alpha-chymotrypsin and Thyroid-Neoplasms

Changes in the proteasome chymotrypsin-like activity in mammary and thyroid carcinomas in comparison with the adjacent tissue were studied at stages T(1-4)N(0-3)M(0) and T(2-3)N(0-1)M(0), respectively. The activities changed in a wave-like manner over the course of mammary carcinoma growth in cases with and without metastases. The minimum increment of the activity in the tumor was recorded during the T(2)N(0) stage in the absence of local metastases. The increment of the activity reached the peak in N(1) tumors of the same size with metastases. The activities in the tumor and adjacent tissues virtually did not differ during the T(3-4)N(1-3) stages. The time course of proteasome activity changes in thyroid tumors of the studied stages was similar to that in mammary carcinoma. The results can be used for development of methods for evaluating the aggressiveness of mammary and thyroid tumors.

Topics: Boronic Acids; Bortezomib; Breast; Breast Neoplasms; Chymotrypsin; Drug Resistance, Neoplasm; Female; Humans; Neoplasm Metastasis; Neoplasm Staging; Proteasome Endopeptidase Complex; Pyrazines; Thyroid Gland; Thyroid Neoplasms

Using an avidin-biotin immunoperoxidase technic, the authors studied 29 anaplastic thyroid tumors (ATTs) to determine the frequency of hormonal (thyroglobulin--TG; calcitonin--CT), epithelial (epithelial membrane antigen, monoclonal keratin), or sarcoma (desmin; alpha-1-antichymotrypsin--ACT; vimentin) markers. Their results indicate that 27% of ATTs stain for TG and none for CT. Fifty-five percent showed epithelial markers, 48% marked for ACT, and 47% for vimentin. Coexpression of keratin and vimentin was found in 39% of cases tested. The expression of the tested antigens did not correlate significantly with histologic pattern (epithelial vs. "sarcomatous"). Of note is the fact that 30% of the ATTs the authors tested expressed none of the markers they examined, indicating total lack of differentiation.

Topics: Adult; Aged; Aged, 80 and over; Anaplasia; Calcitonin; Carcinoma; Chymotrypsin; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Middle Aged; Mucin-1; Sarcoma; Thyroglobulin; Thyroid Neoplasms; Vimentin

Messenger RNA extracted from rat medullary carcinoma of the thyroid directs the synthesis in cell-free translation systems of a precursor of calcitonin, Mr = 15,000, substantially larger than the mature form of the hormone, Mr = 3,500. When translations of the mRNA were carried out in the presence of microsomal membranes prepared from a canine pancreas, a larger product (apparent Mr = 17,000) was observed by electrophoresis of the labeled proteins in the translation mixtures on sodium dodecyl sulfate-polyacrylamide gels. This membrane-processed product of Mr = 17,000 was specifically immunoprecipitated by an antiserum to synthetic calcitonin and bound to concanavalin A-Sepharose. Incubation of the proteins synthesized in the cell-free translations performed in the presence of microsomal membranes with the glycosidase, endo-beta-N-acetylglucosaminidase H, reduced the apparent molecular weight of the membrane-processed precursor from 17,000 to 12,000. In addition, the processed Mr = 17,000 calcitonin-related precursor, but not the initial, unprocessed precursor of Mr = 15,000, was resistant to proteolytic digestion by a mixture of trypsin and chymotrypsin. These results indicate that the biosynthesis of calcitonin involves the glycosylation and proteolytic cleavage of a newly synthesized precursor along with sequestration of the processed precursor within microsomal vesicles. Thus, the calcitonin precursor undergoes extensive co- and post-translational processing to the smaller, unglycosylated hormone that is secreted.

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Chymotrypsin; Glycoproteins; Molecular Weight; Neoplasms, Experimental; Peptide Fragments; Protein Biosynthesis; Protein Precursors; Rats; RNA, Messenger; Thyroid Neoplasms; Trypsin

Topics: Adult; Amino Acid Sequence; Animals; Antibody Specificity; Calcitonin; Carcinoma; Cattle; Chymotrypsin; Dose-Response Relationship, Immunologic; Humans; Immune Sera; Isoelectric Focusing; Oxidation-Reduction; Peptide Fragments; Rabbits; Radioimmunoassay; Rats; Species Specificity; Swine; Thyroid Gland; Thyroid Neoplasms; Time Factors; Trypsin