Aud Svindland - Academia.edu (original) (raw)

Papers by Aud Svindland

Research paper thumbnail of 1061 Detection of the index tumor and tumor volume in prostate cancer using T2w and DW MRI alone

European Urology Supplements, Apr 1, 2014

Research paper thumbnail of Localization of atherosclerotic lesions in the bifurcation of the main left coronary artery

Atherosclerosis, 1983

The detailed distribution of atherosclerotic lesions in the branching region of the left main cor... more The detailed distribution of atherosclerotic lesions in the branching region of the left main coronary artery in man was studied. Tissue cubes of the hearts, containing the left coronary arteries, were removed, and 1.5-mm-thick parallel and consecutive slices were cut perpendicular to the main coronary artery. Histological sections of the slices were stained and photographed.

Research paper thumbnail of Abstract 2210: Scavenging for lethal prostate cancer biomarkers in FFPE tissue

Cancer Research, 2017

The aim of this study was to identify protein biomarkers that can be used to stratify indolent an... more The aim of this study was to identify protein biomarkers that can be used to stratify indolent and aggressive prostate cancer using formalin-fixed paraffin-embedded tissue (FFPE) from radical prostatectomy specimens. The protein expression profiles of benign and malign samples from 23 patients, who had either died of prostate cancer or were alive 10 years after diagnosis, were determined using an Easy nLC1000 Nano-LC system connected to a quadrupole-Orbitrap (Q Exactive) mass spectrometer equipped with a nanoelectrospray ion source. The generated MS raw files were submitted to MaxQuant software for protein identification. Differential expression of LFQ-normalized intensities was tested by Cox proportional hazards modeling and LASSO (least absolute shrinkage and selection operator) regression analysis within the R software environment. The label free Orbitrap analysis identified 3523 unique proteins from the FFPE tissue samples. LASSO of protein expression profiles of indolent and ag...

Research paper thumbnail of The effect of bicalutamide on prostate histology

The Prostate, 2001

Nonsteroidal antiandrogens are commonly used in the treatment of prostate cancer, but more clinic... more Nonsteroidal antiandrogens are commonly used in the treatment of prostate cancer, but more clinical and laboratory studies on patients with benign as well as malignant prostate diseases are required to define their exact role. Light microscopic examination of perineal prostate biopsies of 21 men with BPH was performed pretreatment, after 24 weeks of therapy with 50 mg bicalutamide (Casodex) or placebo and 24 weeks after end of treatment. We assessed whether it was possible to distinguish between patients having received bicalutamide or placebo based on a general histological examination. In addition, the volume fractions of the prostatic epithelial, luminal, and stromal compartments were determined by morphometry. Histological changes following treatment were uncharacteristic and patients treated with bicalutamide were not identified. At morphometry prior to therapy, the prostates of the study participants consisted of 91.8% stroma (range 78.9-97.2), 5.5% epithelium (range 1.4-14.1) and 2.7% glandular lumen (range 0.8-7.5). Changes in the relative content of the three tissue components following treatment were not statistically significant. We did not observe consistent morphological changes in the prostate following treatment with bicalutamide at a dose of 50 mg daily. However, this dose is lower than the 150 mg dose presently recommended for bicalutamide monotherapy.

Research paper thumbnail of Robotic salvage pelvic lymph node dissection for locoregional recurrence after radical prostatectomy: a single institution experience

Scandinavian Journal of Urology, 2021

Objectives: To assess treatment response (PSA < 0.2 ng/ml), need for additional therapy and compl... more Objectives: To assess treatment response (PSA < 0.2 ng/ml), need for additional therapy and complication rate after robot assisted salvage pelvic lymph node dissection (sPLND) Material and Methods: Analysis of outcomes data from radical prostatectomy (RP) patients consecutively operated with robot assisted sPLND due to biochemical recurrence and positron-emission tomography (PET)/computed tomography (CT)-detected nodal recurrence of pelvic lymph nodes. Results: Sixty-nine patients underwent robotic sPLND after a median time of 47 months post-RP. Sixty-four patients (93%) had malignant lymph nodes upon histological assessment of sPLND specimen. Twenty patients (29%) achieved PSA < 0.2 ng/ml 6 weeks postoperatively. After median (IQR) follow-up of 15 months (10-27), fourteen patients (20%) still had PSA < 0.2 ng/ml without additional therapy and forty-one patients (59%) had started additional therapy. No significant predictor for treatment response was found. Postoperative complications occurred in 14 patients (20%). Eleven of these complications were classified as Clavien-Dindo grade 1 Conclusion: Oncological benefit of sPLND as the only salvage procedure seems to be limited, though almost one third of patients achieved treatment response. Clinical trials are needed to determine if sPLND as part of a multimodal treatment may improve outcome.

Research paper thumbnail of A Randomized Controlled Trial To Assess and Compare the Outcomes of Two-core Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound Images and Traditional 12-core Systematic Biopsy

European urology, Jan 7, 2015

Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging (MRI) and transr... more Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) images (MRI group) has not yet been compared with 12-core random biopsy (RB; control group) in a randomized controlled trial (RCT). To compare the rate of detection of clinically significant prostate cancer (csPCa) between the two groups. This RCT included 175 biopsy-naïve patients with suspicion for prostate cancer, randomized to an MRI group (n=86) and a control group (n=89) between September 2011 and June 2013. In the MRI group, two-core targeted biopsy (TB) guided by computer-assisted fusion of MRI/TRUS images of MRI-suspicious lesions was followed by 12-core RB. In the control group, both two-core TB for abnormal digital rectal examination (DRE) and/or TRUS-suspicious lesions and 12-core RB were performed. In patients with normal MRI or DRE/TRUS, only 12-core RB was performed. The detection rates for any cancer and csPCa were compared between the two groups a...

Research paper thumbnail of Does Preoperative Magnetic Resonance Imaging Reduce the Rate of Positive Surgical Margins at Radical Prostatectomy in a Randomised Clinical Trial?

European urology, Jan 23, 2015

Magnetic resonance imaging (MRI) has the potential to help the surgeon tailor radical prostatecto... more Magnetic resonance imaging (MRI) has the potential to help the surgeon tailor radical prostatectomy (RP) more accurately according to the location and extent of the tumour and thereby reduce the rate of positive surgical margins (PSMs). To evaluate the benefit of performing MRI prior to RP. This single-institution randomised trial included 438 patients between December 2009 and June 2012 who were scheduled for robot-assisted laparoscopic prostatectomy. The study was registered (ClinicalTrials.gov identifier NCT01347320). Patients were preoperatively randomly assigned to non-MRI or MRI groups. The primary end point was the difference in the PSM rates between the two groups. Secondary end points were the rates of PSMs in clinical subgroups. Summary statistics were extracted from descriptive analyses, chi-square, or Fisher exact test, and logistic regression was used to analyse the data according to the intention-to-treat principle. A total of 216 patients were randomised to non-MRI; 2...

Research paper thumbnail of Does a surgeon's annual radical prostatectomy volume predict the risk of positive surgical margins and urinary incontinence at one-year follow-up? - Findings from a prospective national study

Scandinavian Journal of Urology, 2012

This study aimed to assess the prevalence of positive surgical margins (PSM) and urinary incontin... more This study aimed to assess the prevalence of positive surgical margins (PSM) and urinary incontinence (UI) in relation to surgeons&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; annual radical prostatectomy (RP) volume. This national study prospectively assessed 521 preoperatively continent patients with prostate cancer (PCa), scheduled for RP by surgeons with high (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50), medium (20-50) or low annual volume (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;20) at 14 urological departments in Norway. Patients responded to UI questions from the Expanded Composite prostate cancer index (EPIC-50) before and 1 year after RP. UI was defined as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;use of pad(s)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and/or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;a moderate or severe urinary leakage problem (ULP)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;. Preoperative prediction of PSMs and UI was explored in multivariate regression analyses with the following independent variables: surgeons&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; annual RP volume, type of hospital (university versus community), patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s health, sociodemographic features and PCa characteristics. Based on histopathological reports, the overall PSM rate was 26%, with differences between the high- (18%), medium- (28%) and low-volume (44%) groups. Increasing PSM rates were predicted by surgeons belonging to the low- and medium-volume categories, prostate-specific antigen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 10 µg/l, Gleason score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;7, patient age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;65 years and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;12 years of education. At 1-year follow-up 40% reported UI, without…

Research paper thumbnail of Regulation of PBX3 in Prostate Cancer

European Urology Supplements, 2008

Research paper thumbnail of O-GlcNAc Transferase Integrates Metabolic Pathways to Regulate the Stability of c-MYC in Human Prostate Cancer Cells

Cancer Research, 2013

Metabolic disruptions that occur widely in cancers offer an attractive focus for generalized trea... more Metabolic disruptions that occur widely in cancers offer an attractive focus for generalized treatment strategies. The hexosamine biosynthetic pathway (HBP) senses metabolic status and produces an essential substrate for O-linked β-N-acetylglucosamine transferase (OGT), which glycosylates and thereby modulates the function of its target proteins. Here, we report that the HBP is activated in prostate cancer cells and that OGT is a central regulator of c-Myc stability in this setting. HBP genes were overexpressed in human prostate cancers and androgen regulated in cultured human cancer cell lines. Immunohistochemical analysis of human specimens (n = 1987) established that OGT is upregulated at the protein level and that its expression correlates with high Gleason score, pT and pN stages, and biochemical recurrence. RNA interference–mediated siliencing or pharmacologic inhibition of OGT was sufficient to decrease prostate cancer cell growth. Microarray profiling showed that the princip...

Research paper thumbnail of The Movember Global Action Plan 1 (GAP1): Unique Prostate Cancer Tissue Microarray Resource

Cancer Epidemiology, Biomarkers & Prevention, 2022

Background: The need to better understand the molecular underpinnings of the heterogeneous outcom... more Background: The need to better understand the molecular underpinnings of the heterogeneous outcomes of patients with prostate cancer is a pressing global problem and a key research priority for Movember. To address this, the Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project constructed a set of unique and richly annotated tissue microarrays (TMA) from prostate cancer samples obtained from multiple institutions across several global locations. Methods: Three separate TMA sets were built that differ by purpose and disease state. Results: The intended use of TMA1 (Primary Matched LN) is to validate biomarkers that help determine which clinically localized prostate cancers with associated lymph node metastasis have a high risk of progression to lethal castration-resistant metastatic disease, and to compare molecular properties of high-risk index lesions within the prostate to regional lymph node metastases resected at the time of prostatectomy. TMA2 (Pre vs. Pos...

