thymic-factor--circulating and Carcinoma

The experiments were conducted on a model of intraorganic growth of Geren carcinoma (GC) in spleen of non-linear mice. It has been shown that titer of thymic serum activity (TSA) decreased sharply in the blood at a stage of settling transplants down (7th day), while the level of an inhibitor for thymic serum factor (FTS) increased in a statistically significant way. At progressive tumor growth, the level of TSA in the circulation raised a little on the 10th day but it was still reduced in comparison with that before inoculation of GC. Traces of the inhibitor for FTS were detected only in 18 and 25 days of tumor growth. We have found resemblance between these substances and those in low-molecular extracts of lymphocytes (LEL). The LEL from cells of the spleen and the thymus of intact rats contained TSA and FTS inhibitor, both of T-cell origin, in ratio 1:1. Production of TCA and the FTS inhibitor was peculiar to immature cortisone-sensitive T-lymphocytes. Anti-FTS serum in vitro completely neutralized TSA in both the blood and an extract of thymocytes but it effected neither the contents of TSA in the LEL of the spleen nor the level of FTS inhibitor in all the samples investigated. The data received testify to an important role of FTS inhibitor in the pathogenesis of tumor progression.

Topics: Animals; Carcinoma; Cell Extracts; Cortisone; Mice; Molecular Weight; Neoplasm Transplantation; Neoplasms; Splenic Neoplasms; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland; Time Factors

Adrenalectomy prevents thymic atrophy but not splenomegaly in mice implanted with Lewis Lung carcinoma cells. Surprisingly, the presence of the tumor does not lead to increased levels of corticosterone, which argues against an exclusive role of stress in the tumor-induced involution of the thymus. Interestingly, serum from tumor-bearing hosts in vitro displays strong cytolytic activity against normal syngeneic thymocytes. This thymocytotoxicity depends upon the stage of tumor development, i.e., the size of the local tumor, and is concomitant with the severe thymic atrophy. Treatment of donor mice with zinc chloride or excision of the local tumor, both of which have been shown to prevent this involution of the thymus, also abolishes the cytotoxic effect of the serum. The active component of the serum is a nonimmunoglobulin fraction of molecular weight greater than 25,000 Da. The possible mechanisms of tumor-dependent thymic atrophy as well as the in vivo relevance of this serum-mediated thymocytotoxicity are discussed.

Topics: Adrenalectomy; Animals; Antilymphocyte Serum; Atrophy; Carcinoma; Cell Count; Cell Survival; Corticosterone; Cytotoxicity, Immunologic; Female; Killer Cells, Natural; Lung Neoplasms; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Organ Size; Spleen; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland

Conditions for the reproducible measurement of thymic hormonal effect on the functional activity of human peripheral blood lymphocytes (PBL) were determined using a mixed lymphocyte-tumor culture assay. Three thymic hormonal preparations (thymopoietin, thymic humoral factor and TP-1) were tested by this assay and found to have a significant enhancing effect on the blastogenic response. Essential for the demonstration of the hormonal effect was the selection of suboptimal stimulation conditions, with the appropriate cell lines, including the number of stimulating cells and the time in culture. The most reproducible results were achieved when 1 x 10(5) PBL were co-cultured for 4 days with 1 x 10(4) mitomycin-C treated Raji lymphoma cells, after 1 h preincubation with one of the thymic preparations. However, strong enhancing effects of the thymic preparations could also be demonstrated with other tumor cel lines, especially IgR3 melanoma cells.

Topics: Adenocarcinoma; Burkitt Lymphoma; Carcinoma; Cell Line; Cells, Cultured; Colonic Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Lymphocyte Activation; Lymphocytes; Melanoma; Thymic Factor, Circulating; Thymopoietins; Thymus Extracts; Thymus Hormones; Uterine Neoplasms