bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary documents from Targeting Colon Luminal Lipid Peroxidation Limits Colon Carcinogenesis Associated with Red Meat Consumption
Authors: Martin Océane C.B. , Naud Nathalie , Taché Sylviane , Debrauwer Laurent , Chevolleau Sylvie , Dupuy Jacques , Chantelauze Céline , Durand Denis , Pujos-Guillot Estelle , Blas-Y-Estrada Florence , Urbano Christine , Kuhnle Gunter G.C. , Santé-Lhoutellier Véronique , Sayd Thierry , Viala Didier , Blot Adeline , Meunier Nathalie , Schlich Pascal , Attaix Didier , Guéraud Françoise , Scislowski Valérie , Corpet Denis E. , Pierre Fabrice H.F.
Published: April 2023

Supplementary figure, tables and results Supplementary Figure S1. Flowchart of the 6 studies Supplementary Table S1. Transitions and collision energies used for the quantification (Bold) and confirmation (Italic) of AAH on the triple quadrupole instrument. Supplementary Table S2. Active compounds (extract, molecule and family), used quantity and radical scavenger activity results of marinade used in the study 1. Supplementary Table S3. Effect of grape-olive marinade and of cooking on lipid peroxidation (TBARs) and on iron levels in fresh red meats. Data are presented as mean {plus minus} SD. a two-way ANOVA assessing marinade and cooking factors. Supplementary Table S4. Effect of meat, marinade and cooking on heme content and lipoperoxidation biomarkers in feces from rats fed a no-meat control diet or experimental red meats for 14 days. Data are presented as mean {plus minus} SD. a The effect of meat intake was evaluated by a one-way ANOVA and the effect of marinated and cooked meat intake by two-way ANOVA.
Figure S3 from Early Exposure to a High Fat/High Sugar Diet Increases the Mammary Stem Cell Compartment and Mammary Tumor Risk in Female Mice
Authors: Lambertz Isabel U. , Luo Linjie , Berton Thomas R. , Schwartz Scott L. , Hursting Stephen D. , Conti Claudio J. , Fuchs-Young Robin
Published: April 2023

Figure S3 shows the FACS gating strategy used to isolate MaSCs.
Supplementary tables 1-4 from Risk Stratification System for Oral Cancer Screening
Authors: Pereira Lutécia H. Mateus , Reis Isildinha M. , Reategui Erika P. , Gordon Claudia , Saint-Victor Sandra , Duncan Robert , Gomez Carmen , Bayers Stephanie , Fisher Penelope , Perez Aymee , Goodwin W. Jarrard , Hu Jennifer J. , Franzmann Elizabeth J.
Published: April 2023

Supplementary Table 1. Stage and HPV status by disease site among 150 cases. Supplementary Table 2. SolCD44/Total Protein test by HPV status and stage. Supplementary Table 3. Characteristics of hospital-based cases and controls and community controls. Supplementary Table 4. Prognostic Significance of CD44 and Total Protein Levels.
Supplementary Data S1 from Sedentary Behavior and Prostate Cancer: A Systematic Review and Meta-Analysis of Prospective Cohort Studies
Authors: Berger Felix F. , Leitzmann Michael F. , Hillreiner Andrea , Sedlmeier Anja M. , Prokopidi-Danisch Maria Eleni , Burger Maximilian , Jochem Carmen
Published: April 2023

PRISMA Checklist
Supplementary Table 2C from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
Authors: Guerrero-Preston Rafael , Valle Blanca L. , Jedlicka Anne , Turaga Nitesh , Folawiyo Oluwasina , Pirini Francesca , Lawson Fahcina , Vergura Angelo , Noordhuis Maartje , Dziedzic Amanda , Pérez Gabriela , Renehan Marisa , Guerrero-Diaz Carolina , De Jesus Rodríguez Edgar , Diaz-Montes Teresa , Rodríguez Orengo José , Méndez Keimari , Romaguera Josefina , Trock Bruce J. , Florea Liliana , Sidransky David
Published: April 2023

Profiling of HPV TrDNA 456 reads by tiered mapping.
Supplementary Table 2A from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
Authors: Guerrero-Preston Rafael , Valle Blanca L. , Jedlicka Anne , Turaga Nitesh , Folawiyo Oluwasina , Pirini Francesca , Lawson Fahcina , Vergura Angelo , Noordhuis Maartje , Dziedzic Amanda , Pérez Gabriela , Renehan Marisa , Guerrero-Diaz Carolina , De Jesus Rodríguez Edgar , Diaz-Montes Teresa , Rodríguez Orengo José , Méndez Keimari , Romaguera Josefina , Trock Bruce J. , Florea Liliana , Sidransky David
Published: April 2023

Dual Sequence capture of high risk HPV in TrDNA aligned to HPV 16 and HPV 18.
Figure S5 from Post Genome-Wide Gene–Environment Interaction Study Using Random Survival Forest: Insulin Resistance, Lifestyle Factors, and Colorectal Cancer Risk
Authors: Jung Su Yon , Papp Jeanette C. , Sobel Eric M. , Zhang Zuo-Feng
Published: April 2023

The second stage of RSF by SFA
Figure S3 from Post Genome-Wide Gene–Environment Interaction Study Using Random Survival Forest: Insulin Resistance, Lifestyle Factors, and Colorectal Cancer Risk
Authors: Jung Su Yon , Papp Jeanette C. , Sobel Eric M. , Zhang Zuo-Feng
Published: April 2023

The first stage of RSF
Supplementary Figure 4 from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
Authors: Guerrero-Preston Rafael , Valle Blanca L. , Jedlicka Anne , Turaga Nitesh , Folawiyo Oluwasina , Pirini Francesca , Lawson Fahcina , Vergura Angelo , Noordhuis Maartje , Dziedzic Amanda , Pérez Gabriela , Renehan Marisa , Guerrero-Diaz Carolina , De Jesus Rodríguez Edgar , Diaz-Montes Teresa , Rodríguez Orengo José , Méndez Keimari , Romaguera Josefina , Trock Bruce J. , Florea Liliana , Sidransky David
Published: April 2023

GenoScape - example of HPV genotype profiling report and visualization. Number, characteristics and percentage of reads that map to thirteen (13) HPV types, human, bacteria and unknown genomes after profiling reads of the clinical sample TrDNA-456 by tiered read mapping.
Supplementary Figure 2C from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
Authors: Guerrero-Preston Rafael , Valle Blanca L. , Jedlicka Anne , Turaga Nitesh , Folawiyo Oluwasina , Pirini Francesca , Lawson Fahcina , Vergura Angelo , Noordhuis Maartje , Dziedzic Amanda , Pérez Gabriela , Renehan Marisa , Guerrero-Diaz Carolina , De Jesus Rodríguez Edgar , Diaz-Montes Teresa , Rodríguez Orengo José , Méndez Keimari , Romaguera Josefina , Trock Bruce J. , Florea Liliana , Sidransky David
Published: April 2023

MethylScape - Large scale and close up visualization of HPV methylome. Large-scale view shows exact or smoothed (bsmooth) methylation levels along the HPV genome/contigs. Close-up view shows bisulfite 'alignments' of individual CpG methylation sites.
Supplementary Tables from HCV Eradication in Primary or Secondary Prevention Optimizes Hepatocellular Carcinoma Curative Management
Authors: Nahon Pierre , Layese Richard , Cagnot Carole , Asselah Tarik , Guyader Dominique , Pol Stanislas , Pageaux Georges-Philippe , De Lédinghen Victor , Ouzan Denis , Zoulim Fabien , Audureau Etienne
Published: April 2023

Suppl Tables
Supplementary Figure 1C from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
Authors: Guerrero-Preston Rafael , Valle Blanca L. , Jedlicka Anne , Turaga Nitesh , Folawiyo Oluwasina , Pirini Francesca , Lawson Fahcina , Vergura Angelo , Noordhuis Maartje , Dziedzic Amanda , Pérez Gabriela , Renehan Marisa , Guerrero-Diaz Carolina , De Jesus Rodríguez Edgar , Diaz-Montes Teresa , Rodríguez Orengo José , Méndez Keimari , Romaguera Josefina , Trock Bruce J. , Florea Liliana , Sidransky David
Published: April 2023

Phase 2 Biomarker Development Trial was performed to develop a clinical assay based on a specimen that can be obtained noninvasively. Promoter methylation of FKBP6, ZNF516 and INTS1 was quantified with qMSP in samples from three cohorts of women who underwent biopsy after colposcopy and were diagnosed with no intraepithelial lesions or malignancy (NILM) or Cervical Intraepithelial Neoplasia (CIN) grades 1-3. The first was a retrospective cohort of cervical brush samples (n=214) obtained from women in Chile who had a biopsy diagnosed with NILM (n=37), CIN1 (n=34), CIN2 (n=33), CIN3 (n=20), and squamous cell carcinoma (n=90). The second was a prospective cohort of liquid-based cytology samples (n=67) collected from women in Puerto Rico, which was used to confirm with qMSP the results previoulsy obtained in this experiment. The third was another prospective cohort (n=40) of samples collected from women in Puerto Rico who provided paired liquid-based cytology, plasma and urine samples. hrHPV status for cervical brush and liquid biopsy samples in each cohort was confirmed with a PCR based assay that quantifies E6 and E7 in genomic DNA. qMSP primers and probes for HPV16L1 gene were also used to test the cohorts from Puerto Rico.
Supplementary Figure 1B from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
Authors: Guerrero-Preston Rafael , Valle Blanca L. , Jedlicka Anne , Turaga Nitesh , Folawiyo Oluwasina , Pirini Francesca , Lawson Fahcina , Vergura Angelo , Noordhuis Maartje , Dziedzic Amanda , Pérez Gabriela , Renehan Marisa , Guerrero-Diaz Carolina , De Jesus Rodríguez Edgar , Diaz-Montes Teresa , Rodríguez Orengo José , Méndez Keimari , Romaguera Josefina , Trock Bruce J. , Florea Liliana , Sidransky David
Published: April 2023

Immunohistochemistry (IHC) was performed to identify the differential distribution and localization of expressed proteins for INTS1, FKBP6, and ZNF516 in a separate cohort of 59 normal cervical mucosa samples and 63 cervical carcinoma tissue samples which were mounted on tissue microarrays. Paraffin sections of tissue microarrays were mounted on xylene-coated slides, dewaxed, rehydrated, and incubated for 15 minutes with 3% hydrogen peroxide to block endogenous peroxidase activity. The antigenic sites were unmasked by heating in a steamer for 30 minutes in 0.01 M citrate buffer. The sections were incubated for 1 hour in the dark with antibodies for FKBP6 (Abcam, Cambridge, USA), ZNF516 (Sigma Aldrich, St. Louis, USA), INTS1 (Sigma Aldrich St. Louis, USA) and GGTLA4 (GenWay, San Diego, USA) diluted in Tris buffer. Sections were then rinsed in Tris buffer and incubated at room temperature with Envision (Dako, Glastrup, Denmark) 1:2 Tris buffer as a secondary antibody for 30 minutes in the dark. Slides were developed using 3-3' diamninobenzidine as the chromogen. Immunoreactivity score was determined by tabulating the percentage of cells with different levels of reactivity to the target antibodies.
Supplemental Experimental Procedures from Molecular Triage of Premalignant Lesions in Liquid-Based Cervical Cytology and Circulating Cell-Free DNA from Urine, Using a Panel of Methylated Human Papilloma Virus and Host Genes
Authors: Guerrero-Preston Rafael , Valle Blanca L. , Jedlicka Anne , Turaga Nitesh , Folawiyo Oluwasina , Pirini Francesca , Lawson Fahcina , Vergura Angelo , Noordhuis Maartje , Dziedzic Amanda , Pérez Gabriela , Renehan Marisa , Guerrero-Diaz Carolina , De Jesus Rodríguez Edgar , Diaz-Montes Teresa , Rodríguez Orengo José , Méndez Keimari , Romaguera Josefina , Trock Bruce J. , Florea Liliana , Sidransky David
Published: April 2023

