tbuckley/cabot-search huggingface dataset:
Abstract 329: δ-Opioid Receptor Mediated Regulation of Cortical MicroRNAs in the Rat Under Hypoxia
Authors: Yilin Yang, Feng Zhi, Xiaozhou He, Meredith L Moore, Xuezhi Kang, Dongman Chao, Rong Wang, Dong H Kim, Ying Xia
Journal: Circulation Research (2012)

Cardiovascular disorders may reduce blood/oxygen supply to the brain, causing serious neurological disabilities. Activation of the delta-opioid receptor (DOR) induces cortical protection against hypoxic/ischemic insults. However, the mechanism underlying DOR protection is largely unclear yet. We have recently found that DOR activation modulates microRNA expression in the kidney exposed to hypoxic stress, suggesting that DOR protection may involve a microRNA mechanism. To determine if the microRNAs expressed in the cortex mediate DOR neuroprotection, we examined nineteen microRNAs, that are previously identified as hypoxia- and DOR-regulated microRNAs in the kidney, in the cortex treated with DOR activation in hypoxic condition. Total RNA for qPCR was isolated from the cortex of control or hypoxic rats as well as those animals treated with UFP-512, a potent and specific DOR agonist. Of the 19 microRNAs tested, 17 were significantly altered by hypoxia and/or DOR activation with the direction and amplitude dependent on hypoxic duration and times of DOR treatment. Several microRNAs such as miR-29b, 101b, -298, 324-3p, -347 and 466b were significantly depressed by hypoxia for 24 hours. The similar changes were seen in normoxic condition 24 hours after DOR activation with one time treatment of UFP-512. In contrast, some miRNAs were more tolerant to hypoxic stress and did not show any significant reduction until 5-days (e.g., miR-31 and -186) or 10-days (e.g., miR-29a, let-7f and -511), while DOR activation had differential effects on these miRNAs. Moreover, some miRNAs like miRs-363* and -370 were affected only by the combination of hypoxia and DOR treatment, with reductions greater than 70% in 5-day group. These data suggest that cortical microRNAs are significantly altered in response to hypoxia with differential hypoxia sensitivity among them and that DOR activation is able to modify, enhance or resolve the changes in microRNAs that are predicted to target ion transport, HIF, axonal guidance, free radical signaling, apoptosis and many other functions.
Detecting substitution-rate heterogeneity among regions of a nucleotide sequence.
Authors: B S Gaut, B S Weir
Journal: Molecular Biology and Evolution (1994)

Likelihood-ratio statistics are proposed to test for heterogeneity in nucleotide substitution rate among regions of a DNA sequence. The tests examine three-sequence phylogenies, and two specific tests are proposed: a test to detect rate heterogeneity among genic regions within a sequence, over all evolutionary lineages; and a test to detect rate heterogeneity among regions in a specific evolutionary lineage. Simulations examine the ability of tests to detect a single region that varies in nucleotide substitution rate relative to the remainder of the sequence. A 50-bp region with a fivefold substitution-rate increase can be detected > or = 90% of the time when it is found in all three lineages of the phylogeny, and a 50-bp region of fivefold rate increase can be detected with approximately 70% power when it is found in only one evolutionary lineage. Simulation also examines the effect of transition- and transversion-rate differences. The tests are applied to published DNA sequences. While the tests are powerful, significant results can be difficult to interpret biologically.
Abstract 1984: SOCS3 regulates IDO proteasomal degradation and inflammatory signaling in triple negative breast cancer
Authors: Maria Ouzounova, EunMi Lee, Ena Novakovic, Satish Kumar Noonepalle, Raziye Piranlioglu, Huidong Shi, Max Wicha, Hasan Korkaya
Journal: Cancer Research (2015)

