Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Background/Aims: Three-dimensional cultures of human pancreatic cancer tissue also known as “organoids” have largely been developed from surgical specimens. Given that most patients present with locally advanced and/or metastatic disease, such organoids are not representative of the majority of patients. Therefore, we used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to collect pancreatic cancer tissues from patients with advanced pancreatic cancer to create organoids, and evaluated their utility in pancreatic cancer research. Methods: Single-pass EUS-FNA samplings were employed to obtain the tissue for organoid generation. After establishment of the organoid, we compared the core biopsy tissues with organoids using hematoxylin and eosin staining, and performed whole exome sequencing (WES) to detect mutational variants. Furthermore, we compared patient outcome with the organoid drug response to determine the potential utility of the clinical application of such organoid-based assays. Results: Organoids were successfully generated in 14 of 20 tumors (70%) and were able to be passaged greater than 5 times in 12 of 20 tumors (60%). Among them, we selected eight pairs of organoid and core biopsy tissues for detailed analyses. They showed similar patterns in hematoxylin and eosin staining. WES revealed mutations in KRAS, TP53, CDKN2A, SMAD4, BRCA1, and BRCA2 which were 93% homologous, and the mean nonreference discordance rate was 5.47%. We observed moderate drug response correlations between the organoids and clinical outcomes in patients who underwent FOLFIRINOX chemotherapy. Conclusions The established organoids from EUS-FNA core biopsies can be used for a suitable model system for pancreatic cancer research

Intussusception and acute appendicitis are common emergency conditions in children. They should be promptly differentiated in pediatric patients presenting with suggestive symptoms.However, both diseases may occur simultaneously. Herein, we present two cases of intussusception of the appendix accompanied with appendicitis.

PURPOSE: Patients' gender, which can be one of the most important determinants of traumatic brain injury (TBI) outcomes, is also likely to interact with many other outcome variables of TBI. This multicenter descriptive study investigated gender differences in epidemiological, clinical, treatment, mortality, and variable characteristics in adult TBI patients. METHODS: The selection criteria were defined as patients who had been diagnosed with TBI and were admitted to the hospital between January 1, 2016 and December 31, 2018. A total of 4468 adult TBI patients were enrolled at eight University Hospitals. Based on the list of enrolled patients, the medical records of the patients were reviewed and they were registered online at each hospital. The registered patients were classified into three groups according to the Glasgow coma scale (GCS) score: mild (13-15), moderate (9-12), and severe (3-8), and the differences between men and women in each group were investigated. The risk factors of moderated and severe TBI compared to mild TBI were also investigated. RESULTS: The study included 3075 men and 1393 women and the proportion of total males was 68.8%. Among all the TBI patients, there were significant differences between men and women in age, past history, and GCS score. While the mild and severe TBI groups showed significant differences in age, past history, and clinical symptoms, the moderate TBI group showed significant differences in age, past history, cause of justice, and diagnosis. CONCLUSION To the best of our knowledge, this multicenter study is the first to focus on gender differences of adult patients with TBI in Korea. This study shows significant differences between men and women in many aspects of adult TBI. Therefore, gender differences should be strongly considered in TBI studies.
Adult ; Brain Injuries ; Brain Injuries, Traumatic/epidemiology* ; Female ; Glasgow Coma Scale ; Humans ; Male ; Prospective Studies ; Sex Factors

Intussusception and acute appendicitis are common emergency conditions in children. They should be promptly differentiated in pediatric patients presenting with suggestive symptoms.However, both diseases may occur simultaneously. Herein, we present two cases of intussusception of the appendix accompanied with appendicitis.

In order to investigate the antioxidant effect of alkylhydroxide peroxidase (ahpC) of Helicobacter pylori (H. pylori) 26695, an ahpC-deficient mutant (H. pylori 26695 ahpC::cat) was generated. ahpC-deficient mutant was grown slowly at lower pressure of oxygen (5% oxygen) compared to the H. pylori 26695. Whole cell proteins isolated form H. pylori 26695 and H. pylori 26695 ahpC::cat were analyzed by MALDI-TOF and tandem-MS. The expression of 15 proteins, including Ppa, HypB, GrpE, Elp, RecA, GroES, Mda66, RibE, NapA, GlnA, BioB, TrxB, Tsf, FumC and Icd, was more than doubled in H. pylori 26695 ahpC::cat. Production of 10 proteins such as UreG, FabE, Adk, Pnp, OorC, AtpA, AtpD, Nqq3, Pfr, and TagD decreased below 50% in H. pylori 26695 ahpC::cat compared to the H. pylori 26695. In microarray analysis, 9 genes including sul1, amiE, frxA, fecA, hyuA, and katA increased in transcription level in H. pylori 26695 ahpC::cat compared to H. pylori 26695. A total of 24 genes, including flaB, protein kinase C inhibitor, cag16, pabC, and sabA, reduced in transcription. 27 genes, including HP0889, showed common expression changes in ahpC, katA, and sodB-deficient mutations. As a result of this study, there were not many genes whose expression was commonly changed by the deletion of each of the three major antioxidant enzymes of H. pylori. These results showed the functions and regulation of the three antioxidant enzymes were different in H. pylori.
Antioxidants ; Helicobacter pylori ; Helicobacter ; Microarray Analysis ; Oxygen ; Peroxidase ; Protein Kinase C ; Proteome ; Ribes

Helicobacter pylori (H. pylori), a causative agent of chronic gastritis and gastric cancer, has several virulent factors for own survival and progression toward gastric diseases in human stomach. Of those, H. pylori produces mainly urease (10~15% total protein weight) that neutralize the gastric acid for survival. Here, we identified the antigenic epitope of urease and then developed an ELISA using the antigen including the epitope of urease. We identified the antigenic epitope of urease that induces IgA antibodies in human using truncated mutants. Eight kinds of serially-truncated mutant of UreA and UreB were prepared and subjected to immunoblot using pooled sera of patients with gastric disorders. UreBEnd protein containing UreB epitope was produced and investigated its diagnostic value via ELISA in children. As a result, mutants having last 24 amino acid residues of UreB carboxyl terminus deleted did not show IgA-reactive band. The clones that contained the downstream of 448(th) amino acid in UreB showed IgA-reactive band. The serodiagnostic value of the UreBEnd recombinant protein including identified epitope was confirmed via IgA ELISA and shown to have 97% sensitivity and 100% specificity. These results demonstrated that carboxyl terminal region of UreB carries an antigenic epitope for IgA response in human. It may be useful for detecting H. pylori infection with improved test accuracy and minimum use of endoscopy.
Antibodies ; Child* ; Clone Cells ; Endoscopy ; Enzyme-Linked Immunosorbent Assay ; Epitopes* ; Gastric Acid ; Gastritis ; Helicobacter pylori* ; Helicobacter* ; Humans ; Immunoglobulin A* ; Sensitivity and Specificity ; Stomach ; Stomach Diseases ; Stomach Neoplasms ; Urea* ; Urease*

BACKGROUND AND OBJECTIVES: Dizziness is not uncommon in children. The etiology of dizziness varies according to different studies due to different methods of examination or characteristics of the dizziness center. To assess meaningful causes of dizziness in children, a multidisciplinary approach would be needed. The purpose of this study was to analyze the main pathologies associated with vertigo and dizziness in children, paying particular attention to recent diagnostic advances with a multidisciplinary approach. SUBJECTS AND METHOD: A total of 73 children, aged between 4-18 years, who visited the Pediatric Dizziness Clinic of the University Hospital from January 2016 to June 2016 were included in this study. Medical records were reviewed retrospectively. All of the subjects were examined by history, questionnaires, physical examinations, electrocardiogram, hematologic tests, brain MRI scan, audiogram and vestibular function tests. Patients who had orthostatic symptoms additionally underwent a tilt table test, and in selective cases, a caloric and vestibular evoked myogenic potential tests as well. RESULTS: Vestibular migraine (VM) and benign paroxysmal vertigo of childhood (BPVC) were found in 35.6% and 27.4% of the children with dizziness, respectively. The incidence of orthostatic hypotension and postural orthostatic tachycardia syndrome were 12.3% each, both of which are higher than other previous reports. Other causes were Meniere's disease, benign paroxysmal positional vertigo, vestibular neuritis and so on. CONCLUSION: VM and BPVC were the most common causes of pediatric dizziness. Also, the incidence of orthostatic dizziness was rather high in pediatric population. The evaluation of dizziness in children should include a thorough check of history (questionnaire), neurotological examination, vestibular function tests and a tilt table test.
Benign Paroxysmal Positional Vertigo ; Brain ; Child ; Dizziness* ; Electrocardiography ; Hematologic Tests ; Humans ; Hypotension, Orthostatic ; Incidence ; Magnetic Resonance Imaging ; Medical Records ; Meniere Disease ; Methods ; Migraine Disorders ; Pathology ; Physical Examination ; Postural Orthostatic Tachycardia Syndrome ; Retrospective Studies ; Tilt-Table Test ; Vertigo ; Vestibular Function Tests ; Vestibular Neuronitis

