tbuckley/cabot-search huggingface dataset:
Phase I trial of continous infusion 5-fluorouracil (CI-5FU) and escalating doses of oxaliplatin (OXA) given weekly with concurrent radiation (RT) in locally advanced esophageal squamous cell carcinoma (ESCC)
Authors: B. L. Brücher, F. Zimmermann, J. Riera, K. Becker, N. Roethling, T. Seroneit, M. Molls, C. Peschel, J. R. Siewert, F. Lordick
Journal: Journal of Clinical Oncology (2005)

4266 Background: Biweekly Oxa plus 5FU and radiation has shown significant activity in esophageal cancer (JCO 2002; 20: 2844–50). We have now conducted a phase I trial adding concurrent RT to weekly OXA and CI-5FU in locally advanced ESCC. Methods: Patients (pts) with potentially resectable ESCC (uT3 category) receive neoadjuvant external beam radiotherapy (45 Gy, 1.8 Gy daily fractions). CI-5FU is fixed at 225mg/m2 daily during RT. OXA is given on days 1, 8, 15, 22 and 29 at escalating doses (40, 45, 50 mg/m2). Resection is scheduled 4–6 weeks after RT. Dose limiting toxicity (DLT) is defined as grade 3/4 toxicity necessitating the premature termination of neoadjuvant treatment or the need for a more than 2-wk delay of surgery. Results: 19 pts have been entered. Median age XY years, XY males. All pts have completed the first three dose levels and are evaluable for toxicity. 1 pt refused the operation, 1 pt was developped lung metastases during RT and therefore did nor undergo surgery. XY pts achieved a major histological remission (XY10% residual tumor cells in the resected specimen). DLT’s occurred in 4 pts: 1/7 pts in cohort 1 (OXA 40mg/m2) with oral and pharyngeal mucositis, radiation induced dermatitis and pneumonia; 1/6 pts in cohort 2 (OXA 45mg/m2) with toxic colitis and severe diarrhoea. 2/6 pts in cohort 3 (OXA 50mg/m2), 1 with oral mucositis and 1 with diarrhoea, respectively. Conclusions: The addition of concurrent radiation with 45Gy to weekly OXA plus CI-5FU is feasible and shows promising activity in ESCC. We will continue the study as a phase II trial with OXA 45mg/m2 once weekly plus CI-5FU 225mg/m2 which revealed to be the maximal tolerated dose. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi Sanofi Sanofi Sanofi
Abstract MP26: Sleep duration and risk of stroke mortality among Chinese adults in Singapore: the Singapore Chinese Health Study
Authors: An Pan, Jian-Min Yuan, Woon-Puay Koh
Journal: Circulation (2014)

Introduction: Short or long sleep hours are associated with adverse health outcomes, including diabetes, hypertension, coronary heart disease (CHD) and total mortality. However, the prospective relation between sleep duration and stroke risk is less studied, particularly in Asians. Thus, we assessed the hypothesis that short (≤5 hours) and long (≥9 hours) sleep durations were related to increased risk of stroke mortality among Chinese adults residing in Singapore. Methods: The Singapore Chinese Health Study is a population-based cohort that recruited 63,257 Chinese adults aged 45-74 years during 1993 and 1998. Sleep duration was assessed at baseline and categorized to five groups: ≤5, 6, 7, 8 or ≥9 hours. Death information was identified via registry linkage up to December 31, 2011, with ICD-9 codes 430-438 for all stroke deaths, 430-432 for hemorrhagic, and 433-438 for ischaemic or non-specified stroke deaths. Cox proportional hazard models were used to calculate hazard ratios (HRs) with adjustment for socio-demographic, lifestyle and comorbidities. Results: We documented 1,381 total stroke deaths (322 hemorrhagic and 1,059 ischaemic or non-specified strokes) during 926,752 person-years of follow-up. Compared to the reference group of sleeping for 7 hours, the multivariate-adjusted HR (95% confidence interval) for total stroke mortality was 1.25 (1.05-1.50) for ≤5 hours, 1.01 (0.87-1.18) for 6 hours, 1.09 (0.95-1.26) for 8 hours, and 1.54 (1.28-1.85) for ≥9 hours. The increased risk was also observed for ischaemic or non-specified stroke deaths with short (1.37; 1.12-1.68) and long (1.68; 1.36-2.06) sleep durations, but not for hemorrhagic stroke deaths (0.92 [0.62-1.36] and 1.14 [0.76-1.72], respectively). We observed significant interaction with baseline hypertension (P-interaction=0.04): positive association was found for short (1.54; 1.16-2.03) and long (1.95; 1.48-2.57) sleep durations among individuals with baseline hypertension, but not among those without baseline hypertension (1.07 [0.85-1.36] and 1.27 [0.98-1.63], respectively). Furthermore, in participants without baseline CHD/stroke, short and long sleep durations were related to an increased risk (HR 1.30 [1.07-1.57] and 1.43 [1.16-1.76], respectively); while in CHD/stroke patients, only long sleep duration was associated with an increased risk (2.34; 1.53-3.57), but not the short sleep duration (0.96; 0.57-1.62). Conclusions: In this large cohort study of Chinese adults, both short and long sleep durations were significantly associated with increased risks of stroke mortality. The associations were significant and stronger in hypertensive participants, but not in those without hypertension. Further studies are needed to confirm the interaction with hypertension and explore the mechanisms linking sleep quantity and stroke mortality.
Serum Cholinesterase – An Old Wine in a New Bottle! A Marker to Differentiate Cirrhotic From Noncirrhotic Portal Hypertension
Authors: V. Kunal, K. Ajit, B. Sukanya, Y. Raghavender, N. Joshi, S. Nikhil, R. Maidur, K.P. Bubun
Journal: Clinical Gastroenterology and Hepatology (2015)
Effect of fulvestrant in an experimental model of hepato-pulmonary syndrome (HPS) in rats
Authors: Monique Oswald-Mammosser, Sherzad Rashid, Nelly Boehm, Arnaud Agin, Bernard Geny, Valérie Shini-Kerth, Anne Charloux
Journal: European Respiratory Journal (2013)

