bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus
Authors: Critchley-Thorne Rebecca J. , Davison Jon M. , Prichard Jeffrey W. , Reese Lia M. , Zhang Yi , Repa Kathleen , Li Jinhong , Diehl David L. , Jhala Nirag C. , Ginsberg Gregory G. , DeMarshall Maureen , Foxwell Tyler , Jobe Blair A. , Zaidi Ali H. , Duits Lucas C. , Bergman Jacques J.G.H.M. , Rustgi Anil , Falk Gary W.
Published: March 2023

Abstract
Background: There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC.

Methods: We performed a multi-institutional case–control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days).

Results: The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P < 0.0001]. The classifier also provided independent prognostic information that outperformed the subspecialist and generalist diagnosis.

Conclusions: A tissue systems pathology test better predicts prevalent HGD/EAC in Barrett's esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test.

Impact: A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240–8. ©2016 AACR.
Data from Body Mass Index and Risk of Gastric Cancer: A Meta-analysis of a Population with More Than Ten Million from 24 Prospective Studies
Authors: Chen Yi , Liu Lingxiao , Wang Xiaolin , Wang Jianhua , Yan Zhiping , Cheng Jieming , Gong Gaoquan , Li Guoping
Published: March 2023

Abstract
Background: To provide a quantitative assessment of the association between body mass index (BMI) and the risk of gastric cancer, we summarized the evidence from prospective studies.

Methods: Eligible studies published up to November 30, 2012, were retrieved via computer searches of MEDLINE and EMBASE as well as manual review of references. Summary relative risks (SRR) with their corresponding 95% confidence intervals (CI) were calculated using a random-effects model.

Results: A total of 24 prospective studies of BMI and gastric cancer risk with 41,791 cases were included in our analysis. Overall, both overweight (BMI, 25–30 kg/m2) and obesity (BMI, ≥30 kg/m2) were not associated with risk of total gastric cancer (overweight: SRR, 1.01; 95% CI, 0.96–1.07; obesity: SRR, 1.06; 95% CI, 0.99–1.12). Furthermore, we found increased BMI was positively associated with the risk of gastric cardia cancer (GCC; SRR = 1.21 for overweight and 1.82 for obesity), but not with gastric non-cardia cancer (GNCC; SRR = 0.93 for overweight and SRR = 1.00 for obesity). Similar results were observed in a linear dose–response analysis.

Conclusion: On the basis of meta-analysis of prospective studies, we find high BMI is positively associated with the risk of GCCs but not with GNCCs.

Impact: (i) On the basis of more definite and quantitative evidence than previously available, we found that increasing BMI was not a clear risk factor for total gastric cancer. (ii) Increased BMI was positively associated with risk of GCC but not with GNCCs. Cancer Epidemiol Biomarkers Prev; 22(8); 1395–408. ©2013 AACR.
Data from Association between Upper Digestive Tract Microbiota and Cancer-Predisposing States in the Esophagus and Stomach
Authors: Yu Guoqin , Gail Mitchell H. , Shi Jianxin , Klepac-Ceraj Vanja , Paster Bruce J. , Dye Bruce A. , Wang Guo-Qing , Wei Wen-Qiang , Fan Jin-Hu , Qiao You-Lin , Dawsey Sanford M. , Freedman Neal D. , Abnet Christian C.
Published: April 2023

Abstract
Background: The human upper digestive tract microbial community (microbiota) is not well characterized and few studies have explored how it relates to human health. We examined the relationship between upper digestive tract microbiota and two cancer-predisposing states, serum pepsinogen I/pepsinogen II ratio (PGI/II; predictor of gastric cancer risk) and esophageal squamous dysplasia (ESD; the precursor lesion of esophageal squamous cell carcinoma; ESCC) in a cross-sectional design.

Methods: The Human Oral Microbe Identification Microarray was used to test for the presence of 272 bacterial species in 333 upper digestive tract samples from a Chinese cancer screening cohort. Serum PGI and PGII were determined by ELISA. ESD was determined by chromoendoscopy with biopsy.

Results: Lower microbial richness (number of bacterial genera per sample) was significantly associated with lower PGI/II ratio (P = 0.034) and the presence of ESD (P = 0.018). We conducted principal component (PC) analysis on a β-diversity matrix (pairwise difference in microbiota), and observed significant correlations between PC1, PC3, and PGI/II (P = 0.004 and 0.009, respectively), and between PC1 and ESD (P = 0.003).

Conclusions: Lower microbial richness in upper digestive tract was independently associated with both cancer-predisposing states in the esophagus and stomach (presence of ESD and lower PGI/II).

Impact: These novel findings suggest that the upper digestive tract microbiota may play a role in the etiology of chronic atrophic gastritis and ESD, and therefore in the development of gastric and esophageal cancers. Cancer Epidemiol Biomarkers Prev; 23(5); 735–41. ©2014 AACR.
Data from Pectoral Muscle Attenuation as a Marker for Breast Cancer Risk in Full-Field Digital Mammography
Authors: Cheddad Abbas , Czene Kamila , Hall Per , Humphreys Keith
Published: April 2023

Abstract
Background: Mammographic percent density is an established marker of breast cancer risk. In a study of screen film mammograms, we recently reported a novel feature from the pectoral muscle region to be associated with breast cancer risk independently of area percent density (APD). We now investigate whether our novel feature is associated with risk in a study based on full-field digital mammography (FFDM).

Methods: We carried out a breast cancer risk analysis using a data set of 3,552 healthy controls and 278 cases. We included three image-based measures in our analyses: volumetric percent density (VPD), APD, and the mean intensity of the pectoral muscle (MIP). The datasets comprised different machine vendors and models. In addition, the controls dataset was used to test for the association of our measures against rs10995190, in the ZNF365 gene, a genetic variant known to be associated with mammography density and breast cancer risk.

