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1.
Biomed Pharmacother ; 150: 113036, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35489285

RESUMO

BACKGROUND: Inherent or developed during treatment drug resistance is the main reason for the low effectiveness of chemotherapy in ovarian cancer. IFI16 is a cytoplasmic/nuclear protein involved in response to virus's infection and cell cycle arrest associated with the cellular senescence. METHODS: Here we performed a detailed IFI16 expression analysis in ovarian cancer cell lines sensitive (A2780) and resistant to doxorubicin (DOX) (A2780DR1 and A2780DR2) and paclitaxel (PAC) (A2780PR1). IFI16 mRNA level, protein level in the nuclear and cytoplasmic fraction (Western blot analysis), the protein expression in cancer cells and nuclei (immunofluorescence analysis) and cancer patient lesions (immunohistochemistry) were performed in this study. RESULTS: We observed upregulation of IFI16 expression in drug resistant cell lines with dominant cytoplasmic localization in DOX-resistant cell lines and nuclear one in the PAC-resistant cell line. The most abundantly overexpressed isoforms of IFI16 were IFI16A and IFI16C. Finally, an analysis of a histological type of ovarian cancer (immunohistochemistry) showed expression in serous ovarian cancer. CONCLUSIONS: Expression of IFI16 in drug-resistant cell lines suggests its role in drug resistance development in ovarian cancer. Expression in serous ovarian cancer suggests its role in the pathogenesis of this histological type.


Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Interferon gama , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fosfoproteínas/metabolismo
2.
Int J Mol Sci ; 20(16)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412536

RESUMO

One of the main obstacles to the effective treatment of ovarian cancer patients continues to be the drug resistance of cancer cells. Osteoblast-Specific Factor 2 (OSF-2, Periostin) is a secreted extracellular matrix protein (ECM) expressed in fibroblasts during bone and teeth development. Expression of OSF-2 has been also related to the progression and drug resistance of different tumors. The present study investigated the role of OSF-2 by evaluating its expression in the primary serous ovarian cancer cell line, sensitive (W1) and resistant to doxorubicin (DOX) (W1DR) and methotrexate (MTX) (W1MR). The OSF-2 transcript (real-time PCR analysis), protein expression in cell lysates and cell culture medium (western blot), and expression of the OSF-2 protein in cell lines (immunofluorescence) were investigated in this study. Increased expression of OSF-2 mRNA was observed in drug-resistant cells and followed by increased protein expression in cell culture media of drug-resistant cell lines. A subpopulation of ALDH1A1-positive cells was noted for W1DR and W1MR cell lines; however, no direct co-expression with OSF-2 was demonstrated. Both drugs induced OSF-2 expression after a short period of exposure of the drug-sensitive cell line to DOX and MTX. The obtained results indicate that OSF-2 expression might be associated with the development of DOX and MTX resistance in the primary serous W1 ovarian cancer cell line.


Assuntos
Antineoplásicos/farmacologia , Moléculas de Adesão Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/genética , Família Aldeído Desidrogenase 1/genética , Família Aldeído Desidrogenase 1/metabolismo , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Proteínas da Matriz Extracelular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Ovarianas/metabolismo , Retinal Desidrogenase/genética , Retinal Desidrogenase/metabolismo
3.
J Cancer ; 9(23): 4413-4421, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519347

RESUMO

Background: Low effectiveness of chemotherapy in ovarian cancer results from development of drug resistance during treatment. Topotecan (TOP) is a chemotherapeutic drug used in second-line chemotherapy of this cancer. Unfortunately, during treatment cancer can develop diverse cellular and tissue specific mechanisms of resistance to cytotoxic drugs. Methods: We analyzed development of TOP resistance in ovarian cancer cell lines (A2780 and W1). On the base of our previous results where a set of "new genes" with different functions that can be related to TOP-resistance was described hereby we performed detailed analysis of MYOT expression. MYOT mRNA level (real time PCR analysis), protein expression in cell lysates and cell culture medium (western blot analysis) and protein expression in cancer cells (immunofluorescence analysis) were determined in this study. Results: We observed increased expression of MYOT in TOP resistant cell lines at both mRNA and protein level. MYOT, together with extracellular matrix molecules like COL1A2 and COL15A1 were also secreted to corresponding cell culture media. Conclusion: Our results suggest that upregulation of MYOT can be related to TOP resistance in ovarian cancer cell lines.

