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Browsing by Author "Diaz, Michael J."

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    A Review of Current and Pipeline Drugs for Treatment of Melanoma
    (MDPI, 2024-02-07) Natarelli, Nicole; Aleman, Sarah J.; Mark, Isabella M.; Tran, Jasmine T.; Kwak, Sean; Botto, Elizabeth; Aflatooni, Shaliz; Diaz, Michael J.; Lipner, Shari R.; Medicine, School of Medicine
    Malignant melanoma is the most aggressive form of skin cancer. Standard treatment options include surgery, radiation therapy, systemic chemotherapy, targeted therapy, and immunotherapy. Combining these modalities often yields better responses. Surgery is suitable for localized cases, sometimes involving lymph node dissection and biopsy, to assess the spread of the disease. Radiation therapy may be sometimes used as a standalone treatment or following surgical excision. Systemic chemotherapy, while having low response rates, is utilized as part of combination treatments or when other methods fail. The development of resistance to systemic chemotherapies and associated side effects have prompted further research and clinical trials for novel approaches. In the case of advanced-stage melanoma, a comprehensive approach may be necessary, incorporating targeted therapies and immunotherapies that demonstrate significant antitumor activity. Targeted therapies, including inhibitors targeting BRAF, MEK, c-KIT, and NRAS, are designed to block the specific molecules responsible for tumor growth. These therapies show promise, particularly in patients with corresponding mutations. Combination therapy, including BRAF and MEK inhibitors, has been evidenced to improve progression-free survival; however, concerns about resistance and cutaneous toxicities highlight the need for close monitoring. Immunotherapies, leveraging tumor-infiltrating lymphocytes and CAR T cells, enhance immune responses. Lifileucel, an FDA-approved tumor-infiltrating lymphocyte therapy, has demonstrated improved response rates in advanced-stage melanoma. Ongoing trials continue to explore the efficacy of CAR T-cell therapy for advanced melanoma. Checkpoint inhibitors targeting CTLA-4 and PD-1 have enhanced outcomes. Emerging IL-2 therapies boost dendritic cells, enhancing anticancer immunity. Oncolytic virus therapy, approved for advanced melanoma, augments treatment efficacy in combination approaches. While immunotherapy has significantly advanced melanoma treatment, its success varies, prompting research into new drugs and factors influencing outcomes. This review provides insights into current melanoma treatments and recent therapeutic advances.
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    Association between alopecia areata and atopic dermatitis: A nested case-control study of the All of Us database
    (Elsevier, 2023) Diaz, Michael J.; Haq, Zaim; Abdi, Parsa; Tran, Jasmine T.; Guttman-Yassky, Emma; Ungar, Benjamin; Dermatology, School of Medicine
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    Cutaneous Manifestations of Rheumatoid Arthritis: Diagnosis and Treatment
    (MDPI, 2023-10-10) Diaz, Michael J.; Natarelli, Nicole; Wei, Aria; Rechdan, Michaela; Botto, Elizabeth; Tran, Jasmine T.; Forouzandeh, Mahtab; Plaza, Jose A.; Kaffenberger, Benjamin H.; Medicine, School of Medicine
    Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by inflammatory arthritis and periarticular structural damage. Available evidence suggests that RA results from complex interactions between genetic susceptibility (e.g., HLA-DRB1), environmental factors (e.g., smoking), and immune dysregulation. Alongside joint-related symptoms, individuals with RA may also experience a wide array of skin issues, including the development of nodules, neutrophilic dermatoses, vasculitis, and vasculopathy. Treatment strategies for these manifestations vary but routinely involve corticosteroids, disease-modifying anti-rheumatic drugs, and biologics, with individualized approaches guided by disease severity. In this review, we provide comprehensive insights into the skin-related issues associated with RA, outlining their clinical characteristics and histopathological findings. Our aim is to facilitate early diagnosis and personalized treatment to improve the quality of life of affected individuals.
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    Dietary Interventions, Supplements, and Plant-Derived Compounds for Adjunct Vitiligo Management: A Review of the Literature
    (MDPI, 2025-01-20) Diaz, Michael J.; Tran, Jasmine T.; Rose, Drake; Wei, Aria; Lakshmipathy, Deepak; Lipner, Shari R.; Medicine, School of Medicine
    Vitiligo is a chronic autoimmune pigmentation disorder shaped by a complex interplay of genetic predispositions and environmental triggers. While conventional therapies-phototherapy, corticosteroids, and immunosuppressants-can be effective, their benefits are often partial and temporary, with recurrence common once treatment stops. As such, there is increasing interest in exploring complementary approaches that may offer a more sustainable impact. Emerging evidence suggests that macronutrient and micronutrient-level changes could be beneficial for managing progression and, in some cases, facilitating repigmentation. Antioxidant-rich foods, such as apples, green tea, Indian gooseberry, onions, and peppers, may help mitigate oxidative stress, while inflammatory foods, such as gluten and high-phenol nuts and berries, may exacerbate the condition. Certain supplements, including high-dose vitamin D, vitamin C, vitamin E, and selenium, may enhance phototherapy outcomes. Omega-3 and other unsaturated fatty acids, in addition to prebiotics and probiotics, are under active investigation for their roles in gut health and immune regulation. Notably, plant-derived compounds, i.e., Ginkgo biloba, have demonstrated promise in promoting repigmentation and managing disease progression. However, it must be emphasized that these nutritional interventions remain exploratory, and more research is needed to establish their efficacy, safety, and optimal usage before they can be recommended as part of a standard treatment regimen.
