Accumulation of nanoparticles in solid tumors depends on their extravasation, but their efficacy is often compromised by intrinsic physiological heterogeneity in tumors. The conventional solutions to circumvent this problem are size control of nanoparticles or increasing the vascular permeability. The aim of this study is to investigate the combination effect of size variation of stimuli-responsive nanoparticles and improved vascular permeability triggered by near-infrared (NIR) light irradiation. Doxorubicin (DOX), a clinically proven drug for bladder cancer, was encapsulated in the nanocomposites with high loading content up to 45%. We show that NIR light-responsive size-switchable nanocarriers could considerably enhance the tumor-targeting of DOX in bladder tumor-bearing mice. Moreover, a combination of NIR-induced hyperthermia and DOX-mediated chemotherapy resulted in remarkable inhibition of tumor growth in mice. Histological results suggest that the change in morphology of tumor microvasculature may account for enhanced extravasation and accumulation of the nanodrugs upon NIR irradiation. Together, these data suggest that external stimuli-responsive drug delivery system offers a safe and effective means of targeted chemo/photothermal therapy.
The WW domain-containing oxidoreductase (WWOX) gene is a tumor suppressor gene, the abnormal expression of which will lead to osteosarcoma tumorigenesis. Polymorphisms of the WWOX gene are associated with the risk of several malignancies. We hypothesized that genetic variations in the WWOX gene were related to osteosarcoma risk and outcome. In this case-control study, we recruited 276 young osteosarcoma patients and 286 controls from the East Chinese population and genotyped seven tag single-nucleotide polymorphisms (SNPs) of the WWOX gene (rs10220974C>T, rs12918952G>A, rs3764340C>G, rs1074963C>G, rs383362G>T, rs1424110A>G, and rs12828A>G). We discovered that two SNPs (rs3764340C>G and rs383362G>T) were associated with osteosarcoma risk. The CG genotype and dominant model of rs3764340 indicated elevated risk of osteosarcoma, and similar results were found for rs383362. Furthermore, rs3754340C>G was also related to grade and metastasis risk of osteosarcoma. Taken together, our results provide the first evidence that WWOX gene polymorphisms have the potential to be predictive factors for assessing risk and outcome of osteosarcoma.
To validate its efficacy in the context of the human immune system, a novel therapeutic vaccine of hGM-CSF/hTNFα surface-modified PC-3 cells against human prostate cancer was evaluated in the human peripheral blood lymphocytes-severe combined immunodeficiency (huPBL-SCID) chimeric mouse model. The hGM-CSF or/and hTNFα modified vaccines inhibited prostate cancer growth effectively so as to prolong the mouse survival significantly. The splenocytes from the hGM-CSF/hTNFα vaccine-inoculated mice showed the strongest tumor-specific cytotoxicity against PC-3 cells and the highest production of IFNɤ. These features indicated that type 1 protective immune response was induced efficiently against human prostate cancer and further enhanced through synergetic adjuvant effects of hGM-CSF and hTNFα.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0175-8) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.