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1.
Vestn Oftalmol ; 136(6. Vyp. 2): 147-154, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33371643

RESUMO

PURPOSE: To compare the effectiveness and safety of panretinal laser photocoagulation targeting far-periphery (sPRP) versus conventional panretinal laser photocoagulation (cPRP) in patients with ischemic central retinal vein occlusion (iCRVO) in terms of the degree of macular edema. MATERIAL AND METHODS: The study included eight (5 males and 3 females, mean age 59.4±17.2 years) and seven (6 males and 1 female, mean age 75.7±9.1 years) patients in sPRP and cPRP groups, respectively. iCRVO was defined as a CRVO case with baseline best corrected visual acuity (BCVA) of <0.2, central retinal thickness (CRT) of >500 µm and severe intraretinal hemorrhages. sPRP included dense photocoagulation of far-periphery over 360˚ and standard photocoagulation of the mid-periphery. Primary outcome measures were CRT and macular volume at the end of the follow-up. BCVA served as the secondary outcome measure. RESULTS: The median of the follow-up period was 9.5 months (ranged from 1.5 to 19 months). In the sPRP group, at the end of the follow-up both CRT and macular volume significantly decreased from 892.0±149.4 µm to 391.8±131.2 µm (p<0.001) and from 16.6±4.1 mm3 to 9.7±1.4 mm3, respectively (p=0.008). In the cPRP group, at the end of the follow-up CRT and macular volume changes were statistically insignificant: from 761.0±162.1 µm to 705.0±181.8 µm (p=0.46) and from 13.6± 3.2 mm3 to 11.8±1.7 mm3, respectively (p=0.38). At the end of the follow-up, cPRP group did not have changes in BCVA, while in the sPRP group BCVA increased statistically significantly from 1.45±0.6 LogMAR (≈0.06) to 1.1±0.6 LogMAR (≈0.14) (p=0.03). There were no adverse events or complications associated with laser treatment in any of the study patients. CONCLUSION: This study demonstrates the superiority of sPRP compared with cPRP for treatment of patients with iCRVO, showing that selective laser treatment of the far-periphery results in significant reduction of macular edema associated with severe retinal ischemia.


Assuntos
Oclusão da Veia Retiniana , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Feminino , Humanos , Injeções Intravítreas , Isquemia , Fotocoagulação a Laser , Lasers , Masculino , Pessoa de Meia-Idade , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/cirurgia , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
2.
Vestn Oftalmol ; 136(6. Vyp. 2): 227-234, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33371654

RESUMO

Age-related macular degeneration is an advanced chronic disease and the main cause of vision loss in geriatric patients. Optical coherence tomography (OCT) is a modern method of retinal imaging allowing to detect different types of fluid: intraretinal fluid (IRF), subretinal fluid (SRF) and fluid under pigment epithelial detachment (PED). Finding relevant imaging biomarkers is necessary for identification of basic activity criteria of the disease, choosing treatment algorithms, determining treatment duration and termination criteria, and predicting the outcomes. Presence of IRF is associated with poor functional outcomes. Its presence is an indication for early beginning of treatment aimed at full resorption of the fluid with further possible careful extension of anti-VEGF therapy intervals with a regular follow-up. Degenerative intraretinal cysts developing in the background of subretinal fibrosis in absence of choroidal neovascularization (CNV) should be a sign for discontinuation of anti-VEGF therapy due to the lack of targets. Presence of SRF is associated with favorable outcomes and good treatment prognosis and is not a barrier to the extension of treatment intervals even up to the maximum of 16 weeks as described in existing randomized controlled trials, on the condition of no other CNV activity. PED with active CNV is one of the biomarkers that reveal the need for long-term aggressive therapy. In case of its size gain, it is necessary to restart the anti-VEGF treatment to prevent visual loss in the long-term. Combination of different fluid types is a sign of lasting disease history with a poor outcome prognosis. In this case, anti-VEGF treatment should be started as soon as possible with long-term fixed regimen or Treat-and-extend (T&E) with minimal suitable interval for the patient and precise monitoring of the condition of retina until complete suppression of activity. Developing a personalized approach in each case plays an important role in preserving visual functions.


