Roberto Velazquez
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View article: A bispecific antibody-drug conjugate targeting pCAD and CDH17 has antitumor activity and improved tumor-specificity
A bispecific antibody-drug conjugate targeting pCAD and CDH17 has antitumor activity and improved tumor-specificity Open
P-cadherin (pCAD) and LI-cadherin (CDH17) are cell-surface proteins belonging to the cadherin superfamily that are both highly expressed in colorectal cancer. This co-expression profile presents a novel and attractive opportunity for a dua…
View article: A bispecific antibody-drug conjugate targeting pCAD and CDH17 has antitumor activity and improved tumor specificity
A bispecific antibody-drug conjugate targeting pCAD and CDH17 has antitumor activity and improved tumor specificity Open
P-cadherin (pCAD) and LI-cadherin (CDH17) are cell surface proteins belonging to the cadherin superfamily that are both highly expressed in colorectal cancer. This co-expression profile presents a novel and attractive opportunity for a dua…
View article: Experimental Studies of Metaverse Streaming
Experimental Studies of Metaverse Streaming Open
Metaverse aims to construct a large, unified, immersive, and shared digital\nrealm by combining various technologies, namely XR (extended reality),\nblockchain, and digital twin, among others. This article explores the Metaverse\nfrom the …
View article: Supplementary Figure 4 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Figure 4 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
Evaluation of the in vivo combination benefit and the MAPK pathway suppression of MEK and SHP2 inhibitors in MIA PaCa-2 xenograft and a colon cancer PDX model.
View article: Supplementary Figure 5 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Figure 5 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
Changes in phospho-SHP2 levels following MEKi treatment in studied KRAS mutant lines.
View article: Supplementary Material and Methods from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Supplementary Material and Methods from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Material and Methods. File contains the following: Transcriptome sequencing and analysis, Soft agar assay, 2D and 3D Cell proliferation screen and compound characterization information.
View article: Supplementary Table 3 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Table 3 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
mRNA levels (TPM, transcripts per million reads in RNAseq) of SHP2, RTKs, and their ligands in all cell lines tested.
View article: Figure S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Figure S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
(A) In vivo primary human colorectal xenograft model HCOX4087 treated with trametinib (0.3 mg/kg QD), SHP099 (100 mg/kg QD), and a pan-RTK inhibitor, Dovitinib (100 mg/kg QD). (B-C) In vivo efficacy of selective VEGFR2 inhibitor, BFH772 (3…
View article: Table S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 2: List of all cell lines in the CCLE where sensitivity to SHP099 was evaluated in 2D. Lineage and genetic status of KRAS and BRAF are shown. Blank cells represent cell line data where genetic or screening data do not e…
View article: Supplementary Figure 3 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Figure 3 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
Evaluation of the in vitro synergy in anti-proliferation and the MAPK pathway suppression of MEK and SHP2, PI3K, or RTK inhibitors.
View article: Supplementary Figure 2 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Figure 2 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
Validation of HRAS/NRAS double knock-out clones and the contribution of mutant KRAS to the feedback activation in NCI-H358 and MIA PaCa-2.
View article: Supplementary Figure 1 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Figure 1 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
Schematic illustration of MEKi-induced MAPK pathway feedback activation, SHP099 dose-dependent reduction of p-MEK induction by MEKi, and MEKi-induced p-AKT levels.
View article: Data from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Data from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
KRAS, an oncogene mutated in nearly one third of human cancers, remains a pharmacologic challenge for direct inhibition except for recent advances in selective inhibitors targeting the G12C variant. Here, we report that selective in…
View article: Table S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 4: List of cell lines evaluated for sensitivity to SHP099 (Tab 1) or an RTK-inhibitor (Tab 2) in 2D or 3D. Included is the lineage and the KRAS mutation status. Where data are blank, no viable data was available, or the…
View article: Supplementary Material and Methods from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Supplementary Material and Methods from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Material and Methods. File contains the following: Transcriptome sequencing and analysis, Soft agar assay, 2D and 3D Cell proliferation screen and compound characterization information.
