CONCLUSION: This review will be the first to summarize the expression of LGMN in common cancers, as well as its roles in tumorigenesis and metastasis. This review also discusses the current developments and future prospects of targeting LGMN through the development of DNA vaccines, azopeptides, small molecule inhibitors and LGMN activated prodrugs, highlighting the potential of LGMN as a target for cancer therapeutics.
MATERIALS AND METHODS: ARPE-19 cells were pre-treated with LUT, ZEA, or both for 24 h before 200 μM H2O2 challenge. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. DICER1 and Alu RNA were quantified by western blotting and real-time polymerase chain reaction, respectively.
RESULTS: H2O2 increased cell Alu RNA expression and decreased cell viability of ARPE-19, but had no significant impact on the DICER1 protein level. LUT, alone and in combination with ZEA pre-treatment, prior to H2O2 challenge significantly improved cell viability of ARPE-19 and reduced the level of Alu RNA compared to the negative control.
CONCLUSIONS: These results support the use of LUT alone, and in combination with ZEA, in AMD prevention and treatment. This study is also the first to report LUT modulating effects on Alu RNA.
METHODS: ARPE-19 cells were cultured in Dulbecco's Modified Eagle Medium-F-12 supplemented with 10% foetal bovine serum and 1% penicillin-streptomycin in a humidified 5% CO2 incubator maintained at 37°C. Cells were treated with 247 µmol/L lutein, 49 µmol/L zeaxanthin and 1% (v/v) of either coconut oil, corn oil, peanut oil, olive oil, sunflower oil, soybean oil, castor oil, or linseed oil for 48h. Lutein and zeaxanthin concentration in the cells were quantified by high performance liquid chromatography.
RESULTS: Among the oils tested, the highest lutein and zeaxanthin uptake was observed with coconut oil while the lowest was observed with linseed oil.
CONCLUSION: ARPE-19 uptake of lutein and zeaxanthin are found to be dependent on the type of oils.
MAIN BODY: In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME.
CONCLUSIONS: It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.
METHODS: The effects of LPS-induced NLRP3 activation in the presence or absence of MCC950, NLRP3-specific inhibitor, was tested on a panel of three pancreatic cancer cell lines (SW1990, PANC1 and Panc10.05). Western blotting, cell viability kits and ELISA kits were used to examine the effects of LPS-induced NLRP3 activation and inhibition by MCC950 on NLRP3 expression, cell viability, caspase-1 activity and cytokine IL-1β, respectively.
RESULTS: LPS-induced inflammation in the presence of ATP activates NLRP3 that subsequently increases pancreatic cancer cell proliferation by increasing caspase-1 activity leading to overall production of IL-1β. The inhibition of the NLRP3 inflammasome activation via the specific NLRP3 antagonist MCC950 was able to reduce the cell viability of pancreatic cancer cells. However, the efficacy of MCC950 varies between cell types which is most probably due to the difference in ASC expressions which have a different role in inflammasome activation.
CONCLUSION: There is a dynamic interaction between inflammasome that regulates inflammasome-mediated inflammation in pancreatic adenocarcinoma cells.