Degradation of the extracellular matrix is necessary for invasion and metastasis by cancer cells. Two gelatinolytic matrix metalloproteinase enzymes, MMP-2 and MMP-9, are supposed to be key enzymes in this process. The purpose of this study was to correlate the presence of MMP-2, MMP-9 and their inhibitors with the tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 RNA using reverse transcriptase PCR technique with tumor stage in 17 samples of renal cell carcinoma. The ratio of tissues expressing MMP-2 and MMP-9 to those expressing TIMP-1 and TIMP-2 was defined to be 1 in normal kidney tissue. This MMP:TIMP ratio was significantly increased to 2.43 (standard deviation, SD = 0.8) in locally confined renal cell carcinoma and to 4.86 (SD = 1.1) in advanced carcinoma (p <0.01). In primary tumor cell lines the ratio of MMP:TIMP expression was 3.44 (SD = 0.6). These data suggest that the balance of MMP-2 and MMP-9 to TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of renal cell carcinoma.
In this comparative study, microcalorimetric measurements were carried out on a total of 96 tumorous and nontumorous tissue samples taken from organs of the urogenital tract using a thermal activity monitor (TAM). Changes in the heat emission of the tissue samples were measured at 1-min intervals and graphically displayed as a function of time. The aim of the study was to compare the microcalorimetric results with impulse-cytophotometric and histological findings and provide evidence for the metabolic activity of tumorous and nontumorous tissue. In order to obtain the variation in metabolic activity, the maxima (Pmax) of the curves were determined as a value of the maximum thermal power of a tissue sample, the mean values (P) were determined by the mean thermal power and the contour integrals (W) were defined by the behavior of the energy reserves and their mobilization. The first part of the study was carried out to investigate whether tumorous and nontumorous tissue samples differ in general according to their metabolic activity. We discovered, using the parameters described above, that in general tumorous tissue exhibited a higher metabolic activity than nontumorous tissue samples. For example, both W and P in tumorous prostate tissue samples were eightfold higher and the (Pmax) value was 8.4-fold higher than in normal tissue. Additional investigations on testicle and kidney tissues were performed to find a possible correlation between microcalorimetric results and histological grading. We found that an increasing malignancy correlated with a higher metabolic activity of the tissue. Based upon these results we were able to differentiate the various histological gradings of these tumorous tissues by microcalorimetric measurements. The results show it is possible to differentiate between normal and tumorous tissue samples by microcalorimetric measurement based on the distinctly higher metabolic activity of malignant tissue. Furthermore, microcalorimetry allows a differentiation and classification of tissue samples into their histological grading. With the help of microcalorimetry, it might be possible in future to detect and record the metabolic processes of isolated tissue structures and changes in these activities as a result of medical intervention such as cytostatic treatment.
Objective To examine the role of temperature in the irreversible changes that occur within 4–6 h as ischaemic atrophy develops in the testis during testicular torsion, by determining effects on testicular pH, lactate accumulation and morphology.
Materials and methods Tissue acidification (pH), tissue lactate and structural changes were measured at temperatures of 35, 25, 15 and 5°C in 34 human testes obtained as orchidectomy specimens from patients with metastatic prostatic cancer, and in 19 testes taken from young dogs.
Results At a normal testicular temperature of 35°C, the pH decreased to 6.0 within 2 h of the onset of ischaemia; cooling to 15°C extended this delay to 6 h. Tissue lactate increased from 25 μmol/g dry weight to about 200 μmol/g at 35°C. Semi‐thin sections of the canine testes showed swelling of the intratubular tissue with loss of interstitial space; lower temperatures delayed these changes.
Conclusions In the present study, 6 h of torsion was relatively prolonged, in that the pH decreased to 5.8 and testicular tissue was destroyed. Acidification and histological damage can be prevented by cooling. The critical pH of the testis beyond which irreversible changes occur is unknown; a pH of <6.0 is likely to provoke such changes.
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