bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Therapeutic Targeting of CD146/MCAM Reduces Bone Metastasis in Prostate Cancer
Authors: Zoni Eugenio , Astrologo Letizia , Ng Charlotte K.Y. , Piscuoglio Salvatore , Melsen Janine , Grosjean Joël , Klima Irena , Chen Lanpeng , Snaar-Jagalska Ewa B. , Flanagan Kenneth , van der Pluijm Gabri , Kloen Peter , Cecchini Marco G. , Kruithof-de Julio Marianna , Thalmann George N.
Published: April 2023

Abstract
Prostate Cancer is the most common cancer and the second leading cause of cancer-related death in males. When prostate cancer acquires castration resistance, incurable metastases, primarily in the bone, occur. The aim of this study is to test the applicability of targeting melanoma cell adhesion molecule (MCAM; CD146) with a mAb for the treatment of lytic prostate cancer bone metastasis. We evaluated the effect of targeting MCAM using in vivo preclinical bone metastasis models and an in vitro bone niche coculture system. We utilized FACS, cell proliferation assays, and gene expression profiling to study the phenotype and function of MCAM knockdown in vitro and in vivo. To demonstrate the impact of MCAM targeting and therapeutic applicability, we employed an anti-MCAM mAb in vivo. MCAM is elevated in prostate cancer metastases resistant to androgen ablation. Treatment with DHT showed MCAM upregulation upon castration. We investigated the function of MCAM in a direct coculture model of human prostate cancer cells with human osteoblasts and found that there is a reduced influence of human osteoblasts on human prostate cancer cells in which MCAM has been knocked down. Furthermore, we observed a strongly reduced formation of osteolytic lesions upon bone inoculation of MCAM-depleted human prostate cancer cells in animal model of prostate cancer bone metastasis. This phenotype is supported by RNA sequencing (RNA-seq) analysis. Importantly, in vivo administration of an anti-MCAM human mAb reduced the tumor growth and lytic lesions. These results highlight the functional role for MCAM in the development of lytic bone metastasis and suggest that MCAM is a potential therapeutic target in prostate cancer bone metastasis.
Implications:
This study highlights the functional application of an anti-MCAM mAb to target prostate cancer bone metastasis.
Data from Loss of MAP3K7 Sensitizes Prostate Cancer Cells to CDK1/2 Inhibition and DNA Damage by Disrupting Homologous Recombination
Authors: Washino Satoshi , Rider Leah C. , Romero Lina , Jillson Lauren K. , Affandi Trisiani , Ohm Angela M. , Lam Elaine T. , Reyland Mary E. , Costello James C. , Cramer Scott D.
Published: April 2023

Abstract
The combined loss of CHD1 and MAP3K7 promotes aggressive prostate cancer by unknown mechanisms. Because both of these genes are lost genetically in prostate cancer, they cannot be directly targeted. We applied an established computational systems pharmacology approach (TRAP) to identify altered signaling pathways and associated druggable targets. We compared gene expression profiles of prostate cancer with coloss of CHD1 and MAP3K7 with prostate cancer diploid for these genes using The Cancer Genome Atlas patient samples. This analysis prioritized druggable target genes that included CDK1 and CDK2. We validated that inhibitors of these druggable target genes, including the CDK1/CDK2 inhibitor dinaciclib, had antiproliferative and cytotoxic effects selectively on mouse prostate cells with knockdown of Chd1 and Map3k7. Dinaciclib had stronger effects on prostate cells with suppression of Map3k7 independent of Chd1 and also compared with cells without loss of Map3k7. Dinaciclib treatment reduced expression of homologous recombination (HR) repair genes such as ATM, ATR, BRCA2, and RAD51, blocked BRCA1 phosphorylation, reduced RAD51 foci formation, and increased γH2AX foci selectively in prostate cells with suppression of Map3k7, thus inhibiting HR repair of chromosomal double-strand breaks. Dinaciclib-induced HR disruption was also observed in human prostate cells with knockdown of MAP3K7. Cotreatment of dinaciclib with DNA-damaging agents or PARP inhibitor resulted in a stronger cytotoxic effect on prostate cells with suppression of MAP3K7 compared with those without loss of MAP3K7, or to each single agent.
Implications:
These findings demonstrate that loss of MAP3K7 is a main contributing factor to drug response through disruption of HR in prostate cancer.
Data from Genomic Alterations Associated with Recurrence and TNBC Subtype in High-Risk Early Breast Cancers
Authors: Wilson Timothy R. , Udyavar Akshata R. , Chang Ching-Wei , Spoerke Jill M. , Aimi Junko , Savage Heidi M. , Daemen Anneleen , O'Shaughnessy Joyce A. , Bourgon Richard , Lackner Mark R.
Published: April 2023

Abstract
The identification of early breast cancer patients who may benefit from adjuvant chemotherapy has evolved to include assessment of clinicopathologic features such as tumor size and nodal status, as well as several gene-expression profiles for ER-positive, HER2-negative cancers. However, these tools do not reliably identify patients at the greatest risk of recurrence. The mutation and copy-number landscape of triple-negative breast cancer (TNBC) subtypes defined by gene expression is also largely unknown, and elucidation of this landscape may shed light on novel therapeutic opportunities. The USO01062 phase III clinical trial of standard chemotherapy (with or without capecitabine) enrolled a cohort of putatively high-risk patients based on clinical features, yet only observed a 5-year disease-free survival event rate of 11.6%. In order to uncover genomic aberrations associated with recurrence, a targeted next-generation sequencing panel was used to compare tumor specimens from patients who had a recurrence event with a matched set who did not. The somatic mutation and copy-number alteration landscapes of high-risk early breast cancer patients were characterized and alterations associated with relapse were identified. Tumor mutational burden was evaluated but was not prognostic in this study, nor did it correlate with PDL1 or CD8 gene expression. However, TNBC subtypes had substantial genomic heterogeneity with a distinct pattern of genomic alterations and putative underlying driver mutations.
Implications:
The present study uncovers a compendium of genomic alterations with utility to more precisely identify high-risk patients for adjuvant trials of novel therapeutic agents.
Data from De Novo Fatty Acid Synthesis-Driven Sphingolipid Metabolism Promotes Metastatic Potential of Colorectal Cancer
Authors: Jafari Naser , Drury James , Morris Andrew J. , Onono Fredrick O. , Stevens Payton D. , Gao Tianyan , Liu Jinpeng , Wang Chi , Lee Eun Y. , Weiss Heidi L. , Evers B. Mark , Zaytseva Yekaterina Y.
Published: April 2023

Abstract
Metastasis is the most common cause of death in colorectal cancer patients. Fatty acid synthase (FASN) and sphingosine kinase-1 and -2 (SPHK1 and 2) are overexpressed in many cancers, including colorectal cancer. However, the contribution of FASN-mediated upregulation of sphingolipid metabolism to colorectal cancer metastasis and the potential of these pathways as targets for therapeutic intervention remain unknown. This study determined that sphingosine kinases (SPHK) are overexpressed in colorectal cancer as compared with normal mucosa. FASN expression significantly correlated with SPHK2 expression in data sets from The Cancer Genome Atlas (TCGA) and a colorectal cancer tumor microarray. FASN, SPHK1, and SPHK2 colocalized within invadopodia of primary colorectal cancer cells. Moreover, FASN inhibition decreased SPHK2 expression and the levels of dihydrosphingosine 1-phosphate (DH-S1P) and sphingosine 1-phosphate (S1P) in colorectal cancer cells and tumor tissues. Inhibition of FASN using TVB-3664 and sphingolipid metabolism using FTY-720 significantly inhibited the ability of primary colorectal cancer cells to proliferate, migrate, form focal adhesions, and degrade gelatin. Inhibition of the FASN/SPHK/S1P axis was accompanied by decreased activation of p-MET, p-FAK, and p-PAX. S1P treatment rescued FASN-mediated inhibition of these proteins, suggesting that FASN promotes metastatic properties of colorectal cancer cells, in part, through an increased sphingolipid metabolism. These data demonstrate that upregulation of the FASN/SPHK/S1P axis promotes colorectal cancer progression by enhancing proliferation, adhesion, and migration.
Implications:
This study provides a strong rationale for further investigation of the interconnection of de novo lipogenesis and sphingolipid metabolism that could potentially lead to the identification of new therapeutic targets and strategies for colorectal cancer.
Data from IGF2 Autocrine-Mediated IGF1R Activation Is a Clinically Relevant Mechanism of Osimertinib Resistance in Lung Cancer
Authors: Manabe Tadashi , Yasuda Hiroyuki , Terai Hideki , Kagiwada Harumi , Hamamoto Junko , Ebisudani Toshiki , Kobayashi Keigo , Masuzawa Keita , Ikemura Shinnosuke , Kawada Ichiro , Hayashi Yuichiro , Fukui Kazuhiko , Horimoto Katsuhisa , Fukunaga Koichi , Soejima Kenzo
Published: April 2023

Abstract
EGFR-mutated lung cancer accounts for a significant proportion of lung cancer cases worldwide. For these cases, osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is extensively used as a first-line or second-line treatment. However, lung cancer cells acquire resistance to osimertinib in 1 to 2 years. Thus, a thorough clarification of resistance mechanisms to osimertinib is highly anticipated. Recent next-generation sequencing (NGS) of lung cancer samples identified several genetically defined resistance mechanisms to osimertinib, such as EGFR C797S or MET amplification. However, nongenetically defined mechanisms are not well evaluated. For a thorough clarification of osimertinib resistance, both genetic and nongenetic mechanisms are essential. By using our comprehensive protein phosphorylation array, we detected IGF1R bypass pathway activation after EGFR abolishment. Both of our established lung cancer cells and patient-derived lung cancer cells demonstrated IGF2 autocrine-mediated IGF1R pathway activation as a mechanism of osimertinib resistance. Notably, this resistance mechanism was not detected by a previously performed NGS, highlighting the essential roles of living cancer cells for a thorough clarification of resistance mechanisms. Interestingly, the immunohistochemical analysis confirmed the increased IGF2 expression in lung cancer patients who were treated with osimertinib and met the established clinical definition of acquired resistance. The findings highlight the crucial roles of cell-autonomous ligand expression in osimertinib resistance. Here, we report for the first time the IGF2 autocrine-mediated IGF1R activation as a nongenetic mechanism of osimertinib resistance in lung cancer at a clinically relevant level.
Implications:
Using comprehensive protein phosphorylation array and patient-derived lung cancer cells, we found that IGF2 autocrine-mediated IGF1R pathway activation is a clinically relevant and common mechanism of acquired resistance to osimertinib.
Data from Metastasis-Specific Gene Expression in Autochthonous and Allograft Mouse Mammary Tumor Models: Stratification and Identification of Targetable Signatures
Authors: Ross Christina , Szczepanek Karol , Lee Maxwell , Yang Howard , Peer Cody J. , Kindrick Jessica , Shankarappa Priya , Lin Zhi-Wei , Sanford Jack D. , Figg William D. , Hunter Kent W.
Published: April 2023

Abstract
Breast cancer metastasis is a leading cause of cancer-related death of women in the United States. A hurdle in advancing metastasis-targeted intervention is the phenotypic heterogeneity between primary and secondary lesions. To identify metastasis-specific gene expression profiles we performed RNA-sequencing of breast cancer mouse models; analyzing metastases from models of various drivers and routes. We contrasted the models and identified common, targetable signatures. Allograft models exhibited more mesenchymal-like gene expression than genetically engineered mouse models (GEMM), and primary culturing of GEMM-derived metastatic tissue induced mesenchymal-like gene expression. In addition, metastasis-specific transcriptomes differed between tail vein and orthotopic injection of the same cell line. Gene expression common to models of spontaneous metastasis included sildenafil response and nicotine degradation pathways. Strikingly, in vivo sildenafil treatment significantly reduced metastasis by 54%, while nicotine significantly increased metastasis by 46%. These data suggest that (i) actionable metastasis-specific pathways can be readily identified, (ii) already available drugs may have great potential to alleviate metastatic incidence, and (iii) metastasis may be influenced greatly by lifestyle choices such as the choice to consume nicotine products. In summary, while mouse models of breast cancer metastasis vary in ways that must not be ignored, there are shared features that can be identified and potentially targeted therapeutically.
Implications:
The data we present here exposes critical variances between preclinical models of metastatic breast cancer and identifies targetable pathways integral to metastatic spread.
Visual Overview:
http://mcr.aacrjournals.org/content/molcanres/18/9/1278/F1.large.jpg.
Data from The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator
Authors: Feldman Dafna , Roniger Maayan , Bar-Sinai Allan , Braitbard Ori , Natan Carmit , Love Dona C. , Hanover John A. , Hochman Jacob
Published: April 2023