Johne's disease (JD) is a chronic, debilitating disease of ruminants including cows, and is caused by Mycobacterium avium subsp. paratuberculosis (MAP). MAP is not only important in animal husbandry, but also in public health as it is associated with the onset of Crohn's disease, a chronic inflammatory bowel disease in humans. JD, like other mycobacterial diseases including tuberculosis, is classified into different stages based on the progression of infection. In addition, development of diagnostic assays that can distinguish between subclinical and clinical stages of JD is essential to control mycobacterial infection by providing an effective treatment. For the development of novel diagnostic methods of JD, it is important to investigate and understand the mRNA expression of the various immune markers in individuals at each stage of infection. In this study, we measured the levels of Th1-type chemokines, CXCR3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11 in MAP-infected bovine blood by interferon (IFN)-γ release assay (IGRA) using IFN-γ as an alternative biomarker. The association of mRNA expression patterns of these chemokines with the MAP infection stages was analyzed and IFN-γ, CCL5, and CXCL10 were found to be significantly upregulated compared to IFN-γ, the biomarker used in IGRA. Our results further indicate that IFN-γ levels significantly increased in individuals with MAP-specific antibody, and CCL5 and CXCL10 levels significantly increased in those with MAP DNA. In particular, CCL5 was significantly upregulated in individuals, in which both MAP-specific antibody and MAP DNA were detected, but the expression of CXCL10 was specifically elevated in MAP DNA-detected individuals without MAP-specific antibody.
Animal Husbandry ; Animals ; Biomarkers ; Cattle* ; Chemokines* ; Crohn Disease ; DNA ; Gene Expression* ; Humans ; Inflammatory Bowel Diseases ; Interferons ; Mycobacterium avium subsp. paratuberculosis ; Mycobacterium avium* ; Mycobacterium* ; Paratuberculosis ; Public Health ; RNA, Messenger ; Ruminants ; Transcriptome* ; Tuberculosis

A 46-year-old female with abnormal radiologic finding was diagnosed with pancreatic neuroendocrine tumor and multiple hepatic metastasis. Molecular targeted therapy (everolimus) and two times of transarterial chemoembolizations (TACE) were performed before pylorus-preserving pancreaticoduodenectomy (PPPD). After 2nd TACE and PPPD, grade 2 pancreatic neuroendocrine tumor was pathologically confirmed. Four times of additional TACE was done. After size increase of several probable hepatic metastasis in the both lobes of liver, laparoscopic left lateral sectionectomy of liver was performed. After two and half years of left lateral sectionectomy, 7th TACE was performed and the patients have survived without further disease progression. This case suggests that patients with pancreatic neuroendocrine tumor and hepatic metastasis can be treated by TACE, primary tumor resection, surgery for liver metastasis and molecular targeted therapy. Therefore, aggressive multidisciplinary approaches need to be considered for long term survival of patients with pancreatic neuroendocrine tumor with hepatic metastasis.
Disease Progression ; Female ; Humans ; Liver ; Middle Aged ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Neuroendocrine Tumors* ; Pancreas ; Pancreaticoduodenectomy