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Metastatic Melanoma - BioProject

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Last Updated: 23 April 2022

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The BAMM Trial: BRAF, Autophagy and MEK inhibition in Metastatic Melanoma: A phase I/II trial of dabrafenib, trametinib and hydroxychloroquine in patients with advanced BRAF mutant melanoma

In BRAF mutant melanoma, autophagy has been identified as a defense mechanism against BRAF and MEK inhibition. In the BRAF mutant melanoma patients, hydroxychloroquine was used to reduce autophagy in combination with dabrafenib and trametenib. Patients were screened and evaluated for toxicity, and 34 patients were evaluable for 1-year PFS rate between December 2014 and January 2020, according to the main Outcome, A prospective clinical trial was conducted in four centers. There was no dose restricting toxicity of HCQ in either 400 n=3 or 600 mg po bid mixed with D+T in the phase I trial. Conlusion and Relevance: The ORR was 88% in a predefined subgroup study in 18 patients with elevated LDH, and median PFS was 8 months, but not meet the predetermined goals for success in a 1-year PFS study. The National Clinical Trial Network is a networked trial of a controlled placebo controlled trial of dabrafenib and trametinib in advanced BRAF mutant melanoma patients with elevated LDH and previously treated with immunotherapy.

Source link: https://www.ncbi.nlm.nih.gov/bioproject/795153


Comprehensive molecular profiling of UV-induced metastatic melanoma in Nme1/Nme2-deficient mice reveals novel genes associated with progression and survival in human patients

Purpose: Herein we show that UV-induced melanomas of low metastatic risk in mice that overexpress HGF and harbor deletion of the Ink4a/p16 locus are converted to highly metastatic forms by hemizygous deletion of the metastasis suppressor genes Nme1 and Nme2. A simple way for determining molecular profiles associated with metastatic activity was provided by the striking difference in metastatic activity between HP and HPN melanomas strains.

Source link: https://www.ncbi.nlm.nih.gov/bioproject/751058


Transcriptional profiling of macrophages in situ in metastatic melanoma reveals localization dependent phenotypes and function

Therapeutic interventions that enhance immune function at the tumor site may be able to reduce cancer outcomes. Here we examined metastatic melanoma, a tumor form that is highly responsive to T-cell therapies, and discovered that the tumor-infiltrating T cells are closer to CD14+ monocytes/macrophages rather than to melanoma cells. Localized in tumor cells, CD14+ cells localized in tumor stroma had a specific transcriptional signature distinct from CD14+ cells localized in tumor stroma. The gene module of stromal macrophages distinguished patients with significantly longer survival in cutaneous melanoma and other cancers such as uveal melanoma, bladder urothelial carcinoma, and lower grade glioma when applied to TCGA cohorts. Therefore, stromal CD14+ cell signature, as a new candidate biomarker, and targeted reprogramming of stromal macrophages to DC function may be a therapeutic option for metastatic cancer. We have 2 samples per patient for CD14+ and cancer cell cultures.

Source link: https://www.ncbi.nlm.nih.gov/bioproject/746595


DNA methylation-based prediction of response to immune checkpoint inhibition in metastatic melanoma

A novel strategy of reference-free deconvolution of large-scale DNA methylation data allowed for the creation of a machine learning classifier based on CpG sites that allowed for patient allocation to prognostic clusters, allowing for a novel strategy of reference-free deconvolution of large-scale DNA methylation data. Patients participating in AJCC Stage IV were analyzed using the Illumina Infinium MethylationEPIC BeadChip. Overall scheme: 65 specimens of melanoma skin metastasis were analyzed using the Illumina Infinium MethylationEPIC BeadChip.

Source link: https://www.ncbi.nlm.nih.gov/bioproject/733214


The use of immunohistochemistry as an accurate tool in the assessment of BRAF V600E and TP53 mutations in primary and metastatic melanoma

Metastatic melanoma is a fatal disease with poor prognosis, and it can be fatal. The main aim of the present study was to determine whether BRAF and p53 IHC are reliable surrogates for mutation detection. BRAF mutation and nine TP53 mutations were found in a study of 55 cases, of which 21 patients had BRAF mutations and nine TP53 mutations in a series of 55 cases. Compared to NGS, IHC had a 95. 92% diagnostic accuracy for BRAF V600E and 74. 4 percent for TP53. The kappa coefficient for BRAF V600E 0. 851 is 0. 667 and for BRAF V600E 0. 851. Conclusions: Our results showed that IHC staining was a reliable surrogate for NGS in identifying the BRAF V600E mutation, making it a useful screening device. The p53 IHC aberrant expression is sometimes associated with TP53 mutations, but no clear link can be established, so there is no direct link can be established.

Source link: https://www.ncbi.nlm.nih.gov/bioproject/724344


Pathway Signatures Derived from On-treatment Tumor Specimens Predict Response to Anti-PD1 Blockade in Metastatic Melanoma

In four independent datasets with RNAseq and clinical response data available for both pre- and on-treatment metastatic melanomas, we developed pathway-based signatures that predict metastatic melanoma response to anti-PD1-based therapies. At pre-treatment and on-treatment time points, respectively, we first identified pathway signatures that were significantly enhanced in tumor specimens from anti-PD1 responders and non-responders. In addition, we also established pathway signatures that were inconsistently expressed in pre-treatment samples obtained from R. We also investigated the capability of the two signatures in predicting the response of metastatic melanoma to anti-PD1 therapies in comparison with existing gene expression signatures. We also investigated the effect of biopsy centers at the same biopsy time point on predictive success of anti-PD1 therapy response. Overall, we show that pathway-based signatures obtained from on-treatment tumor specimens are highly predictive of responses to anti-PD1 blockade therapy in patients with metastatic melanoma.

Source link: https://www.ncbi.nlm.nih.gov/bioproject/706446


scRNA-Seq of peripheral CD8 T cells from patients with metastatic melanoma taking ICI therapy.

Patients with metastatic melanoma have been treated with the latest class of immuno checkpoint inhibitors. In circulating CD8+ T cells isolated by cell sorting from 20 patients who were followed for 6 months, single-cell RNA-sequencing was carried out. After the first and second cycle of ICI therapy, the overall scheme: scRNA-Seq of peripheral CD8 T cells obtained from 20 melanoma patients before.

Source link: https://www.ncbi.nlm.nih.gov/bioproject/699546


Circulating microRNA enriched in plasma small extracellular vesicles profiling in a preclinical model of metastatic human melanoma in the mouse brain

Patients with melanoma brain metastases have a dismal prognosis, with a 6-month median overall survival rate. We discovered a small number of circulating miRNAs in sEVs that correspond to melanoma metastatic disease onset and progression. Our findings add to the growing role of liquid biopsy for the detection of metastatic melanoma in the brain.

Source link: https://www.ncbi.nlm.nih.gov/bioproject/690358


Niraparib treatment of metastatic melanoma in vivo

Twenty four NSG mice were injected subcutaneously with melanoma PDX cells. In MM-425 tumors from three mice treated with niraparib compared to three mice treated with vehicle, RNA-Seq was performed to determine transcriptomic profiles modified following niraparib treatment. Using the RNeasy tissue kit after tissue disruption using ruptor disposable probes and the concentration determined by Qubit RNA HS Assay Kit, tissue RNA was extracted from PDX tumor tissues using the RNeasy tissue kit.

Source link: https://www.ncbi.nlm.nih.gov/bioproject/686436


Tumor and gut biopsies from refractory metastatic melanoma patients before and after treatment with fecal microbiota transplantation (FMT) and anti-PD-1 re-induction (Baruch et al, Science 2020)

In patients with anti-PD-1-refractory metastatic melanoma, we conducted a phase I clinical trial to determine the safety and efficacy of fecal microbiota transplantation and re-induction of anti-PD-1 immunotherapy in patients with anti-PD-1-refractory metastatic melanoma. FMT donors were two metastatic melanoma patients with no apparent response. Patients in FMT recipient patients with metastatic melanoma disease and who had no one anti-PD-1 line of therapy, according to a metastatic melanoma patient. From just one of the two donors, each recipient patient received FMT implants from FMT. Notably, treatment with FMT has been associated with improved immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. Before starting medical therapy, biopsies from the sigmoid colon and remote tumor metastasis were obtained from a healthy treatment recipient patient. On day 31 of therapy, repeating sigmoid colon biopsies were discovered.

Source link: https://www.ncbi.nlm.nih.gov/bioproject/681864

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions