Ranitidine and cimetidine differ in their in vitro and in vivo effects on human colonic cancer growth

Lawson, J A; Adams, Warwick J.; Dl, Morris

doi:10.1038/bjc.1996.155

Cited by 49 publications

(43 citation statements)

References 18 publications

(8 reference statements)

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“…Together, these findings suggest that the anti-tumor effects of cimetidine require a stimulating effect of histamine toward tumor cell growth, which is mediated via histamine H 2 receptors on tumor cells. However, other H 2 receptor antagonists such as ranitidine and famotidine did not exert anti-tumor effects in previous in vitro and in vivo studies, despite their stronger acid-inhibiting activity as compared to cimetidine (29)(30)(31). In a cell proliferating assay previously performed, famotidine did not have an effect on either histamine-stimulated or basal proliferation of HCC cell lines (data not shown), which shows that the mechanisms of the inhibitory effects of cimetidine on tumor cell proliferation are not limited to blocking the H 2 receptor.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosamine-treated rats

Furuta

Sato²,

Miyake³

et al. 2008

Oncol Rep

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Abstract. Cimetidine is known to have an anti-tumor effect on certain types of malignancies, though on hepatocellular carcinomas (HCCs), its effect remains unclear. We studied the anti-tumor effects of cimetidine on chemically-induced HCCs in rats. Four-week-old male Wistar rats (n=105) were divided into 4 groups. Those in groups A and B were administered diethylnitrosamine (DEN) intraperitoneally at 100 mg/kg body weight every week for 6 weeks, during which rats in group A were given tap water and those in group B received cimetidine (100 mg/kg/day) in their drinking water. Rats in groups C and D were administered saline instead of DEN and given tap water with 100 mg/kg/day of cimetidine, respectively. The animals were sacrificed at 7, 12, 22 and 32 weeks after the first administration of drugs and examined. Liver nodules were observed only in groups A and B, with the number of nodules, maximum diameter of the largest nodule, and liver weight significantly lower in group B. Immunohistochemistry findings showed that glutathione S-transferase placental-positive preneoplastic foci were significantly decreased in group B. Cimetidine treatment decreased the number of proliferating cell nuclear antigen-positive hepatocytes and tended to enhance natural killer (NK) cell activity in splenic lymphocytes. In addition, flow cytometry revealed that the proportion of NK cells among total splenic lympocytes was not affected by cimetidine treatment. Our results showed that cimetidine has an inhibiting effect on hepatocarcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Anti-tumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosamine-treated rats

Furuta

Sato²,

Miyake³

et al. 2008

Oncol Rep

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“…It has long been observed that histamine was a growth factor for certain cancers and could, by itself, stimulate tumor cell proliferation [18][19][20] . As one of the many important chemo-mediators involved in immune responses, histamine had inhibitory effects on immune response [35][36][37][38] via its H 2 receptors [39] .…”

Section: Discussionmentioning

confidence: 99%

“…Administration of CIM has been found to preserve, to some degree, the patients' perioperative immunity [5,6] , to improve the survival of patients with colorectal cancer, melanoma, and renal cell cancer [7][8][9][10][11][12][13][14][15] . Although it is not clear whether this effect of CIM on cancer is direct or indirect, it has been proposed that CIM may act by enhancing the host immune response to tumor cells [16,17] or by blocking the cell growth-promoting activity of histamine in cancer cell lines [14,[16][17][18][19][20] . In this study, we used CIM in the perioperative period as an adjuvant immunomodulatory agent, and studied its effects on peripheral blood lymphocytes, NK cells and TIL in a randomized controlled clinical trial in patients with GI cancer.…”

Section: Introductionmentioning

confidence: 99%

Perioperative cimetidine administration promotes peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: Results of a randomized controlled clinical trial

Cai¹,

Bai²,

Yuan³

et al. 2004

WJG

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AIM:To study the effects of perioperative administration of cimetidine (CIM) on peripheral blood lymphocytes, natural killer (NK) cells and tumor infiltrating lymphocytes (TIL) in patients with gastrointestinal (GI) cancer. METHODS:Forty-nine GI cancer patients were randomized into treatment group, who took CIM in perioperative period, and control group, who did not take the drug. The treatment was initiated 7 days before operation and continued for 10 days after surgery. At baseline examination before operation, on the 2nd and 10th postoperative days, total T lymphocytes, T helper cells, T suppressor cells, and NK cells in peripheral blood were measured respectively by immunocytochemical method using mouse-anti human CD 3 , CD 4 , CD 8 and CD 57 monoclonal antibodies. Blood samples from 20 healthy volunteers were treated in the same way as normal controls. Surgical specimens were examined during routine histopathological evaluation for the presence of TIL in tumor margin. Immunohistochemical study was performed to measure the proportion of T and B lymphocytes in TIL population. T and B lymphocytes were detected respectively using mouse-anti-human CD 3 and CD 20 monoclonal antibodies. RESULTS:In comparison with normal controls, both the treatment and control groups had decreased T cells, T helper cells and NK cells at baseline. In control group, total T cells, T helper cells and NK cells declined continuously with the disease progression and the decrease became more obvious after operation. From baseline to the 2nd postoperative day, the proportion of total T cells, T helper cells, and NK cells went down from 60.5±4.6% to 56.2±3.8%, 33.4±3.7% to 28.1±3.4%, and 15.0±2.8% to 14.2±2.2%, respectively. On the other hand, there were significant improvements in these parameters after CIM treatment. On the 10th postoperative day, the treatment group had significantly higher percentages of total T cells, T helper cells and NK cells than control group. Moreover, CIM treatment also boosted TIL response, as was reflected by findings that 68% (17/25) of the patients in treatment group had significant TIL responses and only 25% (6/24) of the cases had discernible TIL responses (P<0.01). CONCLUSION:Perioperative application of CIM to GI cancer patients could help restore the diminished cellular immunity induced by tumor burden and surgical maneuver. The drug could also boost TIL responses to tumor. These effects suggest that the drug be used as an immunomodulator for GI cancer patients.

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“…Because famotidine behaves as a specific H 2 receptor antagonist with a molar potency four to eight times greater than that of cimetidine (Peden et al, 1982;Feldman and Burton, 1990), it is Molecular and Cellular Pathology (Morris and Adams, 1995;Lawson et al, 1996). Kobayashi et al (2000) showed that cimetidine can block the adhesion of colorectal cancer cells to the endothelial cells, suppressing the metastases of cancer cells.…”

Section: Molecular and Cellular Pathologymentioning

confidence: 99%

Cimetidine modulates the antigen presenting capacity of dendritic cells from colorectal cancer patients

et al. 2002

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Cimetidine, a H 2 receptor antagonist, has been reported to improve survival in gastrointestinal cancer patients. These effects have largely been attributed to the enhancing effects of cimetidine on the host's antitumour cell-mediated immune response, such as inhibition of suppressor T lymphocyte activity, stimulation of natural killer cell activity and increase of interleukin-2 production from helper T lymphocytes. We conducted an in vitro study on the effects of cimetidine on differentiation and antigen presenting capacity of monocyte-derived dendritic cells from advanced colorectal cancer patients and normal controls. As a result, an investigation of expression of surface molecules associated with dendritic cells by flow cytometric analyses showed that cimetidine had no enhancing effect on differentiation of dendritic cells from cancer patients and normal controls. An investigation of [ 3 H]thymidine incorporation by allogeneic mixed lymphocyte reactions revealed that cimetidine increased the antigen presenting capacity of dendritic cells from both materials. Moreover, a higher antigen presenting capacity was observed in advanced cancer patients compared to normal controls. These effects might be mediated via specific action of cimetidine and not via H 2 receptors because famotidine did not show similar effects. Our results suggest that cimetidine may enhance the host's antitumour cell-mediated immunity by improving the suppressed dendritic cells function of advanced cancer patients.

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Ranitidine and cimetidine differ in their in vitro and in vivo effects on human colonic cancer growth

Cited by 49 publications

References 18 publications

Anti-tumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosamine-treated rats

Anti-tumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosamine-treated rats

Perioperative cimetidine administration promotes peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: Results of a randomized controlled clinical trial

Cimetidine modulates the antigen presenting capacity of dendritic cells from colorectal cancer patients

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