Recent evidence suggests that integrins are involved in the multi-step process of tumour metastas... more Recent evidence suggests that integrins are involved in the multi-step process of tumour metastasis. The biological relevance of alpha(v) integrins and associated beta-subunits in ovarian cancer metastasis was examined by analysing the expression of these cell surface receptors in nine ovarian cancer cell lines and also in the primary human ovarian surface epithelial cell line (HOSE). beta1, beta3 and beta5 subunits were present in all ten ovarian cell lines. beta6 subunit was present at varying levels in eight out of nine cancer cell lines but was absent in the HOSE cell line. Immunohistochemical staining showed that beta6 was present in both non-invasive (borderline) and high-grade ovarian cancer tissues but was absent in benign and normal ovarian tissue. High alpha(v)beta6 integrin expressing ovarian cancer cell lines had high cell surface expression of uPA and uPAR. Ovarian cancer cell lines expressing high to moderate level of alpha(v)beta6 integrin demonstrated ligand-independ...
Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety o... more Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety of solid tumors. Therefore, the expression of plasminogen, matrix metalloproteinases (MMP-2 and MMP-9), and of the serine protease urokinase-type plasminogen activator (uPA) in serous epithelial carcinoma of the ovary were investigated.
Background
Current methods widely deployed for colorectal cancers (CRC) screening lack the necess... more Background Current methods widely deployed for colorectal cancers (CRC) screening lack the necessary sensitivity and specificity required for populationbased early disease detection. Cancerspecific protein biomarkers are thought to be produced either by the tumor itself or other tissues in response to the presence of cancers or associated conditions. Equally, known examples of cancer protein biomarkers (e.g., PSA, CA125, CA199, CEA, AFP) are frequently found in plasma at very low concentration (pg/mLng/ mL). New sensitive and specific assays are therefore urgently required to detect the disease at an early stage when prognosis is good following surgical resection. This study was designed to meet the longstanding unmet clinical need for earlier CRC detection by measuring plasma candidate biomarkers of cancer onset and progression in a clinical stagespecific manner. EDTA plasma samples (1 μL) obtained from 75 patients with Dukes’ staged CRC or unaffected controls (age and sex matched with stringent inclusion/exclusion criteria) were assayed for expression of 92 human proteins employing the Proseek® Multiplex Oncology I proximity extension assay. An identical set of plasma samples were analyzed utilizing the BioPlex Pro™ human cytokine 27plex immunoassay. Results Similar quantitative expression patterns for 13 plasma antigens common to both platforms endorsed the potential efficacy of Proseek as an immunebased multiplex assay for proteomic biomarker research. Proseek found that expression of Carcinoembryonic Antigen (CEA), IL8 and prolactin are significantly correlated with CRC stage. Conclusions CEA, IL8 and prolactin expression were found to identify between control (unaffected), nonmalignant (Dukes’ A + B) and malignant (Dukes’ C + D) stages.
The low molecular weight (LMW; <10kDa)* plasma peptidome has been considered a
source of useful d... more The low molecular weight (LMW; <10kDa)* plasma peptidome has been considered a source of useful diagnostic biomarkers and potentially therapeutic molecules, as it contains many cytokines, peptide hormones, endogenous peptide products and potentially bioactive fragments derived from the parent proteome. The small size of the peptides allows them almost unrestricted vascular and interstitial access, and hence distribution across bloodbrain barriers, tumour and other vascular permeability barriers. Therefore, the peptidome may carry specific signatures or fingerprints of an individual’s health, wellbeing or disease status. This occurs primarily because of the advantage the peptidome has in being readily accessible in human blood and/or other biofluids. However, the co-expression of highly abundant proteins (>10kDa) and other factors present inherently in human plasma make direct analysis of the blood peptidome one of the most challenging tasks faced in contemporary analytical biochemistry. A comprehensive compendium of extraction and fractionation tools has been collected concerning the isolation and micromanipulation of peptides. However, the search for a reliable, accurate and reproducible single or combinatorial separation process for capturing and analysing the plasma peptidome remains a challenge. This review outlines current techniques used for the separation and detection of plasma peptides and suggests potential avenues for future investigation.
