quetiapine-fumarate and Brain-Neoplasms

Lesion-based investigations of psychopathology have preceded contemporary network-neuroscience initiatives. However, brain-lesions detected in routine psychiatric practice are often considered incidental and therefore ignored. Here, we illustrate a strategy to combine individual subject-level lesion information with open-source normative functional-connectomics data to make putative, neuroscience-informed symptom interpretation. Specifically, we report a patient with left precuneus granulomatous lesion and seizures followed by two distinct symptoms - kinetopsia and delusions of nihilism and guilt - which had a differential treatment response. The lesion-based brain-mapping approach could identify correlated (default-mode) and anti-correlated (temporo-parieto-occipital) networks, which enabled a neurobiological formulation of these diverse clinical manifestations.

Topics: Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Brain Mapping; Brain Neoplasms; Depressive Disorder, Major; Diagnosis, Differential; Electroconvulsive Therapy; Female; Fluoxetine; Granuloma; Humans; Magnetic Resonance Imaging; Middle Aged; Parietal Lobe; Phenytoin; Quetiapine Fumarate; Schizophrenia, Paranoid; Seizures

Constructed from a theoretical framework, the coordinated undermining of survival paths in glioblastoma (GBM) is a combination of nine drugs approved for non-oncological indications (CUSP9; aprepitant, auranofin, captopril, celecoxib, disulfiram, itraconazole, minocycline, quetiapine, and sertraline) combined with temozolomide (TMZ). The availability of these drugs outside of specialized treatment centers has led patients to embark on combination treatments without systematic follow-up. However, no experimental data on efficacy using the CUSP9 strategy in GBM have been reported.. Using patient-derived glioblastoma stem cell (GSC) cultures from 15 GBM patients, we described stem cell properties of individual cultures, determined the dose-response relationships of the drugs in the CUSP9, and assessed the efficacy the CUSP9 combination with TMZ in concentrations clinically achievable. The efficacy was evaluated by cell viability, cytotoxicity, and sphere-forming assays in both primary and recurrent GSC cultures.. We found that CUSP9 with TMZ induced a combination effect compared to the drugs individually (p < 0.0001). Evaluated by cell viability and cytotoxicity, 50% of the GSC cultures displayed a high sensitivity to the drug combination. In clinical plasma concentrations, the effect of the CUSP9 with TMZ was superior to TMZ monotherapy (p < 0.001). The Wnt-signaling pathway has been shown important in GSC, and CUSP9 significantly reduces Wnt-activity.. Adding experimental data to the theoretical rationale of CUSP9, our results demonstrate that the CUSP9 treatment strategy can induce a combination effect in both treatment-naïve and pretreated GSC cultures; however, predicting response in individual cultures will require further profiling of GSCs.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Auranofin; Brain Neoplasms; Captopril; Celecoxib; Disulfiram; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Glioblastoma; Humans; Itraconazole; Mice; Mice, SCID; Minocycline; Neoplastic Stem Cells; Quetiapine Fumarate; Reproducibility of Results; Sertraline; Signal Transduction; Temozolomide; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

As a major contributor of chemotherapy resistance and malignant recurrence, glioma stem cells (GSCs) have been proposed as a target for the treatment of gliomas. To evaluate the therapeutic potential of quetiapine (QUE), an atypical antipsychotic, for the treatment of malignant glioma, we established mouse models with GSCs-initiated orthotopic xenograft gliomas and subcutaneous xenograft tumors, using GSCs purified from glioblastoma cell line GL261. We investigated antitumor effects of QUE on xenograft gliomas and its underlying mechanisms on GSCs. Our data demonstrated that (i) QUE monotherapy can effectively suppress GSCs-initiated tumor growth; (ii) QUE has synergistic effects with temozolomide (TMZ) on glioma suppression, and importantly, QUE can effectively suppress TMZ-resistant (or -escaped) tumors generated from GSCs; (iii) mechanistically, the anti-glioma effect of QUE was due to its actions of promoting the differentiation of GSCs into oligodendrocyte (OL)-like cells and its inhibitory effect on the Wnt/β-catenin signaling pathway. Together, our findings suggest an effective approach for anti-gliomagenic treatment via targeting OL-oriented differentiation of GSCs. This also opens a door for repurposing QUE, an FDA approved drug, for the treatment of malignant glioma.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cell Differentiation; Cell Line, Tumor; Dacarbazine; Drug Repositioning; Drug Synergism; Glioma; Humans; Mice, Inbred C57BL; Mice, Nude; Neoplasms, Experimental; Neoplastic Stem Cells; Oligodendroglia; Quetiapine Fumarate; Temozolomide; Tumor Burden

Several studies have reported the findings of fluorine-18-labeled fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) in benign lung disease with diffuse pulmonary injury; however, the characteristics and effectiveness of FDG-PET imaging for interstitial pneumonitis have not been substantiated. We report two cases of drug-induced pneumonitis in two patients treated for breast cancer who were diagnosed by FDG-PET examination. Both the cases showed diffuse interstitial infiltration in the bilateral lungs on computed tomography, but the degree of FDG accumulation was different. It is probable that the degree of FDG accumulation reflected the activity of the drug-induced pneumonitis. The present cases show very interesting FDG-PET imaging findings of diffuse lung disease.

Topics: Aged; Anxiety Disorders; Brain Neoplasms; Breast Neoplasms; Dibenzothiazepines; Female; Fluorodeoxyglucose F18; Humans; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Pneumonia; Positron-Emission Tomography; Quetiapine Fumarate; Sensitivity and Specificity; Tomography, X-Ray Computed; Whole Body Imaging