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1.
J Obstet Gynaecol ; : 1-6, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32608278

RESUMO

The chronic course of endometriosis suggests that the immune system may play a role in its aetiology. There may be resistance to cell lysis, as well as an immune defect underlying endometriosis. Granzyme B is a serine protease that is secreted by Natural Killer (NK) cells and cytotoxic T lymphocytes during a cellular immune response and can induce apoptosis. The aim of this study was to evaluate the relationship between both Granzyme B levels and Granzyme B gene polymorphisms in endometriosis patients. Women between the ages of 20 - 45 were included in the study. The patients were divided into two groups: those diagnosed with endometriosis and those who had not been diagnosed with endometriosis. In the blood samples, Granzyme B gene polymorphisms and serum levels of Granzyme B were studied. There was no difference between the groups in terms of median Granzyme B levels and the presence of AA, AG, and GG genotypes. There was a difference in median granzyme levels for the control group; the GG genotype was found at a lower frequency. The immune defect within endometriosis-related immune cells may not be exclusively due to Granzyme B. Other mediators that are secreted from immune cells may have additive effects.IMPACT STATEMENTWhat is already known on this subject? NK cells are cytotoxic and inhibit the implantation of autologous endometrial cells that are spilled into the peritoneum by retrograde menstruation. Thus, a reduction in NK cell activity may facilitate the progression of endometriosis. The literature review reveals that there are studies suggesting that NK cell activity may be insufficient in endometriosis. Granzyme B is a serine protease that is secreted by NK cells and cytotoxic T lymphocytes during a cellular immune response.What do the results of this study add? Granzyme B is one of the cytotoxic granules in NK and cytotoxic T lymphocyte cells and its genetic polymorphisms were tested in endometriosis. We found that median Granzyme B levels were significantly different in patients with the GG genotype in the control group, compared to those with the AA and AG genotype. However, this difference was not detected between the control and endometriosis groups.What are the implications of these findings for clinical practice and/or further research? Our results contribute to uncovering the pathogenesis of endometriosis since there are no previous studies in the literature regarding this topic. Although we did not find a difference, our results will inform further studies made on this topic. Studies with different molecules and an increased number of patients are needed. The immune defect of endometriosis may not be due exclusively to Granzyme B. Other mediators that are secreted from immune cells may have mutual effects and interactions.

2.
Gene ; 737: 144428, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32045658

RESUMO

Hepatocellular carcinoma (HCC) is the most common type of liver tumors. There is only one chemodrug for treatment called sorafenib that is an effective multikinase inhibitor. However, most of the patients gain resistance to sorafenib treatment in six months. Thus, there is a limitation for treatment of HCC. Apigenin is a natural flavonoid that has been used for many years as an antioxidant and anti-inflammatory agent. The aim of this study is to investigate the combined therapeutic effects of sorafenib and apigenin upon apoptosis and cell cycle on HepG2 cell line. Cytotoxic effects of sorafenib and apigenin on HepG2 cells were determined by XTT assay. Effects of single and combined treatment on cell migration, invasion and colony formation were analysed by wound healing, transwell matrigel invasion assay and colony formation assay, respectively. TUNEL assay was performed for analyse apoptosis rates. Expression changes of genes related with apoptosis and cell cycle were analysed by quantitative real-time PCR. Combined treatment of sorafenib and apigenin has more decreasing effects on cell viability than single treatment groups. Also, combination group caused significant increase of apoptotic cells. Migration and invasion capability of cells in combined treatment group are decreased. Lastly, quantitative real-time PCR results showed that combination of both drugs arrested cell cycle and increased apoptotic gene expressions more than single treatment groups. This is the first study that investigating the combined treatment of sorafenib and apigenin on HCC in vitro. By combined treatment, apigenin potentiates sorafenib cytotoxicity on HepG2 cells. Effects of combined treatment on migration, invasion, apoptosis and gene expressions showed that may sorafenib and apigenin have synergistic effect.


