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1.
J Cell Mol Med ; 24(2): 1300-1310, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31863623

RESUMO

The PI3K/AKT pathway is frequently activated in endometrial carcinoma. BMI-1 (B-lymphoma Mo-MLV insertion region 1) protein affects expression of PTEN (phosphatase and tensin homolog) in some cancers, but its significance for endometrial tumorigenesis is not known. The objective of this study was to determine the relationship between BMI-1 and expression of factors affecting AKT (protein kinase B) phosphorylation level in endometrial cancer. The expression of proteins and mRNAs was investigated in endometrial cancer specimens and samples of non-neoplastic endometrial tissue by Western blot and RT-PCR, respectively. The impact of BMI-1 down-regulation on AKT phosphorylation and expression of genes coding for several phosphatases were studied in HEC1A cells. The results showed that BMI-1 depletion caused increase in PHLPP1 and PHLPP2 (PH domain and leucine-rich repeat protein phosphatases 1/2) expression and decrease in phospho-AKT (pAKT) level. In more advanced tumours with higher metastatic potential, the expression of BMI-1 was lower compared to tumours less advanced and without lymph node metastasis. There were significant inverse correlations between BMI-1 and PHLPPs, especially PHLPP1 in normal endometrial samples. The inverse correlation between BMI-1 and PHLPP1/PHLPP2 expression was observed in PTEN positive but not PTEN negative cancers. Low PHLPP2 expression in tumours predicted poorer overall survival. BMI-1 impacts on AKT phosphorylation level in endometrial cells by regulation of PHLPP expression.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Endométrio/patologia , Proteínas Nucleares/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Proliferação de Células , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Nucleares/genética , PTEN Fosfo-Hidrolase/genética , Fosfoproteínas Fosfatases/genética , Fosforilação , Complexo Repressor Polycomb 1/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Taxa de Sobrevida , Células Tumorais Cultivadas
2.
Tumour Biol ; 42(8): 1010428320951057, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32829673

RESUMO

The exchange of metabolites between mitochondria and cytosol occurs through pores formed by voltage-dependent anion channel proteins. Voltage-dependent anion channels appear to be master regulators of mitochondrial bioenergetics and the intracellular flow of energy. Deregulation of voltage-dependent anion channels expression is thought to be related to mitochondrial dysfunction in cancer. The aim of this study was to investigate the mRNA and protein expression levels of VDAC1, VDAC2, and VDAC3 in relation to clinicopathological characteristics of endometrial cancer as well as the prognostic significance of voltage-dependent anion channels expression for overall survival. VDAC1 and VDAC3 expressions were significantly higher in cancer compared to normal tissues. Kaplan-Meier analysis indicated that high expression of all VDAC genes or high VDAC2 protein level predicted poor overall survival. Multivariate analysis identified the VDAC1 and VDAC2 mRNA levels as well as VDAC2 protein level as independent prognostic factors. Our results suggest that increased expression of voltage-dependent anion channels correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer.


Assuntos
Neoplasias do Endométrio/patologia , Mitocôndrias/patologia , Proteínas de Transporte da Membrana Mitocondrial/genética , Canal de Ânion 1 Dependente de Voltagem/genética , Canal de Ânion 2 Dependente de Voltagem/genética , Canais de Ânion Dependentes de Voltagem/genética , Sequência de Aminoácidos , Biomarcadores Tumorais/genética , Citoplasma/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/biossíntese , Prognóstico , RNA Mensageiro/genética , Canal de Ânion 1 Dependente de Voltagem/biossíntese , Canal de Ânion 2 Dependente de Voltagem/biossíntese , Canais de Ânion Dependentes de Voltagem/biossíntese
3.
Ginekol Pol ; 89(10): 563-567, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30393845

