Publications by authors named "Mineto Ohta"

7 Publications

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The anti-angiogenic agent lenvatinib induces tumor vessel normalization and enhances radiosensitivity in hepatocellular tumors.

Med Oncol 2021 Apr 21;38(6):60. Epub 2021 Apr 21.

Department of Medical Physics, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.

The evaluation of angiogenesis inhibitors requires the analysis of the precise structure and function of tumor vessels. The anti-angiogenic agents lenvatinib and sorafenib are multi-target tyrosine kinase inhibitors that have been approved for the treatment of hepatocellular carcinoma (HCC). However, the different effects on tumor vasculature between lenvatinib and sorafenib are not well understood. In this study, we analyzed the effects of both drugs on vascular structure and function, including vascular normalization, and investigated whether the normalization had a positive effect on a combination therapy with the drugs and radiation using micro X-ray computed tomography with gold nanoparticles as a contrast agent, as well as immunohistochemical analysis and interstitial fluid pressure (IFP) measurement. In mice subcutaneously transplanted with mouse HCC cells, treatment with lenvatinib or sorafenib for 14 days inhibited tumor growth and reduced the tumor vessel volume density. However, analysis of integrated data on vessel density, rates of pericyte-covering and perfused vessels, tumor hypoxia, and IFP measured 4 days after drug treatment showed that treatment with 3 mg/kg of lenvatinib significantly reduced the microvessel density and normalized tumor vessels compared to treatment with 50 mg/kg of sorafenib. These results showed that lenvatinib induced vascular normalization and improved the intratumoral microenvironment in HCC tumors earlier and more effectively than sorafenib. Moreover, such changes increased the radiosensitivity of tumors and enhanced the effect of lenvatinib and radiation combination therapy, suggesting that this combination therapy is a powerful potential application against HCC.
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http://dx.doi.org/10.1007/s12032-021-01503-zDOI Listing
April 2021

Surgical resection for liver metastasis and local recurrence of pheochromocytoma 16 years after primary surgery: A case report.

Int J Surg Case Rep 2021 Apr 27;81:105712. Epub 2021 Feb 27.

Department of Surgery, Graduate School of Medicine, Tohoku University, Japan.

Introduction And Importance: Pheochromocytomas arise from the adrenal medulla and are rare. Pheochromocytomas metastasize to bone, lung and liver, and surgery might be the curative treatment. However, few cases are detected when they are resectable lesions because of difficulty in diagnosis and rapid growth. We herein report a patient who underwent resection of liver metastasis and local recurrence of pheochromocytoma.

Case Presentation: A 74-year-old woman visited our hospital for treatment for liver and retroperitoneal tumors. She had undergone left adrenal gland resection for pheochromocytoma 16 years earlier. Eleven years after primary surgery, breast cancer was diagnosed and resected. During the breast cancer follow-up, a liver tumor was identified with computed tomography. Breast cancer recurrence and metastasis were considered, so chemotherapy was administered first. However, the liver tumor gradually enlarged, and another lesion appeared in the retroperitoneum. The tumors were diagnosed as pheochromocytoma recurrence using I-metaiodobenzylguanidine scintigraphy, and she underwent resection of the local recurrence and liver metastasis. She was discharged on postoperative day 25 without complications, and no evidence of recurrence occurred more than 3.5 years postoperatively.

Clinical Discussion: All pheochromocytomas have metastatic potential; however, there are no reliable markers to predict malignancy. Early detection of recurrence by regular imaging and complete resection are important in the treatment. If the recurrence was oligometastasis and tumor growth is slow, surgical resection may be eligible.

Conclusion: A favorable outcome resulted from complete resection for liver metastasis and local recurrence of pheochromocytoma.
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http://dx.doi.org/10.1016/j.ijscr.2021.105712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941035PMC
April 2021

Bleeding from jejunal varices formed at the Roux-en-Y jejunum site caused by the compression of the left renal vein after living donor liver transplantation with renoportal anastomosis.

Surg Case Rep 2021 Feb 6;7(1):43. Epub 2021 Feb 6.

Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan.

Background: Renoportal anastomosis is an option for the portal vein reconstruction of a liver transplantation with grade 4 portal vein thrombosis and a splenorenal shunt. Here, we report the case of gastrointestinal bleeding who underwent living donor liver transplantation (LDLT) with renoportal anastomosis.

Case Presentation: Six-year-old female patient who underwent LDLT with renoportal anastomosis at 1 year of age had severe anemia with normal liver function during the follow-up period. The varices at the Roux-en-Y jejunum were considered the source of bleeding, and the compression of the left renal vein, which is known as a cause of Nutcracker syndrome, seemed to induce venous hypertension through the splenorenal shunt, which might induce the formation of the varices. She underwent percutaneous transhepatic sclerotherapy of the varices, and the anemia improved at her last follow-up, 6 months after sclerotherapy. This is the first reported case of Roux-en-Y jejunal varices bleeding related to the compression of the left renal vein after LDLT was performed with renoportal anastomosis.

Conclusions: Although renoportal anastomosis should be cautiously performed when there are no options for severe portal vein thrombosis, the status of the left renal vein and new collateral formation should be observed carefully during the follow-up period in pediatric cases of renoportal anastomosis.
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http://dx.doi.org/10.1186/s40792-021-01129-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867670PMC
February 2021

Quantitative analyses of amount and localization of radiosensitizer gold nanoparticles interacting with cancer cells to optimize radiation therapy.

Biochem Biophys Res Commun 2019 01 12;508(4):1093-1100. Epub 2018 Dec 12.

Department of Medical Physics, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, 980-8575, Japan. Electronic address:

Previous studies showed that gold nanoparticles (AuNPs) are useful radiosensitizers which optimize radiation therapy under low-dose radiation. However, the mechanisms of AuNP radiosensitization, including the amount and localization of the AuNPs interacting with cancer cells, has not yet been quantified. To answer these questions, we prepared AuNPs conjugated with anti-human epidermal growth factor receptor type 2 (HER2) antibody via polyethylene glycol (PEG) chains (AuNP-PEG-HER2ab). AuNP-PEG-HER2ab specifically bound to the HER2-expressing cancer cells and entered the cells via endocytosis. Whether endocytosis of AuNP-PEG-HER2ab occurred had no effect on radiosensitization efficacy by AuNP-PEG-HER2ab in vitro. The radiosensitization efficacy in vitro depended on dose of AuNP-PEG-HER2ab or dose of X-ray. Moreover, AuNP-PEG-HER2ab administrated into tumor-bearing mice was localized to both the periphery of the tumor tissue and near the nuclei in cancer cells in tumor deep tissue. The localization of AuNP-PEG-HER2ab in tumor tissues was important factors for in vivo powerful radiosensitization efficacy.
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http://dx.doi.org/10.1016/j.bbrc.2018.12.016DOI Listing
January 2019

Surgical resection of recurrent extrahepatic hepatocellular carcinoma with tumor thrombus extending into the right atrium under cardiopulmonary bypass: a case report and review of the literature.

Surg Case Rep 2016 Dec 11;2(1):110. Epub 2016 Oct 11.

Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, 1-1 Seiryou, Aoba, Sendai, 980-8574, Japan.

Background: Recurrent hepatocellular carcinoma accompanied by a right atrial tumor thrombus is rare. No standard treatment modality has been established. Surgical treatment may be the only curative treatment; however, surgery has been considered high risk. We herein describe a patient who underwent resection of a recurrent right atrial tumor thrombus under normothermic cardiopulmonary bypass on a beating heart.

Case Presentation: A 60-year-old man underwent a right hepatectomy for hepatocellular carcinoma with diaphragm invasion. During the preoperative cardiac screening, he was diagnosed with an old myocardial infarction with triple-vessel coronary disease. Percutaneous coronary intervention was performed for the left anterior descending artery and left circumflex coronary artery. High-grade stenosis remained in his right coronary artery. Nine months later, computed tomography showed recurrent hepatocellular carcinoma in the diaphragm and a tumor thrombus extending from the suprahepatic inferior vena cava into the right atrium. Surgical resection of the recurrent tumor was performed through a right subcostal incision with xiphoid extension and median sternotomy. The recurrent tumor was incised with the diaphragm and pericardium. Intraoperative ultrasonography revealed that the tumor thrombus was free from right atrium wall invasion and that the right atrium could be clamped just proximal to the tumor thrombus. The right atrium, infrahepatic vena cava, left and middle hepatic veins, and hepatoduodenal ligament were encircled. Cardiopulmonary bypass was performed to prevent ischemic heart disease caused by intraoperative hypotension. Total hepatic vascular exclusion was then performed under normothermic cardiopulmonary bypass on heart beating. The inferior vena cava wall was incised. The tumor thrombus with the diaphragmatic recurrent tumor was resected en bloc. The patient had a favorable clinical course without any complications.

Conclusion: The recurrent hepatocellular carcinoma in the diaphragm and the right atrial tumor thrombus were safely resected using normothermic cardiopulmonary bypass on heart beating.
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http://dx.doi.org/10.1186/s40792-016-0241-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056913PMC
December 2016

Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus.

J Biol Chem 2013 May 28;288(19):13592-601. Epub 2013 Mar 28.

Department of Biochemistry and Center for Regulatory Epigenome and Disease, Graduate School of Medicine, Tohoku University, Seiryo-machi 2-1, Sendai 980-8575, Japan.

Background: MATII biosynthesizes AdoMet, which supplies methyl group for methylation of molecules, including histone.

Results: MATII interacts with histone methyltransferase SETDB1 and inhibits COX-2 gene expression.

Conclusion: AdoMet synthesis and histone methylation are coupled on chromatin by a physical interaction of MATII and SETDB1 at the MafK target genes.

Significance: MATII may be important for both gene-specific and epigenome-wide regulation of histone methylation. Methionine adenosyltransferase (MAT) synthesizes S-adenosylmethionine (AdoMet), which is utilized as a methyl donor in transmethylation reactions involving histones. MATIIα, a MAT isozyme, serves as a transcriptional corepressor in the oxidative stress response and forms the AdoMet-integrating transcription regulation module, affecting histone methyltransferase activities. However, the identities of genes regulated by MATIIα or its associated methyltransferases are unclear. We show that MATIIα represses the expression of cyclooxygenase 2 (COX-2), encoded by Ptgs2, by specifically interacting with histone H3K9 methyltransferase SETDB1, thereby promoting the trimethylation of H3K9 at the COX-2 locus. We discuss both gene-specific and epigenome-wide functions of MATIIα.
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http://dx.doi.org/10.1074/jbc.M112.429738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650394PMC
May 2013

Methionine adenosyltransferase II serves as a transcriptional corepressor of Maf oncoprotein.

Mol Cell 2011 Mar;41(5):554-66

Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.

Protein methylation pathways comprise methionine adenosyltransferase (MAT), which produces S-adenosylmethionine (SAM) and SAM-dependent substrate-specific methyltransferases. However, the function of MAT in the nucleus is largely unknown. MafK represses or activates expression of heme oxygenase-1 (HO-1) gene, depending on its heterodimer partners. Proteomics analysis of MafK revealed its interaction with MATIIα, a MAT isozyme. MATIIα was localized in nuclei and found to form a dense network with chromatin-related proteins including Swi/Snf and NuRD complexes. MATIIα was recruited to Maf recognition element (MARE) at HO-1 gene. When MATIIα was knocked down in murine hepatoma cell line, expression of HO-1 was derepressed at both basal and induced levels. The catalytic activity of MATIIα, as well as its interacting factors such as MATIIβ, BAF53a, CHD4, and PARP1, was required for HO-1 repression. MATII serves as a transcriptional corepressor of MafK by interacting with chromatin regulators and supplying SAM for methyltransferases.
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http://dx.doi.org/10.1016/j.molcel.2011.02.018DOI Listing
March 2011