Diabatic Mechanisms of Higher-Order Harmonic Generation in Solid-State Materials under High-Intensity Electric Fields.

We theoretically investigate mechanisms of higher-order harmonic generation in solid-state materials under a high-intensity ac electric field. A new theoretical framework presented in this Letter holds the legitimacy of Bloch's theorem even under the influence of the high-intensity electric field and provides an exact treatment of the diabatic processes of Bloch electrons. Utilizing this framework, we first discovered that the diabatic processes, namely, ac Zener tunneling and semimetallization of semiconductors, are key factors for nonperturbative mechanisms of HHG. These mechanisms are classified by the field intensity and could be understood by an extended simple man model based on an analogy between tunnel ionization in gaseous media and Zener tunneling in semiconductors. These conclusions would stimulate the universal understanding of HHG mechanisms in both atomic and solid cases.

Novel therapeutic strategy for uterine arteriovenous fistulas: case report.

BACKGROUND: The major presenting symptom of uterine arteriovenous fistulas is massive, torrential vaginal bleeding, the degree of which often leads to a shock state. CASE: A 35-year-old woman, gravida 3, para 2 presented with massive vaginal hemorrhage at the first menstruation six months after delivery. Uterine arteriovenous fistulas were diagnosed by color Doppler ultrasonography (US), dynamic computer tomography (CT), and conventional angiography. The patient underwent hysterectomy after bloodstream decrease by bilateral uterine artery embolization. CONCLUSION: The extent of uterine arteriovenous fistulas was diagnosed by color Doppler US, CT, and pelvic angiography, and this precise evaluation led to an adequate therapeutic strategy for uterine arteriovenous fistulas.

Expression of the inhibitor of DNA-binding (ID)-1 protein as an angiogenic mediator in tumour advancement of uterine cervical cancers.

The ID protein, an inhibitor of basic helix-loop-helix (HLH) transcription factors, has been involved in multiple cellular processes. To investigate the association between tumour advancement and ID expressions of uterine cervical cancers, the levels of ID-1, ID-2 and ID-3 mRNAs were determined by real-time reverse transcription-polymerase chain reaction and the histoscore with the localisation of ID-1 was determined by immunohistochemistry and patient survival in 60 patients. ID-1 histoscores and mRNA levels both significantly (P<0.05) increased in uterine cervical cancers according to clinical stage regardless of histopathological type or lymph node metastasis. Furthermore, the 36-month survival rate of the 30 patients with high ID-1 was poor (60%), whereas that of the other 30 patients with low ID-1 was significantly higher (83%). ID-1 histoscores and mRNA levels significantly (P<0.0001) correlated with microvessel counts in uterine cervical cancers. Tumour cells show mostly diffuse to strong cytoplasmic expression of ID-1 and also very faint expression in endothelial cells. Moreover, ID-1 expression not only correlated with microvessel counts but also correlated significantly with histoscore. Therefore, ID-1 might work on tumour advancement through angiogenic activity and is considered to be a candidate for a prognostic indicator in uterine cervical cancers.

Clinical implication of medroxyprogesterone acetate against advanced ovarian carcinoma: a pilot study.

PURPOSE OF INVESTIGATION: The present study was performed to identify the effects of medroxyprogesterone acetate (MPA) plus adjuvant chemotherapy on advanced epithelial ovarian carcinoma (FIGO Stage III/IV). METHODS: A total of 50 patients were enrolled in this study. A relatively low dose of MPA (200 mg/day) after surgery was administered in combination with platinum-based chemotherapy and the treatment was continued for two years. Patients' backgrounds were also analyzed. RESULTS: Relapse-free survival (p < 0.05) and overall survival (p < 0.001) rates in FIGO Stage III/IV ovarian cancer patients with MPA combined chemotherapy were significantly longer than the control group. The effect was more prominent in the higher progesterone receptor expression group. The chemotherapy regimens (cyclophosphamide, doxorubicin and cisplatin vs paraplatin plus cyclophosphamide or paclitaxel) did not affect prognosis. CONCLUSION: MPA with platinum-based chemotherapy as an adjuvant therapy might improve the prognosis in FIGO Stage III/IV epithelial ovarian cancer cases. A randomized controlled study is still needed for further analyses.

