DM2 negatively regulates the human telomerase RNA gene promoter (2005)
Zhao, J., Bilsland, A., Jackson, K., Keith, W.N.
Background We have previously demonstrated that NF-Y and Sp1 interact with the human telomerase RNA (hTR) promoter and play a central role in its regulation. We have also shown that pRB activates the...
Dysregulated expression of the major telomerase components in leukaemic stem cells (2005)
Drummond, M.W, Hoare, S.F., Monaghan, A., Graham, S.M., Alcorn, M.J., Keith, W.N., ...
Telomere loss is rapid during the progression of chronic myeloid leukaemia (CML) and correlates with prognosis. We therefore sought to measure expression of the major telomerase components (hTR and...
Westra, J. L., Hollema, H., Schaapveld, M., Platteel, I., Oien, K. A., Keith, W. N., ...
Background: The predictive value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression on long-term survival by influencing 5-fluorouracil (5-FU) effect were determined in...
Westra, J. L., Hollema, H., Schaapveld, M., Platteel, I., Oien, K. A., Keith, W. N., ...
Background: The predictive value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression on long-term survival by influencing 5-fluorouracil (5-FU) effect were determined in...
Keith, W.N., Vulliamy, T., Zhao, J., Ar, C., Erzik, C., Bilsland, A., ...
Background Mutations in the gene coding for the RNA component of telomerase, hTERC, have been found in autosomal dominant dyskeratosis congenita (DC) and aplastic anemia. Paroxysmal nocturnal...
Boyd, M., Mairs, R.J., Keith, W.N., Ross, S.C., Welsh, P., Akabani, G., ...
BackgroundTargeted radiotherapy achieves malignant cell-specific concentration of radiation dosage by tumour-affinic molecules conjugated to radioactive atoms. Combining gene therapy with targeted...
Oien, K.A., McGregor, F., Butler, S., Ferrier, R.K., Downie, I., Bryce, S., ...
Through previous large-scale gene expression profiling we identified a transcript that was abundant in normal stomach and down-regulated in gastric cancer. Genes expressed at similar levels included...
Groot-Wassink, T., Aboagye, E.O., Wang, Y.H., Lemoine, N.R., Keith, W.N., Vassaux, G.
We have assessed the feasibility of positron emission tomography (PET) and ex vivo gamma-counting to measure the pattern of expression of telomerase promoter fragments in vivo. Promoter fragments...
From stem cells to cancer: balancing immortality and neoplasia (2004)
In this issue of Oncogene, Serakinci et al show that adult stem cells can be targets for neoplastic transformation. After transducing human adult mesenchymal stem cells (hMSC) with the telomerase...
Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of prostate (2004)
Fullerton, N.E., Boyd, M., Mairs, R.J., Keith, W.N., Alderwish, O., Brown, M.M., ...
A targeted radiotherapy/gene therapy approach for prostate cancer, using the radiopharmaceutical [1311]meta- iodobenzylguanidine ([1311]MIBG), would restrict the effects of radiotherapy to malignant...
Going, J.J., Fletcher-Monaghan, A.J., Neilson, L., Wisman, B.A., Stuart, R.C., ...
Glandular dysplasia in Barrett's esophagus may regress spontaneously but can also progress to cancer. The human telomerase RNA template and the human telomerase reverse transcriptase enzyme which do...
Cancer cell immortality: telomerase as a target for novel cancer gene therapies (2004)
Keith, W.N., Bilsland, A., Hardie, M., Evans, T.R.J.
Untangling the complex pathways underlying the major cancer phenotypes remains a significant challenge, but deregulated expression of a single multi-component enzyme, telomerase, is implicated as a...
Intra-Peritoneal Administration of Genetic Therapies: promises and pitfalls (2004)
Rapid advances in our understanding of the molecular basis of cancer development and progression over the past 3 decades have led to the design of new potential cancer therapies based on the...
Oien, K.A., Vass, J.K., Downie, I., Fullarton, G., Keith, W.N.
Gastric carcinoma is the fourth most common cause of cancer death worldwide but its molecular biology is poorly understood. We catalogued the genes expressed in two gastric adenocarcinomas and normal...
Zhao, J.Q., Bilsland, A., Hoare, S.F., Keith, W.N.
The proximal promoter of the telomerase RNA gene, hTR, contains four Sp1 sites and one CCAAT box. We have carried out a functional analysis of the role of these sequence elements. Two Sp1 sites...
Bilsland, A.E., Anderson, C.J., Fletcher-Monaghan, A.J., McGregor, F., Evans, T.R.J., Ganly, I., ...
Reactivation of telomerase maintains telomere function and is considered critical to immortalization in most human cancer cells. Elevation of telomerase expression in cancer cells is highly specific:...
Going, J.J., Keith, W.N., Neilson, L., Stoeber, K., Stuart, R.C., Williams, G.H.