Recent evidence suggests that integrins are involved in the multi-step process of tumour metastas... more Recent evidence suggests that integrins are involved in the multi-step process of tumour metastasis. The biological relevance of alpha(v) integrins and associated beta-subunits in ovarian cancer metastasis was examined by analysing the expression of these cell surface receptors in nine ovarian cancer cell lines and also in the primary human ovarian surface epithelial cell line (HOSE). beta1, beta3 and beta5 subunits were present in all ten ovarian cell lines. beta6 subunit was present at varying levels in eight out of nine cancer cell lines but was absent in the HOSE cell line. Immunohistochemical staining showed that beta6 was present in both non-invasive (borderline) and high-grade ovarian cancer tissues but was absent in benign and normal ovarian tissue. High alpha(v)beta6 integrin expressing ovarian cancer cell lines had high cell surface expression of uPA and uPAR. Ovarian cancer cell lines expressing high to moderate level of alpha(v)beta6 integrin demonstrated ligand-independ...
Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety o... more Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety of solid tumors. Therefore, the expression of plasminogen, matrix metalloproteinases (MMP-2 and MMP-9), and of the serine protease urokinase-type plasminogen activator (uPA) in serous epithelial carcinoma of the ovary were investigated.
Background
Current methods widely deployed for colorectal cancers (CRC) screening lack the necess... more Background Current methods widely deployed for colorectal cancers (CRC) screening lack the necessary sensitivity and specificity required for populationbased early disease detection. Cancerspecific protein biomarkers are thought to be produced either by the tumor itself or other tissues in response to the presence of cancers or associated conditions. Equally, known examples of cancer protein biomarkers (e.g., PSA, CA125, CA199, CEA, AFP) are frequently found in plasma at very low concentration (pg/mLng/ mL). New sensitive and specific assays are therefore urgently required to detect the disease at an early stage when prognosis is good following surgical resection. This study was designed to meet the longstanding unmet clinical need for earlier CRC detection by measuring plasma candidate biomarkers of cancer onset and progression in a clinical stagespecific manner. EDTA plasma samples (1 μL) obtained from 75 patients with Dukes’ staged CRC or unaffected controls (age and sex matched with stringent inclusion/exclusion criteria) were assayed for expression of 92 human proteins employing the Proseek® Multiplex Oncology I proximity extension assay. An identical set of plasma samples were analyzed utilizing the BioPlex Pro™ human cytokine 27plex immunoassay. Results Similar quantitative expression patterns for 13 plasma antigens common to both platforms endorsed the potential efficacy of Proseek as an immunebased multiplex assay for proteomic biomarker research. Proseek found that expression of Carcinoembryonic Antigen (CEA), IL8 and prolactin are significantly correlated with CRC stage. Conclusions CEA, IL8 and prolactin expression were found to identify between control (unaffected), nonmalignant (Dukes’ A + B) and malignant (Dukes’ C + D) stages.
The low molecular weight (LMW; <10kDa)* plasma peptidome has been considered a
source of useful d... more The low molecular weight (LMW; <10kDa)* plasma peptidome has been considered a source of useful diagnostic biomarkers and potentially therapeutic molecules, as it contains many cytokines, peptide hormones, endogenous peptide products and potentially bioactive fragments derived from the parent proteome. The small size of the peptides allows them almost unrestricted vascular and interstitial access, and hence distribution across bloodbrain barriers, tumour and other vascular permeability barriers. Therefore, the peptidome may carry specific signatures or fingerprints of an individual’s health, wellbeing or disease status. This occurs primarily because of the advantage the peptidome has in being readily accessible in human blood and/or other biofluids. However, the co-expression of highly abundant proteins (>10kDa) and other factors present inherently in human plasma make direct analysis of the blood peptidome one of the most challenging tasks faced in contemporary analytical biochemistry. A comprehensive compendium of extraction and fractionation tools has been collected concerning the isolation and micromanipulation of peptides. However, the search for a reliable, accurate and reproducible single or combinatorial separation process for capturing and analysing the plasma peptidome remains a challenge. This review outlines current techniques used for the separation and detection of plasma peptides and suggests potential avenues for future investigation.
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Papers by Mark Baker
Current methods widely deployed for colorectal cancers (CRC) screening lack the necessary sensitivity and specificity required for populationbased
early disease
detection. Cancerspecific
protein biomarkers are thought to be produced either by the tumor itself or other tissues in response to the presence of cancers or
associated conditions. Equally, known examples of cancer protein biomarkers (e.g., PSA, CA125, CA199,
CEA, AFP) are frequently found in plasma at very low
concentration (pg/mLng/
mL). New sensitive and specific assays are therefore urgently required to detect the disease at an early stage when prognosis is good
following surgical resection. This study was designed to meet the longstanding unmet clinical need for earlier CRC detection by measuring plasma candidate
biomarkers of cancer onset and progression in a clinical stagespecific
manner. EDTA plasma samples (1 μL) obtained from 75 patients with Dukes’ staged CRC or
unaffected controls (age and sex matched with stringent inclusion/exclusion criteria) were assayed for expression of 92 human proteins employing the Proseek®
Multiplex Oncology I proximity extension assay. An identical set of plasma samples were analyzed utilizing the BioPlex
Pro™ human cytokine 27plex
immunoassay.
