Assessing the Impact of Visual and Audio Media on Sunscreen Use Among People of Color: Pre- and Post-Survey.

BACKGROUND: Poor melanoma outcomes in people of color (POC) are attributed to a variety of factors, including healthcare literacy, socioeconomic status, and healthcare access barriers.  Methods: We designed a survey to determine if visual and audio media (VAM) would increase POC's understanding of the need for sunscreen and their willingness to use it. Patients recruited at a dermatology clinic were asked to watch a 2.5-minute video on sun protection and complete a pre- and post-survey assessing their knowledge. RESULTS: Forty-one (41) patients were recruited, 43.9% of whom identified as POC and 31.7% as Hispanic or Latino. In the post-survey, 100% of participants agreed that daily sunscreen use helps prevent sun-related risks, compared to 68% before (P<.0001). 71% of the participants intended to use sunscreen daily after watching the video, compared to 24% who did so before (P<.0001). One-hundred percent (100%) of Black participants in the post-survey agreed that sunscreen wear helps prevent risks associated with sun exposure, compared to 46% in the pre-survey (P= 0.0052); no significant difference among White participants (80% vs 100%; P=0.1121). LIMITATIONS: Small sample size, no long-term follow-up. CONCLUSIONS: This study demonstrates the persistence of health disparities and the effectiveness of VAM in enhancing Black patients' healthcare literacy. J Drugs Dermatol. 2024;23(7):525-528.     doi:10.36849/JDD.7821.

Antitumor activity of anlotinib in malignant melanoma: modulation of angiogenesis and vasculogenic mimicry.

Malignant melanoma presents a formidable challenge due to its aggressive metastatic behavior and limited response to current treatments. To address this, our study delves into the impact of anlotinib on angiogenesis and vasculogenic mimicry using malignant melanoma cells and human umbilical vein endothelial cells. Evaluating tubular structure formation, cell proliferation, migration, invasion, and key signaling molecules in angiogenesis, we demonstrated that anlotinib exerts a dose-dependent inhibition on tubular structures and effectively suppresses cell growth and invasion in both cell types. Furthermore, in a mouse xenograft model, anlotinib treatment resulted in reduced tumor growth and vascular density. Notably, the downregulation of VEGFR-2, FGFR-1, PDGFR-ß, and PI3K underscored the multitargeted antitumor activity of anlotinib. Our findings emphasize the therapeutic potential of anlotinib in targeting angiogenesis and vasculogenic mimicry, contributing to the development of novel strategies for combating malignant melanoma.

Identification of RNA-binding protein hnRNP C targeting the 3'UTR of the TAP-associated glycoprotein tapasin in melanoma.

Deregulation or loss of the human leukocyte antigen class I (HLA-I) molecules on tumor cells leading to inhibition of CD8+ T cell recognition is an important tumor immune escape strategy, which could be caused by a posttranscriptional control of molecules in the HLA-I pathway mediated by RNA-binding proteins (RBPs). So far, there exists only limited information about the interaction of RBPs with HLA-I-associated molecules, but own work demonstrated a binding of the heterogeneous ribonucleoprotein C (hnRNP C) to the 3' untranslated region (UTR) of the TAP-associated glycoprotein tapasin (tpn). In this study, in silico analysis of pan-cancer TCGA datasets revealed that hnRNP C is higher expressed in tumor specimens compared to corresponding normal tissues, which is negatively correlated to tpn expression, T cell infiltration and the overall survival of tumor patients. Functional analysis demonstrated an upregulation of tpn expression upon siRNA-mediated downregulation of hnRNP C, which is accompanied by an increased HLA-I surface expression. Thus, hnRNP C has been identified to target tpn and its inhibition could improve the HLA-I surface expression on melanoma cells suggesting its use as a possible biomarker for T-cell-based tumor immunotherapies.

Faecalibaterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors.

Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of Faecalibacterium prausnitzii have been associated with a positive response to ICI in multiple cancer types. Here, based on fecal shotgun metagenomics data, we show in two independent cohorts of patients with non-small cell lung cancer and advanced melanoma that a high level of F. prausnitzii at baseline is positively associated with a better clinical response to ICI. In MCA205 tumor-bearing mice, administration of F. prausnitzii strain EXL01, already in clinical development for Inflammatory Bowel Disease, restores the anti-tumor response to ICI in the context of antibiotic-induced microbiota perturbation at clinical and tumor transcriptomics level. In vitro, EXL01 strain enhances T cell activation in the presence of ICI. Interestingly, oral administration of EXL01 strain did not induce any change in fecal microbiota diversity or composition, suggesting a direct effect on immune cells in the small intestine. F. prausnitzii strain EXL01 will be evaluated as an adjuvant to ICI in multiple cancers in the near future.

A case of melanoma in situ of the central forehead repair by V-Y advancement flap and Burow graft.

Large defects on the face after Mohs surgery have posed significant reconstructive challenges. A 90-year-old man presented with melanoma in situ of the central forehead, which resulted in a 4.5cmx4.3cm defect after multiple stages of Mohs surgery. Although different approaches for forehead repair with nasal root involvement are possible, we demonstrate that the V-Y advancement flap and subsequent Burrow graft for nasal root repair represents a viable closure technique for large circular defects of the central forehead.

[Epidemiological signatures and surveillance bias in cancer]. / Signatures épidémiologiques et biais de surveillance du cancer.

Surveillance bias occurs when variations in cancer incidence are the result of changes in screening or diagnostic practices rather than increases in the true occurrence of cancer. This bias is linked to the issue of overdiagnosis and can be apprehended by looking at epidemiological signatures of cancer. We explain the concept of epidemiological signatures using the examples of melanoma and of lung and prostate cancer. Accounting for surveillance bias is particularly important for assessing the true burden of cancer and for accurately communicating cancer information to the population and decision-makers.

Le biais de surveillance se produit lorsque les variations d'incidence d'un cancer sont le résultat d'un changement dans les pratiques de dépistage ou de diagnostic plutôt que d'une augmentation de la fréquence réelle de ce cancer. Ce biais est lié au concept du surdiagnostic et peut être appréhendé en examinant les signatures épidémiologiques des cancers. Nous expliquons le concept de signature épidémiologique à l'aide des exemples du mélanome et des cancers du poumon et de la prostate. La prise en compte des biais de surveillance est particulièrement importante pour évaluer le fardeau réel du cancer et communiquer avec précision l'information sur le cancer à la population et aux décideurs.

[Epigenetic markers of choroidal melanoma]. / Epigeneticheskie markery melanomy khorioidei.

MicroRNAs (miRNAs) are short non-coding RNAs (18-25 nucleotides in length) that are important participants in the regulation of gene expression. In 2003, their active role in oncogenesis was demonstrated. In 2008, the first report on the isolation of miRNAs from uveal melanoma (UM) tissue was published. Four years later (2012), the presence of miRNAs in the plasma of patients with this category was shown. To date, changes in the expression level of 100 miRNAs in the plasma of cancer patients (with cancer of various localizations) out of the 2654 miRNAs described in mirbase.org have been proven. In the plasma of patients with UM, changes in the expression of only 13 miRNAs have been confirmed. As a rule, studies were conducted in patients at the stage of hematogenous metastasis of UM. PURPOSE: This study analyzed the expression pattern of miRNA-223 and miRNA-126 in patients with localized choroidal melanoma (CM) taking into account biometric parameters in the absence of metastases. MATERIAL AND METHODS: Blood plasma of 84 patients with M0N0 CM aged 35-86 years (mean age 63.4±1.2 years) was investigated. The basis for the diagnosis of CM was the results of ophthalmological examination, optical coherence tomography, and ultrasound scanning. In all cases, the absence of metastases was proven (using computed tomography or magnetic resonance imaging). Control - plasma of 28 volunteers (mean age 62.9±1.42 years, age range 45-78 years), who did not have tumoral, autoimmune, or chronic inflammatory processes. The expression levels of miRNAs circulating in blood plasma were determined by real-time polymerase chain reaction. RESULTS: An increase in the expression levels of miRNA-223 and miRNA-126 in the plasma of all 84 patients with CM was confirmed compared to the control group. Features of the miRNA expression pattern that emerged with changes in the tumor's quantitative parameters were identified. CONCLUSION: Evaluation of the levels of miRNA-223 and miRNA-126 in the blood plasma of patients with CM can be used in clinical practice to clarify the diagnosis of CM, as well as to predict the development of hematogenous metastases.

