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  1. Article: Recent and Projected Trends in Oral Tongue Cancer in the United States: A Demographic Shift in Case Burden as Early Onset Increases Among Females Subside.

    Burus, Todd / Damgacioglu, Haluk / Huang, Bin / Christian, W Jay / Hull, Pamela C / Ellis, Amanda R / Arnold, Susanne M / Deshmukh, Ashish A / Kuhs, Krystle A Lang

    Research square

    2023  

    Abstract: Background: Oral tongue cancer (OTC) incidence has increased rapidly among young (< 50 years) non-Hispanic White (NHW) individuals in the United States (U.S.) over the last two decades; however, it is unknown if age-associated trajectories have ... ...

    Abstract Background: Oral tongue cancer (OTC) incidence has increased rapidly among young (< 50 years) non-Hispanic White (NHW) individuals in the United States (U.S.) over the last two decades; however, it is unknown if age-associated trajectories have persisted. Furthermore, incidence trends for all 50 U.S. states and the District of Columbia have never been investigated.
    Materials and methods: Using U.S. Cancer Statistics data, we investigated incidence trends from 2001-2019, overall and according to age, sex, race/ethnicity, and state of residence. We used age-period-cohort analysis to explore temporal patterns among birth cohorts and to project future trends and case counts.
    Results: OTC incidence increased across all age, sex, and racial/ethnic groups, with marked increases observed among the NHWs (2.9%/year; 95%CI, 2.2%-3.7%). Incidence among NHWs increased in most U.S. states, particularly in the Southeast. Increases were significantly greater among NHW females compared to males (3.6%/year vs 2.6%/year;
    Conclusion: The period of rapidly increasing OTC incidence among younger NHW females in the U.S. is tempering and giving way to greater increases among older females, suggesting that a birth cohort effect may have influenced previously observed trends. Recent increases among NHWs aged ≥ 50 of both sexes have matched or outpaced younger age groups. Continuing increases among older individuals, particularly females, will lead to a shift in the OTC patient profile over time.
    Language English
    Publishing date 2023-09-22
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-3359293/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma

    Faden, Daniel L. / Kuhs, Krystle A. Lang / Lin, Maoxuan / Langenbucher, Adam / Pinheiro, Maisa / Yeager, Meredith / Cullen, Michael / Boland, Joseph F. / Steinberg, Mia / Bass, Sara / Lewis, James S. / Lawrence, Michael S. / Ferris, Robert L. / Mirabello, Lisa

    Viruses. 2021 Aug. 23, v. 13, no. 8

    2021  

    Abstract: APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC- ... ...

    Abstract APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC-induced mutations observed in both human cancers and HPV genomes are directly linked. We performed sequencing of host somatic exomes, transcriptomes, and HPV16 genomes from 79 HPV + OPSCC samples, quantifying APOBEC mutational burden and activity in both host and virus. APOBEC was the dominant mutational signature in somatic exomes. In viral genomes, there was a mean of five (range 0–29) mutations per genome. The mean of APOBEC mutations in viral genomes was one (range 0–5). Viral APOBEC mutations, compared to non-APOBEC mutations, were more likely to be low-variant allele fraction mutations, suggesting that APOBEC mutagenesis actively occurrs in viral genomes during infection. HPV16 APOBEC-induced mutation patterns in OPSCC were similar to those previously observed in cervical samples. Paired host and viral analyses revealed that APOBEC-enriched tumor samples had higher viral APOBEC mutation rates (p = 0.028), and APOBEC-associated RNA editing (p = 0.008), supporting the concept that APOBEC mutagenesis in host and viral genomes is directly linked and occurrs during infection. Using paired sequencing of host somatic exomes, transcriptomes, and viral genomes, we demonstrated for the first-time definitive evidence of concordance between tumor and viral APOBEC mutagenesis. This finding provides a missing link connecting APOBEC mutagenesis in host and virus and supports a common mechanism driving APOBEC dysregulation.
    Keywords Papillomaviridae ; RNA ; alleles ; head and neck squamous cell carcinoma ; humans ; mutagenesis ; mutagens ; squamous cell carcinoma ; transcriptome ; viral genome ; viruses
    Language English
    Dates of publication 2021-0823
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13081666
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: APOBEC Mutagenesis Is Concordant between Tumor and Viral Genomes in HPV-Positive Head and Neck Squamous Cell Carcinoma.

    Faden, Daniel L / Kuhs, Krystle A Lang / Lin, Maoxuan / Langenbucher, Adam / Pinheiro, Maisa / Yeager, Meredith / Cullen, Michael / Boland, Joseph F / Steinberg, Mia / Bass, Sara / Lewis, James S / Lawrence, Michael S / Ferris, Robert L / Mirabello, Lisa

    Viruses

    2021  Volume 13, Issue 8

    Abstract: APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC- ... ...

    Abstract APOBEC is a mutagenic source in human papillomavirus (HPV)-mediated malignancies, including HPV+ oropharyngeal squamous cell carcinoma (HPV + OPSCC), and in HPV genomes. It is unknown why APOBEC mutations predominate in HPV + OPSCC, or if the APOBEC-induced mutations observed in both human cancers and HPV genomes are directly linked. We performed sequencing of host somatic exomes, transcriptomes, and HPV16 genomes from 79 HPV + OPSCC samples, quantifying APOBEC mutational burden and activity in both host and virus. APOBEC was the dominant mutational signature in somatic exomes. In viral genomes, there was a mean of five (range 0-29) mutations per genome. The mean of APOBEC mutations in viral genomes was one (range 0-5). Viral APOBEC mutations, compared to non-APOBEC mutations, were more likely to be low-variant allele fraction mutations, suggesting that APOBEC mutagenesis actively occurrs in viral genomes during infection. HPV16 APOBEC-induced mutation patterns in OPSCC were similar to those previously observed in cervical samples. Paired host and viral analyses revealed that APOBEC-enriched tumor samples had higher viral APOBEC mutation rates (
    MeSH term(s) APOBEC Deaminases/genetics ; APOBEC Deaminases/metabolism ; Adult ; Aged ; Female ; Genome, Viral ; Human papillomavirus 16/genetics ; Human papillomavirus 16/physiology ; Humans ; Male ; Middle Aged ; Mutagenesis ; Mutation ; Papillomavirus Infections/enzymology ; Papillomavirus Infections/genetics ; Papillomavirus Infections/virology ; Squamous Cell Carcinoma of Head and Neck/enzymology ; Squamous Cell Carcinoma of Head and Neck/genetics ; Squamous Cell Carcinoma of Head and Neck/virology
    Chemical Substances APOBEC Deaminases (EC 3.5.4.5)
    Language English
    Publishing date 2021-08-23
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13081666
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A prognostic gene expression signature for oropharyngeal squamous cell carcinoma.

    Liu, Xinyi / Liu, Ping / Chernock, Rebecca D / Kuhs, Krystle A Lang / Lewis, James S / Luo, Jingqin / Gay, Hiram A / Thorstad, Wade L / Wang, Xiaowei

    EBioMedicine

    2020  Volume 61, Page(s) 102805

    Abstract: Background: Robust prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is important for developing individualized treatment plans. This study was conducted to develop and validate a clinically feasible prognostic ... ...

    Abstract Background: Robust prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is important for developing individualized treatment plans. This study was conducted to develop and validate a clinically feasible prognostic classifier based on transcriptome-wide gene expression profiles.
    Methods: Tumor tissues were collected from 208 OPSCC patients treated at Washington University in St. Louis and 130 OPSCC patients treated at Vanderbilt University, used for model training and validation, respectively. OPSCC patients (n = 70) from the TCGA cohort were also included for independent validation. Based on RNA-seq profiling data, Cox proportional hazards regression analysis was performed to identify genes associated with disease outcomes. Then, Lasso-penalized multivariate survival models were constructed to identify biomarker genes for developing a prognostic gene signature.
    Findings: A 60-gene signature was identified by RNA-seq profiling analysis. Computed risk score of the gene signature was significantly predictive of 5-year overall survival of the training cohort (Hazard ratio (HR) 28·32, P = 4·3E-41). Subgroup analysis stratified by HPV status revealed that the signature was prognostic in HPV-positive OPSCC patients (HR 30·55, P = 7·0E-37) and was independent of clinical features. Importantly, the gene signature was validated in two independent patient cohorts, including the TCGA cohort (HR 3·94, P = 0·0018) and the Vanderbilt cohort (HR 8·50, P = 5·7E-09) for overall survival.
    Interpretation: The prognostic gene signature is a robust tool for risk stratification of OPSCC patients. The signature remains prognostic among HPV-positive OPSCC patients.
    Funding: National Institutes of Health.
    MeSH term(s) Adult ; Aged ; Biomarkers, Tumor ; Cell Line, Tumor ; Computational Biology/methods ; Disease Susceptibility ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; High-Throughput Nucleotide Sequencing ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Squamous Cell Carcinoma of Head and Neck/diagnosis ; Squamous Cell Carcinoma of Head and Neck/genetics ; Squamous Cell Carcinoma of Head and Neck/mortality ; Transcriptome
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2020-10-07
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2020.102805
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  5. Article: HPV16 E6 seropositivity among cancer-free men with oral, anal or genital HPV16 infection.

    Beachler, Daniel C / Waterboer, Tim / Pierce Campbell, Christine M / Ingles, Donna J / Kuhs, Krystle A Lang / Nyitray, Alan G / Hildesheim, Allan / Pawlita, Michael / Kreimer, Aimée R / Giuliano, Anna R

    Papillomavirus research (Amsterdam, Netherlands)

    2016  Volume 2, Page(s) 141–144

    Abstract: Antibodies against the Human papillomavirus 16 (HPV16) E6 oncoprotein appear years prior to clinical diagnosis of anal and oropharyngeal cancer, but whether they develop around the time of HPV infection is unclear. Serum samples from 173 cancer-free men ... ...

    Abstract Antibodies against the Human papillomavirus 16 (HPV16) E6 oncoprotein appear years prior to clinical diagnosis of anal and oropharyngeal cancer, but whether they develop around the time of HPV infection is unclear. Serum samples from 173 cancer-free men from the Human Papillomavirus Infection in Men (HIM) Study were tested for HPV antibodies and DNA. HPV16 E6 seropositivity was low among men with oral HPV16-infection (1/28; 3.6%, 95%CI=0.0%-18.4%), anal HPV16-infection (1/61; 1.6%, 95%CI=0.0%-8.8%), and 24-month persistent genital HPV16-infection (1/84; 1.2%, 0.0-6.5%). This suggests E6 seroconversion may not occur around the time of oral, anal, or genital HPV16 acquisition.
    Language English
    Publishing date 2016
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2837553-1
    ISSN 2405-8521
    ISSN 2405-8521
    DOI 10.1016/j.pvr.2016.07.003
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  6. Article ; Online: Structure-activity relationships and molecular modeling of the N-(3-pivaloyloxy-2-benzylpropyl)-N'-[4-(methylsulfonylamino)benzyl] thiourea template for TRPV1 antagonism.

    Bhondwe, Rahul S / Kang, Dong Wook / Kim, Myeong Seop / Kim, Ho Shin / Park, Seul-gi / Son, Karam / Choi, Sun / Kuhs, Krystle A Lang / Pavlyukovets, Vladimir A / Pearce, Larry V / Blumberg, Peter M / Lee, Jeewoo

    Bioorganic & medicinal chemistry letters

    2012  Volume 22, Issue 11, Page(s) 3656–3660

    Abstract: The structure-activity relationships of N-(3-acyloxy-2-benzylpropyl)-N'-4-[(methylsulfonylamino)benzyl] thioureas, which represent simplified RTX-based vanilloids, were investigated by varying the distances between the four principal pharmacophores and ... ...

    Abstract The structure-activity relationships of N-(3-acyloxy-2-benzylpropyl)-N'-4-[(methylsulfonylamino)benzyl] thioureas, which represent simplified RTX-based vanilloids, were investigated by varying the distances between the four principal pharmacophores and assessing binding and antagonistic activity on rTRPV1. The analysis indicated that a 3-pivaloyloxy-2-benzylpropyl C-region conferred the best potency in binding affinity and antagonism. The molecular modeling of this best template with the tetrameric homology model of rTRPV1 was performed to identify its binding interactions with the receptor.
    MeSH term(s) Animals ; Binding Sites ; CHO Cells ; Cricetinae ; Cricetulus ; Molecular Dynamics Simulation ; Protein Structure, Tertiary ; Rats ; Structure-Activity Relationship ; TRPV Cation Channels/agonists ; TRPV Cation Channels/antagonists & inhibitors ; TRPV Cation Channels/metabolism ; Thiourea/chemical synthesis ; Thiourea/chemistry
    Chemical Substances TRPV Cation Channels ; Trpv1 protein, rat ; Thiourea (GYV9AM2QAG)
    Language English
    Publishing date 2012-04-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2012.04.034
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