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Papers by s c
Revue Scientifique et Technique de l'OIE, 2005
This paper describes an indirect enzyme-linked immunosorbent assay (I-ELISA) and a fluorescence p... more This paper describes an indirect enzyme-linked immunosorbent assay (I-ELISA) and a fluorescence polarisation assay (FPA), each capable of detecting antibody in several species of hosts to smooth and rough members of the genus Brucella. The I-ELISA uses a mixture of smooth lipopolysaccharide (SLPS) and rough lipopolysaccharide (RLPS) as the antigen, and a recombinant protein A/G conjugated with horseradish peroxidase as the detection reagent. When using individually determined cutoff values, the SLPS/RLPS combined-antigen I-ELISA detected antibody in slightly more animals exposed to SLPS or to RLPS than did I-ELISA procedures using each individual antigen separately. Similarly, the assay using combined antigens detected antibody in slightly fewer animals not exposed to Brucella sp. When a universal cutoff of 10% positivity was used (relative to strongly positive control sera of each species), the overall performance index (percentage sensitivity plus percentage specificity) value decreased by 1.0 (from 199.4 to 198.4). In the FPA, it was not possible to use a universal cutoff without significant loss of performance. The overall sensitivity value for the FPA using the combined FPA antigen was 1.0% lower than using the O-polysaccharide (OPS) from SLPS and 9.1% higher than using the core antigen (CORE) from RLPS. When the combined antigen was used, the FPA specificity was slightly higher (1.2%) than from only the OPS, and considerably higher (12.6%) than the CORE. Overall, both the I-ELISA and the FPA with combined antigens were suitable as screening tests for all species of Brucella in the animal species tested.
ChemInform, 2010
Regioselective Lipase-Catalyzed Acylation of 4,6-O-Benzylidene-αand-β-D-pyranoside Derivatives Di... more Regioselective Lipase-Catalyzed Acylation of 4,6-O-Benzylidene-αand-β-D-pyranoside Derivatives Displaying a Range of Anomeric Substituents.-In the presence of PFL and lipase P, α-D-pyranoside derivatives undergo regiospecific C-2-O-acylation, whereas β-D-pyranosides undergo regioselective C-3-O-acylation.-(GRIDLEY,
Revista portuguesa de pneumologia
Introduction: Lung cancer is one of the main causes of death worldwide. 80% as NSCLC and the majo... more Introduction: Lung cancer is one of the main causes of death worldwide. 80% as NSCLC and the majority is inoperable. In surgical stages surgery is the best option being the only possibility of cure. Objectives: To characterize the universe of patients with Surgical stage lung cancer of our Unit in a 4-year period (2001/2004); to evaluate the prognostic role of tumour markers. To compare this series with a previous one of our Unit. Methodology: Retrospective analysis. Demographic data, diagnostic method, tumour marker profile and survival. Results: In the period 2001/04 493 cases of lung cancer were diagnosed, 446 of which were NSCLC; 83 had a surgical stage. Male:Female 71:12; mean age 65.9 years; PS 0/1/2/3 - 36/38/5/4; 56 ex or current smokers. Diagnosis made by: TTNA 30, thoracotomy 23, bronchial biopsy 13, bronchial lavage 9, bronchial brushing 8; Histology type: Adenocarcinoma 34, Scamous Ca 22, NSCLC 13, Neuroendocrine tumour 8, Bronchial-alveolar 5, Large Cells Ca 1; Staging ...
ChemInform, 2010
ChemInform Abstract Das Benzothiopyranon (I) wird im Eintopfverfahrenüber das Lithiumenolat (II) ... more ChemInform Abstract Das Benzothiopyranon (I) wird im Eintopfverfahrenüber das Lithiumenolat (II) und das Dithioderivat (III) in das Dimethyldithioderivat (IV)übergeführt, dessen Ausb. auf (I) bezogen ist. Umsetzen von (IV) mit LiCuMez liefert das 3-tert.-Butylderivat (V) es Thiopyranons (I).
