Neo-Antigen-Reactive T Cells Immunotherapy for Colorectal Cancer: A More Personalized Cancer Therapy Approach.

Colorectal cancer (CRC) is the second most common malignancy in women and the third most frequent cancer in men. Evidence has revealed that the survival of patients with metastatic CRC is very low, between one and three years. Neoantigens are known proteins encoded by mutations in tumor cells. It is theorized that recognizing neoantigens by T cells leads to T cell activation and further antitumor responses. Neoantigen-reactive T cells (NRTs) are designed against the mentioned neoantigens expressed by tumor cells. NRTs selectively kill tumor cells without damage to non-cancerous cells. Identifying patient-specific and high immunogen neoantigens is important in NRT immunotherapy of patients with CRC. However, the main challenges are the side effects and preparation of NRTs, as well as the effectiveness of these cells in vivo. This review summarized the properties of neoantigens as well as the preparation and therapeutic outcomes of NRTs for the treatment of CRC.

Does the Microbiota Composition Influence the Efficacy of Colorectal Cancer Immunotherapy?

Colorectal cancer (CRC) is the second most common malignancy globally, and many people with CRC suffer the fate of death. Due to the importance of CRC and its negative impact on communities, treatment strategies to control it or increase patient survival are being studied. Traditional therapies, including surgery and chemotherapy, have treated CRC patients. However, with the advancement of science, we are witnessing the emergence of novel therapeutic approaches such as immunotherapy for CRC treatment, which have had relatively satisfactory clinical outcomes. Evidence shows that gastrointestinal (GI) microbiota, including various bacterial species, viruses, and fungi, can affect various biological events, regulate the immune system, and even treat diseases like human malignancies. CRC has recently shown that the gut microorganism pattern can alter both antitumor and pro-tumor responses, as well as cancer immunotherapy. Of course, this is also true of traditional therapies because it has been revealed that gut microbiota can also reduce the side effects of chemotherapy. Therefore, this review summarized the effects of gut microbiota on CRC immunotherapy.

[Luminescence Mechanism of Near-Infrared Quantum Dots].

Near-infrared quantum dots have unique optical properties, such as high fluorescence quantum yield, long fluorescent life, tunable fluorescence emission wavelength, half peak width and large stokes shift, resisting light bleaching etc. The advantage of "near infrared biological window" gives them great potential application value in biological fluorescent tags, solar cells, quantization calculation, photocatalysis, chemical analysis, food detection, vivo imaging and other fields. At present, the luminescence mechanism research of near-infrared quantum dots is still not comprehensive enough. In this paper, the luminescent principle of three different types of near-infrared quantum dots is summarized, including core/shell structure quantum dots (CdTe/CdSe, CdSe/CdTe/ZnSe, etc), ternary quantum dots (Cu-In-Se, CuInS2, etc) and doped quantum dots (Cu∶InP, etc). The luminescence mechanism of Type Ⅱ core/shell structure is most likely to attribute to the interband recombination luminescence, the ternary structure of quantum dots light emitting mechanism is considered to be due to the intrinsic structure defects, and the luminescence mechanism of doped quantum dots is deemed to result from the impurity defects. The existing problems of near-infrared luminescent principle of quantum dots are also discussed and their development tendency is explored t in this review. A systematic study of luminescence mechanism of near-infrared quantum dots will not only help to understand the luminescent properties of near infrared quantum dots, but also contribute to improve the synthesis methods of quantum dots with similarly high quality.

The effect of cell cycle and expression of cyclin B1 and cyclin C protein in hepatocellular carcinoma cell line HepG2 and SMMC-7721 after of silencing ß-catenin gene.

BACKGROUND/AIMS: Abnormalities in cell cycle regulation are reported to be strongly associated with tumorigenesis and progression of tumors. Wnt/ß-catenin signaling pathway and cell cycle play key roles during the genesis and development of hepatocellular carcinoma (HCC). Current studies indicated that expressions of cyclin A, E and D1 were affected after silencing of ß-catenin gene in HCC, but it is unclear if other cyclins are affected. METHODOLOGY: To determine the relation, small interference RNA (siRNA) against ß-catenin was transfected into HCC cell lines HepG2 and SMMC-7721, and cell cycle and cyclin B1 and cyclin C protein expression were detected. RESULTS: Cell cycle was arrested in G0/G1 at 72h after transfection and the cell cycle began to transfer from G0/G1 to G2/M through S and had a trend to revert at 96h. In addition, ß-catenin protein expression was decreased at both 72 and 96h, although the level was slightly higher at 96h than that at 72h. However, cyclin B1 expression decreased at 72h and increased at 96h, cyclin C expression increased at 72h and decreased at 96h. CONCLUSIONS: These findings suggest that silencing ß-catenin gene may induce the changes of cell cycle and cyclin B1 and cyclin C protein expression. Wnt/ß-catenin signaling pathway probably takes part in the genesis and development of HCC through regulating cell cycle and the expression of cyclin B1 and cyclin C.

beta-catenin siRNA regulation of apoptosis- and angiogenesis-related gene expression in hepatocellular carcinoma cells: potential uses for gene therapy.

The molecular mechanism responsible for hepatocellular carcinoma (HCC) development remains to be defined although a number of gene pathways have been shown to play an active role, such as Wnt/beta-catenin signaling. In this study, beta-catenin small interfering RNA (siRNA) was designed, synthesized, and transfected into HCC HepG2 cells. RT-PCR and western blot assays were performed to detect expression of altered genes and proteins, and the MTT assay was used to detect cell viability. Our data showed that beta-catenin mRNA and protein expression levels were effectively knocked down by beta-catenin siRNA and subsequently, tumor cell proliferation was significantly suppressed. Flow cytometry assay showed that tumor cells were arrested at the G0/G1 phase of the cell cycles. Molecularly, expression of Smad3, p-caspase-3, and Grp78 protein were upregulated after 72 h of beta-catenin siRNA transfection, whereas expression of TERT, caspase-3, XIAP, MMP-2, MMP-9, VEGF-A, VEGF-c, and bFGF protein were reduced. However, there was no change between the expression of STAT3 and the HSP27 protein following transfection. The results from the current study demonstrated the importance of the Wnt/beta-catenin signaling pathway in regulation of gene expression in HCC. Further studies are required to investigate the role of this pathway in HCC development and targeting of this pathway to control HCC.