Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation.

Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) where aberrant signaling downstream of this receptor contributes to tumor growth. EGFR variant III (EGFRvIII) is the most commonly altered form of EGFR and contains a truncated ligand-binding domain. We previously reported that EGFRvIII is expressed in up to 40% of HNSCC tumors where it is associated with increased proliferation, tumor growth and chemoresistance to antitumor drugs including the EGFR-targeting monoclonal antibody cetuximab. Cetuximab was FDA-approved in 2006 for HNSCC but has not been shown to prevent invasion or metastasis. This study was undertaken to evaluate the mechanisms of EGFRvIII-mediated cell motility and invasion in HNSCC. We found that EGFRvIII induced HNSCC cell migration and invasion in conjunction with increased signal transducer and activator of transcription 3 (STAT3) activation, which was not abrogated by cetuximab treatment. Further investigation showed that EGF-induced expression of the STAT3 target gene HIF1-α, was abolished by cetuximab in HNSCC cells expressing wild-type EGFR under hypoxic conditions, but not in EGFRvIII-expressing HNSCC cells. These results suggest that EGFRvIII mediates HNSCC cell migration and invasion by increased STAT3 activation and induction of HIF1-α, which contribute to cetuximab resistance in EGFRvIII-expressing HNSCC tumors

Elemente compozite din lemn și beton

Fișierul atașat conține: Rezumat, Abstract, Cuprins, Lista figurilor, Introducere.În lucrarea dată, care cuprinde 4 capitole , este cercetată placa din elemente compozite lemn și beton. Prumul capitol este unu introductiv unde se descrie în linii generale elementele compozite. În capitolul doi , intitulat ” Elemente compozite lemn – beton ” , este cercetată conlucrarea dintre aceste două elemente . De asemenea sunt analizate diferite tipuri de conectori folosite ca de exemplu cuie, șuruburi cu cap hexagonal, bare de armătură, table de oțel ș.a. Din susrele bibliografice indicate, au fost extrase tabele cu datele experimentae obținute în urma verificării conectorilor la forfecare și stabilit modulul de alunecare, care permite să stabilim dacă a fost obșinută o acțiune compozită. În următorul subcapitol sunt descrise principalele tipuri și soluții constructive care stau la baza executării clădirilor cu planșee compozite ( sisteme SEPA, HBV, cadre M ) . Ultimu capitol este unu aplicativ, unde este prezentat un calcul a plăcii lemn – beton în baza EuroCod-ului .In this paper-work, comprising four chapters, it is research plate of composite timber and concrete. Prum introductory chapter is one where outline the composite elements. In the second chapter, entitled "Elements of composite wood - concrete" is researched collaboration between the two. They also analyze various types of connectors used like nails, hex bolts, reinforcing bars, steel sheets, etc. Susrele of bibliographic indicated, were extracted tables with data obtained from the checking experimentae shear connectors sliding and fixed module, which allows to determine whether an action composite was obtained. The next chapter describes the main types and constructive solutions that underpin execution buildings with composite floors (SEPA systems, HBV, frames M). Ultimu chapter is practical one, in which a wooden plate calculation - based concrete EuroCoDe community

Case studies in teaching business English

CHIOSEA, Angela. Case studies in teaching business English. În: Competitivitatea şi inovarea în economia cunoaşterii [online]: culegere de articole selective: conf. şt. intern., 28-29 sept., 2018. Chişinău: ASEM, 2018, vol. 2, pp. 159-164. E-ISBN 978-9975-75-933-5.The article deals with the problem of using active methods of teaching on the example of case study. The notion of active methods of teaching, the description of case study and the stages of preparing case studies are given in the paper. The article contains a case study on business English. It presents realistic, complex, and contextually rich situation and often involve a dilemma, conflict, or problem that one or more of the characters in the case must negotiate. The peculiarity of active methods of teaching is that it develops practical and critical thinking. This helps the students not only to memorize and render the material which was given by the teacher but involves them in the process of active thinking and practice. Case studies give students practice identifying the parameters of a problem, recognizing and articulating positions, evaluating courses of action, and arguing different points of view. JEL: A21, A22, A23

The degree of intratumor mutational heterogeneity varies by primary tumor sub-site

Citation: Ledgerwood, L. G., Kumar, D., Eterovic, A. K., Wick, J., Chen, K., Zhao, H., . . . Thomas, S. M. (2016). The degree of intratumor mutational heterogeneity varies by primary tumor sub-site. Oncotarget, 7(19), 27185-27198. doi:10.18632/oncotarget.8448Additional Authors: Chien, J.;Mills, G. B.;Grandis, J. R.;Thomas, S. M.In an era where mutational profiles inform treatment options, it is critical to know the extent to which tumor biopsies represent the molecular profile of the primary and metastatic tumor. Head and neck squamous cell carcinoma (HNSCC) arise primarily in the mucosal lining of oral cavity and oropharynx. Despite aggressive therapy the 5-year survival rate is at 50%. The primary objective of this study is to characterize the degree of intratumor mutational heterogeneity in HNSCC. We used multi-region sequencing of paired primary and metastatic tumor DNA of 24 spatially distinct samples from seven patients with HNSCC of larynx, floor of the mouth (FOM) or oral tongue. Full length, in-depth sequencing of 202 genes implicated in cancer was carried out. Larynx and FOM tumors had more than 69.2% unique SNVs between the paired primary and metastatic lesions. In contrast, the oral tongue HNSCC had only 33.3% unique SNVs across multiple sites. In addition, HNSCC of the oral tongue had fewer mutations than larynx and FOM tumors. These findings were validated on the Affymetrix whole genome 6.0 array platform and were consistent with data from The Cancer Genome Atlas (TCGA). This is the first report demonstrating differences in mutational heterogeneity varying by subsite in HNSCC. The heterogeneity within laryngeal tumor specimens may lead to an underestimation of the genetic abnormalities within tumors and may foster resistance to standard treatment protocols. These findings are relevant to investigators and clinicians developing personalized cancer treatments based on identification of specific mutations in tumor biopsies

Structura afecțiunilor biliare la copii

Background. Gallbladder diseases in children nationwide are rarely diagnosed, they have a share of 9.2-8% in the structure of chronic digestive diseases. Objective of the study. To determine the rate and nosological structure of gallbladder diseases in children with chronic digestive diseases hospitalized in the pediatric-gastroenterology clinic of MCCH "Valentin Ignatenco" in 2019. Material and Method. The study was a retrospective, with analysis of clinical data, laboratory, EGDS and abdominal sonography of 694 medical records of children aged 2-18 years treated in the nominated subdivision with chronic digestive pathology. In 28 cases the morphofunctional test with breakfast was performed. Results. Gallbladder diseases in children with chronic digestive pathology were found in 7.6% (53) of cases, the average age being 9.8 years and the predominance of girls (36). All children showed pain in the right hypochondrium and positive signs of gallbladder damage, hepatomegaly <2 cm with normal ALT and AST (18). The nosological structure of the diagnosed gallbladder pathology included: functional disorders of the gallbladder - 88% (47) cases (motor dyskinesias - 28 and spasm of the Oddi sphincter of the gallbladder type - 19) age between 10-14 years; chronic calculous cholecystitis - 7.5% (4) and calculous 3.8% (2) cases. Bilateral sludge was found in 28 children at the same time. Conclusion. Gallbladder diseases in children with chronic digestive pathology are more frequently dominated by motor functional disorders. Introducere. Afecțiunile veziculei biliare la copii în plan național sunt rar diagnosticate, acestea având o pondere de 9,2-8% în structura bolilor digestive cronice. Scopul lucrării. A determina rata și structura nosologică a afecțiunilor veziculei biliare la copiii cu maladii cronice digestive, spitalizați în Clinica pediatrie-gastroenterologie a SCMC „Valentin Ignatenco" în 2019. Material și Metode. Studiul realizat a fost unul retrospectiv, cu analiza datelor clinice, de laborator, EGDS și sonografiei abdominale a 694 de fișe medicale a copiilor cu vârsta 2-18 ani, tratați în subdiviziunea nominalizată cu patologie cronică digestivă. În 28 de cazuri a fost efectuat testul morfofuncțional cu dejun. Rezultate. Afecțiunile veziculei biliare la copiii cu patologie cronică digestivă a fost constatată în 7,6% (53) dintre cazuri, vârsta medie fiind de 9,8 ani și cu predominarea fetelor (36). Toți copiii au prezentat dureri în hipocondrul drept și semne pozitive de afectare a veziculei biliare, hepatomegalie<2cm cu ALT și AST normale (18). Structura nosologică a patologiei veziculei biliare diagnosticate a inclus: dereglări funcționale ale veziculei biliare- 88% (47) cazuri (dischinezii motorice- 28 și spasm al sfincterului Oddi de tip biliar- 19) vârsta între 10-14 ani; colecistită cronică acalculoasă- 7,5%(4) și calculoasă 3,8%(2) cazuri. La 28 de copii concomitent a fost constatat sludge-ul biliar. Concluzii. Afecțiunile veziculei biliare la copiii cu patologie cronică digestivă sunt mai frecvent dominate de dereglările funcționale motorice

Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast adenomyoepitheliomas

Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, of which a subset will progress to invasive or metastatic cancer. We sought to define the genomic landscape of adenomyoepitheliomas. Massively parallel sequencing revealed highly recurrent somatic mutations in HRAS and PI3K-AKT pathway-related genes. Strikingly, HRAS mutations were restricted to estrogen receptor (ER)-negative tumors, all affected codon 61, and all but one co-occurred with PIK3CA or PIK3R1 mutations. To interrogate the functional significance of HRAS Q61 mutations in adenomyoepithelial differentiation, we expressed HRASQ61R alone or in combination with PIK3CAH1047R in non-transformed ER-negative breast epithelial cells. HRASQ61R induced characteristic phenotypes of adenomyoepitheliomas such as the expression of myoepithelial markers and loss of e-cadherin, hyperactivation of AKT signaling, and transformative properties that were arrested by combination therapy with AKT and MEK inhibitors. Our results indicate that breast adenomyoepitheliomas often manifest a unique transformation program featuring HRAS activation

The Motivation of Crossfit Practitioners for Competition

CrossFit is an emerging trend that has captured the attention of many studies in recent years. Despite the high number of research papers covering different aspects of the sport, the motivation of participants in CrossFit competitions remains a topic that is not talked about enough. The purpose of this study is to analyze how competition influences the motivation of CrossFiters. We applied a questionnaire who contains a number of 27 items on a 5-point Likert scale to observe how the participants’ motivation influences their view on the competition. The results indicate that all four variables used to define the motivation of competitors (enjoyment to compete, self-perception, challenges, CrossFit community) are significant, while loss of motivation is not a significant factor. Regarding gender, there is a significant difference between the groups in terms of CrossFit community perception (p< 0.05). In conclusion, competitive experience plays a crucial role in self-perception, competitive satisfaction, and appreciation of the CrossFit community

Primary and Secondary/ Metastatic Salivary Duct Carcinoma Presenting within the Sinonasal Tract

Traditionally, sinonasal adenocarcinomas have been subdivided into intestinal (ITAC) and non-intestinal (non-ITAC) categories. The latter encompasses salivary-type adenocarcinomas originating from the seromucinous glands of the sinonasal mucosa and non-salivary adenocarcinomas. The non-salivary adenocarcinoma category is further subdivided into low-and high-grade variants. Among salivary-type sinonasal adenocarcinomas, tumors recapitulating salivary duct carcinoma (SDC) are exceedingly rare, but some might have been lumped into the high-grade non-ITAC category. To date, only three primary SDCs originating in the sinonasal tract have been reported. We herein describe 7 cases of SDC including one previously reported case (4 primary sinonasal, 3 metastatic/ extension from parotid gland SDC). The primary tumors affected 3 males and one female aged 60 – 75. Different sites were involved by the primary tumors while the secondary tumors affected the sphenoidal (2) and the frontal + maxillary (1) sinuses. Three primary tumors were de novo high-grade SDC and one was confined to contours of a pre-existing pleomorphic adenoma. All 3 secondary tumors were SDC ex pleomorphic adenoma of the parotid with a long history of recurrences, ultimately involving the sinonasal tract. Androgen receptor was positive in 7/7 cases. Four of 6 cases were strongly HER2/neu + (either score 3 + or with verified amplification). This small case series adds to the delineation of primary sinonasal SDC highlighting that almost half of invasive SDC presenting within sinonasal tract indeed represents extension or metastasis from a parotid gland primary. There is a tendency towards overrepresentation of HER2/neu-positive cases in both categories (primary and metastatic), but this needs clarification in larger studies