Publications by authors named "Robert Yu"

160 Publications

Factors Influencing Discussion of Cancer Genetic Testing with Health-Care Providers in a Population-Based Survey.

Public Health Genomics 2021 Apr 22:1-11. Epub 2021 Apr 22.

Department of Biostatistics, UT MD Anderson Cancer Center, Houston, Texas, USA.

Introduction: Discussion of cancer genetic testing with health-care providers (HCPs) is necessary to undergo testing to inform cancer risk assessment and prevention. Given the rapid evolution in genetic testing practice in oncology, we describe the current landscape of population-level cancer genetic testing behaviors.

Methods: A questionnaire including items regarding discussion of cancer genetic testing with HCPs was administered to a nonprobability sample (N = 2,029) of the Texas population.

Results: Overall, 11% of respondents discussed cancer genetic testing with HCPs. In multivariable analysis, discussion was significantly related to having a personal history of breast/ovarian/colon cancer (OR = 11.57, 95% CI = 5.34-25.03), personal history of other cancer (OR = 3.18, 95% CI = 1.69-5.97), and health information-seeking behaviors (OR = 1.73, 95% CI = 1.12-2.66). Surprisingly, respondents who believed that inherited predispositions in addition to other modifiable risk factors cause cancer were less likely to discuss genetic testing compared to those who did not believe that inherited cancer predispositions cause cancer (OR = 0.54, 95% CI = 0.36-0.79).

Discussion: The high discussion rate may be attributed to increased public awareness of genetic testing and adoption of more inclusive clinical genetic testing guidelines. The findings suggest that efforts to increase public awareness of the utility of genetic testing on personalized cancer risk assessment and cancer prevention are needed.
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http://dx.doi.org/10.1159/000515465DOI Listing
April 2021

Genetic Factors associated with Pain Severity, Daily Opioid Dose Requirement, and Pain Response among Advanced Cancer Patients receiving Supportive Care.

J Pain Symptom Manage 2021 Apr 10. Epub 2021 Apr 10.

Department of Palliative care, Rehabilitation Medicine, and Integrative Medicine UT MD Anderson Cancer Center, Houston, United States.

Background: Current understanding of genetic factors associated with pain severity, and improvement of pain with opioids in advanced cancer patients (AC) is inadequate for delivery of personalized pain therapy(PPT). Therefore, the aim of this study was to determine the genetic factors associated with pain severity, daily opioid dose, and pain response in AC patients receiving supportive care.

Methods: In this prospective study, AC patients were eligible if they had cancer pain ≥4/10 on Edmonton Symptom Assessment Scale (ESAS) - Pain Item and needed opioid rotation for pain control by specialist at the outpatient supportive care center. Pain phenotype was assessed using logistic regression models and SKATO (Gene-block) analysis.

Results: 174/178 (98%) patient samples were analyzed. After adjustment for demographic and clinical variables, pain severity was negatively associated with intron variant alleles in OPRM1 rs9322446, P = 0.02; rs2270459, P=0.038; rs62052210, P= 0.038. Opioid daily dose was positively associated NFKBIA rs2233419 P=0.008, rs2233417 P=0.007, rs3138054 P=0.008, rs1050851, P= 0.015;ORPM1 rs9479759, P= 0.046, rs2003185, P= 0.047, rs636433, P= 0.044; COMT (rs9306234, P= 0.014, rs165728, P= 0.014, rs2020917, P= 0.036, rs165728, P= 0.034); ARRB2 (rs1045280, P= 0.045); and pain response to opioids was negatively associated OPRM1 rs1319339 p=0.024, rs34427887 P=0.048, and COMT rs4646316 P=0.03, rs35478083 P=0.028 respectively. SKATO analysis showed association between pain severity and CXCL8 (P=0.0056), and STAT6 (P=0.0297) genes respectively, and pain response with IL-6 (P=0.00499).

