Epidemiology and Risk Factors of Melanoma

The incidence of skin-related neoplasms has generally increased in recent years. Melanoma arises from malignant mutations in melanocytes in the basal layer of the epidermis and is a fatal skin cancer that seriously threatens human health. Isoflavones are polyphenolic compounds widely present in legumes and have drawn scientists’ attention, because they have good efficacy against a variety of cancers, including melanoma, without significant toxic side effects and resistance. In this review article, we summarize the research progress of isoflavones in melanoma, including anti-melanoma roles and mechanisms of isoflavones via inhibition of tyrosinase activity, melanogenesis, melanoma cell growth, invasion of melanoma cells, and induction of apoptosis in melanoma cells. This information is important for the prevention, clinical treatment, and prognosis and survival of melanoma.

Melanoma is one of the most malignant skin tumors, whose high invasion is generally associated with BRAF gene mutation. Although new chemotherapeutic drugs, such as vemurafenib, have been developed to inhibit the growth of melanoma, these drugs are usually administered intravenously or orally, resulting in toxic side effects on major tissues and organs. Tetrahedral framework nucleic acids (tFNAs) are a novel type of DNA nanostructures with excellent biocompatibility and versatility which have been proven to penetrate through skin barrier with ease. In this study, we prepared tFNAs with vemurafenib and connected DNA aptamer AS1411 at the apex of tFNAs (AS1411-tFNAs/vemurafenib). On one hand, AS1411-tFNAs/vemurafenib could kill melanoma cells by blocking the mutated BRAF gene in vitro. Compared with free vemurafenib, AS1411-tFNAs/vemurafenib had no obvious toxicity to normal cells. On the other hand, AS1411-tFNAs could transfer vemurafenib to cross through the skin barrier and permeate into tumor tissues. In vivo, transdermal delivery of AS1411-tFNAs/vemurafenib could inhibit the growth of human A375 melanoma, whose inhibiting effect was stronger than intravenous administration of vemurafenib. These results demonstrated the application prospects of tFNAs combined with chemotherapeutic drugs in skin tumors.

β-acetoxyisovalerylalkannin (β-AIVA) is one of shikonin/alkannin derivative, which were mainly extracted from Boraginaceae family. The effects of β-AIVA on human melanoma A375 cells and U918 cells were investigated in vitro. The CCK-8 assay showed that β-AIVA inhibited proliferation of cells. Results from flow cytometry, ROS assay and JC-1 assay showed that β-AIVA increased late apoptosis rate, induced the production of ROS and promoted mitochondrial depolarization in cells. β-AIVA regulated expressions of BAX and Bcl-2 proteins, and increased the expression of cleaved caspase-9 and cleaved caspase-3. These findings suggest that β-AIVA may be a potential therapeutic drug for treating melanoma.

Melanoma is an aggressive tumor with a poor prognosis that worsens in the metastatic phase. Distruptions of epigenetic mechanisms is known to effect cancer stem cells (CSCs) activity. Malignant melanoma (MM) progression may be promoted by changes in the genetic structure of CSC. Thus, treatments that target epigenetic modifications could be a promising weapon, especially in melanoma. Here, we compared p300, HDAC9, and F-actin proteins in melanoma CSCs (CD133+), non-CSCs (CD133-) and CHL-1 cell line, as well as cell migration and division rates. At 4 and 6 h, P300 protein levels in CHL-1 and CD133 + were remarkably similar, and the CD133- showed increases in expression levels as the incubation period lengthened. HDAC9 protein intensity decreased in CHL-1, increased in the CD133-, and remained relatively unchanged in the CD133+ as the incubation period lengthened. The mean value of F-actin expression level increased in all cell group with time, when the highest increase observed in CHL-1. In conclusion, our studies contribute to the management of metastatic diseases in the future and offer new insight into the molecular basis of the initiation and progression of MM.

Melanoma is a highly lethal form of skin cancer. Although targeted drugs and immunotherapy have definite survival benefits for certain patients, they also encounter systemic toxicity and drug resistance concerns. With nanotechnology developments and the in-depth antigen and receptor study on melanoma cells, nanoparticles functionalized with different ligands (such as antibodies, aptamers, peptides, folate, hyaluronic acid, and transferrin) are utilized in targeted drug delivery systems. In addition, combining biomimetics and nanotechnology provides a developmental platform for constructing cell membrane-camouflaged nanoparticles. Nanoparticles coated with melanoma or immune cell membranes have been scrutinized for melanoma therapy use. These targeting strategies encourage drug accumulation at the tumor site, enhance antitumor efficacy, and reduce systemic toxicity. Exploring new melanoma targets will promote novel target molecule development and high-loading multifunctional targeting nanoparticle production, further improving therapeutic effects. This review highlights recent advances in targeted nanoparticle drug delivery systems for melanoma therapy.

The incidence and mortality of melanoma have increased in the last years in the Caucasian population. This 40-year study of melanoma incidence in Blumenau-SC shows the impact of primary prevention on the decrease of mortality.

To classify cutaneous melanomas and evaluate their incidence in Blumenau from 1980 to 2019.

This retrospective, descriptive and cross-sectional study collected 2,336 histopathological examinations of individuals living in the city, considering sex, age, primary location, histopathological type, invasion level (Clark), and tumor thickness (Breslow). The crude coefficients of annual incidence rates were calculated using the number of melanomas and the population estimated by the Brazilian Institute of Geography and Statistics between 1980 and 2019.

Melanoma incidence rates reached 44.26 cases/100,000 inhabitants/year and the rates by sex reached 52.87 in men and 46.73 cases in women per 100,000 inhabitants. The most affected age group was 70 years old and over, with 421 cases in men and 301 cases/100,000 inhabitants in women. Superficial spreading melanoma occurred in 64.5% of the cases, followed by nodular melanoma in 22.8%. Early diagnoses reached 1900% with Breslow < 0.5 mm.

This study only covers histopathological reports with definitive diagnoses of cutaneous melanoma; therefore, the data are underestimated, consequently resulting in lower rates than in reality.

The incidence of cutaneous melanoma has increased fivefold between 1980 and 2009 and early diagnosis increased as a result of health education and primary prevention.