| 1. |
- Hellstrand, Kristoffer, 1956, et al.
(författare)
-
Alleviating oxidative stress in cancer immunotherapy: a role for histamine?
- 2000
-
Ingår i: Medical oncology (Northwood, London, England). - 1357-0560. ; 17:4, s. 258-69
-
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.
|
|
| 2. |
|
|
| 3. |
- Lindnér, Per, 1956, et al.
(författare)
-
Blood flow in liver tumors--effects of vasoactive drugs estimated with xenon (133Xe) clearance.
- 2004
-
Ingår i: Hepato-gastroenterology. - 0172-6390. ; 51:57, s. 781-6
-
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.
|
|
| 4. |
- Lindner, P., et al.
(författare)
-
Combined treatment with histamine dihydrochloride, interleukin-2 and interferon-alpha in patients with metastatic melanoma
- 2004
-
Ingår i: Anticancer Res. - 0250-7005. ; 24:3b, s. 1837-42
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Histamine inhibits phagocyte-derived production of reactive oxygen species and improves the anti-tumour efficiency of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) in vitro and in tumour-bearing animals. PATIENTS AND METHODS: In a phase-II study, twenty-seven patients with stage IV melanoma received subcutanous injections of histamine dihydrochloride (histamine) 1.0 mg and IL-2 2.4 MIU/m2 twice daily (BID) days 1-5 and 8-12. IFN-alpha 3 MIU once daily was administered throughout a cycle (days 1-28; n=14). Alternatively, bolus doses of IL-2 10 MIU/m2 BID days 1 and 2 and histamine days 1-28 (n=13) were administered. The aim was to study efficiency (survival and tumour response), toxicity and histamine pharmacokinetics. RESULTS: The median survival time was 11.3 (2.5-45) months. One patient achieved a complete response and 3 patients had partial responses. The compounds were safely self-administered with low toxicity. Plasma histamine concentrations significantly increased after an injection of histamine over 10 minutes (3 +/- 1 vs. 63 +/- 27 nmol/l). CONCLUSION: Histamine, IL-2 and IFN-alpha treatment is safe, well-tolerated and tumour responses were observed. The putative efficiency of histamine as an adjunct to cytokine therapy in metastatic melanoma needs to be confirmed in later randomized trials.
|
|
| 5. |
|
|
| 6. |
- Rizell, Magnus, 1963, et al.
(författare)
-
Monotherapy with histamine dihydrochloride suppresses in vivo growth of a rat sarcoma in liver and subcutis.
- 2002
-
Ingår i: Anticancer research. - 0250-7005. ; 22:4, s. 1943-8
-
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.
|
|
| 7. |
|
|
| 8. |
- Sarg, Bettina, et al.
(författare)
-
Characterization of sequence variations in human histone H1.2 and H1.4 subtypes
- 2005
-
Ingår i: The FEBS Journal. - : Wiley InterScience. - 1742-464X .- 1742-4658. ; 272:14, s. 3673 -3683
-
Tidskriftsartikel (refereegranskat)abstract
- In humans, eight types of histone H1 exist (H1.1–H1.5, H1°, H1t and H1oo), all consisting of a highly conserved globular domain and less conserved N- and C-terminal tails. Although the precise functions of these isoforms are not yet understood, and H1 subtypes have been found to be dispensable for mammalian development, it is now clear that specific functions may be assigned to certain individual H1 subtypes. Moreover, microsequence variations within the isoforms, such as polymorphisms or mutations, may have biological significance because of the high degree of sequence conservation of these proteins. This study used a hydrophilic interaction liquid chromatographic method to detect sequence variants within the subtypes. Two deviations from wild-type H1 sequences were found. In K562 erythroleukemic cells, alanine at position 17 in H1.2 was replaced by valine, and, in Raji B lymphoblastoid cells, lysine at position 173 in H1.4 was replaced by arginine. We confirmed these findings by DNA sequencing of the corresponding gene segments. In K562 cells, a homozygous GCC→GTC shift was found at codon 18, giving rise to H1.2 Ala17Val because the initial methionine is removed in H1 histones. Raji cells showed a heterozygous AAA→AGA codon change at position 174 in H1.4, corresponding to the Lys173Arg substitution. The allele frequency of these sequence variants in a normal Swedish population was found to be 6.8% for the H1.2 GCC→GTC shift, indicating that this is a relatively frequent polymorphism. The AAA→AGA codon change in H1.4 was detected only in Raji cells and was not present in a normal population or in six other cell lines derived from individuals suffering from Burkitt's lymphoma. The significance of these sequence variants is unclear, but increasing evidence indicates that minor sequence variations in linker histones may change their binding characteristics, influence chromatin remodeling, and specifically affect important cellular functions.
|
|
| 9. |
|
|
