bluuebunny/crossref_metadata_2025 huggingface dataset:
Data 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

Abstract
An urgent need exists for the development of more efficacious molecular strategies targeting nonmelanoma skin cancer (NMSC), the most common malignancy worldwide. Inflammatory signaling downstream of Toll-like receptor 4 (TLR4) has been implicated in several forms of tumorigenesis, yet its role in solar UV-induced skin carcinogenesis remains undefined. We have previously shown in keratinocyte cell culture and SKH-1 mouse epidermis that topical application of the specific TLR4 antagonist resatorvid (TAK-242) blocks acute UV-induced AP-1 and NF-κB signaling, associated with downregulation of inflammatory mediators and MAP kinase phosphorylation. We therefore explored TLR4 as a novel target for chemoprevention of UV-induced NMSC. We selected the clinical TLR4 antagonist resatorvid based upon target specificity, potency, and physicochemical properties. Here, we confirm using ex vivo permeability assays that topical resatorvid can be effectively delivered to skin, and using in vivo studies that topical resatorvid can block UV-induced AP-1 activation in mouse epidermis. We also report that in a UV-induced skin tumorigenesis model, topical resatorvid displays potent photochemopreventive activity, significantly suppressing tumor area and multiplicity. Tumors harvested from resatorvid-treated mice display reduced activity of UV-associated signaling pathways and a corresponding increase in apoptosis compared with tumors from control animals. Further mechanistic insight on resatorvid-based photochemoprevention was obtained from unsupervised hierarchical clustering analysis of protein readouts via reverse-phase protein microarray revealing a significant attenuation of key UV-induced proteomic changes by resatorvid in chronically treated high-risk SKH-1 skin prior to tumorigenesis. Taken together, our data identify TLR4 as a novel molecular target for topical photochemoprevention of NMSC. Cancer Prev Res; 11(5); 265–78. ©2018 AACR.

See related editorial by Sfanos, p. 251
Data 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

Abstract
We previously reported that the environmental pollutant and tobacco smoke constituent dibenzo[def,p]chrysene (DBP) induced DNA damage, altered DNA methylation and induced oral squamous cell carcinoma (OSCC) in mice. In the present study, we showed that 5% dietary black raspberry (BRB) significantly reduced (P < 0.05) the levels of DBP-DNA adducts in the mouse oral cavity with comparable effect to those of its constitutes. Thus, only BRB was selected to examine if aberrant DNA methylation induced by DBP can be altered by BRB. Using comparative genome-wide DNA methylation analysis, we identified 479 hypermethylated and 481 hypomethylated sites (q < 0.01, methylation difference >25%) between the oral tissues of mice treated with DBP and fed control diet or diet containing BRB. Among the 30 differential methylated sites (DMS) induced by DBP, we found DMS mapped to Fgf3, Qrich2, Rmdn2, and Cbarp were hypermethylated by BRB whereas hypomethylated by DBP at either the exact position or proximal sites; DMS mapped to Vamp3, Ppp1rB1, Pkm, and Zfp316 were hypomethylated by BRB but hypermethylated by DBP at proximal sites. In addition to Fgf3, 2 DMS mapped to Fgf4 and Fgf13 were hypermethylated by BRB; these fibroblast growth factors are involved in regulation of the epithelial–mesenchymal transition (EMT) pathway as identified by IPA. Moreover, BRB significantly reduced (P < 0.05) the tumor incidence from 70% to 46.7%. Taken together, the inhibitory effects of BRB on DNA damage combined with its effects on epigenetic alterations may account for BRB inhibition of oral tumorigenesis induced by DBP.
Significance:
We provided mechanistic insights that can account for the inhibition of oral tumors by BRB, which could serve as the framework for future chemopreventive trials for addicted smokers as well as non- or former smokers who are exposed to environmental carcinogens.
Data from A New Model to Study the Role of Arachidonic Acid in Colon Cancer Pathophysiology
Authors: Fan Yang-Yi , Callaway Evelyn , M. Monk Jennifer , S. Goldsby Jennifer , Yang Peiying , Vincent Logan , S. Chapkin Robert
Published: April 2023

Abstract
A significant increase in cyclooxygenase 2 (COX2) gene expression has been shown to promote cylcooxygenase-dependent colon cancer development. Controversy associated with the role of COX2 inhibitors indicates that additional work is needed to elucidate the effects of arachidonic acid (AA)-derived (cyclooxygenase and lipoxygenase) eicosanoids in cancer initiation, progression, and metastasis. We have recently developed a novel Fads1 knockout mouse model that allows for the investigation of AA-dependent eicosanoid deficiency without the complication of essential fatty acid deficiency. Interestingly, the survival rate of Fads1-null mice is severely compromised after 2 months on a semi-purified AA-free diet, which precludes long-term chemoprevention studies. Therefore, in this study, dietary AA levels were titrated to determine the minimal level required for survival, while maintaining a distinct AA-deficient phenotype. Null mice supplemented with AA (0.1%, 0.4%, 0.6%, 2.0%, w/w) in the diet exhibited a dose-dependent increase (P < 0.05) in AA, PGE2, 6-keto PGF1α, TXB2, and EdU-positive proliferative cells in the colon. In subsequent experiments, null mice supplemented with 0.6% AA diet were injected with a colon-specific carcinogen (azoxymethane) in order to assess cancer susceptibility. Null mice exhibited significantly (P < 0.05) reduced levels/multiplicity of aberrant crypt foci (ACF) as compared with wild-type sibling littermate control mice. These data indicate that (i) basal/minimal dietary AA supplementation (0.6%) expands the utility of the Fads1-null mouse model for long-term cancer prevention studies and (ii) that AA content in the colonic epithelium modulates colon cancer risk. Cancer Prev Res; 9(9); 750–7. ©2016 AACR.
Data from Effect of Aspirin on Melanoma Incidence in Older Persons: Extended Follow-up of a Large Randomized Double-blind Placebo-controlled Trial
Authors: Yan Mabel K. , Orchard Suzanne G. , Adler Nikki R. , Wolfe Rory , McLean Catriona , Rodriguez Luz María. , Woods Robyn L. , Gibbs Peter , Chan Andrew T. , Haydon Andrew , Mar Victoria J.
Published: April 2023

Abstract
The effects of aspirin on melanoma are unclear, with studies reporting conflicting results. Data from two periods of the ASPirin in Reducing Events in the Elderly (ASPREE) study; the randomized placebo-controlled trial period examining daily 100 mg aspirin in older adults with a median follow-up of 4.7 years, and the second period, an additional 2 years of observational follow-up, were utilized in this secondary analysis to examine whether aspirin exposure is associated with a reduced cutaneous melanoma incidence. All melanoma cases were adjudicated and Cox proportional hazards models were used to compare incidence between randomized treatment groups. ASPREE recruited 19,114 participants with a median age of 74 years. During the trial period, 170 individuals (76 aspirin, 94 placebo) developed an invasive melanoma, and no significant effect of aspirin was observed on incident melanoma [HR = 0.81; 95% confidence interval (CI), 0.60–1.10]. Including the additional 2 years of observational follow-up (median follow-up of 6.3 years), 268 individuals (119 aspirin, 149 placebo) developed an invasive melanoma, and similar results were observed (HR = 0.81; 95% CI, 0.63–1.03). A reduced number of events was observed with aspirin among females in a subgroup analysis (HR = 0.65; 95% CI, 0.44–0.92); however, the interaction effect with males (HR = 0.92; 95% CI, 0.68–1.25) was nonsignificant (P = 0.17). Our findings from this randomized trial do not provide strong support that aspirin is associated with a reduced risk of invasive melanoma in older individuals. Additional studies are required to further explore this relationship.
Prevention Relevance:
Melanoma prevention is an important strategy to improve outcomes and while preventive efforts have largely focused on sun protection, the role of potential chemopreventive agents such as aspirin warrants investigation.
Data from Genome-Wide Meta-analysis of Gene–Environmental Interaction for Insulin Resistance Phenotypes and Breast Cancer Risk in Postmenopausal Women
Authors: Jung Su Yon , Mancuso Nick , Yu Herbert , Papp Jeanette , Sobel Eric , Zhang Zuo-Feng
Published: April 2023

Abstract
Insulin resistance (IR)–related genetic variants are possibly associated with breast cancer, and the gene–phenotype–cancer association could be modified by lifestyle factors including obesity, physical inactivity, and high-fat diet. Using data from postmenopausal women, a population highly susceptible to obesity, IR, and increased risk of breast cancer, we implemented a genome-wide association study (GWAS) in two steps: (1) GWAS meta-analysis of gene–environmental (i.e., behavioral) interaction (G*E) for IR phenotypes (hyperglycemia, hyperinsulinemia, and homeostatic model assessment–insulin resistance) and (2) after the G*E GWAS meta-analysis, the identified SNPs were tested for their associations with breast cancer risk in overall or subgroup population, where the SNPs were identified at genome-wide significance. We found 58 loci (55 novel SNPs; 5 index SNPs and 6 SNPs, independent of each other) that are associated with IR phenotypes in women overall or women stratified by obesity, physical activity, and high-fat diet; among those 58 loci, 29 (26 new loci; 2 index SNPs and 2 SNPs, independently) were associated with postmenopausal breast cancer. Our study suggests that a number of newly identified SNPs may have their effects on glucose intolerance by interplaying with obesity and other lifestyle factors, and a substantial proportion of these SNPs’ susceptibility can also interact with the lifestyle factors to ultimately influence breast cancer risk. These findings may contribute to improved prediction accuracy for cancer and suggest potential intervention strategies for those women carrying genetic risk that will reduce their breast cancer risk.
Data from Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on Breast Cancer Risk Biomarkers in High-Risk Women: A Pilot Study
Authors: Fabian Carol J. , Nye Lauren , Powers Kandy R. , Nydegger Jennifer L. , Kreutzjans Amy L. , Phillips Teresa A. , Metheny Trina , Winblad Onalisa , Zalles Carola M. , Hagan Christy R. , Goodman Merit L. , Gajewski Byron J. , Koestler Devin C. , Chalise Prabhakar , Kimler Bruce F.
Published: April 2023

Abstract
Interventions that relieve vasomotor symptoms while reducing risk for breast cancer would likely improve uptake of chemoprevention for perimenopausal and postmenopausal women. We conducted a pilot study with 6 months of the tissue selective estrogen complex bazedoxifene (20 mg) and conjugated estrogen (0.45 mg; Duavee) to assess feasibility and effects on risk biomarkers for postmenopausal breast cancer. Risk biomarkers included fully automated mammographic volumetric density (Volpara), benign breast tissue Ki-67 (MIB-1 immunochemistry), and serum levels of progesterone, IGF-1, and IGFBP3, bioavailable estradiol and testosterone. Twenty-eight perimenopausal and postmenopausal women at increased risk for breast cancer were enrolled: 13 in cohort A with baseline Ki-67 < 1% and 15 in cohort B with baseline Ki-67 of 1% to 4%. All completed the study with > 85% drug adherence. Significant changes in biomarkers, uncorrected for multiple comparisons, were a decrease in mammographic fibroglandular volume (P = 0.043); decreases in serum progesterone, bioavailable testosterone, and IGF-1 (P < 0.01), an increase in serum bioavailable estradiol (P < 0.001), and for women from cohort B a reduction in Ki-67 (P = 0.017). An improvement in median hot flash score from 15 at baseline to 0 at 6 months, and menopause-specific quality-of-life total, vasomotor, and sexual domain scores were also observed (P < 0.001). Given the favorable effects on risk biomarkers and patient reported outcomes, a placebo-controlled phase IIB trial is warranted.
Data from Long-Term Glucocorticoid Use and Cancer Risk: A Population-Based Cohort Study in South Korea
Authors: Oh Tak Kyu , Song In-Ae
Published: April 2023

Abstract
Long-term glucocorticoid (GC) exposure causes immunosuppression; therefore, the risk of cancer may be increased in long-term GC users. We investigated whether long-term GC use is associated with a higher risk of cancer in the population without cancer. A population-based cohort study using data from the National Health Insurance Service was conducted among the South Korean adult population in 2010. Long-term GC users were defined as those who were prescribed a continuous supply of oral GC for ≥30 days. The primary endpoint was a new cancer diagnosis from January 1, 2011, to December 31, 2015. Among 770,880 individuals included in the analysis, 1,602 (0.2%) were long-term GC users and 36,157 (4.7%) were newly diagnosed with cancer from January 2011 to December 2015. In the multivariable Cox regression analysis, the risk of cancer among long-term GC users was 1.23-fold higher than that of the unexposed individuals [95% confidence interval (CI), 1.06–1.43; P = 0.007]. In the competing risk analyses, the risks of liver cancer and lung cancer were 1.46-fold (95% CI, 1.03–2.07; P = 0.034) and 1.52-fold (95% CI, 1.04–2.21; P = 0.029) higher in the long-term GC users than that of the unexposed individuals, respectively. We found that long-term GC exposure might be associated with a higher risk of overall cancer, and this association was more evident for lung and liver cancer risk. However, because there might be unmeasured and potential confounders in this study, the results should be interpreted carefully, and future studies should be performed to confirm these findings.
Impact:
Long-term glucocorticoid therapy might be associated with a higher cancer risk. This association was more evident for lung and liver cancer risk. Our findings suggest that long-term prescriptions of glucocorticoids should be administered carefully considering the risk of cancer.
Data from Breast Cancer Risk and Use of Nonsteroidal Anti-inflammatory Agents After a Benign Breast Biopsy
Authors: Sherman Mark E. , Vierkant Robert A. , Kaggal Suneetha , Hoskin Tanya L. , Frost Marlene H. , Denison Lori , Visscher Daniel W. , Carter Jodi M. , Winham Stacey J. , Jensen Matthew R. , Radisky Derek C. , Vachon Celine M. , Degnim Amy C.
Published: April 2023

Abstract
Over one million women in the United States receive biopsy diagnoses of benign breast disease (BBD) each year, which confer a 1.5–4.0-fold increase in breast cancer risk. Studies in the general population suggest that nonsteroidal anti-inflammatory agents (NSAID) lower breast cancer risk; however, associations among women with BBD are unknown. We assessed whether NSAID use among women diagnosed with BBD is associated with lower breast cancer risk. Participants included 3,080 women (mean age = 50.3 ± 13.5 years) in the Mayo BBD surgical biopsy cohort diagnosed between January 1, 1992 and December 31, 2001 who completed breast cancer risk factor questionnaires that assessed NSAID use, and whose biopsies underwent detailed pathology review, masked to outcome. Women were followed from date of BBD biopsy to breast cancer diagnosis (main outcome) or censoring (death, prophylactic mastectomy, reduction mammoplasty, lobular carcinoma in situ or last contact). Median follow-up time was 16.4 ± 6.0 years. Incident breast cancer was diagnosed among 312 women over a median follow-up of 9.9 years. Regular non-aspirin NSAID use was associated with lower breast cancer risk [HR = 0.63; 95% confidence interval (CI) = 0.46–0.85; P = 0.002] with trends of lower risk (highest tertiles of use vs. nonuse) for greater number of years used [HR = 0.55; 95% CI = 0.31–0.97; Ptrend = 0.003), days used per month (HR = 0.51; 95% CI = 0.33–0.80; Ptrend = 0.001) and lifetime number of doses taken (HR = 0.53; 95% CI = 0.31–0.89; Ptrend = 0.003). We conclude that nonaspirin NSAID use is associated with statistically significant lower breast cancer risk after a BBD biopsy, including a dose–response effect, suggesting a potential role for NSAIDs in breast cancer prevention among patients with BBD.
Data from Risk of De Novo Hepatocellular Carcinoma Following Use of Direct Acting Antiviral Medications for Treatment of Chronic Hepatitis C
Authors: Antwi Samuel O. , Van Houten Holly K. , Sangaralingham Lindsey R. , Patel Tushar
Published: April 2023

Abstract
Direct-acting antivirals (DAA) are now the mainstay of treatment for patients with chronic hepatitis C virus (HCV); however, there is some controversy over whether use of DAAs for HCV, as compared with IFN-based regimens, leads to an increased risk for hepatocellular carcinoma (HCC) development. We investigated the association between use of DAAs and subsequent development of HCC in longitudinal data from patients with HCV from diverse backgrounds (various ages, ethnicities, and geographic regions) across the United States. The design was a retrospective study performed using medical and pharmacy claims from OptumLabs. HCV treatment exposure was categorized as DAA-only, DAA + IFN, any-DAA, or IFN-only. To account for confounding by indication, inverse probability of treatment weighting was performed. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). We identified 5,781 patients with HCV with no history of HCC at baseline. Compared with IFN-only regimen, no significant increase in HCC risk was found for use of DAA-only (HR, 1.53; 95% CI, 0.73–3.23), DAA + IFN (HR, 1.02; 95% CI, 0.51–2.06), or any-DAA (HR, 1.04; 95% CI, 0.65–1.65). When stratified by sustained virological response (SVR), we noted a higher HCC risk for DAA-only among patients who achieved SVR post-treatment (HR, 7.53; 95% CI, 1.48–38.34), but the CIs were wide, which might be due to the small sample size of the subgroups. Among those who did not achieve SVR, no association was found for use of DAA-only (HR, 0.59; 95% CI, 0.19–1.91). These findings do not provide compelling evidence for the conception that use of DAAs for HCV is associated with increased risk of HCC development.
Data from Cost Effectiveness of Whole Population BRCA Genetic Screening for Cancer Prevention in Israel
Authors: Michaan Nadav , Leshno Moshe , Safra Tamar , Sonnenblick Amir , Laskov Ido , Grisaru Dan
Published: April 2023

Abstract
With the growing technical ease and reduction in genetic screening costs, whole population BRCA screening may be a feasible option. Our objective was to investigate the cost effectiveness of whole population screening for BRCA mutations in Israel, for varying degrees of BRCA carrier state. Lifetime costs of whole female population screening for BRCA mutation carrier state versus nonscreening were compared using a Markovian process decision analysis model. Model parameters including ovarian and breast cancer risks were obtained from previously published data. Screening and other treatment-related costs were received from the Israeli Ministry of Health pricing list according to specified codes. Quality-adjusted life years were used for cost-effectiveness analysis. Sensitivity analysis was conducted to evaluate model uncertainties, specifically varying degrees of BRCA prevalence. Results show that whole population BRCA screening in Israel is cost effective across a wide range of BRCA prevalence rates with an incremental cost-effectiveness ratio of 81,493 new Israeli Shekels for a BRCA prevalence of 2.5%, increasing to 250,000 new Israeli Shekels for a 0.75% prevalence rate, per quality-adjusted life year gained. Discount rate and population BRCA prevalence and rate of risk reduction salpingo-oophorectomy are the most influential parameters in the model. Whole population screening for BRCA mutations should be offered as part of general health screening strategies by national medical insurance providers, even for non-Ashkenazi Jews. Our algorithm can be applied for other countries, adjusting local costs of screening and treatment.
Prevention Relevance:
Whole population BRCA mutation screening in Israel is cost effective across a wide prevalence rate and should be offered as part of general health screening strategies by national medical insurance providers for cancer prevention.
Data from A Systematic Review on Cost-effectiveness Studies Evaluating Ovarian Cancer Early Detection and Prevention Strategies
Authors: Sroczynski Gaby , Gogollari Artemisa , Kuehne Felicitas , Hallsson Lára R. , Widschwendter Martin , Pashayan Nora , Siebert Uwe
Published: April 2023

Abstract
Ovarian cancer imposes a substantial health and economic burden. We systematically reviewed current health-economic evidence for ovarian cancer early detection or prevention strategies. Accordingly, we searched relevant databases for cost-effectiveness studies evaluating ovarian cancer early detection or prevention strategies. Study characteristics and results including quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were summarized in standardized evidence tables. Economic results were transformed into 2017 Euros. The included studies (N = 33) evaluated ovarian cancer screening, risk-reducing interventions in women with heterogeneous cancer risks and genetic testing followed by risk-reducing interventions for mutation carriers. Multimodal screening with a risk-adjusted algorithm in postmenopausal women achieved ICERs of 9,800–81,400 Euros/QALY, depending on assumptions on mortality data extrapolation, costs, test performance, and screening frequency. Cost-effectiveness of risk-reducing surgery in mutation carriers ranged from cost-saving to 59,000 Euros/QALY. Genetic testing plus risk-reducing interventions for mutation carriers ranged from cost-saving to 54,000 Euros/QALY in women at increased mutation risk. Our findings suggest that preventive surgery and genetic testing plus preventive surgery in women at high risk for ovarian cancer can be considered effective and cost-effective. In postmenopausal women from the general population, multimodal screening using a risk-adjusted algorithm may be cost-effective.
Data from Using Digital Pathology to Understand Epithelial Characteristics of Benign Breast Disease among Women Undergoing Diagnostic Image-Guided Breast Biopsy
Authors: Mullooly Maeve , Puvanesarajah Samantha , Fan Shaoqi , Pfeiffer Ruth M. , Olsson Linnea T. , Hada Manila , Kirk Erin L. , Vacek Pamela M. , Weaver Donald L. , Shepherd John , Mahmoudzadeh Amir , Wang Jeff , Malkov Serghei , Johnson Jason M. , Hewitt Stephen M. , Herschorn Sally D. , Sherman Mark E. , Troester Melissa A. , Gierach Gretchen L.
Published: April 2023

Abstract
Delayed terminal duct lobular unit (TDLU) involution is associated with elevated mammographic breast density (MD). Both are independent breast cancer risk factors among women with benign breast disease (BBD). Prior digital analyses of normal breast tissues revealed that epithelial nuclear density (END) and TDLU involution are inversely correlated. Accordingly, we examined associations of END, TDLU involution, and MD in BBD clinical biopsies. This study included digitized images of 262 representative image-guided hematoxylin and eosin–stained biopsies from 224 women diagnosed with BBD, enrolled within the cross-sectional BREAST-Stamp project that were visually assessed for TDLU involution (TDLU count/100 mm2, median TDLU span and median acini count per TDLU). A digital algorithm estimated nuclei count per unit epithelial area, or END. Single X-ray absorptiometry of prebiopsy ipsilateral craniocaudal digital mammograms measured global and localized MD surrounding the biopsy region. Adjusted ordinal logistic regression models assessed relationships between tertiles of TDLU and END measures. Analysis of covariance examined mean differences in MD across END tertiles. TDLU measures were positively associated with increasing END tertiles [TDLU count/100 mm2, ORT3vsT1: 3.42, 95% confidence interval (CI), 1.87–6.28; acini count/TDLUT3vsT1, OR: 2.40, 95% CI, 1.39–4.15]. END was significantly associated with localized, but not, global MD. Relationships were most apparent among patients with nonproliferative BBD. These findings suggest that quantitative END reflects different but complementary information to the histologic information captured by visual TDLU and radiologic MD measures and merits continued evaluation in assessing cellularity of breast parenchyma to understand the etiology of BBD.
Data from Comparison between Urine and Cervical Samples for HPV DNA Detection and Typing in Young Women in Colombia
Authors: Cómbita Alba Lucía , Gheit Tarik , González Paula , Puerto Devi , Murillo Raúl Hernando , Montoya Luisa , Vorsters Alex , Van Keer Severien , Van Damme Pierre , Tommasino Massimo , Hernández-Suárez Gustavo , Sánchez Laura , Herrero Rolando , Wiesner Carolina
Published: April 2023

Abstract
Urine sampling for HPV DNA detection has been proposed as an effective method for monitoring the impact of HPV vaccination programs; however, conflicting results have been reported. The goal of this study was to evaluate the performance of optimized urine HPV DNA testing in women aged 19 to 25 years. Optimization process included the use of first void urine, immediate mixing of urine with DNA preservative, and the concentration of all HPV DNA, including cell-free DNA fragments. Urine and cervical samples were collected from 535 young women attending cervical screening at health centers from two Colombian cities. HPV DNA detection and genotyping was performed using an HPV type-specific multiplex genotyping assay, which combines multiplex polymerase chain reaction with bead-based Luminex technology. Concordance between HPV DNA detection in urine and cervical samples was determined using kappa statistics and McNemar tests. The accuracy of HPV DNA testing in urine samples was evaluated measuring sensitivity and specificity using as reference the results obtained from cervical samples. Statistical analysis was performed using STATA11.2 software. The findings revealed an overall HPV prevalence of 60.00% in cervical samples and 64.72% in urine samples, HPV-16 being the most frequent HPV type detected in both specimens. Moreover, our results indicate that detection of HPV DNA in first void urine provides similar results to those obtained with cervical samples and can be used to monitor HPV vaccination trials and programs as evidenced by the substantial concordance found for the detection of the four vaccine types. Cancer Prev Res; 9(9); 766–71. ©2016 AACR.
Data from Saliva and Lung Microbiome Associations with Electronic Cigarette Use and Smoking
Authors: Ying Kevin L. , Brasky Theodore M. , Freudenheim Jo L. , McElroy Joseph P. , Nickerson Quentin A. , Song Min-Ae , Weng Daniel Y. , Wewers Mark D. , Whiteman Noah B. , Mathe Ewy A. , Shields Peter G.
Published: April 2023

Abstract
The microbiome has increasingly been linked to cancer. Little is known about the lung and oral cavity microbiomes in smokers, and even less for electronic cigarette (EC) users, compared with never-smokers. In a cross-sectional study (n = 28) of smokers, EC users, and never-smokers, bronchoalveolar lavage and saliva samples underwent metatranscriptome profiling to examine associations with lung and oral microbiomes. Pairwise comparisons assessed differentially abundant bacteria species. Total bacterial load was similar between groups, with no differences in bacterial diversity across lung microbiomes. In lungs, 44 bacteria species differed significantly (FDR < 0.1) between smokers/never-smokers, with most decreased in smokers. Twelve species differed between smokers/EC users, all decreased in smokers of which Neisseria sp. KEM232 and Curvibacter sp. AEP1-3 were observed. Among the top five decreased species in both comparisons, Neisseria elongata, Neisseria sicca, and Haemophilus parainfluenzae were observed. In the oral microbiome, 152 species were differentially abundant for smokers/never-smokers, and 17 between smokers/electronic cigarette users, but only 21 species were differentially abundant in both the lung and oral cavity. EC use is not associated with changes in the lung microbiome compared with never-smokers, indicating EC toxicity does not affect microbiota. Statistically different bacteria in smokers compared with EC users and never-smokers were almost all decreased, potentially due to toxic effects of cigarette smoke. The low numbers of overlapping oral and lung microbes suggest that the oral microbiome is not a surrogate for analyzing smoking-related effects in the lung.
Prevention Relevance:
The microbiome affects cancer and other disease risk. The effects of e-cig usage on the lung microbiome are essentially unknown. Given the importance of lung microbiome dysbiosis populated by oral species which have been observed to drive lung cancer progression, it is important to study effects of e-cig use on microbiome.
Data from Dietary Methyl Donor Depletion Suppresses Intestinal Adenoma Development
Authors: Hanley Matthew P. , Kadaveru Krishna , Perret Christine , Giardina Charles , Rosenberg Daniel W.
Published: April 2023

Abstract
The role of folate one-carbon metabolism in colorectal cancer development is controversial, with nutritional intervention studies producing conflicting results. It has been reported that ApcMin/+ mice maintained on a diet deficient in the methyl donors folic acid, methionine, choline, and vitamin B12, and supplemented with homocysteine, show a greater than 95% reduction in intestinal tumor development. The present study extends these findings and shows that tumor protection afforded by dietary methyl donor deficiency (MDD) is long-lasting. After 11 weeks of MDD, tumor protection persisted for at least an additional 7 weeks of methyl donor repletion (22.2 ± 3.5 vs. 70.2 ± 4.6 tumors per mouse; P < 0.01). Sustained tumor protection was associated with a reduction in intestinal crypt length (26%, P < 0.01), crypt cell division and crypt fission, and an increase in apoptosis of both normal crypts and tumors (4.9- and 3.2-fold, respectively, P < 0.01). MDD also caused a significant reduction in the number of Dclk1-positive cells in the intestine (62%, P < 0.01), a long-lived crypt cell with cancer stem cell potential. Several undesirable effects associated with methyl donor restriction (e.g., reduced body weight gain) were shown to be transient and readily reversible following methyl donor repletion. Taken together, these results indicate that even temporary dietary methyl donor restriction in adenoma-prone mice can induce persistent changes to the intestinal epithelium and provide long-lasting tumor protection. These data also suggest that transient reductions in dietary methyl donor consumption should be considered when studying the impact of folate on colon cancer risk in humans. Cancer Prev Res; 9(10); 812–20. ©2016 AACR.
Data from Withaferin A Inhibits Fatty Acid Synthesis in Rat Mammary Tumors
Authors: Singh Krishna B. , Hahm Eun-Ryeong , Kim Su-Hyeong , Singh Shivendra V.
Published: April 2023

Abstract
Withaferin A (WA), which is a small molecule derived from a medicinal plant (Withania somnifera), inhibits growth of human breast cancer xenografts and mammary tumor development in rodent models without any toxicity. However, the mechanism underlying inhibition of mammary cancer development by WA administration is not fully understood. Herein, we demonstrate that the fatty acid synthesis pathway is a novel target of WA in mammary tumors. Treatment of MCF-7 and MDA-MB-231 cells with WA resulted in suppression of fatty acid metabolizing enzymes, including ATP-citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A). Expression of FASN and CPT1A was significantly higher in N-methyl-N-nitrosourea–induced mammary tumors in rats when compared with normal mammary tissues. WA-mediated inhibition of mammary tumor development in rats was associated with a statistically significant decrease in expression of ACC1 and FASN and suppression of plasma and/or mammary tumor levels of total free fatty acids and phospholipids. WA administration also resulted in a significant increase in percentage of natural killer cells in the spleen. The protein level of sterol regulatory element binding protein 1 (SREBP1) was decreased in MDA-MB-231 cells after WA treatment. Overexpression of SREBP1 in MDA-MB-231 cells conferred partial but significant protection against WA-mediated downregulation of ACLY and ACC1. In conclusion, circulating and/or mammary tumor levels of fatty acid synthesis enzymes and total free fatty acids may serve as biomarkers of WA efficacy in future clinical trials.
Prevention Relevance:
The present study shows that breast cancer prevention by WA in rats is associated with suppression of fatty acid synthesis.
Data 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

Abstract
Accurate breast cancer risk prediction could improve risk-reduction paradigms if thoughtfully used in clinical practice. Identification of at-risk women is the first step in tailoring risk screening and risk-reduction protocols to women's needs. Using the UK Biobank, we validated a simple risk model to predict breast cancer risk in the general population. Our simple breast cancer risk (BRISK) model integrates a combination of impactful breast cancer-associated risk factors including extended family history and polygenic risk allowing for the removal of moderate factors currently found in comprehensive traditional models. Using two versions of BRISK, differing by 77-single-nucleotide polymorphisms (SNP) versus 313-SNP polygenic risk score integration, we found improved discrimination and risk categorization of both BRISK models compared with one of the most well-known models, the Breast Cancer Risk Assessment Tool (BRCAT). Over a 5-year period, at-risk women classified ≥3% 5-year risk by BRISK had a 1.829 (95% CI = 1.710–1.956) times increased incidence of breast cancer compared with the population, which was higher than the 1.413 (95% CI = 1.217–1.640) times increased incidence for women classified ≥3% by BCRAT.
Prevention Relevance:
In this prospective population-based cohort study, we show the improved performance of a new risk assessment model compared with a gold-standard model (BCRAT). The classification of at-risk women using this new model highlights the opportunity to improve risk stratification and implement existing clinical risk-reduction interventions.
Supplementary Figure 4 from A Molecularly Annotated Platform of Patient-Derived Xenografts (“Xenopatients”) Identifies HER2 as an Effective Therapeutic Target in Cetuximab-Resistant Colorectal Cancer
Authors: Bertotti Andrea , Migliardi Giorgia , Galimi Francesco , Sassi Francesco , Torti Davide , Isella Claudio , Corà Davide , Di Nicolantonio Federica , Buscarino Michela , Petti Consalvo , Ribero Dario , Russolillo Nadia , Muratore Andrea , Massucco Paolo , Pisacane Alberto , Molinaro Luca , Valtorta Emanuele , Sartore-Bianchi Andrea , Risio Mauro , Capussotti Lorenzo , Gambacorta Marcello , Siena Salvatore , Medico Enzo , Sapino Anna , Marsoni Silvia , Comoglio Paolo M. , Bardelli Alberto , Trusolino Livio
Published: April 2023

PDF file - 226K
Interview with Dr. Polyak from Evolutionary Pathways in BRCA1-Associated Breast Tumors
Authors: Martins Filipe C. , De Subhajyoti , Almendro Vanessa , Gönen Mithat , Park So Yeon , Blum Joanne L. , Herlihy William , Ethington Gabrielle , Schnitt Stuart J. , Tung Nadine , Garber Judy E. , Fetten Katharina , Michor Franziska , Polyak Kornelia
Published: April 2023

mp3 file (9 MB). In the June edition of the Cancer Discovery podcast, Science Writer Elizabeth McKenna talks with Kornelia Polyak about her paper, which uses a combined experimental and computational approach to reveal that the loss of wild-type BRCA1 may not be the first event in the majority of BRCA1-associated breast tumors and may not be present in all cancer cells within tumors.
Supplementary Table S1 from A Drug Repositioning Approach Identifies Tricyclic Antidepressants as Inhibitors of Small Cell Lung Cancer and Other Neuroendocrine Tumors
Authors: Jahchan Nadine S. , Dudley Joel T. , Mazur Pawel K. , Flores Natasha , Yang Dian , Palmerton Alec , Zmoos Anne-Flore , Vaka Dedeepya , Tran Kim Q.T. , Zhou Margaret , Krasinska Karolina , Riess Jonathan W. , Neal Joel W. , Khatri Purvesh , Park Kwon S. , Butte Atul J. , Sage Julien
Published: April 2023

- PDF file 94K, Top 100 FDA-approved drugs identified by a bioinformatics drug- repositioning approach
Supplementary Figure 1 Legend from PI3Kδ Inhibitors in Cancer: Rationale and Serendipity Merge in the Clinic
Authors: Fruman David A. , Rommel Christian
Published: April 2023

PDF file - 64K
Supplementary Video 2 from IDO Is a Nodal Pathogenic Driver of Lung Cancer and Metastasis Development
Authors: Smith Courtney , Chang Mee Young , Parker Katherine H. , Beury Daniel W. , DuHadaway James B. , Flick Hollie E. , Boulden Janette , Sutanto-Ward Erika , Soler Alejandro Peralta , Laury-Kleintop Lisa D. , Mandik-Nayak Laura , Metz Richard , Ostrand-Rosenberg Suzanne , Prendergast George C. , Muller Alexander J.
Published: April 2023

AVI file - 2.5MB, 360 degree views of the lungs of an Ido1-/- KrasG12D mouse prior to Ad-cre virus infection. Vasculature is colored red (exterior)/orange (interior) with surrounding lung tissue colored translucent green
Supplementary Video 1 from IDO Is a Nodal Pathogenic Driver of Lung Cancer and Metastasis Development
Authors: Smith Courtney , Chang Mee Young , Parker Katherine H. , Beury Daniel W. , DuHadaway James B. , Flick Hollie E. , Boulden Janette , Sutanto-Ward Erika , Soler Alejandro Peralta , Laury-Kleintop Lisa D. , Mandik-Nayak Laura , Metz Richard , Ostrand-Rosenberg Suzanne , Prendergast George C. , Muller Alexander J.
Published: April 2023

AVI file - 1.9MB, 360 degree views of the lungs of a Lox-KrasG12D mouse prior to Ad-cre virus infection. Vasculature is colored red (exterior)/orange (interior) with surrounding lung tissue colored translucent green
Supplementary Figure 2 from IDO Is a Nodal Pathogenic Driver of Lung Cancer and Metastasis Development
Authors: Smith Courtney , Chang Mee Young , Parker Katherine H. , Beury Daniel W. , DuHadaway James B. , Flick Hollie E. , Boulden Janette , Sutanto-Ward Erika , Soler Alejandro Peralta , Laury-Kleintop Lisa D. , Mandik-Nayak Laura , Metz Richard , Ostrand-Rosenberg Suzanne , Prendergast George C. , Muller Alexander J.
Published: April 2023

PDF file - 158K, Additional characterization of the impact of IDO1 loss on mice engrafted with metastatic 4T1 tumors
Supplementary Figure 1 from IDO Is a Nodal Pathogenic Driver of Lung Cancer and Metastasis Development
Authors: Smith Courtney , Chang Mee Young , Parker Katherine H. , Beury Daniel W. , DuHadaway James B. , Flick Hollie E. , Boulden Janette , Sutanto-Ward Erika , Soler Alejandro Peralta , Laury-Kleintop Lisa D. , Mandik-Nayak Laura , Metz Richard , Ostrand-Rosenberg Suzanne , Prendergast George C. , Muller Alexander J.
Published: April 2023

PDF file - 1MB, Additional characterization of the impact of IDO1 loss on Ad-cre infected, Lox-KrasG12D mice
Supplementary Data Figure Legends from Hypoxia Induces Phenotypic Plasticity and Therapy Resistance in Melanoma via the Tyrosine Kinase Receptors ROR1 and ROR2
Authors: O'Connell Michael P. , Marchbank Katie , Webster Marie R. , Valiga Alexander A. , Kaur Amanpreet , Vultur Adina , Li Ling , Herlyn Meenhard , Villanueva Jessie , Liu Qin , Yin Xiangfan , Widura Sandy , Nelson Janelle , Ruiz Nivia , Camilli Tura C. , Indig Fred E. , Flaherty Keith T. , Wargo Jennifer A. , Frederick Dennie T. , Cooper Zachary A. , Nair Suresh , Amaravadi Ravi K. , Schuchter Lynn M. , Karakousis Giorgos C. , Xu Wei , Xu Xiaowei , Weeraratna Ashani T.
Published: April 2023

PDF file 110K, Figure legends for Supplementary Data
Supplementary Tables 1-4 from Genome-wide DNA Methylation Events in TMPRSS2–ERG Fusion-Negative Prostate Cancers Implicate an EZH2-Dependent Mechanism with miR-26a Hypermethylation
Authors: Börno Stefan T. , Fischer Axel , Kerick Martin , Fälth Maria , Laible Mark , Brase Jan C. , Kuner Ruprecht , Dahl Andreas , Grimm Christina , Sayanjali Behnam , Isau Melanie , Röhr Christina , Wunderlich Andrea , Timmermann Bernd , Claus Rainer , Plass Christoph , Graefen Markus , Simon Ronald , Demichelis Francesca , Rubin Mark A. , Sauter Guido , Schlomm Thorsten , Sültmann Holger , Lehrach Hans , Schweiger Michal R.
Published: April 2023

PDF file - 175K, Table S1 Clinical data and sequencing statistics. Table S2: Oligonucleotides for library construction and quantification and BS-MS-primers used for validation of MeDIP-Seq data. Table S3 Top 100 differentially methylated regions between tumor and normal (a) and between FUS+ and FUS- samples (b). Table S4 Correlation of EZH2 expression to expression of homeobox (Holland et al. 2007) and target genes (Yu et al. 2007) and target promoter methylation (+-2kb)
Supplementary Figures 9-11 from The mTORC1 Inhibitor Everolimus Prevents and Treats Eμ-Myc Lymphoma by Restoring Oncogene-Induced Senescence
Authors: Wall Meaghan , Poortinga Gretchen , Stanley Kym L. , Lindemann Ralph K. , Bots Michael , Chan Christopher J. , Bywater Megan J. , Kinross Kathryn M. , Astle Megan V. , Waldeck Kelly , Hannan Katherine M. , Shortt Jake , Smyth Mark J. , Lowe Scott W. , Hannan Ross D. , Pearson Richard B. , Johnstone Ricky W. , McArthur Grant A.
Published: April 2023

PDF file - 1.1MB, Quantitation of SA-B-gal and immunostaining. SF10: Markers of senescence. SF11: Overall survival of mice transplanted with a p53 mutant lymphoma
Supplementary Figures 1-5 from Rescue Screens with Secreted Proteins Reveal Compensatory Potential of Receptor Tyrosine Kinases in Driving Cancer Growth
Authors: Harbinski Fred , Craig Vanessa J. , Sanghavi Sneha , Jeffery Douglas , Liu Lijuan , Sheppard Kelly Ann , Wagner Sabrina , Stamm Christelle , Buness Andreas , Chatenay-Rivauday Christian , Yao Yao , He Feng , Lu Chris X. , Guagnano Vito , Metz Thomas , Finan Peter M. , Hofmann Francesco , Sellers William R. , Porter Jeffrey A. , Myer Vic E. , Graus-Porta Diana , Wilson Christopher J. , Buckler Alan , Tiedt Ralph
Published: April 2023

PDF file - 310K, This file contains additional experimental data relating to ligand-mediated rescue and drug combinations in cancer cell lines
Supplementary Table S2 from Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia
Authors: Pemovska Tea , Kontro Mika , Yadav Bhagwan , Edgren Henrik , Eldfors Samuli , Szwajda Agnieszka , Almusa Henrikki , Bespalov Maxim M. , Ellonen Pekka , Elonen Erkki , Gjertsen Bjørn T. , Karjalainen Riikka , Kulesskiy Evgeny , Lagström Sonja , Lehto Anna , Lepistö Maija , Lundán Tuija , Majumder Muntasir Mamun , Marti Jesus M. Lopez , Mattila Pirkko , Murumägi Astrid , Mustjoki Satu , Palva Aino , Parsons Alun , Pirttinen Tero , Rämet Maria E. , Suvela Minna , Turunen Laura , Västrik Imre , Wolf Maija , Knowles Jonathan , Aittokallio Tero , Heckman Caroline A. , Porkka Kimmo , Kallioniemi Olli , Wennerberg Krister
Published: April 2023

- XLSX file 977K, Drug sensitivity profiles of AML and control samples
Supplementary Methods , Table 1 from Dual Roles of PARP-1 Promote Cancer Growth and Progression
Authors: Schiewer Matthew J. , Goodwin Jonathan F. , Han Sumin , Brenner J. Chad , Augello Michael A. , Dean Jeffry L. , Liu Fengzhi , Planck Jamie L. , Ravindranathan Preethi , Chinnaiyan Arul M. , McCue Peter , Gomella Leonard G. , Raj Ganesh V. , Dicker Adam P. , Brody Jonathan R. , Pascal John M. , Centenera Margaret M. , Butler Lisa M. , Tilley Wayne D. , Feng Felix Y. , Knudsen Karen E.
Published: April 2023

PDF file - 91K
Supplementary Figure 3 from A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition
Authors: Whittaker Steven R. , Theurillat Jean-Philippe , Van Allen Eliezer , Wagle Nikhil , Hsiao Jessica , Cowley Glenn S. , Schadendorf Dirk , Root David E. , Garraway Levi A.
Published: April 2023

Supplementary Figure 3 PDF file - 474K, A375 cells lacking NF1 display resistance to selective RAF and MEK inhibitors in a colony formation assay but pan-RAF inhibition and ERK inhibition is more effective at suppression. (A) A375 cells infected with the indicated shRNAs/ORFs were seeded at low density (300 cells/well in a 12-well plate) and treated with either DMSO, 3 �M PLX4720, 3 �M GDC0879, 1 �M PLX4032, 0.2 �M AZD6244, 0.2 �M AZ628 or 1 �M ERKi for 10 d. Colony formation was assessed by staining with crystal violet. (B) Quantification of relative cell growth in (A) by resuspension of the dye in 10% acetic acid, and measurement of absorbance at 595 nm
Supplementary Figure 2 from A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition
Authors: Whittaker Steven R. , Theurillat Jean-Philippe , Van Allen Eliezer , Wagle Nikhil , Hsiao Jessica , Cowley Glenn S. , Schadendorf Dirk , Root David E. , Garraway Levi A.
Published: April 2023

Supplementary Figure 2 PDF file - 45K, Resistance to the MEK inhibitor AZD6244 induced by loss of NF1 is reversed by combined suppression of C-RAF by RNA interference. A375 cells were infected with the indicated shRNAs and then exposed to a 10-point titration of the MEK inhibitor AZD6244 for 4 d. Cell proliferation was assessed using cell-titer glo
Supplementary Figures from Clinical Response to a Lapatinib-Based Therapy for a Li-Fraumeni Syndrome Patient with a Novel HER2V659E Mutation
Authors: Serra Violeta , Vivancos Ana , Puente Xose S. , Felip Enriqueta , Silberschmidt Daniel , Caratù Ginevra , Parra Josep-Lluís , De Mattos-Arruda Leticia , Grueso Judit , Hernández-Losa Javier , Arribas Joaquín , Prudkin Ludmila , Nuciforo Paolo , Scaltriti Maurizio , Seoane Joan , Baselga José
Published: April 2023

Supplementary Figures - PDF file 585K, Supplementary Figure 1. Fluorescence in situ hybridization (FISH) of HER2. Supplementary Figure 2. EGFR and HER2 mutations identified. Supplementary Figure 3. Comparisons of allele frequencies. Supplementary Figure 4. HER2-V659E response to erlotinib and neratinib in MCF10A cells
Supplementary Figure 1 from Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors
Authors: Shi Hubing , Moriceau Gatien , Kong Xiangju , Koya Richard C. , Nazarian Ramin , Pupo Gulietta M. , Bacchiocchi Antonella , Dahlman Kimberly B. , Chmielowski Bartosz , Sosman Jeffrey A. , Halaban Ruth , Kefford Richard F. , Long Georgina V. , Ribas Antoni , Lo Roger S.
Published: April 2023

PDF file - 181K, Patient tissues harboring concurrent and somatic B-RAF and MEK1 mutations. Chromatograms showing B-RAF exon 15 at V600 codon and MEK1 exon 3 at I111 or P124 codons in patient-matched normal tissue, baseline melanomas (prior to B-RAFi therapy), and melanomas on disease progression (i.e. at acquisition of B-RAFi resistance). Specific codons in red; N/A, not available.
Supplementary Figure 6 from Cancer-Specific Requirement for BUB1B/BUBR1 in Human Brain Tumor Isolates and Genetically Transformed Cells
Authors: Ding Yu , Hubert Christopher G. , Herman Jacob , Corrin Philip , Toledo Chad M. , Skutt-Kakaria Kyobi , Vazquez Julio , Basom Ryan , Zhang Bin , Risler Jennifer K. , Pollard Steven M. , Nam Do-Hyun , Delrow Jeffery J. , Zhu Jun , Lee Jeongwu , DeLuca Jennifer , Olson James M. , Paddison Patrick J.
Published: April 2023

PDF file - 120K, Supplemental data for Figure 5