tbuckley/cabot-search huggingface dataset:
Effect of fas signaling on regulation of miR-23a-3p, miR-92a-3p, miR-138-5p, and miR-155-5p in gastric cancer cells.
Authors: Meng Shi, Xiaobing Cui, Bo Jiang
Journal: Journal of Clinical Oncology (2014)

e15077 Background: The Fas signaling pathway has been shown to promote cancer cell metastasis and motility through the epithelial-mesenchymal transition (EMT) in gastric cancer. Recent studies reported specific miRNAs associated with EMT and cancer metastasis. We hypothesized that miRNAs may partially mediate this actions of Fas signaling in gastric cancer cells. Methods: Human gastric cancer cells AGS were treated with 12.5 ng/mL FasL for 6 and 12 h. A miRNA-based microarray chip assay was perfomred to examine FasL-induced changes in the miRNA profile of AGS cells. Quantitative RT-PCR assays were carried out to validate the microarray data. MiRNA targets were predictied using Tarbase, miRecord and TargetScan. Functional annotation of the idnetified miRNA targets was done using Ingenuity and KEGG pathway analysis. Results: Thirty-five percent (175/500) of the human mature miRNAs in FasL-treated AGS cells exhibited at least a 2-fold difference in expression from non-treated AGS cells and 150 miRNAs were downregulated and 25 miRNAs were upregulated. Quantitative RT-PCR assays showed that 4 of these miRNAs, miR-23a-3p, miR-92a-3p, miR-138-5p, and miR-155-5p, were downregulated and one miRNA, miR-205-3p, was upregulated in FasL-treated AGS cells (P<0.05). Tarbase, miRecord and TargetScan identified β-catenin, Smad4, Snail1, Rac1, Cdc42 and MAPK3 as potential target genes of miR-23a-3p, miR-92a-3p, miR-138-5p, and miR-155-5p. Ingenuity pathway analysis showed that miR-23a-3p, miR-92a-3p, miR-138-5p, and miR-155-5p were associated with gastric cancer and molecular pathways involving the adherens junction, MAPK signaling, ErbB signaling and cell cycles. KEGG analysis demonstrated that the adherens junction pathway was the main pathway associated with the six predicted target genes. Conclusions: Activated Fas signaling induces broad changes in the miRNA expression profile of gastric cancer cells, and the four miRNAs, miR-23a-3p, miR-92a-3p, miR-138-5p, and miR-155-5p with the six predicted target genes are involved in cell-cell adhesion regulation and EMT process in response to Fas signaling.
Economic burden of tyrosine kinase inhibitor (TKI) treatment failure in patients with chronic myeloid leukemia (CML).
Authors: Yaozhu J Chen, Hui Huang, Victoria Divino, Shibani Pokras, Shawn Hallinan, Julie Munakata, Catherine Taylor, Lisa McGarry, Daniel Ng, Christopher Nieset, Kevin B. Knopf
Journal: Journal of Clinical Oncology (2014)

7091 Background: Treatment failure due to TKI resistance or intolerance is a significant challenge in managing CML; however, there are limited data quantifying the associated real-world health care utilization and cost burden. Methods: Treatment episodes for adult patients with a CML diagnosis (ICD-9-CM 205.1x) initiating a TKI of interest (index TKI) during 6/2008-12/2011 were identified from the IMS PharMetrics Plus Health Plan Claims Database. Inclusion required 120-days pre- and 360-days post-index continuous enrollment and no clinical trial participation. A patient could contribute ≥1 episode. Treatment failure was defined as switch to a non-index TKI or discontinuation of index TKI (gap of ≥60 days) observed over 1 year post index. Episodes with failure were matched to those without, based on propensity scores generated by logistic regression including baseline demographic and clinical characteristics, index TKI, and therapy line. Mean all-cause 1-year post-index health care utilization and costs (in 2012 USD) per episode were compared between matched episodes. Results: Of 1,774 eligible episodes from 1,624 CML patients (mean age=52.9, 47.8% female), 547 Failure episodes (Fs) were matched to 547 Non-Failure episodes (NFs). As expected, compared to Fs, NFs had more TKI fills (F: 7.1; NF: 11.2; p<.05) over the 1 year post index. However, Fs had significantly higher % hospitalized (28.9% v 13.9%), more inpatient days (22.2 v. 8.5), more outpatient visits (24.1 v. 17.8) and more non-TKI prescription fills (34.0 v. 28.7) (all p<.05). Overall, Fs incurred lower pharmacy costs ($51,238 v. $72,450), but higher medical costs ($52,618 v. $18,180, including $31,305 v. $5,287 for hospitalization), and higher total costs ($103,857 v. $90,630) than NFs (all p<.05). A sensitivity analysis excluding 18 episodes (17 Fs, 1NF) with bone marrow or stem cell transplant yielded qualitatively similar results. Conclusions: Although TKI failures have lower pharmacy burden, their overall economic burden is higher, primarily due to increased inpatient days. These findings suggest that minimizing TKI failure through more efficacious treatment may decrease the overall health care burden and costs of managing CML.
Comparison of RCC surveillance guidelines: Competing tradeoffs.
Authors: Tracey Lynn Krupski, Marc Nelson, Jennifer Mason, Kasey Morrison
Journal: Journal of Clinical Oncology (2014)

