tbuckley/cabot-search huggingface dataset:
Serum periostin in asthma: A potential biomarker for stratification in severe treatment-resistant asthma
Authors: Hitasha Rupani, Laurie Lau, Junya Ono, Shoichiro Ohta, Clair Barber, Scott Elliot, Tom Brown, Ramesh Kurukulaaratchy, Anoop Chauhan, Kenji Izuhara, Peter Howarth
Journal: European Respiratory Journal (2014)

Rationale: Serum periostin has been proposed as a biomarker of Th2 airway inflammation in asthma. We thus measured serum periostin in a large cohort of patients with severe asthma as well as in those with milder asthma and healthy controls, to gain insight into the value of this biomarker in asthma stratification.

Methods: Serum samples from 126 healthy controls (HC), 93 non-steroid treated mild asthmatics (MA), 35 asthmatics on low dose corticosteroids +/- LABA (ModA) and 276 severe treatment-resistant asthmatics (SA) were assayed for serum periostin by ELISA (Shino-Test Corporation, Kanagawa, Japan) and the results related to clinical and inflammatory markers. Results: Group median serum periostin levels were significantly (p<0.0001) lower in both the steroid treated asthma groups (ModA and SA) than the HC or MA groups, although there was greater spread in SA with 21% of values ± the normal range. Tertile analysis of the SA serum periostin identified that those in the upper tertile (≥79 ng/ml) had significantly higher sputum eosinophils (p=0.001), peripheral blood eosinophilia (p=0.002), FeNO (p=0,001) and total IgE (p=0.01) as well as lower FEV1 % predicted (p=0.02) than those in the lowest tertile (≤58ng/ml). Serum periostin measures did not appear related to age, BMI or atopic status.

Conclusion: Steroid treatment in asthma is associated with significantly lower serum periostin measures than in non-steroid treated asthma, although a sub-population of severe asthmatics have levels that associate with eosinophilic inflammation.

Funding: WSAC was funded by the Medical Research Council UK.
Myeloid cell-derived LRG attenuates adverse cardiac remodelling after myocardial infarction
Authors: Shohei Kumagai, Hiroyuki Nakayama, Minoru Fujimoto, Hiromi Honda, Satoshi Serada, Hatsue Ishibashi-Ueda, Atsushi Kasai, Masanori Obana, Yasushi Sakata, Yoshiki Sawa, Yasushi Fujio, Tetsuji Naka
Journal: Cardiovascular Research (2015)

AimsLeucine-rich α2-glycoprotein (LRG) is considered as a biomarker of the clinical activities of chronic inflammatory diseases, including heart failure. However, its pathophysiological roles in cardiac remodelling after myocardial infarction (MI) remain to be clarified. In this study, we have addressed functional roles of LRG in cardiac remodelling after MI.
A phase II trial of sorafenib in patients with relapsing and resistant multiple myeloma (MM) previously treated with bortezomib (S0434)
Authors: G. Srkalovic, M. Hussein, V. Bolejack, A. Hoering, J. Zonder, B. Barlogie
Journal: Journal of Clinical Oncology (2009)

e19517 Background: The multikinase inhibitor sorafenib targets several serine/threonine and receptor tyrosine kinases by blocking RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway regulated by the Ras oncogene, which is mutated both in primary patient samples and in human MM lines (35–50%). As the frequency of these mutations increases with advancing disease and increasing drug resistance, inhibition of the RAF/MEK/ERK signaling pathway, as well the angiogenic VEGFR-2/PDGFR beta cascade by sorafenib may be a useful new approach for the treatment of MM. Methods: SWOG evaluated the effect of sorafenib as a single agent in relapsed/refractory MM patients. In this phase II study we assessed response rate, overall (OS) and progression-free survival (PFS) as well as toxicities associated with this treatment. Twenty-three heavily pretreated MM patients were enrolled in the study. Sorafenib was started at oral dose of 400 mg daily until progression or toxicity. This dose was based on the label for metastatic renal cell carcinoma. Results: The study was closed as planned due to lack of efficacy in first 18 patients who were assessable for toxicity and response. Three patients experienced Grade 4 toxicity consisting of thrombocytopenia, anemia and renal failure. 8 cases suffered Grade 3 toxicities including thrombocytopenia, neutropenia, anemia, hand-foot syndrome, diarrhea and dyspnea. No responses were observed. 3 patients had stable disease (2.4–15.9 months) and the remainder progressed. Median PFS is one month, and OS at 12 months is 50%. Conclusions: Thus, single agent sorafenib did not show activity in this group of heavily pretreated MM patients previously exposed to bortezomib. As the frequency of RAS oncogene mutations increases resulting in resistance to traditional chemotherapeutic agents as well as possibly supporting cytokine resistance to immune modulators, sorafenib might have a supportive role in combination therapy with bortezomib, lenalidomide or everolimus in relapsed/refractory MM which is currently being evaluated in ongoing studies. No significant financial relationships to disclose.
Targeted Cancer Screening After Solid-Organ Transplantation
Authors: Marianne Schmid, Felix K.-H. Chun, Quoc-Dien Trinh
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
EGFR and C-Kit immunostaining in advanced or recurrent thymic epithelial neoplasms staged according to the WHO: An Eastern Cooperative Oncology Group Study
Authors: S. C. Aisner, M. R. Hameed, W. Wang, J. H. Schiller, D. H. Johnson, D. S. Ettinger, P. J. Loehrer
Journal: Journal of Clinical Oncology (2004)

9637 Background: Advanced or recurrent non-resectable thymic epithelial tumors have shown modest responses to standard chemotherapy. Recent studies have demonstrated activity with octreotide and prednisone. The aim of this study was to identify new biological markers with potential chemotherapeutic advantage. Two markers, EGFR and c-kit, were selected for evaluation in patients with advanced thymic epithelial tumors. Methods: 34 cases of thymic tumors (WHO 1 A, 1 AB, 10 B1, 11 B2, 8 B3, 3C) had available tissue for immunhistologic study. All pts had been entered on an ECOG phase II trial evaluating octreotide with or without prednisone. Each tumor was assessed as to having 0, 1+, 2+ or 3+ immunoreactivity. Results: Strong EGFR immunoreactivity (+2, +3) was associated with more aggressive thymic tumors (B2, B3). However strong EGFR immunoreactivity was not consistently seen with type C thymic neoplasms (thymic carcinoma). C-kit immunoreactivity was minimal and did not correlate with WHO tumor type. The response rate to octreotide +/− prednisone was significantly higher for the EGFR+ vs. EGFR- patients (10/26 vs. 1/8; p=0.044) with a positive trend for overall survival(p=0.064). Conclusions: EGFR demonstrated higher immunoreactivity in more aggressive thymic neoplasms as staged according to the WHO. EGFR may be a useful prognostic marker, but needs further confirmation. C-kit immunoreactivity appears to be minimal in thymoma. Anti-EGFR antibody treatment should be studied in patients with EFGR positive advanced thymic malignancies. No significant financial relationships to disclose.
Phase II study of vorinostat in patients with advanced melanoma.
Authors: N. B. Haas, E. McWhirter, D. Hogg, L. P. Martin, R. Polintan, S. Litwin, L. Wang, R. K. Alpaugh, J. A. Zwiebel, A. M. Oza
Journal: Journal of Clinical Oncology (2010)

8530 Background: Vorinostat inhibits class I and II histone deacetylases with angiogenic and apoptotic activity. We evaluated vorinostat 400 mg po daily in patients with advanced melanoma who had ≤ 1 prior therapies in a multi-institutional investigational setting. Methods: The 1° endpoint was objective response rate by RECIST, with time to progression as 2° endpoint. The study was designed to distinguish a RR of 20% from a RR of 5% (90% power and 7% Type I error). The study distinguished a 2 month median progression-free survival from one of 3.1 months with 80% power and 5% type I error. The study proceeded to the second stage of accrual without pausing following 1 of 16 responses. The treatment was of interest if the proportion of patients progression-free at 2 months was at least 30%. Results: 32 patients were registered by 3 institutions from Sep 2005-July 2008. Follow-up is available for 118 cycles of treatment given to 32 patients. 12 of 32 patients had 1 prior systemic therapy, 12 had no prior therapy and 10 patients had previous radiotherapy. Most common metastatic sites were lung, liver, and lymph nodes and most patients had a performance status of 0 or 1 (17/14). Therapy was moderately well tolerated. The most frequent adverse events experienced were fatigue (28 [88%] patients across 100 cycles), hyperglycemia (24 [75%] patients across 59 cycles, anemia 20 [63%] patients across 60 cycles, nausea (19 [59%] patients across 46 cycles), lymphopenia (15 [47%] patients across 47 cycles), and 19 [59%] patients across 39 cycles experienced at least 1 grade 3 or 4 adverse event. There were 1 PR, 18 SD and 13 PD observed for best response. In addition 2 patients scored as SD had early unconfirmed PRs with subsequent progression. The median PFS was 4 mo. (range 1-8)(95% CI: 1.8-4 mo.) and thus the secondary activity criteria was met. Furthermore, patients with stable disease or partial response (n = 12) had a median PFS of 5 mo. (range 2-12 mo.). Conclusions: These findings suggest that HDAC inhibition is a therapeutic strategy worth exploring further in melanoma. Correlative studies exploring the basis of activity of vorinostat are in progress. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck
Docetaxel-cisplatin-5FU (TCF) versus docetaxel-cisplatin (TC) versus epirubicin-cisplatin-5FU (ECF) as systemic treatment for advanced gastric carcinoma (AGC): A randomized phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)
Authors: A. D. Roth, R. Maibach, S. Falk, R. Stupp, P. Saletti, D. Kãberle, M. M. Borner, H.-P. Honegger, M. Leslie, N. Fazio
Journal: Journal of Clinical Oncology (2004)

4020 Background: ECF is currently considered by many as a standard regimen in AGC in Europe. Based on the high efficacy reported with TC and TCF in AGC (Ann. Oncol 11; 301, 2000, ASCO Proc. 18, 245a, 1999), we launched a randomized 3-arm phase II trial to assess which of TC or TCF would be the more promising regimen to compare to ECF in a future phase III trial. Methods: Patients (pts) with AGC, without prior palliative chemotherapy, with bidimentionally measurable disease, PS≤1, normal blood counts, hepatic and renal functions, were randomized to receive up to 8 cycles q3w of TC (docetaxel 85mg/m2, ciplatine 75mg/m2), TCF (like TC + 5-FU continuous infusion (CI) 300mg/m2/d for 2w) or ECF (epirubicin 50mg/m2, cisplatin 60mg/m2, 5-FU CI 200mg/m2/d for 3w). Results: Among 121pts enrolled, 119 were treated and included in the analysis. 5 pts are still on treatment (3 ECF and 2 TCF). Preliminary results are summarized below. A total of 554 treatment cycles are documented up to now. A median of 5, 4.5 and 4 cycles of ECF, TC and TCF were given, respectively. Hematotoxicity was the main toxicity in all 3 arms with grade ≥3 granulopenia in 73%, 76% and 58% of the pts for TC, TCF and ECF, respectively. Febrile neutropenia (FN) occurence in 10 of the first 21 pts enrolled in docetaxel based regimens led to decrease docetaxel from 85 to 75mg/m2 in TC and TCF, resulting in lesser FN occurence. Grade ≥3 non-hematologic toxicity was infrequent (<10% of pts) apart from alopecia (3 arms), nausea (18% in TC and TCF pts) and diarrhea (15% in TCF pts). Conclusions: Despite an increased toxicity, docetaxel based regimens seem to be more efficacious than ECF. In terms of RR and TTP, TCF is the more promising regimen and should be chosen for formal comparison with ECF. This trial is supported in part by Aventis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Coarctation of the Aorta with Report of Three Cases.
Authors: G F Strong
Journal: Annals of Internal Medicine (1932)

II 12 €0-?0 " 10 ?0-92 " 2 4 :E'rom this it is easily seen that the lesion threatet'le individuals in the prime of youth or early part of middle age.This ie the period of greatest economic and physical activity.Insofar ae sex is concerned, Evans (1933) and Abbott disagree.ETane states that this anomaly occurs with nearly equal frequency in males and females whereas Abbott found in a review of 195 cases there was a
Abstract #LB-15: Targeting androgen-induced androgen receptor (AR)-independent pro-survival signaling in prostate cancer
Authors: Sowmyalakshmi Srinivasan, Raj Kumar, Srinivas Koduru, Chendil Damodaran
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Androgen ablation therapy (AAT) is initially effective in inhibiting prostate tumor growth, but eventually relapses to hormone-refractory prostate cancer (PCa). The failure of AAT might be due to activation of alternative survival signaling regardless of AR status in PCa cells. Thus, the focus of our study is to delineate DHT-mediated prosurvival signaling pathways, identify and target these signaling by combining AR inhibitors with other pharmacological inhibitors , which might successfully inhibit PCa growth. Our results suggested that DHT caused a simultaneous activation of multiple survival signaling pathways namely Akt, mTOR, NF-\#954;B and AR (only in androgen-dependent) in AR-positive and -negative PCa cells. So, we used specific inhibitors LY294002 (Akt), PD098059 (ERK), [SCH51344][1] (Ras/Rac), Rapamycin (mTOR), \[6-Amino-4-(4-phenoxyphenylethylamino)quinazoline\] (NF-\#954;B) and casodex (AR), all of which failed to inhibit DHT-mediated cell proliferation and survival in PCa cells. So, we screened a panel of dietary compounds that are known to exhibit anti-cancer activity in PCa cells; our results suggested that psoralidin inhibits DHT-mediated pro-survival signaling (AR, Akt, mTOR, ERK, Ras/Raf and NF-\#954;B) thereby resulting in the inhibition of cell proliferation in PCa cells, indicating that psoralidin may have multiple targets within a cellular environment. Currently, we are combining AR inhibitors with other specific inhibitors to determine which combination is the most useful in inhibiting PCa growth. Also, our ongoing studies are focused on the effect of psoralidin on DHT-mediated prostate tumor growth in vivo models. The outcome of this study may enable development new therapeutic strategies to inhibit PCa growth.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-15.