Results
Similar quantitative expression patterns for 13 plasma antigens common to both platforms endorsed the potential efficacy of Proseek as an immunebased
multiplex
assay for proteomic biomarker research. Proseek found that expression of Carcinoembryonic Antigen (CEA), IL8
and prolactin are significantly correlated with CRC
stage.
Conclusions
CEA, IL8
and prolactin expression were found to identify between control (unaffected), nonmalignant
(Dukes’ A + B) and malignant (Dukes’ C + D) stages.
source of useful diagnostic biomarkers and potentially therapeutic molecules, as it contains
many cytokines, peptide hormones, endogenous peptide products and potentially bioactive
fragments derived from the parent proteome. The small size of the peptides allows them
almost unrestricted vascular and interstitial access, and hence distribution across bloodbrain
barriers, tumour and other vascular permeability barriers. Therefore, the peptidome
may carry specific signatures or fingerprints of an individual’s health, wellbeing or disease
status. This occurs primarily because of the advantage the peptidome has in being readily
accessible in human blood and/or other biofluids.
However, the co-expression of highly abundant proteins (>10kDa) and other factors present
inherently in human plasma make direct analysis of the blood peptidome one of the most
challenging tasks faced in contemporary analytical biochemistry. A comprehensive
compendium of extraction and fractionation tools has been collected concerning the isolation
and micromanipulation of peptides. However, the search for a reliable, accurate and
reproducible single or combinatorial separation process for capturing and analysing the
plasma peptidome remains a challenge.
This review outlines current techniques used for the separation and detection of plasma
peptides and suggests potential avenues for future investigation.
Current methods widely deployed for colorectal cancers (CRC) screening lack the necessary sensitivity and specificity required for populationbased
early disease
detection. Cancerspecific
protein biomarkers are thought to be produced either by the tumor itself or other tissues in response to the presence of cancers or
associated conditions. Equally, known examples of cancer protein biomarkers (e.g., PSA, CA125, CA199,
CEA, AFP) are frequently found in plasma at very low
concentration (pg/mLng/
mL). New sensitive and specific assays are therefore urgently required to detect the disease at an early stage when prognosis is good
following surgical resection. This study was designed to meet the longstanding unmet clinical need for earlier CRC detection by measuring plasma candidate
biomarkers of cancer onset and progression in a clinical stagespecific
manner. EDTA plasma samples (1 μL) obtained from 75 patients with Dukes’ staged CRC or
unaffected controls (age and sex matched with stringent inclusion/exclusion criteria) were assayed for expression of 92 human proteins employing the Proseek®
Multiplex Oncology I proximity extension assay. An identical set of plasma samples were analyzed utilizing the BioPlex
Pro™ human cytokine 27plex
immunoassay.
Results
Similar quantitative expression patterns for 13 plasma antigens common to both platforms endorsed the potential efficacy of Proseek as an immunebased
multiplex
assay for proteomic biomarker research. Proseek found that expression of Carcinoembryonic Antigen (CEA), IL8
and prolactin are significantly correlated with CRC
stage.
Conclusions
CEA, IL8
and prolactin expression were found to identify between control (unaffected), nonmalignant
(Dukes’ A + B) and malignant (Dukes’ C + D) stages.
source of useful diagnostic biomarkers and potentially therapeutic molecules, as it contains
many cytokines, peptide hormones, endogenous peptide products and potentially bioactive
fragments derived from the parent proteome. The small size of the peptides allows them
almost unrestricted vascular and interstitial access, and hence distribution across bloodbrain
barriers, tumour and other vascular permeability barriers. Therefore, the peptidome
may carry specific signatures or fingerprints of an individual’s health, wellbeing or disease
status. This occurs primarily because of the advantage the peptidome has in being readily
accessible in human blood and/or other biofluids.
However, the co-expression of highly abundant proteins (>10kDa) and other factors present
inherently in human plasma make direct analysis of the blood peptidome one of the most
challenging tasks faced in contemporary analytical biochemistry. A comprehensive
compendium of extraction and fractionation tools has been collected concerning the isolation
and micromanipulation of peptides. However, the search for a reliable, accurate and
reproducible single or combinatorial separation process for capturing and analysing the
plasma peptidome remains a challenge.
This review outlines current techniques used for the separation and detection of plasma
peptides and suggests potential avenues for future investigation.