1,721,010 research outputs found
Differential cytotoxic activity of potassium dichromate on nucleoside uptake in BHK fibroblasts.
No full textMonete
No full textIn Lessinia nel corso di una serie prolungata di ricerche di superficie sono stati rinvenuti molti reperti, testimonianza della vita e del lavoro dei pastori in un arco temporale molto lungo. Sono state recuperate anche più di 400 monete, prevalentemente di bronzo del XV secolo, alcune sono anche di età romana e provengono da pascoli a quota molto alta
DMET? (Drug-Metabolizing Enzymes and Transporters) microarray analysis of colorectal cancer patients with severe 5-fluorouracil-induced toxicity.
No full textPURPOSE: 5-fluorouracil (5-FU) has been widely used since the 1980s, and it remains the backbone of many chemotherapeutic combination regimens. However, its use is often limited by the occurrence of severe toxicity. Although several reports have shown the detrimental effect of some dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthase (TYMS) gene polymorphisms in patients undergoing 5-FU-based treatment, they account for only a minority of toxicities.
METHODS: Looking for new candidate genetic variants associated with 5-FU-induced toxicity, we used the innovative genotyping microarray Affymetrix Drug-Metabolizing Enzymes and Transporters (DMET)TM Plus GeneChip that interrogates 1,936 genetic variants distributed in 231 genes involved in drug metabolism, excretion, and transport. To reduce variability, we analyzed samples from colorectal cancer patients who underwent fairly homogenous treatments (i.e., Machover or Folfox) and experienced G3 or G4 toxicity; control patients were matched for therapy and selected from those who did not disclose toxicity (G0-G1).
RESULTS: Pharmacogenetic genotyping showed no significant difference in DPYD and TYMS genetic variants distribution between cases and controls. However, other polymorphisms could account for 5-FU-induced toxicity, with the CHST1 rs9787901 and GSTM3 rs1799735 having the strongest association.
CONCLUSIONS: Although exploratory, this study suggests that genetic polymorphisms not directly related to 5-FU pharmacokinetics and pharmacodynamics are involved in 5-FU-induced toxicity. Our data also indicates DMETTM microarray as a valid approach to discover new genetic determinants influencing chemotherapy-induced toxicity
Altered protein kinase activities of lymphoid cells transformed by Abelson and Moloney leukemia viruses.
No full textAnalysys of Tax-expressing cell lines generated from HTLV-I Tax-transgenic mice: correlation between C-MYC overexpression and neoplastic potential.
Full text linkHuman T-cell leukemia/lymphotropic virus type I (HTLV-I) infection causes a variety of human diseases, including adult T-cell leukemia/lymphoma. The viral transactivator Tax has been implicated as a key factor in the HTLV-I-induced transformation pathway. To investigate the components of this pathway, we derived fibroblast-like cell lines, designated T6 and T9, from tail biopsies of tax-transgenic C57BL/6 mice that do not develop tumors. Phenotypic characterization of T6 and T9 cells and T6-derived subclones revealed that they differ in their abilities to form foci in vitro and tumors in vivo. The observed differences in the levels of Tax expression did not correlate with their degree of neoplastic potential. However, a control cell line derived from a nontransgenic C57BL/6 mouse did not form foci in vitro or tumors in vivo, indicating that Tax was required for the transformation process. Results of Northern analyses showed that the T9 cells and the highly malignant derivatives of T6 cells expressed elevated levels of c-myc mRNA. These findings suggest that progression of the tax-transgenic cells toward a more malignant phenotype might involve c-myc deregulation
The monosialoganglioside GM1 induces internalisation and degradation of the CD4 antigen in U937 cells.Evidence for a novel mechanism of CD4 down-modulation in p56lck-negative cell line,which is independent of protein kinase C activation
No full textSialated glycosphingolipids (gangliosides) were recently shown to induce internalisation of the CD4 Ag in lymphoid cells and dissociation of p56lck from CD4 (Repke et al. (1992) J. Immunol. 149, 2585-2591; Saggioro et al. (1993) J. Biol. Chem. 268, 1368-1375). The findings presented in this paper show that GM1 induces internalisation and the eventual degradation of the CD4 Ag also in the monocytic cell line U937. GM1 effects are independent of a possible activation of protein kinase C, as enzyme inhibitors which effectively blocked phorbol esters effects did not prevent GM1-induced CD4 internalisation and degradation. GM1 effects were also independent of a possible action on a CD4 associated kinase activity as we show that U937 cells lack any CD4-associated kinase activity
Abelson murine leukemia virus-induced thymic lymphomas: transformation of a primitive lymphoid precursor.
No full textFor the investigation of whether Abelson murine leukemia virus (A-MuLV) is able to transform in vivo lymphocytes other than those of the B-cell lineage, newborn BALB/c and C57BL/6 mice were given an injection of A-MuLV directly into the thymus. Thymic lymphomas appeared with a short latent period of 4-5 weeks in BALB/c mice and 8 weeks in C57BL/6 mice. Cell lines derived from some thymic lymphomas presented a very immature phenotype and did not express cellular markers of either T-cells (Thy 1.2, Lyt 1.2, and Lyt 2.2) or B-cells (cytoplasmic IgM) even after treatment with several differentiation inducers. Molecular analysis showed that T-cell receptor (TCR) beta chain genes were never rearranged; in one case only, rearrangement of TCR gamma chain genes could be demonstrated, confirming the immaturity of the presumptive T-cell lines studied. Furthermore, the cell lines consistently carried diversity (D)-joining (J) but not variable (V)-D-J rearrangements of the immunoglobulin heavy chain genes. On the whole, these findings suggest that following intrathymic A-MuLV injection neoplastic transformation does involve lymphocytes possibly of T-cell lineage, at a very early stage of differentiation
In vitro malignant progression of cells derived from Abelson murine leukaemia virus-induced thymic lymphomas.
Full text linkCell lines derived from A-MuLV induced thymic lymphomas in BALB/c and C57BL/6 mice were analysed for their in vivo and in vitro potential of growth. Despite their immunogenicity, cell lines of BALB/c origin readily grew in syngeneic recipients. On the contrary, all cell lines of C57BL/6 origin failed to grow in immunocompetent hosts even though they were able to form tumours in immunosuppressed syngeneic mice. Among C57BL/6 lymphoma cells progression toward a more malignant phenotype was observed in TB6-3 cells, and in their derived clones, after several in vitro passages. This event was accompanied by the in vitro loss of requirement for exogenous growth factor(s) when tumorigenic TB6-3 cells were plated at high density. Moreover, culture medium from fully malignant TB-3 cells was mitogenic for mature T-lymphoma cells suggesting the involvement of an autocrine mechanism in the control of cell proliferation. Apparently, the viral oncogene (v-abl) is not directly involved in malignant progression since no differences between nontumorigenic and tumorigenic cells could be detected in A-MuLV integration patterns, v-abl specific mRNA expression, and P160gag-abl productio
Ras signaling contributes to survival of human T-cell leukemia/lymphoma virus type 1 (HTLV-1) Tax-positive T-cells
Full text linkRas signaling pathways play an important role in cellular proliferation and survival, and inappropriate activation of Ras frequently results in cell transformation and cancer. Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) is the etiological agent of the adult T-cell leukemia/lymphoma (ATLL), a severe malignancy that has a poor prognosis and exhibits resistance to conventional chemotherapy. Although the mechanisms involved in cell transformation by HTLV-1 have not been completely clarified, it is generally thought that Tax plays a pivotal role in the process. We have previously proposed that a functionally active Ras protein is needed for efficient anti-apoptotic activity of Tax. In this study we report data indicating that the apoptotic resistance of cells expressing Tax, constitutively or transiently, is linked to the intracellular levels of Ras-GTP. Indeed, we found that Tax-positive cells have a high content of active Ras, and that inhibition of Ras signaling, using the antagonist farnesyl thyosalicylic acid (FTS), increases their sensitivity to apoptosis. FTS treatment was also accompanied by a decrease in ERK, but not Akt, phosphorylation. Thus, all together our data suggest that the interaction between Tax and Ras could be important to ATLL pathogenesis, and indicate Ras as a possible target for therapeutic intervention in ATLL patients
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