Prognostic significance of the detection of micrometastatic disease in peripheral blood and bone marrow in patients with sage B2 and C colorectal cancer

Purpose: To evaluate the clinical relevance of circulating CEACAM5mRNA-positive cells in patients with operable colorectal cancer (CRC). Methods: Peripheral blood was obtained from 265 patients with operable CRC before the initiation of adjuvant systemic therapy, from 96 normal donors and the Lovo cell line as negative and positive controls, respectively. The detection of CEACAM5mRNA-positive cells was performed using a real time-PCR assay. The association with known prognostic factors and the effect of CEACAM5mRNA-positive cells on patients' prognosis was investigated. Results: The analytical detection limit of the method was found to correspond to 0.7 Lovo cell equivalence/5 μg RNA, with a sensitivity of 1 tumor cell/105 normal cells and a specificity of 97%. Ninety-eight (37%) patients had detectable circulating CEACAM5mRNA-positive cells. Detection of CEACAM5mRNA-positive cells was significantly associated with higher relapse rate (p<0.001), decreased Disease-Free Survival (DFS; p <0.001), higher death rate (p=0.017) and decreased median overall survival (p=0.025). Multivariate analysis revealed that the detection of circulating CEACAM5 mRNA-positive cells was an independent prognostic factor for decreased DFS (HR=3.4; 95% CI: 2.0-5.9; p<0.001). Conclusions: Detection of peripheral blood CEACAM5mRNA-positive cells is an adverse prognostic factor correlated with poor clinical outcome in patients with operable CRC.Σκοπός: Να εκτιμήσουμε την κλινική σημασία των κυκλοφορούντων CEACAM5mRNA - θετικών κυττάρων σε ασθενείς με χειρουργήσιμο ορθοκολικό καρκίνο ( CRC ). Μέθοδοι: Περιφερικό αίμα λήφθηκε από 265 ασθενείς με χειρουργήσιμο CRC πριν από την έναρξη της συμπληρωματικής χημειοθεραπείας και από 96 φυσιολογικούς δότες, και το RNA παρασκευάσθηκε από τις Lovo κυτταρικές σειρές καρκίνου παχέος εντέρου και ARH-77 λευχαιμικές κυτταρικές σειρές, χρησιμοποιήθηκαν ως θετικοί και αρνητικοί μάρτυρες, αντίστοιχα. Η ανίχνευση των CEACAM5mRNA - θετικών κυττάρων έγινε χρησιμοποιώντας μια μέθοδο PCR πραγματικού χρόνου. Η σχέση με γνωστούς προγνωστικούς παράγοντες και η επίδραση των CEACAM5mRNA - θετικών κυττάρων στην πρόγνωση των ασθενών μελετήθηκε. Αποτελέσματα: Το αναλυτικό όριο ανίχνευσης της μεθόδου βρέθηκε να αντιστοιχεί σε 0,7 Lovo κυτταρικά ισοδύναμα / 5 μg RNA, με ευαισθησία 1 καρκινικού κυττάρου/105 φυσιολογικά κύτταρα και μια ειδικότητα 97 %. Ενενήντα οκτώ ( 37 %) ασθενείς είχαν ανιχνεύσιμα CEACAM5mRNA θετικά κυκλοφορούντα κύτταρα. Η ανίχνευση των CEACAM5mRNA - θετικών κυττάρων σχετίσθηκε σημαντικά με υψηλότερο ποσοστό υποτροπών (p <0,001), μειωμένη ελεύθερη νόσου επιβίωση ( DFS; p <0,001 ), υψηλότερο ποσοστό θανάτων (p = 0,017) και μειωμένη διάμεση συνολική επιβίωση (p = 0,025). Η πολυπαραγοντική ανάλυση έδειξε ότι η ανίχνευση των κυκλοφορούντων CEACAM5 mRNA - θετικών κυττάρων ήταν ανεξάρτητος προγνωστικός παράγοντας για μειωμένη DFS ( HR = 3,4; 95% CI: 2,0 - 5,9; p <0,001). Συμπεράσματα: Η ανίχνευση στο περιφερικό αίμα των CEACAM5mRNA - θετικών κυττάρων είναι ένας δυσμενής προγνωστικός παράγοντας σχετιζόμενος με φτωχή κλινική έκβαση σε ασθενείς με χειρουργήσιμο CRC

Spatiotemporal Data Mining Problems and Methods

Many scientific fields show great interest in the extraction and processing of spatiotemporal data, such as medicine with an emphasis on epidemiology and neurology, geology, social sciences, meteorology, and a great interest is also observed in the study of transport. Spatiotemporal data differ significantly from spatial data, since spatiotemporal data refer to measurements, which take into account both the place and the time in which they are received, with their respective characteristics, while spatial data refer to and describe information related only to place. The innovation brought about by spatiotemporal data mining has caused a revolution in many scientific fields, and this is because through it we can now provide solutions and answers to complex problems, as well as provide useful and valuable predictions, through predictive learning. However, combining time and place in data mining presents significant challenges and difficulties that must be overcome. Spatiotemporal data mining and analysis is a relatively new approach to data mining which has been studied more systematically in the last decade. The purpose of this article is to provide a good introduction to spatiotemporal data, and through this detailed description, we attempt to introduce descriptive logic and gain a complete knowledge of these data. We aim to introduce a new way of describing them, aiming for future studies, by combining the expressions that arise by type of data, using descriptive logic, with new expressions, that can be derived, to describe future states of objects and environments with great precision, providing accurate predictions. In order to highlight the value of spatiotemporal data, we proceed to give a brief description of ST data in the introduction. We describe the relevant work carried out to date, the types of spatiotemporal (ST) data, their properties and the transformations that can be made between them, attempting, to a small extent, to introduce constraints and rules using descriptive logic, introducing descriptive logic into spatiotemporal data by type, when initially presenting the ST data. The data snapshots by species and similarities between the cases are then described. We describe methods, introducing clustering, dynamic ST clusters, predictive learning, pattern mining frequency, and pattern emergence, and problems such as anomaly detection, identifying time points of changes in the behavior of the observed object, and development of relationships between them. We describe the application of ST data in various fields today, as well as the future work. We finally conclude with our conclusions, with the representation and study of spatiotemporal data can, in combination with other properties which accompany all natural phenomena, through their appropriate processing, lead to safe conclusions regarding the study of problems, and also with great precision in the extraction of predictions by accurately determining future states of an environment or an object. Thus, the importance of ST data makes them particularly valuable today in various scientific fields, and their extraction is a particularly demanding challenge for the future

Α multicenter phase II study of pegylated liposomal doxorubicin in combination with irinotecan as second-line treatment of patients with refractory small-cell lung cancer

International audienc

Salvage treatment in metastatic breast cancer with weekly paclitaxel and bevacizumab

Weekly paclitaxel (P) in combination with bevacizumab (B) is an effective regimen as initial treatment of metastatic breast cancer (MBC). We investigated in a phase II study the activity of the same regimen as salvage therapy in MBC. Pretreated women with MBC received weekly P (90 mg/m(2) days 1, 8, 15) and B (10 mg/kg days 1, 15) every 28 days. B could continue after discontinuing P until disease progression. This was second-line chemotherapy for 30% and third-line or more for 70% of patients. A total of 40 patients were enrolled. Median age: 61 (range 32-80) years; postmenopausal: 80%; baseline ECOG performance status &lt; 2 in 80% of patients. Two patients (5%) achieved complete response, 10 (25%) partial response (overall response rate 30%; 95% CI 15.8-44.2), and 10 (25%) stable disease. The response rate was 28% for the patients who had previously received taxanes. After a median follow-up of 20.6 months, the median time to progression was 4.8 months (95% CI 1.7-7.8), median survival 13.0 months (95% CI 10.3-15.7), and the probability of 1-year survival 55.5%. Main grade 3-4 toxicities were neutropenia 42.5%, febrile neutropenia 5%, and asthenia 10%. There was one toxic death due to sepsis. The PB regimen is well tolerated and active as salvage therapy in pretreated women with MBC. It could be an effective option even for patients exposed to taxanes during prior treatments

Salts of Clopidogrel: Investigation to Ensure Clinical Equivalence: A 12-Month Randomized Clinical Trial

Background: In the present clinical trial, we compared the efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulfate (CHS) salt in patients eligible to receive clopidogrel. Methods: A prospective 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n = 1864) were screened and 1800 were enrolled in the trial and randomized to CHS or CB. Primary efficacy end point was the composite of myocardial infarction, stroke, or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium criteria. Results: At 12-month follow-up, no differences were observed between CB (n = 759) and CHS (n = 798) in primary efficacy and safety end points (age, sex, history of percutaneous coronary intervention adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.21 and OR, 0.81; 95% CI, 0.51-1.29, respectively) between CHS and CB. Analyses of efficacy and safety in subgroups that were defined according to the qualifying diagnosis revealed that there was no difference between CHS and CB. Conclusion: The efficacy and safety of CB administered for 12 months for the secondary prevention of atherothrombotic events are similar to that of CHS