Abstract
Mouse mammary tumor virus (MMTV) is associated primarily with mammary carcinomas and lymphomas. The signal peptide of the MMTV envelope precursor is uniquely targeted to nucleoli of cells that harbor the virus, where it can function as a nuclear export factor for intron-containing transcripts. Antibodies to this signal peptide, which we refer to as p14, were previously shown to label nucleoli in a subset of human breast cancers. To look for additional cellular functions of p14, different mutants were ectopically expressed in the MCF-7 human breast cancer cell line. This approach identified motifs responsible for its nucleolar targeting, nucleocytoplasmic shuttling, target protein (B23, nucleophosmin) binding, and phosphorylation at serine 18 and 65 both in situ and in vitro. To test the role of these phosphorylation sites, we carried out in vivo tumorigenesis studies in severe combined immunodeficient mice. The findings show that the p14-Ser65Ala mutation is associated with impaired tumorigenicity, whereas the p14-Ser18Ala mutation is associated with enhanced tumorigenicity. Microarray analysis suggests that phosphorylation at serine 18 or at serine 65 is associated with transcriptional regulation of the L5 nucleolar ribosomal protein (a p14 target) and the Erb-B signal transduction pathway. Taken together, these results show that the phosphorylation status of p14 determines whether it functions as a pro-oncogenic or antioncogenic modulator. Mol Cancer Res; 10(8); 1077–86. ©2012 AACR.
Data from Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells
Authors: McBrearty Noreen , Cho Christina , Chen Jinyun , Zahedi Farima , Peck Amy R. , Radaelli Enrico , Assenmacher Charles-Antoine , Pavlak Clarice , Devine Anne , Yu Pengfei , Lu Zhen , Zhang Hongru , Li Jinyang , Pitarresi Jason R. , Astsaturov Igor , Cukierman Edna , Rustgi Anil K. , Stanger Ben Z. , Rui Hallgeir , Fuchs Serge Y.
Published: April 2023

Abstract
Cholesterol dependence is an essential characteristic of pancreatic ductal adenocarcinoma (PDAC). Cholesterol 25-hydroxylase (CH25H) catalyzes monooxygenation of cholesterol into 25-hydroxycholesterol, which is implicated in inhibiting cholesterol biosynthesis and in cholesterol depletion. Here, we show that, within PDAC cells, accumulation of cholesterol was facilitated by the loss of CH25H. Methylation of the CH25H gene and decreased levels of CH25H expression occurred in human pancreatic cancers and was associated with poor prognosis. Knockout of Ch25h in mice accelerated progression of Kras-driven pancreatic intraepithelial neoplasia. Conversely, restoration of CH25H expression in human and mouse PDAC cells decreased their viability under conditions of cholesterol deficit, and decelerated tumor growth in immune competent hosts. Mechanistically, the loss of CH25H promoted autophagy resulting in downregulation of MHC-I and decreased CD8+ T-cell tumor infiltration. Re-expression of CH25H in PDAC cells combined with immune checkpoint inhibitors notably inhibited tumor growth. We discuss additional benefits that PDAC cells might gain from inactivation of CH25H and the potential translational importance of these findings for therapeutic approaches to PDAC.
Implications:
Loss of CH25H by pancreatic cancer cells may stimulate tumor progression and interfere with immunotherapies.
Perspective on this Article from Ovarian Adenocarcinomas in the Laying Hen and Women Share Similar Alterations in p53, ras, and HER-2/neu
Authors: Hakim Amy A. , Barry Catherine P. , Barnes H. John , Anderson Kenneth E. , Petitte James , Whitaker Regina , Lancaster Jonathan M. , Wenham Robert M. , Carver Donna K. , Turbov Jane , Berchuck Andrew , Kopelovich Levy , Rodriguez Gustavo C.
Published: April 2023

Perspective on this Article from Ovarian Adenocarcinomas in the Laying Hen and Women Share Similar Alterations in p53, ras, and HER-2/neu
Supplementary Figure 1 from Effect of Intermittent Dosing Regimens of Erlotinib on Methylnitrosourea-Induced Mammary Carcinogenesis
Authors: Lubet Ronald A. , Szabo Eva , Iwata Kenneth K. , Gill Stanley C. , Tucker Chris , Bode Ann , Steele Vernon E. , Juliana M. Margaret , Nicastro Holly L. , Grubbs Clinton J.
Published: April 2023

PDF file - 40K, Effect of Erlotinib (6 mg/kg BW/day) on Time of Appearance of Methylnitrosourea- Induced Mammary Cancers in Female Sprague-Dawley Rats.
Related Article from Exercise for Secondary Prevention of Breast Cancer: Moving from Evidence to Changing Clinical Practice
Authors: Schmitz Kathryn H.
Published: April 2023

Related Article from Exercise for Secondary Prevention of Breast Cancer: Moving from Evidence to Changing Clinical Practice
Supplementary Table 7 from Novel Susceptibility Loci for Second Primary Tumors/Recurrence in Head and Neck Cancer Patients: Large-Scale Evaluation of Genetic Variants
Authors: Wu Xifeng , Spitz Margaret R. , Lee J. Jack , Lippman Scott M. , Ye Yuanqing , Yang Hushan , Khuri Fadlo R. , Kim Edward , Gu Jian , Lotan Reuben , Hong Waun K.
Published: April 2023