Assuntos
Neovascularização de Coroide , Degeneração Macular , Idoso , Inibidores da Angiogênese/uso terapêutico , Biomarcadores , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologia , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Prognóstico , Ranibizumab/uso terapêutico , Retina , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual
3.
Drugs Today (Barc) ; 56(11): 699-704, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33332477

RESUMO

Given the success in stabilizing vision with current anti-vascular endothelial growth factor (VEGF) options, one main target for future anti-VEGF drug development includes creating medications with longer durations of action. Achieving this goal will decrease the number of overall injections and follow-up visits required to ensure better patient compliance. The smallest anti-VEGF created so far is brolucizumab (Beovu; Novartis). It is a 26-kDa IgG single-chain antibody fragment that delivers 11 times more anti-VEGF per injection than aflibercept. Brolucizumab was approved by the U.S. Food and Drug Administration (FDA) in late 2019 for the treatment of wet age-related macular degeneration, and has been also approved for the same indication in Japan and the European Union in 2020. In this article, we compare brolucizumab to current FDA-approved anti-VEGF treatments, address the studies associated with brolucizumab, discuss brolucizumab's side effects, and conclude with recommendations.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Degeneração Macular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Humanos , Injeções Intravítreas , Japão , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão
4.
Bull Cancer ; 107(12): 1260-1273, 2020 Dec.
Artigo em Francês | MEDLINE | ID: mdl-33160607

RESUMO

Meningeal fibrous solitary tumors/hemangiopericytoma are rare and aggressive mesenchymal neoplasms considered as sarcomas. They represent less than 1% of intracranial tumors and derive from the pericytes of Zimmerman which permit capillary contraction. They tend to occur more often in males in the fifth decade. They are often revealed by intracranial hypertension. Some scannographic and MRI characteristics permit to distinguish meningeal fibrous solitary tumor/hemangiopericytoma from other meningeal tumors. Meningeal hemangiopericytoma and fibrous solitary tumors were considered as different entities until 2016. Following the discovery of an identical genetic event, the locus 12q13 chromosome inversion leading to a NAB2-STAT6 fusion with nuclear immunoreactivity for STAT6 protein, the 2016 WHO classification defines these tumors as a single entity. Meningeal fibrous solitary tumors/hemangiopericytoma have a high recurrence rate. Long-term recurrences may occur. Local relapses are more frequent than extracranial metastasis. A multimodal management is recommended to treat a localized disease. It involves a complete resection followed by adjuvant radiotherapy. When local recurrences occur, surgery or stereotactic radiosurgery permit sometimes a local control. Metastatic disease has a poor prognostic and a weak chimiosensitivity. Targeted therapies, like pazopanib, are a hopeful option.


Assuntos
Hemangiopericitoma , Neoplasias Meníngeas , Doenças Raras , Tumores Fibrosos Solitários , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Inversão Cromossômica , Cromossomos Humanos Par 12 , Ensaios Clínicos como Assunto , Embolização Terapêutica , Feminino , Hemangiopericitoma/diagnóstico por imagem , Hemangiopericitoma/genética , Hemangiopericitoma/patologia , Hemangiopericitoma/terapia , Humanos , Hipertensão Intracraniana/etiologia , Imagem por Ressonância Magnética , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/terapia , Recidiva Local de Neoplasia , Proteínas de Fusão Oncogênica/genética , Inibidores de Proteínas Quinases/uso terapêutico , Radioterapia Adjuvante , Doenças Raras/diagnóstico por imagem , Doenças Raras/genética , Doenças Raras/patologia , Doenças Raras/terapia , Proteínas Repressoras/genética , Fator de Transcrição STAT6/genética , Tumores Fibrosos Solitários/diagnóstico por imagem , Tumores Fibrosos Solitários/genética , Tumores Fibrosos Solitários/patologia , Tumores Fibrosos Solitários/terapia , Tomografia Computadorizada de Emissão , Ultrassonografia
5.
Yonsei Med J ; 61(12): 1042-1049, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33251778

RESUMO

PURPOSE: Malignant gliomas are aggressive spinal cord tumors. In this study, we hypothesized that combination therapy using an anti-angiogenic agent, bevacizumab, and hypoxia-inducible glioblastoma-specific suicide gene could reduce tumor growth. MATERIALS AND METHODS: In the present study, we evaluated the effect of combination therapy using bevacizumab and pEpo-NI2-SV-TK in reducing the proliferation of C6 cells and tumor growth in the spinal cord. Spinal cord tumor was generated by the injection of C6 cells into the T5 level of the spinal cord. Complexes of branched polyethylenimine (bPEI)/pEpo-NI2-SV-TK were injected into the spinal cord tumor. Bevacizumab was then administered by an intraperitoneal injection at a dose of 7 mg/kg. The anti-cancer effects of combination therapy were analyzed by histological analyses and magnetic resonance imaging (MRI). The Basso, Beattie and Bresnahan scale scores for all of the treatment groups were recorded every other day for 15 days to assess the rat hind-limb strength. RESULTS: The complexes of bPEI/pEpo-NI2-SV-TK inhibited the viability of C6 cells in the hypoxia condition at 5 days after treatment with ganciclovir. Bevacizumab was decreased in the cell viability of human umbilical vein endothelial cells. Combination therapy reduced the tumor size by histological analyses and MRI. The combination therapy group showed improved hind-limb function compared to the other groups that were administered pEpo-NI2-SV-TK alone or bevacizumab alone. CONCLUSION: This study suggests that combination therapy using bevacizumab with the pEpo-NI2-SV-TK therapeutic gene could be useful for increasing its therapeutic benefits for intramedullary spinal cord tumors.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Glioma/patologia , Neoplasias da Medula Espinal/terapia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Terapia Combinada , Células Endoteliais/patologia , Elementos Facilitadores Genéticos , Eritropoetina/genética , Genes Reporter , Genes Transgênicos Suicidas , Glioblastoma/patologia , Membro Posterior/diagnóstico por imagem , Injeções Intraperitoneais , Imagem por Ressonância Magnética , Ratos , Neoplasias da Medula Espinal/patologia
7.
Proc Natl Acad Sci U S A ; 117(45): 27811-27819, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33109723

RESUMO

Oxygen heterogeneity in solid tumors is recognized as a limiting factor for therapeutic efficacy. This heterogeneity arises from the abnormal vascular structure of the tumor, but the precise mechanisms linking abnormal structure and compromised oxygen transport are only partially understood. In this paper, we investigate the role that red blood cell (RBC) transport plays in establishing oxygen heterogeneity in tumor tissue. We focus on heterogeneity driven by network effects, which are challenging to observe experimentally due to the reduced fields of view typically considered. Motivated by our findings of abnormal vascular patterns linked to deviations from current RBC transport theory, we calculated average vessel lengths [Formula: see text] and diameters [Formula: see text] from tumor allografts of three cancer cell lines and observed a substantial reduction in the ratio [Formula: see text] compared to physiological conditions. Mathematical modeling reveals that small values of the ratio λ (i.e., [Formula: see text]) can bias hematocrit distribution in tumor vascular networks and drive heterogeneous oxygenation of tumor tissue. Finally, we show an increase in the value of λ in tumor vascular networks following treatment with the antiangiogenic cancer agent DC101. Based on our findings, we propose λ as an effective way of monitoring the efficacy of antiangiogenic agents and as a proxy measure of perfusion and oxygenation in tumor tissue undergoing antiangiogenic treatment.


Assuntos
Circulação Sanguínea/fisiologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/fisiopatologia , Inibidores da Angiogênese/uso terapêutico , Animais , Biomarcadores Tumorais/fisiologia , Linhagem Celular Tumoral , Eritrócitos/metabolismo , Heterogeneidade Genética , Hematócrito , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Biológicos , Modelos Teóricos , Neoplasias/tratamento farmacológico , Oxigênio/metabolismo , Perfusão
8.
Cesk Slov Oftalmol ; 76(2): 88-93, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33126803

RESUMO

PURPOSE: To assess the effect of intravitreal aflibercept on pigment epithelial detachment (PED) secondary to occult choroidal neovascularization (CNV) in treatment-naive patients. PATIENTS AND METHODS: Retrospective analysis of thirty-six patients (thirty-eight eyes) with mean age 77 (SD ± 7), who were treated with aflibercept 2.0 mg (Eylea, Bayer) at the Department of Ophthalmology of 1st Faculty of Medicine of the Charles University and the Military University Hospital Prague. All patients were treated in fixed regimen, which means 3 loading doases 1 month apart, followed by further 2-monthly doses over total 12-month period. Best corrected visual acuity (BCVA) was evaluated on Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Diameters as PED height, width and central retinal thickness (CRT) were assesed using spectral-domain optical coherence tomography. All previously mentioned were analyzed et the baseline and than at every visit. Therapy complications were also evaluated. RESULTS: Borderline significant improvement in the mean of BCVA score of 3.2 letters (SD ± 11.6, p = 0.05) at the end of follow-up period was observed. Mean PED height at 12 months significantly decreased by 140 µm (SD ± 238, p < 0.01). Reductions in PED height were correlated with reductions in central macular thickness (R = 0.94, p < 0.001) simultaneously with PED width (R = 0.45, p < 0.01). There was no significant correlation between PED height decrease and visual acuity. PED rupture was observed in 3 eyes (8 %). CONCLUSION: Aflibercept intravitreal therapy in fixed regimen in patients with PED secondary to occult CNV shows great anatomical effect. However, correlation between PED diameters and visual acuity was not observed.


