Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Tumour Biol ; 41(4): 1010428319846803, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31018830

RESUMO

Mesenchymal stem cells have therapeutic properties that are related to their potentials for trans-differentiation, immunomodulation, anti-inflammatory, inhibitory effect on tumor proliferation, and induction of apoptosis. This study was performed to analyze the role of mesenchymal stem cells as an alternative for cellular signaling growth factors involved in the pathogenesis of leukemogenesis in rats. Treatment of rats with 7,12-dimethyl benz [a] anthracene induced leukemogenesis appeared as a significant decrease in hematological parameters with concomitant significant increase in bone marrow oxidative and inflammatory indices (transforming growth factor beta and interleukin-6) in comparison with normal groups. On the contrary, Western immunoblotting showed a significant increase in the signaling growth factors: PI3K, AKT, mTOR proteins and a significant decrease in PTEN in 7,12-dimethyl benz [a] anthracene-treated group. In addition, a significant increase in the transcript levels of B cell lymphoma-2 protein gene in the 7,12-dimethyl benz [a] anthracene group, while that of C-X-C motif chemokine receptor-4 and B cell lymphoma-2 protein associated x-protein were significantly downregulated compared to controls. Meanwhile, therapeutic mesenchymal stem cells treatment predict a significant improvement versus 7,12-dimethyl benz [a] anthracene group through the modulation of growth factors that confront bone marrow dysplasia. In the same direction treatment of 7,12-dimethyl benz [a] anthracene group with mesenchymal stem cells, it induced apoptosis and increased the homing efficacy to bone marrow. In conclusion, mesenchymal stem cells improve hematopoiesis and alleviate inflammation, and modulated PI3K/AKT signaling pathway contributed to experimental leukemogenesis.


Assuntos
Leucemia/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Proteína Oncogênica v-akt/genética , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Apoptose/genética , Células da Medula Óssea/patologia , Diferenciação Celular/genética , Proliferação de Células/genética , Modelos Animais de Doenças , Humanos , Leucemia/induzido quimicamente , Leucemia/genética , Leucemia/patologia , PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases/genética , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Fator de Crescimento Transformador beta/genética
2.
Tumour Biol ; 39(10): 1010428317728480, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29022496

RESUMO

Considerable attention has been paid to the introduction of novel naturally occurring plant-derived radiosensitizer compounds in order to augment the radiation efficacy and improve the treatment outcome of different tumors. This study was therefore undertaken to evaluate the antitumor, antiangiogeneic, and synergistic radiosensitizing effects of apigenin, a dietary flavonoid, and/or cryptotanshinone, a terpenoid isolated from the roots of Salvia miltiorrhiza, against the growth of solid Ehrlich carcinoma in female mice. Apigenin (50 mg/kg body weight) and/or cryptotanshinone (40 mg/kg body weight) was intraperitoneally (i.p.) injected into non-irradiated or γ-irradiated (6.5 Gy whole-body γ-irradiation) solid Ehrlich carcinoma-bearing mice for 30 consecutive days. Investigations included molecular targets involved in proliferation, inflammation, angiogenesis, and tumor invasiveness. Treatment with apigenin and/or cryptotanshinone significantly suppressed the growth of solid Ehrlich carcinoma tumors and demonstrated a synergistic radiosensitizing efficacy together with γ-irradiation. These effects were achieved through downregulating the expression of angiogenic and lymphangiogenic regulators, including signal transducer and activator of transcription 3, vascular endothelial growth factor C, and tumor necrosis factor alpha, suppressing matrix metalloproteinase-2 and -9 activities, which play a key role in tumor invasion and metastasis, and enhancing apoptosis via inducing cleaved caspase-3 and granzyme B levels. Histological findings of solid Ehrlich carcinoma tumors verified the recorded data. In conclusion, a synergistic radiosensitizing efficacy for apigenin and cryptotanshinone was demonstrated against Ehrlich carcinoma in the current in vivo murine model, representing therefore a potential therapeutic strategy for increasing the radiation response of solid tumors.


Assuntos
Apigenina/administração & dosagem , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/radioterapia , Radiossensibilizantes/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Carcinoma de Ehrlich/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Modelos Animais de Doenças , Feminino , Raios gama , Humanos , Camundongos , Fenantrenos/administração & dosagem , Irradiação Corporal Total
3.
Mol Carcinog ; 50(8): 625-34, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21557333

