RESUMEN
OBJECTIVE: To investigate the expression of aquaporin-8 (AQP8) and apoptosis associated bcl-2 protein in human cervical carcinoma and their relationship. METHODS: The expression of AQP8 and bcl-2 protein in 74 cases of cervical carcinoma (46 cases of squamous-cell carcinoma of the uterine cervix, 28 cases of adenocarcinoma of the uterine cervix), 34 cases of cervical intraepithelial neoplasia (CIN) and 15 cases of normal cervices were detected by immunohistochemical technique, and their clinical significance were analyzed. RESULTS: The expression of AQP8 and bcl-2 protein were detected in intracytoplasm of atypia cells in CIN, squamous-cell carcinoma and adenocarcinoma of the uterine cervix. The positive rates of AQP8 and bcl-2 in squamous-cell carcinoma, adenocarcinoma, CIN and normal cervical epithelium were 98%, 74%; 61%, 71%; 71%, 53% ; 53%, 20% respectively. There were significant differences between squamous-cell carcinoma of the uterine cervix and other groups in AQP8 (P < 0.01), but no significant differences were found in any other groups. There were significant differences between squamous-cell carcinoma of the uterine cervix and CIN or normal cervical epithelium in bcl-2, so were between adenocarcinoma of the uterine cervix. The expression of AQP8 was positively correlated with bcl-2 in human cervical carcinoma( r(s) = 0.463, P = 0.000). CONCLUSIONS: There is a close relationship between high expression of AQP8 and development of human cervical carcinoma. The expression of AQP8 protein is positively correlated with bcl-2 protein in human cervical carcinoma. AQP8 protein may have anti-apoptosis function, although the detailed mechanism in human cervical carcinoma remains to be clarified.
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Acuaporinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Cuello del Útero/metabolismo , Cuello del Útero/patología , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: To evaluate the influence of superovulation by GnRHa protocol and pregnant mare's serum gonadotropin (PMSG) alone on the expression of estrogen receptor (ER), progesterone receptor (PR) and leukemia inhibitory factor (LIF) mRNA on endometrium. METHODS: Forty-five female ICR mice were randomly allocated into 3 groups:(1) GnRHa+PMSG group: alarelin was give first for desensitizing the pituitary, then superovulation with PMSG; (2) PMSG group: mice were injected with PMSG only; (3) Natural cycle group: mice were given with same volume of saline. Endometrium samples were taken at 48 hours after given hCG or ovulation (control group). ER and PR in glandular cells were detected with SP immunohistochemistry semiquantitatively. Expression of LIF mRNA on endometrium was detected with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. RESULT: The positive rate(%) and expression intense (AU) of ER and PR on glandular epithelium cells were significantly lower in GnRHa+PMSG group and PMSG group than those in natural cycle group (all P <0.01). The expression of LIF mRNA was significantly lower in GnRHa+PMSG group and PMSG group than that in natural cycle group (all P <0.01); but the expressions of ER, PR and LIF in GnRHa+PMSG group were higher than those in PMSG group. CONCLUSION: The protocol with GnRHa down regulates the expressions of ER, PR and the LIF mRNA on the mice of secretive phase endometrium, suggesting it may have an adverse effect on the endometrial receptivity in mice, but it may still be better than PMSG alone.
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Endometrio/metabolismo , Factor Inhibidor de Leucemia/metabolismo , Inducción de la Ovulación/métodos , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Superovulación/metabolismo , Animales , Protocolos Clínicos , Femenino , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/farmacología , Gonadotropinas/farmacología , Ratones , Ratones Endogámicos ICR , ARN Mensajero/metabolismo , Distribución AleatoriaRESUMEN
OBJECTIVE: To assess the value of computed tomography( CT) in the staging and predicting respectability of primary advanced ovarian carcinoma. METHODS: The data of preoperative abdomen and pelvis CT scan in 64 women with Stage II or IV ovarian carcinoma were collected from tumor registry database. All CT scans were analyzed retrospectively without knowledge of the operative findings, and the stage as based on CT was compared with the surgical and pathological findings. Residual lesion of < or = 2 cm in maximal diameter was considered as an optimal surgical result. Twenty-senven of these 64 patients (42.2%) underwent optimal cytoreduction surgery for residual disease C2 cm in diameter. Based on the ability of each parameter in predicting cytoreductive surgery outcome, 11 radiographic features were selected for the final model. Each predictive parameter was assigned a numeric value (1 to 7). Sensitivity, specificity, positive predictive value( PPV) , negative predictive value( NPV),and accuracy were calculated for each predictive parameter. Receiver operating characteristic( ROC) curve was used to assess the ability of the model to predict surgical outcome. The correlation between CT stage and surgical-pathologic stage was analyzed by Chi-square test and Spearman's rho analysis. RESULTS: The overall accuracy of CT staging for advanced ovarian carcinoma was 87. 5% ; 86. 5% and 91.7% for stage III and IV patients respectively. The correlation between CT stage and surgicopathologic stage was found to be comformable. In the final predictive index model, when a predictive index scoreed > or = 2, the overall accuracy, sensitivity and specificity was 70. 3% , 67.6% and 74. 1% for identifying patients for suboptimal surgery. The PPV and the NPV was 78. 1% and 62. 5% , respectively. The ROC curve was generated with an area under the curve = 0. 792+/-0. 055 using the predictive index scores. CONCLUSION: CT has a high accuracy in staging and a moderate ability to predict resectability for advanced ovarian carcinoma. Therefore, the predictive index model may be useful in the management of ovarian carcinoma patients.
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Adenocarcinoma/diagnóstico por imagen , Cistadenocarcinoma/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adolescente , Adulto , Anciano , Cistadenocarcinoma/patología , Cistadenocarcinoma/cirugía , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To study the inhibitory effect of antisense oligonucleotides against telomerase RNA on the growth of human choriocarcinoma transplant in nude mice. METHODS: Choriocarcinoma xenografts were established by transplanting JAR cells subcutaneously to female nude mice, and were treated with high and low doses of antisense oligonucleotides. Control groups were treated with NS, random sequence and actinomycin D (Act-D). Tumor growth was monitored once every other day. Telomerase relative activity was assayed by TRAP-ELISA. Western blotting was used to detect expression of hTERT. RESULTS: Low and high doses antisense oligonucleotides, and Act-D inhibited tumor growth by 76.6%, 93.8% and 85.4% respectively, which were significantly different when compared with random sequence and NS groups. Expression of telomerase relative activity and hTERT were decreased as well. But the differences among the first three groups had no significance. CONCLUSION: Telomerase RNA antisense oligonucleotide inhibits growth of human choriocarcinoma xenografts in nude mice. It may be a novel approach to the treatment of choriocarcinoma.
Asunto(s)
Coriocarcinoma/patología , Proteínas de Unión al ADN/metabolismo , Oligonucleótidos Antisentido/farmacología , Telomerasa/genética , Neoplasias Uterinas/patología , Animales , Antibióticos Antineoplásicos/farmacología , Línea Celular Tumoral , Coriocarcinoma/enzimología , Dactinomicina/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Oligonucleótidos Antisentido/administración & dosificación , Embarazo , Telomerasa/metabolismo , Neoplasias Uterinas/enzimologíaRESUMEN
OBJECTIVE: To detect the expression of aromatase P450 and estrogen receptor (ER) in eutopic and ectopic endometrium in endometriosis and their correlation with endometriosis. METHODS: Forty patients who had undergone operation because of endometriosis (all were stage III-IV according to the revised American Fertility Society classification) were enrolled and 83 tissue specimens from different locations of disease foci were obtained and divided into five groups according to the location: group I, eutopic endometrium of 25 cases; Group II, ovarian endometriosis tissues of 23 cases; Group III, vagina-rectum endometriosis tissues of 11 cases; Group IV, peritoneum endometriosis tissues of eight cases; and group V, uterine serosa endometriosis tissues of 16 cases. Control group consisted of normal endometrium taken from 20 fertile women who had endometrial curettage before placement of intrauterine device. The routine two-step immunohistochemical technique was used to measure the expression of aromatase P450 and ER in endometrial cells. RESULTS: Expressions of aromatase P450 and ER in group I [histochemistry score (H-score), 2.6 +/- 1.0, 3.8 +/- 0.5] were significantly higher than those in control group (both P < 0.01), group II (1.4 +/- 1.0, 1.9 +/- 1.6) (P < 0.05, P < 0.01), and group III (1.2 +/- 0.9, 1.8 +/- 1.6) (both P < 0.05). Expressions of aromatase P450 and ER had positive correlation in all groups (r = 0.577, P < 0.01). CONCLUSIONS: Aromatase P450 could increase estrogen and estrogen receptor levels in the local ectopic tissues, thus promoting the growth and implantation of endometriosis. Different types of endometriosis focus have different levels of hormone regulation.
