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1.
Eur Urol Focus ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38688825

ABSTRACT

BACKGROUND AND OBJECTIVE: Accurate magnetic resonance imaging (MRI) reporting is essential for transperineal prostate biopsy (TPB) planning. Although approved computer-aided diagnosis (CAD) tools may assist urologists in this task, evidence of improved clinically significant prostate cancer (csPCa) detection is lacking. Therefore, we aimed to document the diagnostic utility of using Prostate Imaging Reporting and Data System (PI-RADS) and CAD for biopsy planning compared with PI-RADS alone. METHODS: A total of 262 consecutive men scheduled for TPB at our referral centre were analysed. Reported PI-RADS lesions and an US Food and Drug Administration-cleared CAD tool were used for TPB planning. PI-RADS and CAD lesions were targeted on TPB, while four (interquartile range: 2-5) systematic biopsies were taken. The outcomes were the (1) proportion of csPCa (grade group ≥2) and (2) number of targeted lesions and false-positive rate. Performance was tested using free-response receiver operating characteristic curves and the exact Fisher-Yates test. KEY FINDINGS AND LIMITATIONS: Overall, csPCa was detected in 56% (146/262) of men, with sensitivity of 92% and 97% (p = 0.007) for PI-RADS- and CAD-directed TPB, respectively. In 4% (10/262), csPCa was detected solely by CAD-directed biopsies; in 8% (22/262), additional csPCa lesions were detected. However, the number of targeted lesions increased by 54% (518 vs 336) and the false-positive rate doubled (0.66 vs 1.39; p = 0.009). Limitations include biopsies only for men at clinical/radiological suspicion and no multidisciplinary review of MRI before biopsy. CONCLUSIONS AND CLINICAL IMPLICATIONS: The tested CAD tool for TPB planning improves csPCa detection at the cost of an increased number of lesions sampled and false positives. This may enable more personalised biopsy planning depending on urological and patient preferences. PATIENT SUMMARY: The computer-aided diagnosis tool tested for transperineal prostate biopsy planning improves the detection of clinically significant prostate cancer at the cost of an increased number of lesions sampled and false positives. This may enable more personalised biopsy planning depending on urological and patient preferences.

2.
Klin Padiatr ; 235(6): 317-321, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37673091

ABSTRACT

A possible negative consequence of cancer treatment is the fertility impairment of young cancer survivors. However, most former patients express the wish to have biological children. Fertility-preserving measures are available and are - under certain circumstances - financed by health insurance. Separate information at the time of diagnosis and during follow-up care should be adapted to the individual risk and enable those affected to make a self-determined decision about cryopreservation of germ cells or germ cell tissue. Hyopgonadotropic hypogonadism can be treated by the pulsatile administration of gonadotropins. Affected individuals can be reassured. A health restriction of the offspring due to the cancer treatment is not to be expected, even after artificial insemination.


Subject(s)
Cancer Survivors , Neoplasms , Child , Humans , Adolescent , Neoplasms/drug therapy , Fertility , Cryopreservation
3.
Breast Cancer Res ; 25(1): 6, 2023 01 18.
Article in English | MEDLINE | ID: mdl-36653787

ABSTRACT

BACKGROUND: A challenge in human mammary epithelial cell (HMEC) culture is sustaining the representation of competing luminal, myoepithelial, and progenitor lineages over time. As cells replicate in culture, myoepithelial cells come to dominate the composition of the culture with serial passaging. This drift in composition presents a challenge for studying luminal and progenitor cells, which are prospective cells of origin for most breast cancer subtypes. METHODS: We demonstrate the use of postconfluent culture on HMECs. Postconfluent culture entails culturing HMECs for 2-5 weeks without passaging but maintaining frequent feedings in low-stress M87A culture medium. In contrast, standard HMEC culture entails enzymatic subculturing every 3-5 days to maintain subconfluent density. RESULTS: When compared to standard HMEC culture, postconfluent culture yields increased proportions of luminal cells and c-Kit+ progenitor cells. Postconfluent cultures develop a distinct multilayered morphology with individual cells showing decreased physical deformability as compared to cells in standard culture. Gene expression analysis of postconfluent cells shows increased expression of lineage-specific markers and extracellular matrix components. CONCLUSIONS: Postconfluent culture is a novel, useful strategy for altering the lineage composition of HMECs, by increasing the proportional representation of luminal and progenitor cells. We speculate that postconfluent culture creates a microenvironment with cellular composition closer to the physiological state and eases the isolation of scarce cell subtypes. As such, postconfluent culture is a valuable tool for researchers using HMECs for breast cancer research.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast , Epithelial Cells/metabolism , Tumor Microenvironment
5.
Int Urol Nephrol ; 54(10): 2477-2483, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35877030

