| 1. |
|
|
| 2. |
- Kristensen, G B, et al.
(författare)
-
First-line treatment of ovarian cancer FIGO stages IIb-IV with paclitaxel/epirubicin/carboplatin versus paclitaxel/carboplatin.
- 2003
-
Ingår i: International Journal of Gynecological Cancer. - : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 13:s2, s. 172-177
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to compare the safety and efficacy of carboplatin plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the treatment of epithelial ovarian, peritoneal, or tubal carcinoma. Between March 1999 and August 2001, 887 patients were randomized to receive six to nine cycles of paclitaxel (175 mg/m2, 3 h intravenously) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m2 intravenously prior to paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free survival. Demographic information: Residual disease <1 cm was reported on 41% of patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had achieved a clinical complete response, and 18 and 25% a clinical partial response resulting in an overall response rate of 83% in the TEC and 80% in the TC arm, whereas 7 and 9% had progressive disease, respectively. The three-drug combination produced a markedly higher myelotoxicity, resulting in a higher frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients) and a higher number of dose reductions and treatment delays. Cycle prolongation above seven days was seen in 7 and 5% of cycles in the TEC and TC arm, respectively. Stomatitis > or = grade 3 was also higher with TEC (4% TEC and 0.5% TC). Reductions in left ventricular ejection fraction of more than 15% after six courses were slightly more common with the TEC regimen (3% versus 1.5%), but the difference was not statistically significant (P = 0.2). In conclusion, treatment with the TEC combination produced a higher rate of complete responses than treatment with the TC combination. Toxicity was manageable. Long-term survival data are awaited.
|
|
| 3. |
- Smits, KM, et al.
(författare)
-
Association of metabolic gene polymorphisms with tobacco consumption in healthy controls
- 2004
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 110:2, s. 266-270
-
Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the association between polymorphisms in several metabolic genes and the consumption of tobacco in a large sample of healthy individuals. The database of the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens was used. All the individuals who were controls from the case-control studies included in the data set with information on smoking habits and on genetic polymorphisms were selected (n = 20,938). Sufficient information was available on the following genes that are involved in the metabolism of tobacco smoke constituents: CYPIAI, GSTMI, GSTTI, NAT2 and GSTPI. None of the tested genes was clearly associated with smoking behavior. Information on smoking dose, available for a subset of subjects, showed no effect of metabolic gene polymorphisms on the amount of smoking. No association between polymorphisms in the genes studied and tobacco consumption was observed; therefore, no effect of these genes on smoking behavior should be expected.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Otzen, Daniel E, et al.
(författare)
-
Designed protein tetramer zipped together with a hydrophobic Alzheimer homology: A structural clue to amyloid assembly
- 2000
-
Ingår i: PNAS. - : Proceedings of the National Academy of Sciences. ; , s. 9907-12
-
Tidskriftsartikel (refereegranskat)abstract
- Limited solubility and precipitation of amyloidogenic sequences such as the Alzheimer peptide (-AP) are major obstacles to a molecular understanding of protein fibrillation and deposition processes. Here we have circumvented the solubility problem by stepwise engineering a -AP homology into a soluble scaffold, the monomeric protein S6. The S6 construct with the highest -AP homology crystallizes as a tetramer that is linked by the -AP residues forming intermolecular antiparallel -sheets. This construct also shows increased coil aggregation during refolding, and a 14-mer peptide encompassing the engineered sequence forms fibrils. Mutational analysis shows that intermolecular association is linked to the overall hydrophobicity of the sticky sequence and implies the existence of "structural gatekeepers" in the wild-type protein, that is, charged side chains that prevent aggregation by interrupting contiguous stretches of hydrophobic residues in the primary sequence.
|
|
| 7. |
- Rasmussen, Tine, et al.
(författare)
-
The Faroe-Shetland Gateway: Late Quaternary water mass exchange between the Nordic seas and the northeastern Atlantic
- 2002
-
Ingår i: Marine Geology. - 0025-3227. ; 188:1-2, s. 165-192
-
Tidskriftsartikel (refereegranskat)abstract
- Thirteen piston and gravity cores from the Faroe-Shetland area were investigated for their planktic and benthic foraminiferal and oxygen isotopic distributions. Eight time-slices between 18 ka BP and the present were reconstructed to study variations in surface and deep water exchange between the SE Norwegian Sea and the northeast Atlantic Ocean. Today, a relatively strong northward flow of warm North Atlantic surface water is counterbalanced by a southward outflow of newly convected cold bottom water, the Norwegian Sea Overflow Water. During the last glacial maximum at 18 ka BP both the surface and bottom flows were slow and the climate conditions were Arctic. The convection north of the Faroe area was weak and unstable. The first indication of the deglaciation is a decrease in the planktic oxygen isotope values discernible southwest of the Faroe Islands at 15.5 ka BP. The deglaciation proceeded northeast and eastward synchronous with a gradual intensification of northward flowing warmer Atlantic Intermediate Water along the sea bottom. Meltwater fluxes increased between 14 and 13 ka BP producing cold surface waters, and the climatic cooling was extreme. There was no southward overflow of cold bottom water during this time period and the exchange of water masses between the Nordic seas and the North Atlantic Ocean was essentially reversed, i.e. estuarine. During the Bolling Interstadial at 12.5 ka BP northward flowing warm surface water was present to the east of the Faroe-Shetland Channel, wedged below a tongue of polar water spreading from the northwest and reaching into the Faroe-Shetland Channel. Convection in the Nordic seas and overflow of cold deep water started during the Bolling Interstadial. The polar water spread more eastward and southward during the following cold spell, the Younger Dryas, around 10.3 ka BP. The polar water was overlying the warmer, but more saline Atlantic water, which flowed northward below the cold surface water. The overflow of cold bottom water was supposedly only slightly weaker than during the Bolling Interstadial. Strong inflow of warm surface water took place during the Early Holocene at 9.5 ka BP and relatively dense cold water flowed southward along the bottom. The rate of water mass exchange reached a maximum at 6.5 ka BP, when both the inflow of warm Atlantic surface water and the outflow of cold dense bottom water appear to have been stronger than today.
