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1.
Tumour Biol ; 37(3): 3017-24, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26419593

RESUMO

Metastasis occurs due to migration of the cells from primary tumor toward other tissues by gaining invasive properties. Since metastatic invasion shows a strong resistance against conventional cancer treatments, the studies on this issue have been focused. Within this context, inhibition of migration and determination of the relationships at the gene level will contribute to treatment of metastatic cancer cases. We have aimed to demonstrate the impact of TGF-ß1 and fluvastatin on human breast cancer (MCF-7) and human hepatocellular carcinoma (Hep3B) cell cultures via Real-Time Cell Analyzer (RTCA) and to test the expression levels of some genes (NDRG1, SGK1, TWIST1, AMPKA2) and to compare their gene expression levels according to RTCA results. Both of cell series were applied TGF-ß1 and combinations of TGF-ß1/fluvastatin. Primer and probes were synthesized using Universal Probe Library (UPL, Roche) software, and expression levels of genes were tested via qPCR using the device LightCycler 480 II (Roche). Consequently, fluvastatin dose-dependently inhibited migration induced by TGF-ß1 in both groups. This inhibition was accompanied by low level of SGK1 messenger RNA (mRNA) and high levels of NDRG1 and AMPKA2 mRNA. Thus, we conclude that fluvastatin plays an important role in reducing resistance to chemotherapeutics and preventing metastasis.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Proteínas de Ciclo Celular/genética , Ácidos Graxos Monoinsaturados/farmacologia , Proteínas Imediatamente Precoces/genética , Indóis/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Metástase Neoplásica/prevenção & controle , Proteínas Serina-Treonina Quinases/genética , Proteínas Quinases Ativadas por AMP/genética , Neoplasias da Mama/patologia , Carcinoma Hepatocelular/patologia , Movimento Celular/efeitos dos fármacos , Feminino , Fluvastatina , Humanos , Neoplasias Hepáticas/patologia , Células MCF-7 , Proteínas Nucleares/genética , RNA Mensageiro/análise , Fator de Crescimento Transformador beta1/farmacologia , Proteína 1 Relacionada a Twist/genética
2.
Clin Lab ; 62(3): 401-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27156330

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cause of cancer diagnosed in males and the second in females. Survival is strongly related to stage at diagnosis. There is an urgent need to find a noninvasive biomarker that can be commonly applied for screening diagnosis, early detection of recurrence, and monitoring of metastatic CRC. Protein caveolin-1 (CAV-1) has been known to be expressed abnormally in colon cancer and appears to contribute to aberrant signaling and protein trafficking. There are controversial results regarding the role of CAV-1 in cancer. We hypothesized that levels of CAV-1 in serum of patients with CRC might be important to estimate the progression of the disease. Therefore, the purpose of this study is to investigate whether serum CAV-1 might be used as a factor determining progression of CRC. METHODS: A total of 61 patients with CRC (26 male, 35 female) and 46 controls (38 male, 8 female) were enrolled. Serum CAV-1 levels were measured by ELISA. The relationship between CAV-1 and progression-free survival (PFS) was analyzed with use of receiver operating characteristic (ROC) and Kaplan-Meier analysis. Results were given as median (95% CI). Mann-Whitney test was used for the comparison of groups. RESULTS: CAV-1 levels were found to be 11.5 ng/mL (10.4-12.9) in CRC and 11.9 ng/mL (10.7-14.4) in controls (p = 0.465). The serum CAV-1 levels in CRC patients with disease progression and without progression were respectively 10.0 ng/mL (8.5-11.3) and 12.2 ng/mL (11.1-14.8) (p = 0.023). In ROC analysis, if CAV-1 levels are equal or lesser than 10.73 ng/mL, it might show presence of progression with a sensitivity 73.3% and specificity 66.7% in patients with CRC (area under the ROC curve (AUC) = 0.697, p = 0.005). The mean PFS time was found to be 29.7 months (19.8-39.7, 95% CI for the mean) in patients who have CAV-1 level ≤ 10.73 ng/mL and 61.9 months (44.2-79.6) in patients who have CAV-1 level > 10.73 ng/mL [hazard ratios (HR) with 95% CI = 3.49 (1.26 - 9.68) (p = 0.017)]. CONCLUSIONS: Our results strongly suggest that CAV-1 levels might be used as a marker to determine progression of CRC. When considered in combination with other biomarkers of CRC, CAV-1 is clinically informative and instructive.


