tbuckley/cabot-search huggingface dataset:
High XRCC1 Protein Expression Is Associated with Poorer Survival in Patients with Head and Neck Squamous Cell Carcinoma
Authors: Mei-Kim Ang, Mihir R. Patel, Xiao-Ying Yin, Sneha Sundaram, Karen Fritchie, Ni Zhao, Yufeng Liu, Alex J. Freemerman, Matthew D. Wilkerson, Vonn Walter, Mark C. Weissler, William W. Shockley, Marion E. Couch, Adam M. Zanation, Trevor Hackman, Bhishamjit S. Chera, Stephen L. Harris, C. Ryan Miller, Leigh B. Thorne, Michele C. Hayward, William K. Funkhouser, Andrew F. Olshan, Carol G. Shores, Liza Makowski, D. Neil Hayes
Journal: Clinical Cancer Research (2011)

Abstract Purpose: We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome. Experimental Design: XRCC1 protein expression was assessed by immunohistochemical (IHC) staining of pretreatment tissue samples in 138 consecutive HNSCC patients treated with surgery (n = 31), radiation (15), surgery and radiation (23), surgery and adjuvant chemoradiation (17), primary chemoradiation (51), and palliative measures (1). Results: Patients with high XRCC1 expression by IHC (n = 77) compared with patients with low XRCC1 expression (n = 60) had poorer median overall survival (OS; 41.0 months vs. OS not reached, P = 0.009) and poorer progression-free survival (28.0 months vs. 73.0 months, P = 0.031). This association was primarily due to patients who received chemoradiation (median OS of high- and low-XRCC1 expression patients, 35.5 months and not reached respectively, HR 3.48; 95% CI: 1.44–8.38; P = 0.006). In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression. In multivariable analysis, high XRCC1 expression and p16INK4a-positive status were independently associated with survival in the overall study population (HR = 2.62; 95% CI: 1.52–4.52; P &amp;lt; 0.001 and HR = 0.21; 95% CI: 0.06–0.71; P = 0.012, respectively) and among chemoradiation patients (HR = 6.02; 95% CI: 2.36–15.37; P &amp;lt; 0.001 and HR = 0.26; 95% CI: 0.08–0.92, respectively; P = 0.037). Conclusions: In HNSCC, high XRCC1 protein expression is associated with poorer survival, particularly in patients receiving chemoradiation. Future validation of these findings may enable identification of HNSCC expressing patients who benefit from chemoradiation treatment. Clin Cancer Res; 17(20); 6542–52. ©2011 AACR.
Assessment of the Medial Dorsal Cutaneous, Dorsal Sural, and Medial Plantar Nerves in Impaired Glucose Tolerance and Diabetic Patients With Normal Sural and Superficial Peroneal Nerve Responses
Authors: Sun Im, Sung-Rae Kim, Joo Hyun Park, Yang Soo Kim, Geun-Young Park
Journal: Diabetes Care (2011)

This study evaluated the nerve conduction study (NCS) parameters of the most distal sensory nerves of the lower extremities-namely, the medial dorsal cutaneous (MDC), dorsal sural (DS), and medial plantar (MP) nerves-in diabetic (DM) and impaired glucose tolerance (IGT) patients who displayed normal findings on their routine NCSs.Standard NCSs were performed on healthy control (HC), DM, and IGT groups (N = 147). The bilateral NCS parameters of the MDC, DS, and MP nerves were investigated. The Toronto Clinical Scoring System (TCSS) was assessed for the DM and IGT groups.The mean TCSS scores of the IGT and DM groups were 2.5 ± 2.3 and 2.8 ± 2.2, respectively. No significant differences between the two groups were observed. After adjustment of age and BMI, the DM group showed significant NCS differences in DS and MDC nerves compared with the HC group (P < 0.05). These differences were also exhibited in the left DS of the IGT group (P = 0.0003). More advanced NCS findings were observed in the DM group. Bilateral abnormal NCS responses in these distal sensory nerves were found in 40 and 16% of DM and IGT patients, respectively.These results showed that the simultaneous assessment of the most distal sensory nerves allowed the detection of early NCS changes in the IGT and DM groups, even when the routine NCS showed normal findings.
MicroRNA-26b suppresses the NF-κB signaling and enhances the chemosensitivity of hepatocellular carcinoma cells by targeting TAK1 and TAB3
Authors: Na Zhao, Ruizhi Wang, Liangji Zhou, Ying Zhu, Jiao Gong, Shi-Mei Zhuang
Journal: Molecular Cancer (2014)

Abnormal activation of the NF-κB pathway is closely related to tumorigenesis and chemoresistance. Therefore, microRNAs that possess the NF-κB inhibitory activity may provide novel targets for anti-cancer therapy. miR-26 family members have been shown to be frequently downregulated in hepatocellular carcinoma (HCC) and correlated with the poor survival of HCC patients. To date, there is no report disclosing the regulatory role of miR-26 on the NF-κB pathway and its biological significance. The effects of miR-26b on the NF-κB signaling pathway and the chemosensitivity of cancer cells were examined in two HCC cell lines, QGY-7703 and MHCC-97H, using both gain- and loss-of-function studies. The correlation between miR-26b level and apoptosis rate was further investigated in clinical HCC specimens. Both TNFα and doxorubicin treatment activated the NF-κB signaling pathway in HCC cells. However, the restoration of miR-26b expression significantly inhibited the phosphorylation of IκBα and p65, blocked the nuclear translocation of NF-κB, reduced the NF-κB reporter activity, and consequently abrogated the expression of NF-κB target genes in TNFα or doxorubicin-treated HCC cells. Furthermore, the ectopic expression of miR-26b dramatically sensitized HCC cells to the doxorubicin-induced apoptosis, whereas the antagonism of miR-26b attenuated cell apoptosis. Consistently, the miR-26b level was positively correlated with the apoptosis rate in HCC tissues. Subsequent investigations revealed that miR-26b inhibited the expression of TAK1 and TAB3, two positive regulators of NF-κB pathway, by binding to their 3'-untranslated region. Moreover, knockdown of TAK1 or TAB3 phenocopied the effects of miR-26b overexpression. These data suggest that miR-26b suppresses NF-κB signaling and thereby sensitized HCC cells to the doxorubicin-induced apoptosis by inhibiting the expression of TAK1 and TAB3. Our findings highlight miR-26b as a potent inhibitor of the NF-κB pathway and an attractive target for cancer treatment.
Thalidomide-induced cardiotoxicity in multiple myeloma patients: An underestimated but clinically relevant issue.
Authors: E. Arboscello, A. Bellodi, C. Passalia, P. Spallarossa, E. Balleari, I. Ponassi, A. Calvia, L. Canepa, M. C. Casale, R. Ghio
Journal: Journal of Clinical Oncology (2010)

e18544 Background: The benefits derived from the use of thalidomide in clinical practice, beside of the already more common toxicities as the neurological, gastro-intestinal and vascular ones, must face a unknown range of others related toxicities; among them, cardiotoxicity seems to be an important issue. The more frequent cardiac side-effects described as due to thalidomide involve heart frequency and rhythm. The potential severity of some of these events focused our attention on the problem Methods: We firstly retrospectively evaluated the incidence and severity of cardiotoxicity in patients with multiple myeloma (MM) previously treated with of thalidomide in our Centre, confirming a cardiac toxicity which is in keeping with the licterature. Therefore we began a prospective study which aim is a systematic evaluation of cardiac function during the treatment with thalidomide in MM. Patients affected by MM in therapy with melphalan, prednisone, thalidomide (100 mg/daily) are included into the study. Patients already in therapy with anti-arhythmic drugs, or affected by ischemic cardiopathy or diabete mellitus are excluded. The patients are evaluated every three months with history and objective examination, serum markers of cardiac injury such as I-troponin and NT-pro-BNP and instrumental examinations (ECG, Holter ECG and echocardiography), and any clinical cardiac event and laboratory data indicative for cardiac dysfunction are recorded Results: in 6 from 25 MM patients (24 %) retrospectively evaluated, four patients presented sinus bradycardia (HR < 60 b/m) symptomatic for hypotension and dyspnoea; one patient developed heart failure with bradycardia and another one showed atrial tachyfibrillation. As far as the first 3 patients prospectively enrolled are concerned, we already observed a case of bradycardia and syncope in a patient in therapy. Conclusions: The study is nowadays at this initial stage, but it might give new data on the real incidence of cardiotoxicity due to thalidomide. The events observed underline the importance of a regular cardiologicafollow-up in these patients and this approach should become integrant part of the monitoring of patients treated with thalidomide. No significant financial relationships to disclose.
Rare RHCE phenotypes in black individuals of Afro-Caribbean origin: identification and transfusion safety
Authors: France Noizat-Pirenne, Ketty Lee, Pierre-Yves Le Pennec, Philippe Simon, Philippe Kazup, Dora Bachir, Anne-Marie Rouzaud, Michèle Roussel, Geneviève Juszczak, Cècile Ménanteau, Philippe Rouger, Rami Kotb, Jean-Pierre Cartron, Hélène Ansart-Pirenne
Journal: Blood (2002)
Effectiveness of a Strategy to Improve Adherence to Tuberculosis Treatment in a Resource-Poor Setting
Authors: Sylla Thiam, Andrea M. LeFevre, Fatoumata Hane, Alimatou Ndiaye, Fatoumata Ba, Katherine L. Fielding, Moustapha Ndir, Christian Lienhardt
Journal: JAMA (2007)