Supplementary Table 7 from Novel Susceptibility Loci for Second Primary Tumors/Recurrence in Head and Neck Cancer Patients: Large-Scale Evaluation of Genetic Variants
Related Article from Trials and Tribulations of Interrogating Biomarkers to Define Efficacy of Cancer Risk Reductive Interventions
Authors: Brenner Dean E. , Hawk Ernest
Published: April 2023

Related Article from Trials and Tribulations of Interrogating Biomarkers to Define Efficacy of Cancer Risk Reductive Interventions
Supplementary Table S4 from Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-Related Gene Expression during Early TRAMP Prostate Carcinogenesis
Authors: Wan Lei , Tan Hsueh-Li , Thomas-Ahner Jennifer M. , Pearl Dennis K. , Erdman John W. , Moran Nancy E. , Clinton Steven K.
Published: April 2023

Supplementary Table S4. Canonical pathways predicted to be significantly different in early prostate carcinogenesis and in response to castration.
Supplementary Figure 1 from Metformin Inhibits Skin Tumor Promotion in Overweight and Obese Mice
Authors: Checkley L. Allyson , Rho Okkyung , Angel Joe M. , Cho Jiyoon , Blando Jorge , Beltran Linda , Hursting Stephen D. , DiGiovanni John
Published: April 2023

PDF file - 1781K, Effect of metformin on epidermal phospho-ULK1 in the absence or presence of TPA treatment.
Supplementary Table 5 from A DRD1 Polymorphism Predisposes to Lung Cancer among Those Exposed to Secondhand Smoke during Childhood
Authors: Robles Ana I. , Yang Ping , Jen Jin , McClary Andrew C. , Calhoun Kara , Bowman Elise D. , Vähäkangas Kirsi , Greathouse K. Leigh , Wang Yi , Olivo-Marston Susan , Wenzlaff Angela S. , Deng Bo , Schwartz Ann G. , Ryan Bríd M.
Published: April 2023

Main unadjusted effects of smoking, childhood and adult exposure to tobacco smoke and lung cancer risk.
Supplementary Table 2 from Class I HDACs Are Mediators of Smoke Carcinogen–Induced Stabilization of DNMT1 and Serve as Promising Targets for Chemoprevention of Lung Cancer
Authors: Brodie Seth A. , Li Ge , El-Kommos Adam , Kang Hyunseok , Ramalingam Suresh S. , Behera Madhusmita , Gandhi Khanjan , Kowalski Jeanne , Sica Gabriel L. , Khuri Fadlo R. , Vertino Paula M. , Brandes Johann C.
Published: April 2023

PDF file - 65K, Pathway analysis of differentially methylated genes.
Supplementary Table S1 from Hepatitis B Virus Combo Mutations Improve the Prediction and Active Prophylaxis of Hepatocellular Carcinoma: A Clinic-Based Cohort Study
Authors: Yin Jianhua , Wang Junxue , Pu Rui , Xin Haiguang , Li Zixiong , Han Xue , Ding Yibo , Du Yan , Liu Wenbin , Deng Yang , Ji Xiaowei , Wu Ming , Yu Min , Zhang Hongwei , Wang Hongyang , Thompson Timothy C. , Ni Wu , Cao Guangwen
Published: April 2023

Supplementary Table S1. Cox regression analysis of factors significantly affected liver death in patients with chronic hepatitis B virus infection.
Legends to Supplementary Figures from Hepatitis B Virus Combo Mutations Improve the Prediction and Active Prophylaxis of Hepatocellular Carcinoma: A Clinic-Based Cohort Study
Authors: Yin Jianhua , Wang Junxue , Pu Rui , Xin Haiguang , Li Zixiong , Han Xue , Ding Yibo , Du Yan , Liu Wenbin , Deng Yang , Ji Xiaowei , Wu Ming , Yu Min , Zhang Hongwei , Wang Hongyang , Thompson Timothy C. , Ni Wu , Cao Guangwen
Published: April 2023

Legends to Supplementary Figures.
Supplementary Figure2A from Improved Innate Immune Responses by Frondanol A5, a Sea Cucumber Extract, Prevent Intestinal Tumorigenesis
Authors: Janakiram Naveena B. , Mohammed Altaf , Bryant Taylor , Lightfoot Stan , Collin Peter D. , Steele Vernon E. , Rao Chinthalapally V.
Published: April 2023

Supplementary Figure 2A. CD163 protein expression in the control and Frondanol A5-treated colon
Supplementary Figure 2B from Improved Innate Immune Responses by Frondanol A5, a Sea Cucumber Extract, Prevent Intestinal Tumorigenesis
Authors: Janakiram Naveena B. , Mohammed Altaf , Bryant Taylor , Lightfoot Stan , Collin Peter D. , Steele Vernon E. , Rao Chinthalapally V.
Published: April 2023

Supplementary Figure 2B. CD163 protein expression in the control and Frondanol A5-treated small intestinal tumors
Supplemental Figure 1 from Vitamin D Repletion Reduces the Progression of Premalignant Squamous Lesions in the NTCU Lung Squamous Cell Carcinoma Mouse Model
Authors: Mazzilli Sarah A. , Hershberger Pamela A. , Reid Mary E. , Bogner Paul N. , Atwood Kristopher , Trump Donald L. , Johnson Candace S.
Published: April 2023

Supplemental Figure 1. Controls IHC stains
Supplementary Figure Legend from TFF2–CXCR4 Axis Is Associated with BRAF V600E Colon Cancer
Authors: Gala Manish K. , Austin Thomas , Ogino Shuji , Chan Andrew T.
Published: April 2023

Supplementary Figure Legend.
Supplemental figure 1 from Effect of Combined Treatment with Ursolic Acid and Resveratrol on Skin Tumor Promotion by 12-O-Tetradecanoylphorbol-13-Acetate
Authors: Cho Jiyoon , Rho Okkyung , Junco Jacob , Carbajal Steve , Siegel Dionicio , Slaga Thomas J. , DiGiovanni John
Published: April 2023