Primary endodermal sinus tumor of the vulva in a 52-year-old woman with long-term survival: a case report.

A postmenopausal 52-year-old Japanese woman with a 5-month history of a right labial tumor was referred to the Department of Obstetrics and Gynecology. The resected tumor had been diagnosed as a primary endodermal sinus tumor of the vulva with pT2N0M0 in 2001. Six courses of adjuvant chemotherapy using bleomycin, etoposide and cisplatin were administered. The patient was free of recurrence or metastasis 67 months after the initial treatment.

Primary lymphoma of the uterine corpus: an unusual location for a common disease--case report.

A case of a primary uterine corpus lymphoma in a 75-year-old woman is described. Immunohistochemical studies showed diffuse large B-cell type one. Primary lymphoma of the uterine corpus is considered to be an unusual location for a common disease.

Effects of selective estrogen receptor modulators and genistein on the expression of ERalpha/beta and COX-1/2 in ovarectomized mouse uteri.

This study was performed to examine the effects of selective estrogen receptor modulators [tamoxifen (TAM) and toremifene (TOR)] and pure anti-estrogen, ICI-182780 (ICI, Faslodex) and soybean isoflavone, genistein (GE) on the expression of estrogen-stimulated c-fos/jun, ERalpha/beta and COX-1/2 in the uteri of ovarectomized mice. TAM, TOR, ICI and GE treatment significantly decreased the levels of estradiol (E2)-induced c-fos. ICI and GE treatment significantly decreased the levels of E2-induced c-jun and ERalpha expressions. High doses of TOR treatment significantly increased the E2-induced ERbeta expression. In contrast, ICI and GE treatment significantly decreased the levels of E,-induced COX-2 expression, thus suggesting that TOR and GE might prevent E2-related endometrial carcinogenesis.

Pseudomyxoma peritonei and mucinous pyometral fluid arising from an ovarian borderline mucinous tumor: case report.

An extremely rare case of a pseudomyxoma peritonei (PMP) and mucinous pyometral fluid, possibly arising from an ovarian borderline mucinous tumor is reported. A 68-year-old Japanese patient received an expolatory laparatomy under a working diagnosis of a PMP, left ovarian cystic tumor and an umbilical hernia. Surgery and platinum-based chemotherapy induced a 15-month disease-free condition.

Norethindrone scatters silver-stained nucleolar organizer regions of Ishikawa cells.

We investigated the effects of sex steroids on silver-stained nucleolar organizer regions (Ag-NORs) and DNA/RNA kinetics in Ishikawa cells. Norethindrone and its isomer norethynodrel exclusively caused Ag-NORs to scatter in the nuclear matrix, from the nucleolus. No such effect occurred with the other sex steroids tested, including progestational, androgenic, and estrogenic compounds. Nuclear argyrophilic substances induced by norethindrone, as well as nucleolar ones, were neither DNA nor RNA but protein. Electron microscopy showed that norethindrone caused nucleolar segregation, in which the fibrillar components disappeared, and it produced islets, consisting of dense fibrillar materials, in the nucleoplasm. Ag-NORs observed on the fibrillar components in control nucleoli were translocated onto the dense fibrillar materials in the nucleoplasm. Although scattering was preferentially found in the cells synthesizing DNA, the scintillation assay of DNA/RNA kinetics suggested that scattering was related to the inhibition of RNA synthesis. These results imply that norethindrone preferentially interacts with intranucleolar DNA when its duplication is occurring and then interferes with rRNA synthesis. Scattering of Ag-NORs might not be caused by the hormonal activity of these agents but by a pharmacological effect derived from their molecular structures.

The value of platelet-derived endothelial cell growth factor as a novel predictor of advancement of uterine cervical cancers.

Serum platelet-derived endothelial cell growth factor (PD-ECGF) in patients with uterine cervical cancers revealed a significantly positive correlation with clinical stage and tumor size and with the advancement indicators lymph node metastasis, parametrial involvement, and vessel permeation in both squamous cell carcinomas and adenocarcinomas. The prognosis of the patients with high serum PD-ECGF was extremely poor, whereas the 36-month survival rate of the other patients with low serum PD-ECGF was 81.3% in squamous cell carcinomas and 80.0% in adenocarcinomas. Our data indicate that serum PD-ECGF levels reflect the status of advancement of uterine cervical cancers and thus may be recognized as a novel tumor marker for both squamous cell carcinomas and adenocarcinomas of the uterine cervix.

