The liquid biopsy has the potential to improve patient care in the diagnostic and therapeutic set... more The liquid biopsy has the potential to improve patient care in the diagnostic and therapeutic setting in non-small cell lung cancer (NSCLC). Consented patients with epidermal growth factor receptor (EGFR) positive disease (n = 21) were stratified into two cohorts: those currently receiving EGFR tyrosine kinase inhibitor (TKI) therapy (n = 9) and newly diagnosed EGFR TKI treatment-naïve patients (n = 12). Plasma genotyping of cell-free DNA was carried out using the FDA-approved cobas® EGFR mutation test v2 and compared to next generation sequencing (NGS) cfDNA panels. Circulating tumor cell (CTC) numbers were correlated with treatment response and EGFR exon 20 p.T790M. The prognostic significance of the neutrophil to lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) was also investigated. Patients in cohort 1 with an EGFR exon 20 p.T790M mutation progressed more rapidly than those with an EGFR sensitizing mutation, while patients in cohort 2 had a significantly longer progressio...
e19077 Background: We investigated the impact of mutation fraction, tumour sample cellularity, an... more e19077 Background: We investigated the impact of mutation fraction, tumour sample cellularity, and diagnostic specimen type on EGFR TKI response, time to treatment failure (TTF) and overall survival in advanced EGFR mutation positive NSCLC patients. Methods: From March 2010 to May 2012, EGFR testing in the province of Ontario (Canada) was conducted at a single centre, using fragment analysis for exon 19 deletion and Sau961 restriction enzyme digest for exon 21 mutation. Patients with EGFR mutation positive samples were identified, tumour cellularity, mutation fraction (percent tumour cells mutated) and clinical outcome data collected. Regression analysis was undertaken to assess the association between demographic variables, mutation fraction, tumour cellularity and sample type on clinical outcomes. Results: Of 173 patients identified to date, 153 received EGFR TKI and are included in this analysis, with median follow up of 10.6 months (range 0-44). Most are female (73%), never smok...
e20527Background: Survival with EGFR/ALK+ve NSCLC can be prolonged with tyrosine kinase inhibitor... more e20527Background: Survival with EGFR/ALK+ve NSCLC can be prolonged with tyrosine kinase inhibitors (TKIs), but brain metastases (mets) are common. TKIs may control brain mets poorly, and radiation may have neurocognitive toxicity. Deteriorating performance status (PS) due to brain mets may affect the number of lines of treatment. We aimed to evaluate the impact of brain mets on lines of systemic therapy and overall survival (OS). Methods: This retrospective analysis included patients with EGFR/ALK+ve NSCLC treated at Princess Margaret Cancer Centre from 1998-2015. 2 groups were analyzed: those with brain mets at diagnosis of stage IV disease or on 1st line therapy, and those without brain mets. OS was calculated from date of metastatic disease using Kaplan-Meier method, and differences between groups were tested with the log-rank test. Results: 291 patients were included: 141 with and 150 without brain mets. Summary results are shown in the Table. 106/141 had brain mets at diagnosis of stage IV NSCLC. The...
e23034 Background: Neo+/- adjuvant treatment data in older patients with cancer is sparse due to ... more e23034 Background: Neo+/- adjuvant treatment data in older patients with cancer is sparse due to exclusion of this population from clinical trials. We evaluated the management of locally advanced esophagogastric cancer (LAEC) in older Irish patients to determine treatment modalities utilized and identify factors associated with survival. Methods: Patients diagnosed with LAEC (stage II or III) over a 5 year period (2007-2011)were identified from the National Cancer Registry of Ireland. Follow-up was till end 2014.Demographic characteristicswere assessed. Treatment was classified as “best supportive care (BSC)”, “surgery only”, “neo/adjuvant treatment” and “chemo/radiation alone” (ie chemo, radiotherapy or chemoradiotherapy alone in the absence of surgery).Survival was estimated by Kaplan-Meier estimates and Cox models. Clinicopathologic factors and treatment type found to be significant in univariate analysis were included in a multivariate analysis (MVA). Results: 46%(n = 580) of th...
