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Conventional to Novel Targeted Approaches for Brain Tumors: The Role of Nanomedicines for Effective Treatment
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Mahfoozur Rahman, Kainat Alam, Md. Adil Shaharyar, Sarwar Beg, Abdul Hafeez, Vikas Kumar
Intra-arterial (IA) drug administration supersedes intravenous drug administration as the former bypasses the first pass metabolism, yet this factor alone is not sufficient enough to give good clinical results. Temporary disruption of the BBB through osmosis followed by IA drug administration increases the concentration of chemotherapeutic agent in the CNS without affecting neurocognitive functions. IA decreases systemic toxicity (Neuwelt, 2004). This disruption of BBB is carried out by infusing pre-warmed mannitol (25%), it administered through the internal carotid artery at a flow rate of 3–12 mL/s for a short duration of 10 mins and monitoring of the tumor through computed tomography or MRI is carried out. Disruption of BBB can also be carried out using ultrasound which shows no tissue damage (Vykhodtseva, 2008). Amalgamation of IA therapy of anti-cancer drugs and BBB through osmosis gives good result especially in some tumors like germ cell tumors (Jahnke, 2008). Complexity of the procedure limits its usage. Radiotherapy along with temozolomide is the current and conventional treatment in primary and metastatic brain cancers. It is the standard treatment in newly diagnosed gliomas with an advantage of increased permeability of BBB.
Brain cancer
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
William D. Dunn, Rivka R. Colen
Some of the important genomic markers related to glioblastoma are O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, isocitrate dehydrogenase (IDH1) mutation, 1p/19q codeletion, and epidermal growth factor receptor (EGFR) mutation. Promoter methylation status of MGMT is an important prognostic and predictive biomarker for glioblastoma.36,37,45 MGMT is an excision repair enzyme coded by MGMT gene located on chromosome 10q26 that removes alkyl groups from O6-alkylguanine adducts on DNA.46 Alkylating agents, such as temozolomide (TMZ), exert their actions mainly through alkylating the O6-methylguanine position, among other actions, causing it to preferentially pair with thymine during replication, and activating cycles of ineffective mismatch repair (MMR) pathways that lead to double-strand breaks and eventually apoptosis of the cancer cell.47,48 Since the MGMT enzyme is irreversibly inactivated upon binding alkyl groups, it must be continually regenerated to continue its repair activity against the influx of alkylating agents. Therefore, when MGMT is inactivated, through epigenetic silencing by hypermethylation of its promoter region, alkylating agents are better able to exert their anti-tumor activity. As a result, MGMT promoter methylation, seen in roughly 40%–50% of glioblastomas, is used clinically as an indication to suggest a favorable response to alkylating chemotherapeutic agents.36,37,45,48
Pulmonary infection induced by drugs
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Marc B Feinstein, Dorothy A White
Temozolomide is an alkylating agent widely used for treatment of melanoma and brain tumours. During prolonged use, lymphopenia and very low CD4 counts have been noted. This has been associated with documented opportunistic infection with Pneumocystis and Aspergillus pneumonia. In addition, cases of H. simplex and H. zoster have been seen.9
Water-soluble and amphiphilic phospholipid copolymers having 2-methacryloyloxyethyl phosphorylcholine units for the solubilization of bioactive compounds
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Kazuhiko Ishihara, Mingwei Mu, Tomohiro Konno
Poly(MPC) does not show an amphiphilic nature as shown in Figure 2 [26]. However, some hydrophobic bioactive compounds conjugated with the poly(MPC) possess good pharmaceutical properties. Emrick and coworkers prepare a conjugation of hydrophobic doxorubicin (DOX) bound to side chain of poly(MPC) with pH-sensitive hydrazone linkage (DOX-poly(MPC) conjugate) [65–67]. Release rate of DOX from the conjugate is depended on the pH, that is, lowing of the pH circumstances enhances release rate of DOX. The DOX-poly(MPC) conjugate shows intracellular abundance in cancer cells, and low cytotoxicity compared with those of free DOX. Animal experiments demonstrate that the viability of the DOX-poly(MPC) conjugate cancer therapy, and that a simple water-soluble polymer conjugation is applicable for improving solubility of bioactive compounds, and enhancing delivery to target tumor, even without high affinity biomolecules. The same research group has reported synthesis of other drug-poly(MPC) conjugate, that is, the glioblastoma drug temozolomide and anticancer drug camptothecin bound covalently in the poly(MPC) chain [68,69].