It has been postulated that general vasodilatation, and in particular in the lung, observed in portal hypertension is explained in part by an increased level of estradiol most likely through an enhanced endothelial formation of nitric oxide (NO). The present study has investigated the possibility that blockade of the estrogen receptor by fulvestrant (F) is able to decrease the NO formation and thus might improve the HPS. HPS was elicited by chronic bile duct ligation (CBDL). Rats were divided into four groups : CBDL, CBDL+F, sham (S) and S+F. Plasma nitrites and nitrates concentrations were higher in CBDL group compared to the S group; this effect was not affected by F. In the lung, the endothelial nitric oxide synthase (eNOS), and nitrotyrosine protein expressions were increased in CBDL group as compared to the S group, and this effect was significantly reduced by F. Surprisingly the level of pVASP (an indirect marker of NO formation) was decreased in the lungs of the CBDL group, and this effect was not affected by F. In contrast, the immunohistochemical level of vascular endothelial growth factor (VEGF) was increased in the lungs of the CBDL group, and it was unaffected by F.

Thus, the present findings suggest that in the lungs of CBDL rats the excessive formation of NO may be degraded by superoxide anions leading to peroxinitrites and a decreased activation of the cGMP pathway, and that this effect is not affected by F. In addition, they further suggest that vascular remodelling may be promoted in the lungs in the HPS subsequent to the increased expression of VEGF and that this effect was not affected by F.
Correlation between 6-minute pegboard and ring test and upper extremity activities of daily living in patients with chronic obstructive pulmonary disease
Authors: Kenichi Takeda, Yuji Kawasaki, Kazuma Yoshida, Yoji Nishida, Tomoya Harada, Kosuke Yamaguchi, Kiyoshi Hashimoto, Shingo Matsumoto, Akira Yamasaki, Tadashi Igishi, Eiji Shimizu
Journal: European Respiratory Journal (2012)

Background  Upper extremity training is recognized as an important component of pulmonary rehabilitation (PR). 6-minute pegboard and ring test (6PBRT) was developed for testing arm exercise capacity of patients with COPD. The purpose of this study was to apprehend characteristics of this test and to evaluate the relationship between 6PBRT and upper extremity activities of daily living (ADL) in patients with COPD.  Methods  Twenty outpatients with COPD performed 6PBRT, spirometry, maximal inspiratory pressures, maximal expiratory pressures and grip strength. The 6PBRT was done according to the method of Zhan et al. In brief, subjects were asked to move as many rings as possible, and the final score was the number of moved rings during a 6-minutes period. Upper extremity ADL was evaluated with the upper extremity activities subdomain of Pulmonary Functional Status & Dyspnea Questionnaire-Modified Version (PFSDQ-M). Upper extremity ADL was also measured objectively by the wrist accelerometer (Actiwatch2®) all day long for a week.  Results  There was a positive correlation between the 6PBRT scores and inspiratory capacity (IC) (r = 0.71,  p   p   p   p   p    Conclusion  6PBRT may be one of the predictive tests for PR to maintain and improve upper extremity ADL in patients with COPD.
Meningococcal vaccine antigen diversity in global databases
Authors: Carina Brehony, Dorothea M Hill, Jay Lucidarme, Ray Borrow, Martin C Maiden
Journal: Eurosurveillance (2015)

