Growth factors failure

Erythropoietin is a growth factor produced by interstitial cells of the kidney in response to hypoxia. Erythropoietin stimulates haematopoiesis in the bone marrow. Recombinant human erythropoietin is used to treat anemias, e.g. anemia caused by chronic renal failure and anemia in AIDS and cancer patients. 

When hematopoietic growth factors are used clinically, they can be associated with adverse effects. Very often patients who require hematopoietic growth factors are quite ill with their disease (i.e., cancer or kidney failure) or from their treatment (i.e., chemotherapy) and it is difficult to determine if a recombinant growth factor is responsible for a given side effect. Both rHuG-CSF and rHuGM-CSF are associated with mild-to-moderate... 

POEMS is an eponym applied to patients with a variety of plasma cell dyscrasias who present with polyneuropathy, organomegaly, endocrinopathy, an M protein and skin changes this disorder is also referred to as Crow-Fukase syndrome. Additional manifestations of this disorder are pulmonary hypertension, renal failure, a predisposition to thrombosis and congestive heart failure some of these features are likely to be attributable to vascular endothelial growth factor (VEGF) and matrix metalloproteinases, which are often elevated in the plasma of these patients [43]. 

Clinical pharmacology Erythropoietin is instrumental in the production of red cells from the erythroid tissues in the bone marrow. The majority of this hormone is produced in the kidney in response to hypoxia, with an additional 10% to 15% of synthesis occurring in the hver. Erythropoietin functions as a growth factor, stimulating the mitotic activity of the erythroid progenitor cells and early precursor cells. Chronic renal failure patients often manifest the sequelae of renal dysfunction, including anemia. Anemia in cancer patients may be related to the disease itself or the effect of concomitantly administered chemotherapeutic agents. 

A small number of children with growth failure have severe IGF-1 deficiency that is not responsive to exogenous GH. Causes include mutations in the GH receptor and development of neutralizing antibodies to GH. In 2005, the FDA approved mecasermin for treatment of severe IGF-1 deficiency that is not responsive to GH. Mecasermin is a complex of recombinant human IGF-1 (rhIGF-1) and recombinant human insulin-like growth factor-binding protein-3 (rhIGFBP-3). 

In selected patients, erythropoietin may also be useful for the treatment of anemia due to primary bone marrow disorders and secondary anemias. This includes patients with aplastic anemia and other bone marrow failure states, myeloproliferative and myelodysplastic disorders, multiple myeloma and perhaps other chronic bone marrow malignancies, and the anemias associated with chronic inflammation, AIDS, and cancer. Patients with these disorders who have disproportionately low serum erythropoietin levels for their degree of anemia are most likely to respond to treatment with this growth factor. Patients with endogenous erythropoietin levels of less than 100 IU/L have the best chance of response, though patients with erythropoietin levels between 100 and 500 IU/L respond occasionally. These patients generally require higher erythropoietin doses (150-300 IU/kg three times a week) to achieve a response, and responses are often incomplete. 

Dai, C., Yang, J. and Liu, Y. (2002). Single injection of naked plasmid encoding hepatocyte growth factor prevents cell death and ameliorates acute renal failure in mice. J. Am. Soc. Nephrol. 13, 411-422. 

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