tbuckley/cabot-search huggingface dataset:
Abstract 15428: Qsox1 Has a Protective Role in the Myocardium Face to Acute Stress
Authors: Anaïs Caillard, Arthur Cescau, Malha Sadoune, Medhi Meddour, Zhenlin Li, Nicolas Vodovar, Alexandre Mebazaa, Jane-Lise Samuel
Journal: Circulation (2014)

Introduction: QSOX1 was identified as a plasma biomarker of acute heart failure (AHF). As QSOX1 is a sulfhydryl oxidase, we hypothesized that QSOX1 has a protective role in the heart face during AHF. Methods: AHF was provoked by IP injections of Isoproterenol (ISO, 300 mg/kg/12h) for 2 days in mice (Balb-C or C57Bl/6 J) whereas control (C) received NaCl 9‰. Mice were killed at day 3, after echocardiography. Some Balb-C mice received together with ISO antisens oligonucleotides (AOs) directed against QSOX1. In parallel QSOX1 KO (C57Bl/6 J) mice were generated using a QSOX1tm1a embryonic stem cell clone (KOMP). The KO construct contains a promoter-less lacZ gene under the control of the QSOX1 regulatory sequences. The mRNA levels were analyzed by RT-qPCR. Results: The ISO Balb-C mice exhibited a decreased shortening fraction (C = 35.0 ± 0.4 %; ISO = 27.2 ± 3.3 %; p<0.001, n=10/group) and increased lung weight/body weight (C=5.2 ± 0.1 mg/g vs. ISO = 6.1±0.2 mg/g, p<0.001). Cardiac QSOX1 (x2, p<0.01) and BNP (...
Adjuvant imatinib therapy of 208 gastrointestinal stromal tumor (GIST) patients: Dose, duration, and risk assessment.
Authors: J. C. Trent, M. von Mehren, P. W. Pisters, E. Stealey, L. A. Sirulnik, C. D. Blanke
Journal: Journal of Clinical Oncology (2010)

10061 Background: Imatinib (IM) is approved for adjuvant (ADJ) treatment (tx) of adult patients (pts) following complete, gross resection of GIST. In the IM registrational study, IM 400 mg was administered for one year. However, patient characteristics, tumor characteristics, dose, and duration of therapy are not known outside the context of a clinical trial. Methods: We used a data collection tool designed to provide insights into practice patterns surrounding the diagnosis and management of GIST pts (reGISTry) to explore nonclinical trial ADJ dosing in community and academic practices. Results: Since 11/04, 1,053 pts have entered the reGISTry. ADJ IM tx were reported as early as 2001 (n=1) with steady increases in 2007 (n=64) and 2008 (n=43). Most pts (56%) received ADJ therapy for over one year. Pts treated in the community seemed to receive a longer duration of therapy than those at academic centers (424d [2-1,970] vs. 348d [16-1,762]), but not statistically significant (p=0.21). Pts with small intestine primaries appeared to have a slightly longer duration of ADJ tx (433[3-1525] vs 378[2-1970] p=0.43), but no correlation with tumor size or mitotic count. Most pts (87%, 181/208) received IM 400 mg/d as the initial dose. 17.3% of ADJ IM dose changes were due to disease progression. Mitotic count was only reported in 33.6% of pts receiving ADJ tx. Conclusions: We found that most pts with primary GIST receive IM therapy at a dose of 400mg daily for more than one year. Duration of therapy did not appear to closely correlate with tumor size, site, or mitotic rate. Most pts receiving ADJ tx were treated without a known mitotic rate. Adjuvant imatinib in the tx of most pts with GIST does not appear to be based on standard, published, risk factors. Variable Adjuvant therapy N (%) Total = 208 No adjuvant therapy N (%) 1°localized GIST Tumor size >10 cm 73 (35.0) 162/658 (24.6) 2-5 cm 48 (23.0) 201/658 (30.5) Tumor location Stomach 109 (52.4) 397/660* (60.1) Small intestine 64 (30.8) 166/660* (25.1) Mitotic count >10/HPF 37 (17.8) 240/658 (11.9) 6-10/HPF 32 (15.4) 47/658 (7.1) * 2 pts did not have mitotic count or tumor size data available. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
PPAR<i>r</i> agonist, troglitazone induce growth arrest and apoptosis in MDA-MB-231 human breast cancer cell
Authors: J. Park, Y. Lee, H. Yu, M. Han, B. Kim, J. Kim
Journal: Journal of Clinical Oncology (2006)