ABSTRACT

PURPOSE: To evaluate the additional value of systematic biopsies (SB) when performing transperineal MRI/TRUS fusion biopsies (MRI/TRUS TPBx) with needle tracking. METHODS: From January 2019 to March 2021 969 Patients after a MRI/TRUS TPBx were evaluated separately for target biopsies (TB) and systematic biopsies regarding PCa detection and PCa risk evaluation. Needle tracking in the axial sequences of multiparametric MRI was used to assess the localisation of the detected PCa in the biopsy cores related to the reported PI-RADS lesions. RESULTS: The overall cancer detection rate (CDR) for PCa and clinically significant (cs) PCa (ISUP ≥2) with the combination of TB and SB were 66 and 49%. TB detected 46% csPCa and SB 22% csPCa. SB identified 1.5% additional csPCa outside of the reported PI-RADS lesions. 16 patients (1.7%) showed a relevant upgrading from clinically insignificant PCa in TB to csPCa. In 736 patients with unilateral suspicious lesions on MRI, 145 patients (20%) were detected with contralateral PCa-positive SB. 238 patients (25%) showed PCa positive systematic biopsy cores outside of the described PI-RADS lesions. CONCLUSIONS: Needle tracking optimizes the 3D-localisation of cancer in the prostate. Our results show that the added value of SB with a reduced systematic biopsy scheme is low with regard to prostate cancer (PCa) detection and PCa risk evaluation. However, there is a relevant added value for localizing multifocal PCa in the primary diagnostic by a MRI/TRUS fusion biopsy of the prostate.


Subject(s)
Prostate , Prostatic Neoplasms , Humans , Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Male , Prostate/diagnostic imaging , Prostate/pathology , Prostate-Specific Antigen , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology
6.
Lancet Infect Dis ; 22(10): 1465-1471, 2022 10.
Article in English | MEDLINE | ID: mdl-35839791

ABSTRACT

BACKGROUND: The benefit of antibiotic prophylaxis is uncertain when performing transperineal prostate biopsies. Judicious use of antibiotics is required as antimicrobial resistance increases worldwide. We aimed to assess whether antibiotic prophylaxis can be omitted when performing transperineal prostate biopsies under local anaesthesia as an outpatient procedure. METHODS: In this randomised, open-label, non-inferiority trial, we aimed to enrol all patients with a suspicion of prostate cancer undergoing transperineal prostate biopsies at two hospitals in Norway and Germany. Patients with a high risk of infection or ongoing infection were excluded. Patients were randomised (1:1) to receive intramuscular (in Norway) or intravenous (in Germany) 1·5 g cefuroxime antibiotic prophylaxis or not. Follow-up assessments were done after 2 weeks and 2 months. The primary outcome was rate of sepsis or urinary tract infections requiring hospitalisation within 2 months. The secondary outcome was the rate of urinary tract infections not requiring hospitalisation. These outcomes were assessed in all eligible randomly allocated participants with a prespecified non-inferiority margin of 4%. Biopsies were performed using an MRI-transrectal ultrasound fusion transperineal technique under local anaesthesia. Patients with a positive MRI underwent 2-4 biopsies per target; in addition, 8-12 systematic biopsies were performed in biopsy naive and MRI-negative patients. This study is registered with ClinicalTrials.gov, NCT04146142. FINDINGS: Between Nov 11, 2019, and Feb 23, 2021, 792 patients were referred for biopsy, of whom 555 (70%) were randomly allocated to treatment groups. 277 (50%) patients received antibiotic prophylaxis and 276 (50%) did not; two (<1%) patients were excluded after randomisation because of unknown allergy to study drug. Sepsis or urinary tract infections requiring hospitalisation occurred in no patients given antibiotic prophylaxis (0%, 95% CI 0 to 1·37) or not given antibiotic prophylaxis (0%, 0 to 1·37; difference 0% [95% CI -1·37 to 1·37]). Urinary tract infections not requiring hospitalisation occurred in one patient given antibiotic prophylaxis (0·36%, 95% CI 0·01 to 2·00) and three patients not given antibiotic prophylaxis (1·09%, 0·37 to 3·15; difference 0·73% [95% CI -1·08 to 2·81]). The number needed to treat with antibiotic prophylaxis to avoid one infection was 137. INTERPRETATION: The non-inferiority margin of 4% was not exceeded, suggesting rates of infections were not higher in patients not receiving antibiotic prophylaxis before transperineal prostate biopsy than in those receiving it. Therefore, antibiotic prophylaxis might be omitted in this population. FUNDING: Oslo University Hospital, Oslo, Norway and Vivantes Klinikum Am Urban, Berlin, Germany.


