tbuckley/cabot-search huggingface dataset:
Differential effects of light at night and shift rotation pattern on the circadian system in night workers.
Authors: Pedram Razavi, Eva S Schernhammer
Journal: Journal of Clinical Oncology (2012)

1556 Background: Light at night as in shift work suppresses nocturnal secretion of melatonin, a pineal hormone with oncostatic properties. Several studies have associated night shift work with higher risk of cancer, leading WHO in 2007 to classify rotating night shift work as “probably carcinogenic”. We conducted one of the most comprehensive studies, to date, to evaluate the effects of light and night shift work on melatonin measurements in the field. Methods: Study participants were 130 active nurses (84 current rotating night shift workers and 46 day shift workers) participating in NHS2. Each nurse wore a head-mounted light- and accelerometer for a 3-day study period, during which each spontaneous urine was collected for repeated urinary 6-sulfatoxymelatonin (melatonin) measurements. In addition, nurses were asked to fill out paper questionnaires and diaries. We used mixed models to evaluate the influence of light, activity and night shift work on urinary melatonin level adjusting, for age, lifestyle, and occupational history. We log-transformed main variables and report geometric means (GM [standard deviation]). Results: Greater levels of light were associated with lower melatonin (P &lt; 0.0001), independent of activity level. An increase in light intensity from 10 to 100 lux was associated with a 12% decrease in geometric mean of melatonin level; however, this inverse association was only significant at night (P trend = 0.01). At night, each hour increase in exposure to ≥ 20 lux light lowered melatonin level by 5.7% (P trend &lt; 0.0001). A single night shift affected the circadian system by lowering melatonin peak by 22% (day shift: GM = 17.57 [2.73]; night shift: GM = 13.64 [2.54]) and induced a phase shift (PS) of 0.9 hours, -changes that reset to normal by the next day. Two consecutive night shifts had a similar effect as a single shift. However, the effect was worse after three consecutive night shifts (GM = 10.11 [2.77]; PS = 2.2 hours). Conclusions: We found significant inverse associations of intensity and duration of exposure to light at night with urinary melatonin, independent of activity level. Three consecutive night shifts affected the circadian system more strongly than two consecutive, or a single night shift.
Abstract P104: Dietary Polychlorinated biphenyls and Long-chain Omega-3 Fish fatty acids Exposures and Risk of Heart Failure
Authors: Maria Kippler, Carolina Donat Vargas, Marika Berglund, Anders Glynn, Alicja Wolk, Agneta Åkesson
Journal: Circulation (2018)

The potential beneficial effects of fish consumption on heart failure (HF) may be modified by major food contaminants in fish. Polychlorinated biphenyls (PCBs) in particular, have been associated with well-established risk factors of HF such as coronary heart disease, hypertension, and diabetes. Likewise, experimental and cross-sectional studies in humans suggest that PCB exposure may be involved in the development of HF. We aimed to assess the association of both dietary PCB and long-chain omega-3 fish fatty acids exposures with risk of HF in two large population-based prospective cohorts. We used the Swedish Mammography Cohort and the Cohort of Swedish Men, comprising 32,867 women and 36,545 men, free of cancer, heart failure, myocardial infarction and diabetes at baseline in 1997. A questionnaire on diet (96-food items) and lifestyle factors was completed at baseline. We calculated validated estimates of dietary PCB exposure and intake of long-chain omega-3 fish fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. First incident cases of HF were ascertained through computerized linkage to the National Patient Register and the Cause of Death Register, defined as hospitalizations for (listed as the primary diagnosis) or death from HF. We use multivariable-adjusted Cox regression to estimate hazard ratio (HR) and its 95% confidence interval (CI), by quintiles of dietary PCB and EPA/DHA and controlling for known HF risk factors. During an average of 12 years of follow-up, 1,263 and 1,606 first incident cases of HF were ascertained in women and men, respectively. In multivariable-adjusted models, we observed no association between dietary PCB exposure or EPA/DHA intake and risk of HF. However, after additional mutual adjustments for PCBs and EPA/DHA, HRs for dietary PCB exposure were 1.60 (95% CI, 1.08-2.38) among women and 1.40 (95% CI, 0.97-2.02) among men, comparing extreme quintiles. The corresponding HRs for EPA/DHA intake were 0.62 (95% CI, 0.42-0.92) and 0.79 (95% CI, 0.55-1.13), respectively. Dietary exposure to PCBs was associated with an increased risk of HF in women, while EPA/DHA intake was associated with a lower risk of HF. Results for men was less evident but showed a similar trend. The results provide important information regarding the risk-benefit analysis of fish consumption, especially in cardiovascular disease prevention.
Abstract 12804: HIF-1a/HuR Pathway Regulates the Increased Expression of PAI-1 Induced by Sphingosine 1-phosphate in HepG2 Cells Rendered Hypoxic: A Novel Linkage between Thrombosis and Hypoxia
Authors: Akimasa Sanagawa, Soichiro Iwaki, Moyoko Asai, Daisuke Sakakibara, Hiroaki Norimoto, Satoshi Fujii
Journal: Circulation (2013)

Hypoxia is a prothrombotic risk. The mechanisms are not fully described. We have recently shown that in human HepG2 liver cell line sphingosine 1-phosphate (S1P), a bioactive lipid richly endowed in platelets and released upon activation, increases transcription of plasminogen activator inhibitor type-1 (PAI-1), the physiologic inhibitor of fibrinolysis, within 4 hours. In this study we elucidated the molecular mechanisms responsible. S1P (500 nM) increased PAI-1 promoter activity by 2 fold (luciferase assay). Hypoxia and S1P had additive effects and increased PAI-1 promoter activity by 10 fold. S1P did not increase the activity of promoters lacking the hypoxia responsive element (HRE) 2. S1P transiently increased the concentration of hypoxia inducible factor (HIF)-1α, a transcriptional factor capable of binding to HRE (Western blot). When HIF-1α was knocked down by siRNA, the induction of transcription of PAI-1 by S1P was no longer observed, suggesting that S1P and hypoxia increase PAI-1 in relation to H...
Kinetics of the accumulation of group 2 innate lymphoid cells in IL-33-induced and IL-25-induced murine models of asthma: a potential role for the chemokine CXCL16
Authors: Yan Li, Shihao Chen, Yafei Chi, Yiran Yang, Xiwen Chen, Huating Wang, Zhe Lv, Jingjing Wang, Linjie Yuan, Ping Huang, Kewu Huang, Chris J. Corrigan, Wei Wang, Sun Ying
Journal: Cellular and Molecular Immunology (2018)
Abstract 17242: Human Leukocyte Antigen-G Polymorphisms Association to Post Heart Transplant Cardiac Allograft Vasculopathy
Authors: Julieta Lazarte, Livia Goldraich, Cedric Manlhiot, Hiroyuki Kawajiri, Liza Grosman-Rimon, Arash Ghashghai, Vivek Rao, Diego Delgado
Journal: Circulation (2015)

Introduction: Human Leukocyte Antigen (HLA)-G is an immune inhibitor molecule that has been shown to inhibit smooth muscle cell proliferation in vitro and promote vasculature protection against cardiac allograft vasculopathy (CAV). Single polymorphism nucleotides (SNPs) throughout the gene influence the expression of HLA-G. The association between HLA-G SNPs in heart transplant recipients or donors and CAV remains unclear. Objective: To determine the association between HLA-G SNPs from recipient and donor and severe CAV post heart transplant. Methods: Retrospective cohort in which 251 adult heart transplant recipients and 196 matching donors were evaluated for various HLA-G SNPs. The recipients were screened for CAV according to institutional protocol. Coronary angiographies were graded according to the International Society for Heart and Lung Transplantation classification and severe CAV was defined as 2/3 categories. DNA was genotyped for SNPs 5’ URR 201, 3’ UTR 3196, 3187, 3142 and 14bp INDEL using the Sequenom MassARRAY Platform. The association of genotypes and diagnosis of severe CAV were evaluated in parametric hazard regression model. Results: General characteristics: recipient age 48±12 years, 69% males and donor age 35±14 years. Over a median follow-up of 6 years, 20 (8%) recipients were diagnosed with severe CAV. In multivariable analysis adjusting for donor age, donor cause of death and pre-transplant creatinine, the presence of donor SNP 201 (CC vs TT/TC) was associated with increased risk for severe CAV (HR 5.29; CI 1.70-16.20; p= 0.004), as well as donor SNP 3142 (GG vs CG/CC) was associated (HR 10.05; CI 1.40-71.65; p&lt; 0.02). Furthermore, matching between recipient and donor genotypes at SNP 201 was also associated with increased risk (HR 7.50; CI 2.50-22.39; p&lt; 0.001). Conclusions: Donor HLA-G SNPs 3142/201 and recipient/donor genotype matching for SNP 201 were independent risk factors for the diagnosis of severe CAV. This is the first investigation to identify an association between the HLA-G SNPs mentioned and CAV diagnosis. This association suggests that differences in HLA-G polymorphisms constitute a pathogenic pathway to be explored for potential enhancement of diagnostic, preventive and therapeutic strategies for CAV.
Upfront Combination Therapy, Compared With Monotherapy, for Patients Not Previously Treated With a Biologic Agent Associates With Reduced Risk of Inflammatory Bowel Disease-related Complications in a Population-based Cohort Study
Authors: Laura E. Targownik, Eric I. Benchimol, Charles N. Bernstein, Harminder Singh, Lisa Lix, Aruni Tennakoon, Stella Leung, Antonio Aviña, Stephanie Coward, Jennifer Jones, Gil Kaplan, Sanjay K. Murthy, Geoffrey C. Nguyen, Juan Nicolás Peña-Sánchez
Journal: Clinical Gastroenterology and Hepatology (2018)
Coenzyme Q10: A novel bcl-2 drug target for the treatment of melanoma
Authors: Niven R. Narain, Indushekhar Persaud, Kathryn J. Russell, Karrune V. Woan, Lindsey H. Malik, Carlos A. Ricotti, Mehdi Nassiri, Antoni Barrientos, Sung L. Hsia
Journal: Cancer Research (2006)

