Tumor-infiltrating CD4+ T cells in patients with gastric cancer.

BACKGROUND: T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4+ T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients. MATERIALS AND METHODS: Patients with GC diagnosed on the basis of pre-operative staging and laparotomy findings were approached for enrollment between 2014 and 2015 at the Affiliated Cancer Hospital of Zhengzhou University, China. Phenotypic analysis based on isolation of tumor-infiltrating lymphocytes and intracellular IFN-γ staining assay is conducted. Statistical analysis is performed to show significance. RESULTS: The results showed that the percentage of CD4+ T-cells among CD3+ cells in tumors was significantly higher than that in the matched paraneoplastic tissue. CD4+ CD25high CD127low regulatory T-cells (Tregs), PD-1+, Tim-3+, and PD-1+ Tim-3+ cells were up-regulated on tumor infiltrating T-cells from patients with GC compared to their expressions on corresponding peripheral blood and peritumoral T-cells. Blockades of PD-1+ and Tim-3+ were effective in restoring tumor infiltrating T-cells' production of interferon-gamma (IFN-γ). Combined PD-1+ and Tim-3+ inhibition had a synergistic effect on IFN-γ secretion by CD4+ T-cells. CONCLUSION: The results suggested that the composition, inhibitors, and location of the immune infiltrate should be considered when evaluating antitumor immunotherapy. A new insight into the mechanisms underlying T cell dysfunction is provided.

TiO2-Ti3C2 Nanocomposites Utilize Their Photothermal Activity for Targeted Treatment of Colorectal Cancer.

Purpose: The search for effective and low-risk treatment methods for colorectal cancer (CRC) is a pressing concern, given the inherent risks and adverse reactions associated with traditional therapies. Photothermal therapy (PTT) has emerged as a promising approach for cancer treatment, offering advantages such as non-radiation, non-invasiveness, and targeted treatment. Consequently, the development of nanoparticles with high stability, biocompatibility, and photothermal effects has become a significant research focus within the field of PTT. Methods: In this study, TiO2-Ti3C2 nanocomposites were synthesized and characterized, and their photothermal conversion efficiency in the near-infrared region II (NIR-II) was determined. Then studied the in vivo and in vitro photothermal activity and anti-tumor effect of TiO2-Ti3C2 in human colorectal cancer cell lines and nude mice subcutaneous tumor model. Results: The results showed that TiO2-Ti3C2 nanocomposites have strong absorption ability in the NIR-II, and have high photothermal conversion efficiency under 1064 nm (0.5 W/cm2, 6 min) laser stimulation. In addition, in vitro experiments showed that TiO2-Ti3C2 nanocomposites significantly inhibited the invasion, migration, and proliferation of colorectal cancer cells, and induced cell apoptosis; in vivo, experiments showed that TiO2-Ti3C2 nanocomposites-mediated PTT had good biocompatibility and efficient targeted inhibition of tumor growth. Conclusion: In conclusion, TiO2-Ti3C2 nanocomposites can be used as NIR-II absorption materials in PTT to suppress the invasion, migration, and proliferation of colorectal cancer cells, induce colorectal cancer cell apoptosis, and thus inhibit the development of CRC. Therefore, TiO2-Ti3C2 nanocomposites can be used as potential anti-tumor drugs for photothermal ablation of colorectal cancer cells.

RASSF1A methylation as a biomarker for detection of colorectal cancer and hepatocellular carcinoma.