Subject(s)
Sepsis , Urinary Tract Infections , Anti-Bacterial Agents/therapeutic use , Biopsy/adverse effects , Biopsy/methods , Cefuroxime/therapeutic use , Humans , Male , Prostate , Sepsis/drug therapy , Urinary Tract Infections/drug therapy
7.
STAR Protoc ; 3(2): 101182, 2022 06 17.
Article in English | MEDLINE | ID: mdl-35313706

ABSTRACT

Dysregulation of the transcriptional or translational machinery can alter the stoichiometry of multiprotein complexes and occurs in natural processes such as aging. Loss of stoichiometry has been shown to alter protein complex functions. We provide a protocol and associated code that use omics data to quantify these stoichiometric changes via statistical dispersion utilizing the interquartile range of expression values per grouping variable. This descriptive statistical approach enables the quantification of stoichiometry changes without additional data acquisition. For complete details on the use and execution of this protocol, please refer to Hinz et al. (2021).


Subject(s)
Proteins , Proteomics , Proteins/genetics , Proteomics/methods
8.
Mol Cancer Ther ; 21(6): 936-947, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35313331

ABSTRACT

WNT signaling promotes pancreatic ductal adenocarcinoma (PDAC) through diverse effects on proliferation, differentiation, survival, and stemness. A subset of PDAC with inactivating mutations in ring finger protein 43 (RNF43) show growth dependency on autocrine WNT ligand signaling and are susceptible to agents that block WNT ligand acylation by Porcupine O-acyltransferase, which is required for proper WNT ligand processing and secretion. For this study, global transcriptomic, proteomic, and metabolomic analyses were performed to explore the therapeutic response of RNF43-mutant PDAC to the Porcupine inhibitor (PORCNi) LGK974. LGK974 disrupted cellular bioenergetics and mitochondrial function through actions that included rapid mitochondrial depolarization, reduced mitochondrial content, and inhibition of oxidative phosphorylation and tricarboxylic acid cycle. LGK974 also broadly altered transcriptional activity, downregulating genes involved in cell cycle, nucleotide metabolism, and ribosomal biogenesis and upregulating genes involved in epithelial-mesenchymal transition, hypoxia, endocytosis, and lysosomes. Autophagy and lysosomal activity were augmented in response to LGK974, which synergistically inhibited tumor cell viability in combination with chloroquine. Autocrine WNT ligand signaling dictates metabolic dependencies in RNF43-mutant PDAC through a combination of transcription dependent and independent effects linked to mitochondrial health and function. Metabolic adaptations to mitochondrial damage and bioenergetic stress represent potential targetable liabilities in combination with PORCNi for the treatment of WNT ligand-addicted PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Wnt Signaling Pathway , Acyltransferases/antagonists & inhibitors , Acyltransferases/genetics , Acyltransferases/metabolism , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Cell Line, Tumor , Cell Proliferation , Homeostasis , Humans , Ligands , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mitochondria/metabolism , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Proteomics , Pancreatic Neoplasms
9.
Aktuelle Urol ; 53(1): 75-81, 2022 Feb.
Article in German | MEDLINE | ID: mdl-31195415

