1.Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma.
Takuma HAYASHI ; Akiko HORIUCHI ; Kenji SANO ; Nobuyoshi HIRAOKA ; Yae KANAI ; Tanri SHIOZAWA ; Susumu TONEGAWA ; Ikuo KONISHI
Protein & Cell 2010;1(8):711-717
Uterine tumors are the most common type of gynecologic neoplasm. Uterine leiomyosarcoma (LMS) is rare, accounting for 2% to 5% of tumors of the uterine body. Uterine LMS develops more often in the muscle tissue layer of the uterine body than in the uterine cervix. The development of gynecologic tumors is often correlated with female hormone secretion; however, the development of uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Radiographic evaluation combined with PET/CT can be useless in the diagnosis and surveillance of uterine LMS. Importantly, a diagnostic biomarker, which distinguishes malignant LMS and benign tumor leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine LMS in order to establish a method of treatment. LMP2-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ∼40% by 14 months of age. It is therefore of interest whether human uterine LMS shows a loss of LMP2 expression. We found LMP2 expression is absent in human LMS, but present in human LMA. Therefore, defective LMP2 expression may be one of the risk factors for LMS. LMP2 is potentially a diagnostic biomarker for uterine LMS, and gene therapy with LMP2-encording DNA may be a new therapeutic approach.
Animals
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Biomarkers, Tumor
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biosynthesis
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genetics
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Cysteine Endopeptidases
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biosynthesis
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genetics
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Down-Regulation
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Female
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Gene Deletion
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Humans
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Interferon Regulatory Factor-1
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biosynthesis
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genetics
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Leiomyoma
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metabolism
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Leiomyosarcoma
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diagnosis
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genetics
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metabolism
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Mice
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Mice, Knockout
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Proteasome Endopeptidase Complex
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metabolism
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Uterine Neoplasms
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diagnosis
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genetics
;
metabolism
2.Peritoneal dissemination of high-grade serous ovarian cancer: pivotal roles of chromosomal instability and epigenetic dynamics
Ikuo KONISHI ; Kaoru ABIKO ; Takuma HAYASHI ; Koji YAMANOI ; Ryusuke MURAKAMI ; Ken YAMAGUCHI ; Junzo HAMANISHI ; Tsukasa BABA ; Noriomi MATSUMURA ; Masaki MANDAI ;
Journal of Gynecologic Oncology 2022;33(5):e83-
Epithelial ovarian cancer remains the lethal gynecological malignancy in women. The representative histotype is high-grade serous carcinoma (HGSC), and most patients with HGSC present at advanced stages with peritoneal dissemination. Since the peritoneal dissemination is the most important factor for poor prognosis of the patients, complete exploration for its molecular mechanisms is mandatory. In this narrative review, being based on the clinical, pathologic, and genomic findings of HGSC, chromosomal instability and epigenetic dynamics have been discussed as the potential drivers for cancer development in the fallopian tube, acquisition of cancer stem cell (CSC)-like properties, and peritoneal metastasis of HGSC. The natural history of carcinogenesis with clonal evolution, and adaptation to microenvironment of peritoneal dissemination of HGSC should be targeted in the novel development of strategies for prevention, early detection, and precision treatment for patients with HGSC.
3.Clinical Outcomes of Biliary Drainage during a Neoadjuvant Therapy for Pancreatic Cancer: Metal versus Plastic Stents
Masaki KUWATANI ; Toru NAKAMURA ; Tsuyoshi HAYASHI ; Yasutoshi KIMURA ; Michihiro ONO ; Masayo MOTOYA ; Koji IMAI ; Keisuke YAMAKITA ; Takuma GOTO ; Kuniyuki TAKAHASHI ; Hiroyuki MAGUCHI ; Satoshi HIRANO ;
Gut and Liver 2020;14(2):269-273
Neoadjuvant chemotherapyeoadjuvant chemoradiotherapy (NAC/NACRT) can be performed in patients with pancreatic cancer to improve survival. We aimed to clarify the clinical outcomes of biliary drainage with a metal stent (MS) or a plastic stent (PS) during NAC/NACRT. Between October 2013 and April 2016, 96 patients with pancreatic cancer were registered for NAC/NACRT. Of these, 29 patients who underwent biliary drainage with MS or PS before NAC/NACRT and a subsequent pancreatoduodenectomy were retrospectively analyzed with regard to patient characteristics, preoperative recurrent biliary obstruction rate, NAC/NACRT delay or discontinuation rate, and operative characteristics. The median age of the patients was 67 years. NAC and NACRT were performed in 14 and 15 patients, respectively, and MS and PS were used in 17 and 12 patients, respectively. Recurrent biliary obstruction occurred in 6% and 83% of the patients in the MS and PS groups, respectively (p<0.001). NAC/NACRT delay was observed in 35% and 50% of the patients in the MS and PS groups, respectively (p=0.680). NAC/NACRT discontinuation was observed in 12% and 17% of the patients in the MS and PS groups, respectively (p=1.000). The operative time in the MS group tended to be longer than that in the PS group (625 minutes vs 497 minutes, p=0.051), and the operative blood loss volumes and postoperative adverse event rates were not different between the two groups. MS was better than PS from the viewpoint of preventing recurrent biliary obstruction, although MS was similar to PS with regards to perioperative outcomes.