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PACAP inhibits tumor growth and interferes with clusterin in cervical carcinomas
Lee, Ji-Hae,Lee, Ji-Yeon,Rho, Seung Bae,Choi, Jong-Soon,Lee, Dong-Gi,An, Sungwhan,Oh, Taejeong,Choi, Don-Chan,Lee, Seung-Hoon Elsevier 2014 FEBS letters Vol.588 No.24
<P><B>Abstract</B></P> <P>Secretory clusterin (sCLU), an anti-apoptotic protein, is overexpressed in many tumors and enhances tumorigenesis and chemo-resistance. However, the regulation mechanism controlling the sCLU maturation process or activity remains undetermined. In this study, we found PACAP as a negative regulator of CLU. Overexpression of the PACAP gene in cervical cancer cell lines lacking PACAP expression significantly inhibited cell growth and induced apoptosis. We further demonstrated that interaction of PACAP with CLU significantly downregulated CLU expression and secretion, inhibited the Akt–Raf–ERK pathway, and suppressed the growth of human tumor xenografts in nude mice. This novel inhibitory function of PACAP may be applicable for developing novel molecular therapies for tumors with increased sCLU expression.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Over-expression of PACAP inhibits cervical cancer cell growth and induced apoptosis. </LI> <LI> PACAP directly interacts with CLU and the specific binding sites were identified. </LI> <LI> The interaction inhibited expression and secretion of sCLU. </LI> <LI> The interaction results in inhibition of the pro-survival activity of clusterin and of the clusterin downstream Akt/Raf/ERK signaling pathway, resulting in apoptotic cell death. </LI> </UL> </P>
Toward understanding tuberculosis in North Korea
( Sungwhan Lee ),( Changjoon Lee ),( Heejin Kim ),( Youngae Kang ) 대한결핵 및 호흡기학회 2019 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.127 No.-
Background: North Korea is one of the 30 high TB burdened countries with high percentage of drug-resistant TB. This study aimed to perform the comprehensive review of North Korean medical journals about clinical and laboratory research on TB to understand the medial issues and research trend based on numbers and contents of TB in North Korea. Methods: We analyzed nine medical journals (‘Preventive medicine’, ‘Korea Medicine’, ‘Chosun Medicine’, ‘Internal Medicine’, ‘Pediatrics, Obstetrics and Gynecology’, ‘Surgery’, ‘Medicine’, ‘Basic Medicine’, ‘Chosun Pharmacy’) published from 2006 to 2018. All data on the paper’s authors, titles, year of publication and journals were recorded and analyzed based on the contents of the papers. Results: There were 18596 articles in all nine journals and 106 articles were included for the final analysis.. All 106 articles were one or two pages in length and were written in Korean. Of the 106 papers, 43 were reviews, 52 were original articles, and 8 were cases. When we classified the articles by the field of the study, 52 articles (49%) were about the diagnosis of TB, 39 (37%) were for treatment of the TB. There was no study which investigated the commercialized molecular diagnosis system such as Xpert MTB/RIF assay. DOTS strategy was described as a basic principal of treatment. Of the 39 papers for ‘Treatment’ of TB, there were 6 studies using Korean traditional medicine for treatment of TB, one of them with additional snake venom. Conclusions: The format of article was quite short compared to the requirement of international journals. The papers issuing the treatment of MDR-TB was not found. LTBI and NTM were not major issue in North Korean papers. To understand the current burden of TB and research environment, the data from the nine North Korean journals is insufficient.
Seung-Yul Lee,Tae Jeong Oh,Sungwhan An,Seung-Hoon Lee The Korean Society of Developmental Biology 2024 발생과 생식 Vol.28 No.2
This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene expression analysis using cDNA microarray in cervical cancer cell lines revealed significantly reduced expression of the HOXA11 gene. Subsequent investigation of HOXA11 promoter methylation in samples from normal individuals and invasive cervical cancer patients showed over 53.2% higher methylation in cancer scrapes compared to normal scrapes. Furthermore, overexpression of HOXA11, which is downregulated in cervical cancer, strongly suppressed cell growth in cervical cancer cell lines, HeLa and HT3. Additionally, we performed transferase dUTP nick end labeling assay and confirmed that the inhibition of cervical cancer cell proliferation occurred via apoptosis. Mechanistically, overexpression of HOXA11 led to mitochondrial apoptosis characterized by PARP cleavage due to increased c-Myc and enhanced cytochrome C secretion into the cytoplasm. These findings suggest that HOXA11 could potentially serve as a methylation marker for diagnosing cervical cancer and as a novel therapeutic target for its treatment.
( Chang-jun Lee ),( Sungwhan Lee ),( Hee-jin Kim ),( Young Ae Kang ) 대한결핵 및 호흡기학회 2020 Tuberculosis and Respiratory Diseases Vol.83 No.3
Background: North Korea is one of the 30 countries with the highest tuberculosis (TB) and drug-resistant TB burdened. To understand the medical issues and research trends associated with TB in North Korea, we performed a comprehensive review of articles related to clinical and laboratory research on TB published in North Korean medical journals. Methods: We reviewed all types of TB-related articles published in nine North Korean medical journals (Yebang ŭihak: Preventive medicine; Koryo ŭihak: Korea Medicine; Chosŏn ŭihak: Chosun Medicine; Naekwa: Internal Medicine; Soa, sanbuinkwa: Pediatrics, Obstetrics, and Gynecology, Surgery; Ŭihak: Medicine; Kich’o ŭihak: Basic Medicine; and Chosŏn yakhak: Chosun Pharmacy). We classified the articles according to the type and field of study and analyzed the data qualitatively to gain insights. Results: We reviewed 106 articles (one- or two-page length) written in Korean, including reviews (n=43), original articles (n=52), and case reports (n=8). They were classified as follows: articles on diagnosis (n=52, 49%) and treatment (n=39, 37%). None of the studies investigated the commercialized molecular diagnosis systems such as Xpert MTB/RIF. Directly Observed Treatment, Short-course was reported as the basic treatment approach. Furthermore, six studies used Korean traditional medicines for treating TB, with one of them containing snake venom. Conclusion: The articles were not sufficiently detailed. Original articles on the treatment of multi-drug resistant TB were not found, and those on latent tuberculosis infection and nontuberculous mycobacteria were limited. To understand the current medical issues associated with TB in North Korea, articles from these nine journals were not sufficient.
Hwang, Sang-Hyun,Kim, Ki Uk,Kim, Ji-Eun,Kim, Hyung-Hoi,Lee, Min Ki,Lee, Chang Hun,Lee, Sang-Yull,Oh, Taejeong,An, Sungwhan Walter de Gruyter 2011 Clinical chemistry and laboratory medicine Vol.49 No.4
<P>Lung cancer is a leading cause of cancer deaths. Unfortunately, no effective early screening modality exists for lung cancer. We aimed to evaluate the prevalence of HOXA9 promoter methylation in tissue and induced sputum samples from Korean patients with lung cancer.</P>
Keewoo Lee,Sungwhan Cho,이혁수,Jae Young Choi,Yeon Ho Je,Yonggyun Kim 한국응용곤충학회 2005 Journal of Asia-Pacific Entomology Vol.8 No.3
A genome project has been launched andaims to sequence total genome of Cotesia plutellae bracovirus (CpBV). This on-going research has iden-tified several open reading frames (ORFs) including an analyze gene expression of CpBV-ELP1 in the para-sitized diamondback moth, Plutella xylostela. CpBV- ELP genomic DNA contains one intron (78 bp long). Its ORF consists of 726 bp encoding 241 amino acidresidues. The hypothetical CpBV-ELP1 protein ispredicted as 27,787.83 Da and poseses N-terminal signal peptide plus three potential N-glycosylation sites. Its amino acid sequence exhibits high homology with EP1 genes from C. congregata or C. karyai bA reverse transcriptase-polymerase chain reaction(RT-PCR) indicated that CpBV-ELP1 was expressedonly in P. xylostella parasitized by C. plutellae. The expression levels were measured by real time quan-titative RT-PCRs during entire parasitization period at 25℃ culturing temperature. The expression began at the first day of parasitization and increased with the parasitization period. The ORF PCR product wascloned, over-expressed, and molecular weight of thepurified protein was about 30 kDa.
A NEW IMAGE RECONSTRUCTION ALGORITHM FOR REGIONAL ADMITTIVITY CHANGE USING TIME DIFFERENCE DATA
Eunjung LEE,Ts. Munkh-Erdene,Sungwhan KIM,Jin Keun SEO,Eung Je WOO 한국산업응용수학회 2011 한국산업응용수학회 학술대회 논문집 Vol.6 No.2
We propose a new EIT image reconstruction algorithm using multiple boundary voltage data from a planar array of voltage-sensing electrodes. The current injection electrodes are placed so that the induced internal currents approximately flow in the direction parallel to the surface of the voltage-sensing probe. The proposed algorithm uses the interrelationship between the measured voltage differences and the computed current, which allows us to derive a PDE-based Ohms law. Based on the derived voltage-current relation, we produce images of conductivity changes within a local region underneath the voltage-sensing probe. We describe the new image reconstruction algorithm and its numerical simulation results.
Kim, Sungwhan,Lee, Eun Jung,Woo, Eung Je,Seo, Jin Keun Institute of Physics 2012 Inverse problems Vol.28 No.7
<P>There have been numerous studies using multi-frequency electrical impedance tomography to image frequency-dependent admittivity spectra of biological tissues. Considering the fundamental drawback of the static EIT in recovering the absolute admittivity image at a certain frequency, we will focus on a difference imaging method using a currently available EIT system. We are particularly interested in the frequency-difference EIT (fdEIT) in this paper since it may provide spectroscopic admittivity images without requiring a time-reference data. Noting that non-negligible susceptivity values of biological tissues are attributed to thin cell membranes, we analyze the role of the membrane in terms of the sensitivity of the complex voltage data in fdEIT. Such an analysis requires one to study the frequency-dependent behavior of a complex potential in the framework of the elliptic partial differential equation (PDE) with a frequency-dependent complex coefficient representing the admittivity. Due to complicated coupling between the real and imaginary parts of the complex potential, there is little study on the complex elliptic PDE. Although there exist several previous studies using spherical models which allow the potential to be represented as trigonometric series, these approaches are not apt for biological tissues. In this paper, we decouple the real and imaginary parts via a key asymptotic analysis and approximate the real part as a solution of a well-established elliptic PDE with a real coefficient whose value changes with frequency. This more general approach provides a quantitative analysis of the role of the thin membrane in forming a fdEIT image. We perform numerical simulations and phantom experiments on a two-dimensional imaging object containing an anomaly with a thin insulating membrane. The results provide better understanding of the role of the thin membrane in the sensitivity of a multi-frequency current–voltage data.</P>