Supplementary Methods.
Supplement Table 2 from A Calcium-Rich Multimineral Intervention to Modulate Colonic Microbial Communities and Metabolomic Profiles in Humans: Results from a 90-Day Trial
Authors: Aslam Muhammad N. , Bassis Christine M. , Bergin Ingrid L. , Knuver Karsten , Zick Suzanna M. , Sen Ananda , Turgeon D. Kim , Varani James
Published: April 2023

Demographic characteristics of the participant population.
Supplementary Figure from Chronic Exposure to Waterpipe Smoke Elicits Immunomodulatory and Carcinogenic Effects in the Lung
Authors: Hassane Maya , Rahal Zahraa , Karaoghlanian Nareg , Zhang Jiexin , Sinjab Ansam , Wong Justin W. , Lu Wei , Scheet Paul , Lee J. Jack , Raso Maria Gabriela , Solis Luisa M. , Fujimoto Junya , Chami Hassan , Shihadeh Alan L. , Kadara Humam
Published: April 2023

Supplementary Figure from Chronic Exposure to Waterpipe Smoke Elicits Immunomodulatory and Carcinogenic Effects in the Lung
supplementary figure S1 from Noninvasive Molecular Screening for Oral Precancer in Fanconi Anemia Patients
Authors: Smetsers Stephanie E. , Velleuer Eunike , Dietrich Ralf , Wu Thijs , Brink Arjen , Buijze Marijke , Deeg Dorly J.H. , Soulier Jean , Leemans C. René , Braakhuis Boudewijn J.M. , Brakenhoff Ruud H.
Published: April 2023

Figure S1. Follow-up of non-transplanted FA patients Follow-up of the 141 non-transplanted FA patients. Four of 10 patients with LOH and 1 of 100 patients without LOH developed HNSCC.
Supplementary Table 3 from Risk versus Benefit of Chemoprevention among Raloxifene and Tamoxifen Users with a Family History of Breast Cancer
Authors: Anderson Chelsea , Nichols Hazel B. , House Melissa , Sandler Dale P.
Published: April 2023

Supplementary Table 3
Figure S3 from Progestin Significantly Inhibits Carcinogenesis in the Mogp-TAg Transgenic Mouse Model of Fallopian Tube Cancer
Authors: Nelson Omar L. , Rosales Rebecca , Turbov Jane M. , Thaete Larry G. , Cline J. Mark , Rodriguez Gustavo C.
Published: April 2023

Figure S3 shows the effects of progestin on mogp-TAg mouse reproductive tract.
Supplementary Data from Urgent Need for Novel Investigations of Treatments to Quit E-cigarettes: Findings from a Systematic Review
Authors: Palmer Amanda M. , Price Sarah N. , Foster Madeline G. , Sanford Brandon T. , Fucito Lisa M. , Toll Benjamin A.
Published: April 2023

Supplementary Data from Urgent Need for Novel Investigations of Treatments to Quit E-cigarettes: Findings from a Systematic Review
Supplementary Figure 1 from DNA Hypomethylation Contributes to Genomic Instability and Intestinal Cancer Initiation
Authors: Sheaffer Karyn L. , Elliott Ellen N. , Kaestner Klaus H.
Published: April 2023

Supplementary Figure 1. Experimental Schema: Conditional ablation of Dnmt1 in the ApcMin/+ intestinal epithelium ApcMin/+;Dnmt1loxP/loxP mice (controls) and ApcMin/+;Dnmt1loxP/loxP;Villin-Cre-ERT2 mice (mutants) were injected with tamoxifen at 4 weeks of age. Intestines were harvested one week or two months following tamoxifen treatment.
Supplementary Figure Legends from Chemoprevention of Azoxymethane-induced Colon Carcinogenesis by Delta-Tocotrienol
Authors: Husain Kazim , Zhang Anying , Shivers Steve , Davis-Yadley Ashley , Coppola Domenico , Yang Chung S. , Malafa Mokenge P.
Published: April 2023

This document contains the figure legends for Supplementary Figures 1-5.
Supplementary Figure 1 from Primary Care Provider Beliefs and Recommendations About Colorectal Cancer Screening in Four Healthcare Systems
Authors: Ghai Nirupa R. , Jensen Christopher D. , Merchant Sophie A. , Schottinger Joanne E. , Lee Jeffrey K. , Chubak Jessica , Kamineni Aruna , Halm Ethan A. , Skinner Celette Sugg , Haas Jennifer S. , Green Beverly B. , Cannizzaro Nancy T. , Schneider Jennifer L. , Corley Douglas A.
Published: April 2023

Supplementary Figure 1
Supplementary Figure S1 from The Quality of Pap Smears from the Brazilian Cervical Cancer Screening Program According to the Human Development Index
Authors: Costa Ricardo Filipe Alves , Longatto-Filho Adhemar , de Lima Vazquez Fabiana , Pinheiro Céline , Zeferino Luiz Carlos , Fregnani José Humberto Tavares Guerreiro
Published: April 2023

Supplementary Figure S1 shows the distribution of municipalities according to the Municipal Human Development Index (MHDI).
Supplementary Figure Legends from Celecoxib Alters the Intestinal Microbiota and Metabolome in Association with Reducing Polyp Burden
Authors: Montrose David C. , Zhou Xi Kathy , McNally Erin M. , Sue Erika , Yantiss Rhonda K. , Gross Steven S. , Leve Nitai D. , Karoly Edward D. , Suen Chen S. , Ling Lilan , Benezra Robert , Pamer Eric G. , Dannenberg Andrew J.
Published: April 2023

Supplementary Figure Legends.
Figure S1, Panel C and D from Celecoxib Alters the Intestinal Microbiota and Metabolome in Association with Reducing Polyp Burden
Authors: Montrose David C. , Zhou Xi Kathy , McNally Erin M. , Sue Erika , Yantiss Rhonda K. , Gross Steven S. , Leve Nitai D. , Karoly Edward D. , Suen Chen S. , Ling Lilan , Benezra Robert , Pamer Eric G. , Dannenberg Andrew J.
Published: April 2023

Data are rank transformed and displayed as color intensity with low levels indicated by green color and high levels indicated by red color.
Supplementary Figure 1 from A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia
Authors: Kuriakose Moni Abraham , Ramdas Kunnambath , Dey Bindu , Iyer Subramanya , Rajan Gunaseelan , Elango Kalavathy K. , Suresh Amritha , Ravindran Divya , Kumar Rajneesh R. , R Prathiba , Ramachandran Surya , Kumar Nisha Asok , Thomas Gigi , Somanathan Thara , Ravindran Hiran K. , Ranganathan Kannan , Katakam Sudhakar Babu , Parashuram Shivashankar , Jayaprakash Vijayvel , Pillai M. Radhakrishna
Published: April 2023

Patient disposition and clinical follow up results.
Supplementary Table 1 from Low Colorectal Cancer Screening Uptake and Persistent Disparities in an Underserved Urban Population
Authors: Ni Katherine , O'Connell Kelli , Anand Sanya , Yakoubovitch Stephanie C. , Kwon Simona C. , de Latour Rabia Ali , Wallach Andrew B. , Sherman Scott E. , Du Mengmeng , Liang Peter S.
Published: April 2023

Supplementary Table 1
Table S1 from Association Between Diet and Fusobacterium nucleatum in the Feces of Healthy Adults: A Hospital-based Cross-sectional Study
Authors: Narii Nobuhiro , Zha Ling , Sobue Tomotaka , Kitamura Tetsuhisa , Shiba Satoshi , Mizutani Sayaka , Yamada Takuji , Yachida Shinichi
Published: April 2023

Table S1: Odds ratios of the presence of F. nucleatum according to tertiles of intake of dairy products
Supplementary Table S3 from Trends and Factors Associated with Fecal Occult Blood Test Utilization among Hispanic Adults in Puerto Rico and the United States: BRFSS 2012–2020
Authors: Castaneda-Avila Maira A. , Oyinbo Atinuke G. , Epstein Mara M. , Ortiz-Ortiz Karen J. , Tortolero-Luna Guillermo , Lapane Kate L.
Published: April 2023

Supplementary Table S3 factors associated with blood stool test use for colorectal screening among Hispanic adults living in mainland US
Supplementary Table S5 from Safety Run-in of Intramuscular pNGVL4a-Sig/E7(detox)/HSP70 DNA and TA-CIN Protein Vaccination as Treatment for HPV16+ ASC-US, ASC-H, or LSIL/CIN1
Authors: Einstein Mark H. , Roden Richard B.S. , Ferrall Louise , Akin Mark , Blomer Allison , Wu T.C. , Chang Yung-Nien
Published: April 2023

Supplementary Table S5 shows the baseline blood counts and chemistry of study participants
Supplementary Table S4 from Safety Run-in of Intramuscular pNGVL4a-Sig/E7(detox)/HSP70 DNA and TA-CIN Protein Vaccination as Treatment for HPV16+ ASC-US, ASC-H, or LSIL/CIN1
Authors: Einstein Mark H. , Roden Richard B.S. , Ferrall Louise , Akin Mark , Blomer Allison , Wu T.C. , Chang Yung-Nien
Published: April 2023

Supplementary Table S4 shows respiratory rate of study participants at each visit, including immediately pre- and 30 minutes post-vaccination
Supplementary Table S3 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: April 2023

Supplementary Table S3 shows the distribution of differentially methylated regions (DMRs) in the promoter region in control vs. LPS and LPS vs. SAHA comparisons.
Supplementary Fig. S2 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: April 2023

Supplementary Fig. S2 shows the changes in metabolic profile after suberoylanilide hydroxamic acid (SAHA) treatment for 3 and 24 h.
Supplementary Table S3 from Simple Prediction Model for Colorectal Serrated Polyps: Development and External Validation Study in U.S. Prospective Cohorts
Authors: Lyu Zhangyan , Hang Dong , He Xiaosheng , Wu Kana , Cao Yin , Rosner Bernard , Chan Andrew T. , Ogino Shuji , Li Ni , Dai Min , Giovannucci Edward L. , Song Mingyang
Published: April 2023

Supplementary Table S3: Associations of the included predictors with the risk of high-risk SPs in the NHS and NHS2.
Supplementary Methods S1 from Validation of an Abridged Breast Cancer Risk Prediction Model for the General Population
Authors: Spaeth Erika L. , Dite Gillian S. , Hopper John L. , Allman Richard
Published: April 2023

Supplementary Methods S1 describes the calculation of the risk scores
Supplementary Figure S1 from Validation of an Abridged Breast Cancer Risk Prediction Model for the General Population
Authors: Spaeth Erika L. , Dite Gillian S. , Hopper John L. , Allman Richard
Published: April 2023