Assuntos
Descolamento Retiniano , Epitélio Pigmentado da Retina , Idoso , Inibidores da Angiogênese/uso terapêutico , Humanos , Injeções Intravítreas , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Descolamento Retiniano/complicações , Descolamento Retiniano/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica
9.
Cesk Slov Oftalmol ; 76(4): 1-3, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33086850

RESUMO

The issue of macular retinal degeneration is one of the key areas of ophthalmology. Recent advances in the targeted delivery of vascular endothelial growth factor (VEGF) suppressants have significantly impacted the patient's prognosis in the form of a significant deceleration in disease progression. Some of the drugs have gradually found their use in other indications (central retinal vein occlusion or diabetic macular edema). The following text gives a brief look at the physiology of VEGF, but not only in the eye, but throughout the human body, particularly in the context of adverse effects resulting from systemic inhibition of its effects.


Assuntos
Retinopatia Diabética , Degeneração Macular , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual
10.
PLoS One ; 15(10): e0241343, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112920

RESUMO

This study aims to investigate the changes in metamorphopsia after administering the treat-and-extend regimen of anti-vascular endothelial growth factor therapy for branch retinal vein occlusion-associated macular edema. We retrospectively examined 27 patients (27 eyes) with macula edema due to branch retinal vein occlusion who received intravitreal injections of anti-vascular endothelial growth factor agents using the treat-and-extend regimen for ≥18 months. We evaluated best-corrected visual acuity, central macular thickness, macular edema recurrence, and amount of metamorphopsia quantified by M-CHARTS. The best-corrected visual acuity (logarithm of minimum angle of resolution) and central macular thickness significantly improved at 18 months compared to baseline, the median value (interquartile range [IQR]), 0.30 (0.15-0.52) and 459 (373-542) µm at baseline, and 0 (-0.08-0.16) and 267 (232-306) µm at 18 months. The M-CHARTS score (the mean of vertical and horizontal scores) significantly decreased at 1, 6, and 12 months compared to baseline, but worsened at 18 month, the median value (IQR), 0.45 (0.250-0.925), 0.4 (0.15-0.70), 0.4 (0.150-0.625), 0.4 (0.225-0.550) and 0.45 (0.225-0.750) at baseline, 1 month, 6 months, 12 months and 18 months, respectively. The median cumulative number of macular edema recurrences was 2 (IQR, 0.5-3.0) at 18 months. Simple linear regression and multivariate analyses revealed that the change in the mean M-CHARTS score at 18 months was significantly correlated with the baseline score and the cumulative number of macular edema recurrences. Anti-vascular endothelial growth factor therapy using the treat-and-extend regimen improved metamorphopsia in branch retinal vein occlusion-related macular edema in the short to mid-term follow-up period, but not in the long term. Macular edema recurrence may be associated with persistent metamorphopsia.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Edema Macular/complicações , Edema Macular/tratamento farmacológico , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Transtornos da Visão/complicações , Idoso , Inibidores da Angiogênese/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fator A de Crescimento do Endotélio Vascular/metabolismo , Acuidade Visual
11.
Graefes Arch Clin Exp Ophthalmol ; 258(12): 2621-2628, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33009973

