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  • 1
    Language: English
    In: BJU international, December 2013, Vol.112(8), pp.1080-7
    Description: To evaluate the Prostate Imaging Reporting and Data System (PIRADS) in multiparametric magnetic resonance imaging (mpMRI) based on single cores and single-core histology. To calculate positive (PPV) and negative predictive values (NPV) of different modalities of mpMRI. We performed MRI-targeted transrectal ultrasound-guided perineal prostate biopsies on 50 patients (mean age 66 years, mean PSA level of 9.9 ng/mL) with suspicion of prostate cancer. The biopsy trajectories of every core taken were documented in three dimensions (3D) in a 3D-prostate model. Every core was evaluated separately for prostate cancer and the performed biopsy trajectories were projected on mpMRI images. PIRADS scores of 1177 cores were then assessed by a histology 'blinded' uro-radiologist in T2-weighted (T2W), dynamic contrast-enhanced (DCE), diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS). The PIRADS score was significantly higher in cores positive for cancer than in negative cores. There was a significant correlation between the PIRADS score and histopathology for every modality. Receiver operating characteristic (ROC) analysis showed excellent specificity for T2W (90% peripheral zone/97% transition zone) and DWI (98%/97%) images regardless of the prostate region observed. These numbers decreased for DCE (80%/93%) and MRS (76%/83%). All modalities had NPVs of 99%, if a PIRADS score threshold of 2 (for T2W, DCE, and MRS) or 3 (for DWI) was used. However, PPVs were low. Our results show that PIRADS scoring is feasible for clinical routine and allows standardised reporting. PIRADS can be used as a decision-support system for targeting of suspicious lesions. mpMRI has a high NPV for prostate cancer and, thus, might be a valuable tool in the initial diagnostic evaluation.
    Keywords: Pirads-Score ; Biopsy ; Hybrid Imaging ; Mpmri ; Prostate ; Biopsy, Large-Core Needle ; Diffusion Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Prostate -- Pathology ; Prostatic Neoplasms -- Pathology
    ISSN: 14644096
    E-ISSN: 1464-410X
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  • 2
    Language: English
    In: Cancer Research, 04/15/2011, Vol.71(8 Supplement), pp.2144-2144
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 3
    In: Journal Of The National Cancer Institute, 2015, Vol. 107(6)
    Description: Background: Statins have been associated with moderate reductions in mortality among colorectal cancer (CRC) patients, but these studies lacked adjustment for some potentially relevant factors associated with statin use. We aimed to provide more detailed results on this association from a population-based patient cohort study. Methods: Use of statins and other risk or protective factors were assessed in standardized interviews with 2697 patients from southern Germany with a diagnosis of incident CRC between 2003 and 2009 (Darmkrebs: Chancen der Verhutung durch Screening [DACHS] study). Follow-up included assessment of therapy details, recurrence, vital status, and cause of death. Information about molecular pathological subtypes of CRC was available for 1209 patients. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). All statistical tests were two-sided. Results: Patients were age 68 years on average, 412 used statins (15%), and 769 died during follow-up (29%). After a median follow-up time of 3.4 years, use of statins was not associated with overall (HR = 1.10, 95% CI = 0.85 to 1.41), CRC-specific (HR = 1.11, 95% CI = 0.82 to 1.50), or recurrence-free survival (HR = 0.90, 95% CI = 0.63 to 1.27). Analyses in relevant subgroups also showed no association of statin use with overall and CRC-specific survival, and no associations were observed after stratifying for major pathological subtypes. Among stage I and II patients, statin use was associated with better recurrencefree but not with better CRC-specific survival. Conclusions: Statin use was not associated with reduced mortality among CRC patients. Effects reported in previous studies might reflect incomplete control for stage at diagnosis and other factors associated with the use of statins. doi: 10.1093/jnci/djv045
    Keywords: Mortality -- Usage ; Mortality -- Analysis ; Statins -- Usage ; Statins -- Analysis ; Colorectal Cancer -- Usage ; Colorectal Cancer -- Analysis;
    ISSN: 0027-8874
