Tissue expression and sero-reactivity of tumor-specific antigens in colorectal cancer

Gerhardt, Axel; Usener, Dirk; Keese, Michael; Sturm, J.; Schadendorf, Dirk; Eichmüller, Stefan B.

doi:10.1016/j.canlet.2003.11.021

Cited by 22 publications

(9 citation statements)

References 32 publications

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“…The role of CCDC68 in cancer is not known. In colon cancer, CCDC68 is expressed on the cancer cell surface in about 15% of patients (21). In our data this gene is downregulated in 89% of primary tumors (compared with normal tissue) and its expression is highly correlated with the associated gene copy number (r ϭ 0.51; P ϭ 3.6e-5).…”

Section: Candidate Cancer Pathway Genes Correlated With Broad and Focalsupporting

confidence: 50%

Association of survival and disease progression with chromosomal instability: A genomic exploration of colorectal cancer

Sheffer

Bacolod

Zuk

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

332

292

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During disease progression the cells that comprise solid malignancies undergo significant changes in gene copy number and chromosome structure. Colorectal cancer provides an excellent model to study this process. To indentify and characterize chromosomal abnormalities in colorectal cancer, we performed a statistical analysis of 299 expression and 130 SNP arrays profiled at different stages of the disease, including normal tissue, adenoma, stages 1-4 adenocarcinoma, and metastasis. We identified broad (> 1/2 chromosomal arm) and focal (< 1/2 chromosomal arm) events. Broad amplifications were noted on chromosomes 7, 8q, 13q, 20, and X and broad deletions on chromosomes 4, 8p, 14q, 15q, 17p, 18, 20p, and 22q. Focal events (gains or losses) were identified in regions containing known cancer pathway genes, such as VEGFA, MYC, MET, FGF6, FGF23, LYN, MMP9, MYBL2, AURKA, UBE2C, and PTEN. Other focal events encompassed potential new candidate tumor suppressors (losses) and oncogenes (gains), including CCDC68, CSMD1, POLR1D, and PMEPA1. From the expression data, we identified genes whose expression levels reflected their copy number changes and used this relationship to impute copy number changes to samples without accompanying SNP data. This analysis provided the statistical power to show that deletions of 8p, 4p, and 15q are associated with survival and disease progression, and that samples with simultaneous deletions in 18q, 8p, 4p, and 15q have a particularly poor prognosis. Annotation analysis reveals that the oxidative phosphorylation pathway shows a strong tendency for decreased expression in the samples characterized by poor prognosis.colon cancer ͉ DNA copy number ͉ gene expression ͉ SNP arrays

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Section: Candidate Cancer Pathway Genes Correlated With Broad and Focalsupporting

confidence: 50%

Association of survival and disease progression with chromosomal instability: A genomic exploration of colorectal cancer

Sheffer

Bacolod

Zuk

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

332

292

View full text Add to dashboard Cite

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“…Previous studies of CCDC68 have been mainly descriptive. Originally named se57-1 , CCDC68 has been identified as a putative tumor antigen in 21% of cutaneous T-cell lymphoma (21), 17% of renal cell (22) and 15% of colorectal carcinoma patients (23). Simultaneously and consistent with our PDAC findings, the same studies documented dramatic losses of CCDC68 expression in the majority of patients.…”

Section: Discussionmentioning

confidence: 99%

Coiled-coil domain containing 68 (CCDC68) demonstrates a tumor-suppressive role in pancreatic ductal adenocarcinoma

et al. 2014

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Using integrative genomics and functional screening we identified coiled-coil domain containing 68 (CCDC68) as a novel putative tumor suppressor (TSG) in pancreatic ductal adenocarcinoma (PDAC). CCDC68 allelic losses were documented in 48% of primary PDAC patient tumors, 50% of PDAC cell lines, and 30% of primary patient derived xenografts. We also discovered a SNP variant (SNP rs1344011) that leads to exon skipping and generation of an unstable protein isoform CCDC68Δ69–114 in 31% of PDAC patients. Overexpression of full length CCDC68 (CCDC68wt) in PANC-1 and Hs.766T PDAC cell lines lacking CDCC68 expression decreased proliferation and tumorigenicity in scid mice. In contrast, downregulation of endogenous CCDC68 in MIAPaca-2 cells increased tumor growth rate. These effects were not observed with the deletion-containing isoform, CCDC68Δ69–114. In conclusion, our results suggest that CCDC68 is a novel candidate TSG in PDAC.

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“…Furthermore, targeting the tumor specific antigens by treating the antibody specific to the DC-restricted antigen may elevate exposure of the tumor specific antigen. This may promote recognition of tumor specific antigens resulting in a limitation in tumor capacity (34,35). The present study demonstrated that the targeting of the melanoma antigen to DC cells via anti-PD-1 expressed by recombinant adenovirus expressing (rAd)-PD-1 markedly promoted the ability of rAd to induce responses from melanoma antigen-specific cytotoxic T lymphocytes.…”

Section: Introductionmentioning

confidence: 69%

Recombinant adenovirus expressing a dendritic cell‑targeted melanoma surface antigen for tumor‑specific immunotherapy in melanoma mice model

Guo

Wang

et al. 2018

Exp Ther Med

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Abstract. Viral vectors represent a potential strategy for the treatment of human malignant tumors. Currently, recombinant adenovirus vectors are commonly used as gene therapy vehicles, as it possesses a proven safety profile in normal human cells. The recombinant adenovirus system has an ability to highly express exogenous genes and increase the stability of the carrier, which is only transiently expressed in the host cell genome, without integrating. Malignant melanoma cells are produced by the skin, and melanocyte tumors that exhibit higher malignant degrees lead to earlier transfer and higher mortality. In the present study, a recombinant adenovirus (rAd) was generated to express Anti-programmed death-1 (rAd-Anti-PD-1) and used to investigate the efficacy in melanoma cells and tumors. The results demonstrated that B16-F10 cell growth was significantly inhibited and the apoptosis incidence rate was markedly promoted following rAd-PD-1 treatment. The present study demonstrated that the production of α and β interferon was increased, which led to the induction of dendritic cell (DCs) maturation in rAd-anti-PD-1-treated mice. The present study indicated that rAd-anti-PD-1 exhibited the ability to generate more cluster of differentiation (CD)4 + CD8 + T cells and induce a PD-1-specific cytotoxic T lymphocyte through DC-targeted surface antigens in mice. This resulted in a further enhanced recognition of melanoma cells due to DCs being targeted by the rAd-anti-PD-1-encoded PD-1. Notably, mice treated with the rAd-anti-PD-1-targeted PD-1 demonstrated an improved protection compared with tumor-bearing mice from the challenge group treated with a recombinant gutless adenovirus and Anti-PD-1. In conclusion, the present study demonstrated that targeting the melanoma surface antigens via the rAd-anti-PD-1-infected tumor cells enhanced the ability of recombinant adenovirus to induce a potent tumor-inhibitory effect and antigen-specific immune response.

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Tissue expression and sero-reactivity of tumor-specific antigens in colorectal cancer

Cited by 22 publications

References 32 publications

Association of survival and disease progression with chromosomal instability: A genomic exploration of colorectal cancer

Association of survival and disease progression with chromosomal instability: A genomic exploration of colorectal cancer

Coiled-coil domain containing 68 (CCDC68) demonstrates a tumor-suppressive role in pancreatic ductal adenocarcinoma

Recombinant adenovirus expressing a dendritic cell‑targeted melanoma surface antigen for tumor‑specific immunotherapy in melanoma mice model

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