Biomedical subjects

Magnus Hellström

Publications and source records attributed to Magnus Hellström.

10 recordsLinked to original sources

PubMed2006

CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients.

In this study, we investigated whether CD4+CD25high regulatory T cells (Treg) are increased in the tumor tissue and peripheral blood of early-stage prostate cancer patients undergoing prostatectomy. We show that the prevalence of CD4+CD25high T cells inside the prostate was significantly higher in the tumor compared with benign tissue from the same prostate. Furthermore, the frequency of CD4+CD25high T cells in peripheral blood was significantly higher in prostate cancer patients compared with normal donors. A proportion of the CD4+CD25high T cells was also shown to be glucocorticoid-induced TNF receptor, ICOS, and FOXP3 positive. Moreover, CD4+CD25+ T cells from blood and supernatants from cultured prostate tumor tissue samples exhibited immunosuppressive function in vitro. Furthermore, supernatants from cultured prostate tissue samples and prostate cancer ascites fluid induced migration of CD4+CD25+ T cells and were shown to contain the regulatory T cell chemokine CCL22 by ELISA. Our findings indicate that Tregs are an important cellular component of early-stage prostate tumors, and thus new therapeutic strategies aimed at inhibition or depletion of Tregs may improve prostate cancer immunotherapy.

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PubMed2006

Tissue shrinkage after fixation with formalin injection of prostatectomy specimens.

Prostate cancer volume correlates with stage, grade, and progression after prostatectomy. When tumor volume is measured planimetrically, results are multiplied by a correction factor to compensate for tissue shrinkage caused by processing. Injection of formalin into prostatectomy specimens was suggested for improved fixation. Our aim was to investigate how this affects the prostate volume. We studied 142 radical prostatectomy specimens. All prostates were immersed in 10% formalin. In 84 prostates (59%) we also injected 20 ml of formalin before routine fixation. The prostates were weighed unfixed after injection and after final fixation. The specimens were sliced and totally embedded. The transverse diameters of the prostates were measured on unfixed specimens and microscopic sections. The average weight loss after final fixation was 5.8 and 8.6% for formalin-injected specimens and standard-fixed specimens, respectively (p<0.001). However, when total shrinkage was estimated from the transverse diameters, there was no difference related to fixation technique (p=0.59). The average linear shrinkage was 4.5%, corresponding to a volume correction factor of 1.15. We conclude that formalin injection for fixation of prostate tissue does not influence tumor volume calculation compared to conventional fixation.

Artifacts↗

PubMed2006

Evaluation of two sample preparation methods for prostate proteome analysis.

For laboratory techniques that require well-preserved proteins, such as 2-DE, fresh tissue must be harvested and processed as fast as possible to avoid proteolytic degradation. We describe a modified method for harvesting tissue from radical prostatectomy specimens for proteome analysis and compare it with the standard technique. Cells were scraped from cut surfaces of 11 prostate specimens. A fraction of the material was smeared on a glass slide and Giemsa stained for morphological control. The sample was collected in a medium with protease inhibitors, and the protein material was prepared for 2-DE. Filtering and Percoll centrifugation were omitted. Sample locations were noted on a specimen map. From the same area, a tissue block was harvested for comparison. The block was processed with the conventional technique including mechanical disintegration, filtering and Percoll centrifugation. Quality measures of 2-DE were similar with both methods. With the scrape sampling technique, control smears showed abundant epithelial cells and a cleaner background and processing was faster than with tissue block sampling. For proteomic analysis, the scrape sample technique has several advantages over the tissue block method.

Electrophoresis, Gel, Two-Dimensional↗

PubMed2006

Correlation of protein expression, Gleason score and DNA ploidy in prostate cancer.

The prognosis of prostate cancer correlates with tumor differentiation. Gleason score and DNA ploidy are two prognostic factors that correlate with prognosis. We analyzed differences in protein expression in prostate cancer of high and low aggressiveness according to these measures. From 35 prostatectomy specimens, 29 cancer samples and 10 benign samples were harvested by scraping cells from cut surfaces. DNA ploidy was assessed by image cytometry. Protein preparations from cell suspensions were examined by 2-DE. Protein spots that differed quantitatively between sample groups were identified by MS fingerprinting of tryptic fragments and MS/MS sequence analysis. We found 39 protein spots with expression levels that were raised or lowered in correlation with Gleason score and/or DNA ploidy pattern (31 overexpressed in high-malignant cancer, 8 underexpressed). Of these, 30 were identified by MS. Among overexpressed proteins were heat-shock, structural and membrane proteins and enzymes involved in gene silencing, protein synthesis/degradation, mitochondrial protein import (metaxin 2), detoxification (GST-pi) and energy metabolism. Stroma-associated proteins were generally underexpressed. The protein expression of prostate cancer correlates with tumor differentiation. Potential prognostic markers may be found among proteins that are differentially expressed and the clinical value of these should be validated.

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PubMed2005

Differential protein expression in anatomical zones of the prostate.

The prostate has three anatomical zones: the peripheral (PZ), the transition (TZ), and the central (CZ) zone. It is proposed that the CZ may be of mesodermal origin, whereas the other two are of endodermal origin. Proteome patterns in the zones were characterized to test for differences. Cells were scraped from macroscopically normal areas of PZ, TZ, and CZ in radical prostatectomy specimens. After exclusion of samples with cancer or prostatic intraepithelial neoplasia, 18 cases remained for analysis. Cells were collected in a medium with protease inhibitors, and the protein material was prepared for two-dimensional gel electrophoresis. The proteins in spots that differed quantitatively between regions were identified via mass spectrometric fingerprinting of tryptic fragments and selected tandem mass spectrometry sequence analysis. Ten proteins with significant zonal differential expression were identified, eight with underexpression in the CZ versus the PZ and the TZ (arginase II, ATP synthase, cytokeratin 8, lamin A/C, peroxiredoxin 4, protein disulfide isomerase A3, tropomyosin, and vimentin), and two with overexpression in the CZ (peroxiredoxin 2 and creatine kinase B). The PZ and TZ, although differing in terms of incidence of cancer and hyperplasia, have epithelium with highly similar major protein expression profiles. However, the protein profile of the CZ differs from that of the other regions, suggesting functional differences.

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PubMed2005

Geographical variation in incidence of prostate cancer in Sweden.

OBJECTIVE: To investigate the geographical variation in prostate cancer incidence in Sweden, in particular the incidences of screening-detected tumours and curative treatment of prostate cancer. MATERIAL AND METHODS: Data were retrieved from the National Prostate Cancer Register of Sweden for all cases of prostate cancer diagnosed in the year 2000-01. There were a total of 14 376 cases of prostate cancer and the mean total annual age-adjusted incidence was 197/100 000 men. There were 3318 cases in tumour category T1c, i.e. non-palpable tumours diagnosed during work-up for an elevated serum level of prostate-specific antigen, 1006 of which (30%) were asymptomatic and detected at a health check-up. RESULTS: The difference between the counties with the lowest and highest age-adjusted incidences per 100 000 men of total prostate cancer was almost twofold (128 vs 217). The corresponding variation in incidence of category T1c tumours was more than fourfold (13 vs 60); the difference in incidence of T1c tumours detected in asymptomatic men was up to 10-fold (2 vs 20); and there was more than a fourfold variation in incidence of curative treatment between counties (13 vs 67). Measured incidences were mostly highest in urban regions and in counties with university hospitals. CONCLUSION: There are large geographical variations in prostate cancer incidence and in the frequency of curative treatment for prostate cancer in Sweden and there appear to be large geographical variations in the uptake of prostate cancer screening.

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PubMed2005

The National Prostate Cancer Register in Sweden 1998-2002: trends in incidence, treatment and survival.

OBJECTIVES: To provide a descriptive review of the establishment of the National Prostate Cancer Register (NPCR) in Sweden, to present clinical characteristics at diagnosis and to calculate the relative survival of different risk groups after 5 years. MATERIAL AND METHODS: Since 1998, data on all newly diagnosed prostate cancers, including TNM classification, grade of malignancy, prostate-specific antigen (PSA) level and treatment, have been prospectively collected. For the 35,223 patients diagnosed between 1998 and 2002, relative survival in different risk groups has been calculated. RESULTS: Between 1998 and 2002, 96% of all prostate cancer cases diagnosed in Sweden were registered in the NPCR. The number of new cases increased from 6137 in 1998 to 7385 in 2002. The age-standardized rate rose in those aged < 70 years, while it was stable, or possibly declining from 1999, in the older age groups. The proportion of T1c tumours increased from 14% to 28% of all recorded cases. The age-adjusted incidence of advanced tumours (M1 or PSA > 100 ng/ml) decreased by 17%. The proportion of patients receiving curative treatment doubled. Patients with N1 or M1 disease or poorly differentiated tumours (G3 or Gleason score 8-10) had a markedly reduced relative 5-year survival rate. CONCLUSIONS: It is possible to establish a nationwide prostate cancer register including basic data for assessment of the disease in the whole of Sweden. The introduction of PSA screening has increased the detection of early prostate cancer in younger men and, to a lesser extent, decreased the incidence of advanced disease. The effect of these changes on mortality is obscure but the NPCR in Sweden will serve as an important tool in such evaluation.

Age Distribution↗

PubMed2005

Proteomic analysis of protein expression in prostate cancer.

OBJECTIVE: To investigate protein expression in prostate cancer using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry. STUDY DESIGN: Cells were collected from 29 peripheral zone tumors and from benign tissue by scraping cut surfaces of radical prostatectomy specimens. Samples were suspended in a medium with protease inhibitors and prepared for 2-DE. Gels were analyzed, and protein spots that differed quantitatively between tumor and benign tissue were identified via mass spectrometric fingerprinting of tryptic fragments and tandem mass spectrometry sequence analysis. RESULTS: In total, 63 spots differed between cancer and benign samples (p < 0.01); 56 were overexpressed (> 1.5 fold) in cancer and 7 underexpressed (< 0.6 fold). Among overexpressed proteins were transcription factors (nucleoside diphosphate kinase 1) and enzymes involved in gene silencing (chromobox protein), protein synthesis (39S ribosomal protein L12, BiP protein, protein disulfide isomerase), degradation (cytosol aminopeptidase, endopeptidase Clp, inorganic pyrophosphatase) and energy metabolism (acyl-CoA dehydrogenase, isocitrate dehydrogenase, NADH-ubiquinone oxidoreductase, pyruvate dehydrogenase), heat-shock proteins (60 and 70 kd), structural proteins (cytokeratins) and membrane proteins (stomatinlike protein 2). CONCLUSION: The protein profile of prostate cancer differs from that of benign tissue. Several potential target proteins for detection or evaluation of prognosis in prostate cancer were identified.

Electrophoresis, Gel, Two-Dimensional↗

PubMed2004

Health-related quality of life in men after treatment of localized prostate cancer with external beam radiotherapy combined with (192)ir brachytherapy: a prospective study of 93 cases using the EORTC questionnaires QLQ-C30 and QLQ-PR25.

PURPOSE: To describe prospectively the long-term health-related quality of life (HRQOL) and treatment-related symptoms in patients with localized prostate cancer treated with neoadjuvant androgen deprivation therapy and radical radiotherapy (RT), including external beam RT and iridium high-dose-rate brachytherapy, and to compare them with age-matched normative data. METHODS AND MATERIALS: A total of 93 patients with T1-T3a tumors consecutively treated with definitive RT at our institution completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30 and QLQ-prostate specific 25-item (PR25) module twice at an 18-month interval 0-18 months after RT. Subgroups were analyzed regarding acute and late effects on symptoms and quality of life. RESULTS: The main analysis included 80 patients who were disease free at the final assessment. The levels of HRQOL were generally high, did not change over time, and were comparable to the normative data. Symptom development (urinary, bowel, and sexual) correlated well with the known acute and late effects of radical RT and neoadjuvant androgen deprivation therapy. CONCLUSION: Combining external beam RT and HDR brachytherapy when treating prostate cancer did not appear to impair HRQOL and was comparable to that of other brachytherapy methods. The negative contribution from late neoadjuvant androgen deprivation therapy on symptom development seemed to be substantial but mostly transitory. Additional research is needed to determine the long-term HRQOL (3-5 years), and interventional randomized studies are suggested.

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PubMed2003

Non-systematic screening for prostate cancer in Sweden--survey from the National Prostate Cancer Registry.

OBJECTIVE: The large increase in the incidence of prostate cancer is largely due to testing of serum levels of prostate-specific antigen (PSA). Little is known about how PSA testing is used in clinical practice outside of screening programmes. Essentially, PSA can be used in the health check-ups of men without symptoms as a form of non-systematic screening or in the work-up of symptomatic patients. The aim of this study was to investigate the cause of initiating a work-up leading to a diagnosis of prostate cancer, with emphasis on T1c tumours. MATERIAL AND METHODS: Data on the cause of initiation of work-up leading to a diagnosis of prostate cancer were retrieved from the National Prostate Cancer Registry for 6361 incident cases in tumour category T1c and local stages T2, T3 and T4 registered in Sweden in 2000. RESULTS: For 1496 cases in tumour category T1c (non-palpable tumours detected during work-up of elevated PSA), the cause of PSA testing was health check-ups in 32% of cases, work-up of symptoms suspected to emanate from the prostate in 51% and other causes/not reported in 17%. For all stages combined, the cause of initiation of the diagnostic work-up was health check-ups in 18% of cases, symptoms in 68% and other causes/not reported in 14%. CONCLUSION: Non-systematic screening using PSA testing has been introduced in Sweden. However, prostate cancer is still most commonly diagnosed during the work-up of symptomatic patients.

Age Distribution↗