Phylogenetic position of the Atlantic Gnomefish, Scombrops oculatus (Teleostei: Scombropidae), within the genus Scombrops, inferred from the sequences of complete mitochondrial genome and cytochrome c oxidase subunit I genes.

We determined the complete mitochondrial genome of the Atlantic Gnomefish, Scombrops oculatus (Scombropidae). The total length of mitochondrial DNA (mtDNA) was 16,515 bp and included 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one control region. The gene arrangement of S. oculatus was identical to those of three Japanese scombropid species and those of other teleosts. The phylogenetic analysis using the whole mtDNA, excluding the control region, indicates the Atlantic species is distinct from the Japanese clade, whereas that using cytochrome c oxidase subunit I gene showed the Atlantic species is most closely related to the African species.

Species composition of the genus Scombrops (Teleostei, Scombropidae) in the waters around the Japanese Archipelago: detection of a cryptic species.

Current literature states that family Scombropidae consists of a single genus Scombrops comprising three species worldwide, with two of them, Scombrops boops and Scombrops gilberti, distributed in the waters around the Japanese Archipelago. Although these two scombropids are commercially important species, little is known about the ecology of these fishes. It is difficult to discriminate between these two species based on external characteristics because of their morphological similarity. Here, we report two different morphotypes characterized by the relative growth between the otolith size and the standard length (SL) of the scombropid specimens caught in southern waters off Kyushu Island, Japan, and show the genetic relationship between the morphotypes by means of phylogenetic analyses using complete DNA sequences of the cytochrome b gene. The relationship between otolith weight and SL was significantly different between specimens < 505 mm SL and those > 550 mm SL. Phylogenetic analysis demonstrated that the sequences from these scombropid specimens formed three clades: two corresponded to S. boops and S. gilberti, while the third did not correspond to any sequence recorded in databases, suggesting that these specimens are undescribed scombropid species. Almost all the specimens with SL < 505 mm (n = 76) were identified as S. boops, and only nine as S. gilberti. On the other hand, almost all the specimens with SL > 550 mm (n = 41) fell in the unidentified group except for four specimens, whose sequences were identical to that of S. boops.

Complete mitochondrial genome of an undescribed gnomefish of the genus Scombrops (Teleostei, Scombropidae) from southern waters off Kyushu Island, Japan.

The complete mitochondrial genome of an undescribed gnomefish species of the genus Scombrops was determined using a PCR-based method. The total length of mitochondrial DNA (mtDNA) was 16,521 bp, and included 13 protein-coding genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes and one control region. The mitochondrial gene arrangement of this gnomefish species was identical to that of two previously described scombropid species, Scombrops boops and Scombrops gilberti, and also to those of other teleosts. Maximum likelihood analysis showed that the undescribed scombropid species is most closely related to S. boops.

The complete mitochondrial genome of the gnomefish Scombrops boops (Teleostei, Perciformes, Scombropidae) from the Pacific Ocean off the Japanese Islands.

The complete mitochondrial genome of the gnomefish Scombrops boops was determined by a PCR-based method. The total length of mitochondrial DNA (mtDNA) was 16,517 bp, including 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes and one control region. The mitochondrial gene arrangement of the gnomefish mtDNA was identical to those of typical teleosts. This is the first report of the complete mitochondrial genome of a member of the Scombropidae family and will be useful for the development of molecular tools for ecological research.

Phylogenetic position of Scombropidae within teleostei: the complete mitochondrial genome of the gnomefish, Scombrops gilberti.

The complete mitochondrial genome of the Japanese gnomefish, Scombrops gilberti, was determined using a PCR-based method. The total length of mitochondrial DNA (mtDNA) is 16 518 bp, which includes 13 protein-coding genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and one control region. The mitochondrial gene arrangement of S. gilberti was found to be identical to that of other scombropid and indeed, other teleosts as well. Maximum likelihood analysis revealed that Scombropidae forms a sister group to Pempheriformes.

Ovarian small cell carcinoma complicated by carcinomatous meningitis.

