Targeting the Melanocortin 1 Receptor in Melanoma: Biological Activity of α-MSH–Peptide Conjugates DOI Open Access
Ildikó Szabó, Beáta Biri‐Kovács, Balázs Vári

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1095 - 1095

Published: Jan. 16, 2024

Malignant melanoma is one of the most aggressive and resistant tumor types, with high metastatic properties. Because lack suitable chemotherapeutic agents for treatment, 5-year survival rate patients regional distant metastases lower than 10%. Targeted therapy that provides several promising results might be a good option treatment malignant melanomas. Our goal was to develop novel melanoma-specific peptide–drug conjugates targeted therapy. Melanocortin-1-receptor (MC1R) cell surface receptor responsible melanogenesis it overexpressed on cells, providing target. Its native ligand, α-MSH (α-melanocyte-stimulating hormone) peptide, or its derivatives, potential homing devices this purpose. Therefore, we prepared three derivative–daunomycin (Dau) their in vitro vivo antitumor activities were compared. Dau has an autofluorescence property; therefore, preparing (e.g., cellular uptake) experiments. attached peptides via non-cleavable oxime linkage applied efficiently our previous experiments, resulting growth inhibition activity. The indicated conjugate compound which connected side chain Lys (Ac-SYSNleEHFRWGK(Dau=Aoa)PV-NH2). highest uptake by cells demonstrated using compound, detected both mouse (38.6% B16) human uveal (55% OMC-1) cells. effect more pronounced free drug.

Language: Английский

Photo-neuro-immuno-endocrinology: How the ultraviolet radiation regulates the body, brain, and immune system DOI Creative Commons
Radomir M. Slominski, Jake Y. Chen, Chander Raman

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(14)

Published: March 15, 2024

Ultraviolet radiation (UVR) is primarily recognized for its detrimental effects such as cancerogenesis, skin aging, eye damage, and autoimmune disorders. With exception of ultraviolet B (UVB) requirement in the production vitamin D3, positive role UVR modulation homeostasis underappreciated. Skin exposure to triggers local responses secondary induction chemical, hormonal, immune, neural signals that are defined by chromophores extent penetration into compartments. These not random coordinated cutaneous neuro-immuno-endocrine system, which counteracts action external stressors accommodates changing environment. The induces electrical, biological be sent brain, endocrine immune systems, well other central organs, concert regulate body homeostasis. To achieve homeostatic goal, UVR-induced precisely computed locally with transmission through nerves or humoral release circulation activate and/or modulate coordinating centers organs. Such modulatory will dependent on UVA UVB wavelengths. This leads immunosuppression, activation brain centers, modification different organ functions. Therefore, it imperative understand underlying mechanisms electromagnetic energy deep body, impact internal Photo-neuro-immuno-endocrinology can offer novel therapeutic approaches addiction mood disorders; autoimmune, neurodegenerative, chronic pain-generating pathologies involving endocrine, cardiovascular, gastrointestinal, reproductive systems.

Language: Английский

Citations

60
Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances DOI Open Access
Hyun Jee Kim, Yeong Ho Kim

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2984 - 2984

Published: March 4, 2024

Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent advances in molecular pathogenesis have shed light on genetic epigenetic changes that drive melanoma development. This review provides an overview of these developments, focusing mechanisms genesis. It highlights how mutations, particularly the BRAF, NRAS, c-KIT, GNAQ/GNA11 genes, affect critical signaling pathways. The evolution diagnostic techniques, such as genomics, transcriptomics, liquid biopsies, biomarkers for early detection prognosis, also discussed. therapeutic landscape has transformed with targeted therapies immunotherapies, improving patient outcomes. paper examines efficacy, challenges, prospects treatments, including recent clinical trials emerging strategies. potential novel treatment strategies, neoantigen vaccines, adoptive cell transfer, microbiome interactions, nanoparticle-based combination therapy, explored. These emphasize challenges therapy resistance importance personalized medicine. underlines necessity evidence-based selection managing increasing global incidence melanoma.

Language: Английский

Citations

23
Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling DOI Open Access
Radomir M. Slominski, Tae‐Kang Kim, Zorica Janjetović

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(12), P. 2262 - 2262

Published: June 18, 2024

Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and high mortality rate. This review discusses etiologic risk factors for melanoma, diagnostic prognostic tools, including recent advances in molecular biology, omics, bioinformatics, provides an overview its therapy. Since the incidence melanoma rising remains unacceptably high, we discuss inherent properties, melanogenesis, that make this disease resilient treatment propose use AI solve above complex multidimensional problems. We provide on vitamin D anticancerogenic report field can solutions prevention and/or therapy melanoma. Experimental papers clinicopathological studies role status signaling pathways initiated active metabolites prognosis are reviewed. conclude signaling, defined specific nuclear receptors selective activation hydroxyderivatives, benefit new or existing therapeutic approaches. target with computational biology tools solution problem.

Language: Английский

Citations

22
VEGF/VEGFR axis and its signaling in melanoma: Current knowledge toward therapeutic targeting agents and future perspectives DOI
Mohammad Malekan, Nikolas K. Haass,

Ghasem Rahmatpour Rokni

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 345, P. 122563 - 122563

Published: March 18, 2024

Language: Английский

Citations

19
Melatonin and the Skin: Current Progress and Perspectives for Human Health DOI
Andrzej Słomiński, Tae Kim, Zorica Janjetović

et al.

