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101.
Thais Basili Higinio Dopeso Sarah H. Kim Lorenzo Ferrando Fresia Pareja Arnaud Da Cruz Paula Edaise M. da Silva Anthe Stylianou Ana Maroldi Caterina Marchiò Brian P. Rubin Mauro Papotti Britta Weigelt Carlos Gil Moreira Ferreira José Roberto Lapa e Silva Jorge S. Reis-Filho 《International journal of cancer. Journal international du cancer》2020,147(8):2253-2264
Hyalinizing trabecular tumors of the thyroid are rare and mostly benign epithelial neoplasms of follicular cell origin, which have recently been shown to be underpinned by the PAX8-GLIS3 fusion gene. In our study, we sought to investigate the potential oncogenic mechanisms of the PAX8-GLIS3 fusion gene. Forced expression of PAX8-GLIS3 was found to increase proliferation, clonogenic potential and migration of human nonmalignant thyroid (Nthy-ori 3-1) and embryonic kidney (HEK-293) cells. Moreover, in xenografts, Nthy-ori 3-1 PAX8-GLIS3 expressing cells generated significantly larger and more proliferative tumors compared to controls. These oncogenic effects were found to be mediated through activation of the Sonic Hedgehog (SHH) pathway. Targeting of smoothened (SMO), a key protein in the SHH pathway, using the small molecule inhibitor Cyclopamine partially reversed the increased proliferation, colony formation and migration in PAX8-GLIS3 expressing cells. Our data demonstrate that the oncogenic effects of the PAX8-GLIS3 fusion gene are, at least in part, due to an increased activation of the SHH pathway. 相似文献
102.
103.
Renée T. Fortner Anika Hüsing Laure Dossus Anne Tjønneland Kim Overvad Christina C. Dahm Patrick Arveux Agnès Fournier Marina Kvaskoff Matthias B. Schulze Manuela Bergmann Antonia Trichopoulou Anna Karakatsani Carlo La Vecchia Giovanna Masala Valeria Pala Amalia Mattiello Rosario Tumino Fulvio Ricceri Carla H. van Gils Evelyn M. Monninkhof Catalina Bonet José Ramón Quirós Maria-Jose Sanchez Daniel-Ángel Rodríguez-Palacios Aurelio B Gurrea Pilar Amiano Naomi E. Allen Ruth C. Travis Marc J. Gunter Vivian Viallon Elisabete Weiderpass Elio Riboli Rudolf Kaaks 《International journal of cancer. Journal international du cancer》2020,147(5):1325-1333
Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m2), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m2) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks. 相似文献
104.
Fanconi anemia (FA) is a rare genetic disorder, characterized by birth defects, progressive bone marrow failure, and a predisposition to cancer. This devastating disease is caused by germline mutations in any one of the 22 known FA genes, where the gene products are primarily responsible for the resolution of DNA interstrand cross-links (ICLs), a type of DNA damage generally formed by cytotoxic chemotherapeutic agents. However, the identity of endogenous mutagens that generate DNA ICLs remains largely elusive. In addition, whether DNA ICLs are indeed the primary cause behind FA phenotypes is still a matter of debate. Recent genetic studies suggest that naturally occurring reactive aldehydes are a primary source of DNA damage in hematopoietic stem cells, implicating that they could play a role in genome instability and FA. Emerging lines of evidence indicate that the FA pathway constitutes a general surveillance mechanism for the genome by protecting against a variety of DNA replication stresses. Therefore, understanding the DNA repair signaling that is regulated by the FA pathway, and the types of DNA lesions underlying the FA pathophysiology is crucial for the treatment of FA and FA-associated cancers. Here, we review recent advances in our understanding of the relationship between reactive aldehydes, bone marrow dysfunction, and FA biology in the context of signaling pathways triggered during FA-mediated DNA repair and maintenance of the genomic integrity. Environ. Mol. Mutagen. 2020. © 2020 Wiley Periodicals, Inc. 相似文献
105.
Joanne E. Mortimer Laura Kruper Jae Jung Louise Wong Jill Cooper Daphne Stewart Samuel Chung Kim Wai Yu Sanjeet Dadwal Yuan Yuan 《Cancer chemotherapy and pharmacology》2020,85(3):501-507
We update a patient series that reported a high incidence of infection with Gram-positive cocci in women treated with the combination of pertuzumab and trastuzumab and further characterize this clinical problem.
Treating physicians and advanced practice partners identified women who developed infections while on treatment with pertuzumab and trastuzumab alone or in combination with chemotherapy and enrolled them onto this registry trial. Between March, 2014 and May, 2017, 48 patients with HER2-positive breast cancers were reported to have 59 individual infections. The median age was 48 years. Twenty-four patients received neoadjuvant therapy, 17 were treated for metastatic disease, and 7 were treated in the adjuvant setting. Pertuzumab and trastuzumab were combined with carboplatin and docetaxel in 24 (49%) patients, docetaxel in 10 (21%), nab-paclitaxel in 12 (24%), and without other agents in 2 (4%). Granulocyte growth factors were administered in 24 (49%) patients and no patients were documented to be neutropenic. Folliculitis developed in 25 (52%) patients and was counted as a single infection. Abscesses developed at a number of sites in 24 (49%) patients, including a septic knee requiring total knee replacement. Paronychia occurred in 7 (15%) patients, and 5 (10%) developed cellulitis. When cultures were obtained, Gram-positive cocci were consistently identified. Hypogammaglobulinemia was documented in 14 (36%) of the 33 patients tested. Our data continue to support an increased risk of infections with Gram-positive cocci as a potentially serious adverse event in women treated with pertuzumab and trastuzumab. 相似文献
106.
Harinakshi Sanikini David C. Muller Marisa Sophiea Sabina Rinaldi Antonio Agudo Eric J. Duell Elisabete Weiderpass Kim Overvad Anne Tjønneland Jytte Halkjær Marie-Christine Boutron-Ruault Franck Carbonnel Iris Cervenka Heiner Boeing Rudolf Kaaks Tilman Kühn Antonia Trichopoulou Georgia Martimianaki Anna Karakatsani Valeria Pala Domenico Palli Amalia Mattiello Rosario Tumino Carlotta Sacerdote Guri Skeie Charlotta Rylander María-Dolores Chirlaque López Maria-Jose Sánchez Eva Ardanaz Sara Regnér Tanja Stocks Bas Bueno-de-Mesquita Roel C.H. Vermeulen Dagfinn Aune Tammy Y.N. Tong Nathalie Kliemann Neil Murphy Marc Chadeau-Hyam Marc J. Gunter Amanda J. Cross 《International journal of cancer. Journal international du cancer》2020,146(4):929-942
Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers. 相似文献
107.
108.
Won-Ju Park Soo-Hyeon Kim WonYang Kang Ji-Sung Ahn Seunghyeon Cho Dae-Young Lim 《Archives of environmental & occupational health》2020,75(6):333-338
Abstract The aim of this study was to investigate whether elevated blood lead level (BLL) is a risk factor for Helicobacter pylori infection. Upper gastrointestinal endoscopy was performed on 2,625 subjects who visited a university hospital for general health examination. H. pylori infection was detected using histologic examination with Giemsa staining, and BLLs were measured. The mean BLL was 2.83?±?1.31?μg/dL. The prevalence of H. pylori infection was 27.8%. The BLL was significantly higher in the H. pylori infection-positive group compared to the non-infected group (2.96?±?1.33?μg/dL vs. 2.78?±?1.30?μg/dL, p?<?0.001), which remained significant after adjusting for other confounders. H. pylori infection significantly increased as the BLL increased (OR: 1.143, 95% CI 1.068–1.223). We found a relationship between BLL elevation and H. pylori infection rate. 相似文献
109.
School Mental Health - Growing evidence suggests that exposure to early-life adversity poses risk to youth development, with impaired mental health a central concern. This population-representative... 相似文献
110.
Kim Chae-Yong Paek Sun Ha Nam Do-hyun Chang Jong-Hee Hong Yong-Kil Kim Jeong Hoon Kim Oh Lyong Kim Se-Hyuk 《Journal of neuro-oncology》2020,146(3):399-406
Journal of Neuro-Oncology - Tumor treating fields (TTFields) are anti-mitotic, non-invasive loco-regional cancer therapy comprising low intensity, intermediate frequency alternating electric... 相似文献