Cells proliferation

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

D. R. Laves, in H. H. Hiatt, J. D. Watson, and J. A. Winsten, eds.. Origins of Human Cancer, Vol. 4, Cold Spring Haiboi Conferences on Cell Proliferation, Cold Spring Harbor Laboratory, Maine, 1977, p. 357. 

The PBRis distinct from the central BZ receptor although both can be present in the same tissues in differing ratios. PBRs are predominately localized on the outer mitochondrial membrane and are thus intracellular BZ recognition sites. The PBR is composed of three subunits an 18,000 mol wt subunit that binds isoquinoline carboxamide derivatives a 30,000 mol wt subunit that binds BZs and a 32,000 mol wt voltage-dependent anion channel subunit. The porphyrins may be endogenous ligands for the PBR. PBRs are involved in the control of cell proliferation and differentiation and steroidogenesis. 

There are hundreds of topical steroid preparations that are available for the treatment of skin diseases. In addition to their aforementioned antiinflammatory effects, topical steroids also exert their effects by vasoconstriction of the capillaries in the superficial dermis and by reduction of cellular mitosis and cell proliferation especially in the basal cell layer of the skin. In addition to the aforementioned systemic side effects, topical steroids can have adverse local effects. Chronic treatment with topical corticosteroids may increase the risk of bacterial and fungal infections. A combination steroid and antibacterial agent can be used to combat this problem. Additional local side effects that can be caused by extended use of topical steroids are epidermal atrophy, acne, glaucoma and cataracts (thus the weakest concentrations should be used in and around the eyes), pigmentation problems, hypertrichosis, allergic contact dermatitis, perioral dermatitis, and granuloma gluteale infantum (251). 

Disease States. Rickets is the most common disease associated with vitamin D deficiency. Many other disease states have been shown to be related to vitamin D. These can iavolve a lack of the vitamin, deficient synthesis of the metaboUtes from the vitamin, deficient control mechanisms, or defective organ receptors. The control of calcium and phosphoms is essential ia the maintenance of normal cellular biochemistry, eg, muscle contraction, nerve conduction, and enzyme function. The vitamin D metaboUtes also have a function ia cell proliferation. They iateract with other factors and receptors to regulate gene transcription. 

Yamasaki, H., Knitovskikh, V, Mesnil, M., Cohirabano, A., Tsuda, H., and Ito, N. (1993). Gap jurictional intercellular communication and cell proliferation during rat liver carcinogenesis. Academic diss.. University of Helsinki. 

A correlation of enhanced synthesis of polyamines with rapid growth or cell proliferation has been observed 21. From a physiological point of view, polyamines are implicated as regulators of cell proliferative activity 22). It is well known that polyamines, as protonated polycations, can bind with nucleotide and nucleic acid anions 23 241 to affect biochemical reactivities and stabilize tertiary structures 25,26). 

Hypertension/cell proliferation and migration/tubular Na+ resorption... 

Induces dyskinesia/vasodilatation, schizophrenia/4- coordination Vaso constriction/cell proliferation/aldosterone secretion Vaso constriction/cell proliferation/bronchoconstriction 4-memory, sedation/vasodilatation/4 GI motility A blood pressure/4- GI secretion Vagal effects/A blood pressure/tachycardia... 

T No A No A PKA t PKC Brain, lung, skeletal muscle Synaptic plasticity, arrest of cell proliferation... 

U (No CaM) < O Q. CL Heart, kidney, Brain, liver, widespread Cardiac function, Ca2+-dependent regulation, hormonal regulation of gluconeogenesis, cell proliferation, coincidence detector for NO... 

Systematic screening experiments have identified more than 100 synthetic compounds with potent antiangiogenic activity. The mode of action for most of these molecules is not well understood, but some of the 40 compounds are well advanced in clinical trials (Table 3). The first substance to have entered clinical trials was the Fumagillin-derivative AGM 1470. Fumagillin is an antibiotic which inhibits bFGF- and PDGF-induced endothelial cell proliferation. The mechanism of action of AGM 1470 is poorly understood, but it was shown that it binds and inhibits the metalloprotease methionine aminopeptidase (MetAp-2). 

Eflornithine (difluoromethylornithine, DFMO) inhibits the ornithine decarboxylase of the polyamine pathway, in both the trypanosome and the mammalian cell, by acting as an irreversible competitor of the natural substrate ornithine. Inhibition of ornithine decarboxylase results in depletion of the polyamines, putrescine, spermidine and spermine, which are essential for cell proliferation. Eflornithine selectively harms the parasite and not the mammalian cells, despite acting as an ornithine decarboxylase inhibitor in both cell types. This selectivity is explained by the lower rate of ornithine decarboxylase production in the parasite, as compared to mammalian cells. Due to the high turnover rate, mammalian cells are capable of quickly replenishing inhibited ornithine decarboxylase by newly... 

PMURAR a Transcriptional regulator Inhibition of cell proliferation induction of apoptosis increase in sensitivity against ATRA... 

N-ras, H-ras, K-ras Signal transduction pathway Inhibition of cell proliferation and colony formation change in morphology, enhanced melanin synthesis decrease of in vivo tumorigenicity... 

Telomerase Ribonucleoprotein Suppression of telomerase activity inhibition of cell proliferation change in morphology induction of apoptosis... 

Human papilloma virus (HPV) Cervical cancer, oral cancer E6, E7 Inhibition of cell proliferation and colony formation... 

Epstein-Barr virus (EBV) Burkitt s lymphoma, nasopharyngeal carcinoma, lymphoproliterative disorders in immuno-suppressed patients (e.g., AIDS, transplant recipients) EBNA-1 Inhibition of cell proliferation... 

The anthrax toxin is a tripartite toxin and consists ofthe binding component protective antigen (PA), the lethal factor (LF), which is a metalloprotease, and the edema factor (EF), which is a calmodulin-dependent adenylyl-cyclase. Both enzyme components are translocated via PA into target cells. PA is activated by furin-induced cleavage and forms heptamers, which are similar to the binding components of C2 toxin and iota toxin. In the low pH compartment of endosomes, the heptamers form pores to allow translocation of LF and EF. LF cleaves six of the seven MEKs (MAPK-kinases) thereby inhibiting these enzymes. The functional consequence is the blockade of the MAPK pathways that control cell proliferation, differentiation, inflammation, stress response, and survival. Whether this is the reason for the LT-induced cell death of macrophages is not clear [1]. 

Cell division cycle Cell proliferation Cell multiplication... 

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