thymalfasin and Thymus-Neoplasms

Thymosin alpha 1 (Talpha1), initially isolated from thymus, was characterized by Allan Goldstein in 1977. Since the beginning, our studies were aimed at evaluating its immunomodulating effects when used in combination with cytokines and chemotherapy. Combination therapies have now proved to be effective in inhibiting tumoral growth and in controlling infective diseases especially in the immunocompromised host. More recent studies showed that Talpha1 molecule increased major histocompatibility complex (MHC) class-1 and Toll-like receptor expression as well as cytokine production, suggesting its immunoregulatory role. Overall these results led us to start pilot clinical trials on patients with hepatitis C and cancer.

Topics: Amino Acid Sequence; Animals; Cyclophosphamide; Histocompatibility Antigens Class I; History, 20th Century; Humans; Molecular Sequence Data; Thymalfasin; Thymosin; Thymus Neoplasms

Thymosin alpha 1-like immunoreactivity was assessed in human thymus and thymoma tissue extracts by means of a new radioimmunoassay that included an anti-thymosin alpha 1 mouse monoclonal antibody. Thymosin alpha 1-like immunoreactivity levels decreased with age in normal thymuses but not in thymomas. The average thymosin alpha 1-like immunoreactivity level was 45.0 +/- 52.1 ng/mg protein in normal thymuses and 273.9 +/- 205.0 ng/mg protein in thymomas. The average thymosin alpha 1-immunoreactivity level in thymomas was higher than that in normal thymuses. Thymosin alpha 1-like immunoreactivity levels in thymomas appeared to have no relationship to the clinical stage of the thymoma or associated diseases. When viewed according to histologic characteristics, the average thymosin alpha 1-like immunoreactivity level in polygonal cell thymomas (382.5 +/- 192.6 ng/mg protein) was significantly higher than that in the spindle cell thymoma (101.8 +/- 81.2 ng/mg protein). When viewed according to the degree of lymphocyte infiltration, thymomas could be classified according to four grades: absent, scant, moderate, and predominant. In predominant or moderate thymomas, the average thymosin alpha 1-like immunoreactivity level was higher than that in scant or absent thymomas. Also, thymosin alpha 1-like immunoreactivity levels in thymuses of patients with myasthenia gravis were relatively higher than those in patients with normal thymuses.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Neoplasm Staging; Radioimmunoassay; Thymalfasin; Thymoma; Thymosin; Thymus Gland; Thymus Neoplasms

The localization of the three best-defined thymic hormones, namely, thymulin, thymopoietin and thymosin alpha 1 was studied by immunofluorescence using antibodies directed against these three molecules. With both human thymus frozen sections and cultured cells, thymic hormones were found exclusively in the epithelial component (recognized by its keratin content), in normal as well as pathological thymuses. The double-labeling experiments using the different anti-thymic hormone antibodies showed that the same epithelial cells contained the three hormones. These results suggest that the production of different hormones in the thymus is accomplished by the same epithelial cells.

Topics: Cells, Cultured; Fluorescent Antibody Technique; Freezing; Histological Techniques; Humans; Myasthenia Gravis; Thymalfasin; Thymic Factor, Circulating; Thymoma; Thymopoietins; Thymosin; Thymus Gland; Thymus Hormones; Thymus Hyperplasia; Thymus Neoplasms

Thymosin alpha 1 (alpha 1) is a potent thymic polypeptide hormone. With antibodies against synthetic thymosin alpha 1, indirect immunofluorescence was applied to human normal thymus and to hyperplastic, thymomatous or "involuted" thymus of myasthenia gravis (MG) patients. Alpha 1 was localized only in the epithelial cells, lying singly, grouped, in Hassall's corpuscles or proliferated in thymomas. In contrast to normal thymus, which had fewer and more weakly stained cells, MG hyperplastic thymus had many strongly positive epithelial cells: this was markedly evident in thymomas. "Involuted" MG thymus had a few but brightly stained cells lying within the fatty tissue. In tissue cultures of human thymus, anti-alpha 1 stained the epithelial cells, but not fibroblasts. These findings: (a) demonstrate the origin of the thymic hormone alpha 1 to be the thymic epithelial cell; (b) raise the possibility that excess alpha 1 may act pathologically to facilitate and perpetuate the dysimmune mechanism in MG; (c) may partially explain the beneficial effect of thymectomy in MG patients of any age; and (d) suggest that epithelial cells may be autonomous for the production of alpha 1 as evidenced by their positivity in tissue culture.

Topics: Adolescent; Adult; Child; Epithelium; Fluorescent Antibody Technique; Humans; Middle Aged; Myasthenia Gravis; Thymalfasin; Thymoma; Thymosin; Thymus Gland; Thymus Hormones; Thymus Hyperplasia; Thymus Neoplasms