1,343 results match your criteria driven melanoma

Isotope tracing in adult zebrafish reveals alanine cycling between melanoma and liver.

Cell Metab 2021 May 11. Epub 2021 May 11.

Department of Chemistry, Washington University in St. Louis, St. Louis, MO, USA; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA. Electronic address:

The cell-intrinsic nature of tumor metabolism has become increasingly well characterized. The impact that tumors have on systemic metabolism, however, has received less attention. Here, we used adult zebrafish harboring BRAF-driven melanoma to study the effect of cancer on distant tissues. Read More

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Reduced WNT5A signaling in melanoma cells favors an amoeboid mode of invasion.

Mol Oncol 2021 May 9. Epub 2021 May 9.

Experimental Pathology, Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden.

Tumor cells invade and spread via either a mesenchymal or an amoeboid mode of migration. Amoeboid tumor cells have a rounded morphology and pronounced RhoA activity. Here, we investigate how WNT5A signaling, a tumor promotor in melanoma, relates to Rho GTPase activity and amoeboid migration. Read More

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Survivin Promoter-Driven DFF40 Gene Expression Sensitizes Melanoma Cancer Cells to Chemotherapy.

Int J Toxicol 2021 May 7:10915818211014170. Epub 2021 May 7.

Department of Pharmaceutical Biotechnology and Isfahan Pharmaceutical Research Center, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

Downregulation of the apoptotic protein DNA fragmentation factor 40 (DFF40) is correlated with poor overall survival in some malignancies, including melanoma. In this study, DFF40 gene expression driven by survivin promoter, a tumor-specific promoter, was used to selectively induce cytotoxicity in melanoma cells. The activity and strength of survivin promoter were examined in B16F10 murine melanoma, and L929 murine normal fibroblast cell lines using enhanced green fluorescent protein reporter assay and reverse transcription polymerase chain reaction. Read More

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ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma.

Nature 2021 May 5. Epub 2021 May 5.

Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Although RAF monomer inhibitors (type I.5, BRAF(V600)) are clinically approved for the treatment of BRAF-mutant melanoma, they are ineffective in non-BRAF mutant cells. Belvarafenib is a potent and selective RAF dimer (type II) inhibitor that exhibits clinical activity in patients with BRAF- and NRAS-mutant melanomas. Read More

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Pharmacological Wnt ligand inhibition overcomes key tumor-mediated resistance pathways to anti-PD-1 immunotherapy.

Cell Rep 2021 May;35(5):109071

Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Duke Cancer Institute, Durham, NC 27710, USA; Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27708, USA. Electronic address:

While immune checkpoint blockade is associated with prolonged responses in multiple cancers, most patients still do not benefit from this therapeutic strategy. The Wnt-β-catenin pathway is associated with diminished T cell infiltration; however, activating mutations are rare, implicating a role for autocrine/paracrine Wnt ligand-driven signaling in immune evasion. In this study, we show that proximal mediators of the Wnt signaling pathway are associated with anti-PD-1 resistance, and pharmacologic inhibition of Wnt ligand signaling supports anti-PD-1 efficacy by reversing dendritic cell tolerization and the recruitment of granulocytic myeloid-derived suppressor cells in autochthonous tumor models. Read More

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The deacylase SIRT5 supports melanoma viability by influencing chromatin dynamics.

J Clin Invest 2021 May 4. Epub 2021 May 4.

Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States of America.

Cutaneous melanoma remains the most lethal skin cancer, and ranks third among all malignancies in terms of years of life lost. Despite the advent of immune checkpoint and targeted therapies, only roughly half of patients with advanced melanoma achieves a durable remission. SIRT5 is a member of the sirtuin family of protein deacylases that regulate metabolism and other biological processes. Read More

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Beyond the single average tumor: Understanding IO Combinations using a clinical QSP model that incorporates heterogeneity in patient response.

CPT Pharmacometrics Syst Pharmacol 2021 May 3. Epub 2021 May 3.

Merck & Co., Inc, Kenilworth, NJ, USA.

A QSP model for metastatic melanoma was developed for Immuno-Oncology with the goal of predicting efficacy of combination checkpoint therapy with pembrolizumab and ipilimumab. This literature-based model is developed at multiple scales: i) tumor and immune cell interactions at a lesion level, ii) multiple heterogeneous target lesions, non-target lesion growth and appearance of new metastatic lesion at a patient level, and iii) inter-patient differences at a population level. The model was calibrated to pembrolizumab and ipilimumab monotherapy in melanoma patients from Robert, C et al. Read More

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BNIP3 promotes HIF-1α-driven melanoma growth by curbing intracellular iron homeostasis.

