thymosin and Thymoma

Topics: Adolescent; Adult; Aged; Antibodies; Atrophy; Autoimmune Diseases; Child; Child, Preschool; Epithelial Cells; Epithelium; Female; Hematopoietic Stem Cells; Humans; Inclusion Bodies; Infant; Lymphocytes; Lysosomes; Male; Middle Aged; Muscles; Myasthenia Gravis; Neuromuscular Blocking Agents; Neuromuscular Junction; Neurotransmitter Agents; Teratoma; Thymoma; Thymosin; Thymus Gland; Thymus Neoplasms; Vacuoles

Here, we report the results of proteomic analysis of the mouse thymoma EL4 cell line exposed to bis(tri-n-butylin)oxide (TBTO), an immunotoxic organotin compound. The objective of the work was to examine whether TBTO affects the expression of proteins in this cell line and to compare the differentially expressed proteins with the corresponding mRNA expression data. The identified proteins were quantified using a label-free quantitative method based on counting the observed peptides as an index of protein abundance. The calculation of the ratio of peptides obtained from exposed and control samples allowed us to evaluate the effect of TBTO on protein expression and to compare these results to those obtained in gene expression profiling studies. Correlation of some of the differentially expressed proteins and their corresponding mRNAs was observed. The analysis of the protein ratios revealed that 12 proteins were significantly affected. These proteins included cytoskeleton proteins myosin-9, spectrin beta 2 and plectin 8. The first two proteins were down-regulated 3-fold, whereas the third was up-regulated 2-fold. Ras-related Rab1, a GTP binding protein and T-complex protein-1 subunit alpha, a chaperonin, were decreased 2- and 3.6-fold, respectively. The ribosomal S10 and eukaryotic translation factor (eIf4G1), which are involved in protein synthesis, were down-regulated 2.6- and 3.7-fold, respectively. Also, proteins involved in splicing of pre-mRNA and in transcription, splicing factor arginine/serine-rich 2 and chromodomain-helicase-DNA binding protein 4 (Chd4), were decreased 2.6- and 4.5 times, respectively. Nuclear RNA helicase II was reduced 2.8-fold. Finally, prothymosin-alpha (ProTalpha), an essential protein for cell proliferation, and a protein similar to ProTalpha, (with a molecular weight and a pI (3.54) comparable to that of ProTalpha) were also down-regulated 6-and 8-fold, respectively. We propose that the observed down-regulation of the expression level of ProTalpha in the TBTO-exposed cells could account for the previously reported anti-proliferative effect of TBTO.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Chaperonin Containing TCP-1; Cytoskeletal Proteins; Cytostatic Agents; DNA Helicases; Eukaryotic Initiation Factor-4G; Gene Expression Profiling; Mice; Nuclear Proteins; Peptide Fragments; Peptide Initiation Factors; Protein Precursors; Proteomics; rab GTP-Binding Proteins; rab1 GTP-Binding Proteins; Ribonucleoproteins; RNA Helicases; Serine-Arginine Splicing Factors; Thymoma; Thymosin; Toxicogenetics; Trialkyltin Compounds

To understand the thymic hormone production in thymic tumors and the myasthenic thymus, we have studied the concentrations of two thymic hormones (prothmosin alpha and thymosin beta 4) in these tissues. A total of forty four thymus or thymic tumor tissues were obtained from patients who underwent thoracic operation. These tissues consisted of a control group (n = 25) and three study groups including a thymoma group (N = 8), thymic carcinoma group (n = 3) and myasthenic thymus group (n = 8). The age-related curve of the control group, which provided histologically normal thymic tissues for the production of prothymosin alpha and thymosin beta 4, was established. It was found that in the control group the concentrations (microgram/g tissue) of prothymosin alpha and thymosin beta 4 decreased with age, and that the ranges were from 171 micrograms/g to trace and from 243 micrograms/g to trace, respectively. The amounts were highest at puberty and then gradually decreased, and only trace amounts of both polypeptides were present at age 60. Study cases which deviated from the standard curves were identified. Our results indicated that the contents of thymic hormones significantly increased in the tissues of invasive or non-invasive thymoma, decreased in thymic carcinoma, and were not significantly changed in myasthenic thymus as compared with those of the age-related normal thymus tissues. These findings confirm the notion that only thymomas produce significantly higher thymic hormones.

Topics: Adolescent; Adult; Aged; Aging; Amino Acids; Child; Female; Humans; Infant; Male; Middle Aged; Myasthenia Gravis; Protein Precursors; Reference Values; Thymectomy; Thymoma; Thymosin; Thymus Gland; Thymus Neoplasms

A highly malignant case of intrathyroidal thymic carcinoma showing morphological and biochemical evidence identical with mediastinal thymoma is presented. A 32-year-old female, who had previously undergone total colectomy with ileo-proctostomy due to familial adenomatous polypnosis, was operated on for a tumor (3.4 x 4.5 cm) originating from the left thyroid lobe. A minute focus (diam. 0.8 cm) of papillary adenocarcinoma also existed in the upper pole of the right lobe. The main tumor was morphologically an epithelial thymoma with scanty lymphocyte intermixing and showed medullary differentiation with apparent Hassall's corpuscles. Mitosis was frequent and numerous tumor thrombi were in the subcapsular veins. Five months after the total thyroidectomy and lymph node dissection, a subcutaneous recurrence of the tumour (diam. 2.3 cm) appeared in the anterior cervical region. The cystic contents of the recurrent tumor revealed a high titer of thymosin alpha 1-Other organs, including thymus, lungs, and adrenals, had all been free of neoplastic changes clinically and radiologically for 5 months after her first admission until the local tumor recurrence.

Topics: Adult; Cell Differentiation; Female; Histocytochemistry; Humans; Neoplasm Proteins; Thymalfasin; Thymoma; Thymosin; Thyroid 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

Forty five human thymomas were studied immunohistochemically using antibodies to thymosin x-1, thymosin beta-3, cortical epithelium of human thymus (UH-1), mouse thymic nurse cells (Th-3) and Leu-7. Most thymomas were found to contain thymosin x-1 (80%) and thymosin beta-3 (89%). Also used in the study were a new monoclonal antibody (UH-1), which reacts with the epithelial cells forming a meshwork in the cortex of the normal newborn thymus and Leu 7, which reacts with subcapsular epithelial cells in the outer thymic cortex. The combined use of UH-1 and Leu-7 was found to identify neoplastic epithelial cells of thymic cortical origin in thymomas. Approximately 80% (37/45) of the thymomas in the present study reacted with Leu-7, UH-1 or both antibodies, and were thus considered to be derived from cortical thymic epithelium. Of the eight thymomas which were negative with both Leu-7 and UH-1, four were histologically of mixed type characterized by the formation of epithelial cell islands. All four of these thymomas were positive with thymosin and were therefore considered to be of medullary origin. Ten of the thymoma were associated with myasthenia gravis; all were positive with UH-1 and were consider to be of cortical origin.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Humans; Immunohistochemistry; Infant, Newborn; Myasthenia Gravis; Phenotype; 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