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en: Extreme leanness, lower skeletal muscle quality, and loss of muscle mass during treatment are predictors of poor prognosis in cervical cancer treated with concurrent chemoradiation therapy

en: Human papillomavirus vaccination is not widespread in Japan, and the low screening rates result in many cases of locally advanced cervical cancer. We investigated the prognostic significance of sarcopenia in patients with cervical cancer to guide healthcare policies to improve treatment outcomes. This retrospective study included 83 patients with cervical cancer without distant metastasis who underwent primary concurrent chemoradiotherapy between 2013 and 2018. We analyzed the indicators of physical condition and muscle quantity using the SYNAPSE VINCENT software. Muscle mass and the relationship between treatment toxicity and prognosis were evaluated. The patients' median age was 60 (range 33-80) years. Cancer stage distribution was as follows: cT2b or higher, 84.3%; N1, 65.1%; and MA, 27.7%. The overall sarcopenia (skeletal muscle index [SMI] < 38.5) rate was 30.1%, and the rate was 33.9 and 22.2% in patients aged < 64 and ≥ 65 years, respectively. No correlation was observed between clinical stage and musculoskeletal indices. Treatment resulted in decreased body weight and SMI; after treatment, the sarcopenia rate increased to 37.3%. A higher intramuscular adipose tissue content (IMAC) reduced the number of chemotherapy cycles needed. Treatment-associated SMI decreases of ≥ 7% indicated poor prognosis, with significant differences in progression-free survival and overall survival (p = 0.013 and p = 0.012, respectively). Patients who were very lean (body mass index < 18.5 kg/m) before treatment had a poor prognosis (p = 0.016 and p < 0.001). Our findings emphasize the importance of assessing original nutritional status and maintaining muscle mass and quality during the treatment of patients with cervical cancer.

en: International Journal of Clinical Oncology


en: Resveratrol suppresses proliferation and induces apoptosis of uterine sarcoma cells by inhibiting the Wnt signaling pathway.

en: Resveratrol, a natural product and peroxisome proliferator-activated receptor (PPAR) agonist, has been reported to exert anti-cancer effects in several tumor models. A previous study by our group reported that prostaglandin J2, a PPARγ ligand, inhibited cell proliferation in a uterine sarcoma cell line. The aim of the present study was to investigate the role of the Wnt signaling pathway in resveratrol-induced apoptosis and inhibition of cell proliferation in the MES-SA human uterine sarcoma cell line. A WST-1 assay demonstrated that resveratrol inhibited cell proliferation in the MES-SA cell line, and flow cytometry revealed that the number of apoptotic cells increased in a resveratrol dose-dependent manner. The mechanisms underlying these effects of resveratrol were speculated to involve the expression of β-catenin and its target gene, c-myc, which were examined using western blot analysis. The results revealed a dose-dependent downregulation of this β-catenin and c-myc. This effect was blunted by a pharmacological inhibitor of glycogen synthase kinase 3β. Therefore, it is likely that resveratrol inhibited the cell proliferation and increased the number of apoptotic cells, at least partially, via the Wnt signaling pathway. The present results suggest that resveratrol is a potential candidate for the treatment of uterine sarcoma.

en: Experimental and Therapeutic Medicine

ja: Experimental and Therapeutic Medicine


en: What information can change the attitude of teachers toward the human papillomavirus vaccine?

en: We conducted a self-administered survey on the perception of teachers toward human papillomavirus (HPV) vaccine to determine the ways to increase their willingness to encourage its use. Answers were obtained both prior to and after having the teachers read five brief information articles: (i) cervical cancer knowledge, (ii) vaccine knowledge, (iii) result of a survey in Nagoya, (iv) news report of the World Health Organization statement and (v) articles written by Dr Muranaka, a journalist. Most of the respondents (180/247) did not know about the natural history of cervical cancer. Only 36% knew that HPV is the cause of cervical cancer, although 63% knew that HPV vaccine would prevent cervical cancer. Few respondents had knowledge regarding adverse events following immunization and the survey results from Nagoya. Among those who were initially negative for the HPV vaccine, only 43% revealed that they fully understood its safety and only 29% reversed their opinion to recommend vaccination to their daughters and/or students, even after reading our informational material. The most useful information for changing their attitudes was to increase their understanding of vaccines and informing them about Nagoya city survey results. They mostly wanted a proof of the preventive effects of the vaccine on cervical cancer in Japan. Gynecologists and pediatricians must proactively communicate accurate scientific information to the government and the media to spread awareness among people in Japan. Also, we must try to demonstrate the capabilities of this vaccine to prevent cervical cancer and/or its precancerous lesions.

en: The Journal of Obstetrics and Gynaecology Research


en: Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells.

