Prognostic Significance of Epidermal Growth Factor Receptor Expression in Distant Metastatic Melanoma from Primary Cutaneous Melanoma

Lee, Keon Hee; Suh, Hyun Yi; Lee, Mi Woo; Lee, Woojin; Chang, Sung Eun

doi:10.5021/ad.2021.33.5.432

Cited by 3 publications

(7 citation statements)

References 23 publications

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“…These data reveal similar therapeutic activities of EGFR-targeted nanoceria in both of the 2D models, despite the expected increased levels of EGFR expression in more metastatic melanoma. 48,62 The reason for this observation, which is the limitations of the 2D models, is discussed subsequently in Section 3.8.…”

Section: Resultsmentioning

confidence: 99%

“…EGFR is an important biomarker for an array of tumors and can act as a promising target for the diagnosis and treatment of melanoma, especially in metastatic melanoma, revealing the potential of EGFR-targeted theranostics in melanoma management. In the present work, fluorophore-tagged EGF was used as the diagnostic component and nanoceria was used as the therapeutic component.…”

Section: Introductionmentioning

confidence: 99%

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Theranostic Activity of Ceria-Based Nanoparticles toward Parental and Metastatic Melanoma: 2D vs 3D Models

Johnson

Kopecky

Koshy

et al. 2023

ACS Biomater. Sci. Eng.

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The time interval between the diagnosis of tumor in a patient and the initiation of treatment plays a key role in determining the survival rates. Consequently, theranostics, which is a combination of diagnosis and treatment, can be expected to improve survival rates. Early detection and immediate treatment initiation are particularly important in the management of melanoma, where survival rates decrease considerably after metastasis. The present work reports for the first time the application of fluorescein isothiocyanate (FITC)tagged epidermal growth factor receptor (EGFR)-functionalized ceria nanoparticles, which exhibit intrinsic reactive oxygen species (ROS)mediated anticancer effects, for the EGFR-targeted diagnosis and treatment of melanoma. The theranostic activity was demonstrated using two-dimensional (2D) and three-dimensional (3D) models of parental and metastatic melanoma. Confocal imaging studies confirm the diagnostic activity of the system. The therapeutic efficiency was evaluated using cell viability studies and ROS measurements. The ROS elevation levels are compared across the 2D and 3D models. Significant enhancement in the generation of cellular ROS and absence in mitochondrial ROS are observed in the 2D models. In contrast, significant elevations in both ROS types are observed for the 3D models, which are significantly higher for the metastatic spheroids than the parental spheroids, thus indicating the suitability of this nanoformulation for the treatment of metastatic melanoma.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Theranostic Activity of Ceria-Based Nanoparticles toward Parental and Metastatic Melanoma: 2D vs 3D Models

Johnson

Kopecky

Koshy

et al. 2023

ACS Biomater. Sci. Eng.

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“… 13 Consistent with this finding, Lee et al found that in distant metastatic melanoma, the lack of EGFR expression was significantly correlated with ulceration. 66 Of the 12 patients with ulcerated tumors, only one patient had an EGFR positive tumor. 66 However, in a study by Katunaríc et al, the presence of ulceration was correlated with an increase in membrane EGFR in nodular melanoma.…”

Section: Introductionmentioning

confidence: 99%

“… 66 Of the 12 patients with ulcerated tumors, only one patient had an EGFR positive tumor. 66 However, in a study by Katunaríc et al, the presence of ulceration was correlated with an increase in membrane EGFR in nodular melanoma. 63 This discrepancy may be due to the fact that Katunaríc et al focused exclusively on nodular melanomas and suggests that histological type needs to be considered when trying to understand the role of EGFR in melanoma.…”

Section: Introductionmentioning

confidence: 99%

“…Epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase that is overexpressed in several types of cancer, and its downstream signaling has been shown to facilitate cancer cell proliferation and migration. 66 , 67 However, in melanoma, there is conflicting evidence regarding the connection between EGFR expression and ulceration status. In primary ulcerated melanoma, EGFR expression was found to be downregulated compared to non-ulcerated tumors.…”

