Η κλινική σημασία της έκφρασης της πρωτεΐνης HuR στο μη μικροκυτταρικό καρκίνωμα πνεύμονα

Η πρωτεΐνη HuR, μία συνδεόμενη πρωτεΐνη με το RNA, θεωρείται ότι διαδραματίζει ένα κρίσιμο ρόλο στην ανάπτυξη και εξέλιξη του όγκου, σταθεροποιώντας ή ρυθμίζοντας μία ομάδα mRNAs που σχετίζονται με γονίδια που συνδέονται με τον καρκίνο, όπως η COX-2. Η παρούσα μελέτη έχει σαν στόχο να αξιολογήσει την κλινική σημασία της έκφρασης της πρωτεΐνης HuR και του ενζύμου COX-2 στο ΜΜΚΠ. Η έκφραση της πρωτεϊνών HuR και COX-2 εκτιμήθηκε ανοσοϊστοχημικά σε ιστολογικές τομές, μονιμοποιημένων με φορμόλη και εγκλεισμένων σε παραφίνη μικροσυστοιχιών ιστολογικών παρασκευασμάτων προερχόμενων από 81 ασθενείς με ΜΜΚΠ. Τα αποτελέσματα αναλύθηκαν στατιστικά με τις κλινικοπαθολογικές παραμέτρους και την συνολική επιβίωση των ασθενών. Τα υψηλά επίπεδα έκφρασης της συνολικής πρωτεΐνης HuR συσχετίσθηκαν θετικά με τον ιστολογικό τύπο, την παρουσία λεμφαδενικών μεταστάσεων, τον αυξημένο ρυθμό κυτταρικού πολλαπλασιασμού των καρκινικών κυττάρων και την πτωχή επιβίωση των ασθενών (p=0.039, p=0.017, p=0.033, και p=0.022, αντίστοιχα). Η υψηλή έκφραση της πρωτεΐνης COX-2 συσχετίσθηκε θετικά με την παρουσία λεμφαγγειακής διήθησης και με τον αυξημένο ρυθμό κυτταρικού πολλαπλασιασμού των καρκινικών κυττάρων (p=0.031 και p=0.023, αντίστοιχα). Η ταυτόχρονη έκφραση των πρωτεϊνών HuR και COX-2 συσχετίσθηκε θετικά με τον ιστολογικό τύπο και τον αυξημένο ρυθμό κυτταρικού πολλαπλασιασμού των καρκινικών κυττάρων (p=0.002 και p=0.045, αντίστοιχα). Τα αυξημένα επίπεδα έκφρασης της συνολικής και της κυτταροπλασματικής πρωτεΐνης HuR συσχετίσθηκαν στατιστικά σημαντικά με την έκφραση της πρωτεΐνης COX-2 (p=0.015 και p=0.001, αντίστοιχα). Τα αποτελέσματα της παρούσας μελέτης υποστηρίζουν οτι η πρωτεΐνη HuR συμμετέχει στην εξέλιξη του ΜΜΚΠ, ενισχύοντας τον δυνητικό της ρόλο ως πολλά υποσχόμενου θεραπευτικού στόχου στη αντιμετώπιση αυτού του τύπου νεοπλασίας.Hu-antigen R (HuR) is considered to play a central role in tumor formation, growth, and metastasis by binding to messenger RNAs (mRNAs) encoding proteins such as cyclooxygenase- 2 (COX-2) and inducing their expression via mRNA stabilization and/or altered translation. The present study aimed to evaluate the clinical significance of HuR and COX-2 protein expression in non-small-cell lung carcinoma (NSCLC). HuR and COX-2 expression was assessed immunohistochemically on tissue microarrays of 81 surgically resected NSCLC and was analyzed in relation with clinico- pathological characteristics and patients’ survival. Enhanced total HuR expression was significantly associated with tumor histological type and presence of lymph node metastases, as well as with increased tumor proliferative capacity and poor patients’ outcome (p=0.039, p=0.017, p=0.033, and p= 0.022, respectively). Enhanced COX-2 expression was significantly associated with the presence of lymphovascular invasion and increased tumor proliferative capacity (p = 0.031 and p = 0.023, respectively). Concomitant elevated HuR/ COX- 2 expression levels were significantly associated with tumor histological type and increased proliferative capacity (p = 0.002 and p = 0.045, respectively). Enhanced total HuR expression, as well as its cytoplasmic localization, was signif- icantly associated with increased COX-2 expression (p = 0.015 and p = 0.001, respectively). The present study supported ev- idence that HuR may participate in malignant transformation of NSCLC, reinforcing its usefulness as potential therapeutic target in this type of neoplasia

Ephrin (Eph) receptor A1, A4, A5 and A7 expression in human non-small cell lung carcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients’ survival

BACKGROUND: Ephrin (Eph) receptors are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, metastasis and angiogenesis. The present study aimed to evaluate the clinical significance of EphA1, A4, A5 and A7 protein expression in non-small cell lung carcinoma (NSCLC). METHODS: EphA1, A4, A5 and A7 protein expression was assessed immunohistochemically in tissue microarrays of 88 surgically resected NSCLC and was analyzed in relation with clinicopathological characteristics and patients’ survival. RESULTS: Elevated EphA4 expression was significantly associated with low histopathological stage and presence of inflammation (p = 0.047 and p = 0.026, respectively). Elevated EphA7 expression was significantly associated with older patients’ age, presence of fibrosis and smaller tumor size (p = 0.036, p = 0.029 and p = 0.018, respectively). EphA1, A5 and A7 expression were positively associated with tumor proliferative capacity (p = 0.047, p = 0.002 and p = 0.046, respectively). Elevated EphA4, A5 and A7 expression were identified as predictors of favourable patients’ survival at both univariate (Log-rank test, 0 = 0.019, p = 0.006 and p = 0.012, respectively) and multivariate levels (Cox-regression analysis, p = 0.029, p = 0.068 and p = 0.044, respectively). CONCLUSIONS: The present study supported evidence that Ephs may be involved in lung cancer progression, reinforcing their utility as clinical biomarkers for patients’ management and prognosis, as also as potential targets for future therapeutic interventions

Osteoprotegerin, Soluble Receptor Activator of Nuclear Factor- κ

Aims. To evaluate carotid intima-media thickness (cIMT) and biomarkers of the osteoprotegerin/receptor activator of nuclear factor-κB ligand (OPG/RANKL) system in type 1 diabetes (T1DM) children and adolescents and controls. Subjects and Methods. Fifty six T1DM patients (mean ± SD age: 12.0 ± 2.7 years, diabetes duration: 5.42 ± 2.87 years and HbA1c: 8.0 ± 1.5%) and 28 healthy matched controls, were studied with anthropometric and laboratory measurements, including serum OPG, soluble RANKL (sRANKL) and cIMT. Results. Anthropometric, laboratory, and cIMT measurements were similar between T1DM youngsters and controls. However patients with longer diabetes duration (>/7.0 years) had indicatively higher cIMT (cIMT = 0.49 vs 0.44 mm, P 0.072) and triglyceride levels than the rest of the patients (93.7 vs 64.6 mg/dl, P 0.025). Both in the total study population (β 0.418, P 0.027) and among T1DM patients separately (β 0.604, P 0.013), BMI was the only factor associated with cIMT. BMI was further associated with OPG in both groups (β −0.335, P 0.003 and β −0.356, P 0.008 respectively), while sRANKL levels were not associated with any factor. Conclusions. BMI was the strongest independent predictor of cIMT among the whole population, and especially in diabetics, suggesting a possible synergistic effect of diabetes and adiposity on atherosclerotic burden. BMI was overall strongly associated with circulating OPG, but the causes of this association remain unclear

A Malignant Gastrointestinal Stromal Tumor of the Gallbladder Immunoreactive for PDGFRA and Negative for CD 117 Antigen (c-KIT)

Gastrointestinal stromal tumors (GISTs) compose the largest category of well-recognized nonepithelial neoplasms of the gastrointestinal tract (GI). GISTs of the gallbladder are extremely rare tumors. Only four malignant, two benign and one GIST-like tumor of the gall bladder have ever been described. The four malignant GISTs were all positive for CD 117 antigen (c-kit). We present for the first time a malignant gastrointestinal stromal tumor of the gallbladder, immunoreactive for platelet-derived growth factor receptor alpha (PDGFRA) and negative for CD 117 antigen (c-KIT)

Expression and clinical significance of concomitant FAK/SRC and p-Paxillin in mobile tongue squamous cell carcinoma.

Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reservedBACKGROUND/AIM: The focal adhesion kinase (FAK)/SRC phosphorylation cascade and its downstream target paxillin have been implicated in malignant transformation, tumor growth and progression, together with metastasis. The present study aimed to evaluate the clinical significance of concomitant FAK/SRC and p-paxillin expression in mobile tongue squamous cell carcinoma (SCC). MATERIALS AND METHODS: FAK, SRC and phospho-paxillin expression in 48 mobile tongue SCC tissue samples was assessed immunohistochemically and analyzed with respect to clinicopathological characteristics and patient survival. RESULTS: Concomitant high FAK/SRC expression was significantly associated with high grade of tumor differentiation (p=0.048) and longer disease-free patient survival (log-rank test, p=0.019). High p-paxillin expression was significantly associated with greater depth of invasion (p=0.002), lymph node metastasis (p=0.048) and poorer disease-free patient survival (log-rank test, p=0.021; Cox-regression analysis, p=0.031). CONCLUSION: The present study provides evidence that FAK/SRC and paxillin play a role in the pathophysiological aspects of mobile tongue SCC and could constitute therapeutic targets.Final Accepted Versio

Adenoid cystic carcinoma intermingled with ductal carcinoma of the breast: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Adenoid cystic cancer of the breast is a rare condition, and even rarer are the cases where it is histologically mixed with other variants of cancer within a single lesion. In this report, one of the few cases of mixed adenoid cystic breast cancer intermingled with the infiltrating ductal variant is presented. A subsequent review of the relevant literature presents the existing experience in treating mixed breast cancers with adenoid cystic components with regard to diagnosis, treatment, and prognosis.</p> <p>Case presentation</p> <p>We describe a case of mixed adenoid cystic cancer of the breast with infiltrating ductal carcinoma in a 67-year-old Caucasian woman who underwent mastectomy with sentinel node biopsy.</p> <p>Conclusion</p> <p>Surgery remains the cornerstone of treatment of these patients, and radiotherapy is administered when breast-conserving treatment is undertaken or a large tumor with affected lymph nodes is present. Hormonal treatment does not have a role, as estrogen receptors are always absent from both tumor components. Chemotherapy is nearly always administered on the basis of estrogen receptor and progesterone negativity and the more aggressive potential of the non-adenoid cystic component. The de-differentiation of an indolent type of cancer to a more aggressive one may affect the prognosis.</p

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat