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- Hellstrand, Kristoffer, 1956, et al.
(författare)
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Alleviating oxidative stress in cancer immunotherapy: a role for histamine?
- 2000
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Ingår i: Medical oncology (Northwood, London, England). - 1357-0560. ; 17:4, s. 258-69
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-2 is a remarkable activator of lymphocytes with anti-neoplastic properties such as T-cells or natural killer cells, but tumor regression only rarely occurs in interleukin-2-treated cancer patients. In this review, we focus on interactions between monocytes/macrophages and T-cells/natural killer-cells, and in particular the role of such interactions for the outcome of cancer immunotherapy with interleukin-2. We propose that interleukin-2 therapy should be supplemented with compounds that alleviate toxicity inflicted by monocyte/macrophage-derived reactive oxygen metabolites within and around tumors. The hypothesis is founded on data demonstrating that (i) functions of intratumoral lymphocytes in many human malignant tumors are inhibited by reactive oxygen metabolites, generated by neighboring monocytes/macrophages, (ii) interleukin-2 only weakly activates T-cells or natural killer cells in an environment of oxidative stress, and (iii) inhibitors of the formation of reactive oxygen metabolites or scavengers of reactive oxygen metabolites synergize with interleukin-2 to activate these lymphocyte subsets. We also review the preclinical background to the use of histamine dihydrochloride, an inhibitor of reactive oxygen metabolite formation in monocytes/macrophages, as a supplement to cancer immunotherapy with interleukin-2.
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| 2. |
- Rizell, Magnus, 1963, et al.
(författare)
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Monotherapy with histamine dihydrochloride suppresses in vivo growth of a rat sarcoma in liver and subcutis.
- 2002
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Ingår i: Anticancer research. - 0250-7005. ; 22:4, s. 1943-8
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Tidskriftsartikel (refereegranskat)abstract
- The effect of parenterally-administered histamine dihydrochloride (histamine), the role of the histamine H2-receptor and the importance of histamine administration routes on the in vivo growth of a rat Leydig cell sarcoma (LTW) were explored. MATERIALS AND METHODS: Wistar/Furth rats with LTW tumours transplanted into subcutaneous and liver tissue received treatment by daily subcutaneous injections or by an osmotic pump for 10 days. RESULTS: Subcutaneous injections of histamine (0.5 mg/kg) reduced the liver tumour weight by 46+/-8% (p=0.0002) and subcutaneous tumour weight by 41+/-12% (p=0.026) versus animals receiving subcutaneous saline injections. Histamine continuously administered by osmotic pumps at doses of 0.5, 2 and 20 mg/kg/24 hour, did not reduce tumour growth. Ranitidine (50 mg/kg s.c.), inhibited the anti-tumour effect observed by subcutaneous histamine injections. In conclusion, H2-receptor-mediated tumour growth inhibition was accomplished by bolus injections of histamine.
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| 3. |
- Lindnér, Per, 1956, et al.
(författare)
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Blood flow in liver tumors--effects of vasoactive drugs estimated with xenon (133Xe) clearance.
- 2004
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Ingår i: Hepato-gastroenterology. - 0172-6390. ; 51:57, s. 781-6
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to identify in a standardized experimental rat liver tumor system the drugs which are most appropriate in influencing the relationship between liver tumor and normal liver parenchyma blood flow as estimated with 133Xe washout clearance method, and thereby positively influencing the kinetics of chemotherapeutic drugs. A battery of vasoactive drugs, which according to a literature review were considered to be active, were tested.
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