Assuntos
Biomarcadores Tumorais/sangue , Caveolina 1/sangue , Neoplasias Colorretais/sangue , Idoso , Neoplasias Colorretais/mortalidade , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Ren Fail ; 38(8): 1249-55, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27435174

RESUMO

AIM: Contrast medium-induced nephropathy is one of the major complications of intravenous contrast medium use. But its pathogenesis is unclear. Epithelial mesenchymal transition (EMT) is defined as the transformation of the primer epithelial cells to mesenchymal cells. EMT in tubular cells might cause tubulointerstitial damage. In this study, we investigated whether or not EMT has a role in radiocontrast-induced nephropathy. Radiocontrast medium might be triggering reversible EMT via serum and glucocorticoid-regulated kinase 1 (SGK 1). We investigated the effect of different concentrations of the contrast agent iopromide on human proximal tubule cell (HK-2) culture by measuring the level of SGK1, snail family zinc finger 1 (SNAIL1), connective tissue growth factor (CTGF), and collagen type I alpha 1 (COL1A1). METHODS: We conducted a scratch assay and qPCR. HK-2 cells were cultured in the petri dishes/flasks and starved with serum-free medium. The 40, 20, and 10 mg/mL doses of iopromide were administrated to cells. The scratches were photographed immediately and again at the 20th hour. The levels of gene expression of SGK1, SNAIL1, CTGF, and COL1A1 were measured using the real-time qPCR system at the end of the 24th hour. RESULTS: Iopromide caused the breaking of intercellular connections, the disappearance of the cobblestone appearance of cells, and the migration of cells at the 20th hour in the scratch assay. It also increased the expression of SGK1, SNAIL1, CTGF, and COL1A1 genes. CONCLUSION: Our study concluded that certain important markers of EMT increase in different concentrations of the contrast agent. High osmolality might trigger EMT. The relationship between contrast agent and EMT has not been defined before. Further in vivo and in vitro studies are required.


Assuntos
Meios de Contraste/efeitos adversos , Transição Epitelial-Mesenquimal/genética , Iohexol/análogos & derivados , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Túbulos Renais Proximais/metabolismo , Diferenciação Celular , Linhagem Celular , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Fator de Crescimento do Tecido Conjuntivo/genética , Humanos , Proteínas Imediatamente Precoces/genética , Iohexol/efeitos adversos , Proteínas Serina-Treonina Quinases/genética , Fatores de Transcrição da Família Snail/genética
4.
Clin Lab ; 61(12): 1911-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26882815

RESUMO

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by the release of inflammatory mediators. The aim of this study was to compare serum levels of pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) in patients with acute exacerbations of COPD with those of a healthy control group. METHODS: The study included 107 men and 19 women, with mean age of 66.5 (32 - 87) years who were diagnosed with acute COPD exacerbations and 48 healthy individuals as a control group. The serum PTX3 and hs-CRP levels were measured and pulmonary function tests were performed. RESULTS: The mean serum level of the hs-CRP was 39.56 mg/L (10.10 - 262), and it was higher in the COPD group than in the control group (p < 0.0001). The hs-CRP levels increased in accordance with the severity of the COPD (p < 0.0001). The serum PTX3 level was 0.52 pcg/dL (0.42 - 0.56) in acute exacerbations. There was a correlation between the PTX3 levels and the pulmonary function tests, including FEV1, FVC, and FEV1/FVC (r = 0.317, p < 0.001; r = 0.385, p < 0.0001, and r = 0.248, p = 0.001, respectively). CONCLUSIONS: The short pentraxin hs-CRP is elevated in COPD patients with acute exacerbations and correlates with the severity of the disease compared with the long pentraxin PTX3. These results support the idea that hs-CRP can be used as an earlier determinant of inflammation in COPD acute exacerbations and that PTX3 cannot be used as a marker of acute exacerbation and disease severity.


Assuntos
Proteína C-Reativa/análise , Doença Pulmonar Obstrutiva Crônica/sangue , Componente Amiloide P Sérico/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
5.
Tumour Biol ; 35(6): 5945-51, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24622883

RESUMO

Histone deacetylase (HDAC) inhibitors, such as trichostatin A (TSA), and iron chelators, including deferoxamine (DFO) and phenanthroline (PHEN), appear to have anticancer effects. We hypothesized that the HDAC inhibitors and iron chelators would be synergistic with their effect on breast cancer cell line MCF7, because the HDAC inhibitors increase glucose-regulated protein 78 (Grp78) and the iron chelators reduce its expression. Although the administration of TSA alone resulted in a dose-related decrease in the cell index, it did not have an antiproliferative effect except the 62.5 and 500 nM of TSA. However, all doses of TSA produced a cytotoxic effect from the initial hours when combined with 150 µM of DFO and 25 µM of PHEN. DFO and PHEN downregulated Grp78, Grp94, and MRP1 expressions and upregulated CHOP and HO-1 expressions. TSA upregulated all the genes in various rates when used alone but resulted in decreased expression levels when combined with DFO and PHEN. Increased HDAC-1 levels in the Grp78 promoter region indicated that DFO and PHEN either promoted binding of HDAC-1 to this region or inhibited its detachment. We determined that the reduction of increased Grp78, Grp94, HO-1, and MRP1 expressions, which appears to inhibit the chemotherapeutic effect of TSA, through the combination with DFO or PHEN will contribute to the anticancer effect.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Choque Térmico/fisiologia , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Quelantes de Ferro/farmacologia , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/genética , Heme Oxigenase-1/genética , Humanos , Células MCF-7 , Glicoproteínas de Membrana/fisiologia , Regiões Promotoras Genéticas , Fator de Transcrição CHOP/genética
6.
Clin Chem Lab Med ; 52(12): 1823-33, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25153598

RESUMO

BACKGROUND: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. METHODS: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). RESULTS: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. CONCLUSIONS: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.


Assuntos
Proteínas Sanguíneas/análise , Testes de Química Clínica , Compostos Inorgânicos/sangue , Lipídeos/sangue , Compostos Orgânicos/sangue , Adulto , Fatores Etários , Idoso , Análise de Variância , Proteínas Sanguíneas/normas , Índice de Massa Corporal , Testes de Química Clínica/normas , Feminino , Humanos , Compostos Inorgânicos/normas , Lipídeos/normas , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Compostos Orgânicos/normas , Valores de Referência , Turquia
7.
Ren Fail ; 36(7): 1104-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24937012

RESUMO

Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69 M × 10(-5) at 24th hour and 3.93 M × 10(-6) at 48th hour. IC50 dose for pioglitazone was 1.61 M × 10(-3) at 24th hour and 2.85 M × 10(-4) at 48th hour. Although cells were treated the dose of 40,225 mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Creatina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insuficiência Renal/prevenção & controle , Tiazolidinedionas/uso terapêutico , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Humanos , Pioglitazona , Insuficiência Renal/induzido quimicamente
8.
Ren Fail ; 36(7): 1108-13, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24845105

RESUMO

Abstract Cisplatin is one of the commonly used anticancer drugs and nephrotoxicity limits its use. The aim of this study is to investigate the possible protective effect of creatine supplementation on cisplatin-induced nephrotoxicity. Sixty male Sprague-Dawley rats were divided into three groups: Group I: Cisplatin (n=20) (7 mg/kg cisplatin intraperitoneal (i.p.) single dose), group II: Cisplatin+creatine monohydrate (n=20) (7 mg/kg cisplatin i.p. single dose and 300 mg/kg creatine p.o. daily for 30 days starting on first day of cisplatin injection), group III: Control group (n=20) (Serum physiologic, 2.5 mL/kg i.p.). Sacrifications were performed at first week and 30th day. Blood urea nitrogen (BUN) and serum creatinine levels, histopathological evaluation, mitochondrial deoxyribonucleic acid (mtDNA) common deletion rates, and body weights of rats were evaluated. A significant decrease in body weight, higher values of kidney function tests, histopathological scores, and mtDNA deletion ratios were observed in group I compared to control group at days 7 and 30 (p<0.05). In group II, there was a slight decrease in body weight at same days (p=0.931 and 0.084, respectively). Kidney function tests, histopathological scores, and mtDNA common deletion ratios were statistically better in group II than group I at 7th and 30th day (p<0.05). Although creatine significantly reversed kidney functions and pathological findings, this improvement was not sufficient to reach normal control group's results at days 7 and 30. In conclusion, the present study demonstrates that creatine administration is a promising adjuvant protective drug for reducing nephrotoxic effect of cisplatin.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Creatina/uso terapêutico , Insuficiência Renal/prevenção & controle , Animais , Dano ao DNA/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Ratos Sprague-Dawley , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/patologia , Redução de Peso/efeitos dos fármacos
9.
Hepatogastroenterology ; 60(123): 601-4, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23108080

