Some invasive tumours characteristically have an abundant stroma rich in collagen, the production of which is termed the desmoplastic response. It has been suggested that this response may have a protective effect, and act to limit the process of tumour invasion. To investigate this possibility, we have examined various colorectal tumours for inter- and intra-tumoural variations in the desmoplastic response. As markers of this response, the distributions of collagen-I protein and myofibroblasts have been demonstrated by immunocytochemistry, while collagen-I messenger RNA has been demonstrated by in situ hybridization (ISH). Evidence of a desmoplastic response was obvious in carcinomas, but not in non-invasive adenomas. In carcinomas, we found that the response was marked in the tumour centre, where morphological features of active invasion have been reported to be absent. By contrast, we found little evidence of a desmoplastic response at the invasive edge of these carcinomas, where features suggestive of active invasion are prominent: in this location, collagen-I immunostaining was limited and myofibroblasts were sparsely distributed or absent. While our ISH results suggested active collagen-I synthesis in the tumour centre, there was little evidence of collagen-I synthesis in host tissues ahead of the invasion front. On the basis of these and other reported findings, we suggest that, while the desmoplastic response may reduce the invasive activity of neoplastic cells in the tumour centre, it fails to prevent the spread of colorectal cancer because of its deficiency at the invasive edge.

Background-Basic fibroblast growth factor (bFGF) promotes angiogenesis and healing of gastric ulcers in rats, and bFGF expression is up regulated in such ulcers. However, little is known about expression of bFGF in human gastric mucosa. Aims-To investigate bFGF expression in intact human gastric mucosa and gastric ulcers and to determine whether low bFGF content or altered binding by mucosa is associated with ulceration. Subjects-Endoscopy outpatients, gastrectomy patients, and organ donors. Methods-bFGF was isolated by heparin aYnity chromatography and characterised by western blotting and endothelial cell bioassay. bFGF was measured by immunoassay and its distribution defined by immunohistochemistry and in situ hybridisation. Binding of bFGF by heparan sulphate proteoglycans was investigated by sodium chloride and heparin extraction. Results-Bioactive bFGF (19 kDa) was detected in normal mucosa but bFGF mRNA was not found. bFGF expression was up regulated in granulation tissue endothelial cells, mononuclear cells, and epithelial cells at the ulcer rim. Gastric ulcer patients had constitutively low bFGF concentrations in intact antral mucosa which were not explained by changes in binding to heparan sulphate proteoglycans. Conclusions-bFGF expression is up regulated in human gastric ulcers. Low intact mucosal bFGF content is associated with gastric ulceration. (Gut 1998;43:525-536)

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Summary:Case reportA 48-year-old man with refractory kappa light chain myeThe development of GVHD following allogeneic BMT is known to be closely associated with significant antiloma underwent tandem PBSC transplants in 1996. He had presented in August 1995 (urinary Bence-Jones protein leukaemic activity. Immunological graft-versus-leukaemia (GVL) effects are now well established and are (BJP) excretion 2.4 g/l; plasma cell infiltration, 94%; ␤2-microglobulin, 10.8 mg/l) and failed to respond to three commonly exploited in the treatment of leukaemic relapse following allogeneic transplantation by the use courses of VAD chemotherapy followed by a further three courses of cyclophosphamide-VAMP chemotherapy (BJP of donor lymphocyte infusions. More recently a graftversus-myeloma (GVM) effect following allogeneic excretion, 2.8 g/l; plasma cell infiltration, Ͼ50%). He therefore went on to receive two courses of a cyclosporin Atransplantation has been documented, suggesting that eradication of haematological malignancies following VAD regimen in an attempt to block the presumed MDR phenotype. This treatment led to a partial response (BJP allogeneic transplantation is achieved at least in part by immunological mechanisms. It is now also established excretion, 0.84 g/l; 15% plasma cell infiltration). PBSC mobilisation was then performed using cyclophosphamide that spontaneous GVHD can occur following autologous transplantation and can be induced by cyclosporin A 3 g/m 2 and G-CSF 300 g daily and sufficient CD34-positive cells were collected for a tandem transplant. Some of administration. However, there is only limited evidence that the development of autologous GVHD has an antithe cells collected were stored unmanipulated for use after the first transplant whilst the remainder underwent CD34 ϩ tumour effect. We report for the first time the development of autologous GVHD following PBSC transplanselection using the Ceprate (Cellpro, St Pierre, Belgium) column method for use following the second high-dose protation for myeloma apparently resulting in a GVM effect.cedure. PCR on the apheresis products revealed contamination with myeloma as demonstrated by PCR for a known Keywords: autologous graft-versus-host disease (GVHD); multiple myeloma; graft-versus-myeloma (GVM) IgH framework III rearrangement even after CD34 ϩ selection. effect; PBSC transplantation He proceeded to the first unselected PBSCT in March 1996, following conditioning with high-dose melphalan Evidence for a graft-versus-myeloma (GVM) effect following allogeneic transplantation has recently been reported. 1,2 It is known that clinical and histological changes consistent with GVHD can arise in recipients of syngeneic and autologous grafts, but as yet there has been little direct evidence that this can lead to an antitumour effect. We report a patient who spontaneously developed grade II GVHD following a tandem PBSCT which resulted in a significant GVM effect.