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1.
Cytogenet Genome Res ; 142(2): 112-20, 2014.
Article in English | MEDLINE | ID: mdl-24217467

ABSTRACT

Cichlid fishes in the African Great Lakes are known as a spectacular example of adaptive radiation in vertebrates. Four linkage maps have been constructed to identify the genes responsible for adaptation and speciation, and the genetic linkages of those genes are assumed to play an important role during adaptive evolution. However, it is difficult to analyze such linkages because the linkage groups of one species do not match well with those of the other species. Chromosome markers are a powerful tool for the direct identification of linkage homology between different species. We used information about the linkage map of the Lake Malawi cichlid (Labeotropheus fuelleborni/Metriaclima zebra) to isolate bacterial artificial chromosome (BAC) clones from the BAC library of Paralabidochromis chilotes, Lake Victoria. We identified 18 of 22 P. chilotes chromosomes by single- and multi-color BAC fluorescence in situ hybridization using 19 BAC clones. Comparative mapping with the chromosome markers of P. chilotes in Astatotilapia burtoni (2n = 40) from Lake Tanganyika revealed the chromosome rearrangements that have occurred in this lineage. These chromosome markers will be useful for delineating the process of genome and chromosome evolution in African species.


Subject(s)
Chromosome Mapping , Cichlids/genetics , Genetic Linkage/genetics , Africa , Animals , Chromosomes, Artificial, Bacterial/genetics , Gene Library , Genetic Markers/genetics , In Situ Hybridization, Fluorescence , Karyotype
2.
Asian J Endosc Surg ; 5(3): 126-30, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22776684

ABSTRACT

INTRODUCTION: Myomectomy for cervical myoma is problematic because cervical myomas are very close to neighboring structures, such as the ureters, uterine artery, bladder and rectum. There are a few reports on laparoscopic myomectomy for cervical myomas to avoid blood loss, such as occlusion of iliac arteries and clipping of the uterine artery. We evaluated the efficacy and safety of bipolar electrode grasping forceps for laparoscopic myomectomy in uterine cervical myoma. METHODS: From November 2006 to May 2009, eight women with uterine cervical myoma underwent laparoscopic myomectomy. We employed electrode grasping forceps with a combination of two tenaculums for separating and securing hemostatsis. RESULTS: Seven of eight cases were successfully treated by laparoscopic myomectomy, but one patient, with a large 900-g myoma was converted to the laparotomy as a result of blood loss (1800 mL). Among the other seven cases, the average weight of the myoma was 132 g (range, 16-310 g) and the operating time was 176 min. (range, 125-255 min). No complications occurred. Of the four cases who wanted to become pregnant postoperatively, two became pregnant and delivered by Caesarean section. CONCLUSION: These findings indicate that bipolar electrode grasping forceps using two tenaculums for traction of the myoma are useful for laparoscopic myomectomy in cervical myomas.


Subject(s)
Blood Loss, Surgical/prevention & control , Catheter Ablation/instrumentation , Laparoscopy/methods , Myoma/surgery , Uterine Neoplasms/surgery , Adult , Equipment Design , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Myoma/diagnosis , Retrospective Studies , Uterine Neoplasms/diagnosis
3.
Climacteric ; 14(1): 31-40, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21067421

ABSTRACT

OBJECTIVES: Although patients with gynecological malignancies now survive longer due to advances in early diagnosis and therapy, major issues still remain regarding the quality of life for the survivors. Surgical menopause increases the risk of atherosclerosis; however, few studies have investigated the influence of platinum-based adjuvant chemotherapy. This study was conducted to evaluate the effects of platinum-based chemotherapy on atherosclerosis. METHODS: This study enrolled 47 women (26 with ovarian cancers and 21 with endometrial cancers) who underwent surgical treatment, with or without platinum-based adjuvant chemotherapy, according to established protocols between 2007 and 2009. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) performed before surgery, and subsequently at 12 months after treatment. The flow-mediated dilatation of the brachial artery was measured before and immediately following chemotherapy to evaluate the vascular endothelial damage. Human umbilical vein endothelial cells (HUVECs) were used to evaluate cisplatin-induced vascular endothelial dysfunction in vitro. RESULTS: Although there were no significant differences in the baPWV associated with surgical treatment, platinum-based chemotherapy was associated with an increased baPWV. Significant decreases of flow-mediated dilatation were observed immediately following chemotherapy. An in vitro examination demonstrated that cisplatin attenuated nitric oxide production via inhibition of Akt-eNOS cascades in HUVECs. CONCLUSIONS: This research suggests that platinum-based chemotherapy directly induces vascular endothelial dysfunction and may be a risk factor for the development of atherosclerosis. Therefore, gynecologic cancer survivors should be educated about these potential risks, and informed regarding lifestyle modifications that may benefit their general health.