10586 Background: Bevacizumab improves overall survival in metastatic colorectal cancer patients.... more 10586 Background: Bevacizumab improves overall survival in metastatic colorectal cancer patients. Bevacizumab is a first line treatment in all metastatic colorectal cancer patients, however only 38-44% respond. Currently, there is no good marker to depict treatment response. Tumour microvascular density has been shown be a prognostic factor in late stage colorectal cancer patients, however, it does not predict response. Blood vessels mature by the recruitment of pericytes. We hypothesise blood vessels that lack pericytes will be more susceptible to regression and these tumours may benefit from targeting with bevacizumab. METHODS 80 patients had a primary colorectal cancer resection and were subsequently treated with bevacizumab in our tertiary referral centre of excellence. Tumours were stained using dual immunofluorescence staining for factor VIII (an endothelial marker) and α-smooth muscle actin (a pericyte marker). Levels of immature and mature blood vessels were screened using fluorescent microscopy, scoring multiple fields of view. The mean levels of immature and mature blood vessels were scored and correlated with overall and progression free survival using Spearman correlations and multivariate analyses. RESULTS 37 patients were metastatic at diagnosis and 43 were initially Duke's A, B or C at diagnosis (early stage) and subsequently developed metastases. Mean duration on bevacizumab was 10.6 months. Mean overall survival was 38.6 months. Interestingly, there was no difference between levels of immature and mature vessels in tumours of early stage patients and metastatic patients. Patients with higher levels of immature blood vessels had longer survival following treatment (p value = 0.026). This remained significant following multivariate analyses correcting for gender, stage at diagnosis, whether patients received chemotherapy before or after treatment with bevacizumab and whether or not bevacizumab was first line or not. CONCLUSIONS We have shown for the first time that the maturity levels of blood vessels in tumours significantly correlates to survival following treatment with bevacizumab.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 29, 2015
Although epidermal growth factor receptor (EGFR) -mutated adenocarcinomas initially have high res... more Although epidermal growth factor receptor (EGFR) -mutated adenocarcinomas initially have high response rates to EGFR tyrosine kinase inhibitors (TKIs), most patients eventually develop resistance. Patient-derived xenografts (PDXs) are considered preferred preclinical models to study the biology of patient tumors. EGFR-mutant PDX models may be valuable tools to study the biology of these tumors and to elucidate mechanisms of resistance to EGFR-targeted therapies. Surgically resected early-stage non-small-cell lung carcinoma (NSCLC) tumors were implanted into nonobese diabetic severe combined immune deficient (NOD-SCID) mice. EGFR TKI treatment was initiated at tumor volumes of 150 μL. Gene expression analysis was performed using a microarray platform. Of 33 lung adenocarcinomas with EGFR activating mutations, only 6 (18%) engrafted and could be propagated beyond passage one. Engraftment was associated with upregulation of genes involved in mitotic checkpoint and cell proliferation. A...
SUMMARY In the past decade, the identification of mutations in the EGFR gene and the sensitivity ... more SUMMARY In the past decade, the identification of mutations in the EGFR gene and the sensitivity of activating mutations to EGF receptor–tyrosine kinase inhibitors has improved survival in a subset of non-small-cell lung cancer patients. Over 70% of patients with EGFR mutations have a response to gefitinib therapy. Gefitinib, a first-generation EGF receptor–tyrosine kinase inhibitor, is well tolerated and continues to be widely used. However, eventually most patients develop resistance to gefitinib. This article reviews the pharmacology of gefitinib and summarizes the clinical trials that have resulted in its current day indications.
484 Background: Treatment of patients with metastatic colorectal cancer includes chemotherapy and... more 484 Background: Treatment of patients with metastatic colorectal cancer includes chemotherapy and a monoclonal antibody (cetuximab or bevacizumab). Patients who have k-ras mutated tumors are given bevacizumab. However, no biomarker exists to determine those patients who will respond to this targeted treatment. The objective of this study was to investigate the differential protein expression between patients who do and do not respond to bevacizumab and also compare this with normal controls. Methods: Serum from 24 patients diagnosed with metastatic colorectal cancer and 11 normal controls were collected pre-treatment. All patients received bevacizumab along with chemotherapy. Progression free and overall survival data was collected on all patients. Serum was depleted of high abundant proteins and protein expression analysed using fluorescence two-dimensional differential in-gel electrophoresis (2 D-DIGE). Gels were scanned using a Typhoon 9410 Variable Mode Imager (GE Healthcare) an...