RESUMO

The fragile histidine triad gene (FHIT) is a candidate tumor suppressor gene at chromosome 3p14.2. Deletions in FHIT gene were reported in different types of cancer including breast cancer. In this study, we investigated the loss of heterozygosity (LOH) incidence that target FHIT genomic structure and chromosome 3p in cancerous and pre-neoplastic lesions of Egyptian breast patients. Genomic DNA was isolated from tumor tissues and their normal counterparts of 55 Egyptian patients diagnosed with breast cancer and 11 patients diagnosed with preneoplastic breast lesions. LOH was detected in 51% of breast cancer cases in at least one microsatellite marker of the four investigated markers. While, none of the markers showed LOH among the pre-neoplastic breast lesions. We also observed a significant association between LOH and invasive ductal carcinoma (IDC) histopathological type while no association observed between LOH and patients' age, tumor grade, or lymph node involvement. We also investigated FHIT gene expression profiles in breast cancer using Oncomine database. We found that FHIT is significantly reduced in all investigated studies. We conclude that, FHIT is underexpressed in breast cancer tissues compared to their normal counterparts due to the extensive allelic loss that is observed in its gene structure.


Assuntos
Hidrolases Anidrido Ácido/genética , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Cromossomos Humanos Par 3 , Perda de Heterozigosidade , Proteínas de Neoplasias/genética , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Egito , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Repetições de Microssatélites , Pessoa de Meia-Idade
4.
Int J Breast Cancer ; 2011: 325947, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22295218

RESUMO

Fragile histidine triad (FHIT) gene encodes a putative tumour suppressor protein. Loss of Fhit protein in cancer is attributed to different genetic alterations that affect the FHIT gene structure. In this study, we investigated the pattern of homozygous deletion that target the FHIT gene exons 3 to 9 genomic structure in Egyptian breast cancer patients. We have found that 65% (40 out of 62) of the cases exhibited homozygous deletion in at least one FHIT exon. The incidence of homozygous deletion was not associated with patients' clinicopathological parameters including patients' age, tumour grade, tumour type, and lymph node involvement. Using correlation analysis, we have observed a strong correlation between homozygous deletions of exon 3 and exon 4 (P < 0.0001). Deletions in exon 5 were positively correlated with deletions in exon 7 (P < 0.0001), Exon 8 (P < 0.027), and exon 9 (P = 0.04). Additionally, a strong correlation was observed between exons 8 and exon 9 (P < 0.0001).We conclude that FHIT gene exons are homozygously deleted at high frequency in Egyptian women population diagnosed with breast cancer. Three different patterns of homozygous deletion were observed in this population indicating different mechanisms of targeting FHIT gene genomic structure.

5.
Biochem Biophys Res Commun ; 389(2): 211-6, 2009 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-19706288

RESUMO

In the present study, we examined the effects of free fatty acids (FFAs) on insulin sensitivity and signaling cascades in the C2C12 skeletal muscle cell culture system. Our data clearly manifested that the inhibitory effects of PKC on insulin signaling may at least in part be explained by the serine/threonine phosphorylation of IRS-1. Both oleate and palmitate treatment were able to increase the Serine(307) phosphorylation of IRS-1. IRS-1 Serine(307) phosphorylation is inducible which causes the inhibition of IRS-1 tyrosine phosphorylation by either IkappaB-kinase (IKK) or c-jun N-terminal kinase (JNK) as seen in our proteomic kinases screen. Furthermore, our proteomic data have also manifested that the two FFAs activate the IKKalpha/beta, the stress kinases S6 kinase p70 (p70SK), stress-activated protein kinase (SAPK), JNK, as well as p38 MAP kinase (p38MAPK). On the other hand, the antioxidant, Taurine at 10mM concentrations was capable of reversing the oleate-induced insulin resistance in myocytes as manifested from the glucose uptake data. Our current data point out the importance of FFA-induced insulin resistance via multiple signaling mechanisms.


Assuntos
Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Resistência à Insulina , Insulina/metabolismo , Mioblastos Esqueléticos/metabolismo , Proteína Quinase C/metabolismo , Animais , Antioxidantes/farmacologia , Linhagem Celular , Ativação Enzimática , Ácidos Graxos não Esterificados/farmacologia , Insulina/farmacologia , Proteínas Substratos do Receptor de Insulina/metabolismo , Camundongos , Mioblastos Esqueléticos/efeitos dos fármacos , Ácido Oleico/metabolismo , Ácido Oleico/farmacologia , Estresse Oxidativo , Ácido Palmítico/metabolismo , Ácido Palmítico/farmacologia , Fosforilação , Serina/metabolismo , Transdução de Sinais , Taurina/farmacologia
6.
Biochem Biophys Res Commun ; 370(1): 134-9, 2008 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-18358236

RESUMO

In the current study, we show evidence, in a fructose-fed hamster model of insulin resistance, that free fatty acid (FFA) can induce hepatic insulin resistance in part via PKC activation leading to increased production of atherogenic apoB100-containing lipoproteins. Interestingly, IkappaB-kinase beta (IKKbeta)-dependent NF-kappaB was activated in hepatocytes from the fructose-fed hamster as an indication for PKC activation. Treatment of hepatocytes with oleate for 16h showed the activation of the PKC isoforms, PKCalpha/betaII, in a dose dependent manner. Strikingly, the general PKC inhibitor, bisindolylmaleimide-I, Bis-I (5 microM) was found to ameliorate fructose-induced insulin resistance, restoring the phosphorylation status of PKB and suppressing apoB100 overproduction in ex vivo and in vivo. The data suggest that hepatic PKC activation, induced by increased circulating FFA may be an important factor in the development of insulin resistance and dyslipidemia seen in the fructose-fed hamster model.


