scholarly journals Predictive Gene Signature for Pyrazolopyrimidine Derivative c-Src Inhibitor 10a Sensitivity in Melanoma Cells

2020 ◽  
Vol 11 (5) ◽  
pp. 928-932
Author(s):  
Baris Kucukkaraduman ◽  
Can Turk ◽  
Anna L. Fallacara ◽  
Murat Isbilen ◽  
Kerem M. Senses ◽  
...  
Keyword(s):  
Gene Signature ◽  
Melanoma Cells ◽  
Predictive Gene ◽  
Src Inhibitor

scholarly journals Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Michal Lotem ◽  
Sharon Merims ◽  
Stephen Frank ◽  
Tamar Hamburger ◽  
Aviram Nissan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Disease Recurrence ◽  
Gene Signature ◽  
Melanoma Cells ◽  
Delayed Type Hypersensitivity ◽  
Strong Response ◽  
Expression Array ◽  
Melanoma Vaccine ◽  
Melanoma Patients

Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence.Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival.Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p=0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p=0.007).Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.

scholarly journals Predictive Gene Signature of Response to the Anti-TweakR mAb PDL192 in Patient-Derived Breast Cancer Xenografts

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e104227 ◽  
Author(s):  
Ludmilla de Plater ◽  
Anne Vincent-Salomon ◽  
Frédérique Berger ◽  
André Nicolas ◽  
Sophie Vacher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Signature ◽  
Predictive Gene ◽  
Breast Cancer Xenografts

scholarly journals CITED1 is a novel binding partner of MITF that influences the MITF-directed transcriptional profile in melanoma

2017 ◽  
Author(s):  
Barbara Lettiero ◽  
Martin Lauss ◽  
Ake Borg ◽  
Sofia Gruvberger-Saal ◽  
Goran B Jönsson ◽  
...  
Keyword(s):  
Transcriptional Response ◽  
Gene Signature ◽  
Melanoma Cells ◽  
Cell Phenotype ◽  
Chromatin Binding ◽  
Binding Partner ◽  
Nuclear Complex ◽  
Number Of Genes ◽  
First Time

We previously demonstrated how CITED1 knockdown in melanoma cells had the capacity to perturb expression of a significant number of genes that comprised MITF and several of its known transcriptional targets. This manifest as a switch from a more invasive to a more proliferative gene signature phenotype. We now demonstrate by using MITF ChIP-seq, that altered CITED1 expression affects MITF transcription factor binding to its targets across the genome. We show that silencing CITED1 effectively amplifies the MITF chromatin-binding signal response while we also demonstrate for the first time that CITED1 and MITF co-localise in a nuclear complex using an in-situ ligation proximity assay. We propose that CITED1-MITF binding is capable of altering both the affinity of chromatin association and transcriptional response to MITF at the target regions in the genome where MITF is either directly or indirectly bound to DNA. As CITED1/SMAD2 has been shown to mediate TGFβ-driven transcription that induces amoeboid-like invasion in melanoma cells we hypothesis that the MITF/CITED1 driven transcriptional response dominates in MITF-high/low-invasive environment or proliferative signature cell phenotype, whereas the SMAD2/CITED1 transcriptional response is dominant in a low-MITF/ high-invasive signature environment.

scholarly journals CITED1 is a novel binding partner of MITF that influences the MITF-directed transcriptional profile in melanoma

2017 ◽  
Author(s):  
Barbara Lettiero ◽  
Martin Lauss ◽  
Ake Borg ◽  
Sofia Gruvberger-Saal ◽  
Goran B Jönsson ◽  
...  
Keyword(s):  
Transcriptional Response ◽  
Gene Signature ◽  
Melanoma Cells ◽  
Cell Phenotype ◽  
Chromatin Binding ◽  
Binding Partner ◽  
Nuclear Complex ◽  
Number Of Genes ◽  
First Time

