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      • CTCF Regulates Kaposi's Sarcoma-Associated Herpesvirus Latency Transcription by Nucleosome Displacement and RNA Polymerase Programming

        Kang, Hyojeung,Cho, Hyosun,Sung, Gi-Ho,Lieberman, Paul M. American Society for Microbiology 2013 Journal of virology Vol.87 No.3

        <B>ABSTRACT</B><P>CCCTC-binding factor (CTCF) has been implicated in various aspects of viral and host chromatin organization and transcriptional control. We showed previously that CTCF binds to a cluster of three sites in the first intron of the Kaposi's sarcoma-associated herpesvirus (KSHV) multicistronic latency-associated transcript that encodes latency-associated nuclear antigen (LANA), viral cyclin (vCyclin), vFLIP, viral microRNAs, and kaposin. We show here that these CTCF binding sites regulate mRNA production, RNA polymerase II (RNAPII) programming, and nucleosome organization of the KSHV latency transcript control region. We also show that KSHV bacmids lacking these CTCF binding sites have elevated and altered ratios of spliced latency transcripts. CTCF binding site mutations altered RNAPII and RNAPII-accessory factor interactions with the latency control region. CTCF binding sites were required for the<I>in vitro</I>recruitment of RNAPII to the latency control region, suggesting that direct interactions between CTCF and RNAPII contribute to transcription regulation. Histone modifications in the latency control region were also altered by mutations in the CTCF binding sites. Finally, we show that CTCF binding alters the regular phasing of nucleosomes in the latency gene transcript and intron, suggesting that nucleosome positioning can be an underlying biochemical mechanism of CTCF function. We propose that RNAPII interactions and nucleosome displacement serve as a biochemical basis for programming RNAPII in the KSHV transcriptional control region.</P>

      • KCI등재

        DNA hypermethylation induced by Epstein-Barr virus in the development of Epstein-Barr virus-associated gastric carcinoma

        최수진,신유수,강병욱,김종광,원경재,Paul M. Lieberman,조효선,강효정 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.8

        Epstein-Barr virus (EBV)-associated gastriccarcinoma (EBVaGC) is a recently recognized diseaseentity defined by the presence of EBV in gastric carcinomacells. EBV infection causes major epigenetic alterations inthe EBV genome and its cellular host genome, suggestingthat EBV acts as a direct epigenetic driver for EBVaGC. One of the major epigenetic events in the viral and cellulargenomes to control transcription is DNA hypo- or hypermethylation. Particularly, local and global hypermethylationhave been reported in EBVaGC. It is thereforeimportant to understand the molecular mechanisms ofDNA hypermethylation during EBVaGC carcinogenesis. To understand the functional roles of DNA methylationand suggest therapeutic target candidates for EBVaGC, wereviewed recent literature reporting DNA hypermethylationin EBVaGC. We summarized the identified candidategenes that are markedly hypermethylated in EBVaGC,which can potentially be targets for chemotherapies withdemethylating agents.

      • KCI등재

        Bioactive Activities of Natural Products against Herpesvirus Infection

        손명기,이민정,성기호,이태호,Yu Su Shin,Hyosun Cho,Paul M. Lieberman,강효정 한국미생물학회 2013 The journal of microbiology Vol.51 No.5

        More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.

      • KCI등재후보

        Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA): Treatment for Benign Thyroid Diseases

        Gustavo G. Ferná,ndez-Ranvier,Daniela Guevara,Ghayth Alawwa,Aryan Meknat,Benjamin Lieberman,William B Inabnet 대한갑상선-내분비외과학회 2021 The Koreran journal of Endocrine Surgery Vol.21 No.1

        Purpose: Thyroidectomy is often required in the management of benign thyroid disorders. Conventional open thyroidectomy remains the standard of care for various benign and malignant thyroid disorders. We aim to present our experience in performing a transoral endoscopic thyroidectomy vestibular approach (TOETVA) for benign disease of the thyroid gland that is safe, and feasible when compared with open thyroidectomy. Methods: Sixty-six patients who underwent an open thyroidectomy or TOETVA between 2014 and 2019 for a benign thyroid condition were identified and retrospectively studied. Outcomes between the 2 groups, including postoperative complications, operative time, estimated blood loss (EBL), and length of stay, were compared. Patients were followed from 2 weeks up to 2 years postoperatively. Results: Sixty-six patients whose age ranges between 22 and 82 were stratified into an open thyroidectomy group and a TOETVA group with 33 patients in each group. In the TOETVA group, twenty-four (72.2%) patients underwent a total thyroidectomy while the rest underwent a lobectomy. One case of TOETVA was converted to open. There were no significant differences in the EBL, recurrent laryngeal nerve injury, hematoma formation, or hypocalcemia postoperatively between the 2 groups (P>0.05). Conclusion: We conclude that when thyroidectomy, either total or partial, is pursued for the management of benign thyroid disorders, TOETVA in patients with favorable features is a viable alternative to open thyroidectomy with regards to postoperative outcomes and provides superior cosmetic results leaving the patient with no cutaneous scars.

      • SCISCIESCOPUS

        Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case-control study.

        Park, Kyung-Jae,Kano, Hideyuki,Iyer, Aditya,Liu, Xiaomin,Niranjan, Ajay,Flickinger, John C,Lieberman, Frank S,Lunsford, L Dade,Kondziolka, Douglas M. Nijhoff ; Kluwer Academic Publishers 2012 Journal of neuro-oncology Vol.107 No.2

        <P>We evaluated the efficacy and safety of gamma knife stereotactic radiosurgery (GKSR) followed by bevacizumab combined with chemotherapy in 11 patients with recurrent glioblastoma multiforme who experienced tumor progression despite aggressive initial multi-modality treatment. Our experience included eight male and three female patients. The median patient age at GKSR was 62 years (range 46-72 years). At the time of GKSR, seven patients had a first recurrence and four had two or more recurrences. The median interval from the initial diagnosis until GKSR was 17 months (range 5-34.5 months). The median tumor volume was 13.6 cm(3) (range 1.2-45.1 cm(3)) and the median margin dose of GKSR was 16 Gy (range 13-18 Gy). Following GKSR, bevacizumab was administrated with irinotecan in nine patients and with temozolomide in one patient. One patient was treated with bevacizumab monotherapy. The treatment outcomes were compared to 44 case-matched controls who underwent GKSR without additional bevacizumab. At a median of 13.7 months (range 4.6-28.3 months) after radiosurgery, tumor progression was evident in seven patients. The median progression-free survival (PFS) was 15 months (95% confidential interval (CI), 6.5-23.3 months). Six-month and 1-year PFS rates were 73 and 55%, respectively. The median overall survival (OS) from GKSR was 18 months (95% CI, 10.1-25.7 months) and 1-year OS rate was 73%. One patient (9%) experienced grade III toxicity and one patient (9%) had major adverse radiation effects. Compared with patients who did not receive bevacizumab, the patients who received bevacizumab had significantly prolonged PFS (15 months vs. 7 months, P = 0.035) and OS (18 months vs. 12 months, P = 0.005), and were less likely to develop an adverse radiation effect (9 vs. 46%, P = 0.037). The combination of salvage GKSR followed by bevacizumab added potential benefit and little additional risk in a small group of patients with progressive glioblastoma. Further experience is needed to define the efficacy and long-term toxicity with this strategy.</P>

      • KCI등재

        Minimally Invasive Posterior Facet Decortication and Fusion Using Navigated Robotic Guidance: Feasibility and Workflow Optimization

        Christopher R. Good,Lindsay D. Orosz,Ronald A. Lehman,Jeffrey L. Gum,Douglas Fox,Isador H. Lieberman 대한척추신경외과학회 2022 Neurospine Vol.19 No.3

        Minimally invasive spine surgery reduces tissue dissection and retraction, decreasing the morbidity associated with traditional open spine surgery by decreasing blood loss, blood transfusion, complications, and pain. One of the key challenges with a minimally invasive approach is achieving consistent posterior fusion. Although advantageous in all fusion surgeries, solid posterior fusion is particularly important in spinal deformity, revisions, and fusions without anterior column support. A minimally invasive surgical approach accomplished without sacrificing the quality of the posterior fusion has the potential to decrease both short- and long-term complications compared to the traditional open techniques. Innovations in navigated and robotic-assisted spine surgery continue to address this need. In this article, we will outline the feasibility of achieving posterior facet fusion using the Mazor X Stealth Edition Robotic Guidance System.

      • KCI등재

        Endoscopic Gallbladder Drainage for Acute Cholecystitis

        Jessica Widmer,Paloma Alvarez,Reem Z. Sharaiha,Sonia Gossain,Prashant Kedia,Savreet Sarkaria,Amrita Sethi,Brian G. Turner,Jennifer Millman,Michael Lieberman,Govind Nandakumar,Hiren Umrania,Monica Gaid 대한소화기내시경학회 2015 Clinical Endoscopy Vol.48 No.5

        Background/Aims: Surgery is the mainstay of treatment for cholecystitis. However, gallbladder stenting (GBS) has shown promise in debilitated or high-risk patients. Endoscopic transpapillary GBS and endoscopic ultrasound-guided GBS (EUS-GBS) have been proposed as safe and effective modalities for gallbladder drainage. Methods: Data from patients with cholecystitis were prospectively collected from August 2004 to May 2013 from two United States academic university hospitals and analyzed retrospectively. The following treatment algorithm was adopted. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and cystic duct stenting was initially attempted. If deemed feasible by the endoscopist, EUS-GBS was then pursued. Results: During the study period, 139 patients underwent endoscopic gallbladder drainage. Among these, drainage was performed in 94 and 45 cases for benign and malignant indications, respectively. Successful endoscopic gallbladder drainage was defined as decompression of the gallbladder without incidence of cholecystitis, and was achieved with ERCP and cystic duct stenting in 117 of 128 cases (91%). Successful endoscopic gallbladder drainage was also achieved with EUS-guided gallbladder drainage using transmural stent placement in 11 of 11 cases (100%). Complications occurred in 11 cases (8%). Conclusions: Endoscopic gallbladder drainage techniques are safe and efficacious methods for gallbladder decompression in non-surgical patients with comorbidities.

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