Bevacizumab enhances chemosensitivity of hepatocellular carcinoma to adriamycin related to inhibition of survivin expression

Xiong, Ye; Sun, Hui‐Chuan; Zhu, Xiao‐Dong; Zhuang, Peng–Yuan; Zhang, Jubo; Xu, Huaxiang; Kong, Ling‐Bin; Wu, Wei‐Zhong; Qin, Lun–Xiu; Tang, Zhao‐You

doi:10.1007/s00432-010-0914-8

Cited by 13 publications

(13 citation statements)

References 38 publications

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“…In conclusion, this study, together with previously reported results (13)(14)(15), indicates that combination therapy using bevacizumab as a key drug might be a promising regimen for the treatment of HCC. In a bevacizumab-based combination therapy regimen, ACR, which successfully improves HCC patient survival by preventing recurrence (17,18), is a preferred partner for bevacizumab because the combination of these agents significantly suppresses the growth of HCC xenografts by inhibiting cell proliferation and inducing apoptosis in HCC cells.…”

Section: Discussionsupporting

confidence: 75%

“…We consider the suppressive effect of this combination therapy on the tumor growth to be possibly associated with the inhibition of Akt phosphorylation because the activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling plays a critical role in the survival and proliferation of HCC cells and, therefore, targeting this signaling might be an effective strategy for the treatment of HCC (38,39). A recent experimental study showed that bevacizumab enhances the chemosensitivity of HCC by inhibiting the VEGF-PI3K/Akt signaling pathway (14). Phosphorylation of Akt is also one of the targets by which ACR suppresses the growth of HCC cells (26).…”

Section: Discussionmentioning

confidence: 99%

“…Thereafter, mice were injected with bevacizumab (5 mg/kg body weight, groups 2 and 4) or saline (groups 1 and 3) subcutaneously twice a week for 6 wk. The dosage of bevacizumab was determined according to a previous study (14). Groups 1 and 2 were fed the basal diet CRF-1 (Oriental Yeast Co., Ltd., Tokyo, Japan) throughout the experiment.…”

Section: Methodsmentioning

confidence: 99%

“…The administration of bevacizumab significantly improved the survival of mice bearing human HCC tumors orthotopically transplanted in the liver (12). Moreover, several preclinical animal studies have indicated that the anti-tumor effect of bevacizumab on HCC is enhanced when it is combined with other chemotherapeutic agents (13)(14)(15). These findings suggest that the use of bevacizumab either as a single agent or in combination with other agents may be a promising strategy for the treatment of HCC.…”

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confidence: 97%

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Combination of Bevacizumab and Acyclic Retinoid Inhibits the Growth of Hepatocellular Carcinoma Xenografts

Kubota

Shimizu

Baba

et al. 2014

J Nutr Sci Vitaminol

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SummaryThe prognosis of patients with hepatocellular carcinoma (HCC) is poor and the development of effective treatments for this malignancy, including combination chemotherapy, is required. This study examined the possible combined inhibitory effects of bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, and acyclic retinoid (ACR), which can prevent the development of HCC, on the growth of Huh7 human HCC cells. Xenograft tumors were produced by subcutaneously injecting Huh7 cells into nude mice. Starting 1 wk after the tumor cell injection, the mice were treated with bevacizumab alone (5 mg/kg body weight, subcutaneous injection, twice a week), ACR alone (given in a diet containing 0.03%), or their combination for 6 wk, and the effects of these regimens on xenograft growth were examined. Combined treatment with bevacizumab plus ACR significantly suppressed the growth of Huh7 xenografts. The combination of these agents significantly inhibited the phosphorylation of the Akt protein in tumor tissues. With combination therapy, the population of Ki-67-positive cells in xenografts decreased, while that of TUNEL-positive cells increased. The combination of bevacizumab and ACR exerts growth-suppressing effects on HCC cells by inhibiting cell proliferation and inducing apoptosis. This combination might be an effective regimen for the treatment of HCC.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 97%

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Combination of Bevacizumab and Acyclic Retinoid Inhibits the Growth of Hepatocellular Carcinoma Xenografts