6594 Background: Renal cell carcinoma (RCC) is now detected at earlier stages than in the past due to increased use of abdominal imaging for unrelated medical conditions. Three organizations offer differing guidelines for surveillance imaging strategies following partial nephrectomy (PN). We hypothesized that published surveillance patterns would have previously unrecognized sizable differences in intensity, cost, and radiation exposure and real world experience would not adhere to guidelines. Methods: Cost ($2,012) and radiation exposure in millisieverts (mSv) were compared between the following surveillance guidelines:American Urological Association (AUA), Canadian Urology Association (CUA), and the European Association of Urology (EAU). These were stratified into low-risk and high-risk based on tumor characteristics and compared to patients undergoing PN for RCC at the from 2009-2010. The intensity, cost, and estimated radiation exposure were calculated for each subject. We used the Welch’s t-test to test for significant differences in cost and radiation exposure between the low-risk and high-risk groups. Results: The median cost of low risk surveillance from least expensive to most expensive is as follows: CUA ($481), EAU ($928) and AUA ($1,320). For high risk surveillance, least expensive was CUA ($543), EAU ($1,447) and AUA ($2,621). Radiation exposure was least for the CUA guidelines (low and high risk was 16.2 and 16.4 mSv ) and highest for the AUA guidelines at ( low and high risk was 48mSv and 92). The EUA guideline exposures were 23 mSv and 46mSv for low and high risk respectively. For comparison with a real world subset, 43/63 patients undergoing PN had complete records. We identified wide variability in intensity, frequency, and modality of surveillance imaging. These were not correlated to risk category or guidelines. Conclusions: Published surveillance strategies for RCC following PN differ greatly in terms of cost and radiation dose. Practicing clinicians do not seem to stratify patients by tumor-risk category as recommended by the published guidelines. It is important for clinicians to adopt standardized surveillance strategies that limit unnecessary cost and radiation exposure.
Smarcal1 and Zranb3 Protect Replication Forks from Myc-Induced DNA Replication Stress
Authors: Matthew V. Puccetti, Clare M. Adams, Saul Kushinsky, Christine M. Eischen
Journal: Cancer Research (2019)

The cellular DNA replication stress response functions to stabilize DNA replication forks and inhibits genome instability and tumorigenesis induced by oncogenes. However, the specific proteins required for resolving oncogenic stress remain poorly understood. Here we report that Smarcal1 and Zranb3, closely related replication fork-remodeling proteins, have nonredundant functions in resolving Myc-induced DNA replication stress. In Myc-overexpressing primary cells, significant differences in replication fork stalling, collapse, and DNA damage were detected between cells deficient in Smarcal1 or Zranb3, leading to changes in proliferation and apoptosis. These differences were also reflected in Myc-induced lymphoma development; haploinsufficiency of Smarcal1 resulted in accelerated lymphomagenesis, whereas haploinsufficiency of Zranb3 inhibited lymphoma development. Complete loss of either protein resulted in disparate survival outcomes. Our results reveal that endogenous replication stress from Myc in primary cells requires both alleles of Smarcal1 and Zranb3 and demonstrate the requirement of both proteins to stabilize replication forks upon Myc dysregulation in a nonredundant manner. SIGNIFICANCE: Smarcal1 and Zranb3 are essential, but nonredundant, for responding to DNA replication stress and stabilizing replication forks following Myc overexpression.See related commentary by Sotiriou and Halazonetis, p. 1297.
Abstract 14180: Acute and Chronic Experimental Animal Results of the New Self-Expandable Acurate TATM Valve for Transapical Transcatheter Aortic Valve Implantation
Authors: Susanne Pasa, Daniel Wendt, Phillip Kahlert, Rolf-Alexander Janosi, Nicolas Borenstein, Luc Behr, Thomas Konorza, Raimund Erbel, Heinz Jakob, Matthias Thielmann
Journal: Circulation (2012)

