Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 7/2009

01-10-2009 | Research Paper

Impact of Octreotide and SOM-230 on liver metastasis and hepatic lipidperoxidation in ductal pancreatic adenocarcinoma in Syrian Hamster

Authors: M. Kilian, J. I. Gregor, I. Heukamp, K. Helmecke, M. Hanel, B. Wassersleben, M. K. Walz, I. Schimke, G. Kristiansen, F. A. Wenger

Published in: Clinical & Experimental Metastasis | Issue 7/2009

Login to get access

Abstract

Octreotide is a somatostatin analogue binding on two receptor subtypes. In previous trials Octreotide showed inhibitory effects on tumour growth and liver metastasis in experimental pancreatic cancer. Thus we evaluated whether the new somatostatin analogue SOM-230 binding on 4 receptor subtypes has superior effects on carcinogenesis in pancreatic carcinoma. About 120 Syrian hamsters were randomised into six groups (n = 20): Gr.1: Aqua/Aqua, Gr.2: BOP/Aqua, Gr.3: Aqua/Octreotide, Gr.4: BOP/Octreotide, Gr.5: Aqua/SOM-230, Gr.6: BOP/SOM-230. Tumour groups 2,4,6 subcutaneously received 10 mg/kg body weight N-nitrosobis-2-oxopropylamin (BOP) weekly for 10 weeks, healthy control Gr.1,3,5 were given aqua. In the 17th week therapy started with Octreotide and SOM-230 for 16 weeks, after 32 weeks animals were sacrificed. Pancreas and liver were histopathologically analysed. Hepatic lipidperoxidation was determined by activities of antioxidative enzymes gluthation-peroxidase (GSH-Px) and superoxiddismutase (SOD) as well as concentration of thiobarbituric-acid reactive substances (TBARS). Incidence of liver metastases was 88.2% in Gr.2 (BOP/Aqua), it was decreased in Gr.4 (BOP/Octreo: 40%) and Gr.6 (BOP/SOM-230: 50%) (P < 0.05). Mean number/animal and mean-2-dimensional size of liver metastases did not differ between tumour groups. Comparing GSH-Px-activity in intrametastatic and extrametastatic hepatic tissue revealed a significant increase extrametastatically in Gr.2 (BOP/Aqua) and Gr.6 (BOP/SOM-230). SOD-activity in liver metastases was decreased in Gr.2 (1,801) (P < 0.05) versus Gr.4 (8,304) and Gr.6 (7,038). Intrametastatic TBARS concentration was increased in Gr.2 compared to Gr.4 (BOP/Octreotid) and Gr.6 (BOP/SOM-230) (P < 0.05). Octreotide and SOM-230 equally reduced liver metastasis in ductal pancreatic adenocarcinoma probably by a reduction of lipidperoxidation.
Literature
1.
Adams RL, Adams IP, Lindow SW et al (2005) Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium. Br J Cancer 92:1493–1498CrossRefPubMed
2.
Li M, Wang X, Li W et al (2008) Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer. Cancer Sci 99(11):2218–2223CrossRefPubMed
3.
Lamberts SWJ, van der Lely AJ, Hofland LJ (2002) New somatostatin analogs: will they fulfill old promises? Eur J Endocrinol 146:701–705CrossRefPubMed
4.
Nayak TK, Atcher RW, Prossnitz ER (2008) Enhancement of somatostatin-receptor-targeted (177)Lu-[DOTA(0)-Tyr(3)]-octreotide therapy by gemcitabine pretreatment-mediated receptor uptake, up-regulation and cell cycle modulation. Nucl Med Biol 35(6):673–678CrossRefPubMed
5.
Canobbio C, Boccardo F, Cannata D et al (1992) Treatment of advanced pancreatic carcinoma with the somatostatin analogue BIM 23014. Gastroenterology 69:648–650
6.
Fazeny B, Baur M, Prohaska M et al (1997) Octreotide combined with goserelin in the therapy of advanced pancreatic cancer—results of a pilot study and review of the literature. J Cancer Res Clin Oncol 123:45–52CrossRefPubMed