Expression of sex hormone-binding globulin exon VII splicing variant messenger RNA in human uterine endometrial cancers.

We have demonstrated the intracellular expression of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA in human uterine endometrial cancer using the reverse transcription-PCR-Southern blot and DNA sequencing analyses. Analysis of the missing base pairs proved that they corresponded to the entire exon VII, which is considered to encode a portion of the steroid-binding site, suggesting that the steroid-binding affinity of this variant might be different from that of the SHBG wild type. In uterine endometrial cancers, the wild-type mRNA levels significantly (P < 0.01) decreased, and the ratio of the SHBG variant to wild-type mRNA levels (P < 0.01) increased with the advance of histological dedifferentiation. These results suggest that dedifferentiation of endometrial cancers might induce a reduction in their estrogen-dependent properties via intracellular SHBG.

Clinical implications of expression of interleukin 8 related to angiogenesis in uterine cervical cancers.

There was a significant correlation between microvessel counts and interleukin (IL)-8 levels and between infiltrated macrophage counts and IL-8 levels in uterine cervical cancers. Immunohistochemical staining revealed that the localization of IL-8 was similar to that of CD68 for macrophages. The prognosis of the 20 patients with high IL-8 (>1000 pg/mg protein) in uterine cervical cancers was extremely poor, whereas the 24-month survival rate of the other 60 patients with low IL-8 (<1000 pg/mg protein) was 67%. Therefore, this indicates that IL-8 might be a prognostic indicator as an angiogenic factor supplied from macrophages within and around the tumor.

Clinical implication of expression of platelet-derived endothelial cell growth factor (PD-ECGF) in metastatic lesions of uterine cervical cancers.

The platelet-derived endothelial cell growth factor (PD-ECGF) level was significantly (P < 0.05) increased in 8 of 40 metastatic lymph node lesions of uterine cervical cancers. The prognosis of the eight patients with high PD-ECGF (>10,000 pg/mg protein) in metastatic lymph node lesions was extremely poor. On the other hand, the 24-month survival rate of the 32 patients with low PD-ECGF (<10,000 pg/mg protein) in metastatic lymph node lesions was 75%. This indicates that PD-ECGF may contribute to the advancement of metastatic lesions, and that the PD-ECGF level in metastatic lesions may be a prognostic indicator.

Attenuation of telomerase activity by a hammerhead ribozyme targeting the template region of telomerase RNA in endometrial carcinoma cells.

Telomerase activity is found in almost all carcinoma cells but not in most somatic cells, suggesting that telomerase is an excellent target for cancer therapy. We designed hammerhead ribozymes against human telomerase RNA and studied their possible use as a tool for cancer therapy. Three ribozymes targeting the 3' end of the GUC sequence at 33-35 (the template region), 168-170, and 313-315 from the 5' end of telomerase RNA were designed. In a cell-free system, these three hammerhead ribozymes efficiently cleaved the RNA substrate. When these ribozyme RNAs were introduced into Ishikawa cells, which are endometrial carcinoma cells, only a ribozyme targeting the RNA template region could diminish the telomerase activity. Next we subcloned the ribozyme sequence into an expression vector and introduced this into AN3CA cells, which are endometrial carcinoma cells. The clones that were obtained showed reduced telomerase activity and telomerase RNA with expression of the ribozyme. These data suggest that the ribozyme against the RNA template region is a good tool to repress telomerase activity in cancer cells.

PTEN augments staurosporine-induced apoptosis in PTEN-null Ishikawa cells by downregulating PI3K/Akt signaling pathway.

Staurosporine is a potent apoptosis inducer, but its mechanism remains to be clarified. We investigated the involvement of PTEN in staurosporine-induced apoptosis. Ishikawa cells, from an endometrial carcinoma cell line, expressed a high amount of PTEN mRNA but did not express the PTEN protein because of protein truncations. We isolated clones expressing the steady-state level of the PTEN protein from PTEN-null Ishikawa cells by transfection. The obtained clones showed reduced proliferative activity and reduced anchorage-independent cell growth with the augmented p27(Kip1). These cell lines were sensitized to apoptosis by staurosporine. A low concentration of UCN-01 did not affect apoptosis, but a high concentration augmented apoptosis in the PTEN-expressing clone. Alpha-sphingosine and H-7 did not affect apoptosis in these cell lines. PI3K inhibition augmented staurosporine-induced apoptosis in the parental cell line, but not in the PTEN-expressing clone. In the clone, phosho-Akt/PKB and phospho-Bad (Ser-136) were downregulated. Staurosporine reduced the levels of phospho-Akt/PKB and phospho-Bad (Ser-136) in all the cell lines, but the reduction was most significant in the PTEN-expressing clone. These results suggest that inhibition of the PI3K/Akt/PKB signaling pathway might be associated with staurosporine-induced apoptosis in Ishikawa cells.

Effects of dioxin and nutrition on cellular proliferation and dioxin- and estrogen-linked genes in ovarian cancer cell lines.

This study was undertaken to examine the effects of dioxin (TCDD) and nutrition on cellular proliferation and dioxin- and estrogen-linked gene expression in ovarian cancer cell lines. Caov-3 and SK-OV-3 cells were incubated in a medium supplemented with 0.5-10% fetal bovine serum (FBS). Cell proliferation was assayed with an MTT assay. Dioxin- and estrogen-linked genes (AhR, ERalpha, ERbeta, CYP1A1 and ARNT) expressed were determined with the RT-PCR method. Caov-3 cells, but not SK-OV-3 cells, were proliferated with TCDD alone with increased AhR and ERa mRNA expressions when incubated in the low FBS concentration. CYP1A1 and ARNT mRNA expressions of SK-OV-3, but not that of Caov-3, were suppressed in the low FBS (under 1.0%) concentration. In the low FBS concentration medium with dioxin, AhR and ERa expression were increased with the proliferation of Caov-3 cells; CYP1A1 and ARNT were stable. Each ovarian cancer cell line may have its own distinct responsiveness to dioxin depending on the nutritional state.

Contribution of functional groups of 19-nor-progestogens to binding to progesterone and estradiol-17beta receptors in rabbit uterus.

The structural elements of 19-norprogestogens which may be essential for binding to progesterone and estradiol-17beta(E2) receptors were investigated in the rabbit uterine cytosol. The kinetic study showed that 19-nor-progestogens are competitive inhibitors of progesterone-receptor (8S) binding and E2-receptor binding. The affinities of steroids for the progesterone receptor were as follows: norethindrone (Ki of 2.3 X 10(-9)M) greater than 5alpha-dihydronorethindrone greater than norethindrone acetate greater than lynestrenol greater than 17alpha-ethynyl-estra-4-ene-3beta, 17beta-diol greater than ethynodiol diacetate (Ki of 1.3 X 10(-7) M). The affinities of steroids for the E2 receptor were as follows: ethynodiol diacetate (Ki of 1.3 X 10(-7)M) greater than 17alpha-ethynyl-estra-4-ene-3beta, 17beta-diol greater than norethindrone acetate greater than norethindrone greater than 5alpha-dihydronorethindrone greater than lynestrenol (Ki of 8.4 X 10(-7)M). The results indicate that 3-ketone and 17beta-hydroxyl groups, and the plane of ring A/B of 19-norprogestogen are important for binding to the progesterone receptor. The affinities of 19-nor-progestogens for the E2 receptor were very weak. Their affinities for the E2 receptor increased with addition of acetate or hydroxyl groups at the 3beta and 17beta positions, and were decreased by the elimination of a 3 oxygen function or the reduction of ring A.

Expression of platelet-derived endothelial cell growth factor (PD-ECGF) related to angiogenesis in ovarian endometriosis.

Platelet-derived endothelial cell growth factor (PD-ECGF) is expressed in the lining epithelial cells of ovarian endometriomas, and in interstitial cells of the subepithelial area with angiogenesis. The expression of PD-ECGF persists in endometriotic endometrium during the menstrual cycle. This might suggest that PD-ECGF contributes to the growth of ovarian endometriomas via subepithelial angiogenesis independently of the sex steroidal milieu.

