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1.
Adv Exp Med Biol ; 1256: 67-88, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33847998

RESUMEN

Aging is associated with a number of histological changes in the choroid, Bruch's membrane, RPE, and neuroretina. Outside of the normal physiologic aging spectrum of changes, abnormal deposits such as basal laminar deposits, basal linear deposits, and soft drusen are known to be associated with AMD. Progression of AMD to advanced stages involving geographic atrophy, choroidal neovascularization, and/or disciform scars can result in debilitating vision loss. Knowledge of the angiogenic pathway and its components that stimulate neovascularization has led to the development of a new paradigm of intravitreal anti-VEGF pharmacotherapy in the management of neovascular AMD. Currently however, there are no available treatments for the modification of disease progression in non-neovascular AMD, or for the treatment of geographic atrophy. Further understanding of the histopathology of AMD and the molecular mechanisms that contribute to pathogenesis of the disease may reveal additional therapeutic targets.


Asunto(s)
Inhibidores de la Angiogénesis , Degeneración Macular Húmeda , Inhibidores de la Angiogénesis/uso terapéutico , Lámina Basal de la Coroides , Humanos , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual
2.
Adv Exp Med Biol ; 1256: 295-314, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33848007

RESUMEN

Age-related macular degeneration (AMD) remains a leading cause of blindness worldwide. The assessment and management of patients with this condition has evolved in the last decades. In this chapter, current standards for diagnosis, follow-up, and treatment of patients with AMD are reviewed and summarized. Namely, we highlight how current assessment has moved from conventional ophthalmoscopy and fluorescein angiography testing to a multimodal approach, and its important advantages. Alternatives to visual acuity for functional assessment of patients with AMD are also presented. Regarding strategies for follow-up and treatment, we provide specific information for the different stages (i.e., early, intermediate, and late) and forms (for example, choroidal neovascularization and geographic atrophy) of AMD. Specifically, we discuss the relevance and options for self-monitoring and non-pharmacological interventions. Additionally, a summary of the important trials (both on exudative and non-exudative AMD) that have helped inform clinical practice is provided, including data on antiangiogenic agents currently available, and outcomes of the different regimens that have been studied. The influence of advances in imaging on treatment strategies is also discussed.In summary, this chapter is a resource for all clinicians engaged in providing state of the art care for patients with AMD, and can help improve diagnosis, management, and outcomes of individuals with this blinding condition.


Asunto(s)
Neovascularización Coroidal , Degeneración Macular , Inhibidores de la Angiogénesis/uso terapéutico , Angiografía con Fluoresceína , Humanos , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/terapia , Tomografía de Coherencia Óptica
3.
Cell Prolif ; 54(4): e13009, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33655556

RESUMEN

The sites of targeted therapy are limited and need to be expanded. The FGF-FGFR signalling plays pivotal roles in the oncogenic process, and FGF/FGFR inhibitors are a promising method to treat FGFR-altered tumours. The VEGF-VEGFR signalling is the most crucial pathway to induce angiogenesis, and inhibiting this cascade has already got success in treating tumours. While both their efficacy and antitumour spectrum are limited, combining FGF/FGFR inhibitors with VEGF/VEGFR inhibitors are an excellent way to optimize the curative effect and expand the antitumour range because their combination can target both tumour cells and the tumour microenvironment. In addition, biomarkers need to be developed to predict the efficacy, and combination with immune checkpoint inhibitors is a promising direction in the future. The article will discuss the FGF-FGFR signalling pathway, the VEGF-VEGFR signalling pathway, the rationale of combining these two signalling pathways and recent small-molecule FGFR/VEGFR inhibitors based on clinical trials.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias/tratamiento farmacológico , Transducción de Señal , Inhibidores de la Angiogénesis/farmacología , Anticuerpos Monoclonales/uso terapéutico , Factores de Crecimiento de Fibroblastos/metabolismo , Humanos , Neoplasias/patología , Polimorfismo de Nucleótido Simple , Receptores de Factores de Crecimiento de Fibroblastos/genética , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo
4.
Molecules ; 26(4)2021 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-33546106

RESUMEN

Cancer is one of the leading causes of death worldwide, with a mortality rate of more than 9 million deaths reported in 2018. Conventional anti-cancer therapy can greatly improve survival however treatment resistance is still a major problem especially in metastatic disease. Targeted anti-cancer therapy is increasingly used with conventional therapy to improve patients' outcomes in advanced and metastatic tumors. However, due to the complexity of cancer biology and metastasis, it is urgent to develop new agents and evaluate the anti-cancer efficacy of available treatments. Many phytochemicals from medicinal plants have been reported to possess anti-cancer properties. One such compound is known as oridonin, a bioactive component of Rabdosia rubescens. Several studies have demonstrated that oridonin inhibits angiogenesis in various types of cancer, including breast, pancreatic, lung, colon and skin cancer. Oridonin's anti-cancer effects are mediated through the modulation of several signaling pathways which include upregulation of oncogenes and pro-angiogenic growth factors. Furthermore, oridonin also inhibits cell migration, invasion and metastasis via suppressing epithelial-to-mesenchymal transition and blocking downstream signaling targets in the cancer metastasis process. This review summarizes the recent applications of oridonin as an anti-angiogenic and anti-metastatic drug both in vitro and in vivo, and its potential mechanisms of action.


Asunto(s)
Inhibidores de la Angiogénesis , Antineoplásicos Fitogénicos , Diterpenos de Tipo Kaurano , Isodon/química , Neoplasias , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/uso terapéutico , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/uso terapéutico , Humanos , Neoplasias/irrigación sanguínea , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Transducción de Señal/efectos de los fármacos
5.
Vestn Oftalmol ; 137(1): 83-93, 2021.
Artículo en Ruso | MEDLINE | ID: mdl-33610155

RESUMEN

The problem associated with the prevalence of retinal diseases, and age-related macular degeneration (AMD) in particular, is undoubtedly relevant. This aspect is based on steadily growing statistics on morbidity, a high number of randomized controlled trials (RCT) and published real world data (RWD). The analysis of RCT results being published by researchers on 15.05.19 showed 2915 studies were registered on the subject of retinal diseases; that exceeds the number of studies on glaucoma by approximately 1.38 times (2118 studies) and conjunctival lesions by 2.37 times (1230 studies). AMD is one of the leading causes of irreversible vision loss and blindness; its neovascular form leads to blindness in 80-90% of all cases. Even though the topic of nAMD therapy is widely highlighted in modern ophthalmology, today there are many aspects that require targeted solutions. The main controversial issues that determine the complexity of therapy and patient management include discrepancies in determination of reference points (disease activity criteria) for implementation of anti-VEGF dosing regimens, patients' compliance, prioritization issues in treatment, its continuity with potential for the increase of intervals between injections and monitoring visits.


Asunto(s)
Degeneración Macular , Degeneración Macular Húmeda , Inhibidores de la Angiogénesis/uso terapéutico , Humanos , Inyecciones Intravítreas , Degeneración Macular/diagnóstico , Degeneración Macular/tratamiento farmacológico , Ranibizumab/uso terapéutico , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/tratamiento farmacológico
6.
JAMA Netw Open ; 4(2): e2037880, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33616665

