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1.
Ocul Oncol Pathol ; 10(3): 139-145, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39224522

RESUMEN

Introduction: The aim of the study was to describe and evaluate characteristics of ocular tumor lysis syndrome (OTLS) in eyes with uveal melanoma. Methods: Retrospective chart review of all patients with OTLS at the University of Colorado from 2009 to 2021. Data collected included patient demographics, tumor characteristics, radiation dosimetry, gene expression profiling (GEP), OTLS characteristics, management, and outcomes. Results: Seven eyes of seven patients with uveal melanoma treated with I-125 brachytherapy developed OTLS. Average age was 59 years (range 32-83). Mean apical height was 8.6 mm (range 6-11); mean diameter was 12.7 mm (range 8.5-15.3). All tumors were treated with plaques ≥16 mm in diameter. On presentation, 5/7 tumors had subretinal fluid, and 6/7 had collar-button configuration. OTLS presented as extensive pigment dispersion in the vitreous in all eyes, subretinal pigment and/or retinal detachment in 4/7 eyes, vitreous hemorrhage in 2/7 eyes, and anterior chamber pigment in 3/7 eyes. Four tumors were GEP class 1, two were class 2, and one was unclassified. Biopsy route was trans-scleral in 4/7 eyes and trans-vitreal in 3/7 eyes. OTLS occurred 2-4 weeks after an intraocular procedure in 5/7 eyes. All underwent pars plana vitrectomy. Cytology of the vitreous, obtained in five cases, showed pigment laden macrophages and hemorrhage, but only 1/5 eyes had viable malignant cells. Four eyes were stable at the last follow-up, two were enucleated, and one had no light perception from pigmentary glaucoma. Poor vision (<20/200) occurred in 6/7 cases. Three patients died from metastasis (tumors were GEP class 2, GEP class without subclassification, and no GEP classification performed). Conclusions: OTLS is a rare but devastating complication of uveal melanoma. Common characteristics included large plaque diameter, presence of subretinal fluid, and collar-button shape. The extensively dispersed pigment is typically not malignant. Though poor vision is common, enucleation may be avoided in most eyes through vitreoretinal surgical repair.

2.
Cell Biochem Biophys ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38913283

RESUMEN

The occurrence and development of ophthalmic diseases are related to the dysfunction of eye tissues. Ubiquitin is an important form of protein post-translational modification, which plays an essential role in the occurrence and development of diseases through specific modification of target proteins. Ubiquitination governs a variety of intracellular signal transduction processes, including proteasome degradation, DNA damage repair, and cell cycle progression. Studies have found that ubiquitin can play a role in eye diseases such as cataracts, glaucoma, keratopathy, retinopathy, and eye tumors. In this paper, the role of protein ubiquitination in eye diseases was reviewed.

3.
Int J Surg Case Rep ; 115: 109242, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38245941

RESUMEN

INTRODUCTION AND IMPORTANCE: Medulloepithelioma is the second most common primary intraocular malignant tumor in children but is often diagnosed late, which worsens the prognosis. CASE PRESENTATION: We are reporting a 6-year-old boy presenting with a ciliary body (CB) teratoid malignant medulloepithelioma (TMM), which was missed at the initial presentation. We added our case to the 97 previously reported cases in our literature review that were confirmed by cytological or histopathological examination. DISCUSSION: Medulloepithelioma has a wide age range at presentation with a mean of 5.3 ± 4.1 years, and slight male predominance (M: F ratio of 1.15). Clinically, the main symptoms/ signs are reduced visual acuity, lens changes, or a pupil "mass." Almost all reported medulloepitheliomas were unilateral (98 %). Histopathologically, non-teratoid malignant medulloepithelioma (NTMM) (35.7 %) and TMM (34.5 %) were the commonest. Enucleation was the main treatment modality because of the large tumor size of 72.7 %. A combination of chemotherapy and/or radiotherapy was used in 15.1 % and brachytherapy for small lesions in 14.1 %. Orbital exenteration was needed in 3 cases because of orbital invasion. CONCLUSION: A CB medulloepithelioma tumor can be easily missed, diagnosed late, with less chance for globe salvaging. The malignant types are more common and may result in orbital invasion, requiring even more extensive surgery. Therefore, when facing a child with lens changes, a pupil "mass," or raised intraocular pressure, pediatricians and general ophthalmologists must have an earlier suspicion and be aware of this rare entity to improve outcomes and reduce loss of vision or other disease-related morbidity.

4.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1022735

RESUMEN

In recent years,deep learning,a pivotal subset of artificial intelligence machine learning,has achieved noteworthy advancements in the medical domain.It facilitates precise detection,diagnosis and prognostic assessment of various diseases through the analysis of medical images.Within ophthalmology,deep learning techniques have found wide-spread application in the diagnosis and prediction of thyroid-related eye diseases,orbital blowout fracture,melanoma,bas-al cell carcinoma,orbital abscess,lymphoma,retinoblastoma and other diseases.Leveraging images from computed tomo-graphy,magnetic resonance imaging and even pathological sections,this technology demonstrates a capacity to diagnose,differentiate and stage orbital diseases and ocular tumors with a high level of accuracy comparable to that of expert clini-cians.The promising prospects of this technology are expected to enhance the diagnosis and treatment of related diseases,concurrently reducing the time and cost associated with clinical practices.This review consolidates the latest research pro-gress on the application of artificial intelligence deep learning in orbital diseases and ocular tumors,aiming to furnish clini-cians with up-to-date information and developmental trends in this field,thereby furthering the clinical application and widespread adoption of this technology.

5.
Front Oncol ; 13: 1118862, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37404770

RESUMEN

Purpose: The purpose of this study is to describe the clinicopathologic characteristics of ocular surface and orbit tumors in the Southeast of China and explore the method to differentiate the benign and malignant masses. Materials and methods: 3468 patients undergoing mass resection from January 2015 to December 2020 were selected as observation subjects and were classified into benign and malignant masses according to postoperative pathology. The clinicopathologic characteristics were collected, including gender, age, pathological tissue signs, and pathological signs. Multivariate Logistic regression analysis of independent risk factors of malignant mass was applied to establish a diagnostic model and the efficacy was evaluated by the subject working characteristics (ROC) curve. Results: Benign tumors accounted for 91.5% of all cases, and malignant tumors accounted for 8.5%. The most common ocular benign tumors were nevi (24.2%), granuloma (17.1%), and cysts (16.4%). The most common ocular malignant tumors were malignant lymphoma (32.1%) and Basal cell carcinoma (20.2%). As for the histologic origin, melanocytic origin was on the list with 819 (23.6%), mesenchymal 661 (19.1%), epithelial 568 (16.3%), cystic 521 (15.0%), skin adnexal 110 (3.1%), lymphoid 94 (2.8%), and Neural 25(0.8%). Based on the gender, age, tumor location, and the pathological tissue image feature (including differentiation, structural atypia, covering epithelial, keratosis, nest structure/distribution, nuclear atypia, cytoplasmic change and nuclear division), the diagnostic model had predictive value to differentiate the benign and malignant masses. Conclusion: Most ocular surface and orbit tumors are benign. Tumor diagnosis is relative to the patient's age, gender, tumor location, and pathologic characteristics. We generated a satisfactory diagnostic model to differential diagnosis of benign and malignant masses.

6.
BMC Ophthalmol ; 23(1): 92, 2023 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-36894878

RESUMEN

BACKGROUND: To report a rare case of IgG4-related ophthalmic disease (IgG4-ROD) manifesting as intraocular masses and scleritis in both eyes in a 61-year-old male and to investigate the changes in multimodal imaging features of the lesion sites and helper T-cell type 1 (Th 1)/Th 2/Th 17 cytokine levels in the aqueous humor. CASE PRESENTATION: A patient with IgG4-ROD seemingly manifested with an intraocular tumor in the left eye and sequentially, with an inflammatory mass in the ciliary body and scleritis in the right eye. The patient complained of vision loss of 6 months duration in the left eye at his first visit. With a preliminary diagnosis of an intraocular tumor, enucleation of the left eyeball and histopathological examination were performed. Approximately 3 months later, the patient started to experience headache, eye pain, and declining vision in the right eye. Ophthalmic imaging revealed a ciliary mass and scleritis. Th 1/Th 2/Th 17 cytokine levels and multimodal imaging findings were analyzed before and after corticosteroid treatment. Histopathological examination and immunohistochemistry (IHC) of the enucleated left eye demonstrated lymphoplasmacytic infiltration with an IgG4+/IgG+ cell ratio of approximately 40%, pointing to the diagnosis of probable IgG4-ROD. Long-term treatment with corticosteroids led to significant improvement in the signs and symptoms of the left eye. Th 1/Th 2/Th 17 cytokine profile monitoring of the aqueous humor and multimodal imaging of the right eye showed gradual regression of the mass and attenuation of ocular inflammation during treatment. CONCLUSIONS: Patients with an atypical presentation of IgG4-ROD, such as intraocular masses and scleritis, are likely to experience a significant delay in diagnosis. This case demonstrates the significance of IgG4-ROD in the differential diagnosis of intraocular tumors and ocular inflammation. IgG4-RD is a newly diagnosed disease with multi-organ involvement and little is known about its pathogenesis, particularly in the eye. The present case will open new challenges in the clinico-pathological diagnosis and research of this disease. Combined investigations of multimodal imaging and cytokine level detection of intraocular fluid provide a new and effective way to monitor disease progression.


Asunto(s)
Enfermedad Relacionada con Inmunoglobulina G4 , Escleritis , Neoplasias de la Úvea , Masculino , Humanos , Persona de Mediana Edad , Escleritis/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/patología , Cuerpo Ciliar/patología , Neoplasias de la Úvea/diagnóstico , Corticoesteroides , Inflamación , Inmunoglobulina G
7.
International Eye Science ; (12): 694-699, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-965803

RESUMEN

AIM: To analyze the clinical and histopathological composition of orbital tumors and tumor-like lesions.METHODS: Retrospective case-series study. The clinical histopathological data of 699 cases(707 eyes)with orbital tumor and tumor-like lesions who treated in the orbital disease and ophthalmic plastic department of Tianjin Eye Hospital between January 2010 and December 2020 were collected. All the pathology diagnosis results were divided into three categories which were benign tumor, borderline tumor and malignant tumor according to the eighth edition of the American Joint Committee on Cancer staging system and the 2018 World Health Organization Classification of tumors of the eye. All cases were divided into four groups according to age, including 0~17 years old, 18~39 years old, 40~59 years old, 60 years and above. The histological composition of each group was analyzed.RESULTS: Among the 699 cases(707 eyes), 311 patients(316 eyes)were male and 388 patients(391 eyes)were female. The patient's age at diagnosis ranged from 1 to 84 years(mean 39.9±2.2)years. The right orbit was involved in 307 patients, the left orbit in 384 patients, and 8 patients in bilateral orbit. There were 598 patients(604 eyes, 85.6%)with benign tumor and tumor-like lesions, 7 patients(7 eyes, 1.0%)with borderline tumor, and 94 patients(96 eyes, 13.4%)with malignant tumors. The top 5 benign tumor and tumor-like lesions were cavernous hemangioma(110 cases, 15.7%), dermoid cysts(96 cases, 13.7%), pleomorphic adenomas(54 cases, 7.7%), inflammatory pseudotumors(38 cases, 5.4%), and schwannomas(29 cases, 4.1%)respectively. The top 5 borderline and malignant tumors were non-Hodgkin lymphomas(42 cases, 41.6%), solitary fibrous tumors(12 cases, 11.9%), adenoid cystic carcinomas(11 cases, 10.9%), metastatic tumor(9 cases, 8.9%), and rhabdomyosarcoma(8 cases, 7.9%), respectively. Among the common orbital benign tumors and tumor-like lesions, cavernous hemangioma and pleomorphic adenoma showed a female predominance. Among the common borderline and malignant tumors, non-Hodgkin lymphoma and mesenchymal chondrosarcoma showed a male predominance. The most common benign and malignant tumors were dermoid cysts, rhabdomyosarcomas respectively in group under 18 years old. And dermoid cysts and solitary fibrous tumors were the most common benign and malignant tumors respectively in patients between 18 and 39 years old. Cavernous hemangioma and non-Hodgkin lymphomas were the most common benign and malignant tumors respectively in patients between 40 and 59 years old. While cavernous hemangioma and non-Hodgkin lymphomas were the most common benign and malignant tumors respectively in cases over 60 years old.CONCLUSION: Most orbital tumors and tumor-like lesions are benign. The most common benign orbital tumor is cavernous hemangioma, followed by dermoid cyst. Non-Hodgkin lymphoma is the most common malignant orbital tumor.

8.
Biomedicines ; 10(12)2022 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-36551800

RESUMEN

Ocular metastases are the most frequent ocular malignant tumors; their prevalence is estimated around 5-10% and is even higher in patients with breast or lung cancer. They represent various clinical situations, but they share the same hierarchical multidisciplinary therapeutic challenge with respect to the way systemic and local therapies should be selected in combination or sequentially in the personalized medical history of a patient. The challenges include tumor control, eye preservation, and the minimization of iatrogenic damage to sensitive tissues surrounding the tumor in order to preserve vision. These aims should further contribute to maintaining quality of life in patients with metastases. Many patients with choroidal metastases have systemic molecular treatment for their primary tumor. However, secondary resistance to systemic treatment is common and may ultimately be associated with cancer relapse, even after an initial response. Therefore, it makes sense to propose local treatment concomitantly or after systemic therapy to provide a more sustainable response. The aim of this review is to present current therapeutic strategies in ocular metastases and discuss how to tailor the treatment to a specific patient.

9.
Ophthalmologie ; 119(7): 664-674, 2022 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-35925409

RESUMEN

BACKGROUND: Malignant lymphomas of the eye and its adnexal structures account for approximately 5-15% of extranodal lymphomas. According to anatomic and biological criteria, two large groups of lymphomas in and around the eye need to be distinguished: (1) primary lymphomas of intraocular structures and (2) primary lymphomas of ocular adnexa. Furthermore, there is a large spectrum of secondary manifestations of malignant lymphomas in ocular and periocular structures. OBJECTIVE: This article gives a summary of the classification and molecular pathology of various intraocular and periocular lymphomas as well as oncological systemic treatment with a focus on primary vitreoretinal lymphomas. METHODS: A selective literature search was carried out in PubMed on the topic of intraocular and periocular lymphomas and own experiences are presented. RESULTS: The treatment of primary vitreoretinal lymphomas (PVRL) is an interdisciplinary challenge and despite the apparently localized disease, systemic treatment concepts are necessary to reduce the high risk of secondary involvement of the central nervous system (CNS). Therefore, it is crucial that the substances used can penetrate the CNS, and protocols should be chosen in accordance with the treatment concepts for primary CNS lymphomas. The knowledge on the genetics and biology of ocular lymphomas generated by modern high throughput methods enable not only improved diagnostics using molecular methods but also provide rationales for targeted therapeutic approaches. CONCLUSION: A deep understanding of the biological and molecular principles of intraocular and periocular lymphomas forms a basic prerequisite for precise diagnostics and the use of targeted systemic treatment.


Asunto(s)
Neoplasias del Ojo , Linfoma de Células B , Linfoma no Hodgkin , Linfoma , Neoplasias del Ojo/diagnóstico , Humanos , Linfoma/diagnóstico , Linfoma de Células B/terapia
10.
Cureus ; 14(2): e22578, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35371675

RESUMEN

In this case report, we aim to describe a rare case of recurrent diffuse large B-cell lymphoma (DLBCL) reportedly in remission presenting with primary anterior segment findings and use of intravitreal bevacizumab and methotrexate to treat the sequelae. The patient presented with hypopyon and neovascularization of the iris (NVI). Anterior chamber studies including flow cytometry and imaging revealed DLBCL recurrence with central nervous system (CNS) involvement. Over one month, he was treated with one intravitreal injection of bevacizumab, repeat injections of methotrexate, and systemic therapies with the resolution of ocular symptoms but persistent systemic disease. This case highlights the utility of anterior chamber paracentesis in diagnosis and intravitreal bevacizumab and methotrexate in the treatment for anterior segment manifestations of intraocular lymphoma (IOL).