Results: MIP was associated with breast cancer risk [per SD OR, 0.811; 95% confidence interval (CI), 0.707–0.930; P = 0.0028] after adjusting for conventional covariates and VPD. It was also associated with the genetic variant rs10995190 after adjusting for VPD and other covariates (per allele effect = 0.111; 95% CI, 0.053–0.170; P = 1.8 × 10−4). Results were similar when adjusting for APD instead of VPD.

Conclusion: MIP is a novel mammographic marker, which is associated with breast cancer risk and the genetic variant rs10995190 independently of PD measures.

Impact: Inclusion of MIP in risk models should be considered for studies using PD from FFDM. Cancer Epidemiol Biomarkers Prev; 24(6); 985–91. ©2015 AACR.
Data from Adolescent Exercise in Association with Mortality from All Causes, Cardiovascular Disease, and Cancer among Middle-Aged and Older Chinese Women
Authors: Nechuta Sarah J. , Shu Xiao Ou , Yang Gong , Cai Hui , Gao Yu-Tang , Li Hong-Lan , Xiang Yong-Bing , Zheng Wei
Published: April 2023

Abstract
Background: Little is known regarding the role of early-life exercise, a potentially modifiable factor, in long-term adult morbidity and mortality. We utilized the Shanghai Women's Health Study (SWHS) to investigate adolescent exercise in association with cancer, cardiovascular disease (CVD), and all-cause mortality among middle-aged and older women.

Methods: The SWHS is a prospective cohort of 74,941 Chinese women ages 40 to 70 years recruited from 1996 to 2000. In-person interviews at enrollment assessed adolescent and adult exercise history, medical and reproductive history, and other lifestyle and socioeconomic (SES) factors. Mortality follow-up occurs via annual linkage to the Shanghai Vital Statistics Registry. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were derived from Cox regression models.

Results: Adjusting for birth year and other adolescent factors, adolescent exercise was associated with reduced risk of cancer, CVD, and total mortality [HRs (95% CI), 0.83 (0.72–0.95), 0.83 (0.70–0.98), and 0.78 (0.71–0.85), respectively for ≤1.33 hours (h)/week, and 0.83 (0.74–0.93), 0.62 (0.53–0.72), and 0.71 (0.66–0.77), respectively for >1.33 h/week (reference = none)]. Results were attenuated after adjustment for adult SES and lifestyle factors. Participation in sports teams was inversely associated with cancer mortality [HR (95% CI), 0.86 (0.76–0.97)]. Joint adolescent and adult exercise was associated with reduced risk of all-cause, CVD, and cancer mortality [HRs (95% CIs), 0.80 (0.72–0.89), 0.83 (0.69–1.00), and 0.87 (0.74–1.01), respectively], adjusting for adult/adolescent factors, and adolescence exercise only was inversely associated with cancer mortality [HR (95% CI), 0.84 (0.71–0.98)].

Conclusions: Adolescent exercise participation, independent of adult exercise, was associated with reduced risk of cancer, CVD, and all-cause mortality.

Impact: Results support promotion of exercise in adolescence to reduce mortality in later life. Cancer Epidemiol Biomarkers Prev; 24(8); 1270–6. ©2015 AACR.
Supplementary Figures Legends from A Novel E2F/Sphingosine Kinase 1 Axis Regulates Anthracycline Response in Squamous Cell Carcinoma
Authors: Hazar-Rethinam Mehlika , de Long Lilia Merida , Gannon Orla M. , Topkas Eleni , Boros Samuel , Vargas Ana Cristina , Dzienis Marcin , Mukhopadhyay Pamela , Simpson Fiona , Endo-Munoz Liliana , Saunders Nicholas A.
Published: April 2023

The file contains figure legends for 6 supplementary figures
Supplemental Figure S3 from Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells
Authors: Yoon Changhwan , Cho Soo-Jeong , Aksoy Bülent Arman , Park Do Joong , Schultz Nikolaus , Ryeom Sandra W. , Yoon Sam S.
Published: April 2023

Expression of Akt, ERK, JNK, p38, and effects of Akt inhibition on migration and invasion.
Supplementary Tables S1qc-S3qc from Functional Subclone Profiling for Prediction of Treatment-Induced Intratumor Population Shifts and Discovery of Rational Drug Combinations in Human Glioblastoma
Authors: Reinartz Roman , Wang Shanshan , Kebir Sied , Silver Daniel J. , Wieland Anja , Zheng Tong , Küpper Marius , Rauschenbach Laurèl , Fimmers Rolf , Shepherd Timothy M. , Trageser Daniel , Till Andreas , Schäfer Niklas , Glas Martin , Hillmer Axel M. , Cichon Sven , Smith Amy A. , Pietsch Torsten , Liu Ying , Reynolds Brent A. , Yachnis Anthony , Pincus David W. , Simon Matthias , Brüstle Oliver , Steindler Dennis A. , Scheffler Björn
Published: April 2023

Patient data. AND Drug and compound details. AND Primer sequences for qRT-PCR.
Supplementary Figures from Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors
Authors: Hawinkels Lukas J.A.C. , de Vinuesa Amaya Garcia , Paauwe Madelon , Kruithof-de Julio Marianna , Wiercinska Eliza , Pardali Evangelia , Mezzanotte Laura , Keereweer Stijn , Braumuller Tanya M. , Heijkants Renier C. , Jonkers Jos , Löwik Clemens W. , Goumans Marie-José , ten Hagen Timo L. , ten Dijke Peter
Published: April 2023

Supplementary figure 1. A, Immunohistochemical analysis of BMP9 expression in human tumor samples. Supplementary figure 2. A CD31 staining in head and neck model. Images takes from melanomas after treatment with Fc or ALK1-Fc, magnification 200x. Supplementary figure 3. A, Western blotting showing expression of Fc constructs on stable overexpressing cells. Supplementary figure 4. A, Changes in the number of pericytes in breast tumors generated after inoculation of KEP1-11 cells carrying expression constructs for Fc, ALK1-Fc, ALK2-Fc or Flt-Fc. Supplementary figure 5. A, Cytotoxic effect of cisplatin treatment on KEP1-11 cells. Cells were incubated with increasing doses of cisplatin and the number of viable cells was assessed after 72 hours of treatment.
Supplemental Figure 1 from Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder
Authors: Wang Wei-Jan , Li Chien-Feng , Chu Yu-Yi , Wang Yu-Hui , Hour Tzyh-Chyuan , Yen Chia-Jui , Chang Wen-Chang , Wang Ju-Ming
Published: April 2023