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Descriptive study of patients with peritoneal carcinomatosis and colorectal cancer: An overall survival clinical prognostic score
Authors: A. Pisa, M. Calvo, X. Pérez, M. Martínez Villacampa, G. Soler, B. Laquente, C. Santos, E. Kreissler, R. Salazar, J. R. Germà Lluch
Journal: Journal of Clinical Oncology (2008)

15051 Background: Peritoneal carcinomatosis (PC) is a poor prognostic complication for colorrectal cancer (CRC). Peritoneal surgery and intraperitoneal chemotherapy achieve 12–34 months OS in phase II-III trials. The most important criteria for patient selection are laparoscopic findings. The aim of this study is to determine clinical prognostic factors for risk stratification in the selection of candidates for such complex treatments. Methods: A prospective series of sequential patients with CRC from 1995 to 2005 was analyzed. Cases who developed PC were selected excluding appendix primaries. The objectives of the study were to analyze OS and to define a prognostic score. Data analyzed were age, gender, PS score, intestinal occlusion, primary tumour location, metastasic location, type of surgery, chemotherapy, pathologic data and CT image. Results: Two hundred and twenty-six out of 2,717 patients (8,3%) diagnosed of CRC developed PC. Median age was 65 (23–96) and 53% were male. PC as the only metastasic location and PC and liver only locations occurred in 37% and 35% of cases, respectively. Fifty-three percent received palliative chemotherapy, 40 (18%) patients underwent palliative peritoneal surgery and 142 (62%) had their primaries removed. None received complex treatments. Median OS was 10.6 months (7.6–13.6). Statistically significant prognostic factors in the multivariate analysis were: PS, CT image, nuclear grade and liver M1. A clinical prognostic score (CPS) was generated with the following equation: CPS=4.75×PS + 1.76×CT + 1.78×Liver M1 + 1.93×Grade, which defines 3 groups with statistically significant differences in OS (p<0.001) (table 1). Conclusions: PS<2, no CT image, no liver M1 and nuclear grade<3 are independent clinical factors which predict a longer OS in patients with CRC and PC. CPS must be validated in independent series, which would help stratification of patients in the design of clinical trials of complex treatment modalities. Median OS (months) HR CPS < 2 23.2 (18.6 - 27.8) 1 CPS 2 - 5 14.5 (6.7 - 22.3) 1.7 (0.9–3.3) CPS > 5 3.2 (1.3 - 5.0) 8.3 (3.9- 17.3) No significant financial relationships to disclose.
Pharmacogenetic prediction for tumor response, toxicity, and survival of NSCLC patients treated with irinotecan and cisplatin chemotherapy
Authors: J. Han, S. Lee, D. Lee, H. Kim, J. Lee
Journal: Journal of Clinical Oncology (2007)

