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1.
Appl. cancer res ; 40: 1-9, Oct. 19, 2020. ilus, tab
Article in English | LILACS, Inca | ID: biblio-1281398

ABSTRACT

Background: Ovarian cancer is the most common gynecological malignancy. In patients with advanced ovarian cancer, some biological parameters have prognostic implementations. P27kip1 is an inhibitor of a cycline-dependent kinase, its loss, can contribute to tumor progression. Objective: This study aimed to examine the importance of P27KIP1 protein in predicting the prognosis and response to neoadjuvant chemotherapy in patients with advanced ovarian epithelial cancer and to compare the outcomes of immunohistochemistry with Quantitative Real-time PCR. Patients and methods: We have studied P27KIP1expression by both immunohistochemistry and Quantitative Realtime PCR from 88 patients with advanced ovarian carcinomas undergone radical debulking surgery and received Paclitaxel followed by Cisplatin every 3 weeks for a total of 6 cycles. We also studied their association with both chemotherapy response and patient survival. Results: Nuclear expression of p27KIP1 protein was intense in 86 normal ovarian tissues and 42 of 88 carcinomas. The P27kip1mRNA expression level by qRT-PCR was very low in ovarian cancer tissues relative to its adjacent normal tissues. The results were statistically significant by both methods of determination. p27KIP1 expression was significantly related to good prognostic parameters as low stage tumors, differentiated tumors, absence of ascites, residual disease < 2 cm, and response to chemotherapy but not with histopathological type in case of determination by immunohistochemistry. Comparison of P27kip1 by both immunohistochemistry and qRTPCR with different prognostic parameters revealed no significant difference between both methods in the assessment of these parameters. In 4 years of follow-up, 20.5% of patients were alive without evidence of disease. 6.8% were alive with disease. The disease-related four -year survival rate for the whole group was 28.2%. In multivariate analysis, residual disease, histological type, tumor differentiation, ascites was of independent prognostic significance. Conclusion: In ovarian cancer, patients with loss of p27KIP1 expression are at a greater likelihood of disease progression, p27KIP1 may be used as a molecular marker to predict response to chemotherapy and prognosis. Both immunohistochemistry and qRT-PCR have equal reliability in the determination of p27 KIP1


Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Young Adult , Ovarian Neoplasms/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Carcinoma, Ovarian Epithelial/metabolism , Ovarian Neoplasms/drug therapy , Prognosis , Immunohistochemistry , Neoadjuvant Therapy , Real-Time Polymerase Chain Reaction , Carcinoma, Ovarian Epithelial/drug therapy , Neoplasm Staging
2.
Braz. j. med. biol. res ; 53(6): e8885, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132519

ABSTRACT

In this study, we aimed to analyze the anti-cancer effects of β-elemene combined with paclitaxel for ovarian cancer. RT-qPCR, MTT assay, western blot, flow cytometry, and immunohistochemistry were used to analyze in vitro and in vivo anti-cancer effects of combined treatment of β-elemene and paclitaxel. The in vitro results showed that β-elemene+paclitaxel treatment markedly inhibited ovarian cancer cell growth, migration, and invasion compared to either paclitaxel or β-elemene treatment alone. Results demonstrated that β-elemene+paclitaxel induced apoptosis of SKOV3 cells, down-regulated anti-apoptotic Bcl-2 and Bcl-xl gene expression and up-regulated pro-apoptotic P53 and Apaf1 gene expression in SKOV3 cells. Administration of β-elemene+paclitaxel arrested SKOV3 cell cycle at S phase and down-regulated CDK1, cyclin-B1, and P27 gene expression and apoptotic-related resistant gene expression of MDR1, LRP, and TS in SKOV3 cells. In vivo experiments showed that treatment with β-elemene+paclitaxel significantly inhibited ovarian tumor growth and prolonged the overall survival of SKOV3-bearing mice. In addition, the treatment inhibited phosphorylated STAT3 and NF-κB expression in vitro and in vivo. Furthermore, it inhibited migration and invasion through down-regulation of the STAT-NF-κB signaling pathway in SKOV3 cells. In conclusion, the data suggested that β-elemene+paclitaxel can inhibit ovarian cancer growth via down-regulation of the STAT3-NF-κB signaling pathway, which may be a potential therapeutic strategy for ovarian cancer therapy.


