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Cancer Oct 2021
Topics: Bevacizumab; Colorectal Neoplasms; Humans
PubMed: 34374076
DOI: 10.1002/cncr.33648 -
Journal of Translational Medicine Jan 2020Melanoma patients with metastatic growth in the meninges have poor prognosis and few treatment options. Although treatment with BRAF inhibitors or immune checkpoint...
BACKGROUND
Melanoma patients with metastatic growth in the meninges have poor prognosis and few treatment options. Although treatment with BRAF inhibitors or immune checkpoint inhibitors has provided promising results, most patients with advanced melanoma are resistant to these treatments and develop severe side effects. Novel treatment strategies are needed for patients with meningeal melanoma metastases, and the potential of antiangiogenic therapy was investigated in this preclinical study.
METHODS
Two GFP-transfected melanoma models (A-07 and D-12) differing substantially in VEGF-A expression were included in the study, and the anti-VEGF-A antibody bevacizumab was used as therapeutic agent. Meningeal metastases were initiated in BALB/c nu/nu mice by intracranial inoculation of melanoma cells, and bevacizumab treatment was given twice a week in i.p. doses of 10 mg/kg until the mice became moribund. Therapeutic effects were evaluated by determining tumor host survival time, assessing tumor growth and angiogenic activity by quantitative analyses of histological preparations, and measuring the expression of angiogenesis-related genes by quantitative PCR.
RESULTS
Meningeal A-07 melanomas showed higher expression of VEGF-A than meningeal D-12 melanomas, whereas the expression of ANGPT2 and IL8, two important angiogenesis drivers in melanoma, was much higher in D-12 than in A-07 tumors. Bevacizumab treatment inhibited tumor angiogenesis and prolonged host survival in mice with A-07 tumors but not in mice with D-12 tumors. Meningeal A-07 tumors in bevacizumab-treated mice compensated for the reduced VEGF-A activity by up-regulating a large number of angiogenesis-related genes, including ANGPT2 and its receptors TIE1 and TIE2. Melanoma cells migrated from meningeal tumors into the cerebrum, where they initiated metastatic growth by vessel co-option. In the A-07 model, the density of cerebral micrometastases was higher in bevacizumab-treated than in untreated mice, either because bevacizumab treatment increased mouse survival or induced increased tumor gene expression.
CONCLUSIONS
The development of antiangiogenic strategies for the treatment of meningeal melanoma metastases is a challenging task because the outcome of treatment will depend on the angiogenic signature of the tumor tissue, treatment-induced alterations of the angiogenic signature, and the treatment sensitivity of metastatic lesions in other intracranial sites.
Topics: Adult; Angiogenesis Inhibitors; Animals; Bevacizumab; Female; Humans; Melanoma; Meningeal Neoplasms; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A
PubMed: 31915016
DOI: 10.1186/s12967-020-02212-3 -
The Oncologist Feb 2015Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect.... (Review)
Review
Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect. Because some bevacizumab-related adverse events can be life threatening, it is important to identify risk factors and to establish treatment protocols to minimize treatment-related morbidity and mortality. In glioblastoma patients, the risk of developing certain side effects, such as gastrointestinal perforation, venous thromboembolism, and intracranial hemorrhages, is slightly higher than in patients treated with bevacizumab for other tumor types. We performed a systematic review of the side effects of bevacizumab and their incidence, causal mechanisms, and available treatments. Finally, we identified risk factors and proposed preventive and therapeutic measures for these adverse events.
Topics: Angiogenesis Inhibitors; Bevacizumab; Disease Management; Glioblastoma; Humans; Venous Thromboembolism
PubMed: 25568148
DOI: 10.1634/theoncologist.2014-0330 -
Angiogenesis Feb 2024Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume...
Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology. AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24 h. Thalidomide and bevacizumab, both VEGF inhibitors, were tested for their ability to prevent the formation of circular networks and proliferation of CD31 endothelial AVM cells. Furthermore, the effect of thalidomide and bevacizumab on stretched endothelial AVM cells was evaluated. In response to mechanical stress, VEGF gene and protein expression increased in patient AVM endothelial cells. Thalidomide and bevacizumab reduced endothelial AVM cell proliferation. Bevacizumab inhibited circular network formation of endothelial AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. With promising in vitro results, bevacizumab was used to treat three patients with unresectable AVMs or to prevent regrowth after incomplete resection. Bevacizumab controlled bleeding, pulsation, and pain over the follow up of eight months with no patient-reported side effects. Overall, mechanical stress increases VEGF expression in the microenvironment of AVM cells. The monoclonal VEGF antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. The clinical application of bevacizumab in AVM treatment demonstrates effective symptom control with no side effects.
