Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea

ObjectivesTo assess the efficacy of hydroxychloroquine on mild-moderate COVID-19 patients in South Korea. MethodsA retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 (COVID-19) patients was conducted. 226 patients met inclusion criteria for analysis. Propensity score matching (PSM) and Cox regression method were utilized to control and adjust for confounding factors. Mild to moderate COVID-19 patients were managed with hydroxychloroquine (HQ) plus antibiotics (n = 31) or conservative treatment (n = 195). ResultsKaplan-Meier curves drawn using propensity score-matched data revealed no differences between the length of time to viral clearance and duration of hospital stay between the two treatment arms (p=0.18, p=0.088). Multivariable Cox regression analysis similarly showed that time to viral clearance(Hazard ratio (HR) 0.97, [95%-confidence interval (CI): 0.57-1.67]) and symptom duration(HR 1.05, [95%-CI: 0.62-1.78]) were not different between groups. No severe adverse event or death was observed in either group. ConclusionsHQ with antibiotics was not associated with better clinical outcomes in terms of time to viral clearance, length of hospital stay, and duration of symptoms compared to conservative treatment alone. Large prospective randomized trials are necessary for definitive conclusions.

Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis of confounder-adjusted 20212 hospitalized patients

ObjectiveTo evaluate the comparative efficacy and safety of pharmacological interventions used in treating COVID-19 and form a basis for an evidence-based guideline of COVID-19 management by evaluating the level of evidence behind each treatment regimen in different clinical settings. DesignSystematic review and network meta-analysis Data SourcesPubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov up to June 9th, 2020. Study SelectionPublished and unpublished randomized controlled trials (RCTs) and baseline-adjusted observational studies which met our predefined eligibility criteria. Main Outcome MeasuresThe outcomes of interest were mortality, progression to severe disease (severe pneumonia or admission to intensive care unit (ICU)), time to viral clearance, QT prolongation, fatal cardiac complications, and non-cardiac serious adverse events. The level of evidence behind each outcome was also measured using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results49 studies with a total of 20212 confounder-adjusted patients were included for analysis. The risk of progression to severe pneumonia or ICU admission was significantly reduced with tocilizumab (GRADE low), anakinra (GRADE very low), and remdesivir (GRADE high) compared to standard care. Tocilizumab was shown to reduce mortality rate for both moderate-severe patients in the non-ICU setting at admission (Odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18 to 0.54, GRADE low) and critically ill patients in the ICU setting (OR 0.67, 95% CI 0.50 to 0.91, GRADE low). High dose IVIG reduced death rate (GRADE low) while corticosteroids increased mortality for critically ill patients (GRADE moderate). Convalescent plasma and hydroxychloroquine were shown to promote viral clearance (OR 11.39, 95% CI 3.91 to 33.18, GRADE low and OR 6.08, 95% CI 2.74 to 13.48, GRADE moderate, respectively) while not altering mortality or progression to the severe courses. The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 1,85, 95% CI 1.05 to 3.26, GRADE low) and fatal cardiac complications in cardiac-impaired populations (OR 2.26, 95% CI 1.26 to 4.05, GRADE low). High-dose (>600mg/day) hydroxychloroquine monotherapy was significantly associated with increased non-cardiac serious adverse events (GRADE moderate). ConclusionAnti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve outcomes of hospitalized COVID-19 patients. Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks, especially in the vulnerable population. Only 20% of current evidence on pharmacological management of COVID-19 is on moderate and high evidence certainty and can be considered in practice and policy; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions. Systematic Review RegistrationPROSPERO 2020: CRD42020186527. Summary BoxO_ST_ABSSection 1: What is already known on this topicC_ST_ABS- Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for COVID-19. - Results from numerous studies are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective. - Level of evidence behind each outcome from diverse studies remains unknown. Section 2: What this study adds- Anti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve clinical outcomes of COVID-19. - Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks. - Only 20% of current evidence on pharmacological management of COVID-19 is on moderate/high evidence certainty and can be considered in practice and policy; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions.