Kubota

Shimizu

Baba

et al. 2014

J Nutr Sci Vitaminol

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“…15 In HCC, its activity as a single agent or in combination has been suggested in several phase 2 studies. 6,7,[16][17][18] Interestingly, a randomized phase 3 study presented in abstract form showed that the combination of oxaliplatin and fluorouracil (FOLFOX4) is more effective and less toxic compared with the more traditional cytotoxic chemotherapy agent doxorubicin in advanced and metastatic HCC. 19 Our data demonstrate good tolerability as well, with mild to moderate grade 3/4 toxicity (<10% hematologic grade 3/4 toxicities), which is less than what is seen with other combination regimens with relatively newer chemotherapy agents, [19][20][21] despite a relatively less optimal performance status patient population in our study.…”

Section: Discussionmentioning

confidence: 99%

Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advanced hepatocellular carcinoma

Sun

Sohal

Haller

et al. 2011

Cancer

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BACKGROUND: Anti‐angiogenesis agents have shown effectiveness in treatment of hepatocellular carcinoma (HCC). It is important to investigate more effective and safe systemic treatment options for patients with advanced HCC. This phase 2 study was designed to determine the efficacy and toxicity of the combination of bevacizumab, capecitabine, and oxaliplatin in patients with advanced unresectable and untransplantable HCC. METHODS: Chemotherapy‐naive patients with advanced unresectable and untransplantable HCC were treated with bevacizumab 5 mg/kg and oxaliplatin 130 mg/m2 on day 1 of each cycle, and capecitabine 825 mg/m2 orally twice a day from days 1 to 14 of a 21‐day cycle. RESULTS: Forty patients were enrolled to the study, in which 40% had Child‐Pugh B disease. Forty percent had an Eastern Cooperative Oncology Group performance status (PS) of 0, 55% had PS of 1, and 5% had PS of 2. Forty percent of patients had hepatitis B virus infection. The median progression‐free survival was 6.8 months (95% CI, 3.4‐9.1 months), and the median overall survival was 9.8 months (95% CI, 5.2‐12.1 months). Eight patients (20%) achieved partial response; 23 patients had stable disease with overall 77.5% disease control rate. The combination was tolerable with limited grade 3/4 toxicity, mainly peripheral neurotoxicity and fatigue. CONCLUSIONS: The combination appeared effective and safe, and the results were encouraging. Further investigation should be considered. Cancer 2011. © 2011 American Cancer Society.

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Phase 2 trial of concurrent bevacizumab and transhepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma

Buijs¹,

Reyes²,

Pawlik³

et al. 2012

Cancer

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Background Vascular endothelial growth factor is upregulated in hepatocellular carcinoma(HCC) and is further upregulated following transhepatic arterial chemoembolization. We conducted a phase II trial to evaluate safety and efficacy of bevacizumab combined with chemoembolization in patients with unresectable HCC. Methods Patients with Eastern Cooperative Oncology Group status 0–2, Child-Pugh score A–B and Barcelona Clinic Liver Cancer stage B–C were eligible. Treatment consisted of bevacizumab every two weeks and chemoembolization in week three, in a 6-week cycle, up to 3 cycles in 6 months. Primary endpoints were safety and efficacy. Results Twenty-five patients received chemoembolization and bevacizumab. The most common grade 3–4 events following cycle 1 were leukocytopenia(12%), fatigue(12%), hyponatremia(12%). Serious toxicities known to be associated with bevacizumab were observed in 4 patients. 30-day mortality was 0%. Median time-to-tumor progression of the targeted lesion(s) and overall survival were not reached and 10.8 months, respectively. The objective response rate was 60% using enhancement response evaluation criteria while the disease control rate was 100%. Conclusions Concurrent treatment with bevacizumab and chemoembolization is safe in carefully selected patients and shows antitumor activity in patients with unresectable HCC. These results support further development of bevacizumab combined with chemoembolization as a treatment for unresectable HCC.

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Bevacizumab enhances chemosensitivity of hepatocellular carcinoma to adriamycin related to inhibition of survivin expression

Cited by 13 publications

References 38 publications

Combination of Bevacizumab and Acyclic Retinoid Inhibits the Growth of Hepatocellular Carcinoma Xenografts

Combination of Bevacizumab and Acyclic Retinoid Inhibits the Growth of Hepatocellular Carcinoma Xenografts

Phase 2 trial of bevacizumab, capecitabine, and oxaliplatin in treatment of advanced hepatocellular carcinoma

Phase 2 trial of concurrent bevacizumab and transhepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma

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