Section: Introductionmentioning

confidence: 99%

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Ulcerated Cutaneous Melanoma: A Review of the Clinical, Histologic, and Molecular Features Associated with a Clinically Aggressive Histologic Phenotype

Barricklow¹,

DiVincenzo²,

Carson³

et al. 2022

CCID

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The presence of ulceration in melanoma is associated with poor clinical outcomes and is the third most powerful predictor of survival in the AJCC Melanoma Staging System after tumor thickness and mitotic activity. The aggressive biological behavior associated with ulceration has been hypothesized to be the result of an intrinsic biological attribute that favors dissemination and presents locally with the loss of epidermal integrity. Among the features of ulcerated melanoma, many show promise as potential prognostic tools, markers of differential immunogenicity and indicators of oncogenic drivers of invasion and metastasis. The incidence of ulcerated melanoma is greater in males, increases with age and with systemic inflammatory risk factors (diabetes, smoking, low vitamin D, elevated body mass index). Patients with ulcerated primary tumors seem to exclusively benefit from adjuvant interferon (IFN) therapy, which is likely the consequence of an altered tumor microenvironment. When ulceration is present, there is a higher density of macrophages and dendritic cells and enhanced expression of pro-inflammatory cytokines, such as IL-6. There is also an increased expression of proteins involved in tumor antigen presentation in ulcerated melanomas. Histologically, vascular density, vasculogenic mimicry and angiotropism are all significantly correlated with ulceration in melanoma. The presence of ulceration is associated with reduced protein expression of E-cadherin and PTEN and elevated levels of N-cadherin and the matrix metalloproteinases. Differential microRNA expression also holds promise as a potential prognostic biomarker of malignancy and disease spread within the setting of ulceration. However, the molecular and cellular differences associated with the ulcerated state are complex and further study will aid in determining how these differences can be harnessed to improve care for patients with melanoma.

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Anticancer Effect of Cold Atmospheric Plasma in Syngeneic Mouse Models of Melanoma and Colon Cancer

et al. 2023

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Cold atmospheric plasma (CAP) may have applications in treating various types of malignant tumors. This study assessed the anticancer effects of CAP using melanoma and colon cancer cell lines. CAP treatment significantly reduced the in vitro viability of melanoma and colon cancer cell lines and had a negligible effect on the viability of normal human melanocytes. Additionally, CAP and epidermal growth factor receptor (EGFR) inhibitor had an additive anticancer effect in a CAP-resistant melanoma cell line. Reactive oxygen and nitrogen species known to be generated by CAP enhanced the anticancer effects of CAP and EGFR inhibitors. The in vivo anticancer activities of CAP were evaluated by testing its effects against syngeneic tumors induced in mice by melanoma and colon cancer cells. CAP treatment reduced tumor volume and weight in both cancer models, with the extent of tumor reduction dependent on the duration and number of CAP treatments. Histologic examination also revealed the tumoricidal effects of CAP in both tumor models. In conclusion, CAP inhibits the growth of mouse melanoma and colon cancer cell lines in vitro and shows tumoricidal effects against mouse models of melanoma and colon cancer in vivo.

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Prognostic Significance of Epidermal Growth Factor Receptor Expression in Distant Metastatic Melanoma from Primary Cutaneous Melanoma

Cited by 3 publications

References 23 publications

Theranostic Activity of Ceria-Based Nanoparticles toward Parental and Metastatic Melanoma: 2D vs 3D Models

Theranostic Activity of Ceria-Based Nanoparticles toward Parental and Metastatic Melanoma: 2D vs 3D Models

Ulcerated Cutaneous Melanoma: A Review of the Clinical, Histologic, and Molecular Features Associated with a Clinically Aggressive Histologic Phenotype

Anticancer Effect of Cold Atmospheric Plasma in Syngeneic Mouse Models of Melanoma and Colon Cancer

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