en: Uterine cervical adenocarcinoma has a poor clinical prognosis when compared with squamous cell carcinoma. Therefore, the development of new treatment strategies for uterine cervical adenocarcinoma is necessary. Src is a proto-oncogene that is important in cancer progression. Dasatinib is a Src inhibitor that has been reported to be effective when used in combination with anticancer drugs. The present study aimed to confirm Src expression in human cervical adenocarcinoma cell lines and to determine the mechanism underlying the inhibitory effect of dasatinib on Src signaling . Western blot analysis was performed to investigate Src expression in cervical adenocarcinoma cell lines (HeLa and TCO-2 cells). The cells were cultured for 48 h with the addition of different concentrations of anticancer drugs (paclitaxel or oxaliplatin). Viable cell count was measured using a colorimetric (WST-1) assay. The concentrations of anticancer agents were fixed according to the results obtained, and the same experiments were performed using the drugs in combination with dasatinib at various concentrations to determine the concentrations that significantly affected the number of viable cells. The presence or absence of apoptosis was investigated using a caspase-3/7 assay. Signal transduction in each cell line was examined using western blotting. Src was activated in the two cell lines, and cell proliferation was significantly suppressed by each anticancer drug in combination with 10 µM dasatinib. Caspase-3/7 activity was also increased and Src signaling was suppressed by each anticancer drug in combination with dasatinib. In conclusion, Src is overexpressed in cervical adenocarcinoma cell lines, and dasatinib inhibits intracellular Src signaling and causes apoptosis. The results of the present study suggest that Src may be targeted in novel therapeutic strategies for cervical adenocarcinoma.


en: 術前に卵巣原発胚細胞性腫瘍を疑ったが, 傍卵巣の平滑筋肉腫であった一例

ja: 術前に卵巣原発胚細胞性腫瘍を疑ったが, 傍卵巣の平滑筋肉腫であった一例

en: Modern Trends in Obstetrics & Gynecology

ja: 現代産婦人科


en: Mismatch repair deficiency in young patients of reproductive age with endometrial cancer and atypical endometrial hyperplasia

ja: 生殖年齢期に発生した子宮内膜癌・異型内膜増殖症におけるミスマッチ修復蛋白発現に関する検討

en: MPA therapy is widely administered to patients with early-stage endometrial cancer and atypical endometrial hyperplasia (AEH) who desire a fertility-preserving treatment modality. We examined the relationship between MMR protein expression and the effects of MPA therapy, risk of relapse, prognosis, and familial history in 21 patients. We observed MMR deficiency in 7 patients (MLH1: 4, PMS2: 5, MSH2: 2, and MSH6: 2). All patients with lymph node metastasis or who died had MLH1 deficiency. In 13 of 21 patients, we performed MPA therapy for fertility preservation and confirmed MMR deficiency in 2. After the initial treatment, ovarian cancer developed in 2 patients, one of whom had Peutz-Jeghers syndrome. Due to the small sample size of this study, we found no significant association between MMR deficiency and the effects of MPA therapy or the risk of relapse. Many young patients with endometrial tumors may have inherited diseases, although not necessarily with MMR deficiency. Therefore, clinical assessment considering their past history and family history should be performed prior to each treatment. Our findings will serve as a catalyst for future studies with larger sample sizes.

ja: 妊孕性温存療法希望の早期子宮体癌および異型内膜増殖症症例にMPA療法を行うも不応や再燃症例も経験する．徳島大学産科婦人科で初回治療を行った若年子宮体癌および異型内膜増殖症21症例を対象にミスマッチ修復(mismatch repair;MMR)蛋白発現と，MPA療法の効果，再燃リスク，および予後との関連について検討した．MMR蛋白の発現欠失は7例で認め，MLH1欠失4例，PMS2欠失5例，MSH2欠失2例，MSH6欠失2例であった．リンパ節転移例と再発原病死例はいずれもMLH1欠失例であった．MPA療法施行13例中，MMR欠失を2例で認めたが，いずれもMPA奏効・無病生存例であった．初回治療後，異時性卵巣癌発症を2例に認め，このうちの1例はPeutz-Jeghers症候群であった．本検討では対象例が少なく，MMR蛋白発現とMPA療法の効果および再燃リスクとの間に有意な関連は確認できなかった．しかしMMR欠失を認めなくとも， 遺伝性疾患を背景にもつハイリスク症例もあり，家族歴を考慮した適切な医学的管理が必要であると考えられた．

en: Journal of Hereditary Tumors

ja: 遺伝性腫瘍


en: 嚢胞状帝王切開瘢痕部が着床部結節から成っていた一例

ja: 嚢胞状帝王切開瘢痕部が着床部結節から成っていた一例