Subject(s)
Antineoplastic Agents/therapeutic use , Atherosclerosis/physiopathology , Cisplatin/therapeutic use , Endothelium, Vascular/drug effects , Nitric Oxide Synthase Type III/metabolism , Ankle Brachial Index , Blood Flow Velocity , Brachial Artery/diagnostic imaging , Calcimycin/pharmacology , Carboplatin/therapeutic use , Cells, Cultured , Chemotherapy, Adjuvant , Endometrial Neoplasms/therapy , Endothelial Cells/drug effects , Endothelium, Vascular/physiopathology , Female , Humans , Ionophores/pharmacology , Middle Aged , Oncogene Protein v-akt/metabolism , Ovarian Neoplasms/therapy , Paclitaxel/therapeutic use , Phosphorylation , Triglycerides/blood , Ultrasonography , Umbilical Veins/cytology
4.
Oncogene ; 27(19): 2737-45, 2008 Apr 24.
Article in English | MEDLINE | ID: mdl-18193094

ABSTRACT

Although there is growing evidence that estrogens promote tumor progression in epithelial ovarian cancer, the molecular mechanisms accounting for this are still unclear. Selective estrogen receptor modulators (SERMs) mimic estrogen action in certain tissues while opposing it in others. The molecular mechanisms of the effects of SERMs such as raloxifene on the tumor progression of epithelial ovarian cancer are also still unclear. Here, we show that various genomic actions of estrogen differ from those of raloxifene in human ovarian cancer cell lines expressing estrogen receptor alpha (ERalpha). 17beta-Estradiol (E2) induced the gene expression of c-Myc and IGF-1 and increased the binding of ERalpha to the AP1 site of the promoters of c-Myc and IGF-1. ERalpha silencing abolished the E2-stimulated c-Myc expression. E2 induced the recruitment of co-activators such as SRC-1, SRC-3 and CBP to the promoters of c-Myc and IGF-1, and SRC-1 silencing abolished both the E2-stimulated c-Myc expression and cell-cycle progression. In contrast, although raloxifene increased the binding of ERalpha to the AP1 site of the promoters of c-Myc and IGF-1, raloxifene had no effect on the gene expression of c-Myc or IGF-1. Raloxifene induced the recruitment of co-repressors such as HDAC2, N-CoR and SMRT to the promoter of IGF-1. Thus, the difference between the genomic actions exerted by estrogen and raloxifene in human ovarian cancer cell lines expressing ERalpha appear to be dependent on the recruitment of co-regulators.


Subject(s)
Estrogens/physiology , Genome, Human/drug effects , Ovarian Neoplasms/drug therapy , Raloxifene Hydrochloride/pharmacology , Selective Estrogen Receptor Modulators/pharmacology , Cell Line, Tumor , Estrogen Receptor alpha/biosynthesis , Estrogen Receptor alpha/genetics , Female , Humans , Insulin-Like Growth Factor I/biosynthesis , Insulin-Like Growth Factor I/genetics , Ovarian Neoplasms/metabolism , Proto-Oncogene Proteins c-myc/biosynthesis , Proto-Oncogene Proteins c-myc/genetics
5.
Int J Gynecol Cancer ; 16 Suppl 1: 179-82, 2006.
Article in English | MEDLINE | ID: mdl-16515587

ABSTRACT

Single-nucleotide polymorphism at -670 of Fas gene promoter (A/G) was examined in a total of 354 blood samples from normal healthy women and gynecological cancer patients. They consisted of 95 normal, 83 cervical, 108 endometrial, and 68 ovarian cancer cases. Eighty-three patients with cervical cancer had statistically higher frequency of GG genotype and G allele than 95 controls (P= 0.0353 and 0.0278, respectively). There was no significant difference in the genotype or allele prevalence between control subjects and endometrial or ovarian cancer patients. The Fas -670 GG genotype was associated with an increased risk for the development of cervical cancer (OR = 2.56, 95% CI = 1.08-6.10) compared with the AA genotype. The G allele also increased the risk of cervical cancer (OR = 1.60, 95% CI = 1.05-2.43) compared with the A allele. Germ-line polymorphism of Fas gene promoter -670 may be associated with the risk of cervical cancer in a Japanese population.


