| 1. |
- Nyström, Hanna, 1980-, et al.
(författare)
-
Liver-metastatic potential of colorectal cancer is related to the stromal composition of the tumour
- 2012
-
Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:12, s. 5183-5191
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The tumour stroma is an important modulator of cancer cell behaviour. The aim of this study was to compare the stromal composition between primary colorectal cancer (CRC) and colorectal liver metastases (CLM).Materials and Methods: The stromal composition in matched tissue sections of CRC and subsequent CLM was analysed, and related to clinical parameters.Results: Differences in the expression pattern of type I collagen and type IV collagen in CRC was related to a higher risk of CLM. Two types of CLM the desmoplastic and pushing type were identified. The time between CRC and diagnosis of CLM was shorter (p=0.047) for desmoplastic CLM. The mortality rate was higher for pushing CLM due to frequent extrahepatic disseminated disease. A difference in the overall survival rate between patients with desmoplastic and those with pushing CLM was seen at follow-up of more than 60 months (p=0.046).Conclusion: The liver-metastasizing potential is related to the stromal composition of primary CRC. There are distinct growth patterns in CLM with differences in stromal composition and clinical outcome.
|
|
| 2. |
- Holmberg, Stig B, 1946, et al.
(författare)
-
Cytotoxicity of liver macrophages against liver tumours. Influence of betamethasone, indomethacin and allopurinol.
- 1991
-
Ingår i: Anticancer research. - 0250-7005. ; 11:5, s. 1827-30
-
Tidskriftsartikel (refereegranskat)abstract
- Macrophage activation with zymosan has an inhibitory effect on tumour take and initial tumour growth in the rat liver. 91 rats with syngeneic transplanted hepatoma in the liver were treated with zymosan (46) or saline (45). Betamethasone (glucocorticoid), indomethacin (prostaglandin synthesis inhibitor), allopurinol (oxygen radical scavenger) or saline were administered concomitantly. Tumour take, tumour growth and relative spleen weight were used as in vivo parameters of liver macrophages cytotoxicity and general macrophage activation. Zymosan inhibition of tumour take was counteracted by betamethasone, indomethacin and allopurinol. Betamethasone increased the growth rate of the non-zymosan treated tumours during seven days. Indomethacin decreased the growth rate of the tumours in non-zymosan treated rats up to 14 days. Allopurinol significantly blocked the zymosan inhibition of tumour take and tumour growth after 7 and 14 days. Allopurinol blocked zymosan induced increased relative spleen weight. It is proposed that the liver macrophage cytotoxicity induced by zymosan is in part mediated via production of oxygen radicals.
|
|
| 3. |
- Jørkov, Andreas Schjellerup, et al.
(författare)
-
Immune response in blood and tumour tissue in patients with metastatic malignant melanoma treated with IL-2, IFN alpha and histamine dihydrochloride.
- 2003
-
Ingår i: Anticancer research. - 0250-7005. ; 23:1B, s. 537-42
-
Tidskriftsartikel (refereegranskat)abstract
- Interleukin-2 and interferon-alpha are pleiotropic immuno-activating cytokines with clinical efficacy in malignant melanoma. The anti-melanoma activity of these cytokines is believed to result from the triggering of lymphocyte-mediated killing of tumour cells. In ongoing clinical trials, histamine dihydrochloride is used as an adjuvant to IL-2 and IFN-alpha with a view to protecting lymphocytes from oxidative inhibition induced by tumour-infiltrating monocyte/macrophages. In this study, we have serially monitored mononuclear cells in peripheral blood and tumour biopsies from 13 patients with metastatic malignant melanoma treated under a protocol comprising histamine, IFN-alpha and low-dose IL-2. One complete and 3 partial responses were observed, while 3 patients had stable disease and 6 progressed. A trend towards a gradual increase in the absolute number of circulating CD56+/CD3- NK cells in patients maintaining stable disease during therapy was noted. In tumour tissues, the extent of leukocyte infiltration prior to treatment correlated with tumour response. Additional infiltration by NK cells (CD56+) and monocytes during treatment was seen only in responding patients. Patients with progressive disease exhibited a low density of leukocytes infiltrating tumour tissues at the onset of treatment as compared to the surrounding tissues. Our data indicate that the degree and localization of mononuclear infiltration before and during immunotherapy under this protocol may determine therapeutic anti-tumour responses.
|
|
| 4. |
- Lindnér, Per, 1956, et al.
(författare)
-
Biochemical modulation of intraperitoneal fluorouracil by allopurinol-the effect on an experimental adenocarcinoma in the liver.
- 1994
-
Ingår i: Anticancer research. - 0250-7005. ; 14:3A, s. 847-52
-
Tidskriftsartikel (refereegranskat)abstract
- In a rat liver tumour system with a nitrosoguanidine-induced carcinoma and in an in vitro system with the same tumour, the effect of allopurinol on the toxicity and antitumour effect of 5-fluorouracil (5-FU) was explored. Two doses of 5-FU, 30 and 60 mg/kg b.w. intraperitoneally (i.p.), were tested with a large dose of allopurinol subcutaneously (s.c.( (300 mg) in rats. The drugs were given for three consecutive days. The lethal toxicity of 60 mg 5-FU i.p. could not be counteracted by allopurinol. Allopurinol and 30 mg 5-FU reduced the tumour growth rate more than 5-FU alone. The spleen was smaller, as a sign of increased toxicity, without allopurinol. The concentration of allopurinol and its metabolites in the general circulation was high. In vitro, there was no additive or specific effect of allopurinol. These results indicate some in vivo metabolic modulation of 5-FU efficacy by allopurinol if 5-FU is administered intraperitoneally and allopurinol systemically.
|
|
| 5. |
- 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.
|
|
| 6. |
- Mattsson, J, et al.
(författare)
-
Intratumoral distribution of microspheres.
- 1986
-
Ingår i: Anticancer research. - 0250-7005. ; 6:4, s. 563-6
-
Tidskriftsartikel (refereegranskat)abstract
- Fifteen mu carbonized microspheres injected in two transplantable rat tumors, a hepatoma transplanted to the dorsum of one hindpaw and an adenocarcinoma transplanted into the liver, were found to be unevenly distributed and often in aggregates that seemed to fill intratumoral vessels. This finding can partly explain the increased vascular resistance in tumors after microsphere injection and makes the technique with repeated injections of microspheres disputable.
|
|
| 7. |
- 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.
|
|
