Genome-Wide Gene Expression Profiling Reveals the Direct Effect of Dienogest on Ovarian Endometriotic Stromal Cells.

Endometriosis affects up to 10% of women of reproductive age, causing dysmenorrhea, chronic pelvic pain, and infertility. The current key drug for endometriosis is dienogest, a progestin with high specificity for the progesterone receptor. To reveal the direct anti-endometriotic effect of dienogest on ovarian endometriotic cells, we investigated the genome-wide gene expression profiles of ovarian endometriotic stromal cells with (Dienogest group) or without dienogest treatment (Control group) and compared the groups' gene expression profiles. We performed a gene ontology (GO) analysis and Ingenuity pathway analysis using these data. To validate the microarray data, we performed real-time RT-PCRs and immunohistochemistry for the differentially expressed genes between the two groups. Of 647 genes differentially expressed between the two groups, 314 genes were upregulated and 333 were downregulated in the Dienogest group versus the Control group. The GO analysis showed that the regulation of macrophage chemotaxis, the collagen catabolic process, and the proteoglycan biosynthetic process are the main biological processes closely associated with the differentially expressed genes. We identified 20 canonical pathways that were most significantly differentially expressed in the Dienogest group versus the Control group. We observed that matrix metalloproteinases (MMPs) are the genes in these pathways that are most closely associated with dienogest treatment. Of components involved in the regulation of macrophage chemotaxis, colony-stimulating factor 1 and macrophage-stimulating 1 are potential upstream regulators of MMPs and were observed herein to be suppressed by dienogest. Our results suggest that dienogest may thus exert its anti-endometriotic effect by directly suppressing MMPs.

The frequent shift to intermediate flora in preterm delivery cases after abnormal vaginal flora screening.

The effect of screening and treatment for abnormal vaginal flora on the reduction of preterm deliveries remains controversial. We evaluated whether this screening and treatment reduces the preterm delivery rate for general-population pregnant women. Pregnant women of the Intervention group (n = 574) underwent the screening test and the treatment of vaginal metronidazole during the early second trimester, and those of the Control group (n = 1,161) did not. We compared the preterm delivery rate between these two groups. We also compared the profiles of vaginal flora of the preterm delivery cases with those of the pregnant women with a normal course. There was no significant difference in the preterm delivery rate between these two groups. However, in the preterm delivery cases, a frequent shift to intermediate flora was observed not before but after the screening in the Intervention group. This shift may explain why most of the previous studies failed in regard to the prevention of preterm deliveries.

True incidence of uterine adenomatoid tumors.

Uterine adenomatoid tumors (UATs) are benign tumors of the uterine serosa and myometrium that originate from the mesothelium and forming gland-like structures. This study was conducted in order to determine the true incidence of UATs, which are usually an incidental finding during uterine surgery performed for other causes. UATs may resemble pre-existing vessels and lymphatic ducts, as well as metastatic adenocarcinomas. A total of 199 consecutive surgical operations (134 hysterectomies and 65 uterus-preserving tumor excisions) were performed by a single team of gynecologists and examined by a single attending pathologist, who performed a thorough macro- and microscopic examination of all the specimens. UATs were identified in nine (5%) out of the 199 cases [six (5%) out of the 134 hysterectomies and three (5%) out of the 65 uterus-preserving tumor excisions]. Therefore, the true incidence of UATs may be significantly higher than 1%, which is the incidence reported in the presently available literature.

[A case of large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix successfully treated by postoperative CPT-11+CDDP chemotherapy after non-curative surgery].

A 31-year-old woman, gravida 3 para 3, visited a local clinic because of post-coital bleeding. She was diagnosed as having a uterine-cervical tumor and was referred to our hospital. Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix was pathologically shown by biopsy. The patient was initially treated by radical hysterectomy. Postoperative pathological examination revealed a direct invasion to the parametrium and the positive resection margin. Postoperatively, she was treated by CPT-11+CDDP. One course of treatment was 60mg/m² of CPT-11 administered on day 1, 8 and 15, and 60 mg/m² of CDDP on day 1, with an intermission after administration for 7 days. Six courses were carried out. This treatment resulted in complete remission. A follow-up at the outpatient clinic revealed the patient had been tumor-free for one year and three months after the first treatment. We suggest that postoperative chemotherapy with CPT-11+CDDP might be useful in the treatment of patients with LCNEC of the uterine cervix.