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Metformin: A possible drug for treatment of endometrial cancer

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Open Journal of Obstetrics and Gynecology 2012年第1期2卷 1-6页

作者： Kosuke Tsuji Iori Kisu Kouji Banno Megumi Yanokura Arisa Ueki Kenta Masuda Yusuke Kobayashi Wataru Yamagami Hiroyuki Nomura nobuyuki susumu Daisuke Aoki Department of Obstetrics and Gynecology School of Medicine Keio University Tokyo Japan

Metformin is a widely used first-line drug for treatment of type 2 diabetes mellitus. In recent years, it has been reported that administration of metformin can reduce carcinogenic risk and inhibit proliferation of cancer cells including those from glioma and breast cancer. The underlying mechanism is thought to involve increased LKB-1 phosphorylation induced by metformin, followed by LKB-1 phosphorylation and activation of AMP-activated protein kinase (AMPK), which then inhibits the mammalian target of rapamycin (mTOR) pathway and results in inhibition of cell proliferation. In endometrial cancer, metformin causes cell cycle arrest in vitro, reduces hTERT mRNA, inhibits the mTOR pathway via AMPK, and is involved in inhibition of phosphorylation of S6 ribosomal protein (S6RP). Metformin promotes expression of progesterone receptor by an action opposite to that of insulin-like growth factor-2 (IGF-2) when used in combination with medroxyprogesterone acetate. This enhances the antitumor effect and this approach may be applicable in a clinical setting.

关键词： Metformin Endometrial Cancer Type 2 Diabetes Mellitus Mammalian Target of Rapamycin (mTOR) Progesterone Receptor (PR)

Epigenetic Aberrant Hypermethylation of DNA in Endometrial Cancer: Application as a Biomarker

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Journal of Cancer Therapy 2011年第5期2卷 610-615页

作者： Asuka Ono Iori Kisu Kouji Banno Megumi Yanokura Kenta Masuda Yusuke Kobayashi Kosuke Tsuji Arisa Ueki Wataru Yamagami Hiroyuki Nomura nobuyuki susumu Daisuke Aoki 不详

Endometrial cancer is the seventh most common cancer worldwide among females and accounts for about 40% of cancers of the uterus in Japan. An increase in incidence and a reduction in onset age of this disease are also likely, which makes it important to define the pathogenesis and develop effective treatment. However, the mechanism of canceration in the endometrium is unclear and development of endometrial cancer cannot be explained only by mutations of cancer-related genes. In contrast, epigenetic analyses have shown the importance of aberrant DNA hypermethylation in the canceration mechanism. In development of type 1 endometrial cancer, breakdown of the DNA mismatch repair system plays a large role, with changes in the human mutL homologue 1 (hMLH1) gene being of most importance. Studies to detect aberrant DNA hypermethylation of cancer cells present in microscopic amounts in vivo and to apply these data to diagnosis of cancer have been started. Epigenetic changes have also been examined as a marker of sensitivity to anticancer drugs. Aberrant hypermethylation of checkpoint with forkhead-associated and ring finger (CHFR), a mitotic phase checkpoint gene, is correlated with sensitivity to treatment with microtubule inhibitors and may be a marker for the response of endometrial cancer to anticancer drugs. Epigenetic aberrant DNA methylation of other genes may also be useful as clinical biomarkers for diagnosis and treatment of endometrial cancer.

关键词： Epigenetics Endometrial Cancer Aberrant DNA Hypermethylation hMLH1 CHFR Biomarker

Atypical Polypoid Adenomyoma (APAM) of the Uterine: Relationship with Endometrial Cancer

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Journal of Cancer Therapy 2011年第4期2卷 458-462页

作者： Iori Kisu Kouji Banno Megumi Yanokura Yusuke Kobayashi Arisa Ueki Asuka Ono Kennta Masuda Wataru Yamagami Hiroyuki Nomura Akira Hirasawa nobuyuki susumu Daisuke Aoki 不详