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Aromatasa/genética , Endometriosis/genética , Regulación de la Expresión Génica , Receptores de Estrógenos/genética , Adulto , Aromatasa/metabolismo , Endometriosis/metabolismo , Estrógenos/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Receptores de Estrógenos/metabolismoRESUMEN
OBJECTIVE: To investigate protein and mRNA expression of aquaporin-1 (AQP1) in epithelial ovarian tumors and its clinic significance. METHODS: The protein and mRNA expressions of AQP1 were measured by immunohistochemical technique, western blot and RT-PCR in 65 cases of epithelial ovarian tumors and 13 cases of normal ovary tissue. RESULTS: AQP1 located in microvascular and small vessel epithelial cells. The protein and mRNA expressions of AQP1 in ovarian cancer (0.39 +/- 0.12, 0.93 +/- 0.51, respectively) and ovarian borderline tumors (0.43 +/- 0.21, 0.95 +/- 0.34, respectively) were significantly higher than that of ovarian benign tumors (0.27 +/- 0.13, 0.51 +/- 0.41, respectively; P < 0.05) and normal ovary tissue (0.24 +/- 0.13, 0.34 +/- 0.29, respectively; P < 0.05). Of all ovarian cancers, expression of AQP1 in cases with ascites more than 1000 ml (0.46 +/- 0.13, 1.25 +/- 0.57, respectively) was higher than that of ascites less than 1 approximately 499 ml (0.35 +/- 0.11, 0.75 +/- 0.45, respectively; P < 0.05). CONCLUSION: Over-expression of AQP1 plays an important role in development of epithelial ovarian tumors, and may be related with formation of ascites of ovarian carcinoma.
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Acuaporina 1/genética , Neoplasias Ováricas/patología , Adulto , Acuaporina 1/biosíntesis , Western Blotting , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: To survey incidence of gestational trophoblastic disease (GTD) in China and to provide useful information for prevention and better treatment of the disease. METHODS: The survey was retrospectively carried out from 1991 to 2000 and included 143 hospitals in the following seven Chinese provinces: Zhejiang, Jiangsu, Fujian, Anhui, Jiangxi, Shanxi and Henan. RESULTS: Excluding incomplete data, data from 118 hospitals from seven provinces were finally analyzed. The total numbers of pregnancy and GTD were 3,674, 654 and 14,222, respectively. The GTD cases occurred mainly among 20 - 34 year old women, which accounted for 85.5% of total GTD. The incidence of GTD was 3.87 per thousand. There were 9,194 cases (64.6%) of hydatidiform, 3,452 cases (24.3%) of invasive mole, 1521 cases (10.7%) of choriocarcinoma, 55 cases (0.4%) of placenta-site trophoblastic tumor, respectively. CONCLUSIONS: The results of this survey are reliable and representative due to large sampling and hospital-based data collection. The incidences of GTD decreased significantly compared with 1950s'. It is important to take pathological examination for GTD and to diagnose complate mole and partial mole correctly.
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Enfermedad Trofoblástica Gestacional/epidemiología , Neoplasias Uterinas/epidemiología , Adulto , China/epidemiología , Coriocarcinoma/diagnóstico , Coriocarcinoma/epidemiología , Femenino , Enfermedad Trofoblástica Gestacional/diagnóstico , Enfermedad Trofoblástica Gestacional/prevención & control , Humanos , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/epidemiología , Incidencia , Embarazo , Estudios Retrospectivos , Tumor Trofoblástico Localizado en la Placenta/diagnóstico , Tumor Trofoblástico Localizado en la Placenta/epidemiología , Neoplasias Uterinas/diagnósticoRESUMEN
OBJECTIVE: To study the role of mast cells in the differential diagnosis of cellular leiomyoma and endometrial stromal sarcoma of uterus and its mechanism. METHODS: Using SP immunohistochemical technique, the expression of proliferating cell nuclear antigen (PCNA) and mast cells in 25 cellular leiomyoma (CL) and 26 endometrial stromal sarcoma (ESS) of uterus were examined. The expression of estrogen receptor (ER) and CD44v3 in cellular leiomyoma was also studied. RESULTS: The expression of PCNA was not significantly different from CL or ESS (P > 0.05), while mast cell count was statistically different between them (P < 0.01). Using a value of less than 7 mast cells per high power field was useful for the diagnosis of ESS, yielding 100% sensitivity and 92.0% specificity. There was a positive correlation between the mast cell count and CD44v3 in CL (r(s) = 0.589, P < 0.01), though no correlation was observed between mast cell count and PCNA or ER. CONCLUSION: Number of mast cells is valuable for the discrimination of CL from ESS in the uterus. The mechanism and the role of higher quantity of mast cells in CL need further study.
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Leiomioma/patología , Mastocitos/patología , Sarcoma Estromático Endometrial/patología , Neoplasias Uterinas/patología , Adulto , Anciano , Femenino , Humanos , Receptores de Hialuranos/análisis , Leiomioma/química , Persona de Mediana Edad , Antígeno Nuclear de Célula en Proliferación/análisis , Receptores de Estrógenos/análisis , Sarcoma Estromático Endometrial/química , Neoplasias Uterinas/químicaRESUMEN
OBJECTIVE: To evaluate the inhibitory effect of tumor suppressor PTEN on cell growth of endometrial carcinoma. METHODS: The exogenous wild PTEN cDNA via an adenoviral vector (Ad-PTEN) was introduced into Ishikawa cells. The expression of PTEN protein was detected by Western blot. The growth of Ishikawa cells was evaluated by trypan blue exclusion method and MTT. RESULTS: The expression of PTEN protein was induced on day 1, and greatly increasing on day 3 - 5 after Ad-PTEN infection. The expression of PTEN significantly inhibited the growth of Ishikawa cells, and also significantly inhibited the growth of Ishikawa cells induced by IGF-II. CONCLUSION: Adenovirus-mediated introduction of exogenous PTEN into human endometrial carcinoma cells can induce growth suppression. PTEN gene may be a novel therapeutic agent for endometrial carcinoma.
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Adenoviridae/genética , Neoplasias Endometriales/patología , Monoéster Fosfórico Hidrolasas/biosíntesis , Proteínas Supresoras de Tumor/biosíntesis , Proliferación Celular , Neoplasias Endometriales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Factor II del Crecimiento Similar a la Insulina/farmacología , Fosfohidrolasa PTEN , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/fisiología , Recombinación Genética , Transfección , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/fisiologíaRESUMEN
OBJECTIVE: To determine candidate genes of endometrial adenocarcinoma. METHODS: To compare the gene expression profile in 2 endometrial adenocarcinoma tissues and 2 normal endometria by HGEC-40s GeneChip probe including 4096 genes array. Expression differences between normal and malignant tissue groups were measured by GenePixPro3.0 software. RESULTS: 350 genes with a ratio below 0.5 and above 2.0 showed discrimination between normal and malignant groups. Thirty three genes with ratio above 3 were up-regulated, forty-four genes with ratio below 0.3 were down-regulated. CONCLUSION: The overexpression of oncogenes with their disturbed or constitutively activated signal transduction cascades alone or in combination with the mutation-induced silencing of tumor suppressor genes is associated with malignant transformation.
