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RISS 인기검색어
- 검색키워드
- 저자 : Haruko Kunitomi (검색결과 3 건)
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LAMC1 expression patterns and associated clinical features of endometrial cancer
( Haruko Irie-kunitomi ),( Yusuke Kobayashi ),( Kouji Banno ),( Kenta Masuda ),( Megumi Yanokura ),( Eichiro Tominaga ),( Daisuke Aoki ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-
Objective: Laminins are one of the major components of the extracellular matrix. Recent studies have indicated the relationship between specific laminin expression profiles and cancer progression. Upregulation of LAMC1, which encodes laminin-γ1, is of particular note because this is related to aggressive behavior of cancer cells of various origins. This study aimed to analyze the influence of LAMC1 expression on the clinical features of endometrial cancer. Methods: The subjects were patients with endometrial cancer (EC), atypical endometrial hyperplasia complex (AEHC) or normal endometrium (NE) who underwent hysterectomy during January 2008 and December 2011 at our institute. The study included 100 cases of EC, 9 of AEHC, and 16 NE. LAMC1 immunohistochemical staining was evaluated as negative or positive by two independent evaluators blinded from clinical information. Patient characteristics and clinical outcomes were obtained retrospectively from clinical records. This study was approved by our institutional review board. Results: LAMC1 expression was significantly elevated in EC compared to AEHC and NE (p<0.05). Endometrioid (EM) grade 3, serous and clear cell adenocarcinoma indicated frequent LAMC1 expression compared to EM grade 1 and 2 (85.2% vs. 51.3%, p<0.05). Patients with advanced FIGO surgical stage (stage III and IV) and positive lymphovascular space invasion had a significantly higher LAMC1 expression rate compared to early stage cases (83.7% vs. 63.2%, p<0.05) and cases without lymphovascular space invasion (86.3% vs. 61.0%, p<0.05), respectively. Kaplan-Meier analysis revealed that LAMC1 positive cases had a significantly shorter progression-free survival (p<0.05) and a tendency to have a reduced overall survival (p=0.052). Conclusion: In endometrial cancer, LAMC1 expression is related to aggressive tumor behavior and reduced progression free survival.
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LAMC1 is a prognostic factor and a potential therapeutic target in endometrial cancer
Haruko Kunitomi,Yusuke Kobayashi,Ren-Chin Wu,Takashi Takeda,Eiichiro Tominaga,Kouji Banno,Daisuke Aoki 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.2
Objective: With the emerging significance of genetic profiles in the management of endometrial cancer, the identification of tumor-driving genes with prognostic value is a pressing need. The LAMC1 gene, encoding the laminin subunit gamma 1 (LAMC1) protein, has been reported to be involved in the progression of various malignant tumors. In this study, we aimed to investigate the role of LAMC1 in endometrial cancer and elucidate the underlying mechanism. Methods: We evaluated the immunohistochemical expression of LAMC1 in atypical endometrial hyperplasia and endometrial cancer. Within the endometrial cancer cases, we analyzed the association of LAMC1 overexpression with clinicopathological factors and prognosis. Furthermore, to identify genes influenced by LAMC1 overexpression, we transfected HEC50B and SPAC-S cells with siRNA targeting LAMC1 and conducted microarray gene expression assays. Results: While none of the atypical endometrial hyperplasia specimens exhibited LAMC1 overexpression, endometrial cancer possessed a significantly higher LAMC1 overexpression rate. LAMC1 overexpression was strongly associated with histological type, lymphovascular space invasion, lymph node metastasis, advanced International Federation of Gynecology and Obstetrics stage, and poor overall survival in endometrial cancer. Gene expression microarray analysis identified 8 genes correlated with tumor progression (LZTFL1, TAPT1, SEL1L, PAQR6, NME7, TMEM109, CCDC58, and ANKRD40) that were commonly influenced in HEC50B and SPAC-S by LAMC1 silencing. Conclusion: LAMC1 overexpression is a potent biomarker for identifying endometrial cancer patients needing aggressive adjuvant therapy. We elucidated 8 candidate genes that may mediate progression of LAMC1 overexpressing cancer. Further investigation of the underlying mechanism should lead to the discovery of new therapeutic targets.
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Current state and outlook for drug repositioning anticipated in the field of ovarian cancer
Yusuke Kobayashi,Kouji Banno,Haruko Kunitomi,Eiichiro Tominaga,Daisuke Aoki 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.1
Ovarian cancer is the seventh most common cancer and the eighth most common cause of cancer mortality in women. Although standard chemotherapy is the established treatment for ovarian cancer, the prognosis remains poor, and it is highly anticipated that new drugs will be developed. New drugs, such as humanized anti-vascular endothelial growth factor monoclonal antibodies and poly ADP-ribose polymerase inhibitors, are expected to improve clinical outcomes of ovarian cancer. However, long-term, costly research is required to develop such new drugs, and soaring national healthcare costs are becoming a concern worldwide. In this social context, drug repositioning, wherein existing drugs are used to develop drugs with new indications for other diseases, has recently gained attention. Because trials have already confirmed the safety in humans and the pharmacokinetics of such drugs, the development period is shorter than the conventional development of a new drug, thereby reducing costs. This review discusses the available basic experimental and clinical data on drugs used for other types of cancer for which drug repositioning is anticipated to repurpose the drug for the treatment of ovarian cancer. These include statins, which are used to treat dyslipidemia; bisphosphonate, which is used to treat osteoporosis; metformin, which is used to treat diabetes; non-steroidal anti-inflammatory drugs; ivermectin, an antiparasitic agent; and itraconazole, an anti-fungal agent. These drugs will play an important role in future drug repositioning strategies for ovarian cancer. Furthermore, drug repositioning is anticipated to extend not only to ovarian cancer treatment but also to ovarian cancer prevention.
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