Joan Kyula
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View article: Xevinapant plus Chemoradiotherapy Negatively Sculpts the Tumor-Immune Microenvironment in Head and Neck Cancer
Xevinapant plus Chemoradiotherapy Negatively Sculpts the Tumor-Immune Microenvironment in Head and Neck Cancer Open
Xevinapant is an orally bioavailable antagonist of select members of the inhibitor of apoptosis protein family. Despite promising phase II data, combining xevinapant with chemoradiotherapy (CRT) failed to improve outcomes in the phase III …
View article: The PARP inhibitor talazoparib synergizes with reovirus to induce cancer killing and tumour control in vivo in mouse models
The PARP inhibitor talazoparib synergizes with reovirus to induce cancer killing and tumour control in vivo in mouse models Open
Reovirus type 3 Dearing (RT3D) is an oncolytic, double-stranded RNA virus. To identify potential RT3D drug-viral sensitizer, here we use a high-throughput screen of therapeutic agents and find a PARP-1 inhibitor, talazoparib, as a top hit.…
View article: Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion
Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion Open
Cytoplasmic pattern recognition receptors (PRR) for double-stranded RNA, such as RIG-I/MDA5, are key mediators of anti-viral responses. Here we screen for synergistic drug-virotherapy combinations and find that the reovirus type III Dearin…
View article: Supplementary Figure 1 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues
Supplementary Figure 1 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues Open
CD3 expression across time course and examination of CXCL12 expression after irradiation in primary fibroblasts in vitro.
View article: Supplementary Figure 2 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues
Supplementary Figure 2 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues Open
Knockdown sequence selection for CXCL12 and proof of modulation of CXCL12 in vitro and in vivo. Primary fibroblasts were modified with lentivirus to overexpress CXCL12 with a FLAG-epitope tag to allow clear detection of CXCL12 at protein l…
View article: Supplementary Figure 5 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues
Supplementary Figure 5 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues Open
Analysis of metastasis in in vivo samples A) Animals were culled at tumour severity limits per model described in figure 5B. Livers, spleens, lungs and ormental mesenteric tissue were harvested for examination of metastasis. Every 10th and…
View article: Supplementary Figure 3 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues
Supplementary Figure 3 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues Open
RTOG acute effects after 50 Gy/3 Fr and cumulative later RTOG toxicities for LVSCR/PBS/LVOeCXCL12
View article: Data from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues
Data from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues Open
Radiation-induced fibrosis (RIF) is a progressive pathology deleteriously impacting cancer survivorship. CXCL12 is an immune–stromal signal implicated in fibrosis and innate response. We hypothesized that modulation of CXCL12 would phenoty…
View article: Supplementary Table 1 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues
Supplementary Table 1 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues Open
Description of RTOG scoring for Acute and Late Toxicities
View article: Supplementary Table 2 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues
Supplementary Table 2 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues Open
Summary of Western blot density data
View article: Supplementary Figure 4 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues
Supplementary Figure 4 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues Open
Flow Cytometry of digested flap tissue: Macrophage subtype at day 90 and T-Cell subtype examination at day 21
View article: Supplementary Table 3 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues
Supplementary Table 3 from CXCL12-Targeted Immunomodulatory Gene Therapy Reduces Radiation-Induced Fibrosis in Healthy Tissues Open
Summative Data Table for Differential Gene Expression presented in Figure 4A Heatmap (LVSCR vs. LVShCXCL12 samples)
View article: Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy
Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent adjuvant immunotherapy Open
The combination of radiotherapy/chemoradiotherapy and immune checkpoint blockade can result in poor outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Here, we show that combining ATR inhibition (ATRi…
View article: Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T-cell receptor signalling
Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T-cell receptor signalling Open
Background Over the past decade, cancer immunotherapies have revolutionized the treatment of melanoma; however, responses vary across patient populations. Recently, baseline tumor size has been identified as an independent prognostic facto…
View article: Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T cell receptor signalling
Combination of oncolytic Maraba virus with immune checkpoint blockade overcomes therapy resistance in an immunologically cold model of advanced melanoma with dysfunctional T cell receptor signalling Open
Background Over the past decade, cancer immunotherapies have revolutionised the treatment of melanoma; however, responses vary across patient populations. Recently, baseline tumour size has been identified as an independent prognostic fact…
View article: PARP inhibitors enhance reovirus-mediated cell killing through the death-inducing signaling complex (DISC) with an associated NF-κB-regulated immune response
PARP inhibitors enhance reovirus-mediated cell killing through the death-inducing signaling complex (DISC) with an associated NF-κB-regulated immune response Open
Oncolytic Reovirus type 3 Dearing (RT3D), is a naturally occurring double-stranded (ds) RNA virus that is under development as an oncolytic immunotherapy We used an unbiased high-throughput cytotoxicity screen of different targeted therape…
View article: Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent anti-PD-L1- and anti-NKG2A-based adjuvant immunotherapy
Sculpting the tumour microenvironment by combining radiotherapy and ATR inhibition for curative-intent anti-PD-L1- and anti-NKG2A-based adjuvant immunotherapy Open
Despite some success in other cancer types, the results of combining radiotherapy/chemoradiotherapy and immune checkpoint blockade have been disappointing in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). For…
View article: CCR Translation for this Article from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer
CCR Translation for this Article from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer Open
CCR Translation for this Article from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer
View article: Supplementary Data from PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma
Supplementary Data from PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma Open
Supplementary tables and figures
View article: Data from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer
Data from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer Open
Purpose: We have shown previously that exposure to anticancer drugs can trigger the activation of human epidermal receptor survival pathways in colorectal cancer (CRC). In this study, we examined the role of ADAMs (a disintegrin and metall…
View article: CCR Translation for this Article from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer
CCR Translation for this Article from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer Open
CCR Translation for this Article from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer
View article: Data from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer
Data from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer Open
Purpose: We have shown previously that exposure to anticancer drugs can trigger the activation of human epidermal receptor survival pathways in colorectal cancer (CRC). In this study, we examined the role of ADAMs (a disintegrin and metall…
View article: Supplementary Data from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer
Supplementary Data from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer Open
Supplementary Figures S1-S9.
View article: Data from PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma
Data from PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma Open
Purpose:The prevention and treatment of metastatic sarcoma are areas of significant unmet need. Immune checkpoint inhibitor monotherapy has shown little activity in sarcoma and there is great interest in identifying novel treatment combina…
View article: Supplementary Data from PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma
Supplementary Data from PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma Open
Supplementary tables and figures
View article: Supplementary Data from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer
Supplementary Data from Chemotherapy-Induced Activation of ADAM-17: A Novel Mechanism of Drug Resistance in Colorectal Cancer Open
Supplementary Figures S1-S9.
View article: Data from PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma
Data from PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma Open
Purpose:The prevention and treatment of metastatic sarcoma are areas of significant unmet need. Immune checkpoint inhibitor monotherapy has shown little activity in sarcoma and there is great interest in identifying novel treatment combina…
View article: Supplementary Figure 4 from Src and ADAM-17–Mediated Shedding of Transforming Growth Factor-α Is a Mechanism of Acute Resistance to TRAIL
Supplementary Figure 4 from Src and ADAM-17–Mediated Shedding of Transforming Growth Factor-α Is a Mechanism of Acute Resistance to TRAIL Open
Supplementary Figure 4 from Src and ADAM-17–Mediated Shedding of Transforming Growth Factor-α Is a Mechanism of Acute Resistance to TRAIL
View article: Data from Oncogenic <i>Kras</i> Promotes Chemotherapy-Induced Growth Factor Shedding via ADAM17
Data from Oncogenic <i>Kras</i> Promotes Chemotherapy-Induced Growth Factor Shedding via ADAM17 Open
Oncogenic mutations in Kras occur in 40% to 45% of patients with advanced colorectal cancer (CRC). We have previously shown that chemotherapy acutely activates ADAM17, resulting in growth factor shedding, growth factor receptor activation,…