|
|
| 8. |
- Smits, KM, et al.
(författare)
-
Interaction between smoking, GSTM1 deletion and colorectal cancer: results from the GSEC study
- 2003
-
Ingår i: Biomarkers. - : Informa UK Limited. - 1366-5804 .- 1354-750X. ; 8:3-4, s. 299-310
-
Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoking has inconsistently been associated with an increased risk of colorectal cancer. One of the enzymes responsible for the detoxification of the carcinogenic compounds present in tobacco smoke is glutathione S-transferase-mu (GST-mu). The gene that codes for this enzyme is GSTM1. In this study, we evaluated the associations and interaction between GSTM1 deletion, smoking behaviour and the development of colorectal cancer. We performed a pooled analysis within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). We selected six studies on colorectal cancer, including 1130 cases and 2519 controls, and restricted our analyses to Caucasians because the number of patients from other races was too limited. In addition we performed a meta-analysis including the studies from the GSEC database and other studies identified on MEDLINE on the same subject. The prevalence of the GSTM1 null genotype was within the range reported in other studies: 51.8% of the cases had the GSTM1 null genotype versus 56.6% of the controls. No significant association between the GSTM1 null genotype and colorectal cancer was found (odds ratio 0.92, 95% confidence interval 0.73-1.14). Our results suggest a possible positive association between lack of the GST-mu enzyme and colorectal cancer for non-smoking women (odds ratio 1.47, 95% confidence interval 0.80-2.70). There was no interaction between the effects of smoking and GSTM1 genotype on colorectal cancer risk in men and women (chi(2) = 0.007, p = 0.97). Our findings do not support an association between the GSTM1 null genotype and colorectal cancer. In addition, we did not find any modification of the smoking-induced colorectal cancer risk by GSTM1 genotype.
|
|
| 9. |
|
|
| 10. |
- Tropé, C, et al.
(författare)
-
Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument
- 2000
-
Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 0923-7534. ; 11:3, s. 8-281
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Adjuvant chemotherapy versus observation and chemotherapy at progression was evaluated in 162 patients in a prospective randomized multicenter study. We also evaluated DNA-measurements as an additional prognostic factor.PATIENTS AND METHODS: Patients received adjuvant carboplatin AUC 7 every 28 days for six courses (n = 81) or no adjuvant treatment (n = 81). Eligibility included surgically staged and treated patients with FIGO stage I disease, grade 1 aneuploid or grade 2 or 3 non-clear cell carcinomas or clear cell carcinomas. Disease-free (DFS) and disease-specific (DSS) survival were end-points.RESULTS: Median follow-up time was 46 months and progression was observed in 20 patients in the treatment group and 19 in the control group. Estimated five-year DFS and DSS were 70% and 86% in the treatment group and 71% and 85% in the control group. The hazard ratio was 0.98 (95% confidence interval (95% CI): 0.52-1.83) regarding DFS and 0.94 (95% CI: 0.37-2.36) regarding DSS. No significant differences in DFS or DSS could be seen when the log-rank test was stratified for prognostic variables. Therefore, data from both groups were pooled for the analysis of prognostic factors. DNA-ploidy (P = 0.003), extracapsular growth (P = 0.005), tumor rupture (P = 0.04), and WHO histologic grade (P = 0.04) were significant independent prognostic factors for DFS with P < 0.0001 for the model in the multivariate Cox analysis. FIGO substage (P = 0.01), DNA ploidy (P < 0.05), and histologic grade (P = 0.05) were prognostic for DSS with a P-value for the model < 0.0001.CONCLUSIONS: Due to the small number of patients the study was inconclusive as regards the question of adjuvant chemotherapy. The survival curves were superimposable, but with wide confidence intervals. DNA-ploidy adds objective independent prognostic information regarding both DFS and DSS in early ovarian cancer.
|
|
