Influence of sCD40L on gastric cancer cell lines

Li, Rui; Chen, Weichang; Pang, Xiaoming; Tian, Wenyan; Zhang, Xueguang

doi:10.1007/s11033-011-0702-9

Cited by 9 publications

(3 citation statements)

References 30 publications

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“…The expression of CD40 was elevated in gastric cancer tissues and increased as T stage increased in our study, in agreement with previous research that found that CD40 was markedly higher in cancer than in normal gastric mucosa, and that CD40 levels are helpful in early diagnosis of gastric cancer [2,7,20,21]. Our results contrast with a report that high expression of CD40 was associated with metastasis to the liver [6], as we found that CD40 expression was unrelated to cancer cell differentiation, lymph node metastasis, N stage, or M stage.…”

Section: Discussionsupporting

confidence: 93%

Markers CD40, VEGF, AKT, PI3K, and S100 Correlate with Tumor Stage in Gastric Cancer

Tian¹,

Chen²,

Li³

et al. 2013

Oncol Res Treat

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Background: To better understand gastric cancer occurrence and prognosis, we explored the expression of molecules in the CD40 pathway and their correlation with gastric cancer prognosis. Patients and Methods: We measured the expression of CD40, VEGF, AKT, PI3K, and S100 in gastric cancer tissues and adjacent normal tissues from 128 patients by immunohistochemistry. Results: The expression of CD40, VEGF, AKT, and PI3K were significantly higher in tumor tissue than in normal tissue, while S100 expression in dendritic cells (DC) was lower. Expression of CD40, VEGF, AKT, and PI3K significantly increased with T stage, while S100 expression decreased with T stage. Lymph node metastasis was associated with low or negative S100 expression. PI3K expression increased with clinical stage, while negative S100 expression was associated with higher clinical stages. Multivariate analysis did not indicate significant associations between any of these markers and recurrence or mortality. Conclusion: The correlation between T stage of gastric cancer and the higher expression of CD40, VEGF, AKT, and PI3K, along with lower S100 expression in DC, may provide insights into future targets for more effective immunotherapy for cancer.

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Section: Discussionsupporting

confidence: 93%

Markers CD40, VEGF, AKT, PI3K, and S100 Correlate with Tumor Stage in Gastric Cancer

Tian¹,

Chen²,

Li³

et al. 2013

Oncol Res Treat

Self Cite

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“…The reason why post-CRT sCD40L levels are significantly reduced in High-R is not known, but it is known that, in addition to the immunomodulatory effects, the CD40 signaling pathway also plays an important role in proliferation, differentiation and apoptosis of cancer cells. Many tumor cells also express CD40 (29)(30)(31)(32), and evidence suggests that ligation of CD40 might promote either cell proliferation or apoptosis, depending on the intensity of CD40L signaling (33,34). Although we did not investigate the expression of CD40 in cancer cells, it can be speculated that sCD40L may induce antitumor effects, either through binding to immune cells, stimulating an antitumor immunity, or through the direct binding to cancer cells, inducing their apoptotic cell death; in both situations, sCD40L levels are reduced by consumption.…”

Section: D Venous Invasionmentioning

confidence: 99%

Changes in the plasma levels of cytokines/chemokines for predicting the response to chemoradiation therapy in rectal cancer patients

et al. 2013

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In the present study, we aimed to characterize the predictive value of cytokines/chemokines in rectal cancer (RC) patients receiving chemoradiation therapy (CRT). Blood samples were obtained pre- and post-CRT from 35 patients with advanced RC, who received neoadjuvant CRT followed by surgery, and the correlation between plasma levels of cytokines/chemokines and the response to CRT was analyzed. The pre-CRT levels of soluble CD40-ligand (sCD40L) and the post-CRT levels of chemokine ligand-5 (CCL-5) were significantly associated with the depth of tumor invasion and with venous invasion. In addition, a significant decrease in sCD40L and CCL-5, as well as in platelet counts, was associated with a favorable response to CRT. A significant correlation between pre-CRT platelet counts and sCD40L was observed in patients with a favorable response. By contrast, higher post-CRT interleukin (IL)-6 was associated with a poor response. Platelets, immune system and cancer cells, cross-linked through various cytokines/chemokines, appear to play an important role in the response to CRT, and by understanding their roles, new approaches for the improvement of the therapy might be proposed.

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“…Preclinical studies have suggested that this approach can result in enhanced antitumor activity but human data has been lacking heretofore (11). Soluble CD40L (sCD40L) has been shown to mediate various antitumor activities in vitro and in vivo including direct growth inhibition and induction of apoptosis in different human tumor types (11)(12)(13). CD40L immunotherapy has also been shown to target the chemoresistant subpopulation of cancer cells (14) and has been suggested to sensitize chemoresistant tumors to cytotoxic drugs (15,16).…”

Section: Introductionmentioning

confidence: 99%

Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

et al. 2012

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The immunosuppressive environment of advanced tumors is a primary obstacle to the efficacy of immunostimulatory and vaccine approaches. Here, we report an approach to arm an oncolytic virus with CD40 ligand (CD40L) to stimulate beneficial immunologic responses in patients. A double-targeted chimeric adenovirus controlled by the hTERT promoter and expressing CD40L (CGTG-401) was constructed and nine patients with progressing advanced solid tumors refractory to standard therapies were treated intratumorally. No serious adverse events resulting in patient hospitalization occurred. Moderate or no increases in neutralizing antibodies were seen, suggesting effective Th1 immunologic effects. An assessment of the blood levels of virus indicated 17.5% of the samples (n ¼ 40) were positive at a low level early after treatment, but not thereafter. In contrast, high levels of virus, CD40L, and RANTES were documented locally at the tumor. Peripheral blood mononuclear cells were analyzed by IFN-g ELISPOT analysis and induction of both survivin-specific and adenovirus-specific T cells was seen. Antitumor T-cell responses were even more pronounced when assessed by intracellular cytokine staining after stimulation with tumor type-specific peptide pools. Of the evaluable patients, 83% displayed disease control at 3 months and in both cases in which treatment was continued the effect was sustained for at least 8 months. Injected and noninjected lesions responded identically. Together, these findings support further clinical evaluation of CGTG-401. Cancer Res; 72(7); 1621-31. Ó2012 AACR.

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Influence of sCD40L on gastric cancer cell lines

Cited by 9 publications

References 30 publications

Markers CD40, VEGF, AKT, PI3K, and S100 Correlate with Tumor Stage in Gastric Cancer

Markers CD40, VEGF, AKT, PI3K, and S100 Correlate with Tumor Stage in Gastric Cancer

Changes in the plasma levels of cytokines/chemokines for predicting the response to chemoradiation therapy in rectal cancer patients

Oncolytic Immunotherapy of Advanced Solid Tumors with a CD40L-Expressing Replicating Adenovirus: Assessment of Safety and Immunologic Responses in Patients

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