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1.
Histol Histopathol ; 37(6): 527-541, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35146728

ABSTRACT

OBJECTIVE: Quantifying protein expression in immunohistochemically stained histological slides is an important tool for oncologic research. The use of computer-aided evaluation of IHC-stained slides significantly contributes to objectify measurements. Manual digital image analysis (mDIA) requires a user-dependent annotation of the region of interest (ROI). Others have built-in machine learning algorithms with automated digital image analysis (aDIA) and can detect the ROIs automatically. We aimed to investigate the agreement between the results obtained by aDIA and those derived from mDIA systems. METHODS: We quantified chromogenic intensity (CI) and calculated the positive index (PI) in cohorts of tissue microarrays (TMA) using mDIA and aDIA. To consider the different distributions of staining within cellular sub-compartments and different tumor architecture our study encompassed nuclear and cytoplasmatic stainings in adenocarcinomas and squamous cell carcinomas. RESULTS: Within all cohorts, we were able to show a high correlation between mDIA and aDIA for the CI (p<0.001) along with high agreement for the PI. Moreover, we were able to show that the cell detections of the programs were comparable as well and both proved to be reliable when compared to manual counting. CONCLUSION: mDIA and aDIA show a high correlation in acquired IHC data. Both proved to be suitable to stratify patients for evaluation with clinical data. As both produce the same level of information, aDIA might be preferable as it is time-saving, can easily be reproduced, and enables regular and efficient output in large studies in a reasonable time period.


Subject(s)
Algorithms , Image Processing, Computer-Assisted , Diagnostic Imaging , Humans , Image Processing, Computer-Assisted/methods , Proteomics , Staining and Labeling
2.
Urologe A ; 59(4): 461-468, 2020 Apr.
Article in German | MEDLINE | ID: mdl-32016505

ABSTRACT

BACKGROUND: The prostate biopsy report is key for risk stratification of prostate cancer patients and subsequent therapeutic decision-making. However, due to the inclusion of a multitude of additional parameters its interpretation is becoming more challenging. OBJECTIVES: We aimed to determine how urologists currently interpret prostate biopsy reports, in particular how they consider different histopathological parameters for therapy decision-making. MATERIALS AND METHODS: A survey was sent to all urology practices in Germany with the help of the BDU (Berufsverband der Deutschen Urologen e. V.). In total, there were 106 complete responses that could be included for further analyses. RESULTS: Most urologists consider the number of positive cores and relative tumor burden (%) per core as crucial for the assessment of tumor extension. In case of targeted biopsies, the majority of urologists prefers a separate statement of positive cores per random biopsy scheme and per region of interest, respectively. The core with the highest Gleason score is mostly the basis for therapy decision-making (versus the overall Gleason score). Proportion of Gleason 4 pattern also seems to be critical for prostate cancer management. Only half of the urologists demand reporting of the new ISUP/WHO (International Society of Urological Pathology/World Health Organization) grade groups. Additional parameters claimed are Ki67, prostate-specific membrane antigen status, presence of intraductal or neuroendocrine component of the tumor. CONCLUSIONS: Our survey shows that there is no standardized reporting for prostate biopsies and that the interpretation of prostate biopsy reports varies among urologists. Further studies and guideline recommendations are necessary to establish a standardized reporting scheme for prostate biopsies.


Subject(s)
Biopsy, Needle/methods , Pathologists , Prostatic Neoplasms/pathology , Urologists , Germany , Humans , Male , Neoplasm Grading , Practice Patterns, Physicians' , Surveys and Questionnaires , Tumor Burden
3.
World J Urol ; 38(3): 657-662, 2020 Mar.
Article in English | MEDLINE | ID: mdl-30941561

ABSTRACT

PURPOSE: To systematically and comprehensively review and summarize the most recent literature assessing the value of the new grading system introduced by the International Society of Urological Pathology (ISUP) in 2014 and accepted by the World Health Organization (WHO) in 2016. METHODS: A systematic literature search in the PubMed database was performed up to November 2018. Overall, 15 studies in the period from 2016 to 2018 evaluating the new grading system have been selected for evidence synthesis. RESULTS: The main goals of the new ISUP 2014/WHO 2016 grading system were to establish (I) a more accurate and simplified grade stratification, (II) less overtreatment of indolent prostate cancer as well as (III) an improved patient communication. The majority of the studies chose biochemical recurrence as an endpoint for evaluation and statistically assigns the new ISUP 2014/WHO 2016 grading system a higher prognostic accuracy than the former Gleason grading. However, in only a subset of studies it was clearly evident that the historical samples were not only re-grouped according to the new grade groups but also re-graded according to the new histomorphological 2014 ISUP criteria. CONCLUSIONS: The vast majority of the studies support an improved prognostic accuracy of the ISUP 2014/WHO 2016 grade groups and endorse its worldwide application.


Subject(s)
Adenocarcinoma/pathology , Neoplasm Recurrence, Local/epidemiology , Practice Guidelines as Topic , Prostatic Neoplasms/pathology , Adenocarcinoma/blood , Humans , Kallikreins/blood , Male , Neoplasm Grading , Neoplasm Recurrence, Local/blood , Prognosis , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , World Health Organization
5.
Urologe A ; 57(2): 148-154, 2018 Feb.
Article in German | MEDLINE | ID: mdl-29147733

ABSTRACT

Although prostate cancer responds well to primary endocrine therapies, tumor progression with castration resistant tumor cells almost invariably occurs within a few years. Unfortunately, some CRPC patients do not respond to second-line therapies with abiraterone or enzalutamide. Moreover, patients who initially responded well to second-line hormone therapy develop resistance to abiraterone and/or enzalutamide within a short period of time. Besides an increase of intracellular androgen receptor (AR) levels, the predominant resistance mechanisms include AR aberrations (point mutations, AR splice variants) occurring predominantly at the androgen or ligand binding domain of the AR. The following review delineates recent progress in the development of AR inhibitors that do not depend on androgen binding and represent a putative third generation of AR inhibitors.


Subject(s)
Androgen Receptor Antagonists/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Receptors, Androgen/drug effects , Drug Resistance, Neoplasm , Humans , Male , Protein Domains
6.
Phys Rev Lett ; 84(15): 3265-9, 2000 Apr 10.
Article in English | MEDLINE | ID: mdl-11019066

ABSTRACT

We have measured the cross section for quasielastic 1p-shell proton knockout in the 16O(e,e(')p) reaction at omega = 0.439 GeV and Q2 = 0.8 (GeV/c)(2) for missing momentum P(miss)

7.
Basic Res Cardiol ; 77(3): 323-32, 1982.
Article in English | MEDLINE | ID: mdl-7052057

ABSTRACT

Isolated muscle cells from adult rat heart have been used to study the effect of temperature and enzymic digestion on the binding of 125I-labelled insulin. Equilibrium binding studies were performed at both 4 and 37 degrees C, using insulin concentrations ranging from 2.5 X 10(-11) mol/l to 10(-6) mol/l. The empty site affinity constant decreased by 51% from 1.0 X 10(8) l/mol at 4 degrees C to 4.9 X 10(7) l/mol at 37 degrees C, whereas the total receptor concentration remained unaltered at both temperatures. The rate of dilution induced dissociation was enhanced by the presence of native insulin at 37 degrees C, confirming the presence of negative cooperativity among the receptor sites at physiological temperatures. Treatment of isolated heart cells with trypsin and beta-galactosidase led to a decrease in specific binding of 125I-labelled insulin. Myocytes treated with neuraminidase exhibited a significant increase in insulin binding, which was shown to be due to an increase in insulin-receptor affinity. These studies provide new information on the molecular characteristics of insulin receptors in the heart muscle.


Subject(s)
Insulin/metabolism , Myocardium/enzymology , Receptor, Insulin/metabolism , Animals , Galactosidases/metabolism , Iodine Radioisotopes , Male , Neuraminidase/metabolism , Rats , Rats, Inbred Strains , Temperature , Trypsin/metabolism
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