CEBPD expression had significant worse MeFS in UCUB patients. A and B, Kaplan-Meier plots discloses the predictive significances of CEBPD immunoexpression for metastasis-free survival in UCUB.
Supplementary Figures 1-8 and Supplementary Tables 2 and 5-7 from Comprehensive Molecular Characterization of Salivary Duct Carcinoma Reveals Actionable Targets and Similarity to Apocrine Breast Cancer
Authors: Dalin Martin G. , Desrichard Alexis , Katabi Nora , Makarov Vladimir , Walsh Logan A. , Lee Ken-Wing , Wang Qingguo , Armenia Joshua , West Lyndsay , Dogan Snjezana , Wang Lu , Ramaswami Deepa , Ho Alan L. , Ganly Ian , Solit David B. , Berger Michael F. , Schultz Nikolaus D. , Reis-Filho Jorge S. , Chan Timothy A. , Morris Luc G.T.
Published: April 2023

Figure S1. Coverage and quality of whole exome sequencing. Figure S2. Coverage and quality of RNA sequencing. Figure S3. Detection of somatic mutations by RNA sequencing. Figure S4. Focal copy number alterations. Figure S5. Fusion genes. Figure S6. SDC histology and immunohistochemistry. Figure S7. Genetic alterations in cohort 2. Figure S8. Consensus clustering of SDC and basal-like breast cancer. Table S2. PCR primers used in this study. Table S5. Clinical information cohort 2. Table S6. Missense mutations in HRAS and PIK3CA. Table S7. Potentially targetable alterations.
Figure S4 from KRAS Mutation and Consensus Molecular Subtypes 2 and 3 Are Independently Associated with Reduced Immune Infiltration and Reactivity in Colorectal Cancer
Authors: Lal Neeraj , White Brian S. , Goussous Ghaleb , Pickles Oliver , Mason Mike J. , Beggs Andrew D. , Taniere Philippe , Willcox Benjamin E. , Guinney Justin , Middleton Gary W.
Published: April 2023

CIRC is largely non-overlapping with immune cell type signatures.
Supplementary Table 1 and 2 from Deletion of 11q in Neuroblastomas Drives Sensitivity to PARP Inhibition
Authors: Sanmartín Elena , Muñoz Lisandra , Piqueras Marta , Sirerol J. Antoni , Berlanga Pablo , Cañete Adela , Castel Victoria , Font de Mora Jaime
Published: April 2023

Supplementary Table 1: Summary of clinico-pathological features of 412 neuroblastoma patients included in the study. Supplementary Table 2: clinico-pathological features in relation to MYCN status and 11q status
Supplementary Figure 5 from Deletion of 11q in Neuroblastomas Drives Sensitivity to PARP Inhibition
Authors: Sanmartín Elena , Muñoz Lisandra , Piqueras Marta , Sirerol J. Antoni , Berlanga Pablo , Cañete Adela , Castel Victoria , Font de Mora Jaime
Published: April 2023

SK-N-AS cells have truncated TP53 lacking exons 10 and 11.
Supplementary Statistical Methods from Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases
Authors: Chan Nancy , Willis Amy , Kornhauser Naomi , Ward Maureen M. , Lee Sharrell B. , Nackos Eleni , Seo Bo Ri , Chuang Ellen , Cigler Tessa , Moore Anne , Donovan Diana , Vallee Cobham Marta , Fitzpatrick Veronica , Schneider Sarah , Wiener Alysia , Guillaume-Abraham Jessica , Aljom Elnaz , Zelkowitz Richard , Warren J. David , Lane Maureen E. , Fischbach Claudia , Mittal Vivek , Vahdat Linda
Published: April 2023

This section contains details of all mixed models utilized in the statistical analyses. The inferential tests performed in this paper necessitates a multiple comparisons adjustment, and details of the adjustment procedure is included in this section as well.
Supplementary tables and figures from Circulating Tumor Cells with Stem-Like Phenotypes for Diagnosis, Prognosis, and Therapeutic Response Evaluation in Hepatocellular Carcinoma
Authors: Guo Wei , Sun Yun-Fan , Shen Min-Na , Ma Xiao-Lu , Wu Jiong , Zhang Chun-Yan , Zhou Yan , Xu Yang , Hu Bo , Zhang Min , Wang Gang , Chen Wei-Qin , Guo Lin , Lu Ren-Quan , Zhou Chao-Hui , Zhang Xin , Shi Ying-Hong , Qiu Shuang-jian , Pan Bai-shen , Cao Ya , Zhou Jian , Yang Xin-Rong , Fan Jia
Published: April 2023

Table S1, Primer pairs and probes used for quantitative real-time PCR assays; Table S2, Diagnostic performance of CTC markers in training set by logistic regression; Table S3, Performance of CTC panel and serum AFP in diagnosing various BCLC stages of HCC; Table S4, Performance of CTC panel in diagnosing HCC, stratified by AFP status; Table S5. Cox regression analyses for time to recurrence in the training and validation groups; Figure S1, Multimarker CTC screening in patients with HCC; FigureS2, The detection of stem-like phenotypes CTC subpopulations with immunofluorescent method and single-cell transcriptional analysis; Figure S3, Expression of selected CTCs in training set; Figure S4, Expression of selected CTCs in validation set; Figure S5, CTC panel positivity rates in training and validation set; Figure S6, X-tile analysis of CTC panel in training set; Figure S7, Comparison of CTC panel and EpCAM for HCC diagnosis and prognosis in training and validation sets; Figure S8, Relative expression of EMT transition markers in patients with HCC and in healthy controls
Supplemental legend from Long Noncoding RNA NEAT1, Regulated by the EGFR Pathway, Contributes to Glioblastoma Progression Through the WNT/β-Catenin Pathway by Scaffolding EZH2
Authors: Chen Qun , Cai Jinquan , Wang Qixue , Wang Yunfei , Liu Mingyang , Yang Jingxuan , Zhou Junhu , Kang Chunsheng , Li Min , Jiang Chuanlu
Published: April 2023