Assuntos
Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sorafenibe/farmacologia , Apigenina/administração & dosagem , Sinergismo Farmacológico , Células Hep G2 , Humanos , Sorafenibe/administração & dosagem
3.
J Cell Biochem ; 120(3): 3506-3513, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30417420

RESUMO

Coriander (Coriandrum sativum L.) is such an herb from the Apiaceae family, used both for its medicinal and nutritional properties for many centuries. In this study, the effects of C. sativum extract on gene expression, viability, colony formation, migration, and invasion of PC-3 and LNCaP prostate cancer cell lines have been investigated. The half maximal inhibitory concentration (IC50 ) dose in PC-3 and LNCaP cells was detected to be 2 and 5 mg/mL at the 24th hour, respectively. C. sativum extracts have been observed to cause a significant decrease in the expression of Akt and Bcl-2 in the PC-3 cells and just Akt in LNCaP cells while increasing in the expression of p53, caspase-9, caspase-10, PTEN, DR5, TRADD, PUMA, and NOXA. DR4 expression was increased in LNCaP cell line but not PC-3, and APAF and BID had increased expression in PC-3 but not the LNCaP cells. Our observations have shown that C. sativum extract decreased colony formation while inhibiting cell invasion and migration. Cell migration was hindered in PC-3 but not the LNCaP cells. In conclusion, this data present a valuable addition to the very limited data available out there on the potential use of C. sativum in prostate cancer treatment.

4.
Eurasian J Med ; 50(3): 168-172, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30515037

RESUMO

Objective: Isoorientin (ISO) is a flavonoid compound extracted from plant species. The goal of this study was to determine the potential antiproliferative effects of ISO in HT-29 human colorectal adenocarcinoma cell line in vitro, specifically on cell viability, apoptosis, and cell cycle pathways. Materials and Methods: The cytotoxic effect of ISO isolated from E. spectabilis was measured using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in HT-29 cell lines. Total RNA was isolated using Tri-Reagent protocol. The effects of ISO on apoptosis-related gene were detected using real-time polymerase chain reaction (RT-PCR). The findings were analyzed using "Delta-Delta CT" ΔΔCT method and evaluated using a computer program. Volcano plot analysis was used for comparing groups and the data obtained were statistically analyzed using Student t test. Results: According to XTT result analysis, the 50% inhibitory concentration (IC50) value of ISO was 125 µM at the 48th h in HT-29 cells. The RT-PCR analysis in HT-29 cells showed that Cyclin D1 (CCND1 ), Cyclin-dependent kinase 6 (CDK6), BAX, BCL-2, Checkpoint kinase 1-2 (CHEK1, CHEK2) and Excision repair cross-complementing 1 (ERCC1) expressions were reduced in ISO-treated cells compared with those in the control group of cells. P53, P21, Caspase-3 (CASP-3), Caspase-8 (CASP-8), and Caspase-9 (CASP-9) gene expressions were increased Ataxia Telengiectasia and Rad-3 related (ATR) was activated in the ISO-treated group of cells compared with those in the control group of cells (p<0.05). Conclusion: ISO affected the proliferation of colorectal cancer (CRC) cells via cell cycle pathways. It also altered apoptosis gene expression. These results demonstrated that ISO can be a therapeutic agent for CRC treatment; however, more studies are needed to investigate its mechanism of actions.

5.
Urol Oncol ; 35(12): 674.e11-674.e17, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28843340

RESUMO

PURPOSE: Toll-like receptors (TLRs) have an important role in the activation of both innate and adaptive immunity in response to pathogens and endogenous danger signals from damaged or dying cells. The aim of this study was to determine the relationship between urothelial carcinoma (UC) and TLR expression. BASIC PROCEDURES: Real-time polymerase chain reaction evaluation was made of the messenger RNA expression of TLRs 1-10 in 24 UC samples and 46 nontumoral bladder tissue samples. The levels of proinflammatory cytokines (IL-1ß, IL-6, and IL-8) in the urine samples were also determined with enzyme-linked immunosorbent assay. MAIN FINDINGS: TLR2-7 and TLR10 expressions were significantly higher in UC than in the control group (P<0.05 for all comparisons). No concordance was found between matched tumor tissue and urine samples in terms of TLR expression. IL-1ß, IL-6, and IL-8 levels were significantly higher in urine specimens of patients with UC (P = 0.033, P = 0.001, and P = 0.008, respectively). PRINCIPAL CONCLUSIONS: The results of this study demonstrated that the TLR gene expression profiles reflect the heterogeneity within UC. These results might also prompt further investigation to better understand the role of the TLR gene family expression in the tumor progression of UC.


