tbuckley/cabot-search huggingface dataset:
Abstract P366: A High-carbohydrate Diet Increases Serum HDL-C and Apolipoprotein A-I and Decreases Weight and BMI in the Male A Carriers of the <i>APOA1</i> -75G/A Polymorphism
Authors: Yong Yan Song, Ren Rong Gong, Min Shan Hu, Zhen Zhang, Hui Liu, Xing Chun Zhu, Rong Rong Zhang, Zhe Jiang, Mei Fan, Yuan Hao Li, Ding Zhi Fang
Journal: Circulation (2012)

Both apolipoprotein gene polymorphism and high-carbohydrate diet have been found to be associated with serum lipid levels. However, the effects of their interaction on serum lipid profiles have not been well elucidated yet. We assessed the hypothesis that the subjects with different genotypes of the -75G/A polymorphism in the promoter region of the apolipoprotein A-I gene ( APOA1 ) have different serum lipid responses upon a high-carbohydrate diet. Fifty-six healthy university students (27 males and 29 females, 22.89&amp;#177;1.80 years) were given a washout diet of 54% carbohydrates for seven days, followed by a high-carbohydrate diet of 70% carbohydrates for six days without total energy restriction. Anthropometric indexes and serum lipids at baseline, after the washout diet, and after the high-carbohydrate diet, as well as the APOA1 -75G/A polymorphism were analyzed. The male A carriers of the APOA1 -75G/A polymorphism consistently had higher levels of apolipoprotein A-I ( p =0.008 at baseline, p =0.031 after the washout diet, and p =0.009 after the high-carbohydrate diet diet), but higher levels of high-density lipoprotein cholesterol (HDL-C) only at baseline ( p =0.048) and after the high-carbohydrate diet ( p =0.042) than the males with the GG genotype, and experienced increases in HDL-C ( p =0.023) and apolipoprotein A-I ( p =0.012) and decreases in body weight ( p =0.017) and body mass index (BMI) ( p =0.018) after the high-carbohydrate diet when compared to those after the washout diet. In conclusion, the high-carbohydrate diet can increase the serum HDL-C and apolipoprotein A-I concentrations in the males carrying the A allele of the APOA1 -75G/A polymorphism. The effects are associated with the decreases of body weight and BMI. These results may provide experimental evidences for the personalized dietary interference in the country with the largest population in the world.
Phase II trial of CKD-602, a new camptothecin analogue, in patients with small cell lung cancer (SCLC)
Authors: J. H. Lee, S. J. Lee, J. S. Kim, R. B. Yeol, K. Park, N. K. Kim, D. S. Heo, S. W. Kim, C. Suh, J. S. Lee
Journal: Journal of Clinical Oncology (2004)

7210 Background: CKD-602 (Camtobell, Chong Kun Dang Pharm, Seoul, Korea) is a new camptothecin analogue. The objective of this phase II multicenter trial was to investigate the safety and efficacy of CKD-602 in patients with SCLC. Methods: Eligibility included newly diagnosed patients with extensive disease (group 1) or previously treated patients with limited disease who responded to first-line treatment and progressed after response duration of 90 days or more (group 2). Patients were required to have measurable disease, Karnofsky performance score over 60%, and adequate organ function. Treatment consisted of CKD-602 on days 1 to 5 of a 3-week cycle. At the first cycle, all patients received 0.5 mg/m2/day of CKD-602. From the second cycle, the daily dose of CKD-602 was adjusted to one of three dose levels, 0.4, 0.5, or 0.6 mg/m2/day, based on the toxicities after the first cycle. Results: A total of 27 patients, 19 in group 1 and 8 in group 2, were enrolled onto this study. Median age was 62 years. The dose level of CKD-602 from the second cycle was 0.4 mg/m2/day in 4 patients, 0.5 in 11, and 0.6 in 7. A total of 103 cycles of CKD-602 were delivered with a median of 4 cycles. All patients were assessable for toxicity and 21 for response. There was no treatment-related death. The most frequent grade 3/4 toxicities were related to myelosuppression including neutropenia in 75% of patients and thrombocytopenia in 30%. Grade 3/4 non-hematological toxicities were uncommon. There were 1 complete response and 8 partial responses. Overall objective response rates were 42.9% (95% CI, 21.7–64.1); 46.6% for group 1 and 33.3% for group 2. Response rates were not significantly different according to the dose level. With a median follow-up duration of 65 weeks among surviving patients, 7 of 9 responded patients progressed after a median response duration of 30 weeks. Eight patients died and median survival for all enrolled patients was 78 weeks. Conclusions: CKD-602, a new camptothecin analogue, was active in SCLC patients with reversible myelosuppression being the main toxicity. This promising result warrants further investigation of CKD-602 in combination with less myelosuppressive agents. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chong Kun Dang Pharmaceutical Corp.
Phase III study comparing cyclophosphamide, doxorubicin, and etoposide (CDE) to carboplatin and paclitaxel (CP) in patients (pts) with extensive disease small cell lung cancer (ED SCLC)
Authors: E. F. Smit, H. J. M. Groen, B. Biesma, S. van der Wilt, M. G. J. Koolen, W. K. De Jong, H. V. Tinteren, A. V. Bochove
Journal: Journal of Clinical Oncology (2005)

7045 Background: CP has shown activity in CDE resistant pts with ED SCLC (Groen JCO 1999). We performed a RCT comparing CDE and CP in chemonaïve pts with ED SCLC. Methods: Primary end point: progression free survival (PFS), secondary: objective response rate (ORR), survival and toxicity. The study is powered to detect improvement PFS from 5.7 months to 8.4 months (α= 0.05, β= 0.80). Eligibility criteria: ED SCLC, PS 0–2, measurable disease, normal bone marrow and organ reserve. February 1999 to September 2004 98 pts were randomised to iv Cyclophosphamide 1000 mg/m2 (d1), Doxorubicin 45 mg/m2 (d1), Etoposide 100 mg/m2 (d1–3) q 3 weeks x 5 (CDE group) and 99 to iv Carboplatin (AUC 7) (d1) and Paclitaxel 175 mg/m2 (d1) q 3 weeks x 5 (CP group). Results: Pts characteristics are balanced between both arms; 84% pts ECOG PS 0–1. 81% of pts have died. Median number courses both arms 5, 47% vs 44% of pts had dose reductions. No difference in PFS (141 vs 102 days, p=0.89) was observed. ORR CDE group 64%, CP group 67%, median survival CDE group 6.5 mo, CP group 6.7 mo (p=0.68). The only significant difference in toxicity was grade 4 leucopenia (CDE group 59% pts, CP group 9% pts; p<0.0001) leading to febrile neutropenia in 24% vs 7% pts (p=0008). Conclusion: Treatment with CP does not improve PFS over CDE in ED SCLC. Hematological toxicity is significantly lower in pts treated with CP. No significant financial relationships to disclose.
Abstract 231: Decreased Parasympathetic Activity in the Ovulatory Phase of the Menstrual Cycle
Authors: Andrew Tweedell, Matthew Tenan, Anthony C Hackney, Matthew Brothers, Lisa Griffin
Journal: Circulation Research (2013)

The Heart rate variability (HRV) power spectrum is a non-invasive index of parasympathetic and sympathetic branches of the autonomic nervous system (ANS). Sex hormone oscillations may affect autonomic nervous system function; however, no systemic difference in HRV across the menstrual cycle has been shown. The purpose of this study is to test the hypothesis that there are changes in HRV spectral power components across the menstrual cycle. Method: Eleven women (24.4±3.6 years) volunteered for this experiment. Menstrual cycle phase was determined via basal body temperature mapping. Participants were tested once in each cycle phase. A 3 lead ECG was sampled at 1000 Hz. A piezoelectric force transducer, placed around the chest, recorded breathing rate. After 20 minutes of quiet seated rest, 5 minutes of data was collected in the upright seated position. Power spectral density analysis was performed on the R-R interval variations by fast Fourier transformation. The spectrum was divided into low (0.04-0.15, Hz) and high (0.15-0.40 Hz) frequency components. In order to attain data normality, the components were transformed with a natural logarithm. A repeated measures ANCOVA was used with a piece-wise covariate function for breathing rates higher and lower than 10 breaths per minute. Results: A significant decrease in total power spectrum was observed at the ovulatory phase (P=0.04) compared to the early follicular, late follicular and mid luteal phases. Furthermore, high-frequency oscillations were lower (P=0.04) in the ovulatory phase compared to late follicular phase. There were no changes observed (P&gt;0.05) in the low frequency power spectrum across the menstrual cycle. Conclusions: The decrease in the high-frequency components of the HRV power spectrum during the ovulatory phase indicates a decrease in parasympathetic regulation of the heart. The ovulatory phase is characterized by an elevated level of progesterone, follicle stimulating and luteinizing hormones, and a moderate level of estradiol. Thus, the changes in these hormones during ovulation appear to affect ANS function.
A novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704.
Authors: Gregory M. Heestand, James Don Murphy, Jennifer Moughan, William Regine, Jia Luo, Madeline Sydney Graber, Pamela L. Kunz, George A. Fisher, Chandan Guha, Bryan Lin, Rex B. Mowat, Rakesh Gaur, Mark K. Buyyounouski, Yuhchyau Chen, Daniel Tandel Chang, Albert Koong
Journal: Journal of Clinical Oncology (2014)

176 Background: RTOG 9704 was an adjuvant pancreatic adenocarcinoma trial. Patients with resected stage I-III disease were randomized to receive 5-FU vs. gemcitabine (GEM) chemotherapy pre and post 5-FU chemoradiation. Prior to adjuvant therapy, patients had baseline serum samples drawn and archived for future study. Methods: To better understand the biology of pancreatic cancer, investigators involved with this project have evaluated numerous proteins of interest via literature review and gene expression data. By using the multiplex capabilities and high sensitivity detection of the proximity ligation assay (PLA), a probe panel was built from commercially available antibodies capable of quantifying 42 key proteins from 24 uL of patient serum. To determine if any of these proteins corresponded with survival or predicted response, the baseline serum specimens were obtained for assay with our PLA panel. Clinical endpoints were overall (OS) and disease-free survival (DFS). Univariate and multivariate statistical techniques were used. Using a Bonferroni correction, a p-value of &lt;0.0012 was considered statistically significant. Results: Of the 451 eligible patients, 213 had samples available for study – 112 (53%) in the 5-FU arm and 101 (47%) in the GEM arm. As expected, decreased levels of CEA and CA 19-9 were prognostic for improved OS in all patients. Low levels of matrix metalloproteinase-7 (MMP-7) predicted an OS benefit from adjuvant GEM, but not 5-FU. Conclusions: PLA is a powerful tool for identifying potential biomarkers from archived, small volume serum samples. These data suggest that pancreatic cancer patients with low MMP-7 serum levels were most likely to benefit from adjuvant GEM. Supported by RTOG grants U10 CA21661, CCOP grant U10 CA37422, and RTOG Biospecimen Resource grant U24 CA114734 from the National Cancer Institute. [Table: see text]
Null allele polymorphisms in the <i>GSTT1</i> and <i>GSTM1</i> genes in 705 women from a mammographic breast cancer screening program (NMPOA) in southern Brazil
Authors: E. Aguiar, J. Giacomazzi, E. I. Palmero, L. Kalakun, L. Schuler-Faccini, D. Duarte Filho, G. Skonieski, M. Caleffi, R. Giugliani, P. Ashton-Prolla
Journal: Journal of Clinical Oncology (2007)

21091 Background: Several genetic polymorphisms in genes related with metabolism have been associated with breast cancer (BC) risk. Among these, the gluthatione-S-transferase M1 and T1 null genotypes have been associated with slightly increased BC risk in some populations. In Brazil, BC is a significant public health problem, due to its high incidence and mortality rates. In Porto Alegre, Brazil`s southernmost capital, a multidisciplinary BC Prevention Project - the Nucleo Mama Porto Alegre Cohort (NMPOA)- was started in 2004 and includes a mammographic screening program for women ages 40–69 years. Goal:Determine the allelic and genotypic frequencies of GSTM1 and GSTT1 null alleles in women undergoing annual mammographic screening and correlate its presence with mammography results and presence of additional BC risk factors at baseline and after 10 years. Methods: A sample of 705 women from the NMPOA BC screening program was consecutively enrolled from November/2005 until March/2006. Mammography results (BIRADS categories) and BC risk information (5-yr and vital estimates using the Gail model, family history of BC, body mass index) were obtained by chart review. Genotyping was performed by multiplex polymerase chain reaction (PCR). Results: Of the 705 patients studied, 145 (20.6%) and 314 (44.5%) had the GSTT1 and GSTM1 null alleles, respectively. Genotypically, 67 (9,5%) were null homozygous for both genes (GSTM1- and GSTT1- ); 78 (11,1%) were GSTT1- and non-null for GSTM1 (GSTT1- and GSTM1+); 247 (35%) were GSTT1+ and GSTM1- and 313(44,4%) were GSTM+ and GSTT+. There was a statistically significant association of the GSTT1+ allele with low-risk mammographic findings (category BIRADS 1; p&lt;0,05). Conclusions: The genotypic and allelic frequencies of the GSTT1 and GSTM1 null alleles were not significantly different from those reported previously for other populations. The non-null GSTT1 allele was associated with lower category mammographic findings. Prospective clinical evaluation of the women followed in this program and correlation of genotype with clinical findings may elucidate additional risks associated with the presence of these polymorphisms. No significant financial relationships to disclose.
Molecular profiling of pulmonary pleomorphic carcinoma: Implications for targeted treatment of a rare lung malignancy.
Authors: Y. Kim, S. Lee, Y. Choi, J. Park, J. Lee, Y. Park, J. Ahn, K. Park, M. Ahn
Journal: Journal of Clinical Oncology (2010)

