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The term “oligometastatic prostate cancer” refers to a heterogeneous group of disease states currently defined solely on the basis of clinical features. Oligorecurrent disease, de novo oligometastases, and oligoprogressive disease likely have unique biologic underpinnings and natural histories. Evidence suggesting the existence of a subset of patients who harbor prostate cancer with limited metastatic potential currently includes disparate and overwhelmingly retrospective reports. Nevertheless, emerging prospective data have corroborated the “better-than-expected,” retrospectively observed outcomes, particularly in the setting of oligorecurrent prostate cancer. Improved functional imaging with prostate-specific membrane antigen-targeted strategies may enhance the identification of patients with oligometastatic prostate cancer in the short term. In the long term, refinement of the oligometastatic case definition likely will require biologic risk-stratification schemes. To determine optimal treatment strategies and identify patients most likely to benefit from metastasis-directed therapy, future efforts should focus on conducting high-quality, prospective trials with much-needed molecular correlative studies. 相似文献
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Elizabeth P. Young W. Susan Cheng Melanie B. Bernhardt Lisa L. Wang Nino Rainusso Jennifer H. Foster 《Pediatric blood & cancer》2020,67(4)
High‐dose methotrexate (HD‐MTX; 12 g/m2) is part of standard therapy for pediatric osteosarcoma (OS). Risk factors associated with MTX toxicity in children with OS are not well defined. We investigated the association between peak MTX levels (four‐hour) and delayed MTX clearance or treatment toxicity. Information was retrieved from electronic medical records of 33 OS patients treated with HD‐MTX at Texas Children's Hospital from 2008 to 2015. We found that the four‐hour MTX level did not contribute to toxicity or delayed MTX clearance. We demonstrated that certain demographic characteristics are associated with delayed clearance and increased toxicity. 相似文献
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Rupa Narayan MD Traci M. Blonquist MS Ashkan Emadi MD PhD Robert P. Hasserjian MD Meghan Burke BS Christopher Lescinskas BS Donna S. Neuberg ScD Andrew M. Brunner MD Gabriela Hobbs MD Hanno Hock MD PhD Steven L. McAfee MD Yi-Bin Chen MD Eyal Attar MD Timothy A. Graubert MD Christina Bertoli MSN Jenna A. Moran MSN Meghan K. Bergeron MSN Julia E. Foster MSN Aura Y. Ramos BSN Tina T. Som BSN Megan K. Vartanian BSN RN Jennifer L. Story LPN Kristin McGregor MS Molly Macrae BS Tanya Behnan BS Margaret C. Wey PhD Jessica Rae BSN Frederic I. Preffer PhD Patricia Lesho BA Vu H. Duong MD Mason L. Mann BA Karen K. Ballen MD Christine Connolly BS Philip C. Amrein MD Amir T. Fathi MD 《Cancer》2020,126(6):1264-1273
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James A. Akingbasote Alison J. Foster Ian Wilson Sunil Sarda Huw B. Jones J. Gerry Kenna 《Archives of toxicology》2016,90(4):853-862
Hepatic NADPH-cytochrome P450 oxidoreductase null (HRN?) mice exhibit normal hepatic and extrahepatic biotransformation enzyme activities when compared to wild-type (WT) mice, but express no functional hepatic cytochrome P450 activities. When incubated in vitro with [14C]-diclofenac, liver microsomes from WT mice exhibited extensive biotransformation to oxidative and glucuronide metabolites and covalent binding to proteins was also observed. In contrast, whereas glucuronide conjugates and a quinone-imine metabolite were formed when [14C]-diclofenac was incubated with HRN? mouse liver, only small quantities of P450-derived oxidative metabolites were produced in these samples and covalent binding to proteins was not observed. Livers from vehicle-treated HRN? mice exhibited enhanced lipid accumulation, bile duct proliferation, hepatocellular degeneration and necrosis and inflammatory cell infiltration, which were not present in livers from WT mice. Elevated liver-derived alanine aminotransferase, glutamate dehydrogenase and alkaline phosphatase activities were also observed in plasma from HRN? mice. When treated orally with diclofenac for 7 days, at 30 mg/kg/day, the severities of the abnormal liver histopathology and plasma liver enzyme findings in HRN? mice were reduced markedly. Oral diclofenac administration did not alter the liver histopathology or elevate plasma enzyme activities of WT mice. These findings indicate that HRN? mice are valuable for exploration of the role played by hepatic P450s in drug biotransformation, but poorly suited to investigations of drug-induced liver toxicity. Nevertheless, studies in HRN? mice could provide novel insights into the role played by inflammation in liver injury and may aid the evaluation of new strategies for its treatment. 相似文献