RESUMO

OBJECTIVES: Endometrial cancer is the most common cancer of the female genital organs in developed countries, accounting for approximately 50% of all gynecological cancers. The Klotho gene was discovered in 1997 as an anti-aging gene that, when overexpressed, may extend the lifespan, but when disrupted, may be a factor responsible for premature aging syndrome. The aim of the study is to assess the relationship between the clinical and pathological features of endometrial cancer and ßKlotho gene expression. MATERIAL AND METHODS: The expression of ßKlotho gene was studied in 138 cases of endometrioid endometrial carcinoma specimens using Real Time PCR reaction in RNA isolated tissue samples by commercial tests. The expression profile was correlated with the clinicopathological characteristics of endometrial carcinoma. The chi-square independence test and Fisher's test for four-field tables were used to assess the statistical significance of the observed relationships. RESULTS: Significant relationships were found between ßKlotho gene expression and FIGO clinical stage, the degree of histological differentiation and the presence of metastases in the lymph nodes. Higher levels of gene expression correlate with lower degrees of clinical staging according to FIGO, the presence of highly-differentiated endometrial cancer (G1) and the absence of lymph node metastases. CONCLUSIONS: The ßKlotho gene expression might be involved in endometrioid endometrial cancer tumorgenesis. The ßKlotho may in future be used as an useful indicator for endometrial cancer, although further studies are needed.


Assuntos
Carcinoma Endometrioide/genética , Neoplasias do Endométrio/genética , Proteínas de Membrana/genética , Reação em Cadeia da Polimerase em Tempo Real , Adulto , Feminino , Expressão Gênica , Humanos , Proteínas Klotho , Pessoa de Meia-Idade , Estadiamento de Neoplasias
4.
Tumour Biol ; 39(3): 1010428317695017, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28349832

RESUMO

Ten-eleven translocation proteins are α-ketoglutarate-dependent dioxygenases involved in the conversion of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine, and 5-carboxylcytosine that play a significant role in DNA demethylation. Deregulation of TET genes expression and changes in the level of 5-hmC are thought to be associated with the onset and progression of several types of cancer, but there are no such data related to endometrial cancer. The aim of the work was to investigate the messenger RNA expression levels of TET1, TET2, and TET3 in relation to clinicopathological characteristics of endometrial cancer as well as the correlation between expression of TET genes and the level of 5-hmC/5-mC. The prognostic significance of TETs expression for overall survival was established. We found that TET1 and TET2 messenger RNA expression was lower and TET3 was higher in cancers compared to normal tissues. Positive correlation between 5-hmC and the relative expression of TET1 and TET2 was found, but no correlation was observed in the case of TET3. Decreased expression of TET1 and TET2 was significantly associated with increased lymph node metastasis and International Federation of Gynecology and Obstetrics stage. Kaplan-Meier analysis indicated that low TET1 expression predicted poor overall survival (p = 0.038). Multivariate analysis identified the TET1 expression in endometrial cancer as an independent prognostic factor. Our results suggest that decreased expression of TET1 correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer.


Assuntos
Metilação de DNA/genética , Proteínas de Ligação a DNA/biossíntese , Dioxigenases/biossíntese , Neoplasias do Endométrio/genética , Oxigenases de Função Mista/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Idoso , Citosina/análogos & derivados , Citosina/metabolismo , Proteínas de Ligação a DNA/genética , Dioxigenases/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Oxigenases de Função Mista/genética , Prognóstico , Proteínas Proto-Oncogênicas/genética
5.
Ginekol Pol ; 86(5): 340-5, 2015 May.
Artigo em Polonês | MEDLINE | ID: mdl-26117970

