tbuckley/cabot-search huggingface dataset:
Racial/ethnic differences in adequacy of information and peer support for women with breast cancer
Authors: N. K. Janz, M. Mujahid, S. Hawley, A. Hamilton, S. Katz
Journal: Journal of Clinical Oncology (2007)

9085 Background: Existing disparities in quality of care for women with breast cancer suggest the need to explore the adequacy of information and care support provided to patients. This study investigated whether racial/ethnic variation existed in receipt and usefulness of cancer-related information and availability of peer support. Methods: 2,030 women diagnosed with non-metastatic breast cancer and reported to the Los Angeles County, Surveillance Epidemiologic and End Results registry between 8/05–5/06, were identified and mailed a survey shortly after initial treatment. Latina and African American (AA) women were oversampled. Outcomes included self-reported receipt and perceived usefulness of treatment-related (recovery from surgery, radiation, chemotherapy) and survivorship-related (sexual functioning, relationships, nutrition, anxiety) information and experiences with other women with breast cancer. We report results on a 50% respondent sample (N=742) that will be updated based on a final sample of 1,400 women (projected response rate, 72%). Results: More women received information and found it useful regarding treatment than survivorship issues. After adjusting for age and education, a higher percentage of Latina women, compared to white and AA women, desired more information on treatment-related issues and survivorship-related issues (p&lt;.01). A higher percentage of Latina women also reported having no contact with other women with breast cancer, either through the health care system or a family/friend (p&lt;.001), and reported a desire for more contact as compared to white or AA women (42%, vs. 15% and 29%, respectively). Overall, women rated the benefit of talking to other women high, particularly in helping with emotional issues and few endorsed potentially negative consequences. Conclusions: Women with breast cancer expressed the need for more useful information and care support, especially about managing survivorship concerns. Particular focus is warranted with Latina women to provide desired information and greater opportunities for peer contact. No significant financial relationships to disclose.
Microarray analysis using paraffin embedded samples of gastric cancer (GC)
Authors: H. Uetake, M. Inokuchi, K. Sugihara, K. Danenberg, P. V. Danenberg
Journal: Journal of Clinical Oncology (2007)

15089 Background: In the 42nd annual meeting of ASCO, we reported our phase I/II study of S-1 plus CPT-11 study for metastatic GC. In the present study, microarray analysis using paraffin embedded samples of those patients were performed. Methods: Patients’ background; Histologically proven CRC with measurable metastatic lesions, PS 0–2, age&lt; 80, adequate organ functions, and written informed consent. No prior chemotherapy except adjuvant setting was allowed. S-1 was administered orally, 80 mg/m 2 /day on 14 consecutive days with 14 days’ rest for 4 weeks, and CPT-11 was infused at the 80 mg/m 2 (RD)on days 1 and 8. Objective responses according to RECIST criteria were observed in 26 of the 42 pts (RR=62%). Median survival time was 444 days. Microarray analysis; Microarray analysis using paraffin embedded samples were performed (Responsegenetics Inc.). Results: In the scatter plotting, gene expression pattern of the stable disease (SD) group was similar to that of partial response (PR) group. Cluster analysis was successfully performed, that separated progressive disease (PD) group from SD/PR group (p&lt;0.03). In pathway analysis, FGF signaling pathway and nicotinate and nicotinamide metabolism pathway was significantly important to predict the response to S-1 plus CPT-11 therapy. Conclusions: In S-1 plus biweekly CPT-11 therapy for metastatic GC, gene expression profile was supposed to be important for the prediction of the response and patient survival. No significant financial relationships to disclose.
Loss of life expectancy from air pollution compared to other risk factors: a worldwide perspective
Authors: Jos Lelieveld, Andrea Pozzer, Ulrich Pöschl, Mohammed Fnais, Andy Haines, Thomas Münzel
Journal: Cardiovascular Research (2020)

