Evaluation of C-X-C chemokine receptor type 4 (CXCR4) and Peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in colorectal carcinoma: Relation to the available clinicopathological parameters.

Background: Colorectal carcinoma (CRC) is the most common malignancy of the gastrointestinal tract, representing an incredible health problem. It is essential to develop drugs against novel targets--involved in CRC tumorigenesis and progression--to improve the management of the disease. The aim of this study was to evaluate C-X-C chemokine receptor type 4 (CXCR4) and Peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in CRC, and to associate their expression with the available clinicopathological parameters. Materials and Methods: This study included 50 cases of primary CRC. All cases were stained by CXCR4 and PPAR-γ antibodies to assess their immunohistochemical expression. The relations between their expression and clinicopathological variables were assessed. Results: CXCR4 expression was detected in 76% of studied cases. High CXCR4 expression showed significant associations with the depth of tumor invasion (P = 0.024), lymph node metastasis (P = 0.009), advanced tumor stage (P = 0.001) and the presence of vascular invasion (P = 0.035). PPAR-γ expression was detected in 78% of studied cases. PPAR-γ expression showed a statistically significant inverse relation with histologic types (P = 0.001), tumor grade (P = 0.005), depth of tumor invasion (P = 0.001), lymph node status (P = 0.001), TNM stage (P = 0.002), and vascular invasion (P = 0.001). Conclusions: High CXCR4 and decreased PPAR-γ expressions are related to high tumor grade, advanced stage, and vascular invasion in colorectal carcinoma.

Luteolin and 5-flurouracil act synergistically to induce cellular weapons in experimentally induced Solid Ehrlich Carcinoma: Realistic role of P53; a guardian fights in a cellular battle.

BACKGROUND: Solid Ehrlich Carcinoma (SEC) is an undifferentiated tumor used in tumor studies and chemotherapy investigations. AIM: to assess the anti-tumor potential of luteolin when used either alone or combined to 5-fluorouracil (5-FU) against SEC. METHOD: SEC was induced in 40 female mice; they were categorized into 4 equal groups; group I (untreated SEC), group II (5-FU treated SEC), group III (luteolin treated SEC) and group IV (5-FU + luteolin treated SEC). Tumor volume and weight were calculated. P53, p21, caspase 3 and damage regulated autophagy modulator (DRAM) were assessed. Biomarkers of oxidant/antioxidant status in addition to immunohistochemistry for cylin D1 were evaluated. RESULTS: combined administration of luteolin and 5-FU in SEC model increased levels of p53, p21, caspase 3, DRAM and survivability while, tumor volume, weight, thioredoxin reductase one (TR1) activity and cyclin D1 expression showed the reverse with restoration of oxidant/antioxidant indices. CONCLUSION: current results proved the antitumor therapeutic effects of luteolin alone or combined with 5-FU as a novel strategy for cancer therapy.

Carbonic anhydrase enzyme as a potential therapeutic target for experimental trichinellosis.

Trichinellosis is a globally distributed helminthic infection. There is a considerable interest in developing new anti-helminthic drugs affecting all the developmental stages of Trichinella. Acetazolamide (carbonic anhydrase (CA) inhibitor) involves a novel mechanism of action by inhibiting such an essential enzyme for parasite metabolism. This work aimed to study the effect of acetazolamide against different stages of T. spiralis in experimental animals. Mice were divided into three groups: group I: infected and treated with acetazolamide on day 2 post infection (P.I.), group II: infected and treated with acetazolamide on day 12 P.I., and group III: infected non-treated. From each group, small intestine and muscles were removed for histopathological and immunohistochemical studies. Also, total adult and muscle larval count were estimated. We found that acetazolamide was effective in reduction of both adult and muscle larval counts. When given early, the effect was more pronounced on the adults (62.7 %). However, the efficacy of the drug against muscle larvae was increased when given late (63 %). Improvement of the intestinal histopathological changes was observed in all the treated groups. Degeneration of encysted larvae with minimal pathologic changes of infected skeletal muscle was observed in the treated groups. Expression of matrix metalloproteinase-9 showed a statistically significant decrease in the intestinal and muscle tissues in all treated groups as compared to the control group. In conclusion, the present study revealed that acetazolamide, carbonic anhydrase inhibitor, could be a promising drug against both adults and larvae of T. spiralis.