tbuckley/cabot-search huggingface dataset:
Abstract 3299: Socio-demographic and lifestyle factors associated with the neutrophil-to-lymphocyte ratio: A systematic evaluation of the United States National Health and Nutrition Examination Survey
Authors: Rachel Howard, Aaron Scheiner, Kathleen M. Egan
Journal: Cancer Research (2019)

Abstract Background: The neutrophil-to-lymphocyte ratio (NLR) is an established marker of subclinical inflammation, and a high NLR is associated with poorer clinical outcomes in cancer patients. Despite this, factors that influence the magnitude of NLR independently of disease are poorly understood. Here, we systematically assess the influence of socio-demographic and lifestyle factors on NLR to identify a) potential confounders and effect modifiers in the relationship between NLR and cancer outcomes, and b) possible targets for intervention in patients with high NLR at diagnosis. Methods: Based on a total participant cohort of 48,023 adults with available NLR data, we identified 20 factors of interest relating to patient demographics, socioeconomic status and lifestyle that were included in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2016. Multivariable regression analysis identified factors significantly associated with the magnitude of NLR after adjusting for comorbidities and medications. Interactions between factors of interest were evaluated, and effect modification by demographic characteristics including age, sex and race was quantified. Results: Seven demographic and lifestyle factors were found to be significantly and independently associated with NLR: age, sex, race, marital status, physical activity, smoking history and alcohol use. Females, under 60s and non-Hispanic blacks demonstrated significantly lower NLR than males, over 60s and non-Hispanic whites. Participation in vigorous activity for at least ten minutes at a time was associated with decreased NLR, as was never-smoker status. Moderate drinking was also associated with a decreased NLR as compared to complete abstinence from alcohol. Conclusions: Multiple demographic and lifestyle factors are independently associated with elevated NLR. For an accurate assessment of the prognostic power of the NLR in the clinical setting, these factors should be routinely adjusted for in studies of the association between NLR and cancer outcomes. The present study reiterates that physical activity may have the potential to improve clinical outcomes by way of reducing systemic inflammation. Citation Format: Rachel Howard, Aaron Scheiner, Kathleen M. Egan. Socio-demographic and lifestyle factors associated with the neutrophil-to-lymphocyte ratio: A systematic evaluation of the United States National Health and Nutrition Examination Survey [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3299.
Abstract 2860: RCP augments oral cancer cell invasion through Zeb1 and Slug expression
Authors: Jin Young Kim, Kyung Hwa Cho, Bo Young Jeong, Zi Hae Song, Chang Gyo Park, Hoi Young Lee
Journal: Cancer Research (2019)

Abstract Background: Rab coupling protein (RCP), also called family interacting protein 1 (Rab11fip1) is a protein encoded by the RAB11FIP1 gene and has been known to augment cancer tumorigenesis, invasion, and metastasis. Recently, RCP was reported to aggravate cancer cell invasion and metastasis by stabilizing beta1 integrin and inducing epithelial-mesenchymal transition (EMT) in breast and ovarian cancer. Further, a high RCP expression was significantly correlated with shorter overall survival and disease-free survival of HNSCC patients. However, the molecule mechanisms by which RCP increases HNSCC invasion and metastasis are unclear. In the present study, we demonstrate the role of RCP in oral cancer cell invasiveness and its underlying mechanism. Methods: Oral cancer YD-10B and YD-38 cells were transiently transfected with RCP constructs. siRNAs were used to analyze the role of specific proteins for Slug and Zeb1 expression. Immunoblotting and immunofluorescence were used to analyze protein expression. Matrigel-coated in vitro insert and wound healing assay were used to analyze cancer cell invasion and migration, respectively. Results: We observed that ectopic expression of RCP induces invasion of oral cancer cells. Conversely, silencing of RCP expression increased E-cadherin expression and reduced oral cancer cell invasion. In addition, RCP upregulated Zeb1 and Slug expression that is important for RCP-induced oral cancer cell EMT and invasion. Furthermore, we identified that silencing of beta1 integrin efficiently attenuates RCP-induced Zeb1 and Slug expression. In addition, we observed that a selective inhibitor of EGFR kinase activity, Gefitinib, significantly reduces RCP-induced Zeb1 and Slug expression and that RasN17 recovers RCP-induced Zeb1 expression. Finally, RCP increased the viability of oral cancer cells against a chemotherapeutic agent cisplatin. Conclusion: Collectively, we demonstrate that RCP augments oral cancer cell EMT and invasiveness through a beta1 integrin/EGFR/Ras/Slug and Zeb1 signaling axis, providing potential biomarkers for oral cancer patients therapy. Citation Format: Jin Young Kim, Kyung Hwa Cho, Bo Young Jeong, Zi Hae Song, Chang Gyo Park, Hoi Young Lee. RCP augments oral cancer cell invasion through Zeb1 and Slug expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2860.
