Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing. This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve (B. breve). A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing. The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography (micro-CT). Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay (ELISA). The senescence and biological functions were tested in oral mucosal stem cells (OMSCs) treated with sunitinib. Ligated loop experiments were used to investigate the effect of oral B. breve. Neutralizing antibody for interleukin-10 (IL-10) was used to prove the critical role of IL-10 in the pro-healing process derived from B. breve. Results showed that sunitinib caused oral mucosal wound healing impairment in mice. In vitro, sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation, migration, and differentiation. Oral administration of B. breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells (DCs)-derived IL-10. IL-10 reversed cellular senescence caused by sunitinib in OMSCs, and IL-10 neutralizing antibody blocked the ameliorative effect of B. breve on oral mucosal wound healing under sunitinib treatment conditions. In conclusion, sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B. breve could improve wound healing impairment via intestinal DCs-derived IL-10.
Animals ; Mice ; Interleukin-10 ; Bifidobacterium breve ; Up-Regulation ; Angiogenesis Inhibitors ; Sunitinib ; X-Ray Microtomography ; Administration, Oral ; Wound Healing ; Antibodies, Neutralizing

BACKGROUNDEndostatin is a potent inhibitor of tumor angiogenesis. In the preliminary studies, we developed a mutant endostatin containing Arg-Gly-Asp-Arg-Gly-Asp (RGDRGD) sequences. In this study, we compared the antitumor effects of mutant endostatin and Bcl-2 antisense oligonucleotides both in combination and individually.

METHODSThe artificially synthesized Bcl-2 ASODN (antisense oligonucleotides) included a translation-initiation site and was transfected into the bladder cancer cells by Lipofectamine. Cell growth was investigated by the tumor cell growth chart, MTT assay, caspase-3 activity detection assay, AO/EB fluorescein stain, and the annexin V-FITC apoptosis detection assay. In the in vivo study, UM-UC-3 bladder cancer cells were subcutaneously implanted into nude mice and the growth of tumor was examined. The ultrastructure of the tumor tissues in the treated and control groups were observed.

RESULTSThe cell growth chart showed that the cell population of the treated combination group decreased by 52.04% compared to the control group. The inhibition rate of the treated combination group was (79.66 ± 6.79)%, whereas those of the individual ASODN and ES groups were (53.39 ± 3.22)% and (50.22 ± 5.46)% respectively. In the caspase-3 activity detection using AO/EB fluorescein stain and annexin V-FITC apoptosis detection assay, the co-inhibitory effect was higher than the individual inhibitory effects (P < 0.05). There were significant differences in the inhibition of the solid tumor growth in the in vivo study.

CONCLUSIONSOur findings indicated that Bcl-2 antisense oligonucleotides enhance the antitumor effects of mutant endostatin both in vitro and in vivo. We noted the synergistic effects of Bcl-2 antisense oligonucleotides combined with mutant endostatin.

Angiogenesis Inhibitors ; administration & dosage ; Animals ; Cell Line, Tumor ; Drug Synergism ; Endostatins ; administration & dosage ; Mice ; Thionucleotides ; administration & dosage ; Urinary Bladder Neoplasms ; pathology

PURPOSE: The purpose of this study was to investigate the myotoxicity of bevacizumab on extraocular muscles in a rabbit model. METHODS: Thirty New Zealand white rabbits were used for this study. The animals were evenly divided into two groups. In the first group, 15 rabbits were treated with intramuscular injections of bevacizumab (1.25 mg/0.05 mL) in the right superior rectus muscle and normal saline solution (0.05 mL) in the left superior rectus muscle. In the second group, 15 rabbits were treated with subconjunctival injections of bevacizumab (2.5 mg/0.1 mL) in the right superior subconjunctival area and normal saline solution (0.1 mL) in the left superior subconjunctival area. Five rabbits in each group were sacrificed at one day, two weeks and four weeks after the injections. Extraocular muscle samples were prepared for light microscopic (LM) and electron microscopic (EM) examination. Degrees of acute inflammation were evaluated via CD-11b immunohistochemistry, and global muscle change was investigated using hematoxylin and eosin stains. Intensity of fibrosis was evaluated using Masson trichrome stains, and ultrastructural changes were observed on EM. RESULTS: We observed no significant inflammatory cell infiltration, muscle necrosis or fibrotic change in treated and control eyes. EM findings revealed no significant damage to muscle or vascular tissue after bevacizumab injection. CONCLUSIONS: We found no signs of extraocular muscle toxicity after LM and EM intramuscular and subconjunctival bevacizumab injections in a rabbit model.
Angiogenesis Inhibitors/*administration & dosage/toxicity ; Animals ; Antibodies, Monoclonal, Humanized/*administration & dosage/toxicity ; Conjunctiva/drug effects ; Injections ; Oculomotor Muscles/*drug effects ; Rabbits

