S. S. Ngoi

Expression of nitric oxide synthase, cyclooxygenase, and p53 in different stages of human gastric cancer

The present study evaluated the significance of nitric oxide synthase (NOS), cyclooxygenase (COX) expression and p53 status in 55 patients with gastric adenocarcinoma and relationship of these molecular markers to tumor characteristics and metastatic potential. Immunohistochemical technique was used to identify the cellular location and distribution of the enzymes in the specific cells of gastric tumors. In gastric cancer tissue, the expression of inducible enzymes, iNOS and COX-2, increased significantly with increasing tumor stage (P=0.015, P=0.001, respectively), size (P=0.025, P=0.001, respectively) and the presence of metastases (P=0.002, P=0.015, respectively). The expression of constitutive enzymes, ecNOS and COX-1, followed the opposite pattern. COX-1 was significantly reduced in advanced gastric tumors (P=0.007) and tumors larger than 5 cm (P=0.007). Reduced expression of ecNOS was also observed in advanced gastric tumors; however, this did not reach statistical significance. 53% of gastric tumors showed accumulation of p53. This was significantly higher in advanced tumors (P=0.004), larger than 5 cm (P=0.015) with metastases (P<0.001). Gastric tumors positive for accumulation of p53 had significantly stronger expression of iNOS (P=0.018) and COX-2 (P=0.01) enzymes than tumors negative for this nucleophosphoprotein. We conclude, that tumor-associated nitric oxide production, as well as COX-2 overexpression, may promote gastric cancer progression by providing a selective growth advantage to tumor cells with non-functioning p53.

Randomized trial of periportal peritoneal bupivacaine for pain relief after laparoscopic cholecystectomy

The aim of this study was to determine whether injection of a long‐acting local anaesthetic, in relation to the port sites at the level of the parietal peritoneum, would reduce postoperative pain following laparoscopic cholecystectomy. Patients were entered into a randomized, prospective, double‐blind study comparing the effects of a standard technique, in which bupivacaine (total of 20 ml, 0–5 per cent) was injected into the subcutaneous periportal tissue around the four port sites, and a technique in which bupivacaine (total of 20 ml, 0.25 per cent) was injected into the subcutaneous periportal tissue as above with the addition of periportal parietal peritoneal injection of bupivacaine (total of 20 ml, 0–25 per cent). Two scores for pain, with the patient at rest, and on movement, were assessed 6 and 18 h after surgery using a visual analogue pain scale. Median pain score was significantly higher in patients who received standard technique (n = 40) than in those given peritoneal injection (n = 40) at both 6 (rest = 3.0 versus 1.0, movement = 5.0 versus 2.9) and 18 h (rest =1.9 versus 0, movement = 3.2 versus 1.2). Both opiate and oral analgesic requirements were reduced in patients administered peritoneal injection, although this was not statistically significant. The addition of periportal injection of bupivacaine at the level of the parietal peritoneum, performed under direct vision, reduces pain after laparoscopic cholecystectomy.

Differential expression of adenosine A1 receptors in colorectal cancer and related mucosa

Adenosine A1 receptors (A1R) are known to inhibit while the A2 receptors (A2R) stimulate the G-protein cAMP second messenger system and may play a role in cell growth and carcinogenesis. Using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method, mRNA for A1R and A2R was measured in human colorectal adenocarcinomas and individual peritumoural colon tissues. There was differential expression of the mRNA for A1R with tumour tissues having significantly higher amounts compared to peritumoural normal tissues. The mRNA for A2R was not found to be differentially expressed. The increase in the inhibitory A1 receptor in tumour tissues may be in response to increased adenosine release from the hypoxic cells found in malignant tumour tissues, thus indicating a possible role for the adenosine A1 receptor in carcinogenesis.

Nitric Oxide and Cancer

The possibility that the overall process of carcinogenesis may be linked to the deficiency of nitric oxide in a biological cell is examined. A hypothetical model of how this might operate to produce subtle changes in a cell resulting in and/or facilitating carcinogenesis is suggested.