Background: Minichromosome maintenance (Mcm) proteins are essential for eukaryotic DNA replication, and their expression implies potential for cell proliferation. Expression is dysregulated in...
Dennis, J.L., Vass, J.K., Wit, E.C., Keith, W.N., Oien, K.A.
Patients presenting with metastatic adenocarcinoma of unknown origin are a common clinical problem. Their optimal management and therapy are facilitated by identification of the primary site, yet...
Telomerase-Directed Molecular Therapeutics (2002)
Keith, W.N., Bilsland, A., Evans, T.R.J., Glasspool, R.M.
The management of malignant disease remains one of the most challenging areas of modern medicine. The lifetime risk of developing cancer in the western world is estimated to be as high as 1 in 3....
'Senescence-associated' beta-galactosidase activity in the upper gastrointestinal tract (2002)
Going, J.J., Stuart, R.C., Downie, M., Fletcher-Monaghan, A.J., Keith, W.N.
beta-galactosidase activity at pH 6 is associated in vitro with senescence and cellular death, but in vivo data are sparse. This study undertook firstly to map 'senescence-associated'...
Going, J.J., Keith, W.N., Neilson, L., Stoeber, K., Stuart, R.C., Williams, G.H.
Background: Minichromosome maintenance (Mcm) proteins are essential for eukaryotic DNA replication, and their expression implies potential for cell proliferation. Expression is dysregulated in...
Expression of telomerase RNA in oesophageal and oral cancer (2001)
Downey, M.G., Going, J.J., Stuart, R.C., Keith, W.N.
Background: Telomerase is detectable in 85% of cancers, but is largely repressed in normal tissues. Human telomerase RNA (hTR) inhibition is a promising anti-cancer strategy, but requires...
Boyd, M., Mairs, R.J., Mairs, S.C., Wilson, L., Livingstone, A., Cunningham, S.H., ...
One of the most effective ways to kill cancer cells is by treatment of tumours with radiation. However, the administered dose of radiation to the tumour is limited by normal tissue toxicity....
Plumb, J.A., Bilsland, A., Kakani, R., Zhao, J.Q., Glasspool, R.M., Knox, R.J., ...
Telomerase activation is considered to be a critical step in cancer progression due to its role in cellular immortalization. The prevalence of telomerase expression in human cancers makes it an...
Telomerase and cancer: time to move from a promising target to a clinical reality (2001)
Keith, W.N., Evans, T.R.J., Glasspool, R.M.
The past 25 years have seen unparalleled advances in our understanding of the molecular basis of cancer. As a result, novel molecular targets have been identified that provide great potential for the...
Hoare, S.F., Bryce, L.A., Wisman, G.B.A., Burns, S., Going, J.J., ...
The immortal phenotype of most human cancers is attributable to telomerase expression. However, a number of immortal cell lines and tumors achieve telomere maintenance in the absence of telomerase...
Telomerase in (pre)neoplastic cervical disease (2000)
Wisman, G.B.A., De Jong, S., Meersma, G.J., Helder, M.N., Hollema, H., ...
This study was performed to determine upregulation of the human telomerase RNA component (hTR) and mRNA of the catalytic subunit of telomerase (hTERT) in (pre)malignant cervical lesions, to analyze...
Bryce, L.A., Morrison, N., Hoare, S.F., Muir, S., Keith, W.N.
Telomerase, the enzyme that maintains the ends of chromosomes, is absent from the majority of somatic cells but is present and active in most tumours. The gene for the reverse transcriptase component...
Zhao, J.Q., Glasspool, R.M., Hoare, S.F., Bilsland, A., Szatmari, I., Keith, W.N.
Expression of the human telomerase RNA component gene, hTERC is essential for telomerase activity, The hTERC gene is expressed during embryogenesis and then downregulated during normal development,...
Russell, A.J., Sibbald, J., Haak, H., Keith, W.N., McNicol, A.M.
The investigation of chromosomal aberrations in adrenocortical tumours has been limited by the difficulties of applying classical cytogenetics to tumours with low levels of proliferation. We have...
Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells (1999)
Agochiya, M., Brunton, V.G., Owens, D.W., Parkinson, E.K., Paraskeva, C., Keith, W.N., ...
Focal adhesion kinase (pp125FAK) is present at sites of cell/extracellular matrix adhesion and has been implicated in the control of cell behaviour. In particular, as a key component of...
Is small cell lung cancer the perfect target for anti- telomerase treatment? (1999)
Sarvesvaran, J., Going, J.J., Milroy, R., Kaye, S.B., Keith, W.N.
Small cell lung cancer (SCLC) is common in men and women, has a very poor prognosis, and is therefore a major cause of premature mortality. As such, any prospects for improved therapy are of great...
Al Mulla, F., Keith, W.N., Pickford, I.R., Going, J.J., Birnie, G.D.
We have analyzed 26 tumors from 12 patients with metastatic colorectal adenocarcinoma by comparative genomic hybridization (CGH). Primary tumors and their lymph node metastases from five Dukes' C...
Cloning and characterization of human and mouse telomerase RNA gene promoter sequences (1998)
Zhao, J.Q., Hoare, S.F., McFarlane, R., Muir, S., Parkinson, E.K., Black, D.M., ...
Variation in telomerase activity is correlated with cellular senescence and tumour progression. However, although the enzymatic activity of telomerase has been well studied, very little is known...
Soder, A.I., Going, J.J., Kaye, S.B., Keith, W.N.
Maintenance of telomere structure by the ribonucleoprotein enzyme telomerase is considered central to the development of most human cancers, However, regulatory mechanisms governing telomerase...
Mckay, J.A., Murray, G.I., Keith, W.N., Mcleod, H.L.
Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of chromosomal alterations in formalin fixed paraffin wax embedded sections of colorectal cancer. However, initial...
Gause, P.R., LluriaPrevatt, M., Keith, W.N., Balmain, A., Linardopolous, S., Warneke, J., ...
The TP-ras transgenic mouse line expresses an activated human T24 Ha-ras gene with a mutation in codon 12, regulated by a mouse tyrosinase promoter. The transgene is expressed in melanocytes of the...
Parkinson, E.K., Newbold, R.F., Keith, W.N.
Normal human keratinocytes have a finite replicative lifespan which culminates in senescence. Chromosomal telomere length may act as a mediator of replicative senescence, signalling cell cycle arrest...
Soder, A.I., Hoare, S.F., Muire, S., Balmain, A., Parkinson, E.K., Keith, W.N.
No abstract available.
Soder, A.I., Hoare, S.F., Muir, S., Going, J.J., Parkinson, E.K., Keith, W.N.
Telomere length is maintained by the enzyme, telomerase, which has been linked to cellular immortality and tumour progression, However, the reasons for the high levels of telomerase found in human...
Hoare, S.F., Freeman, C.A., Coutts, J.C., Varley, J.M., James, L., Keith, W.N.
The molecular cytogenetic techniques of comparative genomic hybridization (GGH) and reverse in situ hybridization (REVISH) allow the entire genomes of tumours to be screened for genetic changes...
DM2 negatively regulates the human telomerase RNA gene promoter
Zhao, J., Bilsland, A., Jackson, K., Keith, W.N.
Background We have previously demonstrated that NF-Y and Sp1 interact with the human telomerase RNA (hTR) promoter and play a central role in its regulation. We have also shown that pRB activates the...
Keith, W.N., Vulliamy, T., Zhao, J., Ar, C., Erzik, C., Bilsland, A., ...
Background Mutations in the gene coding for the RNA component of telomerase, hTERC, have been found in autosomal dominant dyskeratosis congenita (DC) and aplastic anemia. Paroxysmal nocturnal...
Russell, A.J., Sibbald, J., Haak, H., Keith, W.N., McNicol, A.M.
The investigation of chromosomal aberrations in adrenocortical tumours has been limited by the difficulties of applying classical cytogenetics to tumours with low levels of proliferation. We have...
Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells
Agochiya, M., Brunton, V.G., Owens, D.W., Parkinson, E.K., Paraskeva, C., Keith, W.N., ...
Focal adhesion kinase (pp125FAK) is present at sites of cell/extracellular matrix adhesion and has been implicated in the control of cell behaviour. In particular, as a key component of...
Is small cell lung cancer the perfect target for anti- telomerase treatment?
Sarvesvaran, J., Going, J.J., Milroy, R., Kaye, S.B., Keith, W.N.
Small cell lung cancer (SCLC) is common in men and women, has a very poor prognosis, and is therefore a major cause of premature mortality. As such, any prospects for improved therapy are of great...
Al Mulla, F., Keith, W.N., Pickford, I.R., Going, J.J., Birnie, G.D.
We have analyzed 26 tumors from 12 patients with metastatic colorectal adenocarcinoma by comparative genomic hybridization (CGH). Primary tumors and their lymph node metastases from five Dukes' C...
Dysregulated expression of the major telomerase components in leukaemic stem cells
Drummond, M.W, Hoare, S.F., Monaghan, A., Graham, S.M., Alcorn, M.J., Keith, W.N., ...
Telomere loss is rapid during the progression of chronic myeloid leukaemia (CML) and correlates with prognosis. We therefore sought to measure expression of the major telomerase components (hTR and...
Boyd, M., Mairs, R.J., Keith, W.N., Ross, S.C., Welsh, P., Akabani, G., ...
BackgroundTargeted radiotherapy achieves malignant cell-specific concentration of radiation dosage by tumour-affinic molecules conjugated to radioactive atoms. Combining gene therapy with targeted...
