| 1. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
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| 3. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 9. |
- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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- 2019
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Journal article (peer-reviewed)
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| 14. |
- Horwich, A, et al.
(author)
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EAU–ESMO consensus statements on the management of advanced and variant bladder cancer - an international collaborative multi-stakeholder effort : under the auspices of the EAU and ESMO Guidelines Committees
- 2019
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In: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:11, s. 1697-1727
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Journal article (peer-reviewed)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
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| 15. |
- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 16. |
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| 17. |
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| 18. |
- Mansouri, Kamel, et al.
(author)
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CoMPARA : Collaborative Modeling Project for Androgen Receptor Activity
- 2020
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In: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 128:2, s. 1-17
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Journal article (peer-reviewed)abstract
- BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling.OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP).METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast (TM) metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast (TM)/Tox21 HTS in vitro assays.RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set.DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of similar to 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment.
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| 19. |
- Walker, Steven M, et al.
(author)
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Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology
- 2017
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:4, s. 509-518
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Journal article (peer-reviewed)abstract
- BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.OBJECTIVE: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy.DESIGN, SETTING, AND PARTICIPANTS: Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis.RESULTS AND LIMITATIONS: A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation.CONCLUSIONS: The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential.PATIENT SUMMARY: The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.
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| 20. |
- Witjes, J. Alfred, et al.
(author)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
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In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
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Journal article (peer-reviewed)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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| 21. |
- Abdel-Hamid, Mohamed, et al.
(author)
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Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma
- 2007
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In: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 88:5, s. 1526-1531
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Journal article (peer-reviewed)abstract
- Egypt has one of the world's highest prevalences of hepatitis C virus (HCV) infection, with a majority of genotype 4 infections. To explore the genetic diversity of HCV in Egypt, sera from 131 Egyptians [56 from community studies, 37 chronic hepatitis patients, 28 hepatocellular carcinoma (HCC) patients and 10 patients with non-Hodgkin's lymphoma] were genotyped by restriction fragment-length polymorphism and phylogenetic analyses of sequences from the mid-core and non-structural 5B regions. The different genotyping methods showed good agreement. The majority of the viruses (83 of 131; 63 %) were of subtype 4a, but five other subtypes within genotype 4 were also observed, as well as three genotype 1b, five genotype 1g and one genotype 3a samples. Interestingly, subtype 4o, which was easily identifiable in all three genomic regions, 3 showed an association with HCC (P=0.017), which merits further investigation.
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| 22. |
- Bruins, Harman M, et al.
(author)
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The impact of the extent of lymphadenectomy on oncologic outcomes in patients undergoing radical cystectomy for bladder cancer : a systematic review
- 2014
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In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 66:6, s. 1065-1077
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Journal article (peer-reviewed)abstract
- CONTEXT: Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS: Twenty-three studies reporting on 19 793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS: Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY: The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.
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| 23. |
- Costa, Yuri M, et al.
(author)
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Orofacial pain education in dentistry : A path to improving patient care and reducing the population burden of chronic pain
- 2021
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In: Journal of Dental Education. - : John Wiley & Sons. - 0022-0337 .- 1930-7837. ; 85:3, s. 349-358
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Journal article (peer-reviewed)abstract
- Dentists stand in an optimal position to prevent and manage patients suffering from chronic orofacial pain (OFP) disorders, such as temporomandibular disorders, burning mouth syndrome, trigeminal neuralgia, persistent idiopathic dentoalveolar pain, among others. However, there are consistent reports highlighting a lack of knowledge and confidence in diagnosing and treating OFP among dental students, recent graduates, and trained dentists, which leads to misdiagnosis, unnecessary costs, delay in appropriate care and possible harm to patients. Education in OFP is necessary to improve the quality of general dental care and reduce individual and societal burden of chronic pain through prevention and improved quality of life for OFP patients. Our aims are to emphasize the goals of OFP education, to identify barriers for its implementation, and to suggest possible avenues to improve OFP education in general, postgraduate, and continuing dental education levels, including proposed minimum OFP competencies for all dentists. Moreover, patient perspectives are also incorporated, including a testimony from a person with OFP. General dentists, OFP experts, educators, researchers, patients, and policy makers need to combine efforts in order to successfully address the urgent need for quality OFP education.
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| 24. |
- El-Sherif, Dina M., et al.
(author)
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Environmental risk, toxicity, and biodegradation of polyethylene : a review
- 2022
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In: Environmental Science and Pollution Research. - : Springer. - 0944-1344 .- 1614-7499. ; 29:54, s. 81166-81182
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Research review (peer-reviewed)abstract
- Polyethylene is the second-most-commonly-used commercial polymer. It is used in various industries, including agricultural mulches, composite materials, and packaging. Since polyethylene is not biodegradable, it can persist for a long time in water and soil, strangling otherwise fruitful land. The ecological and toxicological consequences and the fate of polyethylene have only recently been revealed. As a result, the primary goal of this review is to shed light on the reported toxicity of polyethylene to the environment and living creatures and highlight recent research on its degradation process through bibliometric analysis. To do that, we searched Web of Science database literature up to August 2021 and performed the bibliometric analysis using VOSviewer. We found that relative research interest showed a positive trend, particularly in the last 5 years. China and the Chinese Academy of Sciences had the highest published papers. Methods for polyethylene biodegradation by invertebrates, bacteria, and fungi were also reported indicating the need for future research to investigate and develop new biodegradation technologies.
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| 25. |
- Elkinany, Sherif, et al.
(author)
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Is Aortic Z-score an Appropriate Index of Beneficial Drug Effect in Clinical Trials in Aortic Aneurysm Disease?
- 2021
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In: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 143
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Journal article (peer-reviewed)abstract
- Aortic Z-score (Z-score) is utilized in clinical trials to monitor the effect of medications on aortic dilation rate in Marfan (MFS) patients. Z-scores are reported in relation to body surface area and therefore are a function of height and weight. However, an information void exists regarding natural, non-pharmacological changes in Z-scores as children age. We had concerns that Z-score decrease attributed to “therapeutic” effects of investigational drugs for Marfan disease connective tissue diseases might simply reflect normal changes (“filling out” of body contour) as children age. This investigation studies natural changes with age in Z-score in normal and untreated MFS children, teasing out normal effects that might erroneously be attributed to drug benefit. (1) We first compared body mass index (BMI) and Z-scores (Boston Children's Hospital calculator) in 361 children with “normal” single echo exams in four age ranges (0 to 1, 5 to 7, 10 to 12, 15 to 18 years). Regression analysis revealed that aging itself decreases ascending Z-score, but not root Z-score, and that increase in BMI with aging underlies the decreased Z-scores. (2) Next, we examined Z-score findings in both “normal” and Marfan children (all pharmacologically untreated) as determined on sequential echo exams over time. Of 27 children without aortic disease with sequential echos, 19 (70%) showed a natural decrease in root Z-score and 24 (89%) showed a natural decrease in ascending Z- score, over time. Of 25 untreated MFS children with sequential echos, 12 (40%) showed a natural decrease in root Z-score and 10 (33%) showed a natural decrease in ascending Z-score. Thus, Z-score is over time affected by natural factors even in the absence of any aneurysmal pathology or medical intervention. Specifically, Z-score decreases spontaneously as a natural phenomenon as children age and with fill out their BMI. Untreated Marfan patients often showed a spontaneous decrease in Z-score. In clinical drug trials in aneurysm disease, decreasing Z-score has been interpreted as a sign of beneficial drug effect. These data put such conclusions into doubt.
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| 26. |
- Hu, J., et al.
(author)
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The effects of chemotherapeutic drugs on human monocyte-derived dendritic cell differentiation and antigen presentation
- 2013
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In: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 172:3, s. 490-499
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Journal article (peer-reviewed)abstract
- Recent studies indicate that chemotherapeutic agents may increase the anti-tumoral immune response. Based on the pivotal role of dendritic cells (DCs) in host tumour-specific immune responses, we investigated the effect of commonly used chemotherapeutic drugs dexamethasone, doxorubicin, cisplatin and irinotecan and glucocorticoids on monocyte-derived DCs (moDCs). Dexamethasone displayed the strongest inhibitory effect on DC differentiation. The effect of cisplatin and irinotecan was moderate, while only weak effects were noticed for doxorubicin. Surprisingly, when the functional consequence of chemotherapy-treated CD14+ monocytes and their capacity to activate CD4+ T responders cells were investigated, cisplatin-treated monocytes gave rise to increased T cell proliferation. However, dexamethasone, doxorubicin and irinotecan-pretreated monocytes did not stimulate any increased T cell proliferation. Further investigation of this observation revealed that cisplatin treatment during DC differentiation up-regulated significantly the interferon (IFN)- transcript. By contrast, no effect was evident on the expression of interleukin (IL)-1, tumour necrosis factor (TNF)-, IL-6 or IFN- transcripts. Blocking IFN- attenuated the cisplatin-enhanced T cell proliferation significantly. In conclusion, cisplatin treatment enhanced the immune stimulatory ability of human monocytes, a mechanism mediated mainly by the increased production of IFN-.
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| 27. |
- Kumar, Archana Vijaya, et al.
(author)
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HS3ST2 modulates breast cancer cell invasiveness via MAP kinase- and Tcf4 (Tcf7l2)-dependent regulation of protease and cadherin expression
- 2014
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:11, s. 2579-2592
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Journal article (peer-reviewed)abstract
- Heparan sulfate 3-O-sulfotransferase 2 (HS3ST2), an enzyme mediating 3-O-sulfation of heparan sulfate (HS), is silenced by hypermethylation in breast cancer. As HS has an important co-receptor function for numerous signal transduction pathways, the phenotypical changes due to HS3ST2 reexpression were investigated in vitro using high and low invasive breast cancer cell lines. Compared to controls, highly invasive HS3ST2-expressing MDA-MB-231 cells showed enhanced Matrigel invasiveness, transendothelial migration and motility. Affymetrix screening and confirmatory real-time PCR and Western blotting analysis revealed increased expression of several matrix metalloproteinases, cadherin-11, E-cadherin and CEACAM-1, while protease inhibitor and annexin A10 expression were decreased. Low invasive HS3ST2 -expressing MCF-7 cells became even less invasive, with no change in gelatinolytic MMP activity. HS3ST2 expression increased HS-dependent basal and FGF2-specific signaling through the constitutively active p44/42 MAPK pathway in MDA-MB-231 cells. Increased MAPK activation was accompanied by upregulation of beta-catenin in MDA-MB-231, and of the transcription factor Tcf4 in both cell lines. Dysregulation of Tcf4-regulated ion transporters and increased cytosolic acidification were observed in HS3ST2-expressing MDA-MB-231 cells, which is a possible underlying cause of increased chemosensitivity towards doxorubicine and paclitaxel in these cells. This study provides the first in vitro evidence of the involvement of HS3ST2 in breast cancer cell invasion and chemosensitivity.
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| 28. |
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| 29. |
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| 30. |
- Liedberg, Fredrik, et al.
(author)
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Bladder cancer and the sentinel node concept
- 2003
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In: Aktuelle Urologie. - : Georg Thieme Verlag KG. - 0001-7868 .- 1438-8820. ; 34, s. 115-
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Journal article (peer-reviewed)abstract
- Purpose: Lymph node status is one of the most important prognostic factors in muscle-invasive bladder cancer. The extent of lymphadenectomy performed in conjunction with cystectomy and the question as to whether this is a staging or therapeutic intervention are matters of discussion. The aim of this study was to evaluate the sentinel node (SN) concept and to correlate findings with tumour status in excised regional lymph nodes. Material and method: 26 patients scheduled for cystectomy were investigated with preoperative lymphoscintigraphy, peroperative dye detection (Patent Blue) and dynamic lymphoscintigraphy (Nanocoll or Albures 50 MBq/ml). The substances were injected adjacent to the tumour in the detrusor muscle. Results: Sentinel nodes were detected in 21 of the 26 of the investigated patients. 7/21 SN were located outside the obturator fossa. Of the eight patients with lymph node metastasis, five displayed metastasis in lymph nodes outside the obturator fossa. There was one false negative SN in a patient with multifocal tumour, while in the other seven patients with lymph node metastasis, these were detected in the SN. Conclusion: Sentinel node detection is possible in most cases of bladder cancer scheduled for cystectomy. The significance of utilizing this method to detect lymph node metastasis outside the obturator fossa warrants further investigation.