Subject(s)
Animals , Male , Female , Rabbits , Ovarian Neoplasms/drug therapy , Sesquiterpenes/administration & dosage , Cell Movement/drug effects , NF-kappa B/adverse effects , Paclitaxel/administration & dosage , Apoptosis/drug effects , Cell Proliferation/drug effects , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Immunohistochemistry , Transfection , Signal Transduction , Blotting, Western , NF-kappa B/metabolism , Cell Line, Tumor , Real-Time Polymerase Chain Reaction , Mice, Inbred BALB C
3.
Biol. Res ; 53: 10, 2020. tab, graf
Article in English | LILACS | ID: biblio-1100916

ABSTRACT

BACKGROUND: The aim of this study was to investigate the effect role and mechanism of miR-30b-3p on ovarian cancer cells biological function. METHODS: The expression of miR-30b-3p was detected in ovarian cancer cell lines and normal ovarian epithelial cell line by qRT-PCR. Mir-30b-3p mimic was transfected into OVCAR3 cells. Cell-counting kit-8 (CCK-8) assay was conducted to explore the effect of mir-30b-3p on the OVCAR3 cells' proliferation. Cell cycle and apoptosis were detected by Flow cytometry. Cell invasion ability was detected by Transwell test. The regulation of putative target of miR-30b-3p was verified by double luciferase reporter assays and Western blot. RESULT: We found that miR-30b-3p was downregulated in OVCAR3 cells. Overexpression of miR-30b-3p suppressed proliferation, promoted apoptosis, slowed cell cycle and inhibited migration and invasion of OVCAR3 cells. Bioinformatics analysis identified 3'-untranslated region (3'UTR) of Collagen triple helix repeat-containing 1 (CTHRC1) as the presumed binding site for miR-30b-3p. Detection of double luciferase reporter and Western-Blot result confirmed that CTHRC1 was the target gene of miR-30b-3p. Furthermore, E-cadherin, ß-cadherin and Vimentin protein expression level were changed after transfection of miR-30b-3p. CONCLUSION: miR-30b-3p function as an anti-cancer gene. Overexpression of miR-30b-3p can inhibit the biological function of ovarian cancer cells. MiR-30b-3p targets CTHRC1 gene plays an important role in epithelial-mesenchymal transformation (EMT), and supports miR-30b-3p as a potential biological indicator for ovarian cancer in the future.


Subject(s)
Humans , Female , Ovarian Neoplasms/genetics , Gene Expression Regulation, Neoplastic/genetics , Extracellular Matrix Proteins/genetics , MicroRNAs/genetics , Epithelial-Mesenchymal Transition/genetics , Ovarian Neoplasms/metabolism , Signal Transduction , Cell Movement , Extracellular Matrix Proteins/metabolism , Apoptosis , Cell Line, Tumor , Cell Proliferation , Neoplasm Invasiveness
4.
Braz. j. med. biol. res ; 52(7): e8381, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011592

ABSTRACT

Experiments were conducted to determine if the follicle-stimulating hormone (FSH) receptor binding inhibitor (FRBI) impacts the expression levels of AT-rich interactive domain-containing protein 1A (ARID1A) and phosphatase and tensin homolog (PTEN) in ovaries and blood, as well as expressions of follicle-stimulating hormone cognate receptor (FSHR) gene and proteins. Mice in FRBI-10, FRBI-20, FRBI-30, and FRBI-40 groups were intramuscularly injected with 10, 20, 30, and 40 mg FRBI/kg, respectively, for five consecutive days. Western blotting and qRT-PCR were utilized to determine expression levels of ARID1A and PTEN proteins and mRNAs. Serum ARID1A and PTEN concentrations of the FRBI-40 group were higher than the control group (CG) and FSH group (P<0.05). FSHR mRNA levels of FRBI-20, FRBI-30, and FRBI-40 groups were lower than that of CG and FSH groups on day 15 (P<0.05 or P<0.01). Expression levels of FSHR proteins of FRBI-30 and FRBI-40 groups were lower than those of CG and FSH groups (P<0.05). Levels of ARID1A and PTEN proteins of the FRBI-30 group were greater than CG on days 20 and 30 (P<0.05). FRBI doses had significant positive correlations to levels of ARID1A and PTEN proteins. Additionally, ARID1A and PTEN had negative correlations to FSHR mRNAs and proteins. A high dose of FRBI could promote the expression levels of ARID1A and PTEN proteins in ovarian tissues. FRBI increased serum concentrations of ARID1A and PTEN. However, FRBI depressed expression levels of FSHR mRNAs and proteins in mouse ovaries.


Subject(s)
Animals , Female , Rabbits , Ovarian Neoplasms/metabolism , Receptors, FSH/antagonists & inhibitors , Nuclear Proteins/blood , DNA-Binding Proteins/metabolism , PTEN Phosphohydrolase/blood , Follicle Stimulating Hormone/metabolism , Phosphorylation , Transcription Factors , Nuclear Proteins/metabolism , Transcriptional Activation/genetics , Up-Regulation , Blotting, Western , DNA-Binding Proteins/blood , PTEN Phosphohydrolase/metabolism , Real-Time Polymerase Chain Reaction
5.
Yonsei Medical Journal ; : 51-56, 2018.
Article in English | WPRIM | ID: wpr-742505

ABSTRACT

PURPOSE: 14-3-3ζ regulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζ is associated with ovarian cancer prognosis. MATERIALS AND METHODS: We examined 14-3-3ζ expression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζ expression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. RESULTS: Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζ expression, and 14-3-3ζ overexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζ overexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζ expression group, but not reached in the low 14-3-3ζ expression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζ by RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. CONCLUSION: 14-3-3ζ overexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζ could be a therapeutic option that enhances the antitumor activity of cisplatin.


Subject(s)
14-3-3 Proteins/metabolism , Adult , Aged , Cell Line, Tumor , Cisplatin/therapeutic use , Disease-Free Survival , Down-Regulation , Female , Gene Knockdown Techniques , Gene Silencing , Humans , Immunohistochemistry , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Prognosis , Young Adult
6.
Biol. Res ; 51: 58, 2018. graf
Article in English | LILACS | ID: biblio-1011402

ABSTRACT

BACKGROUND: Studies have demonstrated that transforming growth factor beta-1 (TGF-ß1) exhibits oncogenic activity in different types of cancer, including ovarian cancer (OC). However, its regulatory mechanism in OC and whether TGF-ß1 is involved in chemosensitivity regulation remains unclear. Thus, the aim of this study was to investigate the role of TGF-ß1 in OC. METHODS: The OC cell line SKOV3 was employed, and TGF-ß1 overexpression or knockdown vectors were constructed. The cell proliferation of SKOV3 was evaluated with the cell counting kit (CCK8) kit after treatment with different concentrations of cis-platinum. Western blot and protein immunoprecipitation were employed to detect changes in BRCA1 and Smad3 expression and their interactions. Tumor growth in nude mice was evaluated. RESULTS: The results showed that TGF-ß1 knockdown increased chemosensitivity by promoting BRCA1 expression and Smad3 phosphorylation. In vivo studies showed that TGF-ß1 knockdown significantly inhibited the growth of tumors, also by upregulating BRCA1 expression and Smad3 phosphorylation. CONCLUSION: Taken together, our results suggest that TGF-ß1 knockdown inhibits tumor growth and increases chemosensitivity by promotion of BRCA1/Smad3 signaling.


Subject(s)
Humans , Animals , Male , Female , Ovarian Neoplasms/metabolism , Down-Regulation/physiology , Genes, BRCA1/physiology , Smad3 Protein/physiology , Transforming Growth Factor beta1/physiology , Ovarian Neoplasms/pathology , Ovarian Neoplasms/drug therapy , Immunohistochemistry , Cells, Cultured , Blotting, Western , Drug Resistance, Neoplasm/physiology , Tumor Suppressor Proteins/physiology , Cell Line, Tumor , Cell Proliferation , Smad3 Protein/analysis , Transforming Growth Factor beta1/analysis , Gene Knockdown Techniques , Real-Time Polymerase Chain Reaction , Mice, Inbred BALB C
7.
Biol. Res ; 51: 50, 2018. graf
Article in English | LILACS | ID: biblio-1011394

ABSTRACT

BACKGROUND: Accumulating studies have demonstrated that high-mobility group A2 (HMGA2), an oncofetal protein, plays a role in tumor development and progression. However, the molecular role of HMGA2 in ovarian carcinoma is yet to be established. MicroRNAs (miRNAs), a group of small noncoding RNAs, negatively regulate gene expression and their dysregulation has been implicated in tumorigenesis. The aim of this study was to investigate the potential involvement of a specific miRNA, miR-219-5p, in HMGA2-induced ovarian cancer. METHODS: The ovarian cancer cell line, SKOV3, was employed, and miR-219-5p and HMGA2 overexpression vectors constructed. The CCK-8 kit was used to determine cell proliferation and the Transwell® assay used to measure cell invasion and migration. RT-PCR and western blot analyses were applied to analyze the expression of miR-219-5p and HMGA2, and the luciferase reporter assay used to examine the interactions between miR-219-5p and HMGA2. Nude mice were employed to characterize in vivo tumor growth regulation. RESULTS: Expression of miR-219-5p led to suppression of proliferation, invasion and migration of the ovarian cancer cell line, SKOV3, by targeting HMGA2. The inhibitory effects of miR-219-5p were reversed upon overexpression of HMGA2. Data from the luciferase reporter assay showed that miR-219-5p downregulates HMGA2 via direct integration with its 3'-UTR. Consistent with in vitro findings, expression of miR-219-5p led to significant inhibition of tumor growth in vivo. CONCLUSION: Our results collectively suggest that miR-219-5p inhibits tumor growth and metastasis by targeting HMGA2.


Subject(s)
Humans , Animals , Female , Mice , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Gene Expression Regulation, Neoplastic/genetics , HMGA2 Protein/metabolism , MicroRNAs/physiology , Ovarian Neoplasms/genetics , Cell Movement/genetics , HMGA2 Protein/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Neoplasm Invasiveness , Neoplasm Metastasis
8.
Braz. j. med. biol. res ; 50(3): e6057, 2017. tab, graf
Article in English | LILACS | ID: biblio-839271

ABSTRACT

Ovarian cancer is one of the most common malignancies in women. Semaphorin 4D (sema 4D) is involved in the progress of multiple cancers. In the presence of estrogen-like ligands, estrogen receptors (ERα and ERβ) participate in the progress of breast and ovarian cancers by transcriptional regulation. The aim of the study was to investigate the role of sema 4D and elucidate the regulatory pattern of ERα and ERβ on sema 4D expression in ovarian cancers. Sema 4D levels were up-regulated in ovarian cancer SKOV-3 cells. Patients with malignant ovarian cancers had significantly higher sema 4D levels than controls, suggesting an oncogene role of sema 4D in ovarian cancer. ERα expressions were up-regulated in SKOV-3 cells compared with normal ovarian IOSE80 epithelial cells. Conversely, down-regulation of ERβ was observed in SKOV-3 cells. Forced over-expression of ERα and ERβ in SKOV-3 cells was manipulated to establish ERα+ and ERβ+ SKOV-3 cell lines. Incubation of ERα+ SKOV-3 cells with ERs agonist 17β-estradiol (E2) significantly enhanced sema 4D expression and rate of cell proliferation. Incubated with E2, ERβ+ SKOV-3 cells showed lower sema 4D expression and cell proliferation. Blocking ERα and ERβ activities with ICI182-780 inhibitor, sema 4D expressions and cell proliferation of ERα+ and ERβ+ SKOV-3 cells were recovered to control levels. Taken together, the data showed that sema 4D expression was positively correlated with the progress of ovarian cancer. ERα positively regulated sema 4D expression and accelerated cell proliferation. ERβ negatively regulated sema 4D expression and inhibited cell multiplication.


Subject(s)
Humans , Female , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Ovarian Neoplasms/metabolism , Semaphorins/metabolism , Biomarkers, Tumor/metabolism , Cell Proliferation , Down-Regulation , Semaphorins/genetics
9.
Yonsei Medical Journal ; : 59-66, 2017.
Article in English | WPRIM | ID: wpr-65062

ABSTRACT

PURPOSE: Loss of AT-rich DNA-interacting domain 1A (ARID1A) has been identified as a driving mutation of ovarian clear cell carcinoma (O-CCC), a triple-negative ovarian cancer that is intermediary between serous and endometrioid subtypes, in regards to molecular and clinical behaviors. However, about half of O-CCCs still express BAF250a, the protein encoded by ARID1A. Herein, we aimed to identify signatures of ARID1A-positive O-CCC in comparison with its ARID1A-negative counterpart. MATERIALS AND METHODS: Seventy cases of O-CCC were included in this study. Histologic grades and patterns of primary tumor, molecular marker immunohistochemistry profiles, and clinical outcomes were analyzed. RESULTS: Forty-eight (69%) O-CCCs did not express BAF250a, which were designated as "ARID1A-negative." The other 22 (31%) O-CCCs were designated as "ARID1A-positive." ARID1A-positive tumors were more likely to be histologically of high grades (41% vs. 10%, p=0.003), ERβ-positive (45% vs. 17%, p=0.011), and less likely to be HNF1β-positive (77% vs. 96%, p=0.016) and E-cadherin-positive (59% vs. 83%, p=0.028) than ARID1A-negative tumors. Patient age, parity, tumor stage were not significantly different in between the two groups. Cancer-specific survival was not significantly different either. CONCLUSION: We classified O-CCCs according to ARID1A expression status. ARID1A-positive O-CCCs exhibited distinct immunohistochemical features from ARID1A-negative tumors, suggesting a different underlying molecular event during carcinogenesis.


