RESUMO
Carcinoma of oral cavity have aâ¯high risk of recurrence after initial treatment with surgery, radiotherapy, surgery with adjuvant radiotherapy, or radio-chemotherapy.The present study investigated the changes in expression, activity and regulation of matrix metalloproteinases (MMP) -2 and -9 in oral squamous cell carcinoma (OSCC) which might help to ascertain the invasive potential of the tumor . Tumor tissues and adjacent normal tissues of OSCC patients [N,37; either sex; 20-70 yrs] were subjected to clinico-pathology, histopathology and TNM grading. The enzyme activity and associated signalling was observed with gelatin zymography, immunohistochemistry, ELISA, western blot and semi quantitative reverse transcriptase PCR. OSCC tissues were observed with elevated MMP-9 activity, enhanced expression of fibronectin (FN), phosphorylated focal adhesion kinase (FAK Try 397), phosphatidyl inositol 3kinase (PI3K), protein kinase Bâ¯(AKT) and reduced expression of tissue inhibitor of metalloproteinase- 1(TIMP-1) than the control tissues.OSCC patients elicited aâ¯predominance of MMP-9 activity via up regulated FAK/PI3K/AKT pathway. Aâ¯routine MMP-9 analysis may ascertain the invasiveness of the tumor and therefore may be professed as aâ¯suitable biomarker for metastatic potential of oral cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Bucais/enzimologia , Adulto , Idoso , Feminino , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
Tumor-associated macrophages (TAMs) are preferentially M2 skewed and promote tumor growth, angiogenesis, invasion, and/or metastasis. In this study, we have analyzed the in vitro immunomodulatory potential of a non-toxic neem leaf glycoprotein (NLGP) in reprogramming Stage III supraglottic laryngeal tumor cell lysate (SLTCL) induced M2 TAMs to their classical anti-tumor shape (M1). Data generated from this study support that NLGP is effective in preventing the SLTCL induced generation (CD68(+)CD206(+)IL-10(high) to CD68(+)CD206(-)IL-10(low) TAMs) and functions (NO(low) to NO(high), MHC-I(low) to MHC-I(high), CD80(low) to CD80(high)) of pro-tumorous M2 macrophages, which in turn associated with sustained anti-tumor effector functions by promoting cytotoxic T cell activities and suppressing regulatory T cells. Furthermore, our data also suggest that NLGP prevents M2 skewness of TAMs by downregulating phosphorylation of targeted STAT3.
Assuntos
Azadirachta/química , Glicoproteínas/farmacologia , Evasão da Resposta Imune/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Neoplasias Laríngeas/imunologia , Macrófagos/efeitos dos fármacos , Folhas de Planta/química , Fator de Transcrição STAT3/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Humanos , Interleucina-10/biossíntese , Interleucina-12/biossíntese , Macrófagos/imunologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Fosforilação , Extratos Vegetais/farmacologia , Interferência de RNA , RNA Interferente Pequeno , Fator de Transcrição STAT3/genética , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologiaAssuntos
Antibacterianos/uso terapêutico , Celulite (Flegmão)/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Militares , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Celulite (Flegmão)/diagnóstico , Celulite (Flegmão)/microbiologia , Cólera/diagnóstico , Cólera/microbiologia , Diagnóstico Diferencial , Farmacorresistência Bacteriana Múltipla , Disenteria Bacilar/diagnóstico , Disenteria Bacilar/microbiologia , Escherichia coli , Infecções por Escherichia coli/diagnóstico , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Reação em Cadeia da Polimerase , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Infecções Cutâneas Estafilocócicas/diagnóstico , Staphylococcus aureus , Reino UnidoRESUMO
AIMS: The influence of carbon-nitrogen and nitrogen-phosphorus ratios of input fertilizers, and that of pond water, on the growth of heterotrophic and phosphate-solubilizing bacteria of water and sediment, was examined in relation to fertilizer mineralization indices using different modes of fertilization through inorganic and organic sources. METHODS AND RESULTS: The first experiment used carbon-nitrogen-phosphorus ratios varying from 12 : 2 : 1 to 151 : 6 : 1, applied at the rate of 0.043 g l(-1) week(-1), whereas in the second ratios varied from 25.6 : 6.2 : 1 to 150 : 12 : 1 applied once at the rate of 3.33 g l(-1). Different fertilizers (cattle dung, poultry droppings, urea, single superphosphate and starch) were mixed in different proportions to achieve the desired carbon-nitrogen-phosphorus ratio. The heterotrophic and phosphate-solubilizing populations were more responsive to an early manuring phase than later, implying that pond fertilization was microbiologically more dynamic in the earlier phase. The carbon-nitrogen and nitrogen-phosphorus ratios of 11.8 (88.6 : 7.5) and 7.5 (7.5 : 1), respectively, of input fertilizers favoured growth of both heterotrophic and phosphate-solubilizing bacterial populations much better than the other ratios tested. Likewise, water carbon-nitrogen and nitrogen-phosphorus ratios of 11.9 and 3.34 induced bacterial growth. The carbon-nitrogen ratios of 12.63 (101 : 8) (input fertilizer)-4.54 (water), and nitrogen-phosphorus ratios of 8 (8 : 1) (input fertilizer)-2.93 (water), gave gross primary productivity values higher than the remaining ratios, exhibiting overall curvilinear relationships. The values of gross primary productivity were the direct function of values of fertilizer mineralization indices for carbon, nitrogen and phosphorus. CONCLUSION: It is concluded that the mixed fertilizer (carbon-nitrogen-phosphorus-88.6 : 7.5 : 1) comprising cattle dung (95%), poultry droppings (2.5%), urea (2%) and single superphosphate (0.5%), applied at the rate of 23,000 kg ha(-1) year(-1), was a suitable cost-effective fertilization option for aquaculture practices. SIGNIFICANCE AND IMPACT OF THE STUDY: As chemical fertilizers are expensive and cause some adverse effects on the soil structure, composition, microflora and other characteristics of the pond, mixed combinations of inorganic and organics with narrow range of carbon-nitrogen-phosphorus ratio can be suitable and cost-effective fertilization tools in aquaculture practices, which is to be linked with the microbial activities of the pond.