To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.

AbstractIntervertebral disc degeneration (IVDD) is one of the common causes of low back pain. Similar to many other multifactorial diseases, it is affected by environmental and genetic factors. Although not completely understood, genetic factors include a wide spectrum of variations, such as single nucleotide polymorphisms, which could play a significant role in the etiology of this disease. Besides, the interactions with environmental factors could make the role of genetic factors more complicated. Genetic variations in disc components could participate in developing degenerative disc disease through altering the normal homeostasis of discs. Gene polymorphisms in disc proteins (collagens I, II, III, IX, and XI), proteoglycans (aggrecan), cytokines (interleukins I, VI, and X), enzymes (matrix metalloproteinases II, III, and IX), and vitamin D receptor seem to play considerable roles in the pathology of this disease. There are also many other investigated genes that could somehow take part in the process. However, it seems that more studies are needed to clarify the exact role of genetics in IVDD.

BackgroundThe aim of this study was to translate the EORTC quality of life questionnaire for brain cancer, the QLQ-BN20, into Persian, and to evaluate its psychometric properties when used among brain cancer patients in Iran.MethodsA standard backward and forward translation procedure was used to generate the Persian language version of the QLQ-BN20. The QLQ-BN20 was administered together with the QLQ-C30 to 194 patients diagnosed with primary brain cancer. Multitrait scaling and confirmatory factor analysis (CFA) were used to evaluate the hypothesized scale structure of the questionnaire. Internal consistency reliability was estimated with Cronbach’s alpha. The ability of the QLQ-BN20 to distinguish between patient subgroups formed on the basis of performance status and cognitive status was evaluated, as was the responsiveness of the questionnaire to changes in performance status over time.ResultsMultitrait scaling and CFA results confirmed the hypothesized scale structure. The measurement model was consistent across men and women. Internal consistency reliability of the multi-item scales ranged from 0.74 to 0.89. The QLQ-BN20 distinguished clearly between patients with relatively good versus poor performance and cognitive status, and changes in scores over time reflected changes observed in performance status ratings.ConclusionsThese results support the validity and reliability of the QLQ-BN20 for use among Iranian patients diagnosed with primary brain cancer. Future studies should examine the psychometrics of the questionnaire when used in patients with brain metastasis.