Conclusions: This study identified that SNPs of OPRM1, COMT, NFKBIA, CXCL8, IL-6, STAT6,and ARRB2 genes were associated with pain severity, opioid daily dose, and pain response in AC receiving supportive care. Additional studies are needed to validate our findings for PPT.

Key Message: This study shows unique SNPs of OPRM1, COMT, NFKBIA, CXCL8, IL-6, STAT6, and ARRB2 genes were associated with cancer pain severity, and pain response after supportive care consultation in advanced cancer patients. Additional studies are needed to validate our findings for personalized pain therapy.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.03.024DOI Listing
April 2021

Genetic determinants of immune-related adverse events in patients with melanoma receiving immune checkpoint inhibitors.

Cancer Immunol Immunother 2021 Jan 7. Epub 2021 Jan 7.

Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Immune checkpoint inhibitors (ICIs) can cause profound immune-related adverse events (irAEs). The host genetic background is likely to play a role in irAE susceptibility because the presentation of toxicity varies among patients and many do not develop irAEs despite continued ICI use. We sought to identify potential genetic markers conferring risk for irAEs.

Methods: We conducted a pilot exploratory study in 89 melanoma patients who received ICIs (44 with irAEs, and 45 without irAEs after at least 1 year from starting treatment). Genotyping was performed using the Infinium Multi-Ethnic Global-8 v1.0 Bead Chip. The genotype data were extracted using PLINK (v1.90b3.34) and processed for quality control. Population structure-based clustering was carried out using IBS matrix, pairwise population concordance test (p < 1 × 10), and phenotype distribution for all study participants, resulting in seven population structure-based clusters. In the analytical stage, 599,931 variants in autosomal chromosomes were included for the association study. The association test was performed using an additive genetic model with exact logistic regression, adjusted for age, sex, and population cluster.

Results: A total of 30 variants or single-nucleotide polymorphisms with p < 1 × 10 were identified; 12 were associated with an increased risk of irAEs, and the remaining 18 were associated with a decreased risk. Overall, nine of the identified single-nucleotide polymorphisms mapped to eight unique genes that have been associated with autoimmunity or inflammatory diseases.

Conclusion: Several genetic variants associated with irAEs were identified. Additional larger studies are needed to validate these findings and establish their potential functional relevance.
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http://dx.doi.org/10.1007/s00262-020-02797-0DOI Listing
January 2021

Association of dual and poly tobacco use with depressive symptoms and use of antidepressants.

Addict Behav 2021 04 30;115:106790. Epub 2020 Dec 30.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. Electronic address:

Background: There is an established link between depression and tobacco use among adults; however, to date, research has not explored the association of use of dual/poly tobacco products with symptoms and use of medication for depression.

Methods: Data were derived from a 2018 Texas population health assessment survey (n = 2034). Multivariable logistic and multinomial regressions were used to examine for associations between self-reported symptoms of depression and use of prescription medications for depression with use of dual/poly tobacco products.

Results: About 20% of adults used one tobacco product, while 9.7% used two or more products. Compared to those without depressive symptoms, those with depressive symptoms had greater odds of single (aOR: 1.66, 95% CI; 1.21 - 2.29) or dual/poly (aOR: 3.09, 95% CI; 1.92 - 4.96) tobacco product use relative to non-users; and relative to single product use, those with depressive symptoms had greater odds of dual/poly tobacco product use (aOR: 2.07; 95% CI, 1.30 - 3.32). Compared to those not using medication for depression, use of medication for depression was associated with a 1.80 (95% CI: 1.15 - 2.84) greater odds of dual/poly tobacco product use relative to non-users; and a 1.91 (95% CI: 1.14 - 3.19) greater odds of dual/poly product use relative to single product users.

Conclusions: Study findings call for primary care providers and psychiatrists to expand screening of individuals experiencing depressive symptoms and using medication for depression, to include assessment for dual/poly tobacco product use.
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http://dx.doi.org/10.1016/j.addbeh.2020.106790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860585PMC
April 2021

Association of Glycolipids and Growth Factor Receptors in Lipid Rafts.

Methods Mol Biol 2021 ;2187:131-145

Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.

The traditional methods to study lipid rafts and their association with membrane proteins are based mainly on the isolation of a detergent-resistant membrane by biochemical fractionation. However, the use of detergents may induce lipid segregation and/or redistribution of membrane proteins during the process of sample preparation. Here, we describe a detergent-free method to study the glycolipid and growth factor receptor interaction and their association with lipid rafts. This method combines the biochemical and immunoblotting tools with confocal microscopic imaging, which allows for evaluation and verification of the membrane protein interaction and association with the lipid rafts components in a multifaceted manner.
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http://dx.doi.org/10.1007/978-1-0716-0814-2_8DOI Listing
March 2021

Distinctive sphingolipid patterns in chronic multiple sclerosis lesions.

J Lipid Res 2020 11 7;61(11):1464-1479. Epub 2020 Aug 7.

Department of Neurology, Medical University of South Carolina, Charleston, SC, USA.

Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease.
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http://dx.doi.org/10.1194/jlr.RA120001022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604719PMC
November 2020

Ganglioside GD3 regulates dendritic growth in newborn neurons in adult mouse hippocampus via modulation of mitochondrial dynamics.

J Neurochem 2021 Mar 13;156(6):819-833. Epub 2020 Aug 13.

Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.

Ganglioside GD3, a major ganglioside species in neural stem cells, plays a crucial role in maintenance of the self-renewal capacity of these cells. However, its bioactivity in postnatally differentiated neurons in the neurogenic regions of adult brains has not been elucidated. Here, we describe for the first time that deletion of GD3 not only impairs neurotrophin-induced stem cell proliferation, but also alters the dendritic structure as well as the number of synapses of nascent neurons in the dentate gyrus of adult brain. When examining the behavioral phenotypes, GD3 synthase-knockout (GD3S-KO) mice displayed impairment in hippocampus-dependent memory function. To further gain insight into its cellular function, we examined GD3-binding partners from mouse brain extract using a GD3-specific monoclonal antibody, R24, followed by LC-MS/MS analysis and identified a mitochondrial fission protein, the dynamin-related protein-1 (Drp1), as a novel GD3-binding protein. Biochemical and imaging analyses revealed mitochondrial fragmentation in GD3-depleted dentate gyrus neurons, suggesting that GD3 is essential for the mitochondrial Drp1 turnover that is required for efficient mitochondrial fission. These results suggest that GD3 is required for proper dendritic and spine maturation of newborn neurons in adult brain through the regulation of mitochondrial dynamics.
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http://dx.doi.org/10.1111/jnc.15137DOI Listing
March 2021

Declining awareness of HPV and HPV vaccine within the general US population.

Hum Vaccin Immunother 2021 Feb 21;17(2):420-427. Epub 2020 Jul 21.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.

Programs aimed at boosting human papillomavirus (HPV)-related awareness are considered one of the most effective strategies for increasing vaccination uptake and eliminating HPV-associated cancers. Several US states have made strong commitments to this effort through legislation and dedicated funds. However, it is not known if these efforts have resulted in population-level increments in HPV awareness overtime. Using the Health Information National Trends Survey data, we examined the awareness of HPV and HPV vaccine in the US, between 2008 and 2018. Prevalence estimates and confidence intervals were calculated for HPV and HPV vaccine awareness. Further, we assessed awareness after stratifying by key sociodemographic characteristics. Overall, the awareness of HPV and HPV vaccine declined over time. The lowest awareness was among racial minorities, rural residents, male respondents, those aged 65 years and older, as well as those with the lowest educational and socioeconomic standing. Between 2013 and 2018, the awareness of HPV and HPV vaccine declined by almost 10% among males, those with a high school level of education or lower, and those who earned less than USD 35,000 per annum. In 2018, the awareness of HPV and HPV vaccine was highest among non-Hispanic whites (65.8% and 66.5%) and female adults (70.5% and 71.4%); however, these figures represented declines of about 5% from rates observed in 2008. Amidst a background of sub-optimal HPV vaccination uptake and a growing incidence of HPV-associated cancers in the US, HPV-related awareness within the general US population has declined over time. This calls for stricter enforcement of legislation aimed at boosting HPV awareness, as well as frequent evaluation of government-funded HPV awareness programs.
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http://dx.doi.org/10.1080/21645515.2020.1783952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899652PMC
February 2021