    E-ISSN: 1460-2105
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  • 4
    Language: English
    In: American Journal of Clinical Nutrition, 2016, Vol.103(6), p.1497(10)
    Description: Background: Studies on the association between alcohol consumption and colorectal cancer (CRC) prognosis have yielded inconsistent results. Objective: The associations of lifetime and 1-y prediagnostic alcohol consumption with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients. Design: In 2003-2010, 3121 patients diagnosed with CRC were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.8 y. With the use of Cox proportional hazard regression, associations between lifetime and recent alcohol consumption and overall, CRC-specific, recurrence-free, and disease-free survival were analyzed. Results: In this patient cohort with a median age of 69 y at diagnosis, lifetime abstainers showed poorer overall [adjusted HR (aHR): 1.25; 95% CI: 1.03, 1.52] and CRC-specific (aHR: 1.37; 95% CI: 1.10, 1.70) survival than lifetime light drinkers (women: 〉0-12 g/d; men: 〉0-24 g/d). Lifetime heavy drinkers showed poorer overall (aHR: 1.37; 95% CI: 1.06, 1.78) and disease-free (aHR: 1.38; 95% CI: 1.09, 1.74) survival. Alcohol abstaining in the year before diagnosis was associated with poorer overall (aHR: 1.42; 95% CI: 1.20, 1.68), CRC-specific (aHR: 1.38; 95% CI: 1.13, 1.68), and disease-free (aHR: 1.23; 95% CI: 1.05, 1.44) survival. Lifetime abstainers with nonmetastatic disease showed poorer CRC-specific (aHR: 1.48; 95% CI: 1.10, 2.00) and recurrence-free (aHR: 1.32; 95% CI: 1.02, 1.70) survival. Wine abstaining but not beer or liquor abstaining was associated with poorer survival. Associations between alcohol consumption and prognosis varied according to presence of diabetes and age. Conclusions: Prediagnostic alcohol abstaining and heavy drinking were associated with poorer survival after a CRC diagnosis than light drinking. The protective effects of light consumption might be restricted to wine, and associations might differ according to age and presence of diabetes mellitus. Am J Clin Nutr 2016;103:1497-506. Keywords: colorectal neoplasms, alcohol consumption, survival, prognosis, recurrence doi: 10.3945/ajcn.115.127092.
    Keywords: Cancer Patients – Alcohol Use ; Colorectal Cancer – Analysis ; Colorectal Cancer – Patient Outcomes ; Drinking (Alcoholic Beverages) – Analysis
    ISSN: 0002-9165
    E-ISSN: 19383207
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  • 5
    In: The American Journal of Clinical Nutrition, 2016, Vol. 104(4), pp.1110-1120
    Description: Background: Studies on the association between body mass index (BMI) and colorectal cancer (CRC) prognosis after diagnosis have yielded inconsistent results. Few studies have investigated associations between prediagnostic BMI change and CRC prognosis. Objective: The associations of BMI at diagnosis and prediagnostic BMI change with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients. Design: A total of 3130 patients diagnosed with CRC between 2003 and 2010 were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.9 y. With the use of Cox proportional hazards regression, associations between BMI at diagnosis and BMI change (difference between 1–10 y before diagnosis and at diagnosis) and overall, CRC-specific, recurrence-free, and disease-free survival were analyzed. Results: Compared with normal weight, overweight [BMI (in kg/m 2 ): 25 to 〈30] and obesity (BMI: ≥30) were associated with improved overall [adjusted HR (aHR): 0.82; 95% CI: 0.70, 0.95 and aHR: 0.80; 95% CI: 0.66, 0.98, respectively] and CRC-specific (aHR: 0.84; 95% CI: 0.71, 1.01 and aHR: 0.78; 95% CI: 0.62, 0.99, respectively) survival, with associations being even stronger when the analysis was restricted to nonmetastatic disease. Compared with stable BMI, a strong prediagnostic BMI decrease of 〉5 was associated with poorer prognosis for all survival outcomes (overall survival—aHR: 1.83; 95% CI: 1.43, 2.34; CRC-specific survival—aHR: 1.78; 95% CI: 1.33, 2.39), and associations were particularly pronounced in men (overall survival—aHR: 2.31; 95% CI: 1.65, 3.22; CRC-specific survival—aHR: 2.56; 95% CI: 1.72, 3.81; P -interaction = 0.08). Conclusions: Overweight and obesity are associated with enhanced survival after a CRC diagnosis. A major decrease in BMI in the years before diagnosis is a strong independent predictor of decreased survival. This trial was registered at www.studybox.de as ST-D066.