View article: Figure S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Figure S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
In vivo efficacy of SHP099 (100 mg/kg, daily) in the KYSE-520 esophageal cancer cell line model. Data are plotted as the treatment mean {plus minus} s.e.m (n=7) ( (B-I) In vivo efficacy data for cell line models represented in Fig. 3E. SHP…
View article: Supplementary Figure 2 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Figure 2 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
Validation of HRAS/NRAS double knock-out clones and the contribution of mutant KRAS to the feedback activation in NCI-H358 and MIA PaCa-2.
View article: Supplementary Figure 3 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Figure 3 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
Evaluation of the in vitro synergy in anti-proliferation and the MAPK pathway suppression of MEK and SHP2, PI3K, or RTK inhibitors.
View article: Supplementary Table 2 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Table 2 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
Quantification of p-MEK and tubulin levels and percentages of p-MEK reduction in the MEKi combination group normalized to tubulin in all cell lines tested.
View article: Supplementary Table 1 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Table 1 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
A list of KRAS mutant cell lines in the study with lineages, zygosity determined by RNAseq, and percentages of p-MEK reduction by 5 micromolar SHP099 in the MEKi combination group.
View article: Supplementary Figure 5 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Figure 5 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
Changes in phospho-SHP2 levels following MEKi treatment in studied KRAS mutant lines.
View article: Table S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 1: List of all cell lines in the CCLE (Cancer Cell Line Encyclopedia) where sensitivity to SHP2 (PTPN11) knockdown was evaluated in 2D. Lineage, and genetic status of KRAS and BRAF are shown. Blank cells represent cell …
View article: Supplementary Table 3 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Table 3 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
mRNA levels (TPM, transcripts per million reads in RNAseq) of SHP2, RTKs, and their ligands in all cell lines tested.
View article: Supplementary Figure 4 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Supplementary Figure 4 from SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors Open
Evaluation of the in vivo combination benefit and the MAPK pathway suppression of MEK and SHP2 inhibitors in MIA PaCa-2 xenograft and a colon cancer PDX model.
View article: Table S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 4: List of cell lines evaluated for sensitivity to SHP099 (Tab 1) or an RTK-inhibitor (Tab 2) in 2D or 3D. Included is the lineage and the KRAS mutation status. Where data are blank, no viable data was available, or the…
View article: Table S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 3: A total of 246 cell lines were evaluated for both SHP2 knockdown and SHP099 sensitivity. Data displays PTPN11 shRNA ATARIS Quantile Score and SHP099 IC50 and Amax for each cell line tested.
View article: Figure S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Figure S3 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
(A) In vivo primary human colorectal xenograft model HCOX4087 treated with trametinib (0.3 mg/kg QD), SHP099 (100 mg/kg QD), and a pan-RTK inhibitor, Dovitinib (100 mg/kg QD). (B-C) In vivo efficacy of selective VEGFR2 inhibitor, BFH772 (3…
View article: Table S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Table S2 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
Supplementary Table 2: List of all cell lines in the CCLE where sensitivity to SHP099 was evaluated in 2D. Lineage and genetic status of KRAS and BRAF are shown. Blank cells represent cell line data where genetic or screening data do not e…
View article: Fig S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Fig S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
(A) Effects of SHP099 and erlotinib on proliferation of EGFR-dependent and RAS/RAF wildtype Detroit-562 and KYSE520 cells grown in 2D monolayer or 3D spheroids (with 20% matrigel) for 6 days. The colored dotted lines at the bottom of graph…
View article: Fig S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Fig S1 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers Open
(A) Effects of SHP099 and erlotinib on proliferation of EGFR-dependent and RAS/RAF wildtype Detroit-562 and KYSE520 cells grown in 2D monolayer or 3D spheroids (with 20% matrigel) for 6 days. The colored dotted lines at the bottom of graph…