Enhanced Susceptibility to Chemoconvulsant-Induced Seizures in Ganglioside GM3 Synthase Knockout Mice.

ASN Neuro 2020 Jan-Dec;12:1759091420938175

Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, United States.

Ganglioside GM3 synthase (α-2,3-sialyltransferase, ST3GAL5, GM3S) is a key enzyme involved in the biosynthesis of gangliosides. ST3GAL5 deficiency causes an absence of GM3 and all downstream biosynthetic derivatives. The affected individuals manifest deafness, severe irritability, intractable seizures, and profound intellectual disability. To investigate whether deficiency of GM3 is involved in seizure susceptibility, we induced seizures with different chemoconvulsants in ST3GAL5 knockout mice. We report here that ST3GAL5 knockout mice are hyperactive and more susceptible to seizures induced by chemoconvulsants, including kainate and pilocarpine, compared with normal controls. In the hippocampal dentate gyrus, loss of GM3 aggravates seizure-induced aberrant neurogenesis. These data indicate that GM3 and gangliosides derived from GM3 may serve as important regulators of epilepsy and may play an important role in aberrant neurogenesis associated with seizures.
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http://dx.doi.org/10.1177/1759091420938175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364800PMC
July 2020

Association of Exposure to Court-Ordered Tobacco Industry Antismoking Advertisements With Intentions and Attempts to Quit Smoking Among US Adults.

JAMA Netw Open 2020 07 1;3(7):e209504. Epub 2020 Jul 1.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston.

Importance: In 2006, a US district court judge ordered tobacco companies to sponsor nationwide antismoking advertising campaigns. This landmark ruling and its subsequent execution represent an unprecedented tobacco control event; however, the association of this campaign with intentions and/or attempts to quit smoking is unknown.

Objectives: To assess the reach of the expanded court-ordered tobacco industry antismoking advertisements (via television, newspapers, tobacco company websites, and/or cigarette packages), to examine associations between exposure to industry antismoking advertisements and intentions and/or attempts to quit smoking among cigarette smokers, and to calculate the numbers of US smokers who would have quit intentions associated with exposure to multiple advertisements.

Design, Setting, And Participants: Data for this study were obtained from 5309 US adults, including 610 smokers, who responded to the Health Information National Trends Survey, a nationally representative cross-sectional survey conducted from January 22 to April 30, 2019. Respondents were representatives of households selected by equal-probability sampling of a database of US residential addresses.

Exposure: Reported exposure to antismoking messages.

Main Outcomes And Measures: Cigarette smoking cessation attempt in the past 12 months and intentions to quit cigarette smoking in the next 6 months. Covariates were age, sex, household annual income, race/ethnicity, educational level, and geographical residence. Data were weighted to be nationally representative after applying survey weights specified for the survey cycle.

Results: The overall sample of 5309 respondents were a mean (SD) age of 55.6 (19.1) years and included 3073 women (51.2%), 3037 non-Hispanic white respondents (59.1%), 4645 respondents who lived in urban US areas (84.7%), and 610 current smokers (12.5%). Findings indicate that 2464 US adults (45.8%; 95% CI, 43.2%-48.5%) and 410 current smokers (66.8%; 95% CI, 61.1%-72.4%) were exposed to antismoking advertisements. Exposure to multiple antismoking messages was associated with 2.19 (95% CI, 1.10-4.34) greater odds of having intentions to quit cigarette smoking but was not associated with attempts to quit (adjusted odds ratio, 1.31; 95% CI, 0.69-2.52). Furthermore, an examination of the association of cumulative exposure to antismoking messages with cessation intentions revealed that, with each additional exposure to an antismoking message, the odds of smoking cessation intentions increased by 1.21 (95% CI, 1.02-1.44). If all smokers were to be exposed to multiple antitobacco messages, there could be an estimated 3.98 million (95% CI, 492 480-7 223 040) current smokers in the United States with intentions to quit.

