bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure 2 from HIST1H2BB and MAGI2 Methylation and Somatic Mutations as Precision Medicine Biomarkers for Diagnosis and Prognosis of High-grade Serous Ovarian Cancer
Authors: Valle Blanca L. , Rodriguez-Torres Sebastian , Kuhn Elisabetta , Díaz-Montes Teresa , Parrilla-Castellar Edgardo , Lawson Fahcina P. , Folawiyo Oluwasina , Ili-Gangas Carmen , Brebi-Mieville Priscilla , Eshleman James R. , Herman James , Shih Ie-Ming , Sidransky David , Guerrero-Preston Rafael
Published: April 2023

Supplementary Figure 2
Supplementary Table 3 from Estimating the Breast Cancer Burden in Germany and Implications for Risk-based Screening
Authors: Quante Anne S. , Hüsing Anika , Chang-Claude Jenny , Kiechle Marion , Kaaks Rudolf , Pfeiffer Ruth M.
Published: April 2023

Supplementary Table 3
Supplementary Table 2 from Estimating the Breast Cancer Burden in Germany and Implications for Risk-based Screening
Authors: Quante Anne S. , Hüsing Anika , Chang-Claude Jenny , Kiechle Marion , Kaaks Rudolf , Pfeiffer Ruth M.
Published: April 2023

Supplementary Table 2
Supplementary tables 1 and 2 from Dietary Weight Loss, Exercise, and Oxidative Stress in Postmenopausal Women: A Randomized Controlled Trial
Authors: Duggan Catherine , Tapsoba Jean de Dieu , Wang Ching-Yun , Campbell Kristin L. , Foster-Schubert Karen , Gross Myron D. , McTiernan Anne
Published: April 2023

Supplemental Table 1 Change in levels of analytes by tertiles of percent change in body fat, compared to controls and Change in levels of analytes by tertiles of in-person nutrition session attendance, compared to controls
Supplementary Table 1 from Estimating the Breast Cancer Burden in Germany and Implications for Risk-based Screening
Authors: Quante Anne S. , Hüsing Anika , Chang-Claude Jenny , Kiechle Marion , Kaaks Rudolf , Pfeiffer Ruth M.
Published: April 2023

Supplementary Table 1
Supplementary Table from Aspirin-Mediated Prevention of Colorectal Adenomas Recurrence is Affected by Blood Biochemistry and Nutritional Intake
Authors: Yoshida Naohisa , Ishikawa Hideki , Otani Takahiro , Goto Chiho , Matsuda Takahisa , Takeuchi Yoji , Sano Yasushi , Itoh Yoshito , Suzuki Sadao , Mutoh Michihiro
Published: April 2023

Supplementary Table from Aspirin-Mediated Prevention of Colorectal Adenomas Recurrence is Affected by Blood Biochemistry and Nutritional Intake
Supplementary Figure from Aspirin-Mediated Prevention of Colorectal Adenomas Recurrence is Affected by Blood Biochemistry and Nutritional Intake
Authors: Yoshida Naohisa , Ishikawa Hideki , Otani Takahiro , Goto Chiho , Matsuda Takahisa , Takeuchi Yoji , Sano Yasushi , Itoh Yoshito , Suzuki Sadao , Mutoh Michihiro
Published: April 2023

Supplementary Figure from Aspirin-Mediated Prevention of Colorectal Adenomas Recurrence is Affected by Blood Biochemistry and Nutritional Intake
Figure S5 from Temporal Efficacy of a Sulforaphane-Based Broccoli Sprout Diet in Prevention of Breast Cancer through Modulation of Epigenetic Mechanisms
Authors: Li Yuanyuan , Buckhaults Phillip , Li Shizhao , Tollefsbol Trygve
Published: April 2023

Gene expressions of Dnmt3a and Dnmt3b, and global DNA methylation change in response to the prenatal/maternal-BSp treatment.
Figure S2 from Temporal Efficacy of a Sulforaphane-Based Broccoli Sprout Diet in Prevention of Breast Cancer through Modulation of Epigenetic Mechanisms
Authors: Li Yuanyuan , Buckhaults Phillip , Li Shizhao , Tollefsbol Trygve
Published: April 2023

RNA sequencing data
Figure S1 from Temporal Efficacy of a Sulforaphane-Based Broccoli Sprout Diet in Prevention of Breast Cancer through Modulation of Epigenetic Mechanisms
Authors: Li Yuanyuan , Buckhaults Phillip , Li Shizhao , Tollefsbol Trygve
Published: April 2023

Broccoli sprout (BSp) diet nutritional profile
Supplementary Methods from The Effect of Mouse Strain, Sex, and Carcinogen Dose on Toxicity and the Development of Lung Dysplasia and Squamous Cell Carcinomas in Mice
Authors: Riolobos Laura , Gad Ekram A. , Treuting Piper M. , Timms Andrew E. , Hershberg Elliot A. , Corulli Lauren R. , Rodmaker Erin , Disis Mary L.
Published: April 2023

Supplementary Methods
Supplementary Table from δ-Tocotrienol is the Most Potent Vitamin E Form in Inhibiting Prostate Cancer Cell Growth and Inhibits Prostate Carcinogenesis in Ptenp−/− Mice
Authors: Wang Hong , Yan William , Sun Yuhai , Yang Chung S.
Published: April 2023

Supplementary Table from δ-Tocotrienol is the Most Potent Vitamin E Form in Inhibiting Prostate Cancer Cell Growth and Inhibits Prostate Carcinogenesis in Ptenp−/− Mice
Supplementary Figure 3 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 3. Neoplastic lesions found in Dnmt1 mutant mice are predominantly adenomas. (A,B) Histopathological scoring methods were used to count total number of lesions displaying gastrointestinal intraepithelial neoplasia (GIN) and adenoma, in mutant and control mice one-month (A) and two months (B) following tamoxifen injection (n=3-8 per group). Intestines were isolated, fixed and embedded in paraffin. One representative section was stained with H&E for each animal. Histopathological scoring was performed using the guidelines published by Boivin et al. (25) by the Comparative Pathology Core at the University of Pennsylvania School of Veterinary Medicine. Data are presented as average{plus minus}SEM; *P<0.05,**P<0.01 by Students's t-test.
Supplementary Table 1 from A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia
Authors: Lam Stephen , Mandrekar Sumithra J. , Gesthalter Yaron , Allen Ziegler Katie L. , Seisler Drew K. , Midthun David E. , Mao Jenny T. , Aubry Marie Christine , McWilliams Annette , Sin Don D. , Shaipanich Tawimas , Liu Gang , Johnson Evan , Bild Andrea , Lenburg Marc E. , Ionescu Diana N. , Mayo John , Yi Joanne (Eunhee) , Tazelaar Henry , Harmsen William S. , Smith Judith , Spira Avrum E. , Beane Jennifer , Limburg Paul J. , Szabo Eva
Published: April 2023

Supplementary data
Supplemental Table 1 from Cancer-related Beliefs and Preventive Health Practices among Residents of Rural versus Urban Counties in Alabama
Authors: Aly Salma , Daniel Casey L. , Bae Sejong , Scarinci Isabel C. , Hardy Claudia M. , Fouad Mona N. , Baskin Monica L. , Hoenemeyer Teri , Acemgil Aras , Demark-Wahnefried Wendy
Published: April 2023

Supplemental Table 1
Supplementary Figure from Reversing the Genomic, Epigenetic, and Triple-Negative Breast Cancer–Enhancing Effects of Obesity
Authors: Bowers Laura W. , Doerstling Steven S. , Shamsunder Meghana G. , Lineberger Claire G. , Rossi Emily L. , Montgomery Stephanie A. , Coleman Michael F. , Gong Weida , Parker Joel S. , Howell Anthony , Harvie Michelle , Hursting Stephen D.
Published: April 2023

Supplementary Figure from Reversing the Genomic, Epigenetic, and Triple-Negative Breast Cancer–Enhancing Effects of Obesity
Supplementary Figure 3 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 3
Figure S1 from Pharmacological TLR4 Antagonism Using Topical Resatorvid Blocks Solar UV-Induced Skin Tumorigenesis in SKH-1 Mice
Authors: Blohm-Mangone Karen , Burkett Nichole B. , Tahsin Shekha , Myrdal Paul B. , Aodah Alhassan , Ho Brenda , Janda Jaroslav , McComas Michelle , Saboda Kathylynn , Roe Denise J. , Dong Zigang , Bode Ann M. , Petricoin Emanuel F. , Calvert Valerie S. , Curiel-Lewandrowski Clara , Alberts David S. , Wondrak Georg T. , Dickinson Sally E.
Published: April 2023

Staining for Ki67 in mouse tumors.
Supplementary Figure 2 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 2
Supplementary Data from Prevention of Skin Carcinogenesis by the Non-β-blocking R-carvedilol Enantiomer
Authors: Liang Sherry , Shamim Md Abdullah , Shahid Ayaz , Chen Mengbing , Cleveland Kristan H. , Parsa Cyrus , Orlando Robert , Andresen Bradley T. , Huang Ying
Published: April 2023

Primer sequence
Supplementary Data 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

Supplemental Tables
Supplementary Table 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 Table S1 shows the number of exams in the target age (25-64 years) according to Brazilian Municipal Human Development Index, from 2006 to 2014.
Figure S2 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

Pathway alterations associated with celecoxib-induced metabolite changes in WT mice.
Supplementary tables 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

Supplementary Table ST1: Results of clinical, histological and combined response evaluation Supplementary Table ST2: Results of clinical response only in patients who have 6 month clinical evaluation completed. Supplementary Table ST3: Summary of association between Clinical and Histological response at 6 months for Curcumin group Supplementary Table ST4: Result of longer-term treatment in subjects with partial response. Supplementary Table ST5: Number and Percentage of Patients with Treatment-Emergent Adverse Events during the Study (Safety Population) Supplementary Table ST6: Summary of results of two systematic review and meta-analysis of chemoprevention trial of oral leukoplakia (26, 27).
Supplementary Figure 2 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

Clinical appearance of different leukoplakia.
Table S1B from Black Raspberry Inhibits Oral Tumors in Mice Treated with the Tobacco Smoke Constituent Dibenzo(def,p)chrysene Via Genetic and Epigenetic Alterations
Authors: Chen Kun-Ming , Sun Yuan-Wan , Kawasawa Yuka Imamura , Salzberg Anna C. , Zhu Junjia , Gowda Krishne , Aliaga Cesar , Amin Shantu , Atkins Hannah , El-Bayoumy Karam
Published: April 2023

