LINE-1 ORF1p is a Promising Biomarker in Cervical Intraepithelial Neoplasia Degree Assessment.

Cervical intraepithelial neoplasia (CIN) represents a spectrum of preinvasive squamous lesions within the cervical epithelium, whose identification is a diagnostic challenge due to subtle histomorphological differences among its categories. This study explores ORF1p, a nucleic acid-binding protein derived from long interspersed nuclear element-1 (LINE-1), as a potential biomarker for enhancing CIN diagnosis. A comprehensive analysis of 143 cervical specimens, encompassing CIN I (n=20), CIN II (n=46), CIN III (n=14), invasive cancer (n=32), and nondysplastic cases (normal cervical epithelia (n=24) and atrophy (n=7) were conducted. ORF1p, Ki67, and p16 expressions were evaluated using immunohistochemistry. ORF1p immunopositivity was detected in the vast majority [110/112 (98.2%)] of dysplastic and neoplastic (CIN and invasive cancer) specimens, whereas 19/24 (79.2%) of normal cervical specimens lacked ORF1p expression. The observed pattern of ORF1p expression showed a progressively increasing extent and intensity with advancing CIN grades. CIN I exhibited mild ORF1p expression in the lower one or two-thirds of the cervical epithelium [14/16 (87.5%)], whereas CIN II demonstrated moderate to strong ORF1p expression spanning the lower two-thirds [29/46 (63.0%)]. Pronounced transepithelial ORF1p immunopositivity characterized CIN III cases [13/14 (92.8%)] and cervical cancer [30/32 (93.8%)]. These findings propose ORF1p as a valuable indicator even for detecting CIN I, effectively discerning them from normal cervical tissue (p < 0.0001). Our findings underscore the potential of ORF1p as an early diagnostic marker for cervical neoplasia.

Complex treatment of residual metastatic germ cell cancer: A single center experience.

BACKGROUND: Testicular cancer is the most common solid malignancy among men aged 15-35. Radical orchiectomy and platinum-based chemotherapy (BEP) are curative in the majority of patients, including advanced, metastatic cases. According to current urooncology guidelines all non-seminoma patients harbouring post-chemotherapy residual masses of ≥ 1 cm should undergo salvage retroperitoneal lymph node dissection (RPLND). However, only 10% of residual tumors contain viable disease. OBJECTIVE: To assess patient outcomes and complications considering different treatment regimens and clinical characteristics. MATERIALS AND METHODS: In a retrospective cross-sectional study patients (n=127) who underwent postchemotherapy RPLND between 2007 and 2023 at our referral center were evaluated. The patients received systemic treatment at various oncology centers. The number of BEP cycles received were occasionally different from standard. Only patients with normal postchemotherapy serum tumor markers and primary testicular or extragonadal germ cell neoplasms were included. Treatment groups were established according to the number of BEP cycles received, and the extent of RPLND (bilateral or modified template). Treatment outcomes and complications were assessed. RESULTS: Standard 3-4 courses of BEP were received by 100 (78,7%) patients, while 11 (8,7%) patients underwent less, and 16 (12,6%) more courses than standard. On histopathologic evaluation viable germ cell tumor, teratoma, and necrosis/fibrosis was present in 26 (20,5%), 67 (52,7%) and 34 (26,8%) of specimen, respectively. In the 5-6 BEP series subgroup high rate of viable disease (37,5%) was found and significantly more nephrectomies were performed, than other chemotherapy subgroups. Extratesticular GCT, viable disease in residual mass or progression after RPLND indicated lower survival. Mild (Clavien-Dindo I-II) or no postoperative complications were reported in 93,7% of cases. CONCLUSIONS: The study suggests no significant benefit from exceeding 3-4 courses of BEP. Timely salvage RPLND should be performed in high volume centers for optimal treatment outcomes with acceptable complication rates. Adherence to the Heidenreich criteria is advisable where practical.

First Results on the Presence of Mycotoxins in the Liver of Pregnant Fallow Deer (Dama dama) Hinds and Fetuses.

