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Monosomy-3 in uveal melanoma (UM) cells increases the risk of fatal metastases. The gene encoding the low-affinity glucose transporter GLUT2 resides on chromosome 3q26.2. Here, we analyzed the expression of the glucose transporters GLUT1, GLUT2, and GLUT3 with regard to the histological and clinical factors by performing immunohistochemistry on the primary tumors of = 33 UM patients. UMs with monosomy-3 exhibited a 57% lower immunoreactivity for GLUT2 and a 1.8×-fold higher ratio of GLUT1 to total GLUT1-3. The combined levels of GLUT1-3 proteins were reduced in the irradiated but not the non-irradiated tumors with monosomy-3. GLUT3 expression was stronger in the irradiated samples with disomy-3 versus monosomy-3, but the ratio of the GLUT3 isoform to total GLUT1-3 did not differ with regard to the monosomy-3 status in the irradiated or non-irradiated subgroups. Systemic metastases were associated with the presence of monosomy-3 in the primary and circulating tumor cells as well as a higher GLUT1 ratio. Upregulation of the high-affinity glucose transporter GLUT1 possibly as a compensation for the low-affinity isoform GLUT2 may be enhancing the basal glucose uptake in the UM cells with monosomy-3. Prevention of hyperglycemia might, therefore, be a valuable approach to delay the lethal UM metastases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762573 | PMC |
http://dx.doi.org/10.3390/ijms21249345 | DOI Listing |
Ophthalmologie
December 2024
Klinik für Augenheilkunde, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23562, Lübeck, Deutschland.
Background: A fundamental prerequisite for the development of clinically manifested metastases in uveal melanoma (UM) is the hematogenous dissemination of melanoma cells, which circulate in the systemic circulation, deposit in organs and can subsequently colonize the organs.
Material And Methods: This article presents a review of the literature on the detection of circulating tumor cells (CTC) from UM and their relevance for the clinical and pathophysiological aspects of the malignancy.
Results: Since the first description of CTC in UM patients 20 years ago, only 20 articles have been published on the detection of intact CTCs in UM.
Lab Invest
December 2024
Department of Ocular Pathology, Dr R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Delhi, India. Electronic address:
High pigmentation and the abundance of M2 macrophages have been identified as negative predictors in uveal melanoma (UM). Risk factors associated with UM that are prevalent in high-risk White populations are still present, although less common, in relatively low-risk Asian populations. Research indicates that proangiogenic M2 macrophages and monosomy 3 play significant roles in UM progression.
View Article and Find Full Text PDFAsia Pac J Ophthalmol (Phila)
October 2024
Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, PR China. Electronic address:
Can J Ophthalmol
August 2024
Department of Clinical Neuroscience, Division of Eye and Vision, Karolinska Institutet, Stockholm, Sweden; Ocular Oncology Service and St. Erik Ophthalmic Pathology Laboratory, St. Erik Eye Hospital, Stockholm, Sweden. Electronic address:
Objective: To develop surveillance programs for uveal melanoma patients, tailored to metastatic risk.
Methods: Surveillance schedules were developed using the number needed to scan (NNS) concept, based on weighted average metastasis-free survival (MFS) rates from systematic review data of 18 prognostic groups (Disomy 3 (D3), Monosomy 3 (M3), EIF1AX-mutation, SF3B1-mutation, BAP1-mutation, high or low nBAP-1 immunohistochemistry, gene expression profiling classes (1;1A;1B;1;1;2;2;2), and V stages I-III).
Results: In a typical surveillance schedule, involving biannual examinations years 1-5 and annual examinations years 6-10, the NNS varies dramatically from 1 to nearly infinity, underscoring the necessity for personalized surveillance approaches.
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