Revista Portuguesa de Pneumologia, 2003
A MULHER E O CANCRO DO PULMÃO A mulher e o cancro do pulmão* Lung cancer and women MESA-REDONDA/R... more A MULHER E O CANCRO DO PULMÃO A mulher e o cancro do pulmão* Lung cancer and women MESA-REDONDA/ROUND TABLE * Textos referentes à mesa-redonda com o mesmo título organizada pela
Revista Portuguesa de Pneumologia (English Edition), 2013
started performing EGFR (Epidermal Growth Factor Receptor) mutation sequencing in selected patien... more started performing EGFR (Epidermal Growth Factor Receptor) mutation sequencing in selected patients with NSCLC and systematically in all patients since 2010, regardless of histology, smoking habits, age or sex. The aim of this study was to characterize the group of patients that carried out the sequencing between 2006-2010, to determine EGFR mutation frequency, to evaluate the overall survival and the survival after the use of tyrosine kinase inhibitors (TKI), in patients who performed this therapy in second and third line, knowing the EGFR mutation status. Methods: Descriptive statistical analysis of patients who did EGFR sequencing in 2006-2010 and of overall survival in patients treated with TKI as 2nd and 3rd line therapy. Record of the material available for analysis and average delay of exam results, according to the material submitted. Results: The sequencing was performed in 374 patients, 71,1% males, 67,1% non/ex-smokers, 32,9% smokers, 57,8% adenocarcinoma and 23,5% squamous cell carcinoma (SCC). The mutation was detected in 49 patients (13,1%). In all studied patients, the mutation rate was 9% in males and 23% in females. Median overall survival after erlotinib use of was 14 months for patients with positive EGFR mutation versus 6 months in not mutated patients (p = 0.003). Conclusion: Our group had an overall mutation rate of 13.1% with female, non-smokers, adenocarcinoma histology predominance. In selected patients (2006/2009), the mutation rate was 16%, in not selected patients (2010) the mutation rate was 10.4%. This study has permitted a better understanding of the EGFR mutation rate in the Portuguese population as welll as an evaluation of the patients survival after the use of of tyrosine kinase inhibitors, in second and third line therapy with previous knowledge of the EGFR mutational status. Statistical significant ଝ Please cite this article as: Castro, AS Estudo da mutação do recetor do fator de crescimento epidérmico, durante 5 anos, numa população de doentes com cancro do pulmão de não pequenas células. Rev Port Pneumol 2012.
Antiviral Chemistry and Chemotherapy, 2000
The synthesis of acyclonucleosides derived from thieno[3,2-c] and thieno[2,3-c][1,2,6]thiadiazine... more The synthesis of acyclonucleosides derived from thieno[3,2-c] and thieno[2,3-c][1,2,6]thiadiazine 2,2-dioxides was achieved following the silylation method. Lipase-mediated methodology was employed for deprotection of the acyclic moieties. The antiviral effects were determined against a broad spectrum of viruses, including cytomegalovirus (CMV) and varicella zoster virus (VZV). Only minor antiviral activity against VZV was observed for those acyclonucleosides carrying a benzyl group.
Cheminform, 2010
Regio-and Enantioselective Allylic Alkylation Catalyzed by a Chiral Monophosphine-Palladium Compl... more Regio-and Enantioselective Allylic Alkylation Catalyzed by a Chiral Monophosphine-Palladium Complex.-Allylic substitution of racemic (I) in the presence of a chiral Pd-catalyst proceeds with high branch selectivity to give enantiopure products of up to 87% e.e.