RESUMO

OBJECTIVE: Retrospective clinical and pathomorphological analysis of patients undergoing surgery due to endometrial carcinoma; analysis of the correlation between histological grading of endometrial cancer and selected pathomorphological results. MATERIAL AND METHODS: Statistical analysis was based on the pathomorphological results in a group of 353 patients operated because of endometrial carcinoma at the Clinical Department of Gynecologic Oncology Medical University of Lodz, between 2003 and 2013. A possible correlation between histological grading, clinical staging, myometrial infiltration, parametrial invasion and nodal metastases to ilio-obturator lymph nodes was investigated. RESULTS: Among poorly differentiated carcinomas G3, myometrial infiltration above half of its thickness was observed in 67.44% of the cases, whereas in the G2 and G1 groups it was detected in 60.82% and 39.33% of the affected individuals, respectively. Parametrial invasion was found in 24.39% of G3 cases, i.e. 4.23 times more often than in G2 (5.76%) and 10.65 times more often than in G1 (2.29%). Nodal metastases to ilio-obturator lymph nodes were present in 27.50% of poorly 10.86% of moderately and 8.11% of well-differentiated carcinomas. Uterine appendages were infiltrated in 23.25% of G3 cases--3.45 times more than in G2 (6.73%) and 6.82 times more than in G1 (3.4 1%). CONCLUSIONS: Histologic grading for carcinoma at the time of diagnosis is significantly related to clinical staging. No correlation between patient age and carcinoma grading or its clinical staging was observed. Risk of lymph node invasion for well-differentiated carcinomas is similar to the risk for moderately differentiated carcinomas, and should also be an indication for lymphadenectomy in that group of patients.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Polônia , Período Pós-Operatório , Estudos Retrospectivos
6.
Ginekol Pol ; 85(7): 521-6, 2014 Jul.
Artigo em Polonês | MEDLINE | ID: mdl-25118504

RESUMO

OBJECTIVES: The aim of the study was to evaluate the cytotoxic effect of metformin on the ovarian cancer cells SKOV-3 and analyze the impact of this compound on the expression of genes coding for O-GlcNAc cycling enzymes, i.e. O-GlcNAc transferase (OGT) and -N-acetylglucosaminidase (OGA). MATERIALS AND METHODS: Viability and proliferation of control cells and cells treated with metformin were evaluated by MTT test and trypan blue staining. OGT and OGA mRNA expressions analysis was performed using real-time PCR method. RESULTS: A metformin concentration-dependent decrease of SKOV-3 cell viability was observed. The IC50 parameter for metformin cytotoxicity was 14 mM. The SKOV-3 cell doubling time was 45 hours. The cell population treated with 10 mM metformin did not double even after 72 hours. There was no significant difference in mRNA level of OGA between control cells and cells treated with metformin. The OGT mRNA level was significantly higher in cells treated with metforrhin for 24 hours as compared to the control cells. The increase of OGT mRNA was dependent on time of incubation. Cells treated with metformin for 48 hour showed higher expression of OGT than cells treated for 24 hours. CONCLUSION: Antiproliferative activity of metformin suggests that this compound may be considered as a candidate for potential chemotherapeutic agent. However taking into account its impact on the expression of O-GlcNAc transferase, further studies on the molecular mechanism of metformin action are necessary


Assuntos
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Metformina/farmacologia , N-Acetilglucosaminiltransferases/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , beta-N-Acetil-Hexosaminidases/genética , beta-N-Acetil-Hexosaminidases/metabolismo , Adulto , Antineoplásicos/farmacologia , Linhagem Celular/efeitos dos fármacos , Citotoxinas/farmacologia , Feminino , Humanos , Concentração Inibidora 50 , N-Acetilglucosaminiltransferases/genética , Neoplasias Ovarianas/patologia
7.
Cytokine ; 61(2): 639-44, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23273598

RESUMO

PURPOSE: Angiogenesis, a multistep process that results in new blood vessel formation from preexisting vasculature is essential for both the growth of solid tumour and for metastasis. Stimulation of vascular endothelial growth factor receptor (VEGFR), a transmembrane glycoprotein, results in mitogenesis. Within this family of receptors, VEGFR 2/kinase-insert-domain containing receptor appears to be principally upregulated during tumorigenesis. The aim of this study was to determine the expression of VEGFR-2/kinase-insert-domain containing receptor (KDR) and its correlation with angiotensin receptor type 1 (AT1-R) and clinical factors in endometrial carcinoma. METHODS: The expression of KDR and AT1-R was studied in endometrial carcinoma and normal endometrium by Real-time RT-PCR and Western blot analysis in 136 samples. The expression profile was correlated with the clinicopathological characteristics of endometrial adenocarcinoma. RESULTS: We noted a significant correlation between the expression of KDR and AT1-R in tumour grade G1, G2 and G3 (R(s)=0.50; p=0.002, R(s)=0.69; p=0.0001, R(s)=0.52; p=0.005, respectively). In stage I and stage II carcinoma, a significant correlation was also found between the expression of KDR and AT1-R (R(s)=0.70, p=0.0001, R(s)=0.67; p=0.001, respectively). Moreover significant correlation was observed between both KDR and AT1-R in tissue with different myometrial invasion (R(s)=0.54, p=0.0001, R(s)=0.68; p=0.0001; respectively for tumours with invasion into the inner half and invasion into the outer half). CONCLUSIONS: Basing on received correlation between AT1-R and KDR expression and previous results we speculate that angiotensin through AT1-R modulates KDR expression and thus have influence on local VEGF level. However, further studies are required to clarify the biological interaction between KDR, AT1-R and other hormonal regulators in endometrial carcinoma.


