Lack of HPV in pterygium with no evidence of autoinoculation and the role of cytokines in pterygium with dry eye

Uthaithammarat, Lita; Kasetsuwan, Ngamjit; Chongpison, Yuda; Kasetsuwan, Pimpetch; Reinprayoon, Usanee; Nilyanimit, Pornjarim; Poovorawan, Yong

doi:10.1038/s41598-021-82114-6

Cited by 8 publications

(4 citation statements)

References 34 publications

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“…The latter confirms our previous results and strengthens our hypothesis that interindividual variability could play an important role, as the VEGF levels are considered elevated with respect to patient-specific healthy values [ 24 ]. On the contrary, Uthaithammarat et al, did demonstrate higher VEGF concentrations in pterygium patients compared to the healthy control group [ 44 ]. Although the exact players and their corresponding contributions still need to be defined and/or further refined, it is important to note that there is a difference in the organization of the vascular network when it belongs to pterygium or a malignant transformed lesion.…”

Section: Uv-induced Damagementioning

confidence: 99%

Pterygium—The Good, the Bad, and the Ugly

Acker

Bogerd

Haagdorens

et al. 2021

Cells

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Pterygium is a multifaceted pathology that displays apparent conflicting characteristics: benign (e.g., self-limiting and superficial), bad (e.g., proliferative and potentially recurrent) and ugly (e.g., signs of preneoplastic transformation). The natural successive question is: why are we lacking reports showing that pterygium lesions become life-threatening through metastasis, especially since pterygium has considerable similarities with UV-related malignancies on the molecular level? In this review, we consider how our pathophysiological understanding of the benign pterygium pathology overlaps with ocular surface squamous neoplasia and skin cancer. The three UV-related disorders share the same initial insult (i.e., UV radiation) and responsive repair mechanisms to the ensuing (in)direct DNA damage. Their downstream apoptotic regulators and other cellular adaptations are remarkably alike. However, a complicating factor in understanding the fine line between the self-limiting nature of pterygium and the malignant transformation in other UV-related diseases is the prominent ambiguity in the pathological evaluation of pterygium biopsies. Features of preneoplastic transformation (i.e., dysplasia) are used to define normal cellular reactions (i.e., atypia and metaplasia) and vice versa. A uniform grading system could help in unraveling the true nature of this ancient disease and potentially help in identifying the earliest intervention point possible regarding the cellular switch that drives a cell’s fate towards cancer.

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Section: Uv-induced Damagementioning

confidence: 99%

Pterygium—The Good, the Bad, and the Ugly

Acker

Bogerd

Haagdorens

et al. 2021

Cells

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“…The pathogenesis of pterygium is not completely understood, however there are the inflammatory and tumoral theories, which would be controlled by the action of the sesquiterpenes. As it was already demonstrated that inflammatory cytokines, including IL-6, IL-8, and vascular endothelial growth factor (VEGF) are elevated in the tears of the patients with pterygium [16][17] the present study investigated the effects of the sesquiterpenes β-caryophyllene and α-humulene (chemical structures in Figure 1A and 1B) on the production of inflammatory cytokines by pterygium fibroblasts, in order to determine if they can be used in the adjuvant treatment of pterygium.…”

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confidence: 99%

Anti-inflammatory effects of α-humulene and β-caryophyllene on pterygium fibroblasts

Viveiros¹,

Costa²,

Oliveira³

et al. 2022

Int J Ophthalmol

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AIM: To investigate the anti-inflammatory effects of the sesquiterpenes α-humulene and β-caryophyllene on pterygium fibroblasts. METHODS: Primary cultures of pterygium fibroblasts were established. Third passage pterygium fibroblasts were exposed to α-humulene and β-caryophyllene separately and together. The cell viability was assessed by 3- (4,5-dimethylthiazolyl-2) -2,5-diphenyltetrazolium bromide (MTT) assay at 12, 24, 48, and 72h after exposure. The levels of the inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α and IL-10 in the conditioned culture medium were assessed by enzyme-linked immunosorbent assay (ELISA) at 12, 24 and 48h after exposure. Data were statistically analyzed using Friedman repeated measures analysis of variances on ranks. RESULTS: The 25 μmol/L β-caryophyllene induced significant decrease in the IL-6 production by pterygium fibroblasts 48h after the exposure (P=0.041). The levels of IL-1β, IL-8, IL-10, and TNF-α were very low and had no statistically significant variations after exposure to α-humulene, β-caryophyllene, or both compounds together. CONCLUSION: The exposure to 25 μmol/L of β-caryophyllene significantly reduce the production of IL-6 by pterygium fibroblasts after 48h. This sesquiterpene may be a potential alternative adjuvant agent for the treatment of pterygium.

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“…In the current study, all of the examined patients demonstrated no history of HPV infection. Concerning the involvement of HPV and other persistent viral infections, including Epstein Barr, in pterygia pathogenesis there are controversial experimental and epidemiological results (40)(41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

c-FOS Expression Analysis in Pterygia Cell Spot Arrays

Mastronikolis

Tsiambas

Pagkalou

et al. 2022

In Vivo

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Background/Aim: Mechanisms of c-FOS activation in the onset and progression of pterygia remain under investigation. Τhis study aimed to comparatively analyze c-FOS proto-oncogene expression levels in neoplastic pterygia and normal epithelia. Materials and Methods:We used a liquid-based cytology assay on thirty (n=30) pterygia cell populations and normal epithelia (n=10) extracted by a smooth scraping of conjunctiva epithelia. Applying a cell spot-based technique, we constructed five (n=5) slides, each containing eight (n=8) cell spots. A modified immune-cytochemistry (ICC) assay for c-FOS protein was used. Additionally, digital image analysis was implemented to calculate c-FOS immunostaining intensity levels. Results: High staining intensity levels of c-FOS were detected in 12/30 (40%), whereas the rest 18/30 (60%) demonstrated moderate expression. c-FOS levels were statistically significantly higher in the pterygia compared to control tissues (p=0.001). c-FOS levels in the pterygia were not associated with the sex of patients (p=0.678), the presence of recurrent lesion (p=0.390) or the location of the lesion (p=0.158). The levels of c-FOS, however, were marginally significantly affected by the morphology of the pterygia (p=0.005). More precisely, the c-FOS levels were significantly higher in pterygia with a fleshy morphology. Conclusion: c-FOS over-expression is observed frequently in pterygia. It seems to be critically involved in the molecular mechanism of the lesion by its over-expression affecting partially their morphological features. Cell spot liquidbased array analysis is an innovative, easy to implement technique for simultaneously evaluating a broad spectrum of molecules in multiple specimens on the same slide.Over-activation of oncogenes critically influences the genomic substrate in pre-malignant neoplastic epithelia transforming them into their malignant cell phenotype. Among oncogene-depended pathways, including those involving transcription factors, the c-FOS/c-JUN complex leads to an aberrant expression of other crucial genes responsible for cell homeostasis (1, 2). Up-regulation of c-FOS and c-JUN proto-oncogenes -due to increased copy numbers (amplification) or intra-genic point mutationscorrelates with aggressive biological behavior of malignancies of different tissue origin (3-5). The FOS protooncogene, also named activator protein-1 (AP-1) transcription factor subunit (c-FOS), belongs to a category of extensively analysed genes involved in the onset and progression of solid malignancies. The FOS super family includes c-FOS, FOSB, FOSL1, and FOSL2 genes. c-FOS is the human homolog of the retroviral oncogene v-FOS (gene locus: 14q24.3). It was first detected and finally cloned in rat fibroblasts as the transforming gene of Finkel-Biskis-Jinkins murine osteogenic sarcoma virus (6). The corresponding gene encodes a 62 kDa protein (380 amino acids), which forms a heterodimer with c-JUN, a transcription factors, resulting in the formation of AP-1 complex. The c-FOS/c-JUN complex influences intrace...

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Lack of HPV in pterygium with no evidence of autoinoculation and the role of cytokines in pterygium with dry eye

Cited by 8 publications

References 34 publications

Pterygium—The Good, the Bad, and the Ugly

Pterygium—The Good, the Bad, and the Ugly

Anti-inflammatory effects of α-humulene and β-caryophyllene on pterygium fibroblasts

c-FOS Expression Analysis in Pterygia Cell Spot Arrays

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