› Forums › General Melanoma Community › New treatment /trial – TH302
- This topic has 6 replies, 2 voices, and was last updated 12 years, 2 months ago by
BrianP.
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- February 13, 2014 at 3:50 am
A friend asked about this trial. She was looking at it in Canada and would like to chat with someone that is envolved in the trial. Her post: I was looking into a trial called TH302, but denied because I am transfusion dependent. Doesn't matter I didn't really want to do it, and I am doing TILS. And I would be the first in Canada to do it with Melanoma. My question is has anyone heard of this yet in the USA? Is a really cool concept for the drugs action.
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- February 14, 2014 at 6:05 pm
Looks like they are looking at this Hypoxia theory in other cancers as well Jerry.
Hypoxia-Driven Gene Expression Is Prognostic in Stage II/III Colon Cancer
Clin. Cancer Res 2014 Jan 31;[EPub Ahead of Print], J Dekervel, D Hompes, H van Malenstein, D Popovic, X Sagaert, B De Moor, E Van Cutsem, A D'hoore, C Verslype, J van Pelt
Research·February 13, 2014{C}{C}
{C}
{C}
TAKE-HOME MESSAGE
- This study looking at gene expression of CaCo-2 cells cultured in hypoxic vs non-hypoxic conditions showed a correlation with clinical outcomes demonstrated in previous microarray experiments. From there, the researchers developed a six-gene colon cancer hypoxia score, which was tested in two separate cohorts and found to be independently prognostic for stage II and III colon cancer.
- The results, which warrant further validation, indicate a role for intra-tumoral hypoxia as a prognostic biomarker in colorectal cancer.
ABSTRACT
Purpose
Hypoxia is considered a major microenvironmental factor influencing cancer behavior. Our aim was to develop a hypoxia-based gene score that could identify high and low risk within stage II and III colon cancer patients.
Experimental design
Differential gene expression of CaCo-2 colon cancer cells cultured in chronic hypoxia versus normoxia was tested for correlation with prognostic variables in published microarray data sets. These data sets were further used to downsize and optimize a gene score, which was subsequently determined in paraffin embedded material of 126 patients with colon cancer treated in our center.
Results
In the CaCo-2 cells, 923 genes with a 2-fold change and Limma corrected p≤0.0001 were found differentially expressed in hypoxia versus normoxia. We identified 21 genes with prognostic value and overlapping in three different training sets and (n=224). With a fourth published data set (n=177), the six gene Colon Cancer Hypoxia Score (CCHS) was developed. Patients with low CCHS showed a significant better disease free survival at three years (77.3%) compared to high CCHS patients (46.4%) (Log rank, p=0.006). This was independently confirmed in an external patient cohort of 90 stage II patients (86.9% vs 52.2%, p=0.001).
Conclusions
Hypoxia driven gene expression is associated with high recurrence rates in stage II and III colon cancer. A 6-gene score was found to be of independent prognostic value in these patients. Our findings require further validation and incorporation in the current knowledgee on molecular classification of colon cancer.
{C}
{C}
Clinical Cancer ResearchHypoxia Driven Gene Expression Is an Independent Prognostic Factor in Stage II and III Colon Cancer Patients
Clin. Cancer Res 2014 Jan 31;[EPub Ahead of Print], J Dekervel, D Hompes, H van Malenstein, D Popovic, X Sagaert, B De Moor, E Van Cutsem, A D'hoore, C Verslype, J van Pelt
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- February 14, 2014 at 6:05 pm
Looks like they are looking at this Hypoxia theory in other cancers as well Jerry.
Hypoxia-Driven Gene Expression Is Prognostic in Stage II/III Colon Cancer
Clin. Cancer Res 2014 Jan 31;[EPub Ahead of Print], J Dekervel, D Hompes, H van Malenstein, D Popovic, X Sagaert, B De Moor, E Van Cutsem, A D'hoore, C Verslype, J van Pelt
Research·February 13, 2014{C}{C}
{C}
{C}
TAKE-HOME MESSAGE
- This study looking at gene expression of CaCo-2 cells cultured in hypoxic vs non-hypoxic conditions showed a correlation with clinical outcomes demonstrated in previous microarray experiments. From there, the researchers developed a six-gene colon cancer hypoxia score, which was tested in two separate cohorts and found to be independently prognostic for stage II and III colon cancer.
- The results, which warrant further validation, indicate a role for intra-tumoral hypoxia as a prognostic biomarker in colorectal cancer.
ABSTRACT
Purpose
Hypoxia is considered a major microenvironmental factor influencing cancer behavior. Our aim was to develop a hypoxia-based gene score that could identify high and low risk within stage II and III colon cancer patients.
Experimental design
Differential gene expression of CaCo-2 colon cancer cells cultured in chronic hypoxia versus normoxia was tested for correlation with prognostic variables in published microarray data sets. These data sets were further used to downsize and optimize a gene score, which was subsequently determined in paraffin embedded material of 126 patients with colon cancer treated in our center.
Results
In the CaCo-2 cells, 923 genes with a 2-fold change and Limma corrected p≤0.0001 were found differentially expressed in hypoxia versus normoxia. We identified 21 genes with prognostic value and overlapping in three different training sets and (n=224). With a fourth published data set (n=177), the six gene Colon Cancer Hypoxia Score (CCHS) was developed. Patients with low CCHS showed a significant better disease free survival at three years (77.3%) compared to high CCHS patients (46.4%) (Log rank, p=0.006). This was independently confirmed in an external patient cohort of 90 stage II patients (86.9% vs 52.2%, p=0.001).
Conclusions
Hypoxia driven gene expression is associated with high recurrence rates in stage II and III colon cancer. A 6-gene score was found to be of independent prognostic value in these patients. Our findings require further validation and incorporation in the current knowledgee on molecular classification of colon cancer.
{C}
{C}
Clinical Cancer ResearchHypoxia Driven Gene Expression Is an Independent Prognostic Factor in Stage II and III Colon Cancer Patients
Clin. Cancer Res 2014 Jan 31;[EPub Ahead of Print], J Dekervel, D Hompes, H van Malenstein, D Popovic, X Sagaert, B De Moor, E Van Cutsem, A D'hoore, C Verslype, J van Pelt
-
- February 14, 2014 at 6:05 pm
Looks like they are looking at this Hypoxia theory in other cancers as well Jerry.
Hypoxia-Driven Gene Expression Is Prognostic in Stage II/III Colon Cancer
Clin. Cancer Res 2014 Jan 31;[EPub Ahead of Print], J Dekervel, D Hompes, H van Malenstein, D Popovic, X Sagaert, B De Moor, E Van Cutsem, A D'hoore, C Verslype, J van Pelt
Research·February 13, 2014{C}{C}
{C}
{C}
TAKE-HOME MESSAGE
- This study looking at gene expression of CaCo-2 cells cultured in hypoxic vs non-hypoxic conditions showed a correlation with clinical outcomes demonstrated in previous microarray experiments. From there, the researchers developed a six-gene colon cancer hypoxia score, which was tested in two separate cohorts and found to be independently prognostic for stage II and III colon cancer.
- The results, which warrant further validation, indicate a role for intra-tumoral hypoxia as a prognostic biomarker in colorectal cancer.
ABSTRACT
Purpose
Hypoxia is considered a major microenvironmental factor influencing cancer behavior. Our aim was to develop a hypoxia-based gene score that could identify high and low risk within stage II and III colon cancer patients.
Experimental design
Differential gene expression of CaCo-2 colon cancer cells cultured in chronic hypoxia versus normoxia was tested for correlation with prognostic variables in published microarray data sets. These data sets were further used to downsize and optimize a gene score, which was subsequently determined in paraffin embedded material of 126 patients with colon cancer treated in our center.
Results
In the CaCo-2 cells, 923 genes with a 2-fold change and Limma corrected p≤0.0001 were found differentially expressed in hypoxia versus normoxia. We identified 21 genes with prognostic value and overlapping in three different training sets and (n=224). With a fourth published data set (n=177), the six gene Colon Cancer Hypoxia Score (CCHS) was developed. Patients with low CCHS showed a significant better disease free survival at three years (77.3%) compared to high CCHS patients (46.4%) (Log rank, p=0.006). This was independently confirmed in an external patient cohort of 90 stage II patients (86.9% vs 52.2%, p=0.001).
Conclusions
Hypoxia driven gene expression is associated with high recurrence rates in stage II and III colon cancer. A 6-gene score was found to be of independent prognostic value in these patients. Our findings require further validation and incorporation in the current knowledgee on molecular classification of colon cancer.
{C}
{C}
Clinical Cancer ResearchHypoxia Driven Gene Expression Is an Independent Prognostic Factor in Stage II and III Colon Cancer Patients
Clin. Cancer Res 2014 Jan 31;[EPub Ahead of Print], J Dekervel, D Hompes, H van Malenstein, D Popovic, X Sagaert, B De Moor, E Van Cutsem, A D'hoore, C Verslype, J van Pelt
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