RESUMO

BACKGROUND/AIMS: Our purpose in this study was to analyze telomere length and telomerase activity before and after eradication treatment in gastric mucosa in patients positive for H. pylori. METHODOLOGY: There were two groups: a control group (n=17) and a study group (n=21). For H. pylori eradication, the patients were administrated proton pump inhibitor (PPI) + clarithromycin + amoxicillin or PPI + metronidazole + tetracycline + bismuth for 14 days. Telomere length was analyzed with RT-PCR and telomerase activity with PCR-ELISA on biopsy specimens from the antrum. The result p<0.05 was considered significant. RESULTS: Prior to eradication, there was no significant difference between telomere lengths of the patient and control groups (2481.2±1823 and 2958.9±1345.7 bp, p=0.11, respectively). The telomere length of the study group became longer after eradication (before 2481.2±1823bp, after 3766.3±1608.8bp, p=0.01). Telomerase activity was not detected in either the patient or the control group. CONCLUSIONS: An increase in telomere length was observed with H. pylori eradication. This finding may indicate the importance of H. pylori eradication to avoid the development of gastric cancer.


Assuntos
Antibacterianos/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/uso terapêutico , Homeostase do Telômero , Telômero/metabolismo , Adulto , Biópsia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Telomerase/metabolismo , Telômero/microbiologia , Fatores de Tempo , Resultado do Tratamento
10.
Int J Vitam Nutr Res ; 83(4): 232-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-25008013

RESUMO

BACKGROUND: Previous studies have shown the relationship between in utero lung development and vitamin D [25(OH)D], but there have been no studies to investigate whether vitamin D deficiency is a risk factor for respiratory distress syndrome (RDS) in preterm babies. OBJECTIVES: In this study, we investigated if 25(OH)D deficiency is a risk factor for RDS. METHODS: One hundred fifty-two preterm newborns, born at 29 - 35 weeks gestational age, were included in the study following informed consent from the parents. Peripheral blood samples were collected within the first 24 hours of life and 25(OH)D levels were measured by liquid chromatography-tandem mass spectrometry. Demographic characteristics of the babies and the diagnosis of RDS were recorded. RESULTS: In 64 % of preterm infants, 25(OH)D levels were compatible with severe deficiency (≤ 10 ng/mL), 33 % with moderate deficiency (10 - 20 ng/mL), and 3 % with mild deficiency (20 - 30 ng/mL). In none of the babies was a normal 25(OH)D level observed. Serum 25(OH)D levels were not correlated with gestational age. Respiratory distress syndrome was more common in preterm babies with severe (28 %) compared to mild-moderate 25(OH)D deficiency (14 %) (p < 0.05). CONCLUSIONS: None of the preterm infants in this study had normal vitamin D level, which underlined the burden of vitamin D deficiency in pregnant women and their offspring. RDS was more common in severely vitamin D-deficient preterms. Determination of vitamin D status of the mothers and appropriate supplementation might be a valuable strategy to reduce RDS, in addition to antenatal steroids. Besides, since vitamin D is a regulatory factor in many organs during fetal development, long-term effects of in utero vitamin D deficiency warrant further studies.


