bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from β-Catenin Up-Regulates the Expression of the Urokinase Plasminogen Activator in Human Colorectal Tumors
Authors: Hiendlmeyer Elke , Regus Susanne , Wassermann Stella , Hlubek Falk , Haynl Angela , Dimmler Arno , Koch Claudia , Knoll Claudia , van Beest Moniek , Reuning Ute , Brabletz Thomas , Kirchner Thomas , Jung Andreas
Published: March 2023

Abstract
Expression of the urokinase plasminogen activator (uPA) increases during the progression of colorectal tumors from adenomas to carcinomas. The highest amounts of uPA are found at the invasion front of carcinomas, which also displays a strong expression of nuclear β-catenin and is therefore a region expressing β-catenin target genes at high levels. Here we show that β-catenin contributes to the transactivation of uPA. Therefore, β-catenin might have an impact on the capacity of colorectal tumors for invasion and metastasis, as well as dormancy, which are hallmarks of cancer.
Data from Disruption of the Gut Microbiota Confers Cisplatin Resistance in Epithelial Ovarian Cancer
Authors: Chambers Laura M. , Esakov Rhoades Emily L. , Bharti Rashmi , Braley Chad , Tewari Surabhi , Trestan Lexie , Alali Zahraa , Bayik Defne , Lathia Justin D. , Sangwan Naseer , Bazeley Peter , Joehlin-Price Amy S. , Wang Zeneng , Dutta Sumita , Dwidar Mohammed , Hajjar Adeline , Ahern Philip P. , Claesen Jan , Rose Peter , Vargas Roberto , Brown J. Mark , Michener Chad M. , Reizes Ofer
Published: March 2023

Abstract
Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer death. Despite initial responses to intervention, up to 80% of patient tumors recur and require additional treatment. Retrospective clinical analysis of patients with ovarian cancer indicates antibiotic use during chemotherapy treatment is associated with poor overall survival. Here, we assessed whether antibiotic (ABX) treatment would impact growth of EOC and sensitivity to cisplatin. Immunocompetent or immunocompromised mice were given untreated control or ABX-containing (metronidazole, ampicillin, vancomycin, and neomycin) water prior to intraperitoneal injection with EOC cells, and cisplatin therapy was administered biweekly until endpoint. Tumor-bearing ABX-treated mice exhibited accelerated tumor growth and resistance to cisplatin therapy compared with control treatment. ABX treatment led to reduced apoptosis, increased DNA damage repair, and enhanced angiogenesis in cisplatin-treated tumors, and tumors from ABX-treated mice contained a higher frequency of cisplatin-augmented cancer stem cells than control mice. Stool analysis indicated nonresistant gut microbial species were disrupted by ABX treatment. Cecal transplants of microbiota derived from control-treated mice was sufficient to ameliorate chemoresistance and prolong survival of ABX-treated mice, indicative of a gut-derived tumor suppressor. Metabolomics analyses identified circulating gut-derived metabolites that were altered by ABX treatment and restored by recolonization, providing candidate metabolites that mediate the cross-talk between the gut microbiome and ovarian cancer. Collectively, these findings indicate that an intact microbiome functions as a tumor suppressor in EOC, and perturbation of the gut microbiota with ABX treatment promotes tumor growth and suppresses cisplatin sensitivity.
Significance:
Restoration of the gut microbiome, which is disrupted following antibiotic treatment, may help overcome platinum resistance in patients with epithelial ovarian cancer.

See related commentary by Hawkins and Nephew, p. 4511
Data from Single-Cell Analysis Reveals a CD4+ T-cell Cluster That Correlates with PD-1 Blockade Efficacy
Authors: Kagamu Hiroshi , Yamasaki Satoshi , Kitano Shigehisa , Yamaguchi Ou , Mouri Atsuto , Shiono Ayako , Nishihara Fuyumi , Miura Yu , Hashimoto Kosuke , Imai Hisao , Kaira Kyoichi , Kobayashi Kunihiko , Kanai Yae , Shibata Tatsuhiro , Horimoto Katsuhisa
Published: March 2023

Abstract
CD4+ T-cell immunity helps clonal proliferation, migration, and cancer cell killing activity of CD8+ T cells and is essential in antitumor immune responses. To identify CD4+ T-cell clusters responsible for antitumor immunity, we simultaneously analyzed the naïve-effector state, Th polarization, and T-cell receptor clonotype based on single-cell RNA-sequencing data. Unsupervised clustering analysis uncovered the presence of a new CD4+ T-cell metacluster in the CD62Llow CD4+ T-cell subpopulation, which contained multicellular clonotypes associated with efficacy of programmed death-ligand 1 (PD-1) blockade therapy. The CD4+ T-cell metacluster consisted of CXCR3+CCR4−CCR6+ and CXCR3−CCR4−CCR6+ cells and was characterized by high expression of IL7 receptor and TCF7. The frequency of these cells in the peripheral blood significantly correlated with progression-free survival and overall survival of patients with lung cancer after PD-1 blockade therapy. In addition, the CD4+ metacluster in the peripheral blood correlated with CD4+ T-cell infiltration in the tumor microenvironment, whereas peripheral Th1 correlated with local CD8+ T-cell infiltration. Together, these findings suggest that CD62Llow CCR4−CCR6+ CD4+ T cells form a novel metacluster with predictive potential of the immune status and sensitivity to PD-1 blockade, which may pave the way for personalized antitumor immunotherapy strategies for patients.
Significance:
The identification of a new CD4+ T-cell metacluster that corresponds with immune status could guide effective tumor treatment by predicting response to immunotherapy using peripheral blood samples from patients.
Data from Shared Cancer Dataset Analysis Identifies and Predicts the Quantitative Effects of Pan-Cancer Somatic Driver Variants
Authors: Landau Jakob , Tsaban Linoy , Yaacov Adar , Ben Cohen Gil , Rosenberg Shai
Published: March 2023