10576 Background: Pulmonary pleomorphic carcinoma (PPC) is rare malignant tumor composed of carcinomatous and sarcomatous cell components which characterized by a more aggressive outcome than other histological subtype of non-small cell lung cancer (NSCLC). Various attempts to establish the clinical features of PPCs have been largely limited by small sample size. Thus, it will be important to further delineate the molecular characteristics of this disease entity to better understand the exact nature of this tumor type. Methods: We retrospectively examined the tumor specimen of 61 patients who underwent surgical resection of the lung in Samsung Medical Center from July 1995 to June 2009. Mutational or gene amplification status of epidermal growth factor receptor (EGFR), K-RAS (rat sarcoma virus), c-kit, FGFR (fibroblast growth factor receptor), c-MET (mesenchymal-epithelial trasition factor) was examined with genomic DNA sequencing, real-time PCR and/or fluorescence in situ hybridization(FISH). Overall survival impact was examined. Results: Out of 61 patients with pleomorphic carcinoma, it was revealed that 13 (21.3%) patients possessed EGFR tyrosine kinase domain deletion mutations in exon 19, point mutations in exon 20,21, 6 (9.8%) with K-ras point mutations in exon 2 and 3 (4.9%) c-kit point mutations in exon 9. High frequency gene copy number of c-met was found in 11 (18.0%) patients including one amplification by FISH and that of FGFR in 7 (11.5%) patients. A subset of patients demonstrated concurrent existence of multiple mutations, including one with EGFR and K-ras mutation simultaneously. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clincopathological variables. Conclusions: We describe mutational analysis of a large set of PPC samples. Given the diverse repertoire of mutational profiles observed from PPC samples, clinical trials based on accurate cancer-genotyping should be considered as a legitimate treatment scheme for this rare disease entity in the future. No significant financial relationships to disclose.
Telephone disclosure of <i>BRCA1/2</i> test results? Experience and opinions of genetic counselors and consumers
Authors: L. J. Patrick-Miller, D. Fetzer, H. Schmidheiser, M. Daly, D. Toppmeyer, O. Olopade, A. Bradbury
Journal: Journal of Clinical Oncology (2009)

1510 Background: BRCA1/2 test results have historically been disclosed in person (IPD) by a certified genetic counselor (GC). Greater consumer demand and access to BRCA1/2 testing, and greater prevalence and acceptance of telemedicine, have interested providers in conducting BRCA1/2 testing and disclosing results by telephone (TD) and internet. GC and consumer experiences and opinions about TD have not been well described. Methods: To determine experience, opinions and interest in TD of BRCA1/2 test results we conducted semi-structured interviews with 194 GC recruited via NSGC Cancer Special Interest Group and with 30 consumers (to date) less than 9 months post IPD of BRCA1/2 test results at two cancer centers. Descriptive statistics characterize GC and consumer experiences and opinions. Results: 98% GC had provided TD; 46% rarely. Most frequent reasons for TD: perceived consumer hardship of IPD (n = 190); consumer preference (n = 49) and medical benefit (n = 30). GC comfort with TD varied by test result (true negative [TN] 77%, indeterminate [IND] 49%; mutation carriers [MC] 37%; variant of unknown significance [VUS] 33%). GC cited consumer convenience (n = 132), medical (n = 71) and psychological benefit (n = 42), and greater GC counseling capacity (n = 33) as TD advantages. No nonverbal communication (n = 161), poorer communication/understanding (n = 67), and difficulty explaining complex results (n = 41) were disadvantages GC most frequently reported. 46% post-IPD consumers reported interest in TD; interest varied by test result (VUS 67%; IND, 63%; TN 57%; MC 25%). Consumers’ perceived advantages: convenience (n = 22) and medical benefit (n = 9); and disadvantage to TD; lack of visual and personal connection with GC (n = 18). Conclusions: Results of the ongoing study suggest many consumers of BRCA1/2 testing are interested in, and nearly all GC have conducted, TD. GC and consumers share perceptions of TD convenience, and of challenges of lack of visual cues, however, GC comfort with, and consumer preference for, TD vary differently by test result. Given consumer and provider interest, longitudinal study of TD impact on knowledge, risk perception, communication, and health behaviors, and their mediators will be critical to develop policy and procedures optimizing adaptive responses to TD. No significant financial relationships to disclose.
Abstract 194: Relaxin Receptor-Ligand Expression in a Fibrotic Environment
Authors: Jamie L Haney, David S Schwartzman, Sanjeev G Shroff
Journal: Circulation Research (2014)

The renin-overproducing transgenic rat (mREN2) has recently been proposed as a model of left ventricular (LV) hypertension and fibrosis. Comparing mREN2 (n=7) to sex- and age-matched Wistar-Han control rats (WHAN, n=11), we have confirmed hypertension (mean blood pressure: 174±9 vs. 107±3 mmHg, P&lt;0.001), hypertrophy (LV weight:body weight: 4.0±0.1 vs. 2.7±0.1 mg/g, P&lt;0.001), and cardiac fibrosis. At the protein level, LV from mREN2 exhibited significantly higher percentage of interstitial collagen per total protein area versus WHAN (5.95±1.01% vs. 1.96±0.06%, P=0.02). At the level of LV function, mREN2 hearts demonstrated significant diastolic dysfunction (increased stiffness coefficient from stress-strain relationship: 198±30 vs. 78±10, P=0.01, and reduced magnitude of dP/dtmin: 1254±125 vs. 2000±110 mmHg/s, P&lt;0.001), and impaired relaxation (increased relaxation time constant: 0.048±0.001 vs. 0.043±0.001 s, P=0.002). The naturally occurring hormone relaxin is known to have antifibrotic properties in multiple organ systems and it affects both synthesis and degradation aspects of collagen homeostasis. It is known that relaxin (RLN1) and receptor (RXFP1) are expressed locally in LV tissue, yet the biological function of the endogenous relaxin message-receptor system is not fully understood. Interestingly, the relative mRNA expressions of relaxin and relaxin receptor were increased in this model of LV fibrosis (2-ΔΔCT by qRT-PCR for RLN1: 3.04±0.56 (mREN2) vs. 1.0±0.18 (WHAN), P=0.001; and RFXP1: 7.06±1.57 (mREN2) vs. 1.00±0.20 (WHAN), P=0.003). Thus, the unregulated endogenous relaxin-receptor system in the mREN2 fibrosis model seems to be an adaptive response which is trying to keep the fibrosis in check. However, this endogenous adaptive response is insufficient to completely block collagen accumulation and prevent LV diastolic dysfunction. We are currently conducting experiments to examine whether exogenous administration of relaxin can assist the endogenous adaptive response and reverse LV fibrosis and normalize diastolic function in this model.
Oxygen-Enhanced MRI Is a Major Advance in Tumor Hypoxia Imaging
Authors: Mark W. Dewhirst, Samuel R. Birer
Journal: Cancer Research (2016)

It is well established that hypoxia is prevalent in human tumors and is associated with resistance to radiotherapy and chemotherapy ([1–3][1]); furthermore, hypoxia contributes to immune checkpoint activation ([4–7][2]), higher likelihood for development of metastasis, and worse overall
Depression is under-recognised in the sport setting: time for primary care sports medicine to be proactive and screen widely for depression symptoms
Authors: Thomas Trojian
Journal: British Journal of Sports Medicine (2015)

An important role of the team physician is to provide care for the whole athlete. This includes mental health issues for instance screening for depression and knowing the factors that affect the onset of depression. The USA Preventive Service Task Force (USPSTF) recommends screening adults for depression when staff-assisted depression care supports are in place to assure accurate diagnosis, effective treatment and follow-up.1 Most studies report prevalence rate of depression among college athletes ranges from as low as 15.6% to as high as 21%.2 Depression levels were significantly higher in current college athletes (about 17%) compared with former, graduated college athletes (8%).

The stress of sports and athletic participation place athletes at risk. Performance failure was significantly associated with depression. The statistically strongest predictors of depression in student-athletes were female gender, lower self-esteem, less social connectedness and decrease sleep. Female student-athletes had 1.32 greater odds (95% CI 1.01 to 1.73) of experiencing symptoms of depression compared to male student-athletes. Freshmen had 3.27 greater odds (95% CI 1.63 to 6.59) of experiencing symptoms of depression than their more senior counterparts.3 

USPSTF recommends the use of one of these three screening tools; 9-Question Patient Health Questionnaire—Depression Screener (PHQ-9), Beck Depression Inventory-II (BDI-II), Depression Screener from the Center for Epidemiologic Studies Depression Scale (CES-D). The PHQ-9, a nine-question survey, when the cut-off is a score of 5 or more has 95% sensitivity and 88.3% specificity when scored with a cut point of 11. The CES-D, 10-question survey, when the cut-off is 22 has sensitivity 84%, specificity 60% and positive predicted value 77%.4 Most recommend a cut-off of 16 to increase sensitivity but it decreases the …