-
Jung Hwa Lee,
Seok-Won Hyung,
Dong-Gi Mun, Hee-Jung Jung,
Hokeun Kim,
Hangyeore Lee,
Su-Jin Kim,
Kyong Soo Park,
Ronald J Moore,
Richard D Smith,
Sang-Won Lee
[show abstract]
[hide abstract]
ABSTRACT: A multifunctional liquid chromatography system that performs 1-dimensional, 2-dimensional (strong cation exchange/reverse phase liquid chromatography or SCX/RPLC) separations and online phosphopeptide enrichment using a single binary nanoflow pump has been developed. With a simple operation of a function selection valve equipped with a SCX column and a TiO2 (titanium dioxide) column, a fully automated selection of three different experiment modes was achieved. Because the current system uses essentially the same solvent flow paths, the same trap column, and the same separation column for reverse-phase separation of 1D, 2D, and online phosphopeptides enrichment experiments, the elution time information obtained from these experiments is in excellent agreement, which facilitates correlating peptide information from different experiments. The final reverse-phase separation of the three experiments is completely decoupled from all of the function selection processes; thereby salts or acids from SCX or TiO2 column do not affect the efficiency of the reverse-phase separation.
Journal of Proteome Research 06/2012; 11(8):4373-81. · 5.11 Impact Factor
-
Seok-Won Hyung,
Min Young Lee,
Jong-Han Yu,
Byunghee Shin, Hee-Jung Jung,
Jong-Moon Park,
Wonshik Han,
Kyung-Min Lee,
Hyeong-Gon Moon,
Hui Zhang,
Ruedi Aebersold,
Daehee Hwang,
Sang-Won Lee,
Myeong-Hee Yu,
Dong-Young Noh
[show abstract]
[hide abstract]
ABSTRACT: Prediction of the responses to neoadjuvant chemotherapy (NACT) can improve the treatment of patients with advanced breast cancer. Genes and proteins predictive of chemoresistance have been extensively studied in breast cancer tissues. However, noninvasive serum biomarkers capable of such prediction have been rarely exploited. Here, we performed profiling of N-glycosylated proteins in serum from fifteen advanced breast cancer patients (ten patients sensitive to and five patients resistant to NACT) to discover serum biomarkers of chemoresistance using a label-free liquid chromatography-tandem MS method. By performing a series of statistical analyses of the proteomic data, we selected thirteen biomarker candidates and tested their differential serum levels by Western blotting in 13 independent samples (eight patients sensitive to and five patients resistant to NACT). Among the candidates, we then selected the final set of six potential serum biomarkers (AHSG, APOB, C3, C9, CP, and ORM1) whose differential expression was confirmed in the independent samples. Finally, we demonstrated that a multivariate classification model using the six proteins could predict responses to NACT and further predict relapse-free survival of patients. In summary, global N-glycoproteome profile in serum revealed a protein pattern predictive of the responses to NACT, which can be further validated in large clinical studies.
Molecular & Cellular Proteomics 07/2011; 10(10):M111.011023. · 7.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To compare sonographically measured cervical length with the Bishop score in determining the requirement for prostaglandin administration for preinduction cervical ripening in nulliparae at term.
One hundred and fifty-four women with singleton pregnancies at term who were scheduled for induction of labor were randomly assigned to receive prostaglandin for preinduction cervical ripening based on the Bishop score or sonographic cervical length. A cervix unfavorable for treatment with prostaglandin for preinduction cervical ripening was defined as having either a Bishop score of ≤ 4 or a cervical length of ≥ 28 mm. The primary outcome measures were induction success (defined as an ability to achieve the active phase of labor) and the percentage of patients treated with prostaglandin for preinduction cervical ripening.
The two groups were similar with respect to maternal demographics, gestational age, cervical length, and Bishop score. The rates of induction success and Cesarean delivery, the interval to active phase of labor, and the interval to delivery were also similar in the two groups. However, in the transvaginal ultrasound group (n = 77), prostaglandin was administered to only 36% of the nulliparae compared with 75% of those in the Bishop score group (n = 77) (P < 0.0001).