Assuntos
Neoplasias do Endométrio/genética , Regulação Neoplásica da Expressão Gênica , Receptor Tipo 1 de Angiotensina/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
8.
Ginekol Pol ; 84(5): 373-6, 2013 May.
Artigo em Polonês | MEDLINE | ID: mdl-23819404

RESUMO

Breast cancer is the most common malignancy in women. Its estimated annual incidence is about one million cases worldwide. A number of risk factor have been identified, among them early menarche, late menopause, nulliparity and positive family history Moreover a number of highly penetrant breast and ovarian cancer susceptibility genes, such as BRCA 1 and BRCA2, have been identified. Recent findings suggest TopBP1 to be a breast and ovarian cancer susceptibility gene. Moreover; TopBPI protein may be an important prognostic marker of breast cancer TopBP1 protein is involved in DNA replication, mitosis and meiosis, as well as DNA repair Deregulation of these processes may have pathological implications in cancer


Assuntos
Neoplasias da Mama/genética , Proteínas de Transporte/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Feminino , Humanos , Mutação/genética , Fatores de Risco , Saúde da Mulher
9.
Ginekol Pol ; 84(11): 910-4, 2013 Nov.
Artigo em Polonês | MEDLINE | ID: mdl-24455846

RESUMO

OBJECTIVES: The metastatic ability of tumors is characteristic for malignant neoplasms and constitutes the main cause of therapeutics failures. Metastasis formation involves the sequence of processes such as proteolytic degradation of the basement membrane, migration, intravasation, extravasation, proliferation and angiogenesis. Cadherins and integrins are groups of proteins directly involved in these processes. In the present study we analyzed the mRNA expression of CDH1 and ITGB1 genes by real-time polymerase chain reaction (RT-PCR). The study included 106 endometrial carcinomas. CDH1 and ITGB1 mRNA expression was found in all of the studied samples. Generally the CDH1 and ITGB1 mRNA expression was significantly higher in well-differentiated rather than poorly differentiated tumors. MATERIALS AND METHODS: The mRNA expression levels of CDH1 and ITGB1 in series of 83 samples of endometrial carcinoma were studied by real time RT-PCR method. Statistical analysis of the obtained results was performed. RESULTS: CDH1 and ITGB1 gene expression was observed in all examined tissues and was correlated with cancer malignancy (G). In high grade malignant tumors (G1), CDH1 and ITGB1 gene expression was the highest, in G2 and G3 tumors the expression of both genes was gradually lowering. Moreover the statistically significant correlation between CDH1 and ITGB1 gene expression was observed. (Spearman test, r=0.29, p

Assuntos
Caderinas/genética , Neoplasias do Endométrio/genética , Regulação Neoplásica da Expressão Gênica , Integrina beta1/genética , RNA Mensageiro/genética , Neoplasias do Colo do Útero/genética , Antígenos CD , Neoplasias do Endométrio/patologia , Feminino , Humanos , Reação em Cadeia da Polimerase , Neoplasias do Colo do Útero/patologia
10.
Tumour Biol ; 33(3): 767-74, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22170435