Atypical polypoid adenomyoma (APAM) is a rare polypoid tumor that generally occurs in women of reproductive age who have abnormal genital bleeding. The tumor was reported as a new disease concept by Mazur in 1981. Pathologically, APAM consist of irregularly proliferated endometrial gland cells and interlacing bundles of smooth muscle cells within the stroma, and have a similar form to adenocarcinoma, adenofibroma, adenosarcoma, and carcinosarcoma. Therefore, differential diagnosis is required in many cases. APAM is pathologically classified as a benign lesion and clinically has a comparatively favorable outcome. However, treatment and follow-up observation should be performed carefully because recurrence and residual lesions occur in many patients after conservative treatment. Concomitant development of endometrial adenocarcinoma also occurs in many cases and it is difficult to differentiate this disease from APAM. Thus, diagnosis of APAM should be made carefully, particularly since the number of cases of endometrial adenocarcinoma has increased in recent years. Furthermore, APAM tends to develop during a woman’s reproductive years, and fertility sparing treatment should be considered. Here, we review the clinicopathological characteristics of APAM, including the difficulty of diagnosis as a benign or malignant uterine tumor, and we examine the relationship between APAM and endometrial cancer.

关键词： Atypical Polypoid Adenomyoma Endometrial Adenocarcinoma Atypical Endometrial Hyperplasia Transcervical Resectoscope Fertility Sparing

Cisplatin-induced activation of TGF-βsignaling contributes to drug resistance

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Oncology Research 2024年第1期32卷 139-150页

作者： SAYAKA IMATSUJI YUKIKO UJIE HIROYUKI ODAKE MASAYA IMOTO susumu ITOH ETSU TASHIRO Department of Biosciences and Informatics Faculty of Science and TechnologyKeio UniversityYokohama223-8522Japan Department of Neurology Juntendo University Graduate School of MedicineTokyo113-8421Japan Laboratory of Biochemistry Showa Pharmaceutical UniversityTokyo194-8543Japan

Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer ***,the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains *** address this issue,we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell *** these clones,the epithelial marker E-cadherin was downregulated,whereas the mesenchymal marker N-cadherin was ***,the expression of EMT-related transcription factors,including Slug,was *** the other hand,the upregulation of other mesenchymal marker Vimentin was weak,suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant *** mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β(TGF-β)receptor kinase inhibitors,indicating that TGF-βsignaling is involved in cisplatin-induced the mesenchymallike phenotypic ***,cisplatin was observed to enhance the secretion of TGF-βinto the culture media without influencing TGF-βgene *** results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-βsecretion,ultimately resulting in drug resistance.

关键词： Cisplatin EMT Chemo-resistance TGF-β

Assessment of corrected time-step method for nominal ionospheric gradient calculation: A comparative analysis with spatial approaches

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Earth and Planetary Physics 2024年第4期8卷 641-649页

作者： Slamet Supriadi Prayitno Abadi susumu Saito Harry Bangkit Dwiko Unggul Prabowo Adi Purwono Ginaldi Ari Nugroho Research Center for Smart Mechatronics National Research and Innovation Agency(BRIN)BandungIndonesia Research Center for Climate and Atmosphere BRINBandungIndonesia School of Electrical Engineering Telkom UniversityKab.BandungIndonesia Electronic Navigation Research Institute National Institute of MaritimePort and Aviation TechnologyTokyoJapan Research Center for Space BRINBandungIndonesia

The effect of ionospheric delay on the ground-based augmentation system under normal conditions can be mitigated by determining the value of the nominal ionospheric gradient(σvig).The nominal ionospheric gradient is generally obtained from Continuously Operating Reference Stations data by using the spatial single-difference method(mixed-pair,station-pair,or satellite-pair)or the temporal single-difference method(time-step).The time-step method uses only a single receiver,but it still contains ionospheric temporal *** introduce a corrected time-step method using a fixed-ionospheric pierce point from the geostationary equatorial orbit satellite and test it through simulations based on the global ionospheric *** also investigate the effect of satellite paths on the corrected time-step method in the region of the equator,which tends to be in a more north–south direction and to have less coverage for the east–west ionospheric *** study also addresses the limitations of temporal variation correction coverage and recommends using only the correction from *** processes are developed under simulations because observational data are still difficult to *** findings demonstrate that the corrected time-step method yieldsσvig values consistent with other approaches.

关键词： ground-based augmentation system nominal ionospheric gradient time-step correction global ionospheric model

Anti-Obesity Effects of Dietary d-Allulose and Medium-Chain Triglycerides in High-Fat Diet-Fed Rats

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Food and Nutrition Sciences 2024年第8期15卷 701-710页

作者： Tatsuhiro Matsuo Chihiro Yokoyama Takako Yamada Tetsuo Iida susumu Mochizuki Akihide Yoshihara Kazuya Akimitsu Faculty of Agriculture Kagawa University Miki-cho Japan Research and Development Matsutani Chemical Industry Co. Ltd. Itami Japan

d-Allulose, a rare sugar, exerts anti-obesity effects by inhibiting hepatic lipogenesis and promoting energy expenditure. Medium-chain triglycerides (MCTs) consist of three medium-chain fatty acids connected by glycerol. MCTs have been extensively investigated for their ability to reduce body fat accumulation. We previously investigated the anti-obesity effects of a combination of dietary d-allulose and MCT (5% - 13%) in rats;however, we could not confirm the anti-obesity effects of MCT or observed synergetic effects between d-allulose and MCT on body fat loss. We speculated that our previous studies were influenced by the excessive amount of MCT in the diets. Therefore, in this study, we aimed to investigate the anti-obesity effects of the simultaneous intake of d-allulose and MCT in rats fed an obesity-inducing high-fat diet with a low amount of MCTs (2%). Thirty-two male Wistar rats (3-week-old) were randomly divided into four groups: control, d-allulose, MCT, and d-allulose + MCT groups. Rats in each group were fed ad libitum on a control (no d-Allulose or MCT), 5% d-allulose, 2% MCT, or 5% d-allulose + 2% MCT diets for 16 weeks. Abdominal adipose tissue weights were significantly lower in the d-allulose diet group than in the control group, whereas no differences were observed between results of the MCT-supplemented groups. The total body fat mass was significantly lower in the d-allulose and MCT diet groups than in the control group, but no differences were observed between the MCT-supplemented groups. These results suggested that anti-obesity effects of dietary d-allulose were observed, and the effects of dietary MCTs were weaker than those of d-allulose. Moreover, we confirmed the interaction between dietary d-allulose and MCT on indicators of obesity. Interestingly, their effects were not synergistic, as MCT supplementation offset the anti-obesity effects of dietary d-allulose. However, the specific mechanisms underlying those effects remain unknown, warran

关键词： Rare Sugar d-Allulose Medium-Chain Triglycerides Body Fat Rat

Epigenetic Aberrant Hypermethylation of DNA in Endometrial Cancer: Application as a Biomarker

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Atypical Polypoid Adenomyoma (APAM) of the Uterine: Relationship with Endometrial Cancer

Journal of Cancer Therapy（癌症治疗） 2011年第5期

作者： Asuka Ono Iori Kisu Kouji Banno Megumi Yanokura Kenta Masuda Yusuke Kobayashi Kosuke Tsuji Arisa Ueki Wataru Yamagami Hiroyuki Nomura nobuyuki susumu Daisuke Aoki

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susumu Tamai MD, PhD——Autobiography

Journal of Cancer Therapy（癌症治疗） 2011年第4期

作者： Iori Kisu Kouji Banno Megumi Yanokura Yusuke Kobayashi Arisa Ueki Asuka Ono Kennta Masuda Wataru Yamagami Hiroyuki Nomura Akira Hirasawa nobuyuki susumu Daisuke Aoki

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中华显微外科杂志 2020年第2期43卷 I0007-I0008页

作者： susumu Tamai 河南省平顶山市湛河骨伤科医院手显微外科河南平顶山467000

I follow a long line of ancestors in my family *** first physician in my family dates back to 1650 and this occupation continues for 370 years up to the present time.I was born March 13,1935,in Kashihara city,in Nara,Japan.I graduated with my medical degree from Nara Medical University in 1959,continuing the line of 21 generations of physicians in my family.

关键词： occupation continue Auto