RESUMO

PURPOSE: To estimate the impact of delayed care during the coronavirus disease 2019 (COVID-19) pandemic on the outcomes of patients with neovascular age-related macular degeneration (AMD). METHODS: Consecutive patients with diagnosis of neovascular AMD were consecutively enrolled between March 9, 2020, and June 12, 2020, (during and immediately after the Italian COVID-19 quarantine). During the inclusion (or pandemic) visit (V0), patients received a complete ophthalmologic evaluation, including optical coherence tomography (OCT). Best-corrected visual acuity (BCVA) and OCT findings from the two preceding visits (V-1 and V-2) were compared with data at V0. RESULTS: One-hundred patients (112 eyes) were enrolled in this study. The time interval between following visits was 110.7 ± 37.5 days within V0 and V-1 and 80.8 ± 39.7 days within V-1 and V-2, respectively (P < 0.0001). BCVA was statistically worse at the V0 visit as compared with the immediately preceding (V-1) visit (0.50 ± 0.43 LogMAR and 0.45 ± 0.38 LogMAR at the V0 and V-1 visits, respectively; P = 0.046). On structural OCT, 91 out of 112 (81.2%) neovascular AMD eyes displayed the evidence of exudative disease activity at the V0 visit, while 77 (68.7%) eyes exhibited signs of exudation at the V-1 visit (P = 0.022). No differences in terms of BCVA and OCT findings were detected between the V-1 and V-2 visits. In multiple regression analysis, the difference in BCVA between V0 and V-1 visits was significantly associated with the interval time within these two visits (P = 0.026). CONCLUSION: The COVID-19 pandemic-related postponement in patient care proved to be significantly associated with worse short-term outcomes in these patients.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Betacoronavirus , Neovascularização de Coroide/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Neovascularização Retiniana/tratamento farmacológico , Tempo para o Tratamento , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/uso terapêutico , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/fisiopatologia , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Pandemias , Quarentena , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Neovascularização Retiniana/diagnóstico por imagem , Neovascularização Retiniana/fisiopatologia , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/diagnóstico por imagem , Degeneração Macular Exsudativa/fisiopatologia
12.
Medicine (Baltimore) ; 99(43): e22349, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120735

RESUMO

BACKGROUND: Lung cancer is one of the most common malignant tumors. Non-small cell Lung cancer (NSCLC) accounts for about 85% of the total lung cancer. For patients with resectable early NSCLC, conventional postoperative adjuvant therapy can significantly prolong the overall survival of patients and reduce the risk of tumor recurrence. With the emergence and maturity of molecular targeted therapy and immunotherapy, the strategy of postoperative chemotherapy for lung cancer patients has changed greatly. To evaluate the efficacy of postoperative chemotherapy (platinum based chemotherapy and immunotherapy) with or without radiotherapy for NSCLC patients, we will conduct a systematic review and meta-analysis of published or unpublished randomized controlled trials. METHODS: We will search Pubmed (Medline), Embase, Google Scholar, Cancerlit, and the Cochrane Central Register of Controlled Trials for related studies published without language restrictions before June 20, 2021. Two review authors will search and assess relevant studies independently. Randomized controlled trials and quasi-randomized controlled trials studies will be included. we will perform subgroup analysis in different methods of postoperative adjuvant therapy for patients with resectable early NSCLC. Because this study will be based on published or unpublished records and studies, there is no need for ethics approval. INPLASY registration number: INPLASY202080064. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will compare the efficacy of platinum chemotherapy and immunotherapy in patients with resectable early NSCLC. Since the large sample randomized trials that meet the inclusion criteria of this study may be inadequate, we will consider incorporating some high quality small sample related tests, which may lead to heterogeneity and affect the reliability of the results.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia , Neoplasias Pulmonares/terapia , Compostos de Platina/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Humanos , Metanálise como Assunto , Terapia de Alvo Molecular , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
13.
Klin Monbl Augenheilkd ; 237(11): 1312-1319, 2020 Nov.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-32869243

RESUMO

PURPOSE: Choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD) undergoing anti-VEGF therapy transforms into a fibrotic lesion. This fibrovascular transformation is associated with a great variety of functional and morphological effects. The aim of this study was to investigate the vascular morphology of fibrotic CNV, to compare it with its surrounding tissue and to identify phenotypes using optical coherence tomography angiography (OCTA). METHODS: In 18 eyes with fibrotic CNV in nAMD spectral domain OCT (SD-OCT) and OCTA were performed. The automated segmentation lines were manually adjusted. A slab from 60 µm beneath Bruch's membrane to the inner edge of the subretinal hyperreflective material was applied. Quantitative analysis of the vascular morphology was performed using skeletonized OCTA images. RESULTS: Compared to the perilesional rim, the number of segments per area was significantly lower (234.75 ± 25.68 vs. 255.30 ± 20.34 1/mm2, p = 0.0003) within the fibrovascular lesion. Two phenotypes could be identified within the lesion. The phenotypic traits of cluster 1 were few, long and thick vascular segments; Cluster 2 was characterized by many, short and thin vascular segments (number of segments per area: 219.4 ± 18.8 vs. 258.8 ± 13.2 1/mm2, p = 0.00009, segment length: 49.6 ± 2.7 vs. 45.0 ± 1.3 µm, p = 0.0002, vascular caliber: 26.6 ± 1.2 vs. 23.5 ± 1.8 µm, p = 0.003). The clusters did not differ significantly regarding visual acuity (0.52 ± 0.44 vs. 0.54 ± 0.18 logMAR, p = 0.25), differentiability of subretinal (OR = 3.43, CI = [0.30, 39.64], p = 0.6) and intraretinal fluid (OR = 5.34, CI = [0.48, 89.85], p = 0.14). Less normalized ellipsoid zone (EZ) loss could be observed in cluster 1 (131.0 ± 161.3 vs. 892.4 ± 955.6 1/m, p = 0.006). CONCLUSION: In this study the vascular morphology of fibrotic CNV was analyzed using OCTA. Differences between the lesion and a perilesional rim could be detected. Two phenotypes within the fibrovascular lesion were identified. These morphological clusters could indicate different patterns of fibrovascular transformation of the CNV under long-term anti-VEGF therapy and be useful identifying possible predictive biomarkers in future studies.


Assuntos
Neovascularização de Coroide , Degeneração Macular , Degeneração Macular Exsudativa , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/tratamento farmacológico , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Degeneração Macular/complicações , Degeneração Macular/diagnóstico por imagem , Degeneração Macular/tratamento farmacológico , Tomografia de Coerência Óptica , Degeneração Macular Exsudativa/complicações , Degeneração Macular Exsudativa/diagnóstico por imagem , Degeneração Macular Exsudativa/tratamento farmacológico
14.
Oncogene ; 39(41): 6480-6492, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32879446

RESUMO

Angiogenesis inhibitors, such as the receptor tyrosine kinase (RTK) inhibitor sunitinib, target vascular endothelial growth factor (VEGF) signaling in cancers. However, only a fraction of patients respond, and most ultimately develop resistance to current angiogenesis inhibitor therapies. Activity of alternative pro-angiogenic growth factors, acting via RTK or G-protein coupled receptors (GPCR), may mediate VEGF inhibitor resistance. The phosphoinositide 3-kinase (PI3K)ß isoform is uniquely coupled to both RTK and GPCRs. We investigated the role of endothelial cell (EC) PI3Kß in tumor angiogenesis. Pro-angiogenic GPCR ligands were expressed by patient-derived renal cell carcinomas (PD-RCC), and selective inactivation of PI3Kß reduced PD-RCC-stimulated EC spheroid sprouting. EC-specific PI3Kß knockout (ΕC-ßKO) in mice potentiated the sunitinib-induced reduction in subcutaneous growth of LLC1 and B16F10, and lung metastasis of B16F10 tumors. Compared to single-agent sunitinib treatment, tumors in sunitinib-treated ΕC-ßKO mice showed a marked decrease in microvessel density, and reduced new vessel formation. The fraction of perfused mature tumor microvessels was increased in ΕC-ßKO mice suggesting immature microvessels were most sensitive to combined sunitinib and PI3Kß inactivation. Taken together, EC PI3Kß inactivation with sunitinib inhibition reduces microvessel turnover and decreases heterogeneity of the tumor microenvironment, hence PI3Kß inhibition may be a useful adjuvant antiangiogenesis therapy with sunitinib.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma de Células Renais/patologia , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Renais/patologia , Neovascularização Patológica/patologia , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/genética , Endotélio Vascular/citologia , Endotélio Vascular/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/tratamento farmacológico , Melanoma Experimental/irrigação sanguínea , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos Knockout , Microvasos/efeitos dos fármacos , Microvasos/patologia , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinonas/farmacologia , Pirimidinonas/uso terapêutico , Sunitinibe/farmacologia , Sunitinibe/uso terapêutico , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
J Cancer Res Clin Oncol ; 146(12): 3079-3096, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32902794

RESUMO

PURPOSE: The formation of new blood vessels from previous ones, angiogenesis, is critical in tissue repair, expansion or remodeling in physiological processes and in various pathologies including cancer. Despite that, the development of anti-angiogenic drugs has great potential as the treatment of cancer faces many problems such as development of the resistance to treatment or an improperly selected therapy approach. An evaluation of predictive markers in personalized medicine could significantly improve treatment outcomes in many patients. METHODS: This comprehensive review emphasizes the anticancer potential of flavonoids mediated by their anti-angiogenic efficacy evaluated in current preclinical and clinical cancer research. RESULTS AND CONCLUSION: Flavonoids are important groups of phytochemicals present in common diet. Flavonoids show significant anticancer effects. The anti-angiogenic effects of flavonoids are currently a widely discussed topic of preclinical cancer research. Flavonoids are able to regulate the process of tumor angiogenesis through modulation of signaling molecules such as VEGF, MMPs, ILs, HIF or others. However, the evaluation of the anti-angiogenic potential of flavonoids within the clinical studies is not frequently discussed and is still of significant scientific interest.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Flavonoides/uso terapêutico , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Humanos , Interleucinas/genética , Metaloproteinases da Matriz/genética , Neoplasias/genética , Neoplasias/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética
16.
Indian J Ophthalmol ; 68(10): 2291-2293, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32971697

RESUMO

Coronavirus disease 2019 (COVID-19) is a form of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been declared a pandemic by the World Health Organization (WHO). Ocular manifestations related to COVID-19 are uncommon with conjunctivitis being reported in a few cases. We report a unique case of vasculitic retinal vein occlusion (RVO) secondary to COVID-19 in a 52-year-old patient who presented with the diminution of vision in the left eye 10 days after he tested positive for SARS-CoV-2. All investigations for vasculitis were negative. This case supports the mechanism of thrombo-inflammatory state secondary to the "cytokine-storm" as the pathogenesis for systemic manifestations of COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Infecções Oculares Virais/virologia , Pneumonia Viral/virologia , Vasculite Retiniana/virologia , Oclusão da Veia Retiniana/virologia , Administração Oral , Inibidores da Angiogênese/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Quimioterapia Combinada , Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/tratamento farmacológico , Angiofluoresceinografia , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravítreas , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Ranibizumab/uso terapêutico , Vasculite Retiniana/diagnóstico , Vasculite Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
17.
Am J Clin Oncol ; 43(9): 621-627, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889831

RESUMO

OBJECTIVES: Despite the initial clinical benefit, resistance to antiangiogenic therapies develops through the activation of alternative pathways. We measured plasma levels of circulating angiogenic factors to explore their predictive role in metastatic renal cell carcinoma (mRCC) patients treated with pazopanib. MATERIALS AND METHODS: mRCC patients receiving first-line pazopanib were prospectively enrolled. The levels of circulating interleuchine (IL)-6, IL-8, stromal derived factor-1, vascular endothelial growth factor-A, hepatocyte growth factor (HGF), osteopontin, and E-selectin were quantified at baseline and every 4 weeks until disease progression (PD). Patients were dichotomized into "low" and "high" subgroups by a cutoff point defined by the respective median circulating angiogenic factor (CAF) value at baseline. Then, association with the objective response was determined. Changes in CAF levels between baseline and PD were also compared. RESULTS: Among 25 patients included in the final data set, 6 patients were still on treatment. As best response, 12 patients presented a partial response (48%), 9 showed stable disease, and 4 showed PD. The median follow-up was 31.9 months. The median progression-free survival was 14.8 months. Low baseline levels of IL-6, IL-8, HGF, and osteopontin were found to be significantly associated with objective response. In addition, patients with low baseline levels of HGF showed longer progression-free survival and overall survival, whereas patients with low baseline levels of IL-8 showed longer overall survival. Among patients experiencing PD, the median plasma levels of stromal derived factor-1 and vascular endothelial growth factor-A were significantly higher compared with the baseline (P=0.01; P=0.011). Conversely, the median levels of E-selectin were significantly lower compared with the baseline (P=0.017). CONCLUSION: Changes in levels of selected CAFs were associated with response/resistance to pazopanib in mRCC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/secundário , Quimiocina CXCL12/sangue , Progressão da Doença , Selectina E/sangue , Feminino , Fator de Crescimento de Hepatócito/sangue , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Neoplasias Renais/sangue , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Osteopontina/sangue , Intervalo Livre de Progressão , Estudos Prospectivos , Critérios de Avaliação de Resposta em Tumores Sólidos , Taxa de Sobrevida , Pesquisa Médica Translacional , Fator A de Crescimento do Endotélio Vascular/sangue
18.
Vestn Oftalmol ; 136(4. Vyp. 2): 207-213, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880141

RESUMO

PURPOSE: To assess the functional results of antiangiogenic therapy in patients with exudative form of age-related macular degeneration (AMD) in real clinical practice. MATERIAL AND METHODS: The study included 90 people (90 eyes) with active choroidal neovascularization (CNV) on the background of AMD. All patients were divided into 6 groups depending on the year of treatment - from 2013 to 2018, all patients were divided into 6 groups and overall the retrospective study sited at Research Institute of Eye Diseases (Moscow) lasted 8 years. All patients underwent standard ophthalmological examination including visometry, biomicroscopy and ophthalmoscopy under drug-induced mydriasis, as well as optical coherence tomography, fundus angiography and OCT-angiography. RESULTS: According to the results of the analysis of OCT data obtained from 2013 to 2017, among all patients with exudative AMD, patients with types I and II of CNV and single patients with RAP prevailed, which explains the high visual acuity - about 0.5 - in all groups after the start of the treatment (table 1 and 2). In 2018, 33.3% of patients were diagnosed with RAP (the same number of eyes as with types I and II of CNV), which can be explained by the introduction of OCT-angiography into wide clinical practice. The lack of increase in visual acuity is most likely associated with a small amount of intravitreal injections (IVI) - 4.8 IVI in the first year and 3.3 IVI in the second injection year. In patients who received more than three IVI in the first year of observation, visual acuity increased from 0.49±0.03 to 0.6±0.03 (p=0.04), in the case of less than three IVI in the first year, visual acuity was not changed, amounting to 0.42±0.1 before and 0.44±0.1 (p=0.655) after the treatment. CONCLUSIONS: Patients of all groups exhibited proportional stabilization of visual acuity, a decrease in the thickness of the retina and total macular volume. The lack of improvements of visual acuity is most likely associated with a small amount of IVI.


Assuntos
Neovascularização de Coroide/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Moscou , Estudos Retrospectivos , Tomografia de Coerência Óptica
19.
Vestn Oftalmol ; 136(4. Vyp. 2): 354-358, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880161

RESUMO

Age-related macular degeneration (AMD) is a leading cause of vision loss both worldwide and in Russia. A distinctive feature of the exudative form of AMD is the presence of choroidal neovascularization (CNV) as a result of pathological angiogenesis of the choroid. With the introduction of optical coherence tomography (OCT) - a non-invasive imaging technique - it has become possible to monitor CNV activity. In the development of CNV, OCT can reveal three types of fluid localization: intraretinal fluid (IRF), subretinal fluid, fluid under retinal pigment epithelium (RPE). Exudative IRF is characterized by the presence of round and/or oval space. This type of fluid is characterized by good response to anti-VEGF therapy. Degenerative IRF («cystoid degeneration¼) is characterized as a small, clearly defined hyporeflective spaces above the area with altered RPE not responding to anti-VEGF therapy. Thus, early diagnosis of AMD and detection of «new activity¼ after therapy with antivascular endothelial growth factor (anti-VEGF) by comparing distribution of the fluid in SD-OCT are critical to maintaining or restoring the best possible visual acuity in patients with this disease.


Assuntos
Neovascularização de Coroide/diagnóstico , Degeneração Macular , Inibidores da Angiogênese/uso terapêutico , Diagnóstico Diferencial , Angiofluoresceinografia , Humanos , Federação Russa , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular
20.
Zhonghua Zhong Liu Za Zhi ; 42(8): 624-628, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867452

RESUMO

Small cell lung cancer (SCLC), a special type of lung cancer, is a highly malignant neuroendocrine tumor with strong invasiveness and rapid progression. SCLC is sensitive to radiotherapy and chemotherapy, so radiotherapy and chemotherapy have been the main first-line treatment of SCLC. However, it is easy to develop drug resistance after treatment. Therefore, the study of anti-angiogenic therapy has attracted more and more attention. At present, anti-angiogenic drugs mainly focus on four categories: monoclonal antibodies (such as bevacizumab), endogenous angiogenesis inhibitors (such as endostar), anti-angiogenic fusion protein (such as aflibercept) and small molecular tyrosine kinase inhibitors (such as anlotinib). There are still some bottlenecks in the research and clinical application of antiangiogenic drugs. It is the right direction to explore better combination therapy and effective dual-field and multi-target drugs.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacologia , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Neovascularização Patológica/patologia , Medicina de Precisão , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
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