Tetrahedron-Asymmetry, 1998
Resolution of 1-(4-amino-3-chloro-5-cyanophenyl)-2-bromo-1-ethanol has been achieved by ethanol e... more Resolution of 1-(4-amino-3-chloro-5-cyanophenyl)-2-bromo-1-ethanol has been achieved by ethanol enantioselective lipase-catalysed alcoholysis, hydrolysis and acylation. Although a good enantioselectivity was observed in the three reactions, the best results were obtained by hydrolysis. This α-bromohydrin is an intermediate in the synthesis of a new adrenergic agent.
Revista Española de Enfermedades Digestivas, 2007
Desde su primera descripción en el año 2000 (1), son 4 los casos descritos de hematoma subcapsula... more Desde su primera descripción en el año 2000 (1), son 4 los casos descritos de hematoma subcapsular hepático secundario a la realización de una CPRE (2,3). La mayoría de los casos se han resuelto de forma conservadora sin necesidad de ningún abordaje quirúrgico.
ChemInform, 2010
ChemInform Abstract The coupling of the nitrile oxides (I) with the acrylates (II) is performed i... more ChemInform Abstract The coupling of the nitrile oxides (I) with the acrylates (II) is performed in the presence of bakers' yeast to yield the isomeric 2-isoxazolines (III) or (III) and (IV) depending on the substitution pattern.
Veterinary Immunology and Immunopathology, 2008
A second generation competitive enzyme immunoassay (CELISA) for detection of bovine antibody to B... more A second generation competitive enzyme immunoassay (CELISA) for detection of bovine antibody to Brucella abortus was developed to eliminate reagent variables in the assay. This assay was different from earlier CELISA formats in that it used recombinant protein A and protein G immunoglobulin receptors (PAG), labelled with horseradish peroxidase, thus eliminating the requirement for polyclonal anti-mouse-enzyme conjugate for detection. This allowed standardization of the assay. The CELISA uses a monoclonal antibody specific for a common epitope of the O-polysaccharide (OPS) of smooth lipopolysaccharide (SLPS) derived from B. abortus S1119.3. This antibody did not react with PAG. This monoclonal antibody was used to compete with antibody in the bovine test serum to the smooth lipopolysaccharide (SLPS) antigen. Reaction of bovine antibody was then measured directly with the PAG enzyme conjugate. In this case, development of colour in the reaction indicated a positive reaction. The performance characteristics of the new CELISA, sensitivity, specificity and exclusion of antibody of B. abortus S19 vaccinated animals, were very similar to those of the classical CELISA and to the indirect enzyme immunoassay (IELISA) when using sera deemed positive by isolation of the bacterium, either from individual animals or from some animals on the premises. All sera were tested by the buffered antigen plate agglutination test (BPAT) and the complement fixation test (CFT). Only samples positive on both BPAT and CFT were considered as positive and only samples negative on both tests were used considered negative. Sufficient samples from cattle, swine, sheep and goats to validate the test were included based on OIE guidelines suggesting inclusion of a minimum of 300 positive and 1000 negative samples.
Tetrahedron: Asymmetry, 2000
N-Blocked-d-glutamic acid diethylesters are g-regioselectively amidated in a reaction catalysed b... more N-Blocked-d-glutamic acid diethylesters are g-regioselectively amidated in a reaction catalysed by Candida antarctica lipase B, carried out in an anhydrous organic solvent. The ratio of g:a-monoamides, as a measure of regioselectivity, depends on the N-protecting group present in the substrate. In the examples reported in this work, we have found that g:a ranges from about 4 (N-group=Cbz) to 35 (N-group= isobutyryl). No diamides were detected.
Tetrahedron Letters, 1997
... 12. (3S)2,5diethoxy3isopropyl3,6dihydropyrazine was prepared from glycine and Lvaline, by tre... more ... 12. (3S)2,5diethoxy3isopropyl3,6dihydropyrazine was prepared from glycine and Lvaline, by treatment of cyclo[(2S)val gly] with triethyloxonium tetrafluorborate. See Rose, JE, Leeson, PD;Gani, DJ Chem. Soc. ... See Rose, JE, Leeson, PD; Gani, D. J. Chem. Soc. Perkin Trans. ...
Tetrahedron, 1995
The synthesis of podands (acyclic crown ethers) including a 1,3-bis(1H-pyrazol-1-yl)propane unit ... more The synthesis of podands (acyclic crown ethers) including a 1,3-bis(1H-pyrazol-1-yl)propane unit in their molecule is described. The key step of this synthesis was a regioselective lipase-catalyzed transesterification of the dipyrazolic tetraethylester 1 with monomethylether polyethyleneglycols. The ionophoric properties of the podands 4a-d as carriers of cations were evaluated. Molecular modelling studies and quantum-chemical calculations were used in order to elucidate the superestructtwes of the complexes with ammonium cations.
Seminars in Oncology, 2001
We evaluated the toxicity and activity of gemcitabine (Gemzar; Eli Lilly and Company, Indianapoli... more We evaluated the toxicity and activity of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and carboplatin on a 3-week (trial A) versus a 4-week (trial B) schedule in patients with advanced/metastatic non-small cell lung cancer. Chemotherapy-naive patients in trial A received gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin area under the curve of 5 on day 1, every 3 weeks. In trial B, patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and carboplatin area under the curve of 6 on day 1, every 4 weeks. Thirty patients were enrolled in trial A and 28 in trial B. Patients received a total of 142 cycles in trial A and 134 in trial B. Despite more frequent treatment delays (82 cycles in trial B and 20 cycles in trial A), and dose reductions/omissions (mainly on day 15), gemcitabine mean dose intensities of both schedules were similar. The principal dose-limiting toxicity was grade 3/4 thrombocytopenia. Objective response rates were 40% in trial A and 68% in trial B (no complete response). Gemcitabine and carboplatin administered on days 1 and 8 every 3 weeks is associated with lower myelotoxicity than that of a 4-week schedule, although both schedules were active against non-small cell lung cancer. Semin Oncol 28 (suppl 10):10-14.
Revue Scientifique et Technique de l'OIE, 2005
This paper describes an indirect enzyme-linked immunosorbent assay (I-ELISA) and a fluorescence p... more This paper describes an indirect enzyme-linked immunosorbent assay (I-ELISA) and a fluorescence polarisation assay (FPA), each capable of detecting antibody in several species of hosts to smooth and rough members of the genus Brucella. The I-ELISA uses a mixture of smooth lipopolysaccharide (SLPS) and rough lipopolysaccharide (RLPS) as the antigen, and a recombinant protein A/G conjugated with horseradish peroxidase as the detection reagent. When using individually determined cutoff values, the SLPS/RLPS combined-antigen I-ELISA detected antibody in slightly more animals exposed to SLPS or to RLPS than did I-ELISA procedures using each individual antigen separately. Similarly, the assay using combined antigens detected antibody in slightly fewer animals not exposed to Brucella sp. When a universal cutoff of 10% positivity was used (relative to strongly positive control sera of each species), the overall performance index (percentage sensitivity plus percentage specificity) value decreased by 1.0 (from 199.4 to 198.4). In the FPA, it was not possible to use a universal cutoff without significant loss of performance. The overall sensitivity value for the FPA using the combined FPA antigen was 1.0% lower than using the O-polysaccharide (OPS) from SLPS and 9.1% higher than using the core antigen (CORE) from RLPS. When the combined antigen was used, the FPA specificity was slightly higher (1.2%) than from only the OPS, and considerably higher (12.6%) than the CORE. Overall, both the I-ELISA and the FPA with combined antigens were suitable as screening tests for all species of Brucella in the animal species tested.
ChemInform, 2010
Regioselective Lipase-Catalyzed Acylation of 4,6-O-Benzylidene-αand-β-D-pyranoside Derivatives Di... more Regioselective Lipase-Catalyzed Acylation of 4,6-O-Benzylidene-αand-β-D-pyranoside Derivatives Displaying a Range of Anomeric Substituents.-In the presence of PFL and lipase P, α-D-pyranoside derivatives undergo regiospecific C-2-O-acylation, whereas β-D-pyranosides undergo regioselective C-3-O-acylation.-(GRIDLEY,
Revista portuguesa de pneumologia
Introduction: Lung cancer is one of the main causes of death worldwide. 80% as NSCLC and the majo... more Introduction: Lung cancer is one of the main causes of death worldwide. 80% as NSCLC and the majority is inoperable. In surgical stages surgery is the best option being the only possibility of cure. Objectives: To characterize the universe of patients with Surgical stage lung cancer of our Unit in a 4-year period (2001/2004); to evaluate the prognostic role of tumour markers. To compare this series with a previous one of our Unit. Methodology: Retrospective analysis. Demographic data, diagnostic method, tumour marker profile and survival. Results: In the period 2001/04 493 cases of lung cancer were diagnosed, 446 of which were NSCLC; 83 had a surgical stage. Male:Female 71:12; mean age 65.9 years; PS 0/1/2/3 - 36/38/5/4; 56 ex or current smokers. Diagnosis made by: TTNA 30, thoracotomy 23, bronchial biopsy 13, bronchial lavage 9, bronchial brushing 8; Histology type: Adenocarcinoma 34, Scamous Ca 22, NSCLC 13, Neuroendocrine tumour 8, Bronchial-alveolar 5, Large Cells Ca 1; Staging ...
ChemInform, 2010
ChemInform Abstract Das Benzothiopyranon (I) wird im Eintopfverfahrenüber das Lithiumenolat (II) ... more ChemInform Abstract Das Benzothiopyranon (I) wird im Eintopfverfahrenüber das Lithiumenolat (II) und das Dithioderivat (III) in das Dimethyldithioderivat (IV)übergeführt, dessen Ausb. auf (I) bezogen ist. Umsetzen von (IV) mit LiCuMez liefert das 3-tert.-Butylderivat (V) es Thiopyranons (I).
Revista Portuguesa de Pneumologia, 2003
A MULHER E O CANCRO DO PULMÃO A mulher e o cancro do pulmão* Lung cancer and women MESA-REDONDA/R... more A MULHER E O CANCRO DO PULMÃO A mulher e o cancro do pulmão* Lung cancer and women MESA-REDONDA/ROUND TABLE * Textos referentes à mesa-redonda com o mesmo título organizada pela
Revista Portuguesa de Pneumologia (English Edition), 2013
started performing EGFR (Epidermal Growth Factor Receptor) mutation sequencing in selected patien... more started performing EGFR (Epidermal Growth Factor Receptor) mutation sequencing in selected patients with NSCLC and systematically in all patients since 2010, regardless of histology, smoking habits, age or sex. The aim of this study was to characterize the group of patients that carried out the sequencing between 2006-2010, to determine EGFR mutation frequency, to evaluate the overall survival and the survival after the use of tyrosine kinase inhibitors (TKI), in patients who performed this therapy in second and third line, knowing the EGFR mutation status. Methods: Descriptive statistical analysis of patients who did EGFR sequencing in 2006-2010 and of overall survival in patients treated with TKI as 2nd and 3rd line therapy. Record of the material available for analysis and average delay of exam results, according to the material submitted. Results: The sequencing was performed in 374 patients, 71,1% males, 67,1% non/ex-smokers, 32,9% smokers, 57,8% adenocarcinoma and 23,5% squamous cell carcinoma (SCC). The mutation was detected in 49 patients (13,1%). In all studied patients, the mutation rate was 9% in males and 23% in females. Median overall survival after erlotinib use of was 14 months for patients with positive EGFR mutation versus 6 months in not mutated patients (p = 0.003). Conclusion: Our group had an overall mutation rate of 13.1% with female, non-smokers, adenocarcinoma histology predominance. In selected patients (2006/2009), the mutation rate was 16%, in not selected patients (2010) the mutation rate was 10.4%. This study has permitted a better understanding of the EGFR mutation rate in the Portuguese population as welll as an evaluation of the patients survival after the use of of tyrosine kinase inhibitors, in second and third line therapy with previous knowledge of the EGFR mutational status. Statistical significant ଝ Please cite this article as: Castro, AS Estudo da mutação do recetor do fator de crescimento epidérmico, durante 5 anos, numa população de doentes com cancro do pulmão de não pequenas células. Rev Port Pneumol 2012.
Antiviral Chemistry and Chemotherapy, 2000
The synthesis of acyclonucleosides derived from thieno[3,2-c] and thieno[2,3-c][1,2,6]thiadiazine... more The synthesis of acyclonucleosides derived from thieno[3,2-c] and thieno[2,3-c][1,2,6]thiadiazine 2,2-dioxides was achieved following the silylation method. Lipase-mediated methodology was employed for deprotection of the acyclic moieties. The antiviral effects were determined against a broad spectrum of viruses, including cytomegalovirus (CMV) and varicella zoster virus (VZV). Only minor antiviral activity against VZV was observed for those acyclonucleosides carrying a benzyl group.
Cheminform, 2010
Regio-and Enantioselective Allylic Alkylation Catalyzed by a Chiral Monophosphine-Palladium Compl... more Regio-and Enantioselective Allylic Alkylation Catalyzed by a Chiral Monophosphine-Palladium Complex.-Allylic substitution of racemic (I) in the presence of a chiral Pd-catalyst proceeds with high branch selectivity to give enantiopure products of up to 87% e.e.
Tetrahedron-Asymmetry, 1998
Resolution of 1-(4-amino-3-chloro-5-cyanophenyl)-2-bromo-1-ethanol has been achieved by ethanol e... more Resolution of 1-(4-amino-3-chloro-5-cyanophenyl)-2-bromo-1-ethanol has been achieved by ethanol enantioselective lipase-catalysed alcoholysis, hydrolysis and acylation. Although a good enantioselectivity was observed in the three reactions, the best results were obtained by hydrolysis. This α-bromohydrin is an intermediate in the synthesis of a new adrenergic agent.
Revista Española de Enfermedades Digestivas, 2007
Desde su primera descripción en el año 2000 (1), son 4 los casos descritos de hematoma subcapsula... more Desde su primera descripción en el año 2000 (1), son 4 los casos descritos de hematoma subcapsular hepático secundario a la realización de una CPRE (2,3). La mayoría de los casos se han resuelto de forma conservadora sin necesidad de ningún abordaje quirúrgico.
ChemInform, 2010
ChemInform Abstract The coupling of the nitrile oxides (I) with the acrylates (II) is performed i... more ChemInform Abstract The coupling of the nitrile oxides (I) with the acrylates (II) is performed in the presence of bakers' yeast to yield the isomeric 2-isoxazolines (III) or (III) and (IV) depending on the substitution pattern.
Veterinary Immunology and Immunopathology, 2008
A second generation competitive enzyme immunoassay (CELISA) for detection of bovine antibody to B... more A second generation competitive enzyme immunoassay (CELISA) for detection of bovine antibody to Brucella abortus was developed to eliminate reagent variables in the assay. This assay was different from earlier CELISA formats in that it used recombinant protein A and protein G immunoglobulin receptors (PAG), labelled with horseradish peroxidase, thus eliminating the requirement for polyclonal anti-mouse-enzyme conjugate for detection. This allowed standardization of the assay. The CELISA uses a monoclonal antibody specific for a common epitope of the O-polysaccharide (OPS) of smooth lipopolysaccharide (SLPS) derived from B. abortus S1119.3. This antibody did not react with PAG. This monoclonal antibody was used to compete with antibody in the bovine test serum to the smooth lipopolysaccharide (SLPS) antigen. Reaction of bovine antibody was then measured directly with the PAG enzyme conjugate. In this case, development of colour in the reaction indicated a positive reaction. The performance characteristics of the new CELISA, sensitivity, specificity and exclusion of antibody of B. abortus S19 vaccinated animals, were very similar to those of the classical CELISA and to the indirect enzyme immunoassay (IELISA) when using sera deemed positive by isolation of the bacterium, either from individual animals or from some animals on the premises. All sera were tested by the buffered antigen plate agglutination test (BPAT) and the complement fixation test (CFT). Only samples positive on both BPAT and CFT were considered as positive and only samples negative on both tests were used considered negative. Sufficient samples from cattle, swine, sheep and goats to validate the test were included based on OIE guidelines suggesting inclusion of a minimum of 300 positive and 1000 negative samples.
Tetrahedron: Asymmetry, 2000
N-Blocked-d-glutamic acid diethylesters are g-regioselectively amidated in a reaction catalysed b... more N-Blocked-d-glutamic acid diethylesters are g-regioselectively amidated in a reaction catalysed by Candida antarctica lipase B, carried out in an anhydrous organic solvent. The ratio of g:a-monoamides, as a measure of regioselectivity, depends on the N-protecting group present in the substrate. In the examples reported in this work, we have found that g:a ranges from about 4 (N-group=Cbz) to 35 (N-group= isobutyryl). No diamides were detected.
Tetrahedron Letters, 1997
... 12. (3S)2,5diethoxy3isopropyl3,6dihydropyrazine was prepared from glycine and Lvaline, by tre... more ... 12. (3S)2,5diethoxy3isopropyl3,6dihydropyrazine was prepared from glycine and Lvaline, by treatment of cyclo[(2S)val gly] with triethyloxonium tetrafluorborate. See Rose, JE, Leeson, PD;Gani, DJ Chem. Soc. ... See Rose, JE, Leeson, PD; Gani, D. J. Chem. Soc. Perkin Trans. ...
Tetrahedron, 1995
The synthesis of podands (acyclic crown ethers) including a 1,3-bis(1H-pyrazol-1-yl)propane unit ... more The synthesis of podands (acyclic crown ethers) including a 1,3-bis(1H-pyrazol-1-yl)propane unit in their molecule is described. The key step of this synthesis was a regioselective lipase-catalyzed transesterification of the dipyrazolic tetraethylester 1 with monomethylether polyethyleneglycols. The ionophoric properties of the podands 4a-d as carriers of cations were evaluated. Molecular modelling studies and quantum-chemical calculations were used in order to elucidate the superestructtwes of the complexes with ammonium cations.
Seminars in Oncology, 2001
We evaluated the toxicity and activity of gemcitabine (Gemzar; Eli Lilly and Company, Indianapoli... more We evaluated the toxicity and activity of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and carboplatin on a 3-week (trial A) versus a 4-week (trial B) schedule in patients with advanced/metastatic non-small cell lung cancer. Chemotherapy-naive patients in trial A received gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin area under the curve of 5 on day 1, every 3 weeks. In trial B, patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and carboplatin area under the curve of 6 on day 1, every 4 weeks. Thirty patients were enrolled in trial A and 28 in trial B. Patients received a total of 142 cycles in trial A and 134 in trial B. Despite more frequent treatment delays (82 cycles in trial B and 20 cycles in trial A), and dose reductions/omissions (mainly on day 15), gemcitabine mean dose intensities of both schedules were similar. The principal dose-limiting toxicity was grade 3/4 thrombocytopenia. Objective response rates were 40% in trial A and 68% in trial B (no complete response). Gemcitabine and carboplatin administered on days 1 and 8 every 3 weeks is associated with lower myelotoxicity than that of a 4-week schedule, although both schedules were active against non-small cell lung cancer. Semin Oncol 28 (suppl 10):10-14.