ContextPoor adherence to treatment remains a major obstacle to efficient tuberculosis (TB) control in developing countries. Innovative strategies to improve access and adherence to treatment are needed.ObjectivesTo assess the effectiveness of a contextualized intervention strategy aimed at improving patients' adherence to treatment and to evaluate its impact on TB control in a resource-poor country in Africa with prevalent TB infection.Design, Setting, and PatientsA cluster randomized controlled trial, conducted between June 2003 and January 2005, at 16 government district health centers in Senegal. Patients older than 15 years with newly diagnosed sputum smear–positive pulmonary TB were randomly assigned to the intervention or control group.InterventionThe intervention strategy included reinforced counseling through improved communication between health personnel and patients, decentralization of treatment, choice of directly observed therapy (DOT) supporter by the patient, and reinforcement of supervision activities. In the control group, the usual TB control program procedures remained unchanged.Main Outcome MeasureProportion of patients successfully completing the 8-month course of treatment and the proportion of patients defaulting from treatment.ResultsA total of 1522 patients were recruited into the study. Treatment was successful for 682 (88%) of 778 patients recruited in the intervention group, and for 563 (76%) of 744 patients recruited in the control group (adjusted risk ratio [RR], 1.18; 95% confidence interval [CI], 1.03-1.34). The proportion of patients defaulting was reduced in the intervention group to 5.5% (n = 43) compared with 16.8% (n = 125) in the control group (adjusted RR, 0.43; 95% CI, 0.21-0.89).ConclusionThe intervention package based on improved patients counseling and communication, decentralization of treatment, patient choice of DOT supporter, and reinforcement of supervision activities led to improvement in patient outcomes compared with the usual TB control procedures. This approach may be generalized in the context of TB control programs in resource-poor countries.Trial Registrationclinicaltrials.gov Identifier: NCT00412009
Production of Hyperlipemia and Early Atherosclerosis in Rabbits by a High Vegetable Fat Diet
Authors: ALFRED STEINER, SEYMOUR DAYTON
Journal: Circulation Research (1956)

Feeding of a high vegetable fat diet made up of ground peanuts and purina chow to rabbits resulted in an increase in the serum cholesterol, as well as other serum lipids, including β-lipoprotein fraction. Microscopic lipid deposits in the intima and underlying media of the ascending and thoracic aorta were present in 10 of 33 rabbits at the end of 5 to 12 months. Small areas of gross atherosclerosis of the aorta were found in two rabbits.
Absence of H-2 restriction in primary and secondary mixed-lymphocyte reactions to strong M1s determinants.
Authors: K Molnar-Kimber, J Sprent
Journal: The Journal of Experimental Medicine (1980)

Negative and positive selection procedures were used to establish whether the strong proliferative response of T cells to M1sa determinants is H-2 restricted. After negative selection of H-2 determinants in vivo, it was shown that T cells give high primary mixed lymphocyte reactions in vitro to M1sa determinants presented on H-2-incompatible stimulator cells. Other studies demonstrated that (a) negative selection of T cells to M1sa determinants on H-2-incompatible cells removed T cells with specificity for M1sa-bearing H-2-compatible cells, and (b) T cells primed in vitro or in vivo to M1sa determinants on H-2-compatible cells gave high secondary responses to M1sa determinants presented either on H-2-compatible or H-2-incompatible stimulator cells. From these data we conclude that T cells recognize M1sa determinants per se rather than an association of M1sa plus self or allo-H-2 determinants.
Histopathological analysis of benign polyps in patients with carcinoma of the colon and rectum
Authors: G. Ekelund, C. Lindstrom
Journal: Gut (1974)

All benign polyps in a 10-year series of 960 patients with colorectal carcinoma from a defined population were analysed. All cases where histological specimens of the polyps were available were reclassified according to morphological type and grade of differentiation. The findings lend support to the assumption of a relationship between benign epithelial neoplasms and adenocarcinoma of the colon and rectum.
Dilate or wait for effective anti-inflammatory treatment for stenotic lesions associated with active inflammatory signs in Crohn's disease
Authors: Y. Ustundag, A. Tezel
Journal: Gut (2011)