Assuntos
Carcinoma de Células de Transição/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Receptores Toll-Like/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/urina , Citocinas/urina , Feminino , Humanos , Mediadores da Inflamação/urina , Masculino , Pessoa de Meia-Idade , Família Multigênica , Isoformas de Proteínas/genética , Isoformas de Proteínas/urina , Neoplasias da Bexiga Urinária/urina
6.
J Surg Res ; 207: 241-248, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27979484

RESUMO

BACKGROUND: Acute renal failure is commonly seen in the perioperative period. Ischemia-reperfusion (IR) injury plays a major role in acute renal failure and delayed graft function. MicroRNAs (miRs), which are pivotal modulators of cell activities, offer a major opportunity for affective diagnosis and treatment strategies because they are tissue specific and in the center of gene expression modulation. The effect of bardoxolone methyl (BM) on miR-21, miR-223-5p, and miR-125b in renal IR injury was evaluated in this study. METHODS: Wistar-Albino rats (12-16 wk old, weighing 300-350 g) were used in the study. Rats (n = 6) were randomized into three groups (control, IR, and BM + IR). Tissue levels of miRs were analyzed with reverse transcription polymerase chain reaction. RESULTS: Significant reduction of urea and total oxidant status, increase of total antioxidant status, and oxidative stress index were identified in the IR + BM group compared with the IR group. Significant increases of miR-21 (2842.82-fold) and miR-125b (536.8-fold) were identified in the IR group compared with the control group; however, miR-223-5p levels did not show any significant difference. Also, miR-21 and miR-125b were significantly reduced in the IR + BM group compared with the IR group. Reduced histopathologic changes were observed in the IR + BM group. A significant decrease in the number of tunel-positive cells was identified in the IR + BM group compared with the IR group. CONCLUSIONS: miR-125b was significantly increased in IR injury; thus, miR-125b can be a potential novel marker that can be used in diagnosis and treatment of renal IR injury. BM reduces miR-21 and miR-125b in case of IR injury and makes functional and histopathologic repairs.


Assuntos
Antioxidantes/farmacologia , Rim/metabolismo , MicroRNAs/metabolismo , Ácido Oleanólico/análogos & derivados , Traumatismo por Reperfusão/diagnóstico , Animais , Antioxidantes/uso terapêutico , Biomarcadores/metabolismo , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Rim/patologia , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
7.
Gene ; 585(2): 241-6, 2016 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-27048831

RESUMO

Recent researches have demonstrated improved survival in oncologic patients treated with low molecular weight heparins (LMWHs) which are anticoagulant drugs. We evaluated "second generation" LMWH bemiparin and its in vitro anti-tumor effects on HepG2 hepatocellular carcinoma and MIA PaCa-2 cancer cells. The aim of the study is to investigate anti-cancer mechanism of bemiparin in HepG2 and Mia-Paca-2 cancer cells. Cytotoxic effects of bemiparin were determined by XTT assay. IC50 dose of bemiparin was found to be 200 IU/mL in the 48th hour in the MiaPaCa-2 cell line and 50 IU/mL in the 48th hour in the HepG2 cell line. CCND1 (cyclin D1), CDK4, CDK6, p21, p16, p53, caspase-3, caspase-9, caspase-8, Bcl-2, BID, DR4, DR5, FADD, TRADD, Bax, gene mRNA expressions were evaluated by Real-time PCR. Real-time PCR analysis showed that CCND1 expression was reduced in HepG2 dose the group cells when compared with the control group cells and p53, caspase-3, caspase p21, caspase-8 and expressions were increased in the dose group cells when compared with the control group cells. CCND1, CDK4 and CDK6 expressions were reduced in MIA PaCa-2 dose group cells when compared with the control group cells and p53 expression was increased in the dose group cells when compared with the control group cells. Other expressions of genes were found statistically insignificant both of cell lines. It was found that bemiparin in HepG2 and MIA PaCa-2 cells suppressed invasion, migration, and colony formation by using matrigel invasion chamber, and colony formation assay, respectively. In conclusion, it is thought that bemiparin indicates anti-tumor activity by affecting cell cycle arrest, apoptosis, invasion, migration, and colony formation on cancer cells.


Assuntos
Antineoplásicos/farmacologia , Heparina de Baixo Peso Molecular/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Genes cdc/efeitos dos fármacos , Humanos
8.
Tumour Biol ; 37(5): 6673-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26646564

RESUMO

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor that affects older people. Although the current therapeutic approaches for GBM include surgical resection, radiotherapy, and chemotherapeutic agent temozolomide, the median survival of patients is 14.6 months because of its aggressiveness. Zoledronic acid (ZA) is a nitrogen-containing bisphosphonate that exhibited anticancer activity in different cancers. The purpose of this study was to assess the potential effect of ZA in distinct signal transduction pathways in U87-MG cells. In this study, experiments performed on U87-MG cell line (Human glioblastoma-astrocytoma, epithelial-like cell line) which is an in vitro model of human glioblastoma cells to examine the cytotoxic and apoptotic effects of ZA. IC50 dose of ZA, 25 µM, applied on U87-MG cells during 72 h. ApoDIRECT In Situ DNA Fragmentation Assay was used to investigate apoptosis of U87MG cells. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) (LightCycler480 System) was carried out for 48 gene expression like NF-κB, Toll-like receptors, cytokines, and inteferons. Our results indicated that ZA (IC50 dose) increased apoptosis 1.27-fold in U87MG cells according to control cells. According to qRT-PCR data, expression levels of the endoplasmic reticulum-nuclei-1 (ERN1), Toll-like receptor 2 (TLR2), and human IFN regulatory factor 5 (IRF5) tumor suppressor genes elevated 2.05-, 2.08-, and 2.3-fold by ZA, respectively, in U87MG cells. Our recent results indicated that ZA have a key role in GBM progression and might be considered as a potential agent in glioma treatment.


Assuntos
Apoptose/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Endorribonucleases/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/genética , Imidazóis/farmacologia , Fatores Reguladores de Interferon/genética , Proteínas Serina-Treonina Quinases/genética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Fragmentação do DNA , Perfilação da Expressão Gênica , Humanos , Receptor 2 Toll-Like/genética , Ácido Zoledrônico
9.
Tumour Biol ; 37(2): 1933-40, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26334619

RESUMO

Ferulic acid (4-hydroxy-3-methoxycinnamic acid; FA), a common dietary plant phenolic compound, is abundant in fruits and vegetables. The aim of present study is to investigate the effects of FA on cell cycle, apoptosis, invasion, migration, and colony formation in the TT medullary thyroid cancer cell line. The effect of FA on cell viability was determined by using CellTiter-Glo assay. IC50 dose in the TT cells was detected as 150 µM. URG4/URGCP (upregulated gene-4/upregulator of cell proliferation) is a novel gene in full-length mRNA of 3.607 kb located on 7p13. It was determined that FA caused a decrease in the expression of novel gene URG4/URGCP, CCND1, CDK4, CDK6, BCL2, MMP2, and MMP9, a significant increase in the expression of p53, PARP, PUMA, NOXA, BAX, BID, CASP3, CASP9, and TIMP1 genes in TT human thyroid cancer cell line by using real-time PCR. It was found that FA in TT cells suppressed invasion, migration, and colony formation by using matrigel invasion chamber, wound healing, and colony formation assay, respectively. In conclusion, it is thought that FA indicates anticarcinogenesis activity by affecting cell cycle arrest, apoptosis, invasion, migration, and colony formation on TT cells.


Assuntos
Carcinoma Neuroendócrino/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Proteínas de Neoplasias/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Apoptose/efeitos dos fármacos , Carcinoma Neuroendócrino/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Glândula Tireoide/metabolismo , Regulação para Cima/efeitos dos fármacos
10.
Tumour Biol ; 37(2): 2647-53, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26399993

RESUMO

Exendin-4 is a GLP-1 analog used for the treatment of type 2 diabetes mellitus in its synthetic form. As women with diabetes have higher breast cancer incidence and mortality, we examined the effect of the incretin drug exendin-4 on breast cancer cells. The aim of the study is to investigate anticancer mechanism of exendin-4 in MCF-7 breast cancer cells. Cytotoxic effects of exendin-4 were determined by XTT assay. IC50 dose in MCF-7 cells were detected as 5 µM at 48th hour. Gene messenger RNA (mRNA) expressions were evaluated by real-time PCR. According to results, caspase-9, Akt, and MMP2 expression was reduced in dose group cells, compared with the control group cells. p53, caspase-3, caspase-8, caspase-10, BID, DR4, DR5, FADD, TRADD, PARP, PTEN, PUMA, NOXA, APAF, TIMP1, and TIMP2 expression was increased in dose group cells, compared with the control group cells. Effects of exendin-4 on cell invasion, colony formation, and cell migration were detected by Matrigel chamber, colony formation assay, and wound-healing assay, respectively. To conclude, it is thought that exendin-4 demonstrates anticarcinogenesis activity by effecting apoptosis, invasion, migration, and colony formation in MCF-7 cells. Exendin-4 may be a therapeutic agent for treatment of breast cancer as single or in combination with other agents. More detailed researches are required to define the pathways of GLP-1 effect on breast cancer cells because of the molecular biology of breast cancer that involves a complex network of interconnected signaling pathways that have role in cell growth, survival, and cell invasion.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Peptídeos/farmacologia , Peçonhas/farmacologia , Anticarcinógenos/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Exenatida , Feminino , Humanos , Células MCF-7 , Transdução de Sinais/efeitos dos fármacos
11.
Gene ; 576(1 Pt 3): 476-82, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26516023

RESUMO

Novel and combinatorial treatment methods are becoming sought after entities in cancer treatment and these treatments are even more valuable for pancreatic cancer. The scientists are always on the lookout for new chemicals to help them in their fight against cancer. In this study, we examine the effects of ferulic acid (FA), a phenolic compound, on gene expression, viability, colony formation and migration/invasion in the cultured MIA PaCa-2 human pancreatic cancer cell. Cytotoxic effects of FA were determined by using trypan blue dye exclusion test and Cell TiterGlo (CTG) assay. IC50 dose in MIA PaCa-2 cells was detected as 500µM/ml at the 72nd hour. Expression profiles of certain cell cycle and apoptosis genes such as CCND1 (cyclin D1),CDK4, CDK6, RB, p21, p16, p53, caspase-3, caspase-9, caspase-8, caspase-10, Bcl-2, BCL-XL,BID, DR4,DR5,FADD,TRADD,PARP, APAF, Bax, Akt, PTEN, PUMA, NOXA, MMP2, MMP9, TIMP1 and TIMP2 were determined by real-time PCR. The effect of FA on cell viability was determined by CellTiter-Glo® Luminescent Cell Viability Assay. Additionally, effects of FA on colony formation and invasion were also investigated. It was observed that FA caused a significant decrease in the expression of CCND1, CDK 4/6, Bcl2 and caspase 8 and 10 in the MIA PaCa-2 cells while causing an increase in the expression of p53, Bax, PTEN caspase 3 and 9. FA was observed to decrease colony formation while inhibiting cell invasion and migration as observed by the BioCoat Matrigel Invasion Chamber guide and colony formation assays. In conclusion, FA is thought to behave as an anti-cancer agent by affecting cell cycle, apoptotic, invasion and colony formation behavior of MIA PaCa-2 cells. Therefore, FA is placed as a strong candidate for further studies aimed at finding a better, more effective treatment approach for pancreatic cancer.


Assuntos
Ácidos Cumáricos/farmacologia , Metástase Neoplásica/prevenção & controle , Neoplasias Pancreáticas/patologia , Linhagem Celular Tumoral , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Cicatrização/efeitos dos fármacos
12.
Adv Med Sci ; 60(1): 94-100, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25625368

RESUMO

PURPOSE: Apelin is an adipokine that plays a role in the regulation of many biological functions in mammals including the neuroendocrine, cardiovascular, immune systems, glucose homeostasis and obesity. It can act via autocrine, paracrine, endocrine, and exocrine signaling. We aimed to identify the role of apelin pathophysiology of diabetes. MATERIAL/METHODS: 37 male Wistar Albino rats aged 8-10 weeks were divided in four experimental groups as: control group (C) control+apelin group (C+A), diabetic group (D) diabetic+apelin group (D+A). Apelin and apelin receptor mRNA gene expressions in heart and aorta tissue were determined by real-time polymerase chain reaction. The plasma levels of insulin and plasma apelin were determined by ELISA. RESULTS: Plasma levels of insulin, glucose, blood pressure levels were significantly lower in D+A group. There was no statistically significant difference for level of apelin between diabetic groups. On the other hand, differences for apelin and APJ mRNA expression in heart and vascular tissue were found significant between groups. CONCLUSIONS: Apelin can be used as a therapeutic agent in the treatment of type II diabetes in the future.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Animais , Apelina , Receptores de Apelina , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas-G/genética
13.
Clin Exp Hypertens ; 35(7): 550-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23387534

