The Gleason Score and Beyond Growth Patterns in Prostate Cancer

Prostate cancer is the second most common cancer among men. The Gleason score is one of the most important parameters for outcome and based on several growth patterns. Among these patterns, cribriform architecture is associated with worse prognosis

Association of quantifiable prostate MRI parameters with any and large cribriform pattern in prostate cancer patients undergoing radical prostatectomy

Purpose: Cribriform pattern has recently been recognized as an important independent risk factor for prostate cancer (PCa) outcome. This study aimed to identify the association of quantifiable prostate magnetic resonance imaging (MRI) parameters with any and large cribriform pattern at radical prostatectomy (RP) specimens. Methods: Preoperative prostate MRI's from 188 men undergoing RP between 2010 and 2018 were retrospectively acquired. RP specimens of the patients were revised for Gleason score (GS), and presence of any and large cribriform pattern. MRI parameters such as MRI visibility, PI-RADS score, lowest apparent diffusion coefficient (ADC) value, lesion size, and radiologic extra-prostatic extension (EPE) were reviewed. The association of prostate MRI parameters for presence of any and large cribriform pattern at RP was analysed using logistic regression. Results: 116/188 (61.7%) PCa patients had any cribriform and 36/188 (19.1%) large cribriform pattern at RP. 171/188 (91.0%) men had MRI-visible lesions; 111/116 (95.7%) tumours with any and 36/36 (100%) with large cribriform pattern were visible at MRI. PCa with any and large cribriform pattern both had lower ADC values than those without (p &lt; 0.001). In adjusted analysis, lowest ADC value was as an independent predictor for any cribriform (Odds Ratio (OR) 0.2, 95% Confidence Interval (CI) 0.1–0.8; p = 0.01) and large cribriform pattern (OR 0.2, 95% CI 0.1–0.7; p = 0.01), while other parameters were not. Conclusions: The majority of PCa with cribriform pattern at RP were visible at MRI, and lowest ADC value was an independent predictor for both any and large cribriform pattern.</p

Interactive tangible objects as play pieces in a digital tabletop game

In this paper we present a new type of tangible interface for a digital tabletop game. This interface consists of an interactive tangible object; a play piece representing a bridge in the game ‘Weathergods’ [1]. The game players can not only physically change the appearance of the bridge to manipulate the digital world, the digital world in return can also affect the appearance of this play piece

Differential interaction of glimepiride and glibenclamide with the β-cell sulfonylurea receptor II

Glimepiride is a novel sulfonylurea for the treatment of type II-diabetic patients exhibiting different receptor binding kinetics to β-cell membranes with 8–9-fold higher koff rate and 2.5–3-fold higher kon rate compared to glibenclamide (see accompanying paper (Müller, G. et al. (1994) Biochim. Biophys. Acta 1191, 267–277)). To elucidate the molecular basis for this differential behaviour of glimepiride and glibenclamide, direct photoaffinity labeling studies using β-cell tumor membranes were performed. [3H]Glimepiride was specifically incorporated into a membrane polypeptide of Mr = 65000 under conditions, which led to predominant labeling of a 140 kDa protein by [3H]glibenclamide (Kramer, W. et al. (1988) FEBS Lett. 229, 355–359). Labeling of the 140 kDa protein by [3H]glibenclamide was inhibited by unlabeled glimepiride and, vice versa, glibenclamide inhibited labeling of the 65 kDa protein by [3H]glimepiride. The 65 kDa protein was also specifically photolabeled by the sulfonylurea [125I]35623, whereas an 4-azidobenzoyl derivative of glibenclamide, N3-[3H]33055, exclusively labeled a 33 kDa protein. Competitive Scatchard analysis of [3H]glimepiride-binding and [3H]glibenclamide-binding to RINm5F cell membranes using glibenclamide and glimepiride, respectively, as heterologous displacing compounds yielded non-linear plots. These findings may be explained by cooperative interactions between the 140 and 65 kDa sulfonylurea-binding proteins. The possibility that sulfonylureas of different structure have different access to the 140 and 65 kDa receptor proteins due to the β-cell membrane barrier was investigated by photoaffinity labeling of solubilized β-cell membrane proteins. Interestingly, solubilization of β-cell tumor membranes led to a shift of specific [3H]glibenclamide binding from the 140 kDa to the 65 kDa binding protein, exclusively, and to an increased labeling of the 65 kDa protein by [3H]glimepiride. The labeling of a unique protein is in agreement with similar Kd values measured for both sulfonylurcas upon solubilization of β-cell tumor and RINm5F cell membranes (see accompanying paper). Furthermore, competitive Scatchard plots of [3H]glimepiride binding to solubilized RINm5F cell membrane proteins in the presence of glibenclamide and vice versa approximate linearity suggesting loss of cooperativity between the 140 kDa glibenclamide-binding and 65 kDa glimepiride-binding proteins upon solubilization. The physiological significance of the differential interaction of glimepiride and glibenclamide with different binding proteins was also substantiated by photoaffinity labeling of RINm5F cells leading to labeling of a 140 kDa protein by [3H]glibenclamide and of a 65 kDa protein by [3H]glimepiride. In conclusion, this report presents the first evidence that different sulfonylurea drugs bind to different components of the sulfonylurea receptor complex which are characterized by different accessibility for the drugs

Automated Detection of Cribriform Growth Patterns in Prostate Histology Images

Cribriform growth patterns in prostate carcinoma are associated with poor prognosis. We aimed to introduce a deep learning method to detect such patterns automatically. To do so, convolutional neural network was trained to detect cribriform growth patterns on 128 prostate needle biopsies. Ensemble learning taking into account other tumor growth patterns during training was used to cope with heterogeneous and limited tumor tissue occurrences. ROC and FROC analyses were applied to assess network performance regarding detection of biopsies harboring cribriform growth pattern. The ROC analysis yielded a mean area under the curve up to 0.81. FROC analysis demonstrated a sensitivity of 0.9 for regions larger than 0.0150 mm2 with on average 7.5 false positives. To benchmark method performance for intra-observer annotation variability, false positive and negative detections were re-evaluated by the pathologists. Pathologists considered 9% of the false positive regions as cribriform, and 11% as possibly cribriform; 44% of the false negative regions were not annotated as cribriform. As a final experiment, the network was also applied on a dataset of 60 biopsy regions annotated by 23 pathologists. With the cut-off reaching highest sensitivity, all images annotated as cribriform by at least 7/23 of the pathologists, were all detected as cribriform by the network and 9/60 of the images were detected as cribriform whereas no pathologist labelled them as such. In conclusion, the proposed deep learning method has high sensitivity for detecting cribriform growth patterns at the expense of a limited number of false positives. It can detect cribriform regions that are labelled as such by at least a minority of pathologists. Therefore, it could assist clinical decision making by suggesting suspicious regions.Comment: 15 pages, 6 figure

Prostate cancer growth patterns beyond the Gleason score: entering a new era of comprehensive tumour grading

The Gleason grading system is one of the most important factors in clinical decision-making for prostate cancer patients, and is entirely based on the classification of tumour growth patterns. In recent years it has become clear that some individual growth patterns themselves have independent prognostic value, and could be used for better personalised risk stratification. In this review we summarise recent literature on the clinicopathological value and molecular characteristics of individual prostate cancer growth patterns, and show how these, most particularly cribriform architecture, could alter treatment decisions for prostate cancer patients

Effects of early nutrition and transport of 1-day-old chickens on production performance and fear response

The importance of optimal early life conditions of broilers to sustain efficient and healthy production of broiler meat is increasingly recognized. Therefore, novel husbandry systems are developed, in which immediate provision of nutrition post hatch is combined with on-farm hatching. In these novel systems, 1-day-old-chick handling and transport are minimized. To study whether early nutrition and reduced transport are beneficial for broiler performance and behavior, the effects of early or delayed nutrition and post-hatch handling and transport were tested from hatch until 35 d of age, in a 2 × 2 factorial arrangement. In total, 960 eggs were hatched in 36 floor pens. After hatch, chicks were given immediate access to water and feed (early nutrition) or after 54 h (delayed nutrition). Eighteen hours after hatch, chicks remained in their pens (non-transported control), or were subjected to short-term handling and transport to simulate conventional procedures. Subsequently, chicks returned to their pens. Compared with delayed-fed chickens, early-fed chickens had greater body weight up to 21 d of age, but not at slaughter (35 d of age). No effects of transport or its interaction with moment of first nutrition were found on performance. At 3 d post hatch, transported, early-fed chicks had a greater latency to stand up in a tonic immobility test than transported, delayed-fed chicks, but only in chicks that were transported. At 30 d post hatch, however, latency was greater in transported, delayed-fed chickens than in transported, early-fed chicks. This may indicate long-term deleterious effects of delayed nutrition on fear response in transported chickens. It is concluded that early nutrition has mainly beneficial effects on performance during the first 2 wk post hatch, but these beneficial effects are less evident in later life. The combination of transport and early nutrition may influence the chicken's strategies to cope with stressful events in early and later life

Clinical outcome comparison of Grade Group 1 and Grade Group 2 prostate cancer with and without cribriform architecture at the time of radical prostatectomy

Aims: Invasive cribriform and intraductal carcinoma are associated with aggressive disease in Grade Group 2 (GG2) prostate cancer patients. However, the characteristics and clinical outcome of patients with GG2 prostate cancer without cribriform architecture (GG2−) as compared with those with Grade Group 1 (GG1) prostate cancer are unknown. The aim of this study was to investigate the clinical and pathological characteristics of GG1 and GG2− prostate cancer in radical prostatectomy specimens. Methods and results: We reviewed 835 radical prostatectomy specimens for Grade Group, pT stage, surgical margin status, and the presence of cribriform architecture. Biochemical recurrence-free survival and metastasis were used as clinical outcomes. GG1 prostate cancer was seen in 207 patients, and GG2 prostate cancer was seen in 420 patients, of whom 228 (54%) showed cribriform architecture (GG2+) and 192 (46%) did not. GG2− patients had higher prostate-specific antigen levels (9.4 ng/ml versus 7.0 ng/ml; P < 0.001), more often had extraprostatic extension (36% versus 11%; P < 0.001) and had more positive surgical margins (27% versus 17%; P = 0.01) than GG1 patients. GG2− patients ha

MMP-14 and CD44 in Epithelial-to-Mesenchymal Transition (EMT) in ovarian cancer

Contains fulltext : 170912.pdf (publisher's version ) (Open Access)BACKGROUND: To investigate the expression of MMP-14 and CD44 as well as epithelial-to-mesenchymal transition(EMT)-like changes in ovarian cancer and to determine correlations with clinical outcome. METHODS: In 97 patients with ovarian cancer, MMP-14 and CD44 expression as determined by immunohistochemistry was investigated in relation to EMT-like changes. To determine this, immunohistochemical staining of E-cadherin and vimentin was performed. RESULTS: Patients with expression of both MMP-14 and CD44 in their tumors had a poor prognosis despite complete debulking. Serous histology in advanced-stage tumors (FIGO IIB-IV) correlated with CD44 (rho .286, p < 0.01). Also, CD44 correlated with percentage vimentin expression (rho .217, p < 0.05). In logistic regression analysis with complete debulking as the outcome parameter, CD44 expression was found to be significant (OR 3,571 (95 % Confidence Interval 1,112-11,468) p = 0.032), though this was not the case for MMP-14 and EMT parameters. CONCLUSION: The subgroup of patients with double expression of MMP-14 and CD44 had a poor prognosis despite complete debulking. Serous subtype in advanced-stage patients and CD44 expression were found to be correlated with vimentin expression, and CD44 expression was found to be significantly correlated with complete debulking. However, a significant correlation between EMT and clinical parameters was not found