Long-term exposure of humans to air pollution enhances the risk of cardiovascular and respiratory diseases. A novel Global Exposure Mortality Model (GEMM) has been derived from many cohort studies, providing much-improved coverage of the exposure to fine particulate matter (PM2.5). We applied the GEMM to assess excess mortality attributable to ambient air pollution on a global scale and compare to other risk factors.We used a data-informed atmospheric model to calculate worldwide exposure to PM2.5 and ozone pollution, which was combined with the GEMM to estimate disease-specific excess mortality and loss of life expectancy (LLE) in 2015. Using this model, we investigated the effects of different pollution sources, distinguishing between natural (wildfires, aeolian dust) and anthropogenic emissions, including fossil fuel use. Global excess mortality from all ambient air pollution is estimated at 8.8 (7.11-10.41) million/year, with an LLE of 2.9 (2.3-3.5) years, being a factor of two higher than earlier estimates, and exceeding that of tobacco smoking. The global mean mortality rate of about 120 per 100 000 people/year is much exceeded in East Asia (196 per 100 000/year) and Europe (133 per 100 000/year). Without fossil fuel emissions, the global mean life expectancy would increase by 1.1 (0.9-1.2) years and 1.7 (1.4-2.0) years by removing all potentially controllable anthropogenic emissions. Because aeolian dust and wildfire emission control is impracticable, significant LLE is unavoidable.Ambient air pollution is one of the main global health risks, causing significant excess mortality and LLE, especially through cardiovascular diseases. It causes an LLE that rivals that of tobacco smoking. The global mean LLE from air pollution strongly exceeds that by violence (all forms together), i.e. by an order of magnitude (LLE being 2.9 and 0.3 years, respectively).
Neoadjuvant chemotherapy for resectable adenocarcinoma of the panctreatic head - a prospective phase II trial
Authors: B. C. Pestalozzi, S. Heinrich, M. Schäfer, C. Pierre-Alain
Journal: Journal of Clinical Oncology (2007)

4610 Background: Pancreatoduodenectomy alone was considered the standard treatment for resectable adenocarcinoma of the pancreatic head in Europe. Recently adjuvant chemotherapy without radiation has become a new standard worldwide. Neoadjuvant chemotherapy has advantages over adjuvant chemotherapy. Methods: Patients (pts) with histologically or cytologically confirmed ductal adenocarcinoma of the pancreatic head judged to be resectable were entered into this single center prospective phase II trial. After written informed consent staging with thoracic/abdominal CT-scans, endoscopic ultrasound, PET-CT and diagnostic laparoscopy were performed. Preoperative chemotherapy consisted of 4 treatments with gemcitabine (1,000mg/m 2 ) and cisplatin (50mg/m 2 ) every 2 weeks. Re-staging was followed by (classic or pylorus-sparing) pancreatoduodenectomy about 8 weeks after the start of chemotherapy. CA 19- 9, prealbumin serum levels, and quality of life (QLQ-30) were also assessed before and after chemotherapy. The primary study end-point was the resectability rate. Results: Twenty-eight pts entered this trial between June 2002 and January 2007, 27 have completed chemotherapy. The resectability rate after chemotherapy was 93% (25/27). Neoadjuvant chemotherapy was well tolerated, although 7 episodes of transient Grade III/IV toxicities occurred in 5 pts. While median recurrence-free survival from diagnosis was 9.2 months (95% CI 7.7–10.8), median overall survival was an excellent 26.5 months (12.2–40.8). CA 19–9 serum levels decreased by 48% (p=0.01) after neoadjuvant chemotherapy, while overall quality of life increased by 24% (p=0.02). Nutritinoal status also improved: Prealbumin levels were normal in 89% after chemotherapy compared to 60% before (p=0.02). Conclusions: Neoadjuvant gemcitabine/cisplatin for two months is well tolerated and does not jeopardize surgical resectability in adenocarcinoma of the pancreatic head. Furthermore, it offers several advantages over primary surgery including patient selection, improvements in nutritional status and quality of life. We are currently planning a randomized study comparing the combination of neoadjuvant and adjuvant chemotherapy versus adjuvant treatment alone. No significant financial relationships to disclose.
Clinician perspective on molecular profiling of non-small-cell lung cancer [Correspondence]
Authors: Marios DeCatris, David Farrugia, Ken O'Byrne
Journal: Journal of Clinical Oncology (2016)