To describe three cases of neovascular glaucoma (NVG) where iris or angle neovascularization regressed remarkably after subconjunctival bevacizumab injections used as the initial treatment before pan retinal photocoagulation (PRP) and/or filtering surgery. Three consecutive NVG patients whose intraocular pressure (IOP) was not controlled with maximal medication were offered an off-label subconjunctival injection of bevacizumab (2.5-3.75 mg/0.1-0.15 mL, Avastin). Bevacizumab was injected into the subconjunctival space close to the corneal limbus in two or three quadrants using a 26-gauge needle. Serial anterior segment photographs were taken before and after the injection. Following subconjunctival injection of bevacizumab, iris or angle neovascularization regressed rapidly within several days. Such regression was accompanied by lowering of IOP in all three cases. The patients underwent subsequent PRP and/or filtering surgery, and the IOP was further stabilized. Our cases demonstrate that subconjunctival bevacizumab injection can be potentially useful as an initial treatment in NVG patients before laser or surgical treatment.
Adult ; Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; *Conjunctiva ; Glaucoma, Neovascular/*drug therapy ; Humans ; Injections, Intraocular ; Iris Diseases/*drug therapy ; Male ; Middle Aged ; Treatment Outcome

Angiogenesis Inhibitors ; administration & dosage ; adverse effects ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Risk Factors ; Thalidomide ; administration & dosage ; adverse effects ; Thromboembolism ; chemically induced ; diagnosis

Adult ; Angiogenesis Inhibitors ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Bevacizumab ; Central Serous Chorioretinopathy ; drug therapy ; Humans ; Intravitreal Injections ; methods ; Male

INTRODUCTIONThe aim of this study was to determine the effectiveness of intraocular injections of bevacizumab for neovascularisation of the iris and neovascular glaucoma.

CLINICAL PICTUREThree patients with neovascularisation of the iris due to various causes were recruited.

TREATMENTPatients were treated with intraocular bevacizumab.

OUTCOMENeovascularisation of the iris was noted to have completely regressed as early as 3 days after the injection and in all the patients (100%) within 8 days after injection. They were followed up for at least 1 month with no clinical evidence of recurrence. Visual acuity remained stable or improved, and the intraocular pressure was controlled in all the 3 patients' eyes. Vitreous haemorrhage also cleared. No signs of inflammation or complications were observed.

CONCLUSIONIntraocular injection of bevacizumab is effective and safe for patients with neovascularisation of the iris and neovascular glaucoma with or without vitreous haemorrhage.

Adult ; Aged ; Angiogenesis Inhibitors ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Bevacizumab ; Glaucoma, Neovascular ; drug therapy ; Humans ; Iris ; blood supply ; Male

Small cell lung cancer (SCLC) is a refractory cancer with high degree of malignancy, rapid disease progression, poor prognosis and easy recurrence. In the past 30 years, the traditional treatment of SCLC, mainly chemotherapy and radiotherapy, has not changed significantly, and the effective treatment method for clinical needs is extremely urgent. The rapid development of precision medicine has revealed the molecular biological characteristics of SCLC, so its diagnosis and treatment will into a new era. At present, some studies have shown that anti-angiogenic drugs, immunotherapy and so on have improved the efficacy of SCLC treatment to some extent, and there are more studies on the diagnosis and treatment of SCLC, so a new field of SCLC treatment are coming and bringing more survival benefits to patients. New studies on targeted therapy, anti-angiogenesis drugs and immunotherapy of molecular pathology of SCLC are emerging. This paper reviews the new diagnosis and treatment methods of SCLC to provide new guidance for its clinical treatment.
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Angiogenesis Inhibitors ; administration & dosage ; Animals ; Humans ; Immunologic Factors ; administration & dosage ; Immunotherapy ; Lung Neoplasms ; diagnosis ; drug therapy ; Small Cell Lung Carcinoma ; diagnosis ; drug therapy

No abstract available.
Angiogenesis Inhibitors/administration & dosage/*therapeutic use ; Antineoplastic Agents, Alkylating/administration & dosage/*therapeutic use ; Humans ; Melphalan/administration & dosage/*therapeutic use ; Multiple Myeloma/*drug therapy ; Prednisone/therapeutic use ; Thalidomide/administration & dosage/*therapeutic use ; Treatment Outcome

No abstract available.
Aged ; Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal/*administration & dosage ; Female ; Glucocorticoids/*administration & dosage ; Humans ; Injections, Intraocular ; Macular Edema/*drug therapy/etiology ; Male ; Middle Aged ; Retinal Vein Occlusion/*complications ; Triamcinolone Acetonide/*administration & dosage ; Vitreous Body