The lack of an anti-capsular vaccine against serogroup B meningococcal disease has necessitated the exploration of alternative vaccine candidates, mostly proteins exhibiting varying degrees of antigenic variation. Analysis of variants of antigen-encoding genes is facilitated by publicly accessible online sequence repositories, such as the Neisseria PubMLST database and the associated Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL). We investigated six proposed meningococcal vaccine formulations by deducing the prevalence of their components in the isolates represented in these repositories. Despite high diversity, a limited number of antigenic variants of each of the vaccine antigens were prevalent, with strong associations of particular variant combinations with given serogroups and genotypes. In the MRF-MGL and globally, the highest levels of identical sequences were observed with multicomponent/multivariant vaccines. Our analyses further demonstrated that certain combinations of antigen variants were prevalent over periods of decades in widely differing locations, indicating that vaccine formulations containing a judicious choice of antigen variants have potential for long-term protection across geographic regions. The data further indicated that formulations with multiple variants would be especially relevant at times of low disease incidence, as relative diversity was higher. Continued surveillance is required to monitor the changing prevalence of these vaccine antigens.
Biologically-active exosomes in plasma of AML patients inhibit innate immunity and promote leukemia progression
Authors: Michael Boyiadzis, Chang-Sook Hong, Theresa L Whiteside
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts AML patients are reported to have impairments of immune cells which contribute to leukemia progression. Tumor-derived exosomes (TEX) have recently emerged as carriers of the molecular and genetic cargo with potent immunosuppressive properties. We showed that plasma of newly-
A multicenter phase I study on preoperative chemoradiotherapy with S-1 and CPT-11 for locally advanced lower rectal cancer (SAMRAI-1).
Authors: Masafumi Noda, Takeo Sato, Kazushige Hayakawa, Naohiro Tomita, Norihiko Kamikonya, Soichiro Ishihara, Daiki Kato, Yoshiharu Sakai, Masahiro Hiraoka, Mitsuo Shimada, Hitoshi Ikushima, Hideo Baba, Natsuo Oya, Masatoshi Oya, Masahiko Oguchi, Masahiro Takeuchi, Masahiko Watanabe
Journal: Journal of Clinical Oncology (2013)

503 Background: Preoperative chemoradiotherapy with 5-FU is a standard therapy for locally advanced lower rectal cancer. This therapy is useful for increasing local control rates and maintaining anal functions, but there is no evidence indicating that this therapy can extend survival. We performed a phase I study with the objective of developing a new chemoradiotherapy with irinotecan (CPT-11) and S-1, containing gimeracil, a dihydropyrimidine dehydrogenase inhibitor with radiosensitizing effect. Methods: Patients with locally advanced lower rectal cancer (T3-4, N0-2) of which the inferior border was located closer to the anal verge than to the peritoneal reflection were used for analysis. The radiation dose was 45 Gy in 25 fractions. The radiation field included the internal iliac, pararectal, and obturator lymph nodes in addition to the primary tumor and enlarged lymph nodes. S-1 was administered for five consecutive days and withdrawn for two consecutive days (administration: Days 1-5, 8-12, 22-26, and 29-33). The dose of S-1 (80, 100, 120 mg/day) was controlled in accordance with the body surface area. CPT-11 was administered on days 1, 8, 22, and 29. The initial dose of CPT-11 was 60 mg/m 2 (Level 1), and the dose was increased gradually. Total mesorectal excision was performed 6-10 weeks after completion of the chemoradiotherapy. Results: 20 patients were enrolled. Excluding 2 patients who discontinued the study, 18 patients were subject to analysis. Dose-limiting toxicity (DLT) was not seen in 3 patients treated with CPT-11 at 80 mg/m 2 (Level 2), but was seen in 3 of the 6 patients treated with CPT-11 at 90 mg/m 2 (Level 3). DLT was seen in 3 other patients administered a Level 2 dose. At Level 2 or Level 3, DLTs, namely neutropenia, thrombocytopenia and diarrhea were seen. Level 2 was regarded as a maximum tolerated dose, and Level 1 as a recommended dose (RD). The pathological complete response rate was 28%, and the downstaging rate 56%. Conclusions: The results of the study suggest that the RD of CPT-11 is 60 mg/m 2 . We plan to perform a phase II study to evaluate the efficacy and safety of chemoradiotherapy with S-1 and CPT-11. Clinical trial information: UMIN000001639.
Case 1: Hodgkins’s Disease Presenting as a Cystic Neck Mass
Authors: James Butera, Nancy J. Freeman
Journal: Journal of Clinical Oncology (2000)