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Adenocarcinoma/genética , Neoplasias Endometriales/genética , Perfilación de la Expresión Génica , Aurora Quinasas , Proteínas de Ciclo Celular , Femenino , Proteínas Ligadas a GPI , Humanos , Proteínas de la Membrana/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas c-kit/genéticaRESUMEN
OBJECTIVE: To study the relationship of changes in gene expression profiles of hydatidiform mole and choriocarcinoma with hyperplasia of trophoblasts. METHODS: The differentially expressed genes were analyzed in two pairs of tissues of hydatidiform mole versus normal villi, and in two pairs of normal primary culture trophoblasts versus JAR cell line of chariocarcinoma, using cDNA microarray containing 4096 genes. To confirm the results of cDNA microarray analysis, expressions of some up-regulated genes related to DNA synthesis in normal villi, hydatidiform mole, and 2 choriocarcinoma cell lines (JAR and JEG-3) were examined by immunohistochemistry, immunoblotting and RT-PCR. RESULTS: A total of 89 genes were differentially expressed in all hydatidiform moles, accounting for 2.2% of the genes arrayed. Of the 89 genes, 24 were up-regulated and 65 were down-regulated. Compared with normal primary trophoblasts, there were 433 genes up-regulated and 380 genes down-regulated in JAR cell line. Forty six genes were up-regulated in both hydatidiform mole and choriocarcinoma, while 13 genes were down-regulated. Some genes associated with cell proliferative inhibition were significantly down-regulated, whereas those associated with cell proliferation, malignant transformation, metastasis and drug resistance were highly up-regulated. The expressions of thymidine kinase 1, the small subunit of ribonucleotide reductase (RRM2) were significantly increased in hydatidiform mole, JAR and JEG-3 cells. CONCLUSION: Abnormal expression of genes exists in hydatidiform mole and choriocarcinoma. Hyperplasia of trophoblasts may be related to over-expression of genes coding for synthetic enzymes.
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Coriocarcinoma/genética , Perfilación de la Expresión Génica , Mola Hidatiforme/genética , Trofoblastos/patología , Neoplasias Uterinas/genética , Adulto , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica , Coriocarcinoma/metabolismo , Coriocarcinoma/patología , Resistencia a Antineoplásicos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Mola Hidatiforme/metabolismo , Hiperplasia , Metástasis de la Neoplasia , Análisis de Secuencia por Matrices de Oligonucleótidos , Embarazo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ribonucleósido Difosfato Reductasa/metabolismo , Timidina Quinasa/metabolismo , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologíaRESUMEN
OBJECTIVE: To explore the more sensitive and specific immunohistochemical markers in differential diagnosis of uterine leiomyosarcoma (ULMS) and the specific subtypes of leiomyoma. METHODS: The routine SP immunohistochemical technique was used to examine the expression of desmin, alpha smooth muscle actin (SMA), calponin h1, h-caldesmon, estrogen receptor (ER), progesterone receptor (PR), proliferating cell nuclear antigen (PCNA), mast cells, and CD44v3 in 82 patients with smooth muscle tumors of the uterus, including 17 patients with leiomyosarcoma (LMS), 25 with cellular leiomyoma (CL), 15 with bizarre leiomyoma (BL) and 25 with ordinary leiomyoma (OL). RESULTS: The expression rates of desmin, SMA, h-caldesmon and CD44v3 in uterine LMS were all lower than those in CL and BL (all P<0.05), but these markers had limited significance in differentiation of ULMS from CL or BL. Compared to those in CL or BL, the expression rates of ER and PR and the number of mast cells were significantly lower in LMS (all P<0.01), while the expression of PCNA in LMS was higher (P<0.01). CONCLUSION: The increase of PCNA and decrease of ER and PR expression help differentiate ULMS from CL and BL. The number of mast cells was helpful in differential diagnosis of ULMS with high sensitivity and specificity.
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Leiomioma/diagnóstico , Leiomiosarcoma/diagnóstico , Neoplasias Uterinas/diagnóstico , Adulto , Proteínas de Unión al Calcio/análisis , Diagnóstico Diferencial , Femenino , Humanos , Receptores de Hialuranos/análisis , Inmunohistoquímica , Leiomioma/química , Leiomiosarcoma/química , Proteínas de Microfilamentos , Persona de Mediana Edad , Antígeno Nuclear de Célula en Proliferación/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Neoplasias Uterinas/química , CalponinasAsunto(s)
Lactobacillus/fisiología , Vagina/microbiología , Vaginosis Bacteriana/microbiología , Vaginosis Bacteriana/terapia , Antibacterianos/uso terapéutico , Femenino , Humanos , Concentración de Iones de Hidrógeno , Lactobacillus/inmunología , Probióticos , Vagina/inmunología , Frotis Vaginal , Vaginosis Bacteriana/diagnósticoRESUMEN
OBJECTIVE: To study effect of the antisense oligodeoxynucleotide (ASODN) of small subunit of human ribonucleotide reductase (RRM2) mRNA on cell line of human choriocarcinoma in vitro. METHODS: Two 20-mer gapmer ASODNs with a full phosphorothioate backbone were artificially synthesized, which were complementary to nucleotides 626-645 (a coding region) and 1572-1591 (a 3'untranslated region) of RRM2, respectively. ASODNs were transfected into JAR cells through oligofectamine. The survival rate was assessed by methyl thiazolyl tetrazolium (MMT) assay, and RRM2 expression was detected by immunoblot and reverse transcriptase polymerase chain reaction (RT-PCR) methods. RESULTS: Antisense oligodeoxynucleotide one (ASODN1) targeting the coding region significantly inhibited growth of JAR cells in a dose- and time-dependent manner and downregulated RRM2 expression in a time-dependent manner. ASODN1 at 100 nmol/L could inhibit significantly cell growth (P = 0.000), and the effects of ASODN1 on JAR cell proliferation were enhanced with increase of ASODN1 concentration and reached the peak point at 400 nmol/L concentration (P = 0.000). Cell growth was significantly inhibited by 200 nmol/L of ASODN1 after 24 h of treatment (P = 0.000). The effect of ASODN1 was at the maximum at 48 h (P = 0.000), and began to decrease at 72 h of treatment. RRM2 expression started to reduce after ASOND1 treatment for 12 hours, and was obviously downregulated at 24 h of treatment, and decreased to the lowest level at 48 h (P < 0.05). RRM2 expression began to recover at 72 h of treatment. Antisense oligodeoxynucleotide two (ASODN2) corresponding to 3'untranslated region and control oligodeoxynucleotides had no significant effect on the proliferation and RRM2 expression, but the combination of ASODN2 and ASODN1 was more effective on reducing RRM2 expression and inhibiting cell proliferation than ASODN1 alone. CONCLUSIONS: ASODN1 of RRM2 can inhibit the proliferation of JAR cells and downregulate RRM2 transcription and translation in a selective and specific manner. The combination of multiple ASODNs targeting different regions of RRM2 mRNA would be an important approach to improve antisense effectiveness.
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Coriocarcinoma/patología , Oligodesoxirribonucleótidos Antisentido/farmacología , Ribonucleótido Reductasas/farmacología , Neoplasias Uterinas/patología , Adulto , Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Femenino , Humanos , Embarazo , ARN Mensajero/farmacología , Células Tumorales CultivadasRESUMEN
OBJECTIVE: The purpose of this study was to investigate the expression and localization of the two known isoforms of hemeoxygenase (HO) in normal human first trimester placenta and third trimester placenta. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were resorted to demonstrate the expression and localization of HO-1 and HO-2 in normal placenta tissue, obtained from 6 approximately 10 week gestation women (20 cases) and the third trimester woman (20 cases). RESULTS: Compared with glyceraldehydes-3-phosphate dehydrogenase (GAPDH), the expression of HO-1 was lower, there was no significant difference between the first trimester (0.31 +/- 0.19) and third trimester (0.28 +/- 0.14) (P > 0.05); the expression of HO-2 was higher, it is significantly higher at third trimester (1.12 +/- 0.58) compared with first trimester placenta (0.70 +/- 0.48) (P < 0.05). The result of immunohistochemistry demonstrated that HO-1 was predominantly localized in villous stroma cell and trophoblast; HO-2 predominantly localized in trophoblast as well as capillaries, with weak staining of villous stroma. The staining score were not normally distributed. The median staining scorse of HO-1 in trophoblast, villous stroma and capillaries at first trimester were 9.0, 2.6 and 2.8, respectively, at third trimester were 8.7, 2.0 and 1.4, there was no difference between the two groups (P > 0.05). The median staining score of HO-2 in capillaries at first trimester was 5.8, significantly lower than that of the third trimester (9.3) (P < 0.05). There was no significant difference between the staining score of HO-2 in trophoblast (10.5, 8.0) and villous stroma (3.6, 2.4) between the first trimester and the third trimester (P > 0.05). CONCLUSIONS: HO-1 and HO-2 as endogenous system may regulate feto-placental circulation, indicated their different roles in placental vascular development and regulation. They may offer protection against cyto-toxic damage in the placenta, and influence immunological function.
