scholarly journals Inhibition of growth and induction of differentiation of metastatic melanoma cells in vitro by genistein: chemosensitivity is regulated by cellular p53

1997 ◽  
Vol 75 (11) ◽  
pp. 1559-1566 ◽  
Author(s):  
S Rauth ◽  
J Kichina ◽  
A Green
Keyword(s):  
Metastatic Melanoma ◽  
Melanoma Cells ◽  
Inhibition Of Growth ◽  
Induction Of Differentiation

Endothelin-3 Is Produced by Metastatic Melanoma Cells and Promotes Melanoma Cell Survival

2008 ◽  
Vol 12 (2) ◽  
pp. 64-70 ◽  
Author(s):  
Liren Tang ◽  
Mingwan Su ◽  
Yi Zhang ◽  
Wency Ip ◽  
Magdalena Martinka ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Signal Transduction Pathway ◽  
Melanoma Cells ◽  
Transduction Pathway ◽  
Paracrine Factor ◽  
Study Results ◽  
Autocrine Stimulation ◽  
Endothelin 3 ◽  
Adult Skin

Background: Endothelin-3 (ET-3) is an essential paracrine factor for the proliferation, migration, and survival of embryonic melanocytes during fetal development. Its expression is tightly regulated, being completely turned off in adult skin. Objective: In this study, results are presented that demonstrate abnormal expression of ET-3 by metastatic melanoma cells in both tissue biopsies and cell culture. Further, in vitro experiments showed that metastatic melanoma cells have the capacity to respond to ET-3 stimulation by increasing survival. Conclusion: Therefore, an abnormal autocrine stimulation pathway involving ET-3 is present in metastatic melanoma cells. Blocking this signal transduction pathway may prove useful for the treatment of metastatic melanoma.

scholarly journals Targeted photodynamic therapy treatment of in vitro A375 metastatic melanoma cells

Oncotarget ◽  
2019 ◽  
Vol 10 (58) ◽  
pp. 6079-6095 ◽  
Author(s):  
Channay Naidoo ◽  
Cherie Ann Kruger ◽  
Heidi Abrahamse
Keyword(s):  
Photodynamic Therapy ◽  
Metastatic Melanoma ◽  
Melanoma Cells ◽  
Targeted Photodynamic Therapy ◽  
Therapy Treatment

scholarly journals Targeting Rad51 as a strategy for the treatment of melanoma cells resistant to MAPK pathway inhibition

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Elena Makino ◽  
Lisa Marie Fröhlich ◽  
Tobias Sinnberg ◽  
Corinna Kosnopfel ◽  
Birgit Sauer ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Metastatic Melanoma ◽  
Mapk Pathway ◽  
Critical Role ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Transcriptional Level ◽  
Mapk Inhibitor

Abstract Rad51 is an essential factor of the homologous recombination DNA repair pathway and therefore plays an important role in maintaining genomic stability. We show that RAD51 and other homologous recombination repair genes are overexpressed in metastatic melanoma cell lines and in melanoma patient samples, which correlates with reduced survival of melanoma patients. In addition, Rad51 expression in melanoma cells was regulated on a transcriptional level by the MAPK signaling pathway with Elk1 as the main downstream transcriptional effector. Most strikingly, melanoma cells which developed resistance towards MAPK inhibitors could be efficiently targeted by Rad51 inhibitors similar to their sensitive counterparts, leading to DNA damage, G2/M arrest and apoptosis. Furthermore, the treatment of MAPK inhibitor resistant cells with Rad51 inhibitors enhances the susceptibility of these cells for MAPK inhibitor treatment in vitro and in vivo. These data indicate that Rad51 plays a critical role in the survival of metastatic melanoma cells and is a promising target for the therapy of melanoma irrespective of its MAPK inhibitor resistance status.

scholarly journals From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2024
Author(s):  
Aikaterini F. Giannopoulou ◽  
Athanassios D. Velentzas ◽  
Athanasios K. Anagnostopoulos ◽  
Adamantia Agalou ◽  
Nikos C. Papandreou ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Epithelial To Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Primary Melanoma ◽  
Melanoma Cells ◽  
Mesenchymal Transition ◽  
Mesenchymal To Epithelial Transition ◽  
Liquid Chromatography Tandem Mass ◽  
Novel Biomarkers