Abstract An intrinsic claudin-low subtype within the TNBC was recently identified based on low/absent expression of luminal differentiation markers, enrichment of epithelial-to-mesenchymal transition (EMT) and stem cell markers. Interleukin-6 (IL6), a potent pleiotropic cytokine, is induced in response to acute and chronic inflammation. IL6 is a key regulator of inflammatory responses and orchestrates these physiological functions by controlling the Suppressor of cytokine signaling 3 (SOCS3) mediated Stat3/NF-κB pathway. SOCS3 is a critical negative regulator of IL6-mediated pathways. We have showed that constitutive activation of inflammatory loop in transformed cells but not in their untransformed counterparts depends on proteolytic degradation of SOCS3. Several studies indicate that activation of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) represents a key pathway suppressing anti-tumor immunity. Moreover a recent study in dendritic cells found that SOCS3 binds IDO via phosphotyrosine-containing peptides and target the IDO/SOCS3 complex for ubiquitination and subsequent proteasomal degradation. IDO is shown to be constitutively expressed by many tumors. We analyzed a panel of breast cancer cell lines and found an inverse correlation between SOCS3 and IDO1 protein levels. Interestingly IDO protein and transcript levels were significantly increased in TNBC compared to luminal cell lines, thus confirming that IL6-JAK-STAT inflammatory loop is responsible for IDO regulation. Enforced expression of stable form of SOCS3, lacking the PEST and SOCS box domain in TNBC cell lines resulted in decreased expression of IDO. Therapeutic targeting of the IDO-IL6-SOCS3 inflammatory loop would revert the immune suppression mediated by IDO in this breast cancer subtype. These studies would provide a strong rationale for development of inflammatory pathway targeted agents for the treatment of TNBC, an aggressive disease that currently lacks molecularly targeted therapeutics. Citation Format: Maria Ouzounova, EunMi Lee, Ena Novakovic, Satish Kumar Noonepalle, Raziye Piranlioglu, Huidong Shi, Max Wicha, Hasan Korkaya. SOCS3 regulates IDO proteasomal degradation and inflammatory signaling in triple negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1984. doi:10.1158/1538-7445.AM2015-1984
Saving Lives with High-Flow Nasal Oxygen
Authors: Michael A. Matthay
Journal: New England Journal of Medicine (2015)

First reported in 1890,1 therapy with oxygen constitutes one of the fundamental advances in clinical medicine. It is an essential treatment for acute and chronic respiratory failure, a supportive therapy for general anesthesia and most surgical procedures, and an adjunctive treatment for patients with shock from sepsis, trauma, or cardiac failure.For spontaneously breathing patients with acute respiratory failure, various methods for providing supplemental oxygen have been studied. Noninvasive positive-pressure ventilation with a tight-fitting face mask reduces morbidity and mortality among selected patients with acute respiratory failure caused by an exacerbation of chronic obstructive pulmonary disease.2,3 Noninvasive ventilation also . . .
Finding Molecular Subgroups of Worse Prognosis Studying the Microenvironment of Gastro-Entero-Pancreatic Neuroendocrine Tumours (Gep-Net).
Authors: J. Barriuso, E. Bernal, L.G. Pastrian, J. Martinez, E. Diaz, V. Heredia, M. Miguel, C. Alvarez-Escola, J. Castell, J. Feliu, E. Burgos, M. Mendiola
Journal: Annals of Oncology (2014)
The effects of soluble recombinant complement receptor 1 on complement-mediated experimental glomerulonephritis.
Authors: W G Couser, R J Johnson, B A Young, C G Yeh, C A Toth, A R Rudolph
Journal: Journal of the American Society of Nephrology (1995)