Assuntos
Doenças do Prematuro/epidemiologia , Recém-Nascido Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Deficiência de Vitamina D/complicações , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez , Fatores de Risco , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia
11.
Indian J Biochem Biophys ; 50(6): 505-10, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24772975

RESUMO

The endoplasmic reticulum (ER) is related to the various signal routes that are activated in unfolded protein response (UPR). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expressions demonstrate UPR activity. In this study, we investigated the UPR gene expressions in larynx epidermoid carcinoma (HEp2) to which dexamethasone (dex) was applied. HEp2 cells were administered for 48 h with different combinations using 0.1 microM and 1 microM dex, 1 mM phenyl butyric acid (PBA) and 100 ng/ml lipopolysaccharide (LPS). The Grp78, Grp94, CHOP, MTJ1 and HMOX1 genes expression was determined using quantitative RT-PCR. The Grp78, MTJ1 and HMOX1 gene expression increased with the administration of 1 microM dex. CHOP expression, on the other hand, decreased with 0.1 microM dex. When dex was combined with LPS, nearly all gene expressions decreased. The increase in Grp78, Grp94, HMOX1 and MTJ1 gene expression was greater in groups in which dex was administered in combination with PBA than in groups in which dex was administered alone. Dex in low dose (0.1 microM) caused a decrease in CHOP expression in HEp2 cells and an increase in Grp78 expression, in particular. The changes in UPR genes expressions may lead to the extended survival of the cells.


Assuntos
Carcinoma de Células Escamosas/patologia , Dexametasona/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Resposta a Proteínas não Dobradas/genética , Apoptose/efeitos dos fármacos , Ácido Butírico/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Interações Medicamentosas , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico/genética , Heme Oxigenase-1/genética , Humanos , Lipopolissacarídeos/farmacologia , Proteínas de Membrana/genética , Fator de Transcrição CHOP/genética
12.
Tumour Biol ; 33(6): 2107-15, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22890828

RESUMO

Our purpose in this study is to analyze mitochondrial DNA (mtDNA) lesion frequencies and mtDNA(4977) deletion in HepG2 cells to examine the effects of ouabain on mtDNA. HepG2 cells were treated with 0.75, 7.5, 75, and 750 nM of ouabain for 24 h in the presence and absence of 10 mM 2-deoxyglucose (2-DG). The frequency of mtDNA(4977) deletions and mitochondrial lesions were determined by real-time polymerase chain reaction. A ≥ 1.2-fold change or greater was considered significant. Ouabain doses of 750, 75, and 7.5 nM alone increased the frequency of mtDNA(4977) deletions 1.39, 1.92, and 1.44 times, respectively. The 750 and 75 nM ouabain doses combined with 2-DG increased the mtDNA(4977) deletion frequency 4.94 and 1.57 times, respectively. The 750 and 75 nM ouabain doses alone increased the mtDNA lesion frequency 2.5 and 1.5 times, respectively. The 750 nM ouabain dose combined with 2-DG increased the mtDNA lesion frequency 2.28 times. The 7.5 nM ouabain dose alone and combined with 2-DG decreased the mtDNA lesion frequency 0.67 and 0.45 times, respectively. Ouabain alone and when combined with 2-DG increases mtDNA lesion and mtDNA(4977) deletion frequencies. This supports the thesis that ouabain creates oxidative stress and induces DNA damage and apoptosis.


Assuntos
Cardiotônicos/farmacologia , Dano ao DNA/efeitos dos fármacos , DNA Mitocondrial/genética , Mitocôndrias/efeitos dos fármacos , Ouabaína/farmacologia , Estresse Oxidativo/efeitos dos fármacos , DNA/genética , DNA/isolamento & purificação , Dano ao DNA/genética , Desoxiglucose/farmacologia , Células Hep G2 , Humanos , Mitocôndrias/genética , Mitocôndrias/patologia , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase em Tempo Real
13.
Int J Colorectal Dis ; 25(2): 205-12, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19888587

RESUMO

PURPOSE: In this study, we have examined the correlation between colorectal cancer (CRC) and serum adiponectin and resistin levels, body mass index and insulin resistance. METHODS: The relation between serum adiponectin and resistin levels, obesity and insulin resistance in 36 CRC patients and 37 controls was examined. RESULTS: Insulin and homeostasis model assessment insulin resistance index (HOMA-IR) levels were higher, and adiponectin levels were significantly decreased in patients versus controls, whereas, resistin levels were significantly increased. A negative correlation between adiponectin, HOMA-IR, and insulin and a positive correlation between HOMA-IR, insulin, and stage were detected. There was no correlation between the stage and resistin. Adiponectin level negatively correlated with the stage. Adiponectin and resistin could play a role in colon cancer carcinogenesis, and adiponectin could be responsible for poor prognosis in colorectal cancer.


Assuntos
Neoplasias Colorretais/sangue , Resistência à Insulina , Resistina/sangue , Adiponectina/sangue , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Neoplasias Colorretais/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
14.
Ren Fail ; 32(3): 368-71, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20370454

RESUMO

AIM: Nephrotoxicity is a major side effect of cisplatin (Cis), a widely used chemotherapeutic drug. Recent studies have strongly suggested that inflammatory mechanisms may play an important role in the pathogenesis of Cis nephrotoxicity. Rosiglitazone (Ros), a peroxisome proliferator-activated receptor-gamma agonist has been recently demonstrated to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The aim of this study was to evaluate the effect of Ros on the prevention of Cis-induced nephrotoxicity. METHODS: Eighteen male Sprague-Dawley rats weighing 150-200 g were included in the study. The rats were randomly divided into three groups: group 1: Cis-treated group; group 2: Cis-Ros-treated group; group 3: saline-treated group. Blood urea nitrogen (BUN) and serum creatinine concentrations were measured. In addition, extent of histological renal tubular injury in each animal was graded histologically. RESULTS: Mean BUN and serum creatinine concentrations were significantly lower in group 3 than in group 1 (p<0.05) and group 2 (p<0.05). There were no significant differences in terms of BUN and serum creatinine concentrations between groups 1 and 2 (p>0.05). Acute tubular injury with karyomegalic changes in corticomedullary junction was significantly higher in groups 1 and 2 than group 3 (p<0.05). However, there were no significant differences between groups 1 and 2 (p>0.05). CONCLUSION: This study indicates that post-insult administration of Ros does not seem to have a beneficial effect on prevention and severity of nephrotoxicity induced by Cis.


Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Rim/efeitos dos fármacos , PPAR gama/farmacologia , Tiazolidinedionas/farmacologia , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Rim/patologia , Necrose Tubular Aguda/induzido quimicamente , Necrose Tubular Aguda/patologia , Masculino , Ratos , Ratos Wistar , Rosiglitazona
15.
Arch Med Sci ; 16(3): 577-583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32399105

RESUMO

INTRODUCTION: Telomeres play an important role in maintaining chromosomal integrity. Functional loss of telomeres increases the risk of cancer by causing genomic instability. Telomere length abnormalities have been reported in several precancerous lesions. There is no study that evaluates telomere length in Billroth II distal gastrectomy, which is known as a risk factor for gastric stump carcinogenesis, in the literature. The aim of this study was to assess the relationship between the telomere length of residual gastric mucosal samples, peripheral blood lymphocytes, and other clinicopathological parameters of patients who had undergone Billroth II distal gastrectomy. MATERIAL AND METHODS: There were two groups: a control group (n = 15) and a patient group (n = 15). In all cases, upper gastrointestinal endoscopy was performed, and biopsies were taken during endoscopy. Telomere lengths were measured by qRT-PCR. RESULTS: It was observed that the lengths of the telomeres were shortened as the time of postoperative period increased in the patient group (r = -0.126) (p > 0.05). Also, the lengths of the telomeres were shortened in chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia. CONCLUSIONS: The telomere length was shortened as the time of postoperative period increased in the patient group. The telomeres were also shorter in chronic inflammation, neutrophil activity, intestinal metaplasia, and glandular atrophy, in all of the study groups. Telomere length abnormalities in gastric stump carcinogenesis process may be a guide for early diagnosis and treatment.

16.
Environ Mol Mutagen ; 49(3): 185-91, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18213655

RESUMO

Pioglitazone (PIO), a member of the thiazolidinedione class of antidiabetic agents, specifically targets insulin resistance. Drugs of this class act as ligands for the gamma subtype of the peroxisome proliferator-activated receptor. Although troglitazone, another drug in this class, displayed unacceptable hepatotoxicity, PIO was approved for human use by the U.S. Food and Drug Administration. To our knowledge, there are no published reports on the genotoxicity of PIO; however, the package insert indicates that it has minimal genotoxicity. In this study, we used the comet assay to investigate the DNA damage in the peripheral blood and liver cells of rats treated with PIO. Sixteen male Sprague-Dawley rats were randomly distributed into four groups, and dosed daily for 14 days by oral gavage with 0, 10, 20, and 40 mg/kg/day PIO. A dose-dependent increase in DNA damage, as assessed by % tail DNA, was observed in both hepatocytes and blood lymphocytes of the PIO-treated groups, with significant increases detected between the rats treated with all the doses of PIO and the control, and between the rats treated with different PIO doses (P < 0.005 to P < 0.0001). Treating nuclei from the exposed animals with an enzyme cocktail containing Fpg and Endonuclease III prior to performing the comet assay increased the level of DNA damage, which reflects oxidized purine and pyrimidine. Taken together, our data indicate that PIO is able to dose-dependently induce DNA damage in both the liver and blood lymphocytes of rats, which is partially due to the generation of oxidative lesions.


Assuntos
Dano ao DNA , Hepatócitos/efeitos dos fármacos , Hipoglicemiantes/toxicidade , Linfócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Tiazolidinedionas/toxicidade , Animais , Ensaio Cometa , Relação Dose-Resposta a Droga , Masculino , Testes de Mutagenicidade , Pioglitazona , Ratos , Ratos Sprague-Dawley
17.
Clin Rheumatol ; 26(6): 927-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17039260

RESUMO

Behçet's disease (BD) related amyloidosis is relatively rare. Serum amyloid A protein (SAA) protein gene polymorphism is one of the factors implicated in the pathogenesis of AA type amyloidosis. The aim of this study is to investigate SAA1 gene polymorphism in different patient groups: (1) BD related amyloidosis, (2) BD without amyloidosis, and (3) healthy controls. One hundred eleven patients from three main groups were included in the study: (1) BD related amyloidosis (n = 9), (2) BD without amyloidosis (n = 39), and (3) healthy controls (n = 63). Homozygous alpha/alpha is present in 78% of patients with BD and amyloidosis. The SAA1 alpha/alpha genotype is significantly more common among patients with BD and amyloidosis. This study demonstrated increased frequency of alpha/alpha genotype in BD related amyloidosis. To our knowledge, the relationship between alpha/alpha genotype and BD related amyloidosis was not studied previously. In conclusion, the SAA1 alpha/alpha genotype is a risk factor for amyloidosis in BD.


Assuntos
Amiloidose/genética , Polimorfismo Genético , Proteína Amiloide A Sérica/genética , Adulto , Alelos , Amiloidose/complicações , Síndrome de Behçet/complicações , Síndrome de Behçet/genética , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Matern Fetal Neonatal Med ; 30(4): 430-433, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27079262

RESUMO

OBJECTIVE: Previous studies have shown the relationship between lung development and glucocorticoids, but no studies have been conducted to investigate if a relationship exists between respiratory distress syndrome (RDS) and glucocorticoid receptor (GR) expression in preterm babies. We intended to investigate whether low GR expression is a risk factor for RDS. METHODS: Forty-one preterm babies, 24-35 weeks of gestation, were included in the study following informed consent from the parents. The relative gene expression of GRalpha and GRbeta was measured in the peripheral mononuclear cells form cord blood samples. The demographic characteristics of the babies and the diagnosis of RDS were recorded. RESULTS: RDS was more frequent in the group with low GRalpha expression: 12 (60%) in the GRalpha-I group and 6 (28%) in the GRalpha-II group (p = 0.043). Oxygen use with a hood, time to reach full enteral feeds and the duration of neonatal intensive care unit stay was shorter, and nosocomial sepsis episodes and number of erythrocyte transfusions were less in the GRbeta-I group. Higher hospital costs were found in the GRbeta-II group. CONCLUSIONS: Less RDS development, and better clinical follow-up was observed in premature babies with higher GR expression.