A gonadotropin-releasing hormone-responsive phosphatase hydrolyses lysophosphatidic acid within the plasma membrane of ovarian cancer cells.

Lysophosphatidic acid (LPA) mediates pleomorphic effects on multiple cell lineages, including an increased proliferative response of ovarian cancer cells both in vitro and in vivo, at least in part through the novel expression of LPA receptors. Thus, LPA hydrolysis is necessary to limit the duration of LPA's action on multiple cell types, including ovarian cancer cells. We determined the principal mechanism of LPA hydrolysis by ovarian cancer cells and its regulation by GnRH, which is known to have antiproliferative actions on ovarian carcinomas. LPA-hydrolyzing activity in cell membranes of ovarian cancer specimens was assessed by measuring the conversion of exogenous [3H-oleoyl]LPA to [3H]oleic acid or mono[3H-oleoyl]glycerol. Approximately 98% of LPA hydrolysis could be accounted for by the dephosphorylation of LPA to yield monoglyceride, with the deacylation reaction accounting for less than 1% of LPA hydrolysis. The phosphatase activity in the plasma membrane ovarian cancer cells was approximately 2.5- and 8-fold higher than those in microsome and homogenate fractions, respectively. The membrane phosphatase was Mg2+ independent and insensitive to inhibition by N-ethylmaleimide, characteristics suggestive of phosphatidic acid phosphatase activity. Incubation of membranes from GnRH receptor-positive ovarian cancer specimens with the GnRH agonist, buserelin, induced a dose-dependent increase in LPA phosphatase activity, with a half-maximal effect occurring with 30 nmol/L buserelin. The stimulatory action of buserelin could be neutralized by displacement of GnRH from its receptor by the GnRH antagonist, antide. The plasma membranes from GnRH receptor-negative ovarian cancer specimens did not respond to GnRH stimulation. LPA phosphatase activity was also increased when the ovarian cancer cell line Caov-3 was exposed to GnRH agonist in intact cells before assay of cell membranes. These data demonstrate that LPA is hydrolyzed in the plasma membrane of ovarian cancer cells by the action of LPA phosphatase and provide initial evidence for functional coupling of LPA phosphatase to GnRH receptor occupancy.

Evidence for tight coupling of gonadotropin-releasing hormone receptor to stimulated Fas ligand expression in reproductive tract tumors: possible mechanism for hormonal control of apoptotic cell death.

Fas ligand induces cell death by means of apoptosis in a variety of cell types when cross-linked with its natural receptor, Fas. GnRH receptor-bearing tumors undergo apoptosis in vivo and in vitro with GnRH agonists. To provide a potential association of the Fas system with the antiproliferative signaling process of GnRH receptor, we have evaluated the regulation of Fas ligand expression in GnRH receptor-positive tumors and cloned cell lines known to have substantial GnRH receptors. Surgically removed uterine endometrial carcinomas and ovarian carcinomas had been screened for GnRH receptor expression before analysis. Fas ligand protein was characterized by immunoblotting of membrane proteins with the specific antibody. Fas ligand messenger RNA was determined by RT-PCR using oligonucleotide primers synthesized according to the published Fas ligand sequence. Incubation with a GnRH analog (1 mumol/L) induced the expression of Fas ligand messenger RNA and immuno-reactive Fas ligand with a lag time of 48 h in cloned cell lines (endometrial carcinoma HHUA cells, and ovarian carcinoma SK-OV-3 and Caov-3 cells). There was no detectable Fas ligand expression within 24 h. The stimulatory effect of GnRH on Fas ligand protein expression revealed a dose dependency; a half-maximal effect occurred with 10 nmol/L GnRH analog (P < 0.01). The stimulated Fas ligand expression could be neutralized by displacement of GnRH from its receptor by GnRH antagonist antide. Cells isolated from GnRH receptor-bearing ovarian carcinomas and uterine endometrial carcinomas gave identical results to those obtained in cloned cell lines. These data demonstrate the functional coupling of stimulated Fas ligand expression to GnRH receptor activation. Increased Fas ligand level within the GnRH receptor-bearing tumors might promote apoptotic cell death through attack on intratumoral Fas-positive cells that could, at least in part, account for the antiproliferative action of the hormone.