A common genetic variation of melanoma inhibitory activity-2 labels a subtype of pancreatic adenocarcinoma with high endoplasmic reticulum stress levels.

HNF1 homeoboxA(HNF1A)-mediated gene expression constitutes an essential component of the secretory pathway in the exocrine pancreas. Melanoma inhibitory activity 2 (MIA2), a protein facilitating protein secretion, is an HNF1A target. Protein secretion is precisely coordinated by the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) system. Here, we demonstrate that HNFA and MIA2 are expressed in a subset of human PDAC tissues and that HNF1A induced MIA2 in vitro. We identified a common germline variant of MIA2 (c.A617G:p.I141M) associated with a secretory defect of the MIA2 protein in PDAC cells. Patients carrying MIA2(I141M) survived longer after tumor resection but the survival benefit was restricted to those patients who received adjuvant chemotherapy. The MIA2(I141M) variant was associated with high expression of ER stress/UPR genes - in particular those of the ERN1/XBP arm - in human PDAC samples. Accordingly, PDAC cell lines expressing the MIA2(I141M) variant expressed high levels of ERN1 and were more sensitive to gemcitabine. These findings define an interaction between the common MIA2(I141M) variant and the ER stress/UPR system and specify a subgroup of PDAC patients who are more likely to benefit from adjuvant chemotherapy

MEASURING THE EFFECT OF SOCIAL MEDIA USE ON HOLIDAY PURCHASE AND HOLIDAY MOTIVATION ON REVISITS

Apart from working hours and personal needs of individuals, they need to spend time for fun, listening, many activities that bring together their interests and personal preferences. One of the most well-known of these needs is tourism activities. Behaviors that affect participation in leisure time tourism activities is an issue that needs to be examined. In this context, the aim of the research is to examine the holiday buying and holiday motivation, revisit behaviors of individuals using social media. The population of the research consists of individuals using social media in Eskişehir. With the convenience sampling method, 409 people from state universities throughout Eskişehir were reached in the form of face-to-face and online forms. In order to collect data, the Effect of Social Media on Tourists' Holiday Decisions developed by (Eşitti & Işık 2015), Purchasing Intent Scale developed by (Pavlou & Gefen, 2004), Tourism Motivation Scale developed by (Carrol & Alexandris, 1997) and finally (Altunışık) v.d, 2001) were used to use the Revisit Intention Scales. In the analysis of the data, SPSS 26 program was used and analyzes were made. In these analyzes, a positive and significant relationship was determined between the individuals' social media use, holiday purchase and holiday motivation, and revisit levels. As a result, it has been concluded that the high level of participation of individuals using social media in purchasing a holiday, together with their socio-economic status, positively affects their holiday motivations and revisit attitudes. In addition, the information obtained can be useful for tourism businesses, travel agencies and businesses serving in the recreation industry

Management of a T-Tube Migration Into the Syrinx Cavity: a Case Report

DergiPark: 889380tmsjAims: To present a rare syringomyelia case that necessitated a revision surgery because of a T-tube migration into the syrinx cavity. Case Report: A 53-year-old female patient was presented with progressive pain in the right arm and numbness in the neck. She had undergone decompression and stabilization surgery at the T6-T9 levels four years ago. One year later, she underwent a T-tube placement operation for syringomyelia. She remained relatively stable until the latest admission. A detailed neurological examination revealed no difference compared to her previous neurological condition. Computerized Tomography and Magnetic Resonance Imaging scans demonstrated that the syrinx had expended and the T-tube had migrated into the syrinx cavity. A revision was carried out, the migrated T-tube was removed through fenestration, and a new T-tube was placed. Her condition had significantly improved at follow-up, and the syrinx had markedly regressed. Conclusion: Syringosubarachnoid shunting operations might lead to rare complications such as T-tube migration, which necessitate revision surgery. Nearly complete relief of symptoms can be achieved with successful revision surgery

Gastrointestinal Tract Multiple Lymphomatous Polyposis Presented As Mantle Cell Lymphoma

DergiPark: 640245tmsjAims: Mantle cell lymphoma is a mature B cell non-Hodgkin lymphoma which may be presented with the involvement of the gastrointestinal tract as multiple lymphomatous polyposis. The aim of this case report is to increase the awareness of including lymphomatoid polyposis as an entity in the differential diagnosis of multiple polyposis of the gastrointestinal tract. Case Report: A 69-year-old male patient was admitted to the Trakya University Emergency Department with acute abdominal pain. His cli-nical findings were anorexia that started 3-4 months ago together with constipation and nausea causing him to lose 10-15 kg in 7-8 months, with denial of other parameters of B-symptoms (fevers and night sweats). Endoscopic biopsies that were taken from bulbus and duodenum were investigated and he was diagnosed with mantle cell lymphoma. The patient went through an ileoce-cal resection due to his intussusception that caused abdominal pain in the first place. Conclusion: Although being an infrequent disease, gastrointestinal lymphomatoid polyposis should be an entity comprised in differential diagnosis for multiple polyposis of the gastrointestinal tract. On the other hand, there is still not a therapeutic protocol with a definitive cure for gastrointestinal tract mantle cell lymphoma. Elderly patients in high risk group such as our patient should be given treatment by taking their conditions into consideration. Keywords: Mantle cell lymphoma, polyp, non-Hodgkin lymphom

