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ABSTRACTMacroautophagy/autophagy is an evolutionarily conserved cellular stress response mechanism. Autophagy induction in the tumor microenvironment (stroma) has been shown to support tumor metabolism. However, cancer cell-derived secreted factors that initiate communication with surrounding cells and stimulate autophagy in the tumor microenvironment are not fully documented. We identified CTF1/CT-1 (cardiotrophin 1) as an activator of autophagy in fibroblasts and breast cancer-derived carcinoma-associated fibroblasts (CAFs). We showed that CTF1 stimulated phosphorylation and nuclear translocation of STAT3, initiating transcriptional activation of key autophagy proteins. Additionally, following CTF1 treatment, AMPK and ULK1 activation was observed. We provided evidence that autophagy was important for CTF1-dependent ACTA2/α-SMA accumulation, stress fiber formation and fibroblast activation. Moreover, promotion of breast cancer cell migration and invasion by activated fibroblasts depended on CTF1 and autophagy. Analysis of the expression levels of CTF1 in patient-derived breast cancer samples led us to establish a correlation between CTF1 expression and autophagy in the tumor stroma. In line with our in vitrodata on cancer migration and invasion, higher levels of CTF1 expression in breast tumors was significantly associated with lymph node metastasis in patients. Therefore, CTF1 is an important mediator of tumor-stroma interactions, fibroblast activation and cancer metastasis, and autophagy plays a key role in all these cancer-related events.Abbreviations:ACTA2/α-SMA: actin, alpha 2, smooth muscle CAFs: cancer- or carcinoma-associated fibroblasts CNT Ab.: control antibody CNTF: ciliary neurotrophic factor CTF1: cardiotrophin 1 CTF1 Neut. Ab.: CTF1-specific neutralizing antibody GFP-LC3 MEF: GFP-fused to MAP1LC3 protein transgenic MEF LIF: leukemia inhibitory factor IL6: interleukin 6 MEFs: mouse embryonic fibroblasts MEF-WT: wild-type MEFs OSM: oncostatin M TGFB/TGFβ: transforming growth factor beta

Abstract Extramedullary plasmacytomas are rare malignancies. Most cases (80%) are seen in the head and neck region, where they represent 1% of all head and neck malignancies. We report a [...]

Unicentric Castleman disease (CD) is a rare lymphoproliferative disorder that is characterized by the enlargement of lymph nodes on the neck, mediastinum, and retroperitoneum. Herein, we present a 6-year-old female patient, referred to our medical center because of recurrent fever accompanied by cervical lymphadenopathy and elevated inflammatory markers since 3 years of age. Fever episodes lasting 1 day continued irregularly without any accompanying symptom. MEditerranean FeVer (MEFV) gene analysis showed no mutations; however, as inflammatory markers including serum amyloid A remained markedly high during attack-free periods, colchicines was initiated. The patient did not respond to maximally tolerated doses of colchicine; therefore, we added canakinumab and systemic methylprednisolone, subsequently. Unresponsiveness to 3 doses of bimonthly canakinumab and new-onset hepatosplenomegaly led us to investigate large-vessel vasculitis and malignancy; therefore, we performed Position emission tomography, which further revealed a hypermetabolic retroperitoneal solid mass. After performing the excisional biopsy, the patient has been diagnosed as suffering from hyaline vascular variant CD, confirmed by histopathology. In conclusion, we report a pediatric unicentric CD, which resembled autoinflammatory diseases and responded well to surgical resection, with the normalization of inflammatory markers 1 month after the procedure. CD, even the unicentric and hyaline vascular variant, should be considered in the differential diagnosis of the patients with an autoinflammatory phenotype.

Abstract??Nitric oxide synthases are isoenzymes that catalyse the synthesis of nitric oxide (NO). NO plays both pathological and physiological roles depending on its rate of synthesis and concentration in cellular source and microenvironment. Apoptosis is an important biological factor in lymphomas. This study evaluates expression of inducible nitric oxide synthase (iNOS) in human lymphomas and its relation with apoptosis.This study comprised 46 cases of B-cell lymphoma. The lymphomas were classified as 3 mantle cell, 5 marginal zone, 4 follicular, 2 Burkitt, 25 diffuse large cell, 2 anaplastic large cell, 3 lymphoblastic, 2 lymphoplasmacytic according to WHO classification of lymphoid neoplasms. Hematoxylin eosin slides of the cases were reviewed and immunoperoxidase technique was performed iNOS and Caspase monoclonal antibodies to selected sections of each case. Antigen staining was carried out with iNOS and Caspase proteins and Ultravision Polyvalent, HRP-AEC kit (Neomarkers-Biogen USA). For the evaluation of iNOS and Caspase, tumor areas with a high density of expression were chosen. Positive stained cells were counted in 5 different areas at a magnification ?40 by an Olympus B ? 51 microscope in each case. The iNOS and Caspase expressions were independently recorded by four pathologists and the results were averaged.All of the cases were positive for the iNOS and Caspase. But there is not a statistically important relation between lymphoma grade and iNOS activity. We could not find a correlation between iNOS and patients age. This study reveals the capacity of B-cell neoplasms to express iNOS in situ. In conclusion, our study revealed that there is a positive relation between iNOS expression and apoptosis (p $=$ 0.032 spearman correlation).

Intracranial chondromas usually arise from the base of the skull. They rarely originate from the convexity dura and falx. Here we describe two cases of intracranial chondroma located at the convexity dura and falx, discuss the genesis, radiologic, histologic features and review the literature.Intracranial chondromas usually arise from the base of the skull. They rarely originate from the convexity dura and falx. Here we describe two cases of intracranial chondroma located at the convexity dura and falx, discuss the genesis, radiologic, histologic features and review the literature.

No relevant conflicts of interest to declare.

Multiple myeloma (MM) is a heterogeneous disease, for which an understanding of the prognostic and predictive value of chromosomal aberrations is necessary to prescribe the most appropriate therapy. We analyzed the frequency of del(17p13), del(13q14), t(11;14) and t(4;14) in 110 Turkish patients with MM bone marrow aspiration samples. Interphase-fluorescent in situ hybridization were applied to all cases using florescent-labeled probes which were TP53/CEP17(Vysis, Abbott Global, US) used for 17p13 deletions, LSI 13 (RB1) (Vysis, Abbott Global) used for 13q14 deletions, LSI IgH/CCDN1and LSI IgH/FGFR3(Vysis, Abbott Global) used to detect t(11;14)(q13;q32) and t(4;14)(p16;q32) translocations, respectively. We studied the clinical effects of bortezomib in 67 patients who were eligible for follow-up. Eighty patients (72.7%) had at least one chromosomal aberration. The most frequently observed aberration was del(17p13) (48.2%), followed by del(13q14) (40.9%), t(11;14) (16.4%), and t(4;14) (11.8%). The results suggest that bortezomib-containing regimens may have beneficial effects on the clinical outcome of patients with del(17p13) and del(13q14).

Malignant melanoma is the seventh most common cancer with increasing incidence rates, which is more than other known cancers. For this reason accurate and early diagnosis is mandatory for the patient’s appropriate management.