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Journal of Cellular Physiology Nov 2023Melanoma is the most aggressive form of skin cancer with rapidly increased incidence worldwide especially in the Caucasian population. Surgical excision represents the...
Melanoma is the most aggressive form of skin cancer with rapidly increased incidence worldwide especially in the Caucasian population. Surgical excision represents the curative treatment choice in patients with early-stage disease. However, the therapeutic outcomes in patients with metastatic melanoma remains unsatisfactory. Thus, understanding molecular mechanisms contributing to metastasis and chemoresistance is critical for new improved therapies of melanoma. Snail1, an important epithelial-mesenchymal transition transcription factors (EMT-TFs), is critical to induce the EMT process, thereby contributing to cancer metastasis. However, the involvement of Snail1 in melanoma metastasis remains elusive and the underlying mechanism to regulate Snail1 in melanoma needs to be further investigated. Here, we identified OTUD4 as a novel deubiquitinase of Snail1 in melanoma. Moreover, the depletion of OTUD4 in melanoma cells markedly inhibited Snail1 stability and Snail1-driven malignant phenotypes both in vitro and in vivo. Overall, our study establishes OTUD4 as a novel therapeutic target in metastasis and chemoresistance of melanoma by stabilizing Snail1 and provides a rationale for potential therapeutic strategies of melanoma.
Topics: Animals; Humans; Mice; Cell Line, Tumor; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Melanoma; Mice, Nude; Skin Neoplasms; Snail Family Transcription Factors; Transcription Factors; Ubiquitin-Specific Proteases
PubMed: 37642406
DOI: 10.1002/jcp.31104 -
Postepy Biochemii Sep 2023Malignant melanoma is a dangerous skin cancer, accounting for the majority of skin cancer-related deaths. Many patients with this cancer have the V600E mutation in the...
Malignant melanoma is a dangerous skin cancer, accounting for the majority of skin cancer-related deaths. Many patients with this cancer have the V600E mutation in the BRAF gene. This mutation causes constitutive activation of the MAPK/ERK signaling pathway, significantly contributing to the process of carcinogenesis. We discuss the drug design process on the example of a specific BRAF V600E inhibitor, vemurafenib. We begin with the most commonly used drug design methods. The second part of the article focuses on vemurafenib. We analyze the invention of this BRAF V600E inhibitor and its analogue as well as the course of three stages of clinical trials. Then we provide information about other popular drugs for malignant melanoma, i.e. dacarbazine, ipilimumab and dabrafenib, and about the advantages of therapy with the simultaneous use of two inhibitors. Finally, we briefly discuss the role of artificial intelligence in the future of drug design.
Topics: Humans; Vemurafenib; Antineoplastic Agents; Proto-Oncogene Proteins B-raf; Artificial Intelligence; Indoles; Sulfonamides; Melanoma; Skin Neoplasms; Protein Kinase Inhibitors; Mutation; Drug Resistance, Neoplasm; Melanoma, Cutaneous Malignant
PubMed: 38019740
DOI: 10.18388/pb.2021_498 -
Journal of Drugs in Dermatology : JDD Sep 2023McCormick ET, Desai S, Nelson K, et al. Fractional laser for prevention of non-melanoma skin cancer. J Drugs Dermatol. 2023;22(9):953-954. doi:10.36849/JDD.NVRN0923.
McCormick ET, Desai S, Nelson K, et al. Fractional laser for prevention of non-melanoma skin cancer. J Drugs Dermatol. 2023;22(9):953-954. doi:10.36849/JDD.NVRN0923.
Topics: Humans; Skin Neoplasms; Lasers
PubMed: 37683071
DOI: 10.36849/JDD.0923 -
Hematological Oncology Dec 2023Patients with cutaneous T-cell lymphoma with progressive disease typically undergo a series of skin-directed and systemic therapy regimens during cycles of response and... (Review)
Review
Patients with cutaneous T-cell lymphoma with progressive disease typically undergo a series of skin-directed and systemic therapy regimens during cycles of response and relapse. Extracorporeal photopheresis (ECP) is an effective and safe systemic treatment option, often reserved for later stages of disease and typically employed after failure of several other therapies. ECP has benefits in response rate, time to next treatment, and tolerability that may support its use earlier in the treatment cycle for advancing/progressing disease.
Topics: Humans; Photopheresis; Mycosis Fungoides; Skin Neoplasms; Neoplasm Recurrence, Local; Lymphoma, T-Cell, Cutaneous
PubMed: 37974524
DOI: 10.1002/hon.3229 -
Archives of Dermatological Research Nov 2023Organ transplant recipients are at high risk for skin cancer. Currently, more than half of the transplant waiting list is composed of skin of color patients. Skin cancer... (Randomized Controlled Trial)
Randomized Controlled Trial
Organ transplant recipients are at high risk for skin cancer. Currently, more than half of the transplant waiting list is composed of skin of color patients. Skin cancer in skin of color is associated with higher morbidity and mortality and has a different clinical presentation and risk factors. Yet, skin cancer prevention resources and efforts are primarily focused on non-skin of color patients. A cross-sectional pilot survey was administered to assess and compare skin cancer attitudes, behaviors, and knowledge especially risk factors and features specific to skin of color between skin of color and non-skin of color organ transplant recipients. Patients from a patient list obtained from the University of Texas Southwestern Medical Center organ transplant center were randomized on Excel and contacted by phone with the choice to participate by phone or online. 219 of 403 patients completed the survey. Skin of color organ transplant recipients was significantly more likely to never practice recommended skin cancer preventative behaviors (p = 0.002, 0.006, 0.02), to hold a lower perceived self-risk (p = 0.02), to worry less about getting skin cancer (p = 0.003), and to have false perceptions about risk factors (p = 0.001, 0.005) in either univariable or multivariable analysis. However, they were more likely (38%, p = 0.02) to recognize human papillomavirus as a risk factor. The knowledge gaps identified can guide the development of skin cancer educational resources that are more comprehensive and relevant to skin of color recipients. This can lead to better outcomes and reduce racial health disparities.
Topics: Humans; Cross-Sectional Studies; Skin Neoplasms; Organ Transplantation; Risk Factors; Attitude; Transplant Recipients
PubMed: 35871186
DOI: 10.1007/s00403-022-02371-x -
Journal of the American Academy of... Aug 2023Conventional excision of female genital skin cancers has high rates of local recurrence and morbidity. Few publications describe local recurrence rates (LRRs) and...
A retrospective case series of Mohs micrographic surgery and interdisciplinary management of female genital skin cancers: Local recurrence rates and patient-reported outcomes.
BACKGROUND
Conventional excision of female genital skin cancers has high rates of local recurrence and morbidity. Few publications describe local recurrence rates (LRRs) and patient-reported outcomes (PROs) after Mohs micrographic surgery (MMS) for female genital skin cancers.
OBJECTIVE
To evaluate LRRs, PROs, and interdisciplinary care after MMS for female genital skin cancers.
METHODS
A retrospective case series was conducted of female genital skin cancers treated with MMS between 2006 and 2021 at an academic center. The primary outcome was local recurrence. Secondary outcomes were PROs and details of interdisciplinary care.
RESULTS
Sixty skin cancers in 57 patients were treated with MMS. Common diagnoses included squamous cell cancer (n = 26), basal cell cancer (n = 12), and extramammary Paget disease (n = 11). Three local recurrences were detected with a mean follow-up of 61.1 months (median: 48.8 months). Thirty-one patients completed the PROs survey. Most patients were satisfied with MMS (71.0%, 22/31) and reported no urinary incontinence (93.5%, 29/31). Eight patients were sexually active at follow-up and 75.0% (6/8) experienced no sexual dysfunction. Most cases involved interdisciplinary collaboration 71.7% (43/60).
LIMITATIONS
Limitations include the retrospective single-center design, heterogeneous cohort, and lack of preoperative function data.
CONCLUSIONS
Incorporating MMS into interdisciplinary teams may help achieve low LRRs and satisfactory function after genital skin cancer surgery.
Topics: Humans; Female; Mohs Surgery; Retrospective Studies; Neoplasm Recurrence, Local; Skin Neoplasms; Genitalia, Female
PubMed: 36918082
DOI: 10.1016/j.jaad.2023.02.050 -
The American Journal of Surgical... Dec 2023Although mostly recognized in the metastatic setting dedifferentiated and undifferentiated melanomas are increasingly recognized as cutaneous and, less commonly, mucosal...
Although mostly recognized in the metastatic setting dedifferentiated and undifferentiated melanomas are increasingly recognized as cutaneous and, less commonly, mucosal primary tumors. Their diagnosis is challenging and dependent on sampling and recognition of a conventional melanoma precursor and/or detection of a mutation in a conventional melanoma driver gene. PRAME immunohistochemistry has recently become an important ancillary tool in the separation of melanoma from benign nevi, but no comprehensive studies exist regarding its value in the detection of dedifferentiated and undifferentiated melanomas and their separation from atypical fibroxanthoma and pleomorphic dermal sarcoma, the main differential diagnoses on sun-damaged skin. After retrieval from archival files, we performed PRAME immunohistochemistry on 11 primary and 10 metastatic dedifferentiated and undifferentiated melanomas, 11 atypical fibroxanthomas, and 10 pleomorphic dermal sarcomas. Nuclear staining was assigned extent (ranging from 0 to 4 and reflecting the percentage of PRAME-positive tumor nuclei) and intensity scores (graded as absent, weak, moderate, and strong, with assigned scores ranging from 0 to 3) with combined scores ranging from 0 to 7. Both primary and metastatic dedifferentiated and undifferentiated melanomas showed strong and diffuse nuclear PRAME staining with median combined scores of 7. Strong and diffuse staining was also seen in all conventional melanoma precursors except for desmoplastic melanoma. In contrast, PRAME staining in atypical fibroxanthoma and pleomorphic dermal sarcoma was patchy and weak with median combined scores of 2. Our data emphasize the diagnostic utility of PRAME staining as a first screening tool in the detection and workup of dedifferentiated and undifferentiated melanomas, both in the primary and metastatic settings. PRAME immunohistochemistry is particularly helpful as it is also positive in tumors without a recognizable conventional melanoma precursor and in those associated with desmoplastic melanomas, where PRAME is typically found to be negative.
Topics: Humans; Biomarkers, Tumor; Melanoma; Skin Neoplasms; Transcription Factors; Diagnosis, Differential; Sarcoma; Antigens, Neoplasm
PubMed: 37727938
DOI: 10.1097/PAS.0000000000002125 -
International Journal of Molecular... Nov 2023Cutaneous melanoma (CM) is an increasingly significant public health concern. Due to alarming mortality rates and escalating incidence, it is crucial to understand its... (Review)
Review
Cutaneous melanoma (CM) is an increasingly significant public health concern. Due to alarming mortality rates and escalating incidence, it is crucial to understand its etiology and identify emerging biomarkers for improved diagnosis and treatment strategies. This review aims to provide a comprehensive overview of the multifactorial etiology of CM, underscore the importance of early detection, discuss the molecular mechanisms behind melanoma development and progression, and shed light on the role of the potential biomarkers in diagnosis and treatment. The pathogenesis of CM involves a complex interplay of genetic predispositions and environmental exposures, ultraviolet radiation exposure being the predominant environmental risk factor. The emergence of new biomarkers, such as novel immunohistochemical markers, gene mutation analysis, microRNA, and exosome protein expressions, holds promise for improved early detection, and prognostic and personalized therapeutic strategies.
Topics: Humans; Melanoma; Skin Neoplasms; Immunohistochemistry; Ultraviolet Rays; Biomarkers; Melanoma, Cutaneous Malignant
PubMed: 37958863
DOI: 10.3390/ijms242115881 -
Journal of the American Academy of... Sep 2023Although there is a higher incidence of melanoma among non-Hispanic White individuals, melanoma is diagnosed at more advanced stages and associated with worse survival... (Review)
Review
Although there is a higher incidence of melanoma among non-Hispanic White individuals, melanoma is diagnosed at more advanced stages and associated with worse survival rates among individuals with skin of color (SOC). The proportions of melanoma subtypes differ across racial groups, with acral lentiginous melanoma and mucosal melanoma representing higher proportions of melanoma diagnoses in individuals with SOC compared to White individuals. The recognition of distinct differences in anatomic locations and dermatoscopic patterns may facilitate the appropriate differentiation of physiologic from pathologic pigmentation. The first article of this continuing medical education series will focus on the epidemiology and clinical presentation of melanoma in individuals with SOC, with the aim of improving early diagnoses and clinical outcomes.
Topics: Humans; Dermoscopy; Melanoma; Skin; Skin Neoplasms; Racial Groups
PubMed: 35533771
DOI: 10.1016/j.jaad.2022.04.056 -
Veterinary Pathology Nov 2023Cutaneous mastocytosis (CM) is a rare condition in young dogs characterized by multicentric cutaneous proliferation of neoplastic mast cells. Clinical data from 8 dogs... (Review)
Review
Cutaneous mastocytosis (CM) is a rare condition in young dogs characterized by multicentric cutaneous proliferation of neoplastic mast cells. Clinical data from 8 dogs that met inclusion criteria (age of onset less than 1.5 years, greater than 3 lesions) were obtained via a standardized survey. Biopsy samples were classified by the Kiupel/Patnaik grading systems and analyzed for mutations. The median age of onset was 6 months (range: 2-17 months). Dogs had 5 to more than 50 lesions characterized as nodules, plaques, and papules. Seven dogs were pruritic. Clinical staging in 2 dogs did not reveal visceral involvement. No dogs had systemic illnesses at diagnosis. Histologically, CM was similar to cutaneous mast cell tumor (cMCT). Two dogs had neoplasms classified as high-grade/grade II while 6 dogs had low-grade/grade II neoplasms. No dogs had mutations in exons 8 and 11. Treatment included antihistamines (8/8), corticosteroids (7/8), lokivetmab (3/8), and toceranib (1/8). Six dogs were alive with lesions at the end of the study with a median follow-up time of 898 days, while 2 dogs were euthanized. In dogs with high-grade/grade II neoplasms, one continued to develop lesions at 1922 days post-diagnosis, while the other dog was euthanized at 56 days post-diagnosis. One dog was euthanized 621 days post-diagnosis due to rupture of a neoplasm. CM occurs in young dogs and is histologically indistinguishable from cMCT. Current histologic grading systems did not apply uniformly to the dogs of the study and further studies are needed.
Topics: Dogs; Animals; Mastocytosis, Cutaneous; Skin; Skin Neoplasms; CME-Carbodiimide; Dog Diseases; Mast Cells
PubMed: 37222130
DOI: 10.1177/03009858231174452