Effect of UA + Res on skin tumor promotion in female ICR mice on the overweight control and DIO diet (Panels A and B, respectively) and on weight gain (Panels C and D, respectively).
Supplementary Figure S5 from St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling
Authors: Manna Soumen K. , Golla Srujana , Golla Jaya Prakash , Tanaka Naoki , Cai Yan , Takahashi Shogo , Krausz Kristopher W. , Matsubara Tsutomu , Korboukh Ilia , Gonzalez Frank J.
Published: April 2023

Supplementary Figure S5: Extracted and integrated ion chromatograms for hypericin showing the relative abundance (area under the curve of the highlighted peak) do not diminish upon storage of the diet at 4{degree sign}C.
Supplementary Table 2 from Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques
Authors: Dewi Fitriya N. , Wood Charles E. , Willson Cynthia J. , Register Thomas C. , Lees Cynthia J. , Howard Timothy D. , Huang Zhiqing , Murphy Susan K. , Tooze Janet A. , Chou Jeff W. , Miller Lance D. , Cline J. Mark
Published: April 2023

Cynomolgus macaque primer sets (forward, F; reverse, R; and sequencing, S) for pyrosequencing assay.
Supplementary Table 4. from Serum Glycans as Risk Markers for Non–Small Cell Lung Cancer
Authors: Ruhaak L. Renee , Stroble Carol , Dai Jianliang , Barnett Matt , Taguchi Ayumu , Goodman Gary E. , Miyamoto Suzanne , Gandara David , Feng Ziding , Lebrilla Carlito B. , Hanash Samir
Published: April 2023

Predictive values of risk factors, pro-SFTPB and the glycan marker panel in the discovery set.
Supplementary Figure 2. from Serum Glycans as Risk Markers for Non–Small Cell Lung Cancer
Authors: Ruhaak L. Renee , Stroble Carol , Dai Jianliang , Barnett Matt , Taguchi Ayumu , Goodman Gary E. , Miyamoto Suzanne , Gandara David , Feng Ziding , Lebrilla Carlito B. , Hanash Samir
Published: April 2023

Typical chromatogram of N-glycans obtained from human serum.
Supplementary Figure S3 from Enhanced Antitumor Effects of Novel Intracellular Delivery of an Active Form of Menaquinone-4, Menahydroquinone-4, into Hepatocellular Carcinoma
Authors: Setoguchi Shuichi , Watase Daisuke , Matsunaga Kazuhisa , Matsubara Misa , Kubo Yohei , Kusuda Mariko , Nagata-Akaho Nami , Enjoji Munechika , Nakashima Manabu , Takeshita Morishige , Karube Yoshiharu , Takata Jiro
Published: April 2023

Supplementary Figure S3. Plasma and liver concentration profiles of MK-4 and MKH-DMG after oral administration of MKH-DMG in mice.
Fig S3 from Loss of BRCA1 in the Cells of Origin of Ovarian Cancer Induces Glycolysis: A Window of Opportunity for Ovarian Cancer Chemoprevention
Authors: Chiyoda Tatsuyuki , Hart Peter C. , Eckert Mark A. , McGregor Stephanie M. , Lastra Ricardo R. , Hamamoto Ryuji , Nakamura Yusuke , Yamada S. Diane , Olopade Olufunmilayo I. , Lengyel Ernst , Romero Iris L.
Published: April 2023

Fig S3 shows BRCA1 knockdown in IOSE and FT does not increase HK1 expression or AMPK activity.
Supplementary Table 1 from Immunohistochemical Phenotype of Breast Cancer during 25-Year Follow-up of the Royal Marsden Tamoxifen Prevention Trial
Authors: Detre Simone I. , Ashley Susan , Mohammed Kabir , Smith Ian E. , Powles Trevor J. , Dowsett Mitch
Published: April 2023

Immunohistochemical analysis of biomarkers.
Supplemental Figure 3A from Calcium-Induced Differentiation of Human Colon Adenomas in Colonoid Culture: Calcium Alone versus Calcium with Additional Trace Elements
Authors: McClintock Shannon D. , Colacino Justin A. , Attili Durga , Dame Michael K. , Richter Aliah , Reddy Anusha R. , Basrur Venkatesha , Rizvi Areeba H. , Turgeon D. Kim , Varani James , Aslam Muhammad N.
Published: April 2023

Higher magnification images of the immunostained colonoid sections. Immunohistology (as shown in Figures 3 and 4). At the end of the 30-day incubation period, colonoids were examined under light-microscopy after immunostaining for CK20, E-cadherin, occluding, cleaved caspase-3 and NF-2. Bars=50 μm.
Supplementary Data from Implementing Strategies at the Workplace Level to Increase Colorectal Cancer Screening Uptake in Argentina: A Controlled Interrupted Time-series Study
Authors: Bardach Ariel Esteban , Pichon-Riviere Andres , Gibbons Luz , Alonso Juan Pedro , Virgilio Sacha Alexis , Belizán María , Comolli Mariana , González Lucas Angel
Published: April 2023

Supplementary Data from Implementing Strategies at the Workplace Level to Increase Colorectal Cancer Screening Uptake in Argentina: A Controlled Interrupted Time-series Study
Table S4 from Uptake and Predictors of Opportunistic Salpingectomy for Ovarian Cancer Risk Reduction in the United States
Authors: Karia Pritesh S. , Joshu Corinne E. , Visvanathan Kala
Published: April 2023

This table shows the results of the multivariable-adjusted analysis of factors associated with OS for sterilization use before and after the release of the clinical practice guideline.
Figure S1 from Combination of Erlotinib and Naproxen Employing Pulsatile or Intermittent Dosing Profoundly Inhibits Urinary Bladder Cancers
Authors: Mohammed Altaf , Miller Mark Steven , Lubet Ronald A. , Suen Chen S. , Sei Shizuko , Shoemaker Robert H. , Juliana Margaret M. , Moeinpour Fariba L. , Grubbs Clinton J.
Published: April 2023

Supplementary Figure 2
Supplementary Data from Treatment Strategies and Mechanisms Associated with the Prevention of NASH-Associated HCC by a Toll-like Receptor 4 Inhibitor
Authors: Kwan Suet-Ying , Slayden Alyssa N. , Coronado Aubrey R. , Marquez Rosamaria C. , Chen Huiqin , Wei Peng , Savage Michelle I. , Vornik Lana A. , Fox Jennifer T. , Sei Shizuko , Liang Dong , Stevenson Heather L. , Wilkerson Gregory K. , Gagea Mihai , Brown Powel H. , Beretta Laura
Published: April 2023