Subject(s)
Adenocarcinoma, Clear Cell/metabolism , Adult , Aged , Biomarkers, Tumor/metabolism , Cadherins/metabolism , Estrogen Receptor beta/metabolism , Female , Humans , Immunohistochemistry , Middle Aged , Mutation , Neoplasm Proteins/metabolism , Nuclear Proteins/metabolism , Ovarian Neoplasms/metabolism , Transcription Factors/metabolism
10.
Braz. j. med. biol. res ; 49(3): e5043, Mar. 2016. graf
Article in English | LILACS | ID: lil-771931

ABSTRACT

Ovarian cancer is one of the most common causes of death from gynecologic tumors and is an important public health issue. Ghrelin is a recently discovered bioactive peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR). Several studies have identified the protective effects of ghrelin on the mammalian reproductive system. However, little research has been done on the effects of ghrelin on ovarian cancer cells, and the underlying mechanisms of these effects. We sought to understand the potential involvement of mitogen-activated protein kinases (MAPKs) in ghrelin-mediated inhibition of growth of the ovarian line HO-8910. We applied different concentrations of ghrelin and an inhibitor of the ghrelin receptor (D-Lys3-GHRP-6) to HO-8910 cells and observed the growth rate of cells and changes in phosphorylation of the MAPKs ERK1/2, JNK and p38. We discovered that ghrelin-induced apoptosis of HO-8910 cells was though phosphorylated ERK1/2, and that this phosphorylation (as well as p90rsk phosphorylation) was mediated by the GHSR. The ERK1/2 pathway is known to play an essential part in the ghrelin-mediated apoptosis of HO-8910 cells. Hence, our study suggests that ghrelin inhibits the growth of HO-8910 cells primarily through the GHSR/ERK pathway.


Subject(s)
Humans , Female , Middle Aged , Gene Expression Regulation, Neoplastic/genetics , Ghrelin/pharmacology , MAP Kinase Signaling System/physiology , Ovarian Neoplasms/genetics , Apoptosis/drug effects , MAP Kinase Signaling System/drug effects , Oligopeptides/metabolism , Ovarian Neoplasms/metabolism , Phosphorylation/drug effects , Receptors, Ghrelin/antagonists & inhibitors , Receptors, Ghrelin/metabolism , Tumor Cells, Cultured
11.
Braz. j. med. biol. res ; 49(12): e5717, 2016. graf
Article in English | LILACS | ID: biblio-828174

ABSTRACT

Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. A previous study has found that propofol can inhibit invasion and induce apoptosis of ovarian cancer cells. However, the underlying mechanisms are not known. miR-9 has been reported to be little expressed in ovarian cancer cells, which has been related to a poor prognosis in patients with ovarian cancer. Studies have also demonstrated that propofol could induce microRNAs expression and suppress NF-κB activation in some situations. In the present study, we assessed whether propofol inhibits invasion and induces apoptosis of ovarian cancer cells by miR-9/NF-κB signaling. Ovarian cancer ES-2 cells were transfected with anti-miR-9 or p65 cDNA or p65 siRNA for 24 h, after which the cells were treated with different concentrations of propofol (1, 5, and 10 μg/mL) for 24 h. Cell growth and apoptosis were detected using MTT assay and flow cytometry analysis. Cell migration and invasion were detected using Transwell and Wound-healing assay. Western blot and electrophoretic mobility shift assay were used to detect different protein expression and NF-κB activity. Propofol inhibited cell growth and invasion, and induced cell apoptosis in a dose-dependent manner, which was accompanied by miR-9 activation and NF-κB inactivation. Knockdown of miR-9 abrogated propofol-induced NF-κB activation and MMP-9 expression, reversed propofol-induced cell death and invasion of ES-2 cells. Knockdown of p65 inhibited NF-κB activation rescued the miR-9-induced down-regulation of MMP-9. In addition, overexpression of p65 by p65 cDNA transfection increased propofol-induced NF-κB activation and reversed propofol-induced down-regulation of MMP-9. Propofol upregulates miR-9 expression and inhibits NF-κB activation and its downstream MMP-9 expression, leading to the inhibition of cell growth and invasion of ES-2 cells.


Subject(s)
Humans , Female , MicroRNAs/drug effects , Neoplasm Invasiveness/prevention & control , NF-kappa B/drug effects , Ovarian Neoplasms/drug therapy , Propofol/therapeutic use , Protective Agents/therapeutic use , Apoptosis/drug effects , Blotting, Western , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Matrix Metalloproteinase 9/metabolism , MicroRNAs/genetics , NF-kappa B/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Polymerase Chain Reaction
12.
Rev. méd. Chile ; 142(5): 593-598, mayo 2014. ilus, tab
Article in Spanish | LILACS | ID: lil-720668

ABSTRACT

Obesity is a risk factor for cancer. Epidemiological evidences associate ovarian cancer with obesity. Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer and accounts for a high rate of mortality. The association between ovarian cancer and obesity could be explained by molecular factors secreted by adipose tissue such as leptin. In EOC, leptin increases cell proliferation and inhibits apoptosis. Additionally, adipose tissue synthesizes endogenous estrogens, which increase cell proliferation of epithelial ovarian cells. Also, obesity associated hyperinsulinism could increase ovarian estrogen secretion.


