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Busch, Christer
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Publications (10 of 22) Show all publications
O'Hurley, G., Busch, C., Fagerberg, L., Hallstrom, B. M., Stadler, C., Tolf, A., . . . Pontén, F. (2015). Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer. PLoS ONE, 10(8), Article ID e0133449.
Open this publication in new window or tab >>Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 8, e0133449Article in journal (Refereed) Published
Abstract [en]

To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-261245 (URN)10.1371/journal.pone.0133449 (DOI)000358942400012 ()26237329 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation
Available from: 2015-09-07 Created: 2015-08-31 Last updated: 2017-12-04Bibliographically approved
Mu, Y., Zang, G., Engström, U., Busch, C. & Landstrom, M. (2015). TGF beta-induced phosphorylation of Par6 promotes migration and invasion in prostate cancer cells. British Journal of Cancer, 112(7), 1223-1231.
Open this publication in new window or tab >>TGF beta-induced phosphorylation of Par6 promotes migration and invasion in prostate cancer cells
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2015 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, no 7, 1223-1231 p.Article in journal (Refereed) Published
Abstract [en]

Background: The Par complex - comprising partition-defective 6 (Par6), Par3, and atypical protein kinase C (aPKC) - is crucial for cell polarisation, the loss of which contributes to cancer progression. Transforming growth factor beta (TGF beta)-induced phosphorylation of Par6 on the conserved serine 345 is implicated in epithelial-to-mesenchymal transition (EMT) in breast cancer. Here we investigated the importance of phosphorylated Par6 in prostate cancer. Methods: We generated a p-Par6(345)-specific antibody and verified its specificity in vitro. Endogenous p-Par6(345) was analysed by immunoblotting in normal human prostate RWPE1 and prostate cancer (PC-3U) cells. Subcellular localisation of p-Par6(345) in migrating TGF beta-treated PC-3U cells was analysed by confocal imaging. Invasion assays of TGF beta-treated PC-3U cells were performed. p-Par6 expression was immunohistochemically analysed in prostate cancer tissues. Results: TGF beta induced Par6 phosphorylation on Ser345 and its recruitment to the leading edge of the membrane ruffle in migrating PC-3U cells, where it colocalised with aPKC zeta. The p-Par6-aPKC zeta complex is important for cell migration and invasion, as interference with this complex prevented prostate cancer cell invasion. High levels of activated Par6 correlated with aggressive prostate cancer. Conclusions: Increased p-Par6Ser(345) levels in aggressive prostate cancer tissues and cells suggest that it could be a useful novel biomarker for predicting prostate cancer progression.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-252201 (URN)10.1038/bjc.2015.71 (DOI)000352145300010 ()25756394 (PubMedID)
Available from: 2015-05-05 Created: 2015-05-04 Last updated: 2017-12-04Bibliographically approved
Bill-Axelson, A., Holmberg, L., Garmo, H., Rider, J. R., Taari, K., Busch, C., . . . Johansson, J.-E. (2014). Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer. New England Journal of Medicine, 370(10), 932-942.
Open this publication in new window or tab >>Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer
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2014 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, 932-942 p.Article in journal (Refereed) Published
Abstract [en]

BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. MethodsBetween 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. ResultsDuring 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). ConclusionsExtended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.) The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-225105 (URN)10.1056/NEJMoa1311593 (DOI)000332309800010 ()
Available from: 2014-05-27 Created: 2014-05-27 Last updated: 2017-12-05Bibliographically approved
Isfoss, B. L., Busch, C., Hermelin, H., Vermedal, A. T., Kile, M., Braathen, G. J., . . . Berner, A. (2014). Stem cell marker-positive stellate cells and mast cells are reduced in benign-appearing bladder tissue in patients with urothelial carcinoma. Virchows Archiv, 464(4), 473-488.
Open this publication in new window or tab >>Stem cell marker-positive stellate cells and mast cells are reduced in benign-appearing bladder tissue in patients with urothelial carcinoma
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2014 (English)In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 464, no 4, 473-488 p.Article in journal (Refereed) Published
Abstract [en]

Survival after invasive bladder cancer has improved less than that of other common non-skin cancers. In many types of malignancy, treatment failure has been attributed to therapy-resistant stem-like cancer cells. Our aim was therefore to determine identities of stem cell marker-positive cells in bladder cancer tissue and to investigate possible associations between these cells and different forms of bladder neoplasia. We investigated tissue from 52 patients with bladder neoplasia and 18 patients with benign bladder conditions, from a cohort that had been previously described with regard to diagnosis and outcome. The samples were analysed immunohistologically for the stem cell markers aldehyde dehydrogenase 1 A1 (ALDH1) and CD44, and markers of cell differentiation. The majority of stem cell marker-positive cells were located in connective tissue, and a smaller fraction in epithelial tissue. Stem cell marker-positive cells exhibiting possible stem cell characteristics included cells in deeper locations of benign and malignant epithelium, and sub-endothelial cells in patients with or without neoplasia. Stem cell marker-positive cells with non-stem cell character included stellate cells, mast cells, endothelial cells, foamy histiocytes, and neurons. Significantly, ALDH1+ stellate cells and ALDH1+ mast cells were reduced in number in stroma of benign-appearing mucosa of bladder cancer patients. The stem cell markers ALDH1 and CD44 label several types of differentiated cells in bladder tissue. ALDH1+ stellate cells and mast cells appear to be reduced in stroma of normal-appearing mucosa of bladder cancer patients, and may be part of a "field effect" in cancer-near areas.

Keyword
Bladder cancer, Tumour microenvironment, Stem cells, Stellate cells, Mast cells, Aldehyde dehydrogenase, CD44
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-224916 (URN)10.1007/s00428-014-1561-2 (DOI)000334174000010 ()
Available from: 2014-05-28 Created: 2014-05-23 Last updated: 2017-12-05Bibliographically approved
Azar, J., Busch, C. & Carlbom, I. (2012). Histological Stain Evaluation for Machine Learning Applications. In: Proceedings of the International Conference on Medical Image Computing and Computer Assisted Intervention: . Paper presented at MICCAI 2012, the 15th International Conference on Medical Image Computing and Computer Assisted Intervention, October 1-5, 2012, Nice, France. .
Open this publication in new window or tab >>Histological Stain Evaluation for Machine Learning Applications
2012 (English)In: Proceedings of the International Conference on Medical Image Computing and Computer Assisted Intervention, 2012Conference paper, Published paper (Refereed)
National Category
Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-183619 (URN)
Conference
MICCAI 2012, the 15th International Conference on Medical Image Computing and Computer Assisted Intervention, October 1-5, 2012, Nice, France
Available from: 2012-10-30 Created: 2012-10-30 Last updated: 2015-01-23
Oosterlinck, W., Kirkali, Z., Sylvester, R., da Silva, F. C., Busch, C., Algaba, F., . . . Bono, A. (2011). Sequential Intravesical Chemoimmunotherapy with Mitomycin C and Bacillus Calmette-Guerin and with Bacillus Calmette-Guerin Alone in Patients with Carcinoma in Situ of the Urinary Bladder: Results of an EORTC Genito-Urinary Group Randomized Phase 2 Trial (30993). European Urology, 59(3), 438-446.
Open this publication in new window or tab >>Sequential Intravesical Chemoimmunotherapy with Mitomycin C and Bacillus Calmette-Guerin and with Bacillus Calmette-Guerin Alone in Patients with Carcinoma in Situ of the Urinary Bladder: Results of an EORTC Genito-Urinary Group Randomized Phase 2 Trial (30993)
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2011 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 59, no 3, 438-446 p.Article in journal (Refereed) Published
Abstract [en]

Background: Bacillus Calmette-Guerin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS). Objective: Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR) is worthy of further study in non-muscle-invasive bladder cancer patients with CIS. Design, setting, and participants: In a noncomparative phase 2 study, 96 patients with primary/secondary/concurrent CIS of the urinary bladder were randomized to sequential MMC plus BCG or to BCG alone after TUR. Intervention: Patients received six weekly instillations of MMC followed by six weekly instillations of BCG or six weekly instillations of BCG, 3 wk rest, and three further weekly instillations of BCG. Complete responders received three weekly maintenance instillations at 6, 12, 18, 24, 30, and 36 mo in accordance with the initial randomization. Measurements: End points were complete response (CR) rate at the first control cystoscopy 16-18 wk after start of treatment, disease-free interval, overall survival, and side effects. Results and limitations: Ninety-six patients were randomized, 48 to each treatment group. Ten patients were ineligible, and three did not start treatment. In all random-ized patients, CR rates on MMC plus BCG and BCG alone were 70.8% and 66.7%, respectively. In 83 eligible patients who started treatment, CR rates were 75.6% and 73.8%, respectively. Based on a median follow-up of 4.7 yr, 25 patients (52.1%) on MMC plus BCG and 22 patients (45.8%) on BCG alone were disease free. Twelve patients stopped treatment due to toxicity: three during induction (two MMC plus BCG, one BCG) and nine during maintenance (three MMC plus BCG, six BCG). Conclusions: In the treatment of patients with CIS, sequential chemoimmunotherapy with MMC plus BCG had acceptable toxicity. CR and disease-free rates were similar to those on BCG alone and to previous publications on sequential chemoimmunotherapy.

Keyword
Bacillus Calmette-Guerin, Carcinoma in situ, Intravesical therapy, Mitomycin C, Non-muscle-invasive bladder cancer, Randomized clinical trial, Urinary bladder
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-148966 (URN)10.1016/j.eururo.2010.11.038 (DOI)000286658600030 ()
Available from: 2011-03-14 Created: 2011-03-14 Last updated: 2017-12-11Bibliographically approved
Grundmark, B., Garmo, H., Loda, M., Busch, C., Holmberg, L. & Zethelius, B. (2010). The Metabolic Syndrome and the Risk of Prostate Cancer under Competing Risks of Death from Other Causes. Cancer Epidemiology, Biomarkers and Prevention, 19(8), 2088-2096.
Open this publication in new window or tab >>The Metabolic Syndrome and the Risk of Prostate Cancer under Competing Risks of Death from Other Causes
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2010 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 8, 2088-2096 p.Article in journal (Refereed) Published
Abstract [en]

Background:

Associations between metabolic syndrome (MetS) components and prostate cancer development have not been studied comprehensively; results have been divergent. Using the National Cholesterol Education Program Adult Treatment panel III (NCEP) and International Diabetes Federation (IDF) definitions of the MetS, we investigated such associations taking competing risks of death into consideration.

Methods:

In the prospective Uppsala Longitudinal Study of Adult Men of 2,322 Caucasian men with 34 years of follow-up baseline, MetS measurements at age 50 years were used. Cumulative incidence of prostate cancer and death with/without the MetS were calculated. Competing risk of dying was taken into account by calculating the conditional probability of prostate cancer with/without the MetS.

Results:

Two hundred and thirty-seven prostate cancers were identified. Prostate cancer probability by age 80 years with baseline MetS compared with without MetS was nonsignificantly higher [5.2 percent units (confidence interval (CI), -0.8% to 11.3%; NCEP); 2.7 percent units (CI, -2.7% to 8.0%; IDF)]; cumulative incidence proportions of death was significantly higher [19.3 percent units (CI, 13.4-25.3%; NCEP); 15.3 percent units (CI, 9.5-21.1%; IDF)]; and conditional probability of prostate cancer considering death from other causes was significantly higher [7.3 percent-units (CI, 0.2-14.5%); odds ratio of 1.64 (CI, 1.03-2.23; NCEP)] and nonsignificantly higher [5.0 percent-units (CI, -1.6% to 11.6%); odds ratio of 1.43 (CI, 0.89-1.90; IDF].

Conclusions:

The MetS by the NCEP definition is associated with prostate cancer, taking the competing risk of early death from other causes into account. Impact: The results further highlight the public health effect of the increasing prevalence of MetS and the importance of considering competing risks when studying risk factors for cancer.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-135608 (URN)10.1158/1055-9965.EPI-10-0112 (DOI)000280675000023 ()20647401 (PubMedID)
Available from: 2010-12-07 Created: 2010-12-07 Last updated: 2017-12-11Bibliographically approved
Glaessgen, A., Busch, C., Norberg, M., Häggman, M., Nilsson, B. & Egevad, L. (2006). Prediction of percent Gleason grade 4/5 by multiple core biopsies. Scandinavian Journal of Urology and Nephrology, 40(6), 465-471.
Open this publication in new window or tab >>Prediction of percent Gleason grade 4/5 by multiple core biopsies
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2006 (English)In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 40, no 6, 465-471 p.Article in journal (Refereed) Published
Abstract [en]

