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Purpose Angiogenesis is a crucial phenomenon in the development and progression of breast cancer (BC), but the clinical significance of angiogenesis-related proteins in metastatic BC remains unknown. This study investigates the prognostic value of vascular endothelial growth factor receptors 1, 2, 3 (VEGFR1, VEGFR2, VEGFR3) as well as vascular endothelial growth factors A and C (VEGFA and VEGFC) in metastatic BC patients treated with trastuzumab-based regimens.Materials and Methods Two hundred female patients were included. Protein and mRNA expression of the studied angiogenesis-related factors were evaluated by immunohistochemistry and quantitative polymerase chain reaction, respectively.Results High expression of VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 in the tumor cells was observed in 43.5%, 24.2%, 36%, 29.5%, and 43%, respectively. Stromal elements expressed high levels of VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 in 78.9%, 93.3%, 90.7%, 90.2%, and 74.8% of tumors with available data. High tumor cell expression of VEGFR1 was a favorable prognosticator for survival among patients with human epidermal growth factor receptor 2 (HER2)–positive tumors (hazard ratio [HR], 0.55; p=0.013). A trend towards longer progression-free survival was detected univariately for patients with HER2-negative tumors and high expression of VEGFR2 (HR, 0.60; p=0.059).Conclusion VEGFR1 and VEGFR2 seem to have significant prognostic value in BC patients with metastatic disease treated with trastuzumab-based regimens.

A growing number of studies have shed light on the role of small extracellular vesicles (sEVs), including exosomes, in colorectal cancer (CRC). Available data regarding the clinical significance of molecular players in CRC, implicated in sEVs biogenesis, is limited. In this study, we assessed the expression of the most important genes which are implicated in sEVs biogenesis and their association with sEVs plasma levels, investigated with a double sandwich ELISA assay, as well as with the clinical outcome of patients with CRC. Our study shows that RAB27A, RAB27B, RAB2B, and RAB3B mRNA levels were lower in tumor tissues compared to tumor adjacent, non-malignant tissues (p < 0.001, p = 0.009, p = 0.011, and p < 0.001, respectively). In addition, high tumor expression of RAB27A, RAB27B, RAB9A, RAB11B, and STX1A was favorable of a 5-year survival (p = 0.038, p = 0.015, p = 0.008, p = 0.002, and p = 0.028, respectively). Furthermore, patients with adenomas had lower overall plasma sEVs concentrations, compared to healthy volunteers (p = 0.026), while no statistically significant differences were observed in the overall or tumor-derived plasma sEVs concentration (p = 0.885 and p = 0.330, respectively) of CRC patients. In conclusion, sEVs biogenesis has a potentially significant role in CRC, with RAB27A, RAB27B, RAB9A, RAB11B, and STX1A having a promising role in survival outcomes.

To report a case of isolated optic neuritis associated with pembrolizumab immunotherapy for metastatic non-small cell lung carcinoma.A 76-year-old man, with a history of metastatic non-small cell lung carcinoma, presented with vision loss in his left eye for the past week. He had been treated with pembrolizumab for the underlying disease for 2 months. On presentation, best corrected visual acuity was 20/30 in the right eye and 20/200 in the left eye. Fundoscopy revealed optic nerve edema in the left eye. Visual fields examination in right eye revealed an enlarged blind spot and an extended defect in the inferior nasal quadrant. In the left eye a partial superior arcuate defect and an extended defect in the inferior hemisphere was observed. The mean deviation was -12.15 dB in the right eye and -13.70 dB in left eye. Pembrolizumab was withheld and corticosteroids were administered for a total of nine weeks, first intravenously and then slowly tapered orally, resulting in resolution of optic neuritis, restoration of visual acuity and in relative improvement in the visual field defects after 3 months. Calculated Naranjo Nomogram score was 7, indicating a 'highly probable' correlation.Optic neuritis is a relatively rare immune-related adverse event after exposure to checkpoint inhibitors cancer immunotherapy. Prompt discontinuation of the offending agent and early initiation of corticosteroid therapy is the mainstay of the treatment.

Thirty-four years since its discovery, NF-κB remains a transcription factor with great potential for cancer therapy. However, NF-κB–targeted therapies have yet to find a way to be clinically translatable. Here, we focus exclusively on the role of NF-κB in non-small cell lung cancer (NSCLC) and discuss its contributing effect on cancer hallmarks such as inflammation, proliferation, survival, apoptosis, angiogenesis, epithelial–mesenchymal transition, metastasis, stemness, metabolism, and therapy resistance. In addition, we present our current knowledge of the clinical significance of NF-κB and its involvement in the treatment of patients with NSCLC with chemotherapy, targeted therapies, and immunotherapy.

Integrin-linked kinase (ILK) forms a heterotrimeric protein complex with PINCH and PARVIN (IPP) in Focal Adhesions (FAs) that acts as a signaling platform between the cell and its microenvironment regulating important cancer-related functions. We aimed to elucidate the role of ILK in lung adenocarcinoma (LUADC) focusing on a possible link with KRAS oncogene. We used immunohistochemistry on human tissue samples and KRAS-driven LUADC in mice, analysis of large scale publicly available RNA sequencing data, ILK overexpression and pharmacological inhibition as well as knockdown of KRAS in lung cancer cells. ILK, PINCH1 and PARVB (IPP) proteins are overexpressed in human LUADC and KRAS-driven LUADC in mice representing poor prognostic indicators. Genes implicated in ILK signaling are significantly enriched in KRAS-driven LUADC. Silencing of KRAS, as well as, overexpression and pharmacological inhibition of ILK in lung cancer cells provide evidence of a two-way association between ILK and KRAS. Upregulation of PINCH, PARVB and Ras suppressor-1 (RSU1) expression was demonstrated in ILK overexpressing lung cancer cells in addition to a significant positive correlation between these factors in tissue samples, while KRAS silencing downregulates IPP and RSU1. Pharmacological inhibition of ILK in KRAS mutant lung cancer cells suppresses cell growth, migration, EMT and increases sensitivity to platinum-based chemotherapy. ILK promotes an aggressive lung cancer phenotype with prognostic and therapeutic value through functions that involve KRAS, IPP complex and RSU1, rendering ILK a promising biomarker and therapeutic target in lung adenocarcinoma.