Subject(s)
Female , Humans , Obesity/complications , Ovarian Neoplasms/etiology , Obesity/metabolism , Ovarian Neoplasms/metabolism
13.
Indian J Exp Biol ; 2008 Jan; 46(1): 22-6
Article in English | IMSEAR | ID: sea-62843

ABSTRACT

Tumor cells intensely utilize glutamine as the major source of respiratory fuel. Glutamine-analogue acivicin inhibits tumor growth and tumor-induced angiogenesis in Ehrlich ascites carcinoma. In the present study, antitumor properties of acivicin in combination with glutaminase enzyme is reported. Acivicin along with E. coli glutaminase synergistically reduced in vitro proliferation and matrigel invasion of human MCF-7 and OAW-42 cells. Effects of single and combined treatments with acivicin and glutaminase on angiogenic factors were also analyzed in these cell lines. Co-administration of the treatment agents inhibits the release of VEGF and MMP-9 by cells in culture supernatant significantly than single agent treatments. The result suggests that combination of acivicin with glutaminase may provide a better therapeutic option than either of them given separately for treating human breast and ovarian cancer. However, further studies are required to be conducted in vivo for its confirmation.


Subject(s)
Antimetabolites, Antineoplastic/chemistry , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation , Collagen/chemistry , Drug Combinations , Female , Glutaminase/metabolism , Glutamine/chemistry , Humans , Isoxazoles/chemistry , Laminin/chemistry , Matrix Metalloproteinase 9/metabolism , Neoplasm Invasiveness , Ovarian Neoplasms/metabolism , Proteoglycans/chemistry , Tetrazolium Salts/pharmacology , Thiazoles/pharmacology , Vascular Endothelial Growth Factor A/metabolism
14.
Article in English | WPRIM | ID: wpr-59827

ABSTRACT

Lysophosphatidic acid (LPA) is a bioactive phospholipids and involves in various cellular events, including tumor cell migration. In the present study, we investigated LPA receptor and its transactivation to EGFR for cyclooxygenase-2 (COX-2) expression and cell migration in CAOV-3 ovarian cancer cells. LPA induced COX-2 expression in a dose-dependent manner, and pretreatment of the cells with pharmacological inhibitors of Gi (pertussis toxin), Src (PP2), EGF receptor (EGFR) (AG1478), ERK (PD98059) significantly inhibited LPA- induced COX-2 expression. Consistent to these results, transfection of the cells with selective Src siRNA attenuated COX-2 expression by LPA. LPA stimulated CAOV-3 cell migration that was abrogated by pharmacological inhibitors and antibody of EP2. Higher expression of LPA2 mRNA was observed in CAOV-3 cells, and transfection of the cells with a selective LPA2 siRNA significantly inhibited LPA-induced activation of EGFR and ERK, as well as COX-2 expression. Importantly, LPA2 siRNA also blocked LPA-induced ovarian cancer cell migration. Collectively, our results clearly show the significance of LPA2 and Gi/Src pathway for LPA-induced COX-2 expression and cell migration that could be a promising drug target for ovarian cancer cell metastasis.


Subject(s)
Butadienes/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cyclooxygenase 2/biosynthesis , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Female , Flavonoids/pharmacology , GTP-Binding Protein alpha Subunits, Gi-Go/antagonists & inhibitors , Humans , Lysophospholipids/pharmacology , Nitriles/pharmacology , Ovarian Neoplasms/metabolism , Pertussis Toxin/pharmacology , Protein-Tyrosine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Pyrimidines/pharmacology , ErbB Receptors/antagonists & inhibitors , Receptors, Lysophosphatidic Acid/metabolism , Receptors, Prostaglandin E/metabolism , Signal Transduction , Transcriptional Activation , Tyrphostins/pharmacology
15.
Indian J Pathol Microbiol ; 2007 Jul; 50(3): 489-92
Article in English | IMSEAR | ID: sea-75403

ABSTRACT

To evaluate the expression of HER-2/neu in various ovarian lesions, 75 cases of ovarian tissues (25 cases of benign lesions and 50 cases of carcinoma) were studied in the department of pathology, Pt. B.D. Sharma PGIMS, Rohtak. Besides conventional H&E staining, representative sections were processed for immunohistochemical staining for HER-2/neu detection. Two (8%) of benign cases were 1+ positive and 19 (38.0%) of malignant lesions were positive for HER-2/neu staining with intensity 1+/2+ in 16 cases (32.0%), 3+ in 2 cases (4%) and 4+ in 1 case (2%). It was observed that HER-2/neu expression was significantly associated with high grade ovarian tumours, however intensity of positivity did not correlate with the grade of tumour.