Objective. To evaluate whether percent Gleason grade 4/5 (i.e. the proportion of a tumor occupied by high-grade cancer) can be predicted by multiple needle biopsies. Material and methods. In 115 men, 8-14 (mean 10) biopsies were taken, including eight from standardized positions (apex, mid-medial, mid-lateral and base). Biopsies were reviewed and cancer lengths measured. All men underwent radical prostatectomy. The prostatectomy specimens were totally embedded and tumor volume measured planimetrically. Gleason scores and percent Gleason grade 4/5 were assessed for both biopsy and prostatectomy specimens. Results. Percent Gleason grade 4/5 in prostatectomy specimens was predicted correctly in 34% of cases and within 10%, 20% and 30% in 55%, 64% and 73% of cases, respectively. Biopsies had a sensitivity, specificity and accuracy for Gleason grade 4/5 of 62%, 87% and 69%, respectively. Positive and negative predictive values were 93% and 45%, respectively. The weighted kappa value for agreement was slightly higher for Gleason score (0.685) than for percent Gleason grade 4/5 (0.573). The univariate correlation for percent Gleason grade 4/5 in biopsies and the main tumor was r = 0.62, r(2) = 0.39 (p < 0.001). In univariate logistic regression, percent Gleason grade 4/5 on biopsies predicted the presence of any Gleason grade 4/5 cancer in the main tumor (p = 0.009). Conclusions. Gleason grade 4/5 in prostatectomy specimens correlates with findings in preoperative biopsies. Whether this measure will be used in routine practice remains to be seen.

Keyword
prostatectomy, needle biopsies, Gleason grading, pathology of prostatic neoplasms, classification of prostatic neoplasms
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-11032 (URN)10.1080/00365590600917578 (DOI)000242333000004 ()17130098 (PubMedID)
Available from: 2008-02-11 Created: 2008-02-11 Last updated: 2017-12-11Bibliographically approved
Kirkali, Z., Chan, T., Manoharan, M., Algaba, F., Busch, C., Cheng, L., . . . Weider, J. (2005). Bladder cancer: epidemiology, staging and grading, and diagnosis.. Urology, 66(6 Suppl 1), 4-34.
Open this publication in new window or tab >>Bladder cancer: epidemiology, staging and grading, and diagnosis.
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2005 (English)In: Urology, ISSN 1527-9995, Vol. 66, no 6 Suppl 1, 4-34 p.Article in journal (Refereed) Published
Keyword
Bladder Neoplasms/classification/*diagnosis/*epidemiology/etiology, Environmental Exposure, Humans, Incidence, Neoplasm Staging, Risk Factors
Identifiers
urn:nbn:se:uu:diva-80667 (URN)16399414 (PubMedID)
Available from: 2006-05-19 Created: 2006-05-19 Last updated: 2011-01-11
Oosterlinck, W., Solsona, E., Akaza, H., Busch, C., Goebell, P. J., Malmstrom, P.-U., . . . Sved, P. (2005). Low-grade Ta (noninvasive) urothelial carcinoma of the bladder.. Urology, 66(6 Suppl 1), 75-89.
Open this publication in new window or tab >>Low-grade Ta (noninvasive) urothelial carcinoma of the bladder.
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2005 (English)In: Urology, ISSN 1527-9995, Vol. 66, no 6 Suppl 1, 75-89 p.Article in journal (Refereed) Published
Keyword
Algorithms, Bladder Neoplasms/diagnosis/*pathology/therapy, Carcinoma; Transitional Cell/diagnosis/*pathology/therapy/urine, Combined Modality Therapy, Cystoscopy, Humans, Kidney Neoplasms/secondary, Prognosis, Reproducibility of Results, Tumor Markers; Biological/urine, Ureteral Neoplasms/secondary
Identifiers
urn:nbn:se:uu:diva-80666 (URN)16399417 (PubMedID)
Available from: 2007-04-16 Created: 2007-04-16 Last updated: 2011-01-11
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