BACKGROUND/AIM The aim of the present study was to investigate the clinical significance of 7 single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor A (VEGFA), endothelin receptor type A (EDNRA), nibrin (NBS1) and Fas cell surface death receptor (FAS) genes in patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS Genomic DNA was extracted from the peripheral blood specimens of 60 patients. Genotyping of 4 VEGFA polymorphisms, namely VEGFA -1154 G/A (rs1570360), -2578 A/C (rs699947), -1498 C/T (rs833061) and +936 C/T (rs3025039), as well as EDNRA SNP p.His323 (rs5333), NBS1 p.E185Q (rs1805794) and FAS -671 A/G (rs1800682) was performed by using Sanger sequencing. RESULTS The VEGFA +936 CC genotype was more frequent in tumors with bilateral infiltration of pterygoid plates compared to those with ipsilateral (76.9% vs. 69.6%, p=0.008) and no infiltration of pterygoid plates (76.9% vs. 68.8%, p=0.023). VEGFA -2578, VEGFA -1154 and VEGFA +936 were significantly associated with infiltration to the pterygoid processes (p=0.011, p=0.041 and p=0.032, respectively). EDNRA H323H TT genotype was marginally associated with infiltration to the ipsilateral medial pterygoid muscles (p=0.045). A trend towards longer overall survival was observed for VEGFA -2578 CC as compared to AC (HR=0.24, p=0.060). CONCLUSION The studied VEGFA SNPs seem to be associated with the local extension of the NPC and maybe with the clinical outcome of this patient group.

In the present study, we evaluated the expression of JUNB and CXCR4 in circulating tumor cells (CTCs) of lung cancer patients and investigated whether these proteins have prognostic clinical relevance. Peripheral blood from 30 patients with non-small-cell lung cancer (NSCLC) was filtered using ISET membranes, and cytospins from 37 patients with small-cell lung cancer (SCLC) were analyzed using confocal and VyCAP microscopy. Both JUNB and CXCR4 were expressed in the vast majority of lung cancer patients. Interestingly, the phenotypic patterns differed between NSCLC and SCLC patients; the (CK+/JUNB+/CXCR4+) phenotype was present in 50% of NSCLC vs. 71% of SCLC patients. Similarly, the (CK+/JUNB+/CXCR4–) was present in 44% vs. 71%, the (CK+/JUNB–/CXCR4+) in 6% vs. 71%, and the (CK+/JUNB–/CXCR4–) phenotype in 38% vs. 84%. In NSCLC, the presence of ≥1 CTCs with the (CK+/JUNB+/CXCR4+) phenotype was associated with worse progression-free survival (PFS) (p = 0.007, HR = 5.21) while ≥2 with poorer overall survival (OS) (p < 0.001, HR = 2.16). In extensive stage SCLC patients, the presence of ≥4 CXCR4-positive CTCs was associated with shorter OS (p = 0.041, HR = 5.01). Consequently, JUNB and CXCR4 were expressed in CTCs from lung cancer patients, and associated with patients’ survival, underlying their key role in tumor progression.

Current research often refers to cultural competence to improve health care delivery. In addition, it focuses on the cultural uniqueness of each health service user for optimal personalized care. This study aimed to collect self-assessment data from health professionals regarding their cultural competence and to identify their development needs. A mixed methods design was adopted using the Cultural Competence Self-assessment Checklist of the Central Vancouver Island Multicultural Society. This was translated into Greek, validated, and then shared with health professionals in Cyprus. Subsequently, a semi-structured interview guide was designed and utilized. This was structured in exactly the same question categories as the questionnaire. Data collection took place between October 2021 and May 2022, and convenience sampling was used to recruit 499 health scientists in Cyprus. The sample comprised doctors, nurses, psychologists, midwives, social workers, and physiotherapists. Subsequently, 62 interviews were conducted with participants from the same specialties. The results showed that (compared to other health professionals) nurses and psychologists are more sensitive to issues of cultural competence. It would appear that the more socially oriented sciences had better-prepared healthcare staff to manage diversity in context. However, there is a gap between knowledge and skills when comparing doctors to nurses; they seem to be more skilled and willing to intervene actively in cases of racist behavior or problem-solving. In conclusion, participants identified the importance of their cultural competence; they also realized the importance of optimal planning of personalized health care. There is a significant need for continuous and specialized cultural competence training for all health professions.

Μία από τις πλέον σημαντικές και μελετημένες οικογένειες μεταγραφικών παραγόντων στον καρκίνο είναι αυτή του NF-κB. Αν και το κλασικό μονοπάτι του NF-κB έχει γίνει αντικείμενο εντατικής έρευνας από δεκαετιών, το εναλλακτικό μονοπάτι μόλις πρόσφατα συσχετίσθηκε με την καρκινογένεση, ενώ ελάχιστα δεδομένα υπάρχουν για τον ρόλο του στο μη-μικροκυτταρικό καρκίνωμα του πνεύμονα (ΜΜΚΠ). Σκοπός της παρούσας μελέτης ήταν ο προσδιορισμός της έκφρασης των μορίων NF-κB2, RELB, NIK και BCL3 σε επίπεδο πρωτεΐνης και mRNA και η συσχέτιση της με τα κλινικοπαθολογοανατομικά δεδομένα και την επιβίωση ασθενών με ΜΜΚΠ. Επίσης, εκτιμήθηκε η κλινική σημασία των μονονουκλεοτιδικών πολυμορφισμών rs7897947, rs11574852, rs12769316 του γονιδίου NF-κB2 και rs8100239 του γονιδίου BCL3 στον ΜΜΚΠ. Για το σκοπό αυτό χρησιμοποιήθηκαν 268 δείγματα αίματος και δείγματα μονιμοποιημένων σε παραφίνη ιστών (παρακείμενων στην εξεργασία, μη νεοπλασματικών) ασθενών με ΜΜΚΠ και 279 δείγματα αίματος υγιών δοτών από τα οποία απομονώθηκε DNA με τη χρήση ολοκληρωμένων συστημάτων αντιδραστηρίων. Η παρουσία των 4 πολυμορφισμών ανιχνεύτηκε με τη χρήση πραγματικού χρόνου αλυσιδωτής αντίδρασης πολυμεράσης (real-time PCR). Η έκφραση των μορίων NF-κB2, RELB, ΝΙΚ και BCL3 σε επίπεδο πρωτεΐνης και mRNA προσδιορίστηκε με ανοσοϊστοχημικές μεθόδους και με τη χρήση real-time RT-PCR, αντιστοίχως. Τα κύρια αποτελέσματα της μελέτης μπορούν να συνοψισθούν ως εξής:1)Όσον αφορά την πρωτεϊνική έκφραση:-Τα μόρια NF-κB2, RELB, BCL3 και NIK υπερεκφράζονται στα καρκινικά κύτταρα σε σχέση με τον παρακείμενο μη νεοπλασματικό ιστό (PA) συσχετίσθηκε με τον κίνδυνο ανάπτυξης ΜΜΚΠ (P=0,003), ενώ ασθενείς σταδίου Ι φορείς του αλληλομόρφου A (rs12769316) εμφάνισαν καλύτερη τριετή επιβίωση χωρίς όμως αυτή η τάση να φτάσει το όριο στατιστικής σημαντικότητας (P=0,057). Αντιθέτως, οι ομοζυγώτες GG (rs12769316) του σταδίου ΙΙ παρουσίασαν χειρότερη πενταετή επιβίωση σε σύγκριση με τους φορείς του αλληλομόρφου A (P=0,012). Επίσης, ο πολυμορφισμός rs12769316 σχετίσθηκε με την πρωτεϊνική έκφραση του NF-κB2 (P=0,001), με το στάδιο της νόσου (P=0,042) και με τη μέγιστη διάμετρο του όγκου (P=0,025).-Η κατανομή των αλληλομόρφων του πολυμορφισμού rs7897947 (NF-κB2) διαφέρει μεταξύ των ασθενών και των υγιών (P=0,024) και σχετίζεται με το στάδιο της νόσου και το μέγεθος του όγκου (P=0,016 και P=0,04 αντιστοίχως).-Ο πολυμορφισμός rs11574852 (NF-κB2) σχετίζεται με τη συχνότητα υποτροπής της νόσου (P=0,045), με τον ιστολογικό υπότυπο, το βαθμό διαφοροποίησης, τη διετή επιβίωση (P=0,036, P=0,004, P=0,05 και αντιστοίχως) και με την πρωτεϊνική έκφραση του NF-κB2 (P