Supplementary Data from Treatment Strategies and Mechanisms Associated with the Prevention of NASH-Associated HCC by a Toll-like Receptor 4 Inhibitor
Table 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

Second RSF by SFA
Supplementary Table 1b from Risk Prediction Models for Colorectal Cancer: A Systematic Review
Authors: Usher-Smith Juliet A. , Walter Fiona M. , Emery Jon D. , Win Aung K. , Griffin Simon J.
Published: April 2023

Details of development of models from cohort studies.
Supplementary Table S1, Table S2, Table S3, Table S4, Table S5 from Common Analgesic Use for Menstrual Pain and Ovarian Cancer Risk
Authors: Sasamoto Naoko , Babic Ana , Vitonis Allison F. , Titus Linda , Cramer Daniel W. , Trabert Britton , Tworoger Shelley S. , Terry Kathryn L.
Published: April 2023

Supplementary Table S1 shows characteristics among ovarian cancer cases, Supplementary Table S2 shows the association between duration of analgesic use and ovarian cancer risk, Supplementary Table S3 shows the association between frequency of analgesic use and ovarian cancer risk, Supplementary Table S4 shows the association between age at first use of analgesics and ovarian cancer risk, Supplementary Table S5 shows the associations between analgesic use and ovarian cancer risk stratified by oral contraceptive use and history of endometriosis
Supplementary Data from Implementation of HPV-based Cervical Cancer Screening Combined with Self-sampling Using a Midwifery Network Across Rural Greece: The GRECOSELF Study
Authors: Agorastos Theodoros , Chatzistamatiou Kimon , Tsertanidou Athena , Mouchtaropoulou Evangelia , Pasentsis Konstantinos , Kitsou Anastasia , Moysiadis Theodoros , Moschaki Viktoria , Skenderi Alkmini , Katsiki Evangelia , Aggelidou Stamatia , Venizelos Ioannis , Ntoula Maria , Daponte Alexandros , Vanakara Polyxeni , Garas Antonios , Stefos Theodoros , Vrekoussis Thomas , Lymberis Vasilis , Kontomanolis Emmanuel N. , Makrigiannakis Antonis , Manidakis George , Deligeoroglou Efthimios , Panoskaltsis Theodoros , Decavalas George O. , Michail George , Kalogiannidis Ioannis , Koukoulis George , Zempili Paraskevi , Halatsi Despina , Truva Theoni , Piha Vaia , Agelena Georgia , Chronopoulou Athanasia , Vaitsi Violetta , Chatzaki Ekaterini , Paschopoulos Minas , Adonakis George , Kaufmann Andreas M. , Hadzidimitriou Anastasia , Stamatopoulos Kostas
Published: April 2023

Suppl. 1. Comparison of different storage and transportation conditions
Supplementary Data from Genistein Prevents Development of Spontaneous Ovarian Cancer and Inhibits Tumor Growth in Hen Model
Authors: Sahin Kazim , Yenice Engin , Bilir Birdal , Orhan Cemal , Tuzcu Mehmet , Sahin Nurhan , Ozercan Ibrahim H. , Kabil Nashwa , Ozpolat Bulent , Kucuk Omer
Published: April 2023

Supplementary Table 1
Supplementary Figures Legends from Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population
Authors: Duarte-Salles Talita , Misra Sandeep , Stepien Magdalena , Plymoth Amelie , Muller David , Overvad Kim , Olsen Anja , Tjønneland Anne , Baglietto Laura , Severi Gianluca , Boutron-Ruault Marie-Christine , Turzanski-Fortner Renee , Kaaks Rudolf , Boeing Heiner , Aleksandrova Krasimira , Trichopoulou Antonia , Lagiou Pagona , Bamia Christina , Pala Valeria , Palli Domenico , Mattiello Amalia , Tumino Rosario , Naccarati Alessio , Bueno-de-Mesquita H.B(as). , Peeters Petra H. , Weiderpass Elisabete , Quirós J. Ramón , Agudo Antonio , Sánchez-Cantalejo Emilio , Ardanaz Eva , Gavrila Diana , Dorronsoro Miren , Werner Mårten , Hemmingsson Oskar , Ohlsson Bodil , Sjöberg Klas , Wareham Nicholas J. , Khaw Kay-Tee , Bradbury Kathryn E. , Gunter Marc J. , Cross Amanda J. , Riboli Elio , Jenab Mazda , Hainaut Pierre , Beretta Laura
Published: April 2023

Supplementary Figures Legends
Supplementary Figure from Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older Individuals
Authors: Bakshi Andrew , Cao Yin , Orchard Suzanne G. , Carr Prudence R. , Joshi Amit D. , Manning Alisa K. , Buchanan Daniel D. , Umar Asad , Winship Ingrid M. , Gibbs Peter , Zalcberg John R. , Macrae Finlay , McNeil John J. , Lacaze Paul , Chan Andrew T.
Published: April 2023

Supplementary Figure from Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older Individuals
Supplementary Figures and Tables from Circulating 27-hydroxycholesterol and Risk of Colorectal Adenomas and Serrated Polyps
Authors: Passarelli Michael N. , Thompson Bonne M. , McDonald Jeffrey G. , Snover Dale C. , Palys Thomas J. , Rees Judy R. , Barry Elizabeth L. , Baron John A.
Published: April 2023

Supplementary Figures 1-2 and Tables 1-7
Table S1 from Interventions to Reduce Future Cancer Incidence from Diesel Engine Exhaust: What Might Work?
Authors: Carey Renee N. , Fritschi Lin , Driscoll Timothy R. , Peters Susan , Glass Deborah C. , Benke Geza , Reid Alison
Published: April 2023

Sensitivity Analysis - Bladder
Supplementary tables from Association of Aspirin, Metformin, and Statin Use with Gastric Cancer Incidence and Mortality: A Nationwide Cohort Study
Authors: Cho Mi Hee , Yoo Tae Gon , Jeong Su-Min , Shin Dong Wook
Published: April 2023

Supplementary tables show the results of subgroup analyses stratified by sex, age, body mass index, smoking status, and alcohol consumption.
Supplementary Table 2 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

Characteristics of prostate cancer cases by status of NSAID use in the past year in the post-diagnostic NIH-AARP and PLCO cohorts.
Table S3 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 S3: Odds ratios of the presence of bacteria associated with colorectal cancer according to tertiles of intake of each dietary food
Supplementary Table S2 from Benign Breast Disease, NSAIDs, and Postmenopausal Breast Cancer Risk in the CPS-II Cohort
Authors: Sherman Mark E. , Vierkant Robert A. , Masters Matthew , Radisky Derek C. , Winham Stacey J. , Degnim Amy C. , Vachon Celine M. , Patel Alpa V. , Teras Lauren R.
Published: April 2023

Supplementary Table S2: Associations of demographic and clinical characteristics with risk of breast cancer.
Supplementary Table S1 from Benign Breast Disease, NSAIDs, and Postmenopausal Breast Cancer Risk in the CPS-II Cohort
Authors: Sherman Mark E. , Vierkant Robert A. , Masters Matthew , Radisky Derek C. , Winham Stacey J. , Degnim Amy C. , Vachon Celine M. , Patel Alpa V. , Teras Lauren R.
Published: April 2023

Supplementary Table S1: Distributions of demographic and clinical characteristics by Ever NSAID use.
Supplementary Table S1 from Estrogen-DNA Adducts and Breast Cancer Risk in Premenopausal Asian Women
Authors: Lin Ching-Hung , Zahid Muhammad , Kuo Wen-Hung , Hu Fu-Chang , Wang Ming-Yang , Chen I-Chun , Beseler Cheryl L. , Mondal Bodhisattwa , Lu Yen-Shen , Rogan Eleanor G. , Cheng Ann-Lii
Published: April 2023

Supplementary Table S1: Data of demographics, estrogen-DNA adduct ratios, gene polymorphisms of the study population
Supplementary Table S1 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 S1 shows Diastolic blood pressure of study participants at each study visit, including immediately pre- and 30 minutes post-vaccination
Data from Breast Cancer Cell Apoptosis with Phytoestrogens Is Dependent on an Estrogen-Deprived State
Authors: Obiorah Ifeyinwa E. , Fan Ping , Jordan V. Craig
Published: April 2023

Abstract
Phytoestrogens have been investigated as natural alternatives to hormone replacement therapy and their potential as chemopreventive agents. We investigated the effects of equol, genistein, and coumestrol on cell growth in fully estrogenized MCF7 cells, simulating the perimenopausal state, and long-term estrogen-deprived MCF7:5C cells, which simulate the postmenopausal state of a woman after years of estrogen deprivation, and compared the effects with that of steroidal estrogens: 17β estradiol (E2) and equilin present in conjugated equine estrogen. Steroidal and phytoestrogens induce proliferation of MCF7 cells at physiologic concentrations but inhibit the growth and induce apoptosis of MCF7:5C cells. Although steroidal and phytoestrogens induce estrogen-responsive genes, their antiproliferative and apoptotic effects are mediated through the estrogen receptor. Knockdown of ERα using siRNA blocks all estrogen-induced apoptosis and growth inhibition. Phytoestrogens induce endoplasmic reticulum stress and inflammatory response stress–related genes in a comparable manner as the steroidal estrogens. Inhibition of inflammation using dexamethasone blocked both steroidal- and phytoestrogen-induced apoptosis and growth inhibition as well as their ability to induce apoptotic genes. Together, this suggests that phytoestrogens can potentially be used as chemopreventive agents in older postmenopausal women but caution should be exercised when used in conjunction with steroidal anti-inflammatory agents due to their antiapoptotic effects. Cancer Prev Res; 7(9); 939–49. ©2014 AACR.
Data from Body Mass Index and the Risk for Developing Invasive Breast Cancer among High-Risk Women in NSABP P-1 and STAR Breast Cancer Prevention Trials
Authors: Cecchini Reena S. , Costantino Joseph P. , Cauley Jane A. , Cronin Walter M. , Wickerham D. Lawrence , Land Stephanie R. , Weissfeld Joel L. , Wolmark Norman
Published: April 2023

Abstract
High body mass index (BMI) has been associated with an increased risk for breast cancer among postmenopausal women. However, the relationship between BMI and breast cancer risk in premenopausal women has remained unclear. Data from two large prevention trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) were used to explore the relationship between baseline BMI and breast cancer risk. The analyses included 12,243 participants with 253 invasive breast cancer events from the Breast Cancer Prevention Trial (P-1) and 19,488 participants with 557 events from the Study of Tamoxifen and Raloxifene (STAR). Both studies enrolled high-risk women (Gail score ≥ 1.66) with no breast cancer history. Women in P-1 were pre- and postmenopausal, whereas women in STAR (P-2) were all postmenopausal at entry. Using Cox proportional hazards regression, we found slight but nonsignificant increased risks of invasive breast cancer among overweight and obese postmenopausal participants in STAR and P-1. Among premenopausal participants, an increased risk of invasive breast cancer was significantly associated with higher BMI (P = 0.01). Compared with BMI less than 25, adjusted HRs for premenopausal women were 1.59 for BMI 25 to 29.9 and 1.70 for BMI 30 or more. Our investigation among annually screened, high-risk participants in randomized, breast cancer chemoprevention trials showed that higher levels of BMI were significantly associated with increased breast cancer risk in premenopausal women older than 35 years, but not postmenopausal women. Cancer Prev Res; 5(4); 583–92. ©2012 AACR.
Data from Endocytosis of Resveratrol via Lipid Rafts and Activation of Downstream Signaling Pathways in Cancer Cells
Authors: Colin Didier , Limagne Emeric , Jeanningros Sylvie , Jacquel Arnaud , Lizard Gérard , Athias Anne , Gambert Philippe , Hichami Aziz , Latruffe Norbert , Solary Eric , Delmas Dominique
Published: April 2023

Abstract
trans-Resveratrol has been proposed to prevent tumor growth and to sensitize cancer cells to anticancer agents. Polyphenol entry into the cells has remained poorly understood. Here, we show that [3H]-resveratrol enters colon cancer cells (SW480, SW620, HT29) and leukemia U937 cells through a monensin (5–20 μmol/L) -sensitive process that suggests clathrin-independent endocytosis. Uptake of the molecule can be prevented by methyl-β-cyclodextrin (2–12 mg/mL), nystatin (12 ng/mL), and filipin (1 μg/mL), which all disrupt plasma membrane lipid rafts. Accordingly, radiolabeled resveratrol accumulates in sphingomyelin- and cholesterol-enriched cell fractions. Interestingly, extracellular signal–regulated kinases (ERK), c-Jun NH2-terminal kinases (JNK), and Akt also accumulate in lipid rafts on resveratrol exposure (IC50 at 48 h ≈ 30 μmol/L in SW480 and U937 cells). In these rafts also, resveratrol promotes the recruitment, by the integrin αVβ3 (revealed by coimmunoprecipitation with an anti-integrin αVβ3 antibody), of signaling molecules that include the FAK (focal adhesion kinase), Fyn, Grb2, Ras, and SOS proteins. Resveratrol-induced activation of downstream signaling pathways and caspase-dependent apoptosis is prevented by endocytosis inhibitors, lipid raft–disrupting molecules, and the integrin antagonist peptide arginine-glycine-aspartate (500 nmol/L). Altogether, these data show the role played by lipid rafts in resveratrol endocytosis and activation of downstream pathways leading to cell death. Cancer Prev Res; 4(7); 1095–106. ©2011 AACR.
Data from Resveratrol-Induced Apoptosis Is Mediated by Early Growth Response-1, Krüppel-Like Factor 4, and Activating Transcription Factor 3
Authors: Whitlock Nichelle C. , Bahn Jae Hoon , Lee Seong-Ho , Eling Thomas E. , Baek Seung Joon
Published: April 2023

Abstract
Resveratrol, a dietary phytoalexin readily available in the diet, is reported to possess antitumorigenic properties in several cancers, including colorectal. However, the underlying mechanism(s) involved is not completely understood. In the present study, we investigated the effect of resveratrol treatment on gene modulation in human colorectal cancer cells and identified activating transcription factor 3 (ATF3) as the most highly induced gene after treatment. We confirmed that resveratrol upregulates ATF3 expression, both at the mRNA and protein level, and showed resveratrol involvement in ATF3 transcriptional regulation. Analysis of the ATF3 promoter revealed the importance of early growth response-1 (Egr-1; located at −245 to −236) and Krüppel-like factor 4 (KLF4; located at −178 to −174) putative binding sites in resveratrol-mediated ATF3 transactivation. Specificity of these sites to the Egr-1 and KLF4 protein was confirmed by electrophoretic mobility shift and chromatin immunoprecipitation assays. Resveratrol increased Egr-1 and KLF4 expression, which preceded ATF3 expression, and further suggests Egr-1 and KLF4 involvement in resveratrol-mediated activity. We provide evidence for Egr-1 and KLF4 interaction in the presence of resveratrol, which may facilitate ATF3 transcriptional regulation by this compound. Furthermore, we demonstrate that induction of apoptosis by resveratrol is mediated, in part, by increased ATF3 expression. Taken together, these results provide a novel mechanism by which resveratrol induces ATF3 expression and represent an additional explanation of how resveratrol exerts its antitumorigenic effects in human colorectal cancer cells. Cancer Prev Res; 4(1); 116–27. ©2011 AACR.
Data from Reducing HPV-Associated Cancer Globally
Authors: Lowy Douglas R. , Schiller John T.
Published: April 2023

Abstract
Human papillomavirus (HPV)-related cancers are a major worldwide public health concern. Virtually all cervical cancer is HPV related, with 70% caused by HPV16 and -18. Variable proportions of certain noncervical cancers (e.g., anal, vulvar, and oropharyngeal) are HPV related; more than 90% of the HPV-related ones are caused by HPV16, -18. The HPV-related cancers are dominated by cervical cancer in the developing world, where cervical cancer screening is limited. In this setting, widespread uptake of current HPV vaccines by adolescent girls could reduce this cancer's incidence and mortality by approximately two-thirds, with cost-effective screening programs of adult women having the potential to reduce mortality more rapidly. In the industrialized world, some noncervical HPV-related cancers, especially oropharyngeal, are rapidly increasing, and now rival the incidence of cervical cancer, whose rates continue to decline thanks to established cervical screening programs. Therefore, reducing HPV-associated noncervical cancers with HPV vaccination has greater importance in the industrialized world, especially because there are no approved screening programs for these cancers. Preventing the substantial number of noncervical HPV cancers in men will require either “herd” immunity through high-vaccination rates in females or male vaccination. Current HPV vaccination can complement cervical screening in protecting against cervical cancer and may permit the safe reduction of screening intensity in industrialized countries. Second-generation HPV vaccines (active against a broader array of cervical cancer–related HPV types) could prevent an even higher proportion of cervical precancer and cancer and might permit further reductions in screening intensity. Cancer Prev Res; 5(1); 18–23. ©2012 AACR.
Data from Cardiovascular Risk Markers and Mechanisms in Targeting the COX Pathway for Colorectal Cancer Prevention
Authors: Oates John A.
Published: April 2023

Abstract
COX-2 inhibition reduces the incidence of colorectal neoplasia. The increased risk of thrombotic cardiovascular events produced by selective or nonselective COX-2 inhibitors, however, has confounded the consideration of employing them in cancer prevention. Developing a strategy for preventing colorectal cancer by inhibiting COX-2 depends on research advances in several key areas, including predictive biomarkers to identify people at the lowest risk for cardiovascular events, the molecular mechanisms whereby interdicting the COX-2 pathway produces thrombotic events, and the pharmacology of the widely divergent agents that act on COX-2 and its downstream pathway. Cancer Prev Res; 4(8); 1145–8. ©2011 AACR.