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Hemo Oxigenasa (Desciclizante)/análisis , Placenta/enzimología , Adulto , Citoprotección , Femenino , Hemo Oxigenasa (Desciclizante)/genética , Hemo Oxigenasa (Desciclizante)/fisiología , Hemo-Oxigenasa 1 , Humanos , Proteínas de la Membrana , Placenta/irrigación sanguínea , Placenta/citología , Embarazo , ARN Mensajero/análisis , Flujo Sanguíneo RegionalRESUMEN
OBJECTIVE: To screen genes which may associate with the development and malignant transformation of hydatidiform mole. METHOD: The differentially expressed genes were analyzed between the tissues of two cases of hydatidiform mole and the normal placental tissues of two cases of pregnancy which had almost the same pregnant ages as hydatidiform mole, using cDNA chips containing 4,096 genes. RESULTS: There were total 89 genes significantly differently expressed in all hydatidiform moles, counting for 2.2% of total genes. Compared with normal villi, 24 genes in hydatidiform mole were up-regulated and 65 genes were down-regulated. Bioinformatical analysis of genes showed genes associated with cell proliferative inhibition, such as Ras GTPase activating protein, TGF-beta IIR alpha, BTG2 were significantly down-regulated, whereas genes associated with cell proliferation, malignant transformation and tumor metastasis as thymidine kinase, ribonucleotide reductase, glucose transport protein were highly up-regulated. CONCLUSION: cDNA chip technique is one kind of very effective methods in screening associated genes in hydatidiform mole.
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Mola Hidatiforme/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Vellosidades Coriónicas/metabolismo , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Mola Hidatiforme/metabolismo , Mola Hidatiforme/patología , Embarazo , ARN Mensajero/biosíntesis , Receptores de Factores de Crecimiento Transformadores beta/biosíntesis , Trofoblastos/metabolismo , Proteínas ras/biosíntesisRESUMEN
OBJECTIVE: To investigate the expression of heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2) in placenta tissue of pregnancy induced hypertension (PIH), and the relationship between HO protein expression and enzymatic activity. METHODS: Protein expression was analyzed qualitatively and semi-quantitatively by Western blotting in placental tissue of PIH (PIH group, n = 30) and normal late pregnant women (control group, n = 30). The levels of HO enzymatic activity in placental tissue were measured with the double wavelength scanning by spectrophotometer. RESULTS: (1) Western blotting analysis demonstrated that the relative protein levels of HO-1 and HO-2 in placental samples of control group were 0.7 +/- 0.4 and 0.8 +/- 0.4 respectively, there were no significant difference between HO-1 and HO-2 protein levels (P > 0.05). (2) The relative levels of HO-1 were 0.6 +/- 0.4 in PIH group, there was no significant difference from those in the control group (P > 0.05); the relative levels of HO-2 protein were 0.6 +/- 0.3 in PIH group, that were obviously lower than those in the control group (P < 0.01). The levels of HO enzymatic activity of PIH group were (0.3 +/- 0.2) nmol x mg(-1) x h(-1), significantly lower than that of the control group [(0.5 +/- 0.3) nmol x mg(-1) x h(-1)] (P < 0.01). The levels of HO activity correlated with HO-2 protein levels. CONCLUSIONS: The expression levels of HO-2 protein were decreased and HO enzymatic activity reduced in PIH group. HO may play a role in the pathophysiology of poor placental perfusion and tissue damage in placenta of PIH.
