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...
S_mary Human colorectal cancer tissue and matched uninvolved mucosa from 21 patients were examined by radioligand displacement for the presence of binding sites for bombesin-like peptides. Five cancers, but no univolved mucosa, expressed high-affinity, low-capacity bombesin binding sites (KYd = 6.53 nM, B.. = 58.6 fmol mg-' protein) of the gastrin-releasing peptide (GRP)-preferring subtype (IC50 4.8 nM).Bombesin-like peptides may have a role in the pathogenesis of colorectal cancer, and bombesin receptor antagonists may be of value in the treatment of receptor-positive tumours.
percutaneous therapeutic interventions under X-ray control were performed in patients with exudative complications. Results: Sensitivity, specificity and diagnostic accuracy of ultrasound imaging were respectively 84.7%, 73.4% and 78.8%. Sensitivity, specificity and diagnostic efficiency of cytological and microbiological examination of our data were, respectively, 86.9%, 95.2% and 91.6%. 737 miniinvasive percutaneous interventions were hold totaly. The implementation of miniinvasive percutaneous interventions helped to stop the disease process and to avoid open surgical procedures in 91.7% of cases. Conclusion: Fine-needle diagnostic puncture is a highly informative method for diagnosis of the nature and details of tissue damage and pathological process phase. The timely refining ultrasound diagnosis of various clinical and morphological forms of acute pancreatitis combined with diagnostic fine-needle puncture conducting allows to approach differentiately to the implementation of miniinvasive percutaneous interventions and to justify a strategic position in the surgical treatment of destructive pancreatitis.
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 ...
Bombesin-like peptides and their receptors are widely distributed throughout the gut and are potential mitogens for a number of gastrointestinal (GI) cancers. We have analysed the expression of bombesin-like peptides and their receptor subtypes in normal and neoplastic colorectal tissue. Expression was analysed by reverse transcription polymerase chain reaction (RT-PCR) using receptor and ligand subtype-specific primers and then expression localized by in situ hybridization (ISH) with riboprobes synthesized by in vitro transcription of cloned PCR products. Colorectal cancer tissue and matched normal mucosa from 23 patients were studied. Two of these patients had synchronous adenomatous polyps and two had synchronous hepatic metastases which were also studied. An additional two patients with adenomatous polyps were studied along with matched normal mucosa. Gastrin releasing peptide (GRP) receptor and ligand expression was present in all samples but with overall greater expression in the tumour samples. Neuromedin B (NMB) receptor expression was not detectable. NMB ligand was detected in all but one mucosal sample with overall overexpression in the tumour samples. Bombesin receptor subtype 3 (BRS-3) receptor expression was not detectable. These data support the possibility that GRP may be an autocrine growth factor in colorectal cancer. © 2000 Cancer Research Campaign
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