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| 31. |
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| 32. |
- Liedberg, Fredrik, et al.
(author)
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Transitional cell carcinoma der Prostata im Zystoprostatektomiepräparat
- 2003
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In: Aktuelle Urologie. - : Georg Thieme Verlag KG. - 0001-7868 .- 1438-8820. ; 34:5, s. 333-336
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Journal article (peer-reviewed)abstract
- Purpose: Transitional cell carcinoma (TCC) of the prostate/prostatic urethra is a risk factor for urethral recurrence after radical cystoprostatectomy for TCC. Using conventional sectioning techniques, prostate involvement (prostatic urethra, acini, ducts and/ or stroma) has been detected in a range of 10-20% of the patients, whereas transversal whole mount sectioning has revealed 43% prostate involvement in two reported series. Due to different mechanisms of prostate involvement (intraurethral, extravesical and direct overgrowth into the prostatic stroma), preoperative transurethral biopsies of the prostate might not accurately determine such involvement. In this study we examine the prostate using a longitudinal whole mount sectioning technique, correlate TCC of the prostate with the characteristics of the bladder tumour and, thus, validate the preoperative transurethral resection biopsies. Material and methods: Patients scheduled for cystoprostatectomy or cystoprostatourethrectomy were investigated by preoperative resection biopsies from the prostatic urethra and mapping of the bladder. The cystectomy specimen was fixated with the bladder filled with formalin, and the prostate and bladder neck examined using longitudinal whole mount sectioning. Results: In 13 of the 43 (30%), patients TCC was identified in the prostate. Of these 13 patients, 9 had been identified in the preoperative resection biopsies from the prostatic urethra. Of the patients with prostatic involvement, 46% had carcinoma in situ (Cis) in the bladder neck/trigone and 38% had multifocal Cis in the bladder. Comparing this to the group of patients without prostatic involvement, the respectively figures are 20% and 23%. A tumour in the trigone, either invasive or Cis, was detected in 5/13 patients with prostatic involvement as compared to one patient (3%) without TCC of the prostate. Multiple bladder tumours were more common in patients with prostatic involvement and were larger (3.2 cm compared to 2.2 cm). Conclusions: Preoperative resection biopsies from the prostatic urethra do not always detect TCC in the prostate. Cis in the bladder neck/trigone or multifocal and multiple bladder tumours could be risk factors for prostate involvement of TCC.
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| 33. |
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| 34. |
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| 35. |
- Mansouri, Kamel, et al.
(author)
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CERAPP : Collaborative Estrogen Receptor Activity Prediction Project
- 2016
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:7, s. 1023-1033
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Journal article (peer-reviewed)abstract
- BACKGROUND: Humans are exposed to thousands of man-made chemicals in the environment. Some chemicals mimic natural endocrine hormones and, thus, have the potential to be endocrine disruptors. Most of these chemicals have never been tested for their ability to interact with the estrogen receptor (ER). Risk assessors need tools to prioritize chemicals for evaluation in costly in vivo tests, for instance, within the U.S. EPA Endocrine Disruptor Screening Program. OBJECTIVES: We describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) and demonstrate the efficacy of using predictive computational models trained on high-throughput screening data to evaluate thousands of chemicals for ER-related activity and prioritize them for further testing. METHODS: CERAPP combined multiple models developed in collaboration with 17 groups in the United States and Europe to predict ER activity of a common set of 32,464 chemical structures. Quantitative structure-activity relationship models and docking approaches were employed, mostly using a common training set of 1,677 chemical structures provided by the U.S. EPA, to build a total of 40 categorical and 8 continuous models for binding, agonist, and antagonist ER activity. All predictions were evaluated on a set of 7,522 chemicals curated from the literature. To overcome the limitations of single models, a consensus was built by weighting models on scores based on their evaluated accuracies. RESULTS: Individual model scores ranged from 0.69 to 0.85, showing high prediction reliabilities. Out of the 32,464 chemicals, the consensus model predicted 4,001 chemicals (12.3%) as high priority actives and 6,742 potential actives (20.8%) to be considered for further testing.CONCLUSION: This project demonstrated the possibility to screen large libraries of chemicals using a consensus of different in silico approaches. This concept will be applied in future projects related to other end points.
