Purpose: Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). Materials and Methods: We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. Results: CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively).Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. Conclusions CLDN18.2 expression was reduced in patients with PM but significantly intactin those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.

Purpose: Expanded indications for endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) remain controversial due to the potential risk of undertreatment after adequate lymph node dissection (LND). Regional LND (RLND) is a novel technique used for limited lymphadenectomy to avoid gastrectomy. This study established the safety and effectiveness of RNLD as an additional treatment option after ESD for expanded indications. Materials and Methods: A total of 69 patients who met the expanded indications for ESD were prospectively enrolled from 2014 to 2017. The tumors were localized using intraoperative esophagogastroduodenoscopy (EGD) before RLND. All patients underwent RLND first, followed by conventional radical gastrectomy with LND. The locations of the preoperative and intraoperative EGD were compared. Pathologic findings of the primary lesion and the RLND status were analyzed. Results: The concordance rates of tumor location between the preoperative and intraoperative EGD were 79.7%, 76.8%, and 63.8% according to the longitudinal, circumferential, and regional locations, respectively. Of the 4 patients (5.7%) with metastatic LNs, 3 were pathologically classified as beyond the expanded indication for ESD and 1 had a single LN metastasis in the regional lymph node. Conclusions RLND is a safe additional option for the treatment of EGC in patients meeting expanded indications after ESD.

Macrophages play an important role in both the innate and adaptive immune responses. These include phagocytosis, killing of microorganisms, antigen presentation, and induction of immune cytokines and antimicrobial genes. Macrophage activity is reported to be controlled by diverse exogenous antigenic or endogenous metabolic molecules, and the underlying mechanisms are well documented in human and mouse macrophage cells. Bacterial lipopolysaccharide (LPS) is known to be one of the most potent stimuli activating macrophages through the toll like receptor 4 (TLR4) signaling pathway. There are other antigenic molecules, such as muramyl dipeptide (MDP) and outer membrane protein A (OmpA), that are also known to activate immune cells. On the other hand, short chain fatty acids (SCFAs) such as acetate and butyrate are produced by gut microbiota and control host energy metabolism and signal transduction through GPR receptors. However, there are few studies demonstrating the effects of these molecules in macrophages from domestic animals, including domestic pigs. In this study, we attempted to characterize gene expression regulation in porcine macrophages (PoM2, Pig Monocytes clone 2) following treatment with LPS, MDP, OmpA, and two short chain fatty acids using porcine genome microarray and RT-PCR techniques. A number of novel porcine genes, including anti-microbial peptides and others, appeared to be regulated at the transcriptional level. Our study reports novel biomarkers such as SLC37A2, TMEN184C, and LEAP2 that are involved in the porcine immune response to bacterial antigen LPS and two short chain fatty acids.
Acetylmuramyl-Alanyl-Isoglutamine ; Animals ; Animals, Domestic ; Antigen Presentation ; Biomarkers ; Butyrates ; Clone Cells ; Cytokines ; Energy Metabolism ; Fatty Acids* ; Gene Expression Regulation ; Genome ; Hand ; Homicide ; Humans ; Macrophages* ; Membrane Proteins ; Mice ; Microbiota ; Monocytes ; Oligonucleotide Array Sequence Analysis ; Peptides ; Phagocytosis ; Signal Transduction ; Sus scrofa ; Toll-Like Receptor 4

OBJECTIVE: To evaluate the prevalence of known risk factors for contrast-induced nephropathy (CIN) and their association with the actual occurrence of CIN in patients undergoing intravenous contrast-enhanced computed tomography (CECT) in Korea. MATERIALS AND METHODS: Patients who underwent CECT in 2008 were identified in the electronic medical records of 16 tertiary hospitals of Korea. Data on demographics, comorbidities, prescriptions and laboratory test results of patients were collected following a standard data extraction protocol. The baseline renal function was assessed using the estimated glomerular filtration rate (eGFR). We identified the prevalence of risk factors along the eGFR strata and evaluated their influence on the incidence of CIN, defined as a 0.5 mg/dL or 25% increase in serum creatinine after CECT. RESULTS: Of 432425 CECT examinations in 272136 patients, 140838 examinations in 101487 patients met the eligibility criteria for analysis. The mean age of the participants was 57.9 +/- 15.5 years; 25.1% of the patients were older than 70 years. The prevalence of diabetes mellitus was 11.9%, of hypertension 13.7%, of gout 0.55% and of heart failure was 1.7%. Preventive measures were used in 40238 CECT examinations (28.6%). The prevalence of risk factors and use of preventive measures increased as the renal function became worse. A CIN was occurred after 3103 (2.2%) CECT examinations, revealing a significant association with decreased eGFR, diabetes mellitus, and congestive heart failure after adjustment. CONCLUSION: Risk factors for CIN are prevalent among the patients undergoing CECT. Preventive measures were seemingly underutilized and a system is needed to improve preventive care.
Adult ; Aged ; Aged, 80 and over ; Comorbidity ; Contrast Media/*adverse effects ; Female ; Glomerular Filtration Rate ; Humans ; Incidence ; Kidney Diseases/*chemically induced/epidemiology/*radiography ; Male ; Middle Aged ; Prevalence ; Republic of Korea/epidemiology ; Risk Factors ; Tomography, X-Ray Computed/*methods

In this study, we examined the therapeutic effects of an immune-stimulating peptide, WKYMVm, in ulcerative colitis. The administration of WKYMVm to dextran sodium sulfate (DSS)-treated mice reversed decreases in body weight, bleeding score and stool score in addition to reversing DSS-induced mucosa destruction and shortened colon. The WKYMVm-induced therapeutic effect against ulcerative colitis was strongly inhibited by a formyl peptide receptor (FPR) 2 antagonist, WRWWWW, indicating the crucial role of FPR2 in this effect. Mechanistically, WKYMVm effectively decreases intestinal permeability by stimulating colon epithelial cell proliferation. WKYMVm also strongly decreases interleukin-23 and transforming growth factor-beta production in the colon of DSS-treated mice. We suggest that the potent immune-modulating peptide WKYMVm and its receptor FPR2 may be useful in the development of efficient therapeutic agents against chronic intestinal inflammatory diseases.
Adjuvants, Immunologic/pharmacology/*therapeutic use ; Animals ; Caco-2 Cells ; Cell Proliferation ; Colitis, Ulcerative/*drug therapy/metabolism ; Colon/pathology ; Humans ; Interleukin-23/genetics/metabolism ; Intestinal Mucosa/drug effects/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Oligopeptides/pharmacology/*therapeutic use ; Permeability ; Receptors, Formyl Peptide/antagonists & inhibitors ; Transforming Growth Factor beta/genetics/metabolism

The present study was carried out to examine the toxicity and target organs of oral cholera vaccine (OCV) after repeated oral administration in Sprague-Dawley rats for 6 weeks (3 administrations, once every 2 weeks). OCV is an inactivated oral cholera vaccine that contains Vibrio cholerae and confers protection against cholera caused by V. cholera serogroups O1 (Inaba and Ogawa serotypes) and O139 (strain 4260B). The animals were orally administered either OCV placebo (negative control) or OCV at a dose equivalent to 240 times the anticipated human dose. Throughout the administration period, no significant change was detected in clinical signs, body weight, food or water consumption, urinalysis results, hematological and clinical biochemistry test results, organ weights, necropsy, or histopathological examination results. Minor changes were found in hematological and clinical biochemistry tests; however, these changes were within normal ranges. The above results suggest that oral administration of OCV in rats did not induce any toxicologically meaningful changes, and the target organs could not be determined. This study was conducted in accordance with the guidelines established by Good Laboratory Practice (2009-183, KFDA, December 22, 2009) and the OECD Principles of Good Laboratory Practice (1997).
Administration, Oral ; Animals ; Biochemistry ; Body Weight ; Cholera ; Drinking ; Humans ; Organ Size ; Rats ; Rats, Sprague-Dawley ; Reference Values ; Urinalysis ; Vibrio cholerae

BACKGROUND: The identification of monoclonality has been widely used for making diagnoses of lymphoproliferative lesions. Awareness of the sensitivity and detection limit of the technique used would be important for the data to be convincing. METHODS: We investigated the minimum requirement of cells and sensitivity of gel electrophoresis (GE) and laser-induced fluorescence capillary electrophoresis (LFCE) for identifying IgH gene rearrangement using BIOMED-2 protocols. DNA extracted from Raji cells were diluted serially with peripheral blood mononuclear cells (PBMNCs) DNA. DNA from mixtures of diffuse large B-cell lymphoma (DLBCL) and reactive lymph nodes were also serially diluted. RESULTS: For Raji cells, the detection limit was 62 and 16 cell-equivalents for GE and LFCE, respectively. In the condition with PBMNCs mixture, 2.5% and 1.25% of clonal cells was the minimum requirement for GE and LFCE, respectively. In 23% of DLBCL cells in tissue section, the detection limit was 120 and 12 cell-equivalents for GE and LFCE, respectively. In 3.2% of DLBCL cells, that was 1,200 and 120 cell-equivalents for GE and LFCE, respectively. CONCLUSIONS: These results show that LFCE method is more sensitive than GE and the sensitivity of clonality detection can be influenced by the amount of admixed normal lymphoid cells.
B-Lymphocytes ; Capillaries ; DNA ; Electrophoresis ; Electrophoresis, Capillary ; Fluorescence ; Gene Rearrangement ; Limit of Detection ; Lymph Nodes ; Lymphocytes ; Lymphoma, B-Cell ; Lymphoproliferative Disorders ; Multiplex Polymerase Chain Reaction

