Existing Drug Repurposing for Glioblastoma to Discover Candidate Drugs as a New Approach

Aims: Repurposing of drugs has been hypothesized as a means of identifying novel treatment methods for certain diseases. Background: Glioblastoma (GB) is an aggressive type of human cancer; the most effective treatment for glioblastoma is chemotherapy. Whereas, when repurposing drugs, a lot of time and money can be saved. Objective: Repurposing of the existing drug may be used to discover candidate drugs for individualized treatments of GB. Method: We used the bioinformatics method to obtain the candidate drugs. In addition, the drugs were verified by MTT assay, Transwell® assays, TUNEL staining, and in vivo tumor formation experiments, as well as statistical analysis. Result: We obtained 4 candidate drugs suitable for the treatment of glioma: camptothecin, doxorubicin, daunorubicin, and mitoxantrone by expression spectrum data, IPAS algorithm analysis, and drug-pathway connectivity analysis. These validation experiments showed that camptothecin was more effective at treating the GB, such as MTT assay, Transwell® assays, TUNEL staining, and in vivo tumor formation. Conclusion: With regard to personalized treatment, this present study may be used to guide the research of new drugs via verification experiments and tumor formation. The present study also provides a guide to systematic, individualized drug discovery for complex diseases and may contribute to the future application of individualized treatments.

Stage IV Colorectal Cancer Patients with High Risk Mutation Profiles Survived 16 Months Longer with Individualized Therapies

Personalized treatment vs. standard of care is much debated, especially in clinical practice. Here we investigated whether overall survival differences in metastatic colorectal cancer patients are explained by tumor mutation profiles or by treatment differences in real clinical practice. Our retrospective study of metastatic colorectal cancer patients of confirmed European ancestry comprised 54 Americans and 54 gender-matched Germans. The Americans received standard of care, and on treatment failure, 35 patients received individualized treatments. The German patients received standard of care only. Tumor mutations, tumor mutation burden and microsatellite status were identified by using the FoundationOne assay or the IDT Pan-Cancer assay. High-risk patients were identified according to the mutational classification by Schell and colleagues. Results: Kaplan–Meier estimates show the high-risk patients to survive 16 months longer under individualized treatments than those under only standard of care, in the median (p < 0.001). Tumor mutation profiles stratify patients by risk groups but not by country. Conclusions: High-risk patients appear to survive significantly longer (p < 0.001) if they receive individualized treatments after the exhaustion of standard of care treatments. Secondly, the tumor mutation landscape in Americans and Germans is congruent and thus warrants the transatlantic exchange of successful treatment protocols and the harmonization of guidelines.

Taste and dissolution of theophylline extended-release dry syrups

Objectives In this study, we examined the taste and dissolution of theophylline extended-release dry syrups using one branded and six generic formulations. Methods Healthy volunteers underwent sensory testing to assess the syrup taste. Drug dissolution was examined using in vitro dissolution tests. Results and discussion: Syrup taste, including sweetness, bitterness, and aftertaste, was different between formulations. These differences can likely be attributed to the presence of different pharmaceutical additives between formulations. Our results indicated that syrup aftertaste was dependent on the level of sweetness and bitterness. In addition, dissolution behaviors were different between formulations, suggesting bio-inequivalence between formulations. These differences likely reflect the use of different controlled-release technologies between formulations. Conclusions This study provides useful information for selecting branded or generic theophylline extended-release dry syrups for individualized treatments.

Anorectal Malformations

Anorectal malformation are common congenital problems occurring in 1 in 5,000 births and have a spectrum of anatomical presentations, requiring individualized treatments for the newborn, sophisticated approaches to the definitive reconstruction, and management of long-term treatments and outcomes. Associated anomalies related to the cardiac, renal, gynecologic, orthopedic, spinal, and sacral systems impact care and prognosis. Long-term results are good provided there is an accurate anatomical reconstruction and a focus on maximizing of functional results.