RESUMO
Metastasis in breast cancer is a leading cause of mortality among women in many countries. This study investigated the anti-cancer role of benzoimidazoquinazoline and benzimidazotriazin; two novel compounds that were designed, synthesized, structurally elucidated, and biologically evaluated as potent anti-angiogenic agents that act through inhibition of vascular endothelial growth factor receptor-2 (VEGFR2). Breast cancer was induced by inoculation of Ehrlich Ascites Carcinoma (EAC) cells. Seventy swiss albino mice were randomly divided into 7 groups, 10 animals each: (1) normal, (2) control EAC group, (3) cisplatin treated group, (4&5) benzoimidazoquinazoline treated (5 mg/kg and 10 mg/kg), (6&7) benzimidazotriazin treated (5 mg/kg and 10 mg/kg). The expression of miR-122 was assessed in the tumor tissue by quantitative PCR, and the VEGF level was determined in serum by ELISA. VEGFR2 and cluster of differentiation (CD)34 were assessed by immunohistochemistry. Serum ALT, AST, creatinine, and urea were measured. Treatment with benzoimidazoquinazoline and benzimidazotriazin decreased tumor weight and serum levels of VEGF, and down-regulated expression of VEGFR2 and CD34 in the tumor tissue. miR-122 was upregulated, particularly in the benzimidazotriazin (10 mg/kg) group. Relative to cisplatin, the novel compounds were less toxic to kidneys. Benzoimidazoquinazoline and benzimidazotriazin are promising anti-cancer agents that act through inhibition of angiogenesis and thus provide a new strategy for advancement of chemotherapy.
Assuntos
Inibidores da Angiogênese/farmacologia , Neoplasias da Mama/tratamento farmacológico , Carcinoma de Ehrlich/tratamento farmacológico , Compostos Heterocíclicos/farmacologia , MicroRNAs/metabolismo , Neovascularização Patológica , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/síntese química , Animais , Antígenos CD34/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma de Ehrlich/genética , Carcinoma de Ehrlich/metabolismo , Carcinoma de Ehrlich/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Compostos Heterocíclicos/síntese química , Humanos , Células MCF-7 , Camundongos , MicroRNAs/genética , Transdução de Sinais , Carga Tumoral/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
BACKGROUND: Blastocystis is a group of cosmopolitan gastrointestinal parasite of humans and a wide variety of animals. These anaerobic protozoans include more than 17 specific small-subunit ribosomal RNA subtypes, of which nine are found in humans with a variable geographical distribution. Until now, no study has described the Blastocystis subtypes present in Saudi Arabia. METHODS: In total, 1,262 faecal samples were collected from patients with gastrointestinal complaints and asymptomatic individuals visiting two major hospitals. All samples were analysed by F1/R1 diagnostic PCR, microscopy and culture methods. The subtypes of Blastocystis sp. isolates were determined by the sequenced-tagged site (STS)-based method. RESULTS: One-hundred-thirty-three positive cases were detected by F1/R1 diagnostic PCR, of which 122 were also positive by the culture method and 83 by direct microscopy. The sensitivities of direct microscopy and the culture method were 62% and 92%, respectively. Subtype (ST3) was the most prevalent (80.5%), followed by ST1 (14.5%) and ST2 (5%). ST4, ST5, ST6 and ST7 were not detected in this study. ST3 infections were significantly predominant (P < 0.05) among symptomatic patients. CONCLUSIONS: To our knowledge, this study provides the first run-through information on Blastocystis sp. epidemiology in Makkah city, revealing a rather moderate prevalence of 10.5% and the presence of three subtypes, ST1, ST2, and ST3. ST3 was the most predominant, particularly among symptomatic patients.
Assuntos
Infecções por Blastocystis/parasitologia , Blastocystis/isolamento & purificação , Infecções Assintomáticas , Blastocystis/classificação , Blastocystis/genética , DNA de Protozoário/genética , DNA Ribossômico/genética , Fezes/parasitologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arábia SauditaRESUMO
The SDS-PAGE and immunoblot methods were used to identify Trichomonas vaginalis specific target antigen(s). Ten T. vaginalis isolates, cultured on TYM media, were analyzed by Sodium Dodecyl Sulphate Poly Acrylamide Gel Electrophoresis (SDS-PAGE), revealed 34 distinct bands. Immunoblotting against a hyperimmune rabbit serum, showed 20 reactive bands ranging from 14-205 kDa. There was isolate to isolate variability among 8 isolates, while 2 isolates (6,7) showed a similar antigenic patterns. Imunoblotting of the isolates showed a total of 20 molecular weight bands, 80% of isolates gave positive immunologic reactions above 100 kDa, while below 100 Kda all the isolates recognized the different molecular weight bands. Out of 20 reacting bands, 5 main bands were detected, 29, 66, 84, 95 & 115 kDa gave positive percent of 60, 60, 60, 90 & 80% among the 10 isolates respectively.