11.
Cancers (Basel) ; 14(5)2022 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-35267502

RESUMEN

The eye is an exemplarily challenging organ to treat when considering ocular tumors. It is at the crossroads of several major aims in oncology: tumor control, organ preservation, and functional outcomes including vision and quality of life. The proximity between the tumor and organs that are susceptible to radiation damage explain these challenges. Given a high enough dose of radiation, virtually any cancer will be destroyed with radiotherapy. Yet, the doses inevitably absorbed by normal tissues may lead to complications, the likelihood of which increases with the radiation dose and volume of normal tissues irradiated. Precision radiotherapy allows personalized decision-making algorithms based on patient and tumor characteristics by exploiting the full knowledge of the physics, radiobiology, and the modifications made to the radiotherapy equipment to adapt to the various ocular tumors. Anticipation of the spectrum and severity of radiation-induced complications is crucial to the decision of which technique to use for a given tumor. Radiation can damage the lacrimal gland, eyelashes/eyelids, cornea, lens, macula/retina, optic nerves and chiasma, each having specific dose-response characteristics. The present review is a report of non-cancer effects that may occur following ionizing irradiation involving the eye and orbit and their specific patterns of toxicity for a given radiotherapy modality.

12.
Neurosignals ; 30(S1): 1-10, 2022 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-35333486

RESUMEN

The goal of radiotherapy in the treatment of eyelid and ocular surface tumors is to eradicate tumor burden in a manner that maintains visual function and preserve surrounding sensitive ocular tissue. Interventional radiotherapy (IRT-brachytherapy) is a radiotherapy technique associated with a highly focal dose distribution, with the advantage of boosting limited size target volumes to very high dose while sparing normal tissue. The reduction in the ocular and adnexal complications that result from this form of therapy, has led in recent years, to an increase in the use of IRT for the treatment of eyelid and ocular surface tumors. For eyelid malignancies, IRT is used as an independent treatment in small eyelids tumors, in postoperative treatment of high-risk patients and as well as salvage therapy in local recurrences. In the treatment of conjunctival malignancies, due to the high risk of local recurrence, the use of adjuvant therapies as IRT has shown to improve outcomes. In this review, we focus on eyelid and ocular surface IRT techniques and provide an overview of indication, outcomes and toxicity of IRT for the treatment of naïve and recurrent eyelid and conjunctival tumors.


Asunto(s)
Braquiterapia , Carcinoma Basocelular , Neoplasias de los Párpados , Carcinoma Basocelular/patología , Carcinoma Basocelular/radioterapia , Neoplasias de los Párpados/patología , Neoplasias de los Párpados/radioterapia , Párpados/patología , Humanos , Recurrencia
13.
Am J Ophthalmol Case Rep ; 25: 101340, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35146204

RESUMEN

PURPOSE: To report a case of iris implantation cysts occurring 24 years after penetrating keratoplasty and its management. OBSERVATIONS: A 60-year-old man was referred for diagnosis and management of white iris masses of the right eye. He had undergone bilateral penetrating keratoplasty 24 years before without complication. The clinical findings were suggestive of iris implantation cysts and Ultrasound Biomicroscopy (UBM) and anterior-segment optical coherence tomography confirmed the diagnosis. The patient did not develop any ocular complications from the cysts after one-year follow-up from the diagnosis of iris implantation cysts. CONCLUSIONS AND IMPORTANCE: Iris implantation cysts are rare benign tumors that develop after the ectopic implantation of epithelial cells within the iris stroma. They can be congenital or secondary to penetrating trauma or surgery. Their diagnosis relies on clinical examination and UBM. In case of intraocular complications, treatment may be required, otherwise observational follow-up is appropriate.

14.
Ocul Immunol Inflamm ; 30(7-8): 1798-1802, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34379046

RESUMEN

PURPOSE: The purpose of this study is to investigate matrix metalloproteinases (MMPs) expression in human intraocular lymphoma (IOL). METHODS: Two enucleated eyes and seven cell-block samples obtained from patients with IOL who underwent vitrectomy were used. Immunopathological examinations were performed for detection of MMP-2, MMP-9, and TIMP-4 expressions. RESULTS: In the enucleated eye with primary IOL (PIOL), MMP-2 was negative, and MMP-9 and TIMP-4 were positive in the lymphoma cells, while in the enucleated eye with secondary IOL (SIOL), all the molecules were positive. Among the cell-block samples with PIOL, the positive rate in lymphoma cells of MMP-2, MMP-9, and TIMP-4 was 75%, 100%, and 75%, respectively. In the cell-block samples with SIOL, the positive rates of MMP-2, MMP-9, and TIMP-4 were all 100%. CONCLUSIONS: MMP-2, MMP-9, and TIMP-4 were expressed in lymphoma cells using the specimens of human IOL, suggesting that MMPs may play an important role in the development of IOL.


Asunto(s)
Linfoma Intraocular , Metaloproteinasa 2 de la Matriz , Humanos , Metaloproteinasa 9 de la Matriz , Linfoma Intraocular/diagnóstico
15.
Vet Res Forum ; 12(3): 391-393, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34815854

RESUMEN

Ocular tumors are rarely seen in farm animals. Iridociliary epithelial tumors are the second most common tumor of the eye in dogs and cats, but there is just one report of this tumor in sheep. This case report described the history, clinical signs, histopathological and immunohistochemical findings, and surgical management of an iridociliary adenoma tumor in a 3-year-old Iranian Shaal sheep with signs of anorexia, depression, loss of vision, and a mass covering the left eye. The mass had protruded from the left eye globe but had not penetrated the periocular tissues. Enucleation was performed to excise the tumor. Periodic acid-Schiff (PAS) and Alcian blue staining methods were done for the mass, but the result for both of them was negative. Slides were also immunostained for antibodies against cytokeratin AE1/AE3, vimentin, and S-100 protein. The results were positive for vimentin but negative for cytokeratin and S-100. According to the results of histopathology and immunohistochemistry, the type of tumor was diagnosed as iridociliary adenoma. To our knowledge, it was the second report of the iridociliary tumor in the sheep and the first report of this tumor in the Iranian Shaal breed.

16.
Front Med (Lausanne) ; 8: 774624, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35155464

RESUMEN

The pathogenesis and etiology of various ocular tumors remain largely unclear, limiting the development of diagnostic and treatment approaches for such tumors. Tissue samples from patients are also valuable resource to elucidate mechanisms underlying tumorigenesis. Here we present the early phase setup of an ocular tumor biobank at Xiangya Hospital. Blood and tissue samples along with associated clinical data were obtained from patients who underwent surgery in the Department of Ophthalmology of Xiangya Hospital from December 1, 2018 to January 31, 2020. Standardized operating protocols were developed for the collection, transportation, processing and preservation of ocular tumor samples. A total of 92 clinical cases suffered from 21 types of eye tumors and several undiagnosed eye diseases were covered. A total of 846 samples were preserved in the ocular tumor biobank, including 356 blood samples (42.1%), 324 plasma samples (38.3%), and 166 tissue samples (19.6%). Using the clinical data, we analyzed the prevalence of malignant ocular tumors in association with variables of age, gender, tumors' location and size, and presenting complaints of lump and proptosis. The factors predictive of malignant ocular tumors, included gender (B = 1.599; P = 0.025) and the symptom of proptosis (B = -2.534; P = 0.001). Overall, the setup of clinically-based ophthalmologic biobank could support pathological and translational research into ocular tumors.

17.
J Cell Physiol ; 236(4): 2318-2332, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32840881

RESUMEN

Retinoblastoma (RB) is a pediatric ocular tumor mostly occurring due to the biallelic loss of RB1 gene in the developing retina. Early studies of genomic aberrations in RB have provided a valuable insight into how RB can progress following the tumor-initiating RB1 mutations and have established a notion that inactivation of RB1 gene is critical to initiate RB but this causative genetic lesion alone is not sufficient for malignant progression. With the advent of high-throughput sequencing technologies, we now have access to the comprehensive genomic and epigenetic landscape of RB and have come to appreciate that RB tumorigenesis requires both genetic and epigenetic alterations that might be directly or indirectly driven by RB1 loss. This integrative perspective on RB tumorigenesis has inspired research efforts to better understand the types and functions of epigenetic mechanisms contributing to RB development, leading to the identification of multiple epigenetic regulators misregulated in RB in recent years. A complete understanding of the intricate network of genetic and epigenetic factors in modulation of gene expression during RB tumorigenesis remains a major challenge but would be crucial to translate these findings into therapeutic interventions. In this review, we will provide an overview of chromatin regulators identified to be misregulated in human RB among the numerous epigenetic factors implicated in RB development. For a subset of these chromatin regulators, recent findings on their functions in RB development and potential therapeutic applications are discussed.


Asunto(s)
Ensamble y Desensamble de Cromatina , Epigénesis Genética , Neoplasias de la Retina/metabolismo , Retinoblastoma/metabolismo , Factores de Transcripción/metabolismo , Animales , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Ensamble y Desensamble de Cromatina/efectos de los fármacos , ADN Helicasas/genética , ADN Helicasas/metabolismo , Metilación de ADN , Factores de Transcripción E2F/genética , Factores de Transcripción E2F/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Epigénesis Genética/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Terapia Molecular Dirigida , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/genética , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/genética , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/genética , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
18.
Ocul Surf ; 19: 16-30, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33238207

RESUMEN

Local chemotherapy is increasingly used, either in combination with surgery or as monotherapy, for management of ocular tumors. Yet many of the local chemotherapeutic agents used for ocular tumors are cytotoxic drugs that are frequently associated with toxicities in normal ocular tissues. Understanding and managing these side effects are important because they affect treatment tolerability, outcome and quality of vision. Herein, we review local anticancer drugs administered for the treatment of ocular tumors, with an emphasis on their toxicities to the ocular surface, adnexa and lacrimal drainage system. We provide the underlying mechanisms and management strategies for the ocular side effects. Recent innovations in anticancer immunotherapy and ocular drug delivery systems also are discussed as new potential therapeutic modalities for alleviation of side effects.


Asunto(s)
Antineoplásicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias del Ojo , Antineoplásicos/efectos adversos , Sistemas de Liberación de Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Ojo , Neoplasias del Ojo/tratamiento farmacológico , Humanos
19.
Ocul Oncol Pathol ; 6(5): 311-317, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33123522

RESUMEN

A 74-year-old woman with Carney complex (CNC) and complaints of poor vision was found, on ophthalmic examination, to have a pigmented tumor involving the peripheral choroid and ciliary body in her right eye. The eye was enucleated and showed a ciliochoroidal melanoma with marked pleomorphism. The tumor did not recur or metastasize after almost 10 years of follow-up, and the patient died of unrelated causes. Molecular studies revealed a complex genome with multiple whole-chromosome losses including monosomy of chromosomes 1, 2 (including loss of CNC2at 2p16), 14, 17 (including loss of a copy of PRAKA1 at 17q24.2), 18, 19, 21, 22, and X. No monosomy 3 was observed. This is only the second case of uveal melanoma in a patient with CNC, raising the possibility that this might represent a rare component of this syndrome.

20.
Vet Ophthalmol ; 23(3): 579-587, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32237209

RESUMEN

OBJECTIVE: To report the surgical excision of an iridociliary adenoma and iridal melanocytoma using a postero-anterior cyclo-iridectomy in two dogs. PROCEDURE: A 7 year old neutered male English springer spaniel (case 1) and a 7 year old neutered male Labrador mix (case 2) were presented for evaluation of an intrairidal mass OS. RESULTS: Complete ophthalmic examination revealed a large, dorsonasal, well-demarcated, intrairidal mass OS. A tan to pink intrairidal mass extending into the iridocorneal angle (case 1) and a pigmented intrairidal mass (case 2) were present. B-mode ultrasonography showed a focal, soft tissue, homogenous mass within the uvea adjacent to and contacting the lens. Neither pars plana involvement nor vitreal extension was present. A postero-anterior cyclo-iridectomy was performed through a polyhedral scleral flap. Thermocautery was used to complete the cyclo-iridectomy (case 1) and partial iridectomy (case 2) to excise the mass en bloc. Histopathology revealed a completely excised iridociliary adenoma (case 1) and iris melanocytoma (case 2). The surgery sites healed without complication. Mild uveitis (cases 1 and 2), scant vitreal hemorrhage (case 1), and mild hyphema (case 2) were present three days postoperatively but had resolved ten days postoperatively. The patients remain visual twenty-two months (case 1) and seven months (case 2) postoperatively with a normal intraocular examination other than an iridal defect and mild dorsonasal lens capsular opacities. CONCLUSIONS: The surgical approach described in these cases is utilized in physician-based medicine. This approach and the use of thermocautery provide a viable surgical option for excision of large iridociliary tumors in dogs.


Asunto(s)
Adenoma/veterinaria , Cuerpo Ciliar/patología , Enfermedades de los Perros/cirugía , Neoplasias del Iris/veterinaria , Melanoma/veterinaria , Adenoma/cirugía , Animales , Perros , Iridectomía/veterinaria , Neoplasias del Iris/cirugía , Masculino , Melanoma/cirugía , Linaje
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