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| 36. |
- Menghrajani, Kamal, et al.
(author)
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Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML
- 2022
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:3, s. 828-847
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Journal article (peer-reviewed)abstract
- Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.
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| 37. |
- Percival, Mary-Elizabeth, et al.
(author)
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Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation
- 2021
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In: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 56:9, s. 2108-2117
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Journal article (peer-reviewed)abstract
- Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.
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| 38. |
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| 39. |
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| 40. |
- Sullivan, Richard, et al.
(author)
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Global cancer surgery: delivering safe, affordable, and timely cancer surgery
- 2015
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In: The Lancet Oncology. - 1474-5488. ; 16:11, s. 1193-1224
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Journal article (peer-reviewed)abstract
- Surgery is essential for global cancer care in all resource settings. Of the 15.2 million new cases of cancer in 2015, over 80% of cases will need surgery, some several times. By 2030, we estimate that annually 45 million surgical procedures will be needed worldwide. Yet, less than 25% of patients with cancer worldwide actually get safe, aff ordable, or timely surgery. This Commission on global cancer surgery, building on Global Surgery 2030, has examined the state of global cancer surgery through an analysis of the burden of surgical disease and breadth of cancer surgery, economics and fi nancing, factors for strengthening surgical systems for cancer with multiple-country studies, the research agenda, and the political factors that frame policy making in this area. We found wide equity and economic gaps in global cancer surgery. Many patients throughout the world do not have access to cancer surgery, and the failure to train more cancer surgeons and strengthen systems could result in as much as US$ 6.2 trillion in lost cumulative gross domestic product by 2030. Many of the key adjunct treatment modalities for cancer surgery-eg, pathology and imaging-are also inadequate. Our analysis identifi ed substantial issues, but also highlights solutions and innovations. Issues of access, a paucity of investment in public surgical systems, low investment in research, and training and education gaps are remarkably widespread. Solutions include better regulated public systems, international partnerships, super-centralisation of surgical services, novel surgical clinical trials, and new approaches to improve quality and scale up cancer surgical systems through education and training. Our key messages are directed at many global stakeholders, but the central message is that to deliver safe, aff ordable, and timely cancer surgery to all, surgery must be at the heart of global and national cancer control planning.
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| 41. |
- Witjes, J. Alfred, et al.
(author)
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EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer : Summary of the 2013 Guidelines
- 2014
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In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 65:4, s. 778-792
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Journal article (peer-reviewed)abstract
- CONTEXT: The European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic bladder cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis of the 2013 guidelines document, with emphasis on the latest developments.OBJECTIVE: To provide graded recommendations on the diagnosis and treatment of patients with muscle-invasive BCa (MIBC), linked to a level of evidence.EVIDENCE ACQUISITION: For each section of the guidelines, comprehensive literature searches covering the past 10 yr in several databases were conducted, scanned, reviewed, and discussed both within the panel and with external experts. The final results are reflected in the recommendations provided.EVIDENCE SYNTHESIS: Smoking and work-related carcinogens remain the most important risk factors for BCa. Computed tomography (CT) and magnetic resonance imaging can be used for staging, although CT is preferred for pulmonary evaluation. Open radical cystectomy with an extended lymph node dissection (LND) remains the treatment of choice for treatment failures in non-MIBC and T2-T4aN0M0 BCa. For well-informed, well-selected, and compliant patients, however, multimodality treatment could be offered as an alternative, especially if cystectomy is not an option. Comorbidity, not age, should be used when deciding on radical cystectomy. Patients should be encouraged to actively participate in the decision-making process, and a continent urinary diversion should be offered to all patients unless there are specific contraindications. For fit patients, cisplatinum-based neoadjuvant chemotherapy should always be discussed, since it improves overall survival. For patients with metastatic disease, cisplatin-containing combination chemotherapy is recommended. For unfit patients, carboplatin combination chemotherapy or single agents can be used.CONCLUSIONS: This 2013 EAU Muscle-invasive and Metastatic BCa guidelines updated summary aims to increase the quality of care and outcome for patients with muscle-invasive or metastatic BCa.PATIENT SUMMARY: In this paper we update the EAU guidelines on Muscle-invasive and Metastatic bladder cancer. We recommend that chemotherapy be administered before radical treatment and that bladder removal be the standard of care for disease confined to the bladder.