Assuntos
Apolipoproteína B-100/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Hiperlipoproteinemias/etiologia , Resistência à Insulina , Fígado/metabolismo , NF-kappa B/metabolismo , Proteína Quinase C/metabolismo , Animais , Cricetinae , Modelos Animais de Doenças , Frutose/administração & dosagem , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hiperlipoproteinemias/metabolismo , Indóis/farmacologia , Fígado/citologia , Fígado/efeitos dos fármacos , Masculino , Maleimidas/farmacologia , Mesocricetus , Ácido Oleico/farmacologia , Fosforilação , Proteína Quinase C/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia
7.
J Egypt Soc Parasitol ; 33(1): 145-62, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12739808

RESUMO

In Egypt, schistosomiasis is still a major public health problem and praziquantel is the drug of choice for its treatment, whereas diazinon is globally used as an insecticide for controlling pests. They adversely affect the environment. Therefore, the authors studied the effect of 1/20 LD50 diazinon given orally to healthy and Schistosoma mansoni infected mice for 5 successive days up to 9 and 17 weeks coupled with a therapeutic dose (2 x 500 mg/kg Bwt) of praziquantel, 2 weeks before sacrificing. The results showed that non significant differences were obtained from total proteins, albumin, globulins, and albumin/globulin ratio. However, significant differences were revealed from alpha1-, alpha2-, beta1-, beta2-, and gamma-globubins in addition to plasma ceruloplasmin. Diazinon changed the levels of alpha2-, beta1-, and gamma-globubins, while diazinon coupled with schistosomiasis affected the levels of most studied parameters. Consequently, exposure to insecticides should be avoided specially in the rural areas where schistosomiasis is still endemic.


Assuntos
Proteínas Sanguíneas/análise , Diazinon/efeitos adversos , Inseticidas/efeitos adversos , Praziquantel/efeitos adversos , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/sangue , Esquistossomose mansoni/tratamento farmacológico , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/efeitos adversos , Anti-Helmínticos/uso terapêutico , Diazinon/administração & dosagem , Interações de Medicamentos , Saúde , Inseticidas/administração & dosagem , Dose Letal Mediana , Masculino , Camundongos , Praziquantel/administração & dosagem , Praziquantel/uso terapêutico , Esquistossomose mansoni/parasitologia
8.
J Egypt Soc Parasitol ; 33(1): 245-60, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12739815

RESUMO

In Egypt, infection with Schistosoma mansoni (S.m.) and residues of pesticides have been considered as major environmental pollutants that adversely affect health. Effects of diazinon (DZN) and/or praziquantel (PZQ) on the levels of plasma triiodothyronine (T3), thyroxine (T4), activities of brain acetylcholinesterase (AchE) and liver alanine aminotransferase (ALT) in addition to blood reduced glutathione (GSH) in healthy and S.m. infected mice were investigated after 9 and 17 weeks of either infection or intoxication with DZN. Triiodothyronine showed significant differences among the different treatments. The group of mice treated with PZQ showed the highest levels of T3 at both time intervals. Thyroxine level showed significant differences between the two time intervals. The lowest levels of T4 were observed in the infected-PZQ group at week 17. The maximum inhibition of brain AchE activity was noticed in DZN-PZQ treated group after 9 and 17 weeks. The different treatments significantly reduced the activities of liver ALT. The highest decrease was recorded in the infected-DZN-PZQ group at week 9. All treatments significantly lowered the levels of blood GSH after 9 weeks.


Assuntos
Diazinon/efeitos adversos , Praziquantel/efeitos adversos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/metabolismo , Acetilcolinesterase/metabolismo , Alanina Transaminase/metabolismo , Animais , Encéfalo/enzimologia , Diazinon/administração & dosagem , Interações de Medicamentos , Fígado/enzimologia , Masculino , Camundongos , Praziquantel/administração & dosagem , Praziquantel/uso terapêutico , Schistosoma mansoni , Esquistossomose mansoni/sangue , Esquistossomose mansoni/enzimologia , Tiroxina/sangue , Fatores de Tempo , Tri-Iodotironina/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA