tbuckley/cabot-search huggingface dataset:
Abstract 13047: Differential Myocardial Proteomic Profiling in Mutant Myopalladin Knock-in Mice Models of Restrictive Cardiomyopathy
Authors: Ruben Martherus, Uzmee Mendsaikhan, Nan Gong, Kristen Kramer, Zaza Khuchua, Jeffrey A Towbin, Enkhsaikhan Purevjav
Journal: Circulation (2013)

Background: Myopalladin (MYPN) gene mutations cause autosomal dominant cardiomyopathies in humans with variable penetrance. Knock-in MypnWT/Q529X mice recapitulate human restrictive cardiomyopathy ...
Eomesodermin Regulates The Early Activation Of Alloreactive CD4 T Cells and Is Critical For Both Gvh and GVL Responses
Authors: Barbara Du Rocher, Odette M Smith, Andrew M. Intlekofer, Jarrod A Dudakov, Emily Levy, Fabiana Kreiners, Steven Reiner, Eliana Abdelhay, Marcel R.M. van den Brink, Alan M Hanash
Journal: Blood (2013)
Phase III double-blind randomized trial of radiation therapy for stage IIIB cervical cancer in combination with low or high dose Z-100, immunomodulator widely used in Japan
Authors: K. Fujiwara, Y. Ohashi, H. Nakayama, R. Nishimura, K. Shimizu, N. Mitsuhashi, M. Hatae, K. Ochiai, K. Hatano, K. Noda
Journal: Journal of Clinical Oncology (2004)

5029 Background: The Specific Substance of Maruyama (SSM) is a well-known immunomodulator that has been used in Japan as an unapproved drug in the treatment of over 240,000 cancer-bearing patients since 1970. Z-100 is the same agent as SSM, used in different concentrations. The aim of this study is to investigate whether Z-100 enhances the efficacy of radiation therapy (RT) for locally advanced cervical cancer of the uterus. Methods: Between 1995 and 1999, 221 (217 evaluable) patients with stage IIIb squamous cell carcinoma of the uterine cervix were randomly assigned to treatment with either 0.2 μg Z-100 (Group L: n=109) or 40 μg Z-100 (Group H: n=108) in a double-blind manner in combination with conventional RT. Z-100 was administered twice a week during the RT, and it was continuously administered every two weeks after RT for as long as possible ≥ 2 years, or until recurrence or progression was noted. The endpoints were tumor response, progression-free survival (PFS) and overall survival (OS). Results: There was no difference in the tumor-regression effect of Z-100 between two groups. The 5-year survival of Group H was 41.5%, (95%CI: 31.7–51.3%), which was equivalent to that of Japanese historical controls treated by RT alone (35–42%), or to the 4-year survival rate of the RT plus hydroxyurea arms of GOG120 study (50%). The 5-year survival of Group L was 58.2% (95% CI: 48.7–67.7%). Compared with Group H, Group L showed a 30% reduction in the death rate (hazard ratio: 0.670 [95% CI: 0.458 - 0.980], log-rank test, p=0.0387). PFS was also significantly improved in favor of Group L (hazard ratio: 0.667 [95% CI: 0.447 - 0.997], p=0.0482). OS and PFS of Group L were equivalent to those of concurrent cisplatin-based chemoradiation arms of the GOG study. Conclusions: It was suggested that RT combined with the immunomodulator Z-100 improved the survival of patients with locally advanced cervical cancer. However, more was not better, suggesting that the dose response to immunomodulators is different from the responses to conventional cytotoxic agents. A randomized placebo controlled trial is under planning. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Zeria Pharmaceuticals Aventis; Bristol; GlaxoSmithKline; Roche; AstraZeneca; Zeria
In atrial fibrillation, the ATRIA risk score better predicted stroke than CHADS<sub>2</sub>and CHA<sub>2</sub>DS<sub>2</sub>-VASc scores
Authors: Brandon W. Calenda, Christopher B. Granger
Journal: Annals of Internal Medicine (2016)

Source Citation van den Ham HA, Klungel OH, Singer DE, Leufkens HG, van Staa TP. Comparative performance of ATRIA, CHADS2, and CHA2DS2-VASc risk scores predicting stroke in patients with atrial fibrillation: results from a national primary care database. J Am Coll Cardiol. 2015;66:1851-9. 26493655
Incidence of lymphedema thirty to sixty months after breast cancer surgery.
Authors: J. M. Armer, R. P. Shook, B. R. Stewart
Journal: Journal of Clinical Oncology (2010)

e19520 Background: Breast cancer (BC) survivors are at lifetime risk for developing lymphedema (LE), although the majority of the literature does not report incidence and prevalence beyond short-term follow-up. Utilizing a prospective study design with baseline measurements occurring before surgery for BC, the goal of this research was to describe LE occurrence 5 years after surgery. Methods: Participants were enrolled following diagnosis of BC but before surgery and followed every 3 months for 12 months, then every 6 months thereafter (through 60 months, N = 211). Limb volume changes (LVC) were measured using: (a) circumferences at 4 cm intervals, (b) perometry, and (c) symptom experience (SS) via interview. Four diagnostic criteria for LE were used: (i) 2 cm circumferential change; (ii) 200 mL perometry LVC; (iii) 10% perometry LVC; and (iv) report of limb heaviness/swelling, “now” or “in the past year.” Additionally, the objective measures (criteria i-iii) were applied either: ipsilateral limb versus contralateral limb at a given visit, or ipsilateral limb at a given visit versus ipsilateral limb pre-surgery. Results: At 5 years post-surgery, LE occurrence in this cohort of BC survivors ranged between 43-94%, compared to 38-87% at 2.5 years, based on the criteria used in this analysis. When compared to data at 2.5 years, the most liberal method at 5 years to identify LE in this preliminary analysis was 2 cm circumferential change (87% vs. 94%), followed by 200 mL LVC (65% vs. 83%), 10% LVC (40% vs. 53%), and self-reporting of heaviness/swelling (38% vs. 43%). In this cohort, mean time to LE diagnosis ranged from 15-40 months based on the various criterions, with 2 cm the shortest and report of heaviness/swelling the longest. Conclusions: This updated analysis suggests breast cancer survivors continued to be at risk for the development of LE, as demonstrated by an increase of LE occurrence between 2.5 to 5 years for all criteria applied. From 2.5 to 5 years, 200 mL LVC becomes the criteria to most commonly identify LE, whereas 2 cm was the most common criteria from baseline to 2.5 years. No significant financial relationships to disclose.
TGF-β 1 suppresses IRF-1 expression in pulmonary fibroblasts and modulates its induction by IFN α and IFN γ
Authors: Patricia Leoni, Xu Shi-Wen, Carmel Stock, David Abraham, Andrew Nicholson, Toby Maher, Athol Wells, Elizabeth Renzoni, Gisela Lindahl
Journal: European Respiratory Journal (2011)

Background:  In our microarray study of lung fibroblasts from control subjects (n=10) and patients with scleroderma-associated interstitial lung disease (SSc-ILD) (n=8), the Interferon Stimulated Genes (ISGs) are an overrepresented group of genes with reduced expression in SSc-ILD fibroblasts. Since interferon gamma is known to interfere with TGF-β signalling and reduce the expression of individual pro-fibrotic genes, we asked whether TGF-β signalling could in turn downregulate ISGs in lung fibroblasts, and whether TGF-β could affect the induction of ISGs by interferons. In this study, we have focused on the expression of IRF-1, a key transcription factor regulating ISGs.   Methods:  Human primary pulmonary fibroblasts were grown to near confluence, serum starved in 0.1% BSA for 24 hrs, and treated with or without TGF-β (2ng/ml), IFNα (2500u/ml), and IFNγ (10ng/ml), for a further 24 hrs. Specific antibodies were used to assess protein expression in cell layers by Western blot analysis.   Results:  IRF-1 mRNA expression was significantly reduced in SSc-ILD fibroblasts (-3.6-fold, p=0.0001). TGF-β treatment suppressed baseline IRF-1 protein expression to undetectable levels in fibroblast preparations from control and SSc-ILD lungs. In both SSc-ILD and control fibroblasts, TGF-β had no effect on IFNγ-induced IRF-1 protein expression, but completely inhibited the induction of IRF-1 by IFNα. By contrast, IFNγ reduced TGF-β induced CTGF expression, while IFNα had no effect.   Conclusion:  TGF-β signalling suppresses baseline and IFNα-induced IRF-1 expression in lung fibroblasts, suggesting a possible mechanism for the reduced expression of ISGs expression observed in SSc-ILD fibroblasts.
Recombinant IL-21 (rIL-21) in combination with sorafenib: Interim results from a phase 1/2 study in patients with metastatic renal cell cancer (mRCC)
Authors: S. Bhatia, B. D. Curti, M. S. Gordon, D. I. Quinn, J. A. Thompson, T. A. DeVries, M. G. Dodds, N. N. Hunder, D. F. Hausman
Journal: Journal of Clinical Oncology (2008)

16008 Background: Despite the impact of tyrosine kinase inhibitors on the outcome for mRCC, complete responses are rare and long term survival remains poor. rIL-21, a cytokine that enhances CD8+ T cell and NK cell activity, demonstrated single agent anti-tumor activity in Phase 1 studies. To explore the combined use of rIL-21 with sorafenib in patients with mRCC, a Phase 1/2 dose escalation study was initiated. Results from the Phase 1 dose escalation are reported here. Methods: First or 2nd-line patients received sorafenib at 400 mg BID plus rIL-21 at 1 of 4 dose levels (10, 30, 40, or 50 μg/kg IV) on days 1–5 and 15–19 of a 6-week treatment course. Safety, pharmacokinetics (PK), and tumor response per RECIST were assessed. In Phase 2, 30 patients will receive 2nd or 3rd-line therapy with rIL-21 at the maximum tolerated dose + sorafenib. Results: 14 patients were treated at 3 consecutive dose levels of 10, 30, and 50 μg/kg. After documentation of DLT in 2 subjects at 50 μg/kg, an intermediate dose level cohort at 40 μg/kg was opened. 3 patients have currently been treated at this dose level. Most adverse events (AEs) were Grade 1 or 2, and consistent with the known toxicity of rIL-21 and sorafenib. Treatment-related Grade 3 AEs were hypophosphatemia (n=6), hand-foot syndrome (n=5), rash (n=2), fatigue (n=2), hyponatremia (n=2), elevated liver transaminases (n=2), fever (n=1), and dehydration (n=1). DLTs of diffuse erythroderma with hand-foot syndrome were reported in 1 of 6 patients at 10 μg/kg and 2 of 4 patients at 50 μg/kg. Sorafenib and rIL-21 PK estimates were within the expected range for single agent therapy. To date, 10 patients have been evaluable for tumor response. Per investigator assessment, all 10 had tumor shrinkage at first evaluation, and all received additional courses (2–5). 5 patients had ≥ 30% tumor shrinkage as best response to date, including one confirmed PR at 50 μg/kg. 11 subjects continue on study. Conclusions: rIL-21 plus sorafenib can be administered in the outpatient setting and is associated with anti-tumor activity. Sorafenib PK data suggests that rIL-21 does not increase plasma levels of sorafenib. The Phase 1 results have justified initiation of the Phase 2 portion to confirm the anti-tumor effect of the combination. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration ZymoGenetics, Inc. ZymoGenetics, Inc. ZymoGenetics, Inc. ZymoGenetics, Inc.
Polyurethane scaffold with in situ swelling capacity for nucleus pulposus replacement
Authors: Zhen Li, Gernot Lang, Xu Chen, Hagit Sacks, Carmit Mantzur, Udi Tropp, Kerstin T. Mader, Thomas C. Smallwood, Chris Sammon, R. Geoff Richards, Mauro Alini, Sibylle Grad
Journal: Biomaterials (2016)
Impact of atelectasis on survival in emphysema patients treated with bronchoscopic lung volume reduction
Authors: Rafael Rambo, Amarilio Vieira de Macedo Neto, Hugo de Oliveira
Journal: European Respiratory Journal (2013)

Recent studies show long-term improvement of emphysema patients following bronchoscopic lung volume reduction (BLVR), as well as an association of atelectasis with increased survival (Venuta, F., et al. Eur Respir J 2012;39: 1084–9; Hopkinson, N.S., et al. Eur Respir J 2011; 37: 1346–51). We have treated 68 patients with BLVR at our Emphysema Center. In the present study, we focus on an analysis of survival in 12 patients with lobar exclusion and radiological atelectasis and 32 patients with lobar exclusion without atelectasis. At baseline (day of treatment), mean age was 67.94 years. Mean heterogeneity score (difference between lobes in % area with parenchymal density
Filaggrin-null mutations are associated with increased maturation markers on Langerhans cells
Authors: Claire S. Leitch, Eenass Natafji, Cunjing Yu, Sharizan Abdul-Ghaffar, Nayani Madarasingha, Zoë C. Venables, Roland Chu, Paul M. Fitch, Andrew J. Muinonen-Martin, Linda E. Campbell, W.H. Irwin McLean, Jürgen Schwarze, Sarah E.M. Howie, Richard B. Weller
Journal: Journal of Allergy and Clinical Immunology (2016)

