P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

Terashima, Toshio; Mizukoshi, Eishiro; Arai, Kuniaki; Yamashita, Tatsuya; Yoshida, Minoru; Ota, Hajime; Onishi, Ichiro; Kayahara, Masato; Ohtsubo, Koushiro; Kagaya, Takashi; Honda, Masao; Kaneko, Shuichi

doi:10.1007/s00262-014-1529-8

Cited by 16 publications

(12 citation statements)

References 40 publications

(22 reference statements)

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“…18,19 Thus, p53 protects against tumor development via the Akt, NF-kb, and hTERT pathways. [20][21][22] In addition, a few studies have reported that p38 is regulated by p53 to induce cancer cell apoptosis, 23,24 and our results have shown that the expression of p38 is not affected by amarogentin in liver cancer cells. In our study, amarogentin also suppressed the expression of Akt, NF-kb, and hTERT.…”

Section: Discussionsupporting

confidence: 61%

Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice

Huang

Li²,

Zhang

et al. 2016

Technol Cancer Res Treat

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Background and Objective: Amarogentin has been reported to have a preventive effect on liver cancer via inducing cancer cell apoptosis. We attempted to elucidate the roles of p53-associated apoptosis pathways in the chemopreventive mechanism of amarogentin. The findings of this study will facilitate the development of a novel supplementary strategy for the treatment of liver cancer. Materials and Methods: The purity of amarogentin was assessed by high-performance liquid chromatography. The inhibitory ratios of the liver cell lines were determined using a Cell Counting Kit-8 following treatment with a gradient concentration of amarogentin. Cell apoptosis was detected by flow cytometry using annexin V-fluorescein isothiocyanate/propidium iodide kits. The gene and protein expression of p53-associated molecules, such as Akt, human telomerase reverse transcriptase, RelA, and p38, was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining in liver cancer cells and mouse tumor tissues after treatment with amarogentin. Results: The inhibitory effect of amarogentin on cell proliferation was more obvious in liver cancer cells, and amarogentin was more likely to induce the apoptosis of liver cancer cells than that of normal liver cells. The gene and protein expression levels of Akt, RelA, and human telomerase reverse transcriptase were markedly higher in the control group than in the preventive group and treatment groups. Only the expression of human telomerase reverse transcriptase was downregulated, accompanied by the upregulation of p53. Conclusion: The results of our study suggest that amarogentin promotes apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase and prevents the malignant transformation of these cells.

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Section: Discussionsupporting

confidence: 61%

Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice

Huang

Li²,

Zhang

et al. 2016

Technol Cancer Res Treat

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“…Multiple studies demonstrate that the highly immunosuppressive tumor microenvironment plays an important role in the development and progression of PC 5‐8 . T‐cell dysfunction and depletion caused by failure of the immune system are considered responsible for generating an immunosuppressive tumor microenvironment 9,10 . However, the detailed mechanics of the interactions between tumors and T lymphocytes are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Pancreatic cancer‐derived exosomes induce apoptosis of T lymphocytes through the p38 MAPK‐mediated endoplasmic reticulum stress

et al. 2020

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Pancreatic cancer is the fourth most lethal malignancy and is characterized by poor immunogenicity. Pancreatic cancer cells have various strategies to suppress host immune response, evade immune defenses, and facilitate tumor growth and development. As a mode of long‐range intercellular communication, cancer‐derived exosomes contribute to impairment of the immune system. However, the mechanisms that induce changes in the activities of signal transduction pathways in immune cells, which are influenced by tumor‐derived exosomes, are poorly understood. We (1) treated peripheral T lymphocytes with pancreatic cancer‐derived exosomes, tagged CD63 with tdTomato, to trace exosome transfer from pancreatic cancer cells to T lymphocytes; (2) carried out a cytotoxicity assay of exosome‐treated T lymphocytes using the Real Time Cellular Analysis system; (3) performed RNA sequencing and gene set enrichment analysis to explore the pivotal signaling pathway that mediates apoptosis in exosome‐treated T lymphocytes; and (4) demonstrated the role of p38 mitogen‐activated protein kinase (MAPK) and endoplasmic reticulum (ER) stress in exosome‐induced T‐lymphocyte apoptosis. In conclusion, these results indicate that pancreatic cancer cells secrete exosomes, which are taken up by T lymphocytes to activate p38 MAPK, and then induce ER stress‐mediated apoptosis, ultimately causing immunosuppression.

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“…The observed frequency of TAA-specific IFNγ-producing T cells in the peripheral blood was 10-219 cells/3 × 10 5 PBMCs. Previous findings from HCC and pancreatic adenocarcinoma demonstrated 10-60.5 and 10-46 cells/3 × 10 5 PBMCs, 42,44 respectively, suggesting that cholangiocarcinoma has high immunogenicity.…”

Section: Ta B L E 4 Epitopes That Elicited Patient-specific Immune Rementioning

confidence: 88%

Immune responses against tumour‐associated antigen‐derived cytotoxic T lymphocyte epitopes in cholangiocarcinoma patients

Kida

Mizukoshi

Tamai

et al. 2018

Liver International

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P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

Cited by 16 publications

References 40 publications

Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice

Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice

Pancreatic cancer‐derived exosomes induce apoptosis of T lymphocytes through the p38 MAPK‐mediated endoplasmic reticulum stress

Immune responses against tumour‐associated antigen‐derived cytotoxic T lymphocyte epitopes in cholangiocarcinoma patients

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