RESUMO

In Poland, endometrial carcinoma takes second place after breast cancer among all cancers in women and is considered the most common genital cancer. It has been repeatedly reported that angiotensin is involved in the development and invasion of some cancers including breast, ovarian, and pancreatic ones. It is suggested that angiotensin two and its receptors are actively involved in tumour biology in endometrial adenocarcinoma. In the present study, we identify a possible relationship between the expression of AT1-R, AT2-R, ERα, and VEGF and clinicopathological characteristics of primary endometrial adenocarcinoma. We determined the above components both at the mRNA (real-time RT-PCR) and protein levels (Western Blot assay). Our results indicate that in patients with grade G3 adenocarcinoma, the expression of AT1-R significantly decreased in comparison with G1 patients (p = 0.034), but the level of ERα was the highest in G2 and the lowest in G3. Moreover, the level of VEGF mRNA significantly increased between G2 and G3 (p = 0.034). We also noted a significant correlation between the expression of AT1-R and AT2-R in FIGO stage 1 (R (s) = 0.9636; p = 0.0001) and that of AT2-R and VEGF (R (s) = 0.5377; p = 0.005). In grade G1 and G2 carcinoma, a significant correlation was also found between the expression of AT1-R and AT2-R (R (s) = 0.9924; p = 0.0001; R (s) = 0.8717, p = 0.0005, respectively), but in grade G1, a negative correlation was observed between AT1-R and VEGF (R (s) = -0.8945, p = 0.0005). Further studies are required to clarify the biological function of the angiotensin receptor in regulating VEGF expression in endometrial carcinoma.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Receptor Tipo 1 de Angiotensina/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Ginekol Pol ; 83(5): 363-7, 2012 May.
Artigo em Polonês | MEDLINE | ID: mdl-22708334

RESUMO

Breast and ovarian cancer are among the most common malignancies of women in the world. About 5 - 10% of the cases are considered familial. Germline mutations in the BRCA1 and BRCA2 genes are strong predictors of breast and/or ovarian cancer development. However currently known susceptibility genes including BRCA1, BRCA2, ATM, Chk2, PALB2, and BRIP1 explain less than 25% of familial breast and/ovarian cancers. Other genes, such as TopBP1 are also likely to be involved in hereditary predisposition to breast and/or ovarian cancer TopBP1 protein displays structural and functional similarities with BRCA1, and these two proteins have been suggested to function partially in the same cellular processes. TopBP1 protein is involved in DNA repair and cell cycle checkpoint control. Moreover TopBP1 interacts with transcription factors, such as E2F1, p53, Miz-1, HPV16 E2, and regulates their activity.


Assuntos
Neoplasias da Mama/genética , Proteínas de Transporte/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Análise Mutacional de DNA , Feminino , Humanos , Mutação/genética , Fatores de Risco
12.
Ginekol Pol ; 83(1): 22-6, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22384635

RESUMO

OBJECTIVES: O-GlcNAcylation is an abundant modification of cellular proteins which consist of single N-acetylglucosamine residues attached by O-linkage to serine or threonine residues. Abnormal O-GlcNAcylation seems to be a feature of malignant cancer cells. The aim of the present study was to determine the relationship between the expression of genes encoding O-GlcNAc cycling enzymes (OGT and MGEAS) and clinicopathological parameters of endometrial carcinomas. MATERIALS AND METHODS: The mRNA expression levels of O-GlcNAc cycling enzymes in series of 76 samples of endometrial carcinoma were studied by real time RT-PCR method. RESULTS: The OGT and MGEA5 mRNA expression was significantly higher in tumors of higher histological grade than in well-differentiated tumors. Statistically significant association was found between OGT and MGEA5 mRNA expression and depth of myometrial invasion. Both OGT and MGEA5 expression profiles showed no significant association with the clinical stage of endometrial cancer. CONCLUSION: O-GlcNAcylation may be an important regulatory modification involved in endometrial cancer pathogenesis but the actual significance of this modification for endometrial cancer progression needs to be investigated further.


Assuntos
Neoplasias do Endométrio/enzimologia , Neoplasias do Endométrio/genética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , beta-N-Acetil-Hexosaminidases/genética , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Gradação de Tumores
13.
J Clin Med ; 9(10)2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32987826

RESUMO

We investigated single nucleotide polymorphism (SNP) of the betaglycan gene (TGFBR3) encoding the TGFß co-receptor in endometrial cancer (EC) and its association with betaglycan expression. The study group included 153 women diagnosed with EC and 248 cancer-free controls. SNP genotyping and gene expression were analyzed using TaqMan probes. Three out of the eight SNPs tested, i.e., rs12566180 (CT; OR = 2.22; 95% CI = 1.15-4.30; p = 0.0177), rs6680463 (GC; OR = 2.34; 95% CI = 1.20-4.53; p = 0.0120) and rs2296621 (TT; OR = 6.40; 95% CI = 1.18-34.84; p = 0.0317) were found to be significantly associated with increased risk of EC (adjusted to age, body mass index, menarche and parity). Among the analyzed SNPs, only rs2296621 demonstrated the impact on the increased cancer aggressiveness evaluated by the WHO grading system (G3 vs. G1/2, GT-OR = 4.04; 95% CI = 1.56-10.51; p = 0.0026; T-OR = 2.38; 95% CI = 1.16-4.85; p = 0.0151). Linkage disequilibrium (LD) analysis revealed high LD (r2 ≥ 0.8) in two haploblocks, constructed by rs2770186/rs12141128 and rs12566180/rs6680463, respectively. In the case of C/C haplotype (OR = 4.82; 95% CI = 1.54-15.07; p = 0.0116-Bonferroni corrected) and T/G haplotype (OR = 3.25; 95% CI = 1.29-8.15; p = 0.0328-Bonferroni corrected) in haploblock rs12566180/rs6680463, significantly higher frequency was observed in patients with EC as compared to the control group. The genotype-phenotype studies showed that SNPs of the TGFBR3 gene associated with an increased risk of EC, i.e., rs12566180 and rs2296621 may affect betaglycan expression at the transcriptomic level (rs12566180-CC vs. TT, p < 0.01; rs2296621-GG vs. TT, p < 0.001, GT vs. TT, p < 0.05). Functional consequences of evaluated TGFBR3 gene SNPs were supported by RegulomeDB search. In conclusion, polymorphism of the TGFBR3 gene may be associated with an increased EC occurrence, as well as may be the molecular mechanism responsible for observed betaglycan down-regulation in EC patients.

14.
Ginekol Pol ; 91(8): 439-446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32902840

RESUMO

INTRODUCTION: Malignant neoplasm of the endometrium is the most common malignant neoplasm of the female reproductive system. Toll Like Receptors (TLR) play a significant role in innate and late-immunity against infections or damaged tissues. TLRs are also involved in the development of tumors in their natural microenvironment. TLRs play an important role in angiogenesis, necessary for survival and growth of the tumor. Hypoxia playing a critical role in angiogenesis, carcinogenesis, tumor progression and distant metastasis is primarily mediated through hypoxia inducible factors (HIFs). Vascular endothelial growth factor family proteins (VEGF) are also strongly involved in tumor angiogenesis and their action is strongly associated with TLR receptors. OBJECTIVES: The aim of the study was to correlate the expression of selected TLRs and VEGFR's as well as HIF1α with clinicopathological data of endometrial cancer patients. MATERIAL AND METHODS: 123 neoplastic endometrial samples were included in the study. 51 samples of healthy endometrium served as control. The expression of TLR1, TLR2, TLR3, TLR4, VEGFR1 and VEGFR2, VEGF-A and HIF1α was examined after RNA isolation at the mRNA level by Real Time-PCR. RESULTS: We have noted a significant correlation between the expression of selected TLR and VEGFR's and clinical stage as well as pathological grading of endometrial cancer. CONCLUSIONS: Received correlations confirm a significant contribution of some TLR expression and the receptor for VEGF in the pathogenesis of epithelial endometrial cancer.


Assuntos
Neoplasias do Endométrio/metabolismo , Endométrio/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Transdução de Sinais/fisiologia
15.
Ginekol Pol ; 79(4): 259-63, 2008 Apr.
Artigo em Polonês | MEDLINE | ID: mdl-18592863

RESUMO

OBJECTIVE: The risk of metastatic ovarian tumor is significantly higher in case of women with a history of colorectal cancer. Additionally, the possibility of developing ovarian cancer due to congenital mutations in suppressor genes should be assessed. DESIGN: The purpose of the study was to evaluate the clinical presentation and histopathology of adnexal tumors in case of female patients with a history of colorectal adenocarcinoma. MATERIAL AND METHODS: A retrospective study on 13 women (each with a history of colorectal carcinoma, operated due to adnexal tumor between 2004 and 2007), has been conducted. Subject characteristics, ultrasound, CT, serum tumor markers levels, histopathology and findings at surgery were analyzed. RESULTS: Time distance between colorectal cancer surgery and ovarian tumor operation - measured in months -was shorter in cases of malignant neoplasms (10.13 +/- 3.98) than in benign tumors (26.2 +/- 19.37). Ultrasound examination showed solid-cystic adnexal tumors in 8 malignant cases, and ovarian cysts in 5 benign conditions. The use of ultrasound with plasma levels of CEA, CA 19.9 and CA 125 improved the validity of the preoperative differentiation of ovarian masses. Total abdominal hysterectomy with bilateral salphingo-oophorectomy was performed in eleven cases. Unilateral adnexectomy only took place in one case of benign tumor and in one case of disseminated neoplasmatic disease. CONCLUSIONS: When evaluating a patient with an adnexal tumor, a history of malignancy strongly suggests a metastatic nature. The use of ultrasound associated with plasma levels of Ca 125, Ca 19-9 and CEA, represents a useful method of preoperative assessment of ovarian tumors.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/secundário , Adulto , Antígeno Ca-125/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/terapia , Polônia , Estudos Retrospectivos , Medição de Risco , Ultrassonografia Doppler em Cores/métodos
16.
Ginekol Pol ; 79(2): 141-5, 2008 Feb.
Artigo em Polonês | MEDLINE | ID: mdl-18510095

RESUMO

UNLABELLED: Primary Burkitt lymphoma is a lymphoblastic B-cell malignant tumor with very aggressive course. Its abdominal form involving internal genital organs is very rare. CASE: We report the case of 27-year-old woman treated for abdominal Burkitt lymphoma. The patient presented bilateral ovarian tumors with ascites, pain and elevated CA 125 over 900 IU/ml. During laparotomy an advanced neoplasmatic disease involving internal genital organs has been diagnosed. Bilateral salphingo-oophorectomy and omentectomy have been performed. Additionally, the neoplasmatic tumor from ileo-coecal region has been ressected in order to prevent ileus. Pathologic examination has revealed an abdominal Burkitt lymphoma. After surgery, polychemotherapy has been administered (COP followed by CODOX-M+IVAC). The patient, 36 months after surgical treatment, remains under the control of our Department. No signs of recurrence have been detected so far. CONCLUSIONS: The presence of primary abdominal Burkitt lymphoma may include clinical and laboratory findings suggesting the presence of ovarian cancer. Chemotherapy appears to be an essential therapeutic management for all forms of Burkitt lymphoma. Clinically advanced Burkitt lymphoma may be successfully managed with chemotherapy.


Assuntos
Neoplasias Abdominais/patologia , Neoplasias Abdominais/cirurgia , Linfoma de Burkitt/patologia , Linfoma de Burkitt/cirurgia , Neoplasias Abdominais/complicações , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/complicações , Antígeno Ca-125/sangue , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovariectomia/métodos , Dor Pélvica/etiologia , Resultado do Tratamento
17.
Pathophysiology ; 13(2): 81-4, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16546357

RESUMO

The influence of subcutaneous low molecular weight heparin (LMWH) compared with physiologic saline on the healing of abdominal wounds with and without prolene mesh was studied in rats. The collagen concentration was determined in the wound tissue and in prolene mesh 14, 21, 28 and 42 days after the skin incision in controls and in two groups of rats treated either with LMWH for 7 (I group) or 14 (II group) days after skin incision and prolene insertion. LMWH administration resulted in a significant increase of collagen content both in wound and in prolene mesh in total dose-dependent manner.

