tbuckley/cabot-search huggingface dataset:
Aberrant methylation in breast cancer and correlate with tumor phenotypes, prognostic factors, and patient outcome
Authors: Joaquina Martinez-Galan, Juan Ramón Delgado-Perez, Blanca Torres-Torres, Pedro Ballesteros, Encarnación Gonzalez-Flores, Javier Valdivia, Raquel Luque, Veronica Conde, Jose Antonio Ortega, Mariano Ruiz de Almodovar
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Posttranslational modifications are known to be altered in cancer cells, and loss of selected histone acetylation and methylation marks has recently been shown to predict patient outcome in human carcinoma. Materials: Since January 2002 to June 2005, 107 women with breast cancer and 108 control subjects were recruited. A sensitive SYBR green methylation-specific PCR quantitative technique was used to analyze the utility of circulating DNA with CpG island hypermethylation of APC, RAR-β, E-cadherin, ESR1 and 14-3-3σ gene promoter regions as breast cancer biomarkers. Sera were collected in 107 operable breast cancer patients (pts) previously surgery and in 60 of those pts after treatment. Respect controls, 34 had benign breast disease and 74 with no evidence of breast disease Results: Mean serum values of methylated ESR1 and 14-3-3σ gene promoters significantly differed between breast cancer patients and healthy controls (p = 0.0112 for ESR1 and p= 0.0047 for 14-3-3- σ). When their results were combined, it was found that hypermethylation of these two genes differentiated between breast cancer patients and healthy controls (p≤0.0001) with a sensitivity of 81% (95% confidence interval: 72—88%) and specificity of 88% (95% CI: 78—94%). Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p = 0.0179); and presence of methylated 14-3-3-σ was associated with T3-4 stage (OMS) (p&amp;lt; 0.05) and nodal positive status (p&amp;lt; 0.05). We observed lower methylated ERS1 or 14-3-3-σ values after surgery, respect pretreatment levels, but without an overall statistically significant difference. With a median follow up of 6 years, we found that patients with a significant decrease of sera methylated levels of both genes after surgery had better time to progression an overall survival respect patients without this observation Conclusions: These results also suggest that this panel of genes detected in ductal lavage and blood specimens could be useful to biomarkers for early detection breast cancer. These findings cast some doubts on the utility for early cancer diagnosis of highly sensitive techniques to identify hypermethylation of specific gene promoters in DNA extracted from serum. Although numerous issues remain to be resolved, the quantitative measurement of circulating methylated DNA is a promising tool for cancer risk assessment.
Phase 2 trials of SU11248 show antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma (RCC)
Authors: R. J. Motzer, B. I. Rini, M. D. Michaelson, B. G. Redman, G. R. Hudes, G. Wilding, R. M. Bukowski, D. J. George, S. T. Kim, C. M. Baum
Journal: Journal of Clinical Oncology (2005)

4508 Background: SU11248 is an oral multi-targeted tyrosine kinase inhibitor of PDGFR and VEGFR with antiangiogenic and antitumor activity. Methods: Antitumor activity against metastatic RCC has been studied in 2 independent single-arm trials. Eligibility for both trials included measurable disease, failure of one prior cytokine therapy, and adequate organ function. Repeat cycles of SU11248 were given orally at 50 mg daily for 4 weeks followed by a 2-week rest period. Best response was assessed by RECIST. Trial 1 accrued 63 pts from 1/03 to 7/03 and Trial 2 accrued 106 pts from 2/04 through 11/04. Results: Of 63 pts enrolled in Trial 1, 25 (40%) pts achieved a partial response (PR) (95% CI: 28%, 53%), 21 (33%) pts had stable disease, and 17 (27%) pts had progression as best response. Of 25 pts who achieved a PR, the median duration of response is 10+ months (range 2 - 19+); 9 remain progression-free (including 2 PRs rendered disease-free by surgery [surgical complete responses (CRs)]); and 5 show continuous response of >12 months duration. The median time to progression (TTP) is 8.3 months, the median survival is 16 months, and 9 pts remain on therapy. Adverse events were mostly grade 1 and 2 and included fatigue, nausea, diarrhea, and stomatitis. Of 106 pts enrolled in Trial 2, 83 have completed at least 2 cycles of treatment and are assessable for response; it is too early to assess the remaining 23 pts. In this preliminary report, 24 (29%) of the 83 assessable pts have ≥30% decrease in tumor size by RECIST including 1 with a CR, 16 with confirmed PR, and 7 awaiting confirmation of PR status. Conclusions: Two consecutively conducted phase II trials in 169 pts show that SU11248 has substantial antitumor activity as second-line therapy for pts with metastatic RCC. The PR proportion of 40%, TTP of 8.3 months and median survival of 16 months observed in Trial 1 are particularly noteworthy when compared to prior studies of second-line therapy in RCC (JCO 2004;22:454). Trial 2 has confirmed anti-tumor activity in an independent group of patients and, having completed accrual, seeks to validate the degree of efficacy observed in the earlier study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
Selecting Targeted Therapies for Patients With Renal Cell Carcinoma
Authors: Elizabeth R. Plimack, Gary R. Hudes
Journal: Journal of the National Comprehensive Cancer Network (2011)

Advanced renal cell carcinoma (RCC) is a heterogeneous disease with variable histology, biology, and response to treatment. In the past 5 years, 6 new agents have been approved for the treatment of RCC, and many more are in clinical development. With an ever-increasing number of treatment options, selecting among them for a particular patient can be a daunting task for clinicians. This article describes how treatment choice can be guided by the disease setting and histology, as well as patient characteristics, comorbidities, and preference within the context of available data. Results from clinical trials are combined with practical considerations to make recommendations for first-line and subsequent treatment of patients with clear cell and non-clear cell RCC. These recommendations should supplement the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for the treatment of advanced RCC.
Trichosporon beigelii pneumonitis following busulphan-induced leucopenia
Authors: K Yamauchi, T Sato
Journal: European Respiratory Journal (1992)

We present a 41 yr old male, who died of respiratory failure due to infiltration of Trichosporon beigelii (cutaneum) into the pulmonary interstitial spaces with systemic dissemination. Busulphan-induced leucopenia in the chronic phase of chronic myelogenous leukaemia had progressed before this infection developed. In leukaemic patients with profound leucopenia, interstitial pneumonitis due to T. beigelii should be considered as a possible cause of otherwise unexplained hypoxaemia.
Obstructive sleep apnea among patients with chronic renal failure on regular hemodialysis in Saudi Arabia
Authors: Siraj Wali, Abeer AlKhouli, Mohannad Howladar, Saad Alshuhaib, Ibrahim Ahmad, Saeed Alghamdi, Ayman Krayem
Journal: European Respiratory Journal (2014)

Introduction   In Chronic Renal Failure patients (CRF), sleep apnea may worsen and clinical symptoms and aggravate the cardiovascular complications of end-stage renal disease (ESRD). Sleep apnea was reported to be in more than half of ESRD patients, while it was reported to range from 5 to 20 percent in the general population. Locally, there is only a single report on the prevalence of OSA in Saudi ESRD patients.   Aim   The aim of this study is to investigate the prevalence of OSA in patients with chronic renal failure on hemodialysis (HD) in multiple centers.   Methods   This cross-sectional study was carried out in three dialysis centers in Jeddah, Saudi Arabia, from June 2012 to September 2013. OSA was assessed using Berlin questionnaire and Epworth Sleepiness Scale (ESS) was used to asses excessive daytime sleepiness. In addition, detailed information about medical, clinical and laboratory results were also obtained.   Results   Among 355 enrolled patients, the mean patient age was 45.5 years ± 15.4 years; 61% were male. The overall prevalence of OSA as defined by Berlin questionnaire was 46.3%. Prevalence was 47% in males and 44% in females, ( P : 0.658). The prevalence of excessive daytime sleepiness was (74%). Sleep apnea was significantly associated with diabetes mellitus, hypertension, and hepatitis C ( P -values: 0.01,    Conclusion   OSA is quite more common in the ESRD patients than in the general population and affects both genders equally. Interestingly, there is significant association of OSA with hepatitis C that would need further confirmation.
Protection by N-acetylcysteine against pulmonary endothelial cell damage induced by oxidant injury
Authors: R Sala, E Moriggi, G Corvasce, D Morelli
Journal: European Respiratory Journal (1993)

