ROLE OF STC1 IN THE ACTIVATION OF FIBROBLASTS IN THE CONTEXT OF BREAST CANCER

The tumor microenvironment (TME) is now recognized as an important factor in breast cancer progression and is crucial in determining the response to anti-cancer therapies. Fibroblasts are one component of the TME that are activated in the early stages of oncogenesis and remodel the TME as an early tissue repair response. In the later stages of tumor progression, these activated fibroblasts get transformed into cancer associated fibroblasts (CAFs) that promote tumor progression. The mechanisms underlying this transformation of fibroblasts from normal activated fibroblasts to CAFs remain largely unknown. To address this, bone marrow derived mesenchymal stromal cells (MSCs) that are known to be a significant source of CAFs were treated with conditioned media of a breast cancer cell line, namely, MDA-MB-23, to induce a CAF-like - phenotype. Activation of MSCs was confirmed by assessing their contractility and expression of CAF markers. Gene expression and secretome analysis was performed to identify differentially expressed genes and differentially secreted factors upon activation. Stanniocalcin 1 (STC1), a CAF-secreted protein implicated in metastasis and therapy resistance, was found to be upregulated upon conditioned media treatment. Therefore, the aim of this study was to understand the mechanism of STC1 upregulation and its involvement in the activation of fibroblasts. STC1 knockdown using RNAi both in conditioned media treated MSCs and patient derived activated CAFs showed inhibitory effects on activation status of these cells. Moreover, this down-regulation resulted in a decrease in the expression of several proteins such as NOTCH3, NOTCH4 and β-catenin suggesting possible mechanisms by which STC1 regulates the activation of fibroblasts. Furthermore, the upregulation of STC1 upon conditioned media treatment was found to be dependent on RELA and RELB transcription factors indicating that NF-κB signaling might be involved in its transcriptional regulation. In conclusion, this study demonstrates STC1 as an important factor in the activation of CAFs. Investigating the mechanism of the involvement of STC1 in the unabated activation of CAFs will enable a deeper understanding of the tumor microenvironment and its role in the tumor progression

Deep learning for diagnosis of malign pleural effusion on computed tomography images

Background: The pleura is a serous membrane that surrounds the lungs. The visceral surface secretes fluid into the serous cavity and the parietal surface ensures a regular absorption of this fluid. If this balance is disturbed, fluid accumulation occurs in the pleural space called “Pleural Effusion”. Today, accurate diagnosis of pleural diseases is becoming more critical, as advances in treatment protocols have contributed positively to prognosis. Our aim is to perform computer-aided numerical analysis of Computed Tomography (CT) images from patients showing pleural effusion images on CT and to examine the prediction of malignant/benign distinction using deep learning by comparing with the cytology results. Methods: The authors classified 408 CT images from 64 patients whose etiology of pleural effusion was investigated using the deep learning method. 378 of the images were used for the training of the system; 15 malignant and 15 benign CT images, which were not included in the training group, were used as the test. Results: Among the 30 test images evaluated in the system; 14 of 15 malignant patients and 13 of 15 benign patients were estimated with correct diagnosis (PPD: 93.3%, NPD: 86.67%, Sensitivity: 87.5%, Specificity: 92.86%). Conclusion: Advances in computer-aided diagnostic analysis of CT images and obtaining a pre-diagnosis of pleural fluid may reduce the need for interventional procedures by guiding physicians about which patients may have malignancies. Thus, it is cost and time-saving in patient management, allowing earlier diagnosis and treatment.

Cutaneous syncytial myoepithelioma: A potential pitfall in the differential diagnosis of superfi cial dermal tumors

In the spectrum of myoepithelial tumors of the skin, cutaneous myoepithelioma is composed solely of myoepithelial cells. Cutaneous syncytial myoepithelioma as a rare histological variant of cutaneous myoepithelioma has been fi rst described in the last decade. This tumor is benign and rarely shows recurrence when incompletely resected. In addition to its distinctive common histological and immunohistochemical features, cutaneous syncytial myoepithelioma shares the same changes for most cases in molecular testing (EWS RNA binding protein 1 gene rearrangement). The differential diagnosis of other superfi cial dermal tumors is one of the major diffi culties in the diagnosis of this tumor. In the current study, we present our fi ndings of a 56 year-old woman who was diagnosed as cutaneous syncytial myoepithelioma.</p

Süt molar diş çekimi sırasında 3D video gözlük kullanımının çocuklarda ağrı ve anksiyete üzerine etkisi

Amaç: Çocuk diş hekimleri, dental tedaviler sırasında hastalarının ağrı ve anksiyetesini kontrol altına almak için pek çok yöntem kullanmaktadır. Dikkat dağıtma yöntemi, çocuk hastalarda bu amaçla sık kullanılan davranış yönlendirme tekniklerinden biridir. Bu çalışmanın amacı, görsel ve işitsel dikkat dağıtma sağlayan 3D video gözlüğün 6-10 yaş arası çocuklarda süt molar dişlerin çekimi sırasında kullanımının anksiyete ve ağrı üzerine olan etkinliğinin değerlendirilmesidir. Gereç ve Yöntem: 6-10 yaş aralığındaki 60 çocuk, her grupta 15 kız, 15 erkek olacak şekilde rastgele 2 gruba ayrıldı. 1. grupta bulunan 30 hastaya “Anlat-göster-uygula” yöntemi uygulanarak; 2. grupta bulunan 30 hastaya ise 3D video gözlük ile çizgi film izletilerek diş çekimi yapıldı. Çocukların anksiyete değerlendirmeleri tedaviye başlamadan önce, lokal anestezi sırasında ve lokal anestezi yapıldıktan sonra nabız ve oksijen saturasyon ölçümleri ve MCDAS (Modified Child Dental Anxiety Scale) skorları ile yapıldı. Ağrı algısı, hem lokal anestezi sonrası hem de diş çekimi sonrasında Wong-Baker (W-B) skalası ile kaydedildi. Bulgular: “Anlat-göster-uygula” ve “3D video gözlük” grupları karşılaştırıldığında nabız ve MCDAS skala değerleri bakımından aralarında anlamlı farklılık bulunmadı. Tüm zamanlarda yapılan ölçümlerde “3D video gözlük” grubunun saturasyon değerleri, “Anlat-göster-uygula” grubuna göre anlamlı derecede daha düşük bulundu. “3D video gözlük” grubunda diş çekimden sonra kaydedilen W-B değerlerinin “Anlat-göster-uygula” grubuna göre anlamlı derecede düşük olduğu görüldü. “3D video gözlük” grubunda diş çekiminden sonra ölçülen W-B değerinin lokal anestezi sonrasındaki değere göre düşük olduğu gözlendi. Sonuç: Çocuklarda diş çekimi sırasında “3D video gözlük” kullanımının anksiyete değerlerinde beklenen azalmayı sağlamadığı; ağrı algısını ise başarılı bir biçimde azalttığı görülmüştür

Occult cardiac dysfunction in patients with obstructive sleep apnea syndrome revealed by tissue Doppler imaging

Obstructive sleep apnea syndrome has been linked to cardiovascular complications. The diagnosis of effects of sleep apnea on heart may be difficult before apparent examination findings. The aim of the present study was to evaluate changes of myocardial contractile properties in patients affected by sleep apnea showing tissue Doppler imaging, in the face of quite normal myocardial contractility on standard echocardiography. Shortly, tissue Doppler imaging may represent an early stage of myocardial abnormality despite a preserved global function. (C) 2006 Elsevier Ireland Ltd. All rights reserved

Antibodies to DNA repair proteins in headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL) patients

WOS: 000354723700008PubMed ID: 25070837Autoimmune mechanisms have been implicated in the pathogenesis of headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL). Pooled sera of five HaNDL patients and 30 controls (10 multiple sclerosis patients, 10 migraine patients, 10 healthy controls) were screened by protein macroarray. All sera were also individually subjected to immunoprecipitation with neuroblastoma cells and the bound antigens were identified by mass spectrometry. Antibodies to three DNA repair proteins (mitogen-activated protein kinase-4, DNA-dependent protein kinase catalytic subunit, DNA excision repair protein ERCC-6) were identified by both macroarray and immunoprecipitation methods in 3/5 HaNDL sera, but in none of the controls. The presence of DNA repair protein antibodies indicates DNA damage and provides further support for the inflammatory etiology of HaNDL

Do calcium sensitizers affect right ventricular functions in patients with chronic heart failure?

Calcium sensitizers also improve cardiac function by increasing the contraction of the myocardium without significantly increasing intracellular calcium levels. Although right ventricular function is an important role for better cardiac global function, there is no study about effects of levosimendan on right ventricular function measured by tissue Doppler imaging. The aim of the present study was to evaluate changes of myocardial properties in patients with idiopathic dilated cardiomyopathy using tissue Doppler imaging after levosimendan infusion. This tissue Doppler study shows that levosimendan also affects myocardial especially systolic waves of right ventricle and those of left ventricle. (C) 2006 Elsevier Ireland Ltd. All rights reserved