791  Melanoma is the deadliest form of skin cancer and severely affects quality of life. Drug development in cancer has been hampered by a lack of viable drug targets. However, the bcl-2 protein family has become an attractive target in oncology given that it reduces the efficacy of chemotherapeutic drugs by conferring tumor resistance to treatment and preventing apoptosis. Coenzyme Q10 is a naturally occurring molecule mostly resident in the mitochondrial and plasma membranes. Moreover, it is a potent antioxidant, key mediator in oxidative phosphorylation, and stabilizes biological membranes. Recent data from our laboratory has suggested that Coenzyme Q10 selectively induces apoptosis and attenuates tumor angiogenesis in melanoma while leaving normal cells unaffected. Thus, we investigated the effect of Coenzyme Q10 on bcl-2 expression in melanoma using western blot and microarray analysis. The results showed that gene expression of livin and survivin and bcl-2 protein levels were significantly downregulated after 24 hours of treatment with 50μM Coenzyme Q10. In addition, we compared the effect on neonatal fibroblasts. These data revealed that bcl-2 levels were not significantly altered and gene expression of livin and survivin increased in fibroblasts. Taken together, the data suggest that Coenzyme Q10 modulates bcl-2 levels and expression of livin and survivin in a manner that supports the restoration of the apoptotic potential in melanoma whereas it does not negatively impact the metabolism of normal skin cells. Hence, the results herein implies that Coenzyme Q10 induces an anti-oncogenic effect by targeting the bcl-2 protein family and supports its use in the treatment of cutaneous malignacies.
Abstract 20165: Long-term Clinical Outcomes and Optimal Stent Strategy in Left Main Coronary Bifurcation: Result From the KOMATE and COBIS II Registries
Authors: Sungsoo Cho, Tae Soo Kang, Jung-Sun Kim, Sung-Jin Hong, Dong-Ho Shin, Chul-Min Ahn, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Young Bin Song, Joo-Yong Hahn, Seung-Hyuk Choi, Hyeon-Cheol Gwon, Myeong-Ki Hong, Yangsoo Jang
Journal: Circulation (2017)

Introduction: Limited data are available to assess the long-term clinical outcomes after stenting including C-DES in LMCA bifurcation lesion. Hypothesis: This study sought to investigate the long-t...
RIP1 Kinase Drives Macrophage-Mediated Adaptive Immune Tolerance in Pancreatic Cancer
Authors: Wei Wang, Jill M. Marinis, Allison M. Beal, Shivraj Savadkar, Yue Wu, Mohammed Khan, Pardeep S. Taunk, Nan Wu, Wenyu Su, Jingjing Wu, Aarif Ahsan, Emma Kurz, Ting Chen, Inedouye Yaboh, Fei Li, Johana Gutierrez, Brian Diskin, Mautin Hundeyin, Michael Reilly, John D. Lich, Philip A. Harris, Mukesh K. Mahajan, James H. Thorpe, Pamela Nassau, Julie E. Mosley, Joshua Leinwand, Juan A. Kochen Rossi, Ankita Mishra, Berk Aykut, Michael Glacken, Atsuo Ochi, Narendra Verma, Jacqueline I. Kim, Varshini Vasudevaraja, Dennis Adeegbe, Christina Almonte, Ece Bagdatlioglu, Deirdre J. Cohen, Kwok-Kin Wong, John Bertin, George Miller
Journal: Cancer Cell (2018)
Cancer in pregnancy: To treat or not?
Authors: Elaine Walsh, Grainne O'Kane, Karen Anne Cadoo, Donna M. Graham, Grzegorz Korpanty, Derek Gerard Power, Desmond Carney
Journal: Journal of Clinical Oncology (2013)