Reproductive abnormalities have been observed in fallow deer populations in Hungary. We supposed mycotoxin contamination to be one of the possible causes because multi-mycotoxin contamination is known to be dangerous even at low toxin levels, especially for young animals. We investigated the spatial pattern of mycotoxin occurrences and the relationship between maternal and fetal mycotoxin levels. A total of 72 fallow deer embryos and their mothers were sampled in seven forested regions in Hungary in the 2020/2021 hunting season. We analyzed Aflatoxin (AF), Zearalenone (ZEA), Fumonizin B1 (FB1), DON, and T2-toxin concentrations in maternal and fetal livers by ELISA. AF was present in 70% and 82%, ZEA in 41% and 96%, DON in 90% and 98%, T2-toxin in 96% and 85%, and FB1 in 84% and 3% of hind and fetus livers, respectively. All mycotoxins passed into the fetus, but only Fumonizin B1 rarely passed. The individual variability of mycotoxin levels was extremely high, but the spatial differences were moderate. We could not prove a relation between the maternal and fetal mycotoxin concentrations, but we found an accumulation of ZEA and DON in the fetuses. These results reflect the possible threats of mycotoxins to the population dynamics and reproduction of wild fallow deer.

Routine molecular applications and recent advances in breast cancer diagnostics.

Cancer stands as one of the most common and lethal diseases, imposing a substantial burden on global mortality rates. Breast cancer is distinct from other forms of cancer in which it is the primary cause of death for women. Early detection of breast cancer can significantly lower the risk of mortality, improving the prognosis for those who are affected. The death rate of breast cancer has been steadily rising, according to epidemiological data, especially since the COVID-19 pandemic. This emphasizes the necessity of sensitive and precise technologies that can be utilized in early breast cancer diagnosis. In this process, biomarkers play a pivotal role by facilitating the early detection and diagnosis of breast cancer. Currently, a wide variety of cancer biomarkers have been identified, improving the accuracy of cancer diagnosis. These biomarkers can be applied in liquid biopsies as well as on solid tissues. In the context of breast cancer, biomarkers are particularly valuable for determining who is predisposed to the disease, predicting prognosis at the time of diagnosis, and selecting the best course of therapy. This review comprehensively explores the recently developed gene-based biomarkers from biofluids that are used in the context of breast cancer, as well as the conventional and cutting-edge techniques that have been employed for breast cancer diagnosis.

Correlation between fibroblast growth factor receptor mutation, programmed death ligand-1 expression and survival in urinary bladder cancer based on real-world data.

Background: Programmed cell death (PD)-1/PD-ligand 1 (PD-L1) inhibitors have made a breakthrough in the therapy of advanced urothelial bladder cancer (UBC). The impact of Fibroblast Growth Factor Receptor 3 (FGFR3) mutation on the effectiveness of PD-L1 treatment remains still unclear. Objective: Our study aimed to investigate the frequency of FGFR mutations at different tumor stages, and their relation to PD-L1 status and survival. Methods: 310 patients with urothelial bladder cancer and subsequent radical cystectomy were included in a retrospective study over a 10-year study period at the University of Szeged, Hungary. FGFR3 mutations from the most infiltrative areas of the tumor were analyzed by targeted next-generation sequencing and PD-L1 (28-8 DAKO) tests (tumor positive score -TPS and combined positives score-CPS). In T0 cases FGFR3 mutations were analyzed from the earlier resection samples. Survival and oncological treatment data were collected from the National Health Insurance Fund (NHIF). Neoadjuvant, adjuvant and palliative conventional chemotherapies were allowed; immunotherapies were not. The relationship between the covariates was tested using chi-square tests, and survival analysis was performed using the Kaplan-Meier model and Cox proportional hazards regression. Results: PD-L1 and FGFR could be tested successfully in 215 of the 310 UBC samples [pT0cyst 19 (8.8%); St.0-I 43 (20%); St.II 41 (19%); St.III-IV 112 (52%)]. Significant pairwise dependency was found between tumor stage, FGFR3 mutation status and PD-L1 expression (p < 0.01). Samples with FGFR mutation were more common in less advanced stages and were also less likely to demonstrate PD-L1 expression. The effect of all investigated factors on survival was found to correlate with tumor stage. Conclusion: FGFR alteration frequency varied between the different stages of cancer. Higher positivity rates were observed at early stages, but lower levels of PD-L1 expression were detected in patients with FGFR mutations across at all stages of the disease.