Topics: Humans; Endothelial Cells; Vascular Endothelial Growth Factor A; Bevacizumab; Thalidomide; Arteriovenous Malformations; Pain
PubMed: 37733132
DOI: 10.1007/s10456-023-09896-3 -
Journal of Ayub Medical College,... 2016Bevacizmab is still an unlicensed drug for intraocular use in spite of the fact that it has shown comparable efficacy to other anti-vascular endothelial growth factors...
BACKGROUND
Bevacizmab is still an unlicensed drug for intraocular use in spite of the fact that it has shown comparable efficacy to other anti-vascular endothelial growth factors (anti-VEGF) medications in some large sample randomized control trails. Although repackaged bevacizumab has got safety concerns but its use is growing because of easy availability and low cost. Our study focuses on the diverse and growing indications of intravitreal bevacizumab (IVB) and its ocular complications in our geographical setting.
METHODS
This interventional case series was carried out at my private practice in Said Anwar Medical Complex, Dabgari, Peshawar, from January 2008 to July 2015. Total of 6107 injections were given to 4352 eyes. Intravitreal bevacizumab was injected in proper operating room setting. Bevacizumab injections were prepared from same vial by multiple withdrawals taking care of aseptic precautions. Follow up was done at 1 week and 20 days and adverse effects were noted.
RESULTS
Diabetic macular oedema (36%), central retinal vein occlusion (17.6%) and branched retinal vein occlusion (11%) were the top three indications of IVB. Other common indications were proliferative diabetic retinopathy (9.6%), neo-vascular glaucoma (5.9%), proliferative diabetic retinopathy with vitreous bleed (4.4%), proliferative diabetic retinopathy with tractional retinal detachment (3.7%), neo-vascular age related macular degeneration (2.9%), central serous retinopathy (1.48%) and Eale's disease (1.48%). Endohthalmitis occurred in 3 eyes (0.069%) while retinal detachment was found in only 2 eyes (0.046%).
CONCLUSIONS
Common indications of bevacizumab are diabetic macular oedema, central retinal vein occlusion and branched retinal vein occlusion. Complications like endophthalmitis and retinal detachment are rare.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Bevacizumab; Child; Child, Preschool; Female; Humans; Intravitreal Injections; Male; Middle Aged; Retinal Diseases; Young Adult
PubMed: 28718542
DOI: No ID Found -
Journal of Medicine and Life 2015Bevacizumab is a recombinant humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF). Though other VEGF inhibitors are being approved... (Review)
Review
UNLABELLED
Bevacizumab is a recombinant humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF). Though other VEGF inhibitors are being approved for the treatment of ophthalmological conditions, bevacizumab found its way into ophthalmology and clinical practice all around the world. The objective of this review is to present the ophthalmic dosage and administration pathways of bevacizumab in treating refractory glaucoma patients.
ABBREVIATIONS
VEGF = vascular endothelial growth factor, FDA = Food and Drug Administration, AMD = age-related macular degeneration.
Topics: Angiogenesis Inhibitors; Bevacizumab; Dose-Response Relationship, Drug; Glaucoma; Humans
PubMed: 25914729
DOI: No ID Found -
Indian Journal of Ophthalmology Jan 2018
Topics: Angiogenesis Inhibitors; Bevacizumab; Choroidal Neovascularization; Intravitreal Injections; Vascular Endothelial Growth Factor A
PubMed: 29283157
DOI: 10.4103/ijo.IJO_802_17 -
Journal of Ocular Pharmacology and... Apr 2023Bevacizumab-bvzr (Zirabev), a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor and a biosimilar to bevacizumab, is approved for...
Bevacizumab-bvzr (Zirabev), a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor and a biosimilar to bevacizumab, is approved for intravenous administration for various indications worldwide. The objectives of this study were to evaluate the ocular toxicity, systemic tolerability, and toxicokinetics (TKs) of bevacizumab-bvzr following repeat intravitreal (IVT) injection to cynomolgus monkeys. Male monkeys were administered saline, vehicle, or bevacizumab-bvzr at 1.25 mg/eye/dose once every 2 weeks (3 doses total) for 1 month by bilateral IVT injection, followed by a 4-week recovery phase to evaluate the reversibility of any findings. Local and systemic safety was assessed. Ocular safety assessments included in-life ophthalmic examinations, tonometry (intraocular pressure, IOP), electroretinograms (ERGs), and histopathology. In addition, concentrations of bevacizumab-bvzr were measured in serum and in ocular tissues (vitreous humor, retina, and choroid/retinal pigment epithelium) and ocular concentration-time profiles and serum TKs were evaluated. Bevacizumab-bvzr was tolerated locally and systemically, with an ocular safety profile comparable to the saline or vehicle control group. Bevacizumab-bvzr was observed in both serum and in the evaluated ocular tissues. There were no bevacizumab-bvzr-related microscopic changes or effects on IOP or ERGs. Bevacizumab-bvzr-related trace pigment or cells in vitreous humor (in 4 of 12 animals; commonly associated with IVT injection) and transient, nonadverse, mild ocular inflammation (in 1 of 12 animals) were noted upon ophthalmic examination and fully reversed during the recovery phase. Bevacizumab-bvzr was well tolerated via biweekly IVT administration in healthy monkeys, with an ocular safety profile comparable to saline or its vehicle control.
