Irradiation therapeutic

Despite that the thiophene ring is considered as a bioisoster of the benzene ring, the synthesis and chemistry of thiophene analogs of heterocycles with therapeutic interest remain poorly studied. One of the most recent examples concerns the synthesis of new substituted thioisatoic anhydrides (6 and 7-arylthieno[3,2-d] [1,3]oxazine-2,4-diones), which were prepared on a large scale under microwave irradiation conditions. A small library of thiophene ureidoacids was easily performed using a Normatron microwave reactor (500 W) with high yields and good purity [4,5] (Scheme 4). 

Patients presenting with stage I/II disease generally are curable with subtotal lymphoid irradiation, which involves treatment of the mantle and paraaortic fields. This therapeutic modality has yielded an overall 90% cure rate, with over a decade of follow-up. However, up to one-third of patients will relapse at the site of original disease presentation. If a patient relapses, then it likely will occur in the first 3 years after therapy has been completed. Fortunately, most of these patients are still curable with salvage chemotherapy. 

Currently, all donors and blood preparations undergo multistage and expensive control to ensure the absence of viral contamination In this respect, the development of affordable methods of inactivation of viruses could be an important step toward safety in hemotransfusion. Currently used treatments such as UV irradiation damage therapeutic components of the blood (Williamson and Cardigan, 2003), so alternative selective approaches are needed for this purpose. Among them, chemotherapy, photochemotherapy (PCT), and photodynamic antibacterial therapy should be noted (Mohr, 2000). 

Vitamin D hormone is derived from vitamin D (cholecalciferol). Vitamin D can also be produced in the body it is formed in the skin from dehydrocholesterol during irradiation with UV light. When there is lack of solar radiation, dietary intake becomes essential, cod liver oil being a rich source. Metaboli-cally active vitamin D hormone results from two successive hydroxylations in the liver at position 25 ( calcifediol) and in the kidney at position 1 ( calci-triol = vit. D hormone). 1-Hydroxylation depends on the level of calcium homeostasis and is stimulated by parathormone and a fall in plasma levels of Ca or phosphate. Vit D hormone promotes enteral absorption and renal reabsorption of Ca and phosphate. As a result of the increased Ca + and phosphate concentration in blood, there is an increased tendency for these ions to be deposited in bone in the form of hydroxyapatite crystals. In vit D deficiency, bone mineralization is inadequate (rickets, osteomalacia). Therapeutic Liillmann, Color Atlas of Pharmacology... 

Later, to improve this powerful MCR synthetic methodology on the way to the combinatorial arrays of therapeutic important moieties, nonclassical approaches were applied. The reactions were carried out under microwave irradiation in the... 

Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991 21(1) 109-122. 

Kovacs CJ, Schenken LL, Burholt DR. Therapeutic potentiation of combined cis-dichlorodiammineplatinum (11) and irradiation by ICRF-159. Int J Radiat Oncol Biol Phys 1979 5 1361-1364. 

Bartelink H, Kallmann RF, RapacchiettaD, Hart A AM. Therapeutic enhancement in mice by clinically relevant dose and fractionation schedules of cis-diamminedichloroplatinum(II) and irradiation. Radiotherap Oncol 1986 6 61-74. 

Therapeutic irradiation is known to have multiple interactions with the vasculature of the irradiated tissue (12). Radiation has direct cytotoxic effects on the vascular endothelium, likely due to induction of oxidative injury. Radiation-induced injury stimulates inflammation and influx of inflammatory cells in addition to creating aprocoagulant state in the vascular space by the transcriptional induction of tissue factor with the subsequent activation of coagulation factors as well as von Willebrand factor and platelets. Experimental evidence suggests that the mechanism by which radiation initiates these responses is in part through the induction of cell-adhesion molecules including ICAM-1, E-selectin, and P-selectin and in part through local cytokine production and release (13). 

A high RBE of a new radiation quality does not per se imply a therapeutic advantage. The therapeutic gain is actually the ratio of the RBE for the effects on the cancer cell population and the RBE for the effects on the normal tissues (under the actual irradiation conditions). 

Proton beam therapy was a significant step towards better physical selectivity, and it is the most straightforward approach to improve the efficacy of therapeutic irradiations. 

Identification of this gene rearrangement is the sine qua non for the diagnosis of CML, and its presence in the hematopoietic cells of virtually all patients with CML made it an ideal target for the development of therapeutic agents. Proof that BCR-ABL 1 was crucial for the development of CML was shown when the hybrid gene was transfected into bone marrow cells of mice which were subsequently transplanted into an irradiated syngeneic recipient and shown to lead to the development of a CML-like syndrome (5). 

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