Asunto(s)
Hemo Oxigenasa (Desciclizante)/biosíntesis , Hipertensión Inducida en el Embarazo/enzimología , Placenta/enzimología , Adulto , Femenino , Hemo Oxigenasa (Desciclizante)/genética , Hemo-Oxigenasa 1 , Humanos , Proteínas de la Membrana , EmbarazoRESUMEN
OBJECTIVE: To establish and optimize the two-dimensional electrophoresis (2-DE) of uterine leiomyoma for the proteome analysis. METHODS: Run immobilized pH gradient (IPG)-isoelectric focusing electrophoresis as the first dimension, then vertical SDS-PAGE electrophoresis as the second dimension. A series of important steps,such as sample solubility, volume of loading, electrophoresis parameters and protocol for staining were optimized. RESULTS: The 2-DE patterns of uterine leiomyoma and myometrium with good quality were obtained. CONCLUSION: With optimal condition the two-dimensional electrophoresis of uterine leiomyoma can be obtained.
Asunto(s)
Leiomioma/química , Proteínas de Neoplasias/análisis , Proteoma/análisis , Neoplasias Uterinas/química , Electroforesis en Gel Bidimensional , Femenino , Humanos , Miometrio/químicaRESUMEN
OBJECTIVE: To observe microvessel density(MVD), epithelial stromal vascular cuffing(VC) and expression of vascular endothelial growth factor(VEGF) in human cervical carcinomas and to clarify their significance in the invasion and metastasis of cervical carcinoma. METHODS: VEGF and CD34 were stained immunohistochemically (SP) in 57 cases of cervical carcinoma (30 cases of squamous cell carcinoma, 20 of adenocarcinoma 7 of glandular and squamous cell carcinoma), 29 cases of cervical intraepithelial neoplasia (CIN) and 16 cases of normal cervices, meanwhile, MVD and VC were also assayed. RESULTS: There were significant differences among the above 5 groups for MVD P<0.01 . The VC pattern showed a significant difference between cervical carcinoma and CIN or control group P<0.01). The positive rates of VEGF in normal cervical epithelium, CIN, squamous cell carcinoma, adenocarcinoma, glandular and squamous cell carcinoma were 18.8% 3/16, 82.8% 24/29), 93.3% 28/30), 100% 20/20 and 7/7(100%), respectively. There were significant differences between these cervical lesion groups and the control group(P<0.001). The MVD showed significant differences between the positive pelvic node metastasis and negative pelvic node metastasis P<0.05). There was no significant correlation between the expression of VEGF and the tumor diameter, clinical stage, pathologic grade and pelvic node metastasis. CONCLUSION: The expression of VEGF may play an important role in the angiogenesis of cervical carcinoma. Degree of malignancy of cervical carcinoma has a close association with microvessel density.
Asunto(s)
Factores de Crecimiento Endotelial/análisis , Péptidos y Proteínas de Señalización Intercelular/análisis , Linfocinas/análisis , Neoplasias del Cuello Uterino/irrigación sanguínea , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Metástasis Linfática , Microcirculación , Persona de Mediana Edad , Neoplasias del Cuello Uterino/química , Neoplasias del Cuello Uterino/patología , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: To study the expression of the small subunit ribonucleotide reductase (R2) in gestational trophoblastic diseases (GTD) and to assess its prognostic value. METHODS: The expression of R2 was detected with immunohistochemical method in 15 cases of normal villi, 38 cases of hydatidiform mole (HM), 42 cases of invasive moles (IM) and 18 cases of choriocarcinoma (CC). RESULTS: R2 expression in HM, IM and CC was significantly increased compared with that of normal villi (P=0.000). There were no significant differences in R2 protein expression among HM, IM and CC. Among 38 cases of HM, R2 expression in 8 cases with malignant transformation was significantly higher than in 30 cases of non-malignant transformation mole (P=0.02). Preoperative chemotherapy of gestational trophoblastic tumor including IM and CC did not influence the R2 expression. Compared with patients of stage I (WHO), the R2 protein in gestational trophoblastic tumor (GTT) patients of stage III or stage II was significantly increased (P=0.023 and P=0.038, respectively). The value of R2 in GTT patients with middle or high risk in WHO prognostic scoring system was higher than in the patients with low risk (P=0.018 and P=0.006, respectively). CONCLUSION: R2 expression in GTD is increased, which may be associated with the hyperplasia of trophoblasts, malignant transformation of hydatidiform mole and drug resistance of trophoblastic tumor.