Topics: Animals; Male; Bevacizumab; Macaca fascicularis; Biosimilar Pharmaceuticals; Vascular Endothelial Growth Factor A; Intravitreal Injections; Toxicokinetics; Retina; Angiogenesis Inhibitors
PubMed: 36880872
DOI: 10.1089/jop.2022.0059 -
Clinical Colorectal Cancer Mar 2021Biosimilars - biological medicines highly similar to a licensed reference product (RP) - can mitigate the risk of drug shortages by providing treatment alternatives and,... (Review)
Review
Biosimilars - biological medicines highly similar to a licensed reference product (RP) - can mitigate the risk of drug shortages by providing treatment alternatives and, with their lower costs, increase patient access to medication and reduce health care expenditure. However, limited knowledge of biosimilar approval processes and lack of confidence in their quality and efficacy can limit their uptake. Importantly, biosimilars are approved based on tightly controlled regulatory pathways to demonstrate that the physical, chemical, and biological properties of the proposed biosimilar are highly similar to the RP, with no clinically meaningful differences. Initially, a battery of highly sensitive in vitro studies are performed, comparing critical quality attributes between the proposed biosimilar and RP. Subsequently, in vivo pharmacodynamic studies compare the activity and physiologic effects of the biosimilar and RP. Finally, clinical studies are conducted, including a pharmacokinetic equivalence study and a confirmatory comparative clinical trial. The latter is performed in the most sensitive patient population for which the RP is licensed, to provide the greatest possibility of identifying any clinically meaningful differences between the proposed biosimilar and RP. When equivalent safety and efficacy have been demonstrated in one setting, the totality of evidence, together with scientific justification that there are no anticipated differences between the RP and proposed biosimilar in mechanism of action, pharmacokinetics, immunogenicity or toxicity, allows extrapolation into indications where clinical studies were not performed with the proposed biosimilar. Here, we review the approval process for biosimilars, focusing on the licensing of bevacizumab biosimilars and their extrapolation to metastatic colorectal cancer.
Topics: Antineoplastic Agents, Immunological; Bevacizumab; Biosimilar Pharmaceuticals; Colorectal Neoplasms; Drug Approval; Equivalence Trials as Topic; Humans; Neoplasm Staging; Progression-Free Survival
PubMed: 33243618
DOI: 10.1016/j.clcc.2020.10.005 -
PloS One 2023Previous work suggested that tenogenic differentiation of tendon stem/progenitor cells (TSPCs) was suppressed by upregulated expression of the angiogenic marker vascular...
Previous work suggested that tenogenic differentiation of tendon stem/progenitor cells (TSPCs) was suppressed by upregulated expression of the angiogenic marker vascular endothelial growth factor (VEGF). The purpose of this study was to test the hypothesis that anti-VEGF antibody, bevacizumab, promotes in vitro tenogenic differentiation and maturation of two distinct types of TSPCs, tendon proper-derived cells (TDCs), and paratenon-derived cells (PDCs) originating from rat Achilles tendon. TDCs and PDCs were isolated from the tendon proper and the paratenon of rat Achilles tendons. TDCs and PDCs were cultured for 3 days on plates with or without VEGF. TDCs and PDCs were also cultured in collagen gel matrix, and the blocking effect of VEGF was examined by the addition of 100 ng/mL of bevacizumab. Effects of bevacizumab on tenogenic differentiation were assessed using real-time PCR, immunofluorescent staining, and western blotting. VEGF significantly attenuated expression of the Tnmd gene in both PDCs and TDCs (P<0.05). Expressions of the Scx, Tnmd, and Col1a1 genes were significantly upregulated by the addition of bevacizumab (P<0.05). Immunofluorescent staining showed that the percentage of tenomodulin-positive PDCs and TDCs was significantly higher with bevacizumab treatment than in control cultures (P<0.05). Western blotting showed that bevacizumab suppressed pVEGFR-2 protein expression in both PDCs and TDCs. Bevacizumab promoted the in vitro tenogenic differentiation and maturation of two distinct TSPCs derived from rat Achilles tendon. Since the previous studies demonstrated that TSPCs have a potential to contribute to tendon repair, attenuating VEGF levels in TSPCs by administration of bevacizumab is a novel candidate therapeutic option for promoting tendon repair.
Topics: Rats; Animals; Vascular Endothelial Growth Factor A; Bevacizumab; Cell Differentiation; Achilles Tendon; Stem Cells
PubMed: 37906574
DOI: 10.1371/journal.pone.0293463