Cahiers d’études médiévales, 2 : La Science de la nature : théories et pratiques, Montréal, Bellarmin et Paris, Vrin, 1974, 199 p.

Background: Sentinel Lymph Node (SLN) sampling may significantly reduce surgical morbidity by avoiding needless radical lymphadenectomy. In gynaecological cancers, the current practice in the UK is testing the accuracy of SLN detection using radioactive isotopes within the context of clinical trials. However, radioactive tracers pose significant logistic problems. We, therefore, conducted a pilot, observational study to assess the feasibility of a novel optical imaging device for SLN detection in gynaecological cancers using near infrared (NIR) fluorescence. Methods: A novel, custom-made, optical imaging system was developed to enable detection of multiple fluorescence dyes and allow simultaneous bright-field imaging during open surgery and laparoscopic procedures. We then evaluated the performance of the system in a prospective study of 49 women with early stage vulval, cervical and endometrial cancer who were scheduled to undergo complete lymphadenectomy. Clinically approved fluorescent contrast agents indocyanine green (ICG) and methylene blue (MB) were used. The main outcomes of the study included SLN mapping detection rates, false negative rates using the NIR fluorescence technique and safety of the procedures. We also examined the association between injection sites and differential lymphatic drainage in women with endometrial cancer by fluorescence imaging of ICG and MB. Results: A total of 64 SLNs were detected during both open surgery and laparoscopy. Following dose optimisation and the learning phase, SLN detection rate approached 100 % for all cancer types with no false negatives detected. Fluorescence from ICG and MB detected para-aortic SLNs in women with endometrial cancer following uterine injection. Percutaneous SLN detection was also achieved in most women with vulval cancer. No adverse reactions associated with the use of either dyes were observed. Conclusions: This study demonstrated the successful clinical application of a novel NIR fluorescence imaging system for SLN detection across different gynaecological cancers. We showcased the first in human imaging, during the same procedure, of two fluorescence dyes in women with endometrial cancer. </p

Survival and Chemosensitivity in Advanced High Grade Serous Epithelial Ovarian Cancer Patients with and without a BRCA Germline Mutation: More Evidence for Shifting the Paradigm towards Complete Surgical Cytoreduction.

Background and Objectives: Approximately 10-15% of high-grade serous ovarian cancer (HGSOC) cases are related to BRCA germline mutations. Better survival rates and increased chemosensitivity are reported in patients with a BRCA 1/2 germline mutation. However, the FIGO stage and histopathological entity may have been confounding factors. This study aimed to compare chemotherapy response and survival between patients with and without a BRCA 1/2 germline mutation in advanced HGSOC receiving neoadjuvant chemotherapy (NACT). Materials and Methods: A cohort of BRCA-tested advanced HGSOC patients undergoing cytoreductive surgery following NACT was analyzed for chemotherapy response and survival. Neoadjuvant chemotherapy served as a vehicle to assess chemotherapy response on biochemical (CA125), histopathological (CRS), biological (dissemination), and surgical (residual disease) levels. Univariate and multivariate analyses for chemotherapy response and survival were utilized. Results: Thirty-nine out of 168 patients had a BRCA ½ germline mutation. No differences in histopathological chemotherapy response between the patients with and without a BRCA ½ germline mutation were observed. Survival in the groups of patients was comparable Irrespective of the BRCA status, CRS 2 and 3 (HR 7.496, 95% CI 2.523-22.27, p &lt; 0.001 & HR 4.069, 95% CI 1.388-11.93, p = 0.011), and complete surgical cytoreduction (p = 0.017) were independent parameters for a favored overall survival. Conclusions: HGSOC patients with or without BRCA ½ germline mutations, who had cytoreductive surgery, showed comparable chemotherapy responses and subsequent survival. Irrespective of BRCA status, advanced-stage HGSOC patients have a superior prognosis with complete surgical cytoreduction and good histopathological response to chemotherapy

Potential role of miR-9 and miR-223 in recurrent ovarian cancer

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease.</p> <p>Results</p> <p>Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6) in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18) and FFPE serous ovarian tumours (n = 22). Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry.</p> <p>Conclusion</p> <p>We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer.</p

Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples

<p>Abstract</p> <p>Background</p> <p>Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs). However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA) data to assess the involvement of cancer stemness signatures in recurrent ovarian disease.</p> <p>Methods</p> <p>Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC) model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples.</p> <p>Results</p> <p>Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC) and embryonic stem (mES) cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component.</p> <p>Conclusion</p> <p>We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p53-p21 mechanism in ovarian disease. Targeting CSCs within ovarian cancer represents a potential therapeutic avenue.</p

Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients

<p>Abstract</p> <p>Background</p> <p>Tumours with high proportions of differentiated cells are considered to be of a lower grade to those containing high proportions of undifferentiated cells. This property may be linked to the differentiation properties of stem cell-like populations within malignancies. We aim to identify molecular mechanism associated with the generation of tumours with differing grades from malignant stem cell populations with different differentiation potentials. In this study we assessed microRNA (miRNA) regulation in two populations of malignant Embryonal Carcinoma (EC) stem cell, which differentiate (NTera2) or remain undifferentiated (2102Ep) during tumourigenesis, and compared this to miRNA regulation in ovarian serous carcinoma (OSC) patient samples.</p> <p>Methods</p> <p>miRNA expression was assessed in NTera2 and 2102Ep cells in the undifferentiated and differentiated states and compared to that of OSC samples using miRNA qPCR.</p> <p>Results</p> <p>Our analysis reveals a substantial overlap between miRNA regulation in 2102Ep cells and OSC samples in terms of miRNA biosynthesis and expression of mature miRNAs, particularly those of the miR-17/92 family and clustering to chromosomes 14 and 19. In the undifferentiated state 2102Ep cells expressed mature miRNAs at up to 15,000 fold increased levels despite decreased expression of miRNA biosynthesis genes Drosha and Dicer. 2102Ep cells avoid differentiation, which we show is associated with consistent levels of expression of miRNA biosynthesis genes and mature miRNAs while expression of miRNAs clustering to chromosomes 14 and 19 is deemphasised. OSC patient samples displayed decreased expression of miRNA biosynthesis genes, decreased expression of mature miRNAs and prominent clustering to chromosome 14 but not 19. This indicates that miRNA biosynthesis and levels of miRNA expression, particularly from chromosome 14, are tightly regulated both in progenitor cells and in tumour samples.</p> <p>Conclusion</p> <p>miRNA biosynthesis and expression of mature miRNAs, particularly the miR-17/92 family and those clustering to chromosomes 14 and 19, are highly regulated in both progenitor cells and tumour samples. Strikingly, 2102Ep cells are not simply malfunctioning but respond to differentiation specifically, a mechanism that is highly relevant to OSC samples. Our identification and future manipulation of these miRNAs may facilitate generation of lower grade malignancies from these high-grade cells.</p

Identification of novel biomarkers in recurrent / chemoresistant ovarian cancer

THESIS 9486The aim of this study was to identify novel biomarkers in recurrent/chemoresistant ovarian cancer, yet an incurable disease. Using cDNA microarrays, we identified distinct patterns of gene expression between primary and recurrent ovarian cancers from different patients with the same histology and from same patients with different histology. Selected targets were validated and correlated with microarray results. Signatures from both cohorts were interrogated against each other and also validated against an independent set of serous papillary ovarian adenocarcinomas. Notably, upregulated genes in the recurrent compared to primary tumours in both cohorts, segregated in the same gene families. Our data propose an integrative model for recurrence in ovarian cancer, in which tumour cells during relapse produce adhesion molecules to mediate attachment, cytokines and inflammatory mediators to stimulate survival and a variety of growth factors bound to their cognate receptors to fully proliferate in order to confront and modulate their immediate environment. Some of the mechanisms involved in recurrence could be specific to the drugs used

Correlates of Team Performance in Volleyball

The overall performance of a Volleyball team depends on many factors, from which decisive are considered to be the execution of skills that lead immediately to winning or losing the rally. These are lost serves, aces, kill- attacks, attack errors and kill-blocks. The analysis of these skills in relation to team performance, as expressed by the ratio of sets won to the total number of sets, lead to the formation of two new correlates. These are the serving efficiency ratio (SER), defined as the ratio of lost serves to aces, and the attack efficiency ratio (AER), defined as the number of kill attacks divided by the sum of attack errors and kill-blocks. Analysis of the data collected from all the matches of the male A1 volleyball professional league of 2005-2006 in Greece proved that the two efficiency ratios were better predictors of the teams overall performance than the five original variables. The findings lead to clear-cut definitions of norms both for the serving and attack efficiency ratio. The leading teams had a SER of around two and an AER of around three. These criteria are valuable tools especially for Volleyball coaches in deciding for the appropriate tactics of their teams

Η επίδραση της αρχικής τοποθέτησης των παικτών στο αποτέλεσμα του αγώνα στην πετοσφαίριση

Η Παγκόσμια Ομοσπονδία της Πετοσφαίρισης (F.I.V.B.), ap;o to 2000 καθιέρωσε αλλαγές στους κανονισμούς, που οδήγησαν στη μείωση της διάρκειας του αγώνα και του αριθμού των περιστροφών που πραγματοποιεί η ομάδα στη διάρκεια ενός σετ. Ο προπονητής καλείται να επιλέξει σε κάθε σετ την αρχική τοποθέτηση των παικτών του. Σκοπός της έρευνας ήταν η διερεύνηση της σχέσης μεταξύ της αρχικής τοποθέτησης των παικτών και της κατάληξης (αποτέλεσμα) κάθε αγωνιστικού επεισοδίου. Τα δεδομένα προήλθαν από όλους τους αγώνες πετοσφαίρισης της Α1 κατηγορίας του Πρωταθλήματος Ελλάδος Ανδρών της αγωνιστικής περιόδου 2005-2006. Συγκεκριμένα περιελάμβαναν (Ν=21469) πόντους προερχόμενους από 132 αγώνες και από 484 σετ των δύο γύρων της κανονικής περιόδου. Η κύρια μηδενική υπόθεση που εξετάστηκε ήταν ότι η έκβαση του αγωνιστικού επεισοδίου για τις ομάδες που κατείχαν το δικαίωμα του σερβίς, δεν εξαρτάται από τη συγκεκριμένη διάταξη των παικτών που προέκυπτε από την εκάστοτε περιστροφή. Η στατική ανάλυση βασίστηκε στον έλεγχο χ2 και πραγματοποιήθηκε με πίνακες συνάφειας 6Χ2, με εξαρτημένη μεταβλητή την επίτευξη πόντου από την ομάδα που κατείχε το δικαίωμα του σερβίς και κύρια ανεξάρτητη μεταβλητή την εκάστοτε διάταξη των παικτών. Η κύρια μηδενική υπόθεση απορρίφθηκε καθώς το ποσοστό των πόντων που κέρδισαν στο σύνολο τους οι ομάδες με δικαίωμα εκτέλεσης του σερβίς, είχε στατιστικά σημαντική εξάρτηση από την τοποθέτηση των παικτών στις έξι θέσεις του γηπέδου, για όλα τα σετ του αγώνα. Επίσης έξι ομάδες του πρωταθλήματος εμφάνισαν, ίδια για τους δύο γύρους των αγώνων, στατιστικά σημαντική εξάρτηση από τις θέσεις των παικτών σε μία θέση (με τον πασαδόρο στη θέση 4), που οφειλόταν στην έδρα διεξαγωγής του αγώνα. Συμπερασματικά, η ομάδα που εκτελούσε το σερβίς είχε λιγότερες πιθανότητες να κερδίσει τον πόντο από την αντίπαλη, γεγονός που εξαρτιόταν από τη θέση της περιστροφής της. Επομένως ο προπονητής θα πρέπει να υπολογίζει την περιστροφή των παικτών της ομάδας του

Predicting complete cytoreduction for advanced ovarian cancer patients using nearest-neighbor models

Abstract Background The foundation of modern ovarian cancer care is cytoreductive surgery to remove all macroscopic disease (R0). Identification of R0 resection patients may help individualise treatment. Machine learning and AI have been shown to be effective systems for classification and prediction. For a disease as heterogenous as ovarian cancer, they could potentially outperform conventional predictive algorithms for routine clinical use. We investigated the performance of an AI system, the k-nearest neighbor (k-NN) classifier, to predict R0, comparing it with logistic regression. Patients diagnosed with advanced stage, high grade serous ovarian, tubal and primary peritoneal cancer, undergoing surgical cytoreduction from 2015 to 2019, was selected from the ovarian database. Performance variables included age, BMI, Charlson Comorbidity Index, timing of surgery, surgical complexity and disease score. The k-NN algorithm classified R0 vs non-R0 patients using 3–20 nearest neighbors. Prediction accuracy was estimated as percentage of observations in the training set correctly classified. Results 154 patients were identified, with mean age of 64.4 + 10.5 yrs., BMI of 27.2 + 5.8 and mean SCS of 3 + 1 (1–8). Complete and optimal cytoreduction was achieved in 62 and 88% patients. The mean predictive accuracy was 66%. R0 resection prediction of true negatives was as high as 90% using k = 20 neighbors. Conclusions The k-NN algorithm is a promising and versatile tool for R0 resection prediction. It slightly outperforms logistic regression and is expected to improve accuracy with data expansion