Publications by authors named "Jieun Yu"

16 Publications

  • Page 1 of 1

Efficacy of add-on therapy with intravenous immunoglobulin in steroid hyporesponsive DRESS syndrome.

Clin Transl Sci 2021 Nov 18. Epub 2021 Nov 18.

Division of Allergy, Asthma, and Clinical Immunology, Department of Internal Medicine, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, potentially life-threatening, delayed, drug-induced hypersensitivity reaction. Immediate withdrawal of the culprit drug and administration of systemic corticosteroids is the most widely accepted treatment. However, it is difficult to manage patients with DRESS syndrome who are not responsive to systemic steroids. We studied the efficacy of intravenous immunoglobulins (IVIGs) in patients with DRESS syndrome unresponsive to systemic steroids. We retrospectively reviewed patients with DRESS syndrome who received IVIG in addition to systemic steroids during 2012-2017 and compared the clinical features and course of DRESS syndrome, before and after IVIG treatment. Eighteen DRESS patients (9 men) were included. The most frequent offending drugs were dapsone in five patients, followed by vancomycin in three patients, and carbamazepine in three patients. Rash, fever, lymphadenopathy, atypical lymphocytes, and hepatic involvement were common clinical findings. IVIG treatment was added within a median time of 7 days from the commencement of systemic steroid therapy. After IVIG treatment (total dosage: 1-2 g/kg), the fever resolved within a median time of 1 day (range, 0-3) and liver enzymes improved substantially within a median time of 13 days (range, 0-27). No severe adverse reactions related to IVIG therapy were observed in this study; however, there was one case of mortality. The addition of IVIG in DRESS syndrome in cases refractory to systemic steroid treatment may be helpful in hastening recovery. However, comparative studies using a placebo group are needed.
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http://dx.doi.org/10.1111/cts.13201DOI Listing
November 2021

The process of National Health Insurance coverage for Chuna Manual Therapy in Korea: A qualitative study.

Integr Med Res 2022 Mar 26;11(1):100746. Epub 2021 May 26.

Division of Humanities and Social Medicine, School of Korean Medicine, Pusan National University, Yangsan, Korea.

Background: Chuna Manual Therapy (CMT) has been widely used in Korea, and coverage in Korean National Health Insurance (NHI) was finally implemented in 2019. The objectives of this study were to analyze the process of NHI coverage for CMT qualitatively, and to summarize important roles, streams, and implications regarding its inclusion in the modern public health insurance system.

Methods: Related literature was collected and 8 key personnel involved in the policy-making process were qualitatively interviewed, and Zahariadis' version of the Multiple Streams Framework (MSF) was applied to analyze the policy agenda setting and the roles of stakeholders.

Results: Through the collaborative efforts of various stakeholders, a pilot coverage project for CMT was implemented in 2017, and coverage was expanded nationwide in 2019. MSF showed that it was mainly achieved through three streams: governmental change (political stream), demand from the general public and KM doctors (problem stream), and strengthening/reinforcement of the feasibility and acceptability of the policy (policy steam). Also, the roles of policy entrepreneurs and resulting changes were shown to be significant for the overall process.

Conclusion: NHI coverage for CMT was realized through collective policy and research efforts from the government and academic sectors. The roles of stakeholders were shown to be significant in the overall process, and documentation of their involvement is hoped to be of use of other countries that utilize traditional and/or manual medicine.
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http://dx.doi.org/10.1016/j.imr.2021.100746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267429PMC
March 2022

Neuroendocrine control of appetite and metabolism.

Exp Mol Med 2021 Apr 9;53(4):505-516. Epub 2021 Apr 9.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.

Body homeostasis is predominantly controlled by hormones secreted by endocrine organs. The central nervous system contains several important endocrine structures, including the hypothalamic-pituitary axis. Conventionally, neurohormones released by the hypothalamus and the pituitary gland (hypophysis) have received much attention owing to the unique functions of the end hormones released by their target peripheral organs (e.g., glucocorticoids released by the adrenal glands). Recent advances in mouse genetics have revealed several important metabolic functions of hypothalamic neurohormone-expressing cells, many of which are not readily explained by the action of the corresponding classical downstream hormones. Notably, the newly identified functions are better explained by the action of conventional neurotransmitters (e.g., glutamate and GABA) that constitute a neuronal circuit. In this review, we discuss the regulation of appetite and metabolism by hypothalamic neurohormone-expressing cells, with a focus on the distinct contributions of neurohormones and neurotransmitters released by these neurons.
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http://dx.doi.org/10.1038/s12276-021-00597-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102538PMC
April 2021

Educational exercise program affects to physical fitness and gross motor function differently in the severity of autism spectrum disorder.