A Minimum Of 100 Tumor Cells in a Single Biopsy Sample Is Required to Assess Programmed Cell Death Ligand 1 Expression in Predicting Patient Response to Nivolumab Treatment in Nonsquamous Non–Small Cell Lung Carcinoma
Authors: Tomoyuki Naito, Hibiki Udagawa, Jun Sato, Hidehito Horinouchi, Shuji Murakami, Yasushi Goto, Shintaro Kanda, Yutaka Fujiwara, Noboru Yamamoto, Yoshitaka Zenke, Keisuke Kirita, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Noriko Motoi, Yuichiro Ohe, Genichiro Ishii, Koichi Goto
Journal: Journal of Thoracic Oncology (2019)
Abstract 4754: CHTOP is a novel therapeutic target for chemoresistant epithelial ovarian cancer therapy
Authors: Xupeng Bai, Xiaojie Feng, Jie Ni, Julia Beretov, Junli Deng, Ying Zhu, Peter Graham, Yong Li
Journal: Cancer Research (2019)

Abstract Background: Chemotherapy is the mainstay treatment for ovarian cancer (OC). Chemoresistance is a major challenge in epithelial ovarian cancer (EOC) therapy. CHTOP was identified as a potential chemoresistant biomarker in chemoresistant EOC cell lines using label-free LC-MS/MS proteomic technique. However, the role of CHTOP in EOC chemoresistance is still unclear. Aim: In this study, we aimed to investigate whether CHTOP can be used as a therapeutic target in chemoresistant EOC cells and to reveal the mechanism underlying chemosensitization. Methods: The expression difference of CHTOP was detected in chemoresistant and metastatic EOC cell lines by immunofluorescence (IF) and Western blot (WB). The expression of CHTOP in human EOC tissues was examined using immunohistochemistry (IHC). The effect of CHTOP knockdown (KD) on metastasis was examined using the Transwell® matrigel invasion and wound healing assays. Flow cytometry and TUNEL assay were employed to determine the association of CHTOP with apoptosis, while mammary sphere formation assay and IF were used to evaluate its regulation on EOC-cis cell stemness. Results: The higher expression of CHTOP was found in EOC-cis (A2780-cis and IGROV-1-cis) and metastatic EOC (SKOV-3 and OV-90) cells as compared to normal epithelial ovarian cells (HOSE) by IF and WB. Also, high expression of CHTOP was found in human EOC tissues and associated with poor prognosis in patients. In contrast, CHTOP KD significantly reduced the metastatic potential of EOC-cis cells and increased their apoptosis at the presence of cisplatin. Furthermore, CHTOP KD decreased the stemness of EOC-cis cells. Conclusion: Our findings suggest that CHTOP is associated with metastasis, apoptosis, and stemness in chemoresistant EOC cells, the survival in EOC patients, and might be a promising therapeutic target to overcome chemoresistance in EOC treatment. Keywords: ovarian cancer, chemoresistance, CHTOP, metastasis, apoptosis, stemness Citation Format: Xupeng Bai, Xiaojie Feng, Jie Ni, Julia Beretov, Junli Deng, Ying Zhu, Peter Graham, Yong Li. CHTOP is a novel therapeutic target for chemoresistant epithelial ovarian cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4754.