Background Heart failure is a chronic disease with a serious impact on patients' quality of life which is influenced by several factors. Aims The purpose of this study is to evaluate the quality of life of patients with heart failure in the city of Limassol in Cyprus. Methods The proposed study is characteristically descriptive quantitative research. The sample includes 99 patients with heart failure in Limassol Hospital, using the Minnesota Living with Heart Failure Questionnaire in the Greek Language. The data were collected from October 2017 to November 2017. Findings Our sample consisted of 99 individuals from the Limassol district, 40 (40.4%) were females and the average age of the patients was 68.5±14 years. Patients with heart failure who had a primary education averaged 9.69 points on the quality of life scale. This is lower than patients with higher education (b=9.69 P=0.057), lower physical health by 7.35 points (b=7.35 P=0.008) and lower by 2.26 Social health units (b=2.26 P=0.030). Conclusion Patients with heart failure experience many and complex problems. Through this research, it appears that different dimensions of quality of life are affected, such as physical, social and emotional health. The older the age of the patient, the lower levels of education and the sex of the patient have an impact on the quality of life of patients with heart failure.

Renal cell carcinoma (RCC) is one of the most aggressive malignancies of the genito-urinary tract, having a poor prognosis especially in patients with metastasis. Surgical resection remains the gold standard for localized renal cancer disease, with radiotherapy (RT) receiving much skepticism during the last decades. However, many studies have evaluated the role of RT, and although renal cancer is traditionally considered radio-resistant, technological advances in the RT field with regards to modern linear accelerators, as well as advanced RT techniques have resulted in breakthrough therapeutic outcomes. Additionally, the combination of RT with immune checkpoint inhibitors and targeted agents may maximize the clinical benefit. This review article focuses on the role of RT in the therapeutic management of renal cell carcinoma.

Highlights • Cancer-associated cachexia is mainly characterized by skeletal muscle and adipose loss, release of pro-cachectic factors by cancer and immune cells and energy imbalance. • Cancer cachexia is prominent in many types of cancer and it is associated with poor prognosis. • MiRNAs and lncRNAs implicated in muscle atrophy, lipolysis, adipose browning and inflammation are deregulated in muscle or adipose tissue in cancer cachexia patients or animal models of cancer cachexia. • Deregulated ncRNAs are found in circulation or in circulating exosomes in cancer cachexia patients., Cachexia is a multifactorial syndrome characterized by skeletal muscle loss, with or without adipose atrophy, irreversible through nutritional support, in the context of systemic inflammation and metabolic disorders. It is mediated by inflammatory reaction and affects almost 50% of all cancer patients, due to prominent systemic inflammation associated with the disease. The comprehension of the molecular mechanisms that are implicated in cancer cachexia sheds light on its pathogenesis and lays the foundations for the discovery of new therapeutic targets and biomarkers. Recently, ncRNAs, like microRNAs as well as lncRNAs and circRNAs seem to regulate pathways that are implicated in cancer cachexia pathogenesis, as it has been observed in animal models and in cancer cachexia patients, highlighting their therapeutic potential. Moreover, increasing evidence highlights the involvement of circulating and exosomal ncRNAs in the activation and maintenance of systemic inflammation in cancer and cancer-associated cachexia. In that context, the present review focuses on the clinical significance of ncRNAs in cancer-associated cachexia., Graphical abstract Image, graphical abstract

Simple Summary Angiogenesis and apoptosis play a pivotal role in the pathogenesis and clinical course not only of nasopharyngeal cancer (NPC), but also of other subgroups of head and neck cancer (HNC), such as laryngeal cancer. Thus, the aim of this study was to investigate the clinical significance of genetic polymorphisms in four pivotal angiogenesis- and apoptosis-related genes (VEGFA, FAS, EDNRA and NBS1) in HNC patients. Thirty-four genetic variants located in the studied genes were assessed. Two of them (VEGFA rs13207351 and FAS rs2234768) were associated with overall survival for patients with laryngeal cancer and NPC, respectively, with VEGFA rs13207351 showing the most promise for its prognostic value in the subgroup of laryngeal cancer patients. This study suggests that genetic variations in angiogenesis- and apoptosis-related genes may be useful in the management of HNC patients. Abstract Head and neck cancer (HNC) is a significantly heterogeneous disease and includes malignancies arising from different anatomical sites, such as nasopharyngeal cancer (NPC) and laryngeal cancer (LC). In the current study, polymorphisms located in angiogenesis- and apoptosis-related genes (VEGFA, FAS, EDNRA and NBS1) were evaluated regarding their clinical significance in HNC patients. In total, 333 HNC patients were enrolled in this study and 34 variants located on the aforementioned genes were genotyped via Sanger sequencing. LC patients, homozygous A for VEGFA rs13207351, had shorter overall survival (OS) as opposed to homozygous G (Hazard ratio (HR) = 2.06, Wald’s p = 0.017) upon adjustment for age, disease stage, and surgery. Following the dominant model, LC patients carrying the A allele had a marginally significantly higher risk for death (HR = 1.72, p = 0.059). NPC patients heterozygous (CT) for FAS rs2234768 had a marginal but significantly higher risk of death compared to those with homozygosity for the T allele (HR = 2.22, p = 0.056). In conclusion, rs13207351 (VEGFA) and rs2234768 (FAS) polymorphisms seem to have prognostic significance in HNC, with VEGFA rs13207351 showing the most promise in this subgroup of LC patients.

