Importance of the neoadjuvant rectal (NAR) score to the outcome of neoadjuvant chemotherapy alone for locally advanced rectal cancer.

Purpose: The neoadjuvant rectal (NAR) score is a promising indicator of survival after preoperative chemoradiotherapy for rectal cancer. However, its effectiveness after neoadjuvant chemotherapy (NAC) alone has not been fully investigated.

Methods: We analyzed data retrospectively on 61 patients with rectal cancer, who received NAC followed by surgical resection between 2010 and 2015, and evaluated the impact of the NAR score on survival.

Endometrial Stromal Sarcoma Arising from Endometrial Polyp: A Case Report.

Endometrial stromal sarcoma (ESS) is a rare malignant tumor of the uterus. We report an uncommon case of ESS composed of both low-grade ESS and high-grade ESS arising from an endometrial polyp. On the findings of magnetic resonance imaging and contrast computed tomography, a patient was suspected of having uterine malignant tumor.

Aggressive Granulosa Cell Tumor of the Ovary with Rapid Recurrence: a Case Report and Review of the Literature.

Aggressive adult granulosa cell tumor (AGCT) of the ovary remains uncommon. We report a case of aggressive AGCT of the ovary who had rapid recurrence at two months after surgery. A patient was referred for further examination of a pelvic tumor.

Coexistence of endometrioid adenocarcinoma in atypical polypoid adenomyoma.

Atypical polypoid adenomyoma (APA) is a rare polypoid tumor of the uterus composed of atypical endometrial glands and smooth muscle cells. Concomitant development of endometrial adenocarcinoma in APA remains infrequent. We report a case of the coexistence of endometrioid adenocarcinoma in APA.

ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues.

Lessons learned from the preclinical drug discovery of asoprisnil and ulipristal for non-surgical treatment of uterine leiomyomas.

Introduction: Uterine leiomyoma is the most common benign tumor in women during the reproductive years. Menorrhagia is the common symptom and accounts for the most frequent indication for hysterectomy. Thus, development of a novel drug for non-surgical treatment of uterine leiomyoma is needed for the betterment of women's health.

Translational research with progesterone receptor modulator motivated by the use of levonorgestrel-releasing intrauterine system.

The use of levonorgestrel-releasing intrauterine system (LNG-IUS) is effective for management of menorrhagic women with uterine myomas because of reduction in menorrhagia. However, the size of myomas during use of LNG-IUS increased in some but decreased in other instances. This prompted us to characterize the effects of progesterone (P4) on cultured leiomyoma cell growth.

Cell-type specific actions of progesterone receptor modulators in the regulation of uterine leiomyoma growth.

Although the traditional concept supports a crucial role of estrogen in promoting leiomyoma growth, unequivocal evidence has emerged indicating that progesterone also plays a vital role in the regulation of leiomyoma growth. Recent clinical trials have demonstrated the efficacy of asoprisnil, a selective progesterone receptor modulator, and CDB-2914, a novel progesterone receptor modulator, for the treatment of women with symptomatic leiomyomata. These compounds significantly reduced leiomyoma and uterine volume and improved leiomyoma-related symptoms without serious complications.

Suppression of progesterone production by stresscopin/urocortin 3 in cultured human granulosa-lutein cells.

Background: Corticotropin-releasing hormone (CRH) and its receptors have been identified in female reproductive tissues. CRH regulates follicular maturation, ovulation, luteolysis and steroidgenesis. A CRH-related peptide stresscopin (SCP), or urocortin III (Ucn3), has recently been identified, but its functions in the ovary remain to be elucidated.

Gingival metastasis from ovarian mucinous cystadenocarcinoma as an initial manifestation (a rare case report).

The metastasis of malignant tumors to the oral cavity remains a rare clinical entity. Most metastatic tumors have the propensity for involving the mandible rather than the oral soft tissues. Herein, we describe an unusual case of ovarian mucinous cystadenocarcinoma that metastasized to the mandibular gingiva as an initial manifestation.

Percutaneous pelvic perfusion with extracorporeal chemofiltration for advanced uterine cervical carcinoma.

This review was focused on a new intra-arterial infusion system with an extracorporeal chemofiltration circuit. After inferior vena cava isolation was percutaneously achieved by balloon catheter technique, cisplatin (140-240 mg/m(2)) was administered by intrauterine arterial infusion, with inferior and superior gluteal arterial embolization. The platinum-containing blood was pumped through an extracorporeal charcoal chemofiltration circuit.

Effects of corticotropin-releasing hormone and stresscopin on vascular endothelial growth factor mRNA expression in cultured early human extravillous trophoblasts.

Corticotropin-releasing hormone (CRH) takes a role in the regulation of the onset of parturition. Stresscopin (SCP) is a high affinity ligand for CRH receptor (CRHR)-2. CRHR-2 inhibits VEGF-induced neovascularization.

Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer.

Background: A recent clinical trial demonstrated that selective progesterone receptor modulator asoprisnil is effective in reducing uterine leiomyoma volume. We investigated the effects of asoprisnil in vitro on the expression of the extracellular matrix (ECM)-remodeling enzymes and collagens in cultured leiomyoma and matching normal myometrial cells.

Methods: The expression of extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs) and collagens were assessed by western blot analysis.

Progesterone receptor modulator CDB-2914 induces extracellular matrix metalloproteinase inducer in cultured human uterine leiomyoma cells.

Effects of progesterone receptor modulator CDB-2914 on the expression of the extracellular matrix (ECM) components were examined in cultured human uterine leiomyoma and myometrial cells. ECM metalloproteinase inducer (EMMPRIN), matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMPs) and collagen levels were assessed by Western blot analysis, MMP activity assay and real-time RT-PCR. RNA interference (RNAi) of EMMPRIN was performed using small interfering mRNA.

Comparative effects of SPRM asoprisnil (J867) on proliferation, apoptosis, and the expression of growth factors in cultured uterine leiomyoma cells and normal myometrial cells.

Progesterone plays a pivotal role in controlling uterine leiomyoma growth. The authors review studies they conducted to evaluate the comparative effects of asoprisnil on proliferation, apoptosis, and growth factor expression in cultured leiomyoma and normal myometrial cells. Treatment with asoprisnil decreased the proliferating cell nuclear antigen-positive rate and the number of viable cells and increased the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling- positive rate in cultured leiomyoma cells in a dose-dependent manner ( P < .

Vascular endothelial growth factor +936 C/T polymorphism is associated with an increased risk of endometriosis in a Japanese population.

Background: Vascular endothelial growth factor (VEGF) concentration in endometriosis patients is higher than controls, in serum and ascites, suggesting that VEGF may play an important role in the pathogenesis of endometriosis. In this study, we investigated whether polymorphisms in the VEGF gene are associated with endometriosis in a Japanese population.

Methods: Genotyping of VEGF -460 C/T, +405 G/C and +936 C/T polymorphisms were performed in 147 endometriosis cases diagnosed by laparotomy or laparoscopy at a university hospital, and 181 controls, by polymerase chain reaction-restriction fragment length polymorphism analysis.

Association study between epidermal growth factor receptor and epidermal growth factor polymorphisms and endometriosis in a Japanese population.

Objective: We investigated a possible association between endometriosis and polymorphisms in the genes encoding epidermal growth factor (EGF) receptor (EGFR) and EGF in a Japanese population.

Methods: We compared the distribution of the Egfr+2073 A/T and Egf+61 G/A polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis in 146 affected women and 181 controls.

Results: No significant differences in the frequency and genotype distribution of the Egfr+2073 A/T and Egf+61 G/A polymorphisms were found between endometriosis patients with all disease stages and controls.

Selective progesterone receptor modulator asoprisnil induces endoplasmic reticulum stress in cultured human uterine leiomyoma cells.

A recent clinical trial (Chwalisz K, Larsen L, Mattia-Goldberg C, Edmonds A, Elger W, Winkel CA. Fertil Steril 87: 1399-1412, 2007) has demonstrated that the selective progesterone receptor modulator asoprisnil efficiently causes the shrinkage of uterine leiomyoma. The present study was conducted to examine whether asoprisnil elicits endoplasmic reticulum (ER) stress-induced apoptosis in cultured human uterine leiomyoma cells.

Epidermal growth factor receptor and human epidermal growth factor receptor 2 gene polymorphisms in endometrial cancer in a Japanese population.

Endometrial cancer is associated with both EGFR and HER2 receptor activation. The EGFR and HER2 genes could be disease susceptibility candidate genes for this cancer. This study was conducted to investigate a possible association between EGFR and HER2 gene polymorphisms and endometrial cancer and the influence of these polymorphisms on the clinical outcome of endometrial cancer patients in a Japanese population.

Effects of levonorgestrel-releasing IUS and progesterone receptor modulator PRM CDB-2914 on uterine leiomyomas.

We have found that the use of levonorgestrel-releasing IUS results in a remarkable decrease in endometrial proliferation and a remarkable increase in apoptosis in the endometrium; therefore, it is effective for long-term management of menorrhagic women with uterine myomas because of the striking reduction in menorrhagia. This prompted us to characterize the effects of progesterone (P(4)) and progesterone receptor modulator (PRM) CDB2914 on uterine myoma growth. In vitro studies with cultured uterine leiomyoma cells and normal myometrial cells revealed that P(4) stimulated the proliferative activity in leiomyoma cells, but not in normal myometrial cells.

Plasma adiponectin concentrations and placental adiponectin expression in pre-eclamptic women.

This study was conducted to compare maternal plasma adiponectin concentrations and adiponectin expression in term placentas between normotensive pregnant women and pre-eclamptic women. Plasma adiponectin concentrations were assessed by a sandwich enzyme-linked immunosorbent assay in 81 normotensive pregnant women, 27 pre-eclamptic women and 15 non-pregnant healthy women. The expression of adiponectin in the placentas was assessed by immunohistochemistry.

A novel selective progesterone receptor modulator asoprisnil activates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated signaling pathway in cultured human uterine leiomyoma cells in the absence of comparable effects on myometrial cells.

Context: We previously demonstrated that asoprisnil, a selective progesterone receptor modulator, induces apoptosis of cultured uterine leiomyoma cells. This study was conducted to evaluate whether asoprisnil activates TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptotic pathway in cultured uterine leiomyoma and matching myometrial cells.

Objective And Methods: After subculture in phenol red-free DMEM supplemented with 10% fetal bovine serum for 120 h, cultured cells were stepped down to serum-free conditions for 24 h in the absence or presence of graded concentrations of asoprisnil.

Matrix metalloproteinase-1 and -9 promoter polymorphisms and endometrial carcinoma risk in a Japanese population.

Objective: The matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases that degrade all the components of the extracellular matrix (ECM). Several studies have demonstrated association between MMP gene polymorphisms and various cancers. The object of this study was to investigate whether the MMP-1 and MMP-9 gene promoter polymorphisms are associated with endometrial carcinomas in a Japanese population.

Progesterone receptor modulator CDB-2914 down-regulates vascular endothelial growth factor, adrenomedullin and their receptors and modulates progesterone receptor content in cultured human uterine leiomyoma cells.

Background: This study was conducted to evaluate the effects of graded concentrations (10(-8), 10(-7) and 10(-6) M) of progesterone receptor (PR) modulator CDB-2914 on the protein contents of PR, of vascular endothelial growth factor (VEGF), adrenomedullin (ADM) and their receptors in cultured human uterine leiomyoma and matching myometrial cells.

Methods: PR-A, PR-B, VEGF-A, VEGF-B, VEGF receptor (VEGFR)-1, VEGFR-2, ADM and ADM receptor (ADMR) contents were assessed by Western blot analysis.

Results: Treatment with 100 ng/ml progesterone increased VEGF-A, VEGF-B and ADM contents in cultured leiomyoma cells and normal myometrial cells.