Conclusions And Relevance: Although the reach of court-ordered industry advertisements increased among smokers, the reach of these advertisements within the general population remains suboptimal. The finding that industry advertisements helped smokers consider quitting highlights their potential to aid smoking cessation. However, the lack of association with actual attempts to quit suggests that the industry antismoking advertisement campaigns were inadequate. The design and content of industry antismoking advertisement campaigns should be enhanced to help smokers quit.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.9504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341176PMC
July 2020

Reasons for not receiving the HPV vaccine among eligible adults: Lack of knowledge and of provider recommendations contribute more than safety and insurance concerns.

Cancer Med 2020 07 1;9(14):5281-5290. Epub 2020 Jun 1.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: The upward trends of vaccine exemptions in Texas are alarming. While HPV vaccine rates in this State are among the lowest nationwide, factors that contribute to the low HPV vaccination uptake among adults remain unknown. In this study, we examined the main reasons for not receiving HPV vaccination among age-eligible adults.

Methods: The Texas health screening survey (2018), a multistage area probability design-based survey of a representative sample of Texas residents, was used to identify 907 eligible adults (age ≥ 18 years) respondents, including 724 women aged ≤ 26 years in 2007 (≤38 years in 2018), and 183 men aged ≤ 21 years in 2011 (≤28 years in 2018). Participants who reported having never received an HPV shot, where asked the main reason for not receiving the vaccine.

Results: Overall, 58.5% (95%CI: 55.1-62.0) of vaccine eligible adults reported having never received the HPV vaccine. The most commonly reported reasons for not receiving it were: did not know about the vaccine (18.5% (14.9-22.1)), and provider did not recommend (14.1% (10.9-17.4)). In contrast, commonly perceived reasons such as: safety concerns (7.2% (4.8-9.5)), lack of insurance (3.4% (1.7-5.1), and concerns about increasing sexual activity if vaccinated (0.2% (0.0-0.5)), were less frequently reported.

Conclusion: Among vaccine-eligible adults, safety and sexuality concerns do not appear to be the prime factors underlying low HPV vaccination rates. Rather than emphasizing them, educational interventions should aim at improving vaccine's knowledge, and enhancing provider recommendations on the necessity of HPV vaccination.
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http://dx.doi.org/10.1002/cam4.3192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367641PMC
July 2020

Beliefs About HPV Vaccine's Success at Cervical Cancer Prevention Among Adult US Women.

JNCI Cancer Spectr 2019 Dec 27;3(4):pkz064. Epub 2019 Aug 27.

See the Notes section for the full list of authors' affiliations.

Background: Beliefs are known to be a key determinant in vaccines' uptake. However, little is known about beliefs surrounding the success of the human papillomavirus (HPV) vaccine in preventing cervical cancer in the United States.

Methods: Data from the Health Information National Trends Survey 5 Cycle 1 (2017) were analyzed for 1851 female respondents aged 18 years and older. Weighted multinomial logistic regression was employed to determine predictors of beliefs in the success of the HPV vaccine in preventing cervical cancer.