Despite the enormous advances during the last three decades, breast cancer continues to be the most frequent type of cancer as well as one of the most frequent cancer-related causes of death in women. Therapeutic management of patients with hormone receptor-positive breast cancer becomes very often a challenge, since de novo or acquired resistance deprives a significant percentage of the patients from the clinical benefit of the well-tolerated hormone therapy. Several molecular mechanisms are implicated in resistance to endocrine therapy, including changes in hormone receptor signaling, activation of parallel signaling pathways, modifications of cell cycle regulators, activation of different transcription factors as well as changes in stem cells activity. In addition, a growing number of studies supports the pivotal role of epigenetic changes not only in the initiation and progression of breast cancer, but also in resistance to endocrine therapy. These changes refer to DNA methylation, histone post-translational modifications as well as to ncRNAs alterations. In this review, we provide an overview of epigenetic mechanisms underlying the endocrine resistance focusing exclusively on breast cancer patients.

Immunotherapy with immune checkpoint inhibitors (ICIs) has changed the therapeutic management of advanced non-small cell lung cancer (aNSCLC) over the last decade. However, there is an unmet need for clinically useful biomarkers in this patient subgroup. The aim of this study was to combine baseline clinical characteristics of aNSCLC patients, in the form of a scoring system, and to investigate its predictive and prognostic value in NSCLC patients treated with ICIs. A total of 112 patients with advanced (stages IIIA to IV) NSCLC, treated with nivolumab or pembrolizumab, were enrolled in this study. Patras Immunotherapy Score (PIOS) was developed based on four of the studied parameters (performance status (PS), body mass index (BMI), age, and lines of treatment (LOT), which were incorporated into our formula (PS &times, BMI/ LOT &times, age). PIOS score was strongly associated with best overall responses (BOR), with those patients having benefit/good response (stable disease (SD) or partial (PR) or complete response (CR), achieving a higher score compared to patients who developed progressive disease (PD) (p &lt, 0.001). Furthermore, PIOS score was associated with progression-free survival (PFS), since high-score patients had longer PFS (p &lt, 0.001, hazard ratio (HR) = 0.469). Moreover, PIOS was associated with post-immunotherapy overall survival (OS), with high-score patients having improved OS (log-rank p = 0.019). This study suggests that a combination of baseline parameters, which give rise to PIOS score, may predict the best response of NSCLC patients treated with anti-program cell death -1 (PD-1) monotherapy as well as it may have a potent prognostic value for PFS and post immunotherapy OS.

Deregulation of the transcribed ultra-conserved regions (T-UCRs) Uc160, Uc283, and Uc346 has been reported in colorectal cancer (CRC) recently. Here, we investigated promoter methylation of these T-UCRs during the adenoma&ndash, carcinoma sequence and their clinical significance in CRC patients. Methylation levels were assessed in CRC, adenomas, infiltrated lymph nodes, and metastatic tissue specimens. In situ hybridization was performed in representative tissue specimens. T-UCRs expression levels were also evaluated in HT-29 colon cancer cells before and after the acquired resistance to 5-fluorouracil (5-FU) and oxaliplatin. A gradual increase in T-UCRs methylation levels from hyperplastic polyps to adenomas and to in situ carcinomas (ISC) and a gradual decrease from ISC to infiltrative and metastatic carcinomas was observed (p &lt, 0.001 for Uc160 and Uc283, p = 0.018 for Uc346). Uc160 and Uc283 methylation was associated with the grade of dysplasia in adenoma specimens (p = 0.034 and p = 0.019, respectively). Furthermore, higher Uc160 methylation, mainly in stage III and IV patients, was related to improved overall survival (OS) in univariate (p = 0.009, HR, 0.366) and multivariate analysis (p = 0.005, HR, 0.240). Similarly, higher methylation of Uc283 was associated with longer OS (p = 0.030). Finally, T-UCRs expression was significantly reduced in HT-29 cells after resistance to chemotherapy. This study suggests that promoter methylation of Uc160, Uc283, and Uc346 is altered during CRC development and that Uc160 and Uc283 methylation may have prognostic significance for CRC patients.

The aim of the present study was to investigate the clinical significance of 7 single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor A (VEGFA), endothelin receptor type A (EDNRA), nibrin (NBS1) and Fas cell surface death receptor (FAS) genes in patients with nasopharyngeal carcinoma (NPC).Genomic DNA was extracted from the peripheral blood specimens of 60 patients. Genotyping of 4 VEGFA polymorphisms, namely VEGFA -1154 G/A (rs1570360), -2578 A/C (rs699947), -1498 C/T (rs833061) and +936 C/T (rs3025039), as well as EDNRA SNP p.His323 (rs5333), NBS1 p.E185Q (rs1805794) and FAS -671 A/G (rs1800682) was performed by using Sanger sequencing.The VEGFA +936 CC genotype was more frequent in tumors with bilateral infiltration of pterygoid plates compared to those with ipsilateral (76.9% vs. 69.6%, p=0.008) and no infiltration of pterygoid plates (76.9% vs. 68.8%, p=0.023). VEGFA -2578, VEGFA -1154 and VEGFA +936 were significantly associated with infiltration to the pterygoid processes (p=0.011, p=0.041 and p=0.032, respectively). EDNRA H323H TT genotype was marginally associated with infiltration to the ipsilateral medial pterygoid muscles (p=0.045). A trend towards longer overall survival was observed for VEGFA -2578 CC as compared to AC (HR=0.24, p=0.060).The studied VEGFA SNPs seem to be associated with the local extension of the NPC and maybe with the clinical outcome of this patient group.

// Anastasia E. Kottorou 1 , Anna G. Antonacopoulou 1 , Foteinos-Ioannis D. Dimitrakopoulos 1, 3 , Georgia Diamantopoulou 2 , Chaido Sirinian 1 , Melpomeni Kalofonou 1, 6 , Theodoros Theodorakopoulos 2 , Chrysa Oikonomou 3 , Evangelos C. Katsakoulis 2 , Angelos Koutras 1, 3 , Thomas Makatsoris 1, 3 , Nikos Demopoulos 4 , Georgia Stephanou 4 , Michalis Stavropoulos 5 , Konstantinos C. Thomopoulos 2 and Haralabos P. Kalofonos 1, 3 1 Clinical and Molecular Oncology Laboratory, Division of Oncology, Medical School, University of Patras, Patras, Greece 2 Division of Gastroenterology, University Hospital of Patras, Patras, Greece 3 Division of Oncology, University Hospital of Patras, Patras, Greece 4 Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, Patras, Greece 5 Department of Surgery, Medical School, University of Patras, Patras, Greece 6 Institute of Biomedical Engineering, Imperial College London, London, UK Correspondence to: Haralabos P. Kalofonos, email: kalofonos@upatras.gr Keywords: transcribed-ultra conserved regions; colorectal cancer and adenomas; tissue and plasma methylation; screening biomarker; expression levels Received: January 12, 2017 Accepted: March 02, 2018 Published: April 20, 2018 ABSTRACT Expression of Transcribed Ultraconserved Regions (T-UCRs) is often deregulated in cancer. The present study assesses the expression and methylation of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal cancer (CRC) and explores the potential of T-UCR methylation in circulating DNA for the detection of adenomas and adenocarcinomas. Expression levels of Uc160, Uc283 and Uc346 were lower in neoplastic tissues from 64 CRC patients (statistically significant for Uc160, p