7.
Moore MJ (2008) The treatment of advanced pancreatic cancer: current evidence and future challenges. Ann Oncol 19(7):304–308CrossRef
8.
Cartwright T, Richards DA, Boehm KA (2008) Cancer of the pancreas: are we making progress? A review of studies in the US oncology research network. Cancer Control 15(4):308–313PubMed
9.
Schally AV (2008) New approaches to the therapy of various tumors based on peptide analogues. Horm Metab Res 40(5):315–322CrossRefPubMed
10.
Rosenberg L, Barkun AN, Denis MH et al (1995) Low dose Octreotide and tamoxifen in the treatment of adenocarcinoma of the pancreas. Cancer 75:23–28CrossRefPubMed
11.
Wenger FA, Jacobi CA, Siderow A et al (1999) Hormone therapy of postoperative recurrent pancreatic carcinoma with Octreotide and tamoxifen. Chirurg 70:694–699CrossRefPubMed
12.
Wenger FA, Kilian M, Jacobi CA et al (2001) Effects of Octreotide on liver metastasis and intrametastatic lipidperoxidation in experimental pancreatic cancer. Oncology 60:282–288CrossRefPubMed
13.
Wenger FA, Kilian M, Mautsch I et al (2000) Influence of Octreotide and tamoxifen on tumour growth and liver metastasis in N-nitrosobis-2-oxopropylamine-induced pancreatic cancer in syrian hamsters. Horm Res 54:74–77CrossRefPubMed
14.
Wenger FA, Kilian M, Mautsch I et al (2001) Influence of Octreotide on liver metastasis and hepatic lipidperoxidation in BOP-induced pancreatic cancer in syrian hamsters. Pancreas 23:266–272CrossRefPubMed
15.
Pasquali D, Rossi U, Conzo G et al (2008) Effects of somatostatin analogue SOM-230 on cell proliferation, apoptosis and catecholamine levels in cultured pheochromocytoma cells. J Mol Endocrinol 40(6):263–271PubMed
16.
Hoek J, Herder WW, Feelders RA et al (2004) A single dose comparison of the acute effects between the new somatostatin analog SOM-230 and Octreotide in acromegalic patients. J Clin Endocrinol Metab 89(2):638–645CrossRefPubMed
17.
Lewis I, Bauer W, Albert R et al (2003) A novel somatostatin mimic with broad somatotropin release inhibitory factor binding and superior therapeutic potential. J Med Chem 46:2334–2344CrossRefPubMed
18.
Schmid HA, Schoeffter P (2004) Functional activity of the multiligand analog SOM-230 at human recombinant somatostatin receptor subtypes supports its usefulness in neuroendocrine tumours. Neuroendocrinology 80(suppl1):47–50CrossRefPubMed
19.
New York Academy of Sciences’ Ad Hoc committee on animal research: interdisciplinary principles and guidelines for the use of animals in research, marketing and education
20.
UKCCCR (1989) Guidelines for the welfare of animals in experimental neoplasia. Cancer Metastasis Rev 8:82–88CrossRef
21.
Wenger FA, Jacobi CA, Kilian M et al (1999) Does dietary alpha-linolenic acid promote liver metastases in pancreatic carcinoma initiated by BOP in syrian hamster? Ann Nutr Metab 43:121–126CrossRefPubMed
22.
Wenger FA, Kilian M, Jacobi CA et al (2000) Does alpha-linolenic acid in combination with linoleic acid influence liver metastasis and hepatic lipidperoxidation in BOP-induced pancreatic cancer in syrian hamsters? Prostaglandins Leukot Essent Fatty Acids 62:329–334CrossRefPubMed
23.
Meijers M, van Garderen-Hoetmer A, Lamers CB et al (1990) Role of cholecystokinin in the development of BOP-induced pancreatic lesions in hamsters. Carcinogenesis 11:2223–2226CrossRefPubMed
24.
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 95:351–358CrossRefPubMed
25.