Abstract
Driver mutations endow tumors with selective advantages and produce an array of pathogenic effects. Determining the function of somatic variants is important for understanding cancer biology and identifying optimal therapies. Here, we compiled a shared dataset from several cancer genomic databases. Two measures were applied to 535 cancer genes based on observed and expected frequencies of driver variants as derived from cancer-specific rates of somatic mutagenesis. The first measure comprised a binary classifier based on a binomial test; the second was tumor variant amplitude (TVA), a continuous measure representing the selective advantage of individual variants. TVA outperformed all other computational tools in terms of its correlation with experimentally derived functional scores of cancer mutations. TVA also highly correlated with drug response, overall survival, and other clinical implications in relevant cancer genes. This study demonstrates how a selective advantage measure based on a large cancer dataset significantly impacts our understanding of the spectral effect of driver variants in cancer. The impact of this information will increase as cancer treatment becomes more precise and personalized to tumor-specific mutations.
Significance:
A new selective advantage estimation assists in oncogenic driver identification and relative effect measurements, enabling better prognostication, therapy selection, and prioritization.
Data from A Pro-Regenerative Environment Triggers Premalignant to Malignant Transformation of Senescent Hepatocytes
Authors: Wuestefeld Anna , Iakovleva Viktoriia , Yap Shirlyn Xue Ling , Ong Agnes Bee Leng , Huang Daniel Q. , Shuen Timothy Wai Ho , Toh Han Chong , Dan Yock Young , Zender Lars , Wuestefeld Torsten
Published: March 2023

Abstract
Unfortunately, available liver cancer treatments are associated with modest survival advantage. The biggest factor improving survival is early detection, but the current understanding of early transformation events is limited. Therefore, we set up a model to study these early events and investigated the relationship of premalignant, senescent hepatocytes, a regenerative environment, and the influence of secreted factors on liver tumorigenesis. Oncogene-induced senescence (OIS) was triggered in a subset of mouse hepatocytes, which under normal conditions, are eliminated by immunosurveillance. Inducing liver damage and regeneration was sufficient to trigger immunosurveillance escape of OIS hepatocytes, resulting in premalignant to malignant transformation and hepatocellular tumor development. Trefoil factor 3 (TFF3) was found to be overexpressed in OIS hepatocytes and in hepatocellular carcinoma. TFF3 deficiency strongly attenuated malignant transformation by increasing insulin-like growth factor binding protein 5 (IGFBP5) expression, which consequently dampened IGF receptor signaling. Furthermore, analysis of precancerous liver tissue validated TFF3 as an early liver cancer biomarker. Altogether, these findings provide mechanistic insights into early transformation and immunosurveillance escape in liver cancer, revealing TFF3 and IGFBP5 to be important players with opposite roles in tumorigenesis.
Significance:
Liver damage induces a compensatory regenerative response that can drive premalignant to malignant transformation of senescent hepatocytes.
Data from The Oncogenic FOXL2 C134W Mutation Is a Key Driver of Granulosa Cell Tumors
Authors: Llano Elena , Todeschini Anne Laure , Felipe-Medina Natalia , Corte-Torres María D. , Condezo Yazmine B. , Sanchez-Martin Manuel , López-Tamargo Sara , Astudillo Aurora , Puente Xose S. , Pendas Alberto M. , Veitia Reiner A.
Published: March 2023

Abstract
Adult-type granulosa cell tumors (AGCT) are the most common type of malignant ovarian sex cord–stromal tumors. Most AGCTs carry the somatic variant c.402C>G (p.C134W) affecting the transcription factor FOXL2. Germline dominant variants in FOXL2 are responsible for blepharophimosis syndrome, which is characterized by underdevelopment of the eyelid. In this work, we generated a mouse model harboring the C134W variant of FOXL2 to evaluate in vivo the poorly understood oncogenic role of FOXL2. The mutation was dominant regarding eyelid hypoplasia, reminiscent of blepharophimosis syndrome. Interestingly, Foxl2+/C134W female mice had reduced fertility and developed AGCTs through a progression from abnormal ovaries with aberrant granulosa cells to ovaries with stromal hyperplasia and atypia and on to tumors in adut mice. The genes dysregulated in mouse AGCTs exhibited the hallmarks of cancer and were consistent with a gain-of-function of the mutated allele affecting TGFβ signaling. A comparison of these data with previous results on human AGCTs indicated similar deregulated pathways. Finally, a mutational analysis of mouse AGCT transcriptomic data suggested the absence of additional driver mutations apart from FOXL2-C134W. These results provide a clear in vivo example in which a single mutational hit triggers tumor development associated with profound transcriptomic alterations.
Significance:
A newly generated mouse model carrying a FOXL2 mutation characteristic of adult-type granulosa cell tumors shows that FOXL2 C134W shifts the transcriptome towards a signature of granulosa cell cancer and drives tumorigenesis.
Data from HAND2 Assists MYCN Enhancer Invasion to Regulate a Noradrenergic Neuroblastoma Phenotype
Authors: Xu Man , Sun Ming , Zhang Xiyuan , Nguyen Rosa , Lei Haiyan , Shern Jack F. , Thiele Carol J. , Liu Zhihui
Published: March 2023

Abstract
Noradrenergic neuroblastoma is characterized by a core transcriptional regulatory circuitry (CRC) comprised of transcription factors (TF) such as PHOX2B, HAND2, and GATA3, which form a network with MYCN. At normal physiologic levels, MYCN mainly binds to promoters but when aberrantly upregulated as in neuroblastoma, MYCN also binds to enhancers. Here, we investigated how MYCN invades enhancers and whether CRC TFs play a role in this process. HAND2 was found to regulate chromatin accessibility and to assist MYCN binding to enhancers. Moreover, HAND2 cooperated with MYCN to compete with nucleosomes to regulate global gene transcription. The cooperative interaction between MYCN and HAND2 could be targeted with an Aurora A kinase inhibitor plus a histone deacetylase inhibitor, resulting in potent downregulation of both MYCN and the CRC TFs and suppression of MYCN-amplified neuroblastoma tumor growth. This study identifies cooperation between MYCN and HAND2 in neuroblastoma and demonstrates that simultaneously targeting MYCN and CRC TFs is an effective way to treat this aggressive pediatric tumor.
Significance:
HAND2 and MYCN compete with nucleosomes to regulate global gene transcription and to drive a malignant neuroblastoma phenotype.
Data from ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma
Authors: Eichhoff Ossia M. , Stoffel Corinne I. , Käsler Jan , Briker Luzia , Turko Patrick , Karsai Gergely , Zila Nina , Paulitschke Verena , Cheng Phil F. , Leitner Alexander , Bileck Andrea , Zamboni Nicola , Irmisch Anja , Balazs Zsolt , Tastanova Aizhan , Pascoal Susana , Johansen Pål , Wegmann Rebekka , Mena Julien , Othman Alaa , Viswanathan Vasanthi S. , Wenzina Judith , Aloia Andrea , Saltari Annalisa , Dzung Andreas , Krauthammer Michael , Schreiber Stuart L. , Hornemann Thorsten , Distel Martin , Snijder Berend , Dummer Reinhard , Levesque Mitchell P.
Published: March 2023