EMBO J 2021 May 1:e106214. Epub 2021 May 1.

Cell Death Research and Therapy Group, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.

BNIP3 is a mitophagy receptor with context-dependent roles in cancer, but whether and how it modulates melanoma growth in vivo remains unknown. Here, we found that elevated BNIP3 levels correlated with poorer melanoma patient's survival and depletion of BNIP3 in B16-F10 melanoma cells compromised tumor growth in vivo. BNIP3 depletion halted mitophagy and enforced a PHD2-mediated downregulation of HIF-1α and its glycolytic program both in vitro and in vivo. Read More

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Hypoxia-Driven HIF-1α Activation Reprograms Pre-Activated NK Cells towards Highly Potent Effector Phenotypes via ERK/STAT3 Pathways.

Cancers (Basel) 2021 Apr 15;13(8). Epub 2021 Apr 15.

Department of Biochemistry and Molecular Biology, College of Medicine, Korea University, Seoul 02841, Korea.

NK cells are the predominant innate lymphocyte subsets specialized to kill malignant tumor cells. In patients with advanced cancer, hypoxic stress shapes NK cells toward tumor-resistant and immunosuppressive phenotypes, hence a strategy to restore NK function is critical for successful tumor immunotherapy. Here, we present evidence that pre-activation and subsequent HIF-1α-dependent metabolic shift of NK cells from oxidative phosphorylation into glycolysis are keys to overcome hypoxia-mediated impairment in NK cell survival, proliferation, and tumor cytotoxicity. Read More

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PGC1α Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition.

Cancers (Basel) 2021 Apr 8;13(8). Epub 2021 Apr 8.

Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Korea.

PGC1α oppositely regulates cancer metastasis in melanoma, breast, and pancreatic cancer; however, little is known about its impact on lung cancer metastasis. Transcriptome and in vivo xenograft analysis show that a decreased PGC1α correlates with the epithelial-mesenchymal transition (EMT) and lung cancer metastasis. The deletion of a single Pgc1α allele in mice promotes bone metastasis of Kras-driven lung cancer. Read More

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Flavonoids increase melanin production and reduce proliferation, migration and invasion of melanoma cells by blocking endolysosomal/melanosomal TPC2.

Sci Rep 2021 Apr 19;11(1):8515. Epub 2021 Apr 19.

Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.

Two-pore channel 2 (TPC2) resides in endolysosomal membranes but also in lysosome-related organelles such as the melanin producing melanosomes. Gain-of-function polymorphisms in hTPC2 are associated with decreased melanin production and blond hair color. Vice versa genetic ablation of TPC2 increases melanin production. Read More

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Precision oncology in metastatic colorectal cancer - from biology to medicine.

Nat Rev Clin Oncol 2021 Apr 16. Epub 2021 Apr 16.

Department of Oncology, University of Torino, Candiolo, Italy.

Remarkable progress has been made in the development of biomarker-driven targeted therapies for patients with multiple cancer types, including melanoma, breast and lung tumours, although precision oncology for patients with colorectal cancer (CRC) continues to lag behind. Nonetheless, the availability of patient-derived CRC models coupled with in vitro and in vivo pharmacological and functional analyses over the past decade has finally led to advances in the field. Gene-specific alterations are not the only determinants that can successfully direct the use of targeted therapy. Read More

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Cancer immune control dynamics: a clinical data driven model of systemic immunity in patients with metastatic melanoma.

BMC Bioinformatics 2021 Apr 16;22(1):197. Epub 2021 Apr 16.

Department of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: Recent clinical advances in cancer immuno-therapeutics underscore the need for improved understanding of the complex relationship between cancer and the multiple, multi-functional, inter-dependent, cellular and humoral mediators/regulators of the human immune system. This interdisciplinary effort exploits engineering analysis methods utilized to investigate anomalous physical system behaviors to explore immune system behaviors. Cancer Immune Control Dynamics (CICD), a systems analysis approach, attempts to identify differences between systemic immune homeostasis of 27 healthy volunteers versus 14 patients with metastatic malignant melanoma based on daily serial measurements of conventional peripheral blood biomarkers (15 cell subsets, 35 cytokines). Read More

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Dual activity of PD-L1 targeted Doxorubicin immunoliposomes promoted an enhanced efficacy of the antitumor immune response in melanoma murine model.

J Nanobiotechnology 2021 Apr 13;19(1):102. Epub 2021 Apr 13.

Department of Pharmaceutical Technology and Chemistry, School of Pharmacy, University of Navarra, 31008, Pamplona, Navarra, Spain.

Background: The immunomodulation of the antitumor response driven by immunocheckpoint inhibitors (ICIs) such as PD-L1 (Programmed Death Ligand-1) monoclonal antibody (α-PD-L1) have shown relevant clinical outcomes in a subset of patients. This fact has led to the search for rational combinations with other therapeutic agents such as Doxorubicin (Dox), which cytotoxicity involves an immune activation that may enhance ICI response. Therefore, this study aims to evaluate the combination of chemotherapy and ICI by developing Dox Immunoliposomes functionalized with monovalent-variable fragments (Fab') of α-PD-L1. Read More

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Case Report: Single Dose Anti-PD1 in a Patient With Metastatic Melanoma and Cardiac Allograft.

Front Immunol 2021 22;12:660795. Epub 2021 Mar 22.

Hillman Cancer Center, UPMC, Pittsburgh, PA, United States.

Background: Immune-checkpoint inhibition has improved outcomes in metastatic melanoma. However, limited data describes the safety and efficacy of this treatment in the setting of cardiac allograft. Emerging translational and clinical evidence suggests that the majority of the benefit from these therapies is driven by the initial dose(s), and that attenuated dosing schedules may be as effective as continuous treatment. Read More

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Identifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial.

PLoS One 2021 7;16(4):e0248097. Epub 2021 Apr 7.

Translational Genomics Research Institute, Phoenix, AZ, United States of America.

Although combination BRAF and MEK inhibitors are highly effective for the 40-50% of cutaneous metastatic melanomas harboring BRAFV600 mutations, targeted agents have been ineffective for BRAFV600wild-type (wt) metastatic melanomas. The SU2C Genomics-Enabled Medicine for Melanoma Trial utilized a Simon two-stage optimal design to assess whether comprehensive genomic profiling improves selection of molecular-based therapies for BRAFV600wt metastatic melanoma patients who had progressed on standard-of-care therapy, which may include immunotherapy. Of the response-evaluable patients, binimetinib was selected for 20 patients randomized to the genomics-enabled arm, and nine were treated on the alternate treatment arm. Read More

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Antityrosinase Mechanism and Antimelanogenic Effect of Arbutin Esters Synthesis Catalyzed by Whole-Cell Biocatalyst.

J Agric Food Chem 2021 Apr 6;69(14):4243-4252. Epub 2021 Apr 6.

Department of Spine Surgery, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Academy of Orthopedics of Guangdong Province, Guangzhou 510630, China.

Tyrosinase is a key enzyme responsible for enzymatic browning of fruits and vegetables and skin disorders due to overproduction of melanin. Arbutin is an inhibitor of tyrosinase; however, its high polarity and weak transdermal absorption capacity limit its applications. In this paper, a green solvent system was developed to successfully synthesize arbutin esters with improved liposolubilities (Clog values = 0. Read More

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Immune-Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Synopsis of Response Rates.

Oncologist 2021 Apr 5. Epub 2021 Apr 5.

Blacktown Clinical School, Western Sydney University, Sydney, New South Wales, Australia.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. A first-line standard of care, sorafenib results in median overall survival of 12 months in patients with Child-Pugh class A disease and 6 months in patients with Child-Pugh class B disease with objective response rates (ORRs) not exceeding 19%. These low efficacy rates have driven research on alternative therapeutic options, particularly immune-checkpoint inhibitors (ICIs). Read More

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Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study.

Hepatology 2021 Apr 3. Epub 2021 Apr 3.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Recent studies link nonalcoholic fatty liver disease (NAFLD) to an increased incidence of hepatocellular carcinoma (HCC) and extrahepatic cancers. However, prior studies were small or lacked liver histology, which remains the gold standard for staging NAFLD severity. We conducted a population-based cohort study of all adults with histologically defined NAFLD in Sweden from 1966 to 2016 (N=8,892). Read More

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Talimogene Laherparepvec (T-VEC): An Intralesional Cancer Immunotherapy for Advanced Melanoma.

Cancers (Basel) 2021 Mar 18;13(6). Epub 2021 Mar 18.

Hemato-Oncology Division, European Institute of Oncology, IRCCS, 20141 Milan, Italy.

Direct intralesional injection of specific or even generic agents, has been proposed over the years as cancer immunotherapy, in order to treat cutaneous or subcutaneous metastasis. Such treatments usually induce an effective control of disease in injected lesions, but only occasionally were able to demonstrate a systemic abscopal effect on distant metastases. The usual availability of tissue for basic and translational research is a plus in utilizing this approach, which has been used in primis for the treatment of locally advanced melanoma. Read More

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Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy.

Sci Transl Med 2021 Mar;13(587)

Division of Infectious Diseases, Allergy and Immunology and Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.

The functional state of T cells is a key determinant for effective antitumor immunity and immunotherapy. Cellular metabolism, including lipid metabolism, controls T cell differentiation, survival, and effector functions. Here, we report that development of T cell senescence driven by both malignant tumor cells and regulatory T cells is a general feature in cancers. Read More

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MITF induces escape from innate immunity in melanoma.

J Exp Clin Cancer Res 2021 Mar 31;40(1):117. Epub 2021 Mar 31.

Department of Biochemistry and Molecular Biology A, School of Biology, IMIB-University of Murcia, 30100, Murcia, Spain.

Background: The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Read More

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Malignancies after Kidney Transplantation.

Clin J Am Soc Nephrol 2021 Mar 29. Epub 2021 Mar 29.

Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia

Cancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. Read More

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Viral infection of cells within the tumor microenvironment mediates antitumor immunotherapy via selective TBK1-IRF3 signaling.

Nat Commun 2021 03 25;12(1):1858. Epub 2021 Mar 25.

Department of Neurosurgery, Duke University Medical School, Durham, NC, USA.

Activating intra-tumor innate immunity might enhance tumor immune surveillance. Virotherapy is proposed to achieve tumor cell killing, while indirectly activating innate immunity. Here, we report that recombinant poliovirus therapy primarily mediates antitumor immunotherapy via direct infection of non-malignant tumor microenvironment (TME) cells, independent of malignant cell lysis. Read More

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The role of melanocytes in the human choroidal microenvironment and inflammation: Insights from the transcriptome.

Pigment Cell Melanoma Res 2021 Mar 22. Epub 2021 Mar 22.

School of Optometry and Vision Science, University of NSW, Sydney, NSW, Australia.

The choroid within the human eye contains a rich milieu of cells including melanocytes. Human choroidal melanocytes (HCMs) absorb light, regulate free radical production, and were recently shown to modulate inflammation. This study aimed to identify key genes and pathways involved in the inflammatory response of HCMs through the use of RNA-seq. Read More

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Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer.

Int J Epidemiol 2021 Mar 22. Epub 2021 Mar 22.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Background: Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases.

Methods: We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Read More

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Protection Against Solar Ultraviolet Radiation in Outdoor Construction Workers: Study Protocol for a Non-randomized Controlled Intervention Study.

Front Public Health 2021 4;9:602933. Epub 2021 Mar 4.

Amsterdam University Medical Centers, University of Amsterdam, Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam, Netherlands.

Non-melanoma skin cancer (NMSC) incidence is increasing, and occupational solar exposure contributes greatly to the overall lifetime ultraviolet radiation (UVR) dose. This is reflected in an excess risk of NMSC showing up to three-fold increase in outdoor workers. Risk of NMSC can be reduced if appropriate measures to reduce UVR-exposure are taken. Read More

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In Vitro 3D Models of Tunable Stiffness.

Methods Mol Biol 2021 ;2294:27-42

The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Darlinghurst, NSW, Australia.

Three-dimensional models of spheroid formation have been routinely used in the cancer field to test the colony forming capacity of malignant cells in an in vitro setting. Use of such a model provides a robust surrogate for in vivo testing, enabling large-scale interrogation into the effect of certain treatment conditions. This adapted protocol describes a high throughput and readily accessible composite alginate hydrogel system for spheroid formation, within a biomechanically tunable three-dimensional environment. Read More

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January 2021

Modulated Electro-Hyperthermia Facilitates NK-Cell Infiltration and Growth Arrest of Human A2058 Melanoma in a Xenograft Model.

Front Oncol 2021 25;11:590764. Epub 2021 Feb 25.

Institute of Translational Medicine, Semmelweis University, Budapest, Hungary.

Modulated electro-hyperthermia (mEHT), induced by 13.56 MHz radiofrequency, has been demonstrated both in preclinical and clinical studies to efficiently induce tumor damage and complement other treatment modalities. Here, we used a mouse xenograft model of human melanoma (A2058) to test mEHT (~42°C) both alone and combined with NK-cell immunotherapy. Read More

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February 2021