[Alectinib and mixed large cell neuroendocrine carcinoma of the lung.] / Az alectinib és a tüdo kevert nagysejtes neuroendokrin carcinomája.

The treatment of mixed large cell neuroendocrine carcinoma is less studied due to its low incidence. However, the presence of anaplastic lymphoma kinase (ALK) fusion gene is rare in such tumours, ALK inhibitors may represent a promising therapeutic option instead of cytostatic therapy. Routine chest X-ray and then computed tomography (CT) examination revealed a pulmonary tumour in a 52-year-old asymptomatic woman. The neoplasm was removed by lobectomy. Histological examination confirmed papillary predominant lung adenocarcinoma. The patient was treated with postoperative chemotherapy and irradiation. 3 years later, neurologic symptoms were observed, therefore, brain CT was performed. The evaluation confirmed brain metastases which were removed. Histological examination identified metastasis of large cell neuroendocrine carcinoma. Revision and molecular examination of the metastasis and lung specimen revealed pulmonary mixed large cell neuroendocrine carcinoma with ALK-rearrangement. Alectinib (Alecensa) treatment was initiated resulting in regression of the previously observed liver metastases. Progression has not occurred in the last 3 years since the start of treatment. Detection of ALK fusion genes and research of ALK inhibitor therapy focus primarily on lung adenocarcinomas. Our case report would like to draw attention to the evaluation of driver mutations in pulmonary mixed neuroendocrine carcinoma with adenocarcinoma component because targeted treatment may be an effective alternative. Orv Hetil. 2023; 164(14): 548-554.

Prolonged activity of the transposase helper may raise safety concerns during DNA transposon-based gene therapy.

DNA transposon-based gene delivery vectors represent a promising new branch of randomly integrating vector development for gene therapy. For the side-by-side evaluation of the piggyBac and Sleeping Beauty systems-the only DNA transposons currently employed in clinical trials-during therapeutic intervention, we treated the mouse model of tyrosinemia type I with liver-targeted gene delivery using both transposon vectors. For genome-wide mapping of transposon insertion sites we developed a new next-generation sequencing procedure called streptavidin-based enrichment sequencing, which allowed us to identify approximately one million integration sites for both systems. We revealed that a high proportion of piggyBac integrations are clustered in hot regions and found that they are frequently recurring at the same genomic positions among treated animals, indicating that the genome-wide distribution of Sleeping Beauty-generated integrations is closer to random. We also revealed that the piggyBac transposase protein exhibits prolonged activity, which predicts the risk of oncogenesis by generating chromosomal double-strand breaks. Safety concerns associated with prolonged transpositional activity draw attention to the importance of squeezing the active state of the transposase enzymes into a narrower time window.

BC-miR: Monitoring Breast Cancer-Related miRNA Profile in Blood Sera-A Prosperous Approach for Tumor Detection.

Breast cancer is the most frequent cancer with a high fatality rate amongst women worldwide. Diagnosing at an early stage is challenging, and due to the limitations of the currently used techniques, including mammography and imaging diagnostics, it still remains unascertained. Serum biomarkers can be a solution for this as they can be isolated in a less painful, more cost-effective, and minimally invasive manner. In this study, we shed light on the relevant role of multiple microRNAs (miRNAs) as potential biomarkers in breast cancer diagnosis. We monitored the expressional changes of 15 pre-selected miRNAs in a large cohort, including 65 patients with breast cancer and 42 healthy individuals. We performed thorough statistical analyses on the cohort sample set and determined the diagnostic accuracy of individual and multiple miRNAs. Our study reveals a potential improvement in diagnostics by implicating the monitoring of miR-15a+miR-16+miR-221 expression in breast cancer management.

Novel Diagnostic Value of Driver Gene Transcription Signatures to Characterise Clear Cell Renal Cell Carcinoma, ccRCC.

Routine molecular tumour diagnostics are augmented by DNA-based qualitative and quantitative molecular techniques detecting mutations of DNA. However, in the past decade, it has been unravelled that the phenotype of cancer, as it's an extremely complex disease, cannot be fully described and explained by single or multiple genetic variants affecting only the coding regions of the genes. Moreover, studying the manifestation of these somatic mutations and the altered transcription programming-driven by genomic rearrangements, dysregulation of DNA methylation and epigenetic landscape-standing behind the tumorigenesis and detecting these changes could provide a more detailed characterisation of the tumour phenotype. Consequently, novel comparative cancer diagnostic pipelines, including DNA- and RNA-based approaches, are needed for a global assessment of cancer patients. Here we report, that by monitoring the expression patterns of key tumour driver genes by qPCR, the normal and the tumorous samples can be separated into distinct categories. Furthermore, we also prove that by examining the transcription signatures of frequently affected genes at 3p25, 3p21 and 9p21.3 genomic regions, the ccRCC (clear cell renal cell carcinoma) and non-tumorous kidney tissues can be distinguished based on the mRNA level of the selected genes. Our results open new diagnostics possibilities where the mRNA signatures of tumour drivers can supplement the DNA-based approaches providing a more precise diagnostics opportunity leading to determine more precise therapeutic protocols.

A versatile transposon-based technology to generate loss- and gain-of-function phenotypes in the mouse liver.

BACKGROUND: Understanding the contribution of gene function in distinct organ systems to the pathogenesis of human diseases in biomedical research requires modifying gene expression through the generation of gain- and loss-of-function phenotypes in model organisms, for instance, the mouse. However, methods to modify both germline and somatic genomes have important limitations that prevent easy, strong, and stable expression of transgenes. For instance, while the liver is remarkably easy to target, nucleic acids introduced to modify the genome of hepatocytes are rapidly lost, or the transgene expression they mediate becomes inhibited due to the action of effector pathways for the elimination of exogenous DNA. Novel methods are required to overcome these challenges, and here we develop a somatic gene delivery technology enabling long-lasting high-level transgene expression in the entire hepatocyte population of mice. RESULTS: We exploit the fumarylacetoacetate hydrolase (Fah) gene correction-induced regeneration in Fah-deficient livers, to demonstrate that such approach stabilizes luciferase expression more than 5000-fold above the level detected in WT animals, following plasmid DNA introduction complemented by transposon-mediated chromosomal gene transfer. Building on this advancement, we created a versatile technology platform for performing gene function analysis in vivo in the mouse liver. Our technology allows the tag-free expression of proteins of interest and silencing of any arbitrary gene in the mouse genome. This was achieved by applying the HADHA/B endogenous bidirectional promoter capable of driving well-balanced bidirectional expression and by optimizing in vivo intronic artificial microRNA-based gene silencing. We demonstrated the particular usefulness of the technology in cancer research by creating a p53-silenced and hRas G12V-overexpressing tumor model. CONCLUSIONS: We developed a versatile technology platform for in vivo somatic genome editing in the mouse liver, which meets multiple requirements for long-lasting high-level transgene expression. We believe that this technology will contribute to the development of a more accurate new generation of tools for gene function analysis in mice.

The clinical significance of epigenetic and RNAPII variabilities occurring in clear cell renal cell carcinoma as a potential prognostic marker.

Patients diagnosed with clear cell renal cell carcinoma (ccRCC) have poor prognosis for recurrence and approximately 30-40% of them will later develop metastases. For this reason, the appropriate diagnosis and the more detailed molecular characterisation of the primary tumour, including its susceptibility to metastasis, are crucial to select the proper adjuvant therapy by which the most prosperous outcome can be achieved. Nowadays, clinicopathological variables are used for classification of the tumours. Apart from these, molecular biomarkers are also necessary to improve risk classification, which would be the most beneficial amongst modern adjuvant therapies. As a potential molecular biomarker, to follow the transcriptional kinetics in ccRCC patients (n=30), we analysed epigenetic changes (γH2A.X, H3K4me3, and H3K9me3) and the alterations in the level of RNA polymerase II (RNAPII) by immunohistochemical staining on dissected tissue sections. The variabilities between the tumorous and non-tumorous parts of the tissue were detected using quantitative image analysis by monitoring 30 cells from different positions of either the tumorous or the non-tumorous part of the tissue sections. Data obtained from the analyses were used to identify potential prognostic features and to associate them with the progression. These markers might have a value to predict patient outcomes based on their individual cellular background. These results also support that detection of any alteration in the level of H3K4me3, H3K9me3, and γH2A.X can account for valuable information for presuming the progression of ccRCC and the clinical benefits to select the most efficient personalised therapy.

Multifocal Urinary Tract Metastasis of Colorectal Carcinoma.

INTRODUCTION: Secondary urinary tract tumors are uncommon findings and mainly evolve by direct invasion from adjacent organs. Actual metastatic involvement often develops in the urinary bladder, while the upper urinary tract is infrequently affected. In addition, the lungs, breast, and prostate gland are the usual primary sites. Colorectal carcinoma (CRC) may spread to the ureter directly or seeds via vascular or lymphatic channels. It may pose struggles in the differential diagnosis because CRC shares standard pathologic features with the primary adenocarcinoma of the urinary tract. CASE PRESENTATION: We describe the case of an 81-year-old man who was referred to our hospital with a distal ureteral tumor that was treated by a ureteronephrectomy. The histopathological and genetic analysis established the diagnosis of metastatic CRC along with 3 metastases in the renal pelvis. CONCLUSION: This rare case highlights the limitations of conventional histological processing, including immunohistochemistry, and it underlines the role of molecular investigations in certain circumstances.

Fisheye transformation enhances deep-learning-based single-cell phenotyping by including cellular microenvironment.

Incorporating information about the surroundings can have a significant impact on successfully determining the class of an object. This is of particular interest when determining the phenotypes of cells, for example, in the context of high-throughput screens. We hypothesized that an ideal approach would consider the fully featured view of the cell of interest, include its neighboring microenvironment, and give lesser weight to cells that are far from the cell of interest. To satisfy these criteria, we present an approach with a transformation similar to those characteristic of fisheye cameras. Using this transformation with proper settings, we could significantly increase the accuracy of single-cell phenotyping, both in the case of cell culture and tissue-based microscopy images, and we present improved results on a dataset containing images of wild animals.

[Pathology of tumors of the urinary bladder, aspects and expectations of the histological report (TUR, cystectomy)]. / Húgyhólyagtumorok patológiája, szövettani diagnózisának szempontjai, lehetoségei és elvárásai (TUR, cisztektómia).

Urothelial tumors are among the most frequently occurring malignancies. The patients' clinical outcome can be diverse after recognition of the presence of the tumor. The result of the histology report (grade, histologic subtype, stage) makes remarkable impact on treatment strategies. There are innumerable papers (debates) in the literature concerning the best methods in classification, stage determination, application of immunohistochemical markers (to possibly avoid false negative, false positive results) and the use of molecular biological examinations. The authors attempt to draw attention on the everyday diagnostic difficulties of the "general pathologist", through their own experience and the latest reports of the literature.

BC-Monitor: Towards a Routinely Accessible Circulating Tumor DNA-Based Tool for Real-Time Monitoring Breast Cancer Progression and Treatment Effectiveness.

Circulating tumor DNA (ctDNA) is increasingly employed in the screening, follow-up, and monitoring of the continuously evolving tumor; however, most ctDNA assays validated for clinical use cannot maintain the right balance between sensitivity, coverage, sample requirements, time, and cost. Here, we report our BC-monitor, a simple, well-balanced ctDNA diagnostic approach using a gene panel significant in breast cancer and an optimized multiplex PCR-based NGS protocol capable of identifying allele variant frequencies below 1% in cell-free plasma DNA. We monitored a cohort of 45 breast cancer patients prospectively enrolled into our study receiving neoadjuvant chemotherapy or endocrine therapy or palliative therapy for metastatic diseases. Their tumor mutation status was examined in the archived tumor samples and plasma samples collected before and continuously during therapy. Traceable mutations of the used 38-plex NGS assay were found in approximately two-thirds of the patients. Importantly, we detected new pathogenic variants in follow-up plasma samples that were not detected in the primary tumor and baseline plasma samples. We proved that the BC-monitor can pre-indicate disease progression four-six months earlier than conventional methods. Our study highlights the need for well-designed ctDNA monitoring during treatment and follow-up, integrated into a real-time treatment assessment, which could provide information on the active tumor DNA released into the blood.

The Combination of Single-Cell and Next-Generation Sequencing Can Reveal Mosaicism for BRCA2 Mutations and the Fine Molecular Details of Tumorigenesis.

Germline mutations in the BRCA1 and BRCA2 genes are responsible for hereditary breast and ovarian cancer syndrome. Germline and somatic BRCA1/2 mutations may define therapeutic targets and refine cancer treatment options. However, routine BRCA diagnostic approaches cannot reveal the exact time and origin of BRCA1/2 mutation formation, and thus, the fine details of their contribution to tumor progression remain less clear. Here, we establish a diagnostic pipeline using high-resolution microscopy and laser microcapture microscopy to test for BRCA1/2 mutations in the tumor at the single-cell level, followed by deep next-generation sequencing of various tissues from the patient. To demonstrate the power of our approach, here, we describe a detailed single-cell-level analysis of an ovarian cancer patient we found to exhibit constitutional somatic mosaicism of a pathogenic BRCA2 mutation. Employing next-generation sequencing, BRCA2 c.7795G>T, p.(Glu2599Ter) was detected in 78% of reads in DNA extracted from ovarian cancer tissue and 25% of reads in DNA derived from peripheral blood, which differs significantly from the expected 50% of a hereditary mutation. The BRCA2 mutation was subsequently observed at 17-20% levels in the normal ovarian and buccal tissue of the patient. Together, our findings suggest that this mutation occurred early in embryonic development. Characterization of the mosaic mutation at the single-cell level contributes to a better understanding of BRCA mutation formation and supports the concept that the combination of single-cell and next-generation sequencing methods is advantageous over traditional mutational analysis methods. This study is the first to characterize constitutional mosaicism down to the single-cell level, and it demonstrates that BRCA2 mosaicism occurring early during embryogenesis can drive tumorigenesis in ovarian cancer.

Efficient treatment of a preclinical inflammatory bowel disease model with engineered bacteria.

We developed an orally administered, engineered, bacterium-based, RNA interference-mediated therapeutic method to significantly reduce the symptoms in the most frequently used animal model of inflammatory bowel disease. This bacterium-mediated RNA interference strategy was based on the genomically stable, non-pathogenic E. coli MDS42 strain, which was engineered to constitutively produce invasin and the listeriolysin O cytolysin. These proteins enabled the bacteria first to invade the colon epithelium and then degrade in the phagosome. This allowed the delivery of a plasmid encoding small hairpin RNA (shRNA) targeting tumor necrosis factor (TNF) into the cytoplasm of the target cells. The expression levels of TNF and other cytokines significantly decreased upon this treatment in dextran sulfate sodium (DSS)-induced colitis, and the degree of inflammation was significantly reduced. With further safety modifications this method could serve as a safe and side effect-free alternative to biologicals targeting TNF or other inflammatory mediators.

ERG expression can predict the outcome of docetaxel combinedwith androgen deprivation therapy in metastatic hormone-sensitiveprostate cancer.

BACKGROUND: Our study aimed to analyze the potential association between clinical parameters and ERG expression and the outcome of docetaxel chemotherapy among patients with metastatic hormone-sensitive prostate cancer. PATIENTS AND METHODS: Fifty-five patients with metastatic hormone-sensitive prostate cancer were treated with docetaxel in addition to androgen deprivation therapy. Patient characteristics, clinical factors, and tumor expression of ERG by immunohistochemistry were analyzed with respect to therapeutic response and survival data. RESULTS: Relapse free survival (RFS) and overal survival (OS) were 10.5 and 40.4 months, respectively, and both correlated with PSA response (RFS: 16.8 with a ≥50% decrease in PSA vs. 5.9 months in the case of <50% decrease, P < 0.001; OS: 40.4 vs. 11.6 months, respectively, P < 0.001). There was an association between OS and early progression (OS: 40.4 months with progression after 12 months vs. 17.9 months with progression within 12 months, P = 0.009). ERG expression was detected in 21 (42%) samples. ERG positivity was associated with favorable RFS (ERG pos. vs. neg.: 26.0 vs. 11.4 months, P = 0.003). CONCLUSION: ERG expression may have a potential predictive value with respect to the effectiveness and outcome of docetaxel chemotherapy combined with androgen deprivation therapy.

[Edifications and modern strategies of localized prostate cancers' definitive therapy]. / Prosztatarákban szenvedo betegek definitív ellátásának tanulságai és modern stratégiái.

INTRODUCTION: Mortality of prostate carcinoma can be significantly decreased by the use of modern diagnostic and therapeutic options. Patients in early stages can be cured by radical surgery or radiotherapy. AIM: Overview and comparison of previous and present diagnostic and therapeutic methods regarding accuracy of diagnosis, improvement of efficiency and decrease of toxicities. We also aimed to explore general correlations in case of serious complications. METHOD: By the help of two prostate cancer patients we demonstrate the importance of accuracy and change of histological diagnosis, significance of proper imaging techniques, and also show parameters of conventional and modern radiotherapy and their acute and chronic complications. Differences of previous and present methods and their consequences were analyzed. RESULTS: By now, histological findings in the patients' diagnosis have changed. Both patients received conventional three-dimensional definitive radiotherapy in 2009-2011, and their prostate cancer was cured. In one case, urinary bladder also received radiotherapy because prostate carcinoma had infiltrated it. In the other case, the contemporary radiotherapy involved urinary bladder's fundus due to safety margins. Although acute grade 2 cystitis developed in both cases and recovered in several weeks, as late complication bladder shrinkage developed, which after the ineffectiveness of conventional therapies had to be cured by radical cystoprostatectomy - in order to cease bleeding and to cure incontinence. CONCLUSIONS: In case of prostate carcinomas, serious complications can be avoided by the improvement of diagnostic and therapeutic options. Synthesis of data could be more successful if they were analyzed in the light of previous experiences. Orv Hetil. 2018; 159(32): 1317-1325.

Environmental properties of cells improve machine learning-based phenotype recognition accuracy.

To answer major questions of cell biology, it is often essential to understand the complex phenotypic composition of cellular systems precisely. Modern automated microscopes produce vast amounts of images routinely, making manual analysis nearly impossible. Due to their efficiency, machine learning-based analysis software have become essential tools to perform single-cell-level phenotypic analysis of large imaging datasets. However, an important limitation of such methods is that they do not use the information gained from the cellular micro- and macroenvironment: the algorithmic decision is based solely on the local properties of the cell of interest. Here, we present how various features from the surrounding environment contribute to identifying a cell and how such additional information can improve single-cell-level phenotypic image analysis. The proposed methodology was tested for different sizes of Euclidean and nearest neighbour-based cellular environments both on tissue sections and cell cultures. Our experimental data verify that the surrounding area of a cell largely determines its entity. This effect was found to be especially strong for established tissues, while it was somewhat weaker in the case of cell cultures. Our analysis shows that combining local cellular features with the properties of the cell's neighbourhood significantly improves the accuracy of machine learning-based phenotyping.