Assessment of vitamin D and VDR gene expression in colorectal cancer patients

2015 ◽  
Vol 51 (3) ◽  
pp. 193-198
Author(s):  
Joanna Berska ◽  
Jolanta Bugajska ◽  
Diana Hodorowicz-Zaniewska ◽  
Krystyna Sztefko
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Serum Concentration ◽  
Cancer Patients ◽  
Colonic Mucosa ◽  
Tumor Tissue ◽  
Disease Stage ◽  
Control Group ◽  
Normal Colonic Mucosa ◽  
Colorectal Cancer Patients

Background: Vitamin D insufficiency may increase risk and/or progression of cancer. Vitamin D acts through a nuclear receptor (VDR) which binding to vitamin D response elements causes changes in many genes expression. The aim: to assess the serum concentration of 25-hydroxycholecalciferol (25(OH)D3) and tissue VDR expression in colorectal cancer patients in relation to disease stage, tumor localization and disease progression. Material & Methods: The study group consisted of 39 patients with colorectal cancer (mean age 65,5±6,8 yrs, 23/16 male/female) and a control group consisted of 25 patients (mean age 51,0±6,9 yrs; 8/17 male/female) without gastrointestinal disease and without neoplasm. Serum level of 25(OH)D3 was measured by HPLC/UV. RNA was isolated from homogenized normal colonic mucosa and tumor tissue then RT-PCR was performed. Results: The mean serum concentration of 25(OH)D3 was lower in the colorectal cancer patients as compared to the control group. The difference was significantly lower only for the patients with the early stages of the disease (p<0.02) and for the patients with tumor present in rectum (p<0.03). Higher VDR expression in tumor tissue than in normal colonic mucosa was observed. For the patients with the early stages of the disease (stage A, B1, B2) higher expression of VDR as compared to the patients with advanced stages (stage C1, C2, D) was noticed. Moreover, VDR expression was higher in tumor tissue obtained from disease-free patients as compared to the patients with disease progression noted one-year-follow-up (p<0.04). Conclusion: Antitumor effect of vitamin D depends on VDR expression in tumor tissue.

scholarly journals BSM1 Polymorphism Association in Vitamin D Receptor Genes with the Occurrence of Colorectal Cancer in Palembang, Indonesia

2020 ◽  
Vol 55 (6) ◽  
Author(s):  
M. Alsen Arlan ◽  
Sarup Singh ◽  
Efman E.U. Manawan ◽  
M. Hafidh Komar ◽  
Irsan Saleh
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Vitamin D ◽  
Cancer Patients ◽  
Vitamin D Receptor ◽  
Protective Factor ◽  
Control Group ◽  
Exact Test ◽  
Cancer Occurrence ◽  
Colorectal Cancer Patients

This paper analyzed the association between Bsm1 polymorphism in vitamin D receptor genes with colorectal cancer patients in Palembang, Indonesia. This case control study was conducted from June 2019 to December 2019. The genotype was analyzed using polymerase chain reaction-restriction fragment length polymorphism with the Bsm1 restriction enzyme. Findings showed the distribution of BB-Bb-bb genotype among colorectal cancer patients was 18.6%:26.7%:4.7%, whereas the distribution in a control group was 0%:43%:7%. The distribution of B and b alleles in colorectal cancer patients was 32%:18% compared to the control group’s distribution of 21.5%:28.5%. A statistical analysis of Fisher's exact test was conducted to examine the association of polymorphism with colorectal cancer occurrence. Findings demonstrated that there is a significant association was found between Bsm1 polymorphism of vitamin D receptor genes and colorectal cancer occurrences among patients in Palembang, Indonesia. Detailed analysis revealed that rs1544410 in the genotype BB might be a causal factor for colon cancer occurrence. Allele B on the other hand was reported to be the protective factor against colon cancer.

scholarly journals Interhospital referral of colorectal cancer patients: a Dutch population-based study

2021 ◽  
Author(s):  
A. K. Warps ◽  
◽  
M. P. M. de Neree tot Babberich ◽  
E. Dekker ◽  
M. W. J. M. Wouters ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Waiting Time ◽  
Secondary Care ◽  
Advanced Disease ◽  
Waiting Times ◽  
Tertiary Care ◽  
Disease Stage ◽  
Colorectal Cancer Patients ◽  
Tertiary Care Hospitals

Abstract Purpose Interhospital referral is a consequence of centralization of complex oncological care but might negatively impact waiting time, a quality indicator in the Netherlands. This study aims to evaluate characteristics and waiting times of patients with primary colorectal cancer who are referred between hospitals. Methods Data were extracted from the Dutch ColoRectal Audit (2015-2019). Waiting time between first tumor-positive biopsy until first treatment was compared between subgroups stratified for referral status, disease stage, and type of hospital. Results In total, 46,561 patients were included. Patients treated for colon or rectal cancer in secondary care hospitals were referred in 12.2% and 14.7%, respectively. In tertiary care hospitals, corresponding referral rates were 43.8% and 66.4%. Referred patients in tertiary care hospitals were younger, but had a more advanced disease stage, and underwent more often multivisceral resection and simultaneous metastasectomy than non-referred patients in secondary care hospitals (p<0.001). Referred patients were more often treated within national quality standards for waiting time compared to non-referred patients (p<0.001). For referred patients, longer waiting times prior to MDT were observed compared to non-referred patients within each hospital type, although most time was spent post-MDT. Conclusion A large proportion of colorectal cancer patients that are treated in tertiary care hospitals are referred from another hospital but mostly treated within standards for waiting time. These patients are younger but often have a more advanced disease. This suggests that these patients are willing to travel more but also reflects successful centralization of complex oncological patients in the Netherlands.

Novel CoupledCAR technology for treating colorectal cancer.

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.

Tumor-Infiltrating FOXP3+ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer

2009 ◽  
Vol 27 (2) ◽  
pp. 186-192 ◽  
Author(s):  
Paul Salama ◽  
Michael Phillips ◽  
Fabienne Grieu ◽  
Melinda Morris ◽  
Nik Zeps ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colonic Mucosa ◽  
Tumor Tissue ◽  
Early Stage ◽  
Prognostic Significance ◽  
High Density ◽  
Prognostic Indicators ◽  
Normal Colonic Mucosa ◽  
Solid Cancer ◽  
Histopathologic Features

Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.

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