Supplemental legend
Figure S2 from The Landscape of Viral Expression Reveals Clinically Relevant Viruses with Potential Capability of Promoting Malignancy in Lower-Grade Glioma
Authors: Wang Zheng , Hao Yajing , Zhang Chuanbao , Wang Zhiliang , Liu Xing , Li Guanzhang , Sun Lihua , Liang Jingshan , Luo Jianjun , Zhou Dabiao , Chen Runsheng , Jiang Tao
Published: April 2023

(A) Top 33 expressed virus across TCGA Expression subclasses. (B) Survival analysis for patients who were susceptive to virus infection in contrast to those weren't.
Figure S3 from Further Investigation of the Role of ACYP2 and WFS1 Pharmacogenomic Variants in the Development of Cisplatin-Induced Ototoxicity in Testicular Cancer Patients
Authors: Drögemöller Britt I. , Brooks Beth , Critchley Carol , Monzon José G. , Wright Galen E.B. , Liu Geoffrey , Renouf Daniel J. , Kollmannsberger Christian K. , Bedard Philippe L. , Hayden Michael R. , Gelmon Karen A. , Carleton Bruce C. , Ross Colin J.D.
Published: April 2023

Figure S3 provides a visualization of the interaction between genotype and cisplatin dose
Supplemental legend from Dual Inhibition of IGF-1R and ErbB3 Enhances the Activity of Gemcitabine and Nab-Paclitaxel in Preclinical Models of Pancreatic Cancer
Authors: Camblin Adam J. , Pace Emily A. , Adams Sharlene , Curley Michael D. , Rimkunas Victoria , Nie Lin , Tan Gege , Bloom Troy , Iadevaia Sergio , Baum Jason , Minx Charlene , Czibere Akos , Louis Chrystal U. , Drummond Daryl C. , Nielsen Ulrik B. , Schoeberl Birgit , Pipas J. Marc , Straubinger Robert M. , Askoxylakis Vasileios , Lugovskoy Alexey A.
Published: April 2023

Supplemental legend
Supplementary Table S4 from A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases
Authors: Montfort Anne , Pearce Oliver , Maniati Eleni , Vincent Benjamin G. , Bixby Lisa , Böhm Steffen , Dowe Thomas , Wilkes Edmund H. , Chakravarty Probir , Thompson Richard , Topping Joanne , Cutillas Pedro R. , Lockley Michelle , Serody Jonathan S. , Capasso Melania , Balkwill Frances R.
Published: April 2023

Tumor histology, age, disease stage and treatment of patients from the cohort used for tumor IgG1,2,3 and 4 dosage
Supplementary Figures 1-3 from A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) in Patients with Advanced Solid Tumors and Lymphomas
Authors: Infante Jeffrey R. , Cassier Philippe A. , Gerecitano John F. , Witteveen Petronella O. , Chugh Rashmi , Ribrag Vincent , Chakraborty Abhijit , Matano Alessandro , Dobson Jason R. , Crystal Adam S. , Parasuraman Sudha , Shapiro Geoffrey I.
Published: April 2023

Fig. S1. Waterfall plot of duration of exposure vs. best percentage change from baseline; Figure S2. Duration of exposure in patients with stable disease treated for at least four cycles; Figure S3. Duration of exposure, best percentage change in target lesion, and genetic profile for the 53 patients with available genetic data.
Figure S1 from Shaping the Tumor Stroma and Sparking Immune Activation by CD40 and 4-1BB Signaling Induced by an Armed Oncolytic Virus
Authors: Eriksson Emma , Milenova Ioanna , Wenthe Jessica , Ståhle Magnus , Leja-Jarblad Justyna , Ullenhag Gustav , Dimberg Anna , Moreno Raphael , Alemany Ramon , Loskog Angelica
Published: April 2023

Supplementary Figure S1. Schematic figure The LOAd703 genome is displayed in the Figure. The adenovirus serotype 5 genome was modified to include E2F sites and a Sp-1 site upstream of E1A. The E1A has the delta 24 deletion. Further E3 was deleted of the genes 6.7K and gp19K. At the L5 segment, the serotype 5 fiber was converted to that of serotype 35 (shaft and knob). About 600 bp downstream of L5, a CMV promoter was added together with a transgene cassette encoding human 4-1BBL and TMZ-CD40L.
Supplementary Table 2 from Combination of Imatinib Mesylate and AKT Inhibitor Provides Synergistic Effects in Preclinical Study of Gastrointestinal Stromal Tumor
Authors: Zook Phillip , Pathak Harsh B. , Belinsky Martin G. , Gersz Lawrence , Devarajan Karthik , Zhou Yan , Godwin Andrew K. , von Mehren Margaret , Rink Lori
Published: April 2023

CI values determined using CalcuSyn.
Supplemental figure 1 from Early Detection of Lung Cancer Using DNA Promoter Hypermethylation in Plasma and Sputum
Authors: Hulbert Alicia , Jusue-Torres Ignacio , Stark Alejandro , Chen Chen , Rodgers Kristen , Lee Beverly , Griffin Candace , Yang Andrew , Huang Peng , Wrangle John , Belinsky Steven A. , Wang Tza-Huei , Yang Stephen C. , Baylin Stephen B. , Brock Malcolm V. , Herman James G.
Published: April 2023