Treatment Response to Hydroxychloroquine, Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First Report on the Pharmacological Outcomes from South Korea

The authors have withdrawn this manuscript because of the controversy about hydroxychloroquine and potential changes in results after peer-review, the authors intend to share their results in formal publication. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Characterization of Oncolytic Vaccinia Virus Harboring the Human IFNB1 and CES2 Transgenes / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to assess characteristics of SJ-815, a novel oncolytic vaccinia virus lacking a functional thymidine kinase-encoding TK gene, and instead, having two human transgenes: the IFNB1 that encodes interferon β1, and the CES2 that encodes carboxylesterase 2, which metabolizes the prodrug, irinotecan, into cytotoxic SN-38. @*Materials and Methods@#Viral replication and dissemination of SJ-815 were measured by plaque assay and comet assay, respectively, and compared to the backbone of SJ-815, a modified Western Reserve virus named WI. Tumor cytotoxicity of SJ-815 (or mSJ-815, which has the murine IFNB1 transgene for mouse cancers) was evaluated using human and mouse cancer cells. Antitumor effects of SJ-815, with/without irinotecan, were evaluated using a human pancreatic cancer-bearing mouse model and a syngeneic melanoma-bearing mouse model. The SN-38/ irinotecan ratios in mouse melanoma tissue 4 days post irinotecan treatment were compared between groups with and without SJ-815 intravenous injection. @*Results@#SJ-815 demonstrated significantly lower viral replication and dissemination, but considerably stronger in vitro tumor cytotoxicity than WI. The combination use of SJ-815 plus irinotecan generated substantial tumor regression in the human pancreatic cancer model, and significantly prolonged survival in the melanoma model (hazard ratio, 0.11; 95% confidence interval, 0.02 to 0.50; p=0.013). The tumor SN-38/irinotecan ratios were over 3-fold higher in the group with SJ-815 than those without (p < 0.001). @*Conclusion@#SJ-815 demonstrates distinct characteristics gained from the inserted IFNB1 and CES2 transgenes. The potent antitumor effects of SJ-815, particularly when combined with irinotecan, against multiple solid tumors make SJ-815 an attractive candidate for further preclinical and clinical studies.

Longitudinal follow-up to near final height of auxological changes in girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analog and grouped by pretreatment body mass index level

PURPOSE: Reported changes in body mass index (BMI) in central precocious puberty (CPP) during and after gonadotropin-releasing hormone analog (GnRHa) treatment are inconsistent. We, therefore, investigated auxological parameters in GnRHa-treated girls with idiopathic CPP (ICPP) until attainment of near final height (NFH). METHODS: From the medical records of 59 ICPP girls who attained NFH after GnRHa therapy, auxological changes were compared between overweight (BMI≥85th percentile) and normal-weight (BMI < 85th percentile) groups. BMIs were changed into standard deviation scores (BMISDSs) for subject chronologic age (BMISDS-CA) and bone age (BMISDS-BA). RESULTS: The incidence of overweight including obesity was high at the start of therapy (35.6%). The predicted adult height (PAH) at start of therapy was significantly shorter than the midparental height (MPH), whereas PAH at end of therapy approached MPH, and NFH was greater than MPH. Height velocity (HV) in the overweight group was higher during GnRHa therapy than that in the normal-weight group, but those in the two groups were not different after therapy until NFH. Both BMISDS-CA and BMISDS-BA increased significantly during therapy, but both BMISDSs decreased significantly after therapy until NFH. At NFH, neither BMISDS was different from that at baseline. In the normal-weight group, both BMISDSs increased during therapy and were maintained until NFH. In the overweight group, neither BMISDS changed during therapy, but there was a decrease after therapy until NFH. CONCLUSIONS: The different patterns of BMISDS change during and after GnRHa therapy until NFH between the 2 groups were related to the different HV during GnRHa therapy.

A Case of Ankyloblepharon-Ectodermal Defect-Cleft Lip and/or Palate (AEC) Syndrome with Missense Mutation in TP63 1657(th)

Ankyloblepharon-ectodermal defects-cleft lip and/or palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare autosomal dominant disorder characterized by congenital ectodermal dysplasia. It is caused by mutations in p63 gene. Six isoforms are generated from the TP63 gene mutation and the main isoform expressed in postnatal skin is Np63a, which functions as a key regulator of epidermal integrity. We have experienced a 1-day-old female baby with skin erosions, ankyloblepharosis, and cleft palate that require treatment for skin care and feeding difficulties. Missense mutation in TP63 1657(th) T → A transition was found in the genetic test performed in the patient, and this genotype has not been reported in a previously variant. The patient was found dead at 91days of birth and the cause of death was estimated by aspiration.

Seasonal Patterns of Asthma in Children and Adolescents Presenting at Emergency Departments in Korea

PURPOSE: Seasonal variations in asthma-related hospitalizations and emergency department visits have long been recognized. This study aimed to investigate the seasonal patterns of asthma in children and adolescents who presented at emergency departments in Korea. METHODS: We analyzed the National Emergency Department Information System records from 117 emergency departments in Korea that comprised all of the patients with asthma who were aged 3-18 years and who presented at the emergency departments from 2007 to 2012. The children and adolescents were divided into 3 groups based on their ages, namely, 3-6 years, 7-12 years, and 13-18 years. The data were tabulated, and graphs were created to show the seasonal trends in the monthly numbers of emergency department visits as a consequence of asthma. RESULTS: A total of 41,128 subjects were identified, and the male-to-female ratio was 1:0.5. General ward admissions comprised 42.6% (n=17,524 patients) of the emergency department visits, and intensive care unit admissions comprised 0.8% (n=335 patients) of the emergency department visits. The monthly numbers of emergency department visits for asthma varied according to the season, with high peaks during fall, which was from September to November, and low levels in summer, which was from June to August. CONCLUSIONS: Important differences in the seasonal patterns of emergency department visits for asthma were evident in children and adolescents. Identifying seasonal trends in asthma-related emergency department visits may help determine the causes and reduce the likelihood of asthma exacerbation.

Rhamnogalacturonan II is a Toll-like receptor 4 agonist that inhibits tumor growth by activating dendritic cell-mediated CD8+ T cells

We evaluated the effectiveness of rhamnogalacturonan II (RG-II)-stimulated bone marrow-derived dendritic cells (BMDCs) vaccination on the induction of antitumor immunity in a mouse lymphoma model using EG7-lymphoma cells expressing ovalbumin (OVA). BMDCs treated with RG-II had an activated phenotype. RG-II induced interleukin (IL)-12, IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) production during dendritic cell (DC) maturation. BMDCs stimulated with RG-II facilitate the proliferation of CD8+ T cells. Using BMDCs from the mice deficient in Toll-like receptors (TLRs), we revealed that RG-II activity is dependent on TLR4. RG-II showed a preventive effect of immunization with OVA-pulsed BMDCs against EG7 lymphoma. These results suggested that RG-II expedites the DC-based immune response through the TLR4 signaling pathway.

Effect of aldosterone on the amplification of oncolytic vaccinia virus in human cancer lines / 대한간학회지

BACKGROUND/AIMS: JX-594 is an oncolytic virus derived from the Wyeth vaccinia strain that causes replication-dependent cytolysis and antitumor immunity. Starting with a cross-examination of clinical-trial samples from advanced hepatocellular carcinoma patients having high levels of aldosterone and virus amplification in JX-594 treatment, we investigated the association between virus amplification and aldosterone in human cancer cell lines. METHODS: Cell proliferation was determined by a cell-counting-kit-based colorimetric assay, and vaccinia virus quantitation was performed by quantitative polymerase chain reaction (qPCR) and a viral plaque assay. Also, the intracellular pH was measured using a pH-sensitive dye. RESULTS: Simultaneous treatment with JX-594 and aldosterone significantly increased viral replication in A2780, PC-3, and HepG2 cell lines, but not in U2OS cell lines. Furthermore, the aldosterone treatment time altered the JX-594 replication according to the cell line. The JX-594 replication peaked after 48 and 24 hours of treatment in PC-3 and HepG2 cells, respectively. qPCR showed that JX-594 entry across the plasma membrane was increased, however, the changes are not significant by the treatment. This was inhibited by treatment with spironolactone (an aldosterone-receptor inhibitor). JX-594 entry was significantly decreased by treatment with EIPA [5-(N-ethyl-N-isopropyl)amiloride; a Na+/H+-exchange inhibitor], but aldosterone significantly restored JX-594 entry even in the presence of EIPA. Intracellular alkalization was observed after aldosterone treatment but was acidified by EIPA treatment. CONCLUSIONS: Aldosterone stimulates JX-594 amplification via increased virus entry by affecting the H+ gradient.

The Relationship between Change of Parental Weight and Change of Child's Weight over 2 Years

BACKGROUND: The purpose of this study was to examine the association between the change of parental weight status and the change of their child's weight status over 2 years. METHODS: A total of 379 children ages 11??13 years were measured their height and weight in 2001 and 2003. Their parents completed a questionnaire including self-reported parental weight and height during the same period. Parental weight status was classified as overweight (BMI> or =25 kg/m(2)) and non-overweight (BMI<25 kg/m(2)). Children's weight status was classified as overweight and non-overweight using the age and gender-specific BMI established by the Korean Academy of Pediatrics. The weight status over 2 years was categorized as a group of persistent overweight, persistent non-overweight, shifting overweight to non-overweight, and shifting non-overweight to overweight. RESULTS: After adjusting for the child's gender and the father's weight status, the odds ratio for being persistently overweight over 2 years in a child having a mother with persistent overweight was 2.8 (95% CI: 0.9-8.5) compared to a child having a mother with persistent non-overweight. Likewise, the odds ratio for being persistently overweight over 2 years in a child having a father with persistent overweight was 2.9 (95% CI: 1.4-6.1) compared to the child having a father with persistent non-overweight. CONCLUSION: Parental weight status over 2 years was associated with the 2-year weight status in children. The parents- and family-based intervention are needed to prevent and manage childhood obesity.

Cotransplantation of Cord Blood Hematopoietic Stem Cells and Culture-Expanded and GM-CSF-/SCF-Transfected Mesenchymal Stem Cells in SCID Mice

Mesenchymal stem cells (MSC) are multipotent in nature and believed to facilitate the engraftment of hematopoietic stem cells (HSC) when transplanted simultaneously in animal studies and even in human trials. In this study, we transfected culture-expanded MSC with granulocyte macrophage-colony stimulating factor (GMCSF) and stem cell factor (SCF) cytokine genes and then cotransplanted with mononuclear cells (MNC) to further promote HSC engraftment. MNC were harvested from cord blood and seeded in long-term culture for ex vivo MSC expansion. A total of 1 x 10(7) MNC plus MSC/microliter were introduced to the tail vein of nonobese diabetic/severe combined immunodeficiency mice. After 6-8 weeks later, homing and engraftment of human cells were determined by flow cytometry and fluorescence in situ hybridization studies. The total nucleated cell count and the engraftment of CD45+/CD34+ cells and XX or XY positive human cells were significantly increased in cotransplanted mice and even higher with the cytokine gene-transfected MSC (GM-CSF>SCF, p<0.05) than in transplantation of MNC alone. These results suggest that MSC transfected with hematopoietic growth factor genes are capable of enhancing the hematopoietic engraftment. Delivering genes involved in homing and cell adhesions, CXCR4 or VLA, would further increase the efficiency of stem cell transplantation in the future.

Anti-tumoral Effect of Recombinant Vaccinia Virus through US Guided Injection in a Rabbit Model of Hepatic VX2 Carcinoma

PURPOSE: The purpose of this study was to evaluate the anti-tumoral effect of recombinant vaccinia virus (rVV) (Thymidine kinase (-)/GM-CSF (+)) that was administered as a US guided intratumoral injection in a rabbit model of hepatic VX2 carcinoma. MATERIALS AND METHODS: VX2 carcinoma was implanted in the livers of 12 rabbits. US was performed at every week interval to detect hepatic mass after the implantation of VX2 carcinoma. The accurate tumor size and volume was evaluated with CT when the tumor was detected on US. US guided injection of rVV (109 pfu/ml) was preformed in three rabbits, intravenous injection of the same dose of rVV was done in two rabbits and another seven rabbits that were without any treatment were selected as a control group. We evaluated the change of the hepatic tumor size and extrahepatic metastasis on serial CT. Tumor specimens were harvested from rabbits that were killed at 8 weeks after VX2 implantation. These tissues were histoimmuopathologically compared to each other (the virus injection group and the control group). The differences between these groups were statistically assessed with student t-tests. RESULTS: Tumor growth was significantly suppressed in the US guided injection group compared with the intravenous injection group or the control group (p< 0.01). The intravenous injection group showed statistically significant tumor suppression compared to the control group (p< 0.01) until 2 weeks after virus injection. Quantification of the pulmonary metastatic nodules was performed in view of both the number and volume. The average number or volume of the pulmonary metastatic nodules in the US injection group was much smaller than these in the control group. Histopathologically, the tumors of the US guided injection group showed less extensive necrosis than those of the control group. Immunohistochemically, the tumor of the US guided injection group showed more prominent infiltration of CD4 (+) and CD8 (+) lymphocytes than did the tumors of the other group. CONCLUSION: rVV was markedly effective in suppressing hepatic tumor growth and extrahepatic metastasis in a rabbit model of hepatic VX2 carcinoma. US guided intra-tumoral injection was more effective than systemic intravenous injection.

Gene Expression Profile of Volume-Overloaded Human Ventricular Myocardium Prior to Developing Heart Failure

BACKGROUND AND OBJECTIVES: Left ventricle burdened by longstanding volume-overload, undergoes various structural and functional alterations. Accordingly, the expressions of multiple classes of genes are likely to be altered. However, the profile of gene expressions, specifically in a volume-overloaded left ventricle in humans, has not been explored. SUBJECTS AND METHODS: The pattern of gene expression was studied, using a cDNA microarray, in myocardium from 4 normal subjects and 5 patients with chronic regurgitant valvular heart disease whose end-diastolic left ventricular dimension measures 65 mm or more, but whose systolic function remained preserved. RESULTS: We identified 58 differentially expressed genes that were functionally classifiable in the volume-overloaded myocardium. Those genes involved in cell cycle/growth (up/down-regulation: 9/1), signal transduction (4/1) were mostly overexpressed in the volume-overloaded myocardium. The distributions of the gene expressions were variable for those involved in transcription/translation (up/down-regulation: 6/7) and apoptosis (2/2). The genes related to the myocyte structure (troponin T3, tropomyosin, etc)(up/down-regulation: 1/10), as well as those related to metabolism (2/5), were underexpressed. The gene expression patterns from RT-PCR and Western blot, with randomly selected genes, were similar to those from the cDNA microarray. CONCLUSION: Altered expression was identified in multiple genes in the volume-overloaded human left ventricle prior to the development of heart failure. The genes related to cell growth and signal transduction were mostly overexpressed, while those related to cellular structure and metabolism appeared to be underexpressed. These results might help in the elucidation of cellular mechanisms for the remodeling process associated with chronic volume-overloading.

Non-Surgical Gene Transfer to Rabbit Renal Glomeruli via Percutaneous Arterial Catheterization / 대한신장학회잡지

BACKGROUND: Transfer of foreign genes to the renal glomerular cells is an important step for the gene therapy of renal diseases in which the primary pathology is confined to the glomeruli. We developed a non-surgical method of gene transfer to rabbit renal glomeruli using percutaneous arterial catheterization without any laparatomy procedure. METHODS: The recombinant adenovirus type 5, containing a nuclear-targeted beta-galactosidase gene and driven by a cytomegalovirus promoter, was slowly infused into the unilateral renal artery via percutaneous arterial catheterization. The animals were sacrificed 3 days after virus infusion and lacZ staining was done on the fresh harvested tissue. RESULTS: Only the animals those received 6x10(12) particles/rabbit for 120 minutes show lacZ expression in 90.6+/-5% (n=3) of glomeruli. Mostly, it was the endothelial cells and mesangial cells those were positive for the stain. CONCLUSION: This non-surgical method for gene transduction of the renal glomeruli can be applied to human trials of glomerulus-directed gene therapy.

Expressions of Matrix Metalloproteinase-7 and -9 and their Prognostic Significances in Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes. MMPs are known to be involved in tumor invasion, and several have been implicated in tumor prognosis. The aim of this study was to evaluate the prognostic significances of the expressions of MMP-7 and -9 in rectal cancer. MATERIALS AND METHODS: The tumor tissues of 87 patients with stage II or III rectal carcinoma that underwent potentially curative resection followed by postoperative adjuvant chemoradiation and 5-fluorouracil based chemotherapy, were investigated immunohistochemically using monoclonal antibodies against MMP-7 and MMP-9. Clinical information, including tumor grades, carcinoembryonic antigen (CEA) levels, and disease-free survival and overall survival were evaluated with respect to the expressions of MMP-7 and -9. RESULTS: Median follow-up duration was 53.2 months, and median patient age was 55+/-11 years (range 32~75). MMP-7 expression in tumor tissue was found to be significantly correlated with the presence of nodal metastasis (p=0.029), whilst MMP-9 expression correlated with depth of tumor invasion (p=0.019). No relatio- nships were found between the expressions of MMP-7 or -9 and age, sex, tumor size, tumor grade, or CEA level. Univariate analysis showed that MMP-7 expression was associated with poor 5-year overall survival (12.8 months vs. 65.3 months, p=0.0405). Multivariate analysis confirmed that MMP-7 was independently associated with an adverse outcome (Relative risk: 1.415, p=0.027). However, MMP-9 expression was not found to be related to clinical outcome. CONCLUSION: MMP-7 expression in tumor tissue is associated with lymph node metastasis and a poor 5-year overall survival in rectal cancer patients.

Antitumor Activity of TRAIL Recombinant Adenovirus in Human Malignant Glioma Cells

Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) has been reported to specifically kill malignant cells but to be relatively nontoxic to normal cells. One of disadvantages to previous in vivo protocols was the need for large quantities of TRAIL recombinant protein to suppress tumor growth. To evaluate the antitumor activity and therapeutic value of the TRAIL gene, we constructed adenoviral vectors expressing the human TRAIL gene (Ad.hTRAIL) and transferred them into malignant glioma cells in vitro and tumors in vivo, as an alternative to recombinant soluble TRAIL protein. The results show that TRAIL-sensitive glioma cells infected Ad.hTRAIL undergo apoptosis through the production and expression of TRAIL protein. The in vitro transfer elicited apoptosis, as demonstrated by the quantification of viable or apoptotic cells and by the analysis of cleavage of poly (ADP-ribose) polymerase. Furthermore, in vivo administration of Ad.hTRAIL at the site of tumor implantation suppressed the outgrowth of human glioma xenografts in SCID mice. These results further define Ad.hTRAIL as an anti-tumor therapeutic and demonstrate its potential use as an alternative approach to treatment for malignant glioma.

The appearence of proinflammatory cytokines in temporomandibular joint disorders after arthrocentesis and lavage

The purpose of this study is that evaluate the distribution and biological roles of TNF-a, interleukin-1beta(IL-1beta), interleukin-6(IL-6) and tissue inhibitors of metalloproteinase-1(TIMP-1) in the synovial fliud of patients with non-inflammatory chronic temporomandibular joint(TMJ) disorders in relation to pain during joint movements and magnetic resonance imaging(MRI) findings. TMJ synovial fluids aspirates were obtained from 36 patients (36 joints) with chronic TMJ disorders and from 8 controls(8 joints). Patients were divided to four groups. The control group was from healthy volunteers(8 joints), group I(18 joints) was patients with anterior disc displacement with reduction, group II(5 joints) was patients with disc displacement without reduction and group III (5 joints) was osteoarthritis. The TNF-alpha, IL-1beta and IL-6 levels in the aspirates were determined by using an enzyme-linked immunosorbent assay and the TIMP-1 level was measured by an enzyme immunoassay. Following examinations for pain during joint movements and MRI observations, these cytokines'level and frequencies of detection were compared. The level of IL-1beta was not significant different in all groups. but the level of TNF-alpha, IL-6 and TIMP-1 were significant different among groups. The level of IL-6 and TIMP-1 were correlated to pain during movement(p <0.01) and the level of TNF-a(p <0.05). Also, the level of IL-6 was correlated to the level of TIMP-1(p <0.01). Especially, The level of the TIMP-1 level was significantly correlated to the pain during movement and showed very high levle of Pearson's correlation coefficient (r=0.833)(p <0.001). The results indicated that the TNF-alpha, IL-6 and TIMP-1 levels in the TMJ aspirates of patients with chronic TMJ disorders have been raised. Especially, IL-6 and TIMP-1 were very high levels in the patients who were degraded in the TMJ. Also, TNF-alpha, IL-6 and TIMP-1 showed the significant correlation in the chronic temporomandibular joint disorders. Therefore I suggest that these cytokines were also correlated to the pain during movement in the chronic temporomandibular joint disorders.

Gene Expression Profiling of Breast Cancers with Emphasis of beta-Catenin Regulation

To gain molecular understanding of carcinogenesis of breast cancer, gene expression profiles were analyzed using cDNA microarray representing 4,600 cDNAs in 10 breast cancer samples and the adjacent noncancerous breast tissues from the same patients. The alterations in gene expression levels were confirmed by reversetranscription PCR in four randomly selected genes. Genes that were differently expressed in cancer and noncancerous tissues were identified. 106 (of which 55 were known) and 49 (of which 28 were known) genes were up- or down-regulated, respectively, in greater than 60% of the breast cancer samples. In cancer tissues, genes related to cell cycle, transcription, metabolism, cell structure/motility and signal transduction were mostly up-regulated. Furthermore, three cancer tissues showing immunohistochemically aberrant accumulation of beta-catenin in the nucleus and/or cytoplasm revealed down-regulation of Siah and Axin genes and up-regulation of Wnt and c-myc genes. These findings were highly consistent with Wnt signaling pathway associated with beta-catenin regulation previously suggested by others. Our studies, therefore, provide not only a molecular basis to understand biological processes of breast cancer but also useful resources to define the mechanism of beta-catenin expression in tumorigenesis of breast cancer.

Gene Expression Profiling of Non-Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: cDNA microarray provided a powerful alternative, with an unprecedented view scope, in monitoring gene expression levels, and led to the discovery of regulatory pathways involved in complicated biological processes. This study was performed to gain better understanding of the molecular mechanisms underlying the carcinogenesis and progression of lung cancer. MATERIALS AND METHODS: Using a cDNA microarray, representing 4, 600 cDNA clusters, we studied the expression profiles in 10 non-small cell lung cancer (NSCLC) samples and the adjacent noncancerous lung tissues form the same patients. The alterations in the levels of gene expression were confirmed by reverse-transcription PCR in 10 randomly selected genes. RESULTS: Genes that were differently expressed in the cancerous and noncancerous tissues were identified. One hundred and nine genes (of which 68 were known) and 69 cDNAs (of which 32 were known) were up- and down-regulated in>70% of the NSCLC samples, respectively. In the cancerous tissues, the genes related to the cell cycle, metabolism, cell structure and signal transduction, were mostly up-regulated. Furthermore, we identified a few putative tumor suppressor genes that had previously been proposed by other workers. CONCLUSIONS: These results provide, not only a new molecular basis for understanding the biological properties of NSCLC, but also useful resources for the future development of diagnostic markers and therapeutic targets for NSCLC.

A Gene Expression in Study Human Gastric Adenocarcinoma Using a cDNA Microarray / 대한소화기학회지

BACKGROUND/AIMS: cDNA microarray provides a powerful alternative with an unprecedented view scope in monitoring gene expression levels and leads to discoveries of regulatory pathways involved in complicated biological processes. Our aim was to explore the different gene expression patterns in early and advanced gastric cancer. METHODS: By using a cDNA microarray representing 4,608 cDNA clusters, we studied the expression profiling in 10 paired gastric adenocarcinoma samples and the adjacent noncancerous gastric tissues. The alterations in gene expression levels were confirmed by Northern blot and reverse-transcription (RT) PCR. Results: Genes that were differently expressed in cancer and noncancerous tissues were identified. Forty-four and 92 (26 and 43 of them were known, respectively) genes or cDNA were up- and down-regulated, respectively, in more than 80% of gastric adenocarcinoma samples. The semi-quantitative RT-PCR results were consistent with the microarray findings. To distinguish between early and advanced gastric cancers, we used a supervised learning classification approach. When we used 16 and 20 genes as predictors, the prediction was all yielded statistically significant. Moreover, when we used 9 genes, we could predict with the highest accuracy. CONCLUSIONS: These results may provide not only a new molecular basis for understanding biological properties of gastric adenocarcinoma, but also useful resources for future development of therapeutic targets and diagnostic markers for gastric adenocarcinoma.