Assuntos
Lactente Extremamente Prematuro/sangue , Receptores de Glucocorticoides/sangue , Síndrome do Desconforto Respiratório do Recém-Nascido/sangue , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Sangue Fetal , Expressão Gênica , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Glucocorticoides/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Estudos Retrospectivos , Estatísticas não Paramétricas , Adulto Jovem
19.
Int J Antimicrob Agents ; 49(5): 595-602, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28373116

RESUMO

Nephrotoxicity has been associated with nucleos(t)ide analogues other than telbivudine (LdT). This study investigated the potential effects of LdT and lamivudine (LAM) on renal function in an experimental rat model of gentamicin-induced acute nephrotoxicity. A total of 28 healthy Wistar albino rats were randomly divided into four experimental groups: negative control; positive control (PC); LdT; and LAM. Nephrotoxicity was induced by gentamicin in the LdT, LAM and PC groups. LdT and LAM were administered to two groups for 6 weeks starting on the ninth day. Blood samples were collected weekly and cystatin C levels were measured by ELISA. Animals were sacrificed on the 50th day and the kidneys were removed for histological examination. Serum cystatin C levels differed significantly between the LdT and LAM groups (P <0.007) and between the LdT and PC groups (P <0.001). Renal function was significantly improved in the LdT group at the start of antiviral treatment on Day 8 and at the end of treatment on Day 50 (P = 0.001 and 0.007). Glomerular injury, acute tubular necrosis and total injury score were significantly reduced in the LdT group relative to the PC and LAM groups upon histopathological examination. LdT was associated with significant improvements in renal function as measured by biochemical and histopathological methods. The acute kidney injury model data should be supported by clinical studies to suggest that LdT treatment may have advantages for patients with underlying chronic kidney disease receiving chronic hepatitis B treatment.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Gentamicinas/efeitos adversos , Lamivudina/uso terapêutico , Inibidores da Síntese de Proteínas/uso terapêutico , Timidina/análogos & derivados , Injúria Renal Aguda/prevenção & controle , Animais , Cistatina C/sangue , Gentamicinas/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Projetos Piloto , Inibidores da Síntese de Proteínas/efeitos adversos , Ratos , Ratos Wistar , Telbivudina , Timidina/uso terapêutico
20.
Environ Mol Mutagen ; 47(9): 718-24, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17078099

RESUMO

Rosiglitazone (RSG), a member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by increasing insulin sensitivity. The therapeutic mode of action of RSG involves its activity as a highly selective and potent agonist for peroxisome proliferator-activated receptor-gamma. Although other drugs in this class have displayed unacceptable hepatotoxicity, RSG was approved for human use. The package insert indicates that RSG has minimal genotoxicity, but information on the genotoxicity of RSG is not available in the published literature. In this study, we used the single cell gel electrophoresis (SCGE)/Comet assay to investigate the DNA damage in peripheral blood and liver cells of rats treated with RSG. Sixteen male Sprague-Dawley rats were randomly distributed into four groups, and dosed daily by oral gavage with 0.0, 0.5, 1.0, and 2.0 mg/kg/day RSG. The rats dosed with 2.0 mg/kg/day RSG received an approximately 10-times the area under the curve concentration of the maximum recommended human daily dose. After 14 days of treatment, the rats were euthanized, and peripheral blood and liver were collected and processed for the Comet assay. A dose-dependent increase in DNA damage (as assessed by % tail DNA and Olive Tail Moment) was observed in the hepatocytes of RSG-treated groups, with significant increases detected between rats treated with all the doses of RSG and the control, and between rats treated with different RSG doses (P < 0.05 - P < 0.0001). In contrast, DNA damage was detected in peripheral blood lymphocytes only in rats treated with the higher RSG doses (1.0 and 2 mg/kg/day). Taken together, the data indicate that RSG is able to induce primary DNA damage in rats, with greater damage being detected in liver cells than lymphocytes.


Assuntos
Dano ao DNA , Hipoglicemiantes/toxicidade , Tiazolidinedionas/toxicidade , Animais , Ensaio Cometa , Fígado/citologia , Fígado/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Rosiglitazona
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