Mutations in the gene encoding filaggrin (FLG), an epidermal structural protein, are the strongest risk factor identified for the development of atopic dermatitis (AD). Up to 50% of patients with moderate-to-severe AD in European populations have FLG-null alleles compared with a general population frequency of 7% to 10%.This study aimed to investigate the relationship between FLG-null mutations and epidermal antigen-presenting cell (APC) maturation in subjects with and without AD. Additionally, we investigated whether the cis isomer of urocanic acid (UCA), a filaggrin breakdown product, exerts immunomodulatory effects on dendritic cells.Epidermal APCs from nonlesional skin were assessed by using flow cytometry (n = 27) and confocal microscopy (n = 16). Monocyte-derived dendritic cells from healthy volunteers were used to assess the effects of cis- and trans-UCA on dendritic cell phenotype by using flow cytometry (n = 11).Epidermal APCs from FLG-null subjects had increased CD11c expression. Confocal microscopy confirmed this and additionally revealed an increased number of epidermal CD83(+) Langerhans cells in FLG-null subjects. In vitro differentiation in the presence of cis-UCA significantly reduced costimulatory molecule expression on monocyte-derived dendritic cells from healthy volunteers and increased their ability to induce a regulatory T-cell phenotype in mixed lymphocyte reactions.We show that subjects with FLG-null mutations have more mature Langerhans cells in nonlesional skin irrespective of whether they have AD. We also demonstrate that cis-UCA reduces maturation of dendritic cells and increases their capacity to induce regulatory T cells, suggesting a novel link between filaggrin deficiency and immune dysregulation.
A randomized phase II trial of pemetrexed (P) plus cisplatin (cis) or carboplatin (carbo) in extensive stage small cell lung cancer (ES-SCLC)
Authors: M. A. Socinski, C. H. Weissman, L. L. Hart, J. T. Beck, J. K. Choksi, J. P. Hanson, D. Prager, L. P. Bloss, Z. Ye, C. K. Obasaju
Journal: Journal of Clinical Oncology (2005)

7165 Background: ES-SCLC is a chemotherapy-sensitive disease. Phase I combination trials of P + a platinum compound (cis or carbo) have demonstrated that these agents have anti-tumor activity in mesothelioma and Non-Small-Cell Lung Cancer (NSCLC). This trial was conducted to assess the anti-tumor activity of P-platinum doublets in ES-SCLC. Methods: Eighty ES-SCLC pts were randomized to P 500mg/m2 + either cis 75mg/m2 (Arm A) or carbo AUC 5 (Arm B) administered q 21 days for up to 6 cycles. Pts received folic acid, vitamin B12, and steroid prophylaxis. Conclusions: P + cis or carbo in ES-SCLC have activity and a favorable toxicity profile. Updated response, disease progression, and survival data from this study will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly, Lilly Oncology, Bristol-Meyers Squibb, Pfizer, AstraZeneca, Aventis, Amgen Eli Lilly, Lilly Oncology, Bristol-Meyers Squibb, Pfizer, AstraZeneca, Aventis, Amgen
Abstract 620: Hyperintense Plaque Visualized on Noncontrast T1-Weighted Magnetic Resonance Coronary Plaque Imaging is Associated With High-Risk Coronary Plaque
Authors: Atsushi Tanaka, Tomohiro Kawasaki, Shoichi Koga, Yoshihiro Hiramatsu, Takaya Fukuyama, Nobuhiko Koga
Journal: Circulation (2009)

Magnetic resonance (MR) imaging is well known to have the excellent soft tissue characterization and a great potential to evaluate the properties of the vessel wall and atherosclerotic plaque, alth...
Prospective center-randomized trial of melanoma surveillance in 3,833 patients: An analysis of the early detection of recurrences
Authors: C. Garbe, U. M. Leiter, M. Weichenthal, A. Figl, D. Schadendorf, A. Hauschild
Journal: Journal of Clinical Oncology (2007)

8516 Prospective center-randomized trial of melanoma surveillance in 3,833 patients: An analysis of the early detection of recurrences Garbe C, Leiter U, Weichenthal M, Figl A, Schadendorf D and Hauschild A Background: A follow up strategy with reduced imaging techniques in melanoma = 1.0mm, performed at the department of dermatology in Tuebingen (arm A) was compared to the previous more extended follow up schedule at the departments of dermatology in Kiel and Mannheim (arm B), table 1 . Methods: Follow up examinations were evaluated in stage I-III melanoma patients for a time period of two years. The early detection of recurrences (size of metastasis = 2 cm in diameter, &lt;10 metastases, R0 resection) was the primary endpoint of the study. Results: 2,577 (arm A) and 1,256 (arm B) patients were documented with 12,965 physical examinations, 7,610 blood tests and 10,599 examinations with imaging techniques. 211 patients (112 arm A, 99 arm B) presented with 452 recurrences (240 arm A, 212 arm B). Of these 55.4 % were classified as early detected (arm A 64.3%, arm B 45.5%). A reduction of clinical and technical examinations in stage I melanoma (= 1.0 mm) did not have an effect on the early detection of recurrences. Loco-regional recurrences were mainly detected by physical examinations and lymph node ultrasound and were discovered earlier in arm A (P=0.01). This may be attributed to lymph node ultrasound which is more frequently applied in melanoma &gt;1.0mm and stage III patients. No difference was observed in the detection of distant metastases, where CT scans and S100 blood tests had the highest diagnostic impact. Conclusions: A reduction of physical and technical examinations in primary melanoma =1.0mm, application of lymph node ultrasound in melanoma &gt; 1.0 mm and an intensified follow up program in stage III may be considered as appropriate follow-up strategy. No significant financial relationships to disclose. [Table: see text]
First-line pemetrexed (P) for the treatment of hormone refractory prostate cancer (HRPC): A phase I/II study
Authors: J. Lehmann, M. Hack, H. Büttner, M. Stöckle
Journal: Journal of Clinical Oncology (2007)

15597 Background: Evaluation of maximum tolerated dose (MTD), efficacy and toxicity of pemetrexed as first-line treatment in HRPC. Methods: Patients (pts) with metastatic and/or unresectable HRPC and progression received P monotherapy 500 mg/m 2 i.v. d1 q21d-cycle for 6 cycles with VitB 12 and folate supplementation until progression or dose-limiting toxicity. Corticosteroids were given 8 mg p.o. 3 d around P infusion. The primary outcome measure was PSA (serological) response (PSAr), defined as = 50% decline from baseline, confirmed at least 3 wks later. If no metastatic disease, baseline PSA &gt; 5 ng/mL was required. Results: Patient characteristics: 12 pts were treated; median age was 67 yrs (61–76), median baseline PSA 138.6 ng/ml (9.4–2662), median Karnofsky status 95 (80–100). Cycles: A total of 55 treatment cycles was administered with a median of 5 cycles (1–6) per pt. Due to dose limiting toxicities (DLT) during the first cycle in 2/6 pts, P dose was reduced to 400 mg/m 2 d1 q21d-cycle for the following 6 pts. One pt experienced a DLT during his first cycle with P 400 mg/m 2 . Dose needed to be reduced in 3/12 pts, treatment discontinuation occurred in 6/12 pts. Adverse Effects: 6 of 12 (50%) pts experienced a total of 18 grade 3 events according to CTC criteria, including neutropenia, anemia and pain. 4 of 12 (33%) pts experienced a total of 7 grade 4 events, mainly neutropenia and leucopenia. 1 death occurred after one dose of P 500 mg/m 2 ; relationship to P could not be ruled out. Response: 11/12 pts were evaluable for response. On 500 mg/m 2 1 pt showed serological response, 1 partial tumor-response in metastatic lymph-node disease was seen. Overall, 7 patients remained serologically stable (63.6%), 3 PSA progressions (27.3%) were seen. Stable serological status could be maintained for 3–43 wks. Conclusions: P 400 mg/m 2 was determined the recommended dose for a potential phase II, with an acceptable toxicity profile in this patient population. Serological stability could be achieved in &gt; 60% of patients for up to 43 wks. However, as no confirmed PSA response was achieved with P 400 mg/m 2 , in a potential phase II a schedule with P 400 mg/m 2 but higher dose-density should be pursued as a first-line approach in pts with HRPC. No significant financial relationships to disclose.
Reduction of Rat Liver Carcinogenicity of α-Nitrosomorpholine by a-Deuterium Substitution 2
Authors: William Lijinsky, H. Wayne Taylor, Larry K. Keefer
Journal: JNCI Journal of the National Cancer Institute (1976)

Groups of 30 males Sprague-Dawley rats were given 4-nitrosomorpholine-3,3,5,5-d in their drinking water at concentrations of 0.35 and 0.07 X 10(-3) M for 30 weeks. Two similar groups of rats were simultaneously given unlabeled 4-nitrosomorpholine (NM) at the same malar concentrations; all animals were observed throughout their lives. Those receiving the alpha-deuterium-labeled compound had significantly fewer liver tumors than did the corresponding animals receiving the unlabeled compound. The difference in potency appeared to be at least fivefold, a magnitude consistent with a primary kinetic isotope effect on the carcinogenic action of NM. Thus breakage of a bond linking a hydrogen (deuterium) atom with carbon adjacent to the nitrosamino function may be involved in a rate-limiting step of carcinogenesis by NM.