4.
Int J Mol Sci ; 20(1)2018 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-30583585

RESUMO

A major contributor leading to treatment failure of ovarian cancer patients is the drug resistance of cancer cell. CSCs- (cancer stem cells) and ECM (extracellular matrix)-related models of drug resistance are described as independently occurring in cancer cells. Lysyl oxidase (LOX) is another extracellular protein involved in collagen cross-linking and remodeling of extracellular matrix and has been correlated with tumor progression. The expression of LOX, COL1A2, COL3A1, and ALDH1A1 was performed in sensitive (A2780, W1) and resistant to paclitaxel (PAC) (A2780PR1 and W1PR2) and topotecan (TOP) (W1TR) cell lines at the mRNA (real-time PCR analysis) and protein level (Western blot and immunofluorescence analysis). The ALDH1A1 activity was measured with the ALDEFLUOR test and flow cytometry analysis. The protein expression in ovarian cancer tissues was determined by immunohistochemistry. We observed an increased expression of LOX and collagens in PAC and TOP resistant cell lines. Subpopulations of ALDH1A1 positive and negative cells were also noted for examined cell lines. Additionally, the coexpression of LOX with ALDH1A1 and COL1A2 with ALDH1A1 was observed. The expression of LOX, collagens, and ALDH1A1 was also detected in ovarian cancer lesions. In our study LOX, ALDH1A1 and collagens were found to be coordinately expressed by cells resistant to PAC (LOX, ALDH1A1, and COL1A2) or to TOP (LOX and ALDH1A1). This represents the study where molecules related with CSCs (ALDH1A1) and ECM (LOX, collagens) models of drug resistance are described as occurring simultaneously in ovarian cancer cells treated with PAC and TOP.


Assuntos
Aldeído Desidrogenase/metabolismo , Colágeno Tipo I/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Ovarianas/metabolismo , Proteína-Lisina 6-Oxidase/metabolismo , Aldeído Desidrogenase/genética , Família Aldeído Desidrogenase 1 , Linhagem Celular Tumoral , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Matriz Extracelular/metabolismo , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Cultura Primária de Células , Proteína-Lisina 6-Oxidase/genética , Retinal Desidrogenase , Topotecan/farmacologia
5.
Eur J Obstet Gynecol Reprod Biol ; 231: 43-47, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30321787

RESUMO

OBJECTIVES: Intrauterine fetal death (IUFD) is a multifactorial disorder and one of the most severe obstetrical complications. Our primary aim was to study the possible associations between polymorphic variants of the PEMT gene and IUFD in the Polish population. STUDY DESIGN: The case-control study involved 76 mothers with IUFD occurrence and 215 mothers of healthy children. Genetic analysis of the four single nucleotide polymorphisms in the PEMT gene (rs4646406, rs4244593, rs897453 and rs12325817) was performed with the PCR/RFLP method. RESULTS: Three oef the analyzed PEMT polymorphisms (rs4646406, rs4244593, and rs8974) were significantly associated with IUFD in the Polish population. Among them, PEMT variant rs4244593 was associated with increased risk of IUFD in three genetic inheritance models. Results were statistically significant even after applying Bonferroni correction for multiple comparisons (p < 0.0125). The distribution of all haplotypes except TAGC was not different between cases and controls, however, after applying permutation test, none of the haplotypes showed a relation with IUFD. CONCLUSIONS: The present findings indicate that PEMT polymorphisms may be associated with the susceptibility to IUFD in the Polish population.