Patterns and trends in melanoma mortality in the United States, 1999-2020.

INTRODUCTION: Melanoma, a deadly form of skin cancer, has witnessed a notable increase in incidence over the past decades. Despite advancements in treatment, it remains a significant cause of cancer mortality. Understanding demographic trends and variations in melanoma mortality is crucial for addressing disparities and implementing effective interventions. METHODS: Using the Centers for Disease Control Wide Ranging Online Data for Epidemiologic Research (CDC WONDER) database, we analyzed melanoma mortality data in the United States from 1999 to 2020. Data were stratified by demographic and regional variables, and age-adjusted mortality rates were calculated. Descriptive analysis was performed and Joinpoint regression analysis was employed to identify temporal trends. RESULTS: Between 1999 and 2020, there were 184,416 melanoma-related deaths in the United States Overall, the age-adjusted mortality rate declined from 2.7 to 2.0 per 100,000 people at a rate of -1.3% annually, with significant variations across demographic groups and regions. Men, non-Hispanic White individuals, and those aged > 65 experienced higher mortality rates. Non-Hispanic White individuals noted the steepest decrease in AAMR after 2013 at a rate of -6.1% annually. Disparities were seen by geographic density, with rural populations exhibiting higher mortality compared to their urban and suburban counterparts. CONCLUSION: The study highlights a significant reduction in melanoma mortality in the U.S. since 2013, potentially attributed to advancements in diagnostic techniques such as dermoscopy and the introduction of immune checkpoint inhibitors. Disparities persist, particularly among rural populations. Targeted interventions focusing on increased screening and education are warranted to further mitigate melanoma mortality and address demographic disparities.

Single cell RNA-sequencing in uveal melanoma: advances in heterogeneity, tumor microenvironment and immunotherapy.

Uveal melanoma (UM) is a highly aggressive and fatal tumor in the eye, and due the special biology of UM, immunotherapy showed little effect in UM patients. To improve the efficacy of immunotherapy for UM patients is of great clinical importance. Single-cell RNA sequencing(scRNA-seq) provides a critical perspective for deciphering the complexity of intratumor heterogeneity and tumor microenvironment(TME). Combing the bioinformatics analysis, scRNA-seq could help to find prognosis-related molecular indicators, develop new therapeutic targets especially for immunotherapy, and finally to guide the clinical treatment options.

Polyamine and EIF5A hypusination downstream of c-Myc confers targeted therapy resistance in BRAF mutant melanoma.

BACKGROUND: BRAF inhibitors are widely employed in the treatment of melanoma with the BRAF V600E mutation. However, the development of resistance compromises their therapeutic efficacy. Diverse genomic and transcriptomic alterations are found in BRAF inhibitor resistant melanoma, posing a pressing need for convergent, druggable target that reverse therapy resistant tumor with different resistance mechanisms. METHODS: CRISPR-Cas9 screens were performed to identify novel target gene whose inhibition selectively targets A375VR, a BRAF V600E mutant cell line with acquired resistance to vemurafenib. Various in vitro and in vivo assays, including cell competition assay, water soluble tetrazolium (WST) assay, live-dead assay and xenograft assay were performed to confirm synergistic cell death. Liquid Chromatography-Mass Spectrometry analyses quantified polyamine biosynthesis and changes in proteome in vemurafenib resistant melanoma. EIF5A hypusination dependent protein translation and subsequent changes in mitochondrial biogenesis and activity were assayed by O-propargyl-puromycin labeling assay, mitotracker, mitoSOX labeling and seahorse assay. Bioinformatics analyses were used to identify the association of polyamine biosynthesis with BRAF inhibitor resistance and poor prognosis in melanoma patient cohorts. RESULTS: We elucidate the role of polyamine biosynthesis and its regulatory mechanisms in promoting BRAF inhibitor resistance. Leveraging CRISPR-Cas9 screens, we identify AMD1 (S-adenosylmethionine decarboxylase 1), a critical enzyme for polyamine biosynthesis, as a druggable target whose inhibition reduces vemurafenib resistance. Metabolomic and proteomic analyses reveal that polyamine biosynthesis is upregulated in vemurafenib-resistant cancer, resulting in enhanced EIF5A hypusination, translation of mitochondrial proteins and oxidative phosphorylation. We also identify that sustained c-Myc levels in vemurafenib-resistant cancer are responsible for elevated polyamine biosynthesis. Inhibition of polyamine biosynthesis or c-Myc reversed vemurafenib resistance both in vitro cell line models and in vivo in a xenograft model. Polyamine biosynthesis signature is associated with poor prognosis and shorter progression free survival after BRAF/MAPK inhibitor treatment in melanoma cohorts, highlighting the clinical relevance of our findings. CONCLUSIONS: Our findings delineate the molecular mechanisms involving polyamine-EIF5A hypusination-mitochondrial respiration pathway conferring BRAF inhibitor resistance in melanoma. These targets will serve as effective therapeutic targets that can maximize the therapeutic efficacy of existing BRAF inhibitors.

