Renal transplantation is the best treatment for patients with end-stage renal disease. Over the last decades, the introduction of new immunosuppressive agents resulted into the reduction of the incidence of acute rejection and early graft loss. Despite this progress, there has been little improvement in the average life of the transplant. The main reasons of late failure are patient's death due to several complications (e.g. cancer, infectious or metabolic), and progressive deterioration of renal function caused by immunological and non-immunological factors. The immunosuppressive therapy can be distinguished into two components: the induction therapy and the maintenance therapy. The former has the aim to implement intense and immediate immunosuppression. This therapy is mostly useful in transplant with high immunological risk, although it is correlated with an increased risk of cytopenias and viral infections. The latter offers the rationale to prevent organ rejection and minimize drug toxicity. This is generally constituted by the association of two or three drugs with different mechanism of action. The most common application of this scheme includes a calcineurin inhibitor in combination with an antimetabolite and a minimum dose of steroids. Immunosuppressive therapy is also associated to an increased risk of infections and cancer development. For instance, each class of drugs is related to a different profile of toxicity. The choice of treatment protocol should take into account the clinical characteristics of the donor and recipient. Furthermore, this treatment may change anytime when clinical conditions result into complications.
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Virol J
January 2025
Department of Pharmacotherapy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
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Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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Conventional cancer treatments often induce a sustained DNA damage response (DDR) in tumor cells, leading to therapy-induced senescence (TIS), characterized by permanent cell cycle arrest and resistance to apoptosis. These senescent cells secrete senescence-associated secretory phenotypes (SASP), which can promote tumor progression and create an immunosuppressive microenvironment. This study introduces a novel approach to enhance chemotherapy efficacy by using functionalized curcuma-derived extracellular vesicles (DR5-CNV/DOX) to target and eliminate senescent tumor cells and inhibit their SASP.
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