We previously demonstrated how CITED1 knockdown in melanoma cells had the capacity to perturb expression of a significant number of genes that comprised MITF and several of its known transcriptional targets. This manifest as a switch from a more invasive to a more proliferative gene signature phenotype. We now demonstrate by using MITF ChIP-seq, that altered CITED1 expression affects MITF transcription factor binding to its targets across the genome. We show that silencing CITED1 effectively amplifies the MITF chromatin-binding signal response while we also demonstrate for the first time that CITED1 and MITF co-localise in a nuclear complex using an in-situ ligation proximity assay. We propose that CITED1-MITF binding is capable of altering both the affinity of chromatin association and transcriptional response to MITF at the target regions in the genome where MITF is either directly or indirectly bound to DNA. As CITED1/SMAD2 has been shown to mediate TGFβ-driven transcription that induces amoeboid-like invasion in melanoma cells we hypothesis that the MITF/CITED1 driven transcriptional response dominates in MITF-high/low-invasive environment or proliferative signature cell phenotype, whereas the SMAD2/CITED1 transcriptional response is dominant in a low-MITF/ high-invasive signature environment.

Bosutinib, an SRC inhibitor, induces caspase-independent cell death associated with permeabilization of lysosomal membranes in melanoma cells

2017 ◽  
Vol 16 (1) ◽  
pp. 69-76 ◽  
Author(s):  
S. Noguchi ◽  
S. Shibutani ◽  
K. Fukushima ◽  
T. Mori ◽  
M. Igase ◽  
...  
Keyword(s):  
Cell Death ◽  
Melanoma Cells ◽  
Lysosomal Membranes ◽  
Src Inhibitor

scholarly journals COMP-17. LARGE-SCALE TRANSCRIPTOMIC CHARACTERIZATION OF PRIMARY AND RECURRENT GLIOBLASTOMA IDENTIFIES GENE EXPRESSION SIGNATURE OF TUMOR RESPONSE TO STANDARD THERAPY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi64-vi65
Author(s):  
Andrew Dhawan ◽  
Justin Lathia ◽  
David Peereboom ◽  
Gene Barnett ◽  
Gabrielle Yeaney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Standard Therapy ◽  
Therapeutic Response ◽  
Molecular Subtype ◽  
Gene Expression Signature ◽  
Gene Signature ◽  
Response To Therapy ◽  
Computational Method ◽  
Primary Tumors ◽  
Predictive Gene

Abstract A near-universal phenomenon in glioblastoma is disease recurrence following surgical resection and chemoradiotherapy. Development of biomarkers predictive of therapeutic response to better guide care and inform future targeted therapies is crucial. In this work, a total of 84 glioblastoma surgical specimens involving 44 primary tumors and 40 matched samples at time of re-resection, were characterized utilizing RNA-sequencing. Transcriptomic analysis was carried out with the goal of identifying underlying differences between those patients with prolonged response to standard therapy and delayed time to re-resection. We examined individual gene expression, gene coexpression networks, and well-known gene pathways in this dataset that showed consistent association with time to re-resection in both primary and progressed specimens, independent of tumor molecular subtype. Leveraging this large, well-characterized dataset, and using a novel computational methodology based on a seed-gene approach, we identified a predictive gene signature for therapeutic response. Our analyses revealed a striking degree of heterogeneity among gene expression associated with response to standard therapy and time to re-resection, adding to the complexity of signature derivation. The novel signature we obtained for response showed components involving genes such as those in the IGF pathway (IGF2BP2, IGF2BP3) and PDGF-signalling pathway (MYC, FLI1, ARHGAP4, JAK3) predictive of poor response to therapy. Likewise, predictors of positive response to therapy included genes involved in the apoptosis and RAS pathways (RAB4A, CHUK) and DNA replication pathways (SSBP2). In sum, this is among the largest cohorts of well-characterized clinical tumor samples for which there is transcriptomic information from primary and re-resected samples from matched patients. Our results not only highlight an innovative computational method for gene signature derivation in the setting of significant underlying heterogeneity, but also result in a predictive gene signature, offering the potential to give therapy to those who stand to benefit most.

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