J Exerc Rehabil 2020 Oct 27;16(5):410-417. Epub 2020 Oct 27.

Research Institute of Sports and Industry Science (RISIS), Hanseo University, Seosan, Korea.

This study investigated the effects of participating in an educational exercise program on physical fitness and gross motor function (GMF) in adults with varying degrees of autistic spectrum disorder (ASD). The subjects consisted of 35 voluntary male participants between 20 and 29 years of age who were allocated to one of two groups: mild ASD (n=17) group and severe ASD (n=18) group. All selected tests for physical fitness, including body composition and GMF, have been used in previous studies. The results were as follows: first, with the exception of the basal metabolic rate, there were significant differences in the interaction of all other body composition variables. Second, there were significant differences in the interaction of almost all physical fitness variables, except for muscle strength. Finally, although there were significant differences in the interaction of all variables, except the locomotion skill for hopping, there were significant differences in the interaction of all variables of object control skill. Specifically, although the Δ% in the sum of locomotion skill in mild ASD group increased ~19.81%, that of severe ASD group decreased ~4.78%. The Δ% in the sum of object control skill in mild ASD group improved ~29.96%, while that of severe ASD group reduced ~15.2%. In conclusion, it is thought that these results are due to the better understanding of educational exercise and better performance of educational exercise in adults with mild ASD compared to adults with severe ASD.
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http://dx.doi.org/10.12965/jer.2040688.344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609850PMC
October 2020

A mixture of chloromethylisothiazolinone and methylisothiazolinone impairs rat vascular smooth muscle by depleting thiols and thereby elevating cytosolic Zn and generating reactive oxygen species.

Arch Toxicol 2021 02 19;95(2):541-556. Epub 2020 Oct 19.

College of Pharmacy, Integrated Research Institute for Drug Development, and BK21 FOUR team, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea.

Chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) are biocidal preservatives and the active ingredients in Kathon CG, which contains ca. 1.5% mixture of CMIT and MIT at a ratio of 3:1 (CMIT/MIT). CMIT/MIT was misused as humidifier disinfectant products, which caused serious health problems in Korea. Here, the vascular effects of CMIT/MIT were investigated to evaluate claims of putative cardiovascular toxicity observed in humidifier disinfectant users. CMIT/MIT did not affect the basal tension of the rat thoracic aorta up to 2.5 μg/mL in myograph experiments. Instead, pretreatment with CMIT/MIT impaired phenylephrine- or 5-hydroxytryptamine-induced vasoconstriction in a range of 0.5-2.5 μg/mL, which was largely irreversible and not recovered by washing out the CMIT/MIT. Similarly, the application of CMIT/MIT to pre-contracted aorta caused a gradual loss of tension. In primary cultured vascular smooth muscle cells (VSMCs), CMIT/MIT caused thiol depletion, which in turn led to cytosolic Zn elevation and reactive oxygen species (ROS) formation. CMIT/MIT-induced shrinkage, detachment, and lysis of VSMCs depending on the concentration and the treatment time. All events induced by CMIT/MIT were prevented by a thiol donor N-acetylcysteine (NAC). Cytolysis could be inhibited by a Zn chelator TPEN and a superoxide scavenger TEMPOL, whereas they did not affect shrinkage and detachment. In accordance with these results, CMIT/MIT-exposed aortas exhibited dissociation and collapse of tissue in histology analysis. Taken together, CMIT/MIT causes functional impairment and tissue damage to blood vessels by depleting thiol and thereby elevating cytosolic Zn and generating ROS. Therefore, exposure to CMIT/MIT in consumer products may be a risk factor for cardiovascular disorders.
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http://dx.doi.org/10.1007/s00204-020-02930-zDOI Listing
February 2021

Co-degradation of interferon signaling factor DDX3 by PB1-F2 as a basis for high virulence of 1918 pandemic influenza.