13155 Background: Estrogen receptor (ER)-negative breast carcinomas do not respond to hormone therapy, making their effective treatment very difficult. It is recently reported that peroxisome proliferator-activated receptor-gamma (PPAR-γ) has become a potential target for the prevention and treatment of human cancer. Therefore, PPAR-γ agonist, troglitazone has been extensively studied as a chemopreventive or therapeutic agent in several types of cancer. The purpose of this study was to assess whether troglitazone (TRO) would induce cell growth arrest and apoptosis in MDA-MB-231 (ER-negative) human breast cancer cells. Methods: Cytostatic/cytotoxic effects of troglitazone were measured with MTT assay. The cell cycle distribution was evaluated with flow cytometer. The expression of cyclin-dependent kinase inhibitors, p21, p27, and cell cycle dependent kinases was measured with Western blotting. Apoptotic cells were determined by Hoechst staining and TUNEL assay. Results: Troglitazone inhibited cell proliferation by inducing 65% G0/G1 arrest after 48 h. Accumulation of cells in G0/G1 was accompanied by a decrease of Rb protein phosphorylation associated with reduced activities of cell cycle dependent kinases (CDKs) such as cdk2 and cyclin D. Troglitazone increased the expression cyclin kinase inhibitors, p21 and p27 as MDA-MB-231 cell underwent G0/G1 arrest. Apoptotic effect by troglitazone demonstrated that apoptotic cells elevated from 2.5-fold of the control level at 10 uM, to 3.6-fold at 50 uM and to 4.7-fold at 75 uM. Conclusion: These results indicate that activation of PPAR-gamma with troglitazone induces apoptosis through cell cycle inhibition in estrogen receptor-negative breast cancer cell MDA-MB-231. PPAR-gamma therefore represents a putative molecular target for chemopreventive therapy or inhibition of breast cancer growth. No significant financial relationships to disclose.
Long-term outcome after breast conservation (BCT) for early stage breast cancer in a community setting
Authors: S. McCloskey, L. Botnick, C. Rose, A. Malcolm, M. L. Ozohan, R. Mena, M. L. Tao
Journal: Journal of Clinical Oncology (2004)

784 Background: Randomized studies and academic centers have demonstrated favorable outcomes after BCT for early stage breast cancer. There are few modern reports of BCT in community settings, validating its generalizability. We, as a large community practice, retrospectively reviewed our experience in treating early-stage breast cancer with BCT to determine outcomes and clinical, pathologic, and treatment risk factors. Methods: Tumor registry was used to identify breast cancer cases diagnosed between 1/1/87 and 12/31/94 and treated at Providence St Joseph's Hospital, a 455-bed, non-profit hospital in southern California, and 1 free-standing affiliate. Of the 1746 breast cancer cases, 744 were pathologic T1–2, N0 and had ≥ 8 years of potential follow up. Of these, 521 (70%) received BCT and are the topic of this review. We calculated crude rates of first failure at 8 years, classified as local failure (LF), distant or regional node failure (DNF), dead without failure (DWF), or alive without failure (AWF). Polychotomous logistic regression was done to simultaneously assess influence of age at diagnosis, tumor grade, T stage, total radiation (RT) dose to the tumor bed, and use of systemic therapy on the 4-value outcomes. Data were insufficient to assess surgical margin on all 4 outcomes. Results: Patient were characterized as follows: median age = 58 years, 15% had grade 1 tumors, 83% were T1, 4.6% had positive margins, 83% got RT dose ≥ 60 Gy to tumor bed, and 51% had systemic therapy. At 8 years, 7% of patients had LF, 8% DNF, 10% were DWF, and 75% were AWF. Of the co-variates examined, patient age < 40 years had a borderline significant effect on the risk of LF vs. AWF, (OR=3.58, p=0.076) as did tumor grade (well vs other, OR=0.135, p=0.06) and use of systemic therapy (OR=0.43, p=0.076). The effect of RT dose was as expected (OR=0.45 for dose > 60 Gy, p=0.127). Conclusions: Majority of patients in this community were treated with BCT. Almost all had negative margins and received ≥ 60 Gy RT dose to tumor bed. Local control was excellent and comparable to that seen in large academic centers. Younger age, higher grade and lack of systemic therapy were associated with greater risk of LF. No significant financial relationships to disclose.
Abstract P331: Ethnic Differences in Glycoslation Indices in Non-Diabetic Adults: The Diabetes, Heart and Health Survey
Authors: Patricia A Metcalf, Gerhard Sundborn, Rod T Jackson
Journal: Circulation (2015)

