Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection.

The persistence of transcriptionally silent but replication-competent HIV-1 reservoirs in Highly Active Anti-Retroviral Therapy (HAART)-treated infected individuals, represents a major hurdle to virus eradication. Activation of HIV-1 gene expression in these cells together with an efficient HAART has been proposed as an adjuvant therapy aimed at decreasing the pool of latent viral reservoirs. Using the latently-infected U1 monocytic cell line and latently-infected J-Lat T-cell clones, we here demonstrated a strong synergistic activation of HIV-1 production by clinically used histone deacetylase inhibitors (HDACIs) combined with prostratin, a non-tumor-promoting nuclear factor (NF)- kappaB inducer.

Weekly high-dose 5-fluorouracil and folinic acid in metastatic pancreatic carcinoma: a phase II study of the EORTC GastroIntestinal Tract Cancer Cooperative Group.

The aim of the study was to assess the response rate and toxicity of high-dose 24 h infusion of 5-fluorouracil (5FU) in metastatic adenocarcinoma of the pancreas. Patients with measurable disease, performance status 0-2, and no prior chemotherapy were registered to receive cycles of leucovorin (LV) 500 mg/m2 (or l-LV 250 mg/m2 over 1 h followed by 5FU 2.6 g/m2 over 24 h, weekly for 6 weeks, followed by a 2-week rest.

Acute inhibitory effect of excess iodide on ornithine decarboxylase in the thyroid of propylthiouracil-treated rats.

Polyamines such as putrescine, spermidine and spermine have been thought to play an important role in thyroid growth induced by goitrogens. Reduced biosynthesis of these polyamines might play a role in the antigoitrogenic effects of excess iodide. This study was designed to examine the effect of potassium iodide (KI) on ornithine decarboxylase (ODC), a rate-limiting enzyme in the biosynthesis of polyamines.

Regulation of the Max gene expression by different mitogenic pathways in dog primary thyrocytes.

The family of Myc proteins appears to function through heterodimerization with the bHLH-Zip protein Max. We have investigated the regulation of Max mRNA in primary cultured dog thyrocytes whose proliferation is stimulated by three distinct mitogenic pathways: (1) the thyrotropin (TSH) cascade mediated by cyclic AMP, (2) the protein kinase C pathway activated by diacylglycerol and phorbol esters such as 12-O-tetradecanoylphorbol 13-acetate (TPA), (3) a protein tyrosine kinase system activated by epidermal growth factor (EGF). Among these cascades only the first is compatible with differentiation.

Lack of correlation between the activation of the Ca(2+)-phosphatidylinositol cascade and the regulation of DNA synthesis in the dog thymocyte.

Changes in the [Ca2+]i and/or activation of phospholipase C are thought to participate in the control by several growth factors of the mammalian cell proliferation. It has even been claimed that activation of the Ca(2+)-phosphatidylinositol cascade is sufficient to elicit cell proliferation [Jackson et al. (1988) Nature 335, 437-440; Julius et al.

Differential regulation of protooncogenes c-jun and jun D expressions by protein tyrosine kinase, protein kinase C, and cyclic-AMP mitogenic pathways in dog primary thyrocytes: TSH and cyclic-AMP induce proliferation but downregulate C-jun expression.

The expressions of the protooncogenes c-jun and jun D have been investigated in dog thyrocytes in a primary culture whose proliferation is stimulated by three distinct intracellular signaling pathways (1) the thyrotropin (TSH) or forskolin-cyclic-AMP-mediated cascade; (2) the protein kinase C pathway activated by diacylglycerol (DAG) and phorbol esters (TPA); (3) a protein tyrosine kinase system activated by epidermal growth factor (EGF). While the first cascade is compatible with the differentiated state of the cell, the two latter pathways induce dedifferentiation. Following the stimulation by TPA or EGF, the expression of c-jun was increased and the expression of jun D was faintly increased.

Activation of the cyclic AMP cascade as an oncogenic mechanism: the thyroid example.

Three cascades activate thyroid cell proliferation: the EGF-protein tyrosine kinase pathway, the phorbol ester-protein kinase C pathway and the thyrotropin-cyclic AMP pathway. While the first 2 cascades converge early, they remain distinct from the cyclic AMP cascade until very late in G1. The cyclic AMP cascade is characterized by an early and transient expression of c-myc, which may explain why it induces proliferation and differentiation expression.

Increased levels of c-fos and c-myc mRNA in ATP-stimulated endothelial cells.

In bovine aortic endothelial cells, ATP induced a transient and sequential accumulation of c-fos and c-myc mRNA, which was detected after 1 hour and 3 hours, respectively. The effect of ATP on c-fos mRNA was stronger than that of TNF and bFGF. Both ATP and bFGF increased c-myc mRNA after a 3 hour treatment, whereas TNF did not.

Regulation of protooncogenes c-fos and c-myc expressions by protein tyrosine kinase, protein kinase C, and cyclic AMP mitogenic pathways in dog primary thyrocytes: a positive and negative control by cyclic AMP on c-myc expression.

The proliferation of dog thyrocytes in primary culture is stimulated by three distinct intracellular signaling pathways: (1) the thyrotropin or forskolin-cyclic AMP-mediated cascade which is compatible with the differentiated state of the cell; (2) the protein kinase C pathway activated by diacylglycerol and phorbol esters; and (3) a protein tyrosine kinase system activated by epidermal growth factor. The two latter pathways also induce dedifferentiation. The activation of the three cascades induced the expression of the protooncogenes c-fos and c-myc with dose-response curves similar to those for DNA synthesis.

Function, proliferation and differentiation of the dog and human thyrocyte.

The control of the function, proliferation and differentiation of the dog and human thyrocytes are reviewed. It is shown how this study led by serendipity to the discovery of new receptors, a new modulating intracellular protein (calcyphosin) and of endemic selenium deficiency in Africa.

Stimulation of cell proliferation and inhibition of differentiation expression by tumor-promoting phorbol esters in dog thyroid cells in primary culture.

12-O-Tetradecanoylphorbol-13-acetate (TPA) and 4 beta-phorbol 12, 13-dibutyrate (PDBU) are potent tumor promoters and share several biological activities of epidermal growth factor (EGF). We have shown previously that EGF stimulates DNA synthesis and proliferation and inhibits TSH-induced markers of differentiation in dog thyroid follicle-derived primary cultures. Using this system, we have examined the biological action of TPA and PDBU in reference to that of EGF.

Antagonistic effects of thyrotropin and epidermal growth factor on thyroglobulin mRNA level in cultured thyroid cells.

Both thyrotropin (TSH) and epidermal growth factor (EGF) are potent mitogenic agents when added to dog thyroid cells in primary culture [Roger, P. P. and Dumont, J.