Initiation of T-lymphocyte proliferation by mitogen or antigen involves a cascade of gene activation events. Thus, by the time mitogen-activated T cells have reached the G1/S interface, many genes that are transcriptionally silent in G0, like the c-myc, IL-2, IL-2 receptor (IL-2R) and transferrin receptor (TfR) genes, have been transcriptionally activated. To understand the role of the individual genes in the activation process, one must be able to interfere specifically with the expression or function of each particular gene product. In this way, by blocking the IL-2R with an antibody, it has been demonstrated that IL-2/IL-2R interaction is required to induce TfR expression in activated T cells. When the function or expression of intracellular proteins is to be blocked, however, the need to introduce antibodies into the cytoplasm of viable cells, although possible, is a limiting factor. We have taken another approach, namely the exogenous addition to bulk cell cultures of small antisense oligomers. Sequence-specific antisense oligodeoxyribonucleotides have been reported to inhibit intracellular viral replication without interfering with cellular protein synthesis. Similarly, rabbit globin mRNA translation in a cell-free system and in rabbit reticulocytes has been inhibited by oligomers complementary to the globin mRNA initiation codon region. Recently, a pentadecadeoxyribonucleotide complementary to the initiation codon and four downstream codons of human c-myc mRNA was reported to inhibit the proliferation of the human leukaemic cell line HL-60 specifically. We report here that the same c-myc complementary oligonucleotide inhibits mitogen-induced c-myc protein expression in human T lymphocytes and prevents S phase entry. Interestingly, c-myc antisense treatment did not inhibit G0 to G1 traversal as assessed by morphologic blast transformation, transcriptional activation of the IL-2R and TfR genes, or induction of 3H-uridine incorporation.

Overall, treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma. Clinical trial registered with www.clinicaltrials.gov (NCT00207740).

Comparative nucleotide sequence analysis of a rearranged c-myc gene in a murine plasmacytoma and c-myc cDNA from normal spleen reveals that chromosomal translocation in the plasmacytoma breaks the c-myc gene within the first exon or intron. In the plasmacytoma truncated c-myc RNAs initiate from newly exposed promoter sites. Nevertheless, the myc polypeptide produced in the plasmacytoma is probably the same as that from the intact c-myc gene because the exon lost by breakage and translocation is non-coding. The second and third exons of the mouse c-myc gene are substantially conserved in the v-myc gene of the avian retrovirus, MC29.

Subjects with moderate to severe COPD did not benefit from treatment with infliximab. Although not statistically significant, more cases of cancer and pneumonia were observed in the infliximab-treated subjects. The impact of infliximab on malignancy risk in patients with COPD needs to be further elucidated.

Burkitt lymphoma cells carrying either a rearranged or unrearranged c-myc oncogene were examined with the use of probes from the 5' exon and for the second and third exon of the oncogene. The results indicate that the normal c-myc gene on chromosome 8 and the 5' noncoding and 3' coding segments of the c-myc oncogene separated by the chromosomal translocation are under different transcriptional control in the lymphoma cells. Burkitt lymphoma cells carrying a translocated but unrearranged c-myc oncogene express normal c-myc transcripts. In contrast, lymphoma cells carrying a c-myc gene rearranged head to head with the immunoglobulin constant mu region gene express c-myc transcripts lacking the normal untranslated leader.