BACKGROUND: Studies have validated the potential of methylated cell-free DNA as a biomarker in various tumors, and methylated DNA in plasma may be a potential biomarker for cancer. AIM: To evaluate the diagnostic value of RASSF1A methylation in plasma for colorectal cancer (CRC) and hepatocellular carcinoma (HCC). METHODS: A total of 92 CRC patients, 67 colorectal polyp (CRP) patients, 63 HCC patients, and 66 liver cirrhosis (LC) patients were enrolled. The plasma DNA was subjected to DNA extraction, double-strand DNA concentration determination, bisulfite conversion, purification, single-strand DNA concentration determination, and digital polymerase chain reaction (PCR) detection. The methylation rate was calculated. The diagnostic value was evaluated by the area under the curve (AUC). RESULTS: The age and sex in the CRC and CRP groups and the HCC and LC groups were also matched. The DNA methylation rate of RASSF1A in plasma in the CRC group was 2.87 ± 1.80, and that in the CRP group was 1.50 ± 0.64. DNA methylation of RASSF1A in plasma showed a significant difference between the CRC and CRP groups. The AUC of RASSF1A methylation for discriminating the CRC and CRP groups was 0.82 (0.76-0.88). The AUCs of T1, T2, T3 and T4 CRC and CRP were 0.83 (0.72-0.95), 0.87 (0.78-0.95), 0.86 (0.77-0.95), and 0.75 (0.64-0.85), respectively. The DNA methylation rate of RASSF1A in plasma in the HCC group was 4.45 ± 2.93, and that in the LC group was 2.46 ± 2.07. DNA methylation of RASSF1A in plasma for the HCC and LC groups showed a significant difference. The AUC of RASSF1A methylation for discriminating the HCC and LC groups was 0.70 (0.60-0.79). The AUCs of T1, T2, T3 and T4 HCC and LC were 0.80 (0.61, 1.00), 0.74 (0.59-0.88), 0.60 (0.42-0.79), and 0.68 (0.53-0.82), respectively. CONCLUSION: RASSF1A methylation in plasma detected by digital PCR may be a potential biomarker for CRC and HCC.

Multiple cytokine profiling in serum for early detection of gastric cancer.

AIM: To investigate the value of multiparameter joint analysis in the early diagnosis of gastric cancer (GC) in clinical practice. METHODS: Concentrations of CEA, CA724 and three kinds of cytokines (TNF-α, IL-6 and IL-8) in 176 GC patients, 117 atypical hyperplasia patients, and 204 healthy control individuals were used for building the diagnostic model, then 58 GC patients, 41 atypical hyperplasia patients, and 66 healthy control individuals were enrolled independently. The joints of the indicators were analyzed by binary logistic regression analysis method. RESULTS: For discriminating the healthy control group and the GC group, IL-6 had the best diagnostic value, and the area under curve (AUC) of joint analysis was 0.95 (0.93-0.97). For the early stage and advanced stage GC, the AUC were 0.95 (0.92-0.98) and 0.95 (0.92-0.97). For discriminating the atypical hyperplasia group and GC group, CA724 had the best diagnostic value, and the AUC of joint analysis was 0.97 (0.95-0.99). For the early stage and advanced stage GC groups, the AUC were 0.98 (0.96-0.99) and 0.96 (0.94-0.98). After evaluation, for discriminating the GC, early stage GC and advanced cancer group from the healthy control group, the diagnostic sensitivity was 89.66%, 84.21% and 92.31%, respectively, and the specificity was 92.42%, 90.91% and 90.91%. For discriminating the GC, early stage GC and advanced cancer groups from the atypical hyperplasia group, the diagnostic sensitivity was 87.93%, 78.95% and 92.31%, respectively, and the specificity was 87.80%, 85.37% and 90.24%. CONCLUSION: We have built a diagnostic model including CEA, CA724, IL-6, IL-8, and TNF-α. It may provide potential assistance as a screening method for the early detection of GC.

miR-542-3p inhibits colorectal cancer cell proliferation, migration and invasion by targeting OTUB1.

Although miR-542-3p has been found to be aberrantly downregulated in variety of human tumors, little is known about its role in colorectal cancer (CRC). This study was designed to assess the prognostic value of miR-542-3p in CRC by examining the expression profile of miR-542-3p in patients with CRC and investigate the possible molecular mechanism underlying the function of miR-542-3p. Our results showed that low levels of miR-542-3p were significantly associated with advanced tumor stage and lymph node metastasis and miR-542-3p can serve as an independent prognostic marker for CRC. Furthermore, ectopic induced expression of miR-542-3p significantly suppressed cell proliferation, induced apoptosis, inhibited migration and invasion in vitro and in vivo. Mechanistically, we identified OTUB1 as a direct and functional target for miR-542-3p, at least partly responsible for the anti-tumor effect of miR-542-3p in CRC. Our study demonstrates the importance of miR-524-3p/OTUB1 signaling in CRC development and suggests that targeting this signaling may highlight a new therapeutic approach for treatment of CRC.