Background: Transcatheter aortic valve implantation (TAVI) as a minimally invasive technique is currently expanding rapidly worldwide, however all currently available prostheses share some fundamen...
Intestinal Goblet Cells Play a Protective Role Against GVHD Via a Lypd8-Dependent Manner after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Takahide Ara, Daigo Hashimoto, Eiko Hayase, Noizat Clara, Ryu Okumura, Kiyoshi Takeda, Takanori Teshima
Journal: Blood (2018)
Central Nervous System Metastasis in Patients with HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival from SystHERs
Authors: Sara A. Hurvitz, Joyce O'Shaughnessy, Ginny Mason, Denise A. Yardley, Mohammad Jahanzeb, Adam Brufsky, Hope S. Rugo, Sandra M. Swain, Peter A. Kaufman, Debu Tripathy, Laura Chu, Haocheng Li, Vincent Antao, Melody Cobleigh
Journal: Clinical Cancer Research (2018)

Patients with HER2-positive metastatic breast cancer (MBC) with central nervous system (CNS) metastasis have a poor prognosis. We report treatments and outcomes in patients with HER2-positive MBC and CNS metastasis from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs).SystHERs (NCT01615068) was a prospective, U.S.-based, observational registry of patients with newly diagnosed HER2-positive MBC. Study endpoints included treatment patterns, clinical outcomes, and patient-reported outcomes (PRO).Among 977 eligible patients enrolled (2012-2016), CNS metastasis was observed in 87 (8.9%) at initial MBC diagnosis and 212 (21.7%) after diagnosis, and was not observed in 678 (69.4%) patients. White and younger patients, and those with recurrent MBC and hormone receptor-negative disease, had higher risk of CNS metastasis. Patients with CNS metastasis at diagnosis received first-line lapatinib more commonly (23.0% vs. 2.5%), and trastuzumab less commonly (70.1% vs. 92.8%), than patients without CNS metastasis at diagnosis. Risk of death was higher with CNS metastasis observed at or after diagnosis [median overall survival (OS) 30.2 and 38.3 months from MBC diagnosis, respectively] versus no CNS metastasis [median OS not estimable: HR 2.86; 95% confidence interval (CI), 2.05-4.00 and HR 1.94; 95% CI, 1.52-2.49]. Patients with versus without CNS metastasis at diagnosis had lower quality of life at enrollment.Despite advances in HER2-targeted treatments, patients with CNS metastasis continue to have a poor prognosis and impaired quality of life. Observation of CNS metastasis appears to influence HER2-targeted treatment choice.
BRCA testing patterns and survival in platinum-sensitive recurrent (PSR) ovarian cancer (OC).
Authors: David D. Stenehjem, Sudhir K. Unni, Hillevi Bauer, Kuan-Ling Kuo, Rishi Deka, Marisa Brailsford, Brianna C Cajacob, Sanjeev Balu, Ceri Hirst, Vanessa Stevens, Diana I. Brixner
Journal: Journal of Clinical Oncology (2014)