Research paper thumbnail of Histological Analysis of a Long Term Patent Subintimal Canal in the Superficial Femoral Artery

EJVES Vascular Forum, 2021

Introduction Subintimal angioplasty (SIA) was introduced in the late 1980s and is a supplement to... more Introduction Subintimal angioplasty (SIA) was introduced in the late 1980s and is a supplement to bypass surgery. Adaptation of the technique has been hampered by high rates of early intervention to maintain patency, but the long term assisted patency is good. Report The superficial femoral and popliteal artery containing a patent subintimal canal were explanted from a patient who died in the authors' ward. Histological analysis indicated that the lumen was created in the medial layer of the vessel wall. A collagen rich neointima and fragmented internal elastic lamina were observed, presumably as a result of activated smooth muscle cells. The luminal surface was partly covered by a single layer of CD31, von Willebrand factor, and partly CD144 positive cells. An early atherosclerotic lesion was observed distally in the subintimal canal. Discussion Remodelling and neo-cellularisation of the vascular wall after SIA are described. Notably, hallmarks of early and late stage atheroscl...

Research paper thumbnail of Proteomic analyses identify major vault protein as a prognostic biomarker for fatal prostate cancer

Carcinogenesis, 2021

The demographic shift toward an older population will increase the number of prostate cancer case... more The demographic shift toward an older population will increase the number of prostate cancer cases. A challenge in the treatment of prostate cancer is to avoid undertreatment of patients at high risk of progression following curative treatment. These men can benefit from early salvage treatment. An explorative cohort consisting of tissue from 16 patients who underwent radical prostatectomy, and were either alive or had died from prostate cancer within 10 years postsurgery, was analyzed by mass spectrometry analysis. Following proteomic and bioinformatic analyses, major vault protein (MVP) was identified as a putative prognostic biomarker. A publicly available tissue proteomics dataset and a retrospective cohort of 368 prostate cancer patients were used for validation. The prognostic value of the MVP was verified by scoring immunohistochemical staining of a tissue microarray. High level of MVP was associated with more than 4-fold higher risk for death from prostate cancer (hazard rat...

Research paper thumbnail of Abstract A01: ADRB2 regulates phase II steroid metabolism and determines development of castration-resistant prostate cancer

Molecular Cancer Research, 2016

The underlying mechanisms responsible for the development of castration-resistant prostate cancer... more The underlying mechanisms responsible for the development of castration-resistant prostate cancer (CRPC) are not fully understood. The β2-adrenergic receptor (ADRB2) is a key regulator of a wide range of metabolic processes in the body, and it has been implicated in androgen receptor signaling and development of CRPC. We have unpublished data which shows that low expression of ADRB2 predicts a more rapid development of CRPC. Based on this finding, we wanted to investigate whether the ADRB2 level/activity impacts cellular features to help explain how and why the receptor has prognostic value in prostate cancer. We stably transfected androgen-dependent LNCaP cells with shRNAs to mimic the clinical situation where patients have differential levels of ADRB2 in their prostate epithelial carcinomas. Gene expression profiling revealed changes in expression of several metabolic genes. Among the most regulated were two androgen-glucuronidating UDP-glucuronosyltransferase 2B (UGT2B) enzymes, ...

Research paper thumbnail of Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA

Clinical nutrition (Edinburgh, Scotland), Jun 30, 2016

The effect of lycopene-containing foods in prostate cancer development remains undetermined. We t... more The effect of lycopene-containing foods in prostate cancer development remains undetermined. We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen (PSA) in prostate cancer patients. Prior to their curative treatment, 79 patients with prostate cancer were randomized to a nutritional intervention with either 1) tomato products containing 30 mg lycopene per day; 2) tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice, and green/black tea (tomato-plus); or 3) control diet for 3 weeks. The main analysis, which included patients in all risk categories, did not reveal differences in changes of PSA-values between the intervention and control groups. Post-hoc, exploratory analyses within intermediate risk (n = 41) patients based on tumor classification and Gleason score post-surgery, revealed that median PSA decreased significantly in the tomato group as compared to controls (-2.9% and +6.5% respecti...

Research paper thumbnail of Preoperative magnetic resonance imaging for detecting uni- and bilateral extraprostatic disease in patients with prostate cancer

World Journal of Urology, 2014

Research paper thumbnail of Morphometry of benign prostatic hyperplasia during androgen suppressive therapy. Relationships among epithelial content, PSA density, and clinical outcome

Scandinavian journal of urology and nephrology. Supplementum, 1996

We performed light microscopic morphometry on prostate biopsies of 41 patients who underwent andr... more We performed light microscopic morphometry on prostate biopsies of 41 patients who underwent androgen suppressive therapy for 24 weeks with the luteinizing hormone releasing hormone (LHRH) agonist leuprolide depot for symptomatic benign prostatic hyperplasia (BPH). Before treatment started, the prostates consisted of 88.4% stroma, 9.0% epithelium and 2.6% glandular lumen. After completion of therapy, the percentages were 94.7, 3.0 and 2.3, respectively. The absolute reductions of volume were 27% for stroma, 77% for epithelium and 40% for lumen. Correlations between pretreatment parameters (epithelial content, stromal epithelial ratio and prostate specific antigen density (PSAD)) and the clinical outcome parameters (prostate volume reduction, improvement in maximum flow rate, reduction of symptom score and reduction in outflow resistance) were not statistically significant, indicating that the histological composition of BPH tissue or PSAD are poor parameters to predict differences i...

Research paper thumbnail of Can prostate epithelial content predict response to hormonal treatment of patients with benign prostatic hyperplasia?

Urology, 2000

There are large interindividual differences in response to medical therapy for men with benign pr... more There are large interindividual differences in response to medical therapy for men with benign prostatic hyperplasia. Selection of patients for alpha-blocker versus hormonal treatment is often based more on assumptions than on well-documented knowledge. A more scientifically based decision of therapy has a potential for economical savings and increased effectiveness. We performed morphometry on prostate biopsy specimens and determined the amount of stroma, epithelium, and glandular lumen (pretreatment characteristics) in 34 men with benign prostatic hyperplasia before 24 weeks of androgen suppressive therapy. Androgen suppressive therapy consisted of either the luteinizing hormone-releasing hormone agonist leuprolide depot (3.75 mg intramuscularly every 28 days) or the nonsteroidal antiandrogen bicalutamide (50 mg/day orally). The evaluation of the clinical response (effectiveness parameters) was based on changes in prostate volume, peak urinary flow rate, symptom score, and bladder outlet obstruction. A large prostate volume before treatment was associated with more pronounced symptom score improvement, but neither prostate-specific antigen nor any of the parameters of tissue composition used (percentage of epithelium, epithelial volume, and stromal/epithelial ratio) predicted a favorable response to hormonal treatment. The pretreatment variables that are readily available at present have a limited role in helping clinicians to decide the optimal medical treatment for patients with benign prostatic hyperplasia.

Research paper thumbnail of Abstract A46: Effects of genistein supplementation on genome-wide DNA methylation and gene expression in patients with localized prostate cancer

Cancer Research, 2016

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer ... more Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer death among men in the United States, with an estimated 220,800 new cases and 27,540 deaths in 2015. Epidemiological studies have shown that dietary compounds have significant effects on prostate carcinogenesis. Among dietary agents, genistein, the major isoflavone in soybean, is of particular interest because high consumption of soy products has been associated with a low incidence of prostate cancer, suggesting a preventive role of genistein in prostate cancer. In spite of numerous studies to understand the effects of genistein on prostate cancer, the mechanisms of action have not been fully elucidated. Here, we investigated the differences in methylation and gene expression levels of prostate specimens from a clinical trial of genistein supplementation prior to prostatectomy (Lazarevic B, et al. Nutr Cancer 2011). This study was a randomized, placebo-controlled, double-blind clinical trial on forty-seven Norwegian patients who received 30 mg genistein or placebo capsules daily for 3-6 weeks before prostatectomy. Whole genome methylation and expression profiling identified significantly differentially methylated sites and expressed sites between placebo and genistein groups. Differentially regulated genes were involved in developmental processes, stem cell markers, proliferation, and transcriptional regulation. These findings highlight the effects of genistein on global changes in DNA methylation and gene expression in prostate cancer, and provide additional insight into the multiple molecular pathways involved in prostate tumorigenesis. Citation Format: Birdal Bilir, Jeongseok Edward Lee, Nitya V. Sharma, Bato Lazarevic, Aud Svindland, Omer Kucuk, Carlos S. Moreno. Effects of genistein supplementation on genome-wide DNA methylation and gene expression in patients with localized prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr A46.

Research paper thumbnail of Prognostic, predictive and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer

Molecular oncology, Jan 14, 2018

We aimed to refine the value of CDX2 as an independent prognostic and predictive biomarker in col... more We aimed to refine the value of CDX2 as an independent prognostic and predictive biomarker in colorectal cancer (CRC) according to disease stage and chemotherapy sensitivity in preclinical models. CDX2 expression was evaluated in 1045 stage I-IV primary CRCs by gene expression (n=403) or immunohistochemistry (n=642) and in relation to 5-year relapse-free survival (RFS), overall survival (OS), and chemotherapy. Pharmacogenomic associations between CDX2 expression and 69 chemotherapeutics were assessed by drug screening of 35 CRC cell lines. CDX2 expression was lost in 11.6% of cases and showed independent poor prognostic value in multivariable models. For individual stages, CDX2 was prognostic only in stage IV, independent of chemotherapy. Among stage I-III patients not treated in an adjuvant setting, CDX2 loss was associated with a particularly poor survival in the BRAF-mutated subgroup, but prognostic value was independent of microsatellite instability status and the consensus mole...

Research paper thumbnail of 1061 Detection of the index tumor and tumor volume in prostate cancer using T2w and DW MRI alone

European Urology Supplements, Apr 1, 2014

Research paper thumbnail of Localization of atherosclerotic lesions in the bifurcation of the main left coronary artery

Atherosclerosis, 1983

The detailed distribution of atherosclerotic lesions in the branching region of the left main cor... more The detailed distribution of atherosclerotic lesions in the branching region of the left main coronary artery in man was studied. Tissue cubes of the hearts, containing the left coronary arteries, were removed, and 1.5-mm-thick parallel and consecutive slices were cut perpendicular to the main coronary artery. Histological sections of the slices were stained and photographed.

Research paper thumbnail of Abstract 2210: Scavenging for lethal prostate cancer biomarkers in FFPE tissue

Cancer Research, 2017

The aim of this study was to identify protein biomarkers that can be used to stratify indolent an... more The aim of this study was to identify protein biomarkers that can be used to stratify indolent and aggressive prostate cancer using formalin-fixed paraffin-embedded tissue (FFPE) from radical prostatectomy specimens. The protein expression profiles of benign and malign samples from 23 patients, who had either died of prostate cancer or were alive 10 years after diagnosis, were determined using an Easy nLC1000 Nano-LC system connected to a quadrupole-Orbitrap (Q Exactive) mass spectrometer equipped with a nanoelectrospray ion source. The generated MS raw files were submitted to MaxQuant software for protein identification. Differential expression of LFQ-normalized intensities was tested by Cox proportional hazards modeling and LASSO (least absolute shrinkage and selection operator) regression analysis within the R software environment. The label free Orbitrap analysis identified 3523 unique proteins from the FFPE tissue samples. LASSO of protein expression profiles of indolent and ag...

Research paper thumbnail of The effect of bicalutamide on prostate histology

The Prostate, 2001

Nonsteroidal antiandrogens are commonly used in the treatment of prostate cancer, but more clinic... more Nonsteroidal antiandrogens are commonly used in the treatment of prostate cancer, but more clinical and laboratory studies on patients with benign as well as malignant prostate diseases are required to define their exact role. Light microscopic examination of perineal prostate biopsies of 21 men with BPH was performed pretreatment, after 24 weeks of therapy with 50 mg bicalutamide (Casodex) or placebo and 24 weeks after end of treatment. We assessed whether it was possible to distinguish between patients having received bicalutamide or placebo based on a general histological examination. In addition, the volume fractions of the prostatic epithelial, luminal, and stromal compartments were determined by morphometry. Histological changes following treatment were uncharacteristic and patients treated with bicalutamide were not identified. At morphometry prior to therapy, the prostates of the study participants consisted of 91.8% stroma (range 78.9-97.2), 5.5% epithelium (range 1.4-14.1) and 2.7% glandular lumen (range 0.8-7.5). Changes in the relative content of the three tissue components following treatment were not statistically significant. We did not observe consistent morphological changes in the prostate following treatment with bicalutamide at a dose of 50 mg daily. However, this dose is lower than the 150 mg dose presently recommended for bicalutamide monotherapy.

Research paper thumbnail of Robotic salvage pelvic lymph node dissection for locoregional recurrence after radical prostatectomy: a single institution experience

Scandinavian Journal of Urology, 2021

Objectives: To assess treatment response (PSA < 0.2 ng/ml), need for additional therapy and compl... more Objectives: To assess treatment response (PSA < 0.2 ng/ml), need for additional therapy and complication rate after robot assisted salvage pelvic lymph node dissection (sPLND) Material and Methods: Analysis of outcomes data from radical prostatectomy (RP) patients consecutively operated with robot assisted sPLND due to biochemical recurrence and positron-emission tomography (PET)/computed tomography (CT)-detected nodal recurrence of pelvic lymph nodes. Results: Sixty-nine patients underwent robotic sPLND after a median time of 47 months post-RP. Sixty-four patients (93%) had malignant lymph nodes upon histological assessment of sPLND specimen. Twenty patients (29%) achieved PSA < 0.2 ng/ml 6 weeks postoperatively. After median (IQR) follow-up of 15 months (10-27), fourteen patients (20%) still had PSA < 0.2 ng/ml without additional therapy and forty-one patients (59%) had started additional therapy. No significant predictor for treatment response was found. Postoperative complications occurred in 14 patients (20%). Eleven of these complications were classified as Clavien-Dindo grade 1 Conclusion: Oncological benefit of sPLND as the only salvage procedure seems to be limited, though almost one third of patients achieved treatment response. Clinical trials are needed to determine if sPLND as part of a multimodal treatment may improve outcome.

Research paper thumbnail of A Randomized Controlled Trial To Assess and Compare the Outcomes of Two-core Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound Images and Traditional 12-core Systematic Biopsy

European urology, Jan 7, 2015

Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging (MRI) and transr... more Prostate biopsy guided by computer-assisted fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) images (MRI group) has not yet been compared with 12-core random biopsy (RB; control group) in a randomized controlled trial (RCT). To compare the rate of detection of clinically significant prostate cancer (csPCa) between the two groups. This RCT included 175 biopsy-naïve patients with suspicion for prostate cancer, randomized to an MRI group (n=86) and a control group (n=89) between September 2011 and June 2013. In the MRI group, two-core targeted biopsy (TB) guided by computer-assisted fusion of MRI/TRUS images of MRI-suspicious lesions was followed by 12-core RB. In the control group, both two-core TB for abnormal digital rectal examination (DRE) and/or TRUS-suspicious lesions and 12-core RB were performed. In patients with normal MRI or DRE/TRUS, only 12-core RB was performed. The detection rates for any cancer and csPCa were compared between the two groups a...

Research paper thumbnail of Does Preoperative Magnetic Resonance Imaging Reduce the Rate of Positive Surgical Margins at Radical Prostatectomy in a Randomised Clinical Trial?

European urology, Jan 23, 2015

Magnetic resonance imaging (MRI) has the potential to help the surgeon tailor radical prostatecto... more Magnetic resonance imaging (MRI) has the potential to help the surgeon tailor radical prostatectomy (RP) more accurately according to the location and extent of the tumour and thereby reduce the rate of positive surgical margins (PSMs). To evaluate the benefit of performing MRI prior to RP. This single-institution randomised trial included 438 patients between December 2009 and June 2012 who were scheduled for robot-assisted laparoscopic prostatectomy. The study was registered (ClinicalTrials.gov identifier NCT01347320). Patients were preoperatively randomly assigned to non-MRI or MRI groups. The primary end point was the difference in the PSM rates between the two groups. Secondary end points were the rates of PSMs in clinical subgroups. Summary statistics were extracted from descriptive analyses, chi-square, or Fisher exact test, and logistic regression was used to analyse the data according to the intention-to-treat principle. A total of 216 patients were randomised to non-MRI; 2...

Research paper thumbnail of Does a surgeon's annual radical prostatectomy volume predict the risk of positive surgical margins and urinary incontinence at one-year follow-up? - Findings from a prospective national study

Scandinavian Journal of Urology, 2012

This study aimed to assess the prevalence of positive surgical margins (PSM) and urinary incontin... more This study aimed to assess the prevalence of positive surgical margins (PSM) and urinary incontinence (UI) in relation to surgeons&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; annual radical prostatectomy (RP) volume. This national study prospectively assessed 521 preoperatively continent patients with prostate cancer (PCa), scheduled for RP by surgeons with high (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50), medium (20-50) or low annual volume (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;20) at 14 urological departments in Norway. Patients responded to UI questions from the Expanded Composite prostate cancer index (EPIC-50) before and 1 year after RP. UI was defined as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;use of pad(s)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; and/or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;a moderate or severe urinary leakage problem (ULP)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;. Preoperative prediction of PSMs and UI was explored in multivariate regression analyses with the following independent variables: surgeons&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; annual RP volume, type of hospital (university versus community), patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s health, sociodemographic features and PCa characteristics. Based on histopathological reports, the overall PSM rate was 26%, with differences between the high- (18%), medium- (28%) and low-volume (44%) groups. Increasing PSM rates were predicted by surgeons belonging to the low- and medium-volume categories, prostate-specific antigen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 10 µg/l, Gleason score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;7, patient age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;65 years and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;12 years of education. At 1-year follow-up 40% reported UI, without…

Research paper thumbnail of Regulation of PBX3 in Prostate Cancer

European Urology Supplements, 2008

Research paper thumbnail of O-GlcNAc Transferase Integrates Metabolic Pathways to Regulate the Stability of c-MYC in Human Prostate Cancer Cells

Cancer Research, 2013

Metabolic disruptions that occur widely in cancers offer an attractive focus for generalized trea... more Metabolic disruptions that occur widely in cancers offer an attractive focus for generalized treatment strategies. The hexosamine biosynthetic pathway (HBP) senses metabolic status and produces an essential substrate for O-linked β-N-acetylglucosamine transferase (OGT), which glycosylates and thereby modulates the function of its target proteins. Here, we report that the HBP is activated in prostate cancer cells and that OGT is a central regulator of c-Myc stability in this setting. HBP genes were overexpressed in human prostate cancers and androgen regulated in cultured human cancer cell lines. Immunohistochemical analysis of human specimens (n = 1987) established that OGT is upregulated at the protein level and that its expression correlates with high Gleason score, pT and pN stages, and biochemical recurrence. RNA interference–mediated siliencing or pharmacologic inhibition of OGT was sufficient to decrease prostate cancer cell growth. Microarray profiling showed that the princip...

Research paper thumbnail of The Movember Global Action Plan 1 (GAP1): Unique Prostate Cancer Tissue Microarray Resource

Cancer Epidemiology, Biomarkers & Prevention, 2022

Background: The need to better understand the molecular underpinnings of the heterogeneous outcom... more Background: The need to better understand the molecular underpinnings of the heterogeneous outcomes of patients with prostate cancer is a pressing global problem and a key research priority for Movember. To address this, the Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project constructed a set of unique and richly annotated tissue microarrays (TMA) from prostate cancer samples obtained from multiple institutions across several global locations. Methods: Three separate TMA sets were built that differ by purpose and disease state. Results: The intended use of TMA1 (Primary Matched LN) is to validate biomarkers that help determine which clinically localized prostate cancers with associated lymph node metastasis have a high risk of progression to lethal castration-resistant metastatic disease, and to compare molecular properties of high-risk index lesions within the prostate to regional lymph node metastases resected at the time of prostatectomy. TMA2 (Pre vs. Pos...

Research paper thumbnail of Histological Analysis of a Long Term Patent Subintimal Canal in the Superficial Femoral Artery

EJVES Vascular Forum, 2021

Introduction Subintimal angioplasty (SIA) was introduced in the late 1980s and is a supplement to... more Introduction Subintimal angioplasty (SIA) was introduced in the late 1980s and is a supplement to bypass surgery. Adaptation of the technique has been hampered by high rates of early intervention to maintain patency, but the long term assisted patency is good. Report The superficial femoral and popliteal artery containing a patent subintimal canal were explanted from a patient who died in the authors' ward. Histological analysis indicated that the lumen was created in the medial layer of the vessel wall. A collagen rich neointima and fragmented internal elastic lamina were observed, presumably as a result of activated smooth muscle cells. The luminal surface was partly covered by a single layer of CD31, von Willebrand factor, and partly CD144 positive cells. An early atherosclerotic lesion was observed distally in the subintimal canal. Discussion Remodelling and neo-cellularisation of the vascular wall after SIA are described. Notably, hallmarks of early and late stage atheroscl...

Research paper thumbnail of Proteomic analyses identify major vault protein as a prognostic biomarker for fatal prostate cancer

Carcinogenesis, 2021

The demographic shift toward an older population will increase the number of prostate cancer case... more The demographic shift toward an older population will increase the number of prostate cancer cases. A challenge in the treatment of prostate cancer is to avoid undertreatment of patients at high risk of progression following curative treatment. These men can benefit from early salvage treatment. An explorative cohort consisting of tissue from 16 patients who underwent radical prostatectomy, and were either alive or had died from prostate cancer within 10 years postsurgery, was analyzed by mass spectrometry analysis. Following proteomic and bioinformatic analyses, major vault protein (MVP) was identified as a putative prognostic biomarker. A publicly available tissue proteomics dataset and a retrospective cohort of 368 prostate cancer patients were used for validation. The prognostic value of the MVP was verified by scoring immunohistochemical staining of a tissue microarray. High level of MVP was associated with more than 4-fold higher risk for death from prostate cancer (hazard rat...

Research paper thumbnail of Abstract A01: ADRB2 regulates phase II steroid metabolism and determines development of castration-resistant prostate cancer

Molecular Cancer Research, 2016

The underlying mechanisms responsible for the development of castration-resistant prostate cancer... more The underlying mechanisms responsible for the development of castration-resistant prostate cancer (CRPC) are not fully understood. The β2-adrenergic receptor (ADRB2) is a key regulator of a wide range of metabolic processes in the body, and it has been implicated in androgen receptor signaling and development of CRPC. We have unpublished data which shows that low expression of ADRB2 predicts a more rapid development of CRPC. Based on this finding, we wanted to investigate whether the ADRB2 level/activity impacts cellular features to help explain how and why the receptor has prognostic value in prostate cancer. We stably transfected androgen-dependent LNCaP cells with shRNAs to mimic the clinical situation where patients have differential levels of ADRB2 in their prostate epithelial carcinomas. Gene expression profiling revealed changes in expression of several metabolic genes. Among the most regulated were two androgen-glucuronidating UDP-glucuronosyltransferase 2B (UGT2B) enzymes, ...

Research paper thumbnail of Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA

Clinical nutrition (Edinburgh, Scotland), Jun 30, 2016

The effect of lycopene-containing foods in prostate cancer development remains undetermined. We t... more The effect of lycopene-containing foods in prostate cancer development remains undetermined. We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen (PSA) in prostate cancer patients. Prior to their curative treatment, 79 patients with prostate cancer were randomized to a nutritional intervention with either 1) tomato products containing 30 mg lycopene per day; 2) tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice, and green/black tea (tomato-plus); or 3) control diet for 3 weeks. The main analysis, which included patients in all risk categories, did not reveal differences in changes of PSA-values between the intervention and control groups. Post-hoc, exploratory analyses within intermediate risk (n = 41) patients based on tumor classification and Gleason score post-surgery, revealed that median PSA decreased significantly in the tomato group as compared to controls (-2.9% and +6.5% respecti...

Research paper thumbnail of Preoperative magnetic resonance imaging for detecting uni- and bilateral extraprostatic disease in patients with prostate cancer

World Journal of Urology, 2014

Research paper thumbnail of Morphometry of benign prostatic hyperplasia during androgen suppressive therapy. Relationships among epithelial content, PSA density, and clinical outcome

Scandinavian journal of urology and nephrology. Supplementum, 1996

We performed light microscopic morphometry on prostate biopsies of 41 patients who underwent andr... more We performed light microscopic morphometry on prostate biopsies of 41 patients who underwent androgen suppressive therapy for 24 weeks with the luteinizing hormone releasing hormone (LHRH) agonist leuprolide depot for symptomatic benign prostatic hyperplasia (BPH). Before treatment started, the prostates consisted of 88.4% stroma, 9.0% epithelium and 2.6% glandular lumen. After completion of therapy, the percentages were 94.7, 3.0 and 2.3, respectively. The absolute reductions of volume were 27% for stroma, 77% for epithelium and 40% for lumen. Correlations between pretreatment parameters (epithelial content, stromal epithelial ratio and prostate specific antigen density (PSAD)) and the clinical outcome parameters (prostate volume reduction, improvement in maximum flow rate, reduction of symptom score and reduction in outflow resistance) were not statistically significant, indicating that the histological composition of BPH tissue or PSAD are poor parameters to predict differences i...

Research paper thumbnail of Can prostate epithelial content predict response to hormonal treatment of patients with benign prostatic hyperplasia?

Urology, 2000

There are large interindividual differences in response to medical therapy for men with benign pr... more There are large interindividual differences in response to medical therapy for men with benign prostatic hyperplasia. Selection of patients for alpha-blocker versus hormonal treatment is often based more on assumptions than on well-documented knowledge. A more scientifically based decision of therapy has a potential for economical savings and increased effectiveness. We performed morphometry on prostate biopsy specimens and determined the amount of stroma, epithelium, and glandular lumen (pretreatment characteristics) in 34 men with benign prostatic hyperplasia before 24 weeks of androgen suppressive therapy. Androgen suppressive therapy consisted of either the luteinizing hormone-releasing hormone agonist leuprolide depot (3.75 mg intramuscularly every 28 days) or the nonsteroidal antiandrogen bicalutamide (50 mg/day orally). The evaluation of the clinical response (effectiveness parameters) was based on changes in prostate volume, peak urinary flow rate, symptom score, and bladder outlet obstruction. A large prostate volume before treatment was associated with more pronounced symptom score improvement, but neither prostate-specific antigen nor any of the parameters of tissue composition used (percentage of epithelium, epithelial volume, and stromal/epithelial ratio) predicted a favorable response to hormonal treatment. The pretreatment variables that are readily available at present have a limited role in helping clinicians to decide the optimal medical treatment for patients with benign prostatic hyperplasia.

Research paper thumbnail of Abstract A46: Effects of genistein supplementation on genome-wide DNA methylation and gene expression in patients with localized prostate cancer

Cancer Research, 2016

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer ... more Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer death among men in the United States, with an estimated 220,800 new cases and 27,540 deaths in 2015. Epidemiological studies have shown that dietary compounds have significant effects on prostate carcinogenesis. Among dietary agents, genistein, the major isoflavone in soybean, is of particular interest because high consumption of soy products has been associated with a low incidence of prostate cancer, suggesting a preventive role of genistein in prostate cancer. In spite of numerous studies to understand the effects of genistein on prostate cancer, the mechanisms of action have not been fully elucidated. Here, we investigated the differences in methylation and gene expression levels of prostate specimens from a clinical trial of genistein supplementation prior to prostatectomy (Lazarevic B, et al. Nutr Cancer 2011). This study was a randomized, placebo-controlled, double-blind clinical trial on forty-seven Norwegian patients who received 30 mg genistein or placebo capsules daily for 3-6 weeks before prostatectomy. Whole genome methylation and expression profiling identified significantly differentially methylated sites and expressed sites between placebo and genistein groups. Differentially regulated genes were involved in developmental processes, stem cell markers, proliferation, and transcriptional regulation. These findings highlight the effects of genistein on global changes in DNA methylation and gene expression in prostate cancer, and provide additional insight into the multiple molecular pathways involved in prostate tumorigenesis. Citation Format: Birdal Bilir, Jeongseok Edward Lee, Nitya V. Sharma, Bato Lazarevic, Aud Svindland, Omer Kucuk, Carlos S. Moreno. Effects of genistein supplementation on genome-wide DNA methylation and gene expression in patients with localized prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr A46.

Research paper thumbnail of Prognostic, predictive and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer

Molecular oncology, Jan 14, 2018

We aimed to refine the value of CDX2 as an independent prognostic and predictive biomarker in col... more We aimed to refine the value of CDX2 as an independent prognostic and predictive biomarker in colorectal cancer (CRC) according to disease stage and chemotherapy sensitivity in preclinical models. CDX2 expression was evaluated in 1045 stage I-IV primary CRCs by gene expression (n=403) or immunohistochemistry (n=642) and in relation to 5-year relapse-free survival (RFS), overall survival (OS), and chemotherapy. Pharmacogenomic associations between CDX2 expression and 69 chemotherapeutics were assessed by drug screening of 35 CRC cell lines. CDX2 expression was lost in 11.6% of cases and showed independent poor prognostic value in multivariable models. For individual stages, CDX2 was prognostic only in stage IV, independent of chemotherapy. Among stage I-III patients not treated in an adjuvant setting, CDX2 loss was associated with a particularly poor survival in the BRAF-mutated subgroup, but prognostic value was independent of microsatellite instability status and the consensus mole...