Subject(s)
Uterine Cervical Neoplasms/genetics , fas Receptor/genetics , Adult , Aged , Asian People/genetics , Female , Genital Neoplasms, Female/genetics , Genotype , Germ-Line Mutation , Humans , Middle Aged , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Risk
6.
Int J Gynecol Cancer ; 16(1): 325-8, 2006.
Article in English | MEDLINE | ID: mdl-16445653

ABSTRACT

HER-2 codon 655 polymorphism together with human papillomavirus (HPV) types were examined in a total of 279 cervical smear samples. Forty-nine patients with high-grade squamous intraepithelial lesion had higher frequency of high-risk HPV than 167 patients with low-grade squamous intraepithelial lesion and 63 controls. There was no statistical difference in the frequencies of HER-2 Ile/Ile, Ile/Val, and Val/Val genotypes between squamous intraepithelial lesions (SILs) and controls. When the Ile/Ile genotype was compared to the Ile/Val + Val/Val genotypes, there was also no statistical difference in the genotype prevalence between SILs and controls either in 91 or 188 patients with or without high-risk HPV, respectively. These results suggest that the HER-2 polymorphism at codon 655 in cervical cell samples is unlikely to be associated with HPV status and the onset of cervical cancer in a Japanese population.


Subject(s)
Carcinoma, Squamous Cell/genetics , Papillomavirus Infections/diagnosis , Polymorphism, Genetic , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Base Sequence , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Case-Control Studies , Chi-Square Distribution , Codon , Female , Gene Expression Regulation, Neoplastic , Genes, erbB-2 , Genotype , Humans , Incidence , Japan/epidemiology , Mass Screening , Molecular Sequence Data , Neoplasm Staging , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Risk Assessment , Sampling Studies , Sensitivity and Specificity , Statistics, Nonparametric , Uterine Cervical Neoplasms/epidemiology , Vaginal Smears
7.
Gynecol Endocrinol ; 16(5): 391-402, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12587534

ABSTRACT

Various types of cell adhesion molecules and matrix metalloproteinases (MMPs) seem to play an important role in the invasion process of endometriosis; however, limited investigation has focused on their gene expression in human peritoneal endometriotic lesions. A total of 63 endometriotic tissues were surgically obtained from 35 women with endometriosis, which included 43 pigmented and 20 non-pigmented lesions. Gene expression levels of E-cadherin, alpha- and beta-catenin, MMP-2, MMP-9 and membrane-type 1 (MT1)-MMP in these endometriotic lesions were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. MMP-2, MMP-9 and MT1-MMP mRNA expression in pigmented lesions was significantly higher than that in normal endometrium (p < 0.05), whereas E-cadherin, alpha- and beta-catenin mRNA expression was not suppressed in endometriotic lesions. There was a close correlation between MMP-2 or MT1-MMP and E-cadherin, alpha- or beta-catenin gene expression in 63 endometriotic tissues examined (p < 0.01). Immunohistochemical expression of E-cadherin, alpha- and beta-catenin in glandular epithelial cells was positive not only for all of seven cases with normal eutopic endometrium but also for 9 of 11 with ovarian endometriosis. MMP expression in ectopic endometrium was much greater than that in eutopic endometrium. These results suggest that endometriotic tissues expressing MMPs might be invasive and simultaneously possess cell-to-cell adhesion property in pelvic peritoneal foci.


Subject(s)
Cell Adhesion Molecules/genetics , Endometriosis/metabolism , Gene Expression , Matrix Metalloproteinases/genetics , Cadherins/analysis , Cadherins/genetics , Cytoskeletal Proteins/analysis , Cytoskeletal Proteins/genetics , Endometrium/chemistry , Epithelial Cells/chemistry , Female , Humans , Immunohistochemistry , Matrix Metalloproteinase 2/analysis , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/analysis , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinases, Membrane-Associated , Metalloendopeptidases/analysis , Metalloendopeptidases/genetics , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Trans-Activators/analysis , Trans-Activators/genetics , alpha Catenin , beta Catenin
8.
Mol Biol Evol ; 18(11): 2057-66, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11606702

ABSTRACT

Lake Tanganyika harbors numerous endemic species of extremely diverse cichlid fish that have been classified into 12 major taxonomic groups known as tribes. Analysis of short interspersed element (SINE) insertion data has been acknowledged to be a powerful tool for the elucidation of phylogenetic relationships, and we applied this method in an attempt to clarify such relationships among these cichlids. We studied insertion patterns of 38 SINEs in total, 24 of which supported the monophyly of three clades. The other 14 loci revealed extensive incongruence in terms of the patterns of SINE insertions. These incongruencies most likely stem from a period of adaptive radiation. One possible explanation for this phenomenon is the extensive incomplete lineage sorting of alleles for the presence or absence of a SINE during successive speciation events which took place about 5-10 MYA. The present study is the first to report the successful application of the SINE method in demonstrating the existence of such possible "ancient" incomplete lineage sorting. We discuss the possibility that it might potentially be very difficult to resolve the species phylogeny of a group that radiated explosively, even by resolving the genealogies of more than 10 nuclear loci, as a consequence of incomplete lineage sorting during speciation.