e16522 Background: BRCA mutations (BRCAm) are implicated in 10-15% of epithelial OC. BRCAm-associated OC may be more sensitive to platinum agents and have a distinct prognosis. The purpose of this study was to evaluate BRCAm testing patterns and overall survival (OS) in patients with PSR OC. Methods: Patients with OC treated at the University of Utah Huntsman Cancer Institute (HCI) from 1995 to 2012 were evaluated. All clinical notes, lab reports, and pharmacy databases were systematically reviewed to identify use of carboplatin or cisplatin, evidence of first recurrence, and BRCAm testing. Recurrent patients were categorized as platinum-refractory or PSR. The relationship between BRCAm and OS was evaluated by Kaplan-Meier methodology. Results: The study included 731 patients with OC. Of patients who received initial platinum therapy at HCI (n=509, 69.6%), 247 (48.5%) patients demonstrated no evidence of recurrence until death or last follow-up; 92 (18.1%) developed platinum-refractory, recurrent OC; and 170 (33.4%) developed PSR OC. BRCAm testing was conducted in 40 (23.5%) PSR patients and 11 (27.5%) were documented BRCAm1+, 4 (10.0%) BRCAm2+, and 25 (62.5%) BRCA negative. Median age at OC diagnosis in PSR patients was 49, 63.5, 55, and 61 years in BRCA1+, BRCA 2+, BRCA negative, and untested patients, respectively. PSR patients tested for BRCAm were significantly younger at OC diagnosis than untested patients (55.5 vs 61 years, p=0.0035). Median overall survival from diagnosis of PSR OC was 31.4 months and was significantly greater in BRCAm positive (51.1 months, HR 0.39, 95% CI 0.18-0.72) and negative (68 months, HR 0.39, 95% CI 0.20-0.66) patients compared to those not tested for BRCA (25.1 months). Conclusions: Despite a low rate of BRCAm testing, a high percentage of BRCA mutation carriers were identified indicating that a highly selected population underwent testing. The overall mutation rate was low (8.8%) signifying potentially undetected BRCA mutation carriers. In this PSR population, BRCAm conferred no survival advantage; the survival difference in tested vs untested patients may be impacted by survivorship bias since tested patients were younger and may have been available for testing based on long survival.
Addressing a Core Gap in Cancer Care — The NCI Moonshot Program to Help Oncology Patients Stop Smoking
Authors: Robert T. Croyle, Glen D. Morgan, Michael C. Fiore
Journal: New England Journal of Medicine (2019)

Despite recommendations that all patients with cancer be offered effective treatment to help them quit smoking, such treatment is often neglected. The Cancer Moonshot initiative aims to jump-start smoking-cessation treatment at cancer centers.
Phase II Clinical Trial of Alisertib, an Aurora a Kinase Inhibitor, in Combination with Induction Chemotherapy in High-Risk, Untreated Patients with Acute Myeloid Leukemia
Authors: Andrew M. Brunner, Traci M. Blonquist, Daniel J. DeAngelo, Malgorzata McMasters, Eric S. Winer, Gabriela S. Hobbs, Philip C. Amrein, Hanno Hock, David P. Steensma, Jacqueline S. Garcia, Marlise R. Luskin, Richard M. Stone, Karen K. Ballen, Jacalyn Rosenblatt, David E. Avigan, Steven L McAfee, Jenna A. Moran, Meghan Bergeron, Julia Foster, Christina Bertoli, Kristin McGregor, Kaitlyn Fishman, Molly Macrae, Meghan Burke, Tanya T. Behnan, Tina T. Som, Aura Y. Ramos, Megan K. Vartanian, Nicole Nelson, Emma Logan, Jennifer Lombardi Story, Christine Connolly, Donna S Neuberg, Yi-Bin Chen, Timothy A. Graubert, Amir T. Fathi
Journal: Blood (2018)
Leveraging the Right Technology in Health Care—Having a Cow—Reply
Authors: Navpreet K. Dhillon, Bruce L. Gewertz, Eric J. Ley
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Insulin-like Growth Factor Binding Protein-3 (IGFBP3) Induces Fetal Hemoglobin in Hematopoietic Stem and Progenitor Cells from Patients with Sickle Cell Anemia
Authors: Alireza Paikari, Tian Mi, Yankai Zhang, Evadnie Rampersaud, Guolian Kang, Gang Wu, Jane S. Hankins, Jeremie H. Estepp, Pavel Sumazin, Mitchell J. Weiss, Vivien A Sheehan
Journal: Blood (2018)
Combination of Umbralisib, Ublituximab, and Bendamustine Is Safe and Highly Active in Patients with Advanced Diffuse Large B-Cell Lymphoma and Follicular Lymphoma
Authors: Matthew A. Lunning, Philip Bierman, R. Gregory Bociek, Marshall T. Schreeder, Tanya Siddiqi, Christopher R Flowers, Jonathon B. Cohen, Susan Blumel, Kathy Cutter, Emily K. Pauli, Peter Sportelli, Hari P Miskin, Michael S. Weiss, Julie M. Vose
Journal: Blood (2018)
Abstract 10367: Levels of Oral Inflammation-- not Salivary or Serum Biomarkers-- Predict Worse Functional Status in Hospitalized Patients With Heart Failure
Authors: Rebecca L Dekker, Terry A Lennie, Debra K Moser, Craig S Miller, Jeffrey L Ebersole, Misook L Chung, Charles L Campbell, Alison Bailey, Elizabeth G Tovar
Journal: Circulation (2015)

Introduction: Serum levels of B-type natriuretic peptide (BNP), C-reactive protein (CRP), interleukin-6 (IL-6) and IL-10 are predictors of poor prognosis in patients with heart failure (HF). These biomarkers are detectable in saliva after myocardial infarction; however, they have not been evaluated in patients with HF. Purpose: To describe correlations and agreement between salivary and serum BNP, CRP, IL-6 and IL-10, and determine whether they predict worse NYHA functional class in patients with HF, after controlling for visible levels of oral inflammation. Methods: In this cross-sectional investigation, serum and whole saliva samples were collected from 75 hospitalized patients with HF [57 ± 12 years, 43% female, NYHA Class I (4%), II (43%), and III (53%)] and analyzed using Biosite Triage (BNP) and a Luminex IS100. Levels of oral inflammation were rated by trained research nurses as good, fair, or poor. Spearman’s rho and the Bland Altman method were used to determine salivary-serum correlations and agreement. Logistic regression was used to determine whether each biomarker was a predictor of worse NYHA functional class, controlling for age, gender, and oral inflammation. Results: Median biomarker concentrations were: BNP [serum 361 pg/mL (25th% = 151, 75th% = 777); saliva 9 (4, 29)], CRP [serum 13 ng/mL (6.9, 29.9); saliva 25.6 (5, 51)], IL-6 [serum 19.3 pg/mL (9.1, 38.6); saliva 10.5 (3.7, 28.2)] and IL-10 [serum 64.1 pg/mL (36.2, 135.5); saliva 4.7 (0.1, 20.3)]. There was a strong correlation for serum-salivary CRP (rs = 0.594, p &lt; .001), moderate correlation for serum-salivary IL-6 (rs = 0.288, p = .037), and no correlations between serum-salivary BNP and IL-10. The Bland Altman test showed good serum-salivary agreement for all biomarkers, but as serum concentrations rose, salivary measures underestimated serum levels. In logistic regressions, none of the biomarkers predicted NYHA functional class, but oral inflammation was a predictor of worse functional class in 6 of 8 regression models. Conclusions: Salivary CRP and IL-6 correlated with serum measures; however, only oral inflammation- not biomarkers- predicted worse functional class. Prospective studies are needed to explore the relationship between oral health and outcomes in patients with HF.
HLA-G in testis germ cell tumors.
Authors: Bulent Karagoz, Abdullah Haholu, Alpaslan Ozgun, Oguz Bilgi, Tolga Tuncel, Levent Emirzeoglu, Serkan Celik, Dilaver Demirel
Journal: Journal of Clinical Oncology (2014)

e15620 Background: HLA-G is a nonclassical major histocompatibility complex class I molecule. HLA-G expression has been found in various types of solid or hematological malignancies and in normal testis and epididymal tissue of the male reproductive system. However, expression of HLA-G in testicular germ cell tumors has been not known. We have investigated whether HLA-G protein is present in different components of testicular germ cell tumors. Methods: Thirty-four testicular cancer patients having available tumor tissue were included in the study. Immunohistochemical staining was performed on tissue sections from formalin fixed paraffin-embedded tissue samples. Results: Seven patients (20.6%) have positive HLA-G staining at least in a compartment of tumor samples. In three of seven patients with intratubular germ cell neoplasia (ITGN), staining with HLA-G was seen in this component. All of the choriocarcinoma components were strongly positive. About 40% of teratoma components of tumor tissues were HLA-G positive. The components of seminoma, embriyonal carcinoma, and yolk sac tumor were negative. HLA-G immunopositivity was not associated with tumor, retroperitoneal lymph node, distant metastasis, or relapse/refractory status. Conclusions: This study demonstrated that choriocarcinoma of testis and some teratomas express HLA-G, but not seminoma, embriyonal carcinoma, and yolk sac tumors.