Taken together, these results suggest that quetiapine is a potential anti-inflammatory drug, and may be used as an adjuvant for the treatment of rheumatoid arthritis.
Androgen deprivation therapy (ADT) is one of the typical treatments used for patients with prostate cancer (PCa). ADT, however, may fail when PCa develops castration-resistance. Fatty acid synthase (FASN), a critical enzyme involved in fatty acid synthesis, is found to be upregulated in PCa. Since enzalutamide and ADT are frequently used for the treatment of PCa, this study aimed to unravel the underlying mechanism of combination of orlistat, a FASN inhibitor, and enzalutamide using PC3 cell line; and orlistat and castration in PC3 tumor-bearing animal model. Cytotoxicity was determined by AlamarBlue assay. Drug effects on the cell cycle and protein expressions were assayed by the flow cytometry and Western blot. Electromobility shift assay was used to evaluate the NF-κB activity. The tumor growth delay, expressions of the signaling–related proteins, and histopathology post treatments of orlistat and castration were evaluated in PC3 tumor-bearing mouse model. The results showed that orlistat arrested the PC3 cells at the G1 phase of the cell cycle and enhanced the cytotoxic effects of enzalutamide synergistically. Pretreatment with orlistat combined with castration inhibited the tumor growth significantly compared with those of castration and orlistat treatments alone in PC3 tumor-bearing mice. Combination treatment reduced both fatty acid synthase and NF-κB activities and their downstream effector proteins. The present study demonstrated the synergistic effects of orlistat combined with enzalutamide in vitro and castration in vivo on human prostate cancer.
Glioblastoma, the most common and aggressive brain tumor with low survival rate, is difficult to be cured by neurosurgery or radiotherapy. Mounting evidence has reported the anti-inflammatory and anticancer effects of curcumin on several types of cancer in preclinical studies and clinical trials. To our knowledge, there is no platform or system that could be used to effectively and real-timely evaluate the therapeutic efficacy of curcumin for glioblastoma multiforme (GBM). In this study, we constructed a lentivirus vector with triple-reporter genes (Fluc/GFP/tk) and transduced into rat F98 glioblastoma cells to establish an orthotopic F98/FGT glioma-bearing rat model. In the model, the therapeutic efficacies for curcumin alone, radiation alone, and their combination were evaluated via noninvasive bioluminescent imaging and overall survival measurements. At the cell level, curcumin is capable of causing a G2/M cell cycle arrest and sensitizing the F98 cells to radiation. In animal model, curcumin synergistically enhances the effects of radiotherapy on suppressing the growth of both transplanted glioma cells and in situ brain tumors, and extending the overall survival periods longer than those of curcumin alone and radiation alone treatments. In conclusion, we have demonstrated that curcumin may serve as a novel radiosensitizer to combine with radiotherapy using the triple-reporter F98/FGT animal model for effective and simultaneous evaluation of therapeutic efficacy.
Background/Aim: In precision therapy, liposomal encapsulated chemotherapeutic drugs have been developed to treat cancers by achieving higher drug accumulation in the tumor compared to normal tissues/organs. Materials and Methods: We developed a novel chemoradiotherapeutic approach via nanoliposomes conjugated with vinorelbine (VNB) and 111 In (111 In-VNB-liposome) and examined their pharmacokinetics, biodistribution, maximum tolerance dose, and toxicity in a NOD/SCID mouse model. Results: Pharmacokinetic results showed that the area under the curve (AUC) of PEGylated liposomes was about 17-fold higher than that of the free radioisotope. Tumor growth inhibition by 111 In-VNB-liposome was significantly higher than that of the control (p<0.05). Conclusion: The tumors in NOD/SCID mice bearing HT-29/tk-luc xenografts were significantly suppressed by 111 In-VNB-liposomes. The study proposed repeated treatments with a novel liposome-mediated radiochemotherapy and validation of therapeutic efficacy via imaging. Colorectal cancer is a common malignant tumor in industrialized countries (1-3). From an epidemiological viewpoint, family inheritance, ageing and diabetes may all contribute to a higher risk of colorectal cancer (4-6). Clinically, colorectal cancer has a high mortality rate due to the fact that it remains undetected until later stages of the disease (7). The average five-year overall survival rate for all stages is about 65% based on surgery, adjuvant chemotherapy and radiotherapy (8). Vinorelbine (5'-noranhydrovinblastine, VNB) is a drug widely used in cancer therapy (9, 10). It acts through microtubule disruption, thereby arresting cell division in mitosis. Also, it is less toxicity than the naturally occurring 61 This article is freely accessible online.
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