Melanin In Melanoma Research Articles

New Aspects Regarding the Fluorescence Spectra of Melanin and Neuromelanin in Pigmented Human Tissue Concerning Hypoxia.

Melanin is a crucial pigment in melanomagenesis. Its fluorescence in human tissue is exceedingly weak but can be detected through advanced laser spectroscopy techniques. The spectral profile of melanin fluorescence distinctively varies among melanocytes, nevomelanocytes, and melanoma cells, with melanoma cells exhibiting a notably "red" fluorescence spectrum. This characteristic enables the diagnosis of melanoma both in vivo and in histological samples. Neuromelanin, a brain pigment akin to melanin, shares similar fluorescence properties. Its fluorescence can also be quantified with high spectral resolution using the same laser spectroscopic methods. Documented fluorescence spectra of neuromelanin in histological samples from the substantia nigra substantiate these findings. Our research reveals that the spectral behavior of neuromelanin fluorescence mirrors that of melanin in melanomas. This indicates that the typical red fluorescence is likely influenced by the microenvironment around (neuro)melanin, rather than by direct pigment interactions. Our ongoing studies aim to further explore this distinctive "red" fluorescence. We have observed this red fluorescence spectrum in post-mortem measurements of melanin in benign nevus. The characteristic red spectrum is also evident here (unlike the benign nevus in vivo), suggesting that hypoxia may contribute to this phenomenon. Given the central role of hypoxia in both melanoma development and treatment, as well as in fundamental Parkinson's disease mechanisms, this study discusses strategies aimed at reinforcing the hypothesis that red fluorescence from (neuro)melanin serves as an indicator of hypoxia.

Highly Sensitive Detection of Melanin in Melanomas Using Multi-harmonic Low Frequency EPR

PurposeLow frequency EPR can noninvasively detect endogenous free radical melanin in melanocytic skin lesions and could potentially discriminate between benign atypical nevi and malignant melanoma lesions. We recently succeeded in demonstrating the ability of clinical EPR to noninvasively detect the endogenous melanin free radical in skin lesions of patients. However, the signal-to-noise ratio (SNR) was extremely low warranting further research to boost the sensitivity of detection. In the present study, we assessed the performance of a clinical EPR system with the capability to perform multi-harmonic (MH) analysis for the detection of melanin.ProceduresThe sensitivity of MH-EPR was compared with a classical continuous wave (CW)-EPR (1st harmonic) detection in vitro in melanin phantoms, in vivo in melanoma models with cells implanted in the skin, in lymph nodes and having colonized the lungs, and finally on phantoms placed at the surface of human skin.ResultsIn vitro, we observed an increase in SNR by a factor of 10 in flat melanin phantoms when using MH analysis compared to CW combined with an increase in modulation amplitude. In B16 melanomas having grown in the skin of hairless mice, we observed a boost in sensitivity in vivo similar to that observed in vitro with the capability to detect melanoma cells at an earlier stage of development. MH-EPR was also able to detect non-invasively the melanin signal coming from melanoma cells present in lymph nodes as well as in lungs. We also observed a boost of sensitivity using phantoms of melanin placed at the surface of human skin.ConclusionsOverall, our results are paving the way for new clinical trials that will use MH clinical EPR for the characterization of pigmented skin lesions.

Targeting Melanin in Melanoma with Radionuclide Therapy.

Nearly 100,000 individuals are expected to be diagnosed with melanoma in the United States in 2022. Treatment options for late-stage metastatic disease up until the 2010s were few and offered only slight improvement to the overall survival. The introduction of B-RAF inhibitors and anti-CTLA4 and anti-PD-1/PD-L1 immunotherapies into standard of care brought measurable increases in the overall survival across all stages of melanoma. Despite the improvement in the survival statistics, patients treated with targeted therapies and immunotherapies are subject to very serious side effects, the development of drug resistance, and the high costs of treatment. This leaves room for the development of novel approaches as well as for the exploration of novel combination therapies for the treatment of metastatic melanoma. One such approach is targeting melanin pigment with radionuclide therapy. Advances in melanin-targeting radionuclide therapy of melanoma can be viewed from two spheres: (1) radioimmunotherapy (RIT) and (2) radiolabeled small molecules. The investigation of mechanisms of the action and efficacy of targeting melanin in melanoma treatment by RIT points to the involvement of the immune system such as complement dependent cytotoxicity. The combination of RIT with immunotherapy presents synergistic killing in mouse melanoma models. The field of radiolabeled small molecules is focused on radioiodinated compounds that have the ability to cross the cellular membranes to access intracellular melanin and can be applied in both therapy and imaging as theranostics. Clinical applications of targeting melanin with radionuclide therapies have produced encouraging results and clinical work is on-going. Continued work on targeting melanin with radionuclide therapy as a monotherapy, or possibly in combination with standard of care agents, has the potential to strengthen the current treatment options for melanoma patients.

Sinonasal mucosal melanoma: a 10-year experience of 36 cases in China

BackgroundSinonasal mucosal melanoma (SNMM) is a rare tumor with a poor prognosis. This study aimed to assess the clinical and imaging features, progression, treatment, and possible prognostic factors of SNMM.MethodsThirty-six patients with SNMM were retrospectively reviewed in the Department of Otolaryngology & Head and Neck Surgery of Xinhua Hospital from January 2008 to December 2017.ResultsThe age of the first diagnosis was 67.4±10.8 years; the most common clinical symptoms included epistaxis, nasal obstruction, headache, and facial pain. Most tumors originated in the nasal cavity (63.9%) and at stage IV (77.8%). Melanin in melanoma showed typical signal intensity on magnetic resonance imaging (MRI), T1WI had high signal while T2WI had low signal. 41.6% of patients had the typical MRI findings. Treatment included surgery, surgery with radiotherapy, and radiotherapy only. The follow-up time ranged from 4 to 96 months, with a median time of 22 months, 1-, 3-, and 5-year OS is 80.6%, 36.1%, and 13.9%, respectively. The 3-year OS was better in cases in the T3 stage than the T4 stage (P=0.02). However, tumors that originated from the paranasal sinus had a poorer prognosis than the nasal cavity (P=0.04). The cases receiving postoperative radiotherapy showed poorer prognosis (P=0.02). Other factors were not found to be associated with prognosis, including gender, age, lymph node metastasis, distant metastasis, computed tomography (CT) enhancement, and typical MRI findings.ConclusionsThe SNMM was a devastating tumor with poor outcomes; most cases were diagnosed at late stages, which may account for poor prognosis. Tumors with melanin feature MRI findings do not have a better prognosis. The treatment of postoperative radiotherapy is still controversial.

Melanin presence inhibits melanoma cell spread in mice in a unique mechanical fashion

Melanoma is a highly aggressive cancer that exhibits metastasis to various critical organs. Unlike any other cancer cells, melanoma cells can synthesize melanin in large amounts, becoming heavily pigmented. Until now the role of melanin in melanoma, particularly the effect of melanin presence on the abilities of melanoma cells to spread and metastasize remains unknown. Recently, we have shown that melanin dramatically modified elastic properties of melanoma cells and inhibited the cells invasive abilities in vitro. Here, we inoculated human melanoma cells with different melanin content into nude mice and tested the hypothesis that cell elasticity is an important property of cancer cells for their efficient spread in vivo. The obtained results clearly showed that cells containing melanin were less capable to spread in mice than cells without the pigment. Our findings indicate that the presence of melanin inhibits melanoma metastasis, emphasizing possible clinical implications of such an inhibitory effect.

Nanomechanical Phenotype of Melanoma Cells Depends Solely on the Amount of Endogenous Pigment in the Cells.

Cancer cells have unique nanomechanical properties, i.e., they behave as if they were elastic. This property of cancer cells is believed to be one of the main reasons for their facilitated ability to spread and metastasize. Thus, the so-called nanomechanical phenotype of cancer cells is viewed as an important indicator of the cells’ metastatic behavior. One of the most highly metastatic cancer cells are melanoma cells, which have a very unusual property: they can synthesize the pigment melanin in large amounts, becoming heavily pigmented. So far, the role of melanin in melanoma remains unclear, particularly the impact of the pigment on metastatic behavior of melanoma cells. Importantly, until recently the potential mechanical role of melanin in melanoma metastasis was completely ignored. In this work, we examined melanoma cells isolated from hamster tumors containing endogenous melanin pigment. Applying an array of advanced microscopy and spectroscopy techniques, we determined that melanin is the dominating factor responsible for the mechanical properties of melanoma cells. Our results indicate that the nanomechanical phenotype of melanoma cells may be a reliable marker of the cells’ metastatic behavior and point to the important mechanical role of melanin in the process of metastasis of melanoma.

PP 57 Interaction of 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) with melanoma melanin metabolism and cell death

PP 57 Interaction of 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) with melanoma melanin metabolism and cell death

Metastasis imaging: Current concepts and future challenges

Appearance of metastasis marks progression to lethal cancer and is the focus of considerable investment in the development of novel therapeutic agents. The assessment of the efficacy of such agents in the clinic, although traditionally done with standard morphological imaging to document lesion size, increasingly demands use of functional imaging methodologies that report on characteristics of the tumour other than size, namely their vascularity, metabolism, glucose uptake, proliferative capacity, apoptotic response and matrix turnover. This issue of Cancer Biomarkers attempts to highlight functional imaging methodologies that are both established and developing in preclinical and clinical setting, explore the biological features of tumours that give rise to tumour to background contrast and document the utility of some techniques in specific clinical applications. The first review by Stasinopoulos and Penet et al gives an in-depth account of available imaging technologies in the laboratory used to investigate mechanisms of invasion and metastasis. Techniques such as optical imaging to detect degradative enzyme activity and bioluminescence to understand underlying biological processes in a preclinical setting are discussed. The description of a magnetic resonance imaging (MRI) assay to dynamically track invading cancer cells, including use of iron-oxide particles labels to generate negative image contrast, and labelled positron emission tomography (PET) probes to targeted molecules (e.g melanin in melanoma) or expressed proteins sets the scene for the two functional imaging techniques, MRI and PET, that currently dominate imaging in the clinic. Finally the concept of “theranostic” imaging,

Molecular electron paramagnetic resonance imaging of melanin in melanomas: a proof‐of‐concept

The incidence of malignant melanoma is increasing at an alarming rate. As the clinical outcome of the disease strongly depends on the localization of the lesion, early detection at the initial stages of development is critical. Here, we suggest spatial characterization of melanoma based on the presence of endogenous stable free radicals in melanin pigments. Taking into account the abundance of these naturally occurring free radicals in proliferating melanocytes and their localization pattern, we hypothesized that electron paramagnetic resonance (EPR) imaging could be a unique tool for mapping melanomas with high sensitivity and high resolution. The potential of EPR to image melanoma samples was demonstrated in vitro in animal and human samples. Using EPR systems operating at low frequency, we were also able to record in vivo EPR spectra and images from the melanin present in a subcutaneous melanoma implanted in a mouse. In addition to the proof-of-concept and the achievement of providing the first non-invasive image of an endogenous radical, this technology may represent a key advance in improving the diagnosis of suspected melanoma lesions.

Selective incorporation of 2-thiouracil into melanoma melanin

Palumbo, A.1; Martino, L. De1; Napolitano, A.2; d'Ischia, M.2; Prota, G.2 Author Information