The article by Meric-Bernstam et al1 that was recently published in Journal of Clinical Oncology raises important questions about the clinical application of large-scale genomic testing. We congratulate the authors for this ambitious study, which successfully profiled 2,000 consecutive patients with advanced cancer. The next-generation sequencing (NGS) platform was used for 1,749 of 2,000 patients (87.5%). Of 789 patients with potentially actionable mutations, 83 (11%, or 4% of screened population) were enrolled in a genomically matched clinical study. As the editorial2 accompanying the article by Meric-Bernstam et al1 pointed out, the 4% figure, albeit disappointing, may be an underestimate because cancers such as lung adenocarcinoma and melanoma, for which ≥ 50% of patients have actionable mutations, were under-represented. ...
Phase II Single-Arm Study of Preoperative Letrozole for Estrogen Receptor–Positive Postmenopausal Ductal Carcinoma In Situ: CALGB 40903 (Alliance)
Authors: E. Shelley Hwang, Terry Hyslop, Laura H. Hendrix, Stephanie Duong, Isabelle Bedrosian, Elissa Price, Abigail Caudle, Tina Hieken, Joseph Guenther, Clifford A. Hudis, Eric Winer, Alan P. Lyss, Diana Dickson-Witmer, Richard Hoefer, David W. Ollila, Timothy Hardman, Jeffrey Marks, Yunn-Yi Chen, Gregor Krings, Laura Esserman, Nola Hylton
Journal: Journal of Clinical Oncology (2020)

Primary endocrine therapy for ductal carcinoma in situ (DCIS) as a potential alternative to surgery has been understudied. This trial explored the feasibility of a short-term course of letrozole and sought to determine whether treatment results in measurable radiographic and biologic changes in estrogen receptor (ER)-positive DCIS.
A shared somatic translocation involving CUX1 in monozygotic twins as an early driver of AMKL in Down syndrome
Authors: Iben Bache, Karin Wadt, Mana M. Mehrjouy, Maria Rossing, Olga Østrup, Anna Byrjalsen, Niels Tommerup, Marlen Metzner, Paresh Vyas, Kjeld Schmiegelow, Birgitte Lausen, Mette K. Andersen
Journal: Blood Cancer Journal (2020)
Abstract 43: Circulating Omega-3 Fatty Acid Levels and Total and Cause-specific Mortality: Prospective Evidence From 14 Cohorts in the Fatty Acids and Outcomes Research Consortium
Authors: Nathan Tintle, Julie Bassett, Kuo-Liong Chien, Nita Forouhi, Leanne Kupers, Maria Lankinen, Rozenn Lemaitre, Joan Lindsay, Matti Marklund, Rachel Murphy, Toshiharu Ninomiya, Jennifer G Robinson, Cecilia Samieri, David Siscovick, Jyrki K Virtanen, Alexis Wood, Dariush Mozaffarian, William S Harris
Journal: Circulation (2020)

Background: Several recent studies have linked higher blood levels of the long-chain omega-3 polyunsaturated fatty acids (PUFAs) with lower risk of certain disease outcomes, in particular cardiovascular disease (CVD). Limited studies have evaluated associations between n-3 PUFA levels and total and cause-specific mortality. Methods: We meta-analyzed the association of circulating omega-3 PUFAs with total and cause-specific mortality from 15 distinct cohorts in 10 countries following a total of 36,840 individuals (baseline average age 66 yrs; 47% female; median follow-up 13.7 yrs), with 11,635 deaths. Total mortality, and 3 cause-specific mortalities (CVD, cancer or other), were separately predicted by levels of the long chain omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA) and the Omega-3 index (EPA+DHA), as well as levels of alpha-linolenic acid (ALA, an intermediate chain n-3 PUFA). Using cohort-specific fatty acid levels (range from 10 th to 90 th percentiles), each cohort fit a Cox regression model adjusting for demographics, health related covariates, and n-6 PUFA levels. Cohort-specific estimates were pooled with inverse-variance weighted meta-analysis. Results: Higher levels of EPA, DPA, DHA and the Omega-3 index were all associated with lower all-cause mortality [EPA meta-analysis Hazard Ratio (HR)=0.90 (95% CI: 0.85, 0.95), DPA HR=0.84 (95% CI: 0.77, 0.91), DHA HR=0.84 (95% CI: 0.75, 0.93), Omega-3 index HR = 0.84 (95% CI 0.77, 0.92) (Figure)], as well as for each cause-specific mortality (CVD, cancer and other; HRs from 0.85 to 0.92). ALA showed no association with total-mortality or cause-specific mortality [HRs from 0.97 to 1.00)]. Conclusions: We have found strong evidence of inverse associations between long-chain omega-3 PUFA levels and all-cause and cause-specific mortality. Further controlled studies are needed in order to determine the extent to which these observations represent a causal or coincidental relationships.
Abstract 29: Metabolomic Signatures of Sedentary Behavior and Cardiometabolic Traits in US Hispanics/Latinos: Hispanic Community Health Study / Study of Latinos (HCHS/SOL)
Authors: Jin Choul Chai, Jee-Young Moon, Bing Yu, Guochong Chen, Mariaelisa Graff, Martha L DAVIGLUS, Queenie M Chan, Bharat Thyagarajan, Sheila Castaneda, Megan Grove, Xiaonan Xue, Eric Boerwinkle, Robert Kaplan, Qibin Qi
Journal: Circulation (2020)

