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Biomedical subjects

P G McCulloch

Publications and source records attributed to P G McCulloch.

10 recordsLinked to original sources
PubMed1999

Reduction in membranous expression of beta-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer.

beta-catenin, a component of the E-cadherin-catenin cell adhesion complex, also plays a separate intracellular signalling role, interacting with APC protein. Intracellular accumulation of beta-catenin is common in colorectal neoplasia. beta-catenin abnormalities are associated with poor survival in gastric cancer, but previous studies do not differentiate between membrane-associated and intracellular beta-catenin. In this study we aimed to determine which type of expression abnormalities for E-cadherin, beta-catenin and alpha-catenin correlate with clinico-pathological features and survival in gastric cancer. Immunoperoxidase staining of paraffin-embedded sections from 40 gastric cancers was performed for E-cadherin, alpha- and beta-catenins using microwave unmasking and an avidin-biotin technique. Clinical data were obtained from case records and cancer registry records. Reduced membranous expression of beta-catenin occurred in 10/12 (83%) diffuse and 8/28 (29%) intestinal tumours (P= 0.0014), and was associated with poor differentiation (P= 0.0015) and short survival (P= 0.032), but not with age, sex, tumour size or nodal status. Nuclear expression of beta-catenin was uncommon; cytoplasmic expression was observed in 13/40 cases (33%) but did not correlate with histology, tumour grade or survival. Reduced E-cadherin membrane expression was associated with lymph node metastasis (P= 0.02). Neither E-cadherin or alpha-catenin expression correlated with survival. Reduced membranous expression of beta-catenin predicts poor prognosis in gastric cancer, whilst ectopic intracellular expression is relatively rare. The apparent differences in beta-catenin expression from those found in colon cancer merit further study.

Cadherins↗
PubMed1998

Variability of mitomycin C adsorption by activated charcoal.

A saline suspension of mitomycin C adsorbed on activated charcoal and administered intraperitoneally has been reported to be safe and effective in the treatment of gastric carcinoma. Activated charcoal specifically targets tumour and lymph-node tissues and the sustained higher local drug concentration is thought to be beneficial. The charcoal particles used in these suspensions have varied in size from > 147 microm to < 20 nm in diameter, but no data have been published to show how this might affect drug adsorption and delivery. Any variability in drug adsorption could pose a serious clinical risk for drugs with a narrow therapeutic index. We have, therefore, investigated the adsorption of mitomycin C on activated charcoal in-vitro. Activated charcoal was ground and sieved to yield four size-fractions between 180 and 53 microm. Adsorption isotherms (n > or = 3) were constructed and applied to the Freundlich model with 0-l00 microg mL(-1) mitomycin C measured by HPLC with detection at 365 nm. Adsorption of mitomycin C by activated charcoal varied by a factor of three under identical conditions at room temperature (21 degrees C) and at 37 degrees C. The specific adsorption (microg mitomycin C (mg activated charcoal)(-1)) was generally higher at 37 degrees C than at room temperature. The variability of mitomycin C adsorption was greatly reduced by addition of the surface-active agent polyvinylpyrollidone, used to determine that adsorption of mitomycin C was independent of activated charcoal particle size. The characteristics of adsorption of mitomycin C by activated charcoal are complex and should be thoroughly investigated to discover the critical controlling factors before submitting the suspensions for further clinical evaluation.

Adsorption↗
PubMed1995

Comparison of the molecular genetics of c-erb-B2 and p53 expression in stomach cancer in Britain and Japan.

BACKGROUND: Differences in the epidemiology and treatment outcome of stomach cancer have led to the suggestion that in Japan, this disease may be biologically less aggressive than that found in the West. The authors compared p53b and c-erb-B2 expression, trying to identify genetic differences in Japanese compared with Western stomach cancers. METHODS: Paraffin embedded formalin fixed tissues from 89 British and 89 matched Japanese patients were examined by immunohistochemistry after microwave treatment. Cases were matched for T-stage, year of surgery, and histopathologic grade. RESULTS: Tumors from 48 British and 46 Japanese patients expressed p53, whereas those of 27 British and 28 Japanese patients expressed c-erb-B2. No significant difference in the density or distribution of protein expression was found between the two populations. The distribution of expression between diffuse and intestinal types and the proportion of cases expressing both antigens were similar in the two groups. CONCLUSIONS: p53 and c-erb-B2 are expressed in the same way in stomach carcinomas from Japanese and British patients. This study found no evidence of genetic differences in the cancers from the two countries.

Gene Expression↗
PubMed1993

Effects of surgery on the generation of lymphokine-activated killer cells in patients with breast cancer.

Natural killer (NK) cell activity and the capacity to generate lymphokine-activated killer (LAK) cell activity were studied in 43 patients with operable breast cancer before and after surgery. Results were compared with those from ten healthy subjects. Patients with breast cancer had normal LAK and NK cell activity before surgery. A subgroup of patients with stage III disease had depressed LAK cell activity (P < 0.013). NK cell activity decreased by over 50 per cent on the first day after surgery and did not return to preoperative levels by day 7 (P < 0.0005). Generation of LAK cell activity was unaffected by surgery. The addition of 10 per cent autologous plasma to the culture medium during the induction of LAK cell activity in vitro did not suppress LAK cell activity in patients with breast cancer. These results suggest that perioperative adjuvant immunotherapy based on interleukin 2 and LAK cells is not ruled out by systemic suppressive effects from either cancer or surgery.

Adult↗
PubMed1986

A prospective comparison of gentamicin and metronidazole and moxalactam in the prevention of septic complications associated with elective operations of the colon and rectum.

Bacteriologic evidence suggests that Latamoxef (moxalactam) is effective against colonic bacteria which cause infection during colonic and rectal operations. In a prospective comparative study, 86 patients undergoing colorectal operations were randomized to receive intravenously 24 hour antibiotic cover with either gentamicin and metronidazole or moxalactam. Six patients (13 per cent) in the gentamicin and metronidazole group and five (12 per cent) in the moxalactam group had wound sepsis develop. Perineal wound sepsis (31 per cent) was significantly more common than abdominal wound sepsis (7 per cent). No complications were noted from the use of moxalactam. No clinical evidence of abnormal bleeding was seen and the results of studies on coagulation and platelet function postoperatively were normal. The results suggest that moxalactam provides effective, safe prophylaxis comparable with established antibiotic combinations in patients undergoing colorectal operations.

Adult↗