Hypomethylated loci identified in oral tissues of mice treated with DBP and fed control diet or mice treated with DBP and fed 5% BRB diet.
Supplementary Table 1 from Fluvastatin Inhibits HMG-CoA Reductase and Prevents Non–Small Cell Lung Carcinogenesis
Authors: Zhang Tianshun , Bai Ruihua , Wang Qiushi , Wang Keke , Li Xiang , Liu Kangdong , Ryu Joohyun , Wang Ting , Chang Xiaoyu , Ma Weiya , Bode Ann M. , Xia Qingxin , Song Yongping , Dong Zigang
Published: April 2023

Supplementary Table 1
Supplementary Figures S1-7 from Fluvastatin Inhibits HMG-CoA Reductase and Prevents Non–Small Cell Lung Carcinogenesis
Authors: Zhang Tianshun , Bai Ruihua , Wang Qiushi , Wang Keke , Li Xiang , Liu Kangdong , Ryu Joohyun , Wang Ting , Chang Xiaoyu , Ma Weiya , Bode Ann M. , Xia Qingxin , Song Yongping , Dong Zigang
Published: April 2023

Figure S1-7
Supplementary Tables from Complementary Longitudinal Serum Biomarkers to CA125 for Early Detection of Ovarian Cancer
Authors: Simmons Archana R. , Fourkala Evangelia Ourania , Gentry-Maharaj Aleksandra , Ryan Andy , Sutton Margie N. , Baggerly Keith , Zheng Hui , Lu Karen H. , Jacobs Ian , Skates Steven , Menon Usha , Bast Robert C.
Published: April 2023

Tables 1-4
Tables S1 to S4 from Addressing Disparities in Cancer Screening among U.S. Immigrants: Progress and Opportunities
Authors: Fang Carolyn Y. , Ragin Camille C.
Published: April 2023

Supplementary Tables
Supplementary Table 7 from Do Aspirin and Other NSAIDs Confer a Survival Benefit in Men Diagnosed with Prostate Cancer? A Pooled Analysis of NIH-AARP and PLCO Cohorts
Authors: Zhou Cindy Ke , Daugherty Sarah E. , Liao Linda M. , Freedman Neal D. , Abnet Christian C. , Pfeiffer Ruth , Cook Michael B.
Published: April 2023

Four-level frequency of post-diagnostic NSAID use in relation to mortality.
Supplemental Figure 3 from Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis
Authors: Jiang Guosong , Wu Amy D. , Huang Chao , Gu Jiayan , Zhang Liping , Huang Haishan , Liao Xin , Li Jingxia , Zhang Dongyun , Zeng Xingruo , Jin Honglei , Huang Haojie , Huang Chuanshu
Published: April 2023

The MMP-2 stable transfectant and its vector control transfectant were subjected to cell migration and invasion assay in presence of either vehicle or 20 μM of ISO for 24 hours.
R script from Inhibition of miR-21 Regulates Mutant KRAS Effector Pathways and Intercepts Pancreatic Ductal Adenocarcinoma Development
Authors: Chu Nina J. , Anders Robert A. , Fertig Elana J. , Cao Minwei , Hopkins Alexander C. , Keenan Bridget P. , Popovic Aleksandra , Armstrong Todd D. , Jaffee Elizabeth M. , Zimmerman Jacquelyn W.
Published: April 2023

R script of TCGA computational analysis
Table S2 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 S2: Odds ratios of a high level of F. nucleatum according to tertiles of intake of each dietary food and nutrient
Figure 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

Figure S1: Relative abundance of F. nucleatum
Supplementary Table S2 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 S2 shows Systolic blood pressure of study participants at each visit, including immediately pre- and 30 minutes post-vaccination
Supplementary Table S4 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 S4 shows the genes analyzed for significant differential expression in control vs. LPS and LPS vs. SAHA groups.
Supplementary Fig. S1 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. S1 shows the top metabolites regulated by suberoylanilide hydroxamic acid (SAHA) treatment in lipopolysaccharide (LPS)-treated BEAS-2B cells.
Supplementary Materials 1 from Determinants of Lung Cancer Screening in a Minnesota Urban Indigenous Community: A Community-Based, Participatory, Action-Oriented Study
Authors: Anderson Madison D. , Pickner Wyatt J. , Begnaud Abbie
Published: April 2023

Supplementary Materials 1: Patient Participant Focus Group Questions
Supplementary Table S1 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 S1: Characteristics of study participants in the NHS and NHS2 by high-risk SPs.
Supplementary Table S2 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 Table S2 shows the study eligibility criteria
Supplementary Figure 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 Figure S3: The calibration plot of the simple risk prediction model for a composite endpoint of high-risk high-risk serrated polyps (SPs) and high-risk conventional adenoma (HRAs) across deciles of predicted risk in women and men.
Supplementary Table 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 Table S1 shows the relative risks assigned for first-degree family history of breast cancer
Supplementary Figure S1 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 Figure S1: The flowchart for inclusion and exclusion of study participants in the NHS, NHS2, and HPFS.
Supplemental Table 1 from Breastfeeding and Mammographic Breast Density: A Cross-sectional Study
Authors: Getz Kayla R. , Adedokun Babatunde , Xu Shuai , Toriola Adetunji T.
Published: April 2023

Supplemental Table 1 shows results from IPW analysis.
Data from Transcriptional Attenuation in Colon Carcinoma Cells in Response to Butyrate
Authors: Daroqui Maria C. , Augenlicht Leonard H.
Published: April 2023

Abstract
The short-chain fatty acid sodium butyrate (NaB), produced in the colonic lumen, induces cell cycle arrest, differentiation, and/or apoptosis in colorectal carcinoma cells in vitro, establishing a potential role for NaB in colon cancer prevention. We have previously shown that butyrate decreases cyclin D1 and c-myc expression, each essential for intestinal tumor development, by transcriptional attenuation. Here, we determined that butyrate-induced transcriptional attenuation of the cyclin D1 and c-myc genes in SW837 human colorectal adenocarcinoma cells occurs at ∼100 nucleotides downstream of the transcription start site, with a similar positioning in Caco-2 cells. A concomitant decrease in RNA polymerase II occupancy at the 5′ end of each gene was observed. Because transcriptional regulation is associated with chromatin remodeling, we investigated by chromatin immunoprecipitation whether the histone deacetylase inhibitory activity of butyrate altered chromatin structure at the attenuated loci. Although the distributions of histone H3 trimethylated on K4 and K36 along the cyclin D1 and c-myc genes were consistent with current models, butyrate induced only modest decreases in these modifications, with a similar effect on acetylated H3 and a modest increase in histone H3 trimethylated on K27. Finally, transcriptome analysis using novel microarrays showed that butyrate-induced attenuation is widespread throughout the genome, likely independent of transcriptional initiation. We identified 42 loci potentially paused by butyrate and showed that the transcription patterns are gene specific. The biological functions of these loci encompass a number of effects of butyrate on the physiology of intestinal epithelial cells. Cancer Prev Res; 3(10); 1292–302. ©2010 AACR.
Data from EZH2 Promotes Malignant Phenotypes and Is a Predictor of Oral Cancer Development in Patients with Oral Leukoplakia
Authors: Cao Wei , Younis Rania H. , Li Jiang , Chen Haiyan , Xia Ronghui , Mao Li , Chen Wantao , Ren Hening
Published: April 2023

Abstract
Oral leukoplakia (OL) is the most common premalignancy in the oral cavity. A small proportion of OLs progresses to oral squamous cell carcinoma (OSCC). To assess OSCC risk of OLs, we investigated the role of the transcriptional repressor enhancer of zeste homolog 2 (EZH2) in oral tumorigenesis and its clinical implication as an OSCC risk predictor. Immunohistochemistry was used to measure EZH2 expression in OLs from 76 patients, including 37 who later developed OSCC and 39 who did not. EZH2 expression was associated with clinicopathologic parameters and clinical outcomes. To determine the biological role of EZH2 in OL, EZH2 level was reduced using EZH2 siRNAs in Leuk-1 cells, its impact on cell cycle, anchorage-dependent/independent growth, and invasion was assessed. We observed strong EZH2 expression in 34 (45%), moderate expression in 26 (34%), and weak/no expression in 16 (21%) of the OLs. The higher EZH2 levels were strongly associated with dysplasia (P < 0.001) and OSCC development (P < 0.0001). Multivariate analysis indicated that EZH2 expression was the only independent factor for OSCC development (P < 0.0001). At 5 years after diagnosis, 80% of patients whose OLs expressed strong EZH2 developed OSCC whereas only 24% patients with moderate and none with weak/no EZH2 expression did so (P < 0.0001). In Leuk-1 cells, EZH2 downregulation resulted in G1 arrest; decreased invasion capability, decreased anchorage-independent growth; downregulation of cyclin D1 and upregulation of p15INK4B. Our data suggest that EZH2 plays an important role in OL malignant transformation and may be a biomarker in predicting OSCC development in patients with OLs. Cancer Prev Res; 4(11); 1816–24. ©2011 AACR.
Data from DNA Methylation Markers for Prostate Cancer with a Stem Cell Twist
Authors: Jerónimo Carmen , Esteller Manel
Published: April 2023

Abstract
This perspective on Ibragimova et al. (beginning on page 1084 in this issue of the journal) highlights the potential role of DNA methylation–based markers in the early detection of prostate cancer (PCa), with a focus on the global reactivation of expression of genes epigenetically silenced in PCa cell lines. Novel findings of these investigators identified four genes methylated specifically in PCa, including the stem cell marker TACSTD2, which seems to discriminate PCa (methylated TACSTD2) from prostatic intraepithelial neoplasia (unmethylated). These genes add significantly to the list of epigenetic markers showing promise for clinical early detection of PCa in the near future. Cancer Prev Res; 3(9); 1053–5. ©2010 AACR.
Data from Associations between Oral HPV16 Infection and Cytopathology: Evaluation of an Oropharyngeal “Pap-Test Equivalent” in High-Risk Populations
Authors: Fakhry Carole , Rosenthal Barbara T. , Clark Douglas P. , Gillison Maura L.
Published: April 2023

Abstract
Human papillomavirus (HPV) is responsible for the rising incidence of oropharyngeal squamous cell cancers (OSCC) in the United States, and yet, no screening strategies have been evaluated. Secondary prevention by means of HPV detection and cervical cytology has led to a decline in cervical cancer incidence in the United States. Here, we explored an analogous strategy by evaluating associations between HPV16 infection, cytopathology, and histopathology in two populations at elevated risk for OSCCs. In the first, a cross-sectional study population (PAP1), cytology specimens were collected by means of brush biopsy from patients presenting with oropharyngeal abnormalities. In the second (PAP2), a nested case–control study, bilateral tonsillar cytology samples were collected at 12-month intervals from HIV-infected individuals. The presence of cytopathologic abnormality in HPV16-positive tonsil brush biopsies (cases) was compared with HPV16-negative samples (controls) matched on age and gender. HPV16 was detected in samples by consensus primer PCR and/or type-specific PCR. Univariate logistic regression was used to evaluate associations. In PAP1, HPV16 alone (OR: 6.1, 95% CI: 1.6–22.7) or in combination with abnormal cytology (OR: 20, 95% CI: 4.2–95.4) was associated with OSCC. In PAP2, 4.7% (72 of 1,524) of tonsillar cytology specimens from HIV-infected individuals without oropharyngeal abnormalities were HPV16 positive. Tonsillar HPV16 infection was not associated with atypical squamous cells of unknown significance (ASCUS), the only cytologic abnormality identified. Therefore, HPV16 was associated with OSCCs among individuals with accessible oropharyngeal lesions but not with cytologic evidence of dysplasia among high-risk individuals without such lesions. An oropharyngeal Pap-test equivalent may not be feasible, likely due to limitations in sampling the relevant tonsillar crypt epithelium. Cancer Prev Res; 4(9); 1378–84. ©2011 AACR.
Data from Lycopene Attenuated Hepatic Tumorigenesis via Differential Mechanisms Depending on Carotenoid Cleavage Enzyme in Mice
Authors: Ip Blanche C. , Liu Chun , Ausman Lynne M. , von Lintig Johannes , Wang Xiang-Dong
Published: April 2023

Abstract
Obesity is associated with increased liver cancer risks and mortality. We recently showed that apo-10′-lycopenoic acid, a lycopene metabolite generated by beta-carotene-9′,10′-oxygenase (BCO2), inhibited carcinogen-initiated, high-fat diet (HFD)–promoted liver inflammation, and hepatic tumorigenesis development. The present investigation examined the outstanding question of whether lycopene could suppress HFD-promoted hepatocellular carcinoma (HCC) progression, and if BCO2 expression is important using BCO2-knockout (BCO2-KO) and wild-type male mice. Results showed that lycopene supplementation (100 mg/kg diet) for 24 weeks resulted in comparable accumulation of hepatic lycopene (19.4 vs. 18.2 nmol/g) and had similar effects on suppressing HFD-promoted HCC incidence (19% vs. 20%) and multiplicity (58% vs. 62%) in wild-type and BCO2-KO mice, respectively. Intriguingly, lycopene chemopreventive effects in wild-type mice were associated with reduced hepatic proinflammatory signaling (phosphorylation of NK-κB p65 and STAT3; IL6 protein) and inflammatory foci. In contrast, the protective effects of lycopene in BCO2-KO but not in wild-type mice were associated with reduced hepatic endoplasmic reticulum stress–mediated unfolded protein response (ERUPR), through decreasing ERUPR-mediated protein kinase RNA-activated like kinase–eukaryotic initiation factor 2α activation, and inositol requiring 1α–X-box–binding protein 1 signaling. Lycopene supplementation in BCO2-KO mice suppressed oncogenic signals, including Met mRNA, β-catenin protein, and mTOR complex 1 activation, which was associated with increased hepatic microRNA (miR)-199a/b and miR214 levels. These results provided novel experimental evidence that dietary lycopene can prevent HFD-promoted HCC incidence and multiplicity in mice, and may elicit different mechanisms depending on BCO2 expression. Cancer Prev Res; 7(12); 1219–27. ©2014 AACR.
Data from Licochalcone A, a Natural Inhibitor of c-Jun N-Terminal Kinase 1
Authors: Yao Ke , Chen Hanyong , Lee Mee-Hyun , Li Haitao , Ma Weiya , Peng Cong , Song Nu Ry , Lee Ki Won , Bode Ann M. , Dong Ziming , Dong Zigang
Published: April 2023

Abstract
The c-Jun N-terminal kinases (JNK) play an important role in many physiologic processes induced by numerous stress signals. Each JNK protein appears to have a distinct function in cancer, diabetes, or Parkinson's disease. Herein, we found that licochalcone A, a major phenolic constituent isolated from licorice root, suppressed JNK1 activity but had little effect on JNK2 in vitro activity. Although licochalcone A binds with JIP1 competitively with either JNK1 or JNK2, a computer simulation model showed that after licochalcone A binding, the ATP-binding cleft of JNK1 was distorted more substantially than that of JNK2. This could reduce the affinity of JNK1 more than JNK2 for ATP binding. Furthermore, licochalcone A inhibited JNK1-mediated, but not JNK2-mediated, c-Jun phosphorylation in both ex vivo and in vitro systems. We also observed that in colon and pancreatic cancer cell lines, JNK1 is highly expressed compared with normal cell lines. In cancer cell lines, treatment with licochalcone A or knocking down JNK1 expression suppressed colon and pancreatic cancer cell proliferation and colony formation. The inhibition resulted in G1 phase arrest and apoptosis. Moreover, an in vivo xenograft mouse study showed that licochalcone A treatment effectively suppressed the growth of HCT116 xenografts, without affecting the body weight of mice. These results show that licochalcone A is a selective JNK1 inhibitor. Therefore, we suggest that because of the critical role of JNK1 in colon cancer and pancreatic carcinogenesis, licochalcone A might have preventive or therapeutic potential against these devastating diseases. Cancer Prev Res; 7(1); 139–49. ©2013 AACR.
Data from Smoking Attenuates Transforming Growth Factor-β–Mediated Tumor Suppression Function through Downregulation of Smad3 in Lung Cancer
Authors: Samanta Debangshu , Gonzalez Adriana L. , Nagathihalli Nagaraj , Ye Fei , Carbone David P. , Datta Pran K.
Published: April 2023

Abstract
Epidemiologic studies have shown that most cases of lung cancers (85%–90%) are directly attributable to cigarette smoking. Although much information has been gained about the effects of cigarette smoking on various signaling pathways causing lung cancer, nothing is known about the effect of cigarette smoking on the TGF-β–induced tumor suppressor function in lung cancer. To address this issue, lung adenocarcinoma A549 and immortalized bronchial epithelial HPL1A cells were chronically treated with cigarette smoke condensate (CSC) and dimethyl sulfoxide (as a control) to mimic the conditions of long-term cigarette smoking. Prolonged exposure of these cells to CSC resulted in a decrease in Smad3 and Smad4 complex formation and TGF-β–mediated transcription due to reduced expression of Smad3. Long-term CSC treatment reduced apoptosis, increased cell viability, decreased TGF-β–mediated growth inhibition, and enhanced tumorigenicity. The decrease in apoptosis is due to the upregulation of Bcl-2, which is a downstream target of Smad3. Re-expression of Smad3 in the CSC-treated cells restored TGF-β signaling, increased apoptosis, and decreased cell viability and tumorigenicity. Withdrawal of CSC treatment resulted in the restoration of Smad3 expression, reduction in cell viability, and increased TGF-β–mediated growth inhibition. Expression of Smad3 is lower in lung tumors of current smokers than that observed in never-smokers. Collectively, these data provide evidence that cigarette smoking promotes tumorigenicity partly by abrogating TGF-β–mediated growth inhibition and apoptosis by reducing expression of Smad3. Cancer Prev Res; 5(3); 453–63. ©2012 AACR.
Data from NF-κB Fans the Flames of Lung Carcinogenesis
Authors: Wong Kwok-Kin , Jacks Tyler , Dranoff Glenn
Published: April 2023

Abstract
This perspective on Deng et al. (beginning on p. 424 in this issue of the journal) examines the link between NF-κB and lung tumorigenesis. Experiments in genetically engineered mouse models of lung cancers are elucidating protumorigenic roles of NF-κB activation in lung cancer pathogenesis. Our growing understanding of the tumor-promoting NF-κB downstream effector pathways could lead to the development of novel approaches for lung cancer therapy and chemoprevention. Cancer Prev Res; 3(4); 403–5. ©2010 AACR.
Data from Preventive Effects of NSAIDs, NO-NSAIDs, and NSAIDs Plus Difluoromethylornithine in a Chemically Induced Urinary Bladder Cancer Model
Authors: Nicastro Holly L. , Grubbs Clinton J. , Margaret Juliana M. , Bode Ann M. , Kim Mi-Sung , Lu Yan , You Ming , Milne Ginger L. , Boring Daniel , Steele Vernon E. , Lubet Ronald A.
Published: April 2023

Abstract
Urinary bladder cancer prevention studies were performed with the nonsteroidal anti-inflammatory drugs (NSAID) naproxen (a standard NSAID with a good cardiovascular profile), sulindac, and their nitric oxide (NO) derivatives. In addition, the effects of the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO), alone or combined with a suboptimal dose of naproxen or sulindac was examined. Agents were evaluated at their human equivalent doses (HED), as well as at lower doses. In the hydroxybutyl(butyl)nitrosamine (OH-BBN) model of urinary bladder cancer, naproxen (400 or 75 ppm) and sulindac (400 ppm) reduced the incidence of large bladder cancers by 82%, 68%, and 44%, respectively, when the agents were initially given 3 months after the final dose of the carcinogen; microscopic cancers already existed. NO-naproxen was highly effective, whereas NO-sulindac was inactive. To further compare naproxen and NO-naproxen, we examined their effects on gene expression in rat livers following a 7-day exposure. Limited, but similar, gene expression changes in the liver were induced by both agents, implying that the primary effects of both are mediated by the parent NSAID. When agents were initiated 2 weeks after the last administration of OH-BBN, DFMO at 1,000 ppm had limited activity, a low dose of naproxen (75 ppm) and sulindac (150 ppm) were highly and marginally effective. Combining DFMO with suboptimal doses of naproxen had minimal effects, whereas the combination of DMFO and sulindac was more active than either agent alone. Thus, naproxen and NO-naproxen were highly effective, whereas sulindac was moderately effective in the OH-BBN model at their HEDs. Cancer Prev Res; 7(2); 246–54. ©2013 AACR.
Data from Cotargeting Cyclin D1 Starts a New Chapter in Lung Cancer Prevention and Therapy
Authors: Kim Edward S. , Lee J. Jack , Wistuba Ignacio I.
Published: April 2023

Abstract
Lung cancer has limited effective therapy and no effective prevention. Cytotoxic chemotherapy has not improved when combined with the epidermal growth factor receptor (EGFR) inhibitor erlotinib (standard lung cancer therapy) or with the rexinoid bexarotene. Combining erlotinib and bexarotene, however, to cotarget cyclin D1 via the retinoid X receptor and EGFR was active preclinically in KRAS-driven lung cancer cells derived from transgenic mice and in two clinical studies in lung cancer (including wild-type EGFR tumors, with or without KRAS mutations), as reported in this issue of the journal by Dragnev and colleagues (beginning on page 818). These results, along with closely related clinical results of the BATTLE program, support the promise of this cotargeting approach for lung cancer prevention and therapy and of cyclin D1 as a predictive, personalizing marker for it. Cancer Prev Res; 4(6); 779–82. ©2011 AACR.
Data from Green Tea Polyphenols Prevent UV-Induced Immunosuppression by Rapid Repair of DNA Damage and Enhancement of Nucleotide Excision Repair Genes
Authors: Katiyar Santosh K. , Vaid Mudit , van Steeg Harry , Meeran Syed M.
Published: April 2023

Abstract
UV radiation–induced immunosuppression has been implicated in the development of skin cancers. Green tea polyphenols (GTP) in drinking water prevent photocarcinogenesis in the skin of mice. We studied whether GTPs in drinking water (0.1-0.5%, w/v) prevent UV-induced immunosuppression and (if so) potential mechanisms of this effect in mice. GTPs (0.2% and 0.5%, w/v) reduced UV-induced suppression of contact hypersensitivity (CHS) in response to a contact sensitizer in local (58-62% reductions; P < 0.001) and systemic (51-55% reductions; P < 0.005) models of CHS. Compared with untreated mice, GTP-treated mice (0.2%, w/v) had a reduced number of cyclobutane pyrimidine dimer–positive (CPD+) cells (59%; P < 0.001) in the skin, showing faster repair of UV-induced DNA damage, and had a reduced (2-fold) migration of CPD+ cells from the skin to draining lymph nodes, which was associated with elevated levels of nucleotide excision repair (NER) genes. GTPs did not prevent UV-induced immunosuppression in NER-deficient mice but significantly prevented it in NER-proficient mice (P < 0.001); immunohistochemical analysis of CPD+ cells indicated that GTPs reduced the numbers of UV-induced CPD+ cells in NER-proficient mice (P < 0.001) but not in NER-deficient mice. Southwestern dot-blot analysis revealed that GTPs repaired UV-induced CPDs in xeroderma pigmentosum complementation group A (XPA)–proficient cells of a healthy person but did not in XPA-deficient cells obtained from XPA patients, indicating that a NER mechanism is involved in DNA repair. This study is the first to show a novel NER mechanism by which drinking GTPs prevents UV-induced immunosuppression and that inhibiting UV-induced immunosuppression may underlie the chemopreventive activity of GTPs against photocarcinogenesis. Cancer Prev Res; 3(2); 179–89
Data from Hunting for the Causes of Meningioma—Obesity Is a Suspect
Authors: Rajaraman Preetha
Published: April 2023

Abstract
In this issue of the journal, Michaud and colleagues report a 48% increased risk of meningioma in obese individuals compared with individuals with a normal body mass index (BMI). This large prospective cohort study adds weight to the suggested link between BMI and meningioma, thus contributing to the growing number of cancer sites likely associated with body fatness. Although the exact mechanisms underlying the BMI–meningioma link are unclear, possible mediators include hormonal factors, immunologic response, and levels of insulin or insulin-like growth factors, each of which has been implicated by various levels of evidence in meningioma risk. Understanding the relationships between body fatness, height, and hormonal and immunologic factors could provide important clues to the etiology of meningioma and may have implications for the early detection and prevention of these tumors. Cancer Prev Res; 4(9); 1353–5. ©2011 AACR.
Data from The Parity-Associated Microenvironmental Niche in the Omental Fat Band Is Refractory to Ovarian Cancer Metastasis
Authors: Cohen Courtney A. , Shea Amanda A. , Heffron C. Lynn , Schmelz Eva M. , Roberts Paul C.
Published: April 2023

Abstract
Ovarian cancer is an insidious and aggressive disease of older women, typically undiscovered before peritoneal metastasis due to its asymptomatic nature and lack of early detection tools. Epidemiologic studies suggest that child-bearing (parity) is associated with decreased ovarian cancer risk, although the molecular mechanisms responsible for this phenomenon have not been delineated. Ovarian cancer preferentially metastasizes to the omental fat band (OFB), a secondary lymphoid organ that aids in filtration of the peritoneal serous fluid (PSF) and helps combat peritoneal infections. In the present study, we assessed how parity and age impact the immune compositional profile in the OFB of mice, both in the homeostatic state and as a consequence of peritoneal implantation of ovarian cancer. Using fluorescence-activated cell sorting analysis and quantitative real-time PCR, we found that parity was associated with a significant reduction in omental monocytic subsets and B1-B lymphocytes, correlating with reduced homeostatic expression levels of key chemoattractants and polarization factors (Ccl1, Ccl2, Arg1, and Cxcl13). Of note, parous animals exhibited significantly reduced tumor burden following intraperitoneal implantation compared with nulliparous animals. This was associated with a reduction in tumor-associated neutrophils and macrophages, as well as in the expression levels of their chemoattractants (Cxcl1 and Cxcl5) in the OFB and PSF. These findings define a preexisting “parity-associated microenvironmental niche” in the OFB that is refractory to metastatic tumor seeding and outgrowth. Future studies designed to manipulate this niche may provide a novel means to mitigate peritoneal dissemination of ovarian cancer. Cancer Prev Res; 6(11); 1182–93. ©2013 AACR.
Data from Functional Protein Pathway Activation Mapping of the Progression of Normal Skin to Squamous Cell Carcinoma
Authors: Einspahr Janine G. , Calvert Valerie , Alberts David S. , Curiel-Lewandrowski Clara , Warneke James , Krouse Robert , Stratton Steven P. , Liotta Lance , Longo Caterina , Pellicani Giovanni , Prasad Anil , Sagerman Paul , Bermudez Yira , Deng Jianghong , Bowden G. Timothy , Petricoin Emanuel F.
Published: April 2023

Abstract
Reverse phase protein microarray analysis was used to identify cell signaling derangements in squamous cell carcinoma (SCC) compared with actinic keratosis (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with isolation and enrichment of epithelial cells by laser capture microdissection. Set 1 served as a pilot and a means to identify protein pathway activation alterations that could be further validated in a second independent set. Set 1 was comprised of 4 AK, 13 SCC, and 20 UIA. Set 2 included 15 AK, 9 SCCs, and 20 UIAs. Activation of 51 signaling proteins, known to be involved in tumorigenesis, were assessed for set 1 and showed that the MEK–ERK [mitogen-activated protein (MAP)/extracellular signal-regulated (ERK; MEK)] pathway was activated in SCC compared with AK and UIA, and that epidermal growth factor receptor (EGFR) and mTOR pathways were aberrantly activated in SCC. Unsupervised two-way hierarchical clustering revealed that AK and UIA shared a common signaling network activation architecture while SCC was dramatically different. Statistical analysis found that prosurvival signaling through phosphorylation of ASK and 4EBP1 as well as increased Bax and Bak expression was higher in AK compared with UIA. We expanded pathway network activation mapping in set 2 to 101 key signaling proteins, which corroborated activation of MEK–ERK, EGFR, and mTOR pathways through discovery of a number of upstream and downstream signaling molecules within these pathways to conclude that SCC is indeed a pathway activation–driven disease. Pathway activation mapping of SCC compared with AK revealed several interconnected networks that could be targeted with drug therapy for potential chemoprevention and therapeutic applications. Cancer Prev Res; 5(3); 403–13. ©2012 AACR.
Data from Eflornithine (DFMO) Prevents Progression of Pancreatic Cancer by Modulating Ornithine Decarboxylase Signaling
Authors: Mohammed Altaf , Janakiram Naveena B. , Madka Venkateshwar , Ritchie Rebekah L. , Brewer Misty , Biddick Laura , Patlolla Jagan Mohan R. , Sadeghi Michael , Lightfoot Stan , Steele Vernon E. , Rao Chinthalapally V.
Published: April 2023

Abstract
Ornithine decarboxylase (ODC) is the key rate-limiting enzyme in the polyamine synthesis pathway and it is overexpressed in a variety of cancers. We found that polyamine synthesis and modulation of ODC signaling occurs at early stages of pancreatic precursor lesions and increases as the tumor progresses in Kras-activated p48Cre/+-LSL-KrasG12D/+ mice. Interest in use of the ODC inhibitor eflornithine (DFMO) as a cancer chemopreventive agent has increased in recent years since ODC was shown to be transactivated by the c-myc oncogene and to cooperate with the ras oncogene in malignant transformation of epithelial tissues. We tested the effects of DFMO on pancreatic intraepithelial neoplasias (PanIN) and their progression to pancreatic ductal adenocarcinoma (PDAC) in genetically engineered Kras mice. The KrasG12D/+ mice fed DFMO at 0.1% and 0.2% in the diet showed a significant inhibition (P < 0.0001) of PDAC incidence compared with mice fed control diet. Pancreatic tumor weights were decreased by 31% to 43% (P < 0.03–0.001) with both doses of DFMO. DFMO at 0.1% and 0.2% caused a significant suppression (27% and 31%; P < 0.02–0.004) of PanIN 3 lesions (carcinoma in situ). DFMO-treated pancreas exhibited modulated ODC pathway components along with decreased proliferation and increased expression of p21/p27 as compared with pancreatic tissues derived from mice fed control diet. In summary, our preclinical data indicate that DFMO has potential for chemoprevention of pancreatic cancer and should be evaluated in other PDAC models and in combination with other drugs in anticipation of future clinical trials. Cancer Prev Res; 7(12); 1198–209. ©2014 AACR.
Data from Challenges Related to Developing Serum-Based Biomarkers for Early Ovarian Cancer Detection
Authors: Mai Phuong L. , Wentzensen Nicolas , Greene Mark H.
Published: April 2023

Abstract
In this issue of the journal, Cramer and colleagues and Zhu and colleagues report carefully designed phase 3 assessments of candidate ovarian cancer screening biomarkers. The main conclusion is that CA-125 remains the “best of a bad lot”; the new candidates have fallen short of expectations. We review factors impeding the development of an effective ovarian cancer screening strategy, highlight the requirements related to validating proposed screening biomarkers, and emphasize the risks from premature clinical applications of unvalidated tests, all underscoring the need for new research strategies. Cancer Prev Res; 4(3); 303–6. ©2011 AACR.