Brain tumors treating

It has also been demonstrated that PEGylated liposomal doxorubicin, Caelyx, can cross the BBB with a consequent accumulation in primary and secondary brain lesions [389], In 10 patients with metastatic brain tumors treated with radiolabeled Caelyx concurrent with radiotherapy, the accumulation of the liposomal doxorubicin was 7-13 times higher in the metastatic lesions compared to the normal brain. 

The radioactive source need not aiways be introduced into the body. Inoperable brain tumors can be treated with y rays from an extemai source, usuaiiy a sampie of cobait-60. The patient is placed in a position where the y-ray beam passes through the tumor. The patient is moved so that the y rays irradiate the tumor from several angles. In this manner the tumor receives a much higher dose of radiation than the dose received by any surrounding tissues. 

It is known that 10B collects in brain tumors to a greater extent than in normal tissue. Research has been conducted on the use of the isotope 10B for treating brain tumors. Bombardment of the tumor with slow neutrons leads to the production of alpha particles (4He2+) and lithium nuclei that have enough energy to destroy the abnormal tissue. 

CEO, Stephen Hoffman and VP for clinical studies, Michael Gerber of Alios Therapeutics guided RSR 13 through a series of phase-one and phase-two clinical trials for radiation treatment of brain tumors and for potential use in cardiopulmonary bypass surgery [46, 51-55]. Considering the cost of running a phase-three clinical trial, only one was possible. The very positive phase-two results for use of RSR 13 to treat metastatic brain cancer provided the impetus for selecting that indication for a phase-three trial. 

Kleinberg, L, Grossman, S.A., Carson, K., Lesser, G., O Neill, A., Pearlman, J., Phillips, P., Herman, T., and Gerber, M. Survival of patients with newly diagnosed glioblastoma multiforme treated with RSR13 and radiotherapy results of a phase 11 new approaches to brain tumor therapy CNS consortium safety and efficacy study. J. Clin. Oncol. 2002, 20, 3149-3155. 

The recurrence rate of intracranial tumors has been addressed in a number of large observational studies. Reports from the NCGS database (which includes 1262 children with brain tumors) and from England have shown no increase in intracranial tumor recurrence in patients treated with growth hormone (97,98). For patients with craniopharyngioma, postoperative irradiation reduced the recurrence rate, but growth hormone therapy did not increase the risk (99). 

Moshang T Jr, Rundle AC, Graves DA, Nickas J, Johanson A, Meadows A. Brain tumor recurrence in children treated with growth hormone the National Cooperative Growth Study experience. J Pediatr 1996 128(5 Pt 2) S4-7. 

Carmustine (BCNU), lomustine (CCNU), and semustine (methyl-CCNU) generate alkyl car-bonium ions and isocyanate molecules and hence are able to interact with DNA and other macromolecules. These agents, which are lipid soluble, cross the blood-brain barrier and are therefore effective in treating brain tumors. They are bone marrow depressants. 

Podophyllotoxin, a potentially lethal component of mayapple, blocks cell division and has tumor-inhibiting properties. Two drugs derived from it are approved for use in the U.S. Etoposide is used to treat testicular and small-cell lung cancer. Teniposide is employed with brain tumors and childhood leukemia (see Chapter 62). 

Xanthine oxidase catalyzes the formation of urate and superoxide anion from xanthine. Quercetin and baicalein inhibit both xanthine oxidase and xanthine dehydrogenase. The level of xanthine oxidase is high in patients with hepatitis and brain tumor and select flavonoids might be useful in treating this disorder. 

However, a variety of issues have implications for the use of viral vectors in gene therapy. Obvious potential concerns are the immune and inflammatory responses to viral vectors. Patients who received VEGF-121 via an adenoviral vector had increased levels of serum antiadenoviral neutralizing antibodies, but there was no report on an inflammatory response in these patients (27). The use of adenovirus-mediated gene therapy in treating brain tumors has been reported to lead to active brain inflammation as well as persistent (up to three months after treatment) transgene expression (30). 

With one important exception, dioxoles and oxathioles do not appear to be a particularly toxic class of compounds. The exception is 1,2-oxathiolane 2,2-dioxide (propane sultone) which produces brain tumors, leukaemias and adenocarcinomas of the small intestine in rats treated with 28 mg kg-1 orally twice a week for 60 weeks. If the toxicity is associated with its ability to act as an alkylating agent, then higher homologs should have similar, but reduced, carcinogenic potential. 

---