Prognostic significance of COX-2 and beta-catenin in colorectal carcinoma

The high prevalence of colorectal carcinoma [CRC] is a driver to understand the underlying molecular mechanisms. Chemoprevention strategy using non-steroidal anti- inflammatory drugs [NSAIDs] revealed that these drugs suppress colorectal carcinoma. The best known targets of NSAIDs are cyclooxygenase [COX] enzymes. The function of prostaglandins and cyclooxygenase in cancer pathogenesis is unclear. COX-2 regulation of proliferation, apoptosis, and tumor-blood vessel interaction has been suggested. beta-Catenin is a component of the WNT [wing1ss type] signaling pathway, increased protein concentrations promote transcription of genes important in regulating the cell cycle. To determine the significance of COX-2 and beta-catenin expression in colorectal carcinogenesis and prognosis. Thirty patients with colorectal carcinomas treated by colonic resection were studied for the expression of both COX-2 and beta-catenin by immunohistochemistry. Their expression was interpreted in relation to adjacent normal colonic mucosa and analyzed in correlation with various clinicopathologic parameters and patient's survival after a follow up period of 24 months. Our results showed that in normal adjacent colonic mucosa, COX-2 was completely absent, whereas beta-catenin was specifically located in the plasma membranes. Both proteins were expressed in tumorous tissues, COX-2 showed diffuse cytoplasmic positivity, whereas 3-catenin accumulated in both the cytoplasm and nuclei. We established statistically significant relationships between pathological grade and both beta-catenin, and COX-2 positivity scores, being at the higher end for poorly-differentiated tumors. beta-Catenin expression also correlated significantly with higher tumor stage and LN metastasis. Both COX-2 and beta-catenin expression correlated with a higher incidence of shorter disease free survival

effect of pentoxifylline on hepatocyte growth factor and liver functions in cirrhotic patients undergoing splenectomy and decongestion

High morbidity and mortality rates in cirrhotic patients undergoing intraabdominal surgery underscore the need for identifying a therapy that will decrease postoperative hepatic dysfunction and enhance hepatic regenerative activity. Perioperative administration of pentoxifylline [PTX] is suggested to decrease liver fibrosis and enhance hepatic regenerative activity in cirrhotic patients. Hepatocyte growth factor [HGF] is hepatocyte mitogen, that is suggested to play a role in liver regeneration during injury. The aim of this study is to investigate the value of perioperative administration of PTX on reducing liver injury as reflected by changes in serum level of hepatocyte growth factor [HGF], and standard liver functions in cirrhotic patients undergoing Splenectomy and decongestion. 20 adult patients with cirrhotic liver were randomly allocated into two equal groups. Patients in the first group [PTX Gp], received 300 mg i.v. PTX before induction of general anesthesia followed by 100 mg /h PTX in 500 ml glucose 5% infused in 10 hours. Patients in the second group [control Gp], received 15ml i.v. glucose 5% solution before induction of general anesthesia followed by 500 ml glucose 5% infused in 10 hours. All patients' were Child class A. Hepatocyte growth factor increased significantly at postoperative time when it was compared with preoperative value in control group. Liver enzymes SGOT, SGPT, prothrombin activity, total bilirubin, serum albumin, blood urea and creatinine did not significantly change in the studied groups when postoperative values were compared with preoperative ones or when the studied groups were compared with each other. White blood count and platelets increased significantly postoperatively compared with preoperative values in the studied groups. The current study suggested that perioperative administration of PTX could produce hepatocyte protection during intra-abdominal surgery as hepatocyte growth factor did not significantly increase at postoperative time in PTX group meanwhile, it increased significantly at postoperative time compared to preoperative value in control group. It did not influence liver or kidney functions, as SGOT, SGPT, prothrombin activity, serum albumin, total bilirubin as well as blood urea and creatinine did not significantly change postoperatively compared with preoperative values in both studied groups

Distraction osteogenesis of the grafted bone

Distraction osteogenesis is a well established technique for the lengthening bones and correction of selected craniofacial deformities. Distraction osteogenesis of the grafted bone has the advantage of elongation of the bone stock without the need of another addition of bone graft. Bone graft distraction of is relatively a new technique with few clinical reports. This study was conducted on ten patients who underwent for different reconstructive procedures followed by distraction osteogenesis of the grafted bone. The first group of patients was suffering from T.MJ. ankylosis and reconstructed by costochondral graft. The second group patient had a mandibular continuity defect and reconstructed by autogenous corticocancellous bone block obtained from iliac crest. The third group had deficient alveolar ridge, which augmented by onlay bone graft obtained from iliac crest. After complete take of the graft, distraction osteogenesis was done for the purpose of increasing and improving the bone stock, which led to increasing the efficiency of functional rehabilitation. The postoperative results were favorable with no increased risk due to the previous bone grafting. The technique is recommended for severe cases of bony deformity where either distraction osteogenesis or bone grafting is not enough to treat the patients