Journal of Investigative Dermatology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

4
Neuro–immuno–endocrinology of the skin: how environment regulates body homeostasis DOI
Radomir M. Slominski, Ramesh Chander, Anton M. Jetten

et al.

Nature Reviews Endocrinology, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Language: Английский

Citations

3
Natural tyrosinase enzyme inhibitors: A path from melanin to melanoma and its reported pharmacological activities DOI Open Access
Rajan Logesh,

Sagar Rajendra Prasad,

Sandhya Chipurupalli

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(6), P. 188968 - 188968

Published: Aug. 30, 2023

Language: Английский

Citations

41
Role of stress in the pathogenesis of cancer (Review) DOI Creative Commons
Ioannis Lempesis, Vasiliki Georgakopoulou, Petros Papalexis

et al.

International Journal of Oncology, Journal Year: 2023, Volume and Issue: 63(5)

Published: Sept. 11, 2023

Stress is a state of disrupted homeostasis, triggered by intrinsic or extrinsic factors, the stressors, which are counteracted various physiological and behavioural adaptive responses. has been linked to cancer development incidence for decades; however, epidemiological studies clinical trials have yielded contradictory results. The present review discusses effects stress on underlying mechanisms. Animal revealed clear link between progression, revealing molecular, cellular endocrine processes that implicated in these effects. Thus, hormones, their receptor systems intracellular molecular pathways mediate initiation, progression metastases. mechanisms linking can either be indirect, mediated changes microenvironment immune system dysregulation, direct, through binding neuroendocrine stress‑related signalling molecules cell receptors. affects numerous anti‑ pro‑cancer components, including host resistance metastasis, tumour retention and/or suppression. Chronic psychological elevation catecholamine levels may increase death resistance. On whole, incidence, with stressors playing crucial role. better than human ones, hormones influencing development, migration, invasion proliferation. Randomized controlled required further evaluate long‑term outcomes its management.

Language: Английский

Citations

31
From pain to tumor immunity: influence of peripheral sensory neurons in cancer DOI Creative Commons

Ugo Mardelle,

Ninon Bretaud,

Clara Daher

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 16, 2024

The nervous and immune systems are the primary sensory interfaces of body, allowing it to recognize, process, respond various stimuli from both external internal environment. These work in concert through mechanisms neuro-immune crosstalk detect threats, provide defense against pathogens, maintain or restore homeostasis, but can also contribute development diseases. Among peripheral neurons (PSNs), nociceptive PSNs particular interest. They possess a remarkable capability noxious periphery transmit this information brain, resulting perception pain activation adaptive responses. Pain is an early symptom cancer, often leading its diagnosis, major source distress for patients as disease progresses. In review, we aim overview within tumors that likely induce cancer pain, exploring range factors etiological elements cellular molecular mediators. addition transmitting central system, capable, when activated, produce release neuropeptides (e.g., CGRP SP) their terminals. have been shown modulate immunity cases inflammation, infection, cancer. PSNs, found solid tumors, play significant role tumor microenvironment, potentially influencing growth anti-tumor discuss current state knowledge about degree innervation tumors. We seek understand whether how may influence associated different mouse models Finally, extent which able functions innervate it.

Language: Английский

Citations

15
Reciprocal crosstalk between Th17 and mesothelial cells promotes metastasis‐associated adhesion of ovarian cancer cells DOI Creative Commons
Felix Neuhaus,

Sonja Lieber,

V. A. Shinkevich

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(4)

Published: April 1, 2024

Abstract Background IL‐17A and TNF synergistically promote inflammation tumorigenesis. Their interplay impact on ovarian carcinoma (OC) progression are, however, poorly understood. We addressed this question focusing mesothelial cells, whose interaction with tumor cells is known to play a pivotal role in transcoelomic metastasis formation. Methods Flow‐cytometry immunohistochemistry experiments were employed identify cellular sources of TNF. Changes transcriptomes secretomes determined by bulk single cell RNA sequencing as well affinity proteomics. Functional consequences investigated microscopic analyses adhesion assays. Potential clinical implications assessed survival analyses. Results identified Th17 the main population IL‐17A‐ producers ascites detected their accumulation early omental metastases. Both its receptor subunit IL‐17RC associated short OC patients, pointing progression. induced reprogramming towards pro‐inflammatory mesenchymal phenotype, concomitantly loss tight junctions an impairment monolayer integrity, thereby promoting cancer adhesion. Th17‐promoting cytokines IL‐6 IL‐1β Th17‐attracting chemokine CCL20 indicating reciprocal crosstalk that potentiates tumor‐promoting OC. Conclusions Our findings reveal novel function for microenvironment, which entails IL‐17A/TNF‐mediated induction mesothelial‐mesenchymal transition, disruption layer integrity consequently promotion These effects are potentiated positive feedback loop between cells. Together observed associations micrometastases, our observations point potential metastases formation thus new therapeutic options.

Language: Английский

Citations

10