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1.
Curr Pharm Biotechnol ; 21(12): 1242-1248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32370713

RESUMO

BACKGROUND: A reduced concentration of adiponectin is considered as an independent factor of the risk of inducing endometrial cancer. Cisplatin is a drug used in the therapy of this type of neoplasm. However, knowledge of the effects of cisplatin on the adiponectin level is still limited. OBJECTIVE: The purpose of this study was to assess the impact of cisplatin depending on the concentration and time of exposition of the cells to the drug on the adiponectin level in the endometrial cancer cell line. METHODS: Cells of endometrial cancer cell line Ishikawa were exposed for 12,24 and 48 hour periods to cisplatin with the following concentrations: 2.5µM, 5µM, 10µM. The changes in the expression profile of adiponectin were compared to the RtqPCR reaction and ELISA test. The STATISTICA 13.0 PL program was used for statistical analysis (p<0.05). RESULTS: In the culture without the drug, the concentration of adiponectin was statistically lower than in the cell culture incubated with the drug. Changes on the mRNA level seem to be more specific than on the protein level, although in both cases, the same trend in the expression changes was noted. DISCUSSION: The longer the time of exposition of the cells to the drug, the expression of mRNA, and the adiponectin protein increased. Changes in the expression profile were characterized statistically (p<0.05). CONCLUSION: Cisplatin, in a noticeable way, changes the expression profile of adiponectin. Molecular analysis indicated that in the case of endometrial cancer therapy should be implemented with a concentration of no less than 5 µM.


Assuntos
Adiponectina/biossíntese , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Neoplasias do Endométrio/metabolismo , Expressão Gênica/efeitos dos fármacos , RNA Mensageiro/biossíntese , Adiponectina/genética , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/genética , Feminino , Humanos
2.
Curr Pharm Biotechnol ; 21(11): 1119-1128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32297576

RESUMO

BACKGROUND: Semaphorin 3F (SEMA3F) plays a substantial role in carcinogenesis, because of its role in inducing angiogenesis, and creating a microenvironment for the developing tumor. OBJECTIVE: The purpose of this work was to assess the impact of cisplatin, depending on the concentration and exposure time on the expression pattern of SEMA3F in an endometrial cancer cell line. MATERIALS AND METHODS: Cultures of the Ishikawa endometrial cancer cells were incubated with cisplatin with the following concentrations: 2.5µM; 5µM; and 10µM and for the following periods of time: 12; 24; and 48 hours. Cells not incubated with the drug constituted the control in the experiment. To determine the effect of cisplatin on the expression of SEMA3F, the real-time quantitative reverse transcription reaction (RtqPCR; mRNA) was used, as well as the ELISA assay (protein). The statistical analysis was done with the admission of p<0.05. RESULTS: The silencing of SEMA3F expression on the transcriptome and proteome levels in a culture unexposed to the effects of cisplatin in comparison to endometrial cancer cells under the influence of cisplatin (p<0.05) were noted. Along with an increase in the concentration of the drug used, the number of copies of the gene transcript, during the shortest incubation period had a gradual increase. Only for the highest concentration of the drug, substantial statistical differences in the expression of the SEMA3F protein between 24 and 48 hour incubation periods (p<0.05) were determined. CONCLUSION: Using cisplatin in an endometrial cancer cell culture results in an increased expression of SEMA3F, which advantageously affects the normalization of the neoplastic angiogenic process and lowers the proliferation of the cells making up the mass of the tumor.


Assuntos
Antineoplásicos/farmacologia , Carcinogênese/efeitos dos fármacos , Cisplatino/farmacologia , Neoplasias do Endométrio/metabolismo , Proteínas de Membrana/biossíntese , Proteínas do Tecido Nervoso/biossíntese , RNA Mensageiro/biossíntese , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Inativação Gênica , Humanos , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/genética , Microambiente Tumoral/efeitos dos fármacos
3.
Curr Pharm Biotechnol ; 21(1): 52-59, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31533599

RESUMO

BACKGROUND: Many experimental studies have demonstrated the importance of COX-2 in the tumor angiogenesis. Inducible iNOS is responsible for a high and stable level of nitric oxide and is expressed in response to pro-inflammatory factors. OBJECTIVE: The aim of this study was to evaluate the expression of COX-2 and iNOS at the protein level and to assess their potential prognostic significance in patients with endometrial cancer. METHODS: The study group consisted of 45 women with endometrial cancer divided according to the degree of histological differentiation i.e. G1, 17; G2, 15; G3, 13. The control group consisted of 15 women without neoplastic changes. The expression of studied proteins was determined immunohistochemically with specific polyclonal antibodies. RESULTS: Analysis of the COX-2 expression showed that the optical density of the reaction product in G1 reached 186% in the control group, while the values in G2 and G3 reached 243% and 293%, respectively. In the case of iNOS, the optical density of the reaction product reached the following percentages in the control group: 147% in G1, 243% in G2, and 241% in G3. CONCLUSION: Our findings suggest that changes in the expression of COX-2 and iNOS may be potentially useful in predicting the progression of endometrial cancer and treatment effectiveness.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Neoplasias do Endométrio/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Idoso , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico
4.
Curr Pharm Biotechnol ; 21(1): 45-51, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31544715

RESUMO

BACKGROUND: Semaphorin 5A (SEMA5A) functions not only in the nervous system but also in cancer transformation where its role has not yet been sufficiently studied and described. OBJECTIVE: The aim of the study was to determine the changes in SEMA5A expression in endometrial cancer at various degrees of its differentiation (G1-G3) compared to control. MATERIALS AND METHODS: The study group consisted of 45 patients with endometrial cancer at various grades: G1, 17; G2, 15; G3, 13. The control consisted of 15 women without neoplastic changes in the routine gynecological examination. The statistical analysis of immunohistochemical assessment of SEMA5A level was carried out using the Statistica 12 program based on the Kruskal-Wallis test and Dunn's post-hoc test (p<0.05). RESULTS: The expression of SEMA5A (optical density) was observed in the control group (Me = 103.43) and in the study group (G1, Me = 140.72; G2, Me = 150.88; G3, Me = 173.77). Differences in expression between each grade and control and between individual grades turned out to be statistically significant (p<0.01). The protein level of SEMA5A expression increased with the decreasing degree of endometrial cancer differentiation. CONCLUSION: In our research, we indicated the overexpression of SEMA5A protein in endometrial cancer. It is a valuable starting point for further consideration of the role of SEMA5A as a new supplementary molecular marker in endometrial cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Endométrio/metabolismo , Semaforinas/metabolismo , Diferenciação Celular , Neoplasias do Endométrio/patologia , Endométrio/metabolismo , Feminino , Humanos
5.
Curr Pharm Biotechnol ; 21(7): 635-641, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31880256

RESUMO

BACKGROUND: Endometrial cancer is one of the most common gynecological cancer in the developed countries and occurs mainly in postmenopausal women. Angiogenesis is important for cancer formation as it provides nutrients for growing tumor mass. Most tumors do not show detectable Homeobox A5 (HOXA5 level), suggesting its potential role as a cancer suppressor. It was demonstrated that HOXA5 is involved in the progression of various types of cancer and the loss of its expression correlates with higher pathological grade and poorer outcome. OBJECTIVE: The aim of the study was to evaluate HOXA5 expression at transcriptome and protein levels. MATERIALS AND METHODS: The study enrolled 45 women diagnosed with endometrial cancer and 15 without neoplastic changes. The histopathological examination allowed us to divide cancer tissue samples according to the degree of histological differentiation: G1, 17; G2, 15; G3, 13. The expression of the HOXA5 protein was determined by immunohistochemistry. Microarray and RT-qPCR techniques were used to assess HOXA5 expression at the mRNA level. RESULTS: The reaction to the HOXA5 protein was only visible in glandular cells in G1 endometrial cancer and was lower compared to the control. In grades 2 and 3, reactions were noted at the limit of the method's sensitivity. In addition, reduced HOXA5 expression was observed at the transcriptome level. CONCLUSION: HOXA5 may become a potential complementary molecular marker, allowing early detection of neoplastic changes in the endometrium. It also seems that detection of HOXA5 at the mRNA and protein levels may be helpful in improving the accuracy of diagnosis and planning effective oncological therapy.


Assuntos
Neoplasias do Endométrio/metabolismo , Proteínas de Homeodomínio/metabolismo , Neovascularização Patológica/metabolismo , Transcrição Gênica , Diferenciação Celular/genética , Neoplasias do Endométrio/irrigação sanguínea , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Proteínas de Homeodomínio/genética , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neovascularização Patológica/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
6.
Med Sci Monit ; 25: 4569-4574, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31217417

RESUMO

BACKGROUND SEMA3B is known as an inhibitor of angiogenesis and cell proliferation. During carcinogenesis, the loss of SEMA3B function is observed, which results in the progression of neoplastic changes. The aim of this study was to evaluate the expression profile of SEMA3B in endometrial cancer (G1-G3) in comparison to the control group and to assess whether the observed changes in expression could become a molecular marker in endometrial cancer. MATERIAL AND METHODS The study group consisted of 45 patients diagnosed with endometrial cancer (G1, 17; G2, 15; G3, 13). The control group included 15 patients. SEMA3B expression was assessed using the immunohistochemical method. Statistical analysis was carried out using the Statistica 12 PL program (StatSoft, USA). It included the Kruskal-Wallis test and post hoc Dunn's test (p<0.05). RESULTS Statistically significant differences in the level of SEMA3B expression were observed between all analyzed groups. The expression pattern of SEMA3B was as follows: cancer cells G1>G2>G3; endothelial cells: G3>G1>G2; stromal cells: G2>G1>G3. CONCLUSIONS Analysis of the SEMA3B expression profile shows the complexity of neoplastic transformation, which confirms the different expression of SEMA3B in endometrial cancer cells and endothelial cells. The present results and data in the literature data suggest that SEMA3B expression indicates the progression of carcinogenesis in the context of endometrial cancer.


Assuntos
Neoplasias do Endométrio/genética , Glicoproteínas de Membrana/genética , Semaforinas/genética , Adulto , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica , Neoplasias do Endométrio/metabolismo , Endométrio/metabolismo , Células Endoteliais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Glicoproteínas de Membrana/metabolismo , Estadiamento de Neoplasias , Neovascularização Patológica/metabolismo , Semaforinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/genética
7.
Curr Pharm Biotechnol ; 20(9): 727-732, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31215376

RESUMO

BACKGROUND: In the course of neoplastic diseases, a reduction in SEMA3F expression is observed, which translates into an increase in the proliferative and proangiogenic potential of cells forming the tumor and the surrounding microenvironment. OBJECTIVE: The aim of this study was to determine the changes in SEMA3F level in endometrial cancer depending on its grade. METHODS: The study material consisted of tissue samples: 15 without neoplastic changes (control group) and 45 with endometrial cancer (G1, 17; G2, 15; G3, 13; study group). SEMA3F expression was assessed using the immune-histochemical method. RESULTS: The expression of SEMA3F was observed in the control group (Me = 159.38) and in the study group (G1, Me = 121.32; G2, Me = 0; G3, Me = 130.37). Differences between each grade and control and between individual grades were statistically significant. There were no significant correlations between SEMA3F expression and weight and Body Mass Index (BMI). The reduced SEMA3F expression in tumor tissue compared to healthy tissue indicates that this protein plays key roles in proliferation and angiogenesis. CONCLUSION: We found that depending on the severity of the disease, cancer adopts different survival strategies, where SEMA3F plays an important role. As a molecular marker, SEMA3F is not sensitive to weight and BMI.


Assuntos
Neoplasias do Endométrio/metabolismo , Proteínas de Membrana/metabolismo , Neovascularização Patológica/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Estudos de Casos e Controles , Neoplasias do Endométrio/irrigação sanguínea , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Gradação de Tumores , Projetos Piloto , Microambiente Tumoral/efeitos dos fármacos
8.
Thromb Res ; 135(4): 699-702, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25669600

RESUMO

BACKGROUND/AIM: It is believed that the amniotic fluid-derived TF, in the case of amniotic fluid embolism (AFE), contributes to acute disseminated intravascular coagulation (DIC) and obstetric shock in the mother. However, the role of amniotic fluid-derived contact phase coagulation factors that irrupt into the bloodstream simultaneously with TF is still unknown. Our study objective was to identify and measure the concentrations of CAS components and TF in amniotic fluid. MATERIAL AND METHODS: The study group consisted of 30 healthy parturients with uneventful pregnancy and birth. Amniotic fluid (AF) and maternal blood were sampled at the end of the first stage of labor. The components of ACS, i.e. factors XII and XI (FXII, FXI), prekallikrein (PK), high molecular weight kininogen (HMWK), and tissue factor (TF) were measured by immunoenzymatic method (ELISA). RESULTS: All ACS components were detected in AF; their levels were higher in AF than in the maternal plasma: FXII--29.17 ng/mg protein vs. 0.94 ng/mg protein (medians); FXI--27.28 ng/mg protein vs. 0.92 ng/mg protein (medians); PK--88442.04 ng/mg protein vs. 113.44 ng/mg protein (medians); HMWK--4253.82 ng/mg protein vs. 2857.96 ng/mg protein (medians). The concentration of TF in amniotic fluid was 39.46 pg/mg protein (median) vs. 0.41 pg/mg protein (median) in blood plasma. CONCLUSIONS: 1.The ACS components, i.e. FXII, FXI, PK and HMWK, are the constituents of amniotic fluid. 2.The concentrations of the amniotic fluid-derived factors having a coagulation initiation potential, i.e. TF and contact phase coagulation factors, are higher in amniotic fluid than in mother's blood plasma.


Assuntos
Coagulação Sanguínea/fisiologia , Embolia Amniótica/fisiopatologia , Adulto , Ativação Enzimática , Feminino , Humanos , Gravidez
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