have higher rates of hormone positive tumors, they are less likely to receive adjuvant hormonal therapy. There was a significant trend over time towards more standard therapies in men, such as post-lumpectomy radiation and hormonal therapy use. There has been an improvement of OS in men which mirrors that in women. The disparities in outcomes between male and female patients, however, still require further investigation.
Alternating Ventricular Complexes After Overdose From an Herbal Medication
Authors: Kathy T. Vo, Jeffrey A. Tabas, Craig G. Smollin
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
Abstract NTOC-115: ASSOCIATION BETWEEN NUCLEAR SYK PHOSPHORYLATION AND EGFR/ERBB2 PATHWAY AND POOR SURVIVAL IN HIGH GRADE SEROUS OVARIAN CANCER
Authors: Yu Yu, Laura Ardighieri, Yohan Suryo Rahmanto, Lin Y. Chen, Nayara G. Tessarollo, Taichi Mizushima, Ayse Ayhan, Ben Davidson, Tian L. Wang, Ie M Shih
Journal: Clinical Cancer Research (2017)

Abstract BACKGROUND: Spleen tyrosine kinase (SYK) has emerged as a cancer associated kinase of which aberrant activity contributes to tumor development and drug resistance in several types of human cancer including ovarian carcinoma. To better understand the mechanism how the SYK pathway participates in tumor progression, we studied the biochemistry and transcriptional regulation of SYK in high-grade ovarian serous carcinoma. METHODS: Immunohistochemical analyses were performed for phosphorylated SYK (Y525/526) and total SYK levels in 42 primary serous ovarian carcinomas and 112 tumor ascites formalin-fixed paraffin embedded tissues. The relative expression of SYK long and short isoforms in peritoneal ascites and cell lines were examined by reverse transcriptase-PCR. Transcriptome analysis of gene regulated by SYK inhibition was carried out using Illumina Human HT-12 v4 arrays. Results from array was analyzed for upstream regulators. IHC data was correlated with pEGFR (Y1197) and pERBB2 (Y877) nuclear expression. Association with survival was determined by Kaplan-Meier analysis and the log-rank test. RESULTS: We observed that active phosphorylated SYK (p-SYK, Y525/526) is mainly localized in the nucleus and cytoskeleton in cell lines and tissues. Investigation of SYK mRNA spliced variants in ascites tumors showed predominant SYK long isoform expression, consistent with its nuclear localization. Survival analyses revealed that intense nuclear p-SYK correlated with poor overall survival in two ovarian carcinoma cohorts. Patients with relatively high p-SYK in the nucleus had approximately half the median survival compared to those with undetectable or low nuclear p-SYK. SYK inhibition affected changes in gene expression that are downstream of ERBB2 and EGFR signaling. Correlation analyses in tissues suggested a relationship between p-SYK and pERBB2 or pEGFR signaling. CONCLUSIONS: Our results suggest that activation of the SYK pathway leads to its phosphorylation and localization in cell nucleus. SYK activity plays a role in regulating EGFR and ERBB2 phosphorylation and activation. Thus, SYK may regulate tumor-promoting gene transcription through cross-talks with the EGFR/ERBB2 pathways. Citation Format: Yu, Yu; Ardighieri, Laura; Suryo Rahmanto, Yohan; Chen, Lin Y.; Tessarollo, Nayara G.; Mizushima, Taichi; Ayhan, Ayse; Davidson, Ben; Wang, Tian L., and Shih Ie M. ASSOCIATION BETWEEN NUCLEAR SYK PHOSPHORYLATION AND EGFR/ERBB2 PATHWAY AND POOR SURVIVAL IN HIGH GRADE SEROUS OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr NTOC-115.
Kallikrein 6 as a biomarker for the detection of metastatic cancer cells in blood of ovarian cancer patients
Authors: Katerina Economopoulou, Eleftherios P. Diamandis
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1058 