RESUMEN

Importance: Ten percent of the Medicare Part B budget is spent on aflibercept, used to treat a myriad of ocular neovascular diseases. A substantial portion of these costs can be attributed to a few hundred ophthalmologists, raising concerns regarding the influence of pharmaceutical companies on the choice of medication by a relatively small group of clinicians. One approach to protect patients' health care interests is to include them in deliberations on the choice of therapy for their eye disease. Objective: To examine factors associated with patients' choice between an effective and less expensive off-label drug or a more effective, but also more expensive, US Food and Drug Administration (FDA)-approved drug. Design, Setting, and Participants: This retrospective cohort analysis used data from the satellite office of a tertiary referral center from August 2, 2013, to April 9, 2018. Insured patients initiating treatment with anti-vascular endothelial growth factor were included in the analysis. Data were analyzed from March 26, 2018, to June 10, 2020. Interventions: Patients were asked to choose between bevacizumab (approximately $100 per dose), a chemotherapy that is effective, but not FDA approved, for the treatment of ocular vascular disease, or aflibercept (approximately $2000 per dose), an FDA-approved drug for ocular vascular disease that may be more effective than bevacizumab in some patients. Independent of this choice, patients were separately asked by a study coordinator to participate in an invasive clinical study for which they would not be compensated, there was a small risk for an adverse event, and they would not personally benefit from participating (a surrogate marker for altruism). Main Outcomes and Measures: Factors associated with patients' choice of medication, including age, sex, ocular disease, race, and participation in an invasive clinical study. Results: A total of 189 patients were included in the analysis (106 women [56%]; mean [SEM] age, 74.6 [0.8] years). Despite being told that it may not be as effective as aflibercept, 100 patients (53%) selected bevacizumab for their own eye care. An act of altruism (ie, participation in an invasive clinical study) when the patient was making a choice between the 2 drugs was associated with a patient's choice of bevacizumab (odds ratio [OR], 7.03; 95% CI, 2.27-21.80; P < .001); the OR for selecting bevacizumab for patients who never agreed to participate in the clinical study was 0.45 (95% CI, 0.25-0.83; P = .001). Age (OR, 1.00; 95% CI, 0.97-1.03; P = .86), race (OR, 0.70; 95% CI, 0.41-1.22; P = .21), sex (OR, 0.72; 95% CI, 0.39-1.35; P = .31), presence of diabetes (OR, 1.52; 95% CI, 0.59-3.93; P = .39), and type of eye disease (OR, 0.56; 95% CI, 0.30-1.04; P = .07) were not associated with choice of therapy. Conclusions and Relevance: These findings suggest that clinicians must consider the ethical implications of the influence of altruism when patients participate in the decision between cost-effective vs the most effective medicines for their own health care.


Asunto(s)
Altruismo , Inhibidores de la Angiogénesis/economía , Bevacizumab/economía , Conducta de Elección , Toma de Decisiones , Oftalmopatías/tratamiento farmacológico , Participación del Paciente , Proteínas Recombinantes de Fusión/economía , Afroamericanos , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Americanos Asiáticos , Bevacizumab/uso terapéutico , Estudios de Cohortes , Análisis Costo-Beneficio , Retinopatía Diabética/tratamiento farmacológico , Costos de los Medicamentos , Grupo de Ascendencia Continental Europea , Femenino , Humanos , Degeneración Macular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neovascularización Patológica/tratamiento farmacológico , Oportunidad Relativa , Uso Fuera de lo Indicado , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual
7.
BMC Neurol ; 21(1): 77, 2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33596839

RESUMEN

BACKGROUND: Cerebral radiation injury, including subacute radiation reactions and later stage radiation necrosis, is a severe side effect of brain tumor radiotherapy. A protocol of four infusions of the monoclonal antibody bevacizumab has been shown to be a highly effective treatment. However, bevacizumab is costly and can cause severe complications including thrombosis, bleeding and gastrointestinal perforations. METHODS: We performed a retrospective analysis of patients treated in our clinic for cerebral radiation injury who received only a singular treatment with bevacizumab. Single-shot was defined as a singular administration of bevacizumab without a second administration during an interval of at least 6 weeks. RESULTS: We identified 11 patients who had received a singular administration of bevacizumab to treat cerebral radiation injury. Prior radiation had been administered to treat gliomas (ten patients) or breast cancer brain metastases (one patient). 9 of 10 patients with available MRIs showed a marked reduction of edema at first follow-up. Discontinuation of Dexamethasone was possible in 6 patients and a significant dose reduction could be achieved in all other patients. One patient developed pulmonary artery embolism 2 months after bevacizumab administration. The median time to treatment failure of any cause was 3 months. CONCLUSIONS: Single-shot bevacizumab therefore has meaningful activity in cerebral radiation injury, but durable control is rarely achieved. In patients where a complete protocol of four infusions with bevacizumab is not feasible due to medical contraindications or lack of reimbursement, single-shot bevacizumab treatment may be considered.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Bevacizumab/administración & dosificación , Edema Encefálico/tratamiento farmacológico , Lesiones Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Encéfalo/patología , Traumatismos por Radiación/tratamiento farmacológico , Adulto , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Bevacizumab/uso terapéutico , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/etiología , Lesiones Encefálicas/diagnóstico por imagen , Lesiones Encefálicas/etiología , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Dexametasona/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Glioma/radioterapia , Glucocorticoides/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Necrosis , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
8.
PLoS One ; 16(2): e0247161, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33596257

RESUMEN

Regularly scheduled intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are essential to maintaining and/or improving many ocular conditions including: neovascular age-related macular degeneration (nAMD), diabetic retinopathy, and retinal vein occlusions with macular edema (RVO). This study aims to assess the effect of unintended delays in anti-VEGF treatment during the first wave of the COVID-19 pandemic. This retrospective case series identified patients receiving regularly scheduled anti-VEGF intravitreal injections based on current procedural terminology (CPT) code at two practices in Minnesota. Diagnoses were limited to nAMD, diabetic macular edema (DME), proliferative diabetic retinopathy, and RVO. Patients were divided into two groups based on whether they maintained or delayed their follow-up visit by more than two weeks beyond the recommended treatment interval during the COVID-19 lockdown. The 'COVID-19 lockdown' was defined as the period after March, 28th, 2020, when a lockdown was declared in Minnesota. We then compared the visual acuity and structural changes to the retina using ocular coherence tomography (OCT) to assess whether delayed treatment resulted in worse visual outcomes. A total of 167 eyes from 117 patients met criteria for inclusion in this study. In the delayed group, the average BCVA at the pre- and post-lockdown visits were 0.614 and 0.715 (logMAR) respectively (p = 0.007). Central subfield thickness (CST) increased from 341 to 447 in the DME delayed group (p = 0.03) while the CST increased from 301 to 314 (p = 0.4) in the nAMD delayed group. The results of this pilot study suggests that treatment delays may have a negative impact on the visual and anatomic outcomes of patients with nAMD and DME. Future studies with larger sample sizes are required for further investigation.


Asunto(s)
/epidemiología , Enfermedades de la Retina/tratamiento farmacológico , Tiempo de Tratamiento/estadística & datos numéricos , Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Retinopatía Diabética/tratamiento farmacológico , Femenino , Humanos , Edema Macular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Pandemias/estadística & datos numéricos , Proyectos Piloto , Cuarentena/métodos , Cuarentena/psicología , Oclusión de la Vena Retiniana/tratamiento farmacológico , Estudios Retrospectivos , Agudeza Visual/efectos de los fármacos
9.
J Fr Ophtalmol ; 44(3): 299-306, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33608176

RESUMEN

OBJECTIVES: To investigate the effects of the COVID-19 pandemic on the treatment course of neovascular age-related macular degeneration (nAMD) patients who received anti-VEGF injection therapy with real-life data. METHODS: This retrospective study consisted of 116 eyes of 106 patients. Ophthalmic examination, assessment of best-corrected visual acuity (BCVA), optical coherence tomography (OCT) findings and data of last two visits before restrictions (V-2 and V-1) and the first visit (V0) after the release of national lockdown and subsequent visits (V1 and Vlast) were recorded. The lockdown period was determined by the time interval between March 11 and June 1, 2020. MAIN RESULTS: The injection interval before V-1 was significantly longer than the interval after V0 (2.56±0.9 vs. 2.14±0.8 months, P=0.02). While the median central macular thickness (CMT) was significantly increased at V0 compared to V-1 [274(132-711) vs. 238(136-628), P<0.001], the median CMT was significantly lower at V1 compared to V0 [256 (136-591) vs. 274(132-711), P=0.003]. The median BCVA was 0.67(0.1-1.1) logMAR at V-1 and significantly worsened to 0.78 (0.1-1.2) logMAR at V0 (P=0.003). Although the median BCVA improved to 0.69 logMAR (0.1-1.2) at Vlast, the difference did not reach statistical significance compared to V0 (P=0.08). CONCLUSION: Treatment delay due to the COVID-19 pandemic cause progression of nAMD and visual impairment. To plan more frequent anti-VEGF treatments and visits may be an appropriate approach until the disease stabilizes. However, it should be kept in mind that despite the improvement in OCT findings, the desired success in VA could not be achieved in the short term.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Degeneración Macular , Pandemias , Neovascularización Retiniana , Tiempo de Tratamiento , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Diagnóstico Tardío/estadística & datos numéricos , Progresión de la Enfermedad , Femenino , Humanos , Inyecciones Intravítreas , Degeneración Macular/diagnóstico , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/epidemiología , Degeneración Macular/patología , Masculino , Pandemias/estadística & datos numéricos , Examen Físico/estadística & datos numéricos , Pronóstico , Neovascularización Retiniana/diagnóstico , Neovascularización Retiniana/tratamiento farmacológico , Neovascularización Retiniana/epidemiología , Neovascularización Retiniana/patología , Estudios Retrospectivos , Tiempo de Tratamiento/estadística & datos numéricos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Turquia/epidemiología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/inmunología
10.
Ophthalmologe ; 118(3): 248-256, 2021 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-33555415

RESUMEN

The anti-vascular endothelial growth factor (anti-VEGF) agent brolucizumab has been approved in the USA in October 2019 and in Europe in February 2020 for the treatment of neovascular age-related macular degeneration (nAMD). The approval was based on the randomized, double-blind phase III studies HAWK and HARRIER with a total of 1817 patients. Brolucizumab 6 mg (administered every 12 or 8 weeks depending on the activity of the disease) showed a non-inferior efficacy in terms of best-corrected visual acuity compared to aflibercept 2 mg (administered every 8 weeks). Initial reports on the use of brolucizumab after its approval in the USA indicated a safety signal of rare adverse events termed as retinal vasculitis and/or retinal vascular occlusion that may result in severe loss of vision. Typically, these events occurred in the presence of intraocular inflammation (IOI). A safety review committee (SRC) subsequently carried out an independent analysis of data from the pivotal studies. This article sets out the current state of knowledge and aims to provide users with orientation-from the authors' perspective-in treating brolucizumab-associated IOI. It appears mandatory to provide patients with information about possible symptoms of IOI. Even though the case reports and the SRC review of HAWK/HARRIER may not yet provide sufficient evidence for any final conclusions, it seems crucial to educate patients about signs and symptoms to ensure an early detection and diagnosis in cases of IOI. Once a patient is diagnosed with IOI, retinal vasculitis, and/or retinal vascular occlusive events, physicians should act promptly with an adequate and intensive anti-inflammatory treatment and brolucizumab treatment should be discontinued. It is important to note that these recommendations are primarily based on the authors' expert opinions and should be considered as guidance in managing these events rather than a formal protocol or guidelines.


Asunto(s)
Inhibidores de la Angiogénesis , Receptores de Factores de Crecimiento Endotelial Vascular , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados , Humanos , Inflamación/tratamiento farmacológico , Inyecciones Intravítreas , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes de Fusión , Agudeza Visual
11.
Nat Commun ; 12(1): 814, 2021 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-33547300

RESUMEN

On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesize that the anti-vascular endothelial growth factor (VEGF) drug bevacizumab might be beneficial for treating Covid-19 patients. From Feb 15 to April 5, 2020, we conducted a single-arm trial (NCT04275414) and recruited 26 patients from 2-centers (China and Italy) with severe Covid-19, with respiratory rate ≥30 times/min, oxygen saturation ≤93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O2 ratio (PaO2/FiO2) >100 mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest imaging. Followed up for 28 days. Among these, bevacizumab plus standard care markedly improves the PaO2/FiO2 ratios at days 1 and 7. By day 28, 24 (92%) patients show improvement in oxygen-support status, 17 (65%) patients are discharged, and none show worsen oxygen-support status nor die. Significant reduction of lesion areas/ratios are shown in chest computed tomography (CT) or X-ray within 7 days. Of 14 patients with fever, body temperature normalizes within 72 h in 13 (93%) patients. Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our findings suggest bevacizumab plus standard care is highly beneficial for patients with severe Covid-19. Randomized controlled trial is warranted.


Asunto(s)
Bevacizumab/uso terapéutico , /efectos de los fármacos , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Temperatura Corporal/efectos de los fármacos , China , Femenino , Fiebre/prevención & control , Humanos , Italia , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
12.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33526522

RESUMEN

A 44-year-old woman presented with decreased vision in both eyes. The retina in both eyes had drusen distributed along vascular arcades, central macula and in peripapillary region. Macula had pigmented scarring and exudation. Fundus autofluorescence showed drusen. Optical coherence tomography showed drusen, subretinal and intraretinal fluid. Fundus fluorescein and indocyanine green angiography showed drusen, retinal pigment epithelial atrophy and vascular network. Younger age at presentation, bilateral symmetry, typical distribution of drusen along the arcades in a radiating pattern, peripapillary involvement, scarring and atrophy at macula were suggestive of doyne honeycomb retinal dystrophy. The reduced vision was due to macular atrophy and an active choroidal neovascular membrane. The patient was treated with antivascular endothelial growth factor injections for choroidal neovascular membrane. Our case highlights the importance of pattern recognition and multimodal imaging for diagnosing the type of macular dystrophy as doyne honeycomb retinal dystrophy, while simultaneously managing choroidal neovascular membrane.


Asunto(s)
Neovascularización Coroidal/diagnóstico por imagen , Angiografía con Fluoresceína , Tomografía de Coherencia Óptica , Adulto , Inhibidores de la Angiogénesis/uso terapéutico , Angiografía , Neovascularización Coroidal/complicaciones , Neovascularización Coroidal/tratamiento farmacológico , Colorantes , Femenino , Fondo de Ojo , Humanos , Verde de Indocianina , Inyecciones Intravítreas , Imagen Multimodal , Drusas del Disco Óptico/complicaciones , Drusas del Disco Óptico/congénito , Drusas del Disco Óptico/diagnóstico por imagen , Ranibizumab/uso terapéutico
13.
BMJ Case Rep ; 14(2)2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33526528

RESUMEN

A male infant, born preterm at 32 weeks of gestation, was referred at 36-week postmenstrual age for retinopathy of prematurity (ROP) screening. He had nystagmus, generalised hypopigmentation of skin, hair and eyes with preaxial polydactyly. The fundus was depigmented with prominently visible choroidal vessels. The retinal vessels were dilated, tortuous at zone 1. There was presence of arcading, shunting of vessels with presence of vitreous haemorrhage in the left eye. A diagnosis of aggressive posterior retinopathy of prematurity (APROP) in association with oculocutaneous albinism (OCA) was made.Half-dose intravitreal bevacizumab was used to treat the vascular condition. After 2 weeks, there was complete regression of APROP with a completely mature retina observed at 4 months post-treatment. Herein, we describe the role of red-free light for screening ROP in infants with OCA; challenges in the management of ROP with laser photocoagulation compared with intravitreal anti-vascular endothelial growth factor therapy.


Asunto(s)
Albinismo Oculocutáneo/complicaciones , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Retinopatía de la Prematuridad/tratamiento farmacológico , Humanos , Recién Nacido , Recien Nacido Prematuro , Inyecciones Intravítreas , Masculino , Retinopatía de la Prematuridad/complicaciones , Retinopatía de la Prematuridad/diagnóstico
15.
Int J Mol Sci ; 22(2)2021 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-33451055

RESUMEN

Urothelial carcinoma represents one of the most prevalent types of cancer worldwide, and its incidence is expected to grow. Although the treatment of the advanced disease was based on chemotherapy for decades, the developments of different therapies, such as immune checkpoint inhibitors, antibody drug conjugates and tyrosine kinase inhibitors, are revolutionizing the therapeutic landscape of this tumor. This development coincides with the increasing knowledge of the pathogenesis and genetic alterations in urothelial carcinoma, from the non-muscle invasive setting to the metastatic one. The purpose of this article is to provide a comprehensive review of the different tyrosine kinase targets and their roles in the therapeutic scene of urothelial carcinoma.


Asunto(s)
Biomarcadores de Tumor , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/metabolismo , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/etiología , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Ensayos Clínicos como Asunto , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Humanos , Invasividad Neoplásica , Estadificación de Neoplasias , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/etiología , Neoplasias Urológicas/diagnóstico
16.
Anticancer Res ; 41(2): 567-582, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33517262

RESUMEN

The progress of metastatic colorectal cancer (mCRC) depends essentially on two signaling pathways: the first mediated by vascular endothelial growth factor (VEGF) and the second by epidermal growth factor receptor (EGFR). In colorectal cancer (CRC), the balance between pro-angiogenic and anti-angiogenic factors is disturbed in favor of a pro-angiogenic outcome (angiogenic switch) early in the neoplastic progression of adenomas, thus, resulting in neovascularization and eventually in malignant tumor progression. Furthermore, angiogenesis plays an important role in tumor growth and the formation of metastases. Several angiogenic growth factors have been identified to be highly expressed during the progression and metastatic spread of CRC, but VEGFA is the predominant angiogenic cytokine and the most consistently expressed factor during the metastatic process. Agents targeting VEGF/VEGFR signaling have shown efficacy in the treatment of mCRC and are currently approved in this setting. In this review, we summarize the role of antiangiogenic tyrosine kinase inhibitors (TKIs) in the treatment of mCRC, focusing on regorafenib.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neovascularización Patológica , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Piridinas/uso terapéutico , Inhibidores de la Angiogénesis/efectos adversos , Animales , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Humanos , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Tirosina Quinasas/metabolismo , Piridinas/efectos adversos , Transducción de Señal , Resultado del Tratamiento
17.
Paediatr Drugs ; 23(1): 111-117, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33447937

RESUMEN

Ranibizumab (Lucentis®) is a monoclonal antibody fragment targeted against VEGF-A that is the first approved anti-VEGF agent for the treatment of retinopathy of prematurity (ROP). In the pivotal, randomized, phase III RAINBOW trial in infants with ROP, the majority of intravitreal ranibizumab recipients experienced treatment success at 24 weeks, with a numerically greater treatment success rate in the ranibizumab 0.2 mg (80% of patients) than laser therapy (66%) group without reaching statistical significance for superiority. Long-term effects on vision following ranibizumab treatment are not yet known, but interim analyses from the RAINBOW extension study do not show evidence of degraded vision. Adverse reactions to ranibizumab in pediatric patients were consistent with the known safety profile in adults, with most adverse reactions attributed to the intravitreal injection procedure. Furthermore, systemic VEGF suppression was not observed in clinical trials, which is congruent with the rapid systemic clearance of ranibizumab. Overall, ranibizumab is an effective and generally well tolerated treatment for ROP and is not associated with systemic VEGF suppression. Although results for its long-term effects on vision are not yet available, ranibizumab is a promising alternative option to laser therapy for treating ROP.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Ranibizumab/uso terapéutico , Retinopatía de la Prematuridad/tratamiento farmacológico , Inhibidores de la Angiogénesis/farmacología , Humanos , Recién Nacido , Ranibizumab/efectos adversos , Ranibizumab/farmacología , Resultado del Tratamiento
18.
Int J Mol Sci ; 22(2)2021 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-33466790

RESUMEN

Tumor microenvironments are composed of a myriad of elements, both cellular (immune cells, cancer-associated fibroblasts, mesenchymal stem cells, etc.) and non-cellular (extracellular matrix, cytokines, growth factors, etc.), which collectively provide a permissive environment enabling tumor progression. In this review, we focused on the regulation of tumor microenvironment through ubiquitination. Ubiquitination is a reversible protein post-translational modification that regulates various key biological processes, whereby ubiquitin is attached to substrates through a catalytic cascade coordinated by multiple enzymes, including E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes and E3 ubiquitin ligases. In contrast, ubiquitin can be removed by deubiquitinases in the process of deubiquitination. Here, we discuss the roles of E3 ligases and deubiquitinases as modulators of both cellular and non-cellular components in tumor microenvironment, providing potential therapeutic targets for cancer therapy. Finally, we introduced several emerging technologies that can be utilized to develop effective therapeutic agents for targeting tumor microenvironment.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Ubiquitina/metabolismo , Inhibidores de la Angiogénesis/química , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Bibliotecas de Moléculas Pequeñas/química , Enzimas Activadoras de Ubiquitina/metabolismo , Enzimas Ubiquitina-Conjugadoras/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación/efectos de los fármacos
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