RESUMO

Apelin, a novel multifunctional peptide implicated in the regulation of the cardiovascular system, including blood pressure and cardiac function control, has been postulated to be involved in the pathophysiology of hypertension and hypertensive heart disease. The aim of this study was to investigate, for the first time, whether the effects of apelin's chronic application might be involved in deoxycorticosterone acetate-salt-induced hypertensive rats (DOCA-salt rats). In this study, 8-10-week-old male Wistar rats were divided into four groups: control, control + apelin, DOCA-salt rats, DOCA-salt rats + apelin. Deoxycorticosterone Acetate (25 mg/kg of body weight) was injected subcutaneously, twice a week for 4 weeks. These rats received NaCl 1% instead of tap water for drinking during the experimental period. Later, rats were randomly treated with pyroglutamylated apelin-13 (200 µg. kg(-1). day(-1) intraperitonealy) for 17 days. The concentrations of apelin, endothelin-1, angiotensin-converting enzyme, angiotensinogen, and angiotensin II were analyzed in the plasma. The mRNA level of apelin and apelin receptor were determined in the heart and aorta tissue by real-time polymerase chain reaction, respectively. It was found that apelin reduces blood pressure in DOCA-salt rats. Apelin can be used as a therapeutic agent in the treatment of hypertension in the future.


Assuntos
Hipertensão/etiologia , Hipertensão/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Angiotensina II/sangue , Angiotensinogênio/sangue , Animais , Aorta/metabolismo , Apelina , Receptores de Apelina , Pressão Sanguínea/fisiologia , Acetato de Desoxicorticosterona , Endotelina-1/sangue , Hipertensão/genética , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Miocárdio/metabolismo , Peptidil Dipeptidase A/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/fisiologia , Sistema Renina-Angiotensina/fisiologia
14.
Mol Biol Rep ; 39(1): 335-41, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21553054

RESUMO

Excision Repair Cross-Complementing Group 1 (ERCC1) is an important DNA repair gene, playing critical role in nucleotide excision repair pathway and having a significant influence on genomic instability. Some studies support that ERCC1 might be a potential predictive and prognostic marker in non-small cell lung cancer (NSCLC). ERCC1 has also been shown to be a promising biomarker in NSCLC treated with a cisplatin-based regimen. Therefore, the determination of ERCC1 expression at DNA, mRNA and protein level in different stages of NSCLC is still an important topic in the cancer. Ninety-one formalin-fixed paraffin-embedded tumor samples histopathologically diagnosed as NSCLC were examined in this study. ERCC1 expression at protein level were scored by immunohistochemistry. The gene amplification and mRNA expression levels for ERCC1 were determined by real-time quantitative PCR. There was complete concordance among the three methods in 39 tumor samples (42.9%). A strong correlation was found between DNA amplification and mRNA expression (r=0.662) while there was no correlation between mRNA and protein assessment for ERCC1 expression (r=-0.013). ERCC1 expression at mRNA and DNA level (63.1 and 84.2%, respectively) in tumors at stage III was higher than at the other stages. In contrast, the protein expression at stage II and III (56.6 and 52.6%, respectively) of NSCLC was lower than that of tumors with stage I NSCLC. These results show that the mechanism by which ERCC1 expression might play a role in tumor behavior. This study was also confirmed that the appropriate validation and qualification in methods used for ERCC1 status were needed before its clinical application and implementation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endonucleases/genética , Endonucleases/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Marcadores Genéticos/genética , RNA Mensageiro/genética , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , DNA Complementar/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase em Tempo Real
15.
Genet Test Mol Biomarkers ; 15(5): 357-60, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21288129

RESUMO

Aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of the tumor-related genes including DNA repair genes. The objective of this study was to determine the frequency of promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene as a DNA repair gene in nonsmall cell lung cancer (NSCLC) and to analyze the correlation with clinicopathological parameters including age, gender, smoking status, histological subtype, and clinical stage. Eighty patients with NSCLC were included in this study. The analysis of DNA methylation was performed on formalin-fixed, paraffin-embedded lung cancer tissues. Following DNA isolation and bisulfite treatment, DNA methylation was analyzed by methylation-specific real-time polymerase chain reaction. MGMT promoter methylation was detected in 51 of 80 (64%) NSCLC patients. There was a significant correlation between MGMT methylation and tumor stage (p = 0.01). The frequencies of the promoter methylation of MGMT gene in smokers and older patients were higher than in their counterparts. In conclusion, the present study provides strong evidence for a higher frequency of promoter methylation of the MGMT gene in NSCLC, indicating that it is a common event during the carcinogenesis of NSCLC.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas/genética , Proteínas Supressoras de Tumor/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Supressoras de Tumor/metabolismo
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