Gene promoter methylation amplification curves
Supplemental Tables from An Aggressive Subtype of Stage I Lung Adenocarcinoma with Molecular and Prognostic Characteristics Typical of Advanced Lung Cancers
Authors: Dama Elisa , Melocchi Valentina , Dezi Fabio , Pirroni Stefania , Carletti Rose Mary , Brambilla Daniela , Bertalot Giovanni , Casiraghi Monica , Maisonneuve Patrick , Barberis Massimo , Viale Giuseppe , Vecchi Manuela , Spaggiari Lorenzo , Bianchi Fabrizio , Di Fiore Pier Paolo
Published: April 2023

Supplemental Table 5. TCGA Clinical Info Supplemental Table 6A. TCGA Gene Expression Supplemental Table 6B. TCGA Methylation Supplemental Table 6C. TCGA Protein Expression Supplemental Table 9. IPA Analysis "Upstream Modulator" TCGA Supplemental Table 10. IPA Analysis "Biofunctions" TCGA Supplemental Table 11. IPA Analysis "Upstream Modulator" DCC dataset
Figure S4 from Downregulation of MicroRNA-644a Promotes Esophageal Squamous Cell Carcinoma Aggressiveness and Stem Cell–like Phenotype via Dysregulation of PITX2
Authors: Zhang Jia-Xing , Chen Zhen-Hua , Xu Yi , Chen Jie-Wei , Weng Hui-Wen , Yun Miao , Zheng Zou-San , Chen Cui , Wu Bing-Li , Li En-Min , Fu Jian-Hua , Ye Sheng , Xie Dan
Published: April 2023

MiR-644a inhibits the stemness of Eca-109 cells by regulating PITX2 expression. A-D, enforced overexpression of miR-644a in Eca-109 cells substantially down-regulated the levels of stemness-associated genes (Nanog, Oct-4, Bmi-1, Notch-1 and Smo), multiple drug-resistance transporter genes (ABCC2, ABCG2) and surface antigens associated with cancer stem cells (CD24, CD44, CD133, CD105, and CD166) (A), reduced phere-forming ability (B) and proportion of side-population cells (C), and also largely increased chemosensitivity to cisplatin or radiosensitivity to IR (D). Restoration of PITX2 in miR-644a-overexpressing Eca-109 cells largely rescued the cells' stemness, while knockdown of PITX2 by shPITX2 decreased Eca-109 cells' stemness (A-D). E, tumor formation in nude mice shows reduced tumorigenicity in 3 groups of miR-644a-overexpressing Eca-109 cells indicated, as compared to that in matched control groups. *P<0.05, **P<0.01.
Figure S1 from The Immune-microenvironment Confers Chemoresistance of Colorectal Cancer through Macrophage-Derived IL6
Authors: Yin Yuan , Yao Surui , Hu Yaling , Feng Yuyang , Li Min , Bian Zehua , Zhang Jiwei , Qin Yan , Qi Xiaowei , Zhou Leyuan , Fei Bojian , Zou Jian , Hua Dong , Huang Zhaohui
Published: April 2023

Figure S1. CD68, MDR1 and BCL2 expression in CRC tissues.
Figure S3 from Amplification of 1q32.1 Refines the Molecular Classification of Endometrial Carcinoma
Authors: Depreeuw Jeroen , Stelloo Ellen , Osse Elisabeth M. , Creutzberg Carien L. , Nout Remi A. , Moisse Matthieu , Garcia-Dios Diego A. , Dewaele Michael , Willekens Karen , Marine Jean-Christophe , Matias-Guiu Xavier , Amant Frédéric , Lambrechts Diether , Bosse Tjalling
Published: April 2023

Frequency of amplifications, GISTIC q-value and Cox regression P value for all regions in 1q locus for cluster 2, 3 and 4 ECs (n= 268).
Table S1 from Intertumoral Heterogeneity of CD3+ and CD8+ T-Cell Densities in the Microenvironment of DNA Mismatch-Repair–Deficient Colon Cancers: Implications for Prognosis
Authors: Yoon Harry H. , Shi Qian , Heying Erica N. , Muranyi Andrea , Bredno Joerg , Ough Faith , Djalilvand Azita , Clements June , Bowermaster Rebecca , Liu Wen-Wei , Barnes Michael , Alberts Steven R. , Shanmugam Kandavel , Sinicrope Frank A.
Published: April 2023

Table S1. Inter-tumor heterogeneity of T-cell densities in tumor microenvironment in dMMR vs pMMR stage III colon cancers
Data from A Phase 1 Dose-Escalation Study of Irinotecan in Combination with 17-Allylamino-17-Demethoxygeldanamycin in Patients with Solid Tumors
Authors: Tse Archie N. , Klimstra David S. , Gonen Mithat , Shah Manish , Sheikh Tahir , Sikorski Rachel , Carvajal Richard , Mui Janet , Tipian Caroll , O'Reilly Eileen , Chung Ki , Maki Robert , Lefkowitz Robert , Brown Karen , Manova-Todorova Katia , Wu Nian , Egorin Merrill J. , Kelsen David , Schwartz Gary K.
Published: April 2023

Abstract
Purpose: Both heat shock protein 90 (Hsp90) and checkpoint kinase 1 (Chk1) have emerged as novel therapeutic targets. We conducted a phase I study of irinotecan and the Hsp90 inhibitor 17AAG, which can also down-regulate Chk1, in patients with solid tumors.

Experimental Design: During the dose escalation phase, patients received i.v. irinotecan followed by 17AAG once weekly for 2 weeks in a 21-day cycle. At the maximum tolerated dose (MTD), additional patients were enrolled to undergo pre- and post-17AAG tumor biopsies for pharmacodynamic evaluation. The pharmacokinetics of irinotecan, 17AAG, and their metabolites were characterized. Tumor p53 status as determined by immunohistochemistry was correlated with antitumor activity.

Results: Twenty-seven patients with a variety of solid tumors were enrolled. Four patients developed dose-limiting toxicity at dose level 4 (100 mg/m2 irinotecan and 375 mg/m2 17AAG) including nausea, vomiting, diarrhea, and pulmonary embolism. The pharmacokinetics of 17AAG and its metabolite were not significantly affected by the coadministration of irinotecan, and vice versa. There was no partial response, although tumor shrinkage was observed in six patients. Five of 10 patients with p53-mutant tumor had stable disease as the best response compared with 2 of 6 patients with p53-wildtype tumor (P = 0.63). Evidence for Hsp90 inhibition by 17AAG, resulting in phospho-Chk1 loss, abrogation of the G2-M cell cycle checkpoint, and cell death could be shown in tumor biopsy samples obtained at the MTD.

Conclusions: The combination of irinotecan and 17AAG can be given to patients with acceptable toxicity. The recommended phase II dose of the combination is 100 mg/m2 irinotecan and 300 mg/m2 17AAG.
Data from Tumor Cell Gene Expression Changes Following Short-term In vivo Exposure to Single Agent Chemotherapeutics are Related to Survival in Multiple Myeloma
Authors: Burington Bart , Barlogie Bart , Zhan Fenghuang , Crowley John , Shaughnessy John D.
Published: April 2023

Abstract
Changes in global gene expression patterns in tumor cells following in vivo therapy may vary by treatment and provide added or synergistic prognostic power over pretherapy gene expression profiles (GEP). This molecular readout of drug-cell interaction may also point to mechanisms of action/resistance. In newly diagnosed patients with multiple myeloma (MM), microarray data were obtained on tumor cells prior to and 48 hours after in vivo treatment using dexamethasone (n = 45) or thalidomide (n = 42); in the case of relapsed MM, microarray data were obtained prior to (n = 36) and after (n = 19) lenalidomide administration. Dexamethasone and thalidomide induced both common and unique GEP changes in tumor cells. Combined baseline and 48-hour changes in GEP in a subset of genes, many related to oxidative stress and cytoskeletal dynamics, were predictive of outcome in newly diagnosed MM patients receiving tandem transplants. Thalidomide-altered genes also changed following lenalidomide exposure and predicted event-free and overall survival in relapsed patients receiving lenalidomide as a single agent. Combined with baseline molecular features, changes in GEP following short-term single-agent exposure may help guide treatment decisions for patients with MM. Genes whose drug-altered expression were found to be related to survival may point to molecular switches related to response and/or resistance to different classes of drugs.
Data from T-Cell Coregulatory Molecule Expression in Urothelial Cell Carcinoma: Clinicopathologic Correlations and Association with Survival
Authors: Boorjian Stephen A. , Sheinin Yuri , Crispen Paul L. , Farmer Sara A. , Lohse Christine M. , Kuntz Susan M. , Leibovich Bradley C. , Kwon Eugene D. , Frank Igor
Published: April 2023

Abstract
Purpose: Aberrant expression of T-cell coregulatory molecules has been investigated as a mechanism by which certain cancers may evade host immune surveillance. We evaluated expression of the T-cell coregulators B7-H1, B7-H3, and PD-1 in urothelial cell carcinoma (UCC) of the bladder.

Experimental Design: Immunohistochemistry for B7-H1, B7-H3, and PD-1 was done on paraffin-embedded sections from 318 consecutive patients with UCC who underwent radical cystectomy. Expression was correlated with clinicopathologic outcomes and postoperative survival.

Results: B7-H3 was widely expressed in UCC, as 222 of 314 (70.7%) tumors showed positive staining. Expression of B7-H3 in UCC was significantly increased compared with adjacent, nontumor urothelium, as a median of 70% of tumor cells expressed B7-H3, compared with 20% of cells in nontumor specimens (P < 0.001). The increase in B7-H3 expression was independent of tumor stage (P = 0.13). Expression of B7-H1 by UCC tumors (P < 0.001) and PD-1 by tumor-infiltrating lymphocytes (P = 0.012) were significantly associated with increased pathologic stage. Patients who had received intravesical bacillus Calmette-Guerin before cystectomy tended to show increased expression of B7-H3 (P = 0.023) and PD-1 (P = 0.071) but were less likely to express B7-H1 (P = 0.027). Moreover, for the subset of patients with organ-confined disease (n = 167), B7-H1 expression independently predicted all-cause mortality after cystectomy (hazard ratio, 3.18; 95% confidence interval, 1.74-5.79; P < 0.001).

Conclusions: B7-H3 is highly expressed in UCC across tumor stages, whereas B7-H1 and PD-1 expression are associated with advanced disease. B7-H1 expression predicts mortality after cystectomy for patients with organ-confined tumors. These molecules may represent novel diagnostic or prognostic markers, as well as therapeutic targets, for patients with UCC.
Data from Enhanced Antitumor Efficacy of a DR5-Specific TRAIL Variant over Recombinant Human TRAIL in a Bioluminescent Ovarian Cancer Xenograft Model
Authors: Duiker Evelien W. , de Vries Elisabeth G.E. , Mahalingam Devalingam , Meersma Gert Jan , Boersma-van Ek Wytske , Hollema Harry , Lub-de Hooge Marjolijn N. , van Dam Go M. , Cool Robbert H. , Quax Wim J. , Samali Afshin , van der Zee Ate G.J. , de Jong Steven
Published: April 2023

Abstract
Purpose: Recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) is clinically evaluated as novel anticancer drug. rhTRAIL-DR5, a rhTRAIL variant that specifically binds to DR5 receptor, has recently been developed. We investigated whether rhTRAIL-DR5 is more efficient than rhTRAIL in combination with cisplatin in DR5-expressing human A2780 ovarian cancer cells.

Design: Effect of cisplatin alone or in combination with rhTRAIL or rhTRAIL-DR5 on DR5 surface expression, apoptosis, and cell survival of A2780 was measured. Biodistribution analysis was done in mice with 125I-rhTRAIL administered intravenously versus intraperitoneally. Antitumor efficacy of rhTRAIL-DR5 versus rhTRAIL was determined in an intraperitoneally growing bioluminescent A2780 xenograft model.