Simple Summary The role of exosomes in HIV (human immunodeficiency virus) as well as in cancer patients seems to be pivotal. The aim of our retrospective study was to assess the potential clinical value of CD9-positive plasma exosomes in lung cancer patients, patients with lung granulomas, healthy individuals, and HIV-positive patients with or without lung cancer. This study shows that CD9-positive plasma exosome concentrations differ between healthy controls, patients with immunocompetent pulmonary granulomas and patients with lung cancer. In addition, CD9-positive plasma exosomes are increased in HIV seropositive and HIV seronegative lung cancer patients compared to healthy controls, while chemotherapy-treated lung cancer patients have lower plasma exosome levels. This study also shows that in chemotherapy-naïve patients, plasma exosome levels are directly correlated with a prognosis with higher concentrations being associated with a longer, overall survival. These findings further support previous literature on the translational significance of total plasma exosomes in cancer patients, despite different immunological contexts. Abstract Recently, the role of exosomes in the progression of both cancer and HIV (human immunodeficiency virus) has been described. This study investigates the clinical significance of CD9-positive plasma exosomes in lung cancer patients, healthy individuals, and HIV-positive patients with or without lung cancer. Using a verified with transmission electron microscopy double-sandwich ELISA technique, plasma-derived exosomes were isolated and quantified from 210 lung cancer patients (including 44 metastatic patients with progressive disease after chemotherapy), 49 healthy controls, 20 patients with pulmonary granulomas, 19 HIV+ patients with lung cancer, 31 HIV+ patients without cancer, and 3 HIV+ patients with pulmonary granulomas. Plasma exosome concentrations differed between healthy controls, patients with immunocompetent pulmonary granulomas and patients with lung cancer even after chemotherapy (p < 0.001). Lung cancer patients after chemotherapy had lower exosome concentrations compared to patients with untreated lung cancer or granuloma (p < 0.001 for both). HIV+ patients without lung cancer had significantly higher exosome concentrations compared to HIV+ patients with lung cancer (p = 0.016). Although exosome concentrations differed between all different lung cancer histologies and healthy controls (p < 0.001 for all histologies), adjusted statistical significance was oµy retained for patients with granulomas and SCLC (Small-cell lung cancer, p < 0.001). HIV-induced immunodeficient patients with or without lung cancer had lower plasma exosomes compared to immunocompetent granuloma and lung cancer patients (p < 0.001). Finally, higher plasma exosomes were associated both on univariate (p = 0.044), and multivariate analysis (p = 0.040) with a better 3-year survival in stage II and III NSCLC (Non-small-cell lung carcinoma) patients. In conclusion, our study shows that CD9-positive plasma exosomes are associated with both lung cancer and HIV, prior chemotherapy, as well as with survival, suggesting a possible prognostic value.

Introduction: Aggressive periodontitis (AgP), according to the diagnostic criteria set by the American Academy of Periodontology, is an infrequent periodontal disease. However, certain cases originally diagnosed as AgP due to young age and the involvement of first molars, when not responding to therapy, can diagnostically involve more severe systemic conditions such as the rare disorder Langerhans cell histiocytosis (LCH).Case Presentation: A 25-year-old white male, with no known systemic diseases, was referred to the Postgraduate Clinic of the Department of Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece. Clinical and radiographic examination and comparison with a previous evaluation revealed a rapidly progressive lesion involving the molar region in all quadrants, although the patient had been treated by a periodontist during the last 2 years. Molars were extracted and biopsies taken, which demonstrated morphologic and immunohistochemical cha...

Background: Genetic events cannot account for the complexity of human carcinogenesis alone. Mutations of epigenetic regulators and aberrations of their expression patterns have been detected in various human malignancies. Methylation of histone H3 at lysine 4 (H3K4me), is an evolutionarily conserved histone modification that marks regions of active transcription and regulates cell growth, migration, and invasion. The MLL/KMT2 family of histone methyltransferases specifically methylate histone H3 at lysine 4. Objective: The aim of this study was to explore the role of KMT2C/MLL3 as well as key histone modification activating markers, such as H3K4me2 and H3K4me3 in a cohort of surgically resected human lung adenocarcinomas in an effort to reveal possible biomarkers for lung adenocarcinoma diagnosis and prognosis and potential therapeutic targets. Method: The immunohistochemical expression of KMT2C/MLL3, H3K4me2 and H3K4me3 was analyzed in formalin fixed paraffin embedded tissue from 96 patients with lung adenocarcinoma. Results were associated with clinicopathologic parameters and patient’s prognosis. Results: Nuclear expression of KMT2C/MLL3 in epithelial cells was independently associated with shorter overall survival. Cytoplasmic H3K4me2 expression was associated withT stage and nuclear H3K4me2 expression was associated with female gender and patients’ prognosis. The latter association persisted after multivariate analysis. No association was found between H3K4me3 expression and clinicopathological data or disease outcome in our cohort of patients. Conclusion: These results suggest that the pattern of histone modifications and KMT2C/MLL3 expression can be used as an independent prognostic factor in lung adenocarcinoma, revealing that chromatin remodeling is criticallyinvolved in cancer progression.

A growing number of studies has shed light on the role of the NF-κΒ in non-small-cell lung cancer (NSCLC). To address the significance of major effectors of the NF-κΒ alternative pathway, we investigated the relationship between NF-κΒ2, RelB, NIK and Bcl3 expression (mRNA and protein) and the clinical outcome of NSCLC patients. NF-κΒ2, RelB, NIK and Bcl3 protein expression levels were assessed by immunohistochemistry in tissue samples from 151 NSCLC patients who had curative resection. mRNA levels were also evaluated in 69 patients using quantitative real-time PCR. Although all studied proteins were overexpressed in NSCLC (P RelB mRNA levels were strongly increased in cancerous specimens compared to tumor-adjacent non-neoplastic tissues (P = 0.009). Moreover, NF-κB2, RelB and Bcl3 expression was associated with overall survival (OS). In particular, cytoplasmic and mRNA expression of RelB was related to 5-year OS (P = 0.014 and P = 0.006, respectively). Multivariate analysis also showed that Bcl3 expression (nuclear and cytoplasmic) was associated with increased 5-year OS (P = 0.002 and P = 0.036, respectively). In addition, higher Bcl3 mRNA levels were associated with inferior OS in stages I & II and improved OS in stages III and IV after 5-year follow-up (P = 0.004 and P = 0.001, respectively). Furthermore, stage I patients with lower NF-κB2 mRNA levels had better 5-year survival in univariate and multivariate analysis (P = 0.031 and P = 0.028, respectively). Interestingly, RelB expression (cytoplasmic and mRNA) was inversely associated with relapse rates (P = 0.027 and P = 0.015, respectively), while low NIK cytoplasmic expression was associated with lower relapse rates (P = 0.019). Cytoplasmic NIK expression as well as NF-κB2/ Bcl3 detection was associated with lymph node infiltration (P = 0.039 and P = 0.014, respectively). The present study confirms the deregulation of the NF-κB alternative pathway in NSCLC and also demonstrates the importance of this pathway in prognosis, recurrence and infiltration of regional lymph nodes.

An increasing number of studies implicates the NF-&kappa, B (Nuclear Factor of kappa light chain gene enhancer in B cells) alternative pathway in non-small-cell lung cancer (NSCLC). We assessed the clinical significance of CD40 (Tumor necrosis factor receptor superfamily member 5, TNFRSF5), BAFFR (B-cell activating factor receptor), RANK (Receptor activator of NF-&kappa, B) and LT&beta, R (lymphotoxin &beta, receptor) receptors, which activate the alternative pathway of NF-&kappa, B, in NSCLC. Evaluation of CD40, BAFFR, RANK and LT&beta, R expression was performed based on the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets, while protein expression was assessed by immunohistochemistry in specimens from 119 operated NSCLC patients. CD40 gene overexpression was correlated with improved five-year overall survival (OS) (p &lt, 0.001), while increased BAFFR and LT&beta, R mRNA levels were associated with worse OS in patients with adenocarcinomas (p &lt, 0.001 and p &lt, 0.001, respectively). Similarly, patients with adenocarcinomas exhibited a negative correlation between membranous BAFFR protein expression in carcinoma cells and three- and five-year survival (p = 0.021, HR, 4.977 and p = 0.030, HR, 3.358, respectively) as well as between BAFFR protein overexpression in cancer-associated fibroblasts (CAFs) and two-year survival (p = 0.036, HR, 1.983). Patients with increased LT&beta, R nuclear protein staining or stage II patients with lower cytoplasmic LT&beta, R protein expression had worse five-year OS (p = 0.039 and p = 0.008, respectively). Moreover, CD40 protein expression in tumor infiltrating lymphocytes (TILs) and CAFs was positively associated with metastatic spread while BAFFR protein expression in CAFs was negatively associated with bone metastasis (p = 0.041). Our data suggests that CD40, BAFFR, RANK and LT&beta, R play an important role in NSCLC and further supports the role of NF-&kappa, B alternative pathway in NSCLC.

The aim of this paper is to offer an applicable evaluation framework relating to the right choice of one’s profession via his/her studies. The first part of the paper consists of the basic principles of multicriteria decision-making. To begin with, the paper initially focuses on the MACBETH method. This helps to provide a perspective for procedural types of decisions in which various qualitative and quantitative aspects are incorporated. In the second part of the paper, the abovementioned multicriteria method is applied to a “real-world” case concerning a specific case of a student, Eva. For this specific study, it is concluded that the factors of greatest importance that lead to choosing the university Eva finally chose were four: the cost of undergraduate studies, the reputation-status of the university, its logistics and infrastructure, and its interconnections with other universities and other academic institutions.

Highlights • NF-κB2 and RELB levels were upregulated in CRC and surrounding stroma compared to non-neoplastic tissue and stroma. • RELB protein expression in the tumour had prognostic value for overall survival. • Tumour RELB gene expression in the tumour was associated withTTP and NF-κB2 gene expression was prognostic for survival and TTP. • NFKB2 rs12769316 and rs7897947 were associated with lymph node infiltration and rs12769316 correlated with relapse status. • Rs7897947 G allele was associated with reduced risk for developing CRC., The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family of transcription factors plays an important role in immune responses and cancer development and progression. We have focused on NF-κB2 and RELB of the alternative pathway of NF-κB, which remains largely underexplored in colorectal cancer (CRC). We found that NF-κB2 and RELB protein levels were upregulated in tumour and surrounding stromal tissue compared to distant non-neoplastic tissue (NN) and associated stroma (p

Our aim was to compare pedicled and island nasolabial flaps used for reconstruction of oral defects in terms of postoperative complications, recovery of sensitivity, and quality of life. We organised a retrospective cohort study of 49 patients who had had intraoral reconstruction with nasolabial pedicled (n-=13) and island (n=36) flaps. Twenty- two patients filled in a validated quality-of-life (QoL) questionnaire and we did sensitivity tests (sharp discrimination with the aid of a Semmes-Weinstein™ aesthesiometer). Descriptive and bivariate statistics were computed and probabilities of 0.05 were accepted as significant. There were 11 flap-related complications (22%), and the flap was totally necrotic in three patients (6%), all of whom had island flaps. There was a significant association between flap-related complications and the use of reconstruction plate p=0.001, 95% CI 2.36 to 11.37) and advanced stage (T3 and T4 p=0.01, 95% CI 1.45 to 5.26). Skin sensitivity recovered in both island and pedicled flaps. Patients treated with island flaps had significantly more problems with prosthetic rehabilitation than those treated with pedicled flaps. The relatively low morbidity and adequate functional and aesthetic results make the pedicled nasolabial flap a viable technique. De-epithelialisation of the pedicle in island flaps permits coverage of defects with unilateral flaps in a one-stage reconstruction. However, the pedicle may be excessively stretched, leading to ischaemic complications.

Background Organ transplantation was one of the greatest achievements of medical science during the 20th century. Knowledge, education, and culture all play prominent roles in transplantation because of the complexity of the process from donation to transplantation. Purpose The aim of this research was to determine and analyze the knowledge and attitudes about organ donation and transplantation among the general population in Limassol, Cyprus. Methods A quantitative research approach was followed, and a questionnaire consisting of closed-ended questions was completed by adults from the general population in Limassol. Results One thousand two hundred adults out of the 1,346 adults who were contacted responded to the survey (response rate: 89%) and were included as participants. Of the participants, 93.4% (p < .05) considered organ donation to be lifesaving, 57% expressed interest (and 39.8% expressed disinterest) in becoming organ donors, 80.6% (p < .05) expressed awareness of there being a waiting list for people in need of organ transplantation, 50.4% agreed that brain death must be confirmed before organ removal for transplantation, and 47% recalled having been informed about organ donation through the media, with 31.5% stating that they had never been informed about organ donation. Conclusions The participants demonstrated limited awareness regarding the organ donation system in Cyprus. Furthermore, a significant percentage stated that they lacked a source for obtaining related information. The Cypriot society should be informed and encouraged to participate in organ donation to increase the rate of organ transplantation.

