scholarly journals S100-EPISPOT: A New Tool to Detect Viable Circulating Melanoma Cells

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 755 ◽  
Author(s):  
Laure Cayrefourcq ◽  
Aurélie De Roeck ◽  
Caroline Garcia ◽  
Pierre-Emmanuel Stoebner ◽  
Fanny Fichel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Clinical Utility ◽  
S100 Protein ◽  
Melanoma Cells ◽  
Detection Methods ◽  
Drug Resistant ◽  
Poor Overall Survival ◽  
Homogeneous Population ◽  
Higher Sensitivity

Metastatic melanoma is one of the most aggressive and drug-resistant cancers with very poor overall survival. Circulating melanoma cells (CMCs) were first described in 1991. However, there is no general consensus on the clinical utility of CMC detection, largely due to conflicting results linked to the use of heterogeneous patient populations and different detection methods. Here, we developed a new EPithelial ImmunoSPOT (EPISPOT) assay to detect viable CMCs based on their secretion of the S100 protein (S100-EPISPOT). Then, we compared the results obtained with the S100-EPISPOT assay and the CellSearch® CMC kit using blood samples from a homogeneous population of patients with metastatic melanoma. We found that S100-EPISPOT sensitivity was significantly higher than that of CellSearch®. Specifically, the percentage of patients with ≥2 CMCs was significantly higher using S100-EPISPOT than CellSearch® (48% and 21%, respectively; p = 0.0114). Concerning CMC prognostic value, only the CellSearch® results showed a significant association with overall survival (p = 0.006). However, due to the higher sensitivity of the new S100-EPISPOT assay, it would be interesting to determine whether this functional test could be used in patients with non-metastatic melanoma for the early detection of tumor relapse and for monitoring the treatment response.

scholarly journals NLRP1 Functions Downstream of the MAPK/ERK Signaling via ATF4 and Contributes to Acquired Targeted Therapy Resistance in Human Metastatic Melanoma

2020 ◽  
Vol 14 (1) ◽  
pp. 23
Author(s):  
Zili Zhai ◽  
Prasanna K. Vaddi ◽  
Jenny Mae Samson ◽  
Tomoya Takegami ◽  
Mayumi Fujita
Keyword(s):  
Targeted Therapy ◽  
Protein Kinase ◽  
Metastatic Melanoma ◽  
Therapy Resistance ◽  
Melanoma Cells ◽  
Erk Signaling ◽  
Erk Pathway ◽  
Drug Resistant ◽  
Downstream Effector ◽  
Resistant Cells

The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and its downstream effector responses. Uncovering the hidden downstream effectors can aid in understanding melanoma biology and improve targeted therapy efficacy. The inflammasome sensor, NACHT, LRR, and PYD domains-containing protein 1 (NLRP1), is responsible for IL-1β maturation and itself is a melanoma tumor promoter. Here, we report that NLRP1 is a downstream effector of MAPK/ERK signaling through the activating transcription factor 4 (ATF4), creating regulation in metastatic melanoma cells. We confirmed that the NLRP1 gene is a target of ATF4. Interestingly, ATF4/NLRP1 regulation by the MAPK/ERK pathway uses distinct mechanisms in melanoma cells before and after the acquired resistance to targeted therapy. In parental cells, ATF4/NLRP1 is regulated by the MAPK/ERK pathway through the ribosomal S6 kinase 2 (RSK2). However, vemurafenib (VEM) and trametinib (TRA)-resistant cells lose the signaling via RSK2 and activate the cAMP/protein kinase A (PKA) pathway to redirect ATF4/NLRP1. Therefore, NLRP1 expression and IL-1β secretion were downregulated in response to VEM and TRA in parental cells but enhanced in drug-resistant cells. Lastly, silencing NLRP1 in drug-resistant cells reduced their cell growth and inhibited colony formation. In summary, we demonstrated that NLRP1 functions downstream of the MAPK/ERK signaling via ATF4 and is a player of targeted therapy resistance in melanoma. Targeting NLRP1 may improve the therapeutic efficacy of targeted therapy in melanoma.

scholarly journals Methotrexate sensitizes drug-resistant metastatic melanoma cells to BRAF V600E inhibitors dabrafenib and encorafenib

Oncotarget ◽  
2018 ◽  
Vol 9 (17) ◽  
pp. 13324-13336
Author(s):  
Kayleigh C. Ross ◽  
Kevin F. Chin ◽  
Daehwan Kim ◽  
Christopher D. Marion ◽  
Timothy J. Yen ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Melanoma Cells ◽  
Braf V600e ◽  
Drug Resistant

scholarly journals Abstract 5083: Indoleamine 2-3 dioxygenase expression by metastatic melanoma cells correlates with increased overall survival

2020 ◽  
Author(s):  
Kevin Lynch ◽  
Sarah Gradeki ◽  
Min Kwak ◽  
Alejandro Gru ◽  
Nolan Wages ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Melanoma Cells ◽  
Indoleamine 2

Effect of statins on NF-κB in human metastatic melanoma cells

2013 ◽  
Vol 1 (Suppl. 1) ◽  
pp. A3.7
Author(s):  
Stefan Salzmann
Keyword(s):  
Metastatic Melanoma ◽  
Melanoma Cells

The emerging roles of extracellular vesicles in ovarian cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Yin-xue Wang ◽  
Yi-xiang Wang ◽  
Yi-ke Li ◽  
Shi-yan Tu ◽  
Yi-qing Wang
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Vesicles ◽  
Large Scale ◽  
Current Treatment ◽  
Detection Methods ◽  
Drug Resistant ◽  
Apoptotic Bodies ◽  
Biological Mechanisms ◽  
Gynecological Malignancy ◽  
Resistance To Chemotherapy

: Ovarian cancer (OC) is one of the deadliest gynecological malignancy. Epithelial ovarian cancer (EOC) is its most common form. OC has both a poor prognosis and a high mortality rate due to the difficulties of early diagnosis, the limitation of current treatment and resistance to chemotherapy. Extracellular vesicles is a heterogeneous group of cellderived submicron vesicles which can be detected in body fluids, and it can be classified into three main types including exosomes, micro-vesicles, and apoptotic bodies. Cancer cells can produce more EVs than healthy cells. Moreover, the contents of these EVs have been found distinct from each other. It has been considered that EVs shedding from tumor cells may be implicated in clinical applications. Such as a tool for tumor diagnosis, prognosis and potential treatment of certain cancers. In this review, we provide a brief description of EVs in diagnosis, prognosis, treatment, drug-resistant of OC. Cancer-related EVs show powerful influences on tumors by various biological mechanisms. However, the contents mentioned above remain in the laboratory stage and there is a lack of large-scale clinical trials, and the maturity of the purification and detection methods is a constraint. In addition, amplification of oncogenes on ecDNA is remarkably prevalent in cancer, it may be possible that ecDNA can be encapsulated in EVs and thus detected by us. In summary, much more research on EVs needs to be perform to reveal breakthroughs in OC and to accelerate the process of its application on clinic.

Investigating the photodynamic efficacy of chlorin e6 by millisecond pulses in metastatic melanoma cells

2020 ◽  
pp. 107728
Author(s):  
Julita Kulbacka ◽  
Grzegorz Chodaczek ◽  
Joanna Rossowska ◽  
Anna Szewczyk ◽  
Jolanta Saczko ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Melanoma Cells ◽  
Chlorin E6

scholarly journals Melanoma Brain Metastases in the Era of Targeted Therapy and Checkpoint Inhibitor Therapy

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1489
Author(s):  
John M. Rieth ◽  
Umang Swami ◽  
Sarah L. Mott ◽  
Mario Zanaty ◽  
Michael D. Henry ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Treatment Strategies ◽  
Poor Performance Status ◽  
Poor Overall Survival ◽  
Melanoma Brain Metastases

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.

Hypoxic miRNAs expression are different between primary and metastatic melanoma cells

Gene ◽  
2021 ◽  
pp. 145552
Author(s):  
Yasunori Hino ◽  
Md Mahfuzur Rahman ◽  
Yu-Chang Lai ◽  
Al Asmaul Husna ◽  
Hui-wen Chen ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Melanoma Cells ◽  
Mirnas Expression
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