Tissue levels of oxidative stress markers and antioxidants in colorectal cancer patients

The role of reactive oxygen species in the development of cancer has become well recognized in recent years; however, evidence for a link between oxidative stress and cancer risk has not been fully explored. One of the major cancers whose number of cases has increased significantly in recent years is colon and rectal cancer, which has the second highest mortality rate in Libya. Forty subjects were divided into three groups (20 tumors from colorectal cancer patients, adjacent surrounding tumor tissues, and 20 adjacent normal tissues). Evaluation of oxidative stress indices in the samples was performed by analyzing enzymatic and non-enzymatic parameters including the activity of glutathione peroxidase and catalase as antioxidant enzymes, reduced glutathione as an antioxidant, malondialdehyde MDA levels as an oxidative damage product, nitritc oxide content NO as an inflammatory marker, and total thiols as a measure of redox status. MDA and NO levels were significantly higher in tumor tissues than in adjacent healthy tissue. Also, the surrounding tumor tissue exhibited higher MDA and NO levels compared with control tissues. The oxidant and antioxidant levels in the tumor was significantly lower than those in the surrounding tumor tissue and control healthy tissue. The results suggest that oxidant and antioxidant parameters can be used as indicators of an imbalance in humans, and as this imbalance increases, the human body may be vulnerable to developing cancer.

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Loss of imprinting of IGF2 correlates with hypomethylation of the H19 differentially methylated region in the tumor tissue of colorectal cancer patients

Molecular Medicine Reports ◽

10.3892/mmr.2012.833 ◽

2012 ◽

Cited By ~ 5

Author(s):

Shukui Wang

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Tumor Tissue ◽

Differentially Methylated Region ◽

Loss Of Imprinting ◽

Colorectal Cancer Patients

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Novel CoupledCAR technology for treating colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2528 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2528-2528

Author(s):

Lei Xiao ◽

Song Li ◽

Chengfei Pu ◽

Zhiyuan Cao ◽

Xinyi Yang ◽

...

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

Complete Remission ◽

Cancer Patients ◽

Solid Tumors ◽

Tumor Tissue ◽

Lentiviral Vectors ◽

Safety And Efficacy ◽

Pet Ct ◽

Colorectal Cancer Patients

2528 Background: Chimeric antigen receptor (CAR) T cell therapy has made significant progress in the treatment of blood cancers such as leukemia, lymphoma, and myeloma. However, the therapy faces many challenges in treating solid tumors. These challenges include physical barriers, tumor microenvironment immunosuppression, tumor heterogeneity, target specificity, and limited expansion in vivo. Methods: We designed a CAR lentivirus vector that consisted of a humanized CD19-specific single-chain variable fragment (scFv), a 4-1BB costimulatory domain, and a CD3ζ signaling domain.The lentivirus was produced by transfecting HEK-293T cells with CAR lentiviral vectors and viral packaging plasmids. Patient’s CD3 T cells was cultured in X-VIVO medium containing 125U/mL 1interleukin-2 (IL-2), and transduced with CAR lentivirus at certain MOI 24h after stimulated by anti-CD3/CD28 magnetic beads. Transduction efficiency was evaluated at 7 to 9 days after CAR lentivirus transduction, and quality controls for fungi, bacteria, mycoplasma, chlamydia, and endotoxin were performed. After infusion, serial peripheral blood samples were collected, and the expansion and the cytokine release of CART cells were detected by FACS and QPCR,respectively. The evaluation of response level for patients were performed at month 1,month 3,and month 6 by PET/CT. Results: We engineered CoupledCAR T cells with lentiviral vectors encoding an anti-GCC (guanylate cyclase 2C) CAR molecule. To verify the safety and efficacy of CoupledCAR-T cells for treating solid tumors, we conducted several clinical trials for different solid tumors, including seven patients with colorectal cancer. These seven patients failed multiple rounds of chemotherapy and radiotherapy. In the clinical trial, the metastatic colorectal cancer patients were infused with autologous anti-GCC CoupledCAR-T cells range from 4.9×105/kg to 2.9×106/kg. We observed that CoupledCAR-T cells expanded significantly in the patients and infiltrated tumor tissue sites, demonstrating enhanced anti-tumor activities. PET/CT showed significant tumor shrinkage and SUV max declined, and the ongoing responses were monitored. Patient 3 achieved complete response and the best overall response rate (ORR, include complete remission, complete metabolic response, and partial response.) was 57.1% (4/7), complete remission (CR) rate was 14.3% (1/7). Conclusions: In conclusion, the clinical data demonstrated that CoupledCAR-T cells effectively expanded, infiltrated tumor tissue sites, and kill tumor cells in patients with colorectal cancer. We used immunotherapy to achieve complete remission in patients with advanced colorectal cancer for the first time. We are recruiting more colorectal cancer patients to further test the safety and efficacy of anti-GCC CoupledCAR T cells. Since our CoupledCAR technology is a platform technology, we are expanding it to treat other solid tumors using different target tumor markers.

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