Objective: We examined whether there were ethnic differences in glycosylated haemoglobin concentrations, the glycation gap and haemoglobin glycation index in non-diabetic adults. Research design and methods: We studied 3,318 non-diabetic adults aged 35 to 74 years. Glycoslylated haemoglobin (HbA1c) levels were compared in 1,589 Europeans, 825 Maori, 689 Pacific and 226 Asians. The glycation gap was calculated using the residuals from the regression of HbA1c on mean fasting and 2 hour glucose levels and the haemoglobin glycation index using the residuals from the regression of HbA1c on fructosamine. Results: Mean ± SD HbA1c was 38.0 ± 4.57 mmol/mol. After adjusting for age and gender, mean (se) HbA1c was higher in Maori (38.6 mmol/mol (0.14)), Pacific (40.8 (0.16)) and Asians (37.9 (0.27)) compared with Europeans (36.5 (0.10)) (all P &amp;lt 0.0001 vs. Europeans). In contrast, there was little difference in fructosamine levels between ethnic groups with 231.5 (0.63) μmol/L in Europeans, 230.7 (0.44) in Maori, 237.8 (1.16) in Asians (both P &amp;gt 0.05 versus Europeans), and 232.7 (0.16) in Pacific (P &amp;lt 0.05). After adjusting for age, sex, education, body mass index (BMI), systolic and diastolic blood pressure, fasting and post-glucose load glucose levels, cholesterol, triglycerides, HDL-cholesterol, physical exercise levels, total calorie intake and socioeconomic status, HbA1c levels were 37.0 (0.10) mmol/mol in Europeans, and remained higher in Maori (38.4 (0.13)), Pacific (40.0 (0.15)) and Asians (38.1 (0.25)) (all P &amp;lt 0.001) compared to Europeans. The mean (se) age and gender adjusted glycation gap (based on fructosamine) was -1.50 (0.10) mmol/mol for Europeans, 0.66 (0.14) mmol/mol for Maori, 2.77 (0.16) mmol/mol for Pacific (Both (P &amp;lt 0.0001 vs. Europeans), and -0.37 (0.27) mmol/mol in Asians (P =0.001 vs. Europeans. Similarly, the mean haemoglobin glycation index (based on mean glucose) was -1.34 (0.10) in Europeans, 0.41 (0.13) in Maori, 2.63 (0.15) in Pacific (both P &amp;lt 0.0001 versus Europeans) and -0.45 (0.25) in Asians (P = 0.001 vs. Europeans). Conclusion: There were differences in HbA1c, the glycation gap and the haemoglobin glycation index between Europeans and Maori, Pacific and Asian non-diabetic adults, but there was little difference between ethnic groups for fructosamine. These differences could be due to heritable factors that may vary between the ethnic groups or may be related to high or low glycators.
Research team to look at effect of major reorganisation of cancer surgery
Authors: Jacqui Wise
Journal: BMJ (2015)

Researchers are to evaluate the effect of having fewer hospitals delivering specialist cancer surgery services. Centralisation of such services has just started this month in London and will start in Manchester in December.

The study will be conducted by the same team that evaluated stroke services in London and Manchester. The results of that study, published in The BMJ in 2014,1 convinced Manchester to move to the centralised model used in London.

The new study will look at …
Full report of the TROG 03.01, NCIC CTG ES2 multinational phase III study in advanced esophageal cancer comparing palliation of dysphagia and quality of life in patients treated with radiotherapy or chemoradiotherapy.
Authors: Michael Gordon Penniment
Journal: Journal of Clinical Oncology (2015)

6 Background: RT relieves dysphagia of advanced oesophageal cancer, without data from randomised phase III trials determining response, toxicity, or role of palliative CRT. Aims (1) to establish effective and least toxic treatment for symptom relief (2) determine effects of common cancer treatments on QoL (3) establish an evidence base for patient decision making. Methods: 220 patients were randomised to receive a course of palliative RT [35 Gy in 15 fractions, (n=115) or 30 Gy in 10 fractions (n=105) in Canada and UK], or concomitant CRT with Cisplatin and 5FU (D1-4) (n=111). Dysphagia measured using the Mellow score, toxicity using CTCAE v2, and QoL using EORTC QLQ30, oesophagus module (OES-18). The primary end point was proportion of patients with improved dysphagia measured at week 9 maintained until week 13. Results: Radiotherapy alone showed a dysphagia response (at any point) of 68% compared to CMT 74%, not a significant difference (p=0.343). the primary endpoint of maintained swallowing improvement was achieved in 41% with RT, 47% CMT again not statistically significant(p=0.4163).There was increased toxicity in patients receiving CRT, (nausea (p=0.0019) and vomiting (p=0.0072)). Median survival was 210 days for CRT, 203 days for RT. Although the results of the trial showed equally poor survival prognosis in both arms, there were some patients (n=21) still alive at 2 years post treatment.Quality of life analysis showed no statistical difference between arms. 17 patients in the RT alone arm ultimately received chemotherapy for specific palliative endpoints, thus 92 patients did not require chemotherapy. Conclusions: Although the CRT group had slightly better dysphagia response and median survival, the bowel toxicity was worse. Nearly 10% of patients were alive at 2 years indicating this is a group of patients who should not be denied active cancer treatment, but it should be tailored to offer maximum symptom relief minimising treatment toxicity. This multicentre trial, conducted in the UK, Canada, Australia, and New Zealand reflects practice in several countries. Clinical trial information: ACTRN12606000526572.
Success and consequences of the German quality assurance system for the molecular-pathological detection of KRAS mutations in the treatment of metastatic colorectal cancer.
Authors: A. Jung, G. B. Baretton, M. Dietl, H. E. Gabbert, M. Kloor, H. Kreipe, W. Schlake, A. Tannapfel, T. Kirchner
Journal: Journal of Clinical Oncology (2010)

e14016 Background: One option in the therapy of metastatic colorectal cancer (mCRC) is the targeting of the epidermal growth factor receptor (EGFR) using the antibodies panitumumab or cetuximab. Here, a biomarker, the KRAS gene, allows the prediction of the response on an individual basis as mutated forms of KRAS lead to a deregulation of the EGFR- signaling pathway by which the antibodies become useless. Therefore, the approval of the European Medicines Agency (EMEA) as well as a recommendation by the Food and Drug Administration (FDA) included that anti-EGFR targeted therapy is only valid in case of mCRCs with wildtypic (WT) KRAS sequences. Thus, the correct determination of the sequence of the KRAS oncogene became an important piece of work in the targeted therapy of mCRCs. Methods: Therefore, the German Society for Pathology (DGP) and the Federation of the German Pathologists (BDP) initiated under the umbrella of the Quality Initiative in Pathology (QuIP) a quality assurance (QA) system based on the testing of histological sections of 10 cases of mCRC. Two parameters were defined for passing the QA test: 1) Correctness or quality of the results independent of the applied testing method (table). 2) Time to completion (14 days). Results: 159 institutions for pathology participated in this QA system in the last two years resulting in a network of now 82 institutions in Germany that analyze the mutational status of the KRAS gene fast and with a high grade of quality. This was interestingly independent of the applied method (table-some institutes participated repeatedly). Conclusions: The results and consequences of the German QA system are presented here. Method No. of participants Sensitivity(true positives) Specificity(true negatives) ARMS-PCR 24 0.99 1.00 DHPLC 0 0.99 1.00 Didesoxy-sequencing 75 0.93 0.99 Hybridization 11 0.93 0.99 Melting point analysis 7 1.00 1.00 Other 7 0.97 1.00 Pyrosequencing 21 0.99 1.00 Restriction-fragment-length-polymorphism 3 0.93 0.93 Snapshot 1 1.00 1.00 Single strand conformational polymorphism 2 1.00 1.00 All 151 0.96 0.99 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Merck Serono Amgen, Merck Serono
Cigarette smoking as a strong prognostic factor after first-line chemotherapy in advanced non-small cell lung cancer.
Authors: L. de Lima Araujo, A. C. Melo, I. Á. Small, C. G. Ferreira
Journal: Journal of Clinical Oncology (2010)

e18099 Background: Sex, disease stage, weight loss, and performance status (PS) are well-established clinical prognostic factors after palliative chemotherapy (CT) in non-small cell lung cancer (NSCLC). In contrast, the correlation between smoking status and benefit to chemotherapy is not routinely reported in clinical trials. Methods: We retrospectively reviewed the medical charts of patients treated with first-line CT between 2000 and 2004 at the Brazilian National Cancer Institute. The primary outcome was overall survival (OS) and prognostic factors were analyzed using Cox model. Results: One hundred seventy patients were treated with carboplatin-etoposide combination during the period. Median age was 60 years (22-85), 73% were male, 56.7% had adenocarcinoma, and 81.5% were diagnosed in stage IV disease. Forty-five percent of patients had more than 5% weigh loss documented at the diagnosis, and most patients had PS 0-1 (83.3%). The median number of cycles was 4 (1-8) and only twenty patients received second-line CT (11.5%). Smoking status data was available for 157 patients, being 83.4% ever-smokers and 16.6% never-smokers. The median OS was 7.1 months (95% CI; 6.5-7.6). Smoking status was strongly correlated with OS among PS 0-1 patients (median 7.2 vs 12.4 months for smokers and non-smokers, respectively; p = 0.016), but not in PS 2 (3.7 vs 1.6 months, respectively; p = 0.19). In the multivariate analysis, smoking status (p = 0.019), PS (p < 0.0001), and weigh loss (p = 0.024) were independent prognostic factors. However, the OS was not worst for patients with ≥ 15 pack-years cigarette smoking history when compared to those with < 15 (p = 0.202). Disease stage (p = 0.73) and sex (p = 0.41) did not predict OS. Conclusions: Past smoking history strongly predicted worst outcome after palliative CT in this cohort. This is a unique population, since all the patients received the same CT combination, and nearly 90% was exclusively treated with first-line schema. Since crossover was not an issue, OS is a very reliable outcome. The 7.1-month OS is inferior to the currently described outcomes in the literature, which is probably related to the absence of second-line CT, as well as the use of a second- generation doublet. No significant financial relationships to disclose.
Focal Takotsubo Cardiomyopathy With High-Dose Interleukin-2 Therapy for Malignant Melanoma
Authors: Senthil Damodaran, Ewa Mrozek, David Liebner, Kari Kendra
Journal: Journal of the National Comprehensive Cancer Network (2014)

High-dose interleukin-2 (IL-2) is an available treatment option for patients with metastatic melanoma or renal cell carcinoma, and is associated with sustained complete and partial responses in a subset of patients. IL-2, however, is not devoid of toxicities, most of which involve the cardiovascular system and manifest as hypotension, arrhythmias, and cardiomyopathy. This report describes an unusual presentation of takotsubo cardiomyopathy in a postmenopausal woman receiving high-dose IL-2 for metastatic melanoma.
Abstract P255: Genetic Variation in Chromosome 8p23 is Associated With Sedentary Behavior in Humans
Authors: Tuomo Rankinen, Mark A Sarzynski, Barbara Sternfeld, Steve Sidney, Claude Bouchard
Journal: Circulation (2014)

Sedentary behavior, usually quantified as sitting time, has been shown to be associated with several adverse health outcomes, even among individuals who meet the current recommendations for physical activity. Both twin and family studies have shown that sedentary behavior aggregates in families and is a heritable trait. However, little is known about genes and DNA sequence variants that contribute to propensity to be sedentary. The purpose of our study was to conduct a genome-wide association study to identify genomic regions and DNA sequence variants associated with sedentary time. A total of 67,530 Caucasians (56% female, mean age 62.1 years [SD 12.5]) from the Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) cohort were used for the discovery analyses. Other RPGEH ethnicities (African-Americans: N=2,500; East Asians: N=6,300; Hispanics: N=8,800) were used for replication studies. Information on daily sitting time outside of work was obtained by a questionnaire. A custom panel of 657,184 autosomal single nucleotide polymorphisms (SNPs) was genotyped using Affymetrix platform. Associations between sedentary time (dichotomized; cases 3 hours or more, controls less than 3 hours per day) and the SNPs were tested with PLINK logistic model using age, sex, BMI and admixture principal components as covariates. The strongest evidence of association was detected on chromosome 8p23.1. A total of 24 SNPs within a 1.34 Mb region were associated with sedentary time at genome-wide significance level (p&lt;5x10 -8 ), with SNP rs11774552 showing the peak association (OR=0.924, p= 1.7x10 -12 ). Sex-specific analyses confirmed that the associations were present both in men and women. The same SNPs were not associated with sedentary time in other ethnicities. However, SNP rs28754712, which is located in the immediate vicinity (+456 bp) of rs11774552, showed a significant association with sedentary time (OR=0.795, p=1.2x10 -3 ) in African-Americans. In summary, our results provide the first evidence of genomic region and DNA sequence variants associated with sedentary behavior in humans. If confirmed in additional replication studies, these findings will advance our understanding of biological mechanisms contributing to propensity to be sedentary.