Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production and detailed immunostaining properties of a new rat monoclonal antibody (ICR.2) to epithelial membrane antigen are reported. The antibody was selected for its ability to compete with the polyclonal antiserum (M7), used in the original immunohistological studies, in order that it might serve as a direct replacement in diagnosing epithelial tumours. Most of the staining reactions on normal tissues were identical to those previously reported with M7 but there were some important differences. They included: positivity of renal and adrenal capsular fibroblasts, perineurium, some myoepithelial and smooth muscle cells, occasional osteoblasts and squamous and thyroid follicular epithelium in the normal state. The intercellular canaliculi of sweat glands and secretory canaliculi of gastric oxyntic cells were clearly demonstrated. These staining reactions could be obtained with M7 when a sensitive detection system was used although the results were usually weak and inconsistent. Nearly all adenosquamous and transitional carcinomas were positive. The remaining tumours fell into three major groups: (1) those which were consistently or nearly consistently negative--melanoma, seminoma, rhabdomyosarcoma, alveolar soft part sarcoma, adrenal cortical carcinoma, granulocytic sarcoma, paraganglioma, non-Hodgkin's lymphoma. Hodgkin's disease and embryonal carcinoma: (2) those which were either negative or positive with distinctive patterns of staining--basal cell carcinoma, embryonal tumours: and (3) non-epithelial tumours that were consistently positive--epithelioid sarcoma, synovial sarcoma, osteosarcoma, chordoma and myeloma--or positive in a significant minority of cases--leiomyosarcoma, malignant fibrous histiocytoma, clear cell sarcoma of tendon sheath, various neuroectodermal tumours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detailed investigation of the diagnostic value in tumour histopathology of ICR.2, a new monoclonal antibody to epithelial membrane antigen. 169 88

Tumor cells from patients with renal or adrenocortical carcinomas were tested in vitro for sensitivity to doxorubicin (Dox) and vincristine (Vcr), as well as for the modulation of this sensitivity by resistance modifiers and the immunohistochemical expression of the multidrug resistance associated P-glycoprotein (Pgp). Normal adrenocortical cells from one patient and Pgp-expressing cells of Dox-resistant myeloma RPMI 8226 sublines were included for comparison. The normal adrenocortical cells and cells from one adrenocortical carcinoma showed high Pgp expression, comparable to the most Dox-resistant myeloma cell line, whereas the other tumor samples showed variable but lower expression. The normal adrenocortical as well as the adrenocortical and renal tumor cells were highly resistant to Dox and Vcr. Whereas the cytotoxic effect of Dox was considerably increased by verapamil, cyclosporin A and its non-immunosuppressive analogue SDZ PSC 833 in the Pgp-expressing Dox-resistant sublines, comparatively small effects on the Dox and Vcr sensitivity were observed in the patient samples, irrespective of their Pgp expression. The results indicate that the Dox and Vcr resistance in human adrenocortical and renal carcinomas is mediated by mechanisms other than Pgp and that resistance modulating agents targeting Pgp may be much less efficient in the clinic than in Pgp-expressing cell lines, at least for the tumor types described in the present study.
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PMID:P-glycoprotein expression and activity of resistance modifying agents in primary cultures of human renal and adrenocortical carcinoma cells. 791 6

Adrenocortical carcinoma (ACC) is a highly malignant tumor with poor response to classical antitumor therapy. Steroidogenic acute regulatory (StAR) protein is expressed in most human ACCs. The aim of this study was to induce antitumoral T cells directed against StAR in a murine tumor model. Because a suitable syngenic adrenocortical mouse tumor model is lacking, we established a clone of the mouse myeloma Sp2-0 tumor cell line stably expressing murine StAR (Sp2-mStAR). Using repeated im injections of plasmid DNA encoding mStAR followed by infection with a recombinant vaccinia virus (rVV) expressing mStAR, we induced a cytotoxic T-cell response as measured by enzyme-linked immunospot assay. To demonstrate antitumor activity of the vaccination procedure, mice were treated as follows: group A, mice immunized with plasmids and rVV encoding mStAR receiving Sp2-mStAR cells; control group B, mice immunized with the empty plasmid and the empty rVV receiving Sp2-mStAR cells; control group C, mice immunized with the empty plasmid and rVV encoding P450 side-chain cleavage enzyme receiving Sp2-mStAR cells; and control group D, mice immunized with plasmid and rVV encoding mStAR receiving parental Sp2-0 cells. A high proportion (89-100%) of the control groups B, C, and D developed subcutaneous tumors. In contrast, immunization specific for mStAR (group A) was highly protective against tumor growth (percentage of tumor-free animals, 67%; P < 0.001 vs. controls). In summary, these results show that T-cell tolerance toward mStAR can be broken, resulting in antitumoral immunity. Thus, StAR represents a candidate target antigen for immunotherapeutic strategies against ACC.
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PMID:Steroidogenic acute regulatory (StAR)-directed immunotherapy protects against tumor growth of StAR-expressing Sp2-0 cells in a rodent adrenocortical carcinoma model. 1471 9