ABSTRACT

BACKGROUND: The Onkonet database has been developed and coordinated by the Berliner Tumorzentrum e. V. (http://www.prostata-ca.net) and contains data on pre-, peri- and postoperative parameters of radical prostatectomy documented since January 2005. With its user-friendly interface and its integrated benchmarking tool, the main goal of Onkonet was to outline and improve the surgical care of prostate cancer patients in Germany. This study aimed to analyse all Onkonet data documented from the beginning of the project until June 2018. We focused on the completeness and plausibility of data to investigate and define the possibilities and limits of further analyses. PATIENTS AND METHODS: All patients who underwent radical prostatectomy in one of the urological clinics participating in this project until June 2018 were included in this retrospective study. The completeness of all documented patient data was analysed using Excel 2013. The statistical analysis was descriptive. RESULTS: A total of 21 474 patients were documented in Onkonet. 58,6 % (12 591) of them had a complete dataset including date of birth, date of surgery, dates of hospitalisation and discharge, initial PSA value, Gleason score of the biopsy, clinical T stage, pathological T stage, pathological Gleason score, as well as information on the surgical technique. Mean completeness of pre-operative parameters was 26,8 %, of hospitalisation parameters 64,5 %, and of pathological parameters 58,1 %. Amongst these, the documentation of the pathological T stage was complete in 80,1 %, documentation of N stage in 78,8 %, of M stage in 74,8 %, of pathological Gleason Score in 78,7 %, and of R1 status in 78,7 %. Completeness of follow-up data was 8,1 %, with PSA data being available in 27,2 %, continence data in 23,0 %, and potency data in 13,9 %. CONCLUSIONS: Comprising 21 474 documented patients and over 200 parameters, Onkonet is one of the most comprehensive clinical registers for the documentation of prostate cancer patients in Germany. The data analysis showed that the limitations of such a database are mainly due to the high number of parameters and the high susceptibility to errors due to manual data submission.


Subject(s)
Prostatectomy , Prostatic Neoplasms , Databases, Factual , Germany , Humans , Internet , Male , Neoplasm Grading , Prostate-Specific Antigen , Prostatic Neoplasms/surgery , Retrospective Studies
10.
PLoS One ; 16(10): e0258982, 2021.
Article in English | MEDLINE | ID: mdl-34695165

ABSTRACT

Cellular mechanical properties can reveal physiologically relevant characteristics in many cell types, and several groups have developed microfluidics-based platforms to perform high-throughput single-cell mechanical testing. However, prior work has performed only limited characterization of these platforms' technical variability and reproducibility. Here, we evaluate the repeatability performance of mechano-node-pore sensing, a single-cell mechanical phenotyping platform developed by our research group. We measured the degree to which device-to-device variability and semi-manual data processing affected this platform's measurements of single-cell mechanical properties. We demonstrated high repeatability across the entire technology pipeline even for novice users. We then compared results from identical mechano-node-pore sensing experiments performed by researchers in two different laboratories with different analytical instruments, demonstrating that the mechanical testing results from these two locations are in agreement. Our findings quantify the expectation of technical variability in mechano-node-pore sensing even in minimally experienced hands. Most importantly, we find that the repeatability performance we measured is fully sufficient for interpreting biologically relevant single-cell mechanical measurements with high confidence.


Subject(s)
Microfluidics/methods , Phenotype , Flow Cytometry , Reproducibility of Results , Single-Cell Analysis
11.
Appl Opt ; 60(22): F109-F117, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-34612895

ABSTRACT

Style transfer methods are an important task for domain adaptation of optical imagery to improve the performance of deep learning models when using different sensor systems. For the transformation between datasets, cycle-consistent adversarial networks achieve good results. However, during the style transfer process, characteristic spectral information that is essential for the analysis of vegetation could get lost. This issue is especially important since optical airborne- and spaceborne-based sensors are frequently used to investigate vegetation ground coverage and its condition. In this paper, we present a cycle-consistent adversarial domain adaptation method with four input channels for the segmentation of vegetation areas using index-based metrics. We show that our method preserves the specific ratio between the near-IR and RGB bands and improves the segmentation network performance for the target domain.

12.
iScience ; 24(9): 103026, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34522866

ABSTRACT

Age is the major risk factor in most carcinomas, yet little is known about how proteomes change with age in any human epithelium. We present comprehensive proteomes comprised of >9,000 total proteins and >15,000 phosphopeptides from normal primary human mammary epithelia at lineage resolution from ten women ranging in age from 19 to 68 years. Data were quality controlled and results were biologically validated with cell-based assays. Age-dependent protein signatures were identified using differential expression analyses and weighted protein co-expression network analyses. Upregulation of basal markers in luminal cells, including KRT14 and AXL, were a prominent consequence of aging. PEAK1 was identified as an age-dependent signaling kinase in luminal cells, which revealed a potential age-dependent vulnerability for targeted ablation. Correlation analyses between transcriptome and proteome revealed age-associated loss of proteostasis regulation. Age-dependent proteome changes in the breast epithelium identified heretofore unknown potential therapeutic targets for reducing breast cancer susceptibility.

13.
Sensors (Basel) ; 21(11)2021 Jun 07.
Article in English | MEDLINE | ID: mdl-34200481

ABSTRACT

With the emergence of low-cost robotic systems, such as unmanned aerial vehicle, the importance of embedded high-performance image processing has increased. For a long time, FPGAs were the only processing hardware that were capable of high-performance computing, while at the same time preserving a low power consumption, essential for embedded systems. However, the recently increasing availability of embedded GPU-based systems, such as the NVIDIA Jetson series, comprised of an ARM CPU and a NVIDIA Tegra GPU, allows for massively parallel embedded computing on graphics hardware. With this in mind, we propose an approach for real-time embedded stereo processing on ARM and CUDA-enabled devices, which is based on the popular and widely used Semi-Global Matching algorithm. In this, we propose an optimization of the algorithm for embedded CUDA GPUs, by using massively parallel computing, as well as using the NEON intrinsics to optimize the algorithm for vectorized SIMD processing on embedded ARM CPUs. We have evaluated our approach with different configurations on two public stereo benchmark datasets to demonstrate that they can reach an error rate as low as 3.3%. Furthermore, our experiments show that the fastest configuration of our approach reaches up to 46 FPS on VGA image resolution. Finally, in a use-case specific qualitative evaluation, we have evaluated the power consumption of our approach and deployed it on the DJI Manifold 2-G attached to a DJI Matrix 210v2 RTK unmanned aerial vehicle (UAV), demonstrating its suitability for real-time stereo processing onboard a UAV.

14.
Cancer Prev Res (Phila) ; 14(8): 779-794, 2021 08.
Article in English | MEDLINE | ID: mdl-34140348

ABSTRACT

A robust breast cancer prevention strategy requires risk assessment biomarkers for early detection. We show that expression of ELF5, a transcription factor critical for normal mammary development, is downregulated in mammary luminal epithelia with age. DNA methylation of the ELF5 promoter is negatively correlated with expression in an age-dependent manner. Both ELF5 methylation and gene expression were used to build biological clocks to estimate chronological ages of mammary epithelia. ELF5 clock-based estimates of biological age in luminal epithelia from average-risk women were within three years of chronological age. Biological ages of breast epithelia from BRCA1 or BRCA2 mutation carriers, who were high risk for developing breast cancer, suggested they were accelerated by two decades relative to chronological age. The ELF5 DNA methylation clock had better performance at predicting biological age in luminal epithelial cells as compared with two other epigenetic clocks based on whole tissues. We propose that the changes in ELF5 expression or ELF5-proximal DNA methylation in luminal epithelia are emergent properties of at-risk breast tissue and constitute breast-specific biological clocks. PREVENTION RELEVANCE: ELF5 expression or DNA methylation level at the ELF5 promoter region can be used as breast-specific biological clocks to identify women at higher than average risk of breast cancer.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast/metabolism , Circadian Clocks/genetics , DNA-Binding Proteins/genetics , Transcription Factors/genetics , Adult , Biomarkers, Tumor/genetics , Breast/pathology , Breast Neoplasms/pathology , Cell Transformation, Neoplastic , Cells, Cultured , DNA Methylation , DNA-Binding Proteins/metabolism , Early Detection of Cancer/methods , Female , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease/genetics , Genetic Testing/methods , Humans , Middle Aged , Organ Specificity/genetics , Promoter Regions, Genetic , Transcription Factors/metabolism
15.
Urol Oncol ; 39(7): 432.e1-432.e7, 2021 07.
Article in English | MEDLINE | ID: mdl-33257219