Schimke I, Haberland A, Wirth M et al (1997) Influence of long-term supplementation with α-linolenic acid on myocardial lipidperoxidation and antioxidative capacity in spontaneously hypertensive rats. Prostaglandins Leukot Essent Fatty Acids 57:545–550CrossRefPubMed
26.
Janero DR (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipidperoxidation and peroxidative tissue injury. Free Radic Biol Med 9:515–540CrossRefPubMed
27.
Beauchamp C, Fridovich I (1971) Superoxide dismutase: improved assay and an assay applicable to acrylamide gels. J Anal Biochem 44:276–287CrossRef
28.
Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocytes glutathione peroxidase. J Lab Clin Med 29:143–148
29.
Lowry OH, Rosebrough NJ, Farr AL (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275PubMed
30.
Alexakis N, Halloran C, Raraty M et al (2004) Current standards of surgery for pancreatic cancer. Br J Surg 91:1410–1427CrossRefPubMed
31.
Bartsch H, Hietanen E, Malaveille C (1989) Carcinogenic nitrosamines: free radical aspects of their action. Free Radic Biol Med 7:637–644CrossRefPubMed
32.
Du ZY, Qin RY, Xia W et al (2005) Gene transfer of somatostatin receptor type 2 by intratumoural injection inhibits established pancreatic carcinoma xenografts. World J Gastroenterol 11:516–520PubMed
33.
Kumar M, Liu ZR, Thapa L et al (2004) Antiangiogenic effect of somatostatin receptor subtype 2 on pancreatic cancer cell line: inhibition of vascular endothelial growth factor and matrix metalloproteinase-2 expression in vitro. World J Gastroenterol 10:393–399PubMed
34.
Kumar M, Liu ZR, Thapa L et al (2004) Mechanisms of inhibition of growth of human pancreatic carcinoma implanted in nude mice by somatostatin receptor subtype 2. Pancreas 29:141–151CrossRefPubMed
35.
Kumar M, Liu ZR, Thapa L et al (2004) Anti-angiogenic effects of somatostatin receptor subtype 2 on human pancreatic cancer xenografts. Carcinogenesis 25:2075–2081CrossRefPubMed
36.
Qin RY, Fang RL, Gupta MK et al (2004) Alteration of somatostatin receptor subtype 2 gene expression in pancreatic tumour angiogenesis. World J Gastroenterol 10:132–135PubMed
37.
Shore S, Raraty MGT, Ghaneh P et al (2003) Review article: chemotherapy for pancreatic cancer. Aliment Pharmacol Ther 18:1049–1069CrossRefPubMed
38.
Szepeshazi K, Schally AV, Halmos G et al (2001) Targeting of cytotoxic somatostatin analog AN-238 to somatostatin receptor subtypes 5 and/or 3 in experimental pancreatic cancer. Clin Cancer Res 7:2854–2861PubMed
39.
Vernejoul F, Faure P, Benali N et al (2002) Antitumour effect of in vivo somatostatin receptor subtype 2 gene tranfer in primary and metastatic pancreatic cancer models. Cancer Res 62:6124–6131PubMed
40.
Adams RL, Adams IP, Lindow SW et al (2004) Inhibition of endothelial proliferation by the somatostatin analogue SOM-230. Clin Endocrinol 261:431–436CrossRef
41.
Benzie I (1996) Lipidperoxidation: a review of causes, consequences, measurement and dietary influences. Int J Food Sci Nutr 47:233–261CrossRefPubMed
42.
Van Dam PS, van Asbeck BS, Van Oirschot JF, Biessels GJ, Hamers FP, Marx JJ (2001) Gluthatione and alpha-lipoate in diabetic rats: nerve function, blood flow and oxidative state. Eur J Clin Invest 31(5):417–424CrossRefPubMed
43.
Hollan S (1995) Free radicals in health and disease. Haematologia (Budap) 26:177–189
44.
Kirshenbaum LA, Hill M, Singal PK (1995) Endogenous antioxidants in isolated hypertrophied cardiac myocytes and hypoxia-reoxygenation injury. J Mol Cell Cardiol 27(1):264–272CrossRef
45.
Arias Diaz J, Vara E, Torres Melero J et al (1997) Local production of oxygen free radicals and nitric oxide in rat diaphragm during sepsis: effects of pentoxifylline and somatostatine. Eur J Surg 163:619–625PubMed
46.
Horrobin DF (1990) Essential fatty acids, lipidperoxidation and cancer. In: Horrobin DF (ed) ω-6 Essential fatty acids. Wiley-Liss, New York, pp 351–378
47.
Niedermuhlbichler M, Wiedermann CJ (1992) Suppression of superoxide release from human monocytes by somatostatin related peptides. Regul Pept 41:39–47CrossRefPubMed
48.
Wiedermann CJ, Reinisch N, Niedermuhlbichler M et al (1993) Inhibition of recombinant human growth hormone induced and prolactin induced activation of neutrophils by Octreotide. Naunyn Schmiedebergs Arch Pharmacol 347:336–341CrossRefPubMed
49.
Birt DF, Julius AD, White LT et al (1989) Enhancement of pancreatic carcinogenesis in hamsters fed a high fat diet ad libitum and at a controlled calorie intake. Cancer Res 49:5848–5851PubMed
50.
Herrington MK, Permert J, Kazakoff KR et al (1993) Effects of high fat diet and cholecystokinin receptor blockade on pancreatic growth and tumour initiation in the hamster. Carcinogenesis 14:1021–1026CrossRefPubMed
51.
52.
Lupulescu AP (1996) Control of precancer cell transformation into cancer cells: its relevance to cancer prevention. Cancer Detect Prev 20:634–637PubMed
53.
54.
Skuladottir GV, Shi Hua D, Brodie AE et al (1994) Effects of dietary oils and methyl ethyl ketone peroxide on in vivo lipidperoxidation and antioxidants in rat heart and liver. Lipids 29:351–357CrossRefPubMed
55.
Marepaily R, Michaels D, Sloan A, Hatfield J, Adsay V, Joyrich R, Ullah N, Tobi M (2009) Octreotide uptake in intracranial metastasis of pancreatic ductal adenocarcinoma origin in a patient with a prolonged clinical course. Dig Dis Sci 54(1):188–190CrossRefPubMed
56.
Li M, Wang X, Li W, Li F, Yang H, Wang H, Brunicardi FC, Chen C, Yao Q, Fisher WE (2008) Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer. Cancer Sci 99(11):2218–2223CrossRefPubMed
57.
Guillermet J, Saint-Laurent N, Rochaix P et al (2003) Somatostatin receptor subtype 2 sensitizes human pancreatic cancer cells to death ligand-induced apoptosis. PNAS 100:155–160CrossRefPubMed
Metadata
Title
Impact of Octreotide and SOM-230 on liver metastasis and hepatic lipidperoxidation in ductal pancreatic adenocarcinoma in Syrian Hamster
Authors
M. Kilian
J. I. Gregor
I. Heukamp
K. Helmecke
M. Hanel
B. Wassersleben
M. K. Walz
I. Schimke
G. Kristiansen
F. A. Wenger
Publication date
01-10-2009
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 7/2009
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-009-9271-x

Other articles of this Issue 7/2009

Clinical & Experimental Metastasis 7/2009 Go to the issue

Research Paper

Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma

Research Paper

Activated platelets enhance ovarian cancer cell invasion in a cellular model of metastasis

Research Paper

Expression and functional analysis of the WAP four disulfide core domain 1 gene in human melanoma

Research Paper

Allelic loss at TP53 in metastatic human endometrial carcinomas

Research Paper

Hepatocyte growth factor induced up-regulations of VEGF through Egr-1 in hepatocellular carcinoma cells

Research Paper

Establishment and characterization of a new highly metastatic human osteosarcoma cell line
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits