ocular cancer
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2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kyra N. Smit ◽  
Ruben Boers ◽  
Jolanda Vaarwater ◽  
Joachim Boers ◽  
Tom Brands ◽  
...  

AbstractUveal melanoma (UM) is an aggressive intra-ocular cancer with a strong tendency to metastasize. Metastatic UM is associated with mutations in BAP1 and SF3B1, however only little is known about the epigenetic modifications that arise in metastatic UM. In this study we aim to unravel epigenetic changes contributing to UM metastasis using a new genome-wide methylation analysis technique that covers over 50% of all CpG’s. We identified aberrant methylation contributing to BAP1 and SF3B1-mediated UM metastasis. The methylation data was integrated with expression data and surveyed in matched UM metastases from the liver, skin and bone. UM metastases showed no commonly shared novel epigenetic modifications, implying that epigenetic changes contributing to metastatic spreading and colonization in distant tissues occur early in the development of UM and epigenetic changes that occur after metastasis are mainly patient-specific. Our findings reveal a plethora of epigenetic modifications in metastatic UM and its metastases, which could subsequently result in aberrant repression or activation of many tumor-related genes. This observation points towards additional layers of complexity at the level of gene expression regulation, which may explain the low mutational burden of UM.


Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 587 ◽  
Author(s):  
Quanchi Chen ◽  
Vadde Ramu ◽  
Yasmin Aydar ◽  
Arwin Groenewoud ◽  
Xue-Quan Zhou ◽  
...  

The ruthenium-based photosensitizer (PS) TLD1433 has completed a phase I clinical trial for photodynamic therapy (PDT) treatment of bladder cancer. Here, we investigated a possible repurposing of this drug for treatment of conjunctival melanoma (CM). CM is a rare but often deadly ocular cancer. The efficacy of TLD1433 was tested on several cell lines from CM (CRMM1, CRMM2 and CM2005), uveal melanoma (OMM1, OMM2.5, MEL270), epidermoid carcinoma (A431) and cutaneous melanoma (A375). Using 15 min green light irradiation (21 mW/cm2, 19 J.cm−2, 520 nm), the highest phototherapeutic index (PI) was reached in CM cells, with cell death occurring via apoptosis and necrosis. The therapeutic potential of TLD1433 was hence further validated in zebrafish ectopic and newly-developed orthotopic CM models. Fluorescent CRMM1 and CRMM2 cells were injected into the circulation of zebrafish (ectopic model) or behind the eye (orthotopic model) and 24 h later, the engrafted embryos were treated with the maximally-tolerated dose of TLD1433. The drug was administrated in three ways, either by (i) incubating the fish in drug-containing water (WA), or (ii) injecting the drug intravenously into the fish (IV), or (iii) injecting the drug retro-orbitally (RO) into the fish. Optimally, four consecutive PDT treatments were performed on engrafted embryos using 60 min drug-to-light intervals and 90 min green light irradiation (21 mW/cm2, 114 J.cm−2, 520 nm). This PDT protocol was not toxic to the fish. In the ectopic tumour model, both systemic administration by IV injection and RO injection of TLD1433 significantly inhibited growth of engrafted CRMM1 and CRMM2 cells. However, in the orthotopic model, tumour growth was only attenuated by localized RO injection of TLD1433. These data unequivocally prove that the zebrafish provides a fast vertebrate cancer model that can be used to test the administration regimen, host toxicity and anti-cancer efficacy of PDT drugs against CM. Based on our results, we suggest repurposing of TLD1433 for treatment of incurable CM and further testing in alternative pre-clinical models.


Author(s):  
Upasna Upadhyay ◽  
Raaghav Sen ◽  
Swathi Kaliki ◽  
Jaganmohan R. Jangamreddy

2020 ◽  
Vol 83 (5) ◽  
Author(s):  
Rodrigo Jorge ◽  
Priscilla Ballalai Bordon ◽  
Enzo Augusto Medeiros Fulco ◽  
Daniel Ribeiro ◽  
Jefferson Ribeiro ◽  
...  

Author(s):  
Upasna Upadhyay ◽  
Raaghav Sen ◽  
Swathi Kaliki ◽  
Jaganmohan R. Jangamreddy

2018 ◽  
Vol 25 (3) ◽  
pp. 301-303
Author(s):  
Konstantinos Laios

Wilhelm Fabricius von Hilden (1560-1634) or also known with his Latinized name Guilielmus Fabricius Hildanus is considered the founder of scientific German surgery. He introduced new surgical techniques and invented new surgical instruments for the surgical treatment of nasal polyps, stone bladder, breast and ocular cancer, hydrocele, and ascites, while very ingenious were his amputation techniques. His most important surgical treatise was Observationem et curationem chirurgicam centuriae sex ( Six Hundred Surgical Observations and Treatments) first published in 1606.


Author(s):  
Mark Paterson

Since Descartes, most discussions of blindness have been in terms of what Kleegecalls ‘the Hypothetical Blind Man’, a blank-blind figure, rendered mute. In contrast, the twentieth century offered a number of personal accounts of blindness and the process of going blind, at once furthering the fascination by the sighted reader of what the blind supposedly ‘see’ whilst also personalizing the testimony. We start with what Jorge Luis Borges terms the ‘pathetic moment’ of his own becoming blind (1973) along with other first-person accounts of going blind, including the so-called ‘Blind Traveller’ James Holman, RN, Helen Keller’s celebrated autobiographies, and Oliver Sacks’ recent account of progressive blindness through ocular cancer.


Nukleonika ◽  
2015 ◽  
Vol 60 (3) ◽  
pp. 609-613
Author(s):  
Gabriela Mierzwińska ◽  
Magdalena Kłodowska ◽  
Barbara Michalec ◽  
Anna Pędracka ◽  
Marzena Rydygier ◽  
...  

Abstract Basing on alanine solid state/electron paramagnetic resonance (EPR) dosimetry, a supplementary method of cumulatively recording the therapeutic dose received by ocular cancer patients undergoing fractionated proton radiotherapy is proposed. By applying alanine dosimetry during the delivery of consecutive fractions, the dose received within each fraction can be read out by EPR spectrometry and a final permanent cumulative record of the total dose delivered obtained. The dose response of the alanine detector was found to be practically independent on its position within the extended proton Bragg peak region. Dose measurements based on entrance dose recorded in proton beams individually formed for each patient are presented. The described method will be applied as a complementary Quality Assurance procedure for patients undergoing proton radiotherapy at the Institute of Nuclear Physics, Polish Academy of Sciences, Krakow, Poland (IFJ PAN).


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