1.Inhibition of autophagy protein LC3A as a therapeutic target in ovarian clear cell carcinomas.
Morikazu MIYAMOTO ; Masashi TAKANO ; Tadashi AOYAMA ; Hiroaki SOYAMA ; Tomoyuki YOSHIKAWA ; Hitoshi TSUDA ; Kenichi FURUYA
Journal of Gynecologic Oncology 2017;28(3):e33-
OBJECTIVE: Ovarian clear cell carcinoma (CCC) is one of histological subtypes showing poor prognosis due to chemoresistance. The association of autophagy-related proteins and clinical implementation in CCC has not been determined. METHODS: The present study investigated whether expression of autophagy-related protein, light chain 3A (LC3A), was related with prognoses in the patients with CCC using immuno-histochemical stainings, and whether inhibition of autophagy modified the sensitivity to cisplatin in CCC cells in vitro. RESULTS: High expression of autophagy-related protein, LC3A, was detected in 78 cases (78%) in all CCC cases. The patients with high LC3A expression showed significantly lower response rate to primary chemotherapy (17% vs. 100%, p<0.010), and had worse progression-free survival (PFS) and overall survival (OS) compared with those with LC3A low expression. Furthermore, multivariate analyses revealed that high expression of LC3A was identified as independent worse prognostic factors for PFS and OS. Inhibition of autophagy protein LC3A using hydroxychloroquine (HCQ) increased sensitivity to cisplatin in CCC cells in vitro. CONCLUSION: High expression of LC3A proteins was associated with lower response to platinum therapy, leading to worse prognoses in CCC. Although further studies are needed to confirm the results, inhibition of autophagy by HCQ was associated with platinum sensitivity. Autophagy protein LC3A could be a promising target for treatment for CCC.
Adenocarcinoma, Clear Cell
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Autophagy*
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Cisplatin
;
Disease-Free Survival
;
Drug Therapy
;
Humans
;
Hydroxychloroquine
;
In Vitro Techniques
;
Multivariate Analysis
;
Ovarian Neoplasms
;
Platinum
;
Prognosis
2.The Medial Eminence Line for Predicting Tibial Fracture Risk after Unicompartmental Knee Arthroplasty
Ryo YOSHIKAWA ; Takafumi HIRANAKA ; Koji OKAMOTO ; Takaaki FUJISHIRO ; Yuichi HIDA ; Tomoyuki KAMENAGA ; Yoshitada SAKAI
Clinics in Orthopedic Surgery 2020;12(2):166-170
Background:
Tibial fracture after cementless Oxford unicompartmental knee arthroplasty (OUKA) is a rare but serious complication. It is reported more frequently in Asian countries. The aim of this retrospective study was to assess the morphological characteristics of the tibia by using a simple novel measurement method in patients with tibial fractures after OUKA.
Methods:
Six knees (all women) with tibial fractures after cementless OUKA (fracture group) and 150 knees without an obvious complication after cementless OUKA (control group) were examined retrospectively at our institution between January 2016 and April 2017. We drew a medial eminence line (ME line) defined as a line extending from the tip of the medial intercondylar eminence parallel to the tibial axis. The ME line was classified into two types (intramedullary type [type I] and extramedullary type [type E]), and the proportion of each type was compared between fracture patients and controls.
Results:
In the fracture group, there were four (66.7%) type E cases and two (33.3%) type I cases; in the control group, there were 18 (12%) type E cases and 132 (88%) type I cases. Fisher exact tests showed that the proportion of type E was higher in the fracture group than in the control group (p < 0.01).
Conclusions
Measurement of the ME line can be recommended as a useful method to assess the risk of postoperative fracture after cementless OUKA.
3.Seromucinous component in endometrioid endometrial carcinoma as a histological predictor of prognosis.
Morikazu MIYAMOTO ; Masashi TAKANO ; Tadashi AOYAMA ; Hiroaki SOYAMA ; Tomoyuki YOSHIKAWA ; Hitoshi TSUDA ; Kenichi FURUYA
Journal of Gynecologic Oncology 2018;29(2):e20-
OBJECTIVE: In 2014 World Health Organization criteria, seromucinous carcinoma was defined as a new histological subtype in ovarian carcinomas, but “seromucinous carcinoma” was not defined in endometrial carcinomas. The aim of this study was to identify seromucinous carcinoma resembling ovarian seromucinous carcinoma in endometrial carcinomas, and to evaluate the clinical significance for prognoses of the patients. METHODS: Central pathological review was conducted for patients with endometrioid carcinoma of the endometrium treated by primary surgery at our hospital between 1990 and 2013. RESULTS: Among 340 cases included in the study, no case had all tumor cells resembling ovarian seromucinous carcinoma in all specimens, and 31 cases (9.1%) had seromucinous component in combination with endometrioid carcinomas. Immunohistochemical analysis revealed seromucinous component had positive reactivity for cytokeratin (CK) 7, and negative reactivity for CK20 and caudal type homeobox 2 (CDX2) in all cases. Seromucinous component showed lower immunoreactivity of estrogen receptor and progesterone receptor, compared with endometrioid carcinoma component. Progression-free survival of the cases with seromucinous component was better than those without seromucinous component (p=0.049). CONCLUSION: Seromucinous component was identified in approximately 10% of endometrioid carcinoma, and could be a histological predictor for prognosis.
Carcinoma, Endometrioid
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Disease-Free Survival
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Endometrial Neoplasms*
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Endometrium
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Estrogens
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Female
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Genes, Homeobox
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Humans
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Keratins
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Prognosis*
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Receptors, Progesterone
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World Health Organization