Subject(s)
Cichlids/genetics , Evolution, Molecular , Genetics, Population , Mutagenesis, Insertional/genetics , Phylogeny , Retroelements/genetics , Sequence Analysis, DNA/methods , Alleles , Animals , Fresh Water , Genetic Variation/genetics , Short Interspersed Nucleotide Elements/genetics , Tanzania
9.
J Orthop Sci ; 6(2): 123-7, 2001.
Article in English | MEDLINE | ID: mdl-11484096

ABSTRACT

We developed a new method to measure the nerve conduction velocity of a single digital nerve. In 27 volunteers (27 hands), we separately stimulated each digital nerve on the radial and ulnar sides of the middle and ring fingers. A double-peaked potential was recorded above the median nerve at the wrist joint when either the radial-side nerve or the ulnar-side nerve of the middle finger was stimulated. The first peak of this potential had disappeared after the digital nerve was blocked under the stimulating electrodes, and the peak appeared again coinciding with the decrease of anesthesia. Shifting the stimulating electrodes on the digital nerve resulted in no significant difference in the peak conduction velocity. It is possible that each peak of the potential was attributable to conduction of an action potential along one of the two digital nerves. This new method allows the assessment of a single digital nerve, and may be clinically useful for assessing the rupture of a digital nerve and the sensory nerve action potentials in carpal tunnel syndrome.


Subject(s)
Fingers/innervation , Neural Conduction , Action Potentials , Adult , Carpal Tunnel Syndrome/physiopathology , Female , Humans , Male , Middle Aged
10.
J Cell Physiol ; 188(3): 394-402, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11473366

ABSTRACT

Vascular smooth muscle cell growth-promoting factor (VSGP) was originally isolated from bovine ovarian follicular fluid as a stimulator of vascular smooth muscle cell proliferation. Homology searches indicate that bovine and human VSGPs are orthologs of rat F-spondin. Here, we examined whether recombinant human VSGP/F-spondin affected the biological activities of endothelial cells. VSGP/F-spondin did not affect the proliferation of human umbilical vein endothelial cells (HUVECs); however, it did inhibit VEGF- or bFGF-stimulated HUVEC migration. To clarify the mechanism of this inhibitory effect, we examined the adhesion of HUVECs to extracellular matrix proteins. VSGP/F-spondin specifically inhibited the spreading of HUVECs on vitronectin via the functional blockade of integrin alphavbeta3. As a result, VSGP/F-spondin inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) when HUVECs were plated on vitronectin. Moreover, VSGP/F-spondin inhibited the activation of Akt when HUVECs on vitronectin were stimulated with VEGF. VSGP/F-spondin inhibited tube formation by HUVECs in vitro and neovascularization in the rat cornea in vivo. These results indicate that VSGP/F-spondin inhibits angiogenesis at least in part by the blockade of endothelial integrin alphavbeta3.


Subject(s)
Endothelium, Vascular/drug effects , Growth Substances/pharmacology , Neovascularization, Physiologic/drug effects , Neural Cell Adhesion Molecules/pharmacology , Peptides , Receptors, Vitronectin/antagonists & inhibitors , Animals , CHO Cells , Cell Adhesion/drug effects , Cell Division/drug effects , Cell Movement/drug effects , Cells, Cultured , Cricetinae , Endothelial Growth Factors/pharmacology , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Extracellular Matrix Proteins , Growth Substances/genetics , Humans , Intercellular Signaling Peptides and Proteins , Intracellular Fluid/metabolism , Lymphokines/pharmacology , Neural Cell Adhesion Molecules/genetics , Rats , Recombinant Proteins/genetics , Recombinant Proteins/pharmacology , Signal Transduction/drug effects , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
11.
Gynecol Oncol ; 82(1): 162-6, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11426979

