Bevacizumab combined with chemotherapy for ovarian cancer: an updated systematic review and meta-analysis of randomized controlled trials

Yu, Wu; Lin, Shu-I; Shen, Dan; Xiao-pin, Chen

doi:10.18632/oncotarget.12926

Cited by 53 publications

(47 citation statements)

References 23 publications

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“…However, considering the limitation of single drug therapy, combination therapy is a routine means for clinical tumor treatment [34] . In recent years, the combination of chemotherapeutics and targeted drugs has made signi cant breakthroughs in both basic research and clinical application of OC [19,[35][36] . nab-P is a kind of paclitaxel wrapped by human albumin, which can enter the tumor cells easily, increase the drug concentration in tumor cells, and achieve ideal therapeutic effect on OC.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: The Role of Apatinib Combined with Paclitaxel (aluminum binding type) in Platinum-resistant Ovarian Cancer

Zhao

Wang

et al. 2020

Preprint

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Objective: To assess the anti-tumor activity and side effects of different dosages of paclitaxel (albumin binding type) (hereinafter referred to as nab-P) combined with Apatinib (hereinafter referred to as AP) in platinum-resistant ovarian cancer cell line and xenograft models.Methods: SKOV-3/DDP cell line was selected as the research object in cytology experiment. Firstly, we divided it into three groups for experiments to explore the individual effects of nab-P and AP. a): Control group, blank control, no drug intervention; b): nab-P group, nab-P 40μmol/l; c): AP group, AP 50μmol/l (Drug doses were IC-50 values that detected by MTT assay). Apoptosis related protein(Bax, bcl-2), vascular related protein(p-VEGFR-2), invasion related protein(MMP-2) expression were detected by Western blot and Cellular immunofluorescence, the invasion ability of tumor cells were detected by Transwell and Cell scratch test. Based on these dates, secondly, establishing different doses of nab-P combined with Ap to explore the curative effect of combination therapy. a): Control group, blank control, no drug intervention; b): Group-1, nab-P 5μmol/l + AP 10μmol/l, c): Group-2, nab-P 4.5μmol/l + AP 10μmol/l, d): Group-3, nab-P 4μmol/l + AP 10μmol/l, e): nab-P group, nab-P 5μmol/l, f): AP group, AP 10μmol/l (MTT assay). The combination index was analyzed by Compusyn software, Western blot, Immunofluescence, Transwell and Cell scratch test also were also chose to observe of inhibition effect. Thirdly, we used xenograft models to verify the results of cytological experiments. Tumor-forming BALB/c female nude mice were randomly divided into 4 groups, a): Control group, no drug intervention, only saline injection, b): nab-P 20mg/kg + AP 150mg/kg , c): nab-P 18mg/kg + AP 150mg/kg, d): nab-P 16mg/kg + AP 150mg/kg(The doses were guided by the pharmaceutical manufacturers). The tumor growth curve was analyzed during the experiment. And the apoptosis related protein (Bax, bcl-2), angiogenesis related protein (CD31, p-VEGFR-2) and invasion related protein(MMP-2) were observed by Western blot, Immunofluescence and Immunohistochemistry to analysis the ant-tumor effects. The quality of life in nude mice were observed to analysed the drug-induced side effects.Result: In the separate medication section, (1) The IC-50 value of nab-P was 45.53±4.06 μmol/l, while the AP was 50.66±4.96 umol/L (48h). (2) The expressions of bcl-2 (nab-P group, AP group), p-VEGFR-2 (AP group), MMP-2(nab-P group, AP group) were higher than Control group, while Bax(nab-P group, AP group) lower (P<0.01). (3) The cell invasive ability was decreased after the nab-P and AP intervation (P<0.01). In the combination medication section, (1) Compusyn showed the Combination index (Cl) were all below 1 (Cl<1), that means nab-P and AP are synergism. (2) The combination IC-50 value was nab-P 5.28 μmol/l+AP 10.56 μmol/l (48h). (3) In the detection of related protein expression, the combination of drugs can improve the anti-tumor effect, otherwise, after combined with AP, when nab-P were reduced dose in proper quantity, there were no obvious different in drug effect. (4) After reducing the doses of nab-P, the average food intake of nude mice increased from 4.50 g±0.17 to 5.55 g±0.13, and the one-hour activity increased from 6.11min ±0.16 to 6.34 min ±0.13.Conclusion: nab-P, a chemotherapeutic agent, can play an anti-tumor role in platinum-resistant ovarian cancer, but it can cause adverse effects that increase with dose. When combined with AP, the two drugs have synergistic effect, which can improve the anti-tumor effects of single drug. In addition, when combined with AP, the doses of nab-P can be appropriately reduced under the standard of recommended to reduce the toxicity of chemotherapy drugs, without affecting the anti-tumor effect.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: The Role of Apatinib Combined with Paclitaxel (aluminum binding type) in Platinum-resistant Ovarian Cancer

Zhao

Wang

et al. 2020

Preprint

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“…The first drug approved by the FDA for the antiangiogenic treatment of solid tumors was Bevacizumab, which is a humanized anti-VEGF monoclonal antibody. Bevacizumab, in combination with chemotherapy, has been shown to increase progression-free survival (PFS) and overall survival (OS) (91)(92)(93)(94)(95). Aflibercept is a recombinant protein known as a "VEGF trap" that can bind all VEGF isoforms, along with PLGF, and inhibit their activities.…”