The protective effect of N-acetylcysteine (NAC) against oxidant lung injury was investigated in a model of acute immunological alveolitis in the rat. Intrapulmonary immune complex deposition into rat lungs, induced by intratracheal infusion of immunoglobulin G (IgG) anti-bovine serum albumin (BSA) antibodies and intravenous injection of the antigen, caused lung damage associated with a marked decrease in [14C]5-hydroxytryptamine ([14C]5HT) uptake capacity, taken as a biochemical marker of endothelial cell function. The oral administration of a single dose of NAC (2 mmol.kg-1) 60 min before antigen/antibody (Ag/Ab) treatment was effective in preventing pulmonary endothelial cell [14C]5HT uptake loss induced by immune complex deposition. The mechanisms involved in this lung protective action of NAC were investigated by studying the antioxidant activity of NAC on hypoxanthine/xanthine oxidase-induced lung damage in vitro, and the effectiveness of the drug as lung glutathione (reduced form) (GSH) precursor in diethylmaleate-depleted rats. The results obtained provide further evidence on the ability of NAC to reduce the susceptibility of lung tissue to free radical-induced damage, by potentiating the antioxidant defence systems.
NCCN Task Force: Transfusion and Iron Overload in Patients With Myelodysplastic Syndromes
Authors: Peter L. Greenberg, Cynthia K. Rigsby, Richard M. Stone, H. Joachim Deeg, Steven D. Gore, Michael M. Millenson, Stephen D. Nimer, Margaret R. O'Donnell, Paul J. Shami, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2009)

The National Comprehensive Cancer Network (NCCN) convened a multidisciplinary task force to critically review the evidence for iron chelation and the rationale for treatment of transfusional iron overload in patients with myelodysplastic syndromes (MDS). The task force was charged with addressing issues related to tissue iron toxicity; the role of MRI in assessing iron overload; the rationale and role of treating transfusional iron overload in patients with MDS; and the impact of iron overload on bone marrow transplantation. This report summarizes the background data and ensuing discussion from the NCCN Task Force meeting on transfusional iron overload in MDS.
P0433 : Selective LXR alpha intestinal activation reduces hepatic inflammation and fibrosis during the development of chronic liver injury
Authors: I. Pierantonelli, C. Pinto, E. Mingarelli, S. Saccomanno, L. Agostinelli, C. Rychlicki, L. Trozzi, A. Benedetti, M. Marzioni, A. Moschetta, G. Svegliati-Baroni
Journal: Journal of Hepatology (2015)
Role of caveolin-1 in the pathogenesis of tissue fibrosis by keloid-derived fibroblasts in vitro
Authors: G.-Y. Zhang, Q. Yu, T. Cheng, T. Liao, C.-L. Nie, A.-Y. Wang, X. Zheng, X.-G. Xie, A.E. Albers, W.-Y. Gao
Journal: British Journal of Dermatology (2010)

Recent studies have suggested that caveolin-1 (cav-1) plays an important role in the regulation of transforming growth factor (TGF)-β1 signalling and participates in the pathogenesis of tissue fibrosis. However, its effects on dermal fibrosis keloids are unknown.To investigate the effect of cav-1 in the pathogenesis of tissue fibrosis by keloid fibroblasts.Keloid fibroblasts were cultured and exposed to different concentrations of cav-1 cell-permeable peptides (cav-1p) in the presence of TGF-β1. Keloid fibroblast phenotypes and protein production were analysed by real-time reverse transcriptase-polymerase chain reaction, Western blot, and multiplex enzyme-linked immunosorbent assay techniques. The effect of cav-1p on cell viability was evaluated by MTT assay.Cav-1 was markedly decreased in the keloid-derived fibroblasts. Moreover, cav-1p significantly reduced TGF-β receptor type I levels and Smad2/3 phosphorylation in response to added TGF-β1. Additionally, TGF-β1 decreased cav-1 expression in human skin fibroblasts. Cav-1 was able to suppress TGF-β1-induced extracellular matrix production in cultured keloid fibroblasts through regulation of the mitogen-activated protein kinase pathway.Cav-1 appears to participate in the pathogenesis of tissue fibrosis in keloid. Restoration of cav-1 function by treatment with a cell-permeable peptide corresponding to the cav-1 scaffolding domain may be a novel therapeutic approach in keloid.
Captopril and tubuloglomerular feedback in remnant kidneys of prehypertensive rats.
Authors: W L Wilke, A E Persson
Journal: Journal of the American Society of Nephrology (1992)

The activity and characteristics of tubuloglomerular feedback (TGF) are altered subsequent to reductions in renal mass or blockade of the renin-angiotensin system. This study assessed the combined effects of renal ablation and captopril on TGF. Renal mass was reduced in male Sprague-Dawley rats by the surgical removal of 1 1/2 kidneys. At 2 and 8 wk postsurgery, TGF was studied by micropuncture before and after the administration of captopril (0.5 mg/kg i.v.) Before captopril, TGF in remnant kidneys (NX) was characterized by a higher tubular perfusion rate required for a 50% maximal response (TGF turning point) as compared with intact kidneys of controls (CNT) at both 2 (NX, 35 +/- 3; CNT, = 19 +/- 1 nL/min; P less than 0.05) and 8 wk (NX, 54 +/- 5; CNT, 20 +/- 1 nL/min; P less than 0.05). Captopril significantly increased the turning point in both intact and remnant kidneys at both 2 (NX, 43 +/- 2; CNT, 25 +/- 2 nL/min) and 8 wk (NX, 61 +/- 5; CNT, 28 +/- 2 nL/min) postsurgery. Captopril also significantly reduced the maximal TGF response in both intact and remnant kidneys at 2 (NX from 13 +/- 3 to 7 +/- 1 mm Hg; CNT from 10 +/- 1 to 5 +/- 1 mm Hg) and 8 wk (NX from 15 +/- 1 to 9 +/- 2 mm Hg; CNT from 13 +/- 1 to 7 +/- 1 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment for HCV Genotypes 3 and 4
Authors: Rebecca Voelker
Journal: JAMA (2015)

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Antimicrobial prophylaxis to prevent surgical site infections in a rural sub-Saharan hospital
Authors: J. Fehr, C. Hatz, I. Soka, P. Kibatala, H. Urassa, M. Battegay, Z. Jeffrey, T. Smith, H. Mshinda, R. Frei, A.F. Widmer
Journal: Clinical Microbiology and Infection (2006)
Cisplatin and fluorouracil chemotherapy does not yield long-term benefit in locally advanced head and neck cancer: results from a single institution.
Authors: E E Vokes, R Mick, E P Lester, W R Panje, R R Weichselbaum
Journal: Journal of Clinical Oncology (1991)

Fifty-one patients with locally advanced head and neck cancer were treated with three cycles of cisplatin at 100 mg/m2 followed by 5-day continuous infusion fluorouracil (5-FU) at 1,000 mg/m2/d as induction chemotherapy. Subsequent local therapy consisted of surgery for patients with resectable disease and/or radiotherapy. Three cycles of adjuvant chemotherapy were administered to patients with partial response (PR) or complete response (CR) to induction chemotherapy. Twenty-two patients (43%) had a clinical CR that was pathologically confirmed in 12 patients (24%), and 24 patients (47%) had a PR for an overall response rate of 90%. Local therapy included surgery in 24 patients (47%) and radiotherapy alone in 22 patients (43%). Adjuvant chemotherapy was administered to 32 patients (63%) frequently at great dose reduction. At a median follow-up of 90 months, the median survival is 22 months (95% confidence interval, 15 to 36 months), and the 5-year survival is 25%, with only five patients known to be alive and disease-free at this time. The median time to progression is 14 months, with 29 patients (57%) having documented progression of their head and neck cancer and eight (16%) having progression of a second neoplasm. Seven patients died of intervening medical events. This high incidence of second malignancies supports the continued investigation of chemoprevention for patients in CR. Despite the known high response rates achieved with cisplatin and 5-FU induction chemotherapy, the overall poor survival data reported here should lead to a thorough reexamination of the frequent administration of this regimen in the community.
CT-Based Versus FDG-PET/CT–Based NCCN International Prognostic Index Risk Stratification in DLBCL
Authors: Hugo J.A. Adams, John M.H. de Klerk, Rob Fijnheer, Stefan V. Dubois, Rutger A.J. Nievelstein, Thomas C. Kwee
Journal: Journal of the National Comprehensive Cancer Network (2015)

Background: This study compared CT-based and 18F-fluoro-2-deoxy-D-glucose PET/CT (FDG-PET/CT)–based NCCN International Prognostic Index (NCCN-IPI) risk stratification in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Materials and Methods: This retrospective study included 57 patients with newly diagnosed DLBCL who had undergone both (oral and intravenous contrast-enhanced full-dose) diagnostic CT and FDG-PET/CT. Diagnostic CT only and FDG-PET/CT were evaluated separately, and corresponding NCCN-IPI scores for the 2 datasets (NCCN-IPICT and NCCN-IPIPET/CT) were calculated. Percentages of agreement and weighted k statistic between NCCN-IPICT and NCCN-IPIPET/CT scoring with regard to the formation of low-, low-intermediate–, high-intermediate–, and high-risk groups were calculated. Results: In 47 of 57 patients (82.5%; 95% CI, 70.4–90.4), diagnostic CT alone was in agreement with FDG-PET/CT with regard to the formation of low-, low-intermediate–, high-intermediate–, and high-risk NCCN-IPI groups, but not in the remaining 10 patients (17.5%; 95% CI, 9.6%–29.6%). All NCCN-IPI disagreements between diagnostic CT and FDG-PET/CT were from the detection of additional lesions by the latter, most of them being bone marrow lesions. Agreement between NCCN-IPICT and NCCN-IPIPET/CT with regard to the formation of low-, low-intermediate–, high-intermediate–, and high-risk groups was considered good (k=0.771). Conclusions: Although agreement between NCCN-IPICT and NCCN-IPIPET/CT risk stratification is generally good, FDG-PET/CT results in higher NCCN-IPI risk stratifications in a non-negligible proportion of patients. Future studies should investigate the prognostic implications of these imaging-based differences in NCCN-IPI scoring.
Deletion of the Antiphospholipid Syndrome Autoantigen β<sub>2</sub>‐Glycoprotein I Potentiates the Lupus Autoimmune Phenotype in a Toll‐like Receptor 7–Mediated Murine Model
Authors: Bill Giannakopoulos, Peyman Mirarabshahi, Miao Qi, Chris Weatherall, Jian Cheng Qi, Kumiko Tanaka, Ewan Millar, Leon Vonthethoff, Dominique Gatto, Derek Spielman, Steven A. Krilis
Journal: Arthritis & Rheumatology (2014)

The BXSB.Yaa mouse strain is a model of systemic lupus erythematosus that is dependent on duplication of the Toll-like receptor 7 gene. The objective of this study was to systematically describe the amplified autoimmune phenotype observed when the soluble plasma protein β2 -glycoprotein I (β2 GPI) gene was deleted in male BXSB.Yaa mice. We generated BXSB.Yaa and NZW mouse strains in which the β2 GPI gene had been knocked out by backcrossing the wild-type strains with C57BL/6 β2 GPI(-/-) mice for 10 generations. Sex- and age-matched mice of the various strains were housed under identical conditions and were killed at fixed time intervals. Serum and tissue specimens were collected at various time points. Lupus-associated autoantibodies, inflammatory cytokines, and the type I interferon (IFN) gene signature were measured. Flow cytometric analyses of lymphocyte populations were performed. The severity of glomerulonephritis was graded by 2 independent renal histopathologists. Male BXSB.Yaa β2 GPI(-/-) mice developed significant lymphadenopathy and splenomegaly compared with age-matched controls. Male BXSB.Yaa β2 GPI(-/-) mice also had significantly higher levels of autoantibodies, increased levels of inflammatory cytokines including tumor necrosis factor α, interleukin-6, and BAFF, and more severe glomerulonephritis. The type I IFN gene signature in male BXSB.Yaa β2 GPI(-/-) mice was significantly higher than that in control mice. Male BXSB.Yaa β2 GPI(-/-) mice also had marked dysregulation of various B cell and T cell populations in the spleens and lymph nodes and a disturbance in apoptotic cell clearance. Deletion of β2 GPI accelerates and potentiates the autoimmune phenotype in male BXSB.Yaa mice.
Quantifying lung function in COPD with hyperpolarised 3He MRI
Authors: Samuel Janoff, Helen Marshall, Martin Deppe, Cath Billings, Juan Parra-Robles, Sue Hillis, Sam Miller, David Lipson, Jim Wild, Rod Lawson
Journal: European Respiratory Journal (2012)

Introduction:  Hyperpolarised  3 He MRI can identify regional lung defects and has been found more sensitive than spirometry to early changes in smokers lungs 1 . We aim to quantify change in lung function in response to bronchodilator in COPD using  3 He MRI.   Method:  10 patients with moderate to severe COPD (per NICE) were scanned pre and post bronchodilator at FRC+1L. Lung volume (LV) was defined by region growing algorithms (Slicer 3D, Harvard) on conventional  1 H MRI. Ventilated volume (VV) was defined by a threshold on  3 He MRI. Percentage ventilation (PV) was defined as VV÷LV. Lungs were segmented into 4 regions on each slice with large airways removed.   Results:  Change in ventilation, including recruitment of newly ventilated areas, was seen post treatment.  Regional analysis showed patterns of change in different lung areas which may be hidden in global measures.  FEV 1 % significantly increased post treatment (p 1 , as opposed to global change in gas flow.   Conclusions:  Global MRI measures and spirometry simplify lungs to one unit. Regional analysis explains better change in lung function.   1. JMR21:365-9(2005).