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Thalidomide is now a well known antiangiogenic agent This
Thalidomide is now a well known antiangiogenic agent. This property of thalidomide is being extensively researched upon, for its significant utility in the treatment of various malignant tumors. Studies show that thalidomide efficaciously inhibits various pro-angiogenic factors such as tumor necrosis factor-alpha (TNF-alpha), basic Atazanavir growth factor (bFGF), amongst various others, hence downregulating one of the foremost stimuli for initiation of the process of angiogenesis during various pathological conditions. Phase II studies conducted on the patients of various tumors, namely — multiple myeloma, Waldenstrom's macroglobulinemia (a form of lymphoplasmatocytic lymphoma), AL amyloidosis, myelofibrosis with myeloid metaplasia, myelodysplastic syndrome, acute myeloid leukemia, glioma, glioblastoma, renal cell carcinoma, prostate cancer, advanced melanoma, Kaposi's sarcoma, metastatic breast carcinoma and heavily pretreated metastatic colorectal cancer, showed that the therapy of thalidomide presented positive results in the treatment of the mentioned tumors (to varying extents) [23]. The positive results shown by thalidomide in the treatment of numerous tumors initiated the speculations that its anti-angiogenic properties might also prove useful in treating various other disorders where angiogenesis forms a solid basis of the disease pathophysiology. One such speculated disorder includes diabetic retinopathy. Numerous researches conducted to explore this aspect have concluded that thalidomide, indeed, is responsible for modulating various changes which could be utilized for the prevention of angiogenesis occurring in diabetic retinopathy. The various alterations in different physiological factors/pathways induced by thalidomide for the portrayal of its anti-angiogenic properties have been discussed below. These alterations may effectively prevent the angiogenic events occurring in the retina of a diabetic patient and hence, halt the progression of diabetic retinopathy, making thalidomide an effective therapeutic agent in its treatment.
Various routes for administrating thalidomide into retina have been investigated by researchers and the results drawn from their studies conclude that the drug may effectively be delivered to the angiogenic retinal regions through implants or via oral and parenteral routes. Intravitreal implants have been experimentally found to be efficient in delivering safe doses of thalidomide and exhibit considerable inhibition of angiogenesis [24]. Another study showed significant decrease in neovascularisation as well as prolonged earliest time of its development, in animal models of corneal neovascularization, upon oral administration of thalidomide [25]. Although oral administration of thalidomide is the most common route used during experiments and has shown beneficial results against angiogenesis, the effects of its parenteral administration have also been explored and they, too, have proven equally favorable. In one of such experiments, intraperitoneal administration of thalidomide markedly inhibits basic fibroblast growth factor (bFGF)-induced and vascular endothelial growth factor (VEGF)-induced corneal neovascularisation via a pathway independent of the inhibition of tumor necrosis factor-alpha (TNF-alpha) production [26]. Hence, various routes of administration of thalidomide have been proven useful for the inhibition of angiogenesis during experiments and may, therefore, be effectively utilized in future for therapeutic purposes.
Conclusion
In a paper recently published in , Arai et al discussed some unusual magnetic resonance imaging (MRI) appearances of a glioblastoma multiforme in a patient on chronic lenvatinib therapy (a multireceptor tyrosine kinase inhibitor [TKI] with a mainly antiangiogenic action) for thyroid cancer. Their work underscores how the intersection of radiographic and histologic assessments of treated brain tumors have an evolving role in the future of neuro-oncologic decision making. In their example the reduced vascularity of the tumor after antiangiogenesis therapy was less suggestive of glioma based on classical imaging patterns. Thus providers and diagnosticians should be mindful of the atypical radiographic findings after antiangiogenic treatment.