    Keywords: Colorectal Neoplasms ; Body Composition ; Body Weight Changes ; Prognosis ; Recurrence
    ISSN: 0002-9165
    E-ISSN: 1938-3207
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  • 6
    Language: English
    In: Nature medicine, March 2002, Vol.8(3), pp.216-8
    Description: The development of anticancer therapies that target apoptosis pathways may be hampered by resistance of certain tumor cells to death signals. New findings show that tumor cells lacking the pro-apoptotic protein Bax are resistant to apoptosis induced by the death ligand TRAIL, but that chemotherapeutic drugs can restore their sensitivity to TRAIL.
    Keywords: Proto-Oncogene Proteins C-Bcl-2 ; Apoptosis -- Physiology ; Membrane Glycoproteins -- Metabolism ; Neoplasms -- Metabolism ; Proto-Oncogene Proteins -- Metabolism ; Tumor Necrosis Factor-Alpha -- Metabolism
    ISSN: 1078-8956
    E-ISSN: 1546170X
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  • 7
    Language: English
    In: American Journal of Clinical Nutrition, Jan, 2016, Vol.103(1), p.192(9)
    Description: Background: Little is known about the prognostic impact of red and processed meat intake or about changes in consumption after a diagnosis of colorectal cancer (CRC). Objectives: We investigated associations of baseline red and processed meat with survival outcomes and explored changes in intake among CRC survivors 5 y after diagnosis. Design: A total of 3122 patients diagnosed with CRC between 2003 and 2010 were followed for a median of 4.8 y [DACHS (Darmkrebs: Chancen der Verhiitung durch Screening) study]. Patients provided information on diet and other factors in standardized questionnaires at baseline and at the 5-y follow-up. Cox proportional hazards regression models were used to estimate HRs and 95% CIs. Results: Among patients with stage I-III CRC, baseline red and processed meat intake was not associated with overall (〉1 time/d compared with 〈1 time/d; HR: 0.85; 95% CI: 0.67, 1.09), CRC-specific (HR: 0.83; 95% CI: 0.61, 1.14), cardiovascular disease-specific (HR: 0.92; 95% CI: 0.51, 1.68), non-CRC-specific (HR: 0.88; 95% CI: 0.59, 1.30), and recurrence-free (HR: 1.03; 95% CI: 0.80, 1.33) survival; results among stage IV patients were comparable. An association with worse overall survival was found among patients with Kirsten rat sarcoma viral oncogene homolog (ATMS)-mutated CRC (HR: 1.99; 95% CI: 1.10, 3.56) but not with microsatellite instability or CpG island methylator phenotype (CIMP) positivity. A much lower proportion of survivors reported daily consumption of red and processed meat at the 5-y follow-up than at baseline (concordance rate: 39%; [kappa]-value: 0.10; 95% CI: 0.07, 0.13). Conclusions: Our findings suggest that baseline red and processed meat intake is not associated with poorer survival among patients with CRC. The potential interaction with KRAS mutation status warrants further evaluation. Major changes in consumption measured at the 5-y follow-up may have had an impact on our survival estimates. Keywords: colorectal cancer, molecular subtypes, mortality, red and processed meat, survival doi: 10.3945/ajcn.115.121145
    Keywords: Meat -- Health Aspects ; Nutritional Assessment -- Analysis ; Colorectal Cancer -- Risk Factors ; Colorectal Cancer -- Care And Treatment ; Colorectal Cancer -- Diagnosis
    ISSN: 0002-9165
    Source: Cengage Learning, Inc.
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  • 8
    Language: English
    In: The Journal of Urology, April 2013, Vol.189(4), pp.e260-e260
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 9
    Language: English
    In: International Journal of Cancer, 01 August 2011, Vol.129(3), pp.607-618
    Description: Tumor necrosis factor α (TNF‐α) signaling pathways play important roles during tumorigenesis and inflammation. Ubiquitin‐dependent processes are central to the regulation of TNF‐α and nuclear factor κB (NF‐κB) signaling. We performed a targeted siRNA screen for ubiquitin‐specific proteases (USPs) and identified USP2 as a modulator of TNF‐α‐induced NF‐κB signaling. We showed that USP2 is required for the phosphorylation of IκB, nuclear translocation of NF‐κB and expression of NF‐κB‐dependent target genes and IL‐8 secretion. Our study also provides evidence for isoform‐specific functions of USP2. The immunohistochemical analysis of breast carcinomas revealed that USP2 expression is frequently downregulated. Together, our results implicate USP2 as a novel positive regulator of TNF‐α‐induced NF‐κB signaling and show that its expression is altered in tumor cells.
    Keywords: Rnai ; Signaling ; Nf‐Κb ; Functional Genomics ; Breast Cancer
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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  • 10
    In: International Journal of Cancer, 01 November 2015, Vol.137(9), pp.2104-2113
    Description: Epithelial‐to‐mesenchymal transition (EMT) contributes significantly to tumor progression and metastasis. The assessment of EMT‐associated transcription factors could be a promising approach to identify biomarkers and potential therapeutic targets in colorectal cancer. In our study, we focused on the transcription factor “Sine oculis homeobox” (SIX) 1, which is a member of the superfamily of the homeobox genes and has been described to promote EMT in different types of tumors. Immunohistochemistry against SIX1 was performed on colorectal mucosa, adenomas, carcinomas‐ and primary adenocarcinomas. An expression score was developed and subsequently assessed for its prognostic value in two independent cohorts. Cohort 1 consisted of 128 patients with stage I–III colorectal cancer; cohort 2 included 817 patients with stage I–III colorectal cancer who had participated in the DACHS study. HCT‐116 cells were transfected with SIX1 plasmids and subjected to migration and colony formation assays. The expression of SIX1 increases gradually from mucosa to colorectal adenocarcinomas ( 〉 0.0001). Univariate and multivariate analyses reveal that high expression of SIX1 is associated with decreased overall survival (cohort 1: HR: 4.01, CI: 1.20–14.07,  = 0.025; cohort 2: HR: 1.43, CI: 1.014–2.02,  = 0.047). Overexpression of SIX1 induces a more mesenchymal‐like phenotype in HCT‐116 cells and enhances tumor migration. High expression of SIX1 is an independent prognostic marker in colorectal cancer. It might be a promising biomarker to stratify patients into different risk groups. Moreover, targeting SIX1 might be a novel therapeutic approach in patients with colorectal cancer. What's new? Gains in stem cell‐like properties by tumor cells may be linked to the epithelial‐to‐mesenchymal transition (EMT), suggesting that changes in the expression of EMT‐associated transcription factors are predictive of tumor progression. This study shows that progression of colorectal mucosa from normal to adenomatous to cancerous is accompanied by gradually increasing expression of sine oculis homeobox 1 (SIX1), a transcription factor known to regulate EMT‐related mechanisms. In two separate colorectal patient cohorts, elevated SIX1 expression was found to be associated with decreased overall survival. The results indicate that SIX1 is of prognostic value in colorectal cancer.
    Keywords: Six1 ; Colorectal Cancer ; Prognosis ; Emt
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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