18.
Ginekol Pol ; 77(1): 58-62, 2006 Jan.
Artigo em Polonês | MEDLINE | ID: mdl-16736962

RESUMO

Ovarian cancer constitutes one of the most frequent malignant tumours in the female population not only in Poland. The screening of this tumour type is unsolved. The tumours are usually diagnosed in the advanced stage, thus the survival rate are usually poor. Their histopathological appearance has a wide variety, with the occurrence of numerous metastatic forms. Among the metastatic tumours, the primary tumours of the digestive tract occur the most frequently. They are known as the Krukenberg tumours. In these cases the choice of treatment is more difficult and prognosis is also worse in most cases with fatal outcome in one year. Early diagnosis and complete resection is the only possible hope. In this paper authors present three cases of Krukenberg tumour with nonspecific symptoms, difficulties during diagnostics, late beginning of treatment and poor prognosis.


Assuntos
Tumor de Krukenberg/diagnóstico , Tumor de Krukenberg/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Idoso , Quimioterapia Adjuvante , Diagnóstico Diferencial , Feminino , Humanos , Tumor de Krukenberg/tratamento farmacológico , Tumor de Krukenberg/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/diagnóstico , Prognóstico , Neoplasias Gástricas/diagnóstico
19.
Ginekol Pol ; 76(6): 471-5, 2005 Jun.
Artigo em Polonês | MEDLINE | ID: mdl-16149265

RESUMO

Sclerosing stromal tumor of the ovary (SST) is an extremely rare neoplasm occurring predominantly in the second and third decades of life. It is a distinct benign neoplasm that differs from fibromas, thecomas, luteinized tumors and lipoid cell tumors. It presents most often with non-specific symptoms. We describe the case of a 30-year-old woman who developed menstrual irregularities and pelvic pain. She was diagnosed and treated operatively at our Department. During surgery, a benign tumor was found in the right ovary. Light microscopic and ultrastructural study confirmed the diagnosis of sclerosing stromal tumor of the ovary.


Assuntos
Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia , Adulto , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico por imagem , Ovariectomia/métodos , Esclerose , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia
20.
Ginekol Pol ; 76(1): 49-53, 2005 Jan.
Artigo em Polonês | MEDLINE | ID: mdl-15844566

RESUMO

OBJECTIVES: Conduction anaesthesia is regarded as a very safe method for the mother and for a newborn. This kind of anaesthesia reduces the risk of gastric contents aspiration and does not cause the respiratory depression. However in every case it is essential to take into consideration the woman's opinion, for whom delivering of the child is the particularly important event. DESIGN: The aim of the study was the evaluation the presence and the intensification grade of side effects of the anaesthesia to the caesarean section and establishing, which kind of anaesthesia to this operation: general or conduction is assessed as the best method for the delivering women. RESULTS: In study group among 76 women after cesarean section were 49 (64.5%) after epidural anaesthesia, 22 women (28.9%)--after spinal anaesthesia, and 5 patients (6.6%) were operated in general anaesthesia. The most common side effects after anaesthesia for cesarean section were: weakness and backache. After POP the headache was much more often symptom. CONCLUSIONS: Most of pregnant women preferred epidural anaesthesia during delivering of the child by caesarean section.


Assuntos
Anestesia por Condução/efeitos adversos , Anestesia por Condução/métodos , Anestesia Geral/efeitos adversos , Anestesia Obstétrica , Cesárea , Mães , Adulto , Anestesia Epidural/efeitos adversos , Anestesia Epidural/métodos , Anestesia Geral/métodos , Anestesia Obstétrica/efeitos adversos , Anestesia Obstétrica/métodos , Anestésicos Locais/efeitos adversos , Cesárea/efeitos adversos , Cesárea/métodos , Tomada de Decisões , Feminino , Cefaleia/induzido quimicamente , Humanos , Recém-Nascido , Bem-Estar Materno , Mães/psicologia , Dor Pós-Operatória/induzido quimicamente , Polônia , Gravidez , Inquéritos e Questionários
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