3581 Background: Inherited genetic polymorphisms of the genes involved in the activation and metabolism of irinotecan can affect toxicity and clinical outcome of patients after treatment with irinotecan. We examined 14 polymorphisms within six genes putative influence on irinotecan metabolism to define a pharmacogenetic model for predicting tumor response, toxicity, and survival in NSCLC patients treated with irinotecan/cisplatin chemotherapy. Methods: Blood samples from 81 NSCLC patients treated with irinotecan (80 mg/m 2 D1 &amp; D8) and cisplatin (60 mg/m 2 D1) chemotherapy were used for genotyping UGT1A1 211G&gt;A (*6), UGT1A1*28, UGT1A9 -118(T) 9&gt;10 (*22), ABCB1 1236C&gt;T, 2677G&gt;T/A, 3435C&gt;T, ABCC2 -24C&gt;T, 1249G&gt;A, 3972C&gt;T, ABCG2 34G&gt;A, 421C&gt;A, and SLCO1B1 -11187G&gt;A, 388A&gt;G, and 521T&gt;C polymorphisms. Genotypes were correlated with tumor response, toxicity, and survival by multivariate logistic or Cox regression analysis with adjustment for clinical and histopathologic features. Results: The overall response rate was 47% (36/77), the median progression-free survival was 5.1 months, and the median overall survival (OS) was 14.3 months. The most common severe toxicity was NCI-CTC grade 4 neutropenia, which occurred in 22 (27%) patients. Grade 3 diarrhea was developed in 8 (10%) patients. The presence of ABCC2 3972T allele was predictive for tumor response (odds ratio=3.244, 95% CI 1.219–8.629, p=0.018). The UGT1A1 211AA (*6/*6) genotype was a significant risk factor for grade 4 neutropenia (odds ratio=6.111, 95% CI 1.032–36.197, p=0.046). The UGT1A9*22 allele showed a trend for less grade 3 diarrhea (odds ratio=0.205, 95% CI 1.032–36.197, p=0.054). In multivariate Cox regression analysis, the UGT1A1*6/*6, UGT1A9*22/*22, and squamous cell histology were predictive for worse PFS (p=0.015, 0.049, and 0.026, respectively). Whereas, ABCC2 1249A allele, ECOG PS 2, male gender, and stage IV were predictive for worse OS (p=0.017, 0.014, 0.045, and 0.015, respectively). Conclusions: Patients’ selection based on pretreatment genotyping can minimize irinotecan-related severe toxicity and maximize the clinical benefit of irinotecan-based chemotherapy for patients with advanced NSCLC. No significant financial relationships to disclose.
Abdominal Obesity is an Independent Risk Factor for Sudden Cardiac Death in Non-Smoking Individuals: The Atherosclerosis Risk in Communities Study
Authors: Selcuk Adabag, Faye L Lopez, Alvaro Alonso, Rachel Huxley, Lin Y Chen, Suma Konety, Aaron R Folsom
Journal: Circulation (2013)

Background: Obesity has adverse hemodynamic and electrical consequences on the heart, including left ventricular hypertrophy (LVH), left ventricular dilatation and QT prolongation. We examined whet...
Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy.
Authors: A Santoro, G Bonadonna, P Valagussa, R Zucali, S Viviani, F Villani, A M Pagnoni, V Bonfante, R Musumeci, F Crippa
Journal: Journal of Clinical Oncology (1987)

In an attempt to reduce some of the delayed sequelae associated with combined modality therapy in Hodgkin's disease, we randomly tested stages IIB, IIIA, and IIIB MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) v ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). In 232 previously untreated patients, three cycles of either combination preceded and followed extensive irradiation. The complete remission rate was 80.7% following MOPP and 92.4% following ABVD (P less than .02). The 7-year results indicated that ABVD was superior to MOPP in terms of freedom from progression (80.8% v 62.8%; P less than .002), relapse-free survival (87.7% v 77.2%; P = .06), and overall survival (77.4% v 67.9%; P = .03). Moreover, the comparative iatrogenic morbidity showed that irreversible gonadal dysfunction as well as acute leukemia occurred only in patients subjected to MOPP, while cardiopulmonary studies failed to document significant laboratory differences between the two treatment groups. Present findings indicate that ABVD followed by extensive irradiation represents a valid therapeutic alternative to the widely used alkylating agent-containing regimens plus radiotherapy.
Diastolic relaxation of the heart (2nd ed.): Edited by W. Grossman, B.H. Lorell. 368 pp., 38.00 (hardback). Dordrecht: Kluwer Academic Publishers, 1994. ISBN 0-7923-2611-3
Authors: A. Bril
Journal: Cardiovascular Research (1995)

Diastolic relaxation of the heart (2nd ed.): Edited by W. Grossman, B.H. Lorell. 368 pp., £38.00 (hardback). Dordrecht: Kluwer Academic Publishers, 1994. ISBN 0-7923-2611-3 Get access Antoine Bril Antoine Bril Saint Grégoire, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 2, August 1995, Page 312, https://doi.org/10.1016/S0008-6363(95)90131-0 Published: 01 August 1995