In vitro effect of histamine and histamine H1 and H2 receptor antagonists on cellular proliferation of human malignant melanoma cell lines

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

“…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] .…”

“…Immunohistochemical studies of the specimens revealed that most of the TILs were CD 3 + T lymphocytes clustered around tumor tissues. There were few CD 20 + cells in TIL population. …”

“…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.…”

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

“…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).…”

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

“…Since then, several studies have been published showing major survival advantages in gastrointestinal cancer patients treated with cimetidine Matsumoto, 1995;Kelly et al, 1999). Many studies on the mechanisms of this action have indicated that the antitumour effects of cimetidine might be due to a direct inhibitory effect on tumour growth Reynolds et al, 1996), cell-mediated immunomodulation (Osband et al, 1981;Hellstrand and Hermodsson, 1986;Gifford and Tirberg, 1987), or inhibition of cancer cell metastases (Kobayashi et al, 2000). The mechanisms proposed for cell-mediated immunomodulation of cimetidine include inhibition of suppressor T lymphocyte activity (Osband et al, 1981), stimulation of natural killer (NK) cell activity (Hellstrand and Hermodsson, 1986), and increase of interleukin-2 (IL-2) production in helper T lymphocytes (Gifford and Tirberg, 1987).…”