The loss of BAP1 protein expression predicts poor prognosis in patients with nonmetastatic clear cell renal cell carcinoma with inferior vena cava tumor thrombosis

Objectives

Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC) and is associated with poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts poor prognosis. The aim of this study was to elucidate the association between BAP1 protein expression and clinicopathological outcomes in patients with nonmetastatic ccRCC with an IVC tumor thrombus (IVCTT).

Ppp6c haploinsufficiency accelerates UV-induced BRAF(V600E)-initiated melanomagenesis

According to TCGA database, mutations in PPP6C (encoding phosphatase PP6) are found in c. 10% of tumors from melanoma patients, in which they coexist with BRAF and NRAS mutations. To assess PP6 function in melanoma carcinogenesis, we generated mice in which we could specifically induce BRAF(V600E) expression and delete Ppp6c in melanocytes. In these mice, melanoma susceptibility following UVB irradiation exhibited the following pattern: Ppp6c semi-deficient (heterozygous) > Ppp6c wild-type > Ppp6c-deficient (homozygous) tumor types. Next-generation sequencing of Ppp6c heterozygous and wild-type melanoma tumors revealed that all harbored Trp53 mutations. However, Ppp6c heterozygous tumors showed a higher Signature 1 (mitotic/mitotic clock) mutation index compared with Ppp6c wild-type tumors, suggesting increased cell division. Analysis of cell lines derived from either Ppp6c heterozygous or wild-type melanoma tissues showed that both formed tumors in nude mice, but Ppp6c heterozygous tumors grew faster compared with those from the wild-type line. Ppp6c knockdown via siRNA in the Ppp6c heterozygous line promoted the accumulation of genomic damage and enhanced apoptosis relative to siRNA controls. We conclude that in the presence of BRAF(V600E) expression and UV-induced Trp53 mutation, Ppp6c haploinsufficiency promotes tumorigenesis.     

Effects of indigo carmine intravenous injection on oxygen reserve index (ORi™) measurement

To retrospectively investigate the effects of indigo carmine intravenous injection on oxygen reserve index (ORi?) in 20 patients who underwent elective gynecologic surgery under general anesthesia. The study subjects were patients who underwent elective gynecologic surgery under general anesthesia between April 2016 and January 2017, and were administered a 5-ml intravenous injection of 0.4% indigo carmine for clinical purposes during surgery with ORi monitoring. Changes in ORi within 20 min after indigo carmine injection were observed. A relevant decrease in ORi was defined as ≥?10% reduction in ORi from pre-injection level. ORi rapidly decreased after indigo carmine intravenous injection in all patients. In 10 of 19 patients, ORi decreased to 0 after indigo carmine injection. The median lowest value of ORi was 0 (range 0–0.16) and the median time to reach the lowest value of ORi was 2 min (range 1–4 min) after injection. ORi values returned to pre-injection levels within 20 min in 13 of 19 patients, and the median time to return to pre-injection levels was 10 min (range 6–16 min) after injection. During ORi monitoring it is necessary to consider the rapid reduction in ORi after intravenous injection of indigo carmine.