Results: Cisplatin strongly enhanced DR5 surface expression. Both rhTRAIL and rhTRAIL-DR5 in combination with cisplatin induced high levels of caspase-3 activation, apoptosis, and cell kill, with rhTRAIL-DR5 being most potent. Intraperitoneal administration of 125I-rhTRAIL resulted in a 1.7-fold higher area under the curve in serum, increased tumor exposure, and more caspase-3 activation in the tumor than intravenous administration. Intraperitoneal administration of rhTRAIL-DR5 delayed A2780 tumor progression, reflected in a mean light reduction of 68.3% (P = 0.015), whereas rhTRAIL or rhTRAIL-DR5 plus cisplatin resulted in 85% (P = 0.003) and 97% (P = 0.002) reduction compared with A2780 tumor progression in vehicle-treated animals. Combination of rhTRAIL-DR5 with cisplatin was more effective than cisplatin alone (P = 0.027).

Conclusion: rhTRAIL-DR5 was superior over rhTRAIL in vitro and in vivo against DR5-expressing ovarian cancer also in combination with cisplatin. Intraperitoneal administration of rhTRAIL-DR5 warrants further exploration in ovarian cancer.
Data from Getting Knit-PI3Ky: PIK3CA Mutation Status to Direct Multimodality Therapy?
Authors: Myers Andrea P. , Meyerhardt Jeffrey A. , Cantley Lewis C.
Published: April 2023

Abstract
There is high morbidity associated with local recurrence of rectal cancer. However, the adjuvant therapies given to prevent such recurrences also have significant side effects and associated risks. The ability to select patients with the highest risk of recurrence and greatest therapeutic response will improve rectal cancer care. (Clin Cancer Res 2009;15(22):674850)
Data from Histone Deacetylase Inhibitors Induce a Very Broad, Pleiotropic Anticancer Drug Resistance Phenotype in Acute Myeloid Leukemia Cells by Modulation of Multiple ABC Transporter Genes
Authors: Hauswald Stefanie , Duque-Afonso Jesus , Wagner Michaela M. , Schertl Florian M. , Lübbert Michael , Peschel Christian , Keller Ulrich , Licht Thomas
Published: April 2023

Abstract
Purpose: Histone deacetylase inhibitors (HDACi) are being studied in clinical trials with the aim to induce cellular differentiation, growth arrest, and apoptosis of tumor cells. Recent reports suggest that the multidrug resistance-1 (MDR1) gene is regulated by epigenetic mechanisms. To investigate whether additional drug transporters are regulated by HDACi and how this affects cytotoxicity, acute myeloid leukemia (AML) cells were examined.

Experimental Design: AML cells were cultured in the presence of phenylbutyrate, valproate, suberoylanilide hydroxamic acid, or trichostatin A and analyzed for drug transporter expression and function as well as sensitivity to anticancer drugs.

Results:MDR1, breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins (MRP) 7 and 8 were induced in a dose- and time-dependent manner as shown by semiquantitative PCR. The pattern of gene induction was cell line specific. Phenylbutyrate induced P-glycoprotein and BCRP expression and the efflux of drugs as determined with labeled substrates. KG-1a cells treated with phenylbutyrate developed resistance to daunorubicin, mitoxantrone, etoposide, vinblastine, paclitaxel, topotecan, gemcitabine, and 5-fluorouracil; as a result drug-induced apoptosis was impaired. Chromatin immunoprecipitation revealed the hyperacetylation of histone proteins in the promoter regions of MDR1, BCRP, and MRP8 on valproate treatment. Furthermore, an alternative MRP8 promoter was induced by HDACi treatment.

Conclusions: Exposure of AML cells to HDACi induces a drug resistance phenotype broader than the “classic multidrug resistance,” which might negatively affect treatment effectiveness.
Data from Immune Function Abnormalities in Peripheral Blood Mononuclear Cell Cytokine Expression Differentiates Stages of Cutaneous T-Cell Lymphoma/Mycosis Fungoides
Authors: Chong Benjamin F. , Wilson Adam J. , Gibson Heather M. , Hafner Mikehl S. , Luo Yu , Hedgcock Carrie J. , Wong Henry K.
Published: April 2023

Abstract
Purpose: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma (CTCL) characterized by neoplastic skin-homing T cells. To better understand the immunopathogenesis of MF, we analyzed the functional ability of peripheral blood mononuclear cells (PBMC) from early and late MF/CTCL patients to express cytokine genes. In late stage MF/CTCL, patients were separated into those with blood involvement (+B) and without blood involvement (−B).

Experimental Design: We analyzed TH1 (interleukin 2 (IL-2), IFN-γ), TH2 (IL-4, IL-5, IL-10, IL-13), and TH17 (IL-17) cytokine gene expression from activated PBMCs from normal (n = 12), psoriasis (n = 6), early MF/CTCL (n = 11), and late MF/CTCL+B (n = 4) and MF/CTCL−B (n = 3) by quantitative real-time PCR.

Results: PBMCs from early MF/CTCL and psoriasis showed higher induction of IL-2, IL-4, and IFN-γ genes than those from normal and late MF/CTCL−B and MF/CTCL+B (P < 0.05) in descending order. PBMCs from late MF/CTCL−B exhibited generally the highest level of IL-5, IL-10, IL-13, and IL-17 expression compared with the other groups. PBMCs from early MF/CTCL and late MF/CTCL−B had similarly elevated IL-13 and IL-17. Of all groups, PBMCs from late MF/CTCL+B had the lowest levels of IL-2 (P < 0.05), IL-4, IFN-γ, IL-13, and IL-17.