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| 42. |
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| 43. |
- Wu, Xuanjun, et al.
(author)
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Protective Epitope Discovery and the Design of MUC1 Based Vaccine for Effective Tumor Protections in Immunotolerant Mice
- 2018
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 140:48, s. 16596-16609
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Journal article (peer-reviewed)abstract
- Human mucin-1 (MUC1) is a highly attractive antigen for the development of anticancer vaccines. However, in human clinical trials of multiple MUC1 based vaccines, despite the generation of anti-MUC1 antibodies, the antibodies often failed to exhibit much binding to tumor presumably due to the challenges in inducing protective immune responses in the immunotolerant environment. To design effective MUC1 based vaccines functioning in immunotolerant hosts, vaccine constructs were first synthesized by covalently linking the powerful bacteriophage Qβ carrier with MUC1 glycopeptides containing 20-22 amino acid residues covering one full length of the tandem repeat region of MUC1. However, IgG antibodies elicited by these first generation constructs in tolerant human MUC1 transgenic (Tg) mice did not bind tumor cells strongly. To overcome this, a peptide array has been synthesized. By profiling binding selectivities of antibodies, the long MUC1 glycopeptide was found to contain immunodominant but nonprotective epitopes. Critical insights were obtained into the identity of the key protective epitope. Redesign of the vaccine focusing on the protective epitope led to a new Qβ-MUC1 construct, which was capable of inducing higher levels of anti-MUC1 IgG antibodies in MUC1.Tg mice to react strongly with and kill a wide range of tumor cells compared to the construct containing the gold standard protein carrier, i.e., keyhole limpet hemocyanin. Vaccination with this new Qβ-MUC1 conjugate led to significant protection of MUC1.Tg mice in both metastatic and solid tumor models. The antibodies exhibited remarkable selectivities toward human breast cancer tissues, suggesting its high translational potential.
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| 44. |
- Wu, Xuanjun, et al.
(author)
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Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles
- 2019
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In: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 14:10, s. 2176-2184
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Journal article (peer-reviewed)abstract
- Mucin-1 (MUC1) is a highly attractive antigenic target for anticancer vaccines. Naturally existing MUC1 can contain multiple types of O-linked glycans, including the Thomsen–Friedenreich (Tf) antigen and the Sialyl Thomsen-nouveau (STn) antigen. In order to target these antigens as potential anticancer vaccines, MUC1 glycopeptides SAPDT*RPAP (T* is the glycosylation site) bearing the Tf and the STn antigen, respectively, have been synthesized. The bacteriophage Qβ carrier is a powerful carrier for antigen delivery. The conjugates of MUC1-Tf and -STn glycopeptides with Qβ were utilized to immunize immune-tolerant human MUC1 transgenic (MUC1.Tg) mice, which elicited superior levels of anti-MUC1 IgG antibodies with titers reaching over 2 million units. The IgG antibodies recognized a wide range of MUC1 glycopeptides bearing diverse glycans. Antibodies induced by Qβ-MUC1-Tf showed strongest binding, with MUC1-expressing melanoma B16-MUC1 cells, and effectively killed these cells in vitro. Vaccination with Qβ-MUC1-Tf first followed by tumor challenge in a lung metastasis model showed significant reductions of the number of tumor foci in the lungs of immunized mice as compared to those in control mice. This was the first time that a MUC1-Tf-based vaccine has shown in vivo efficacy in a tumor model. As such, Qβ-MUC1 glycopeptide conjugates have great potential as anticancer vaccines.
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