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Biomedical subjects

S L Parsons

Publications and source records attributed to S L Parsons.

10 recordsLinked to original sources
PubMed1999

A pilot study of the safety and effects of the matrix metalloproteinase inhibitor marimastat in gastric cancer.

The aim of this study was to evaluate the safety and tolerability of 4 weeks administration of marimastat, and to seek evidence of biological activity as observed by changes in the endoscopic appearance of the gastric tumours. 35 patients with advanced, inoperable gastric or gastro-oesophageal tumours were recruited. The dose of marimastat was reduced from the starting dose of 50 mg twice daily (6 patients) to 25 mg once daily (29 patients). 31 completed the 28 day study period. Marimastat was generally well tolerated, with the principal treatment-related toxicity being pain and stiffness of the musculoskeletal system. These symptoms occurred more frequently at the higher-dose, and increased to involve a total of 13 patients (37%) with longer-term treatment. The events were usually rapidly reversible on drug discontinuation. 3 patients receiving prolonged treatment experienced more severe symptoms, with the development of skin thickening and contractures in the hands. At endoscopy, 10 patients showed an increased fibrotic cover of the tumour, 8 had decreased haemorrhagic appearance, and in at least 2 cases where comparative tumour histology was assessable, there was evidence of increased stromal fibrotic tissue.

Adult↗
PubMed1998

Gelatinase (MMP-2 and -9) expression in gastrointestinal malignancy.

The aim of the study was to investigate expression of the active and inactive gelatinases (MMP-2 and -9) in colorectal neoplasia and gastric cancer compared with normal mucosa. A total of 53 colorectal cancers and corresponding normal mucosa were studied using gelatin zymography as well as 15 colorectal adenomas and 13 gastric cancers with corresponding normal mucosa. Overexpression of all the gelatinases occurs in both colorectal and gastric cancer, with activation of MMP-2 appearing to be a feature of the malignant phenotype. Overexpression of MMP-9 occurs in colorectal adenomas. The gelatinases are overexpressed in gastrointestinal neoplasia, suggesting that these enzymes may have an important role in tumour invasion and metastasis.

Adenoma↗
PubMed1998

Dupuytren's disease and frozen shoulder induced by treatment with a matrix metalloproteinase inhibitor.

In a series of 12 patients with inoperable gastric carcinoma who had treatment with a synthetic matrix metalloproteinase inhibitor (Marimastat) for more than one month, six developed a frozen shoulder or a condition resembling Dupuytren's disease. This suggests that the matrix metalloproteinases, a family of naturally occurring proteinases, may be involved in the pathogenesis of these two conditions. Our observation opens avenues for further research which could lead to local or systemic therapeutic interventions for frozen shoulder and Dupuytren's disease.

Adenocarcinoma↗
PubMed1997

Phase I/II trial of batimastat, a matrix metalloproteinase inhibitor, in patients with malignant ascites.

Matrix metalloproteinases have been shown to be important in tumour invasion and metastasis, and the use of matrix metalloproteinase inhibitors in animal models has suggested that these agents may be useful in the control of malignant disease. This article reports the results of an early clinical trial of batimastat, one of the first generation of metalloproteinase inhibitors, in patients with malignant ascites. The drug was well absorbed via the intraperitoneal route and associated with few side-effects. Furthermore, a response to treatment was seen in about half the evaluable patients with advanced malignant disease. The results suggest that further research on the use of matrix metalloproteinase inhibitors in patients with malignant disease is worthwhile.

Aged↗
PubMed1997

Matrix metalloproteinases.

BACKGROUND: The matrix metalloproteinases (MMPs) have a role in gastrointestinal malignancy. This role is reviewed, with particular reference to the gelatinase subgroup of enzymes. METHODS: All relevant papers derived from the Medline and Enbase databases between 1984 and early 1996 were reviewed. RESULT AND CONCLUSION: There is now strong evidence that MMPs play a major role in tumour invasion and metastasis. The development of MMP inhibitors may lead to important new treatment for the control of malignant disease.

Clinical Trials as Topic↗
PubMed1996

Malignant ascites.

Investigation and treatment of malignant ascites are often in the hands of the general surgeon and can be difficult. This article considers the aetiology and pathophysiology of malignant ascites and explores the best form of management. Established treatment modalities and new therapeutic options are reviewed and a new management regimen based on a knowledge of the tumour of origin is proposed, which aims to balance potential benefit against morbidity.

Abdominal Neoplasms↗
PubMed1996

Malignant ascites: a 2-year review from a teaching hospital.

In this retrospective review of 164 consecutive patients with malignant ascites it has been shown that ovarian ascites accounts for 28% of the total and is associated with a significantly improved survival compared with other groups (P<0.001). Non-ovarian ascites is associated with a very poor prognosis and many patients in this group are unsuitable for aggressive treatment. In 49% of patients, ascites will be the presenting feature requiring further investigation to ascertain the primary tumour. Thorough investigation of female patients should be performed in order to identify all patients with an ovarian primary so that appropriate chemotherapy can be given. However, thorough investigation in male patients is not justifiable.

Adult↗
PubMed1996

Therapeutic effect of the matrix metalloproteinase inhibitor, batimastat, in a human colorectal cancer ascites model.

The matrix metalloproteinase inhibitor batimastat was administered to a human colorectal cancer ascites model, which was initiated by injection of C170HM2 cells into the peritoneal cavity of SCID mice and resulted in solid tumour deposits and ascites formation. The cell line expressed both the 72 and 92 kDa forms of gelatinase by zymography. Batimastat administered from day 0 (40 mg kg-1) reduced the volume of ascites to 21% of control in mice treated from day 0 (P < 0.002) but not day 10. Formation of solid peritoneal deposits was significantly reduced to 77% of vehicle control when batimastat was administered from day 0 (P < 0.01) and 69% of control when administered from day 10 (P < 0.05). Thus, batimastat has the ability to reduce the volume of ascites forming in SCID mice injected intraperitoneally with the human colorectal cell line, C170HM2, when administered from day 0 but not from day 10. Solid peritoneal tumour deposits were significantly reduced in both treatment groups, highlighting the therapeutic potential of batimastat in this clinical condition.

Animals↗
PubMed1993

A case of bilateral trench foot.

A case of severe bilateral trench foot is presented in a patient who lived rough for 3 weeks without removing his boots. Non-operative management yielded no clinical improvement and bilateral below-knee amputation was necessary. Histology revealed subcutaneous and muscle necrosis with secondary arterial thrombosis.

Adult↗