Supplementary Figure S1 shows the distributions of the 5-year risks for affected and unaffected women for each model
Data from NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project
Authors: Petrick Jessica L. , Sahasrabuddhe Vikrant V. , Chan Andrew T. , Alavanja Michael C. , Beane-Freeman Laura E. , Buring Julie E. , Chen Jie , Chong Dawn Q. , Freedman Neal D. , Fuchs Charles S. , Gaziano John Michael , Giovannucci Edward , Graubard Barry I. , Hollenbeck Albert R. , Hou Lifang , Jacobs Eric J. , King Lindsay Y. , Koshiol Jill , Lee I-Min , Linet Martha S. , Palmer Julie R. , Purdue Mark P. , Rosenberg Lynn , Schairer Catherine , Sesso Howard D. , Sigurdson Alice J. , Wactawski-Wende Jean , Zeleniuch-Jacquotte Anne , Campbell Peter T. , McGlynn Katherine A.
Published: April 2023

Abstract
Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57–0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42–0.98) but not women (HR, 1.34; 95% CI, 0.89–2.01; Pinteraction = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC. Cancer Prev Res; 8(12); 1156–62. ©2015 AACR.
Data from Chemoprevention of Colon and Small Intestinal Tumorigenesis in APCMin/+ Mice by Licofelone, a Novel Dual 5-LOX/COX Inhibitor: Potential Implications for Human Colon Cancer Prevention
Authors: Mohammed Altaf , Janakiram Naveena B. , Li Qian , Choi Chang-In , Zhang Yuting , Steele Vernon E. , Rao Chinthalapally V.
Published: April 2023

Abstract
Preclinical and clinical studies suggest that 5-lipoxygenase (5-LOX), such as COX-2, is a potential target for colon cancer inhibition and, in part, contributes to cardiovascular side effects associated with COX-2 inhibitors. Experiments were designed to assess the chemopreventive effects of a novel dual 5-LOX/COX inhibitor, licofelone {[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl] acetic acid}, in APCMin/+ mouse intestinal tumorigenesis. Six-week-old male and female APCMin/+ mice (n = 10 per group) were fed with control American Institute of Nutrition-76A diet or diets containing 150 or 300 ppm licofelone for 14 weeks (∼100 days), and intestinal tumors were evaluated for tumor multiplicity and size. Licofelone significantly inhibited total intestinal tumor multiplicity and size in a dose-dependent manner (P < 0.0001; mean tumors for 0, 150, and 300 ppm: 48.8, 17, and 8, respectively, in male mice; and 34.3, 8.8, and 5.5, respectively, in female mice). Licofelone at high dose showed more than 83% (P < 0.0001) tumor inhibition in both genders of mice. One hundred and fifty and 300 ppm licofelone resulted in 86% to 97% inhibition of polyps having size greater than 2 mm. One hundred and fifty and 300 ppm licofelone caused more than 72% and 100% inhibition of colonic tumors, respectively. Importantly, in mice fed with licofelone, tumors showed significantly reduced proliferating cell nuclear antigen expression (70%, P < 0.0001), increased terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling–positive cells (75%, P < 0.0001), and there was dose-dependent suppression of serum triglycerides (71%–83%, P < 0.0001), decreased inflammatory cytokines; and decreased COX and 5-LOX activities (57%–64%, P < 0.0001). Also, compared with 300 ppm celecoxib, 300 ppm licofelone provided better efficacy in suppressing tumor growth. These observations show that a novel dual 5-LOX/COX inhibitor dramatically suppresses small intestinal and colonic tumor formation in APCMin/+ mice. Cancer Prev Res; 4(12); 2015–26. ©2011 AACR.
Data from Inactivation of AR/TMPRSS2-ERG/Wnt Signaling Networks Attenuates the Aggressive Behavior of Prostate Cancer Cells
Authors: Li Yiwei , Kong Dejuan , Wang Zhiwei , Ahmad Aamir , Bao Bin , Padhye Subhash , Sarkar Fazlul H.
Published: April 2023

Abstract
The development of prostate cancer and its progression to castrate-resistant prostate cancer (CRPC) after antiandrogen ablation therapy are driven by persistent biological activity of androgen receptor (AR) signaling. Moreover, studies have shown that more than 50% of human prostate cancers overexpress ERG (v-ets avian erythroblastosis virus E26 oncogene related gene) due to AR-regulated TMPRSS2-ERG fusion gene. However, the reported roles of TMPRSS2-ERG fusion in cancer progression are not clear. In this study, we investigated the signal transduction in the AR/TMPRSS2-ERG/Wnt signaling network for studying the aggressive behavior of prostate cancer cells and further assessed the effects of BR-DIM and CDF [natural agents-derived synthetic formulation and analogue of 3,3′-diindolylmethane (DIM) and curcumin, respectively, with improved bioavailability] on the regulation of AR/TMPRSS2-ERG/Wnt signaling. We found that activation of AR resulted in the induction of ERG expression through TMPRSS2-ERG fusion. Moreover, we found that ERG overexpression and nuclear translocation activated the activity of Wnt signaling. Furthermore, forced overexpression of ERG promoted invasive capacity of prostate cancer cells. More important, we found that BR-DIM and CDF inhibited the signal transduction in the AR/TMPRSS2-ERG/Wnt signaling network, leading to the inactivation of Wnt signaling consistent with inhibition of prostate cancer cell invasion. In addition, BR-DIM and CDF inhibited proliferation of prostate cancer cells and induced apoptotic cell death. On the basis of our findings, we conclude that because BR-DIM and CDF downregulate multiple signaling pathways including AR/TMPRSS2-ERG/Wnt signaling, these agents could be useful for designing novel strategies for the prevention and/or treatment of prostate cancer. Cancer Prev Res; 4(9); 1495–506. ©2011 AACR.
Data from Metformin Inhibits Cell Proliferation, Migration and Invasion by Attenuating CSC Function Mediated by Deregulating miRNAs in Pancreatic Cancer Cells
Authors: Bao Bin , Wang Zhiwei , Ali Shadan , Ahmad Aamir , Azmi Asfar S. , Sarkar Sanila H. , Banerjee Sanjeev , Kong Dejuan , Li Yiwei , Thakur Shivam , Sarkar Fazlul H.
Published: April 2023

Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, which is, in part, due to intrinsic (de novo) and extrinsic (acquired) resistance to conventional therapeutics, suggesting that innovative treatment strategies are required for overcoming therapeutic resistance to improve overall survival of patients. Oral administration of metformin in patients with diabetes mellitus has been reported to be associated with reduced risk of pancreatic cancer and that metformin has been reported to kill cancer stem cells (CSC); however, the exact molecular mechanism(s) has not been fully elucidated. In the current study, we examined the effect of metformin on cell proliferation, cell migration and invasion, and self-renewal capacity of CSCs and further assessed the expression of CSC marker genes and microRNAs (miRNA) in human pancreatic cancer cells. We found that metformin significantly decreased cell survival, clonogenicity, wound-healing capacity, sphere-forming capacity (pancreatospheres), and increased disintegration of pancreatospheres in both gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells. Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres. We also found that reexpression of miR-26a by transfection led to decreased expression of EZH2 and EpCAM in pancreatic cancer cells. These results clearly suggest that the biologic effects of metformin are mediated through reexpression of miRNAs and decreased expression of CSC-specific genes, suggesting that metformin could be useful for overcoming therapeutic resistance of pancreatic cancer cells. Cancer Prev Res; 5(3); 355–64. ©2011 AACR.
Data from Methylselenocysteine Resets the Rhythmic Expression of Circadian and Growth-Regulatory Genes Disrupted by Nitrosomethylurea In vivo
Authors: Fang Ming Zhu , Zhang Xun , Zarbl Helmut
Published: April 2023

Abstract
Epidemiologic and animal studies indicate that disruption of circadian rhythm increases breast cancer risk. Previously, we showed that methylselenocysteine reduced the incidence of N-nitroso-N-methylurea (NMU)–induced mammary carcinomas in Fischer 344 rats by 63%. Methylselenocysteine also increased the expression of Period 2 (Per2) and D-binding protein (DBP), providing evidence for a link between circadian rhythm and chemoprevention. Here, we report that NMU disrupted the expression of core circadian genes (Per1, Per2, Cry1, Cry2, and RevErbAα) and circadian-controlled genes, including melatonin receptor 1α (MTNR1A), estrogen receptors (ERα and ERβ), and growth-regulatory genes (Trp53, p21, Gadd45α, and c-Myc) in mammary glands of Fischer 344 rats. By contrast, dietary methylselenocysteine (3 ppm selenium) given for 30 days, significantly enhanced the circadian expression of these genes (except for Cry1 and Cry2). The largest effect was on the levels of the Per2, MTNR1A, and ERβ mRNAs, which showed 16.5-fold, 4.7-fold, and 9.5-fold increases in their rhythm-adjusted means, respectively, and 44.5-fold, 6.5-fold, and 9.7-fold increases in amplitude as compared with the control diet, respectively. Methylselenocysteine also shifted the peak expression times of these genes to Zeitgeber time 12 (ZT12; lights off). Methylselenocysteine also induced rhythmic expression of Trp53, p21, and Gadd45α mRNAs with peak levels at ZT12, when c-Myc expression was at its lowest level. However, methylselenocysteine had no significant effect on the circadian expression of these genes in liver. These results suggest that dietary methylselenocysteine counteracted the disruptive effect of NMU on circadian expression of genes essential to normal mammary cell growth and differentiation. Cancer Prev Res; 3(5); 640–52. ©2010 AACR.
Data from Chronic Nicotine Consumption Does Not Influence 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone–Induced Lung Tumorigenesis
Authors: Murphy Sharon E. , von Weymarn Linda B. , Schutten Melissa M. , Kassie Fekadu , Modiano Jaime F.
Published: April 2023

Abstract
Nicotine replacement therapy is often used to maintain smoking cessation. However, concerns exist about the safety of long-term nicotine replacement therapy use in ex-smokers and its concurrent use in smokers. In this study, we determined the effect of nicotine administration on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumors in A/J mice. Female mice were administered a single dose of NNK (10 μmol) and 0.44 μmol/mL nicotine in the drinking water. Nicotine was administered 2 weeks prior to NNK, 44 weeks after NNK, throughout the experiment, or without NNK treatment. The average weekly consumption of nicotine-containing water was 15 ± 3 mL per mouse, resulting in an estimated daily nicotine dose of 0.9 μmol (0.15 mg) per mouse. Nicotine administration alone for 46 weeks did not increase lung tumor multiplicity (0.32 ± 0.1 vs. 0.53 ± 0.1 tumors per mouse). Lung tumor multiplicity in NNK-treated mice was 18.4 ± 4.5 and was not different for mice consuming nicotine before or after NNK administration, 21.9 ± 5.3 and 20.0 ± 5.4 tumors per mouse, respectively. Lung tumor multiplicity in animals consuming nicotine both before and after NNK administration was 20.4 ± 5.4. Tumor size and progression of adenomas to carcinomas was also not affected by nicotine consumption. In addition, nicotine consumption had no effect on the level of O6-methylguanine in the lung of NNK-treated mice. These negative findings in a commonly used model of human lung carcinogenesis should lead us to question the interpretation of the many in vitro studies that find that nicotine stimulates cancer cell growth. Cancer Prev Res; 4(11); 1752–60. ©2011 AACR.
Data from Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis in Male Mice through Activation of the Wnt/β-Catenin Signaling Pathway
Authors: Mercer Kelly E. , Hennings Leah , Sharma Neha , Lai Keith , Cleves Mario A. , Wynne Rebecca A. , Badger Thomas M. , Ronis Martin J.J.
Published: April 2023