We read with interest the article by Thienpont1 et al regarding the long-term outcomes of endoscopic dilatation in 133 patients with Crohn's disease exhibiting ileal, ileocolonic and anastomotic strictures, on a retrospective basis. They performed multistep dilatation utilising scope balloons starting from 15–16.5 cm and widening to 18 cm at the maximal diameter. They concluded that endoscopic balloon dilatation is an effective method with long-term relief of symptomatology in 54% of patients, without a need for repeat dilatation or surgery in 76% of patients after the first dilatation. They reported the occurrence of 12 (5.1%) serious adverse events in 237 dilatations. They underlined the fact that neither active inflammation at the site of stricture, high serum C-reactive protein levels nor …
Models in the Development of Clinical Practice Guidelines
Authors: J. Dik F. Habbema, Timothy J. Wilt, Ruth Etzioni, Heidi D. Nelson, Clyde B. Schechter, William F. Lawrence, Joy Melnikow, Karen M. Kuntz, Douglas K. Owens, Eric J. Feuer
Journal: Annals of Internal Medicine (2014)

Clinical practice guidelines should be based on the best scientific evidence derived from systematic reviews of primary research. However, these studies often do not provide evidence needed by guideline development groups to evaluate the tradeoffs between benefits and harms. In this article, the authors identify 4 areas where models can bridge the gaps between published evidence and the information needed for guideline development applying new or updated information on disease risk, diagnostic test properties, and treatment efficacy; exploring a more complete array of alternative intervention strategies; assessing benefits and harms over a lifetime horizon; and projecting outcomes for the conditions for which the guideline is intended. The use of modeling as an approach to bridge these gaps (provided that the models are high-quality and adequately validated) is considered. Colorectal and breast cancer screening are used as examples to show the utility of models for these purposes. The authors propose that a modeling study is most useful when strong primary evidence is available to inform the model but critical gaps remain between the evidence and the questions that the guideline group must address. In these cases, model results have a place alongside the findings of systematic reviews to inform health care practice and policy.
Identifying Patients at High Risk of a Cardiovascular Event in the Near Future
Authors: Kim A. Eagle, Geoffrey S. Ginsburg, Kiran Musunuru, William C. Aird, Robert S. Balaban, Susan K. Bennett, Roger S. Blumenthal, Shaun R. Coughlin, Karina W. Davidson, Edward D. Frohlich, Philip Greenland, Gail P. Jarvik, Peter Libby, Carl J. Pepine, Jeremy N. Ruskin, Arthur E. Stillman, Jennifer E. Van Eyk, H. Eser Tolunay, Cheryl L. McDonald, Sidney C. Smith
Journal: Circulation (2010)

a working group to provide basic and clinical research recommendations to the National Heart, Lung, and Blood Institute on the development of an integrated approach for identifying those individuals who are at high risk for a cardiovascular event such as acute coronary syndromes (ACS) or sudden cardiac death in the "near term."The working group members defined near-term as occurring within 1 year of the time of assessment.The participants reviewed current clinical cardiology practices for risk assessment and state-of-the-science techniques in several areas, including biomarkers, proteomics, genetics, psychosocial factors, imaging, coagulation, and vascular and myocardial susceptibility.This report presents highlights of these reviews and a summary of suggested research directions.
Roles of Insulin Receptor Substrates in Insulin-Induced Stimulation of Renal Proximal Bicarbonate Absorption
Authors: Yanan Zheng, Hideomi Yamada, Ken Sakamoto, Shoko Horita, Motoei Kunimi, Yoko Endo, Yuehong Li, Kazuyuki Tobe, Yasuo Terauchi, Takashi Kadowaki, George Seki, Toshiro Fujita
Journal: Journal of the American Society of Nephrology (2005)

Insulin resistance is frequently associated with hypertension, but the mechanism underlying this association remains speculative. Although insulin is known to modify renal tubular functions, little is known about roles of insulin receptor substrates (IRS) in the renal insulin actions. For clarifying these issues, the effects of insulin on the rate of bicarbonate absorption (JHCO3-) were compared in isolated renal proximal tubules from wild-type, IRS1-deficient (IRS1-/-), and IRS2-deficient (IRS2-/-) mice. In wild-type mice, physiologic concentrations of insulin significantly increased JHCO3-. This stimulation was completely inhibited by wortmannin and LY-294002, indicating that the phosphatidylinositol 3-kinase pathway mediates the insulin action. The stimulatory effect of insulin on JHCO3- was completely preserved in IRS1-/- mice but was significantly attenuated in IRS2-/- mice. Similarly, insulin-induced Akt phosphorylation was preserved in IRS1-/- mice but was markedly attenuated in IRS2-/- mice. Furthermore, insulin-induced tyrosine phosphorylation of IRS2 was more prominent than that of IRS1. These results indicate that IRS2 plays a major role in the stimulation of renal proximal absorption by insulin. Because defects at the level of IRS1 may underlie at least some forms of insulin resistance, sodium retention, facilitated by hyperinsulinemia through the IRS1-independent pathway, could be an important factor in pathogenesis of hypertension in insulin resistance.
Integrated genetic and epigenetic analysis of childhood acute lymphoblastic leukemia
Authors: Maria E. Figueroa, Shann-Ching Chen, Anna K. Andersson, Letha A. Phillips, Yushan Li, Jason Sotzen, Mondira Kundu, James R. Downing, Ari Melnick, Charles G. Mullighan
Journal: Journal of Clinical Investigation (2013)

Acute lymphoblastic leukemia (ALL) is the commonest childhood malignancy and is characterized by recurring structural genetic alterations. Previous studies of DNA methylation suggest epigenetic alterations may also be important, but an integrated genome-wide analysis of genetic and epigenetic alterations in ALL has not been performed. We analyzed 137 B-lineage and 30 T-lineage childhood ALL cases using microarray analysis of DNA copy number alterations and gene expression, and genome-wide cytosine methylation profiling using the HpaII tiny fragment enrichment by ligation-mediated PCR (HELP) assay. We found that the different genetic subtypes of ALL are characterized by distinct DNA methylation signatures that exhibit significant correlation with gene expression profiles. We also identified an epigenetic signature common to all cases, with correlation to gene expression in 65% of these genes, suggesting that a core set of epigenetically deregulated genes is central to the initiation or maintenance of lymphoid transformation. Finally, we identified aberrant methylation in multiple genes also targeted by recurring DNA copy number alterations in ALL, suggesting that these genes are inactivated far more frequently than suggested by structural genomic analyses alone. Together, these results demonstrate subtype- and disease-specific alterations in cytosine methylation in ALL that influence transcriptional activity, and are likely to exert a key role in leukemogenesis.
The Sensory Symptoms of Diabetic Polyneuropathy Are Improved With α-Lipoic Acid
Authors: Alexander S. Ametov, Alexei Barinov, Peter J. Dyck, Robert Hermann, Natalia Kozlova, William J. Litchy, Phillip A. Low, Detlef Nehrdich, Maria Novosadova, Peter C. O’Brien, Miroslav Reljanovic, Rustem Samigullin, Klemens Schuette, Igor Strokov, Hans J. Tritschler, Klaus Wessel, Nikolai Yakhno, Dan Ziegler
Journal: Diabetes Care (2003)

Because alpha-lipoic acid (ALA), a potent antioxidant, prevents or improves nerve conduction attributes, endoneurial blood flow, and nerve (Na(+) K(+) ATPase activity in experimental diabetes and in humans and may improve positive neuropathic sensory symptoms, in this report we further assess the safety and efficacy of ALA on the Total Symptom Score (TSS), a measure of positive neuropathic sensory symptoms.Metabolically stable diabetic patients with symptomatic (stage 2) diabetic sensorimotor polyneuropathy (DSPN) were randomized to a parallel, double-blind study of ALA (600 mg) (n = 60) or placebo (n = 60) infused daily intravenously for 5 days/week for 14 treatments. The primary end point was change of the sum score of daily assessments of severity and duration of TSS. Secondary end points were sum scores of neuropathy signs (NIS), symptoms (NSC), attributes of nerve conduction, quantitative sensation tests (QSTs), and an autonomic test.At randomization, the groups were not significantly different by the criteria of metabolic control or neuropathic end points. After 14 treatments, the TSS of the ALA group had improved from baseline by an average of 5.7 points and the placebo group by an average of 1.8 points (P < 0.001). Statistically significant improvement from baseline of the ALA, as compared with the placebo group, was also found for each item of the TSS (lancinating and burning pain, asleep numbness and prickling), NIS, one attribute of nerve conduction, and global assessment of efficacy.Intravenous racemic ALA, a potent antioxidant, rapidly and to a significant and meaningful degree, improved such positive neuropathic sensory symptoms as pain and several other neuropathic end points. This improvement of symptoms was attributed to improved nerve pathophysiology, not to increased nerve fiber degeneration. Because of its safety profile and its effect on positive neuropathic sensory symptoms and other neuropathic end points, this drug appears to be a useful ancillary treatment for the symptoms of diabetic polyneuropathy.