tbuckley/cabot-search huggingface dataset:
Abstract P192: Metabolomic Profiles Associated with Coronary Heart Disease in Women
Authors: Nina P Paynter, Raji Balasubramanian, Shuba Gopal, Franco Giulianini, Leslie Tinker, JoAnn E Manson, Nancy R Cook, Christine M Albert, Clary Clish, Kathy M Rexrode
Journal: Circulation (2016)

Background: Prior studies of metabolomic profiles and coronary heart disease (CHD) have been limited by relatively small case numbers and scant data in women. Methods: The discovery set examined 371 metabolites in 400 confirmed, incident CHD cases and 400 controls (frequency matched on age, race/ethnicity, hysterectomy status and time of enrollment) in the Women’s Health Initiative Observational Study (WHI-OS). All selected metabolites were validated in a separate set of 394 cases and 397 matched controls drawn from the placebo arms of the WHI Hormone Therapy trials and the WHI-OS. Discovery used 4 methods: false-discovery rate (FDR) adjusted logistic regression for individual metabolites, permutation corrected least absolute shrinkage and selection operator (LASSO) algorithms, sparse partial least squares discriminant analysis (PLS-DA) algorithms, and random forest algorithms. Each method was performed with matching factors only and with matching plus both medication use (aspirin, statins, anti-diabetics and anti-hypertensives) and traditional CHD risk factors (smoking, systolic blood pressure, diabetes, total and HDL cholesterol). Replication in the validation set was defined as a logistic regression coefficient of p&lt;0.05 for the metabolites selected by 3 or 4 methods (tier 1), or a FDR adjusted p&lt;0.05 for metabolites selected by only 1 or 2 methods (tier 2). Results: Sixty-seven metabolites were selected in the discovery data set (30 tier 1 and 37 tier 2). Twenty-six successfully replicated in the validation data set (21 tier 1 and 5 tier 2), with 25 significant with adjusting for matching factors only and 11 significant after additionally adjusting for medications and CHD risk factors. Validated metabolites included amino acids, sugars, nucleosides, eicosanoids, plasmologens, polyunsaturated phospholipids and highly saturated triglycerides. These include novel metabolites as well as metabolites such as glutamate/glutamine, which have been shown in other populations. Conclusions: Multiple metabolites in important physiological pathways with robust associations for risk of CHD in women were identified and replicated. These results may offer insights into biological mechanisms of CHD as well as identify potential markers of risk.
Association of Sleep Problems and Melatonin Use in School-aged Children
Authors: M. Elisabeth Koopman-Verhoeff, Michiel A. van den Dries, Judith J. van Seters, Maartje P. C. M. Luijk, Henning Tiemeier, Annemarie I. Luik
Journal: JAMA Pediatrics (2019)

Jingen Li, MD, PhD; Virend K. Somers, MD, PhD; Hao Xu, MD, PhD; Francisco Lopez-Jimenez, MD, MSc; Naima Covassin, PhD
A mismatch between methods and objectives in phase I drug development: Statistical limitations and personalized medicine—A California Cancer Consortium (CCC) study.
Authors: Paul Henry Frankel, Stephen Shibata, Susan G. Groshen, Jeff Longmate, Sumanta Kumar Pal, Stella Khoo, Edward M. Newman
Journal: Journal of Clinical Oncology (2012)

