Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine stimulated in vitro and in vivo growth.

Adams, Warwick J.; Lawson, J A; Morris, David L.

doi:10.1136/gut.35.11.1632

Cited by 121 publications

(77 citation statements)

References 18 publications

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“…The presence of a large number of mast cells, which produce histamine, in colorectal cancer tissue was shown to be associated with a worsened prognosis in patients (26). Adams et al reported that histamine stimulated the proliferation of human colorectal tumor cell lines, which was inhibited by cimetidine treatment, though cimetidine did not affect the basal proliferating ability of these cell lines in the absence of histamine (27). Previously, we used a 3 H-methyl-thymidine incorporation assay with human HCC cell lines (HepG2 and KYN-2 cimetidine tended to inhibit cell growth stimulated by histamine, but did not have an effect on the basal proliferating ability of the cell lines (data not shown).…”

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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“…High concentrations of histamine are known to occur in colorectal cancer tissues (Garcia-Caballero et al, 1993). Histamine stimulates the in vivo growth of experimental colorectal tumours and cimetidine can inhibit this effect (Adams et al, 1994a). However, other, far more potent H 2 receptor antagonists such as ranitidine do not show the same effect either in vitro (Lawson et al, 1996), or in large clinical trials (Nielsen et al, 1998).…”

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confidence: 99%

Cimetidine in colorectal cancer – are the effects immunological or adhesion-mediated?

Eaton

Hawkins

2002

Br J Cancer

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Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine stimulated in vitro and in vivo growth.

Cited by 121 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 in colorectal cancer – are the effects immunological or adhesion-mediated?

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