Oien, K.A., McGregor, F., Butler, S., Ferrier, R.K., Downie, I., Bryce, S., ...
Through previous large-scale gene expression profiling we identified a transcript that was abundant in normal stomach and down-regulated in gastric cancer. Genes expressed at similar levels included...
Noninvasive imaging of the transcriptional activities of human telomerase promoter fragments in mice
Groot-Wassink, T., Aboagye, E.O., Wang, Y.H., Lemoine, N.R., Keith, W.N., Vassaux, G.
We have assessed the feasibility of positron emission tomography (PET) and ex vivo gamma-counting to measure the pattern of expression of telomerase promoter fragments in vivo. Promoter fragments...
From stem cells to cancer: balancing immortality and neoplasia
In this issue of Oncogene, Serakinci et al show that adult stem cells can be targets for neoplastic transformation. After transducing human adult mesenchymal stem cells (hMSC) with the telomerase...
Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of prostate
Fullerton, N.E., Boyd, M., Mairs, R.J., Keith, W.N., Alderwish, O., Brown, M.M., ...
A targeted radiotherapy/gene therapy approach for prostate cancer, using the radiopharmaceutical [1311]meta- iodobenzylguanidine ([1311]MIBG), would restrict the effects of radiotherapy to malignant...
Going, J.J., Fletcher-Monaghan, A.J., Neilson, L., Wisman, B.A., Stuart, R.C., ...
Glandular dysplasia in Barrett's esophagus may regress spontaneously but can also progress to cancer. The human telomerase RNA template and the human telomerase reverse transcriptase enzyme which do...
Cancer cell immortality: telomerase as a target for novel cancer gene therapies
Keith, W.N., Bilsland, A., Hardie, M., Evans, T.R.J.
Untangling the complex pathways underlying the major cancer phenotypes remains a significant challenge, but deregulated expression of a single multi-component enzyme, telomerase, is implicated as a...
Intra-Peritoneal Administration of Genetic Therapies: promises and pitfalls
Rapid advances in our understanding of the molecular basis of cancer development and progression over the past 3 decades have led to the design of new potential cancer therapies based on the...
Profiling, comparison and validation of gene expression in gastric carcinoma and normal stomach
Oien, K.A., Vass, J.K., Downie, I., Fullarton, G., Keith, W.N.
Gastric carcinoma is the fourth most common cause of cancer death worldwide but its molecular biology is poorly understood. We catalogued the genes expressed in two gastric adenocarcinomas and normal...
Zhao, J.Q., Bilsland, A., Hoare, S.F., Keith, W.N.
The proximal promoter of the telomerase RNA gene, hTR, contains four Sp1 sites and one CCAAT box. We have carried out a functional analysis of the role of these sequence elements. Two Sp1 sites...
Bilsland, A.E., Anderson, C.J., Fletcher-Monaghan, A.J., McGregor, F., Evans, T.R.J., Ganly, I., ...
Reactivation of telomerase maintains telomere function and is considered critical to immortalization in most human cancer cells. Elevation of telomerase expression in cancer cells is highly specific:...
Dennis, J.L., Vass, J.K., Wit, E.C., Keith, W.N., Oien, K.A.
Patients presenting with metastatic adenocarcinoma of unknown origin are a common clinical problem. Their optimal management and therapy are facilitated by identification of the primary site, yet...
Telomerase-Directed Molecular Therapeutics
Keith, W.N., Bilsland, A., Evans, T.R.J., Glasspool, R.M.
The management of malignant disease remains one of the most challenging areas of modern medicine. The lifetime risk of developing cancer in the western world is estimated to be as high as 1 in 3....
'Senescence-associated' beta-galactosidase activity in the upper gastrointestinal tract
Going, J.J., Stuart, R.C., Downie, M., Fletcher-Monaghan, A.J., Keith, W.N.
beta-galactosidase activity at pH 6 is associated in vitro with senescence and cellular death, but in vivo data are sparse. This study undertook firstly to map 'senescence-associated'...
Going, J.J., Keith, W.N., Neilson, L., Stoeber, K., Stuart, R.C., Williams, G.H.
Background: Minichromosome maintenance (Mcm) proteins are essential for eukaryotic DNA replication, and their expression implies potential for cell proliferation. Expression is dysregulated in...
Expression of telomerase RNA in oesophageal and oral cancer
Downey, M.G., Going, J.J., Stuart, R.C., Keith, W.N.
Background: Telomerase is detectable in 85% of cancers, but is largely repressed in normal tissues. Human telomerase RNA (hTR) inhibition is a promising anti-cancer strategy, but requires...
Boyd, M., Mairs, R.J., Mairs, S.C., Wilson, L., Livingstone, A., Cunningham, S.H., ...
One of the most effective ways to kill cancer cells is by treatment of tumours with radiation. However, the administered dose of radiation to the tumour is limited by normal tissue toxicity....