Meningeal metastasis is rare in the clinical course of ovarian carcinoma and its prognosis is extremely poor. We experienced a case of carcinomatous meningitis from metastatic ovarian small cell carcinoma. A 33-year-old woman with atypical genital bleeding, was diagnosed with a right ovarian tumor and referred to our department. She underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymphadenectomy. It was an optimal debulking surgery. She was diagnosed with ovarian carcinoma classified as Stage IIIc according to the Féderation Internationale de Gynécologie et d'Obstétrique classification system. Histological findings showed small cell carcinoma of the pulmonary type. The tumor was bilateral with paraaortic lymph node involvement. The patient was treated with irinotecan and cisplatin (CPT-P therapy). After 4 courses of CPT-P therapy, multiple liver metastases and Virchow's lymph node metastases were found. She was treated with amrubicin as a second-line chemotherapy, but the treatment was ineffective. Five months after surgery, the patient complained of severe headache and nausea. Lumbar puncture was performed and cytology was positive. Magnetic resonance brain imaging indicated meningeal thickening. The patient was diagnosed with meningeal metastasis and received 19-Gy whole cranial irradiation. In spite of these treatments, her disease progressed rapidly and she was often drowsy. She died of aspiration pneumonia 6 months after surgery.

Population genetic structure of Scombrops boops (Percoid, Scombropidae) around the Japanese archipelago inferred from the cytochrome b gene sequence in mitochondrial DNA.

The gnomefish (Scombrops boops) is a member of the percoid family Scombropidae, which includes a single genus and three to four species worldwide. Since little is known about the ecology of this species, here, sequencing analysis of the cytochrome b gene (1141 bp) in mitochondrial DNA detected 101 haplotypes from 186 individuals of S. boops collected from waters at seven localities around the Japanese archipelago. A single haplotype (Sb2) was the most abundant in the combined populations of S. boops from various localities. Genetic population structure analyses revealed no significant differences among these populations (Fst = - 0.0313-0.0195; Φst = - 0.0505-0.0615) with high haplotype diversity and low nucleotide diversity. This suggests that S. boops around the Japanese archipelago constitutes a single population, and indicates that the genetic structure of this population may be influenced by larval and egg dispersal in association with warm currents.

A translocator protein ligand PK11195 shows antigrowth activity in human choriocarcinoma cells.

The potential anticancer agent 1-(2-chlorophenyl-N-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a translocator protein ligand (initially described as a ligand for the peripheral benzodiazepine receptor), induces apoptosis in some lines of human tumor cells. We investigated the effect of PK11195 in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of PK11195, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A WST-1 assay showed that BeWo cells were sensitive to the growth inhibitory effect of PK11195. In contrast, the nonsite selective ligand diazepam has a little effect on these cells. Cell cycle analysis indicated that exposure to PK11195 decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine, by the loss of mitochondrial transmembrane potential, and by antibodies directed against histones from fragmented DNA. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that PK11195 may serve as a therapeutic agent for the treatment of choriocarcinoma.

Bufalin, a traditional oriental medicine, induces apoptosis in human cancer cells.

Bufalin is a traditional oriental medicines which induces apoptosis in some lines of human tumor cells. It constitutes the major digoxin-like immunoreactive component of Chan Su, obtained from the skin and parotid venom glands of toads. Bufalin is cardioactive C-24 steroids that exhibits a variety of biological activities, such as cardiotonic, anaesthetic, blood pressure stimulatory, respiratory and antineoplastic effects. In terms of its anti-tumor activity, bufalin has been demonstrated to inhibit the growth of tumors, such as endometrial and ovarian cancers. This commentary introduces biologic and therapeutic effects of bufalin in treating some cancers. The compound is able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in human cancer cells.

Calcium/calmodulin-dependent kinase inhibitor induces growth inhibition, cell cycle arrest, and apoptosis in human choriocarcinoma cells.