Subject(s)
Adenocarcinoma/metabolism , Carcinoma/metabolism , Female , Humans , Immunohistochemistry , Ovarian Neoplasms/metabolism , Ovary/metabolism , Receptor, ErbB-2/genetics , Biomarkers, Tumor/metabolism
16.
Rev. Hosp. Clin. Univ. Chile ; 17(3): 207-216, 2006.
Article in Spanish | LILACS | ID: lil-531917

ABSTRACT

En el ovario normal, la angiogénesis es un proceso finalmente regulado y es fundamental para la función ovárica (esteroidogénesis y ovulación). En el cáncer ovárico epitelial, la angiogénesis se encuentra aumentada y uno de los elementos angiogénicos más importantes en ambos casos es el factor de crecimiento del endotelio vascular (VEGF). Por otra parte, el factor de crecimiento nervioso (NGF), también ha sido considerado un factor angiogénico tanto directo como indirecto a través del aumento de VEGF en tejidos no-neuronales, diferentes del ovario. Antecedentes demuestran la expresión de NGF en ovario de mamíferos, incluyendo el ovario humano. Nuestro objetivo fue examinar la relación entre NGF y VEGF en ovario normal y cáncer ovárico epitelial. Nuestros resultados demuestran que en ovario normal, NGF y su receptor específico (trkA), se expresan en células de la granulosa de folículos pre-antrales y antrales, similar a lo descrito para VEGF. Además, NGF aumenta la expresión de VEGF en células de granulosa humana en cultivo. En cáncer ovárico epitelial, NGF y trkA se sobre-expresan en células epiteliales y NGF al activar a su receptor trkA, aumenta la expresión de VEGF en cultivo de explantes de este tejido. Estos resultados demuestran que NGF y trkA podrían estar involucrados a través de la regulación de la expresión VEGF, en la angiogénesis del ovario normal como en cáncer ovárico epitelial.


In the normal ovary, the angiogenesis is a fundamental and cyclical process that happens in each ovulation. In the epithelial ovarian cancer, the angiogenesis is increased and as it is known, it is essential for the growth of solid tumors. The endothelial growth factor (VEGF) is one of the most important factors in this process. The nerve growth factor (NGF), has been considered as a direct and indirect angiogenic factor through the increase of VEGF expression in non-neuronal tissues, different from the ovary Previous reports have demonstrated NGF expression in mammals ovary, including the human ovary. Our aim was to examine the relation between NGF and VEGF in normal ovary and epithelial ovarian cancer. Our finding demonstrated that in normal ovary, NGF and its specific receptor (trkA) are expressed in granulosa cells from pre-antrals and antrals follicles, similar to those reported for VEGF. In addition, NGF increases the VEGF expression in human granulosa cells in culture. NGF and trkA are over-expressed in epithelial cells and NGF activates its trkA receptor, increasing VEGF expression in cultured explants of epithelial ovarian cancer. These results show that NGF and trkA could be involved in angiogenesis process in normal ovary and epihelial ovarian cancer.


Subject(s)
Humans , Female , Vascular Endothelial Growth Factor A/analysis , Nerve Growth Factor/analysis , Ovarian Neoplasms/metabolism , Ovary/metabolism
17.
Article in English | WPRIM | ID: wpr-640989

ABSTRACT

Full-length coxsackie adenovirus receptor (CAR) eukaryotic expression plasmid was transfected into an ovarian cell line, SKOV3, and its effect on the change of malignant metastasis phenotype was explored. CAR mRNA and protein expression levels among 4 ovarian cancer cell lines (A2780, SKOV3, SW626, CAOV3) and the positive control 293 (a transformed human embryo kidney cell line) was detected by using semi-quantitative RT-RCR and Western blot and compared. CAR-negative SKOV3 was transfected with the eukaryotic expression plasmid containing a full-length CAR cDNA and mock-vector respectively. The positive clones were screened by G418. The biological behavior changes of positive transfected cells were gauged by colony formation in soft agar assay and cell adhesion assay. Among the cell lines, there were obviously different CAR expression levels. CAR could not be detected in SKOV3. In transfected cell group, CAR expression was enhanced obviously as compared with non-transfected or mock-transfected groups. Cell adhesion in the transfected group was promoted. The number of colony formation was reduced significantly in transfected groups (25.32 +/- 8.91) as compared with that in non-transfected group (88.75 +/- 13. 98) and mock-transfected group (82.53 +/- 19.37). Among the 4 ovarian cancer cell lines, CAR expression level was variable. Exogenous CAR expression had a potential role in inhibiting the malignant metastasis phenotype of ovary cancer cells.