Apoptosis, proliferation, and FAS/FASL expression in pancreatic adenocarcinoma

Deregulation of normal cell cycle machinery is integral to neoplastic growth. There is now compelling evidence implicating the loss of cell kinetic balance in the development and progression of most human cancers, including pancreatic carcinoma which caries extremely poor prognosis. Understanding the pathogenesis of pancreatic cancer seems to be of great value in order to determine the mechanisms of the aggressive growth and metastasis. As the tumor growth depends upon the balance between apoptosis and proliferation, herein, we analyzed by immunohistochemistry the expression of Fas and FasL in 20 operative specimens of pancreatic ductal adenocarcinoma. The apoptotic index [AI] was evaluated by TUNEL in relation to the proliferation index [PI] as estimated by Ki67 aiming to correlate [AI and PI] with clinicopathologic variables and apoptosis-regulating proteins Fas and Fas-L. Fas and FasL were inversely correlated and were detected in 40% and 65% of cases respectively. The mean apoptotic index [AI] was 1.40 +/- 0.74%, and the mean proliferation index [PI] was 42.7 +/- 14%. Fas and AI were closely associated and decreased significantly in higher tumor grade and stage; whereas, FasL and PI increased significantly in higher grade and stage. Tumor infiltrating lymphocytes [TIL] showed higher mean apoptotic index in FasL positive than FasL negative tumor tissues. Therefore, it could be suggested that the apoptotic and proliferation indices could be useful prognostic markers in pancreatic ductal adenocarcinoma. Fas expression plays a key role in apoptosis in pancreatic cancer and FasL expressing carcinomas induce marked apoptosis in TIL allowing them to evade immune surveillance. Therefore, we recommend designing new therapeutic approaches for pancreatic adenocarcinoma based on reinforcement of Fas/FasL-induced tumor apoptosis

use of buccal fat pad flap in reconstruction of large maxillary defects

11 patients with large maxillary defects have been reconstructed with buccal pad fat flap. The age of the patients ranged from 23 to 65 years. Unilateral flap was used in 7 patients and 4 patients needed bilateral flaps. Four patients received post-op radiotherapy. The maximum size defect was 7x5.5 cm. Healing was complete in 6 to 8 weeks. In one case there was partial loss of the flap in one side only while further two cases had post-operative dehiscence. All the three cases were treated successfully by local tissue advancement. It is concluded that buccal fat pad flap is a useful technique for reconstruction of large maxillary defects but may be associated with more complications as the size of the reconstructed defect increases

Histological study of the effect of vitamin E supplementation on the damaged skeletal muscle of adult male albino rats

This study investigated whether daily supplementation with vitamin E could modify the histological and ultrastructural indices of muscle damage following a crush injury. For this purpose nine adults [three months old] male albino rats weighing 250-300gm were used in this study. The animals were divided into three equal groups, a control group [group A] and two experimental groups [groups B and C]. The animals of the experimental groups [groups B and C] [3 animal each] were exposed to crush injury. Also the animals of group C received a daily dose of 5000 mg/kg body weight vitamin E orally by nasogasrtric tube for 4 weeks before and 3 days after crush injury. At the time of sacrifice, the animals were anaesthetized with ether inhalation and their tibialis anterior muscles, were carefully dissected out and processed for light and electron microscope examinations. Examination of the muscles of group B revealed haemorrhage and distorted muscle fibers with some apoptotic cells. The damaged segment showed gross tearing and degeneration. A large number of infiltrating cells were seen in the intercellular connective tissue and within the damaged muscle fibers. An increase in the macrophage number were noticed. However examination of group C revealed preserved muscle ultrastructure. Also infiltrating cells and the macrophages activity were decreased. From this study, it could be concluded that vitamin E supplementation reduce histological and ultrastructural indices of muscle damage. So, protective daily dose for sport players or any persons subjected to possible trauma is recommended

Histological study of the effect of cyclosporine-A on the testicular tissue of rats

Ten adult [3-6 months old] male albino rats weighing 250-300gm were used in this study aiming to evaluate the histological alternations in the rat testes received cyclosporine-A [CSA]. The animals were divided into two equal groups [5 animals each], a control group and an experimental one. Animals of the first group were received sterile water orally. Animals of the second group were treated daily with 30 mg/kg of body weight by [CSA] orally for one month. At the time of sacrifice, all the animals were anaesthetized with ether inhalation and their testes were carefully dissected and processed for light and electron microscope examination. Light microscope examination of the testes of treated animals revealed that the seminiferous tubules were widely separated, some of them appeared with irregular outlines, disorganization and sloughing of their germinal epithelium into their lumina. Many exfoliated germ cells appeared with pyknotic nuclei, also, arrest of spermatogenesis in most of the affected tubules were noticed. Also many large cavities also were seen in between the germinal epithelium. Examination by electron microscope of the treated testes showed spermatid with electron dense nuclei, with loss of their membrane and unrecognizable cytoplasmic organelles. Some giant bodies were containing two or more nuclei at different stages of apoptosis and multiple vacuoles were observed within the wall of tubules and in their lumina. Sertoli cells were the only lining in some of the seminiferous tubules, many apoptotic bodies were seen within their cytoplasm. Also, there was disruption of tight junction between their lateral processes. Also deformed sperms were noticed. The cytoplasm of Leydig cells contained many vacuoles. From this study, it could be concluded that cyclosporine impairs spermatogenesis and lead to testicular dysfunction. These finding will have an important bearing for man receiving cyclosporine for long periods to guide the physician adjusting long-term treatment