e12533 Background: Cancer in pregnancy accounts for ~1 in 1,000 pregnancies. Studies show that cytotoxic agents are safe from the second trimester. Long-term follow up has not shown increased malformations or malignancies in children exposed to chemotherapy in utero. There is no evidence of worse outcomes among women diagnosed in pregnancy. Methods: We retrospectively identified women diagnosed with cancer in pregnancy over a 25-year period. Medical records were reviewed for demographics, diagnosis, gestation, timing of treatment and outcomes. We assessed if all cancers need to be treated in pregnancy or if treatment could be safely deferred to allow normal delivery. Results: Twenty-five women were diagnosed with cancer in pregnancy and referred to medical oncology. Of 25 women, 16 (64%) received chemotherapy during pregnancy. These included 13 cases of breast cancer, one Ewing’s sarcoma, one ovarian cancer, and one small cell of cervix. All 16 women received doxorubicin and cyclophosphamide. There were 15 live births and no abnormalities seen in children who received chemotherapy in utero. At a median follow-up of 6 years 11 mothers (69%) are disease free and 4 (25%) have recurrent disease. Of nine mothers who did not receive chemotherapy in pregnancy, seven received chemotherapy immediately post-partum. Six (86%) were diagnosed in early pregnancy (median gestation 13 weeks). There were three cases of Hodgkin lymphoma, two breast cancers, and one ovarian cancer. At a median follow-up of 12 years, all mothers remain disease free. There were no abnormalities seen in these children. Conclusions: We did not identify any adverse outcomes in mothers or infants exposed to chemotherapy during pregnancy. We identified a cohort of patients that do not need immediate treatment during pregnancy. In selected cases, it is safe and appropriate to delay chemotherapy until delivery of the baby. There were no adverse outcomes to mothers due to delayed treatment and no adverse outcomes to babies not exposed to chemotherapy in utero. A multi-disciplinary team is essential to individualize treatment planning. [Table: see text]
Diagnosis and Management of High-Risk Breast Lesions
Authors: Parijatham S. Thomas
Journal: Journal of the National Comprehensive Cancer Network (2018)

Atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) are nonmalignant breast lesions that confer a 4- to 10-fold increased risk for breast cancer in women. Often, AH and LCIS are diagnosed through breast biopsy due to a mammographic or palpable finding. Although AH and LCIS are benign breast disease, further management is necessary due to their high-risk nature and premalignant potential. Over the decades, management of AH and LCIS has changed as more is learned about these disease processes. This review explores the studies evaluating the risk for breast cancer in women with AH or LCIS and the clinical management of these lesions, which can include a combination of surgical excision, surveillance, and risk-reduction therapy.
Knowledge, attitudes, and behaviors toward skin cancer among marine fisheries students of Udayana University, Bali
Authors: S.A.A. Suryantari, A.B.S. Satyarsa, I.G.A.T. Indriani, P. Sudarsa, L.M.M. Rusyati, M.S. Adiguna
Journal: Annals of Oncology (2018)
OP0017 The impact of the duration of bisphosphonate drug holidays on hip fracture rates
Authors: J.R. Curtis, R. Chen, Z. Li, T. Arora, K.G. Saag, N.C. Wright, S. Daigle, M. Kilgore, E. Delzell
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Given FDA warnings, drug holidays (temporary or permanent discontinuation) of bisphosphonates (BPs) after long-term (3–5 years) continuous therapy is becoming increasingly common in the United States (US). However, the benefits and risks of stopping BPs, and the optimal timing to restart, remain unclear. <h3>Objectives</h3> We conducted a population-based cohort study of women on long term BP therapy to evaluate the rate of hip fracture following a drug holiday. <h3>Methods</h3> We used Medicare data (2006–2014) to identify all women with medical and pharmacy coverage who initiated a BP and were at least 80% adherent for ≥3 years ('baseline'), at which follow-up time began. Patients using other bone therapies (e.g. denosumab, oestrogen, teriparatide, calcitonin) were excluded or censored if they started after follow-up began. We calculated crude rates of hip fracture for continuing BP therapy and among those who discontinued, for categories of time since discontinuing (i.e., length of drug holiday), extending up to 3 years. We used Cox proportional hazards models to evaluate the risk of discontinuing per the length of the drug holiday, using age as the time axis and controlling for potentially confounding factors, with and without adjusting for death as a competing risk. <h3>Results</h3> We identified 1 56 236 women who were highly adherent, long-term BP users. The mean (SD) age was 78.5 (7.5) years. The most commonly used BPs were alendronate (71.7% ever use, 52% exclusive use) and zoledronic acid (16.2% ever use, 8.9% exclusive use). During a median (IQR) followup of 2.1 (1.0, 3.3) years, 62 676 (40.1%) of women stopped BP therapy for at least 6 months or more. Among these women, 7947 (12.7%) subsequently restarted any BP. Overall, 16 904 (10.8%) died. A total of 3745 hip fractures occurred during follow-up. Hip fracture rates were lowest among women who were current users, and gradually increased as the length of the drug holiday increased, achieving their maximum with a drug holiday &gt;2 years (table 1). <h3>Conclusions</h3> In a large cohort of U.S. women, a BP drug holiday greater than 2 years was associated with a significantly increased risk for hip fracture of up to 39% compared to continued BP use. <h3>Disclosure of Interest</h3> J. Curtis Grant/research support from: AbbVie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, R. Chen Grant/research support from: Amgen, Z. Li Grant/research support from: Amgen, T. Arora Grant/research support from: Amgen, K. Saag Grant/research support from: Amgen, Merck, Consultant for: Amgen, Merck, Radius, N. Wright: None declared, S. Daigle: None declared, M. Kilgore Grant/research support from: Amgen, E. Delzell: None declared
Bac, Bak-associated apoptosis-activated channel: A new channel involved in apoptosis detected by patch clamping mitochondria
Authors: Pascal Berson, Martina Prochazkova, Francois Ichas, Pierre Vacher
Journal: Cancer Research (2008)

1559   The aim of our research is to identify intracellular cascades causing apoptosis as well as key molecular mechanisms controlling these cascades.  A key early event in the apoptotic cascade in many cell types is the release of cytochrome c and other proapoptotic factors from mitochondria. This event is strictly controlled by oncogenes of the Bax/Bcl2 family, involved in 50% of cancers. The pro-apoptotic members bax and bak of this family, once activation and oligomerisation, would act by forming clusters that destabilize the permeability barrier of the mitochondrial outer membrane (MOM). Actived Bax alone can form in vitro - in artificial membrane- channels allowing the exit of cytochrome c (MAC channel) (Dejean et al, Mol Biol Cell, 2005). Although it has been shown that Bak is also required for MOM permeabilisation, it is still controversial whether Bax and Bak act in a unique and distinct manner or whether they merely exhibit redundant roles. Furthermore, the sizes of the pores formed by these proteins have not been determined by direct measurements in isolated mitochondria.  The improvement of patch clamp technique in “attached mitochondria” configuration enabled us to study, for the first time, the unit activity of MOM channels in intact mitochondria. In order to differentiate the role between Bax and Bak we used Human colon cancer Bax +/- and bax -/- HCT116 cell lines. This technique allowed us to:   1.  establish an inventory of the MOM channel population and to characterize these channels,   2.  identify and characterize on a unit scale a new channel involved in apoptosis, associated to the pro-apoptotic bak protein, and allowing cytochrome c release: BAC channel for Bak-associated Apoptosis-activated Channel. This enables to differentiate Bax from Bak as they form distinct channels,   3.  observe and characterize a new channel activity which differs from MAC channel only by its lower unit conductance and by its earlier appearance after apoptotic induction. We called this channel babyMAC, it would correspond to the early bax relocalisation phase to the MOM, whereas MAC would be due to the later bax oligomerisation phase.  These observations enable to understand the mechanisms by which the proteins Bax and Bak act into the MOM. The formation of bax- or bak- dependent high conductance channels seems to be the key event that induces the release of the pro-apoptotic factors. MAC, BAC and baby MAC, as they are involved in apoptosis signalling, represents potential therapeutic targets.
Solving the Silence
Authors: Olivia J. Killeen, Laura Bridges
Journal: JAMA (2018)

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The study of RET rearrangement in advanced primary non-small cell lung cancer and associated metastatic lesions
Authors: W.-X. Wang, C. Xu, Q.-X. Zhang, W. Zhuang, Y.-W. Tian, J. Zhang, M.-Y. Fang, Y.-P. Chen, G. Chen, T.-F. Lv, Y. Song
Journal: Annals of Oncology (2018)