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    Integrated Analysis of Single-Cell and Bulk RNA Data Reveals Complexity and Significance of the Melanoma Interactome
    (MDPI, 2025-01-05) Diaz, Michael J.; Tran, Jasmine T.; Samia, Arthur M.; Forouzandeh, Mahtab; Grant-Kels, Jane M.; Montanez-Wiscovich, Marjorie E.; Medicine, School of Medicine
    Background: Despite significant strides in anti-melanoma therapies, resistance and recurrence remain major challenges. A deeper understanding of the underlying biology of these challenges is necessary for developing more effective treatment paradigms. Methods: Melanoma single-cell data were retrieved from the Broad Single Cell Portal (SCP11). High-dimensional weighted gene co-expression network analysis (hdWGCNA), CellChat, and ligand-receptor relative crosstalk (RC) scoring were employed to evaluate intercellular and intracellular signaling. The prognostic value of key regulatory genes was assessed via Kaplan-Meier (KM) survival analysis using the 'SKCM-TCGA' dataset. Results: Twenty-seven (27) gene co-expression modules were identified via hdWGCNA. Notable findings include NRAS Q61L melanomas being enriched for modules involving C19orf10 and ARF4, while BRAF V600E melanomas were enriched for modules involving ALAS1 and MYO1B. Additionally, CellChat analysis highlighted several dominant signaling pathways, namely MHC-II, CD99, and Collagen-receptor signaling, with numerous significant ligand-receptor interactions from melanocytes, including CD99-CD99 communications with cancer-associated fibroblasts, endothelial cells, NK cells, and T-cells. KM analysis revealed that higher expression of SELL, BTLA, IL2RG, PDGFA, CLDN11, ITGB3, and SPN improved overall survival, while higher FGF5 expression correlated with worse survival. Protein-protein interaction network analysis further indicated significant interconnectivity among the identified prognostic genes. Conclusions: Overall, these insights underscore critical immune interactions and potential therapeutic targets to combat melanoma resistance, paving the way for more personalized and effective treatment strategies.
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    Primary and Metastatic Cutaneous Melanomas Discriminately Enrich Several Ligand-Receptor Interactions
    (MDPI, 2023-01-08) Diaz, Michael J.; Fadil, Angela; Tran, Jasmine T.; Batchu, Sai; Root, Kevin T.; Tran, Andrew X.; Lucke-Wold, Brandon; Dermatology, School of Medicine
    Introduction: Cutaneous melanoma remains a leading cancer with sobering post-metastasis mortality rates. To date, the ligand-receptor interactome of melanomas remains weakly studied despite applicability to anti-cancer drug discovery. Here we leverage established crosstalk methodologies to characterize important ligand-receptor pairs in primary and metastatic cutaneous melanoma. Methods: Bulk transcriptomic data, representing 470 cutaneous melanoma samples, was retrieved from the Broad Genome Data Analysis Center Firehose portal. Tumor and stroma compartments were computationally derived as a function of tumor purity estimates. Identification of preferential ligand-receptor interactions was achieved by relative crosstalk scoring of 1380 previously established pairs. Results: Metastatic cutaneous melanoma uniquely enriched PTH2-PTH1R for tumor-to-stroma signaling. The Human R-spondin ligand family was involved in 4 of the 15 top-scoring stroma-to-tumor interactions. Receptor ACVR2B was involved in 3 of the 15 top-scoring tumor-to-tumor interactions. Conclusions: Numerous gene-level differences in ligand-receptor crosstalk between primary and metastatic cutaneous melanomas. Further investigation of notable pairings is warranted.
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    Psoriasis and non-Hodgkin’s lymphoma in a diverse sample of US adults: a propensity matched case-control study
    (Elsevier, 2024-03-05) Diaz, Michael J.; Haq, Zaim; Tran, Jasmine T.; Abdi, Parsa; Motaparthi, Kiran; Grant-Kels, Jane M.; Montanez-Wiscovich, Marjorie E.; Dermatology, School of Medicine
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