Cell therapeutics

Platinum complexes are cytotoxic agents yet the paradigm in cancer chemotherapy has moved to a more targeted approach, with special emphasis on signaling pathways. In this respect a remarkable story is that of arsenic trioxide, As203 (Trisenox, Cell Therapeutics Inc, Seattle, USA) which was approved by the FDA in September 2000 for treatment of acute promomyelo-cytic leukemia (APL) in patients who have relapsed or are refractory to retinoid and anthracycline chemotherapy. An estimated 1,500 new cases of APL are diagnosed yearly in the US, of which an... 

Distamycin A (178) Antibiotic Brostallicin (PNU- Oncology DNA minor groove Phase II Cell Therapeutics 870-877... 

Cell Therapeutics Further information available at http //www.celltherapeutics. com/. 

Mechanism of Action A mouth agent that has anti-allergic and anti-inflammatory properties. Appears to inhibit formation and/or release of inflammatory mediators (e g., histamine) from mast cells, neutrophils, mononuclear cells. Therapeutic Effect Alleviates signs and symptoms of aphthous ulcers. 

Mecftanism of Action AGI Hj-blocker and gastric acid secretion inhibitor that inhibits histamine action at histamine 2 receptors of parietal cells Therapeutic Effect Inhibits gastric acid secretion when fasting, at night, or when stimulated by food, caffeine, or insulin. 

Mecftanism of Action Apiperidinethat competes with histamine for Hj-receptor sites on effector cells. Therapeutic Effect Relieves allergic rhinitis symptoms. Pfiarmacokinetics Rapidly absorbed after PO administration. Protein binding 60% 70%. Does not cross the blood-brain barrier. Minimally metabolized. Eliminated in feces and urine. Not removed by hemodialysis. Half-life 14.4 fir (increased in renal impairment). 

Mecfianism of Action A monoclonal antibody that binds to tumor necrosis factor (TNF), inhibiting functional activity of TNF. Reduces infiltration of inflammatory cells. Therapeutic Effect Decreases inflamed areas of the intestine. 

Mechanism of Action Abiologic response modifier that inhibits viral replication in virus-infected cells, suppresses cell proliferation, increases phagocytic action of macrophages, and augments specific cytotoxicity of lymphocytes for target cells. Therapeutic Effect Inhibits viral growth in condylomata acuminata. 

Mecfianism of Action A biologic response modifier t hat interacts with specific cel 1 receptors found on surface of human cells. Therapeutic Effect Possesses antiviral and immunoregulatory activities. 

Mechanism of Action An antidote to folic acid antagonists that may limit methotrexate action on normal cells by competing with methotrexate for the same transport processes into the cells Therapeutic Effect Reverses toxic effects of folic acid antagonists. Reverses folic acid deficiency. 

Mechanism of Action A mast cell stabilizer that prevents increase in cutaneous vascular permeability, antigen-stimulated histamine release, and may prevent calcium influx into mast cells. Therapeutic Effect Inhibits sensitivity reaction. Pharmacokinetics Nondetectable absorption. Half-life 8.5 hr. 

Mechanism of Action A prostaglandin that inhibits basal, nocturnal gastric acid secretion via direct action on parietal cells. Therapeutic Effect Increases production of protective gastric mucus. 

Mecfianism of Action An antineoplasticadjunct that binds to the keratinocyte growth factor receptor, present on epithelial cells of the buccal mucosa and tongue, resulting in the proliferation, differentiation, and migration of epithelial cells. Therapeutic Effect Reduces incidence and duration of severe oral mucositis. 

Mechanism of Action-. A selective vascular endothelial growth factor (VEGF) antagonize that selectively binds and activates receptors located on the surface of vascular endothelial cells. Therapeutic Effect Blocks angiogenesis and vascular permeability and inflammation which contribute to the progression of the neovascular (wet) form of age-related macular degeneration (AMD). 

Mecfianism of Action Inhibits HIV protease, rendering the enzyme incapable of processing the polyprotein precursors needed to generate functional proteins in HIV-infected cells. Therapeutic Effect Interferes with HIV replication, slowing the progression of HIV infection. 

Mechanism of Action An anti-infective that inhibits protein synthesis of bacterial cells. Therapeutic Effect Produces bacterial cell death. 

Mecfianism of Action A nonpeptide HIV-1 protease inhibitor that inhibits the virus-specific processing of polyproteins and HIV-1 infected cells. Therapeutic Effect Prevents formation of mature viral cells. 

Mechanism of Action A retinoid that decreases cohesiveness of follicular epithelial cells. Increases turnover of follicular epithelial cells. Bacterial skin counts are not altered. Transdermal Exerts its effects on growth and differentiation of epithelial cells. Antineoplastic Induces maturation, decreases proliferation of acute promyelocytic leukemia (APL) cells. Therapeutic Effect Causes expulsion of blackheads alleviates fine wrinkles, hyperpigmentation causes repopulation of bone marrow and blood by normal hematopoietic cells. 

Virtual pharma 4000- 5000 Venture capital funded, 1-2 developmental drugs, mainly biopharmaceuticals, small R D, no production, no M S organization Cell Therapeutics, Gilead, Trimeris, Vertex, USA Alizyme, UK Morphosys, Germany Actelion, Speedel, Switzerland... 

With the confirmation that neurogenesis occurs in the adult brain, and the recent isolation and characterization in vitro of neural progenitor and stem cells from the adult CNS, new avenues for the treatment of neurological diseases and injuries are being considered. Cell therapeutic interventions may involve both in vivo stimulation and transplantation of neural progenitor and stem cells. 

Finally, the evidence that neurogenesis occurs in the adult brain, and that NSCs reside in the adult CNSs provides new avenues for cellular therapy. Cell therapeutic intervention may involve the stimulation of endogenous or the transplantation of neural progenitor and stem cells of the adult CNS. However, adult NSCs are yet to be used for therapy. 

Trisenox Arsenic trioxide Cell Therapeutics 6/2000 Acute promyelocytic leukemia NA... 

Dept, of Pharmacology SJ-30, University of Washington, Seattle, WA 98195 and Cell Therapeutics, Inc., Seattle, WA 98195... 

Trade names Fowler s Solution (rarely employed found in pesticides and herbal medicines) Trisonex (Cell Therapeutics) Indications Acute promyelocytic leukemia, psoriasis (in the early 1900s), devitalization of pulp in dental procedures Category Trace element Half-life N/A... 

In summary, there are many stem cell types that have the potential for cardiac repair, but more sophisticated cell culture and TE approaches need to be developed. In addition, the main obstacle influencing cell therapeutic efflcacy is the high death rate of donor stem cells after transplantation. Fabrication of biomaterial scaffolds with suitable nanostructure could be a feasible strategy for optimizing stem cell therapy for cardiac regeneration. 

Man M, Rugo H. Paclitaxel poliglumex. Cell Therapeutics/Chugai Pharmaceutical. IDrugs 2005 Sep 8(9) 739 -754. 

---