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Sökning: WFRF:(Lindh Claes)

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1.
  • Annerstedt, Claes, 1953, et al. (författare)
  • Research-able through Problem-Based Learning
  • 2010
  • Ingår i: Journal of the Scholarship of Teaching and Learning. - 1527-9316. ; 10:2, s. 107-127
  • Tidskriftsartikel (refereegranskat)abstract
    • This research project describes an attempt to move towards a more student centered and participatory approach on learning through problem-based storyboards (themes/scenarios) and a unique opportunity for students to have an academic cross-cultural exchange. The purpose of the study was to analyze students' conceptions of this approach on learning through storyboards, experiential learning and the evolution of assessment methods that reflect and further student capabilities. While student satisfaction with the aims of the course was high and technology facilitated a unique cross-cultural opportunity, the challenges of maintaining reliable technology and matching student expectations proved challenging. Despite critical comments, the overwhelming outcome was positive. (Contains 3 figures and 6 footnotes.)
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2.
  • Bergh Thorén, Fredrik, 1976, et al. (författare)
  • A hepatitis C virus-encoded, nonstructural protein (NS3) triggers dysfunction and apoptosis in lymphocytes: role of NADPH oxidase-derived oxygen radicals
  • 2004
  • Ingår i: Journal of leukocyte biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 76:6, s. 1180-6
  • Tidskriftsartikel (refereegranskat)abstract
    • The persistent infection caused by hepatitis C virus (HCV) is presumably explained by a deficient immune response to the infection, but the basis for the inefficiency of immune-mediated virus eradication is not known in detail. This study addresses mechanisms of relevance to dysfunction of cytotoxic lymphocytes in HCV infection, with a focus on the role of phagocyte-derived oxygen radicals. We show that NS3, a nonstructural, HCV-encoded protein, induces a prolonged release of oxygen radicals from mononuclear and polymorphnuclear phagocytes by activating a key enzyme in radical formation, the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The NS3-activated phagocytes, in turn, induced dysfunction and/or apoptosis in three major subsets of lymphocytes of relevance to defense against HCV infection: CD3+/56- T cells, CD3-/56+ natural killer (NK) cells, and CD3+/56+ NKT cells. Two inhibitors of the NADPH oxidase, histamine and diphenylene iodonium, suppressed the NS3-induced oxygen radical production and efficiently protected lymphocytes against NS3-induced apoptosis and dysfunction. In conclusion, we propose that NS3, by triggering oxygen radical formation in phagocytes, may contribute to the dysfunction of antiviral lymphocytes in HCV-infected liver tissue and that strategies to circumvent oxidative stress may be useful in preventing HCV-associated carcinogenesis and facilitating lymphocyte-mediated clearance of infected cells.
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3.
  • Bramsved, Rebecka, 1982, et al. (författare)
  • Birth Weight, Childhood and Young Adult Overweight, and the Risk of Coronary Heart Disease in Men.
  • 2024
  • Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 44:1, s. 314-321
  • Tidskriftsartikel (refereegranskat)abstract
    • Low birth weight is a known risk factor for adult coronary heart disease (CHD), but the additional effect of weight development during childhood and early adult life has not been studied.We included 35659 men born 1945 to 1961 from the population-based BMI Epidemiology Study Gothenburg, with data available on birthweight, BMI in childhood (8 years), and BMI in young adulthood (20 years). Information on CHD diagnoses was retrieved from national registers. We used Cox proportional hazards regression to estimate hazard ratios and 95% CIs for the risk of early and late CHD (before and after 58.4 years of age, respectively).During follow-up, a total of 3380 cases of CHD (fatal and nonfatal) were registered. Birth weight was inversely associated with the risk of both early (hazard ratio, 0.88 per SD increase [95% CI, 0.84-0.92]) and late (hazard ratio, 0.94 per SD increase [95% CI, 0.90-0.98]) CHD, independently of BMI at 8 years and BMI change during puberty. In a model including birth weight (below or above the median) together with overweight at 8 and 20 years, only birth weight and young adult overweight, but not overweight in childhood, were significantly associated with the risk of CHD. A birth weight below the median, followed by overweight at 20 years of age was associated with a more than doubled risk of early CHD (hazard ratio, 2.29 [95% CI, 1.86-2.81]), compared with the reference (birth weight above the median and normal weight at 20 years of age). This excess risk was even more pronounced for a birthweight below 2.5 kg.We demonstrate that low birth weight and young adult overweight are important developmental markers of risk for adult CHD. These findings motivate a life course perspective for prevention and risk assessment of adult CHD.