Complement is a major mediator of tissue injury in several types of glomerulonephritis. However, no therapeutic agents that inhibit complement activation are available for human use. sCR1 (TP10, BRL 55736) is a recombinant, soluble human complement receptor 1 (CR1) molecule lacking transmembrane and cytoplasmic domains that inhibits C3 and C5 convertase activity by preferentially binding C4b and C3b. To test the efficacy of sCR1 on complement-mediated glomerulonephritis, rats were pretreated with sCR1 (60 mg/kg per day) before and during the induction of three models of complement-dependent glomerulonephritis (concanavalin A and antithymocyte serum models of proliferative glomerulonephritis, passive Heyman nephritis). Daily sCR1 and complement hemolytic activity levels were measured, and renal histology and urine protein excretion were examined. Mean serum sCR1 levels of 100 to 200 micrograms/mL were maintained with a reduction in complement hemolytic activity to less than 15% in most animals. In the antithymocyte serum model, sCR1-treated animals had significant reductions in mesangiolysis, glomerular platelet and macrophage infiltrates, and proteinuria at 48 h. In the concanavalin A model, sCR1 significantly reduced glomerular C3 and fibrin deposits, platelet infiltrates, and proteinuria at 48 h. In passive Heymann nephritis, proteinuria was also significantly reduced (199 +/- 8.5 versus 125 +/- 16 mg/day, P < 0.002) at 5 days. It was concluded that sCR1 significantly reduces both morphologic and functional consequences of several different types of complement-mediated glomerulonephritis and deserves evaluation as a potential therapeutic agent in complement-mediated immune glomerular disease in humans.
MicroRNA-505 functions as a tumor suppressor in endometrial cancer by targeting TGF-α
Authors: Shuo Chen, Kai-Xuan Sun, Bo-Liang Liu, Zhi-Hong Zong, Yang Zhao
Journal: Molecular Cancer (2016)

Endometrial carcinoma (EC) is one of the most lethal gynecologic cancers. Patients frequently have regional or distant metastasis at diagnosis. MicroRNAs are small non-coding RNAs that participate in numerous biological processes. Recent studies have demonstrated that miR-505 is associated with several types of cancer; however, the expression and function of miR-505 have not been investigated in EC. miR-505 expression in normal endometrial tissue, endometrial carcinomas were quantified by Quantitative reverse transcription PCR. The endometrial carcinoma cell lines HEC-1B and Ishikawa were each transfected with miR-505 or scrambled mimics, after which cell phenotype and expression of relevant molecules were assayed. Dual-luciferase reporter assay and a xenograft mouse model were used to examine miR-505 and its target gene TGF-α. RT-PCR results demonstrated that miR-505 was significantly downregulated in human EC tissues compared to normal endometrial tissues. Besides, miR-505 expression was negatively associated with FIGO stage (stage I-II vs. III-IV), and lymph node metastasis (negative vs. positive). In vitro, overexpression of miR-505 significantly suppressed EC cell proliferation, increased apoptosis and reduced migratory and invasive activity. A miR-505 binding site was identified in the 3′ untranslated region of TGF-α mRNA (TGFA) using miRNA target-detecting software; a dual luciferase reporter assay confirmed that miR-505 directly targets and regulates TGFA. RT-PCR and Western-blotting results indicated that overexpressing miR-505 reduced the expression of TGF-α and the TGF-α-regulated proteins MMP2, MMP9, CDK2, while induced Bax and cleaved-PARP expression in EC cells. In vivo, overexpression of miR-505 reduced the tumorigenicity and inhibited the growth of xenograft tumors in a mouse model of EC. Taken together, this study demonstrates that miR-505 acts as tumor suppressor in EC by regulating TGF-α.
Oncology Pathways—Preventing a Good Idea From Going Bad
Authors: Blase N. Polite, Ray D. Page, Chadi Nabhan
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology 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 Oncology journal
Persistence of circulating t(14;18)-positive cells in long-term remission after radiation therapy for localized-stage follicular lymphoma.
Authors: J Finke, J Slanina, W Lange, G Dölken
Journal: Journal of Clinical Oncology (1993)