Subject(s)
Cell Line, Tumor , Lymphatic Metastasis , Neoplasm Invasiveness , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Phenotype , Receptors, Virus/biosynthesis , Receptors, Virus/genetics , Transfection
18.
Article in English | WPRIM | ID: wpr-147612

ABSTRACT

Distinguishing primary ovarian carcinoma from metastatic carcinoma to the ovary is often difficult by histologic examination alone. Recently an immunohistochemical marker CDX-2 was found to be of considerable diagnostic value in establishing the gastrointestinal origin of metastatic tumors. The aim of this study was to determine whether CDX-2 can distinguish between these malignancies. Paraffin-embedded tissue sections from 57 primary ovarian tumors and 40 metastatic tumors to the ovary were immunostained for CDX-2, and results were compared to the ancillary immunohistochemical results for CK7/CK20, CEA, CA125, and her-2/neu. CDX-2 immunoreactivity was observed in most of metastatic carcinomas with colorectal (91%) and appendiceal (100%) origin, however CDX-2 was negative in all primary ovarian carcinomas, except for the mucinous subtype. Almost all primary ovarian carcinomas including the mucinous subtype showed diffuse and strong immunoexpression for CK7. CEA and CA125 were mainly found in metastatic and primary ovarian carcinoma, respectively. Her-2/neu overexpression was only noted in a small proportion of primary and metastatic ovarian carcinomas. These results suggest that CDX-2 is very useful immunohistochemical marker for distinguishing metastatic colorectal carcinoma to the ovary from primary ovarian carcinoma, including the mucinous subtype. Furthermore, combination with CDX-2 and CK7 strengthen the differential diagnosis between these tumors.


Subject(s)
CA-125 Antigen/analysis , Carcinoembryonic Antigen/analysis , Colorectal Neoplasms/metabolism , Diagnosis, Differential , Female , Homeodomain Proteins/analysis , Humans , Immunohistochemistry , Keratins/analysis , Neoplasm Metastasis , Ovarian Neoplasms/metabolism , Receptor, ErbB-2/analysis , Tissue Array Analysis/methods , Trans-Activators/analysis
19.
Indian J Pathol Microbiol ; 2004 Oct; 47(4): 525-8
Article in English | IMSEAR | ID: sea-74973

ABSTRACT

The authors describe two cases of primary fibrosarcoma of the ovary in 48 years and 66 years old women. Patients presented with abdominal masses associated with pain in the first case. USG and CT scan of the abdomen revealed ovarian tumours involving the left side in both cases . Both underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Histological examination showed features of fibrosarcoma grade I and grade III respectively. A clinicopathological study and brief review of literature is presented.


Subject(s)
Aged , Diagnosis, Differential , Female , Fibroma/diagnosis , Fibrosarcoma/metabolism , Humans , Immunohistochemistry , Middle Aged , Ovarian Neoplasms/metabolism
20.
Article in English | WPRIM | ID: wpr-640942

ABSTRACT

The change in serum laminin (LN) level and its clinical significance in epithelial ovarian tumor were investigated. The LN levels in serum and ascites samples from 69 patients with epithelial ovarian tumor and 42 cases as control group before and after operation were analyzed by radioimmunoassay. The results showed that the serum LN levels in the patients with malignant tumors (157.85 +/- 14.37 ng/ml) were significantly higher than that in the control group (125.14 +/- 7.03 ng/ml) and in the patients with benign tumors (128.36 +/- 8.75 ng/ml) (both P < 0.01) before operation. The serum LN levels in the malignant group were decreased significantly after operation as compared with those before operation (P < 0.05). The serum LN levels in low-differentiated tumors was higher than those in moderate-differentiated tumors and high-differentiated tumors (P < 0.05). The LN levels in ascites (172.94 +/- 15.26 ng/ml) was significantly higher than in serum (161.34 +/- 6.59 ng/ml) (P < 0.05) in malignant tumors. The serum LN levels in the patients with lymph node metastasis (165.41 +/- 19.91 ng/ml) was obviously higher than those without lymph node metastasis (152.35 +/- 10.34 ng/ml) (P < 0.05). It was concluded that LN levels in serum and acistis were remarkably increased in malignant epithelial ovarian tumors, suggesting that LN might be one of important diameters reflecting tumor biological characteristics.


Subject(s)
Ascitic Fluid/metabolism , Carcinoma/blood , Carcinoma/metabolism , Laminin/blood , Laminin/metabolism , Ovarian Neoplasms/metabolism , Biomarkers, Tumor/blood , Biomarkers, Tumor/metabolism
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