Kallikreins are a family of secreted serine proteases that have been recently discovered and seem to associate with cancer. The genetic locus of these proteases lies at 19q13.3-13.4. Human Kallikrein 6 (hK6) is a member of this protein family and it is encoded by KLK6 gene. We have previously found that hK6 is elevated in the serum of ovarian cancer patients and over-expression of hK6 tended to be greater at later stages of the disease. These findings suggest a potential role of serum hK6 concentration as a biomarker for ovarian cancer. This present study aims to utilize KLK6 gene transcripts for the detection of disseminated ovarian cancer cells in blood. Previous studies on ovarian, prostate and breast cancer patients, using molecular markers, have detected circulating metastatic cancer cells. In some cases, the methods show high sensitivity and detect metastatic cells at a ratio of around 1 metastatic cell to106 cells not expressing the marker gene. We first identified a cancer cell line, PC3(AR6), that strongly expresses KLK6 and another cell line, ES2, that does not express KLK6. To determine the detection limit of our method we diluted KLK6 transcripts (KLK6-pBluescript plasmid) up to 1 transcript per reaction. Using KLK6 as a marker and Polymerase Chain Reaction (PCR), we were able to detect around 10 transcripts per reaction. We also diluted the PC3(AR6) cells up to 1 cell and using Reverse Transcription PCR (RT-PCR) we were able to detect less than 1 PC3(AR6) cell per reaction. We then mixed PC3(AR6) cells with ES2 cells in ratios up to 1:106. Using RT-PCR, we were able to detect less than 1 PC3(AR6) cell per reaction. We can conclude that we have developed a highly sensitive method for monitoring KLK6 mRNA and cells expressing this gene. In the future we will examine if this technology can detect circulating ovarian cancer cells for the purpose of disease diagnosis and prognosis.
Endocrine therapy non-persistence in young women with early-stage breast cancer.
Authors: Shoshana M. Rosenberg, Shari I. Gelber, Kathryn Jean Ruddy, Rulla Tamimi, Johanna Wasserman, Lidia Schapira, Virginia F. Borges, Steven E. Come, Meghan E Meyer, Ann H. Partridge
Journal: Journal of Clinical Oncology (2017)

531 Background: The greatest age disparity in early stage breast cancer (BC) outcomes is in young women with hormone receptor positive (HR+) BC. While differences in biology may play a role, understanding the role of non-persistence (early discontinuation) with endocrine therapy (ET) is critical given the demonstrated efficacy of ET in this population. Methods: As part of a prospective cohort that enrolled women with BC diagnosed (dx) at age ≤40 between 2006-2016, we identified women with HR+, Stage I-III BC. Socio-demographic and treatment information, fertility concerns and confidence with the ET treatment decision were assessed by survey within 1 yr of dx. Medical record review was used to ascertain stage and HR status. Women who initiated ET but did not report taking tamoxifen or an aromatase inhibitor at 3 yrs post-diagnosis (or last follow-up if &lt;3 yrs) were classified as non-persistent. Chi-square tests were used to compare categorical variables between persisters and non-persisters and stepwise multivariable regression to evaluate predictors of non-persistence. Results: In 538 women who initiated ET, median age at dx was 36; 10% were non-persistent. Discontinuation of ET was more likely in those who were less confident with their ET decision compared to those who were more confident (25/179, 14% vs 18/263, 7%, p=0.01). A greater proportion of women concerned about fertility discontinued vs. women not concerned (29/213,14% vs 25/319, 8%, p=0.03), and fertility concerns were associated with non-persistence in multi-variable analyses (OR: 1.85, 95% CI 1.05-3.26, p=0.03). Age at dx, race, education, employment, financial comfort, marital status, parity, stage, chemotherapy and local therapy were not associated with non-persistence. Conclusions: A significant minority of women with HR+ BC discontinued ET within 3 yrs. The association between fertility concerns expressed soon after dx and non-persistence underscores a need to address psychosocial issues that can impact treatment decisions in young women. Strategies to reduce decisional conflict and increasing confidence with the choice to take ET, may influence persistence. Future work will evaluate the contribution of other factors (eg symptom burden) to non-persistence.