Assuntos
Morte Fetal/etiologia , Fosfatidiletanolamina N-Metiltransferase/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polônia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Gravidez
6.
Int J Mol Sci ; 19(10)2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30257426

RESUMO

The major cause of ovarian cancer treatment failure in cancer patients is inherent or acquired during treatment drug resistance of cancer. Matrix Gla protein (MGP) is a secreted, non-collagenous extracellular matrix protein involved in inhibition of tissue calcification. Recently, MGP expression was related to cellular differentiation and tumor progression. A detailed MGP expression analysis in sensitive (A2780) and resistant to paclitaxel (PAC) (A2780PR) and topotecan (TOP) (A2780TR) ovarian cancer cell lines and their corresponding media was performed. MGP mRNA level (real time PCR analysis) and protein expression in cell lysates and cell culture medium (Western blot analysis) and protein expression in cancer cells (immunofluorescence analysis) and cancer patient lesions (immunohistochemistry) were determined in this study. We observed increased expression of MGP in PAC and TOP resistant cell lines at both mRNA and protein level. MGP protein was also detected in the corresponding culture media. Finally, we detected expression of MGP protein in ovarian cancer lesions from different histological type of cancer. MGP is an important factor that might contribute to cancer resistance mechanism by augmenting the interaction of cells with ECM components leading to increased resistance of ovarian cancer cells to paclitaxel and topotecan. Expression found in ovarian cancer tissue suggests its possible role in ovarian cancer pathogenesis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proteínas de Ligação ao Cálcio/genética , Resistencia a Medicamentos Antineoplásicos , Proteínas da Matriz Extracelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Inibidores da Topoisomerase I/farmacologia , Topotecan/farmacologia , Proteínas de Ligação ao Cálcio/análise , Linhagem Celular Tumoral , Proteínas da Matriz Extracelular/análise , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteína de Matriz Gla
7.
Molecules ; 23(4)2018 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-29649113

RESUMO

Development of drug resistance is the main reason for low chemotherapy effectiveness in treating ovarian cancer. Paclitaxel (PAC) is a chemotherapeutic drug used in the treatment of this cancer. We analysed the development of PAC resistance in two ovarian cancer cell lines. Exposure of drug-sensitive cell lines (A2780 and W1) to PAC was used to determine the primary response. An established response was determined in PAC-resistant sublines of the A2780 and W1 cell lines. qRT-PCR was performed to measure the expression levels of specific genes. We observed decreased expression of the PCDH9, NSBP1, MCTP1 and SEMA3A genes in the PAC-resistant cell lines. Short-term exposure to PAC led to increased expression of the MDR1 and BCRP genes in the A2780 and W1 cell lines. In the A2780 cell line, we also observed increased expression of the C4orf18 gene and decreased expression of the PCDH9 and SEMA3A genes after PAC treatment. In the W1 cell line, short-term treatment with PAC upregulated the expression of the ALDH1A1 gene, a marker of Cancer stem cells (CSCs). Our results suggest that downregulation of the PCDH9, NSBP1, MCTP1 and SEMA3A genes and upregulation of the MDR1, BCRP, C4orf18 and ALDH1A1 genes may be related to PAC resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Redes Reguladoras de Genes , Neoplasias Ovarianas/genética , Paclitaxel/farmacologia , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos
8.
Rev. bras. farmacogn ; 28(2): 179-191, Mar.-Apr. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-958858

RESUMO

ABSTRACT Passiflora caerulea L., P. alata Curtis and P. incarnata L. (synonym for P. edulis Sims), are the most popular representatives of the Passiflora genus in South America. In recent years, a growing attention is paid to the biological activity and phytochemical profiles of crude extracts from various species of Passiflora in worldwide. The aim of this study was to evaluate and to compare of anti-leukemic activity of the dry crude extracts from leaves of three Passiflora species from greenhouse of Poland in two human acute lymphoblastic leukemia cell lines: CCRF-CEM and its multidrug resistant variant. Two systems of liquid chromatography in order to assessment of phytochemical composition of extracts were applied. Extracts of P. alata and P. incarnata showed the potent inhibitory activity against human acute lymphoblastic leukemia CCRF-CEM, while P. caerulea not showed activity (or activity was poor). Despite similarities in quality phytochemical profile of extracts from P. caerulea and P. incarnata, differences in quantity of chemical compounds may determine their various pharmacological potency. For the activity of P. alata extract the highest content of terpenoids and a lack of flavones C-glycosides are believed to be crucial. Summarizing, the crude extract from P. alata leaves may be considered as a substance for complementary therapy for cancer patients.

9.
Oncotarget ; 8(43): 74466-74478, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088800

RESUMO

PURPOSE: The aim of the present study is to determine the expression of LUM in drug-resistant ovarian cancer cell lines. METHODS: Doxorubicin- (DOX), topotecan- (TOP) and vincristine- (VIN) resistant variants of the W1 ovarian cancer cell line were used in this study. We used quantitative real-time polymerase chain reactions to determine LUM mRNA levels. Protein expression was detected using Western blot and immunocytochemistry assays. Protein glycosylation was investigated using PGNase F digestion. Immunohistochemistry assays were used to determine protein expression in ovarian cancer patients. RESULTS: We observed increased expression of LUM in drug-resistant cell lines at both the mRNA and the protein level. The most abundant LUM expression was observed in TOP-resistant cell line. We observed LUM bands that corresponded to different molecular masses, and the most abundant LUM form was the secreted form, which had a mass of 50 kDa. Double immunofluorescence analysis showed co-expression of LUM and COL3A1 as well as the presence of extracellular COL3A1 in the TOP-resistant cell line. Finally, we detected the LUM protein in ovarian cancer tissue. CONCLUSION: The expression of LUM in cytostatic-resistant cell lines suggests its role in drug resistance. The co-expression of LUM and COL3A1 indicates the significance of LUM in collagen fibre assembly. Expression in ovarian cancer tissue suggests that LUM can play a role in ovarian cancer pathogenesis in ways similar to other cancers.

10.
Molecules ; 22(10)2017 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-29027969

RESUMO

Low efficiency of chemotherapy in ovarian cancer results from the development of drug resistance. Cisplatin (CIS) and topotecan (TOP) are drugs used in chemotherapy of this cancer. We analyzed the development of CIS and TOP resistance in ovarian cancer cell lines. Incubation of drug sensitive cell lines (W1 and A2780) with cytostatic drugs was used to determine the primary response to CIS and TOP. Quantitative polymerase chain reaction (Q-PCR) was performed to measure the expression levels of the genes. We observed decreased expression of the MCTP1 gene in all resistant cell lines. We observed overexpression of the S100A3 and HERC5 genes in TOP-resistant cell lines. Increased expression of the S100A3 gene was also observed in CIS-resistant A2780 sublines. Overexpression of the C4orf18 gene was observed in CIS- and TOP-resistant A2780 sublines. A short time of exposure to CIS led to increased expression of the ABCC2 gene in the W1 and A2780 cell lines and increased expression of the C4orf18 gene in the A2780 cell line. A short time of exposure to TOP led to increased expression of the S100A3 and HERC5 genes in both sensitive cell lines, increased expression of the C4orf18 gene in the A2780 cell line and downregulation of the MCTP1 gene in the W1 cell line. Our results suggest that changes in expression of the MCTP1, S100A3 and C4orf18 genes may be related to both CIS and TOP resistance. Increased expression of the HERC5 gene seems to be important only in TOP resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/tratamento farmacológico , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas S100/genética , Topotecan/administração & dosagem , Topotecan/efeitos adversos
11.
Oncotarget ; 8(30): 49944-49958, 2017 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-28611294

RESUMO

PURPOSE: The present study is to discover a new genes associated with drug resistance development in ovarian cancer. METHODS: We used microarray analysis to determine alterations in the level of expression of genes in cisplatin- (CisPt), doxorubicin- (Dox), topotecan- (Top), and paclitaxel- (Pac) resistant variants of W1 and A2780 ovarian cancer cell lines. Immunohistochemistry assay was used to determine protein expression in ovarian cancer patients. RESULTS: We observed alterations in the expression of 22 genes that were common to all three cell lines that were resistant to the same cytostatic drug. The level of expression of 13 genes was upregulated and that of nine genes was downregulated. In the CisPt-resistant cell line, we observed downregulated expression of ABCC6, BST2, ERAP2 and MCTP1; in the Pac-resistant cell line, we observe upregulated expression of ABCB1, EPHA7 and RUNDC3B and downregulated expression of LIPG, MCTP1, NSBP1, PCDH9, PTPRK and SEMA3A. The expression levels of three genes, ABCB1, ABCB4 and IFI16, were upregulated in the Dox-resistant cell lines. In the Top-resistant cell lines, we observed increased expression levels of ABCG2, HERC5, IFIH1, MYOT, S100A3, SAMD4A, SPP1 and TGFBI and decreased expression levels of MCTP1 and PTPRK. The expression of EPHA7, IFI16, SPP1 and TGFBI was confirmed at protein level in analyzed ovarian cancer patients.. CONCLUSIONS: The expression profiles of the investigated cell lines indicated that new candidate genes are related to the development of resistance to the cytostatic drugs that are used in first- and second-line chemotherapy of ovarian cancer.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/genética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Neoplasias Ovarianas/metabolismo
12.
Anticancer Res ; 37(4): 1625-1636, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28373423

