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T Trangas

Publications and source records attributed to T Trangas.

28 records · Page 2Linked to original sources

Dexamethasone caused alterations in poly(A) polymerase levels of a human leukemic cell line.

The effect of glucocorticosteroids upon the poly(A) synthetic and degrading activity has been studied in steroid sensitive and resistant human leukemic cell lines. At least a two-fold increase in the levels of poly(A) polymerase activity was found in soluble, cytoplasmic extracts from the steroid sensitive human malignant T-cells of the MOLT3 line after 24-h treatment with dexamethasone. Longer exposure time of the cultured cells to the steroid resulted in a gradual decrease of the poly(A) polymerase activity level. Pretreatment of the cells with progesterone, a competitive inhibitor of dexamethasone, prevented the dexamethasone induced increase in the level of poly(A) polymerase activity, while progesterone alone had no effect on the enzyme level. In contrast, the levels of poly(A) nucleases activity remained constant following steroid treatment. In the steroid resistant human leukemic B-cell line Daudi no alterations in the poly(A) metabolizing enzymes could be measured in response to dexamethasone. Thus we suggest that poly(A) polymerase levels may be used to predict sensitivity of leukemic cells to glucocorticosteroid treatment.

B-Lymphocytes↗

Poly(A)-polymerase activity in chronic lymphocytic leukemia of the B cell type.

Poly(A)-polymerase enzymic activity was biochemically determined in lymphocytic extracts from 40 patients with chronic lymphocytic leukemia of the B cell type. The enzymic activities of patients with stage A, B and C disease were (U/mg of protein): 4.9 +/- 5.5, 12.5 +/- 7.5 and 20.9 +/- 18.9, respectively. The difference in the enzyme level between stage A and C patients was statistically significant (p less than 0.05). Comparison of the enzyme activity level in relation to the pattern of bone marrow involvement revealed that patients with a diffuse pattern of infiltration had a significantly higher enzyme level (17.9 +/- 15.5 U/mg of protein) than patients with interstitial or mixed infiltration patterns (5.9 +/- 6.6 and 7.9 +/- 7.0 U/mg of protein; p less than 0.025). Finally, patients who required treatment for their disease also had a significantly higher poly(A)-polymerase activity level (14.5 +/- 13.9 U/mg of protein) than patients with stable disease (4.9 +/- 5.5 U/mg of protein; p less than 0.05). Our results indicate that the enzyme poly(A)-polymerase may be used as a biological marker in patients with chronic lymphocytic leukemia.

B-Lymphocytes↗

Polyadenylic acid polymerase activity in normal and leukemic human leukocytes.

Soluble polyadenylic acid [poly(A)] polymerase and poly(A) nucleases content of normal human blood lymphocytes and leukemic blood cell populations was determined. Blood lymphocytes from seven normal individuals were used as controls. Leukemic cells were obtained from 69 patients with various types of acute and chronic leukemias. Chronic lymphocytic leukemias presented poly(A) polymerase values with a mean of 9 +/- 4 (S.D.). Although most of the chronic lymphocytic leukemia cases presented poly(A) polymerase activities similar to those of normal lymphocytes (3 +/- 3), a small number fell into the specific activity values of acute leukemias, which were significantly higher and covered a wider range. The mean values for acute myeloblastic, acute monoblastic, and acute lymphoblastic leukemias were 53 +/- 50, 21 +/- 8, and 29 +/- 14, respectively. A statistically significant difference was found between chronic and acute leukemias (p less than 0.01). The observed differences in poly(A) polymerase levels of acute lymphoblastic leukemia versus chronic lymphocytic leukemia persisted after fractionation of the crude extracts and, furthermore, they could not be attributed to differences in the levels of poly(A)-degrading enzymes [poly(A) endo- and exonucleases]. Fractionation of leukemic extracts on Sephadex G-75 revealed two molecular forms of poly(A) polymerase activity.

Humans↗

delta IK17: an antigen expressed on human lymphocytes.

Anti delta IK17 monoclonal antibody was produced by fusing SP2/0/Ag 14 myeloma with spleen cells of BALB/c mice immunized with normal human thymocytes. a delta IK17 antibody recognizes a 44kD cell surface protein detected on human lymphocytes. delta IK17 is expressed on human thymocytes, CD4+ and CD8+ T cell subsets, B, NK cells, as well as on activated cells. The antigen is detected on cells during the early, intermediate and late stages of lymphocyte maturation. In addition, the expression of the antigen is correlated with ontogenesis. A T+ delta IK17+ subpopulation responded poorly to TPA stimulation and provided a better helper signal for PWM-induced IgM synthesis than T+ delta IK17- cells. In addition, different levels of delta IK17 expression were detected in several hematological diseases tested.

Animals↗

delta IK17 antigen: a possible early marker of cancer development.

delta IK17 is a 44 kD molecule located on the surface of T, B and NK cells in normal peripheral blood mononuclear cells (PBMC) (1). The portion of PBMC expressing delta IK17 was determined in 52 patients with benign breast diseases, 182 patients with breast malignancies and 132 healthy individuals. The percentage of delta IK17-positive cells was significantly lower in the early stages (I-IIA) of malignancy compared to that of healthy donors. However, the percentage of PBMC expressing delta IK17 tended to increase as the stage of the disease advanced. delta IK17 seems to be the only antigen among the other cellular markers tested (CD2, CD4, CD8, HLA-DR) with a statistically significant correlation between a low percentage of positive cells and the early stages of malignancy and between a high expression and advanced disease. Its potential use as a tumor marker in breast cancer is discussed here.

Adult↗

CRD-BP: a c-Myc mRNA stabilizing protein with an oncofetal pattern of expression.

The Coding Region Determinant-Binding Protein (CRD-BP) is an RRM and KH-domain-containing protein that recognizes specifically at least three RNAs. It binds to one of the two c-myc mRNA instability elements, to the 5'Un Translated Region (UTR) of the leader 3 IGF-II mRNA and to the oncofetal H19 RNA. CRD-BP has been assigned a role in stabilizing c-myc mRNA by preventing its endonucleolytic cleavage and in repressing the translation of the leader 3 IGF-II mRNA, the major embryonic species of this message. CRD-BP is normally expressed only in fetal tissues. However, its expression is detected in primary tumors and transformed cell lines of different origins. The vast majority of colon (80%) and breast (60%) tumors and sarcomas (73%) express CRD-BP whereas in other tumor types, for example prostate carcinomas, its expression is rare. CRD-BP expression has also been detected in benign tumors such as breast fibroadenomas, meningiomas and other benign mesenchymal tumors, implying a role for this gene in abnormal cell proliferation. In breast carcinomas, CRD-BP expression and or gene copy number gains in the region encompassing the c-myc locus were detected in approximately 75% of tumors, implying that the deregulated expression of c-myc may be more widespread than previously believed. Infiltrated lymph nodes, corresponding to CRD-BP-positive primary tumors, were also found positive indicating that monitoring for CRD-BP could prove useful for the detection and monitoring of disseminated disease.

Animals↗

c-erbB-2 overexpression may be used as an independent prognostic factor for breast cancer patients.

Insight into correlations between specific gene amplification and the clinical behavior of tumors may provide new prognostic tools High c-erbB-2 expression is an early feature in some breast tumors, whereas c-myc may be involved in the development of neoplasia. After an initial flurry of excitement about their prognostic significance, controversy has arisen about their independent importance. In an attempt to solve this problem, we decided to study c-erbB-2 and c-myc amplification and overexpression in 62 unselected breast carcinomas. This was done in order to correlate them statistically with one another, as well as with other prognostic parameters. A positive correlation was discovered between c-erbB-2 amplification and overexpression (P = 0.02); however, the correlations between c-erbB-2 amplification and c-myc amplification and overexpression (P = 0.06 and P = 0.095 respectively) were found to be negative. In addition, no correlation was found to exist between c-erbB-2 amplification and Cathepsin-D, steroid receptors, node status and menopausal status, as well as between c-erbB-2 overexpression and Cathepsin-D, node invasiveness, tumor status, grade or menopausal status. In conclusion, the c-erbB-2 overexpression has positive correlation with only a few other prognostic parameters, and therefore can be used as an independent prognostic factor.

Breast Neoplasms↗

Cathepsin-D and c-erb-B 2 have an additive prognostic value for breast cancer patients.

In breast cancer, axillary lymph node invasiveness is the major prognostic factor in predicting relapse and metastasis. Nevertheless, since 30% of node-negative tumours also relapse, it is necessary to develop other independent prognostic factors. Oncogene amplification and overexpression as well as the level of cathepsin-D have been proposed as additional prognostic factors. Recent studies suggest that the acidic lysosomal proteinase cath-D, present in all cells and known to be secreted in breast cancer cells, may be implicated in the process of tumour invasion and metastasis. We have compared the cytosolic cath-D level with the amplification and the overexpression of the oncogenes c-myc and c-erb-b-2 in 62 breast carcinomas (52 primary and 10 metastatic). Using a cut-off level of 60 pmol/mg protein, the status of cath-D showed a positive correlation with c-myc amplification (P = 0.01) or overexpression (P = 0.02). In contrast, no correlation was found between cath-D and c-erb-B-2 amplification or overexpression. Also, no correlation was found between cath-D and established prognostic factors such as node invasiveness, steroid receptors, grade and menopausal status. Nevertheless, a weak correlation was found between cath-D levels and tumour status (P = 0.05). In conclusion, in breast cancer, a high cytosolic cath-D concentration is more frequent in tumours with c-myc amplification and overexpression but is dissociated from c-erb-B-2 amplification or overexpression, suggesting that the determination of cath-D, as well as the latter two markers, will have an additional prognostic value.

Breast Neoplasms↗