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mason bartels

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Papers by mason bartels

Research paper thumbnail of Supplementary Figure S5 & Supplementary S5 Legend from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

Research paper thumbnail of Supplementary Figure S4 & Supplementary S4 Legend from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

Research paper thumbnail of Supplementary Figure S4 & Supplementary S4 Legend from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

Research paper thumbnail of Supplementary Figure S6 & Supplementary S6 Legend from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

Tumor volume growth curves for individual mice in each treatment arm.

Research paper thumbnail of Supplementary Table S1 from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

Research paper thumbnail of Data from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

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...

Research paper thumbnail of Supplementary Table S5 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Figure S5 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Materials and Methods S1 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

Supplementary Materials and Methods

Research paper thumbnail of Supplementary Table S1 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Data from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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...

Research paper thumbnail of Supplementary Figure S8 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

IACS-6274 improves survival and is well tolerated in combination with cisplatin in mice.

Research paper thumbnail of Supplementary Figure S1 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

Cisplatin resistant HNSCC cells migrate faster than their Cisplatin sensitive counterparts.

Research paper thumbnail of Supplementary Figure S3 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

Relationship between TP53 status and the NRF2/KEAP1/CUL3 pathway in OCSCC TCGA samples.

Research paper thumbnail of Supplementary Figure S6 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Table S2 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Figure S7 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Table S3 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Table S4 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Figure S4 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

Restoration of wildtype KEAP1 improves survival in mice.

Research paper thumbnail of Supplementary Figure S5 & Supplementary S5 Legend from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

Research paper thumbnail of Supplementary Figure S4 & Supplementary S4 Legend from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

Research paper thumbnail of Supplementary Figure S4 & Supplementary S4 Legend from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

Research paper thumbnail of Supplementary Figure S6 & Supplementary S6 Legend from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

Tumor volume growth curves for individual mice in each treatment arm.

Research paper thumbnail of Supplementary Table S1 from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

Research paper thumbnail of Data from Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress

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...

Research paper thumbnail of Supplementary Table S5 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Figure S5 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Materials and Methods S1 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

Supplementary Materials and Methods

Research paper thumbnail of Supplementary Table S1 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Data from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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...

Research paper thumbnail of Supplementary Figure S8 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

IACS-6274 improves survival and is well tolerated in combination with cisplatin in mice.

Research paper thumbnail of Supplementary Figure S1 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

Cisplatin resistant HNSCC cells migrate faster than their Cisplatin sensitive counterparts.

Research paper thumbnail of Supplementary Figure S3 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

Relationship between TP53 status and the NRF2/KEAP1/CUL3 pathway in OCSCC TCGA samples.

Research paper thumbnail of Supplementary Figure S6 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Table S2 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Figure S7 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Table S3 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Table S4 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

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.

Research paper thumbnail of Supplementary Figure S4 from Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma

Restoration of wildtype KEAP1 improves survival in mice.

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