Section: Antiangiogenic/immunotherapy Combinationmentioning

confidence: 99%

Contribution of Angiogenesis to Inflammation and Cancer

et al. 2019

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During carcinogenesis, advanced tumors are surrounded by both stromal and immune cells, which support tumor development. In addition, inflammation and angiogenesis are processes that play important roles in the development of cancer, from the initiation of carcinogenesis, tumor in situ and advanced stages of cancer. During acute inflammation, vascular hyperpermeability allows inflammatory mediators and immune response cells, including leukocytes and monocytes/macrophages, to infiltrate the site of damage. As a factor that regulates vascular permeability, vascular endothelial growth factor (VEGF) also plays a vital role as a multifunctional molecule and growth factor. Furthermore, stromal and immune cells secrete soluble factors that activate endothelial cells and favor their transmigration to eliminate the aggressive agent. In this review, we present a comprehensive view of both the relationship between chronic inflammation and angiogenesis during carcinogenesis and the participation of endothelial cells in the inflammatory process. In addition, the regulatory mechanisms that contribute to the endothelium returning to its basal permeability state after acute inflammation are discussed. Moreover, the manner in which immune cells participate in pathological angiogenesis release pro-angiogenic factors that contribute to early tumor vascularization, even before the angiogenic switch occurs, is also examined. Also, we discuss the role of hypoxia as a mechanism that drives the acquisition of tumor hallmarks that make certain cancers more aggressive. Finally, some combinations of therapies that inhibit the angiogenesis process and that may be a successful strategy for cancer patients are indicated.

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“…Which was the same as the expected results, after the effects of nab-P and AP, the number of invasive cells decreased significantly, and the 24-hour cell healing rate decreased. Therefore, we can draw the first conclusion that nab-P and AP can play a good anti-tumor effect on drug-resistant SKOV- However, considering the limitation of single drug therapy, combined drugs is a routine means for clinical tumor treatment [34], for the treatment of ovarian cancer, the combination of chemotherapy targeted drugs has made a great breakthrough in the basic research and clinical cases in recent years [19,[35][36]. The nab-P is a kind of paclitaxel wrapped by human serum albumin, which can enter the tumor cells easily, increase the drug concentration in tumor cells, and achieve ideal therapeutic effect on drug-resistant ovarian cancer.…”

Section: Disscusionmentioning

confidence: 99%

WITHDRAWN: The role of Apatinib combined with Paclitaxel (aluminum binding type) in drug-resistant ovarian cancer

Zhao

Wang

et al. 2020

Preprint

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ObjectiveTo assess the antitumor effects and side reactions of different dosages of Paclitaxel (albumin binding) combined with Apatinib in drug-resistant ovarian cancer cell line and xenotransplantation tumor model. MethodsConventional cell experiments were used to evaluate the effects of Apatinib and Paclitaxel (albumin binding), SKOV-3/DDP were selected as research object and divided into 3 groups for study, a): control group, no drug intervention; b): nab-P group, Paclitaxel (albumin binding type) 40 µmol/l; c): Apatinib group, Apatinib 50 µmol/l. The IC-50 value of the drug was detected by MTT test, apoptosis related protein(Bax, bcl-2), vascular related protein(p-VEGFR-2), invasion related protein(MMP-2) expression were detected by Western blot and Cellular immunofluorescence, the invasion and migration ability of tumor cells were detected by Transwell and Cell scratch test. Based on these dates, establishing different dosages of Paclitaxel (albumin binding type) combined with Apatinib, a): Control group, no drug intervention; b): Group-1, Paclitaxel (albumin binding type) 5 µmol/l + Apatinib 10 µmol/l, c): Group-2, Paclitaxel (albumin binding type) 4.5 µmol/l + Apatinib 10 µmol/l, d): Group-3, Paclitaxel (albumin binding type)4 µmol/l + Apatinib 10 µmol/l, the index of combined use was analyzed by Compusyn software, Western blot, Immunofluescence, Transwell, Cell scratch test also were chose to change of inhibition effect. On the other hand, we used xenograft tumor model to verify the results in vivo. BALB/c female nude mice were randomly divided into 4 groups, a): Control group, no drug intervention; b): Paclitaxel (albumin binding type) 20 mg/kg + Apatinib 150 mg/kg, c): Paclitaxel (albumin binding type) 18 mg/kg + Apatinib 150 mg/kg, d): Paclitaxel (albumin binding type) 16 mg/kg + Apatinib 150 mg/kg. The tumor growth curve was analyzed during the test. The apoptosis related protein (Bax, bcl-2), angiogenesis related protein (CD31, p-VEGFR-2) and invasion related protein(MMP-2) were analyzed by Western blot, Immunofluescence and Immunohistochemistry to analysis the effect of antitumor and side reactions Result (1) The IC-50 value of SKOV-3/DDP to paclitaxel (albumin binding type) was 45.53 ± 4.06 µmol/l, while

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Bevacizumab combined with chemotherapy for ovarian cancer: an updated systematic review and meta-analysis of randomized controlled trials

Cited by 53 publications

References 23 publications

WITHDRAWN: The Role of Apatinib Combined with Paclitaxel (aluminum binding type) in Platinum-resistant Ovarian Cancer

WITHDRAWN: The Role of Apatinib Combined with Paclitaxel (aluminum binding type) in Platinum-resistant Ovarian Cancer

Contribution of Angiogenesis to Inflammation and Cancer

WITHDRAWN: The role of Apatinib combined with Paclitaxel (aluminum binding type) in drug-resistant ovarian cancer

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