Regulation of FANCD2 by mTOR

Deregulation of the mTOR pathway is closely associated with tumorigenesis. Accordingly, mTOR inhibitors such as rapamycin and mTOR-selective kinase inhibitors have been tested as cancer therapeutic agents. Inhibition of mTOR results in sensitization to DNA-damaging agents; however, the molecular mechanism is not well understood. We found that an mTOR-selective kinase inhibitor, AZD8055, significantly enhanced sensitivity of a pediatric rhabdomyosarcoma xenograft to radiotherapy and sensitized rhabdomyosarcoma cells to the DNA interstrand cross-linker (ICL) melphalan. Sensitization correlated with drug-induced downregulation of a key component of the Fanconi anemia pathway, FANCD2 through mTOR regulation of FANCD2 gene transcripts via mTORC1-S6K1. Importantly, we show that FANCD2 is required for the proper activation of ATM-Chk2 checkpoint in response to ICL and that mTOR signaling promotes ICL-induced ATM-Chk2 checkpoint activation by sustaining FANCD2. In FANCD2-deficient lymphoblasts, FANCD2 is essential to suppress endogenous and induced DNA damage, and FANCD2-deficient cells showed impaired ATM-Chk2 and ATR-Chk1 activation, which was rescued by reintroduction of wild-type FANCD2. Pharmacologic inhibition of PI3K–mTOR–AKT pathway in Rh30 rhabdomyosarcoma cells attenuated ICL-induced activation of ATM, accompanied with the decrease of FANCD2. These data suggest that the mTOR pathway may promote the repair of DNA double-strand breaks by sustaining FANCD2 and prov...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Therapeutics, Targets, and Chemical Biology Source Type: research

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CONCLUSIONS: AI technologies are growing their role in health care; but, up to now, their "real-life" implementation remains limited. However, in the near future, the potential of AI-driven era could change the clinical practice in Urology, improving overall patient outcomes. PMID: 31833725 [PubMed - as supplied by publisher]
Source: Minerva Urologica e Nefrologica - Category: Urology & Nephrology Tags: Minerva Urol Nefrol Source Type: research
CONCLUSIONS: Our data show high adherence and persistence rates in men on ADT. The overall survival in the super-elderly is not influenced by persistence and/or adherence but rather by co-prescriptions. PMID: 31833723 [PubMed - as supplied by publisher]
Source: Minerva Urologica e Nefrologica - Category: Urology & Nephrology Tags: Minerva Urol Nefrol Source Type: research
CONCLUSIONS: ORP, ePLND and seminal vesicle invasion are independent predictors of the risk of hospital readmission over the long term at a large single tertiary referral center. When surgery is chosen as a primary treatment of PCA, patients should be informed of the risk of hospital readmission and related risk factors. Assessing seminal vesicle invasion by preoperative clinical staging identifies locally advanced disease, which is associated with an increased risk of hospital readmission. PMID: 31833722 [PubMed - as supplied by publisher]
Source: Minerva Urologica e Nefrologica - Category: Urology & Nephrology Tags: Minerva Urol Nefrol Source Type: research
Authors: Brassetti A, Anceschi U, Bertolo R, Ferriero M, Tuderti G, Capitanio U, Larcher A, Garisto J, Antonelli A, Mottire A, Minervini A, Dell'oglio P, Veccia A, Amparore D, Flammia RS, Mari A, Porpiglia F, Montorsi F, Kaouk J, Autorino R, Carini M, Gallucci M, Simone G Abstract BACKGROUND: To improve standard reporting of outcomes after partial nephrectomy, different "Trifecta" systems have been conceived. The subjective assessment of the included parameters and the unreliability for off-clamp procedures limited their reproducibility; their role in predicting functional and oncologic outcomes has never...
Source: Minerva Urologica e Nefrologica - Category: Urology & Nephrology Tags: Minerva Urol Nefrol Source Type: research
CONCLUSIONS: Long-term treatment with 5- ARIs might reduce the risk of bladder tumour recurrence, extension of lesions and increase the recurrence-free survival rate. A long-term, randomized prospective study could definitively assess the possible role of these drugs. PMID: 31833718 [PubMed - as supplied by publisher]
Source: Minerva Urologica e Nefrologica - Category: Urology & Nephrology Tags: Minerva Urol Nefrol Source Type: research
CONCLUSIONSĖ Follow-up schedules for stage I seminoma exposes patients to potential risks of radiation- induced tumors, emotional distress and represent a significant burden for the healthcare system. The current series suggests that a better risk adapted patient-tailored follow-up program is needed in order to avoid unnecessary investigations. PMID: 31833335 [PubMed - as supplied by publisher]
Source: Minerva Urologica e Nefrologica - Category: Urology & Nephrology Tags: Minerva Urol Nefrol Source Type: research
CONCLUSIONS: Three USP steroids resulted significantly altered in our PCa population. These preliminary results, combined with the simplicity and low-cost of the analysis, open to further investigation of the potential role of this restricted USP in PCa diagnosis. PMID: 31833333 [PubMed - as supplied by publisher]
Source: Minerva Urologica e Nefrologica - Category: Urology & Nephrology Tags: Minerva Urol Nefrol Source Type: research
Publication date: January 2020Source: The Annals of Thoracic Surgery, Volume 109, Issue 1Author(s): Francesco Nappi, Ivancarmine Gambardella
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Publication date: January 2020Source: The Annals of Thoracic Surgery, Volume 109, Issue 1Author(s): Safak Alpat, Keir A. Forgie, Isabelle VonderMuhll, Darren H. FreedAortico-left ventricular tunnel is a rare congenital anomaly requiring surgical repair early in childhood. After corrective surgery, such patients are at risk of developing aortic insufficiency and aortic root dilatation. Herein, we describe a valve-sparing aortic root replacement 3 decades after the repair of aortico-left ventricular tunnel.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
ConclusionsOccult nodal disease was frequently identified in peripheral N1 stations (11-13) in patients with small (≤2 cm) clinical N0 NSCLC. Hilar lymphadenectomy is essential for accurate staging in the management of patients with small clinical N0 NSCLC.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
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