| 1. |
- Han, Shuangshuang, et al.
(författare)
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Application value of CyTOF 2 mass cytometer technology at single-cell level in human gastric cancer cells
- 2019
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Ingår i: Experimental Cell Research. - : Elsevier. - 0014-4827 .- 1090-2422. ; 384:1
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy and radiotherapy are main adjuvant therapies for the treatment of gastric cancer, the treatment effects are individual difference, but the specific mechanism is unknown. CyTOF 2 mass cytometer (CyTOF) enables the detecting up to 135 parameters on single cell, the emergence of which is an opportunity for proteomics research. We first tried to apply CyTOF technique to gastric cancer cells. We verified applicability of CyTOF in gastric cancer cells, and analyzed the responses of seventeen proteins to chemoradiotherapy in human gastric cancer AGS cells. To analyze the high dimensional CyTOF data, we used two statistical and visualization tools including viSNE and Citrus. Two specific clusters were found which had differences in protein expression profiles. CyTOF technology is proved feasibility and value at single cell level of gastric cancer.
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| 2. |
- Jiang, Xia, et al.
(författare)
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ITGB4 as a novel serum diagnosis biomarker and potential therapeutic target for colorectal cancer
- 2021
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 10:19, s. 6823-6834
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To develop new and effective biomarkers for the diagnosis of colorectal cancer (CRC). Experimental design The serum expression of ITGB4 (49 CRC and 367 HC) was detected by enzyme-linked immunosorbent assay (ELISA), and its diagnostic value was analyzed using the receiver operating characteristic (ROC) curve. The sensitivity and specificity of ITGB4 in CRC diagnosis were calculated through statistical analysis. The optimal clinical cutoff value was calculated using the Youden index, and diagnostic efficacy was analyzed in a larger serum sample (98 CRC and 1631 non-CRC). The expression of ITGB4 was measured by CyTOF (cell experimental technology) at the single-cell level, and characteristics were analyzed using viSNE and SPADE TREE. Results Serum ITGB4 and CEA levels were significantly higher in CRC patients than in HC and non-CRC patients. The use of serum ITGB4 levels for the diagnosis of CRC has a high sensitivity (79%) but not high specificity when the clinical cutoff value was 0.70 ng/mL. However, the optimal cutoff value was 1.6 ng/mL with 86.2% specificity and 52.0% sensitivity, and the diagnostic efficacy was greatly improved with high specificity (82.0%) and sensitivity (71.4%) when combined with CEA. ITGB4 expression characteristics were measured and related to the expression of EpCAM, Ck8/18, and perforin at the single-cell level. Single-cell analysis showed that cell clusters with low expression of CK8/18 and ITGB4 were more sensitive to 5FU and radiotherapy (RT). Conclusions ITGB4 is an effective diagnostic serum biomarker and a potential therapeutic target for CRC.
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| 3. |
- Liu, Na, et al.
(författare)
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The Critical Role of Dysregulated RhoB Signaling Pathway in Radioresistance of Colorectal Cancer
- 2019
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 104:5, s. 1153-1164
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo explore whether the Rho protein is involved in the radioresistance of colorectal cancer and investigate the underlying mechanisms.Methods and MaterialsRho GTPase expression was measured after radiation treatment in colon cancer cells. RhoB knockout cell lines were established using the CRISPR/Cas9 system. In vitro assays and zebrafish embryos were used for analyzing radiosensitivity and invasive ability. Mass cytometry was used to detect RhoB downstream signaling factors. RhoB and Forkhead box M1 (FOXM1) expression were detected by immunohistochemistry in rectal cancer patients who participated in a radiation therapy trial.ResultsRhoB expression was related to radiation resistance. Complete depletion of the RhoB protein increased radiosensitivity and impaired radiation-enhanced metastatic potential in vitro and in zebrafish models. Probing signaling using mass cytometry–based single-cell analysis showed that the Akt phosphorylation level was inhibited by RhoB depletion after radiation. FOXM1 was downregulated in RhoB knockout cells, and the inhibition of FOXM1 led to lower survival rates and attenuated migration and invasion abilities of the cells after radiation. In the patients who underwent radiation therapy, RhoB overexpression was related to high FOXM1, late Tumor, Node, Metastasis stage, high distant recurrence, and poor survival independent of other clinical factors.ConclusionsRhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathways.
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| 4. |
- Xie, Xuqin, et al.
(författare)
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APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy
- 2023
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Ingår i: Molecular Cancer Therapeutics. - : AMER ASSOC CANCER RESEARCH. - 1535-7163 .- 1538-8514. ; 22:8, s. 947-961
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Tidskriftsartikel (refereegranskat)abstract
- p53 mutation is common and highly related to radiotherapy resistance in rectal cancer. APR-246, asa small molecule, can restore the tumor-suppressor function to mutant p53. As there is currently no existing study on combining APR-246 with radiation in rectal cancer, our objective was to investigate whether APR-246 could enhance the sensitivity of colorectal cancer cells, regardless of their p53 status, to radiation treatment. The combination treatment had synergistic effects on HCT116p53-R248W/- (p53Mut) cells, followed by HCT116p53+/+ [wild-type p53 (p53WT)] cells, and exhibited an additive effect on HCT116p53-/- (p53Null) cells through inhibiting proliferation, enhancing reactive oxygen species, and apoptosis. The results were confirmed in zebrafish xenografts. Mechanistically, p53Mut and p53WT cells shared more activated pathways and differentially expressed genes following the combination treat-ment, compared with p53Null cells, although the combination treatment regulated individual pathways in the different cell lines. APR-246 mediated radiosensitization effects through p53-dependent and-independent ways. The results may provide evidence for a clinical trial of the combination in patients with rectal cancer.
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