ABSTRACT

INTRODUCTION: Transperineal Prostate biopsies (TPBx) are usually performed under general anesthesia without image fusion. This study aimed to evaluate prostate cancer (Pca) detection rates (CDR), pain, and adverse events using a novel, free-hand TPBx technique, based on elastic fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) under local anesthesia. MATERIALS AND METHODS: This multicenter retrospective study included all consecutive patients scheduled for a TPBx. All had clinical suspicion of Pca, active surveillance scheduled for a re-biopsy, or suspicion of local recurrence after previous treatment. Bi-parametric or multiparametric MRI was performed in all patients and classified as positive in the case of Prostate Imaging-Reporting and Data System (PIRADS) suspicion ≥3. At least 1 targeted TPBx was realized from each PIRADS ≥3 index lesion. Six to 12 systematic random TPBx were done in patients with negative MRI. All biopsies were performed under local anesthesia in an outpatient clinic with MRI-TRUS fusion and the 3D navigation system Trinity Perine (Koelis, France). Any- and clinically significant Pca (csPca) (ISUP gr. ≥2) was recorded. Biopsy-related pain and adverse events were reported according to a visual analogue score of 0-10. RESULTS: In total, 377 patients were included for analyses. The mean age was 67 years (95% Confidence Interval: 66-68) and the median prostate-specific antigen was 7.2 ng/ml (interquartile range [IQR] 4.8-11.0). MRI was negative in 6% and positive in 94%. The median MRI prostate volume was 43 ml (IQR 31-60) and the median MRI index tumor volume was 0.9 ml (IQR 0.5-2.1). The median number of TPBx was 4 (IQR 3-4). The overall detection of any- and csPca was 64% and 52%, respectively. The overall CDR according to PIRADS 3, 4, and 5 was 30%, 70%, and 94%, respectively. In patients with negative MRI, any- and csPca was detected in 23% and 9%, respectively. The median visual analogue score score was 2 (IQR 1-3, range 0-7). Two patients (0.5%) developed postbiopsy infection, of which one developed urosepsis. Treatment requiring haematuria or urinary retention did not occur. CONCLUSION: Free-hand MRI/TRUS fusion-guided and systematic random TPBx in LA is a feasible, safe, and well-tolerated technique for diagnosing Pca.


Subject(s)
Magnetic Resonance Imaging , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Adult , Aged , Anesthesia, Local , Humans , Image-Guided Biopsy/methods , Male , Middle Aged , Multimodal Imaging , Perineum , Rectum , Retrospective Studies , Ultrasonography/methods
16.
Nat Aging ; 1(9): 838-849, 2021 09.
Article in English | MEDLINE | ID: mdl-35187501

ABSTRACT

During aging in the human mammary gland, luminal epithelial cells lose lineage fidelity by expressing markers normally expressed in myoepithelial cells. We hypothesize that loss of lineage fidelity is a general manifestation of epithelia that are susceptible to cancer initiation. In the present study, we show that histologically normal breast tissue from younger women who are susceptible to breast cancer, as a result of harboring a germline mutation in BRCA1, BRCA2 or PALB2 genes, exhibits hallmarks of accelerated aging. These include proportionately increased luminal epithelial cells that acquired myoepithelial markers, decreased proportions of myoepithelial cells and a basal differentiation bias or failure of differentiation of cKit+ progenitors. High-risk luminal and myoepithelial cells are transcriptionally enriched for genes of the opposite lineage, inflammatory- and cancer-related pathways. We have identified breast-aging hallmarks that reflect a convergent biology of cancer susceptibility, regardless of the specific underlying genetic or age-dependent risk or the associated breast cancer subtype.


Subject(s)
Breast Neoplasms , Mammary Glands, Human , Humans , Female , Aging/genetics , Breast/pathology , Germ-Line Mutation/genetics , Breast Neoplasms/genetics , BRCA1 Protein/genetics , BRCA2 Protein/genetics
17.
World J Urol ; 38(6): 1501-1507, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31463559

ABSTRACT

BACKGROUND: Patients with localized prostate cancer (PCa) experience biochemical recurrence (BCR) despite a curatively intended radical prostatectomy (RP). The aim of this study was to describe the quality of life (QoL) of patients with a BCR while identifying predictors of early (ER) and late recurrence (LR). METHODS: For this purpose, a total of 330 PCa patients with a BCR following RP at Charité University Hospital in Berlin were analyzed. BCR was defined as two consecutive PSA values ≥ 0.2 after a previous non-detectable level. LR was defined as a BCR after 3 years post-RP. Differences in overall survival (OS) were calculated using the log-rank testing. A logistic regression model was applied to identify predictors of ER and LR. We further evaluated difference between ER and LR with respect to functional outcomes in urinary and sexual domains as well as the patients QoL. RESULTS: Out of 330 patients, 180 patients showed late BCR. Patients rated their global QoL with 64.5% in ER and 68.8% LR as good (EORTC quality of life Questionnaire, question 29 and 30). The questionnaire did not reveal QoL differences in terms of sexual and urinary function within ER and LR. The main predictor for LR was preoperative serum prostate-specific antigen (PSA) levels with a relative risk (RR) of 0.96 (p = 0.011). OS for patients with LR was significant longer than for patients with ER (154.3 vs. 143.2 months, p = 0.018). CONCLUSION: Patients with a BCR show a good quality of life possibly irrespective of the time point of BCR. We further identified preoperative PSA levels as a predictor of LR and noted that patients with LR patients lived longer. Further studies are needed.