Abstract 12338: Measurement of Pulmonary and Systemic Blood Flow in Single Ventricle Patients by Cardiac Magnetic Resonance vs Cardiac Catheterization
Authors: Michael R Hart, Adam L Dorfman, Wendy Whiteside, Sunkyung Yu, Ray Lowery, Maryam Ghadimi Mahani, Prachi P Agarwal, Jimmy C Lu
Journal: Circulation (2018)

Background: Cardiac magnetic resonance (CMR) or cardiac catheterization (cath) may be used to assess patients with single ventricle physiology prior to stage II or Fontan palliation. However, these...
Unfolded protein response down-regulates MatrigelTM invasion of capillary endothelial cells
Authors: Maria Montiel, Uldaeliz Trujillo, Maria Milan, Subiman Saha, Dipak Banerjee
Journal: Cancer Research (2007)

3006  Angiogenesis is a ‘key’ to tumor growth and invasion. A large number of cytokines accelerate the process of angiogenesis by helping to control a switch in the angiogenic phenotype which enhances glycosylation of asparagine-linked (N-linked) glycoproteins. Our objective has been to understand the molecular basis of the angiogenic process so that appropriate glyco-therapeutics could be developed against the breast cancer. Using an antibiotic and a protein N-glycosylation inhibitor tunicamycin our laboratory has recently observed that a non-transformed capillary endothelial cell line when treated with tunicamycin the cell cycle was arrested in G1 and developed apoptosis by inducing unfolded protein response (upr). In addition, there was reduced expression of matrix metalloproteinase-1 (MMP1) in tunicamycin-treated cells. To test the hypothesis that tunicamycin inhibits endothelial cell invasion, a synchronized culture of capillary endothelial cells was seeded on growth factor reduced Matrigel™ coated plates and examined after 24 hours. We have used the conditioned media from MCF-7 human breast cancer cells as a chemoattractant. The results indicated that tunicamycin (1 μg/ml) inhibited the cell migration through the Matrigel™. Supported by NIH U54-CA096297 and the Susan G. Komen Breast Cancer Foundation BCTR58206 grants.
Predictors of oxaliplatin-induced hepatotoxicity: Increase in spleen volume or liver fibrosis and steatosis?
Authors: M. Kreidieh, A. El Chami, F. Haddadin, M. Al Darazi, M. Charafeddine, A. Haydar, N. Muallem, F. Ershaid, W. Faraj, M. Khalifeh, D. Mukherji, S. Temraz, H. Dbouk, A. Shamseddine
Journal: Annals of Oncology (2019)
FREEDOM: A phase 3b efficacy and safety study of fedratinib in intermediate- or high-risk myelofibrosis patients previously treated with ruxolitinib.
Authors: Srdan Verstovsek, Claire N. Harrison, Giovanni Barosi, Jean-Jacques Kiladjian, Daniela Buglio, Vincent Chia, Torsten Gerike, Valerie Jessent-Ciaravino, Joseph Mostillo, Jun Zhang, Ruben A. Mesa
Journal: Journal of Clinical Oncology (2019)

TPS7072 Background: Myelofibrosis (MF) is a serious life-threatening condition characterized by splenomegaly, constitutional symptoms, and shortened survival. Ruxolitinib (RUX) is currently the only approved drug for treatment (Tx) of Intermediate- (Int) or High-risk MF. RUX discontinuation rates are high, mainly due to lack of response, loss of efficacy, intolerance, and drug-induced cytopenias, resulting in an important unmet medical need for a JAK2 inhibitor that is effective after RUX failure. Fedratinib (FEDR) is an oral, JAK2-selective inhibitor that produces substantial spleen volume reduction (SVR) and improves constitutional symptoms as initial therapy of MF (Pardanani, 2015) and in pts resistant to or intolerant of RUX (Harrison, 2017). Methods: This multicenter, open-label, single-arm study (NCT03755518) is enrolling adult pts with primary, post-polycythemia vera, or post-essential thrombocythemia MF; Dynamic International Prognostic Scoring System (DIPSS) Int- or High-risk disease; splenomegaly; ECOG PS ≤2; and platelet counts ≥50 × 10 9 /L. Pts must have received prior RUX Tx for ≥3 mo or during ≥28 days of RUX therapy were RUX-intolerant (developed RBC transfusion dependence [≥2 units/mo for 2 mo] or grade ≥3 thrombocytopenia, anemia, hematoma/hemorrhage). Pts receive continuous FEDR 400 mg QD in 28-day cycles. Spleen volume is assessed by MRI/CT scan at screening, after cycles 3, 6, and 12, and at end of treatment. Primary endpoint is spleen response rate (RR; ≥35% SVR from BL by cycle 6 end). Secondary endpoints include duration of spleen RR, spleen size reduction, rate and duration of symptom response (≥50% reduction in total symptom score on the Myelofibrosis Symptom Assessment Form), and safety. Risk mitigation strategies for gastrointestinal adverse events and Wernicke encephalopathy are evaluated. Exploratory endpoints include survival, patient-reported outcomes, and biomarkers of FEDR efficacy and biochemical activity. The study will enroll ~110 pts. Assuming a spleen RR of 35%, the study will have ~90% power to detect the lower bound of the 95% CI that excludes 20%. Enrollment is ongoing. Clinical trial information: NCT03755518.
Abstract 4398: KDM3A and DCLK1 interactions promote stemness and tumorigenesis in PDAC
Authors: Chandrayee Ghosh, Kankaraj Palaniyandi, Santanu Paul, Prasad Dandawate, Sonia Rawal, Dharmalingam Subramaniam, Subhash Padhye, Sumedha Gunewardena, Sufi Thomas, Maura O'Neil, Roy Jensen, Danny Welch, Sally Milisky, Scott Weir, Tomoo Iwakuma, Shrikant Anant, Animesh Dhar
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the major leading cause of cancer related human death in USA. There is no possible treatment or target available in PDAC. It was proposed that the cancer stem cells (CSCs) can regulates malignancy in PDAC. DCLK1 is one of the quiescent cancer stem cell marker in PDAC that can regulate tumor progression. Identification of the key factors that influence stemness will help to target PDAC. Histone lysine demethylase KDM3A is an enzyme/protein which can regulate stem cell renewability and tumor progression, thereby KDM3A can interact with DCLK1 for tumor progression. KDM3A influences tumor growth and regulates stemness. Therefore, our goal is to find out the the role of KDM3A in tumor progression in PDAC through interactions with DCLK1. We observed expression of KDM3A in both PDAC patients’ samples and cells. Knockdown and overexpression of KDM3A were executed by using lentiviral vector. Tumor progression were also observed in orthotopic mice model. ChIP and RNA seq were performed to validate the data. KDM3A was overexpressed in human PDAC patient tissues and human pancreatic cancer cells with concomitant increase of CSC marker, DCLK1. Moreover, DCLK1 and KDM3A was found to be co-localized in patient tissue samples and identified binding sites of KDM3A with DCLK1 using ChIP-seq. Knockdown of KDM3A abrogates oncogenic potential whereas, overexpressed KDM3A in transformed HPNE cells showed malignant properties with enhanced invasive property, pancosphere formation, foci formation and tumor formation in mouse. Moreover, ChIP-seq and RNA seq suggested that KDM3A regulated DCLK1 expression in tumor progression. In conclusion, co-expression of DCLK1 with KDM3A influenced stemness and enhance tumor progression in PDAC. Citation Format: Chandrayee Ghosh, Kankaraj Palaniyandi, Santanu Paul, Prasad Dandawate, Sonia Rawal, Dharmalingam Subramaniam, Subhash Padhye, Sumedha Gunewardena, Sufi Thomas, Maura O'Neil, Roy Jensen, Danny Welch, Sally Milisky, Scott Weir, Tomoo Iwakuma, Shrikant Anant, Animesh Dhar. KDM3A and DCLK1 interactions promote stemness and tumorigenesis in PDAC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4398.
Tuberculosis following renal transplantation in England, Wales and Northern Ireland: a national registry-based cohort study
Authors: Rishi K. Gupta, Gabriel Rosenberg, Jaran Eriksen, Marc Lipman, Charlotte Jackson, Anjana Roy, Dominik Zenner, Colette Smith, Mark Harber, Colin Campbell, Ibrahim Abubakar
Journal: European Respiratory Journal (2019)

<b>Among a nationwide cohort of renal transplant recipients (n=30 433), TB incidence was highest in the first year post-transplant. Asian ethnicity and CMV seropositivity were independent risk factors for post-transplant TB</b>http://bit.ly/2YSVGt2
Treatment and mortality rates of older cancer patients with a body mass index &lt;20: Results from the IN-GHO registry.
Authors: Friedemann Honecker, Ulrich Wedding, Klaus Rettig, Susanne Huschens, Carsten Bokemeyer
Journal: Journal of Clinical Oncology (2012)

9114 Background: Older cancer patients (pts) compose a heterogeneous population. Data from clinical trials are limited, and little is known about treatment decisions and outcomes. The internet based IN-GHO registry prospectively collects data of cancer pts ≥ 70 years from &gt;100 centers in Germany and Austria. Methods: Data from 1.563 cancer pts were analysed, comparing results between pts with a body mass index (BMI) &lt;20 versus (vs) BMI ≥20 by Chi-square or Mann-Whitney U test. Analyses included results from a comprehensive geriatric assessment, physicians’ rating (fit vs compromised vs frail) and pts’ self rating of fitness for treatment (Likert scale 1= very fit to 6 = very unfit), type (combination vs. monotherapy vs no) and dosage of treatment (full vs adapted), as well as mortality within 5-7 months. Results: Mean BMI of the total cohort was 25.6. 119 (7.6%) pts had a BMI &lt;20. Low BMI showed a positive association with female sex, small height, higher age (classified), adapted dosage of treatment, lower number of comedication, lower ADL, IADL, and Karnofsky index scores, reduced mobility, and a lower mean MMSE score. More pts with BMI &lt;20 were judged compromised or frail, both by physicians’ or pts’ assessment (p&lt;0.001 and p=0.038, respectively). The risk of early mortality was 1.5 fold increased in pts with low BMI compared to pts with BMI ≥20 (35.3% vs 22.3%, p=0.002). Interestingly, none of the following showed an association with lower BMI: comorbidity, type (hematologic vs solid neoplasia), stage (metastatic vs non-metastatic), time since first diagnosis, decision to apply chemotherapy, and curative vs palliative intention of treatment. Conclusions: The internet based registry is useful to gain data on prognostic factors, treatment, and outcome in older cancer pts. Significant differences regarding dosage of treatment and incidence of early mortality were found between pts with BMI &lt;20 and pts with BMI ≥20. Elderly cancer pts with BMI &lt;20 should be considered a high risk population.
Abstract 3577: A p53-responsive long noncoding RNA GUARDIN is essential for genome integrity
Authors: Lei Jin, Wang Lai Hu, An Xu, Yu Fang Wang, Rick F. Thorne, Xu Dong Zhang, Mian Wu
Journal: Cancer Research (2019)

Abstract The list of long non-coding RNAs (lncRNAs) involved in the p53 pathway of the DNA damage response is rapidly expanding, but whether lncRNAs have a role in maintaining the de novo structure of DNA is unknown. Here, we demonstrate that the p53-responsive lncRNA GUARDIN is important for maintaining genomic integrity under steady-state conditions and after exposure to exogenous genotoxic stress. GUARDIN is necessary for preventing chromosome end-to-end fusion through maintaining the expression of telomeric repeat-binding factor 2 (TRF2) by sequestering microRNA-23a. Moreover, GUARDIN also sustains breast cancer 1 (BRCA1) stability by acting as an RNA scaffold to facilitate the heterodimerization of BRCA1 and BRCA1-associated RING domain protein 1 (BARD1). As such, GUARDIN silencing triggered apoptosis and senescence, enhanced cytotoxicity of additional genotoxic stress and inhibited cancer xenograft growth. Thus, GUARDIN may constitute a target for cancer treatment. Citation Format: Lei Jin, Wang Lai Hu, An Xu, Yu Fang Wang, Rick F. Thorne, Xu Dong Zhang, Mian Wu. A p53-responsive long noncoding RNA GUARDIN is essential for genome integrity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3577.
Association of Revised WIC Food Package With Perinatal and Birth Outcomes
Authors: Rita Hamad, Daniel F. Collin, Rebecca J. Baer, Laura L. Jelliffe-Pawlowski
Journal: JAMA Pediatrics (2019)

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) serves more than one-quarter of pregnant and postpartum women. In October 2009, the WIC food package underwent revisions to improve nutritional content. No studies have investigated the downstream effects of this revision on maternal and infant health.To investigate whether the revised WIC food package improved perinatal and birth outcomes among recipients.We conducted a quasi-experimental difference-in-differences analysis, comparing WIC recipients (the treatment group) before and after the package revisions while accounting for temporal trends among nonrecipients (the control group). Multivariable linear regressions were adjusted for sociodemographic covariates. This study was conducted using linked birth certificate and hospital discharge data from California from January 2007 to December 2012. Analysis began July 2018.Whether pregnant women received the revised WIC package, which included more whole grains, fruit, vegetables, and low-fat milk.Measures of maternal and infant health, including maternal preeclampsia, gestational diabetes, and gestational weight gain as well as infant gestational age, birth weight, and hospitalizations.The sample included 2 897 537 infants born to 2 441 658 mothers. WIC recipients were more likely to be Hispanic, less educated, of greater parity, and younger than nonrecipients. The revised WIC food package was associated with reductions in maternal preeclampsia (-0.6% points; 95% CI, -0.8 to -0.4) and more than recommended gestational weight gain (-3.2% points; 95% CI, -3.6 to -2.7), increased likelihood of as recommended (2.3% points; 95% CI, 1.8 to 2.8) and less than recommended (0.9% points; 95% CI, 0.5 to 1.2) gestational weight gain, and longer gestational age (0.2 weeks; 95% CI, 0.001 to 0.034). Among infants, an increased likelihood of birth weight that was appropriate for gestational age was observed (0.9% points; 95% CI, 0.5 to 1.3). Although birth weight itself was reduced (-0.009 SDs; 95% CI, -0.016 to -0.001), this was accompanied by reductions in small for gestational age (-0.4% points; 95% CI, -0.7 to -0.1), large for gestational age (-0.5% points; 95% CI, -0.8 to -0.2), and low-birth-weight infants (-0.2% points; 95% CI, -0.4 to -0.004), suggesting that the revised food package improved distributions of birth weight.The revised WIC food package, intended to improve women's nutrition during pregnancy, was associated with beneficial impacts on maternal and child health. This suggests that WIC policy may be an important lever to reduce health disparities among high-risk women and children at a critical juncture in the life course.
The Roel of High Dose Chemotherapy and Autologous Stem Cell Transplantation (ASCT) In PATIENTS with POEMS SYNDROME: A Retrospective study of the MM Subcommittee of the Chronic Leukemia Working Party of the EBMT,
Authors: Gordon Cook, Laurent Garderet, Anja van Biezen, Anja Henseler, Véronique Leblond, M Rovira, Dominique Bordessoule, Giuseppe Leone, Gert J Ossenkoppele, Jenny Byrne, Mark Cook, D Caballero, Theo M. de Witte, Curly TCM Morris
Journal: Blood (2011)