Introduction: Sedentary behavior is associated with cardiometabolic risk independent of physical activity, but the underlying mechanisms are not fully understood. Hypothesis: Sedentary behavior may influence serum metabolite profiles which are associated with cardiometabolic risk factors. Methods: The analyses included 2711 participants (43% men) of the HCHS/SOL aged 18 to 74 years, free of CVD and other major chronic diseases. Serum metabolomics was performed using an untargeted approach. Physical activity and sedentary behavior were measured by accelerometer (Actical) for a 7-day period. Survey linear regressions were used to examine associations between sedentary behavior and metabolites. Metabolite scores were calculated by summing up z-scores of significant metabolites within the same sub-pathway. Results: Of 624 known metabolites, 95 were significantly associated with sedentary behavior ( P &lt;0.05 after FDR correction), adjusting for socioeconomic and lifestyle factors including moderate to vigorous physical activity ( Figure 1A ). The majority of significant metabolites were clustered into 7 sub-pathways. Three sub-pathway scores (branched-chain amino acids [BCAA], acylcarnitine and medium-chain fatty acid metabolism) were positively associated with sedentary behavior, while the other 4 sub-pathway scores (acylcholine, plasmalogen, nicotinate, and arginine) were inversely associated with sedentary behavior. Among these scores, the BCAA score showed unfavorable correlations with all cardiometabolic traits including obesity measures, glycemic traits, blood lipids and blood pressure. The acylcholine score showed favorable correlations with obesity measures and glycemic traits, though positive correlations with blood lipids were observed ( Figure 1B) . Conclusions: Our study identified multiple serum metabolites associated with sedentary behavior independent of physical activity, suggesting potential mechanistic links between sedentary behavior and cardiometabolic diseases.
Abstract P416: An Externally Validated and Highly Sensitive Artificial Intelligence-driven Integrated Genetic-epigenetic DNA Test for Incident Coronary Heart Disease Prediction
Authors: Meesha Dogan, Robert Philibert
Journal: Circulation (2020)

Despite being largely preventable, every year, coronary heart disease (CHD) affects millions of Americans. Currently, primary prevention of CHD starts with an understanding of several risk factors (e.g. age, gender, diabetes) that are aggregated to derive an incident CHD risk score using risk calculators such as the Framingham Risk Score (FRS) and ASCVD Pooled Cohort Equation (PCE). Unfortunately, this approach involves multiple tests and its lack in sensitivity could result in ineffective treatment recommendations to patients for the prevention of CHD. As an alternative, we have developed and independently validated a single, simpler, AI-driven, digital PCR (dPCR)-based integrated genetic-epigenetic DNA test that can more sensitively estimate the 3-year incident CHD risk for both men and women. Our technology accounts for the inherited and acquired (lifestyle/environment) risks for CHD through three genetic (SNP) and three epigenetic (DNA methylation) biomarkers, respectively, and can be performed on DNA from blood or saliva. The incident CHD risk prediction model was developed using genome-wide DNA methylation and genotype data from the Framingham Heart Study (FHS) Offspring cohort (n=1172 in training set, n=512 in test set) and was validated in an Intermountain Healthcare (IM) cohort (n=80 in validation set, n=79 in test set). The final prediction model is an ensemble of SVM, Random Forest and Logistic Regression models, and its performance in the FHS and IM test sets is summarized in Table 1. The FRS and PCE risk calculators were implemented on all FHS and IM cohort data. A clinically implementable version of this tool as part of its translation into a Laboratory Developed Test incorporates standard Taqman assays for genotyping and custom dPCR assays for DNA methylation quantification. The strong correlation between our dPCR assay values and the Illumina array values are shown in Figure 1, indicating successful dPCR assay translation. We are also extending this tool to include more ethnically diverse cohorts.
Bacteria Boost Mammalian Host NAD Metabolism by Engaging the Deamidated Biosynthesis Pathway
Authors: Igor Shats, Jason G. Williams, Juan Liu, Mikhail V. Makarov, Xiaoyue Wu, Fred B. Lih, Leesa J. Deterding, Chaemin Lim, Xiaojiang Xu, Thomas A. Randall, Ethan Lee, Wenling Li, Wei Fan, Jian-Liang Li, Marina Sokolsky, Alexander V. Kabanov, Leping Li, Marie E. Migaud, Jason W. Locasale, Xiaoling Li
Journal: Cell Metabolism (2020)
Abstract P3-03-12: Obesity promotes the activation of genes and pathways in tumor associated breast fat
Authors: Niel Infante, James Coad, Don Primerano, James Denvir, Linda Vona-Davis
Journal: Cancer Research (2020)