PURPOSE: Heptaplatin (Sunpla) is a cisplatin derivative. A phase IIb trial using heptaplatin resulted in a 34% response rate with mild nephrotoxicity. We conducted a randomized phase III trial of heptaplatin plus 5-FU compared with cisplatin plus 5-FU in patients with advanced gastric cancer. MATERIALS AND METHODS: One hundred seventy-four patients (heptaplatin, n=88; cisplatin, n=86) from 13 centers were enrolled. The eligibility criteria were as follows: patients with pathologically-proven adenocarcinoma, chemonaive patients, or patients who had received only single adjuvant chemotherapy, and who had a measurable or evaluable lesion. On day 1, heptaplatin (400 mg/m2) or cisplatin (60 mg/m2) was given over 1 hour with 5-FU (1 gm/m2) on days 1~5 every 4 weeks. RESULTS: At the time of survival analysis, the median overall survival was 7.3 months in the 5-FU + heptaplatin (FH) arm and 7.9 months in the 5-FU + cisplatin (FP) arm (p=0.24). Of the FH patients, 34.2% (complete response [CR], 1.3%; partial response [PR], 32.9%) experienced a confirmed objective response compared with 35.9% (CR 0%, PR 35.9%) of FP patients (p=0.78). The median-time-to-progression was 2.5 months in the FH arm and 2.3 months in the FP arm. The incidence of neutropenia was higher with FP (28%) than with FH (16%; p=0.06); grade 3~4 nausea and vomiting were more frequent in the FP than in the FH arm (p=0.01 and p=0.05, respectively). The incidence of increased proteinuria and creatininemia was higher with FH than with FP; however, there was no statistical difference. There were no treatment-related deaths. CONCLUSION: Heptaplatin showed similar effects to cisplatin when combined with 5-FU in advanced gastric cancer patients with tolerable toxicities.
Adenocarcinoma ; Arm ; Chemotherapy, Adjuvant ; Cisplatin ; Drug Therapy, Combination ; Fluorouracil ; Humans ; Incidence ; Malonates ; Nausea ; Neutropenia ; Organoplatinum Compounds ; Proteinuria ; Stomach Neoplasms ; Vomiting

Non-Hodgkin lymphoma can involve the female genital tract usually as a manifestation of systemic disease, the vast majority of cases being B cell lineage. We report here one case of nasal type NK/T cell lymphoma arising in the uterus, of a 45-year-old Korean woman. The endometrium and myometrium showed diffuse infiltrative mass with hemorrhage and necrosis. Microscopic examination of the tumor revealed medium-sized atypical lymphoid cells. The tumor cells were positive for cytoplasmic CD3 and CD56, and were negative for vimentin, CD10, smooth muscle actin and desmin. Furthermore, In situ hybridization analysis for Epstein-Barr virus (EBV) RNA was positive. The histopathologic and immunohistochemical findings were consistent with extranodal nasal type NK/T cell lymphoma. We report this case to illustrate that NK/T cell lymphomas can involve, and rarely arise in, the gynecologic tract.
Actins ; Animals ; Cell Lineage ; Cytoplasm ; Desmin ; Endometrium ; Female ; Hemorrhage ; Herpesvirus 4, Human ; Humans ; In Situ Hybridization ; Lymphocytes ; Lymphoma ; Lymphoma, Non-Hodgkin ; Mice ; Middle Aged ; Muscle, Smooth ; Myometrium ; Necrosis ; RNA ; Uterus ; Vimentin

Pneumocystis jirovecii is an atypical fungus that causes severe pneumonia in immune compromised patients. While Pneumocystis jirovecii pneumonia (PCP) is more commonly diagnosed in individuals who have HIV infection, it can occur in individuals with other forms of immunosuppression. Fat embolism most commonly develops after orthopedic injuries, but it has also been reported after other forms of trauma such as severe burns, closed-chest cardiac massage, and liposuction. Overlap in the clinical presentation of these diseases has not yet been reported. We report here on a case of PCP with fat embolism in 52-year-old female patient who had no obvious risk factors for HIV infection. Even if risk factors for HIV or other forms of immunosuppression are not present, PCP can also be seen in patients who present with fat embolism, and the clinical presentation of both conditions can overlap.
Burns ; Embolism, Fat ; Female ; Fungi ; Heart Massage ; HIV ; HIV Infections ; Humans ; Immunosuppression ; Lipectomy ; Middle Aged ; Orthopedics ; Pneumocystis ; Pneumocystis jirovecii ; Pneumonia ; Risk Factors