In comparison with the Bishop score, the use of sonographic cervical length for assessing the cervix prior to induction of labor can reduce the need for prostaglandin administration by approximately 50% without adversely affecting the outcome of induction in nulliparae at term if the cut-off values used are a Bishop score of ≤ 4 and a cervical length of ≥ 28 mm.
Ultrasound in Obstetrics and Gynecology 04/2011; 38(2):198-204. · 3.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To identify maternal and placental risk factors for the occurrence and progression of retinopathy of prematurity (ROP).
This was a retrospective cohort study. The study cohort consisted of 246 infants with gestational age ≤ 32 weeks, with histologic examinations of their placentas. Medical records of eligible preterm infants were retrospectively reviewed. A regression model was constructed with control for known or potential factors associated with ROP. Occurrences of ROP, severe ROP (≥ stage 3), and clinically significant ROP requiring laser treatment were assessed.
ROP was diagnosed in 82 of 246 infants (33.3%), including 49 with mild ROP and 33 with severe ROP. Laser treatment was performed on 27 infants (11%: 27/246). Multivariate regression analysis indicated clinical chorioamnionitis and elevated maternal WBC count on admission to be associated with ROP occurrence [odds ratio (OR) = 4.370, P = 0.046; and OR = 1.104 per 1,000 cells/mm(3) incremental increase, P = 0.019, respectively], while the use of tocolytics was associated with reduced occurrence of ROP (OR = 0.278, P = 0.006). Elevated maternal WBC count on admission was also independently associated with ROP progression requiring laser treatment (OR = 1.171 per 1,000 cells/mm(3) incremental increase, P = 0.026). However, neither histologic chorioamnionitis nor funisitis was associated with the occurrence or progression of ROP.
Clinical chorioamnionitis and elevated maternal WBC count, but not histologic chorioamnionitis, were significantly and independently associated with ROP. These findings support the hypothesis that maternal systemic inflammation may play a role in the pathogenesis of ROP.
Albrecht von Graæes Archiv für Ophthalmologie 04/2011; 250(6):915-23. · 2.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Transcription and replication of mitochondrial DNA (mtDNA) are regulated by nuclear DNA-encoded proteins that are targeted into mitochondria. A decrease in mtDNA copy number results in mitochondrial dysfunction, which may lead to insulin resistance and metabolic syndromes. We analyzed mitochondrial proteins that physically bind to human mitochondrial D-loop DNA using a shot-gun proteomics approach following protein enrichment by D-loop DNA-linked affinity chromatography. A total of 152 D-loop DNA binding proteins were identified by peptide sequencing using ultra high pressure capillary reverse-phase liquid chromatography/tandem mass spectrometry. Bioinformatic analysis showed that 68 were mitochondrial proteins, 96 were DNA/RNA/protein binding proteins and 114 proteins might form a complex via protein-protein interactions. Histone family members of H1, H2A, H2B, H3, and H4, were detected in abundance among them. In particular, histones H2A and H2B were present in the mitochondrial membrane as integral membrane proteins and not bound directly to mtDNA inside the organelle. Histones H1.2, H3 and H4 were associated with the outer mitochondrial membrane. Silencing of H2AX expression inhibited mitochondrial protein transport. Our data suggests that many mitochondrial proteins may reside in multiple subcellular compartments like H2AX and exert multiple functions.
Molecular BioSystems 02/2011; 7(5):1523-36. · 3.53 Impact Factor
-
American Journal of Obstetrics and Gynecology - AMER J OBSTET GYNECOL. 01/2011; 204(1).