e21507 Background: With the exception of programmed death ligand 1 (PD-L1) expression and Tumour Mutational Burden (TMB), which have entered clinical practice, no other clinically useful predictive biomarker for immune checkpoint inhibitors (ICIs) has been established in the daily practice. The purpose of this study was to develop a novel, non-interventional and clinically useful predictive score for NSCLC patients with advanced disease treated with ICIs. Methods: Eighty-nine patients with advanced and histologically confirmed NSCLC (stages III and IV), treated with immunotherapy (nivolumab, pembrolizumab, atezolizumab), were enrolled in the current study. Clinicopathological data as well response rates and clinical outcome data were collected. Based on this data and using a regression model, we developed a predictive score (Patras Immunotherapy Score-PIOS) with regard to the best response to ICIs. Best overall responses (BOR) were based on the immune-based therapeutics (iRECIST) criteria. Results: Four of the studied parameters -Performance Status (PS), Body Mass Index (BMI), age and lines of treatment (LOT)- were incorporated in our formula (PS *BMI/ LOT*age) giving rise to PIOS. This score was strongly associated with BOR, with patients of a good response (SD, PR or CR) having higher PIOS compared to patients with progression disease (PD) (p

During the last decade, a growing number of publications implicate NF-kB2 in NSCLC pathogenesis. Here, we investigated the clinical relevance of NF-kB2 single nucleotide polymorphisms (SNPs) rs7897947, rs11574852 and rs12769316 in NSCLC and their association with NF-kB2 protein and mRNA levels. Our data show that TT (rs7897947T >G) and AA (rs12769316G >A) genotypes were strongly associated with an increased risk for NSCLC (P = 0.019 and P = 0.003, respectively). Additionally, in multivariate analysis, TT (rs7897947T >G) homozygosity was associated with worse 2- and 3-year survival rates (P = 0.030 and P = 0.028, respectively), especially among patients with stages III/IV, who had worse 2, 3 and 5-year survival (P = 0.001, P = 0.022 and P = 0.035, respectively). In chemotherapy-treated patients, TT (rs12769316G >A) homozygosity was also associated with worse 2- and 3-year survival compared to G allele carriers (P = 0.006 and P = 0.014, respectively). Furthermore, rs12769316 was correlated with survival outcome of stage I and II patients (P = 0.031 and P = 0.006, respectively). Interestingly, amongst the patients who developed metastases, A allele carriers had better 5-year survival (P = 0.020). In addition, rs12769316 was associated with NF-kB2 protein (P = 0.001) and mRNA expression (P = 0.017) as well as with tumor maximum diameter (P = 0.025). Overall, this study suggests that rs7897947 and rs12769316 are involved in NSCLC susceptibility, in treatment response and in clinical outcome.

The primary aim of our study was to evaluate the efficacy of mineralized bone allograft alone in sinus floor augmentation with simultaneous implant placement in cases with severe atrophy of the residual maxillary bone (bone height

We sought to assess the role of single nucleotide polymorphisms (SNPs) in genes of the alternative NF-KB pathway, important in regulating different aspects of immune functions in colorectal cancer (CRC). The study comprised DNA samples from 418 patients with CRC and 299 age-matched healthy individuals. Genotyping was performed with real time PCR followed by high resolution melt curve analysis for the following SNPs: CD40 rs1883832 (C/T), BAFFR rs7290134 (A/G), LTβR rs10849448 (A/G). Genotypes of random samples were confirmed by sequencing. Genotype frequencies differed between CRC and healthy individuals for CD40 rs1883832 and LTβR rs10849448 (p = 0.001 and p = 0.016, respectively) but were similar for BAFFR rs7290134. The LTβR rs10849448 G allele was more frequent in CRC patients compared to healthy controls and increased risk for CRC by 61% (p = 0.024). Moreover, the G allele was found more frequently in stage D patients compared to stages A and C while the A allele was more prevalent in stage B patients (p = 0.007). Additionally, most patients with grade III tumors were G allele carriers whereas the majority of grade I tumors were AA homozygotes (p = 0.019). The CD40 rs1883832 T allele was less frequent in CRC patients and reduced risk for CRC by 71% (p = 0.027). The CD40 rs1883832 SNP proved to be a prognostic factor for PFS with the CC individuals displaying a longer PFS compared to T carriers (p = 0.045). The BAFFR rs7290134 SNP was independent of all clinical parameters evaluated. Primary site was independent of genotypes for all three SNPs. SNPs within genes of receptors of the NF-KB alternative pathway, CD40 rs1883832 and LTβR rs10849448, influence PFS and risk for CRC development. Additionally, particular genotypes correlated with stage and grade. Citation Format: Anna Antonacopoulou, Anastasia Kottorou, Angelos Koutras, Foteinos-Ioannis Dimitrakopoulos, Thomas Makatsoris, Haralabos P. Kalofonos. SNPs in the NFKB alternative pathway genes CD40, BAFFR and LTβR in CRC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1343.

Salivary gland trauma is uncommon. Parotid gland and duct injuries are far more common than injuries to submandibular and sublingual glands due to anatomic position. Several methods of treating salivary duct injuries and their complications have been advocated. Optimal treatment outcomes can be achieved with early diagnosis, adequate evaluation, and proper management. This article presents current diagnostic and treatment protocols of salivary gland trauma. The anatomy of the salivary glands is briefly described and clinical cases are also presented to illustrate the treatment options described.

t s i o 8 d t t s m Ameloblastoma is the second most common odontogenic neoplasm after odontoma, accounting for 1% of all jaw tumors. Although the 1992 World Health rganization classification characterizes ameloblasoma as a benign but locally invasive epithelial odonogenic neoplasm, its aggressive biologic behavior vokes wide differences of opinion among investigaors concerning its position in the neoplastic specrum. This has led some investigators to refer to meloblastoma as a low-grade malignant tumor beause it is prone to recur, capable of aggressive local nvasion, and capable of metastasizing to distant ites. Ameloblastoma occurs in all areas of the jaws, but 80% of cases arise in the mandible. Despite being locally aggressive, metastases are not generally expected because they are extremely rare. Nevertheless, regional and distant metastases have been reported in the literature and are well documented. Metastatic meloblastoma is known as malignant ameloblasoma. Malignant ameloblastoma is described in the orld Health Organization classification as a neolasm in which the features of ameloblastoma exist in

A rapid and sensitive method for the direct determination of hexavalent chromium in natural waters has been developed. Anion exchange chromatography was used for the fast separation of chromates from matrix anions, within 15 minutes, using a 35 mM KOH eluant. Mobile phase suppression was employed prior to direct conductivity (CD) detection, comparing two different electrolytic suppressor models and achieving a 10 times lower detection limit. Post column derivatization of Cr(VI) with diphenylcarbazide was used for further selective diode array (PDA) detection. Possible Cr(III) interference was evaluated with the addition of concentrations up to 10 mg/L of Cr(III) in a Cr(VI) positive natural water sample resulting in negligible interference. Both detection techniques gave instrumental LOD of 0.05 µg/L and method LOD of 0.08 µg/L for CD and 0.05 µg/L for PDA detection in underground water. Average repeatability and reproducibility (%RSD) was 1.3% and 5.4% for CD and 1.3% and 6.1% for PDA detection for two c...

PURPOSE.: Brain thalami are important for a wide range of sensorimotor and neuropsychiatric functions. This study was carried out to calculate normative values for thalami volume during fetal life. METHODS.: Fetal thalami volumes were measured using 3D ultrasound in 122 normal, singleton fetuses at 20(+0) -34(+6) weeks' gestation. Virtual Organ Computer-aided AnaLysis (VOCAL) was used to obtain a sequence of six sections of each thalamus, starting from the transthalamic view of the brain at an axial plane. Thalamic contour was drawn manually. Volume contrast imaging was used to enhance image quality when needed. The volume of the thalamus distal to the transducer was also measured by a second operator in 30 randomly selected cases, blind to the measurements of the first, to calculate interobserver agreement. RESULTS.: Thalamic volume increased with gestational age, following a quadratic equation (R(2) = 0.83). There was no significant difference in volume between the right and left thalamus. The mean volume of each thalamus increased from 0.45 ml at 20(+0) weeks, to 1.39 ml at 28(+0) weeks, to 2.17 ml at 34(+0) weeks. The 95% limits of interobserver agreement for thalamic volume were -14.3% to +17.2%. CONCLUSIONS.: The increase in thalamic volume with gestation can be described adequately by a quadratic equation. The moderate interobserver repeatability is attributed to the similar echogenicity between the thalamus and its surrounding structures. (c) 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2012. J Clin Ultrasound

Introduction The presence of intracranial foreign body granulomas is an unusual condition. They can be caused by foreign substances which are either inadvertently or deliberately left in the surgical field. Some foreign materials (textilomas, gossypibomas, gauzomas, muslinomas) along with the resulting foreign body reaction, in the surrounding tissue, can cause infection or abscess formation in an early stage whereas others remain clinically silent for many years. Patient We present the case of a foreign body granuloma (textiloma) caused by a gauze which had been placed, during a corrective craniotomy, in a patient with Apert syndrome at the age of five. At presentation the clinical and radiological findings were suggestive of an infection. Results Surgical exploration of the region demonstrated the presence of gauze, in a frontal bone defect, surrounded by large masses of reactive granular tissue which were extended to the underlying dura mater. The symptoms resolved completely after the foreign body’s retrieval. Conclusion Foreign body granulomas, although rare, must always be taken under consideration in the differential diagnosis of craniofacial masses or procedures; especially in cases where a previous craniofacial operation has taken place.

Introduction In colorectal cancer (CRC), there is scarce information regarding the alternative NF-κB pathway which regulates different aspects of immune functions. Material and methods Formalin-fixed paraffin-embedded (FFPE) tissue samples from 116 patients with CRC were analysed with IHC to assess NF-κB2, Bcl3, RelB and NIK protein expression in tumour (T), adjacent non-neoplastic (adjNN) and non-neoplastic (NN) tissues. Gene expression was assessed with real time RT-PCR. Genotyping for BCL3 rs8100239, NFKB2 rs7897947 and rs12769316 and NIK rs7222094 was performed with High Resolution Melting Curve analysis. Results and discussions NF-κB2 and NIK proteins were found mainly in the cytoplasm, whereas Bcl3 and RelB exhibited cytoplasmic and nuclear expression. T cells exhibited higher cytoplasmic expression of each of the four proteins compared to adjNN and NN tissue from a more distant to the tumour site (p=0.000, for all proteins). Protein levels were variably correlated with mRNA levels. The four molecules presented similar mRNA levels between T and NN tissue except for RELB (p=0.002). Particular protein and mRNA levels and SNPs provided prognostic value regarding PFS and OS. Patients who were rs8100239 A carriers (HR=0.356, 95% CI: 0.148–0.862, p=0.022) or exhibited high RELB T cytoplasmic or nuclear expression (HR=0.276 95% CI: 0.104–0.732, p=0.010 and HR=0.260, 95% CI: 0.081–0.834, p=0.023, respectively) presented with improved OS in both single and multiparametric analysis. Moreover, a longer time to progression was noted for patients who were carriers of the rs7897947 G allele (HR=0.362 95% CI: 0.136–0.960, p=0.041) or the rs8100239 A allele (HR=0.292 95% CI: 0.135–0.631, p=0.002). Similarly, patients with high T mRNA levels of each molecule under study or with high cytoplasmic T RelB (HR=0.165 95% CI: 0.060–0.459, p=0.001) or cytoplasmic T NIK (HR=0.133 95% CI: 0.045–0.395, p=0.000) or nuclear T Bcl3 expression (HR=0.329 95% CI: 0.114–0.947, p=0.039) had longer PFS. Conclusion The alternative NF-κB pathway is deregulated in CRC. Selected genotypes, mRNA and protein levels of NF-κB2, Bcl3, RelB and NIK appear to have prognostic value.

Anatoxin-a is a potent alkaloid neurotoxin produced by a number of cyanobacterial species and released in freshwaters during cyanobacterial blooms. Its high toxicity is responsible for several incidents of lethal intoxications of birds and mammals around the world; therefore anatoxin-a has to be regarded as a health risk and its concentration in lakes and water reservoirs should be monitored. Phenylalanine is a natural amino acid, also present in freshwaters, isobaric to anatoxin-a, with a very similar fragmentation pattern and LC retention. Since misidentification of phenylalanine as anatoxin-a has been reported in forensic investigations, special care must be taken in order to selectively determine traces of anatoxin-a in the presence of naturally occurring phenylalanine. A fast LC tandem MS method was developed by using a 1.8 microm 50 x 2.1 mm C18 column for the separation of anatoxin-a and phenylalanine, achieving a 3-min analysis time. Isotopically labelled phenylalanine-d(5) was employed as internal standard to compensate for electrospray ion suppression and sample preconcentration losses. Both compounds were preconcentrated 1,000-fold on a porous graphitic carbon solid-phase extraction (SPE) cartridge after adjustment of sample pH to 10.5. The method was validated by using lake water spiked at four different levels from 0.01 to 1 microg L(-1). Anatoxin-a recovery ranged from 73 to 97%, intra-day precision (RSD%) ranged from 4.2 to 5.9, while inter-day precision (RSD%) ranged from 4.2 to 9.1%. Limits of detection and quantification were 0.65 and 1.96 ng L(-1) respectively. The method was successfully applied for the detection of anatoxin-a in Greek lakes at concentrations ranging from less than 0.6 to 9.1 ng L(-1).