Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage

Abstract Objectives: Infection, inflammation and bone resorption are closely related events in apical periodontitis development. Therefore, we sought to investigate the role of cyclooxygenase (COX) in osteoclastogenesis and bone metabolism signaling in periapical bone tissue after bacterial lipopolysaccharide (LPS) inoculation into root canals. Methodology: Seventy two C57BL/6 mice had the root canals of the first molars inoculated with a solution containing LPS from E. coli (1.0 mg/mL) and received selective (celecoxib) or non-selective (indomethacin) COX-2 inhibitor. After 7, 14, 21 and 28 days the animals were euthanized and the tissues removed for total RNA extraction. Evaluation of gene expression was performed by qRT-PCR. Statistical analysis was performed using analysis of variance (ANOVA) followed by post-tests (α=0.05). Results: LPS induced expression of mRNA for COX-2 (Ptgs2) and PGE2 receptors (Ptger1, Ptger3 and Ptger4), indicating that cyclooxygenase is involved in periapical response to LPS. A signaling that favours bone resorption was observed because Tnfsf11 (RANKL), Vegfa, Ctsk, Mmp9, Cd36, Icam, Vcam1, Nfkb1 and Sox9 were upregulated in response to LPS. Indomethacin and celecoxib differentially modulated expression of osteoclastogenic and other bone metabolism genes: celecoxib downregulated Igf1r, Ctsk, Mmp9, Cd36, Icam1, Nfkb1, Smad3, Sox9, Csf3, Vcam1 and Itga3 whereas indomethacin inhibited Tgfbr1, Igf1r, Ctsk, Mmp9, Sox9, Cd36 and Icam1. Conclusions: We demonstrated that gene expression for COX-2 and PGE2 receptors was upregulated after LPS inoculation into the root canals. Additionally, early administration of indomethacin and celecoxib (NSAIDs) inhibited osteoclastogenic signaling. The relevance of the cyclooxygenase pathway in apical periodontitis was shown by a wide modulation in the expression of genes involved in both bone catabolism and anabolism.

Indian food ingredients and cancer prevention - an experimental evaluation of anticarcinogenic effects of garlic in rat colon.

The major food items of Indian cuisine include rice, wheat, diary products, and abundant fruits and vegetables. Beside these, there are several kinds of herbs and spices as important ingredients, containing many phytochemicals with medicinal properties, adding taste to Indian cuisine. An impressive body of data exists in support of the concept that Indian food ingredients can be used in preventive strategies aimed at reducing the incidence and mortality of different types of cancers because of their antioxidative, antimutagenic and anticarcinogenic properties. Vital ingredients used in Indian cooking include turmeric, cloves, ginger, aniseed, mustard, saffron, cardamom and garlic Garlic is an indispensable ingredient of Indian food and this report concerns the chemopreventive efficacy of garlic in an azoxymethane induced rodent colon carcinogenesis model. The effect of garlic was evaluated in terms of aberrant crypt foci, putative preneoplastic lesions in the colon. In addition, cell proliferation and levels of apoptosis were determined and the expression of cyclooxygenase-2 protein was analyzed. Following treatment, significant inhibition of cell proliferation and induction of apoptosis, as well as suppression of cyclooxygenase-2 activity were observed, associated with significant reduction in the incidence of aberrant crypt foci. The study points to combined protective effects of garlic components on colon carcinogenesis.

Cyclooxygenase-2 Expression according to Size and Location of Gastric and Colorectal Tubular Adenomas / 대한소화기학회지

BACKGROUND/AIMS: Recent studies have shown that cyclooxygenase-2 (COX-2) may be involved in the process of invasion, growth and apoptosis in colorectal carcinoma and in the growth and tumorigenesis in familial adenomatous polyposis. This study was conducted to determine the significance of the expression of COX-2 in gastric and colorectal adenomas. METHODS: Forty-nine samples of gastric adenoma and fifty-seven samples of colorectal adenoma were obtained by endoscopic mucosal resection or polypectomy from 106 patients from January 2000 to July 2003. COX-2 expression was determined by immunohistochemistry. Correlation between COX-2 expression and several clinical factors were compared in each gastric and colorectal adenomas. RESULTS: The expression of COX-2 in epithelial cells was significantly higher in the group with large adenoma (>1 cm) compared with the group with small adenoma (

Relevância clínica dos carcinomas de grande células pulmonares com relação às características neuroendócrinas, biomoleculares e estromais / Neuroendocrine and biologic features of primary tumors and tissue in pulmonary large cell carcinomas

Avaliou-se p21 e outros marcadores em espécimes cirúrgicos de 61 pacientes com carcinoma de grande células de pulmão. Utilizamos imunohistoquímica para avaliar a proteína p21 e a densidade de microvasos. A análise através do modelo multivariado de Cox mostrou que após o tratamento cirúrgico, o subtipo histológico foi significante com relação a sobrevida (p=0.02), mas a quantificação do tumor para o p21 e a densidade de microvasos adicionaram importante informação ao estudo do prognóstico e foram fatores mais fortemente relacionados com a sobrevida do que o subtipo histológico (P=0.00).We examined p21waf1/cip1 and other markers in tissue from 61 patients with surgically excised large cell carcinoma. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for p21waf1/cip1 and microvessel density. The study outcome was survival time until death from recurrent lung cancer. Multivariate Cox model analysis demonstrated that after surgical excision control, histologic subtypes were significantly related to survival time (P=0.02), but quantitative staining of the tumor for p21waf1/cip1 and microvessel density added prognostic information and were more strongly prognostic than histologic subtype (P=0.00)...

Immunohistochemical Expression of COX-2 in Thyroid Nodules

BACKGROUND: Recent evidence indicates that elevated COX-2 expression is associated with the carcinogenesis of numerous neoplasms. In this study, we investigated COX-2 expression in various thyroid specimens in order to elucidate its physiological role in pathologic conditions, and to evaluate the efficiency of COX-2 protein expression as a molecular marker of malignancy in the thyroid gland. METHODS: COX-2 expression was studied immunohistochemically in 19 papillary carcinomas, 8 follicular carcinomas, 14 follicular adenomas, 2 H rthle cell carcinomas, 4 H rthle cell adenomas, 8 nodular hyperplasias, 3 Graves' diseases, 3 Hashimoto's thyroiditis, 2 medullary carcinomas, 1 anaplastic carcinoma, and 20 normal thyroid tissues. RESULTS: COX-2 staining was not seen in any of the normal thyroid, Graves' disease, or nodular hyperplasia specimens. In contrast, COX-2 staining was observed in all of papillary carcinomas, Hashimoto's thyroiditis, H rthle cell carcinomas, and H rthle cell adenomas tissues. Moreover, 7 of 8 follicular carcinomas and 11 of 14 follicular adenomas showed COX-2 staining. CONCLUSION: These results indicate that COX-2 is not useful as a marker of malignancy. Since COX-2 expression was evident in follicular adenomas and in papillary and follicular carcinomas. Thus, the enzyme may be involved in the early process of thyroid tumorigenesis.