-
Hee-Jung Jung,
Samuel O Purvine,
Hokeun Kim,
Vladislav A Petyuk,
Seok-Won Hyung,
Matthew E Monroe,
Dong-Gi Mun,
Kyong-Chul Kim,
Jong-Moon Park,
Su-Jin Kim, [......],
Gordon W Slysz,
Ronald J Moore,
Rui Zhao,
Joshua N Adkins,
Gordon A Anderson,
Hookeun Lee,
David G Camp,
Myeong-Hee Yu,
Richard D Smith,
Sang-Won Lee
[show abstract]
[hide abstract]
ABSTRACT: Accurate assignment of monoisotopic precursor masses to tandem mass spectrometric (MS/MS) data is a fundamental and critically important step for successful peptide identifications in mass spectrometry based proteomics. Here we describe an integrated approach that combines three previously reported methods of treating MS/MS data for precursor mass refinement. This combined method, "integrated post-experiment monoisotopic mass refinement" (iPE-MMR), integrates steps (1) generation of refined MS/MS data by DeconMSn; (2) additional refinement of the resultant MS/MS data by a modified version of PE-MMR; and (3) elimination of systematic errors of precursor masses using DtaRefinery. iPE-MMR is the first method that utilizes all MS information from multiple MS scans of a precursor ion including multiple charge states, in an MS scan, to determine precursor mass. With the combination of these methods, iPE-MMR increases sensitivity in peptide identification and provides increased accuracy when applied to complex high-throughput proteomics data.
Analytical Chemistry 10/2010; 82(20):8510-8. · 5.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To develop a model based on non-invasive variables to predict the probability of intra-amniotic inflammation in women with preterm labor and intact membranes.
Transvaginal ultrasonography and digital examination for the assessment of cervical length and cervical dilatation were performed, and maternal blood was collected for the determination of C-reactive protein and white blood cell (WBC) count immediately after amniocentesis in 153 consecutive women with preterm labor. Amniotic fluid obtained by amniocentesis was cultured for aerobic and anaerobic bacteria and mycoplasmas, and the WBC was determined. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin-6 concentration (> 2.6 ng/mL). Receiver-operating characteristics (ROC) curves and logistic regression analysis were used for statistical analysis.
The prevalence of a positive amniotic fluid culture was 7.2% (11/153) and the prevalence of intra-amniotic inflammation was 19.6% (30/153). The final logistic regression model was based on non-invasive clinical variables, including gestational age at assessment, cervical length and maternal blood WBC count, which were the best predictors of intra-amniotic inflammation. The model was shown to have an adequate goodness of fit (P = 0.754), and the area under the ROC curve was 0.724, indicating reasonably good discrimination.
In women with preterm labor and intact membranes, the risk for intra-amniotic inflammation can be predicted non-invasively with a risk score based on gestational age, cervical length and maternal blood WBC count.
Ultrasound in Obstetrics and Gynecology 10/2010; 37(1):82-7. · 3.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate whether the degree of cervical length shortening is valuable in predicting the success of serial induction of labor on the second day in women in whom it failed on the first day, and to compare its performance with that of cervical length.
This was a prospective observational study. We enrolled 92 consecutive women with singleton gestations at > 34.0 weeks' gestation who failed labor induction on the first day of serial induction. Transvaginal sonographic measurement of cervical length and determination of the Bishop score were undertaken before performing each labor induction on the first and second days.
The overall success rate of labor induction performed on the second day was 65% (60/92). Multiple logistic regression analysis demonstrated that the degree of cervical length shortening and cervical length were significantly associated with the successful induction of labor after adjustment for body mass index, parity, use of prostaglandin and Bishop score. There were no significant differences between areas under the ROC curves for degree of cervical length shortening and cervical length.
The degree of cervical length shortening is valuable in predicting the success of induction of labor on the second day in women in whom induction failed on the first day. However, compared with sonographic cervical length it is no better at predicting the success of subsequent induction of labor.
Ultrasound in Obstetrics and Gynecology 03/2010; 36(6):749-54. · 3.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Heat shock proteins have been implicated as endogenous activators for dendritic cells (DCs). Chronic expression of heat shock protein gp96 on cell surfaces induces significant DC activations and systemic lupus erythematosus (SLE)-like phenotypes in mice. However, its potential as a therapeutic target against SLE remains to be evaluated. In this work, we conducted chemical approach to determine whether SLE-like phenotypes can be compromised by controlling surface translocation of gp96. From screening of chemical library, we identified a compound that binds and suppresses surface presentation of gp96 by facilitating its oligomerization and retrograde transport to endoplasmic reticulum. In vivo administration of this compound reduced maturation of DCs, populations of antigen presenting cells, and activated B and T cells. The chemical treatment also alleviated the SLE-associated symptoms such as glomerulonephritis, proteinuria, and accumulation of anti-nuclear and -DNA antibodies in the SLE model mice resulting from chronic surface exposure of gp96. These results suggest that surface translocation of gp96 can be chemically controlled and gp96 as a potential therapeutic target to treat autoimmune disease like SLE.