RESUMO

BACKGROUND: Low effectiveness of chemotherapy in ovarian cancer results from development of drug resistance. Topotecan is a drug used as second-line chemotherapy for this cancer type. We analyzed development of topotecan resistance in ovarian cancer cell lines. MATERIALS AND METHODS: A chemosensitivity assay, MTT test, was performed to assess drug resistance. Quantitative polymerase chain reaction (Q-PCR) assays were performed to determine ABCB1, ABCG2, ALDH1A1, IFIH1, SAMD4 and EPHA3 gene expression. RESULTS: We observed dose-dependent responses to topotecan. In all topotecan-resistant cell lines an overexpression of ABCG2, IFIH1 and SAMD4 genes was observed. Expression of ABCB1 gene was observed in one cell line. Expression of ALDH1A1 was up-regulated in A2780 and down-regulated in SKOV-3-resistant cell lines. Short-time exposure led to similar patterns of gene expression for the investigated genes. CONCLUSION: Expression of ABCG2 and ABCB1 genes plays the most important role in topotecan resistance. The role of other investigated genes seems to be complementary.


Assuntos
Biomarcadores Tumorais/genética , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Topotecan/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Ovarianas/patologia , Reação em Cadeia da Polimerase em Tempo Real , Inibidores da Topoisomerase I/farmacologia , Células Tumorais Cultivadas
13.
J Ovarian Res ; 9(1): 65, 2016 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-27756418

RESUMO

BACKGROUND: Multiple drug resistance (MDR) of cancer cells is the main reason of intrinsic or acquired insensitivity to chemotherapy in many cancers. In this study we used ovarian cancer model of acquired drug resistance to study development of MDR. We have developed eight drug resistant cell lines from A2780 ovarian cancer cell line: two cell lines resistant to each drug commonly used in ovarian cancer chemotherapy: cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX) and topotecan (TOP). A chemosensitivity assay - MTT was performed to assess drug cross-resistance. Quantitative real-time polymerase chain reaction and immunofluorescence were also performed to determine mRNA and protein expression of genes/proteins involved in drug resistance (P-gp, BCRP, MRP1, MRP2, MVP). Flow cytometry was used to determine the activity of drug transporters. RESULTS: We could observe cross-resistance between PAC- and DOX-resistant cell lines. Additionally, both PAC-resistant cell lines were cross-resistant to TOP and both TOP-resistant cell lines were cross-resistant to DOX. We observed two different mechanisms of resistance to TOP related to P-gp and BCRP expression and activity. P-gp and BCRP were also involved in DOX resistance. Expression of MRP2 was increased in CIS-resistant cell lines and increased MVP expression was observed in CIS-, PAC- and TOP-, but not in DOX-resistant cell lines. CONCLUSIONS: Effectiveness of TOP and DOX in second line of chemotherapy in ovarian cancer can be limited because of their cross-resistance to PAC. Moreover, cross-resistance of PAC-resistant cell line to CIS suggests that such interaction between those drugs might also be probable in clinic.


Assuntos
Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Expressão Gênica , Genes MDR , Neoplasias Ovarianas/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Perfilação da Expressão Gênica , Humanos , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo
14.
Ginekol Pol ; 87(5): 347-52, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27304650

RESUMO

OBJECTIVES: Recent studies have demonstrated that disorders of bone metabolism, which is regulated by RANK/RANKL/OPG signaling pathway, are the cause of osteoporosis. The aim of the study was to investigate the distribution of genotypes of the RANK 575C>T and RANKL -643C>T polymorphisms and to analyze their relationship with bone parameters in postmenopausal women. MATERIAL AND METHODS: A total of 310 postmenopausal Caucasian women (139 with osteoporosis, 107 with osteopenia, and 64 healthy postmenopausal controls) were included. Bone mineral density (BMD) at the lumbar region of the spine (L2-L4) was measured by dual energy X-ray absorptiometry (DXA). Genetic analysis was performed using the PCR-RFLP method. RESULTS: Analysis of the frequency of genotypes and alleles of the RANK 575C>T and RANKL -643C>T polymorphisms did not show any statistically significant differences between the study groups (osteoporosis and osteopenia) and postmenopausal women with normal t-score value (ns). Notably, a significant association between the RANKL -643C>T polymorphism and body mass, such as BMI values in osteoporotic women (p<0.05), was observed. CONCLUSIONS: Our results suggest lack of association between the 575C>T RANK polymorphism and the development of osteoporosis. The -643C>T RANKL polymorphism, through its significant influence on body weight and BMI value, may contribute to the development of osteoporosis in postmenopausal women.


Assuntos
Ligante RANK/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Absorciometria de Fóton/métodos , Idoso , Densidade Óssea/genética , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/genética , Polimorfismo de Nucleotídeo Único , Transdução de Sinais
15.
Maturitas ; 84: 42-54, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26620113

RESUMO

OBJECTIVE: The aim of the study was assessment of a possible relationship between the polymorphisms of the candidate genes participating in the etiology of some neurological and psychiatric disorders and the risk of depression in perimenopausal and postmenopausal women. METHODS: A total of 167 (54 perimenopausal and 113 postmenopausal) Caucasian women from western Poland, aged 42-67, were recruited as the patient group in the study because of depressive symptoms, and another 321 healthy women (102 perimenopausal and 219 postmenopausal) served as the controls. All study participants were evaluated for climacteric and depressive disorders according to the Kupperman index and Hamilton rating scale for depression (HRSD), respectively. The following candidate genes were selected for the study: 5HTR2A, 5HTR1B, 5HTR2C, TPH1, TPH2, MAOA, COMT, NET, GABRB1, ESR1, MTHFR, MTR and MTHFD1. In each group the frequencies of the polymorphisms were determined using PCR-RFLP analysis. RESULTS: After correcting for Bonferroni multiple tests, we found associations between the MAOA c.1460C>T (SNP 1137070), COMT c.472G>A (SNP 4680), MTHFR c.677C>T (SNP 1801133) and ESR1 454(-351) A>G (SNP 9340799) polymorphisms to mild and moderate depressive symptoms in menopausal women. In the perimenopausal and postmenopausal women, genotype association of the MAOA c.1460 CT and c.1460 CT+TT (OR=1.83; pcorr=0.009 and OR=1.85; pcorr=0.003, resp.), and of the MTHFR c.677 TT and c.677 CT+TT (OR=3.52; pcorr=0.00009 and OR=2.06; pcorr=0.0006, resp.), as well as of the COMT c.472 GA and COMT c.472 GA+AA genotypes (OR=2.23; pcorr=0.03 and OR=2.17; pcorr=0.027, resp.) in the postmenopausal women revealed significantly higher frequencies of these variants in depressed female patients than in controls, whereas the ESR1 454(-351) AG and 454(-351) AG+GG genotypes were associated with lower risk of depression in postmenopausal women (OR=0.48; pcorr=0.012, and OR=0.52; pcorr=0.015, resp.). CONCLUSIONS: Our study substantiates the involvement of the MAOA and MTHFR polymorphisms in climacteric depression and offers evidence that the COMT and ESR1 genes may also play a role in the susceptibility to depressive mood in postmenopausal women.