m6A- and m5C- modified lncRNAs orchestrate the prognosis in cutaneous melanoma and m6A- modified LINC00893 regulates cutaneous melanoma cell metastasis.

BACKGROUND: As the most important modifications on the RNA level, N6-methyladenosine (m6A-) and 5-methylcytosine (m5C-) modification could have a direct influence on the RNAs. Long non-coding RNAs (lncRNAs) could also be modified by methylcytosine modification. Compared with mRNAs, the function of lncRNAs could be more potent to some extent in biological processes like tumorigenesis. Until now, rare reports have been done associated with cutaneous melanoma. Herein, we wonder if the m6A- and m5C- modified lncRNAs could influence the immune landscape and prognosis in melanoma, and we also want to find some lncRNAs which could directly affect the malignant behaviors of melanoma. METHODS: Systematically, we explored the expression pattern of m6A- and m5C- modified lncRNAs in melanoma from datasets including UCSC Xena and NCBI GEO, and the prognostic lncRNAs were selected. Then, according to the expression pattern of lncRNAs, melanoma samples from these datasets were divided into several subtypes. Prognostic model, nomogram survival model, drug sensitivity, GO, and KEGG pathway analysis were performed. Furthermore, among several selected lncRNAs, we identified one lncRNA named LINC00893 and investigated its expression pattern and its biological function in melanoma cell lines. RESULTS: We identified 27 m6A- and m5C- related lncRNAs which were significantly associated with survival, and we made a subtype analysis of melanoma samples based on these 27 lncRNAs. Among the two subtypes, we found differences of immune cells infiltration between these two subtypes. Then, LASSO algorithm was used to screen the optimized lncRNAs combination including ZNF252P-AS1, MIAT, FAM13A-AS1, LINC-PINT, LINC00893, AGAP2-AS1, OIP5-AS1, and SEMA6A-AS1. We also found that there was a significant correlation between the different risk groups predicted based on RS model and the actual prognosis. The nomogram survival model based on independent survival prognostic factors was also constructed. Besides, sensitivity to chemotherapeutic agents, GO and KEGG analysis were performed. In different risk groups, a total of 14 drug molecules with different distributions were obtained, which included AZD6482, AZD7762, AZD8055, camptothecin, dasatinib, erlotinib, gefitinib, gemcitabine, GSK269962A, nilotinib, rapamycin, and sorafenib. A total of 55 significantly related biological processes and 17 KEGG signaling pathways were screened. At last, we noticed that LINC00893 had a relatively lower expression in melanoma tissue and cell lines compared with adjacent tissues and epidermal melanocyte, and down-regulation of LINC00893 could promote the malignant behavior of melanoma cells in A875 and MV3. In these two melanoma cell lines, down-regulation of m6A-related molecules like YTHDF3 and METTL3 could promote the expression of LINC00893. CONCLUSION: We made an analysis of m6A- and m5C- related lncRNAs in melanoma samples and a prediction of these lncRNAs' role in prognosis, tumor microenvironment, immune infiltration, and clinicopathological features. We also found that LINC00893, which is potentially regulated by m6A modification, could serve as a tumor-suppressor in melanoma and play an inhibitory role in melanoma metastasis.

Incidental Breast Cancer Diagnosis From Lymphoscintography Using 99mTc-Labeled Nanocolloid for Cutaneous Melanoma of the Upper Arm.

ABSTRACT: A 51-year-old woman with a 2-mm-Breslow-thickness melanoma on her arm had 99mTc-nanocolloid lymphoscintigraphy to localize the associated sentinel lymph node. A single axillary node was identified, and histology confirmed a micrometastasis of breast tissue origin. Imaging of the patient's breasts and subsequent biopsy confirmed ipsilateral stage III breast cancer, which was treated with lumpectomy and axillary node clearance. This is the first reported case of an incidental solid cancer diagnosis from a sentinel lymph node biopsy undertaken for a different tumor origin. This illustrates the importance of recognizing overlapping lymphatic distribution of sentinel lymph nodes, which can drain multiple organs.

Trends by race and ethnicity in incidence and mortality of acral lentiginous melanoma: analysis of Surveillance, Epidemiology, and End Results 2000-2020.

Limited data describe the epidemiology and risk factors of acral lentiginous melanoma (ALM). In this retrospective analysis, we examined trends in incidence and mortality of ALM among racial and ethnic minoritized populations. We queried 22 Surveillance, Epidemiology, and End Results registries for cases of ALM among Hispanics, non-Hispanic Asians or Pacific Islanders (NHAPIs), non-Hispanic Blacks (NHBs), and non-Hispanic Whites (NHWs) from 2000 through 2020. Age-adjusted incidence and annual percentage changes (APCs) were estimated. Kaplan-Meier curves were stratified by race and ethnicity and compared with log-rank tests. Cox proportional hazard regression models were adjusted for age, sex, race, ethnicity, income, urban-rural residence, stage, and treatment. Of 4188 total cases of ALM with complete data, our study cohort was comprised of 792 (18.9%) Hispanics, 274 (6.5%) NHAPIs, 336 (8.0%) NHBs, and 2786 (66.5%) NHWs. The age-adjusted incidence of ALM increased by 2.48% (P < 0.0001) annually from 2000 to 2020, which was driven by rising rates among Hispanics (APC 2.34%, P = 0.001) and NHWs (APC 2.69%, P < 0.0001). Incidence remained stable among NHBs (APC 1.15%, P = 0.1) and NHAPIs (APC 1.12%, P = 0.4). From 2000 through 2020, 765 (18.3%) patients died from ALM. Compared to NHWs, Hispanics, NHAPIs, and NHBs had significantly increased ALM-specific mortality (all P < 0.0001). Unadjusted and adjusted cause-specific mortality modeling revealed significantly elevated risk of ALM-specific mortality among Hispanics (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.22-1.75; adjusted hazard ratio [aHR] 1.38, 95% CI 1.14-1.66), NHAPIs (HR 1.80, 95% CI 1.41-2.32; aHR 1.58, 95% CI 1.23-2.04), and NHBs (HR 1.98, 95% CI 1.59-2.47; aHR 2.19, 95% CI 1.74-2.76) (all P < 0.001). Our study finds rising incidence of ALM among Hispanics and NHWs along with elevated risk of ALM-specific mortality among racial and ethnic minoritized populations. Future strategies to mitigate health inequities in ALM are warranted.

Spectrum and Frequency of BRAF Mutations in Skin Melanomas in the Dalmatian Region of Croatia.

Mutation of the BRAF oncogene is one of the most common mutations detected in human neoplasia, occurring in 40-60% of all cutaneous melanoma. BRAF is a serine/threonine protein kinase which is an essential part of the mitogen-activated protein kinase (MAPK) pathway. It is physiologically activated by RAS, but in mutated form, due to molecular conformational change, BRAF becomes constitutively active with subsequent persistent activation of downstream cytoplasmic and nuclear proteins (MEK, ERK, ETS), which finally leads to gene expression that promotes cell growth and survival. Inhibition of the altered MAPK pathway by BRAF inhibitors and combined BRAF/MEK inhibitors in BRAF mutated melanoma has become a standard therapeutic approach (1,2). We recently reported the frequency and clinicopathological features of BRAF V600E mutated melanomas in the Dalmatian region of Croatia. This report included 80 cutaneous melanomas with BRAF analyses performed at our institution until the second half of 2017, using a kit which detected only BRAF V600E mutation (3). From the second half of 2017, we started using a kit which detects several types of BRAF mutations along with NRAS mutation. The aim of this report was to determine the spectrum and frequency of different BRAF mutations in a group of skin melanomas in the Dalmatian region of Croatia and to comment on the relationship between type of BRAF mutation and therapeutic response to MAPK pathway inhibition. The analysis included 179 patients with stage 3 and stage 4 cutaneous melanoma with known BRAF/NRAS mutational status. The paraffin blocks were forwarded from four Dalmatian hospitals (Split: 139 cases, Zadar: 17 cases, Sibenik: 13 cases, Dubrovnik: 10 cases). BRAF/NRAS mutation analysis was performed at the Institute of Pathology, Clinical Hospital Center Split, Croatia, in the period from the second half of 2017 to the end of 2022. For DNA extraction analysis, hematoxylin and eosin stained slides from each submitted sample were reviewed by a pathologist, and tumor tissue was identified for analysis. For all tissue specimens, DNA was extracted from sections (10 mm thick) using the cobas® DNA Sample Preparation Kit (Roche Molecular Diagnostics), following the manufacturer's protocol. The amount of genomic DNA was quantified using the Qubit® 2.0 Fluorometer (Life Technologies) and adjusted to a fixed concentration to be added to the amplification/detection mixture. For mutation analysis, the target DNA was amplified and detected on the cobas z 480 analyzer using the amplification and detection reagents provided in the Roche BRAF/NRAS mutation test (LSR) kit, according to the manufacturer's protocol. The test results were reported as follows: BRAF exon 11 mutation detected, BRAF V600E/E2/D mutation detected, BRAF V600K mutation detected, BRAF V600R mutation detected, BRAF K601E mutation detected, NRAS (G12X, G13X, A18T, Q61X, other NRAS Ex3/4) mutation detected, mutation not detected, or invalid result (no result was obtained on the cobas test). BRAF mutation was observed in 87 patients (48.6%), NRAS mutation was found in 27 patients (15.1%), while 65 patients (36.3%) were without BRAF/NRAS mutation (Table 1). In the group of BRAF mutated melanomas, 61 cases (70.1%) had V600E/E2/D mutation, 20 cases (23%) had V600K mutation, 3 cases (3.4%) had exon 11 mutation, 2 cases (2.3%) had V600R mutation, and 1 case (1.2%) had K601E mutation (Table 2). The observed frequency of BRAF mutated melanomas in this study was similar to the frequency reported in our previous study (48.6% and 47.5%, respectively) (3). The vast majority were BRAF V600 mutations, while BRAF non-V600 mutations were rare (95.4% and 4.6%, respectively). In the group of BRAF V600 mutations, V600E/E2/D mutations predominated, followed by V600K mutations, while V600R mutations were rare. Greaves et al. reported similar frequency of BRAF V600 mutations in a group of 499 BRAF-mutated cutaneous melanomas, with V600E/E2/D mutations observed in 77.2% cases, followed by V600K mutations observed in 17.2% cases, and V600R mutations observed in 2.6% cases (4). BRAF non-V600 mutations (exon 11 and K601E mutations) were rarely observed in this study, confirming the findings of other authors (4,5). A three-class system of BRAF mutations was recently proposed that takes into account the differences in their kinase activity, with class I containing mutants with high kinase activity and high response rate to BRAF and BRAF/MEK inhibitors. Class II BRAF mutations have lower kinase activity than class I mutants, but higher than wild-type BRAF, showing resistance to BRAF inhibitor monotherapy and sensitivity to MEK and BRAF/MEK inhibitors. Finally, class III BRAF mutations are characterized by low kinase activity and low response rate to targeted therapy (6). BRAF V600 mutations belong to class I mutations, which means that the large majority of BRAF-positive melanomas in this study (95.4%) were sensitive to targeted therapy. However, the sensitivity to targeted therapy is different among different class I BRAF mutations. While large randomized controlled trials on combined BRAF/MEK inhibition showed good overall response (63-68%) and improvement of progression-free survival (PFS) and overall survival (OS) for the melanomas with most prevalent V600E and V600K mutations, Menzer et al. showed lower response rate to MAPK pathway inhibition (45%) in the group of metastatic melanomas with BRAF V600 mutations other than V600E/K. The overall response rate to MAPK pathway inhibition in the same group of melanomas with BRAF non-V600 mutations (class II and III mutations) was only 18% (7). In our group of BRAF mutated skin metastatic melanomas, we found only 6 cases (6.9%) with expected lower response rate to MAPK pathway inhibition: 2 cases with V600R mutation (class I non-V600E/K mutation), 1 case with K601E mutation (class II mutation), and 3 cases with exon 11 mutation (class II and III mutations).

Genistein transfersome-embedded topical delivery system for skin melanoma treatment: in vitro and ex vivo evaluations.

Skin melanoma is considered the most dangerous form of skin cancer due to its association with high risk of metastasis, high mortality rate and high resistance to different treatment options. Genistein is a natural isoflavonoid with known chemotherapeutic activity. Unfortunately, it has low bioavailability due to its poor aqueous solubility and excessive metabolism. In the current study, genistein was incorporated into transferosomal hydrogel to improve its bioavailability. The prepared transferosomal formulations were characterized regarding: particle size; polydispersity index; zeta potential; encapsulation efficiency; TEM; FTIR; DSC; XRD; in vitro drug release; viscosity; pH; ex vivo anti-tumor activity on 3D skin melanoma spheroids and 1-year stability study at different storage temperatures. The optimized formulation has high encapsulation efficiency with an excellent particle size that will facilitate its penetration through the skin. The transfersomes have a spherical shape with sustained drug release profile. The anti-tumor activity evaluation of genistein transfersome revealed that genistein is a potent chemotherapeutic agent with enhanced penetration ability through the melanoma spheroids when incorporated into transfersomes. Stability study results demonstrate the high physical and chemical stability of our formulations. All these outcomes provide evidence that our genistein transferosomal hydrogel is a promising treatment option for skin melanoma.

Correlation Analysis of Apparent Diffusion Coefficient Histogram Parameters and Clinicopathologic Features for Prognosis Prediction in Uveal Melanoma.

Purpose: To investigate the correlation between apparent diffusion coefficient (ADC) histograms and high-risk clinicopathologic features related to uveal melanoma (UM) prognosis. Methods: This retrospective study included 53 patients with UM who underwent diffusion-weighted imaging (DWI) between August 2015 and March 2024. Axial DWI was performed with a single-shot spin-echo echo-planar imaging sequence. ADC histogram parameters of ADCmean, ADC50%, interquartile range (IQR), skewness, kurtosis, and entropy were obtained from DWI. The relationships between histogram parameters and high-risk clinicopathological characteristics including tumor size, preoperative retinal detachment, histological subtypes, Ki-67 index, and chromosome status, were analyzed by Spearman correlation analysis, Mann-Whitney U test, or Kruskal-Wallis test. Results: A total of 53 patients (mean ± SD age, 55 ± 15 years; 22 men) were evaluated. The largest basal diameter (LBD) was correlated with kurtosis (r = 0.311, P = 0.024). Tumor prominence (TP) was correlated with entropy (r = 0.581, P < 0.001) and kurtosis (r = 0.273, P = 0.048). Additionally, significant correlations were identified between the Ki-67 index and ADCmean (r = -0.444, P = 0.005), ADC50% (r = -0.487, P = 0.002), and skewness (r = 0.394, P = 0.014). Finally, entropy was correlated with monosomy 3 (r = 0.541, P = 0.017). Conclusions: The ADC histograms provided valuable insights into high-risk clinicopathologic features of UM and hold promise in the early prediction of UM prognosis.

Melanoma risk, tumour stage, and melanoma-specific mortality in individuals with diabetes: a systematic review and meta-analysis.

BACKGROUND: Cancer has become the leading diabetes-related cause of death in high-income countries, and more knowledge is needed to clarify the impact of diabetes on site-specific cancers. The purpose of this study is to assess the association between diabetes and malignant melanoma by conducting a comprehensive systematic review and meta-analysis. METHODS: Using predefined eligibility criteria, PubMed, The Cochrane Library and Web of Science were systematically searched up to February 22, 2023. Exposure was defined as diabetes or type 2 diabetes and the outcomes were defined as melanoma incidence, melanoma stage or melanoma-specific mortality. The identified articles were evaluated by two independent reviewers and quality assessment was conducted using the Newcastle-Ottawa Scale for observational studies. Meta-analyses were conducted using RevMan 5.4.1 on melanoma risk using adjusted risk estimates and on melanoma stage using a dichotomous model. RESULTS: The literature search revealed 20 studies in total eligible for inclusion, 14 for the analysis of melanoma risk, 3 for melanoma thickness and ulceration, and 4 for melanoma-specific survival. According to the meta-analyses, diabetes did not impact the risk of developing melanoma (RR:1.05, 95%CI:0.99-1.12, p = 0.10). However, type 2 diabetes was associated with more advanced melanoma stages at the time of diagnosis (Breslow-thickness > 1 mm: RR 1.35, 95%CI: 1.22-1.49, p = < 0.001) and presence of ulceration (RR 1.30, 95%CI: 1.00-1.68, p = 0.05). A meta-analysis on the association between diabetes and melanoma-specific mortality was not feasible due to diverse study designs. CONCLUSION: Our meta-analysis found no association between diabetes and the risk of developing melanoma, but diabetes was associated with increased tumour thickness and the presence of ulceration at the time of diagnosis. Further research is warranted to explore the association between diabetes melanoma stage and prognosis. TRIAL REGISTRATION: PROSPERO ID CRD42023394187.

Beyond the Surface: A Case Report of a Patient with Small Bowel Metastasis and Melanoma History. Diagnosis and Management.

Background: Malignant melanoma (MM) is one of the most prevalent and deadliest forms of skin cancer, resulting from the malignant transformation of melanocytes. It accounts for approximately 1.7% of global cancer diagnoses and is the fifth most common cancer in the US. MM can metastasize to almost any part of the body, with early detection significantly improving prognosis. Case presentation: We report the case of an 81-year-old female with a history of malignant melanoma (primary lesion on the left calf) and various comorbidities. She presented with severe anemia of unknown origin. A CT scan was performed due to her medical history, revealing a circumferential, asymmetrical parietal thickening at the level of a hypogastric ileal loop. The lesion suggested a tumoral substrate. Subsequent colonoscopy showed no metastatic lesions, but surgical intervention confirmed a malignant melanoma ileal metastasis. The patient underwent laparoscopic segmental resection with favorable post-surgery outcomes. Histopathological examination of the resected tissue confirmed the diagnosis of small intestine secondary lesions from the malignant melanoma. Conclusion: This case underscores the necessity of considering metastatic melanoma in patients with a history of MM and vague gastrointestinal symptoms. Early and accurate diagnosis through advanced imaging and endoscopic techniques can significantly improve patient outcomes.

Lumbar Melanoma with Sentinel Lymph Nodes in Multiple Basins - Case Report and Review of the Literature.

Intreduction: Melanoma is an extremely aggressive form of skin neoplasia, an important stage in the diagnostic and treatment is identifying the dissemination at the lymphatic level. For a more accurate staging, the sentinel lymph node biopsy technique is performed, which in most of the time addresses one, respectively 2 locations, but cases with sentinel nodes in 3 lymphatic basins have rarely been described. Case report: We present a case of melanoma located in the right lumbar region, which from the point of view of histopathological features has a Breslow index of 4.2 mm, classified in the pT4b stage. After the CT evaluation was performed, it was decided that there is indication for performing the sentinel lymph node technique and excision with a margin of safety. Scintigraphy revealed that sentinel lymph nodes were identified in 3 different regions, respectively the right axilla and bilateral inguinal. Conclusions: Melanoma located on the trunk can present different lymphatic routes for the sentinel lymph nodes, unlike that on the limbs where certain patterns are present. Identifying these lymph nodes in cases like this involves a challenge both from a diagnostic and surgical point of view.

Benefits of dermoscopy in primary care.

ABSTRACT: Skin cancer is the most common cancer in the United States, with an estimated 9,500 new diagnoses made each day. Dermoscopy (also called dermatoscopy) is an established clinical approach to improving skin cancer evaluation. However, only 8% to 9% of primary care physicians use it, and no data are available for physician associate/assistant or NP use. This article reports a dermoscopy algorithm that primary care providers can use to increase the detection of skin cancer and reduce unnecessary referrals and biopsies.