Abstract Tumor-associated adipocytes play an active role in breast tumor progression. Moreover, obesity has been established as a risk factor in cancer-related mortality. The altered expression of genes and signaling pathways in breast adipose as a result of obesity may create a more favorable microenvironment for tumor progression. To this end, we analyzed transcriptome profiles of human adipose tissue from lean and obese women with invasive breast cancer using RNA sequencing (n=10/group). Within individuals, adipose tissue was sampled proximal and distal (2 cm) to the breast tumor. A heat map of normalized expression values was generated with unsupervised clustering for the most informative genes. A cluster heat map was obtained by the analysis of the express of 35 DEGs with the most significant differences (adjusted p-value P&amp;lt; 0.01 and fold change &amp;gt; 2) recorded. Starting with a list of genes marked as significant in the analysis of lean vs obese, we queried the STRING database. Using ClusterMaker2 and MCL clustering, we performed enrichment analysis and found KEGG pathway hsa05224 breast cancer was enriched with an FDR of 2.7e-40. Using KEGGParser, we over-layed fold changes from lean vs obese data. In examining obese women, there were 16 Hallmark pathways that were statistically significant (adjusted p-value P&amp;lt; 0.10); whereas a subset of these (11 pathways) were significant in lean women. Pathways that were significant in both lean and obese individuals were pathways that regulate EMT, adipogenesis and TGF-β signaling. EMT transcription factors and TGF-β signaling are known to regulate cancer adipogenesis. The results underscore the link between obesity and altered gene expression in mammary fat associated with breast cancer. (Supported by NIH P20GM103434 and NIGMS U54GM104942) Citation Format: Niel Infante, James Coad, Don Primerano, James Denvir, Linda Vona-Davis. Obesity promotes the activation of genes and pathways in tumor associated breast fat [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-12.
Survival differences in patients with brain metastases according to breast cancer subtypes
Authors: B. Nam, K. Lee, T. Kim, J. Ro
Journal: Journal of Clinical Oncology (2007)

11507 Background: Brain metastases (BM) occur in as many as one-third of patients with metastatic breast cancer (MBC). Incidences and prognoses by triple receptor subtypes in BM have not been well delineated. Methods: Retrospectively, prognoses were assessed according to clinical characteristics, triple receptor subtypes, and receipt of trastuzumab therapy by univariate and multivariate analyses. ER/PR/HER2 were tested by IHC with HER2 FISH for IHC 2+ and for all 118 consecutive primary BC. Results: Between 8/2001 and 4/2006, 138 of 805 pts (17.1%) with MBC presented with BM at NCC Korea. More pts with triple negative and HER2+ tumors developed BM (see table ). The median age was 47 years. They were single (9%), multiple (80%), or leptomeningeal disease with or without multiple BM (11%). As initial therapy, 104 pts received WBRT, 8, intrathecal therapy (IT), 9, WBRT with IT, and 17 others. Of 56 HER2+ pts, 45 received trastuzumab either before (n=25) or after (n=13), or continuously before and after BM diagnosed (n=7). By 10/2006, 117 pts died with a median survival of 4.5 months. Multivariate analyses indicated age, tumor receptor subtypes, leptomeningeal presentation and number of extracranial disease sites as significant factors. Receipt of trastuzumab therapy after BM was a significant variable for survival in HER2+ diseases (3.8 vs. 13.4 mo, p=0.0000). Pts with triple negative subtype lived shortest compared with other types (p=0.0035). Conclusions: More pts with triple negative and HER2+ disease developed BM. HER2+ disease gained a significant survival benefit by trastuzumab therapy. Supported by NCC Grant 0610240 and 0510520. [Table: see text] No significant financial relationships to disclose.
Bariatric Surgery and Diabetes Treatment—Finding the Sweet Spot
Authors: Natalie Liu, Luke M. Funk
Journal: JAMA Surgery (2020)

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