The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
C. A. Reis - One of the best experts on this subject based on the ideXlab platform.
-
Differential expression of alpha-2,3-sialyltransferases and alpha-1,3/4-fucosyltransferases regulates the levels of sialyl Lewis a and sialyl Lewis x in Gastrointestinal Carcinoma cells.
International Journal of Biochemistry and Cell Biology, 2009Co-Authors: A. S. Carvalho, A. Harduin-lepers, A. Magalhães, E. Machado, N. Mendes, L. T. Costa, R. Matthiesen, R. Almeida, J. Costa, C. A. ReisAbstract:Sialyl Lewis x and sialyl Lewis a expression depends on sialyltransferases and fucosyltransferases. In this study, we screened for major variations of sialyltransferases and fucosyltransferases involved in the synthesis and regulation of sialyl Lewis x and sialyl Lewis a epitopes in Gastrointestinal Carcinoma cells. Our results show that expression of ST3Gal IV in several Gastrointestinal cell lines is correlated with the expression of sialyl Lewis x at the cell surface. ST3Gal IV overexpressed in the gastric MKN45 cell line, showed exclusive enzymatic activity towards glycoproteins containing terminal Galbeta1-4GlcNAc structure. On the other hand, when ST3Gal III was overexpressed in MKN45, an increase in the expression levels of both sialyl Lewis epitopes was observed. ST3Gal III and ST3Gal IV lead to de novo synthesis of sialyl Lewis x determinant on different molecular weight glycoproteins of MKN45 cells suggesting that each enzyme used different substrates within the available glycoproteome. The final glycosylation step in sialyl Lewis x and sialyl Lewis a biosynthesis in MKN45 cell line was shown to be associated to FUT5, which efficiently fucosylated sialyl Lewis precursors on glycoproteins. Moreover we demonstrate that the expression of sialyl Lewis epitopes in the MKN45 was induced by cell confluence, which can be regarded as a model to study altered glycosylation during tumour progression. This increase was observed together with an increase in mRNA levels of ST3GAL3, FUT5 and FUT6, and a decrease in FUT4 transcript levels in MKN45 confluent cells, suggesting a possible control at the transcriptional level.
Anne Hansen Ree - One of the best experts on this subject based on the ideXlab platform.
-
vorinostat a histone deacetylase inhibitor combined with pelvic palliative radiotherapy for Gastrointestinal Carcinoma the pelvic radiation and vorinostat pravo phase 1 study
Lancet Oncology, 2010Co-Authors: Anne Hansen Ree, Svein Dueland, Sigurd Folkvord, Knut Hakon Hole, Therese Seierstad, Marianne Johansen, Torveig Weum Abrahamsen, Kjersti FlatmarkAbstract:Summary Background Histone deacetylase (HDAC) inhibitors have shown radiosensitising activity in preclinical tumour models. This phase 1 study assessed the use of vorinostat combined with pelvic palliative radiotherapy for Gastrointestinal Carcinoma. Methods Between Feb 14, 2007, and May 18, 2009, eligible patients with histologically confirmed Carcinoma, scheduled to receive pelvic palliative radiation to 30 Gy in 3 Gy daily fractions over 2 weeks, were enrolled into cohorts of escalating vorinostat dose. Vorinostat was administered orally once daily, 3 h before each radiotherapy fraction, at the following dose levels: 100 mg (n=1), 200 mg (n=4), 300 mg (n=6), and 400 mg (n=6). Endpoints included safety, tolerability, and biological activity (tumour histone acetylation). This study is registered with ClinicalTrials.gov, number NCT00455351. Findings One patient withdrew consent after one treatment day, leaving 16 patients evaluable for tolerability. Most recorded adverse events were grade 1 and 2, among which fatigue (all patients) and Gastrointestinal events (all patients) were most common. Grade 3 adverse events included fatigue (n=5), anorexia (n=3), diarrhoea (n=2), hyponatraemia (n=1), hypokalaemia (n=1), and acneiform rash (n=1). Of these, treatment-related grade 3 events (ie, dose-limiting toxicities) were observed in one of six patients at vorinostat 300 mg once daily (fatigue and anorexia), and in two of six patients at vorinostat 400 mg once daily (two events of diarrhoea and one each of fatigue, anorexia, hyponatraemia, and hypokalaemia). The maximum-tolerated dose of vorinostat in combination with palliative radiotherapy was thus determined to be 300 mg once daily. Histone hyperacetylation was detected, indicating biological activity of vorinostat. Interpretation Vorinostat can be safely combined with short-term pelvic palliative radiotherapy. This study highlights the potential use of HDAC inhibitors with radiation, and suggests investigation of vorinostat in long-term curative pelvic radiotherapy—eg, as a component of preoperative chemoradiotherapy for rectal cancer. Funding Merck & Co, Inc, Norwegian Cancer Society, Norwegian Health and Rehabilitation Foundation.
A. S. Carvalho - One of the best experts on this subject based on the ideXlab platform.
-
Differential expression of alpha-2,3-sialyltransferases and alpha-1,3/4-fucosyltransferases regulates the levels of sialyl Lewis a and sialyl Lewis x in Gastrointestinal Carcinoma cells.