2538 Background: Patient variation in drug response and toxicity impacts all phases of drug development. While detailed sample-size calculations and analysis based on statistical methodology are critical for addressing variation in late stage trials, phase I studies pose unique and largely unsolved challenges related to variability. Changes in patient selection during the study, small sample-sizes and large patient variation in toxicity are exactly the kind of problems that statistical methods cannot address in small, isolated phase I studies, regardless of apparent mathematical rigor. We have documented these problems via a physician survey. Methods: A 10-question anonymous survey was sent to 670 oncologists at National Comprehensive Cancer Network (NCCN) and CCC institutions via an online survey. 19 % (126/670) of the oncologists polled responded. 78/126 (62%) specialized in Medical Oncology. The number of years in practice varied from 2-45 yrs with a median of 17 yrs. Results: a) 66% of all respondents stated that non-DLT toxicities on one dose level would impact their patient selection on the following dose level, conflicting with the assumption of random patient selection implicit in simulations used in evaluating statistical designs. b) Only 13% stated a desire to target a non-heme toxicity as high as 20% grade 3, while 87% desired a 10% or less grade 3 rate; c) More than half the respondents would prefer not to escalate if 3/3 patients experienced grade 2 LFTs; d) 82% of the respondents thought the appropriate target toxicity differed for patients depending on their potential for becoming a surgical candidate, furthering the need for personalized dosing. Conclusions: Statistical methods in phase I trials are unable to address many of the salient features of phase I study conduct and investigator goals. We will present several approaches we have initiated to address these limitations, and present future plans to help produce a more reliable estimate of a recommended dose. Supported in part by NCI grants U01CA062505, N01-CM-62209, and NCCN data collection assistance.
Surgical pathology findings of neoadjuvant full-dose irinotecan and cisplatin (IP) with concurrent thoracic radiation therapy (C-TRT) in stage III non-small cell lung cancer (NSCLC).
Authors: Paul R. Walker, Sharon Ben-Or, Jon Moran, Richard Fred Williams, Tithi Biswas, Daniel B. Fried, Julian Rosenman, Suzanne M. Russo, Raid Aljumaily, Mark Bowling, Susan Eubanks, Zenith Nelson, Teresa Parent
Journal: Journal of Clinical Oncology (2012)

e17550 Background: Neoadjuvant C-TRT in stage IIIA NSCLC has become a standard of care. C-TRT sterilizes N2 nodes far better than primary tumors. TRT dose does seem to make a difference. In Intergroup 0139 with 45 Gy pre-op TRT, ypT0N0 was 18% and ypN0 46% (Albain et al Lancet 2009). Pre-op TRT dose escalation to 60+ Gy improves ypN0 clearance up to 80% and ypT0N0 to 45% (Sonett et al Ann Thorac Surg 2004; Cerfolio et al Ann Thorac Surg 2005). However there is no known difference in pathologic response and outcome with different chemotherapy approaches. Irinotecan with radiation therapy has been studied in locally advanced NSCLC with similar outcomes as with any cisplatin doublet and no undue toxicities (Langer et al J Thorac Oncol 2007; Bastos et al J Thorac Oncol 2010). We reviewed our multidisciplinary thoracic oncology program experience with neoadjuvant full-dosing IP and C-TRT in stage IIIA NSCLC assessing ypTN response. Methods: All patients with stage IIIA NSCLC undergoing pre-operative IP and C-TRT between September 2008 and December 2011 were searched through our program database and included. 14 patients were identified. Irinotecan 65mg/m 2 and cisplatin 30mg/m 2 D1 and D8 q 21 days with C-TRT 60-66 Gy was administered followed by surgical resections. Pathologic response (ypT0N0) was assessed. Results: Median age 61 (36-72). 85% males; 85% squamous. PET N2 positive in 85% with 2 patients T3N1. 6/14 (43%) pathologic complete response (pCR)/ypT0N0; plus 4 with &lt; 10% primary tumor viability (one isolated tumor cells on IHC staining, two with just 3 mm residual islands); 70% of patients had a pCR or had &lt; 10% primary tumor viability. 11/12 (91%) downstaged PET N2 to ypN0. Conclusions: Full dose IP with C-TRT 60+ Gy is a very effective neoadjuvant treatment with very high pathologic complete responses and N2 clearance in squamous cell lung cancers. Just as in stage IV NSCLC, histology-based chemotherapy in stage IIIA/IIIB NSCLC C-TRT could well achieve outcome differences.
A Generic Coordination Assembly‐Enabled Nanocoating of Individual Tumor Cells for Personalized Immunotherapy
Authors: Xiaoli Wang, Zuoguan Chen, Chao Zhang, Chuangnian Zhang, Guilei Ma, Jing Yang, Xiaoqing Wei, Hongfan Sun
Journal: Advanced Healthcare Materials (2019)