KN-93, a membrane-permeant calcium/calmodulin- dependent kinase-selective inhibitor, induces apoptosis in some lines of human tumor cells. We investigated the effect of KN-93 in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of KN-93, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A WST-1 assay showed that BeWo cells were sensitive to the growth inhibitory effect of KN-93. Cell cycle analysis indicated that exposure to KN-93 decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine, by the loss of mitochondrial transmembrane potential, and by antibodies directed against histones from fragmented DNA. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that KN-93 may serve as a therapeutic agent for the treatment of choriocarcinoma.

Application of the histone deacetylase inhibitors for the treatment of endometriosis: histone modifications as pathogenesis and novel therapeutic target.

BACKGROUND: Accumulating evidence suggests that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. We investigated the histone acetylation status in endometriosis and the application of the histone deacetylase inhibitors (HDACIs) for the treatment of endometriosis. METHODS: The levels of acetylated histones in the endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) were evaluated. The effects of the HDACIs on cell proliferation, the cell cycle, apoptosis of ECSCs and NESCs, and the expression of genes related to these cellular events were investigated. The effects of HDACIs on histone acetylation in chromatin of the promoter region of the cell cycle regulatory genes in ECSCs were also investigated. RESULTS: The acetylated histone levels were significantly lower in ECSCs than in NESCs (P < 0.025). HDACIs inhibited cell proliferation and induced cell cycle arrest and apoptosis of ECSCs. The effects of HDACIs on NESCs were marginal or weak. These HDACIs induced an accumulation of acetylated histones in total cellular chromatin and in the promoter regions of the p16(INK4a), p21(Waf1/Cip1), p27(Kip1) and cycle checkpoint kinase 2 genes in ECSCs. HDACIs induced the protein expression of these cell cycle regulators and suppressed the protein expression of Bcl-2 and Bcl-X(L) in ECSCs. CONCLUSIONS: The present findings demonstrated that aberrant histone modifications are present in endometriosis and that HDACIs reactivated epigenetically silenced genes, resulting in the suppression of cell proliferation, induction of cell cycle arrest and apoptosis of ECSCs. HDACIs are therefore promising agents for the treatment of endometriosis.

Small cell carcinoma of the endometrium: a report of two cases.

Primary small cell carcinoma of the endometrium is rare and has an extremely poor prognosis. This report describes two cases of small cell carcinoma of the endometrium diagnosed as stage III. Case 1 was diagnosed as stage IIIc. She underwent surgery and chemotherapy. For a locally recurrent tumor, she received radiotherapy. She has been well with no evidence of disease for 4 years. Case 2 was diagnosed as stage IIIa. She underwent surgery. The tumor recurred soon after the surgery, and she died 33 days after the surgery. In the literature, the median survival reported for patients with stage III and IV is only 5 months. Case 1 is the 4th case showing long-term survival with advanced-stage disease. The optimal treatment for this rare tumor has not been established. Considering its rarity and variability, it is difficult to establish an evidence-based therapeutic regimen.

Effects of bufalin on the proliferation of human choriocarcinoma cells.

OBJECTIVE: Bufalin is a traditional Chinese medicine, and it induces apoptosis in some lines of human tumor cells. METHODS: We investigated the effect of bufalin in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of bufalin, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. RESULTS: An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that BeWo cells were sensitive to the growth inhibitory effect of bufalin. Cell cycle analysis indicated that exposure to bufalin decreased the proportion of cells in the synthesis phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by annexin V staining of externalized phosphatidylserine and by the loss of mitochondrial transmembrane potential. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. CONCLUSIONS: These results suggest that bufalin may serve as a therapeutic agent for the treatment of choriocarcinoma.

Novel chemotherapy using histone deacetylase inhibitors in cervical cancer.

Since epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in cervical cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs) in treating cervical cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of genes related to the malignant phenotype in a variety of cervical cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21WAF1 gene in human cervical carcinoma cells. In xenograft models, some HDACIs have demonstrated antitumor activity with only few side effects. Some clinical trials demonstrate that HDACI drugs provide an important class of new mechanism-based therapeutics for cervical cancer. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating cervical cancer, especially focusing on preclinical studies and clinical trials.