International Journal of Biochemistry and Cell Biology, 2009Co-Authors: A. S. Carvalho, A. Harduin-lepers, A. Magalhães, E. Machado, N. Mendes, L. T. Costa, R. Matthiesen, R. Almeida, J. Costa, C. A. ReisAbstract:Sialyl Lewis x and sialyl Lewis a expression depends on sialyltransferases and fucosyltransferases. In this study, we screened for major variations of sialyltransferases and fucosyltransferases involved in the synthesis and regulation of sialyl Lewis x and sialyl Lewis a epitopes in Gastrointestinal Carcinoma cells. Our results show that expression of ST3Gal IV in several Gastrointestinal cell lines is correlated with the expression of sialyl Lewis x at the cell surface. ST3Gal IV overexpressed in the gastric MKN45 cell line, showed exclusive enzymatic activity towards glycoproteins containing terminal Galbeta1-4GlcNAc structure. On the other hand, when ST3Gal III was overexpressed in MKN45, an increase in the expression levels of both sialyl Lewis epitopes was observed. ST3Gal III and ST3Gal IV lead to de novo synthesis of sialyl Lewis x determinant on different molecular weight glycoproteins of MKN45 cells suggesting that each enzyme used different substrates within the available glycoproteome. The final glycosylation step in sialyl Lewis x and sialyl Lewis a biosynthesis in MKN45 cell line was shown to be associated to FUT5, which efficiently fucosylated sialyl Lewis precursors on glycoproteins. Moreover we demonstrate that the expression of sialyl Lewis epitopes in the MKN45 was induced by cell confluence, which can be regarded as a model to study altered glycosylation during tumour progression. This increase was observed together with an increase in mRNA levels of ST3GAL3, FUT5 and FUT6, and a decrease in FUT4 transcript levels in MKN45 confluent cells, suggesting a possible control at the transcriptional level.
Kjersti Flatmark - One of the best experts on this subject based on the ideXlab platform.
-
vorinostat a histone deacetylase inhibitor combined with pelvic palliative radiotherapy for Gastrointestinal Carcinoma the pelvic radiation and vorinostat pravo phase 1 study
Lancet Oncology, 2010Co-Authors: Anne Hansen Ree, Svein Dueland, Sigurd Folkvord, Knut Hakon Hole, Therese Seierstad, Marianne Johansen, Torveig Weum Abrahamsen, Kjersti FlatmarkAbstract:Summary Background Histone deacetylase (HDAC) inhibitors have shown radiosensitising activity in preclinical tumour models. This phase 1 study assessed the use of vorinostat combined with pelvic palliative radiotherapy for Gastrointestinal Carcinoma. Methods Between Feb 14, 2007, and May 18, 2009, eligible patients with histologically confirmed Carcinoma, scheduled to receive pelvic palliative radiation to 30 Gy in 3 Gy daily fractions over 2 weeks, were enrolled into cohorts of escalating vorinostat dose. Vorinostat was administered orally once daily, 3 h before each radiotherapy fraction, at the following dose levels: 100 mg (n=1), 200 mg (n=4), 300 mg (n=6), and 400 mg (n=6). Endpoints included safety, tolerability, and biological activity (tumour histone acetylation). This study is registered with ClinicalTrials.gov, number NCT00455351. Findings One patient withdrew consent after one treatment day, leaving 16 patients evaluable for tolerability. Most recorded adverse events were grade 1 and 2, among which fatigue (all patients) and Gastrointestinal events (all patients) were most common. Grade 3 adverse events included fatigue (n=5), anorexia (n=3), diarrhoea (n=2), hyponatraemia (n=1), hypokalaemia (n=1), and acneiform rash (n=1). Of these, treatment-related grade 3 events (ie, dose-limiting toxicities) were observed in one of six patients at vorinostat 300 mg once daily (fatigue and anorexia), and in two of six patients at vorinostat 400 mg once daily (two events of diarrhoea and one each of fatigue, anorexia, hyponatraemia, and hypokalaemia). The maximum-tolerated dose of vorinostat in combination with palliative radiotherapy was thus determined to be 300 mg once daily. Histone hyperacetylation was detected, indicating biological activity of vorinostat. Interpretation Vorinostat can be safely combined with short-term pelvic palliative radiotherapy. This study highlights the potential use of HDAC inhibitors with radiation, and suggests investigation of vorinostat in long-term curative pelvic radiotherapy—eg, as a component of preoperative chemoradiotherapy for rectal cancer. Funding Merck & Co, Inc, Norwegian Cancer Society, Norwegian Health and Rehabilitation Foundation.
Stephen S Cha - One of the best experts on this subject based on the ideXlab platform.
-
early evaluation of combined fluorouracil and leucovorin as a radiation enhancer for locally unresectable residual or recurrent Gastrointestinal Carcinoma the north central cancer treatment group
Journal of Clinical Oncology, 1994Co-Authors: Charles G Moertel, Leonard L Gunderson, James A Mailliard, Patrick J Mckenna, James A Martenson, Patrick A Burch, Stephen S ChaAbstract:PURPOSETo develop a tolerable regimen of fluorouracil (5-FU), low-dose leucovorin, and radiation, and to obtain an early estimate of therapeutic effectiveness.PATIENTS AND METHODSForty patients with locally unresectable or recurrent Gastrointestinal Carcinoma were studied (pancreas, n = 22; rectum and sigmoid, n = 10; gastric, n = 6; other, n = 2). Irradiation therapy was administered in 1.8-Gy fractions 5 days per week, with total doses ranging from 45 to 54 Gy. 5-FU 400 mg/m2/d plus leucovorin 20 mg/m2/d, both by rapid intravenous injection, were administered for 3 or 4 days during the first and fifth weeks of radiation. 5-FU 425 mg/m2/d plus leucovorin 20 mg/m2/d were administered for 4 days at 4 weeks following radiation and for 5 days at 9 weeks.RESULTSMajor toxicities with upper abdominal treatment were nausea, vomiting, weight loss, and leukopenia. A tolerable dosage regimen was radiation at 45 Gy with 4 days of 5-FU plus leucovorin during the first week and 3 days during the last week with postrad...