Retrospective Analysis of Follicular Lymphoma Patients in Trakya University School of Medicine: a Single Center Experience

DergiPark: 889334tmsjAims: To establish a dataset including demographic features, disease characteristics, and survival rate of follicular lymphoma patients in Trakya Universi- ty School of Medicine and contribute to the database of follicular lymphoma in Turkey. Methods: In this retrospective cross-sectional study, we analyzed data constituting of follicular lymphoma patients over 18 years of age followed during the years of 2015-2020 in Trakya University Division of Hematology. Results: Out of 43 patients, 22 (51.2%) were female and 21 (48.8%) were male. The mean age was 56.56 (standard deviation 13.24) years. There were 5 (11.6%) pa- tients with B symptoms, presence of bone marrow involvement was seen in 17 (39.5%) patients, lastly, there were 18 (41.9%) patients with splenomegaly. Twen- ty-one (48.8%) patients received rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, making it the most common treatment protocol administered in our study. Conclusion: Follicular lymphoma patients usually end up getting diagnosed at an advanced stage of the disease, presenting with incidentally noticed painless lymphadenopathy. Additionally, based on evidence in the literature, a clear gap in the successful diagnosis of follic- ular lymphoma patients can be observed between developed and developing countries. To overcome this hurdle, enhanced cooperation with hematopathology may lead to an increased awareness enabling physicians to make a more accurate diagnosis. Nonetheless, further studies are still needed to fully apprehend the epidemiology of follicular lymphoma patients in Turkey

Cystic colon duplication causing intussusception in a 25-year-old man: report of a case and review of the literature

<p>Abstract</p> <p>Background</p> <p>Colonic intussusception is a rare congenital abnormality, mostly manifesting before the age of two with abdominal pain and acute intestinal obstruction with or without bleeding. In adults it may occur idiopathically or due to an intraluminal tumor mass.</p> <p>Case presentation</p> <p>A 25-year-old man presented with an acute abdomen and severe crampy abdominal pain. The clinical picture mimicked acute appendicitis. Transabdominal ultrasound examination revealed a 5 cm circular mass in the right upper abdomen. The ensuing computed tomography suggested an intussusception in the ascending colon. Intraoperatively, no full thickness invagination was detected. Due to a hard, intraluminal tumor a standard right hemicolectomy with ileotransversostomy was performed. The histopathological analysis revealed a cystic colon duplication leading to mucosal invagination and obstruction.</p> <p>Conclusions</p> <p>In adults, colon intussusception is a rare event causing approximately 1% of all acute intestinal obstructions. Unlike its preferentially nonsurgical management in children, a bowel intussusception in adults should be operated because an organic, often malignant lesion is present in most cases.</p

βIII-tubulin: a novel mediator of chemoresistance and metastases in pancreatic cancer

Pancreatic cancer is a leading cause of cancer-related deaths in Western societies. This poor prognosis is due to chemotherapeutic drug resistance and metastatic spread. Evidence suggests that microtubule proteins namely, β-tubulins are dysregulated in tumor cells and are involved in regulating chemosensitivity. However, the role of β-tubulins in pancreatic cancer are unknown. We measured the expression of different β-tubulin isotypes in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Next, we used RNAi to silence βIII-tubulin expression in pancreatic cancer cells, and measured cell growth in the absence and presence of chemotherapeutic drugs. Finally, we assessed the role of βIII-tubulin in regulating tumor growth and metastases using an orthotopic pancreatic cancer mouse model. We found that βIII-tubulin is highly expressed in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Further, we demonstrated that silencing βIII-tubulin expression reduced pancreatic cancer cell growth and tumorigenic potential in the absence and presence of chemotherapeutic drugs. Finally, we demonstrated that suppression of βIII-tubulin reduced tumor growth and metastases in vivo. Our novel data demonstrate that βIII-tubulin is a key player in promoting pancreatic cancer growth and survival, and silencing its expression may be a potential therapeutic strategy to increase the long-term survival of pancreatic cancer patients

StellaTUM: current consensus and discussion on pancreatic stellate cell research

The field of pancreatic stellate cell (PSC) biology is very young, as the essential in-vitro tools to study these cells (ie, methods to isolate and culture PSC) were only developed as recently as in 1998. Nonetheless, there has been an exponential increase in research output in this field over the past decade, with numerous research groups around the world focusing their energies into elucidating the biology and function of these cells. It is now well established that PSC are responsible for producing the stromal reaction (fibrosis) of two major diseases of the pancreas—chronic pancreatitis and pancreatic cancer. Despite exponentially increasing data, the methods for studying PSC remain variable. Although within individual laboratories methods are consistent, different methodologies used by various research groups make it difficult to compare results and conclusions. This article is not a review article on the functions of PSC. Instead, members of the Pancreatic Star Alliance (http://www.pancreaticstaralliance.com) discuss here and consolidate current knowledge, to outline and delineate areas of consensus or otherwise (eg, with regard to methodological approaches) and, more importantly, to identify essential directions for future research

Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment

This is the peer reviewed version of the following article: Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment. Gut 64.12 (2015): 1921-1935 and which has been published in final form at http://dx.doi.org/10.1136/gutjnl-2014-308935OBJECTIVES: The tumour stroma/microenvironment not only provides structural support for tumour development, but more importantly it provides cues to cancer stem cells (CSCs) that regulate their self-renewal and metastatic potential. This is certainly true for pancreatic ductal adenocarcinomas (PDAC), where tumour-associated fibroblasts, pancreatic stellate cells and immune cells create an abundant paracrine niche for CSCs via microenvironment-secreted factors. Thus understanding the role that tumour stroma cells play in PDAC development and CSC biology is of utmost importance. DESIGN: Microarray analyses, tumour microarray immunohistochemical assays, in vitro co-culture experiments, recombinant protein treatment approaches and in vivo intervention studies were performed to understand the role that the immunomodulatory cationic antimicrobial peptide 18/LL-37 (hCAP-18/LL-37) plays in PDAC biology. RESULTS: We found that hCAP-18/LL-37 was strongly expressed in the stroma of advanced primary and secondary PDAC tumours and is secreted by immune cells of the stroma (eg, tumour-associated macrophages) in response to tumour growth factor-β1 and particularly CSC-secreted Nodal/ActivinA. Treatment of pancreatic CSCs with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumourigenicity via formyl peptide receptor 2 (FPR2)- and P2X purinoceptor 7 receptor (P2X7R)-dependent mechanisms, which could be reversed by inhibiting these receptors. Importantly, in a genetically engineered mouse model of K-Ras-driven pancreatic tumourigenesis, we also showed that tumour formation was inhibited by either reconstituting these mice with bone marrow from cathelicidin-related antimicrobial peptide (ie, murine homologue of hCAP-18/LL-37) knockout mice or by pharmacologically inhibiting FPR2 and P2X7R. CONCLUSIONS: Thus, hCAP-18/LL-37 represents a previously unrecognised PDAC microenvironment factor that plays a critical role in pancreatic CSC-mediated tumourigenesis.CH: ERC Advanced Investigator Grant (Pa-CSC 233460), European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 256974 (EPC-TM-NET) and n° 602783 (CAM-PaC), the Subdirección General de Evaluación y Fomento de la Investigación, Fondo de Investigación Sanitaria (PS09/02129 & PI12/02643) and the Programa Nacional de Internacionalización de la I+D, Subprogramma: FCCI 2009 (PLE2009-0105; both Ministerio de Economía y Competitividad (es), Spain), BSJr: Rámon y Cajal Merit Award from the Ministerio de Economía y Competitividad, Spain and Clinic and Laboratory Integration Program (CLIP) grant from the Cancer Research Institute, NY, NY. MC: La Caixa Predoctoral Fellowshi

Telomerase and pluripotency factors jointly regulate stemness in pancreatic cancer stem cells

© 2021 by the authors.To assess the role of telomerase activity and telomere length in pancreatic CSCs we used different CSC enrichment methods (CD133, ALDH, sphere formation) in primary patient-derived pancreatic cancer cells. We show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted in CSC marker depletion, abrogation of sphere formation in vitro and reduced tumorigenicity in vivo. Furthermore, we identify a positive feedback loop between stemness factors (NANOG, OCT3/4, SOX2, KLF4) and telomerase, which is essential for the self-renewal of CSCs. Disruption of the balance between telomerase activity and stemness factors eliminates CSCs via induction of DNA damage and apoptosis in primary patient-derived pancreatic cancer samples, opening future perspectives to avoid CSC-driven tumor relapse. In the present study, we demonstrate that telomerase regulation is critical for the “stemness” maintenance in pancreatic CSCs and examine the effects of telomerase inhibition as a potential treatment option of pancreatic cancer. This may significantly promote our understanding of PDAC tumor biology and may result in improved treatment for pancreatic cancer patients.This research was funded by a Max Eder Fellowship of the German Cancer Aid (111746), a German Cancer Aid Priority Program ‘Translational Oncology’ 70112505, by a Collaborative Research Centre grant (316249678—SFB 1279) of the German Research Foundation, and by a Hector Foundation Cancer Research grant (M65.1) to P.C.H., B.S.J. is supported by a Rámon y Cajal Merit Award (RYC2012-12104) from the Ministerio de Economía y Competitividad, Spain and a Coordinated grant (GC16173694BARB) from the Fundación Asociación Española Contra el Cáncer (AECC). K.W. is supported by a Baustein 3.2 by Ulm University