A functional analysis of the DNA glycosylase activity of mouse MUTYH protein excising 2-hydroxyadenine opposite guanine in DNA

2-Hydroxy-2-deoxyadenosine triphosphate (2-OH-dATP), generated by the oxidation of dATP, can be misincorporated by DNA polymerases opposite guanine in template DNA during DNA replication, thus causing spontaneous mutagenesis. We demonstrated that mouse MUTYH (mMUTYH) has a DNA glycosylase activity excising not only adenine opposite 8-oxoguanine (8-oxoG) but also 2-hydroxyadenine (2-OH-A) opposite guanine, using purified recombinant thioredoxin-mMUTYH fusion protein. mMUTYH formed a stable complex with duplex oligonucleotides containing an adenine:8-oxoG pair, but the binding of mMUTYH to oligonucleotides containing a 2-OH-A:guanine pair was barely detectable, thus suggesting that mMUTYH recognizes and interacts with these two substrates in a different manner which may reflect the difference in the base excision repair process for each substrate. Mutant mMUTYH with G365D amino acid substitution, corresponding to a G382D germline mutation of human MUTYH found in familial adenomatous polyposis patients, almost completely retained its DNA glycosylase activity excising adenine opposite 8-oxoG; however, it possessed 1.5% of the wild-type activity excising 2-OH-A opposite guanine. Our results imply that the reduced repair capacity of the mutant hMUTYH(G382D), which inefficiently excises 2-OH-A opposite guanine, results in an increased occurrence of somatic G:C to T:A transversion mutations in the APC gene as well as tumorigenesis in the colon

Distinguishing intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma using precontrast and gadoxetic acid-enhanced MRI

PURPOSEWe aimed to gain further insight in magnetic resonance imaging characteristics of mass-forming intrahepatic cholangiocarcinoma (mICC), its enhancement pattern with gadoxetic acid contrast agent, and distinction from poorly differentiated hepatocellular carcinoma (pHCC).METHODSFourteen mICC and 22 pHCC nodules were included in this study. Two observers recorded the tumor shape, intratumoral hemorrhage, fat on chemical shift imaging, signal intensity at the center of the tumor on T2-weighted image, fibrous capsule, enhancement pattern on arterial phase of dynamic study, late enhancement three minutes after contrast injection (dynamic late phase), contrast uptake on hepatobiliary phase, apparent diffusion coefficient, vascular invasion, and intrahepatic metastasis.RESULTSLate enhancement was more common in mICC (n=10, 71%) than in pHCC (n=3, 14%) (P < 0.001). A fat component was observed in 11 pHCC cases (50%) versus none of mICC cases (P = 0.002). Fibrous capsule was observed in 13 pHCC cases (59%) versus none of mICC cases (P < 0.001). On T2-weighted images a hypointense area was seen at the center of the tumor in 43% of mICC (6/14) and 9% of pHCC (2/22) cases (P = 0.018). Other parameters were not significantly different between the two types of nodules.CONCLUSIONThe absence of fat and fibrous capsule, and presence of enhancement at three minutes appear to be most characteristic for mICC and may help its differentiation from pHCC

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer

BackgroundVulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese.ObjectiveThe JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan.MethodsThe guideline was created according to the basic principles in creating the guidelines of JSGO.ResultsThe guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget’s disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions.ConclusionOverall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases

Construction of Photovoltaic Power Generation-storage System Using an Inverter with SiC FET and SBD

Abstract A power storage system using spherical Si solar cells, lithium-ion battery and a direct current-alternating current (DC-AC) converter was constructed. A small and light inverter system was developed by combining a maximum power point tracking charge controller, direct current-direct current (DC-DC) converter, and DC-AC converter. Performance evaluation of the inverter system with SiC field-effect transistors (FET) and Schottky barrier diodes (SBD) was carried out, and the DC-AC conversion efficiencies and their stability of the inverter were improved compared with those of the ordinary Si-FET/SBD based inverter

Different micro/nano-scale patterns of surface materials influence osteoclastogenesis and actin structure

The surface topography of a material can influence osteoclast activity. However, the surface structural factors that promote osteoclast activity have not yet been investigated in detail. Therefore, we investigated osteoclastogenesis by testing various defined patterns with different dimensions and shapes. The systematic patterns, made of a cyclo-olefin polymer, were prepared at a micron-, submicron-, and nano-scale with a groove, hole, or pillar shape with a 1:1 pitch ratio. RAVV264.7 cells were cultured on these patterns in the presence of the receptor activator of NF-kappa B ligand (RANKL). Osteoclast formation was induced in the order: pillar > groove >= hole. The two-dimensional factors also indicated that submicron-sized patterns strongly induced osteoclast formation. The optimal pillar dimension for osteoclast formation was 500 nm in diameter and 2 mu m in height Furthermore, we observed two types of characteristic actin structure, i.e., belt-like structures with small hollow circles and isolated ring-like structures, which formed on or around the pillars depending on size and height. Furthermore, resorption pits were observed mainly on the top of calcium phosphate-coated pillars. Thus, osteoclasts prefer convex shapes, such as pillars for differentiation and resorption. Our results indicate that osteoclastogenesis can be controlled by designing surfaces with specific morphologies

MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain

MutY homolog (MUTYH) excises adenine opposite 8-oxoguanine (8-oxoG) in DNA, thus preventing occurrence of G:C to T:A transversion. In cell-free extract prepared from the thymocytes of wild type but not MUTYH-null mice, adenine opposite 8-oxoG in DNA was excised by MUTYH, however, the generated apurinic (AP) site opposite 8-oxoG mostly remained unincised. Recombinant mouse MUTYH (mMUTYH) efficiently excised adenine opposite 8-oxoG and prevented mouse AP endonuclease (mAPEX1) from incising the generated AP site. In contrast, an AP site opposite 8-oxoG created by uracil DNA glycosylase or tetrahydrofuran opposite 8-oxoG was efficiently incised by mAPEX1 in the presence of an excess amount of mMUTYH. Mutant mMUTYH with R361A or G365D substitution, excised adenine opposite 8-oxoG as efficiently as did wild-type mMUTYH, but failed to prevent mAPEX1 from incising the generated AP site. Wild-type mMUTYH bound duplex oligonucleotides containing A:8-oxoG pair with a lower apparent K(d) than that of the mutants, and prevented OGG1 from excising 8-oxoG opposite adenine or the generated AP site. The G365D mutant failed to prevent OGG1 from excising 8-oxoG opposite the generated AP site, thus indicating that the protection of its own product by mMUTYH is an intrinsic function which depends on the C-terminal domain of mMUTYH

Effect of lipiodol marking before CT-guided cryoablation on the outcome of sporadic renal cell carcinoma

PURPOSEThis retrospective study evaluates the impact of preoperative lipiodol marking on the outcomes of computed tomography (CT)-guided cryoablation for histologically diagnosed sporadic renal cell carcinoma (RCC).METHODSThis study analyzed the data of 173 patients who underwent CT-guided cryoablation for histologically proven sporadic RCC at a single institution between April 2014 and December 2020. The local control rate (LCR), recurrence-free survival rate (RFSR), overall survival rate (OSR), changes in renal function, and complications in patients with (n = 85) and without (n = 88) preoperative lipiodol marking were compared.RESULTSThe 5-year LCR and 5-year RFSR were significantly higher in patients with lipiodol marking (97.51% and 93.84%, respectively) than in those without (72.38% and 68.10%, respectively) (P value <0.01, log-rank test). There were no significant differences between the two groups regarding the 5-year OSR (97.50% vs. 86.82%) or the deterioration in chronic kidney disease stage (12.70% vs. 16.43%). Grade ≥3 complications occurred in patients with lipiodol marking (n = 2, retroperitoneal hematoma and cerebral infarction in 1 patient each) and without (n = 5; urinary fistula in 2, colonic perforation in 2, urinary infection in 1).CONCLUSIONLipiodol marking before CT-guided cryoablation for sporadic RCC is a feasible approach to improving local control and RFS while mitigating the decline in renal function. Additionally, it may help reduce complications