Abstract
Although alcohol effects within the liver have been extensively studied, the complex mechanisms by which alcohol causes liver cancer are not well understood. It has been suggested that ethanol (EtOH) metabolism promotes tumor growth by increasing hepatocyte proliferation. In this study, we developed a mouse model of tumor promotion by chronic EtOH consumption in which EtOH feeding began 46 days after injection of the chemical carcinogen diethylnitrosamine (DEN) and continued for 16 weeks. With a final EtOH concentration of 28% of total calories, we observed a significant increase in the total number of preneoplastic foci and liver tumors per mouse in the EtOH+DEN group compared with corresponding pair-fed (PF)+DEN and chow+DEN control groups. We also observed a 4-fold increase in hepatocyte proliferation (P < 0.05) and increased cytoplasmic staining of active-β-catenin in nontumor liver sections from EtOH+DEN mice compared with PF+DEN controls. In a rat model of alcohol-induced liver disease, we found increased hepatocyte proliferation (P < 0.05); depletion of retinol and retinoic acid stores (P < 0.05); increased expression of cytosolic and nuclear expression of β-catenin (P < 0.05) and phosphorylated-glycogen synthase kinase 3β (p-GSK3β), P < 0.05; significant upregulation in Wnt7a mRNA expression; and increased expression of several β-catenin targets, including, glutamine synthetase (GS), cyclin D1, Wnt1 inducible signaling pathways protein (WISP1), and matrix metalloproteinase-7(MMP7), P < 0.05. These data suggest that chronic EtOH consumption activates the Wnt/β-catenin signaling pathways to increase hepatocyte proliferation, thus promoting tumorigenesis following an initiating insult to the liver. Cancer Prev Res; 7(7); 675–85. ©2014 AACR.
Data from Lung-Cancer Chemoprevention by Induction of Synthetic Lethality in Mutant KRAS Premalignant Cells In Vitro and In Vivo
Authors: Huang Shaoyi , Ren Xiaoyang , Wang Lai , Zhang Ling , Wu Xiangwei
Published: April 2023

Abstract
Lung cancer is the leading cause of cancer death in both men and women in the United States, with a low 5-year survival rate despite improved treatment strategies. These data underscore the great need for effective chemoprevention of this cancer. Mutations and activation of KRAS occur frequently in, and are thought to be a primary driver of the development of, non–small cell lung cancers (NSCLC) of the adenocarcinoma subtype. In this study, we developed a new approach for the chemoprevention of NSCLC involving specific targeting of apoptosis in mutant KRAS cells. This approach is based on a synthetic lethal interaction among TNF-related apoptosis-inducing ligand (TRAIL), the second mitochondria-derived activator of caspase Smac/DIABLO (Smac), and KRAS. Mutational activation of KRAS modulated the expression of TRAIL receptors by upregulating death receptors and downregulating decoy receptors. Furthermore, oncogenic KRAS repressed cellular FADD-like interleukin 1β–converting enzyme (FLICE)-like inhibitory protein (c-FLIP) expression through activation of Erk/mitogen-activated protein kinase (MAPK)-mediated activation of c-Myc. Smac overcame KRAS-induced cell-survival signaling by antagonizing X-linked inhibitor of apoptosis protein (XIAP). Therefore, the combination of TRAIL and a small molecule mimic of Smac induced apoptosis specifically in mutant KRAS cells without harming normal cells. We further showed that short-term, intermittent in vivo treatment with TRAIL and Smac mimic induced apoptosis in tumor cells and reduced tumor burden in a murine model of KRAS-induced lung cancer. These results reflect the potential benefit of a selective therapeutic approach for the chemoprevention of NSCLC. Cancer Prev Res; 4(5); 666–73. ©2011 AACR.
Data from One-Hit Effects and Cancer
Authors: Iniesta Maria D. , Chien Janet , Wicha Max , Merajver Sofia D.
Published: April 2023

Abstract
This perspective on Bellacosa et al. (beginning on p. 48 in this issue of the journal) discusses the important biology of microscopically normal tissues in carriers of germ-line BRCA1 or BRCA2 mutations. The work of Bellacosa et al. is an important step toward discerning which pathways may be altered when one BRCA allele is inactivated. Cancer Prev Res; 3(1); 12–5
Data from Get the Fat Out!
Authors: Ignatenko Natalia A. , Gerner Eugene W.
Published: April 2023

Abstract
Obesity is associated with increased risk of a number of cancers in humans, but the mechanism(s) responsible for these associations have not been established. It is estimated that 68% of adults are overweight or obese and that obesity may be causative in 4% to 7% of cancers in the United States. Several hypotheses have been put forward to explain the association between obesity and cancer including adipose-directed signaling (e.g., mTOR, AMPK), production of factors (e.g., insulin growth factor 1, fibroblast growth factor 1, and/or chronic inflammation associated with obesity. Huffman and colleagues used surgical methods to determine if visceral fat was causally related to intestinal tumorigenesis in the Apc1638/N+ mouse in a manner independent of confounding factors such as caloric restriction. They found that caloric restriction could extend survival in both male and female Apc1638/N+ mice but found that surgical removal of visceral fat was only effective in reducing macroadenomas in females. The results of this study do not identify the specific mechanism of association between visceral fat and intestinal carcinogenesis in female mice but do support the rationale for future cancer prevention trials that evaluate pharmacologic and behavioral strategies to reduce abdominal obesity in humans. Cancer Prev Res; 6(3); 161–4. ©2013 AACR.
Data from Interphase Cytogenetics of Sputum Cells for the Early Detection of Lung Carcinogenesis
Authors: Prindiville Sheila A. , Ried Thomas
Published: April 2023

