Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein, the second CSF, sharing some common effects with granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and interleukin-5 (IL-5). G-CSF is mainly produced by fibroblasts and endothelial cells from bone marrow stroma and by immunocompetent cells (monocytes, macrophages). The receptor for G-CSF (G-CSFR) is part of the cytokine and hematopoietin receptor superfamily and G-CSFR mutations cause severe congenital neutropenia.The main action of G-CSF - G-CSFR linkage is stimulation of the production, mobilization, survival and chemotaxis of neutrophils, but there are many other G-CSF effects: growth and migration of endothelial cells, decrease of norepinephrine reuptake, increase in osteoclastic activity and decrease in osteoblast activity.In oncology, G-CSF is utilized especially for the primary prophylaxis of chemotherapy-induced neutropenia, but it can be used for hematopoietic stem cell transplantation, it can produce monocytic differentiation of some myeloid leukemias and it can increase some drug resistance.The therapeutic indications of G-CSF are becoming more and more numerous: non neutropenic patients infections, reproductive medicine, neurological disturbances, regeneration therapy after acute myocardial infarction and of skeletal muscle, and hepatitis C therapy.
A new N-sulfonamide ligand (HL1= N-(5-(4-methoxyphenyl)-[1,3,4]-thiadiazole-2-yl)-toluenesulfonamide) and two Cu(II) complexes, [Cu(L1) 2 (py) 2 ] (C1) and [Cu(L2) 2 (py) 2 (H 2 O)] (C2) (HL2 = N-(5-(4methylphenyl)-[1,3,4]-thiadiazole-2-yl)-benzenesulfonamide) were synthesized. The X-ray crystal structures of the complexes were determined. In the complex C1, the Cu(II) ion is four-coordinated, forming a CuN 4 chromophore and in the complex C2, the Cu(II) ion is five-coordinated, forming a CuN 4 O chromophore. The ligand acts as monodentate, coordinating the Cu(II) ion through a single N thiadiazole atom. The molecules from the reaction medium (pyridine and water) are also involved in the coordination of the Cu(II) ion. The complexes C1 and C2 are square-planar and a slightly distorted square pyramidal, respectively. The compounds were characterized by FT-IR, electronic, EPR spectroscopic and magnetic methods. The nuclease binding activity studies of the synthesized complexes confirm their capacity to cleave the DNA molecule. The cytotoxicity studies were carried out on melanoma cell line WM35 which confirm that both compounds inhibit the growth of these cells. They have a higher activity compared to a platinum drug, carboplatin.
Novel emerging therapies have changed paradigms in metastatic colorectal cancer. The advantages of molecular targeted treatments, either the anti-angiogenic or the anti-epidermal growth factor receptor drugs, reside in the fact that while their specificity for the cancer cell is higher, their toxicity on normal tissues is significantly lower when compared to chemotherapy. But when it comes to their safety, especially from a cardiovascular point of view, they still need to pass the test of time and further prospective studies are needed. Clinical trial patients are very well selected with regards to comorbidities and therefore, they often differ from real-life patients. In order to maximize the benefits from these drugs, we need to better identify the population at risk, understand and early diagnose their on- and off-target adverse effects and to adequately choose the diagnostic tools; with a better prevention and early treatment, the quality and quantity of our patients’ lives can be significantly improved.
The entry of the generic drugs on the market was an impressive development of the pharmaceutical industry and due to their lower prices also a decrease in the cost
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