Conclusions: The different pattern of cytokine gene expression suggests a change in immune function in MF/CTCL from early MF/CTCL to late MF/CTCL−B to late MF/CTCL+B. These stages are consistent with localized disease associated with an anti-tumor immune response and late MF/CTCL associated with a loss of immune function mediated by malignant T cells that share regulatory T cell–like properties.
Data from Cancer-Testis Antigens: Expression and Correlation with Survival in Human Urothelial Carcinoma
Authors: Sharma Padmanee , Shen Yu , Wen Sijin , Bajorin Dean F. , Reuter Victor E. , Old Lloyd J. , Jungbluth Achim A.
Published: April 2023

Abstract
Purpose: Vaccination against human cancer is a promising therapeutic approach but the optimal antigen or antigens remain undefined. Cancer-testis antigens (CTA), a family of tumor-associated antigens, have both potent immunogenicity and restricted expression patterns in normal adult tissues, highly desirable characteristics for targets of anticancer vaccines. These antigens were evaluated for both the degree of expression and prognostic value in cancer of the urothelium.

Experimental Design: The expression patterns of nine CTAs (NY-ESO-1, LAGE-1, MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, CT7, CT10, and GAGE) were examined by immunohistochemistry and reverse transcription-PCR in a panel of high-grade urothelial carcinomas of the urinary bladder. Also assessed were correlations between the expression of CTAs by immunohistochemistry and both disease-free and overall survival.

Results: At least one CTA was expressed in 77% of samples and 61% of these tumors expressed more than one CTA. Additionally, patients with CT10-positive tumors had an improved disease-free survival (P = 0.008) and overall survival (P = 0.037) compared with patients with CT10-negative tumors.

Conclusions: These findings establish CTAs as potential prognostic markers and as target candidates for vaccine development for patients with urothelial carcinoma.
Data from EPOX Inhibits Angiogenesis by Degradation of Mcl-1 through ERK Inactivation
Authors: Sun Hui-Lung , Tsai An-Chi , Pan Shiow-Lin , Ding Qingqing , Yamaguchi Hirohito , Lin Chun-Nan , Hung Mien-Chie , Teng Che-Ming
Published: April 2023

Abstract
Purpose: Antiangiogenic therapy is considered as an effective strategy for controlling the growth and metastasis of tumors. Among a myriad of biological activities described for xanthone derivatives, the anticancer activity is quite remarkable, but the molecular mechanism is not clearly resolved. In the present study, we investigated the antiangiogenic mechanism of 3,6-di(2,3-epoxypropoxy)xanthone (EPOX), a novel Mcl-1 targeting drug.

Experimental Design: To evaluate the antiangiogenic activity of EPOX, we did cell viability, cell cycle, tube formation assay in vitro, and Matrigel plug assay in vivo. To evaluate the effect of EPOX on the endothelial signaling pathway, we did immunoblotting, immunoprecipitation, and immunofluorescence analysis. Intracellular glutathione levels were determined with the use of monochlorobimane, a glutathione-specific probe.

Results: EPOX induced endothelial cell apoptosis in association with proteasome-dependent Mcl-1 degradation. Down-regulation of Mcl-1 resulted in an increase in Mcl-1–free Bim, activation of Bax, and then signaling of mitochondria-mediated apoptosis. Additionally, glutathione depletion and extracellular signal-regulated kinase (ERK) inactivation was observed in EPOX-treated cells. Glutathione supplementation reversed the inhibitory effects of EPOX on ERK, which increases the phosphorylation of Mcl-1 at T163. Overexpression of mitogen-activated protein/ERK kinase (MEK) partially reversed the effect of EPOX on Mcl-1 dephosphorylation, ubiquitination, and degradation, further implicating ERK in the regulation of Mcl-1 stability.

Conclusions: This study provides evidence that EPOX induces glutathione depletion, ERK inactivation, and Mcl-1 degradation on endothelial cells, which leads to inhibition of angiogenesis. Our results suggest that EPOX is a novel antiangiogenic agent, making it a promising lead compound for further development in the treatment of angiogenesis-related pathologies.
Data from Expression Signature Developed from a Complex Series of Mouse Models Accurately Predicts Human Breast Cancer Survival
Authors: He Mei , Mangiameli David P. , Kachala Stefan , Hunter Kent , Gillespie John , Bian Xiaopeng , Shen H.-C. Jennifer , Libutti Steven K.
Published: April 2023

Abstract
Purpose: The capability of microarray platform to interrogate thousands of genes has led to the development of molecular diagnostic tools for cancer patients. Although large-scale comparative studies on clinical samples are often limited by the access of human tissues, expression profiling databases of various human cancer types are publicly available for researchers. Given that mouse models have been instrumental to our current understanding of cancer progression, we aimed to test the hypothesis that novel gene signatures possessing predictability in clinical outcome can be derived by coupling genomic analyses in mouse models of cancer with publicly available human cancer data sets.

Experimental Design: We established a complex series of syngeneic metastatic animal models using a murine breast cancer cell line. Tumor RNA was hybridized on Affymetrix MouseGenome-430A2.0 GeneChips. With the use of Venn logic, gene signatures that represent metastatic competency were derived and tested against publicly available human breast and lung cancer data sets.

Results: Survival analyses showed that the spontaneous metastasis gene signature was significantly associated with metastasis-free and overall survival (P < 0.0005). Consequently, the six-gene model was determined and showed statistical predictability in predicting survival in breast cancer patients. In addition, the model was able to stratify poor from good prognosis for lung cancer patients in most data sets analyzed.

Conclusions: Together, our data support that novel gene signature derived from mouse models of cancer can be used for predicting human cancer outcome. Our approaches set precedence that similar strategies may be used to decipher novel gene signatures for clinical utility. Clin Cancer Res; 16(1); 249–59
Data from Fluorescence Resonance Energy Transfer Biosensors for Cancer Detection and Evaluation of Drug Efficacy
Authors: Lu Shaoying , Wang Yingxiao
Published: April 2023

Abstract
A sensitive and specific fluorescence resonance energy transfer (FRET) biosensor was developed by Mizutani and colleagues and applied to detect the activity of BCR-ABL kinase in live cells. This biosensor allowed the detection of cancerous and drug-resistant cells, and the evaluation of kinase inhibitor efficacy. Future biosensor development and imaging can increasingly contribute to cancer diagnosis and therapeutics. Clin Cancer Res; 16(15); 3822–4. ©2010 AACR.