Summary The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence. and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 wiare significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.Keywords: E-cadherin; E-selectin; intercellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1); adhesion molecule; colorectal cancer Cellular adhesion molecules play an important role in the process of metastasis. Positive and negative regulation of cell adhesion will influence the process as metastatic cells break away from the primary tumour, travel in the circulation and then adhere to cellular and extracellular matrix elements in particular secondary sites. Several families of cell adhesion molecules have been identified together with specific aberrations in malignant diseases (Zetter, 1993). The cadherins, Ca++-dependent homotypic cell-cell adhesion molecules, are essential for establishing and maintaining intercellular connections. Epithelial cadherin (E-cadherin) plays a crucial role in maintaining the integrity of epithelial tissues and has been positively correlated with tumour differentiation and negatively with infiltrative tumour growth and metastatic potential in a range of cancer types (Takeichi, 1993;Shino et al, 1995). Selectins are transmembrane glycoproteins that mediate heterotypic cell-cell contact through Ca+-dependent interactions with cell surface carbohydrates. In addition to mediating leucocyte adhesion to activated vascular endothelium, endothelial selectin (E-selectin) has been shown to be involved in the adhesion of cancer cells to the vasculature. Stronger adhesion to the endothelium is mediated through other classes of adhesion molecules, namely the integrins and cytokine-inducible endothelial cell adhesion molecules of the immunoglobuli...

Summary Tumour markers CEA, were measured in 33 patients undergoing chemotherapy for advanced colorectal cancer. The aim was to determine whether they could be used to accurately monitor the course of the disease, and reduce the need for imaging. Treatment with a 5-fluorouracil based regimen resulted in a partial response in nine patients (27%), whereas the remainder either had disease stabilisation or suffered from progression. Before treatment the CEA was elevated in 85% of patients and the and CA-242 in 78%. All three markers were elevated in 70% and at least one elevated in 93%. (Hammarstrom, 1985;Gupta et al., 1987;Safi et al., 1987;Sagar et al., 1991;Nilsson et al., 1992). Although none of these markers has proved to be of any particular value in screening for the disease, CEA is commonly used to assess the progress of patients following surgical treatment (Minton et al., 1985) and remains the 'gold standard'. Other markers appear less useful in isolation, but when combined as a panel with CEA may be of greater value than any one marker on its own (Safi et al., 1987;Persson et al., 1989). The aim of this study was to assess whether three tumour markers CEA, are of value in monitoring the progress of patients being treated with systemic chemotherapy for advanced colorectal cancer. Patients and methods PatientsThirty-three patients were studied; 24 were male and nine female, mean ages 58 (range 27-76) and 60 (42-78) respectively. All patients had histologically proven colorectal cancer with metastases. Twenty-six had liver metastases, ten locoregional disease, eight lung metastases, and two with disease at other sites. Several of these patients had disease at more than one site. The patients were a consecutive series in chemotherapy studies which required that the disease was measurable on CT scan. The time interval between presentation with the primary tumour and recurrent disease averaged at 16 months with a range of 0-91 months. Performance status was assessed by means of the Karnofsky scale (Karnofsky et al., 1948), the average being 80 with a range of 70-90.The study was approved by Leeds Eastern District Clinical Research (Ethics) Committee.Treatment schedule All patients received chemotherapy with a 5-fluorouracil (5-FU) based regimen as detailed below. Some of these patients were being treated in a multi-centre study comparing 5-FU and interferon alpha with 5-FU and leucovorin. The results of this study will be published separately. In the 5-FU/ interferon based regimen 5-FU was administered as a continuous intravenous infusion over a period of 5 days at a daily dose of 750 mg m2 followed by weekly intravenous bolus doses also of 750 mg m-2 commencing on day fifteen. Interferon alpha-2a 9 MU, was administered as a subcutaneous injection three times weekly. In the 5-FU/ leucovorin based regimen I-leucovorin 200 mg m-2 was infused over 10 min and followed within 5 min by a bolus of 5-FU at 370 mg m-2 for 5 consecutive days. This cycle was repeated every 4 weeks. Tumour markersA 10 ml sample of ...

Summary The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 45 patients with gastric cancer before treatment and their correlation with clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology, survival and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with gastric cancer in comparison with the group of healthy subjects (P < 0.00001 and P < 0.0001 respectively). Increased serum concentrations of VCAM-1 were associated with locally advanced and metastatic disease whereas ICAM-1 was significantly elevated both in local and in advanced/metastatic disease. Soluble E-cadherin and E-selectin concentrations did not show any significant elevation in gastric cancer patients. Concentrations of soluble adhesion molecules showed significant correlation with each other (except E-selectin and VCAM-1) and with alkaline phosphatase. Soluble ICAM-1 and VCAM-1 were significantly associated with an elevated total white cell count. Patients with elevated VCAM-1 had significantly poorer survival in comparison with patients with normal serum levels (P= 0.0361).

SUMMARY The peri‐operalive cellular immune response is depressed in patients with gastrointestinal cancer, a factor which may facilitate maligtiant dissemination. We have investigated the effects of perioperative rIL‐2 and a combination of rlL‐2 and interferon‐alpha (IFN‐α) on both peripheral blood lymphocyte function and number in patients undergoing surgical resection for colorectal cancer. Fifty‐two patients were randomly allocated to either control, rIL‐2 or rIL‐2 with IFN‐α treatment arms. In vitro studies were performed pre‐operatively and on post‐operative days I, 4, 7 and 10. Natural ikller (NK) and lymphokine‐activated killer (LAK) cell function were profoundly depressed in control patients (P < 0.001; P < 0.001), an effect abrogated in both treatment groups; indeed NK function was augmented in the rIL‐2 and IFN‐α group on the first post‐operative day in association with an increase in the percentage of cells expressing CD16 and CD56 (P < 0.01). Flow cytometric analysis of lymphocyte subsets in the control group was unremarkable, except for an early post‐operative fall in numbers of lymphocytes. Treatment with either rIL‐2 or rIL‐2 and IFN‐α produced an initial profound reduction in T lymphocyte numbers, followed by a ‘rebound’ lymphocytosis of activated CD3+ T cells, as demonstrated by a significant increase in co‐expression of CD25, CD38, and CD45RO. No significant differences were observed between either of the treatment groups. Adjuvant immunotherapy affects peri‐operative anti‐tumour immune responses, and this may influence long term outcome in patients undergoing surgery for gastrointestinal cancer.

Background-Does the use of the histamine H 2 receptor antagonist ranitidine improve the outcome of patients with gastric cancer? Patients-A total of 222 patients with gastric cancer who had received radical or palliative resection or who were deemed inoperable at presentation. Setting-Hospitals within Yorkshire, the participating clinicians being members of the Yorkshire GI Tumour Group. Methods-