Abstract
Clinical management of melanomas with NRAS mutations is challenging. Targeting MAPK signaling is only beneficial to a small subset of patients due to resistance that arises through genetic, transcriptional, and metabolic adaptation. Identification of targetable vulnerabilities in NRAS-mutated melanoma could help improve patient treatment. Here, we used multiomics analyses to reveal that NRAS-mutated melanoma cells adopt a mesenchymal phenotype with a quiescent metabolic program to resist cellular stress induced by MEK inhibition. The metabolic alterations elevated baseline reactive oxygen species (ROS) levels, leading these cells to become highly sensitive to ROS induction. In vivo xenograft experiments and single-cell RNA sequencing demonstrated that intratumor heterogeneity necessitates the combination of a ROS inducer and a MEK inhibitor to inhibit both tumor growth and metastasis. Ex vivo pharmacoscopy of 62 human metastatic melanomas confirmed that MEK inhibitor–resistant tumors significantly benefited from the combination therapy. Finally, oxidative stress response and translational suppression corresponded with ROS-inducer sensitivity in 486 cancer cell lines, independent of cancer type. These findings link transcriptional plasticity to a metabolic phenotype that can be inhibited by ROS inducers in melanoma and other cancers.
Significance:
Metabolic reprogramming in drug-resistant NRAS-mutated melanoma cells confers sensitivity to ROS induction, which suppresses tumor growth and metastasis in combination with MAPK pathway inhibitors.
Supplementary Table 1 from CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium
Authors: Travis Ruth C. , Schumacher Fredrick , Hirschhorn Joel N. , Kraft Peter , Allen Naomi E. , Albanes Demetrius , Berglund Goran , Berndt Sonja I. , Boeing Heiner , Bueno-de-Mesquita H. Bas , Calle Eugenia E. , Chanock Stephen , Dunning Alison M. , Hayes Richard , Feigelson Heather Spencer , Gaziano J. Michael , Giovannucci Edward , Haiman Christopher A. , Henderson Brian E. , Kaaks Rudolf , Kolonel Laurence N. , Ma Jing , Rodriguez Laudina , Riboli Elio , Stampfer Meir , Stram Daniel O. , Thun Michael J. , Tjønneland Anne , Trichopoulos Dimitrios , Vineis Paolo , Virtamo Jarmo , Le Marchand Loïc , Hunter David J.
Published: March 2023

Supplementary Table 1 from CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium
Supplementary Table 1 from Replication of Breast Cancer GWAS Susceptibility Loci in the Women's Health Initiative African American SHARe Study
Authors: Hutter Carolyn M. , Young Alicia M. , Ochs-Balcom Heather M. , Carty Cara L. , Wang Tao , Chen Christina T.L. , Rohan Thomas E. , Kooperberg Charles , Peters Ulrike
Published: March 2023

XLS file - 144K
Supplementary Table 1 from Identifying Genes for Establishing a Multigenic Test for Hepatocellular Carcinoma Surveillance in Hepatitis C Virus-Positive Cirrhotic Patients
Authors: Archer Kellie J. , Mas Valeria R. , David Krystle , Maluf Daniel G. , Bornstein Karen , Fisher Robert A.
Published: March 2023

Supplementary Table 1 from Identifying Genes for Establishing a Multigenic Test for Hepatocellular Carcinoma Surveillance in Hepatitis C Virus-Positive Cirrhotic Patients
Supplementary Figure 1 from DNA Hypermethylation of ESR1 and PGR in Breast Cancer: Pathologic and Epidemiologic Associations
Authors: Gaudet Mia M. , Campan Mihaela , Figueroa Jonine D. , Yang Xiaohong R. , Lissowska Jolanta , Peplonska Beata , Brinton Louise A. , Rimm David L. , Laird Peter W. , Garcia-Closas Montserrat , Sherman Mark E.
Published: March 2023

Supplementary Figure 1 from DNA Hypermethylation of ESR1 and PGR in Breast Cancer: Pathologic and Epidemiologic Associations
Data Supplement from Low Folate Levels Are Associated with Reduced Risk of Colorectal Cancer in a Population with Low Folate Status
Authors: Gylling Björn , Van Guelpen Bethany , Schneede Jörn , Hultdin Johan , Ueland Per Magne , Hallmans Göran , Johansson Ingegerd , Palmqvist Richard
Published: March 2023

Supplementary Table 1: Odds ratios for colorectal cancer by plasma folate, vitamin B12 and total homocysteine concentrations in quintiles.
Supplementary Tables 1 and 2 from Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas
Authors: de Vogel Stefan , Schneede Jörn , Ueland Per Magne , Vollset Stein Emil , Meyer Klaus , Fredriksen Åse , Midttun Øivind , Bjørge Tone , Kampman Ellen , Bretthauer Michael , Hoff Geir
Published: March 2023

Supplementary Tables 1 and 2 from Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas
Supplementary Table 1 from Feasibility of Identifying Pancreatic Cancer Based on Serum Metabolomics
Authors: Bathe Oliver F. , Shaykhutdinov Rustem , Kopciuk Karen , Weljie Aalim M. , McKay Andrew , Sutherland Francis R. , Dixon Elijah , Dunse Nicole , Sotiropoulos Dina , Vogel Hans J.
Published: March 2023

Supplementary Table 1 from Feasibility of Identifying Pancreatic Cancer Based on Serum Metabolomics
Supplemental Tables 1 - 7 from Association of Cancer Susceptibility Variants with Risk of Multiple Primary Cancers: The Population Architecture using Genomics and Epidemiology Study
Authors: Park S. Lani , Caberto Christian P. , Lin Yi , Goodloe Robert J. , Dumitrescu Logan , Love Shelly-Ann , Matise Tara C. , Hindorff Lucia A. , Fowke Jay H. , Schumacher Fredrick R. , Beebe-Dimmer Jennifer , Chen Chu , Hou Lifang , Thomas Fridtjof , Deelman Ewa , Han Ying , Peters Ulrike , North Kari E. , Heiss Gerardo , Crawford Dana C. , Haiman Christopher A. , Wilkens Lynne R. , Bush William S. , Kooperberg Charles , Cheng Iona , Le Marchand Loïc
Published: March 2023

Supplementary Table 1. Summary of Study Design and Case/Control Definitions for participating studies. Supplementary Table 2. Distribution of the incident index and second cancer site among incident multiple primary cancer cases, stratified by study and cancer latency. Supplemental Table 3. Detailed distribution of incident index and second cancer site among incident multiple primary cancer cases for WHI study. Supplemental Table 4. Detailed distribution of incident index and second cancer site among incident multiple primary cancer cases for MEC study. Supplemental Table 5. Frequency and cancer site of IMPC cases with 3 or more cancers. Supplementary Table 6. Meta-analysis of the non-significant associations (p{greater than or equal to}0.05) between 178 risk variants for other cancers and incident multiple primary cancer risk. Supplementary Table 7. Ten SNPsa associated with other cancers and multiple primary cancer risk by race/ethnicityb
Supplementary Table S2 from Shorter Leukocyte Telomere Length Is Independently Associated with Poor Survival in Patients with Bladder Cancer
Authors: Russo Alessia , Modica Federica , Guarrera Simonetta , Fiorito Giovanni , Pardini Barbara , Viberti Clara , Allione Alessandra , Critelli Rossana , Bosio Andrea , Casetta Giovanni , Cucchiarale Giuseppina , Destefanis Paolo , Gontero Paolo , Rolle Luigi , Zitella Andrea , Fontana Dario , Frea Bruno , Vineis Paolo , Sacerdote Carlotta , Matullo Giuseppe
Published: March 2023

Supplementary Table S2. TL quartiles and OS association analysis (Crude Cox regression).
Supplementary Table S1 from Shorter Leukocyte Telomere Length Is Independently Associated with Poor Survival in Patients with Bladder Cancer
Authors: Russo Alessia , Modica Federica , Guarrera Simonetta , Fiorito Giovanni , Pardini Barbara , Viberti Clara , Allione Alessandra , Critelli Rossana , Bosio Andrea , Casetta Giovanni , Cucchiarale Giuseppina , Destefanis Paolo , Gontero Paolo , Rolle Luigi , Zitella Andrea , Fontana Dario , Frea Bruno , Vineis Paolo , Sacerdote Carlotta , Matullo Giuseppe
Published: March 2023

Supplementary Table S1. Description of populations included and not included in the TL study and comparative analysis.
Supplementary Figure 3 from Sheddase Activity of Tumor Necrosis Factor-α Converting Enzyme Is Increased and Prognostically Valuable in Head and Neck Cancer
Authors: Ge Lisheng , Baskic Dejan , Basse Per , Vujanovic Lazar , Unlu Sebnem , Yoneyama Toshie , Vujanovic Andrea , Han Jie , Bankovic Dragic , Szczepanski Miroslaw J. , Hunt Jennifer L. , Herberman Ronald B. , Gollin Susanne M. , Ferris Robert L. , Whiteside Theresa L. , Myers Eugene N. , Vujanovic Nikola L.
Published: March 2023

Supplementary Figure 3 from Sheddase Activity of Tumor Necrosis Factor-α Converting Enzyme Is Increased and Prognostically Valuable in Head and Neck Cancer
Supplementary Table 2 from Manganese Superoxide Dismutase Polymorphism and Risk of Gastric Lesions, and Its Effects on Chemoprevention in a Chinese Population
Authors: Tu Hua-kang , Pan Kai-feng , Zhang Yang , Li Wen-qing , Zhang Lian , Ma Jun-ling , Li Ji-you , You Wei-cheng
Published: March 2023

Supplementary Table 2 from Manganese Superoxide Dismutase Polymorphism and Risk of Gastric Lesions, and Its Effects on Chemoprevention in a Chinese Population
Supplementary Table 1 from Chlamydia pneumoniae Infection and Risk for Lung Cancer
Authors: Chaturvedi Anil K. , Gaydos Charlotte A. , Agreda Patricia , Holden Jeffrey P. , Chatterjee Nilanjan , Goedert James J. , Caporaso Neil E. , Engels Eric A.
Published: March 2023

Supplementary Table 1 from Chlamydia pneumoniae Infection and Risk for Lung Cancer
Supplementary Tables 1-3 and Supplemenary Figure 1 from Radon and Lung Cancer in the American Cancer Society Cohort
Authors: Turner Michelle C. , Krewski Daniel , Chen Yue , Pope C. Arden , Gapstur Susan , Thun Michael J.
Published: March 2023

Supplementary Tables 1-3 and Supplemenary Figure 1 from Radon and Lung Cancer in the American Cancer Society Cohort
Supplementary Table 1 from Associations of Lifestyle Factors and Anthropometric Measures with Repeat PSA Levels During Active Surveillance/Monitoring
Authors: Burton Anya J. , Martin Richard M. , Donovan Jenny L. , Lane J. Athene , Davis Michael , Hamdy Freddie C. , Neal David E. , Tilling Kate
Published: March 2023

PDF file, 77K, Age, recruitment PSA and repeat PSAs by demographic and lifestyle factors.
Supplementary Table 2 from Variations in Chromosomes 9 and 6p21.3 with Risk of Non–Hodgkin Lymphoma
Authors: Wang Sophia S. , Menashe Idan , Cerhan James R. , Cozen Wendy , Severson Richard K. , Davis Scott , Hutchinson Amy , Rothman Nathaniel , Chanock Stephen J. , Bernstein Leslie , Hartge Patricia , Morton Lindsay M.
Published: March 2023

Supplementary Table 2 from Variations in Chromosomes 9 and 6p21.3 with Risk of Non–Hodgkin Lymphoma
Supplementary Table 2 from Risk Prediction Models for Melanoma: A Systematic Review
Authors: Usher-Smith Juliet A. , Emery Jon , Kassianos Angelos P. , Walter Fiona M.
Published: March 2023

PDF file - 34K, Details of study design and participants for cohort studies.
Supplementary Figure 2 from Ordered Subset Analysis Identifies Loci Influencing Lung Cancer Risk on Chromosomes 6q and 12q
Authors: Fang Shenying , Pinney Susan M. , Bailey-Wilson Joan E. , de Andrade Mariza A. , Li Yafang , Kupert Elena , You Ming , Schwartz Ann G. , Yang Ping , Anderson Marshall W. , Amos Christopher I.
Published: March 2023

Supplementary Figure 2 from Ordered Subset Analysis Identifies Loci Influencing Lung Cancer Risk on Chromosomes 6q and 12q
Supplementary Figure S3 from Prognostic Impact of Cigarette Smoking on the Survival of Patients with Established Nasopharyngeal Carcinoma
Authors: OuYang Pu-Yun , Su Zhen , Mao Yan-Ping , Liang Xue-Xia , Liu Qing , Deng Wuguo , Xie Fang-Yun
Published: March 2023

(a)Overall survival, (b) progression-free survivalcurves of heavy smokers versus light smokers according to pack-years inthe intensity-modulated radiotherapy or three-dimensional conformal radiotherapy cohort.A pack-year was defined as the equivalent of smoking one pack of cigarettes per day for one year.
Supplementary Figure S1 from Prognostic Impact of Cigarette Smoking on the Survival of Patients with Established Nasopharyngeal Carcinoma
Authors: OuYang Pu-Yun , Su Zhen , Mao Yan-Ping , Liang Xue-Xia , Liu Qing , Deng Wuguo , Xie Fang-Yun
Published: March 2023

(a)Overall survival, (b) progression-free survival, (c) locoregional relapse-free survival, (d) distant metastasis-free survival curves of smoking history group versus no smoking history group in the entire population.
Data from Circulating Folate, Vitamin B12, Homocysteine, Vitamin B12 Transport Proteins, and Risk of Prostate Cancer: a Case-Control Study, Systematic Review, and Meta-analysis
Authors: Collin Simon M. , Metcalfe Chris , Refsum Helga , Lewis Sarah J. , Zuccolo Luisa , Smith George Davey , Chen Lina , Harris Ross , Davis Michael , Marsden Gemma , Johnston Carole , Lane J. Athene , Ebbing Marta , Bønaa Kaare Harald , Nygård Ottar , Ueland Per Magne , Grau Maria V. , Baron John A. , Donovan Jenny L. , Neal David E. , Hamdy Freddie C. , Smith A. David , Martin Richard M.
Published: March 2023

Abstract
Background: Disturbed folate metabolism is associated with an increased risk of some cancers. Our objective was to determine whether blood levels of folate, vitamin B12, and related metabolites were associated with prostate cancer risk.

Methods: Matched case-control study nested within the U.K. population–based Prostate testing for cancer and Treatment (ProtecT) study of prostate-specific antigen–detected prostate cancer in men ages 50 to 69 years. Plasma concentrations of folate, B12 (cobalamin), holo-haptocorrin, holo-transcobalamin total transcobalamin, and total homocysteine (tHcy) were measured in 1,461 cases and 1,507 controls. ProtecT study estimates for associations of folate, B12, and tHcy with prostate cancer risk were included in a meta-analysis, based on a systematic review.

Results: In the ProtecT study, increased B12 and holo-haptocorrin concentrations showed positive associations with prostate cancer risk [highest versus lowest quartile of B12 odds ratio (OR) = 1.17 (95% confidence interval, 0.95-1.43); Ptrend = 0.06; highest versus lowest quartile of holo-haptocorrin OR = 1.27 (1.04-1.56); Ptrend = 0.01]; folate, holo-transcobalamin, and tHcy were not associated with prostate cancer risk. In the meta-analysis, circulating B12 levels were associated with an increased prostate cancer risk [pooled OR = 1.10 (1.01-1.19) per 100 pmol/L increase in B12; P = 0.002]; the pooled OR for the association of folate with prostate cancer was positive [OR = 1.11 (0.96-1.28) per 10 nmol/L; P = 0.2) and conventionally statistically significant if ProtecT (the only case-control study) was excluded [OR = 1.18 (1.00-1.40) per 10 nmol/L; P = 0.02].

Conclusion: Vitamin B12 and (in cohort studies) folate were associated with increased prostate cancer risk.

Impact: Given current controversies over mandatory fortification, further research is needed to determine whether these are causal associations. Cancer Epidemiol Biomarkers Prev; 19(6); 1632–42. ©2010 AACR.
Data from Sheddase Activity of Tumor Necrosis Factor-α Converting Enzyme Is Increased and Prognostically Valuable in Head and Neck Cancer
Authors: Ge Lisheng , Baskic Dejan , Basse Per , Vujanovic Lazar , Unlu Sebnem , Yoneyama Toshie , Vujanovic Andrea , Han Jie , Bankovic Dragic , Szczepanski Miroslaw J. , Hunt Jennifer L. , Herberman Ronald B. , Gollin Susanne M. , Ferris Robert L. , Whiteside Theresa L. , Myers Eugene N. , Vujanovic Nikola L.
Published: March 2023

Abstract
Tumor necrosis factor α converting enzyme (TACE) is a sheddase overexpressed in cancers that generates cancer cell growth and survival factors, and is implicated in carcinogenesis and tumor growth. This indicates that TACE could be a potentially important cancer biomarker. Unexpectedly, TACE expression in cancer tissues does not correlate with cancer stage or invasiveness. Although TACE sheddase activity is a more direct and potentially better indicator of TACE biology and might be a better cancer biomarker than TACE expression, it has not been studied in cancer tissues. In the present study, we developed a reliable specific assay for quantification of TACE sheddase activity, investigated TACE activity and TACE protein expression in head and neck cancer (HNC) tissues, and examined the correlation of the results with HNC clinical stages and likelihood to recur. We found that HNC cell lines and tissues contained remarkably higher quantities of TACE activity and TACE protein than normal keratinocytes or oral mucosa. siRNA silencing of TACE resulted in the inhibition of release of the tumorogenic factors amphiregulin and transforming growth factor α, and tumor protective factors tumor necrosis factor receptors from HNC cells. Importantly, TACE activity, but not TACE protein expression, was significantly higher in large, T3/T4, primary tumors relative to small, T1/T2, primary tumors, and especially in primary tumors likely to recur relative to those unlikely to recur. These data show that increased TACE activity in cancer is biologically and clinically relevant, and indicate that TACE activity could be a significant biomarker of cancer prognosis. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2913–22)
Data from Genetic Variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF Genes Are Prognostic Markers of Prostate Cancer-Specific Mortality
Authors: Lin Daniel W. , FitzGerald Liesel M. , Fu Rong , Kwon Erika M. , Zheng Siqun Lilly , Kolb Suzanne , Wiklund Fredrik , Stattin Pär , Isaacs William B. , Xu Jianfeng , Ostrander Elaine A. , Feng Ziding , Grönberg Henrik , Stanford Janet L.
Published: March 2023

Abstract
Background: Prostate cancer is the second leading cause of cancer-related deaths in men, accounting for more than 30,000 deaths annually. The purpose of this study was to test whether variation in selected candidate genes in biological pathways of interest for prostate cancer progression could help distinguish patients at higher risk for fatal prostate cancer.

Methods: In this hypothesis-driven study, we genotyped 937 single nucleotide polymorphisms (SNPs) in 156 candidate genes in a population-based cohort of 1,309 prostate cancer patients. We identified 22 top-ranking SNPs (P ≤ 0.01, FDR ≤ 0.70) associated with prostate cancer-specific mortality (PCSM). A subsequent validation study was completed in an independent population-based cohort of 2,875 prostate cancer patients.

Results: Five SNPs were validated (P ≤ 0.05) as being significantly associated with PCSM, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. Compared with patients with 0 to 2 of the at-risk genotypes those with 4 to 5 at-risk genotypes had a 50% (95% CI, 1.2–1.9) higher risk of PCSM and risk increased with the number of at-risk genotypes carried (Ptrend = 0.001), adjusting for clinicopathologic factors known to influence prognosis.

Conclusion: Five genetic markers were validated to be associated with lethal prostate cancer.

Impact: This is the first population-based study to show that germline genetic variants provide prognostic information for prostate cancer-specific survival. The clinical utility of this five-SNP panel to stratify patients at higher risk for adverse outcomes should be evaluated. Cancer Epidemiol Biomarkers Prev; 20(9); 1928–36. ©2011 AACR.
Data from Rapid Mass Spectrometric Metabolic Profiling of Blood Sera Detects Ovarian Cancer with High Accuracy
Authors: Zhou Manshui , Guan Wei , Walker L. DeEtte , Mezencev Roman , Benigno Benedict B. , Gray Alexander , Fernández Facundo M. , McDonald John F.
Published: March 2023

Abstract
Background: Ovarian cancer diagnosis is problematic because the disease is typically asymptomatic, especially at the early stages of progression and/or recurrence. We report here the integration of a new mass spectrometric technology with a novel support vector machine computational method for use in cancer diagnostics, and describe the application of the method to ovarian cancer.

Methods: We coupled a high-throughput ambient ionization technique for mass spectrometry (direct analysis in real-time mass spectrometry) to profile relative metabolite levels in sera from 44 women diagnosed with serous papillary ovarian cancer (stages I-IV) and 50 healthy women or women with benign conditions. The profiles were input to a customized functional support vector machine–based machine-learning algorithm for diagnostic classification. Performance was evaluated through a 64-30 split validation test and with a stringent series of leave-one-out cross-validations.

Results: The assay distinguished between the cancer and control groups with an unprecedented 99% to 100% accuracy (100% sensitivity and 100% specificity by the 64-30 split validation test; 100% sensitivity and 98% specificity by leave-one-out cross-validations).

Conclusion: The method has significant clinical potential as a cancer diagnostic tool. Because of the extremely low prevalence of ovarian cancer in the general population (∼0.04%), extensive prospective testing will be required to evaluate the test's potential utility in general screening applications. However, more immediate applications might be as a diagnostic tool in higher-risk groups or to monitor cancer recurrence after therapeutic treatment.

Impact: The ability to accurately and inexpensively diagnose ovarian cancer will have a significant positive effect on ovarian cancer treatment and outcome. Cancer Epidemiol Biomarkers Prev; 19(9); 2262–71. ©2010 AACR.
Data from Generalizability and Epidemiologic Characterization of Eleven Colorectal Cancer GWAS Hits in Multiple Populations
Authors: He Jing , Wilkens Lynne R. , Stram Daniel O. , Kolonel Laurence N. , Henderson Brian E. , Wu Anna H. , Le Marchand Loic , Haiman Christopher A.
Published: March 2023

Abstract
Background: Genome-wide association studies (GWAS) in populations of European ancestry have identified several loci that confer an increased risk of colorectal cancer (CRC).

Methods: We studied the generalizability of the associations with 11 risk variants for CRC on 8q23 (rs16892766), 8q24 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23 (rs3802842), 14q22 (rs4444235), 15q13 (rs4779584), 16q22 (rs9929218), 18q21 (rs4939827), 19q13 (rs10411210), and 20p12 (rs961253) in a multiethnic sample of 2,472 CRC cases, 839 adenoma cases and 4,466 controls comprised of European American, African American, Native Hawaiian, Japanese American, and Latino men and women. Because findings for CRC and adenoma were similar, we combined both groups in the analyses.

Results: We confirmed the associations with an increased risk of CRC/adenoma for the 8q24, 11q23 and 15q13 loci in European Americans, and observed significant associations between the 8q24 and 20p12 loci with CRC/adenoma risk in African Americans. Moreover, we found statistically significant cumulative effects of risk alleles on CRC/adenoma risk in all populations (odds ratio [OR] per allele = 1.07–1.09, P ≤ 0.039) except in Japanese Americans (OR = 1.01, P = 0.52). We found heterogeneity in the associations by tumor subsite, age of CRC/adenoma onset, sex, body mass index (BMI), and smoking status for some of the variants.

Conclusions: These results provide evidence that the known variants are in aggregate significantly associated with CRC/adenoma risk in multiple populations except Japanese Americans, and the influences may differ across groups defined by clinicopathological characteristics for some variants.

Impact: These results underline the importance of studying the epidemiologic architecture of these genetic effects in large and diverse populations. Cancer Epidemiol Biomarkers Prev; 20(1); 70–81. ©2011 AACR.
Supplementary Figure 4 from Adjuvant therapy with oncolytic adenovirus Delta-24-RGDOX after intratumoral adoptive T-cell therapy promotes antigen spread to sustain systemic antitumor immunity
Authors: Jiang Hong , Shin Dong Ho , Yi Yanhua , Fan Xuejun , Gumin Joy , He Jiasen , Gillard Andrew G. , Lang Frederick F. , Gomez-Manzano Candelaria , Fueyo Juan
Published: March 2023

The effect of combining pmel-1 T cells and Delta-24-RGDOX. A, A cartoon depiction of the treatment scheme for schedule (left) and positions of tumor implantation, T-cell and virus injection (right). s.c.: subcutaneously; i.t.: intratumorally. B, Plots of the bioluminescence of the tumors from the indicated treatment groups. C, Survival plots of the treatment groups. n = 9 except n = 8 for combination group. RGDOX: Delta-24-RGDOX. ns: not significant (p > 0.05); **: p<0.01. log-rank test.
Supplementary Figure 3 from Adjuvant therapy with oncolytic adenovirus Delta-24-RGDOX after intratumoral adoptive T-cell therapy promotes antigen spread to sustain systemic antitumor immunity
Authors: Jiang Hong , Shin Dong Ho , Yi Yanhua , Fan Xuejun , Gumin Joy , He Jiasen , Gillard Andrew G. , Lang Frederick F. , Gomez-Manzano Candelaria , Fueyo Juan
Published: March 2023

Survival plots of mice with s.c./s.c. melanomas treated with PBS or wildtype (WT) CD8+ T cells injected into the s.c. Tumor 1. PBS: n=8; WT CTLs: n=5. ns: not significant (p > 0.05). log-rank test.
Data from Adjuvant Therapy with Oncolytic Adenovirus Delta-24-RGDOX After Intratumoral Adoptive T-cell Therapy Promotes Antigen Spread to Sustain Systemic Antitumor Immunity
Authors: Jiang Hong , Shin Dong Ho , Yi Yanhua , Fan Xuejun , Gumin Joy , He Jiasen , Gillard Andrew G. , Lang Frederick F. , Gomez-Manzano Candelaria , Fueyo Juan
Published: March 2023

Cancer cell heterogeneity and immunosuppressive tumor microenvironment (TME) pose a challenge in treating solid tumors with adoptive cell therapies targeting limited tumor-associated antigens (TAA), such as chimeric antigen receptor T-cell therapy. We hypothesize that oncolytic adenovirus Delta-24-RGDOX activates the TME and promote antigen spread to potentiate the abscopal effect of adoptive TAA-targeting T cells in localized intratumoral treatment. Herein, we used C57BL/6 mouse models with disseminated tumors derived from B16 melanoma cell lines to assess therapeutic effects and antitumor immunity. gp100-specific pmel-1 or ovalbumin (OVA)-specific OT-I T cells were injected into the first subcutaneous tumor, followed by three injections of Delta-24-RGDOX. We found TAA-targeting T cells injected into one subcutaneous tumor showed tumor tropism. Delta-24-RGDOX sustained the systemic tumor regression mediated by the T cells, leading to improved survival rate. Further analysis revealed that, in mice with disseminated B16-OVA tumors, Delta-24-RGDOX increased CD8+ leukocyte density within treated and untreated tumors. Importantly, Delta-24-RGDOX significantly reduced the immunosuppression of endogenous OVA-specific CTLs while increasing that of CD8+ leukocytes and, to a lesser extent, adoptive pmel-1 T cells. Consequently, Delta-24-RGDOX drastically increased the density of the OVA-specific CTLs in both tumors, and the combination synergistically enhanced the effect. Consistently, the splenocytes from the combination group showed a significantly stronger response against other TAAs (OVA and TRP2) than gp100, resulted in higher activity against tumor cells. Therefore, our data demonstrate that, as an adjuvant therapy followed TAA-targeting T cells in localized treatment, Delta-24-RGDOX activates TME and promotes antigen spread, leading to efficacious systemic antitumor immunity to overcome tumor relapse.
Significance:
Adjuvant therapy with oncolytic viruses promotes antigen spread to potentiate localized intratumoral adoptive T-cell therapy with limited TAA targets, leading to sustainable systemic antitumor immunity to overcome tumor relapse.
Apoptose e sistema complemento: mecanismos participantes da neurodegeneração na doença de Huntington
Authors: Elias Karina Maria , Diament Mariela , Lima Mário Luiz B. S. de , Valente Tatiana , Silva Kátia Cristina R. da , Gorescu Rosa Alta
Published: March 2023

A doença de Huntington (DH) é uma patologia neurodegenerativa de herança autossômica dominante, que,geralmente, tem início nas terceira e quarta décadas de vida. Atinge homens e mulheres na mesma proporção, sendo  maior sua prevalência em populações com ascendência da Europa Ocidental. As manifestações clínicas são progressivase abrangem distúrbios de movimentos (como coréia), demência e alterações da personalidade. A característicaanatomopatológica mais marcante é a atrofia cerebral, que predomina nas estruturas do corpo estriado (putâmen, globopálido e núcleo caudado). Estudos realizados em indivíduos portadores de DH levaram à descoberta e caracterizaçãoda proteína huntingtina (HDa), de papel fisiológico desconhecido. Devido a uma mutação, o gene IT-15, localizado no cromossomo 4, passa a codificar a HDa alterada, que possui expansão da poliglutamina em sua extremidade N-terminal. Por mecanismos ainda desconhecidos, esta HDa mutante é apontada como provável fator de indução da neurodegeneração. Têm-se atribuído como causa das manifestações clínicas a ocorrência de apoptose e a ativação do Sistema Complemento, sendo que ambas levam à morte neuronal. Este levantamento bibliográfico tem como objetivo estudar as recentes hipóteses sobre os mecanismos envolvidos na neurodegeneração da DH, bem como o impacto destes no desenvolvimento de futuros tratamentos.
Tratamento cirúrgico das epilepsias
Authors: Marino Junior Raul , Zanetti Marcus V.
Published: March 2023

