| 1. |
- Wortman, J. R., et al.
(author)
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The 2008 update of the Aspergillus nidulans genome annotation: A community effort
- 2009
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In: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
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Journal article (peer-reviewed)abstract
- The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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| 2. |
- Osterlund, P., et al.
(author)
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Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study
- 2022
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In: ESMO Open. - : Elsevier. - 2059-7029. ; 7:3
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Journal article (peer-reviewed)abstract
- Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce.Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity.Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/ infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11).Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.
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| 3. |
- Dias, M M, et al.
(author)
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The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy : a collaborative meta-analysis
- 2014
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In: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 14:5, s. 424-431
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Journal article (peer-reviewed)abstract
- To date, studies of irinotecan pharmacogenetics have mostly focused on the effect of the UGT1A1*28 allele on irinotecan-related toxicity. However, the clinical utility of routine UGT1A1*28 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A1*28 also affects patient survival following irinotecan therapy. Previous observational studies evaluating the influence of UGT1A1*28 on survival have shown contradictory results. A systematic review and meta-analysis of both published and unpublished data were performed to summarize the available evidence of the relationship between the UGT1A1*28 allele and patient survival related to irinotecan therapy. Overall and progression-free survival meta-analysis data were available for 1524 patients and 1494 patients, respectively. The difference in the survival between patients of different UGT1A1*28 genotypes (homozygous, heterozygous or wild-type) who had received irinotecan was not found to be statistically significant. There was also no evidence of irinotecan dose, regimen or line of therapy having an impact on this association.
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| 4. |
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| 5. |
- Åhman, Johan, et al.
(author)
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Improving the pathogenicity of a nematode-trapping fungus by genetic engineering of a subtilisin with nematotoxic activity.
- 2002
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In: Applied and Environmental Microbiology. - 0099-2240. ; 68:7, s. 3408-3415
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Journal article (peer-reviewed)abstract
- Nematophagous fungi are soil-living fungi that are used as biological control agents of plant and animal parasitic nematodes. Their potential could be improved by genetic engineering, but the lack of information about the molecular background of the infection has precluded this development. In this paper we report that a subtilisin-like extracellular serine protease designated PII is an important pathogenicity factor in the common nematode-trapping fungus Arthrobotrys oligospora. The transcript of PII was not detected during the early stages of infection (adhesion and penetration), but high levels were expressed concurrent with the killing and colonization of the nematode. Disruption of the PII gene by homologous recombination had a limited effect on the pathogenicity of the fungus. However, mutants containing additional copies of the PII gene developed a higher number of infection structures and had an increased speed of capturing and killing nematodes compared to the wild type. The paralyzing activity of PII was verified by demonstrating that a heterologous-produced PII (in Aspergillus niger) had a nematotoxic activity when added to free-living nematodes. The toxic activity of PII was significantly higher than that of other commercially available serine proteases. This is the first report showing that genetic engineering can be used to improve the pathogenicity of a nematode-trapping fungus. In the future it should be possible to express recombinant subtilisins with nematicidal activity in other organisms that are present in the habitat of parasitic nematodes (e.g., host plant).
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| 6. |
- Marchand, M, et al.
(author)
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Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2 : A clinical report
- 2003
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In: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 39:1, s. 70-77
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Journal article (peer-reviewed)abstract
- Fifty-seven patients with MAGE-3-positive measurable metastatic cancer, most of them with melanoma, were vaccinated with escalating doses of a recombinant MAGE-3 protein combined with a fixed dose of the immunological adjuvant SBAS-2, which contained MPL and QS21. The immunisation schedule included 4 intramuscular (i.m.) injections at 3-week intervals. Patients whose tumour stabilised or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. The vaccine was generally well tolerated. Among the 33 melanoma patients who were evaluable for tumour response, we observed 2 partial responses, 2 mixed responses and 1 stabilisation. Time to progression in these 5 patients varied from 4 to 29 months. In addition, a partial response lasting 10 months was observed in 1 of the 3 metastatic bladder cancer patients included. None of the tumour responses described above involved visceral metastases. Immunological responses to the vaccine will be reported separately. ⌐ 2002 Elsevier Science Ltd. All rights reserved.
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| 7. |
- White, Helen E., et al.
(author)
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Standardization of molecular monitoring of CML : results and recommendations from the European treatment and outcome study
- 2022
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In: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:7, s. 1834-1842
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Journal article (peer-reviewed)abstract
- Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1(IS) and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.
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