Article Tools Unusual Features of of Hodgkins's Disease Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.5.1150 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10694568 Case 1: Hodgkins’s Disease Presenting as a Cystic Neck Mass James ButeraxJames ButeraSearch for articles by this author , Nancy J. FreemanxNancy J. FreemanSearch for articles by this author Show More Brown University School of Medicine, Providence, RI https://doi.org/10.1200/JCO.2000.18.5.1150 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Abstract 12555: The Dual PPAR-α/γ Agonist Aleglitazar Enhances Arteriogenesis, Angiogenesis and Endothelial Function
Authors: Christian Werner, Stephan H Schirmer, Valerie Pavlickova, Michael Böhm, Ulrich Laufs
Journal: Circulation (2014)

Objective: Peroxisome proliferator-activated receptor (PPAR)-α and -γ agonists modify lipid and glucose metabolism. The aim of the study was to characterize the effects of the dual PPAR-α/γ agonist aleglitazar on endothelial function, neoangiogenesis and arteriogenesis in mice and on human endothelial progenitor cells (EPC). Methods and Results: Male C57Bl/6 wild-type (WT, normal chow) and apolipoprotein E-deficient (apoE-/-) mice on Western-type diet (WTD) were treated with aleglitazar (10 mg/kg i.p.) or vehicle by daily injection. Hindlimb ischemia was induced by right femoral artery ligation (FAL). ApoE-/- mice on WTD treated with aleglitazar before FAL were characterized by an improvement of endothelial-dependent laser Doppler perfusion (right/left foot ratio 0.40±0.03) 1 week after FAL compared to controls (R/L foot ratio 0.24±0.01; p&lt;0.001). Collateral-dependent perfusion measured under conditions of maximal vasodilatation 1 week after FAL using fluorescent microspheres was impaired in apoE-/- on WTD compared to WT mice (R/L leg ratio in WT 78±13 vs. apoE-/- 56±6; p&lt;0.001) and was normalized by aleglitazar treatment. Neoangiogenesis was measured in-vivo by subcutaneously implanting discs covered with cell-impermeable filters. The vascularized area of the discs was quantified after 14 days by perfusion of the animals with space-filling fluorescent microspheres. Aleglitazar increased neoangiogenesis in WT mice by 178±18% compared to vehicle (p&lt;0.05). Endothelium-dependent relaxation of aortic rings was impaired in apoE-/- mice on WTD for 6 weeks (relaxation to 52±5% of max. contraction) compared to WT animals (relaxation to 18±5% of max. contraction) (p&lt;0.001). Aleglitazar treatment improved endothelial function (relaxation to 39±5% of max. contraction; p&lt;0.05). In parallel, number and function of EPC were improved in mice. Studies in human EPC showed that 1) aleglitazar’s effects were mediated by both PPAR-α and -γ signalling and Akt and 2) migration and colony forming units were up-regulated by aleglitazar in cultivated EPC from CAD patients. Conclusion: The study provides evidence for beneficial effects of the dual PPAR-α/γ agonist aleglitazar on vascular function in addition to or mediated by its metabolic actions.
Inorganic Arsenic–Related Changes in the Stromal Tumor Microenvironment in a Prostate Cancer Cell–Conditioned Media Model
Authors: Joseph J. Shearer, Eric A. Wold, Charles S. Umbaugh, Cheryl F. Lichti, Carol L. Nilsson, Marxa L. Figueiredo
Journal: Environmental Health Perspectives (2015)

Background:The tumor microenvironment plays an important role in the progression of cancer by mediating stromal–epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic arsenic (iAs), has also been implicated in the progression of prostate cancer.Objective:The role of iAs exposure in stromal signaling in the tumor microenvironment has been largely unexplored. Our objective was to elucidate molecular mechanisms of iAs-induced changes to stromal signaling by an enriched prostate tumor microenvironment cell population, adipose-derived mesenchymal stem/stromal cells (ASCs).Results:ASC-conditioned media (CM) collected after 1 week of iAs exposure increased prostate cancer cell viability, whereas CM from ASCs that received no iAs exposure decreased cell viability. Cytokine array analysis suggested changes to cytokine signaling associated with iAs exposure. Subsequent proteomic analysis suggested a concentration-dependent alteration to the HMOX1/THBS1/TGFβ signaling pathway by iAs. These results were validated by quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blotting, confirming a concentration-dependent increase in HMOX1 and a decrease in THBS1 expression in ASC following iAs exposure. Subsequently, we used a TGFβ pathway reporter construct to confirm a decrease in stromal TGFβ signaling in ASC following iAs exposure.Conclusions:Our results suggest a concentration-dependent alteration of stromal signaling: specifically, attenuation of stromal-mediated TGFβ signaling following exposure to iAs. Our results indicate iAs may enhance prostate cancer cell viability through a previously unreported stromal-based mechanism. These findings indicate that the stroma may mediate the effects of iAs in tumor progression, which may have future therapeutic implications.Citation:Shearer JJ, Wold EA, Umbaugh CS, Lichti CF, Nilsson CL, Figueiredo ML. 2016. Inorganic arsenic–related changes in the stromal tumor microenvironment in a prostate cancer cell–conditioned media model. Environ Health Perspect 124:1009–1015; http://dx.doi.org/10.1289/ehp.1510090
Surgical treatment of relapsed hydatid disease of lungs
Authors: Davlyathon Maksumov, Rustem Hayaliev, Bahrom Amanov
Journal: European Respiratory Journal (2014)

Hydatid disease - a serious parasitic disease of humans, which is often found in countries with livestock and is endemic to the Central Asian republics, including Uzbekistan. The surgical treatment of hydatid disease of lungs is unique and the most radical, however and after operations the development of relapses is possible. On the data of the literature the relapse of hydatid disease after surgical treatment does not tend to decrease and changes from 4% up to 48%.

We have an experience of treatment 2945 patients with hydatid disease of lungs. From 2945 operated patients concerning the various forms of hydatid disease of lungs relapse of disease from 1 to 7 years we observed in 184 (6,24%) patients. From them: men - 103 (55,9%), women - 81 (44,1%). The age of the patients varied from 9 to 74 years. From 184 patients 152 (82,6%) undergone operations, not operated 32 (17,39%) - the reason was disseminated process, wide distribution of hydatid cysts. 142 (93,4%) patients were performed organsaving operation, 10 (6,6%) patients underwent resections.

In the postoperative period albendazole was administered in a doze 10-12 mg/kg/day, quantity of courses depended on the form of a defeat. Using preventive chemotherapy realistically reduces the risk of the development of the relapse of hydatid disease, hereunder, rescuing patient from the repeated operations and possible complications. The following pictures show relapsed multiple hydatid disease of lungs.

![Figure][1]  [1]: pending:yes
Limitations of QOPI end-of-life (EOL) data use for purposes of accountability: Comparison of sample versus full cohort analysis.
Authors: Carole Kathleen Dalby, Paul J. Catalano, Caitlin C. Donohue, Julie M. Bryar, Andrew David Norden, Judith Kostka, Joseph O. Jacobson
Journal: Journal of Clinical Oncology (2013)

87 Background: Quality Oncology Practice Initiative (QOPI) retrospectively collects process measures at the practice level. Sample size is determined by number of full-time equivalent physicians. Although intended as an improvement program, there is growing pressure to use QOPI for accountability. Methods: We investigated QOPI sampling strategy for EOL measures in a large three-site community oncology practice for all patients meeting QOPI sampling criteria. Analysis period was July 1 to December 31, 2012. We included all patients submitted for the QOPI EOL module and compared the QOPI sample to the full but non-QOPI cohort using Fisher’s exact test. To assess relative precision, we calculated rates and 95% confidence intervals (CI) for the sampled vs. full cohorts (inclusive of QOPI cohort). Results: 246 deaths were analyzed, with 34 (13.8%) from the QOPI sample. No statistically significant differences were found between sampled and full non-QOPI cohorts. However, sampling was associated with wide CIs compared to precision using the full cohort (Table); e.g. #38 yields a CI width of 24.2% QOPI vs. 4.9% full. Similarly, #47 shows CI width of 27.7% vs. 9.0%. Low statistical significance yet wide CIs indicate comparison data are representative but with variability in precision. Conclusions: Although no statistically significant differences were identified, comparing QOPI sampling strategy to full cohort yielded presence of marked differences in precision. We suggest caution in use of current QOPI EOL sampling strategy if used for purposes other than improvement. [Table: see text]