Baseados neste e demais estudos da literatura evidencia-se que a ressecção cirúrgica de áreas epileptogênicas localizadas ocupa um lugar importante no tratamento das epilepsias. Para tanto, a localização dos focos deve ser precisa, devendo situar-se em área cerebral cirurgicamente acessível, por ser possível sua excisão sem conseqüências neuropsicológicas graves. Nossa experiência cirúrgica nos demonstrou que não há intervenções padronizadas para tratar epilepsias, devendo cada caso ser estudado de forma a ser indicado o tipo mais apropriado de cirurgia. A intervenção deve agir sobre o número de crises melhorar o estado neurológico e o ajustamento psicológico dos doentes, possibilitando suareabilitação escolar, profissional e reintegração familiar e social.
Lesão do esôfago e de tronco braquiocefálico em trauma fechado: uma associação incomum
Authors: Kobata Cristina Helena Prado , Neves Murilo Catafesta das , Rocha Felipe Veleirinho de Oliveira , Silva Francisco Salles Collet e , Dutenhefner Simone Elisa , Fidelis Ronald
Published: March 2023

Relato de lesão incomum de esôfago e rara associação desta com lesão em tronco braquiocefálico (TBC) em paciente vítima de trauma fechado. Paciente vítima de acidenteautomobilístico (auto x caminhão), masc., 19a., passageiro do banco traseiro do auto e sem cinto de segurança. Chegou ao PSHC-FMUSP consciente, orientado e estável hemodinamicamente. Exames iniciais evidenciaram alargamento de mediastino. À arteriografia, identificou-se alargamento proximal de TBC sugestivo de pseudoaneurisma e à endoscopia, duas lesões esofágicas de aproximadamente 6cm que acometiam a serosa e a muscular, mas poupavam a mucosa. Foi submetido a uma esternotomia para enxerto do TBC e posterior toracotomia ântero-lateral para correção das lesões esofágicas. Evoluiu bem, sem intercorrências significativas, recebendo alta no 10o PO. Consideram os autores, após revisão da literatura, que lesões de esôfago e de TBC causados por trauma fechado são individualmente raras e, a associação das lesões não foi observada na literatura estudada.
O corpo calloso e as apraxias
Authors: Procopio João
Published: March 2023

Conferencia realisada no Centro Acadêmico “Oswaldo Cruz”, em12-VIII-1916, pelo 4º annista de Medicina, João Procopio
Influência do refluxo bílio-pancreático nas complicações da doença do refluxo gastro-esofágico (DRGE)
Authors: Takeda Flavio Roberto , Szachnowicz Sérgio , Apolônio Rafael , Kawamoto Flávio , Tacconi Marcos Roberto , Cecconello Ivan
Published: March 2023

O refluxo do conteúdo duodenal através do piloro para o estômago é um evento fisiológico, que ocorre predominantemente à noite e no período pós-prandial; e raramente causa sintomas e doenças primárias. Entretanto, quando excessivo, pode ser patogênico, associando-se a complicações como gastrite, úlcera gástrica, carcinoma gástrico, síndromedispéptica e doença do refluxo gastro-esofágico (DRGE). A DRGE é altamente prevalente e incidente, representando a principal doença dentro das afecções gastroenterológicas. A fisiopatologia de suas complicações, como o esôfago de Barrett, é amplamente estudada e cada vez mais, modificações no epitélio esofágico são atribuídas ao refluxo duodeno-gastroesofágico(RDGE), principalmente após o advento de métodos diagnósticos específicos para o RDGE, como a espectrofotometria de bilirrubina (BilitecR). Até então, os métodos de diagnósticos se apresentavam com pouca sensibilidade e pouca especificidade, porém, com a bilimetria iniciaram-se grandes estudos, e ao mesmo tempo surgiram muitas controvérsias. Paralelamente, estudos experimentais relacionam cada vez mais a presença de excessivo RDGE com o desenvolvimento de esôfago de Barrett e adenocarcinoma de esôfago. Este trabalho discute as principais controvérsias desses estudos, avaliando os principais métodos de diagnóstico para o RDGE destacando suas vantagens, desvantagens, sensibilidade e especificidade. Discutiremos a real importância do RDGE na patogênese do esôfago de Barrette suas complicações.
Estudo do desempenho da dopplervelocimetria e dos métodos de avaliação das atividades biofísicas fetais na predição das condições pós-natais adversas
Authors: Rosa Paula Waki Lopes da , Figueira Paula Gabriela Marin , Tomioka Renato Bussadori , Miyadahira Seizo , Francisco Rossana Pulcineli Vieira , Zugaib Marcelo
Published: March 2023

Este estudo retrospectivo e transversal teve como objetivo verificar o desempenho dos exames antenatais, para a predição de resultados pós-natais adversos. Selecionaram-se 1.387 pacientes com alto risco gestacional, no Setor de Avaliação da Vitalidade Fetal, da Clínica Obstétrica do Hospital das Clínicas da FMUSP. O desempenho de todos os exames foi testado, para a predição dos resultados pós-natais adversos, por meio do cálculo da sensibilidade, especificidade, VPP e VPN. O enfoque inédito do estudo foi a divisão da amostra em dois subgrupos, estratificada segundo o risco imposto pelas doenças ou intercorrências obstétricas. O subgrupo de baixo risco composto por 659 casos, e o subgrupo de alto risco,por 728 casos. Os exames antenatais foram: Doppler umbilical, Doppler da artéria cerebralmédia, Doppler do ducto venoso, cardiotocografia e perfil biofísico fetal. Os resultados pós natais foram: prematuridade, desnutrição fetal, depressão neonatal (Apgar < 7) e acidemia no nascimento. Todos os testes demonstraram melhores resultados no subgrupo de alto risco do que no subgrupo de baixo risco. Considerando-se a predição de todos os resultados neonatais adversos, o Doppler umbilical demonstrou melhores resultados.