tbuckley/cabot-search huggingface dataset:
Abstract 11733: Hepatocyte Growth Factor Resistance May Precede Development of Insulin Resistance in Humans: Prospective Study in a General Population
Authors: Eri Tsukagawa, Hisashi Adachi, Yuji Hirai, Mika Enomoto, Ako Fukami, Maki Otsuka, Kuniko Yoshikawa, Eishi Esaki, Kinuka Ogata, Akiko Kasahara, Kanako Yokoi, Kyouko Ohbu, Ayako Yoshimura, Aya Ohbuchi, Tsutomu Imaizumi
Journal: Circulation (2012)
Gender difference as a prognostic factor in patients with non-small cell lung cancer
Authors: H. Kim, J. Uhm, H. Ahn, J. Yi, J. Han, Y. Choi, K. Kim, H. Kim, J. Ahn, M. Ahn, K. Park
Journal: Journal of Clinical Oncology (2008)

22155 Background: Lung cancer has become the leading cause of cancer death among women since 1988. Globally there are differences in the biology, natural history, and response to therapy between men and women with lung cancer. Females appear to have a superior response to treatment and female gender is considered as a favorable prognostic factor for non-small cell lung cancer (NSCLC) in surgical series of stage I and IIB patients. This study was conducted to investigate whether gender is a prognostic factor. Methods: 1,728 consecutive cases of the patients, who were newly diagnosed with NSCLC between 1998 and 2003, were identified from the database at the Samsung Medical Center. Among them, 1,442 patients followed up at least 3 months were reviewed retrospectively. Small cell lung cancer, carcinoid tumors and sarcomas were excluded. The stage was reviewed according to AJCC TNM staging 6th edition and the revised TNM stage by IASLC lung cancer staging projects. Results: There were 1075 men (74.5%) and 367 women (25.5%), with a median age at diagnosis of 62 years in men and 60 in women (p=0.008). There was no significant difference on the history of smoke. 255 (69.5%) of 367 female patients were diagnosed histologically adenocarcinoma. However, 468 (43.5%) and 368 (34.2%) of 1075 male patients were confirmed as squamous cell carcinoma and adenocarcinoma. The median overall survival (OS) was 16.0 months (95% CI, 14.5∼17.5). Female showed longer survival than male (median OS 20.0 months vs. 15.0 months, p=0.001). This trend kept on each staging group according to TNM 6th edition and the revised staging system by IASLC. Notably, male with T1aN0M0 by revised TNM stage by IASLC showed shorter survival than female (5-year survival rate (5-Yr SR) 79.6% vs. 94.7%, p=0.037). In multivariate analyses, gender, stage and age revealed as an independent prognostic factor associated with survival. Conclusion: These results demonstrated that female gender may be considered as an independent favorable prognostic factor for non-small cell lung cancer. No significant financial relationships to disclose.
Polymorphisms in UGT1A gene family and irinotecan toxicity in patients with advanced colorectal cancer
Authors: S. Chiara, S. Lastraioli, P. Marroni, L. Gargiulo, F. Leonardi, A. Ponzanelli, E. Franzini, L. Boni, M. Paganuzzi, R. Notaro
Journal: Journal of Clinical Oncology (2006)

13049 Background: The irinotecan active metabolite, SN38, is inactivated through glucuronidation mainly by uridine diphosphate glucuronosyltransferase (UGT) 1A1. The (TA) 7 allele of a polymorphism in UGT1A1 promoter has been associated with reduced SN38-glucuronidation rate and more severe toxicity. Since other UGT1A family isoforms, the extrahepatic UGT1A7 and the hepatic UGT1A9, are involved in SN38 glucuronidation, it has been suggested that also polymorphic variants of these genes may affect irinotecan toxicity. Methods: 84 patients with advanced colorectal cancer received an irinotecan-based (180 mg/m 2 q.2wks) combination treatment. Polymorphisms of UGT1A1 [(TA) 6&gt;7 ], UGT1A7 [387T &gt; G, 391–2CG &gt; AA, 622T &gt; C] and UGT1A9 [-118(T) 9&gt;10 , -87G &gt; A, 98T &gt; C, I152G &gt; A] were identified by sequencing on DNA from blood samples obtained under an IRB approved protocol. Toxicity has been graded according to NCI-CT criteria. Results: Patient median age was 64 y (range: 31–82); median PS was 0 (range: 0–2). Severe toxicity (diarrhea or/and neutropenia ≥G3) has been observed in 32 patients: diarrhea in 11, neutropenia in 25 (4 patients had both). The estimated allele frequencies were as follows: UGT1A1, (TA) 7 (0.35); UGT1A7, 387T and the completely linked 391–2CG (0.39), 622C (0.39); UGT1A9, -118(T) 10 (0.39), -87A (0.05), T98C (0.02), I152A (0.21). Severe toxicity was significantly associated only with: (a) the UGT1A1 (TA) 7 allele [severe toxicity in 25% of (TA) 6/6, in 46% of (TA) 6/7, in 55% of (TA) 7/7 (Mantel-Haenszel trend test, P &lt; 0.03)]; and (b) the low activity UGT1A7 622C allele [severe toxicity in 26% of 622 T/T, in 39% of 622 T/C, in 67% of 622 C/C (Mantel-Haenszel, P &lt; 0.02)]. In addition, the analysis of the combined genotypes [(TA) 6&gt;7 and 622T &gt; C] has shown severe toxicity in 21% of patients with none of (TA) 7 and of 622C alleles, in 43% of patients in which the sum of the number of (TA) 7 and of 622C alleles is 1 or 2, in 57% of patients in which this sum is ≥3 (the latter includes all patients with both toxicities) (Mantel-Haenszel, P &lt; 0.02). Conclusions: These data show that both the low activity UGT1A1 (TA) 7 and UGT1A7 622C alleles are significantly associated with irinotecan severe toxicity. It is to evaluate if their combined genotype may be a better predictor of toxicity. No significant financial relationships to disclose.
Neoadjuvant treatment in the clinical practice of locally advanced non-small cell lung cancer (NSCLC)
Authors: C. Arcuri, O. Caffo, V. Vanoni, M. Silvestri, F. Valduga, S. Santarossa, E. Galligioni
Journal: Journal of Clinical Oncology (2004)

7345 Background: Surgery followed by radiotherapy (XRT) has obtained disappointing results in the treatment of IIIA(N2)-IIIB NSCLC, while the adoption of neoadjuvant chemotherapy (CT) appears, from clinical studies, able to improve the control of the disease and probably survival in these patients. The combination of cisplatin (C) plus gemcitabine (G), represents one of the most widely used treatment for advanced NSCLC and has been adopted in our institution for the neoadjuvant therapy of NSCLC. Methods: Patients with locally advanced NSCLC, received G 1000 mg/sqm on days 1,8 and C 100 mg/sqm on day 8 every 21 days, followed by a radiological evaluation and, in absence of progressive disease, by surgery and/or radiotherapy. When local treatment was not available in a short time, an additional CG course was planned. Results: From July 2000 to July 2003 we have treated a consecutive series of 26 pts: 16 IIIA(N2) / 10 IIIB –20 M / 6 F - median age 63 y, range 49–75 y. The CT major toxicities consisted of grade 3–4 neutropenia and grade 3 vomiting in 10 and 3 pts respectively. The objective responses consisted of 16 partial responses (61.5%), 3 stable diseases (11.5%), 6 progressions (23%). One patient died after one course of CT for myocardial infarction and was not evaluable. Among pts with no progressive disease after CT, 13 were treated with surgery (plus XRT in 4 cases) and 6 with radiotherapy. The histological specimen of resected pts showed a complete remission in 4 cases, a down staging to stage I-II in 6 and a stage III in 3. After a median follow-up of 7 months (range 1–30 mos), 18 pts are alive and 8 are died; two pts died due to postoperative complications. Out of the 4 pts obtaining a pCR, 2 are alive (7 and 27 mos after surgery) and 2 died in the postoperative period due to complications. Conclusions: Our data, obtained in the context of the clinical practice, appear to confirm the positive impact of the neoadjuvant CT reported in the literature, in terms of both RR (61.5%) and tumour downstaging . A longer follow up however is needed to evaluate any influence on survival. No significant financial relationships to disclose.
Management of bone loss in breast cancer patients: 24-month results from the ARBI trial of anastrozole with risedronate
Authors: C. Markopoulos, E. Tzorakoleftherakis, A. Polychronis, V. Venizelos, G. Xepapadakis, K. Kalogerakos, J. Papadiamantis, V. Zobolas, J. Janinis, U. Dafni
Journal: Journal of Clinical Oncology (2009)

552 Background: The management of bone mineral density (BMD) in postmenopausal, breast cancer (BC) patients (pts) receiveing anastrozole was investigated in this phase III, multicenter, open label trial. Methods: Pretreatment BMD of 217 eligible pts with hormone receptor-positive BC scheduled to receive anastrozole was evaluated at lumbar spine (LS) and hip (HP). Pts with T-score&lt;-2.0 in LS or HP, received anastrozole 1mg/day plus oral risedronate 35 mg/week (A+R) and pts with T-score&gt;-1 in both sites received anastrozole only (A). Pts with T-score&lt;-1 in either site but T-score&gt;-2.0 in both sites were randomized to receive A+R or A alone. All pts received Calcium and Vit D daily. BMD was then assessed at 12 and 24 months. Results: Comparison of randomized arms (A = 33 pts, A+R = 37 pts): T-score change from baseline was significantly different only for LS at 24 months (-0.23 in A vs 0.41 in A+R, Wilcoxon test p = 0.007) and was significantly higher from baseline for the A+R arm (Signed rank test p = 0.01). At 12 months, among A only pts, 4 (12.1%) had a T-score&lt;-2.0 without becoming osteoporotic, while 2(6.1%) moved to the normal BMD region; from A+R pts, only 2(5.4%) had a T-score&lt;-2.0 without becoming osteoporotic, while 9 (24.3%) moved to the normal BMD region. The same trend in BMD changes was also observed at the 24 month evaluation. Group with T-score&lt;-2.0 in either LS or HP (A+R, n = 99): a significant increase for LS both at 12 and 24 months was detected (median increase of T-score by 0.45 and 0.37, p&lt;0.01 for both time points) with a corresponding non-significant change in HP (p = 0.91 and p = 0.15). BMD in 13(13.3%) pts improved to the osteopenic region (-2.0&lt;T-score&lt;-1.0). Group with T-score&gt;-1 in both sites (A, n = 48): significant decrease was detected for HP and LS, both at 12 and 24 months; however, only 11 (22%) pts became osteopenic and 1(2%) became osteoporotic. Conclusions: The addition of oral risedronate in postmenopausal BC patients with osteopenia receiving anastrozole has a favourable effect in BMD at lumbar spine at 24 months. [Table: see text]
Hyperfractionated radiation therapy and concurrent chemotherapy for advanced head and neck cancer.
Authors: K. A. AL Saleh, R. Safwat, A. Bedair, A. AL Basmy
Journal: Journal of Clinical Oncology (2010)

5566 Background: Extensive clinical research aimed at improving locoregional tumor control as well as functional outcome of patients with locally advanced head and neck cancer, using altered radiation fractionation schemes and combination with chemotherapy. We investigated the feasibility of combining hyperfractionated radiotherapy with concomitant chemotherapy, and to assessed its toxicity, in those patients. Progression-free survival, and overall survival, were set as secondary end points. Methods: Between November 2003 and November of 2007, 48 patients with stage III and IV HNC who met the eligibility criteria were enrolled in the study. All the patients had unresectable disease. Hyperfractionated Radiation consisted of 120 cGy twice daily, 6 hours apart, for a total of 69.6 Gys in 58 fractions over 6 weeks. Three cycles of concurrent chemotherapy (cisplatin and 5-fluorouracil) were delivered during weeks 1, 4, and 6 of irradiation. Results: The treatment was delivered in a median overall period of 54 days, with a recorded median delay of 7 days. Grade 4 skin toxicity was experienced by 4.1% of patients only. Therapy was well tolerated (grade 3 mucositis in 21%, grade 4 in 26%, grade 3 leukopenia in 10%). Weight loss more than 10 kg was reported in 10 (16.7%) of the cases. The most common late toxicity was mild to moderate xerostomia which was encountered in 34 (70.8%) cases and improved thereafter. Hypothyroidism was encountered in 7 (14.6%) of the cases. Complete response (CR) was observed in 40 (83.3%) of patients. Partial response (PR) was achieved in the remaining 8 (16.7%) patients. Disease relapse occurred in 9 (18.8%) patients after complete responce. 3 patients relapsed locally, 5 patients developed distant metastasis, and one patient developed both local and distant metastasis. 2 patients (4.1%) died of treatment complications, 8 patients (16.7%) died with progressive locoregional, and metastatic disease. The 2- year disease free survival was 77%. Conclusions: Hyperfractionated radiotherapy and concurrent chemotherapy is tolerable. Results regarding LC and OS are encouraging as compared to conventional radiotherapy and concurrent chemotherapy. No significant financial relationships to disclose.
Procedures available to examine the immunotoxicity of chemicals and drugs.
Authors: J H Dean, M I Luster, G A Boorman, L D Lauer
Journal: Pharmacological Reviews (1982)

The discipline of immunology should provide toxicology with sensitive models to assess toxicity as well as provide better safety assessment. More information on correlations between immune function and host resistance changes and a more standardized panel of methods for immunotoxicity screening will add further credence to the already impressive immunotoxicology data base. Research efforts are needed to evaluate newer in vitro methods with microsome activation systems to screen chemicals for immunotoxicity, to evaluate chemicals for induction of hypersensitization or allergy, and to better determine whether there are chemical structure activity relationships for chemically induced immunotoxicity. The studies described here represent preliminary examples of these approaches.
The correlation between ERCC1 expression and outcome of chemotherapy in patients with advanced colorectal cancer (ACC): A Dutch Colorectal Cancer Group study (DCCG)
Authors: M. Koopman, S. Venderbosch, N. F. Antonini, J. H. van Krieken, C. J. Punt
Journal: Journal of Clinical Oncology (2008)

11042 Background: The excision repair cross-complementing (ERCC) gene family prevents damage to DNA caused by nucleotide excision and repair. The expression of ERCC1 mRNA is related to resistance to platinum compounds. The aim of this study was to investigate the role of ERCC1 as a predictive factor for response to treatment in patients (pts) with ACC. Methods: Paraffin embedded blocks of the primary tumor were collected from 506 pts included in the DCCG CAIRO study (Koopman M. et al. Lancet 2007). In arm A pts received sequential treatment with first-line capecitabine, second-line irinotecan and third-line capecitabine + oxaliplatin (capox). In arm B pts received combination treatment with first-line irinotecan + capecitabine, second-line capox. ERCC1 expression was determined by immunohistochemistry, the percentage of positive tumor cell cores and the intensity of the staining were scored. Results: In 206 pts with ERCC1-negative (41%) and 300 pts with positive (59%) tumors the median overall survival (OS) was 20.0 months (95% CI 17.1–22.2) and 17.6 months (95% CI 14.9–18.8), p=0.209, respectively. The median progression free survival (PFS) for ERCC1 negative vs. ERCC1 positive pts in first-line was 7.8 months (95%CI 6.9–8.4) vs. 6.3 months (95% CI 6.0–6.9), p=0.049; in second-line 11.1 months (95% CI 10.1–12.6) vs. 9.0 months (8.2–9.9), p=0.029; and in third-line treatment: 12.2 months (95%CI 11.0–13.5) vs. 9.9 months (95% CI 9.0–10.8), p=0.039. The objective response rate (RR) in first-line treatment was 39% (95% CI 32–47%) vs. 27% (95% CI 22–33%), p=0.007. For the subgroup of pts treated with capox in third-line (arm A) and second-line (arm B) no significant differences were observed for OS and PFS between negative vs. positive ERCC1 tumors. Conclusions: This is the largest study to date on the expression of ERCC1 in ACC. Pts with a ERCC1-negative tumor have a significantly better PFS and RR, and a non-significant trend towards a better OS. Our results do not confirm the predictive value of ERCC1 for the response to oxaliplatin-based chemotherapy. No significant financial relationships to disclose.
Do heads of government age more quickly? Observational study comparing mortality between elected leaders and runners-up in national elections of 17 countries
Authors: Andrew R Olenski, Matthew V Abola, Anupam B Jena
Journal: BMJ (2015)

<b>Objectives</b>&nbsp;To determine whether being elected to head of government is associated with accelerated mortality by studying survival differences between people elected to office and unelected runner-up candidates who never served. <b>Design</b>&nbsp;Observational study. <b>Setting</b>&nbsp;Historical survival data on elected and runner-up candidates in parliamentary or presidential elections in Australia, Austria, Canada, Denmark, Finland, France, Germany, Greece, Ireland, Italy, New Zealand, Norway, Poland, Spain, Sweden, United Kingdom, and United States, from 1722 to 2015. <b>Participants</b>&nbsp;Elected and runner-up political candidates. <b>Main outcome measure</b>&nbsp;Observed number of years alive after each candidate's last election, relative to what would be expected for an average person of the same age and sex as the candidate during the year of the election, based on historical French and British life tables. Observed post-election life years were compared between elected candidates and runners-up, adjusting for life expectancy at time of election. A Cox proportional hazards model (adjusted for candidate's life expectancy at the time of election) considered years until death (or years until end of study period for those not yet deceased by 9 September 2015) for elected candidates versus runners-up. <b>Results</b>&nbsp;The sample included 540 candidates: 279 winners and 261 runners-up who never served. A total of 380 candidates were deceased by 9 September 2015. Candidates who served as a head of government lived 4.4 (95% confidence interval 2.1 to 6.6) fewer years after their last election than did candidates who never served (17.8 <i>v</i> 13.4 years after last election; adjusted difference 2.7 (0.6 to 4.8) years). In Cox proportional hazards analysis, which considered all candidates (alive or deceased), the mortality hazard for elected candidates relative to runners-up was 1.23 (1.00 to 1.52). <b>Conclusions</b>&nbsp;Election to head of government is associated with a substantial increase in mortality risk compared with candidates in national elections who never served.
Loss of Glycogen Debranching Enzyme AGL Drives Bladder Tumor Growth via Induction of Hyaluronic Acid Synthesis
Authors: Sunny Guin, Yuanbin Ru, Neeraj Agarwal, Carolyn R. Lew, Charles Owens, Giacomo P. Comi, Dan Theodorescu
Journal: Clinical Cancer Research (2015)

Abstract Purpose: We demonstrated that amylo-alpha-1-6-glucosidase-4-alpha-glucanotransferase (AGL) is a tumor growth suppressor and prognostic marker in human bladder cancer. Here we determine how AGL loss enhances tumor growth, hoping to find therapeutically tractable targets/pathways that could be used in patients with low AGL–expressing tumors. Experimental Design: We transcriptionally profiled bladder cell lines with different AGL expression. By focusing on transcripts overexpressed as a function of low AGL and associated with adverse clinicopathologic variables in human bladder tumors, we sought to increase the chances of discovering novel therapeutic opportunities. Results: One such transcript was hyaluronic acid synthase 2 (HAS2), an enzyme responsible for hyaluronic acid (HA) synthesis. HAS2 expression was inversely proportional to that of AGL in bladder cancer cells and immortalized and normal urothelium. HAS2-driven HA synthesis was enhanced in bladder cancer cells with low AGL, and this drove anchorage-dependent and independent growth. siRNA-mediated depletion of HAS2 or inhibition of HA synthesis by 4-methylumbelliferone (4MU) abrogated in vitro and xenograft growth of bladder cancer cells with low AGL. AGL and HAS2 mRNA expression in human tumors was inversely correlated in patient datasets. Patients with high HAS2 and low AGL tumor mRNA expression had poor survival, lending clinical support to xenograft findings that HAS2 drives growth of tumors with low AGL. Conclusions: Our study establishes HAS2-mediated HA synthesis as a driver of growth of bladder cancer with low AGL and provides preclinical rationale for personalized targeting of HAS2/HA signaling in patients with low AGL–expressing tumors. Clin Cancer Res; 22(5); 1274–83. ©2015 AACR.
Adjuvant 5-fluorouracil and leucovorin with or without OK-432 in colorectal cancer: A single-institutional study of long-term follow-up
Authors: S. Hong, S. Shin, C. Im, H. Jeung, S. Rha, H. Chung, J. Roh, S. Lee, H. Ryoo, J. Ahn
Journal: Journal of Clinical Oncology (2008)

15128 Background: This study was to investigate whether adding a streptococcal preparation, OK-432, to chemotherapy of 5- fluorouracil (5-FU) and leucovorin (LV) could improve overall survival in patients who had undergone curative resection for Dukes’ B2 and C colorectal cancer. Patients and Methods: A total of 269 patients with a performance status of 0 to 2 received 5-FU, 400mg/m2, i.v. and LV, 20mg/m2, i.v. (FL), which was given daily for 5 days in every 4 weeks for a maximum of 12 cycles, ± OK-432 (2 KE s.c. weekly during chemotherapy) for colon cancer, and FL and radiotherapy (RTx) (5040 - 5400 cGy) ± OK-432 for rectal cancer. Results: From January 1991 to December 1996, 69 among 139 patients with colon cancer and 62 among 130 patients with rectal cancer were treated with the addition of OK-432 to FL adjuvant therapy. The median follow-up duration was 11.5 years. Regardless of addition of OK-432, there was no statistically significant difference in overall survival between in colon (FL, 75.6%; FL+OK-432, 82.2%, P=0.7449) and rectal (FL + RTx, 60.3%; FL+RTx+OK-432, 76.6%, P=0.139) cancer patients. However, overall survival (FL + RTx, 57.9%; FL+RTx+OK-432, 75.6%, P=0.0478) was different significantly in subgroup with Dukes’ C rectal cancer with addition of OK-432. Toxicities following OK-432 administration were not different, except for the flu-like symptom and rash. Conclusion: Chemoimmunotherapy with a regimen of FL and OK-432 does not improve survival in patients with curatively resected colorectal cancer, but further trials for patients with Dukes’ C rectal cancer are required to study whether chemoimmunotherapy is effective or not. No significant financial relationships to disclose.
ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction
Authors: Elliott M. Antman, Daniel T. Anbe, Paul Wayne Armstrong, Eric R. Bates, Lee A. Green, Mary Hand, Judith S. Hochman, Harlan M. Krumholz, Frederick G. Kushner, Gervasio A. Lamas, Charles J. Mullany, Joseph P. Ornato, David L. Pearle, Michael A. Sloan, Sidney C. Smith, Joseph S. Alpert, Jeffrey L. Anderson, David P. Faxon, Valentin Fuster, Raymond J. Gibbons, Gabriel Gregoratos, Jonathan L. Halperin, Loren F. Hiratzka, Sharon Ann Hunt, Alice K. Jacobs, Joseph P. Ornato
Journal: Journal of the American College of Cardiology (2004)