The effect of chemo- and chemoimmunotherapy on the presence of circulating melanoma cells in peripheral blood. Preliminary results.

Reverse transcription and polymerase chain reaction (RT/PCR) with primers specific for tyrosinase allow for a new method of early detection of individual melanoma cells in peripheral blood. Using this test the effect of chemo- and chemoimmunotherapy on the spread of early micrometastatic cancer cells has been evaluated. No significant correlations have been found between RT/PCR results on the one hand and stage of disease, a kind of the therapy protocol used and usage of the therapy as an adjuvant or palliative on the other hand. Thus, although the RT/PCR test for detection of circulating individual melanoma cells might help in identification of minimal residual disease in some patients, it has no application for routine staging of more advanced disease and in monitoring the response to therapy.

[Preliminary evaluation of a method for detection of individual malignant melanoma cells in peripheral blood while monitoring the course of the malignancy and its treatment]. / Wstepna ocena metody wykrywania pojedynczych komórek czerniaka zlossliwego we krwi obwodowej w monitorowaniu przebiegu choroby nowotworowej i jej leczenia.

Using reverse transcription and polymerase chain reaction (PCR) with primers specific for tyrosinase the individual melanoma cells were detected in peripheral blood of patients in different stages of disease, after excision of primary lesion and prior and after chemotherapy. No relation between stage of disease (including situations with overt generalized spread of melanoma) and probability of positive PCR reaction detecting transcript for tyrosinase gene was found. Many patients in III and IV stages were negative for prolonged periods. Therefore, this method cannot be used for monitoring of all patients, because many of them are negative prior as well as after chemotherapy. With regard to the effects of therapy, the patients differed one to another and although some persons positive prior treatment became negative thereafter, a similar number of initially negative patients became positive after treatment.

Impaired tumor growth in colony-stimulating factor 1 (CSF-1)-deficient, macrophage-deficient op/op mouse: evidence for a role of CSF-1-dependent macrophages in formation of tumor stroma.

Macrophages have been suggested to play a major role in the immune response to cancer. They have also been suggested to stimulate the formation of tumor stroma and to promote tumor vascularization. The availability of the op/op mouse, which has no endogenous colony-stimulating factor 1 (CSF-1) and which possesses a profound macrophage deficiency, provides a new model to verify these notions. Subcutaneous growth of transplantable Lewis lung cancer (LLC) is markedly impaired in the op/op mice compared with normal littermates. Treatment of tumor-bearing op/op mice with human recombinant CSF-1 corrects this impairment. Histological analysis of tumors grown in op/op and normal mice revealed marked differences. Tumors grown in op/op mice display a decreased mitotic index and pronounced necrosis, particularly hemorrhagic. Moreover, particularly in the op/op tumors, peculiar sinusoid-like abortive vessels (not filled with blood) have been observed. These tumors, in contrast to tumors grown in normal mice, are almost deprived of regular arteries and veins. In contrast to tumors grown in normal mice, they exhibit almost no Sirius red-stained collagenous fibers and Gomori silver-stained reticular fibers. Our data suggest that the CSF-1-dependent macrophage subpopulation missing in op/op mice plays a primary role in supporting tumor stroma formation and tumor vascularization in murine LLC tumors.