EMBO J 2019 05 12;38(10). Epub 2019 Apr 12.

Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea

The multifunctional influenza virus protein PB1-F2 plays several roles in deregulation of host innate immune responses and is a known immunopathology enhancer of the 1918 influenza pandemic. Here, we show that the 1918 PB1-F2 protein not only interferes with the mitochondria-dependent pathway of type I interferon (IFN) signaling, but also acquired a novel IFN antagonist function by targeting the DEAD-box helicase DDX3, a key downstream mediator in antiviral interferon signaling, toward proteasome-dependent degradation. Interactome analysis revealed that 1918 PB1-F2, but not PR8 PB1-F2, binds to DDX3 and causes its co-degradation. Consistent with intrinsic protein instability as basis for this gain-of-function, internal structural disorder is associated with the unique cytotoxic sequences of the 1918 PB1-F2 protein. Infusing mice with recombinant DDX3 protein completely rescued them from lethal infection with the 1918 PB1-F2-producing virus. Alongside NS1 protein, 1918 PB1-F2 therefore constitutes a potent IFN antagonist causative for the severe pathogenicity of the 1918 influenza strain. Our identification of molecular determinants of pathogenesis should be useful for the future design of new antiviral strategies against influenza pandemics.
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http://dx.doi.org/10.15252/embj.201899475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518015PMC
May 2019

Complete response of hepatocellular carcinoma with right atrium and pulmonary metastases treated by combined treatments (a possible treatment effect of natural killer cell): A case report and literature review.

Medicine (Baltimore) 2018 Oct;97(42):e12866

Division of Gastroenterology.

Rationale: Hepatocellular carcinomas (HCCs) with metastases to the right atrium (RA) and lungs are rare, with a poor prognosis. Furthermore, the treatment outcomes in patients with advanced HCCs remain unsatisfactory.

Patient Concerns: A 46-year-old man presented to our hospital for dyspnea on exertion and abdominal pain.

Diagnoses: HCC and extra-hepatic metastases to the lung and RA.

Interventions: Multidisciplinary treatment including radiotherapy (RT), transarterial chemoembolization (TACE), and sorafenib. During a follow-up evaluation computed tomography, he experienced a radio-contrast-induced anaphylaxis. After the event, treatment such as RT, TACE, and sorafenib were continued.

Outcomes: His tumor burden decreased, finally leading to a complete response as per the modified Response Evaluation Criteria in Solid Tumors. The patient is still alive, 30 months after the episode. Subsequent blood tests showed increased natural killer (NK) cell activity, which was significantly higher than that seen in other age-matched HCC patients with an identical stage of the tumor, receiving sorafenib. This suggests that the increase in NK cells induced by anaphylaxis influenced the tumor burden.

Lessons: We report here a rare case of long-term survival of an HCC patient with multiple metastases treated with multidisciplinary modalities, in which high NK cell activity was observed after a radio-contrast-induced anaphylactic reaction during follow-up investigations.
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http://dx.doi.org/10.1097/MD.0000000000012866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211840PMC
October 2018

Pigs that recover from porcine reproduction and respiratory syndrome virus infection develop cytotoxic CD4+CD8+ and CD4+CD8- T-cells that kill virus infected cells.

PLoS One 2018 6;13(9):e0203482. Epub 2018 Sep 6.

Gift of life Michigan, Ann Arbor, Michigan, United States of America.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection is difficult to control because the virus undergoes antigenic variation during infection and also modulates the protective host immune response. Although current vaccines do not provide full protection, they have provided insight into the mechanisms of protection. Live PRRSV vaccines induce partial protection before the appearance of neutralizing antibody, suggesting cell-mediated immunity or other mechanisms may be involved. Herein, we demonstrate recovery from infection is associated with development of cytotoxic T-lymphocytes (CTL) that can kill PRRSV-infected target cells. Initial experiments showed survival of PRRSV-infected monocyte derived macrophage (MDM) targets is reduced when overlaid with peripheral blood mononuclear cells (PBMC) from gilts that had recovered from PRRSV infection. Further studies with PBMC depleted of either CD4+ or CD8+ T-cells and positively selected subpopulations of CD4+ and CD8+ T-cells showed that both CD4+ and CD8+ T-cells were involved in killing. Examination of killing at different time points revealed killing was biphasic and mediated by CTL of different phenotypes. CD4+CD8+high were associated with killing target cells infected for 3-6 hours. CD4+CD8- CTL were associated with killing at 16-24 hours. Thus, all the anti-PRRSV CTL activity in pigs was attributed to two phenotypes of CD4+ cells which is different from the anti-viral CD4-CD8+ CTL phenotype found in most other animals. These findings will be useful for evaluating CTL responses induced by current and future vaccines, guiding to a novel direction for future vaccine development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203482PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126854PMC
February 2019

Improvement of anti-cancer drug efficacy via thermosensitive hydrogel in peritoneal carcinomatosis in gastric cancer.

Oncotarget 2017 Dec 6;8(65):108848-108858. Epub 2017 Nov 6.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Peritoneal carcinomatosis (PC) of gastric origin has a poor prognosis with short survival due to lack of effective therapeutic modalities. Here, we evaluated the therapeutic efficacy of an injectable thermosensitive poly (organophosphazene) (PPZ) hydrogel with docetaxel (DTX-gel) to develop an effective therapeutic agent for patient with PC. Three days after inoculation of highly metastatic 44As3Luc cells into peritoneal cavity, the mice were intravenously or intraperitoneally administered with docetaxel alone (DTX-sol IV or IP), and intraperitoneally injected with DTX-gel. The anti-tumor activity was monitored by bioluminescence live imaging system. Compared to DTX-sol IV or IP, the tumor growth was significantly reduced in the DTX-gel treated mice (<0.0001, =0.0001). Furthermore, the survival rate was significantly increased in the DTX-gel treated mice compared to DTX-sol IV or IP treated mice (<0.0001, =0.0068). Our results demonstrated that DTX-gel suppresses peritoneal metastasis by continuing release of chemotherapy agent, which leads to increase the survival rate in a PC model. Therefore, biodegradable thermosensitive hydrogel with docetaxel system can be a good anti-cancer agent for PC.
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http://dx.doi.org/10.18632/oncotarget.22312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752486PMC
December 2017

Gastric Carcinogenesis in the miR-222/221 Transgenic Mouse Model.

Cancer Res Treat 2017 Jan 23;49(1):150-160. Epub 2016 Jun 23.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Purpose: MicroRNAs (miRNAs) regulate various cellular functions, including development, cell proliferation, apoptosis, and tumorigenesis. Different signatures associated with various tissue types, diagnosis, progression, prognosis, staging, and treatment response have been identified by miRNA expression profiling of human tumors. miRNAs function as oncogenes or as tumor suppressors. The relationship between gastric cancer and miRNA garnered attention due to the high incidence of gastric cancer in Asian countries. miR-222/221 expression increases in gastric tumor tissues. The oncogenic effect of miR-222/221 was previously determined in functional studies and xenograft models. In this study, transgenic mice over-expressing miR-222/221 were generated to confirm the effect of miR-222/221 on gastric carcinogenesis.

Materials And Methods: At 6 weeks of age, 65 transgenic mice and 53 wild-type mice were given drinking water containing -nitroso--methylurea (MNU) for 5 alternating weeks to induce gastric cancer. The mice were euthanized at 36 weeks of age and histologic analysis was performed.

Results: Hyperplasia was observed in 3.77% of the wild-type mice and in 18.46% of the transgenic mice (p=0.020). Adenoma was observed in 20.75% of the wild-type mice and 26.15% of the transgenic mice (p=0.522). Carcinoma was observed in 32.08% of the wild-type mice and 41.54% of the transgenic mice (p=0.341). The frequency of hyperplasia, adenoma, and carcinoma was higher in transgenic mice, but the difference was statistically significant only in hyperplasia.

Conclusion: These results suggest that hyperplasia, a gastric pre-cancerous lesion, is associated with miR-222/221 expression but miR-222/221 expression does not affect tumorigenesis itself.
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http://dx.doi.org/10.4143/crt.2015.462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266385PMC
January 2017

Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis.

Cancer Res Treat 2015 Oct 2;47(4):718-26. Epub 2015 Feb 2.

Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.

Purpose: The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis.

Materials And Methods: Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed ≥ 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse-transcriptase-polymerase chain reaction (RT-PCR) using five AGC patients, and tissue-microarray (TMA) comprising 47 AGC patients.

Results: CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI-1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393).

Conclusion: DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC.
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http://dx.doi.org/10.4143/crt.2014.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614183PMC
October 2015

Comprehensive genome- and transcriptome-wide analyses of mutations associated with microsatellite instability in Korean gastric cancers.

Genome Res 2013 Jul 4;23(7):1109-17. Epub 2013 Jun 4.

CHA Cancer Institute, CHA University, Seoul 135-081, Korea.

Microsatellite instability (MSI) is a critical mechanism that drives genetic aberrations in cancer. To identify the entire MS mutation, we performed the first comprehensive genome- and transcriptome-wide analyses of mutations associated with MSI in Korean gastric cancer cell lines and primary tissues. We identified 18,377 MS mutations of five or more repeat nucleotides in coding sequences and untranslated regions of genes, and discovered 139 individual genes whose expression was down-regulated in association with UTR MS mutation. In addition, we found that 90.5% of MS mutations with deletions in gene regions occurred in UTRs. This analysis emphasizes the genetic diversity of MSI-H gastric tumors and provides clues to the mechanistic basis of instability in microsatellite unstable gastric cancers.
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http://dx.doi.org/10.1101/gr.145706.112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698504PMC
July 2013

Up-regulated expression of sulfatases (SULF1 and SULF2) as prognostic and metastasis predictive markers in human gastric cancer.

J Pathol 2012 Sep 18;228(1):88-98. Epub 2012 Jul 18.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Gastric cancer (GC) is the fourth most common cancer worldwide. In spite of the mortality incidence associated with GC, no reliable prognostic biomarkers are currently available for this malignancy. The sulfatases (or SULFs), SULF1 and SULF2, play a critical role in the pathogenesis of a variety of human cancers. We sought to evaluate the potential of SULFs as biomarkers for GC. Thirty pairs of GC and corresponding normal tissues were analysed for the expression and methylation status of SULFs. Furthermore, the functional role of SULF overexpression was investigated in GC cell lines and tumour xenograft animal models. Lastly, we validated the expression of SULF1 protein in a large cohort of 450 GC patients. GC tissues showed conspicuously higher expression of SULF1 (p = 0.0002) and SULF2 (p = 0.001) compared to normal mucosa, which was correlated with its promoter hypomethylation. Furthermore, high expression of SULFs caused marked acceleration in the growth of xenograft tumours in nude mice. The expression of SULF1 protein significantly correlated with higher recurrence rates (p = 0.0002) and worse overall survival (p < 0.0001) in GC patients. Multivariate analysis revealed that SULF1 is an independent prognostic (p = 0.0123) and lymph node metastasis predictive factor (p = 0.0003) in patients with GC. We provide novel evidence that hypomethylation of promoter CpG islands within SULF genes imparts them with oncogenic potential in GC. Moreover, our data suggest that SULF1 may serve as a promising biomarker for patients with GC.
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http://dx.doi.org/10.1002/path.4055DOI Listing
September 2012

Dissemination of free cancer cells from the gastric lumen and from perigastric lymphovascular pedicles during radical gastric cancer surgery.

Ann Surg Oncol 2011 Oct 1;18(10):2818-25. Epub 2011 Apr 1.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Background: Manipulation and improper handling of a tumor during surgery may increase the risk of cancer cell dissemination after a curative gastrectomy. This study investigated the effect of improper handling of lymphovascular pedicles of stomach on tumor spillage during surgical procedure.

Methods: Thirty-eight gastric cancer patients were enrolled. Three pairs of wash samples were obtained from each patient: (1) intraperitoneal wash samples obtained before (P0) and after gastrectomy (P1), (2) intragastric wash samples obtained before any manipulation (G0) and just before resection of the stomach (G1), and (3) ex vivo wash samples obtained by rinsing resected stomach with the lymphovascular pedicles closed by clips (S0) or with the pedicles open (S1). Cytologic examination was performed from all washes, and real-time reverse transcriptase-polymerase chain reaction analysis for carcinoembryonic antigen was performed from washes P0, P1, S0, and S1.

Results: Cytologic examination detected cancer cells in 34.2% (13 of 38) of G0 samples and in 39.5% (15 of 38) of G1 samples. The rate of conversion from G0-negative to G1-positive increased as T stage increased. Cytologic examination detected cancer cells in 2.6% (1 of 38) of S0 samples and in 13.2% (5 of 38) of S1 samples. The carcinoembryonic antigen mRNA level of the S1 sample was 2-fold greater than that of the S0 sample in 50.0% (7 of 14).

Conclusions: Free cancer cells can be released from gastric lumen or lymphovascular pedicles opened during gastric cancer surgery, especially in advanced-stage disease. Care should be taken to minimize spillage from the gastric lumen and lymphovascular pedicles.
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http://dx.doi.org/10.1245/s10434-011-1620-8DOI Listing
October 2011

The antitumor effect of a thermosensitive polymeric hydrogel containing paclitaxel in a peritoneal carcinomatosis model.

Invest New Drugs 2012 Feb 29;30(1):1-7. Epub 2010 Jul 29.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

The prognosis of peritoneal carcinomatosis is regarded as poor because safe, effective therapeutic modalities are lacking. Intraperitoneal chemotherapy is one treatment option, involving the delivery of a high concentration of chemotherapeutic drugs into the abdominal cavity, but the severe side effects associated with such treatment are a major obstacle in clinical application. We evaluated the anti-cancer effects of intraperitoneal delivery of a thermosensitive polymeric hydrogel containing chemotherapeutics in an animal model of carcinomatosis. The progress of peritoneal carcinomatosis, introduced by injecting a luciferase-transfected human gastric cancer cell line (HSC44Luc) into the peritoneal cavity of nude mice, was quantitatively evaluated by in vivo bioluminescence imaging. Three days after intraperitoneal (IP) injection of HSC44Luc cells, treatment solutions were injected into the peritoneal cavity. Mice were categorized into four groups depending on treatment method; these were (1) a control PBS group (n = 5), (2) a hydrogel-only group (n = 5), (3) a paclitaxel solution (30 mg/kg) group (n = 3), and (4) a hydrogel-with-paclitaxel (15 mg/kg) group (n = 5). Quantitative photon counting was performed weekly in each animal. Mice were sacrificed on the 5th or 28th day after treatment, for pathologic evaluation. In vivo bioluminescence imaging showed that photon counts in the hydrogel-with-paclitaxel and paclitaxel solution groups were significantly lower than in the PBS group over the entire experimental period. Although neither group of responding mice showed any peritoneal nodules on the 28th day after treatment, only the paclitaxel solution group exhibited dilated edematous changes in the intestine; these side effects were absent in animals treated with hydrogel-with-paclitaxel group. In conclusion, a thermosensitive hydrogel containing paclitaxel may be a safe and effective treatment option for peritoneal carcinomatosis.
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http://dx.doi.org/10.1007/s10637-010-9499-yDOI Listing
February 2012

Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer.

Nucleic Acids Res 2009 Apr 19;37(5):1672-81. Epub 2009 Jan 19.

Department of Biological Sciences, Seoul National University, Seoul, Korea.

microRNAs (miRNAs) play integral roles in diverse processes including tumorigenesis. miRNA gene loci are often found in close conjunction, and such clustered miRNA genes are transcribed from a common promoter to generate polycistronic primary transcript. The primary transcript (pri-miRNA) is then processed by two RNase III proteins to release the mature miRNAs. Although it has been speculated that the miRNAs in the same cluster may play related biological functions, this has not been experimentally addressed. Here we report that the miRNAs in two clusters (miR-106b approximately 93 approximately 25 and miR-222 approximately 221) suppress the Cip/Kip family members of Cdk inhibitors (p57(Kip2), p21(Cip1) and p27(Kip1)). We show that miR-25 targets p57 through the 3'-UTR. Furthermore, miR-106b and miR-93 control p21 while miR-222 and miR-221 regulate both p27 and p57. Ectopic expression of these miRNAs results in activation of Cdk2 and facilitation of G1/S phase transition. Consistent with these results, both clusters are abnormally upregulated in gastric cancer tissues compared to the corresponding normal tissues. Ectopic expression of miR-222 cluster enhanced tumor growth in the mouse xenograft model. Our study demonstrates the functional associations between clustered miRNAs and further implicates that effective cancer treatment may require a combinatorial approach to target multiple oncogenic miRNA clusters.
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http://dx.doi.org/10.1093/nar/gkp002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2655672PMC
April 2009
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