Melanoma is classified among the most notoriously aggressive human cancers. Despite the recent progress, due to its propensity for metastasis and resistance to therapy, novel biomarkers and oncogenic molecular drivers need to be promptly identified for metastatic melanoma. Hence, by employing nano liquid chromatography-tandem mass spectrometry deep proteomics technology, advanced bioinformatics algorithms, immunofluorescence, western blotting, wound healing protocols, molecular modeling programs, and MTT assays, we comparatively examined the respective proteomic contents of WM115 primary (n = 3955 proteins) and WM266-4 metastatic (n = 6681 proteins) melanoma cells. It proved that WM115 and WM266-4 cells have engaged hybrid epithelial-to-mesenchymal transition/mesenchymal-to-epithelial transition states, with TGF-β controlling their motility in vitro. They are characterized by different signatures of SOX-dependent neural crest-like stemness and distinct architectures of the cytoskeleton network. Multiple signaling pathways have already been activated from the primary melanoma stage, whereas HIF1α, the major hypoxia-inducible factor, can be exclusively observed in metastatic melanoma cells. Invasion-metastasis cascade-specific sub-routines of activated Caspase-3-triggered apoptosis and LC3B-II-dependent constitutive autophagy were also unveiled. Importantly, WM115 and WM266-4 cells exhibited diverse drug response profiles, with epirubicin holding considerable promise as a beneficial drug for metastatic melanoma clinical management. It is the proteome navigation that enables systemic biomarkering and targeted drugging to open new therapeutic windows for advanced disease.

scholarly journals Expansion of Melanoma-specific Cytolytic CD8+ T Cell Precursors in Patients with Metastatic Melanoma Vaccinated with CD34+ Progenitor-derived Dendritic Cells

2004 ◽  
Vol 199 (11) ◽  
pp. 1503-1511 ◽  
Author(s):  
Sophie Paczesny ◽  
Jacques Banchereau ◽  
Knut M. Wittkowski ◽  
Giovanna Saracino ◽  
Joseph Fay ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Metastatic Melanoma ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Melanoma Cells ◽  
Tetramer Binding ◽  
Dc Vaccines

Cancer vaccines aim at inducing (a) tumor-specific effector T cells able to reduce/eliminate the tumor mass, and (b) long-lasting tumor-specific memory T cells able to control tumor relapse. We have shown earlier, in 18 human histocompatibility leukocyte antigen (HLA)-A*0201 patients with metastatic melanoma, that vaccination with peptide-loaded CD34–dendritic cells (DCs) leads to expansion of melanoma-specific interferon γ–producing CD8+ T cells in the blood. Here, we show in 9 out of 12 analyzed patients the expansion of cytolytic CD8+ T cell precursors specific for melanoma differentiation antigens. These precursors yield, upon single restimulation with melanoma peptide–pulsed DCs, cytotoxic T lymphocytes (CTLs) able to kill melanoma cells. Melanoma-specific CTLs can be grown in vitro and can be detected in three assays: (a) melanoma tetramer binding, (b) killing of melanoma peptide–pulsed T2 cells, and (c) killing of HLA-A*0201 melanoma cells. The cytolytic activity of expanded CTLs correlates with the frequency of melanoma tetramer binding CD8+ T cells. Thus, CD34-DC vaccines can expand melanoma-specific CTL precursors that can kill melanoma antigen–expressing targets. These results justify the design of larger follow-up studies to assess the immunological and clinical response to peptide-pulsed CD34-DC vaccines.

The PI3K inhibitor BKM120 has potent antitumor activity in melanoma brain metastases in vitro and in vivo.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20050-e20050 ◽  
Author(s):  
Friedegund Elke Meier ◽  
Heike Niessner ◽  
Jennifer Schmitz ◽  
Andreas Schmid ◽  
Carsten Calaminus ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Brain Metastases ◽  
Metastatic Melanoma ◽  
Conditioned Medium ◽  
Melanoma Cells ◽  
Pi3k Inhibitor ◽  
Survival Pathway ◽  
Melanoma Brain Metastases

e20050 Background: In melanoma, the RAF-MEK-ERK and PI3K-AKT signaling pathways play a major role in melanoma progression and drug resistance. On the basis of significant improvement in overall survival, the BRAF inhibitor vemurafenib gained FDA approval for the treatment of patients with metastatic BRAFV600E mutated melanoma. However, vemurafenib appears to be less effective in melanoma brain metastases, and brain metastases are the most common cause of death in patients with metastatic melanoma. In our previous study we reported that the AKT survival pathway is hyperactivated in melanoma brain metastases. Methods: The current study aims to investigate the mechanisms of AKT hyperactivation and the antitumor activity of the PI3K inhibitor BKM120 in melanoma brain metastases in vitro and in vivo. Results: To simulate the tumor environment of brain metastases and extracerebral metastases, brain and matched extracerebral metastatic melanoma cells were stimulated by astrocyte- and fibroblast-conditioned medium, respectively. Both brain and extracerebral metastatic melanoma cells stimulated by astrocyte-conditioned medium showed higher AKT activation and invasiveness in a transwell matrigel invasion assay than cells stimulated by fibroblast-conditioned medium. The PI3K inhibitor BKM120 inhibited the phosphorylation of AKT and the growth of >10 newly isolated cell lines derived from melanoma brain metastases achieving growth inhibition rates of up to 80%. These effects did not depend on BRAF, NRAS or KIT mutation status. Furthermore, BKM120 potently induced apoptosis in brain metastatic melanoma cells and significantly inhibited the tumor growth of human brain metastatic melanoma cells in the brain of nude mice as shown by MRI scans. Conclusions: Brain-derived factors induce hyperactivation of the AKT survival pathway and promote invasiveness and drug resistance of melanoma cells in the brain. The PI3K inhibitor BKM120 inhibits activation of the AKT survival pathway and demonstrates potent antitumor activity in melanoma brain metastases in vitro and in vivo.

scholarly journals The mechanosensitive TRPV2 calcium channel controls melanoma invasiveness and metastatic potential.

2021 ◽  
Author(s):  
Kenji F Shoji ◽  
Elsa Bayet ◽  
Dahiana Le Devedec ◽  
Aude Mallavialle ◽  
Severine Marionneau-lambot ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Metastatic Melanoma ◽  
Metastatic Potential ◽  
Melanoma Cells ◽  
Melanoma Tumor ◽  
Advanced Malignancy ◽  
In Vitro Motility ◽  
Cytoskeleton Remodeling

Discovery of therapeutic targets against metastasis is of primary importance since being the main cause of cancer-related death. Deregulation of calcium homeostasis has been involved in numerous cellular metastatic behaviors, although the molecular determinants supporting these processes remain often unclear. Here, we showed that the expression of the plasma membrane TRPV2 calcium channel is a prominent feature in melanoma progression and dissemination. In fact, TRPV2 activity was sufficient to confer an invasive phenotype to non-invasive melanoma cells. Conversely, the invasive and migratory potential of highly metastatic melanoma cells was abolished upon TRPV2 silencing. Mechanistically, TRPV2 supports melanoma cells aggressiveness by being a new regulator of the calpain-dependent maturation of focal adhesion, and actin cytoskeleton remodeling. Finally, TRPV2 overexpression is a marker of advanced malignancy and bad prognosis in human melanoma tumor samples. Altogether, TRPV2-induced Ca2+ signaling orchestrates in vitro motility and invasiveness of melanoma cells, as well as in vivo metastatic melanoma tumors dissemination.

scholarly journals Lupeol Inhibits Growth of Highly Aggressive Human Metastatic Melanoma Cells In vitro and In vivo by Inducing Apoptosis

2008 ◽  
Vol 14 (7) ◽  
pp. 2119-2127 ◽  
Author(s):  
Mohammad Saleem ◽  
Nityanand Maddodi ◽  
Mohammad Abu Zaid ◽  
Naghma Khan ◽  
Bilal bin Hafeez ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Melanoma Cells

scholarly journals Metastatic melanoma cells are selective affected in vitro by Atropa belladonna 200 c.

2021 ◽  
Vol 17 (2) ◽  
pp. 19-20
Author(s):  
Maria Luiza Ferreira dos Santos ◽  
Jenifer Pendiuk Gonçalves ◽  
Viviana Stephanie Costa Gagosian ◽  
Gustavo Rodrigues Rossi ◽  
Edvaldo Da Silva Trindade ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Metastatic Melanoma ◽  
Survival Rates ◽  
Melanoma Cells ◽  
Chemotherapeutic Agents ◽  
Control Group ◽  
P Value ◽  
Atropa Belladonna ◽  
Antitumor Effects

Abstract Background: Cancers are among the top 10 causes of death worldwide. Melanoma is a skin cancer originated from mutations on melanocytes. Transformed melanocytes can migrate and invade tissues in a process called metastasis. When early diagnosed, melanoma is curable by surgical excision. However, when metastatic, cells are refractory to existing therapies and patient survival rates are low. New therapeutic interventions with effective results on melanoma cells that could increase long term patients’ survival rates are needed. Over the past decade our group has been using cell-based models to determine highly diluted solutions effects. Several compounds have been tested on normal and tumor cells with promising results that could indicate the efficacy of homeopathy on selected cases. Aims: To investigate Atropa belladonna 200 c (Bell200c) in vitro antitumor effects on B16-F10 metastatic murine melanoma cells and its toxicity on Balb/3T3 normal murine fibroblasts. Methodology: Atropa belladonna 200c was produced and kindly donated by “Homeoterápica” compounding pharmacy (Curitiba, Brazil). Cells were treated for up to 72 hours. Assays to determine cytotoxicity, as well as functional and molecular cell patterns were carried out following standard protocols. Water treated cells were used as control group. All data were submitted to Shapiro-Wilk normality test followed by either Mann-Whitney or t-test. P value < 0.05 was considered significant. Results and discussion: Cancer cells accelerated proliferation rates are often target for chemotherapeutic agents. Bell200c modulated cell cycle, leading to a decreased melanoma cell proliferation (44% less cells then control), and an increase in apoptotic cells number. If unspecific, those effects can lead to undesirable toxicity. Amazingly, no effects on fibroblast proliferation and death were observed. Melanoma cells malignancy was also affected, as the following tumor progression related features were modulated. Melanin production was higher in treated cells. N-cadherin and CD44 expression were statistically decreased. Clonogenic capacity was decreased by 35%. Here we have demonstrated Bell200c selective effects on melanoma cells with remarkable capacity of impairing metastatic melanoma characteristics. Conclusion: Atropa belladonna has a prospective use in metastatic melanoma patients as a potential tumor progression regulator. Keywords: in vitro testing, high dilution, B16-F10, melanoma.

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