Assuntos
Catecol O-Metiltransferase/genética , Depressão/genética , Transtorno Depressivo/genética , Receptor alfa de Estrogênio/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Monoaminoxidase/genética , Receptor 5-HT1B de Serotonina/genética , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Adulto , Idoso , Feminino , Genótipo , Humanos , Menopausa/psicologia , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Polimorfismo de Nucleotídeo Único , Escalas de Graduação Psiquiátrica , Receptor 5-HT2A de Serotonina/genética , Receptor 5-HT2C de Serotonina/genética , Receptores de GABA-A/genética , Fatores de Risco , Triptofano Hidroxilase/genética
16.
Przegl Lek ; 72(3): 144-7, 2015.
Artigo em Polonês | MEDLINE | ID: mdl-26731872

RESUMO

Smoking is a significant factor which affects not only reproduction and the process of pregnancy but also the offspring. Endangering for tobacco smoke and nicotine either passive or active has an important influence for shortening the time of pregnancy, the weight of the newborn and the Placenta. The occurrence of complications connected with smoking is probably correlated with the amount of cigarettes smoked per day. The aim of the paper was to analyse the influence of passive and active smoking on the course of pregnancy. The study involved a group of 113 women who gave birth in Gynaecological and Obstetrics Clinical Hospital of the Karol's Marcinkowski University of Medical Sciences in Poznan during the period from January to June 2011. Based on data gained from documentation and mothers three groups were separated: 22 women who were active smokers, 32 passive smokers and 59 women from control group who have never been smoking. There were analyzed selected obstetric data and term of pregnancy, condition and weight of newborn, blood pH and alkaline balance from umbilical vessels. In research there were no correlation between groups and/or results of researches of blood Ph, alkaline balance from umbilical vessels and the assessment of the newborn in Apgar score at 1, 3, 5 minute. In fact passive smoking women were younger (the average 27.84) than actively smoking woman (30.23) and non-smokers (30.25) (p = 0.03). The most of small as for their gestational age infants were in the group of active smoking women (14%). Non-smokers more often did have a miscarriage (84%) in the past than other groups (active smokers 60%, passive 33%) (p = 0.04). Smoking women usually come from countryside or small towns, they were not marriage and they had preterm delivery. In this group there was found the biggest percent of too small newborns for their gestational age--14%.


Assuntos
Aborto Espontâneo/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adulto , Índice de Apgar , Estudos de Casos e Controles , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Humanos , Recém-Nascido , Nicotina/efeitos adversos , Gravidez , Nascimento Prematuro/epidemiologia
17.
Przegl Lek ; 69(10): 929-33, 2012.
Artigo em Polonês | MEDLINE | ID: mdl-23421063

RESUMO

UNLABELLED: Smoking is a significant factor which affects not only reproduction and the process of pregnancy but also the offspring. Endangering for tobacco smoke and nicotine either passive or active has an important influence for shortening the time of pregnancy, the weight of the newborn and the Placenta. The occurrence of complications connected with smoking is probably correlated with the amount of cigarettes smoked per day. TARGET: The target of the paper was to analyse the influence of passive and active smoking on the course of pregnancy. METHODS AND MATERIALS: The study involved a group of 113 women who gave birth in Gynaecological and Obstetrics Clinical Hospital of the Karol's Marcinkowski University of Medical Sciences in Poznan during the period from January to June 2011. Based on data gained from documentation and mothers three groups were separated: 22 women who were active smokers, 32 passive smokers and 59 women from control group who have never been smoking. There were analyzed selected obstetric data and term of pregnancy, condition and weight of newborn, blood pH and alkaline balance from umbilical vessels. RESULTS: in research there were no correlation between groups and/ or results of researches of blood Ph, alkaline balance from umbilical vessels and the assessment of the newborn in Apgar score at 1, 3, 5 minute. In fact passive smoking women were younger (the average 27,84) than actively smoking woman (30,23) and non-smokers (30,25) (p=0,03). The most of small as for their gestational age infants were in the group of active smoking women (14%). Non-smokers more often did have a miscarriage (84%) in the past than other groups (active smokers 60%, passive 33%) (p=0,04). CONCLUSION: smoking women usually come from countryside or small towns, they were not marriage and they had preterm delivery. In this group there was found the biggest percent of too small newborns for their gestational age - 14%.


Assuntos
Aborto Espontâneo/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional , Complicações na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adulto , Fatores Etários , Índice de Apgar , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Recém-Nascido , Polônia/epidemiologia , Gravidez , Saúde da População Rural
18.
Przegl Lek ; 64(10): 622-5, 2007.
Artigo em Polonês | MEDLINE | ID: mdl-18409271

RESUMO

In this survey, we have assessed a socio-economic status of pregnant women smoking during pregnancy and the impact of this status on birth weight of their newborns. The research, we have done on the group of 431 pregnant women. Smoking habit has been declared by 21.6% of women and passive exposure to tobacco smoke has been stated by 32.5% of respondents. We have observed a significant association between active and passive smoking and socio-economic status of respondents. The newborns of actively smoking mothers were lighter of about 216 g according to those ones of mothers who did not smoke and were not exposed to passive smoking, and were lighter than newborns of mothers who were not exposed to passive smoking of about 146 g. We have not observed any significant link between active and passive exposure to tobacco smoke during pregnancy, and a risk of delivering low weighted child. However, in case of newborns weighted above 2500 g., their mothers have not been smoking and have not been exposed to tobacco smoke significantly more often.


Assuntos
Peso ao Nascer , Exposição Materna , Fumar/efeitos adversos , Classe Social , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Comportamento Materno , Gravidez , Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fatores Socioeconômicos
19.
Ginekol Pol ; 73(7): 573-6, 2002 Jul.
Artigo em Polonês | MEDLINE | ID: mdl-12369277

RESUMO

The aim of the study was to evaluate the activity of the pro- and antioxidant systems in cervical mucus of healthy women and women with pathological of disorders cervical. After cervical mucus liquefaction, the activity of superoxide dismutase, catalase and xanthine oxidase was determined by means of chemiluminescence assays. The activity of the antioxidant system in cervical mucus of healthy women was higher as compared to the group with pathological cervical disorders. Moreover, in mucus samples obtained from women with dysplasia, the significantly heightened activity of xanthine oxidase (strong pro-oxidant) was observed. The antioxidant system present in cervical mucus may protect both the cells of the uterine cervix and the viable sperm.


Assuntos
Catalase/análise , Muco do Colo Uterino/enzimologia , Sequestradores de Radicais Livres/análise , Superóxido Dismutase/análise , Displasia do Colo do Útero/enzimologia , Xantina Oxidase/análise , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Medições Luminescentes , Polônia , Estatísticas não Paramétricas , Displasia do Colo do Útero/patologia
20.
Ginekol Pol ; 73(1): 14-8, 2002 Jan.
Artigo em Polonês | MEDLINE | ID: mdl-12001756

RESUMO

DESIGN: The purpose of our study was to determine a prooxidant-antioxidant balance in pregnant women with the newly diagnosed pregnancy-induced hypertension and in normal pregnancies. MATERIALS AND METHODS: The research was performed on 20 pregnancies complicated with hypertension (PIH) and 17 normal pregnancies in the third trimester of gestation. The age, BPs, BPd, edema and proteinuria were noted to characterize the patients. The reduced glutathione concentration and the glutathione peroxidase activity were measured in red blood cell hemolysates. In plasma, the concentrations of the thiobarbituric acid reactive substances such as lipid peroxidation products and the hydrogen peroxide were determined. RESULTS: There were patients of similar age: pregnancies with PIH and uncomplicated pregnancies were 25.7 +/- 3.96 years old and 25.7 +/- 4.54 years old, respectively. Proteinuria was found in five pregnancies with PIH and in one normal pregnant woman. Edema was noted in eight pregnancies with PIH and in three normal pregnancies. In the group of pregnancies complicated with hypertension, BPs and BPd were 147.7 +/- 6.78 mmHg and 94.2 +/- 4.94 mmHg, respectively. In the group of patients with PIH, reduced glutathione concentration significantly decreased and the TBARS levels increased as compared with results noted in normal pregnancies. No differences in the glutathione peroxidase activity and the hydrogen peroxide concentration were noted between groups of patients. CONCLUSIONS: Obtained results of the research allowed us to conclude that the pregnancy-induced hypertension is associated with the overproduction of lipid peroxides and impaired antioxidant defence.


Assuntos
Antioxidantes/metabolismo , Hipertensão/sangue , Complicações Cardiovasculares na Gravidez/sangue , Espécies Reativas de Oxigênio/sangue , Adulto , Eritrócitos/metabolismo , Feminino , Glutationa/sangue , Glutationa Peroxidase/sangue , Humanos , Peróxidos Lipídicos/biossíntese , Gravidez , Terceiro Trimestre da Gravidez
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