mason bartels - Academia.edu (original) (raw)
Related Authors
UERJ - Universidade do Estado do Rio de Janeiro / Rio de Janeiro State University
Uploads
Papers by mason bartels
Tumor volume growth curves for individual mice in each treatment arm.
Despite advances in surgery, chemotherapy, and radiation, there are limited treatment options for... more Despite advances in surgery, chemotherapy, and radiation, there are limited treatment options for advanced head and neck squamous cell carcinoma (HNSCC) and survival remains very poor. Therefore, effective therapies are desperately needed. Recently, selective exploitation of DNA damage and replication stress responses has become a novel approach for cancer treatment. Wee1 kinase and Rad51 recombinase are two proteins involved in regulating replication stress and homologous recombination repair in cancer cells. In this study, we investigated the combined effect of Rad51 inhibitor (B02) and Wee1 inhibitor (AZD1775) in vitro and in vivo in various HNSCC cell lines. Clonogenic survival assays demonstrated that B02 synergized with AZD1775 in vitro in all HNSCC cell lines tested. The synergy between these drugs was associated with forced CDK1 activation and reduced Chk1 phosphorylation leading to induction of excessive DNA damage and replication stress, culminating in aberrant mitosis and...
Supplementary Table S5A. Bulk-level single cell ATAC sequencing analysis showing immediate (short... more Supplementary Table S5A. Bulk-level single cell ATAC sequencing analysis showing immediate (short-term) chromatin openings (peaks) in HN30-P cells following CDDP treatment; Supplementary Table S5B. Bulk-level single cell ATAC sequencing analysis showing long-term chromatin openings (peaks) gained in cisplatin-resistant HN30-R8 cells following CDDP treatment.
NRF2 targeted suppression or restoration of wild type KEAP1 decreases distant metastasis in cispl... more NRF2 targeted suppression or restoration of wild type KEAP1 decreases distant metastasis in cisplatin resistant HNSCC cells.
Supplementary Materials and Methods
In vivo RNA sequencing and pair-wise comparison between 4 distinct groups in HN30-P and HN30-R8 H... more In vivo RNA sequencing and pair-wise comparison between 4 distinct groups in HN30-P and HN30-R8 HNSCC tumors.
Purpose:Cisplatin (CDDP)-based chemotherapy is a first-line treatment for patients with advanced ... more Purpose:Cisplatin (CDDP)-based chemotherapy is a first-line treatment for patients with advanced head and neck squamous cell carcinomas (HNSCC), despite a high rate of treatment failures, acquired resistance, and subsequent aggressive behavior. The purpose of this study was to study the mechanism of CDDP resistance and metastasis in HNSCC. We investigated the role of NRF2 pathway activation as a driven event for tumor progression and metastasis of HNSCC.Experimental Design:Human HNSCC cell lines that are highly resistant to CDDP were generated. Clonogenic survival assays and a mouse model of oral cancer were used to examine the impact of NRF2 activation in vitro and in vivo on CDDP sensitivity and development of metastasis. Western blotting, immunostaining, whole-exome sequencing, single-cell transcriptomic and epigenomic profiling platforms were performed to dissect clonal evolution and molecular mechanisms.Results:Implantation of CDDP-resistant HNSCC cells into the tongues of nude...
IACS-6274 improves survival and is well tolerated in combination with cisplatin in mice.
Cisplatin resistant HNSCC cells migrate faster than their Cisplatin sensitive counterparts.
Relationship between TP53 status and the NRF2/KEAP1/CUL3 pathway in OCSCC TCGA samples.
Cisplatin sensitivity following knockdown of NRF2 or restoration of wildtype KEAP1 in cisplatin r... more Cisplatin sensitivity following knockdown of NRF2 or restoration of wildtype KEAP1 in cisplatin resistant HNSCC cells is not mediated through apoptosis.
NRF2 regulated genes significantly upregulated in distant metastasis compared to paired primary t... more NRF2 regulated genes significantly upregulated in distant metastasis compared to paired primary tumors in HN30-R8 CDDP group.
Restoration of KEAP1/NRF2 pathways increases cisplatin sensitivity in resistant HNSCC cells throu... more Restoration of KEAP1/NRF2 pathways increases cisplatin sensitivity in resistant HNSCC cells through ferroptosis.
Whole exome sequencing showing mutational status in the parental HN30-P versus HN30-R8 cisplatin ... more Whole exome sequencing showing mutational status in the parental HN30-P versus HN30-R8 cisplatin resistant cell lines.
Supplementary Table S4A. The KNC genes enriched in cluster 1 in HNSCC cells; Supplementary Table ... more Supplementary Table S4A. The KNC genes enriched in cluster 1 in HNSCC cells; Supplementary Table S4B. Gene activity score of cell surface markers in cluster 1 in HNSCC cells.
Restoration of wildtype KEAP1 improves survival in mice.
Tumor volume growth curves for individual mice in each treatment arm.
Despite advances in surgery, chemotherapy, and radiation, there are limited treatment options for... more Despite advances in surgery, chemotherapy, and radiation, there are limited treatment options for advanced head and neck squamous cell carcinoma (HNSCC) and survival remains very poor. Therefore, effective therapies are desperately needed. Recently, selective exploitation of DNA damage and replication stress responses has become a novel approach for cancer treatment. Wee1 kinase and Rad51 recombinase are two proteins involved in regulating replication stress and homologous recombination repair in cancer cells. In this study, we investigated the combined effect of Rad51 inhibitor (B02) and Wee1 inhibitor (AZD1775) in vitro and in vivo in various HNSCC cell lines. Clonogenic survival assays demonstrated that B02 synergized with AZD1775 in vitro in all HNSCC cell lines tested. The synergy between these drugs was associated with forced CDK1 activation and reduced Chk1 phosphorylation leading to induction of excessive DNA damage and replication stress, culminating in aberrant mitosis and...
Supplementary Table S5A. Bulk-level single cell ATAC sequencing analysis showing immediate (short... more Supplementary Table S5A. Bulk-level single cell ATAC sequencing analysis showing immediate (short-term) chromatin openings (peaks) in HN30-P cells following CDDP treatment; Supplementary Table S5B. Bulk-level single cell ATAC sequencing analysis showing long-term chromatin openings (peaks) gained in cisplatin-resistant HN30-R8 cells following CDDP treatment.
NRF2 targeted suppression or restoration of wild type KEAP1 decreases distant metastasis in cispl... more NRF2 targeted suppression or restoration of wild type KEAP1 decreases distant metastasis in cisplatin resistant HNSCC cells.
Supplementary Materials and Methods
In vivo RNA sequencing and pair-wise comparison between 4 distinct groups in HN30-P and HN30-R8 H... more In vivo RNA sequencing and pair-wise comparison between 4 distinct groups in HN30-P and HN30-R8 HNSCC tumors.
Purpose:Cisplatin (CDDP)-based chemotherapy is a first-line treatment for patients with advanced ... more Purpose:Cisplatin (CDDP)-based chemotherapy is a first-line treatment for patients with advanced head and neck squamous cell carcinomas (HNSCC), despite a high rate of treatment failures, acquired resistance, and subsequent aggressive behavior. The purpose of this study was to study the mechanism of CDDP resistance and metastasis in HNSCC. We investigated the role of NRF2 pathway activation as a driven event for tumor progression and metastasis of HNSCC.Experimental Design:Human HNSCC cell lines that are highly resistant to CDDP were generated. Clonogenic survival assays and a mouse model of oral cancer were used to examine the impact of NRF2 activation in vitro and in vivo on CDDP sensitivity and development of metastasis. Western blotting, immunostaining, whole-exome sequencing, single-cell transcriptomic and epigenomic profiling platforms were performed to dissect clonal evolution and molecular mechanisms.Results:Implantation of CDDP-resistant HNSCC cells into the tongues of nude...
IACS-6274 improves survival and is well tolerated in combination with cisplatin in mice.
Cisplatin resistant HNSCC cells migrate faster than their Cisplatin sensitive counterparts.
Relationship between TP53 status and the NRF2/KEAP1/CUL3 pathway in OCSCC TCGA samples.
Cisplatin sensitivity following knockdown of NRF2 or restoration of wildtype KEAP1 in cisplatin r... more Cisplatin sensitivity following knockdown of NRF2 or restoration of wildtype KEAP1 in cisplatin resistant HNSCC cells is not mediated through apoptosis.
NRF2 regulated genes significantly upregulated in distant metastasis compared to paired primary t... more NRF2 regulated genes significantly upregulated in distant metastasis compared to paired primary tumors in HN30-R8 CDDP group.
Restoration of KEAP1/NRF2 pathways increases cisplatin sensitivity in resistant HNSCC cells throu... more Restoration of KEAP1/NRF2 pathways increases cisplatin sensitivity in resistant HNSCC cells through ferroptosis.
Whole exome sequencing showing mutational status in the parental HN30-P versus HN30-R8 cisplatin ... more Whole exome sequencing showing mutational status in the parental HN30-P versus HN30-R8 cisplatin resistant cell lines.
Supplementary Table S4A. The KNC genes enriched in cluster 1 in HNSCC cells; Supplementary Table ... more Supplementary Table S4A. The KNC genes enriched in cluster 1 in HNSCC cells; Supplementary Table S4B. Gene activity score of cell surface markers in cluster 1 in HNSCC cells.
Restoration of wildtype KEAP1 improves survival in mice.