Abstract A generic and effective tumor cells encapsulation strategy enabled by metal–organic coordination is developed to prepare a vaccine for personalized immunotherapy. Specifically, an epigallocatechin‐3‐gallate (EGCG)‐Al(III) coordination layer is in situ formed onto individual living cells in aqueous phase and the process can be completed within an hour. 98% of proteins in the cells are entrapped within the microparticles, which are endowed with high antigens loading capacity. The microparticles enhance the uptake efficiency of antigens, protect antigens from degradation in vivo, and delay the retention time of antigens in the lymph nodes. Moreover, dendritic cells (DCs) activation is triggered by the microparticles, and simultaneously, the expression of costimulation marker on DCs and the production of Th1‐related cytokines are significantly upregulated. Moreover, six kinds of tumor cells are utilized and successfully coated with the EGCG/Al(III) layer, suggesting the generalization of this strategy. More importantly, the microparticles exhibit a comparative antitumor effect with polyinosinic–polycytidylic acid (PolyI:C) in B16 pulmonary metastasis model. Overall, the encapsulation strategy enabled by metal–organic coordination can be potentially useful for personalized immunotherapy customized to individual patient's tumor cells.
Early mortality in metastatic cancer: A SEER population data analysis.
Authors: Opher Globus, Shira Sagie, Noy Lavine, Daniel Itshak Barchana, Damien Urban
Journal: Journal of Clinical Oncology (2021)

e18789 Background: Overall survival from cancer has continuously improved over the last thirty years. This is due, in part, to advances in systemic treatment of some cancers resulting in clinically significant increases in long-term survival. Despite these improvements in long-term survival, many patients die quickly after a diagnosis of metastatic cancer, possibly being denied the opportunity to benefit from these recent advances in cancer treatment. To identify the scope and predictors of early mortality in de novo metastatic cancer, we analyzed population-based data, focusing on patients with early mortality. Methods: Using the Survival, Epidemiology and End Results (SEER) Database we analyzed adult patients who presented with de-novo metastatic solid malignancies diagnosed between 2008-2016. We defined early mortality as 1- and 2-month mortality. Factors associated with early mortality were analyzed including primary site of cancer and demographics. Correlations between categorical variables were analyzed with chi squared tests and survival data was derived from life tables using STATA I/C 12.1. Results: Of 519,553 patients identified, 273,976 (53%) were males, 411,041 (79%) were white, 213,325 (41%) had lung cancer, 65,679 (13%) colorectal cancer and 49,139 (10%) pancreatic cancer. One - and two - month cancer specific mortality was 12.4% and 22.5% respectively for the entire cohort. Mortality from cancer in the first two months after diagnosis decreased only marginally between 2008 and 2016 (23.4% and 21.6 %, respectively). Cancers with the highest 2-month cancer specific mortality rates were liver (39.5%), pancreatic (36.3%), lung (26.8%), gastroesophageal (23.7%), and urothelial (21.2%). Cancers with the lowest 2-month mortality rate were breast (10.4%) and prostate cancer (5%). Patients who presented with liver metastases had a clinically significant higher 2- month cancer specific mortality rate (29% vs. 18% p &lt; 0.001), brain metastases were associated with a milder increase in 2-month cancer specific mortality (25%vs 21% p &lt; 0.001) and bone metastases were not associated with a clinically significant difference in 2-month cancer specific mortality (22% vs 21%, p = 0.047). Other factors associated with early mortality included increasing age, low income, and living in a rural area. Conclusions: Over 21% of newly diagnosed metastatic cancer patients die within 2 months of their diagnosis, with little improvement over the last decade, rendering this an urgent unmet need in cancer care. Further research is urgently required to better identify the causative and treatable factors of early mortality in cancer patients.
Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial
Authors: Hyman B. Muss, Mei-Yin C. Polley, Donald A. Berry, Heshan Liu, Constance T. Cirrincione, Maria Theodoulou, Ann M. Mauer, Alice B. Kornblith, Ann H. Partridge, Lynn G. Dressler, Harvey J. Cohen, Patricia A. Kartcheske, Edith A. Perez, Antonio C. Wolff, Julie R. Gralow, Harold J. Burstein, Ahmad A. Mahmood, Linda M. Sutton, Gustav Magrinat, Barbara A. Parker, Ronald D. Hart, Debjani Grenier, Arti Hurria, Aminah Jatoi, Larry Norton, Clifford A. Hudis, Eric P. Winer, Lisa Carey
Journal: Journal of Clinical Oncology (2019)

Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years.Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS.The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients.With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.
Utility of Percutaneous Image-Guided Biopsy to Diagnose Intraabdominal Lymphoma with Coaxial Core Needles,
Authors: Ikuo Shimizu, Keijiro Sato, Yuko Fujikawa, Toshimitsu Ueki, Daigo Akahane, Masahiko Sumi, Mayumi Ueno, Naoaki Ichikawa, Hikaru Kobayashi, Yoichi Okazaki
Journal: Blood (2011)
Role of the longevity gene hSir2(SIRT1) in cancer resistance to chemotherapy
Authors: Fei Chu, Pauline Chou, Xin Zheng, Bernard Mirkin, Abdelhadi Rebbaa
Journal: Cancer Research (2005)

2817  The present investigation addresses putative signaling pathways linking resistance to senescence in aging and resistance to chemotherapy in cancer. Cells in both instances may use similar strategies to live longer and escape the control of a hostile environment detrimental to their survival and proliferative capacity. With the recent discovery that the sir2 gene (that codes for a NAD+−dependent histone deacetylase) inhibits senescence and increases life span both in yeast and worms, we sought to determine whether its human homologue , hSir2, could be associated with cancer resistance to chemotherapy. Expression of the hsir2 gene and its product (Sirt1) were both found to be increased in drug resistant cell lines when compared to their parental drug sensitive counterparts derived from neuroblastoma, osteosarcoma, breast cancer and ovarian cancer. Furthermore, biopsies from cancer patients treated with chemotherapy expressed high level of this molecule at recurrence. Expression of other members of the Sirt1 family was not affected in drug resistant cell lines as well as in tumor specimens. siRNA targeting of Sirt1 significantly reversed the resistance phenotype and down-regulated expression of the multidrug resistance molecule P-glycoprotein suggesting Sirt1 is not only associated with, but also plays an active role in development of drug resistance through control of the mdr1 gene expression. All together, these findings uncovered a novel function of the longevity gene hsir2 in resistance to chemotherapy and cancer recurrence and highlight the role of chromatin remodeling in controlling development of drug resistance. These findings also constitute a prove of principle that signaling pathways leading to drug resistance in cancer may share similarities with those implicated in aging.
Neutralizing antibodies against Mayaro virus require Fc effector functions for protective activity
Authors: James T. Earnest, Katherine Basore, Vicky Roy, Adam L. Bailey, David Wang, Galit Alter, Daved H. Fremont, Michael S. Diamond
Journal: The Journal of Experimental Medicine (2019)

Despite causing outbreaks of fever and arthritis in multiple countries, no countermeasures exist against Mayaro virus (MAYV), an emerging mosquito-transmitted alphavirus. We generated 18 neutralizing mAbs against MAYV, 11 of which had "elite" activity that inhibited infection with EC50 values of <10 ng/ml. Antibodies with the greatest inhibitory capacity in cell culture mapped to epitopes near the fusion peptide of E1 and in domain B of the E2 glycoproteins. Unexpectedly, many of the elite neutralizing mAbs failed to prevent MAYV infection and disease in vivo. Instead, the most protective mAbs bound viral antigen on the cell surface with high avidity and promoted specific Fc effector functions, including phagocytosis by neutrophils and monocytes. In subclass switching studies, murine IgG2a and humanized IgG1 mAb variants controlled infection better than murine IgG1 and humanized IgG1-N297Q variants. An optimally protective antibody response to MAYV and possibly other alphaviruses may require tandem virus neutralization by the Fab moiety and effector functions of the Fc region.
Evaluation of serum extracellular vesicles as noninvasive diagnostic markers of glioma
Authors: Huayi Wang, Dengzhi Jiang, Wenzhe Li, Xiang Xiang, Jun Zhao, Bin Yu, Chen Wang, Zhaohui He, Ling Zhu, Yanlian Yang
Journal: Theranostics (2019)

Rationale: Glioma is the most common malignant primary brain tumor in the central nervous system (CNS).The lack of reliable noninvasive diagnostic and prognostic methods is one of the main reasons for the high mortality of glioma.Serum has become a useful biomarker for the diagnosis and prognosis prediction of glioma because extracellular vesicles (EVs) carry molecular components from their parental cells.Methods: To detect EVs and perform molecular analysis of serum EVs, we established and optimized a microbead-assisted method based on flow cytometry and estimated the efficacy of EGFR protein expression and NLGN3 and PTTG1 mRNA in serum EVs from glioma patients (n=23) and healthy individuals (n=12).We evaluated the ability of EGFR + EVs to differentiate high-grade and low-grade glioma patients and checked the correlation between EGFR in EVs and the ki-67 labeling index (LI) in the tumor tissue.Results: We demonstrated that EGFR + EVs are effective diagnostic and prognostic markers of glioma.The expression of EGFR in serum EVs can accurately differentiate high-grade and low-grade glioma patients, and EGFR in EVs positively correlates with ki-67 LI in the tumor tissue.We also showed the potential of NLGN3 and PTTG1 mRNA in EVs for detecting glioma patients.Conclusions: We demonstrate that the protein expression of EGFR in serum EVs is an effective diagnostic marker of glioma.EGFR in EVs highly correlates with the malignancy of glioma.We also show the potential of NLGN3 and PTTG1 in EVs for detecting glioma.The optimized flow cytometry with the aid of microbead-based EV enrichment show its potential as a noninvasive method for the detection of glioma and will be beneficial to the management of glioma.
Laparoscopic lymphocele fenestration as first-line measure for gynecologic cancer patients after retroperitoneal lymph node dissection: 10-year analysis of safety, feasibility, efficacy, and recurrence rate.
Authors: Ingo B. Runnebaum, Marc P. Radosa, Herbert Diebolder, Harald Winzer, Julia Anschuetz, Oumar Camara
Journal: Journal of Clinical Oncology (2012)

e15566 Background: The occurrence of lymphoceles is a notorious complication occurring after retroperitoneal lymph node dissection (LND) frequently treated by repetitive percutaneous needle punctures associated with a high risk of wound infection or bowel injury. Methods: We analyzed 10 years of single-center experience with laparoscopic lymphocele fenestration as a first-line measure in gynecologic cancer 102 consecutive patients with a history of retroperitoneal LND (53.4 years; range: 22–80) who underwent laparoscopic lymphocele fenestration at our department between January 2001 and December 2010 for a symptomatic lymphocele. Results: A total of 132 lymphoceles have been fenestrated in 102 patients by laparoscopy, onaverage 5.3 months (SD: 6.3 months) after the initial LND. Mean follow-up of the patients was 60.4 months. Mean duration of surgery was 115.6 minutes and the average intra-operative blood loss per patient was 146 ml. Overall conversion rate to laparotomy was 7.8 %. The rate of intraoperative and postoperative minor and major complications was significantly higher in patients after pelvic plus paraaortic LND (23.8 %) compared to those after pelvic LND alone (3.6 %; p&gt;0.01). Two-year cumulative risk of lymphocelerecurrence was only 4.2 % with a total of 7 recurrences of lymphoceles observed. Conclusions: Laparoscopic lymphocele fenestration was safe and feasible as well as efficacious as a surgical first-line treatment option for symptomatic lymphocele following retroperitoneal LND in gynecological cancer patients with a particularly low recurrence rate.
Temporally Distinct Functions of the Cytokines IL-12 and IL-23 Drive Chronic Colon Inflammation in Response to Intestinal Barrier Impairment
Authors: Christina Eftychi, Robin Schwarzer, Katerina Vlantis, Laurens Wachsmuth, Marijana Basic, Prerana Wagle, Markus F. Neurath, Christoph Becker, André Bleich, Manolis Pasparakis
Journal: Immunity (2019)
Phase 1 Study of Elotuzumab and Peripheral Blood Mononuclear Cell Reconstitution in Combination with Autologous Stem Cell Transplantation and Lenalidomide Maintenance for Multiple Myeloma
Authors: Keren Osman, Ajai Chari, Samir Parekh, Adolfo Aleman, Jessica Caro, Gillian Morgan, Erika Florendo, Elaine Chan, Gina Strumolo, Katarzyna Zarychta, Lisa La, John Mandeli, Seunghee Kim-Schultze, Sacha Gnjatic, Sundar Jagannath, Hearn Jay Cho
Journal: Blood (2017)