The results of this study indicate that the elevation of serum levels of either MMP-2 or MMP-3 or both could be new predictors of recurrence in patients with advanced urothelial carcinoma after complete resection.
Summary Serum levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) were evaluated as prognostic indicators of the recurrence of urothelial cancer. Sera were obtained from 127 healthy control subjects and 97 urothelial cancer patients who underwent complete resection and were measured for MMP-2 and TIMP-2 using a one-step enzyme immunoassay. The relationship between the serum MMP-2/TIMP-2 ratio and the recurrence of urothelial cancer was examined. The mean serum MMP-2/TIMP-2 ratio in the 31 advanced urothelial cancer patients with recurrence was significantly higher than that in the 22 patients without recurrence (P = 0.0029) and in the 44 superficial bladder cancer patients (P < 0.0001). The 1-and 3-year disease-free survival rates in the patients with high MMP-2/TIMP-2 ratios (50% and 12%) were significantly poorer than those of the patients with normal ratios (82% and 56%) (P=0.0152). Univariate and multivariate analyses of recurrence demonstrated that the serum MMP-2/TIMP-2 ratio is a significant independent indicator of advanced urothelial cancer. Our results indicate that an imbalance between the serum levels of MMP-2 and TIMP-2 could be a new predictor of recurrence in advanced urothelial cancer patients.Keywords: serum; matrix metalloproteinase-2; tissue inhibitor of metalloproteinases-2; urothelial cancer; recurrence Matrix metalloproteinases (MMPs) has been shown to play a role in the degradation of the vascular basement membrane, whose major component is type IV collagen Nakajima et al, 1991). Matrix metalloproteinase-2 (MMP-2, gelatinase A, a 72-kDa type IV collagenase) is produced by both malignant cells and stromal cells such as fibroblasts, macrophages and vascular endothelial cells (Nakajima et al, 1991). Many investigators have demonstrated that human and rodent metastatic malignant cells produce larger amounts of MMP-2 than do non-metastatic cells, both in vitro and in vivo (Liotta et al, 1980;. Tissue inhibitor of metalloproteinases-2 (TIMP-2), an unglycosylated protein of 21-kDa molecular weight, strongly inhibits the biological activity of MMP-2, and was shown to strongly inhibit cancer invasion, metastasis, growth and angiogenesis in some rodent and human tumours (Stetler-Stevenson et al, 1989;DeClerck et al, 1992). Therefore, it is likely that an imbalance in the MMP-2 and TIMP-2 ratio plays an important role in cancer invasion, metastasis and angiogenesis DeClerck et al, 1994). Some investigators have revealed a relationship between the recurrence and the expression of MMP-2 and TIMP-2 in bladder cancer tissues (Davies et al, 1993;Grignon et al, 1996). However, there are no previous reports concerning the relationship between the serum MMP-2/TIMP-2 ratio and the recurrence of human urothelial cancer. In this study, the serum levels of MMP-2 and TIMP-2 were determined in human urothelial cancer patients, and the relationship between the serum MMP-2/TIMP-2 ratio and invasion and metastasis in urothelial cancer was examined. We discuss the diagno...
We evaluated the diagnostic usefulness of measurement of the soluble cytokeratin 19 fragment, a new tumor marker, in 391 patients with lung cancer and in 424 patients with benign lung diseases. Serum concentrations of cytokeratin 19 fragment were measured by a sandwich ELISA (CYFRA). The cut‐off value was defined as 3.5 ng/ml, which is associated with a specificity of 85% for benign lung diseases. CYFRA had a high sensitivity (57.5%) in all subjects with lung carcinoma, and had a higher sensitivity for squamous cell carcinoma (73.1%, n = 141) than squamous cell carcinoma‐related antigen (61.0%). CYFRA was associated with a relatively high sensitivity (42.1%) in early‐stage squamous cell carcinoma (stage I, based on the classification of the Japan Lung Cancer Society), but the CYFRA titer was higher in advanced squamous cell carcinoma than in early‐stage squamous cell carcinoma. Our findings suggest that CYFRA is potentially useful for diagnosis and monitoring of lung carcinoma, especially for squamous cell carcinoma.
The results of this study indicate that the elevation of serum levels of either MMP-2 or MMP-3 or both could be new predictors of recurrence in patients with advanced urothelial carcinoma after complete resection.
Background: We describe a 56-year-old woman admitted to the hospital with a diagnosis of acute myocardial infarction without an increase of serum creatine kinase (CK) activity during her clinical course. She died on the 11th hospital day, and the diagnosis was confirmed by autopsy. The patient had had no previous muscular symptoms.
Methods: Expression of the CK-muscle (CK-M) protein in cardiac tissue was examined by immunoblotting and immunochemical staining. CK-M mRNA expression was estimated by semiquantitative reverse transcription–PCR. Gene structure of CK-M was determined by Southern blotting and direct sequencing of 2251 bp. Existence of a point mutation in the CK-M gene was examined by restriction fragment length polymorphism analysis of PCR products (PCR-RFLP) in the patient and in 108 controls.
Results: CK-M protein in the myocardial tissue of the patient was substantially lower (103 ± 7 ng/mg protein) than in control myocardial tissue (35 800 ± 2860 ng/mg protein). Immunoreactive CK-M in the patient tissue sample was 0.3% of the value for the control sample. CK-M mRNA was 53-fold less in the patient sample compared with the control. This very low expression of CK-M mRNA was considered to be the primary reason for CK-M deficiency. Direct sequencing revealed a point mutation at residue 54 in exon 2, which was specific for the patient. No other abnormalities were found in the CK-M gene of the patient.
Conclusions: This report identifies a molecular abnormality in human CK deficiency and discusses the physiologic relevance of CK-M.
The clinicopathological correlation between serum‐CEA (s‐CEA) and immunohistological tissue‐CEA (t‐CEA) was studied on 63 cases of operated lung cancers. T‐CEA was examined by peroxidase anti‐peroxidase (PAP) method. T‐CEAs were detected in 36/39 cases (92.3%) of adenocarcinoma, 16/16 cases (100%) of epidermoid carcinoma, 2/5 cases (40%) of large cell carcinoma, and 1/ 3 case (33.3%) of small cell carcinoma. T‐CEAs in adenocarcinoma and large cell carcinoma with much exhibited moderate to strong reactivity with diffuse distribution, and also s‐CEA of these cases indicated high levels. On the contrary, in epidermoid carcinoma t‐CEAs showed a weak reactivity with focal distribution, and s‐CEAs also demonstrated low levels. In adenocarcinoma it was suggested that the more cancers were differentiated, the more t‐CEA and s‐CEA were increased, and about two third of cases showed a balance between t‐CEA and much content in cancer tissue. S‐CEAs were not correlated with the size of the primary lesion or the extent of lymph node metastasis, but with the histological types, i.e. high levels of s‐CEA in adenocarcinoma and large cell carcinoma with mucin. ACTA PATHOL. JPN. 34: 1209–1219, 1984.
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