Malignant Melanoma – from Classical Histology towards Molecular Genetic Testing

Ryška, Aleš; Horký, Ondřej; Berkovcová, Jitka; Tichá, Ivana; Kalinová, Markéta; Matějčková, Milada; Bóday, Arpád; Drábek, Jir̆ı́; Martínek, Petr; Šimová, Jarmila; Sieglová, Kateřina; Vošmiková, Hana

doi:10.14735/amko2017182

Cited by 9 publications

(8 citation statements)

References 42 publications

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“…MM is a catastrophic skin cancer with aggressive biological actions, resistance to chemotherapy, and poor results (2). MM has a complex progress and it is hard to fully elucidate the underlying mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, MM accounted for 60–80% of skin-cancer related deaths (1). Recent studies have indicated that MM is not a single entity but a set of various kinds of neoplasms with different causes, biological behaviors, and outcomes (2). Unfortunately, despite the development of technology and medicine, the survival rate for advanced MM has not improved significantly in the past eight years (3).…”

Section: Introductionmentioning

confidence: 99%

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Schizandrin A exerts anti-tumor effects on A375 cells by down-regulating H19

Wang

et al. 2019

Braz J Med Biol Res

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Malignant melanoma (MM) is one of the malignant tumors with highly metastatic and aggressive biological actions. Schizandrin A (SchA) is a bioactive lignin compound with strong anti-oxidant and anti-aging properties, which is stable at room temperature and is often stored in a cool dry place. Hence, we investigated the effects of SchA on MM cell line A375 and its underlying mechanism. A375 cells were used to construct an in vitro MM cell model. Cell viability, proliferation, apoptosis, and migration were detected by Cell Counting Kit-8, BrdU assay, flow cytometry, and transwell two-chamber assay, respectively. The cell cycle-related protein cyclin D1 and cell apoptotic proteins (Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9) were analyzed by western blot. Alteration of H19 expression was achieved by transfecting with pEX-H19. PI3K/AKT pathway was measured by detecting phosphorylation of PI3K and AKT. SchA significantly decreased cell viability in a dose-dependent manner. Furthermore, SchA inhibited cell proliferation and cyclin D1 expression. SchA increased cell apoptosis along with the up-regulation of pro-apoptotic proteins (cleaved-caspase-3, cleaved-caspase-9, and Bax) and the down-regulation of anti-apoptotic protein (Bcl-2). Besides, SchA decreased migration and down-regulated matrix metalloproteinases (MMP)-2 and MMP-9. SchA down-regulated lncRNA H19. Overexpression of H19 blockaded the inhibitory effects of SchA on A375 cells. SchA decreased the phosphorylation of PI3K and AKT while H19 overexpression promoted the phosphorylation of PI3K and AKT. SchA inhibited A375 cell growth, migration, and the PI3K/AKT pathway through down-regulating H19.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Schizandrin A exerts anti-tumor effects on A375 cells by down-regulating H19

Wang

et al. 2019

Braz J Med Biol Res

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“…Malignant melanoma is the most aggressive tumour of the skin, which arises from the transformation of melanocytes. Its incidence has increased significantly in the last decades [1]. Over the past few years thanks to the development of immunotherapy with immune checkpoint inhibitors and targeted therapy against kinases of the RAS/BRAF/MAPK pathway, the clinical outcome has improved dramatically with the achievement of long term benefit in approximately 50% of patients with metastatic disease [2,3].…”

Section: Introductionmentioning

confidence: 99%

ErbB3 Phosphorylation as Central Event in Adaptive Resistance to Targeted Therapy in Metastatic Melanoma: Early Detection in CTCs during Therapy and Insights into Regulation by Autocrine Neuregulin

Ruggiero

Malpicci

Fattore

et al. 2019

Cancers

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In recent years the introduction of target therapies with BRAF and MEK inhibitors (MAPKi) and of immunotherapy with anti-CTLA-4 and anti-PD-1 monoclonal antibodies have dramatically improved survival of metastatic melanoma patients. Despite these changes drug resistance remains a major hurdle. Several mechanisms are at the basis of drug resistance. Particular attention has been devoted over the last years to unravel mechanisms at the basis of adaptive/non genetic resistance occurring in BRAF mutated melanomas upon treatment with to MAPKi. In this paper we focus on the involvement of activation of ErbB3 receptor following early exposure of melanoma cells to BRAF or MEK inhibitors, and the following induction of PI3K/AKT pathway. Although different mechanisms have been invoked in the past at the basis of this activation we show here with a combination of approaches that autocrine production of neuregulin by melanoma cells is a major factor responsible for ErbB3 phosphorylation and downstream AKT activation. Interestingly the kinetic of neuregulin production and of the ensuing ErbB3 phosphorylation is different in different melanoma cell lines which underscores the high degree of tumor heterogeneity. Moreover, heterogeneity is further highlighted by the evidence that in different cell lines neuregulin upregulation can occur at the transcriptional or at the post-transcritpional level. Finally we complement our study by showing with a liquid biopsy assay that circulating tumor cells (CTCs) from melanoma patients undergo upregulation of ErbB3 phosphorylation in vivo shortly after initiation of therapy.

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“…It has been estimated that its incidence in PLWH is 2.6 times higher than in those uninfected (Marra et al, 2017). This increased incidence is due both to the reduced efficacy of the host immune response in eliminating potentially malignant cells and to the increased survival of PLWH after the introduction of HAART (Ryška et al, 2017). Moreover, in HIVinfected people, melanoma has generally a more aggressive behavior and lower survival compared to uninfected people (Coghill, Shiels, Suneja, & Engels, 2015).…”

Section: Risk Of Malignant Melanoma In Hiv-infected Peoplementioning

confidence: 99%

Malignant melanoma in HIV: Epidemiology, pathogenesis, and management

Facciolà

Rullo

Ceccarelli

et al. 2019

Dermatologic Therapy

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People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV-infected people is 2.6-fold higher than in uninfected ones.In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV-negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV-positive patients regardless of their CD4 + count and the use of standard surgical margins for re-excision procedures. In case of diagnosis of melanoma in HIV-positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV-positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow-up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint-based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.

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Malignant Melanoma – from Classical Histology towards Molecular Genetic Testing

Cited by 9 publications

References 42 publications

Schizandrin A exerts anti-tumor effects on A375 cells by down-regulating H19

Schizandrin A exerts anti-tumor effects on A375 cells by down-regulating H19

ErbB3 Phosphorylation as Central Event in Adaptive Resistance to Targeted Therapy in Metastatic Melanoma: Early Detection in CTCs during Therapy and Insights into Regulation by Autocrine Neuregulin

Malignant melanoma in HIV: Epidemiology, pathogenesis, and management

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