Plumb, J.A., Bilsland, A., Kakani, R., Zhao, J.Q., Glasspool, R.M., Knox, R.J., ...
Telomerase activation is considered to be a critical step in cancer progression due to its role in cellular immortalization. The prevalence of telomerase expression in human cancers makes it an...
Telomerase and cancer: time to move from a promising target to a clinical reality
Keith, W.N., Evans, T.R.J., Glasspool, R.M.
The past 25 years have seen unparalleled advances in our understanding of the molecular basis of cancer. As a result, novel molecular targets have been identified that provide great potential for the...
Hoare, S.F., Bryce, L.A., Wisman, G.B.A., Burns, S., Going, J.J., ...
The immortal phenotype of most human cancers is attributable to telomerase expression. However, a number of immortal cell lines and tumors achieve telomere maintenance in the absence of telomerase...
Telomerase in (pre)neoplastic cervical disease
Wisman, G.B.A., De Jong, S., Meersma, G.J., Helder, M.N., Hollema, H., ...
This study was performed to determine upregulation of the human telomerase RNA component (hTR) and mRNA of the catalytic subunit of telomerase (hTERT) in (pre)malignant cervical lesions, to analyze...
Bryce, L.A., Morrison, N., Hoare, S.F., Muir, S., Keith, W.N.
Telomerase, the enzyme that maintains the ends of chromosomes, is absent from the majority of somatic cells but is present and active in most tumours. The gene for the reverse transcriptase component...
Zhao, J.Q., Glasspool, R.M., Hoare, S.F., Bilsland, A., Szatmari, I., Keith, W.N.
Expression of the human telomerase RNA component gene, hTERC is essential for telomerase activity, The hTERC gene is expressed during embryogenesis and then downregulated during normal development,...
Cloning and characterization of human and mouse telomerase RNA gene promoter sequences
Zhao, J.Q., Hoare, S.F., McFarlane, R., Muir, S., Parkinson, E.K., Black, D.M., ...
Variation in telomerase activity is correlated with cellular senescence and tumour progression. However, although the enzymatic activity of telomerase has been well studied, very little is known...
Tumour specific regulation of telomerase RNA gene expression visualized by in situ hybridization
Soder, A.I., Going, J.J., Kaye, S.B., Keith, W.N.
Maintenance of telomere structure by the ribonucleoprotein enzyme telomerase is considered central to the development of most human cancers, However, regulatory mechanisms governing telomerase...
Mckay, J.A., Murray, G.I., Keith, W.N., Mcleod, H.L.
Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of chromosomal alterations in formalin fixed paraffin wax embedded sections of colorectal cancer. However, initial...
Gause, P.R., LluriaPrevatt, M., Keith, W.N., Balmain, A., Linardopolous, S., Warneke, J., ...
The TP-ras transgenic mouse line expresses an activated human T24 Ha-ras gene with a mutation in codon 12, regulated by a mouse tyrosinase promoter. The transgene is expressed in melanocytes of the...
Parkinson, E.K., Newbold, R.F., Keith, W.N.
Normal human keratinocytes have a finite replicative lifespan which culminates in senescence. Chromosomal telomere length may act as a mediator of replicative senescence, signalling cell cycle arrest...
Soder, A.I., Hoare, S.F., Muire, S., Balmain, A., Parkinson, E.K., Keith, W.N.
No abstract available.
Amplification, increased dosage and in situ expression of the telomerase RNA gene in human cancer
Soder, A.I., Hoare, S.F., Muir, S., Going, J.J., Parkinson, E.K., Keith, W.N.
Telomere length is maintained by the enzyme, telomerase, which has been linked to cellular immortality and tumour progression, However, the reasons for the high levels of telomerase found in human...
Identification of genetic changes associated with drug resistance by reverse in situ hybridization
Hoare, S.F., Freeman, C.A., Coutts, J.C., Varley, J.M., James, L., Keith, W.N.
The molecular cytogenetic techniques of comparative genomic hybridization (GGH) and reverse in situ hybridization (REVISH) allow the entire genomes of tumours to be screened for genetic changes...
McKay, J A, Murray, G I, Keith, W N, McLeod, H L
Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of chromosomal alterations in formalin fixed paraffin wax embedded sections of colorectal cancer. However, initial...
McKay, J A, Murray, G I, Keith, W N, McLeod, H L
Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of chromosomal alterations in formalin fixed paraffin wax embedded sections of colorectal cancer. However, initial...
DM2 negatively regulates the human telomerase RNA gene promoter
Zhao, J., Bilsland, A., Jackson, K., Keith, W.N.
Background We have previously demonstrated that NF-Y and Sp1 interact with the human telomerase RNA (hTR) promoter and play a central role in its regulation. We have also shown that pRB activates the...
Keith, W.N., Vulliamy, T., Zhao, J., Ar, C., Erzik, C., Bilsland, A., ...
Background Mutations in the gene coding for the RNA component of telomerase, hTERC, have been found in autosomal dominant dyskeratosis congenita (DC) and aplastic anemia. Paroxysmal nocturnal...
Russell, A.J., Sibbald, J., Haak, H., Keith, W.N., McNicol, A.M.
The investigation of chromosomal aberrations in adrenocortical tumours has been limited by the difficulties of applying classical cytogenetics to tumours with low levels of proliferation. We have...
Increased dosage and amplification of the focal adhesion kinase gene in human cancer cells
Agochiya, M., Brunton, V.G., Owens, D.W., Parkinson, E.K., Paraskeva, C., Keith, W.N., ...
Focal adhesion kinase (pp125FAK) is present at sites of cell/extracellular matrix adhesion and has been implicated in the control of cell behaviour. In particular, as a key component of...
Is small cell lung cancer the perfect target for anti- telomerase treatment?
Sarvesvaran, J., Going, J.J., Milroy, R., Kaye, S.B., Keith, W.N.
Small cell lung cancer (SCLC) is common in men and women, has a very poor prognosis, and is therefore a major cause of premature mortality. As such, any prospects for improved therapy are of great...
Al Mulla, F., Keith, W.N., Pickford, I.R., Going, J.J., Birnie, G.D.
We have analyzed 26 tumors from 12 patients with metastatic colorectal adenocarcinoma by comparative genomic hybridization (CGH). Primary tumors and their lymph node metastases from five Dukes' C...
Dysregulated expression of the major telomerase components in leukaemic stem cells
Drummond, M.W, Hoare, S.F., Monaghan, A., Graham, S.M., Alcorn, M.J., Keith, W.N., ...
Telomere loss is rapid during the progression of chronic myeloid leukaemia (CML) and correlates with prognosis. We therefore sought to measure expression of the major telomerase components (hTR and...
Boyd, M., Mairs, R.J., Keith, W.N., Ross, S.C., Welsh, P., Akabani, G., ...
BackgroundTargeted radiotherapy achieves malignant cell-specific concentration of radiation dosage by tumour-affinic molecules conjugated to radioactive atoms. Combining gene therapy with targeted...
Oien, K.A., McGregor, F., Butler, S., Ferrier, R.K., Downie, I., Bryce, S., ...
Through previous large-scale gene expression profiling we identified a transcript that was abundant in normal stomach and down-regulated in gastric cancer. Genes expressed at similar levels included...
Noninvasive imaging of the transcriptional activities of human telomerase promoter fragments in mice
Groot-Wassink, T., Aboagye, E.O., Wang, Y.H., Lemoine, N.R., Keith, W.N., Vassaux, G.
We have assessed the feasibility of positron emission tomography (PET) and ex vivo gamma-counting to measure the pattern of expression of telomerase promoter fragments in vivo. Promoter fragments...
From stem cells to cancer: balancing immortality and neoplasia
In this issue of Oncogene, Serakinci et al show that adult stem cells can be targets for neoplastic transformation. After transducing human adult mesenchymal stem cells (hMSC) with the telomerase...
Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of prostate
Fullerton, N.E., Boyd, M., Mairs, R.J., Keith, W.N., Alderwish, O., Brown, M.M., ...
A targeted radiotherapy/gene therapy approach for prostate cancer, using the radiopharmaceutical [1311]meta- iodobenzylguanidine ([1311]MIBG), would restrict the effects of radiotherapy to malignant...
Going, J.J., Fletcher-Monaghan, A.J., Neilson, L., Wisman, B.A., Stuart, R.C., ...
Glandular dysplasia in Barrett's esophagus may regress spontaneously but can also progress to cancer. The human telomerase RNA template and the human telomerase reverse transcriptase enzyme which do...
Cancer cell immortality: telomerase as a target for novel cancer gene therapies
Keith, W.N., Bilsland, A., Hardie, M., Evans, T.R.J.
Untangling the complex pathways underlying the major cancer phenotypes remains a significant challenge, but deregulated expression of a single multi-component enzyme, telomerase, is implicated as a...
Intra-Peritoneal Administration of Genetic Therapies: promises and pitfalls
Rapid advances in our understanding of the molecular basis of cancer development and progression over the past 3 decades have led to the design of new potential cancer therapies based on the...
Profiling, comparison and validation of gene expression in gastric carcinoma and normal stomach
Oien, K.A., Vass, J.K., Downie, I., Fullarton, G., Keith, W.N.
Gastric carcinoma is the fourth most common cause of cancer death worldwide but its molecular biology is poorly understood. We catalogued the genes expressed in two gastric adenocarcinomas and normal...
Zhao, J.Q., Bilsland, A., Hoare, S.F., Keith, W.N.
The proximal promoter of the telomerase RNA gene, hTR, contains four Sp1 sites and one CCAAT box. We have carried out a functional analysis of the role of these sequence elements. Two Sp1 sites...
Bilsland, A.E., Anderson, C.J., Fletcher-Monaghan, A.J., McGregor, F., Evans, T.R.J., Ganly, I., ...
Reactivation of telomerase maintains telomere function and is considered critical to immortalization in most human cancer cells. Elevation of telomerase expression in cancer cells is highly specific:...
Dennis, J.L., Vass, J.K., Wit, E.C., Keith, W.N., Oien, K.A.
Patients presenting with metastatic adenocarcinoma of unknown origin are a common clinical problem. Their optimal management and therapy are facilitated by identification of the primary site, yet...
Telomerase-Directed Molecular Therapeutics
Keith, W.N., Bilsland, A., Evans, T.R.J., Glasspool, R.M.
The management of malignant disease remains one of the most challenging areas of modern medicine. The lifetime risk of developing cancer in the western world is estimated to be as high as 1 in 3....
'Senescence-associated' beta-galactosidase activity in the upper gastrointestinal tract
Going, J.J., Stuart, R.C., Downie, M., Fletcher-Monaghan, A.J., Keith, W.N.
beta-galactosidase activity at pH 6 is associated in vitro with senescence and cellular death, but in vivo data are sparse. This study undertook firstly to map 'senescence-associated'...
Going, J.J., Keith, W.N., Neilson, L., Stoeber, K., Stuart, R.C., Williams, G.H.
Background: Minichromosome maintenance (Mcm) proteins are essential for eukaryotic DNA replication, and their expression implies potential for cell proliferation. Expression is dysregulated in...
Expression of telomerase RNA in oesophageal and oral cancer
Downey, M.G., Going, J.J., Stuart, R.C., Keith, W.N.
Background: Telomerase is detectable in 85% of cancers, but is largely repressed in normal tissues. Human telomerase RNA (hTR) inhibition is a promising anti-cancer strategy, but requires...
Boyd, M., Mairs, R.J., Mairs, S.C., Wilson, L., Livingstone, A., Cunningham, S.H., ...
One of the most effective ways to kill cancer cells is by treatment of tumours with radiation. However, the administered dose of radiation to the tumour is limited by normal tissue toxicity....
Plumb, J.A., Bilsland, A., Kakani, R., Zhao, J.Q., Glasspool, R.M., Knox, R.J., ...
Telomerase activation is considered to be a critical step in cancer progression due to its role in cellular immortalization. The prevalence of telomerase expression in human cancers makes it an...
Telomerase and cancer: time to move from a promising target to a clinical reality
Keith, W.N., Evans, T.R.J., Glasspool, R.M.
The past 25 years have seen unparalleled advances in our understanding of the molecular basis of cancer. As a result, novel molecular targets have been identified that provide great potential for the...
Hoare, S.F., Bryce, L.A., Wisman, G.B.A., Burns, S., Going, J.J., ...
The immortal phenotype of most human cancers is attributable to telomerase expression. However, a number of immortal cell lines and tumors achieve telomere maintenance in the absence of telomerase...
Telomerase in (pre)neoplastic cervical disease
Wisman, G.B.A., De Jong, S., Meersma, G.J., Helder, M.N., Hollema, H., ...
This study was performed to determine upregulation of the human telomerase RNA component (hTR) and mRNA of the catalytic subunit of telomerase (hTERT) in (pre)malignant cervical lesions, to analyze...
Bryce, L.A., Morrison, N., Hoare, S.F., Muir, S., Keith, W.N.
Telomerase, the enzyme that maintains the ends of chromosomes, is absent from the majority of somatic cells but is present and active in most tumours. The gene for the reverse transcriptase component...
Zhao, J.Q., Glasspool, R.M., Hoare, S.F., Bilsland, A., Szatmari, I., Keith, W.N.
Expression of the human telomerase RNA component gene, hTERC is essential for telomerase activity, The hTERC gene is expressed during embryogenesis and then downregulated during normal development,...
Cloning and characterization of human and mouse telomerase RNA gene promoter sequences
Zhao, J.Q., Hoare, S.F., McFarlane, R., Muir, S., Parkinson, E.K., Black, D.M., ...
Variation in telomerase activity is correlated with cellular senescence and tumour progression. However, although the enzymatic activity of telomerase has been well studied, very little is known...
Tumour specific regulation of telomerase RNA gene expression visualized by in situ hybridization
Soder, A.I., Going, J.J., Kaye, S.B., Keith, W.N.
Maintenance of telomere structure by the ribonucleoprotein enzyme telomerase is considered central to the development of most human cancers, However, regulatory mechanisms governing telomerase...
Mckay, J.A., Murray, G.I., Keith, W.N., Mcleod, H.L.
Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of chromosomal alterations in formalin fixed paraffin wax embedded sections of colorectal cancer. However, initial...
Gause, P.R., LluriaPrevatt, M., Keith, W.N., Balmain, A., Linardopolous, S., Warneke, J., ...
The TP-ras transgenic mouse line expresses an activated human T24 Ha-ras gene with a mutation in codon 12, regulated by a mouse tyrosinase promoter. The transgene is expressed in melanocytes of the...
Parkinson, E.K., Newbold, R.F., Keith, W.N.
Normal human keratinocytes have a finite replicative lifespan which culminates in senescence. Chromosomal telomere length may act as a mediator of replicative senescence, signalling cell cycle arrest...
Soder, A.I., Hoare, S.F., Muire, S., Balmain, A., Parkinson, E.K., Keith, W.N.
No abstract available.
Amplification, increased dosage and in situ expression of the telomerase RNA gene in human cancer
Soder, A.I., Hoare, S.F., Muir, S., Going, J.J., Parkinson, E.K., Keith, W.N.
Telomere length is maintained by the enzyme, telomerase, which has been linked to cellular immortality and tumour progression, However, the reasons for the high levels of telomerase found in human...
Identification of genetic changes associated with drug resistance by reverse in situ hybridization
Hoare, S.F., Freeman, C.A., Coutts, J.C., Varley, J.M., James, L., Keith, W.N.
The molecular cytogenetic techniques of comparative genomic hybridization (GGH) and reverse in situ hybridization (REVISH) allow the entire genomes of tumours to be screened for genetic changes...
Going, J J, Keith, W N, Neilson, L, Stoeber, K, Stuart, R C, Williams, G H
Background: Minichromosome maintenance (Mcm) proteins are essential for eukaryotic DNA replication, and their expression implies potential for cell proliferation. Expression is dysregulated in...
Coutts, J., Plumb, J. A., Brown, R., Keith, W. N.
Human topoisomerase II enzymes are targets for a number of widely used anticancer agents. We have analysed a lung adenocarcinoma cell line CALU3, which has co-amplified topoisomerase II alpha and...
Retrovirus mediated transfer and expression of GM-CSF in haematopoietic cells.
Keith, W. N., Brown, R., Pragnell, I. B.
Two retrovirus vectors were compared for their ability to express granulocyte-macrophage colony stimulating factor (GM-CSF) in a haematopoietic cell line, FDCP1, which is dependent on GM-CSF for...
Expression of mdr1 and gst-pi in human breast tumours: comparison to in vitro chemosensitivity.
Keith, W. N., Stallard, S., Brown, R.
Increased expression of the mdr1 gene, encoding the 175 kDa P-glycoprotein, and the gst-pi gene, encoding the anionic isozyme of glutathione S-transferase (GST), have previously been detected in...
Identification of genetic changes associated with drug resistance by reverse in situ hybridization.
Hoare, S. F., Freeman, C. A., Coutts, J. C., Varley, J. M., James, L., Keith, W. N.
The molecular cytogenetic techniques of comparative genomic hybridization (CGH) and reverse in situ hybridization (REVISH) allow the entire genomes of tumours to be screened for genetic changes...
Variation in topoisomerase I gene copy number as a mechanism for intrinsic drug sensitivity.
DNA topoisomerase I (topo I) is the principle target for camptothecin and its derivatives such as SN38. Levels of topo I expression vary widely between and within tumour types and the basis for this...
Withoff, S., Keith, W. N., Knol, A. J., Coutts, J. C., Hoare, S. F., Mulder, N. H., ...
A panel of doxorubicin-resistant sublines of the human small-cell lung carcinoma cell line GLC4 displays decreasing DNA topoisomerase II alpha (TopoII alpha) mRNA levels with increasing resistance....
Withoff, S., De Vries, E. G., Keith, W. N., Nienhuis, E. F., Van Der Graaf, W. T., Uges, D. R., ...
Sublines of the human small-cell lung carcinoma (SCLC) cell line GLC4 with acquired resistance to teniposide, amsacrine and mitoxantrone (GLC4/VM20x, GLC4/AM3x and GLC4/MIT60x, respectively) were...
Targeting telomerase for cancer therapeutics
One of the hallmarks of advanced malignancies is continuous cell growth and this almost universally correlates with the reactivation of telomerase. Although there is still much we do not understand...
Cairney, C J, Hoare, S F, Daidone, M-G, Zaffaroni, N, Keith, W N
Telomere length is maintained by two known mechanisms, activation of telomerase or alternative lengthening of telomeres (ALT). The ALT pathway is more commonly activated in tumours of mesenchymal...
Russell, A J, Sibbald, J, Haak, H, Keith, W N, McNicol, A M
The investigation of chromosomal aberrations in adrenocortical tumours has been limited by the difficulties of applying classical cytogenetics to tumours with low levels of proliferation. We have...