ABSTRACT

OBJECTIVE: The correlation between the gene expression of various angiogenic factors and in vitro invasive activity in 16 human gynecological cancer cell lines was investigated. METHODS: Semiquantitative reverse transcription polymerase chain reaction analysis was performed to investigate the mRNA expression levels of vascular endothelial growth factors (VEGF-A, -B, -C, and -D), basic fibroblast growth factor (bFGF), and matrix metalloproteinase (MMP)-2 with beta-actin coamplified as an internal standard. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were evaluated by haptotactic migration and invasion assay. RESULTS: Expression of VEGF-A mRNA was detected in all 16 cell lines, whereas the relative expression levels of other VEGF family members and bFGF, differed markedly among the cell lines. There was a statistical correlation between VEGF-C gene expression and the number of cells that migrated and invaded (P < 0.01). However, expression of mRNAs of other angiogenic factors did not correlate with motility and invasive activity of the cells. Moreover, there was a close correlation between VEGF-C and MMP-2 gene expression levels (P < 0.05). CONCLUSION: Tumor cells that produce VEGF-C may have a higher invasive and metastatic potential because of their capacity to pass through tissue barriers.


Subject(s)
Endometrial Neoplasms/genetics , Endothelial Growth Factors/genetics , Ovarian Neoplasms/genetics , RNA, Messenger/biosynthesis , Uterine Cervical Neoplasms/genetics , DNA, Neoplasm/analysis , Endometrial Neoplasms/metabolism , Endothelial Growth Factors/biosynthesis , Female , Fibroblast Growth Factor 2/biosynthesis , Fibroblast Growth Factor 2/genetics , Gene Expression , Humans , Matrix Metalloproteinases/biosynthesis , Matrix Metalloproteinases/genetics , Neoplasm Invasiveness , Ovarian Neoplasms/metabolism , Phenotype , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , Uterine Cervical Neoplasms/metabolism , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor B , Vascular Endothelial Growth Factor C , Vascular Endothelial Growth Factor D
12.
Nature ; 410(6831): 908-10, 2001 Apr 19.
Article in English | MEDLINE | ID: mdl-11309610

ABSTRACT

The application of a sufficiently strong magnetic field to a superconductor will, in general, destroy the superconducting state. Two mechanisms are responsible for this. The first is the Zeeman effect, which breaks apart the paired electrons if they are in a spin-singlet (but not a spin-triplet) state. The second is the so-called 'orbital' effect, whereby the vortices penetrate into the superconductors and the energy gain due to the formation of the paired electrons is lost. For the case of layered, two-dimensional superconductors, such as the high-Tc copper oxides, the orbital effect is reduced when the applied magnetic field is parallel to the conducting layers. Here we report resistance and magnetic-torque experiments on single crystals of the quasi-two-dimensional organic conductor lambda-(BETS)2FeCl4, where BETS is bis(ethylenedithio)tetraselenafulvalene. We find that for magnetic fields applied exactly parallel to the conducting layers of the crystals, superconductivity is induced for fields above 17 T at a temperature of 0.1 K. The resulting phase diagram indicates that the transition temperature increases with magnetic field, that is, the superconducting state is further stabilized with magnetic field.

13.
No Shinkei Geka ; 29(2): 151-6, 2001 Feb.
Article in Japanese | MEDLINE | ID: mdl-11260892

ABSTRACT

We present a case with brain abscess associated with entrapment of the lateral ventricle appearing more like remarkable brain edema in the temporo-occipital lobe than ventricular dilatation. A 72-year-old man suffering from headache and vomiting visited our clinic. CT and MRI showed brain abscess in the right parieto-occipital lobe, associated with ventriculitis. Lumbar puncture also revealed purulent meningitis. Both symptoms and CSF findings improved after administration of antibiotics. The improved condition continued for two months after admission, but disturbed consciousness and left hemiparesis than appeared. MRI and CT showed entrapment of the lateral ventricle and brain edema of the right temporo-occipital region without ventricular dilatation. Because brain edema was thought to be caused by transudate of the CSF through the ventricular wall, lobectomy of the right temporal lobe and opening of the temporal horn were carried out. Although left hemiparesis and disturbed consciousness and brain edema disappeared after the operation, subdural effusion appeared. Using a subdural-peritoneal shunt, the subdural effusion was prevented and disappeared. In this case, we thought Hounsfield Unit (HU) of the brain edema caused by transudate of CSF through the ventricular wall (12.6) was markedly lower than that of so-called vasogenic edema (25.1) due to active inflammation. Measurement of the HU seemed to be a useful means to differentiate the types of brain edema in this situation from that of vasogenic edema caused by brain abscess, and thus a means for selection of the appropriate treatment.


Subject(s)
Brain Abscess/complications , Brain Edema/etiology , Cerebral Ventricles/pathology , Encephalitis/complications , Nerve Compression Syndromes/etiology , Aged , Brain Abscess/surgery , Brain Edema/surgery , Dilatation , Dilatation, Pathologic/pathology , Encephalitis/surgery , Humans , Male , Nerve Compression Syndromes/surgery
14.
Int J Cancer ; 91(6): 778-82, 2001 Mar 15.
Article in English | MEDLINE | ID: mdl-11275979

ABSTRACT

The correlation between thymidine phosphorylase (dThdPase) expression and invasion phenotype in human uterine cervical carcinoma cells was investigated using 10 cervical carcinoma cell lines. Semi-quantitative reverse transcription-polymerase chain reaction analysis was performed to investigate the mRNA levels of dThdPase and matrix metalloproteinase (MMP)-2 with beta-actin coamplified as an internal standard. dThdPase protein expression levels were detected by highly sensitive enzyme-linked immunosorbent assay. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were evaluated by haptotactic migration and invasion assay. Although dThdPase mRNA and protein expression levels differed remarkably among the cell lines, there was a statistical correlation between them (r = 0.743, p = 0.0139). dThdPase gene and protein expression levels were well correlated with the number of cells that migrated and invaded (p < 0.05). Moreover, there was a close correlation between MMP-2 gene and dThdPase gene and protein expression levels (p < 0.05). Tumor cells that produce dThdPase may have a higher invasive and metastatic potential because of their capacity to pass through tissue barriers.


Subject(s)
Carcinoma, Squamous Cell/enzymology , Phenotype , Thymidine Phosphorylase/metabolism , Uterine Cervical Neoplasms/enzymology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Movement , DNA Primers/chemistry , Female , Humans , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Neoplasm Invasiveness , Reverse Transcriptase Polymerase Chain Reaction , Thymidine Phosphorylase/genetics , Tumor Cells, Cultured , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology
15.
Int J Gynecol Pathol ; 19(4): 354-60, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11109165

ABSTRACT

To clarify biological and clinical significance of tumor angiogenesis in the development of ovarian carcinoma, we investigated the relationship between tumor vascularity, the expression of thymidine phosphorylase (dThdPase), which is an angiogenic factor identical to platelet-derived endothelial cell growth factor (PD-ECGF), and patient outcome in ovarian carcinoma, including serous surface papillary carcinoma (SSPC). Primary tumor specimens (stages I-IV) from 54 patients were examined. Intratumoral microvessel density (IMVD) and dThdPase expression were evaluated immunohistochemically using anti-CD34 and anti-dThdPase antibodies, and results were correlated with clinicopathologic parameters and prognosis. IMVD for the 54 tumors ranged from 22.5 to 120.7 (number/0.73686 mm2/field). Twenty-three tumors were positive, and 31 tumors were negative for dThdPase expression. IMVD positively correlated with the expression of dThdPase (p < 0.01), tumor size, and peritoneal metastases (p < 0.05). However, there was no statistical correlation between IMVD, dThdPase expression, and clinical outcome. Of the 54 patients examined, 30 were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV primary ovarian carcinoma, and 9 were diagnosed with SSPC. There were no significant differences between the two groups with respect to clinicopathologic features, IMVD, dThdPase expression, or patient outcome. In conclusion, angiogenic activity may be necessary for the growth of metastatic implants in ovarian carcinoma and SSPC.


Subject(s)
Cystadenocarcinoma, Papillary/blood supply , Neovascularization, Pathologic , Ovarian Neoplasms/blood supply , Peritoneal Neoplasms/blood supply , Thymidine Phosphorylase/analysis , Cystadenocarcinoma, Papillary/enzymology , Cystadenocarcinoma, Papillary/pathology , Disease-Free Survival , Female , Humans , Immunohistochemistry , Microcirculation/pathology , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Ovarian Neoplasms/enzymology , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/enzymology , Peritoneal Neoplasms/pathology , Prognosis , Survival Rate
16.
Jpn J Cancer Res ; 91(11): 1185-91, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11092985

ABSTRACT

Dihydropyrimidine dehydrogenase (DPD) and pyrimidine nucleoside phosphorylase (PyNPase) are the first and rate-limiting enzymes that regulate 5-fluorouracil (5-FU) metabolism, and tumoral DPD activity appears to be a promising predictor of 5-FU sensitivity. However, the regulatory mechanisms determining these enzyme activities have not been fully understood. We investigated the biological effects of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha on cell growth and tumoral DPD and PyNPase activities, and the subsequent effects on 5-FU sensitivity in uterine cervical carcinoma SKG-IIIb cells. The treatment of tumor cells with EGF or TGF-alpha resulted in a concentration-dependent increase in tumor cell growth and PyNPase activity, whereas tumoral DPD activity was inhibited. Their stimulatory effects on tumor cell growth correlated well with PyNPase activity, but were inversely related to DPD activity (P < 0.01). 5-FU sensitivity of tumor cells increased in the presence of EGF or TGF-alpha. These growth factors were shown to stimulate the first, rate-limiting enzyme activity in 5-FU anabolism and to inhibit that in 5-FU catabolism, leading to enhancement of the antiproliferative action of 5-FU at achievable therapeutic levels. The tumor environmental factors, EGF and TGF-alpha, may act as intrinsic regulators of DPD and PyNPase activities that affect the 5-FU sensitivity of individual tumors.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Epidermal Growth Factor/pharmacology , Fluorouracil/pharmacology , Oxidoreductases/metabolism , Pentosyltransferases/metabolism , Transforming Growth Factor alpha/pharmacology , Antimetabolites, Antineoplastic/metabolism , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/pathology , Cell Division/drug effects , Dihydrouracil Dehydrogenase (NADP) , Drug Synergism , Female , Fluorouracil/metabolism , Humans , Oxidoreductases/antagonists & inhibitors , Pyrimidine Phosphorylases , Tumor Cells, Cultured , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/enzymology , Uterine Cervical Neoplasms/pathology
17.
J Pharmacol Exp Ther ; 295(1): 255-60, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10991987

ABSTRACT

We synthesized a novel phosphodiesterase type 4 (PDE4) inhibitor, YM976, that is structurally different from the other PDE4 inhibitors like rolipram. In the present study, the pharmacological profile of YM976 was investigated. YM976 exhibited a strong and competitive inhibition against PDE4 purified from human peripheral leukocytes with an IC(50) of 2.2 nM. IC(50) values of rolipram and RP73401 were 820 and 0.43 nM, respectively. Test compounds had no effects on the other PDE isozymes, PDE1, -2, -3, and -5. YM976 potentiated prostaglandin E(2)-induced cAMP accumulation in a human mononuclear cell line, U937, and inhibited tumor necrosis factor-alpha production from human peripheral blood mononuclear cells stimulated by lipopolysaccharide. Anti-inflammatory activities of PDE4 inhibitors were compared in rat carrageenan-induced pleurisy models. YM976, rolipram, and RP73401 inhibited the cell infiltration into the pleural cavity with oral ED(30) values of 9.1, 10, and 7.4 mg/kg, respectively. YM976 produced no emesis up to 10 mg/kg, whereas rolipram and RP73401 induced emesis at oral doses of 3 mg/kg. To evidence the dissociation of anti-inflammatory activity from emesis, the anti-inflammatory effect of YM976 was examined in ferrets. YM976 dose dependently reduced carrageenan-induced leukocyte infiltration at the doses of 1, 3, and 10 mg/kg, p.o. On the other hand, rolipram failed to show obvious inhibition at doses that do not induce emesis. In conclusion, YM976 is a novel and orally active PDE4 inhibitor and possesses a good separation of emetogenicity from anti-inflammatory activity.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Phosphodiesterase Inhibitors/pharmacology , Pyridines/pharmacology , Pyrimidinones/pharmacology , Vomiting/chemically induced , Animals , Cyclic AMP/metabolism , Ferrets , Humans , Male , Phosphodiesterase Inhibitors/toxicity , Pleurisy/drug therapy , Pyridines/toxicity , Pyrimidinones/toxicity , Rats , Tumor Necrosis Factor-alpha/biosynthesis , U937 Cells
18.
No Shinkei Geka ; 28(7): 639-45, 2000 Jul.
Article in Japanese | MEDLINE | ID: mdl-10920826

ABSTRACT

Recently, the first choice of therapy for cavernous dural arteriovenous shunts (CdAVS) is transvenous embolization. Usually the approach routes for cavernous sinus are the inferior petrosal sinus (IPS), the superior ophthalmic vein (SOV) in most cases and the superior petrosal sinus (SPS) in rare case. But, it is difficult for us to treat patients in whom there are no extracranial veins through which to approach the cavernous sinus, with transvenous embolization. We presented the case in which intracranial transvenous approach to the cavernous sinus and transvenous embolization were performed and in which we achieve good results. In this article, we presented a case with Barrow's type D CdAVS and cortical venous drainage. At first, transarterial embolization was performed to decrease the amount of venous drainage for the purpose of eliminate convulsions and consciousness disturbance. However, cortical venous drainage continued. Moreover bilateral dilated SOVs normalized and bilateral IPSs were not visible, so we decided that it was impossible to carry out the transvenous embolization via extracranial veins. Transvenous embolization to the left cavernous sinus via the intracranial ophthalmic vein between the superior ophthalmic fissure and the inferior ophthalmic fissure after craniotomy was performed. Then, the transvenous embolization to the right cavernous sinus was carried out through the right superficial middle cerebral vein after craniotomy. The results were good and chemosis and bilateral abducens palsy diminished immediately. Trans-intracranial venous embolization for CdVAS is a very useful therapy when no extracranial veins exist for transvenous embolization.


Subject(s)
Cavernous Sinus/abnormalities , Dura Mater/blood supply , Embolization, Therapeutic/methods , Intracranial Arteriovenous Malformations/therapy , Aged , Cerebral Veins , Craniotomy , Eye/blood supply , Female , Humans , Treatment Outcome
19.
Oncogene ; 19(17): 2138-46, 2000 Apr 20.
Article in English | MEDLINE | ID: mdl-10815805

ABSTRACT

Vascular endothelial growth factor (VEGF) is a principal regulator of vasculogenesis and angiogenesis. VEGF expresses its effects by binding to two VEGF receptors, Flt-1 and KDR. However, properties of Flt-1 and KDR in the signal transduction of VEGF-mediated effects in endothelial cells (ECs) were not entirely clarified. We investigated this issue by using two newly developed blocking monoclonal antibodies (mAbs) against Flt-1 and KDR. VEGF elicits DNA synthesis and cell migration of human umbilical vein endothelial cells (HUVECs). The pattern of inhibition of these effects by two mAbs indicates that DNA synthesis is preferentially mediated by KDR. In contrast, the regulation of cell migration by VEGF appears to be more complicated. Flt-1 regulates cell migration through modulating actin reorganization, which is essential for cell motility. A distinct signal is generated by KDR, which influences cell migration by regulating cell adhesion via the assembly of vinculin in focal adhesion plaque and tyrosine-phosphorylation of focal adhesion kinase (FAK) and paxillin.


Subject(s)
Endothelial Growth Factors/metabolism , Endothelium, Vascular/metabolism , Lymphokines/metabolism , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Growth Factor/metabolism , Signal Transduction , 3T3 Cells/drug effects , 3T3 Cells/metabolism , Actins/metabolism , Actins/ultrastructure , Animals , Antibodies, Monoclonal/pharmacology , Cell Line , Cell Movement/drug effects , Cytoskeletal Proteins/metabolism , DNA/biosynthesis , DNA/drug effects , Endothelial Growth Factors/pharmacology , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Focal Adhesion Kinase 1 , Focal Adhesion Protein-Tyrosine Kinases , Humans , Imidazoles/pharmacology , Indoles/pharmacology , Lymphokines/pharmacology , Maleimides/pharmacology , Mice , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , Paxillin , Phosphoproteins/metabolism , Phosphorylation , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/immunology , Pyridines/pharmacology , Receptor Protein-Tyrosine Kinases/immunology , Receptors, Growth Factor/immunology , Receptors, Vascular Endothelial Growth Factor , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-1 , Vascular Endothelial Growth Factors , Vinculin/metabolism , p38 Mitogen-Activated Protein Kinases
20.
Interv Neuroradiol ; 6 Suppl 1: 237-42, 2000 Nov 30.
Article in English | MEDLINE | ID: mdl-20667256

ABSTRACT

SUMMARY: To date in our hospital, surgical reconstructions and percutaneous transluminal angioplasty (PTA) were carried out in 168 patients with vertebral artery (VA) stenosis at the origin. In this article, we discuss the comparison between surgical reconstructions and PTA, especially regarding long term follow up, patency and complications. PTA is a less invasive treatment for VA stenosis at the origin than surgical reconstructions. However, restenosis after PTA occurred in 20% of the patients. On the other hand, restenosis after surgical reconstructions did not emerge even in long term follow up. An embolism after PTA occurred in 2.6% of the cases. However, the embolism occurred in only the first 10 patients of our series, after that there was no embolism. We concluded that PTA was the first choice for VA stenosis at the origin, if the angiogram did not reveal any PTA difficulty. If restenosis after PTA was performed, we selected surgical reconstruction for VA stenosis at the origin.

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