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Rosa Della Monica Mariella Cuomo Roberta Visconti Annabella di Mauro Michela Buonaiuto Davide Costabile Giulia De Riso Teodolinda Di Risi Elia Guadagno Roberto Tafuto Sabrina Lamia Alessandro Ottaiano Paolo Cappabianca Maria Laura Del Basso de Caro Fabiana Tatangelo Juergen Hench Stephan Frank Salvatore Tafuto Lorenzo Chiariotti 《Oncology research》2020,28(9):837-845
Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches.
Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response
rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation
status of the MGMT gene, as its product, O6
-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we
have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two
different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma
management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing
and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT
methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results,
we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation
status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs. 相似文献
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Marie Warrer Petersen Tine Sylvest Meyhoff Marie Helleberg Maj-Brit Nørregaard Kjær Anders Granholm Carl Johan Steensen Hjortsø Thomas Steen Jensen Morten Hylander Møller Peter Buhl Hjortrup Mik Wetterslev Gitte Kingo Vesterlund Lene Russell Vibeke Lind Jørgensen Klaus Tjelle Thomas Benfield Charlotte Suppli Ulrik Anne Sofie Andreasen Thomas Mohr Morten H. Bestle Lone Musaeus Poulsen Mette Friberg Hitz Thomas Hildebrandt Lene Surland Knudsen Anders Møller Christoffer Grant Sølling Anne Craveiro Brøchner Bodil Steen Rasmussen Henrik Nielsen Steffen Christensen Thomas Strøm Maria Cronhjort Rebecka Rubenson Wahlin Stephan Jakob Luca Cioccari Balasubramanian Venkatesh Naomi Hammond Vivekanand Jha Sheila Nainan Myatra Christian Gluud Theis Lange Anders Perner 《Acta anaesthesiologica Scandinavica》2020,64(9):1365-1375
Introduction
Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.Methods
The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.Discussion
The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.85.
Darren R. Feldman MD Yasser Ged MBBS Chung-Han Lee PhD Andrea Knezevic MS Ana M. Molina MD Ying-Bei Chen PhD Joshua Chaim DO Devyn T. Coskey MS Samuel Murray MS Satish K. Tickoo MD Victor E. Reuter MD Sujata Patil PhD Han Xiao MD Jahan Aghalar MD Arlyn J. Apollo MD Maria I. Carlo MD Robert J. Motzer MD Martin H. Voss MD 《Cancer》2020,126(24):5247-5255
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Jens Henrik Norum Oliver Frings Maria Kasper Helga Bergholtz Helene Zell Thime Åsa Bergström Agneta Andersson Raoul Kuiper Erik Fredlund Therese Sørlie Rune Toftgård 《International journal of cancer. Journal international du cancer》2020,146(4):1125-1138
Increased expression of GLI1, the main Hedgehog signalling pathway effector, is related to unfavourable prognosis and progressive disease of certain breast cancer subtypes. We used conditional transgenic mice induced to overexpress GLI1 in the mammary epithelium either alone or in combination with deletion of one Trp53 allele to address the role of elevated GLI1 expression in breast tumour initiation and progression. Induced GLI1 expression facilitates mammary gland tumour formation and this was further increased upon heterozygous deletion of Trp53. The GLI1-induced primary tumours were of different murine molecular subtypes, including Normal-likeEx, Class8Ex, Claudin-LowEx and Erbb2-likeEx. The gene expression profiles of some of the tumours correlated well with the PAM50 subtypes for human breast cancer. Whole-exome sequencing revealed somatic mutation profiles with only little overlap between the primary tumours. Orthotopically serially transplanted GLI1-induced tumours maintained the main morphological characteristics of the primary tumours for ≥10 generations. Independent of Trp53 status and molecular subtype, the serially transplanted GLI1-induced tumours were able to grow both in the absence of transgenic GLI1 expression and in the presence of the GLI1 inhibitor GANT61. These data suggest that elevated GLI1 expression has a determinant role in tumour initiation; however, additional genetic events are required for tumour progression. 相似文献