Cimetidine and immunoreactivity

Katoh, Junya; Tsuchiya, K; Sato, Wataru; Nakajima, Masahiro; Iida, Yoshinao

doi:10.1016/s0140-6736(05)65021-0

Cited by 14 publications

(8 citation statements)

References 4 publications

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“…They demonstrated that cimetidine could block the expression of E-selectin and thus inhibited the adhesion of tumor cells to the HUVECs and that the cimetidine administration in nude mouse model also inhibited the transsplenic liver metastasis [9]. Other possible effects of cimetidine include (1) inhibition of the activity of suppressor T lymphocytes bearing a histamine type 2 receptor in cancer patients [11,13]; (2) cimetidine, acting as an antioxidant, inhibits tumor growth [14]; (3) prevention of postoperative alterations of lymphocyte subpopulations [15]; and (4) maintenance of natural killer cell activity [16].…”

Section: Discussionmentioning

confidence: 99%

Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma

Tozawa

Okamoto

Kawai

et al. 2005

Kidney International

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Section: Discussionmentioning

confidence: 99%

Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma

Tozawa

Okamoto

Kawai

et al. 2005

Kidney International

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“…However, the exact mechanism by which cimetidine may exert an anticancer effect remains uncertain. cimetidine is thought to exert its effect by blocking high peritumoral concentrations of histamine and increasing systemic immunoreactivity via H 2 receptor antagonism of circulating T suppressor cells or maintenance of natural killer cell activity (19)(20)(21). However, Rajendra et al (22) have demonstrated that cimetidine has a direct antiproliferative effect in the absence of histamine type 2 receptors and the induction of apoptosis.…”

Section: Cimetidine Inhibits the Growth Of Transplantable Tumorsmentioning

confidence: 99%

Cimetidine inhibits the adhesion of gastric cancer cells expressing high levels of sialyl Lewis x in human vascular endothelial cells by blocking E-selectin expression

2011

Int J Mol Med

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Abstract. cimetidine has been shown to have anti-metastatic activity and improves the survival of patients with colorectal cancer. One hypothesis is its modulation of the expression of the cell adhesion molecule by target organ endothelial cells. Because of the inconclusive results in clinical trials of gastric cancer, we investigated the effects of cimetidine on the adhesion of gastric cancer cells to activated endothelial cells and on the expression of some cell adhesion molecules. Human endothelial cells were pre-incubated with cimetidine for 6 h, incubated with the cytokine tumor necrosis factor for 4 h, and the endothelial surface expression of E-selectin was evaluated by flow cytometry, immunostaining and ELISA. Further, we investigated E-selectin mRNA expression by RT-PcR. Three gastric cancer cell lines (SGC-7901, MGC-803, BGC-823) and a normal gastric epithelial cell line, GES-1, were studied for the surface expression of sialyl Lewis x by flow cytometry and immunostaining. Adherence of CFSE-labeled gastric cancer cells and GES-1 cells to endothelial cell monolayers was determined. Cimetidine significantly reduced E-selectin expression of activated endothelial cells, but did not influence E-selectin expression at the mRNA level. Three gastric cancer cell lines expressed high levels of sialyl Lewis x, whereas GES-1 did not. Cimetidine also significantly decreased gastric cancer cell adherence to stimulated endothelial cells. The inhibition of E-selectin expression corresponded to the reduction of tumor cell adherence. The effects of cimetidine on tumor adhesion were almost nullified by pre-incubation with E-selectin and sialyl Lewis x antibody. Furthermore, there was no significant change of GES-1 adherence to endothelial cells by TNF-α, cimetidine, E-selectin and sialyl Lewis x antibody. The inhibiton of gastric cancer cell adherence to cytokinestimulated endothelial cells treated with cimetidine appears to result from blocking endothelial E-selectin expression. These data support the hypothesis that cimetidine may exert its anti-metastatic effects in gastric cancer, in part, by inhibiting E-selectin/sialyl Lewis x-mediated adherence of gastric cancer cells to endothelial cells in the metastasis target organs.

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“…Several studies have suggested various mechanisms underlying the beneficial effect of cimetidine on cancer patients, such as the following: (i) reversal of the pharmacological activity of histamine, tumour growth promoter by blocking histamine receptors on cancer cells Reynolds et al, 1996) or affecting histamine metabolism (Garcia-Caballero et al, 1994); (ii) acting as an antioxidant, thus inhibiting tumour growth (Kimura et al, 1986) and (iii) augmentation of anticancer immune reactivity through receptor antagonism of circulatory suppressor T cells (Kumar, 1990), prevention of postoperative alterations of lymphocyte subpopulations (Hansbrough et al, 1986), or by maintenance of natural killer cell activity (Katoh et al, 1996). In our study, we found that cimetidine could block the expression of E-selectin on the surface of human umbilical vein endothelial cells, thus blocking the tumour cell adhesion to endothelium and preventing the liver metastasis in nude mice model (Kobayashi et al, 2000).…”

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confidence: 99%

Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells

et al. 2002

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Cimetidine has been shown to have beneficial effects in colorectal cancer patients. In this study, a total of 64 colorectal cancer patients who received curative operation were examined for the effects of cimetidine treatment on survival and recurrence. The cimetidine group was given 800 mg day 71 of cimetidine orally together with 200 mg day 71 of 5-fluorouracil, while the control group received 5-fluorouracil alone. The treatment was initiated 2 weeks after the operation and terminated after 1 year. Robust beneficial effects of cimetidine were noted: the 10-year survival rate of the cimetidine group was 84.6% whereas that of control group was 49.8% (P50.0001). According to our previous observations that cimetidine blocked the expression of E-selectin on vascular endothelium and inhibited the adhesion of cancer cells to the endothelium, we have further stratified the patients according to the expression levels of sialyl Lewis antigens X (sL x ) and A (sL a ). We found that cimetidine treatment was particularly effective in patients whose tumour had higher sL x and sL a antigen levels. For example, the 10-year cumulative survival rate of the cimetidine group with higher CSLEX staining, recognizing sL x , of tumours was 95.5%, whereas that of control group was 35.1% (P=0.0001). In contrast, in the group of patients with no or low levels CSLEX staining, cimetidine did not show significant beneficial effect (the 10-year survival rate of the cimetidine group was 70.0% and that of control group was 85.7% (P=n.s.)). These results clearly indicate that cimetidine treatment dramatically improved survival in colorectal cancer patients with tumour cells expressing high levels of sL x and sL a .

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Cimetidine and immunoreactivity

Cited by 14 publications

References 4 publications

Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma

Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma

Cimetidine inhibits the adhesion of gastric cancer cells expressing high levels of sialyl Lewis x in human vascular endothelial cells by blocking E-selectin expression

Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells

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