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Dinja T. Kruger Xanthippi Alexi Mark Opdam Karianne Schuurman Leonie Voorwerk Joyce Sanders Vincent van der Noort Epie Boven Wilbert Zwart Sabine C. Linn 《International journal of cancer. Journal international du cancer》2020,146(8):2348-2359
Preclinical studies indicate that activated IGF-1R can drive endocrine resistance in ER-positive (ER+) breast cancer, but its clinical relevance is unknown. We studied the effect of IGF-1R signaling on tamoxifen benefit in patients and we searched for approaches to overcome IGF-1R-mediated tamoxifen failure in cell lines. Primary tumor blocks from postmenopausal ER+ breast cancer patients randomized between adjuvant tamoxifen versus nil were recollected. Immunohistochemistry for IGF-1R, p-IGF-1R/InsR, p-ERα(Ser118), p-ERα(Ser167) and PI3K/MAPK pathway proteins was performed. Multivariate Cox models were employed to assess tamoxifen efficacy. The association between p-IGF-1R/InsR and PI3K/MAPK pathway activation in MCF-7 and T47D cells was analyzed with Western blots. Cell proliferation experiments were performed under various growth-stimulating and -inhibiting conditions. Patients with ER+, IGF-1R-positive breast cancer without p-IGF-1R/InsR staining (n = 242) had tamoxifen benefit (HR 0.41, p = 0.0038), while the results for p-IGF-1R/InsR-positive patients (n = 125) were not significant (HR 0.95, p = 0.3). High p-ERα(Ser118) or p-ERα(Ser167) expression was associated with less tamoxifen benefit. In MCF-7 cells, IGF-1R stimulation increased phosphorylation of PI3K/MAPK proteins and ERα(Ser167) regardless of IGF-1R overexpression. This could be abrogated by the dual IGF-1R/InsR inhibitor linsitinib, but not by the IGF-IR-selective antibody 1H7. In MCF-7 and T47D cells, stimulation of the IGF-1R/InsR pathway resulted in cell proliferation regardless of tamoxifen. Abrogation of cell growth was regained by addition of linsitinib. In conclusion, p-IGF-1R/InsR positivity in ER+ breast cancer is associated with reduced benefit from adjuvant tamoxifen in postmenopausal patients. In cell lines, stimulation rather than overexpression of IGF-1R is driving tamoxifen resistance to be abrogated by linsitinib. 相似文献
97.
Deborah N. N. Lo‐Fo‐Wong Hanneke C. J. M. de Haes Neil K. Aaronson Doris L. van Abbema Mathilda D. den Boer Marjan van Hezewijk Marcelle Immink Ad A. Kaptein Marian B. E. Menke‐Pluijmers Anna K. L. Reyners Nicola S. Russell Manon Schriek Sieta Sijtsema Geertjan van Tienhoven Mathilde G. E. Verdam Mirjam A. G. Sprangers 《Psycho-oncology》2020,29(3):539-549
98.
Ann Marie Szymanski Blachy Dvila Saldaa Carlos R. Ferreira Brett Loechelt Lawrence Jung 《Pediatric transplantation》2020,24(1)
MA is a rare, autosomal recessive disorder characterized by episodes of inflammation and periodic fevers. In its most severe form, it can result in facial dysmorphism, growth inhibition, ataxia, liver dysfunction, intellectual disability, and at times can be fatal. A number of case reports exist stating that SCT is curative in these patients. We present the case of a patient diagnosed with MA at birth, who underwent SCT at the age of 14 months with intent to cure. She achieved complete engraftment and urine mevalonate became undetectable. However, 18 months following transplant, she developed frequent episodes of fevers, rashes, arthritis, and a rising urinary mevalonate. She was subsequently diagnosed with relapse. She now requires treatment with steroids and canakinumab to manage her disease. This case is the first report of disease relapse following transplant for MA. It runs contrary to prior reports that SCT is fully curative of MA and suggests that transplant may instead provide a means of decreasing disease severity without entirely eradicating the condition. 相似文献
99.
Anita van de Munckhof Katarzyna Krzywicka Diana Aguiar de Sousa Mayte Snchez van Kammen Mirjam R. Heldner Katarina Jood Erik Lindgren Turgut Tatlisumak Jukka Putaala Johanna A. Kremer Hovinga Saskia Middeldorp Marcel Levi Marcel Arnold Jos M. Ferro Jonathan M. Coutinho 《European journal of neurology》2022,29(1):339-344
100.
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