A Somatostatin Analogue, Octreotide, Inhibits the Occurrence of Second Primary Tumors and Lung Metastasis after Resection of Hepatocellular Carcinoma in Mice

Jia, Weidong; Xu, Ge‐Liang; Wang, Wei; Wang, Zhihua; Li, Jiansheng; Ma, Jun; Ren, Weihua; J, Yu; Liu, Wenbin

doi:10.1620/tjem.218.155

Cited by 16 publications

(15 citation statements)

References 27 publications

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“…Furthermore, in an animal study, nude mice were administered with octreotide for 35 days following a surgical removal of human HCC xenografts. Compared with the control group, octreotide at doses of 100 and 200 μg/kg/day significantly inhibited the growth rate of second primary tumors, decreased lung metastasis and prolonged the life span (27). Although other controlled trials have reported no survival benefit for long-acting octreotide compared with placebos (12,13,17–19), certain researchers believe it is possible that octreotide LAR may benefit a subgroup of patients whose tumors express high levels of SSTRs (19).…”

Section: Discussionmentioning

confidence: 99%

Somatostatin receptor subtypes 2 and 5 are associated with better survival in operable hepatitis B-related hepatocellular carcinoma following octreotide long-acting release treatment

Liu

Jiang

2013

Oncology Letters

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Liver resections for hepatocellular carcinoma (HCC) in cirrhotic livers are associated with early recurrence and poor survival. Somatostatin analogues (SSAs) have been reported to inhibit cell proliferation by interacting with specific somatostatin receptors (SSTRs) 2 and 5. The present study investigated whether SSTR expression in HCC was associated with the clinical outcome following octreotide long-acting release (LAR) treatment. Paired tumor and cirrhotic liver samples were obtained following a liver resection from 99 patients with stage I–II HCC and HBV-related cirrhosis. The expression of SSTR2 and 5 was assessed using quantitative (q)PCR and immunohistochemistry. The patients were classified into two groups, the high expression (n=47) and low expression (n=52) groups, based on the gene expression levels. The clinicopathological data and survival results of the two groups were compared. When compared with the surrounding cirrhotic tissue, the SSTR2 and 5 mRNA levels were significantly decreased in the HCC tissue. There were no significant differences between the groups with respect to the baseline characteristics. The tumor recurrence rate was significantly lower in the high expression group compared with that of the low expression group (63.83% vs. 82.69%; P=0.033). The 1-, 3- and 5-year disease-free and overall survival rates of the high expression group were 97, 89 and 71% and 98, 89 and 74%, respectively. The survival time of the members of the high expression group was longer compared with that of the low expression group. The multivariate analysis revealed that the TNM-7 stage and SSTR2 expression were independent prognostic factors for survival. In conclusion, SSTR mRNA expression correlated with survival in patients with early-stage hepatitis B virus (HBV)-related HCC who were treated with octreotide LAR following surgery. The inhibitory effects of SSAs on tumor growth may be mediated by SSTR expression.

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Section: Discussionmentioning

confidence: 99%

Somatostatin receptor subtypes 2 and 5 are associated with better survival in operable hepatitis B-related hepatocellular carcinoma following octreotide long-acting release treatment

Liu

Jiang

2013

Oncology Letters

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“…However, published clinical data suggest that octreotide and lanreotide can have very different efficacies in certain cancers [38,39]. Furthermore, there are both experimental and clinical data that show an anti-cancer activity of octreotide in systems where somatostatin receptors appear not to be expressed [40,41]. Another possibility, however, is that these cell lines do indeed possess SSTRs.…”

Section: Discussionmentioning

confidence: 99%

Screening of well-established drugs targeting cancer metabolism: reproducibility of the efficacy of a highly effective drug combination in mice.

Abolhassani¹,

Guais²,

Sanders³

et al. 2011

Invest New Drugs

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Alterations in metabolic pathways are known to characterize cancer. In order to suppress cancer growth, however, multiple proteins involved in these pathways have to be targeted simultaneously. We have developed a screening method to assess the best drug combination for cancer treatment based on targeting several factors implicated in tumor specific metabolism. Following a review of the literature, we identified those enzymes known to be deregulated in cancer and established a list of sixty-two drugs targeting them. These molecules are used routinely in clinical settings for diseases other than cancer. We screened a first library in vitro against four cell lines and then evaluated the most promising binary combinations in vivo against three murine syngeneic cancer models, (LL/2, Lewis lung carcinoma; B16-F10, melanoma; and MBT-2, bladder cancer). The optimum result was obtained using a combination of α-lipoic acid and hydroxycitrate (METABLOC(TM)). In this study, a third agent was added by in vivo evaluation of a large number of combinations. The addition of octreotide strongly reduced tumor development (T/C% value of 30.2 to 34.5%; P < 0.001) in the same models and prolonged animal survival (P < 0.001) as compared to cisplatin. These results were confirmed in a different laboratory setting using a human xenograft model (NCI-H69, small cell lung cancer). None of these three molecules are known to target DNA. The effectiveness of this combination in several animal models, as well as the low toxicity of these inexpensive drugs, emphasizes the necessity of rapidly setting up a clinical trial.

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“…Besides, octreotide can also induce apoptosis, inhibit the hyperplasia of the tumor cells, and reduce the absolute number of tumor cells and the expression of heparinase. Meanwhile octreotide's anti-tumor function also includes inducing the proliferation, invasion, and differentiation of vascular endothelial cells through the inhibition of VEGF [14,15] .…”

Section: Discussionmentioning

confidence: 99%

“…The incidence of tumor angiogenesis, assessed by measuring the circulating levels of heparinase and vascular endothelial growth factor (VEGF) can be reduced by administration of somatostatin analogs, octreotide in combination with small doses of heparin [9][10][11][12]. Our earlier studies looked at the individual effects of heparin or octreotide on metastasis [13][14][15], but it is not known if the combination would be beneficial. Given this, we hypothesized that a small dose combination treatment of octreotide and heparin would lead to reduced tumor angiogenesis, and in turn metastasis without major adverse effects.…”

Section: Introductionmentioning

confidence: 99%

Post-TACE Combination Therapy of Heparin and Octreotide Results in Decreased Tumor Metastasis in Extrahepatic Tumorigenesis

Jia

Feng²,

Fan³

et al. 2011

Cell Biochem Biophys

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Primary hepatocarcinoma is the most common type of malignant tumor and a leading cause of cancer mortality. Standard treatment for patients with advanced primary hepatocarcinoma for whom surgery is not recommended includes transcatheter arterial chemoembolization (TACE). Within these patients 44% develop metastasis within 1 year. Thus, understanding the events underlying the recurrent tumors and developing therapies in conjunction with TACE would be of great benefit. Reducing tumor angiogenesis by combining the somatostatin analog octreotide with small doses of heparin is one approach in decreasing metastasis rates by targeting VEGF and heparinase, respectively. Given this, we investigated whether a heparin and octreotide combination treatment administered post-TACE would decrease the tumor metastasizing rate in primary hepatocarcinoma. A total of 147 patients diagnosed with primary hepatocarcinoma were admitted to the study and received 2-4 TACE treatments and were monitored for 1 year. Of these 84 received the heparin plus octreotide combination treatment and 63 did not (control group). All patients were monitored for adverse reactions, coagulation ability, and tumor metastasis. We found a significant decrease in the incidence of tumor metastasis in patients receiving the combination treatment post-TACE for up to 1 year with no significant toxic or adverse effects. Thus, we propose using the combination treatment of heparin and octreotide post-TACE in the treatment of recurrent tumorigenesis in primary hepatocarcinoma.

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A Somatostatin Analogue, Octreotide, Inhibits the Occurrence of Second Primary Tumors and Lung Metastasis after Resection of Hepatocellular Carcinoma in Mice

Cited by 16 publications

References 27 publications

Somatostatin receptor subtypes 2 and 5 are associated with better survival in operable hepatitis B-related hepatocellular carcinoma following octreotide long-acting release treatment

Somatostatin receptor subtypes 2 and 5 are associated with better survival in operable hepatitis B-related hepatocellular carcinoma following octreotide long-acting release treatment

Screening of well-established drugs targeting cancer metabolism: reproducibility of the efficacy of a highly effective drug combination in mice.

Post-TACE Combination Therapy of Heparin and Octreotide Results in Decreased Tumor Metastasis in Extrahepatic Tumorigenesis

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