Peroxisomes are organelles that play essential roles in many metabolic processes, but also play r... more Peroxisomes are organelles that play essential roles in many metabolic processes, but also play roles in innate immunity, signal transduction, aging and cancer. One of the main functions of peroxisomes is the processing of very-long chain fatty acids into metabolites that can be directed to the mitochondria. One key family of enzymes in this process are the peroxisomal acyl-CoA oxidases (ACOX1, ACOX2 and ACOX3), the expression of which has been shown to be dysregulated in some cancers. Very little is however known about the expression of this family of oxidases in non-small cell lung cancer (NSCLC). ACOX2 has however been suggested to be elevated at the mRNA level in over 10% of NSCLC, and in the present study using both standard and bioinformatics approaches we show that expression of ACOX2 is significantly altered in NSCLC. ACOX2 mRNA expression is linked to a number of mutated genes, and associations between ACOX2 expression and tumour mutational burden and immune cell infiltrati...
HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic i... more HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma–adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15–3.15) and adjacent non-neoplastic epithelium (n = 152, p < 0.001, HR 2.7, 95% CI 1.59–4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent no...
e21024 Background: Angiogenesis drives cancer growth, tumour progression and metastases. Hypoxic ... more e21024 Background: Angiogenesis drives cancer growth, tumour progression and metastases. Hypoxic tumours initiate recruitment of their own blood supply and enhance expression of vascular endothelial growth factor (VEGF). Bevacizumab is a recombinant humanised monoclonal anti-VEGF antibody which prevents VEGF binding to its receptors and improves overall survival in metastatic colorectal cancer patients when combined with cytotoxic chemotherapy. Currently, Bevacizumab is indicated as a first line treatment in all metastatic colorectal cancer patients, however only 38-44% of these patients will have a response to treatment. There is no good marker to predict treatment response. The role of inflammation and oxidative damage in driving angiogenesis and clinical response to bevacizumab is poorly understood. The aim of this study was to investigate the levels of oxidative damage and inflammation in the tissue and in the circulation of patients receiving Bevacizumab. Methods: Tissue from 8...
6543 Background: Additional biopsies and/or blood sampling (i.e.: germline and plasma markers, ci... more 6543 Background: Additional biopsies and/or blood sampling (i.e.: germline and plasma markers, circulating DNA or tumour cells) may be necessary to complete pharmacogenomic testing (PGT) in some patients. Cancer patients’ perspectives on providing additional biospecimens are important in addressing potential knowledge translation barriers. Methods: 790 clinic patients from the Princess Margaret Cancer Centre (Toronto, Canada) were interviewed with a standardized questionnaire, representing a wide distribution of adult solid and hematological disease sites. Study endpoints included patient preferences and willingness to provide biological samples (new blood, new biopsy, or pre-existing tumor samples) on a 5-point Likert scale. Univariate and multivariate models were created using SAS 9.3. Results: Patients were 49% female; 77% Caucasian/12% Asian; median age 58 years; and 67% had completed high school. Median household income was evenly trichotomized at $50K and $100K. Despite 33% of...
e15134 Background: Aberrant expression of complex carbohydrates, known as glycans, is emerging as... more e15134 Background: Aberrant expression of complex carbohydrates, known as glycans, is emerging as a key driver in oncopathology. Elevated levels of sialic acid sugars affect tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. Changes in sialylation can be associated with malignant transformation and with progression and poor prognosis of carcinomas, which can be explained by the recognition of malignant cells by selectins, causing interactions of tumor cells with platelets, leukocytes and endothelium facilitating metastasis. Secreted or proteolytically released carcinoma mucins bearing unusual forms of sialylation can be detected in the bloodstream and are used as diagnostic and prognostic aids. Bevacizumab directly binds VEGF (a glycoprotein) to inhibit angiogenesis. The aim of this study was to analyze the pool of asparagine-linked complex carbohydrates (i.e. the N-glycome), of whole serum to identify sugars that are associated with survival in mC...
The liquid biopsy has the potential to improve patient care in the diagnostic and therapeutic set... more The liquid biopsy has the potential to improve patient care in the diagnostic and therapeutic setting in non-small cell lung cancer (NSCLC). Consented patients with epidermal growth factor receptor (EGFR) positive disease (n = 21) were stratified into two cohorts: those currently receiving EGFR tyrosine kinase inhibitor (TKI) therapy (n = 9) and newly diagnosed EGFR TKI treatment-naïve patients (n = 12). Plasma genotyping of cell-free DNA was carried out using the FDA-approved cobas® EGFR mutation test v2 and compared to next generation sequencing (NGS) cfDNA panels. Circulating tumor cell (CTC) numbers were correlated with treatment response and EGFR exon 20 p.T790M. The prognostic significance of the neutrophil to lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) was also investigated. Patients in cohort 1 with an EGFR exon 20 p.T790M mutation progressed more rapidly than those with an EGFR sensitizing mutation, while patients in cohort 2 had a significantly longer progressio...
e19077 Background: We investigated the impact of mutation fraction, tumour sample cellularity, an... more e19077 Background: We investigated the impact of mutation fraction, tumour sample cellularity, and diagnostic specimen type on EGFR TKI response, time to treatment failure (TTF) and overall survival in advanced EGFR mutation positive NSCLC patients. Methods: From March 2010 to May 2012, EGFR testing in the province of Ontario (Canada) was conducted at a single centre, using fragment analysis for exon 19 deletion and Sau961 restriction enzyme digest for exon 21 mutation. Patients with EGFR mutation positive samples were identified, tumour cellularity, mutation fraction (percent tumour cells mutated) and clinical outcome data collected. Regression analysis was undertaken to assess the association between demographic variables, mutation fraction, tumour cellularity and sample type on clinical outcomes. Results: Of 173 patients identified to date, 153 received EGFR TKI and are included in this analysis, with median follow up of 10.6 months (range 0-44). Most are female (73%), never smok...
e20527Background: Survival with EGFR/ALK+ve NSCLC can be prolonged with tyrosine kinase inhibitor... more e20527Background: Survival with EGFR/ALK+ve NSCLC can be prolonged with tyrosine kinase inhibitors (TKIs), but brain metastases (mets) are common. TKIs may control brain mets poorly, and radiation may have neurocognitive toxicity. Deteriorating performance status (PS) due to brain mets may affect the number of lines of treatment. We aimed to evaluate the impact of brain mets on lines of systemic therapy and overall survival (OS). Methods: This retrospective analysis included patients with EGFR/ALK+ve NSCLC treated at Princess Margaret Cancer Centre from 1998-2015. 2 groups were analyzed: those with brain mets at diagnosis of stage IV disease or on 1st line therapy, and those without brain mets. OS was calculated from date of metastatic disease using Kaplan-Meier method, and differences between groups were tested with the log-rank test. Results: 291 patients were included: 141 with and 150 without brain mets. Summary results are shown in the Table. 106/141 had brain mets at diagnosis of stage IV NSCLC. The...
e23034 Background: Neo+/- adjuvant treatment data in older patients with cancer is sparse due to ... more e23034 Background: Neo+/- adjuvant treatment data in older patients with cancer is sparse due to exclusion of this population from clinical trials. We evaluated the management of locally advanced esophagogastric cancer (LAEC) in older Irish patients to determine treatment modalities utilized and identify factors associated with survival. Methods: Patients diagnosed with LAEC (stage II or III) over a 5 year period (2007-2011)were identified from the National Cancer Registry of Ireland. Follow-up was till end 2014.Demographic characteristicswere assessed. Treatment was classified as “best supportive care (BSC)”, “surgery only”, “neo/adjuvant treatment” and “chemo/radiation alone” (ie chemo, radiotherapy or chemoradiotherapy alone in the absence of surgery).Survival was estimated by Kaplan-Meier estimates and Cox models. Clinicopathologic factors and treatment type found to be significant in univariate analysis were included in a multivariate analysis (MVA). Results: 46%(n = 580) of th...
10586 Background: Bevacizumab improves overall survival in metastatic colorectal cancer patients.... more 10586 Background: Bevacizumab improves overall survival in metastatic colorectal cancer patients. Bevacizumab is a first line treatment in all metastatic colorectal cancer patients, however only 38-44% respond. Currently, there is no good marker to depict treatment response. Tumour microvascular density has been shown be a prognostic factor in late stage colorectal cancer patients, however, it does not predict response. Blood vessels mature by the recruitment of pericytes. We hypothesise blood vessels that lack pericytes will be more susceptible to regression and these tumours may benefit from targeting with bevacizumab. METHODS 80 patients had a primary colorectal cancer resection and were subsequently treated with bevacizumab in our tertiary referral centre of excellence. Tumours were stained using dual immunofluorescence staining for factor VIII (an endothelial marker) and α-smooth muscle actin (a pericyte marker). Levels of immature and mature blood vessels were screened using fluorescent microscopy, scoring multiple fields of view. The mean levels of immature and mature blood vessels were scored and correlated with overall and progression free survival using Spearman correlations and multivariate analyses. RESULTS 37 patients were metastatic at diagnosis and 43 were initially Duke's A, B or C at diagnosis (early stage) and subsequently developed metastases. Mean duration on bevacizumab was 10.6 months. Mean overall survival was 38.6 months. Interestingly, there was no difference between levels of immature and mature vessels in tumours of early stage patients and metastatic patients. Patients with higher levels of immature blood vessels had longer survival following treatment (p value = 0.026). This remained significant following multivariate analyses correcting for gender, stage at diagnosis, whether patients received chemotherapy before or after treatment with bevacizumab and whether or not bevacizumab was first line or not. CONCLUSIONS We have shown for the first time that the maturity levels of blood vessels in tumours significantly correlates to survival following treatment with bevacizumab.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 29, 2015
Although epidermal growth factor receptor (EGFR) -mutated adenocarcinomas initially have high res... more Although epidermal growth factor receptor (EGFR) -mutated adenocarcinomas initially have high response rates to EGFR tyrosine kinase inhibitors (TKIs), most patients eventually develop resistance. Patient-derived xenografts (PDXs) are considered preferred preclinical models to study the biology of patient tumors. EGFR-mutant PDX models may be valuable tools to study the biology of these tumors and to elucidate mechanisms of resistance to EGFR-targeted therapies. Surgically resected early-stage non-small-cell lung carcinoma (NSCLC) tumors were implanted into nonobese diabetic severe combined immune deficient (NOD-SCID) mice. EGFR TKI treatment was initiated at tumor volumes of 150 μL. Gene expression analysis was performed using a microarray platform. Of 33 lung adenocarcinomas with EGFR activating mutations, only 6 (18%) engrafted and could be propagated beyond passage one. Engraftment was associated with upregulation of genes involved in mitotic checkpoint and cell proliferation. A...
SUMMARY In the past decade, the identification of mutations in the EGFR gene and the sensitivity ... more SUMMARY In the past decade, the identification of mutations in the EGFR gene and the sensitivity of activating mutations to EGF receptor–tyrosine kinase inhibitors has improved survival in a subset of non-small-cell lung cancer patients. Over 70% of patients with EGFR mutations have a response to gefitinib therapy. Gefitinib, a first-generation EGF receptor–tyrosine kinase inhibitor, is well tolerated and continues to be widely used. However, eventually most patients develop resistance to gefitinib. This article reviews the pharmacology of gefitinib and summarizes the clinical trials that have resulted in its current day indications.
484 Background: Treatment of patients with metastatic colorectal cancer includes chemotherapy and... more 484 Background: Treatment of patients with metastatic colorectal cancer includes chemotherapy and a monoclonal antibody (cetuximab or bevacizumab). Patients who have k-ras mutated tumors are given bevacizumab. However, no biomarker exists to determine those patients who will respond to this targeted treatment. The objective of this study was to investigate the differential protein expression between patients who do and do not respond to bevacizumab and also compare this with normal controls. Methods: Serum from 24 patients diagnosed with metastatic colorectal cancer and 11 normal controls were collected pre-treatment. All patients received bevacizumab along with chemotherapy. Progression free and overall survival data was collected on all patients. Serum was depleted of high abundant proteins and protein expression analysed using fluorescence two-dimensional differential in-gel electrophoresis (2 D-DIGE). Gels were scanned using a Typhoon 9410 Variable Mode Imager (GE Healthcare) an...
Peroxisomes are organelles that play essential roles in many metabolic processes, but also play r... more Peroxisomes are organelles that play essential roles in many metabolic processes, but also play roles in innate immunity, signal transduction, aging and cancer. One of the main functions of peroxisomes is the processing of very-long chain fatty acids into metabolites that can be directed to the mitochondria. One key family of enzymes in this process are the peroxisomal acyl-CoA oxidases (ACOX1, ACOX2 and ACOX3), the expression of which has been shown to be dysregulated in some cancers. Very little is however known about the expression of this family of oxidases in non-small cell lung cancer (NSCLC). ACOX2 has however been suggested to be elevated at the mRNA level in over 10% of NSCLC, and in the present study using both standard and bioinformatics approaches we show that expression of ACOX2 is significantly altered in NSCLC. ACOX2 mRNA expression is linked to a number of mutated genes, and associations between ACOX2 expression and tumour mutational burden and immune cell infiltrati...
HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic i... more HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma–adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15–3.15) and adjacent non-neoplastic epithelium (n = 152, p < 0.001, HR 2.7, 95% CI 1.59–4.66), but not stroma. In stage II cases, however, the prognostic value of HLA-DR expression was significant only in adjacent no...
e21024 Background: Angiogenesis drives cancer growth, tumour progression and metastases. Hypoxic ... more e21024 Background: Angiogenesis drives cancer growth, tumour progression and metastases. Hypoxic tumours initiate recruitment of their own blood supply and enhance expression of vascular endothelial growth factor (VEGF). Bevacizumab is a recombinant humanised monoclonal anti-VEGF antibody which prevents VEGF binding to its receptors and improves overall survival in metastatic colorectal cancer patients when combined with cytotoxic chemotherapy. Currently, Bevacizumab is indicated as a first line treatment in all metastatic colorectal cancer patients, however only 38-44% of these patients will have a response to treatment. There is no good marker to predict treatment response. The role of inflammation and oxidative damage in driving angiogenesis and clinical response to bevacizumab is poorly understood. The aim of this study was to investigate the levels of oxidative damage and inflammation in the tissue and in the circulation of patients receiving Bevacizumab. Methods: Tissue from 8...
6543 Background: Additional biopsies and/or blood sampling (i.e.: germline and plasma markers, ci... more 6543 Background: Additional biopsies and/or blood sampling (i.e.: germline and plasma markers, circulating DNA or tumour cells) may be necessary to complete pharmacogenomic testing (PGT) in some patients. Cancer patients’ perspectives on providing additional biospecimens are important in addressing potential knowledge translation barriers. Methods: 790 clinic patients from the Princess Margaret Cancer Centre (Toronto, Canada) were interviewed with a standardized questionnaire, representing a wide distribution of adult solid and hematological disease sites. Study endpoints included patient preferences and willingness to provide biological samples (new blood, new biopsy, or pre-existing tumor samples) on a 5-point Likert scale. Univariate and multivariate models were created using SAS 9.3. Results: Patients were 49% female; 77% Caucasian/12% Asian; median age 58 years; and 67% had completed high school. Median household income was evenly trichotomized at $50K and $100K. Despite 33% of...
e15134 Background: Aberrant expression of complex carbohydrates, known as glycans, is emerging as... more e15134 Background: Aberrant expression of complex carbohydrates, known as glycans, is emerging as a key driver in oncopathology. Elevated levels of sialic acid sugars affect tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. Changes in sialylation can be associated with malignant transformation and with progression and poor prognosis of carcinomas, which can be explained by the recognition of malignant cells by selectins, causing interactions of tumor cells with platelets, leukocytes and endothelium facilitating metastasis. Secreted or proteolytically released carcinoma mucins bearing unusual forms of sialylation can be detected in the bloodstream and are used as diagnostic and prognostic aids. Bevacizumab directly binds VEGF (a glycoprotein) to inhibit angiogenesis. The aim of this study was to analyze the pool of asparagine-linked complex carbohydrates (i.e. the N-glycome), of whole serum to identify sugars that are associated with survival in mC...
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