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4.
  • Caragounis, Eva Corina, et al. (författare)
  • Comparison of HIV-1 pol and env sequences of blood, CSF, brain and spleen isolates collected ante-mortem and post-mortem
  • 2008
  • Ingår i: Acta Neurol Scand. - : Hindawi Limited. - 1600-0404. ; 117:2, s. 108-16
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: HIV-1 infects the central nervous system (CNS) early in the course of infection. However, it is not known to what extent the virus evolves independently within the CNS and whether the HIV-RNA in cerebrospinal fluid (CSF) reflects the viral population replicating within the brain parenchyma or the systemic infection. The aim of this study was to investigate HIV-1 evolution in the CNS and the origin of HIV-1 in CSF. MATERIALS AND METHODS: Longitudinally derived paired blood and CSF samples and post-mortem samples from CSF, brain and spleen were collected over a period of up to 63 months from three HIV-1 infected men receiving antiretroviral treatment and presenting with symptoms of AIDS dementia complex (ADC). RESULTS: Phylogenetic analyses of HIV-1 V3, reverse transcriptase (RT) and protease sequences from patient isolates suggest compartmentalization with distinct viral strains in blood, CSF and brain. We found a different pattern of RT and accessory protease mutations in the systemic infection compared to the CNS. CONCLUSIONS: We conclude that HIV-1 may to some extent evolve independently in the CNS and the viral population in CSF mainly reflects the infection in the brain parenchyma in patients with ADC. This is of importance in understanding HIV pathogenesis and can have implications on treatment of HIV-1 patients.
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5.
  • Garza, D, et al. (författare)
  • Use of a virtual human performance laboratory to improve integration of mathematics and biology in sports science curricula in Sweden and the United States.
  • 2007
  • Ingår i: Studies in Health Technology and Informatics.. ; 2007. Vol. 125, s. 140-142
  • Tidskriftsartikel (refereegranskat)abstract
    • New fields such as bioengineering are exploring the role of the physical sciences in traditional biological approaches to problems, with exciting results in device innovation, medicine, and research biology. The integration of mathematics, biomechanics, and material sciences into the undergraduate biology curriculum will better prepare students for these opportunities and enhance cooperation among faculty and students at the university level. We propose the study of sports science as the basis for introduction of this interdisciplinary program. This novel integrated approach will require a virtual human performance laboratory dual-hosted in Sweden and the United States. We have designed a course model that involves cooperative learning between students at Göteborg University and Stanford University, utilizes new technologies, encourages development of original research and will rely on frequent self-assessment and reflective learning. We will compare outcomes between this course and a more traditional didactic format as well as assess the effectiveness of multiple web-hosted virtual environments. We anticipate the grant will result in a network of original faculty and student research in exercise science and pedagogy as well as provide the opportunity for implementation of the model in more advance training levels and K-12 programs.
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6.
  • Garza, D, et al. (författare)
  • Use of a Virtual Human Performance Laboratory to Improve Integration of Mathematics and Biology in Sports Science Curricula in Sweden and the United States
  • 2007
  • Ingår i: Medicine Meets Virtual Reality 15 - in vivo, in vitro, in silico: Designing the Next in Medicine. Int. Conf., Long Beach Calif., US, 2007. - 9781586037130 ; 15
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • We are designing a course to be taught simultaneously at Göteborg University and Stanford University. We will present two approaches to creating a virtual environment in sport science experiments that are central to the course. The first virtual environment allows students at any location to utilize Marratech web-hosting software to conduct real-time experiments in venues as sophisticated as Lundberg Laboratories in Göteborg and the Stanford Human Performance Laboratory. We have conducted two trials to validate the feasibility of this design, which accommodates simple technologies such as a laptop and consumer devices at the participant site. The second virtual environment is a computer-generated biomechanics laboratory that will allow students to conduct experiments of their own design. Both Göteborg and Stanford will collect motion capture and force plate data on Olympic-caliber and professional athletes. Students will manipulate this data to conduct novel biomechanical investigations under the direction of a set of learning models under development.
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7.
  • Lindh, Claes (författare)
  • Morphological, immunohistochemical and genetic aspects of acinar and ductal adenocarcinoma of the prostate
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Prostate cancer is one of the most common causes of cancer-related death in developed countries. Acinar adenocarcinoma is by far the most common subtype of prostate cancer, with ductal adenocarcinoma being the second most common subtype. Biobanking of prostate cancer tissue is important for basic research, development of new biomarkers and a move towards personalized medicine. Various biobanking techniques have been described but harvesting of tissue is still often based on macroscopic identification of cancer in radical prostatectomy specimens. In the literature, the macroscopic features of prostate cancer in unfixed prostatectomy specimens are incompletely described. In our first study, we investigated the macroscopic features of identifiable tumors and their zonal distribution in 514 radical prostatectomy specimens. Grossly detected findings conclusive for cancer were seen in 52% of cases and suspicious for cancer in 24%. Macroscopic findings conclusive for cancer predicted microscopic identification of prostate cancer on microscopic examination in most cases. Cancers ≥2 mm were present somewhere on the cut surface in the majority of cases even when no suspicious or conclusive cancers had been identified macroscopically. Tumors in the transition zone of the prostate were more difficult to identify macroscopically. In our second study, we report a novel biobanking protocol for harvesting a full horizontal slice of unfixed prostate tissue from 20 radical prostatectomy specimens. In 18 of 20 cases, cancer was found in the biobanked tissue material. The biobanking protocol facilitated harvesting of a large slice of prostatic tissue, allowing studies of multifocal tumors and tumor heterogeneity. Clinical histopathological parameters could be reported from frozen sections of the biobanked material. The morphological quality, using cryogel, and the RNA quality, measured by RNA integrity number (RIN), were excellent. Ductal adenocarcinoma is a high-grade neoplasm with an adverse prognosis compared to acinar adenocarcinoma. The definition of ductal adenocarcinoma is based on histological features. Ductal adenocarcinoma usually presents in mixed tumors together with acinar adenocarcinoma. For a long time, the histogenesis and definition of ductal adenocarcinoma has been controversial. Some studies have suggested that acinar and ductal adenocarcinoma components may have a common clonal background. Expression of Programmed Death Ligand-1 (PD-L1) is a predictive biomarker for a new group of oncological drugs, immune checkpoint inhibitors. The frequency of PD-L1 expression in ductal adenocarcinoma is not well described. Deficient mismatch repair (dMMR) results in an accumulation of mutations in cancer cells. dMMR has been reported to be uncommon in prostate cancer. In our third study, we investigated the expression of PD-L1, dMMR and tumor infiltrating immune cells in acinar and ductal adenocarcinoma using a tissue microarray (TMA). PD-L1 expression in tumor cells was rare but more common in tumor infiltrating immune cells. PD-L1 expression was identified in tumor infiltrating immune cells in 29% of ductal adenocarcinomas. dMMR was rare, identified in only 5% of cases. There was a statistically significant increase in the number of CD8+ lymphocytes in ductal adenocarcinoma compared to acinar adenocarcinoma. In our final study, we investigated the clonal relationship between acinar and ductal adenocarcinoma components in mixed prostate cancers. Targeted sequencing was performed in 15 cases, followed by bioinformatic processing and manual curation of data. A common somatic denominator for both tumor components could be identified in 12 out of 15 cases indicating a common clonal origin. Increased ploidy, which is associated with advanced prostate cancer, was seen in more than half (53%) of ductal adenocarcinomas but not in any acinar adenocarcinoma. PTEN and CTNNB1 mutations were common in ductal adenocarcinoma (40%) but not seen in any acinar adenocarcinoma. In both acinar and ductal adenocarcinomas, ERG gene fusions were detected in 47%. No cases showed microsatellite instability or high tumor mutation burden. The genetic signature of ductal adenocarcinoma was consistent with its characterization of ductal adenocarcinoma as an aggressive form of prostate cancer
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8.
  • Lindh, Jacob, 1971, et al. (författare)
  • Blended learning through global network and interdisciplinary live distance experiments at human performance laboratories.
  • 2009
  • Ingår i: Learning in the Synergy of Multiple Disciplines, 4th European Conference on Technology Enhanced Learning, EC-TEL 2009, Nice, France, September 29 - October 2, 2009.. - : Springer. - 9783642046353 ; 5794 Springer 2009
  • Tidskriftsartikel (refereegranskat)abstract
    • Under a previous grant (2005-2008) we designed an interdisciplinary inquiry-based laboratory course in sports kinesiology, taught simultaneously over the Internet for undergraduate students at the University of Gothenburg and at Stanford University. Student groups developed their own research questions, conducted online distance experiments, processed their unique data with support from an interdisciplinary global network of expert consultants, and presented original scientific results. We will demonstrate one virtual experiment that is central to the course to conference attendees and present a unique set of interactive learning tools for the scientific process. This student-conducted experiment was first tested in a laboratory in Stockholm in 2007, and broadcasted live to three universities, with experts and students actively taking part via Polycom and Marratech. Real-time communication was possible in all directions through a moderator in Stockholm. Our course model seems to improve student learning outcomes while advancing the field of sports science.
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9.
  • Lindh, Jacob, 1971, et al. (författare)
  • Evaluation of Parallel Authentic Research-Based Courses in Human Biology on Student Experiences at Stanford University and the University of Gothenburg
  • 2016
  • Ingår i: Journal of the Scholarship of Teaching and Learning. - 1527-9316. ; 16:5, s. 70-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Under a previous grant (2005-08), researchers and teachers at Stanford University (SU) and the University of Gothenburg (GU) co-designed a ten-week interdisciplinary, research-based laboratory course in human biology to be taught online to undergraduate students. Essentials in the subject were taught during the first four weeks of this course. Subsequently, student groups at SU and GU developed their own research questions, conducted live-streamed experiments remotely, processed their unique data with support from multiple interactive resources, cross-cultural collaboration and an interdisciplinary network of expert consultants, and presented original scientific results remotely. Student course-perceptions were evaluated using online questionnaires, reflective blogs, and observations. In student teams from both universities, the course concept clearly improved student abilities to conduct research using laboratory experiments while learning theoretical basics. A comparison of pre- and post-course scores from student surveys showed that post-course student comfort levels with several research-related tasks increased radically at both universities. All participating staff generally agreed that the methods and tools were valuable in this type of course and should be evaluated at other levels and areas of higher education, and shared in an expanded network of universities.
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10.
  • Lindh, Liselott, et al. (författare)
  • Adsorption of MUC5B and the role of mucins in early salivary film formation
  • 2002
  • Ingår i: Colloids and Surfaces B: Biointerfaces. - : Elsevier. - 1873-4367 .- 0927-7765. ; 25:2, s. 139-146
  • Tidskriftsartikel (refereegranskat)abstract
    • Salivary mucins are known to play important roles in the formation of oral salivary films. The aims of the present study were to investigate the behaviour of salivary mucins at solid surfaces with different wettabilities, as well as the influence of electrolyte on the adsorption behaviour. A pure preparation of human salivary MUC5B was used together with a commercial one of bovine submaxillary mucin (BSM). Amounts adsorbed from freshly prepared solutions onto hydrophilic and hydrophobic surfaces versus time were measured in situ by ellipsometry. At low concentrations, larger amounts were adsorbed onto hydrophobic than onto hydrophilic silica indicating a higher affinity for the former surfaces. Furthermore, on hydrophilic surfaces adsorbed amounts of MUC5B and BSM show good agreement at low concentrations (< 0. 10 mg ml(-1)). However, at higher concentrations MUM adsorbed to a lower extent than BSM. At hydrophobic surfaces, isotherm shapes were similar for the two preparations, but the amounts were shifted to higher values for MUC5B. Finally, the presence of electrolyte increased adsorption and the increase was more pronounced on hydrophilic surfaces. The increased adsorption at a higher ionic strength indicates a more compact structure of the mucin due to electrostatic screening and the fact that the effect was more pronounced on the hydrophilic surfaces points to a higher relative importance of electrostatic interactions in this case. We conclude that the two mucins investigated behave in a qualitatively similar manner and show the highest affinity for hydrophobic surfaces.
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11.
  • Mossberg, Natalia, et al. (författare)
  • Oxygen radical production and severity of the Guillain--Barré syndrome.
  • 2007
  • Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 192:1-2, s. 186-91
  • Tidskriftsartikel (refereegranskat)abstract
    • The NADPH oxidase-dependent formation of reactive oxygen species ("oxygen radicals") by phagocytic cells constitutes an important part of the innate immune defence against microorganisms. Recent studies in animal models imply that a deficient function of the NADPH oxidase may be linked to the development of autoimmunity, but a link between oxygen radical production and severity of autoimmune disease in humans has not been established. We have examined the oxygen radical production in peripheral blood leukocytes from patients with the Guillain-Barré syndrome (GBS). Leukocytes from GBS patients in a stationary phase 1-5 years after their acute episode were activated by the formyl peptide receptor (FPR) ligand formyl-Met-Leu-Phe (fMLF) or the closely related formyl peptide like receptor 1 (FPRL1) ligand Trp-Lys-Tyr-Met-Val-Met-NH2 (WKYMVM). The patients were dichotomized according to severity by 1) the requirement of intensive care unit treatment and 2) the ability to walk independently after 3 months. Our data show that the amount of superoxide release following challenge with either of the two agonists fMLF and WKYMVM was significantly lower in patients requiring intensive care unit treatment or unable to walk after 3 months. Results obtained with the global activator phorbol myristate acetate, as well as with fMLF in TNF alpha-primed leukocytes, suggested that the deficiency of oxygen radical production in patients with severe GBS was the result of a specific deficiency of radical production in response to FPR/FPRL1 ligands rather than an inherent deficiency of NADPH oxidase function.
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12.
  • Nilsson, Markus, et al. (författare)
  • Mapping prostatic microscopic anisotropy using linear and spherical b-tensor encoding : A preliminary study
  • 2021
  • Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 86:4, s. 2025-2033
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Tensor-valued diffusion encoding provides more specific information than conventional diffusion-weighted imaging (DWI), but has mainly been applied in neuroimaging studies. This study aimed to assess its potential for the imaging of prostate cancer (PCa). Methods: Seventeen patients with histologically proven PCa were enrolled. DWI of the prostate was performed with linear and spherical tensor encoding using a maximal b-value of 1.5 ms/µm2 and a voxel size of 3 × 3 × 4 mm3. The gamma-distribution model was used to estimate the mean diffusivity (MD), the isotropic kurtosis (MKI), and the anisotropic kurtosis (MKA). Regions of interest were placed in MR-defined cancerous tissues, as well as in apparently healthy tissues in the peripheral and transitional zones (PZs and TZs). Results: DWI with linear and spherical encoding yielded different image contrasts at high b-values, which enabled the estimation of MKA and MKI. Compared with healthy tissue (PZs and TZs combined) the cancers displayed a significantly lower MD (P <.05), higher MKI (P < 10−5), and lower MKA (P <.05). Compared with the TZ, tissue in the PZ showed lower MD (P < 10−3) and higher MKA (P < 10−3). No significant differences were found between cancers of different Gleason scores, possibly because of the limited sample size. Conclusion: Tensor-valued diffusion encoding enabled mapping of MKA and MKI in the prostate. The elevated MKI in PCa compared with normal tissues suggests an elevated heterogeneity in the cancers. Increased in-plane resolution could improve tumor delineation in future studies.
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13.
  • Sjödahl, Gottfrid, et al. (författare)
  • Different Responses to Neoadjuvant Chemotherapy in Urothelial Carcinoma Molecular Subtypes
  • 2022
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 81:5, s. 523-532
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: For muscle-invasive bladder cancer (MIBC), no tissue biomarkers are available for clinical use to predict response to neoadjuvant chemotherapy.OBJECTIVE: To investigate how molecular subtypes impact pathological response and survival in patients receiving preoperative cisplatin-based chemotherapy.DESIGN, SETTING, AND PARTICIPANTS: Classification of a retrospective cohort of 149 patients was performed by tumor transcriptomic profiling and immunostaining. A cohort treated with radical cystectomy alone and public data sets were used for comparison and external validation.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Complete pathological response in the cystectomy specimen (ypT0N0) and survival were compared in predefined molecular subtypes. Differential gene expression and chemotherapy response were explored beyond molecular subtypes.RESULTS AND LIMITATIONS: Patients with genomically unstable (GU) and urothelial-like (Uro) tumors had higher proportions of complete pathological response (16/31 [52%] and 17/54 [31%]), versus five out of 24 (21%) with the basal/squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Molecular subtype was independently associated with improved survival for patients with GU tumors (hazard ratio [HR] 0.29, 95% confidence interval [CI]: 0.11-0.79) and UroC tumors (HR 0.37, 95% CI: 0.14-0.94) compared with Ba/Sq tumors, adjusting for clinical stage. In addition, expression of the gene coding for osteopontin (SPP1) showed a subtype-dependent effect on chemotherapy response.CONCLUSIONS: Urothelial cancer of the luminal-like (GU and Uro) subtypes is more responsive to cisplatin-based neoadjuvant chemotherapy. A second-generation of subtype-specific biomarkers, for example, SPP1, may be a way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC.PATIENT SUMMARY: This study shows that tumor classification by gene expression profiling and molecular subtyping can identify patients who are more likely to benefit from chemotherapy before radical cystectomy for muscle-invasive bladder cancer. Together with other markers for response, molecular subtypes could have a role in selective administration of such chemotherapy.
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14.
  • Sjödahl, Gottfrid, et al. (författare)
  • Different Responses to Neoadjuvant Chemotherapy in Urothelial Carcinoma Molecular Subtypes.
  • 2022
  • Ingår i: European urology. - : Elsevier. - 1873-7560 .- 0302-2838. ; 81:5, s. 523-532
  • Tidskriftsartikel (refereegranskat)abstract
    • For muscle-invasive bladder cancer (MIBC), no tissue biomarkers are available for clinical use to predict response to neoadjuvant chemotherapy.To investigate how molecular subtypes impact pathological response and survival in patients receiving preoperative cisplatin-based chemotherapy.Classification of a retrospective cohort of 149 patients was performed by tumor transcriptomic profiling and immunostaining. A cohort treated with radical cystectomy alone and public data sets were used for comparison and external validation.Complete pathological response in the cystectomy specimen (ypT0N0) and survival were compared in predefined molecular subtypes. Differential gene expression and chemotherapy response were explored beyond molecular subtypes.Patients with genomically unstable (GU) and urothelial-like (Uro) tumors had higher proportions of complete pathological response (16/31 [52%] and 17/54 [31%]), versus five out of 24 (21%) with the basal/squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Molecular subtype was independently associated with improved survival for patients with GU tumors (hazard ratio [HR] 0.29, 95% confidence interval [CI]: 0.11-0.79) and UroC tumors (HR 0.37, 95% CI: 0.14-0.94) compared with Ba/Sq tumors, adjusting for clinical stage. In addition, expression of the gene coding for osteopontin (SPP1) showed a subtype-dependent effect on chemotherapy response.Urothelial cancer of the luminal-like (GU and Uro) subtypes is more responsive to cisplatin-based neoadjuvant chemotherapy. A second-generation of subtype-specific biomarkers, for example, SPP1, may be a way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC.This study shows that tumor classification by gene expression profiling and molecular subtyping can identify patients who are more likely to benefit from chemotherapy before radical cystectomy for muscle-invasive bladder cancer. Together with other markers for response, molecular subtypes could have a role in selective administration of such chemotherapy.
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15.
  • Tanaka, Nobuyuki, et al. (författare)
  • Whole-tissue biopsy phenotyping of three-dimensional tumours reveals patterns of cancer heterogeneity
  • 2017
  • Ingår i: Nature Biomedical Engineering. - : Nature Publishing Group. - 2157-846X. ; 1:10, s. 796-806
  • Tidskriftsartikel (refereegranskat)abstract
    • Intratumoral heterogeneity is a critical factor when diagnosing and treating patients with cancer. Marked differences in the genetic and epigenetic backgrounds of cancer cells have been revealed by advances in genome sequencing, yet little is known about the phenotypic landscape and the spatial distribution of intratumoral heterogeneity within solid tumours. Here, we show that three-dimensional light-sheet microscopy of cleared solid tumours can identify unique patterns of phenotypic heterogeneity, in the epithelial-to-mesenchymal transition and in angiogenesis, at single-cell resolution in whole formalin-fixed paraffin-embedded (FFPE) biopsy samples. We also show that cleared FFPE samples can be re-embedded in paraffin after examination for future use, and that our tumour-phenotyping pipeline can determine tumour stage and stratify patient prognosis from clinical samples with higher accuracy than current diagnostic methods, thus facilitating the design of more efficient cancer therapies.
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