PURPOSE To determine the prevalence of circulating t(14;18)-positive cells in patients with long-term remission after radiation therapy for stage I and II follicular lymphoma. PATIENTS AND METHODS Peripheral-blood mononuclear cells from 21 patients in continuous remission were examined by a two-step polymerase chain reaction (PCR) assay for the detection of cells carrying a t(14;18) translocation with a breakpoint within the major breakpoint region (MBR) or minor cluster region (mcr). RESULTS Follow-up duration was between 25 and 160 months, with a median of 6.5 years. Thirteen patients (62%) showed negative results on repetitive testing. Cells that were t(14;18)-positive were found in eight patients (38%), all carrying a breakpoint in the MBR. One patient relapsed in each group. CONCLUSION Circulating t(14;18)-positive cells can persist in a high percentage of follicular lymphoma patients in long-term complete remission (CR) after radiation treatment for stage I and II disease. The significance of minimal residual t(14;18)-positive cells with regard to the risk of relapse needs to be investigated in further prospective long-term studies.
Evaluation of Phlebitis Attribute to Chemotherapy in Colorectal Cancer Patients of Our Institution
Authors: Ai Mogi, Yasushi Takamatsu, Mahiru Fukuda, Mayumi Oda, Tomoka Kuboda, Megumi Nishida, Hideki Kakimoto, Yoichiro Yoshida, Yuichi Yamashita, Kazuo Tamura
Journal: Annals of Oncology (2014)
Abstract 15406: Sitagliptin Shows No Significant Benefit on Cardiac Outcomes: Systematic Review and Meta-Analysis
Authors: Raynold V Yin, Danny Tang, Chetak Patel, Jeong Won Yoon, Prabhdeep Sidhu, Olivia J Phung
Journal: Circulation (2014)

Background:  The use of antidiabetic medications has been linked to both increases and decreases in cardiac outcomes, depending on the class of medication or even the specific agent used. We conducted a meta-analysis of existing data from randomized controlled trials (RCTs) evaluating the effect of sitagliptin, a dipeptidyl peptidase 4 inhibitor, on the cardiovascular outcomes of unstable angina (UA), myocardial infarction (MI), congestive heart failure (CHF), and coronary artery disease (CAD) in patients with type 2 diabetes (T2DM).   Methods:  A systematic literature search was conducted using PubMed, Embase, and Cochrane Central through 02/2014 without any language restrictions. Two investigators were responsible for study selection and data extraction, with any discrepancies resolved through discussion. A random effects meta-analysis yielded relative risk (RR) and 95% confidence interval (CI) for UA, MI, CHF, and CAD.   Results:  A total of 10 RCTs (n=4371 patients, mean age range: 49 to 69 years, range: 12 to 54 weeks duration, mean BMI range: 25 to 34 kg/m2 and mean A1C range: 5.4 to 9.9%. Trials evaluated sitagliptin versus placebo either as monotherapy or in addition to a background regimen of metformin (UA: n=4 studies, MI: n=9 studies, CHF: n=3 studies and CAD: n=5 studies). Meta-analysis found that there was no significant effect of sitagliptin compared to placebo on any of these cardiac outcomes: UA RR 0.70 (95%CI 0.03 to 17.90), MI RR 0.82 (95%CI 0.18 to 3.51), CHF RR 2.07 (95%CI 0.05 to 84.32), CAD RR 0.71 (95%CI 0.18 to 2.75). No heterogeneity was detected in any of these analyses.   Conclusion:  These are outcomes that require careful attention in future studies, as the cardiovascular risk associated with the use of sitagliptin cannot be ruled out. The event rates observed in RCTs are quite low, limiting the precision of the results. Additionally, RCTs may not be of sufficient duration to detect and report these outcomes in patients with T2DM. Future analyses of how sitagliptin works in real-world observational settings should be conducted.
Abstract 2657: Diagnostic Accuracy of Electrocardiographic Criteria for Left Ventricular Hypertrophy: Comparison With Computed Tomography
Authors: Mohamad C Sinno, Alawi A Alsheikh-Ali, Rana Mokdad, Mohammad Zaidan, Joseph Chattahi, Mouaz H Al-Mallah
Journal: Circulation (2009)

Introduction: Several electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) exist. However, none of these criteria has been validated against cardiac CT, which provides accurate and reproducible assessment of left ventricular mass (LVM). The aim of this study is to evaluate the diagnostic accuracy of different LVH ECG criteria using cardiac CT as the gold standard.  Methods: We included 353 consecutive patients (mean age 55±12 years, 48% females) who underwent coronary CT angiography for various clinical reasons. LVH on CT was defined as LVM index (LVMI) >103 gm/m2 for men and >89gm/m2 for women. ECGs were interpreted by physicians blinded to the LVMI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and receiver operating curves were calculated for the following LVH ECG criteria using LVMI by CT as the gold standard: Sokolow-Lyon voltage, RaVL, Cornell gender-specific voltage, and Cornell product.  Results: A total of 28 patients (7.9%) had LVH by CT and 57 patients (16.1%) had LVH by any ECG criteria. Patients with LVH were older with higher prevalence of hypertension. All ECG criteria had similarly low sensitivity and PPV for the diagnosis of LVH, but high specificity and NPV. The Cornell and aVL criteria are the most sensitive criteria while the Cornell product criterion is the most specific. The false positive and false negative rates range from 6.3% to 7.1% and from 77.8%– 82.4% respectively.  Conclusion: Using cardiac CT as the gold standard, ECG criteria for diagnosing LVH are very specific, but all have poor sensitivity. The absence of LVH by ECG provides little reassurance of a normal left ventricular mass by cardiac CT.
P86 Does genotype predict response to treatment in children perinatally infected with hepatitis B virus
Authors: J Sira, E Boxall, S Kaskar, J Workman, D Kelly
Journal: Gut (2010)

Introduction  Hepatitis B Virus (HBV) genotype is now thought to correlate to outcome and response to treatment.  Aim  To compare viral genotype with treatment response in children infected perinatally with HBV, who had been treated with subcutaneous Interferon alpha2b (IFN) with or without Prednisolone priming (Pred/IFN), oral antiviral drugs (Lamivudine or Adefovir).  Method  All children who took part in the clinical trials in this unit since 1990 were included. The hepatitis B genotypes were determined using a commercial line probe assay (InnoLipa), which was validated against direct sequencing.  Results  70 children were recruited to clinical trials, 68 of whom had genotype analysis. 5 children had more than one course of therapy: The genotype results correlated with the geographical origin of the families of the children. European and Afro-Caribbean children have genotype A, Oriental children only had genotype B, while the majority of South Asian children had genotype D. Genotype C was uncommon in any of these ethnic groups.  Overall response to treatment was better in children with genotypes A 10/18 (55%) and D 19/39 (49%) compared to those with B and C for all forms of treatment.  Although the response to Interferon alone was better in children with genotype A (50%) compared to D (36%), prednisolone priming improved the response in both genotypes to 67% & 70% respectively.  Conclusion  Pre-treatment assessment of genotype in children may provide a guide to potential response and improve information and choice for families.
High-dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma: a Pediatric Oncology Group study.
Authors: J G Pole, J Casper, G Elfenbein, A Gee, S Gross, W Janssen, P Koch, R Marcus, T Pick, J Shuster
Journal: Journal of Clinical Oncology (1991)

We conducted a pilot protocol at seven Pediatric Oncology Group (POG) institutions to examine the feasibility, toxicity, and efficacy of using a common regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in first or second remission. During a 57-month period, we accrued 101 patients. We report here results for the 81 who completed treatment at least 2 years ago. The HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for six doses. Twenty-three patients also received irradiation consisting of 1.2 Gy twice daily for 10 doses to persisting disease sites. Seventy-four were given autologous and seven allogeneic marrow, 64 autologous marrows being purged immunomagnetically. Fifty-four children were in first complete (CR) or partial (PR) remission and 27 in second CR or PR. As of October 1, 1990, follow-up was from 32 to 72 months. Forty-seven of these 81 children relapsed, 10 died of complications, one of unknown cause, and 23 continue in remission, including 21 of the 54 treated in first remission, and 16 who completed treatment more than 3 years ago. The 2-year actuarial event-free survival (EFS) probabilities are first CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%), and second PR (PR2) 5% (SE 5%). Probability of EFS correlated with remission number (first better than second, P less than .001), with interval from diagnosis to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and with TBI dose (12 Gy better than 9 Gy, P = .031). These encouraging results may partly reflect selection for this treatment of patients with NBL who have a slower disease pace.