Abstract
This perspective on Varella-Garcia et al. (beginning on p. 447 in this issue of the journal) examines the role of interphase fluorescence in situ hybridization for the early detection of lung cancer. This work is an important step toward identifying and validating a molecular marker in sputum samples for lung cancer early detection and highlights the value of establishing cohort studies with biorepositories of samples collected from participants followed over time for disease development. Cancer Prev Res; 3(4); 416–9. ©2010 AACR.
Data from Topical Treatment with Black Raspberry Extract Reduces Cutaneous UVB-Induced Carcinogenesis and Inflammation
Authors: Duncan F J. , Martin Jason R. , Wulff Brian C. , Stoner Gary D. , Tober Kathleen L. , Oberyszyn Tatiana M. , Kusewitt Donna F. , Van Buskirk Anne M.
Published: April 2023

Abstract
Light in the UVB spectrum (280-320 nm) induces a number of changes in the epidermis and dermis of mice and humans, resulting in a robust inflammatory response. A standardized black raspberry extract (BRE) has been effective in reducing signaling pathways commonly initiated by inflammatory stimuli. In this study, we determined whether this extract could reduce cutaneous UVB-induced inflammation and carcinogenesis. In our carcinogenesis model, female SKH-1 hairless mice were exposed to one minimal erythemal dose of UVB thrice weekly on nonconsecutive days for 25 weeks. Immediately after each exposure, the mice were treated topically with either BRE dissolved in vehicle or with vehicle only. Beginning on week 19, mice treated with BRE had a significant reduction in tumor number and in average tumor size. This reduction correlated with a significant reduction in tumor-infiltrating CD3+foxp3+ regulatory T-cells. In the acute model, mice were exposed to a single minimal erythemal dose of UVB and treated topically with BRE or with vehicle. At 48 hours post-UVB exposure, topical BRE treatment significantly reduced edema, p53 protein levels, oxidative DNA damage, and neutrophil activation. The ability of topical BRE to reduce acute UVB-induced inflammation and to decrease tumor development in a long-term model provides compelling evidence to explore the clinical efficacy of BRE in the prevention of human skin cancers.
Data from 6-Shogaol from Dried Ginger Inhibits Growth of Prostate Cancer Cells Both In Vitro and In Vivo through Inhibition of STAT3 and NF-κB Signaling
Authors: Saha Achinto , Blando Jorge , Silver Eric , Beltran Linda , Sessler Jonathan , DiGiovanni John
Published: April 2023

Abstract
Despite much recent progress, prostate cancer continues to represent a major cause of cancer-related mortality and morbidity in men. Prostate cancer is the most common nonskin neoplasm and second leading cause of death in men. 6-Shogaol (6-SHO), a potent bioactive compound in ginger (Zingiber officinale Roscoe), has been shown to possess anti-inflammatory and anticancer activity. In the present study, the effect of 6-SHO on the growth of prostate cancer cells was investigated. 6-SHO effectively reduced survival and induced apoptosis of cultured human (LNCaP, DU145, and PC3) and mouse (HMVP2) prostate cancer cells. Mechanistic studies revealed that 6-SHO reduced constitutive and interleukin (IL)-6–induced STAT3 activation and inhibited both constitutive and TNF-α–induced NF-κB activity in these cells. In addition, 6-SHO decreased the level of several STAT3 and NF-κB–regulated target genes at the protein level, including cyclin D1, survivin, and cMyc and modulated mRNA levels of chemokine, cytokine, cell cycle, and apoptosis regulatory genes (IL-7, CCL5, BAX, BCL2, p21, and p27). 6-SHO was more effective than two other compounds found in ginger, 6-gingerol, and 6-paradol at reducing survival of prostate cancer cells and reducing STAT3 and NF-κB signaling. 6-SHO also showed significant tumor growth inhibitory activity in an allograft model using HMVP2 cells. Overall, the current results suggest that 6-SHO may have potential as a chemopreventive and/or therapeutic agent for prostate cancer and that further study of this compound is warranted. Cancer Prev Res; 7(6); 627–38. ©2014 AACR.
Data from Hepatitis B Virus X Protein Stabilizes Cyclin D1 and Increases Cyclin D1 Nuclear Accumulation through ERK-Mediated Inactivation of GSK-3β
Authors: Chen Xiangmei , Zhang Ling , Zheng Sujun , Zhang Ting , Li Meng , Zhang Xiaolei , Zeng Zhenzhen , McCrae Malcolm A. , Zhao Jingmin , Zhuang Hui , Lu Fengmin
Published: April 2023

Abstract
The Hepatitis B virus X protein (HBx) contributes centrally to the pathogenesis of hepatocellular carcinoma (HCC). It has been suggested that the transcriptional activation of cyclin D1 by HBx is implicated in the development of HCC. However, numerous studies have shown that overexpression of cyclin D1 alone is not sufficient to drive oncogenic transformation. Herein, we investigated whether HBx can stabilize cyclin D1 and induce cyclin D1 protein nuclear accumulation, and thereby accelerate hepatocarcinogenesis. The effects of HBx on cyclin D1 stabilization were assessed in cell-based transfection, Western blot, immunoprecipitation, immunocytofluorescence staining, and flow-cytometric assays. The results demonstrated that ectopic expression of HBx in HCC cells could extend the half-life of cyclin D1 protein from 40–60 minutes to 80–110 minutes. HBx stabilized cyclin D1 primarily in the S phase of the cell cycle, in a manner dependent on the inactivation of GSK-3β, which was mediated by ERK activation. HBx also prompted the nuclear accumulation of cyclin D1, and cotransfection of the constitutively active mutant of GSK-3β along with HBx could reverse the nuclear accumulation and subsequent cell proliferation induced by HBx. Further, a positive correlation between HBx and nuclear cyclin D1 level was established in HCC specimens detected by an immunohistochemical assay. Taken together, our results indicated that HBx could stabilize and increase cyclin D1 nuclear accumulation through ERK-mediated inactivation of GSK-3β. This HBx-induced cyclin D1 upregulation might play an important role in HCC development and progression. Cancer Prev Res; 8(5); 455–63. ©2015 AACR.