Aberrant DNA methylation status of endometriosis: epigenetics as the pathogenesis, biomarker and therapeutic target.

Endometriosis, a common, benign, estrogen-dependent disease affecting 3-10% of women of reproductive age, is characterized by the ectopic growth of endometrial tissue that is found primarily in the peritoneum, ovaries and rectovaginal septum. Recently, endometriosis has been alternatively described as an immune disease, a genetic disease and a disease caused by exposure to environmental factors, in addition to its usual description as a hormonal disease. In addition, accumulating evidence suggests that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. Epigenetic alterations reported to date in endometriosis include the genomic DNA methylation of progesterone receptor-B, E-cadherin, homeobox A10, estrogen receptor-ß, steroidogenic factor-1 and aromatase. Aberrant expression of DNA methyltransferases, which attach a methyl group to the 5-carbon position of cytosine bases in the CpG island of the promoter region and silence the corresponding gene expression, has also been demonstrated in endometriosis. This review summarizes the recent studies on the aberrant DNA methylation status and aberrant expression of DNA methyltransferases, which regulate DNA methylation, in endometriosis. We also discuss the recent information on the diagnostic and therapeutic implications of epigenetic alterations occurring in endometriosis.

Advanced small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy with irinotecan and cisplatin followed by radical surgery.

Small cell carcinoma of the uterine cervix is a rare form of cervical cancer characterized by extreme aggressiveness and poor prognosis because of its rapid growth, frequent distant metastases, and resistance to conventional treatment modalities. We report here a case of advanced-stage small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy, followed by radical surgery, resulting in locoregional disease control. A 39-year-old Japanese woman was diagnosed as having stage IIIb small cell carcinoma of the uterine cervix. She was treated by neoadjuvant chemotherapy with irinotecan/cisplatin, followed by extended radical hysterectomy with pelvic and paraaortic lymphadenectomy. The patient was further treated by adjuvant chemotherapy with irinotecan/cisplatin. Intrapelvic recurrence has not been detected throughout the postoperative course. However, the patient died with distant metastases of the disease, 27 months following the initial treatment. It has been suggested that neoadjuvant chemotherapy therapy followed by radical surgery is a treatment option for advanced-stage small cell carcinoma of the uterine cervix for the locoregional disease control. Further studies are necessary to obtain information regarding multimodal treatment including sequence, duration, frequency, and type of effective chemotherapy agents to be used in the treatment of small cell carcinoma of the uterine cervix.

Erucylphosphocholine induces growth inhibition, cell cycle arrest, and apoptosis in human choriocarcinoma cells.

A membrane-targeted, lipophilic ether lipid of synthetic phospholipid analog, erucylphosphocholine (ErPC), induces apoptosis in some lines of human tumor cells. We investigated the effect of ErPC in the choriocarcinoma cell line, BeWo. BeWo cells were treated with various concentrations of ErPC, and changes in cell growth, the cell cycle, apoptosis, and related parameters were examined. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that BeWo cells were sensitive to the growth inhibitory effect of ErPC. Cell cycle analysis indicated that exposure to ErPC decreased the proportion of cells in the S phase and increased the proportion in the G0/G1 phases of the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of externalized phosphatidylserine and by the loss of mitochondrial transmembrane potential. This induction occurred in conjunction with the altered expression of genes related to cell growth, malignant phenotype, and apoptosis. These results suggest that ErPC may serve as a therapeutic agent for the treatment of choriocarcinoma.

Aberrant expression of apoptosis-related molecules in endometriosis: a possible mechanism underlying the pathogenesis of endometriosis.

Endometriosis, a disease affecting 3% to 10% of women of reproductive age, is characterized by the ectopic growth of endometrial tissue under the influence of estrogen. It is also becoming recognized as a condition in which ectopic endometrial cells exhibit abnormal proliferative and apoptotic regulation in response to appropriate stimuli. Apoptosis plays a critical role in maintaining tissue homeostasis and represents a normal function to eliminate excess or dysfunctional cells. Accumulated evidence suggests that, in healthy women, endometrial cells expelled during menstruation do not survive in ectopic locations because of programmed cell death, while decreased apoptosis may lead to the ectopic survival and implantation of these cells, resulting in the development of endometriosis. Both the inability of endometrial cells to transmit a "death" signal and the ability of endometrial cells to avoid cell death have been associated with increased expression of antiapoptotic factors and decreased expression of preapoptotic factors. Further investigations may elucidate the role of apoptosis-associated molecules in the pathogenesis of endometriosis. Medical treatment with apoptosis-inducing agents may be novel and promising therapeutic strategy for endometriosis.

Impact of positron emission tomography/computed tomography in the management of patients with epithelial ovarian carcinoma after treatment.

PURPOSE: The aims of this study were to compare the usefulness and reliability of integrated whole-body positron emission tomography/computed tomography (PET/CT) using (18)F-fluorodeoxyglucose (FDG) with those of contrast-enhanced multidetector CT during regular follow-up in patients after initial treatment of ovarian cancer, to assess the impact of FDG-PET/CT on the confirmation of recurrence, restaging, and clinical management of patients, and to determine the incremental information provided by PET/CT. METHODS: A retrospective review was performed on 19 ovarian cancer patients who underwent a total of 30 FDG-PET/CT and contrast-enhanced multidetector CT scans. The following information was obtained: the clinical information of the patients; the results of FDG-PET/CT and contrast-enhanced multidetector CT, particularly with regard to the impact on the diagnosis of recurrence; information on the localization and number of diseases; and the impact on subsequent clinical management. RESULTS: Both FDG-PET/CT and contrast-enhanced multidetector CT had very high sensitivity and specificity for the detection of recurrent ovarian cancer. Contrast-enhanced multidetector CT was considered the more accurate imaging modality for detecting recurrence, whereas FDG-PET/CT was proven more effective for detecting large numbers of small lesions. When comparing the impact on the choice of a management plan, both FDG-PET/CT and contrast-enhanced multidetector CT were found to be significantly effective at predicting the locations of recurrence. CONCLUSIONS: Both integrated FDG-PET/CT and contrast-enhanced multidetector CT are sensitive surveillance modalities for the detection of recurrent ovarian cancer; the use of both modalities aids decisions on treatment plans and may ultimately have a favorable impact on prognosis. However, contrast-enhanced multidetector CT is recommended for the regular follow-up for ovarian cancer patients after initial treatment.

Synchronous ovarian endometrioid adenocarcinoma with a functioning stroma and endometrial endometrioid adenocarcinoma by different loss of heterozygosity findings.

PURPOSE: Mucinous epithelial ovarian tumors generally have estrogenic stroma, although the frequency of endometrioid adenocarcinoma with functioning stroma is very low. And while synchronous development of carcinomas in the endometrium and ovaries is a fairly common phenomenon, the distinction of a single clonal tumor with metastasis from two independent primary tumors may present a diagnostic challenge. We present a rare case of a 31-year-old woman with endometrioid adenocarcinoma of the ovary with functioning stroma and endometrial endometrioid adenocarcinoma who showed symptoms of virilization. Her preoperative levels of serum testosterone and estradiol were as high as 553 ng/dL and 177 pg/mL, respectively, and her serum gonadotropin levels were suppressed. After surgery, the serum levels of testosterone and estradiol decreased and that of follicle-stimulating hormone increased. METHODS: To develop a mean of differentiating a single tumor with metastasis from synchronous primary ovarian and endometrial cancers, we performed a microsatellite analysis. Twenty-five dinucleotide microsatellite markers were selected, and microsatellite analysis was performed by a high-resolution method using fluorescence-labeled polymerase chain reaction and laser scanning. RESULTS: In this case, both ovarian carcinoma and endometrial carcinoma demonstrated loss of heterozygosity (LOH). However, the LOH findings of the ovarian tumor and endometrial tumor were different. CONCLUSIONS: Loss of heterozygosity analysis may be helpful to differentiate synchronous primary ovarian and endometrial cancers from a single tumor with metastasis.