PLoS ONE 01/2010; 5(3):e9792. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Determining isotopic clusters and their monoisotopic masses is a first step in interpreting complex mass spectra generated by high-resolution mass spectrometers. We propose a mathematical model for isotopic distributions of polypeptides and an effective interpretation algorithm. Our model uses two types of ratios: intensity ratio of two adjacent peaks and intensity ratio product of three adjacent peaks in an isotopic distribution. These ratios can be approximated as simple functions of a polypeptide mass, the values of which fall within certain ranges, depending on the polypeptide mass. Given a spectrum as a peak list, our algorithm first finds all isotopic clusters consisting of two or more peaks. Then, it scores clusters using the ranges of ratio functions and computes the monoisotopic masses of the identified clusters. Our method was applied to high-resolution mass spectra obtained from a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer coupled to reverse-phase liquid chromatography (RPLC). For polypeptides whose amino acid sequences were identified by tandem mass spectrometry (MS/MS), we applied both THRASH-based software implementations and our method. Our method was observed to find more masses of known peptides when the numbers of the total clusters identified by both methods were fixed. Experimental results show that our method performed better for isotopic mass clusters of weak intensity where the isotopic distributions deviate significantly from their theoretical distributions. Also, it correctly identified some isotopic clusters that were not found by THRASH-based implementations, especially those for which THRASH gave 1 Da mismatches. Another advantage of our method is that it is very fast, much faster than THRASH that calculates the least-squares fit.
Analytical Chemistry 09/2008; 80(19):7294-303. · 5.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Methods for treating MS/MS data to achieve accurate peptide identification are currently the subject of much research activity. In this study we describe a new method for filtering MS/MS data and refining precursor masses that provides highly accurate analyses of massive sets of proteomics data. This method, coined "postexperiment monoisotopic mass filtering and refinement" (PE-MMR), consists of several data processing steps: 1) generation of lists of all monoisotopic masses observed in a whole LC/MS experiment, 2) clusterization of monoisotopic masses of a peptide into unique mass classes (UMCs) based on their masses and LC elution times, 3) matching the precursor masses of the MS/MS data to a representative mass of a UMC, and 4) filtration of the MS/MS data based on the presence of corresponding monoisotopic masses and refinement of the precursor ion masses by the UMC mass. PE-MMR increases the throughput of proteomics data analysis, by efficiently removing "garbage" MS/MS data prior to database searching, and improves the mass measurement accuracies (i.e. 0.05 +/- 1.49 ppm for yeast data (from 4.46 +/- 2.81 ppm) and 0.03 +/- 3.41 ppm for glycopeptide data (from 4.8 +/- 7.4 ppm)) for an increased number of identified peptides. In proteomics analyses of glycopeptide-enriched samples, PE-MMR processing greatly reduces the degree of false glycopeptide identification by correctly assigning the monoisotopic masses for the precursor ions prior to database searching. By applying this technique to analyses of proteome samples of varying complexities, we demonstrate herein that PE-MMR is an effective and accurate method for treating massive sets of proteomics data.
Molecular & Cellular Proteomics 07/2008; 7(6):1124-34. · 7.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It is important to preprocess high-throughput data generated from mass spectrometry experiments in order to obtain a successful proteomics analysis. Outlier detection is an important preprocessing step. A naive outlier detection approach may miss many true outliers and instead select many non-outliers because of the heterogeneity of the variability observed commonly in high-throughput data. Because of this issue, we developed a outlier detection software program accounting for the heterogeneous variability by utilizing linear, non-linear and non-parametric quantile regression techniques. Our program was developed using the R computer language. As a consequence, it can be used interactively and conveniently in the R environment. AVAILABILITY: An R package, OutlierD, is available at the Bioconductor project at http://www.bioconductor.org
Bioinformatics 04/2008; 24(6):882-4. · 5.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Interferons (IFNs) have been shown to negatively regulate osteoclastogenesis. In a proteomic study to assess protein expression during osteoclastogenesis, we discovered that the expression level of Jak1 was significantly decreased during the early stage of osteoclast differentiation from mouse bone marrow macrophages (BMMs) upon stimulation with receptor activator of nuclear factor kappaB ligand (RANKL). RANKL induced Jak1 ubiquitination, and a proteasome inhibitor MG132 efficiently blocked the RANKL-induced degradation of Jak1. The expression level of Jak1 correlated with the susceptibility of osteoclast precursors to the negative regulatory effects of IFN-beta on osteoclastogenesis, since preosteoclasts (pOCs) in which Jak1 expression is significantly reduced could proceed with osteoclastogenesis in the presence of IFN-beta. Forced down-regulation of Jak1 by small interfering RNA (siRNA) resulted in the efficient osteoclast differentiation of BMMs in the presence of inhibitory IFN-beta, while overexpression of Jak1 in pOCs elicited IFN-beta-dependent inhibition of osteoclastogenesis. Furthermore, we found that the IFN-beta-induced inhibition of osteoclastogenesis required STAT3 downstream of Jak1. These data suggest that the regulation of Jak1 expression during osteoclast differentiation might serve as an intrinsic mechanism that determines osteoclast lineage commitment by modulating the negative regulation by IFN-beta.
Blood 02/2008; 111(2):885-93. · 9.90 Impact Factor
-
Bioinformatics. 01/2008; 24:882-884.
-
[show abstract]
[hide abstract]
ABSTRACT: Capillary RPLC/ESI-MS (cRPLC/ESI-MS) is one of the most powerful analytical tools for current proteomic research. The development of cRPLC techniques coupled online to a mass spectrometer has focused on increasing the separation efficiency, detection sensitivity, and throughput. Recently, the use of high-pressure (over 10,000 psi) LC systems that utilize long, small inner diameter capillary columns has gained much attention for proteomic analyses. In this study, we developed an ultrahigh-pressure dual online SPE/capillary RPLC (DO-SPE/cRPLC) system. This LC system employs two online SPE columns and two capillary columns (75 microm inner diameter x 1 m length) in a single separation system, and has a maximum operating pressure of 10,000 psi. This DO-SPE/cRPLC system is capable of providing high-resolution separation in addition to several other advantageous features, such as high reproducibility in terms of the LC retention time, rapid sample injection, online desalting, online sample enrichment of dilute samples, and increased throughput as a result of essentially removing the column equilibration time between successive experiments. We coupled the DO-SPE/cRPLC system online to a tandem mass spectrometer to allow high-throughput proteomic analyses. In this paper, we demonstrate the efficiency of this DO-SPE/cRPLC/MS/MS system by its use in the analyses of proteomic samples exhibiting different levels of complexity.
Electrophoresis 04/2007; 28(6):1012-21. · 3.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The protein encoded by the hepatitis B viral X-gene, HBx, is essential for viral infection and has been shown to regulate gene transcription and the Ras signaling pathway including Raf, MEK, and ERK. To better understand regulatory mechanism of HBx functions, we investigated whether ERK1/2-induced phosphorylation of HBx regulates its transcriptional activity on p21(WAF1/Cip1) promoter. HBx-genotype A (WT1) and its modified HBx (WT2; (38)SSPSPS(43) in WT1 was substituted by (38)PPSSPS(43) in HBx-genotype F) were phosphorylated by ERK1/2 in vitro, although their Ser --> Ala constructs, SA1 (S(43) of WT1 to A) and SA2 (S(41) of WT2 to A), were not. HBx WT1 and WT2, but not SA2, repressed transcription from the p21(WAF1/Cip1) promoter. This repression was blocked by treatment with PD98059, an inhibitor of MEK, or by overexpression of dominant negative MEK1. Furthermore, WT1 and WT2 localized predominantly in the nucleus, whereas SA1 and SA2 localized to the cytoplasm, suggesting that the subcellular localization of HBx is controlled by its phosphorylation. Overall, our findings provide insight that ERK1/2-mediated phosphorylation of HBx regulates HBx function and localization, and may contribute to dysregulation of cell cycle progression leading to hepatocarcinogenesis in HBV-infected cells.
Biochemical and Biophysical Research Communications 07/2004; 319(3):738-45. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The effect of thioamide substitution on the conformational stability of an azaglycine-containing peptide, For-AzaGly-NH2 (1), was investigated for the sake of finding possible applications by using ab initio and DFT methods. As model compounds, For-[psiCSNH]-AzaGly-NH2 (2), For-AzaGly-[psiCSNH]-NH2 (3), and For-[psiCSNH]-AzaGly-[psiCSNH]-NH2 (4) were used. Two-dimensional phi-psi potential energy surfaces (PESs) for 2-4 were calculated at the B3LYP/6-31G*//HF/6-31G* level in gas (epsilon = 1.0) and in water (epsilon = 78.4) by applying the isodensity polarizable continuum model (IPCM) method. On the basis of these PESs, the minimum energy conformations for 2-4 were characterized at the B3LYP level with 6-31G*, 6-311G**, and 6-31+G** basis sets. The remarkable structural effect of thioamide substitution for 2-4 is that beta-strand structure is observed as a global or local minimum. The minima of 2-4 are also compared with those for glycine and thioamide-containing glycine peptides. Our theoretical results demonstrate that compounds 2-4 would be used to design controllable secondary structures.
Journal of Computational Chemistry 02/2004; 25(2):169-78. · 4.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Despite the recent introduction of real-time PCR methods and cDNA microarrays, competitive PCR techniques continue to play an important role in nucleic acid quantification because of the significantly lower cost of equipment and consumables. In this study, we developed a construct, termed tumor suppressor-internal standard (TS-IS) that produced polycompetitive RNA templates as an internal standard to quantify cellular RNA concentration of tumor suppressor genes. This construct is composed of not only sets of primers for detecting the expression of several tumor suppressor genes (such as pRB, p16(INK4A) 15(INK4B), p14(ARF) p53, and p21(WAF1)), but also HPRT as an endogenous marker. Using an internal standard RNA that was synthesized from the TS-IS construct, we were able to establish optimized conditions for the quantification of tumor suppressor genes with minimal amounts (50 ng) of cellular RNA. In addition, the usefulness of this method was confirmed by analyzing the expression levels of tumor suppressor genes in fourteen hepatoma cell lines as a model. The TS-IS assay that we used was inexpensive and a widely applicable method that permitted the reliable and accurate quantification of tumor suppressor genes.
Molecules and Cells 07/2002; 13(3):481-7. · 2.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The protein encoded by the hepatitis B viral X-gene, HBx, is essential for viral infection and has been shown to regulate gene transcription and the Ras signaling pathway including Raf, MEK, and ERK. To better understand regulatory mechanism of HBx functions, we investigated whether ERK1/2-induced phosphorylation of HBx regulates its transcriptional activity on p21WAF1/Cip1 promoter. HBx-genotype A (WT1) and its modified HBx (WT2; 38SSPSPS43 in WT1 was substituted by 38PPSSPS43 in HBx-genotype F) were phosphorylated by ERK1/2 in vitro, although their Ser → Ala constructs, SA1 (S43 of WT1 to A) and SA2 (S41 of WT2 to A), were not. HBx WT1 and WT2, but not SA2, repressed transcription from the p21WAF1/Cip1 promoter. This repression was blocked by treatment with PD98059, an inhibitor of MEK, or by overexpression of dominant negative MEK1. Furthermore, WT1 and WT2 localized predominantly in the nucleus, whereas SA1 and SA2 localized to the cytoplasm, suggesting that the subcellular localization of HBx is controlled by its phosphorylation. Overall, our findings provide insight that ERK1/2-mediated phosphorylation of HBx regulates HBx function and localization, and may contribute to dysregulation of cell cycle progression leading to hepatocarcinogenesis in HBV-infected cells.
Biochemical and Biophysical Research Communications.