Subject(s)
Neoplasm Recurrence, Local/blood , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Quality of Life , Aged , Humans , Male , Middle Aged , Prognosis , Prostatectomy/methods , Retrospective Studies , Time Factors
18.
Aktuelle Urol ; 51(3): 290-298, 2020 06.
Article in German | MEDLINE | ID: mdl-29258130

ABSTRACT

INTRODUCTION: In patients with localised renal cell carcinoma, the only curative treatment option is surgical tumour excision. The aim of this study was to evaluate peri- and postoperative outcomes as well as oncologic and functional long-term results following surgical treatment of patients with renal cell carcinoma (pT1/pT2) at a tertiary referral centre. PATIENTS AND METHODS: This retrospective study included a total of 758 patients with localised renal cell carcinoma (pT1 /pT2), who underwent radical (RN) or partial (PN) nephrectomy between 01/2008 and 10/2014. Pre-, peri- and postoperative parameters were recorded. Oncologic and functional long-term data were retrieved through questionnaires and structured telephone interviews. RESULTS: Laparoscopic RN or PN resulted in less blood loss and lower peri- and postoperative complication rates compared to open procedures. Regarding short- and long-term renal function, a higher increase in serum creatinine levels was detected after RN. No difference was noted in health status and quality of life. Median follow-up was 36 months. A total of 10.4 % of patients died during follow-up. 4.7 % and 8.4 % developed a relapse or metastatic disease. No difference was found between laparoscopic and open RN/PNs in terms of oncologic long-term results. DISCUSSION: In conclusion, all surgical techniques evaluated in this study provided good oncologic and functional short-/long-term outcomes.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Carcinoma, Renal Cell/surgery , Humans , Kidney Neoplasms/surgery , Neoplasm Recurrence, Local , Nephrectomy , Quality of Life , Retrospective Studies , Tertiary Care Centers , Treatment Outcome
19.
Cancer Cell ; 35(1): 1-2, 2019 01 14.
Article in English | MEDLINE | ID: mdl-30645968

ABSTRACT

Potential for cancers to form metastases requires cell dissemination utilizing epithelial-to-mesenchymal transition (EMT) program. In this issue of Cancer Cell, Ishay-Ronen et al. show that plasticity intrinsic to the EMT program can be exploited to divert cancer cells into becoming post-mitotic adipocytes, thus preventing formation of metastases.


Subject(s)
Breast Neoplasms , Adipocytes , Epithelial-Mesenchymal Transition , Humans , Neoplastic Stem Cells
20.
Article in English | MEDLINE | ID: mdl-30200256

ABSTRACT

Inland waters are of great importance for scientists as well as authorities since they are essential ecosystems and well known for their biodiversity. When monitoring their respective water quality, in situ measurements of water quality parameters are spatially limited, costly and time-consuming. In this paper, we propose a combination of hyperspectral data and machine learning methods to estimate and therefore to monitor different parameters for water quality. In contrast to commonly-applied techniques such as band ratios, this approach is data-driven and does not rely on any domain knowledge. We focus on CDOM, chlorophyll a and turbidity as well as the concentrations of the two algae types, diatoms and green algae. In order to investigate the potential of our proposal, we rely on measured data, which we sampled with three different sensors on the river Elbe in Germany from 24 June⁻12 July 2017. The measurement setup with two probe sensors and a hyperspectral sensor is described in detail. To estimate the five mentioned variables, we present an appropriate regression framework involving ten machine learning models and two preprocessing methods. This allows the regression performance of each model and variable to be evaluated. The best performing model for each variable results in a coefficient of determination R 2 in the range of 89.9% to 94.6%. That clearly reveals the potential of the machine learning approaches with hyperspectral data. In further investigations, we focus on the generalization of the regression framework to prepare its application to different types of inland waters.


Subject(s)
Chlorophyll A/analysis , Chlorophyll/analysis , Diatoms/growth & development , Ecosystem , Environmental Monitoring/instrumentation , Humic Substances/analysis , Machine Learning , Spectrum Analysis , Water Quality , Germany
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