Results: Overall, 29.8% of women believed that HPV vaccine is successful in preventing cervical cancer, 6.6% believed it is not successful, and 63.6% did not know if the HPV vaccine is successful. Non-Hispanic blacks (adjusted odds ratio [aOR] = 1.80, 95% confidence interval [CI] = 1.16 to 2.79), women with no more than 12 years of education (aOR = 2.05, 95% CI = 1.17 to 3.60), those who did not know if they were advised by a health-care provider to get an HPV shot within the last 12 months (aOR = 4.19, 95% CI = 1.39 to 12.60), and those unaware of a family cancer history (aOR = 5.17, 95% CI = 1.48 to 18.21) were more likely to not know whether the HPV vaccine prevents cervical cancer. Women younger than 65 years were more likely than elderly to believe that the HPV vaccine is not successful at preventing cervical cancer.

Conclusions: A substantial proportion of US women are uninformed about the HPV vaccine. To accelerate progress in the HPV vaccine's uptake, future interventions should incorporate educational programs, particularly targeting Non-Hispanic blacks, women with a lower level of education, and those younger than 65 years. Health-care providers' participation in promotion of patient education about HPV vaccination should also be increased.
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http://dx.doi.org/10.1093/jncics/pkz064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901081PMC
December 2019

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions for Squamous Cell Carcinoma of the Head and Neck.

Cancer Res 2020 06 10;80(12):2451-2460. Epub 2020 Apr 10.

Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which, 434,839 typed and 7,423,250 imputed SNPs were used as the discovery. SNPs with < 1 × 10 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from databases of Genotypes and Phenotypes. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 ( = 2.96 × 10 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, ) and 6p21.33 (rs1265081, ) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 ( = 2.54 × 10 for the leading SNP rs142021700) was identified for hypopharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and expression quantitative trait loci analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of human leukocyte antigen loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN. SIGNIFICANCE: Two novel risk loci for SCCHN in non-Hispanic white individuals highlight the importance of immunologic mechanism in the disease etiology.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-2360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299763PMC
June 2020

Intracerebroventricular Infusion of Gangliosides Augments the Adult Neural Stem Cell Pool in Mouse Brain.

ASN Neuro 2019 Jan-Dec;11:1759091419884859

Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, GA, USA.

We previously reported that ganglioside GD3 is the predominant species in neural stem cells (NSCs) and reduced postnatal NSC pools are observed in both the subventricular zone and dentate gyrus (DG) of GD3-synthase knockout (GD3S-KO) mouse brains. Specifically, deficiency of GD3 in GD3S-KO animals revealed a dramatic reduction in cellularity in the DG of the hippocampus of the developing mouse brain, resulting in severe behavioral deficits in these animals. To further evaluate the functional role of GD3 in postnatal brain, we performed rescue experiments by intracerebroventricular infusion of ganglioside GD3 in adult GD3S-KO animals and found that it could restore the NSC pools and enhance the NSCs for self-renewal. Furthermore, 5xFAD mouse model was utilized, and GD3 restored NSC numbers and GM1 promoted neuronal differentiation. Our results thus demonstrate that exogenously administered gangliosides are capable to restore the function of postnatal NSCs. Since ganglioside expression profiles are associated not only with normal brain development but also with pathogenic mechanisms of diseases, such as Alzheimer’s disease, we anticipate that the administration of exogenous gangliosides, such as GD3 and GM1, may represent a novel and effective strategy for promoting adult neurogenesis in damaged brain for disease treatment.
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http://dx.doi.org/10.1177/1759091419884859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806120PMC
May 2020

Characteristics of us adults attempting tobacco use cessation using e-cigarettes.

Addict Behav 2020 01 9;100:106123. Epub 2019 Sep 9.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, USA; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Background: Use of e-cigarettes for tobacco cessation efforts is a growing trend in the United States. However, little is known about the factors that determine the use of e-cigarettes for this specific purpose.

Methods: This study examined current and former cigarette smokers that reported ever using e-cigarettes. Data were obtained from a 2018 Texas population health assessment survey (n = 569) and weighted to be representative to Texas. A multivariable logistic regression was used to assess the socio-demographic and behavioral correlates of using e-cigarettes for tobacco cessation.

Results: Overall, 41.3% of e-cigarette users reported using them for tobacco cessation. Among ever e-cigarette users, Non-Hispanic blacks (aOR: 0.21; 95% CI, 0.07-0.64), males (aOR: 0.40; 95% CI, 0.20-0.80), and individuals not confident in obtaining health information (aOR: 0.38; 95% CI, 0.15-0.96) were less likely to use e-cigarettes for tobacco use cessation. Conversely, among ever e-cigarette users, odds of using e-cigarettes for tobacco cessation were higher among those who were 35-44 years old (aOR: 3.68, 95% CI: 1.26-10.71), those who received advice to quit smoking from a healthcare professional (aOR: 2.77, 95% CI, 1.36-5.64), and those with more than 5 years since their last routine checkup (aOR: 3.91; 95% CI, 1.23-12.45).

Conclusion: Findings from this study suggest that both health behaviors and sociodemographic factors predict use of e-cigarettes for the purpose of tobacco cessation. Furthermore, the relationship between use of e-cigarettes as a cessation device and being advised to quit tobacco use by a healthcare professional calls for additional investigation.
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http://dx.doi.org/10.1016/j.addbeh.2019.106123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905082PMC
January 2020

Prevalence and determinants of cervical cancer screening with a combination of cytology and human papillomavirus testing.

Ann Epidemiol 2019 08 21;36:40-47. Epub 2019 Jun 21.

Department of Epidemiology, Houston, TX; Division of Cancer Prevention and Population Science, Houston, TX; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Purpose: In the United States, recommended options for cervical cancer screening in women aged 30 years or older include cytology alone or a combination of cytology and human papillomavirus (HPV) testing (co-testing). Although there is a body of evidence suggesting that co-testing may be the preferred screening option in this group of women, little is known about the characteristics of women who screen for cervical cancer with co-testing.

Methods: A multistage area probability design-based survey was administered to a representative sample of Texas residents. Of the 1348 female respondents, 572 women aged 30 years or older were included in this analysis. Population-weighted survey logistic regression was used to identify determinants of cervical screening with co-testing versus screening with cytology alone.

Results: Women vaccinated against HPV (aOR: 4.48, 95% CI: 1.25-15.97) or hepatitis B virus [aOR: 2.48 (1.52-4.02)], those with a personal cancer history [aOR: 2.96 (1.29-6.77)], and hormonal contraception users [aOR: 2.03 (1.03-3.97)] were more likely to be screened with co-testing than with cytology alone. Moreover, the likelihood of being screened with co-testing decreased with increasing age and decreasing annual household income.

Conclusions: Benefits and indications of co-testing should be better explained to women and health care providers.
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http://dx.doi.org/10.1016/j.annepidem.2019.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732232PMC
August 2019

Exposure to Court-Ordered Tobacco Industry Antismoking Advertisements Among US Adults.

JAMA Netw Open 2019 07 3;2(7):e196935. Epub 2019 Jul 3.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston.

Importance: In 2006, US District Judge Gladys Kessler ordered tobacco companies to make corrective statements through paid advertisements informing the public of their deceptive practices. This landmark ruling and its subsequent execution represent the first time the tobacco industry sponsored a nationwide corrective advertising campaign against its own products.

Objective: To assess the reach of the court-ordered antismoking advertisements within the US adult population, stratified by demographic characteristics and tobacco use.

Design, Setting, And Participants: This nationally representative, population-based cross-sectional survey of US adults included respondents to the 2018 Health Information National Trends Survey 5, Cycle 2. Respondents were representatives of households selected by equal-probability sampling of the Marketing Systems Group database of addresses that included all nonvacant US residential addresses. Data collection was conducted from January to May 2018, and analysis took place from December 2018 to April 2019.

Main Outcomes And Measures: Self-reported exposure to court-ordered antismoking advertisements.

Results: The overall sample of 3484 respondents included 2054 women (weighted percentage, 50.8%), 1976 non-Hispanic white respondents (weighted percentage, 59.9%), 2952 respondents who lived in urban US areas (weighted percentage, 84.9%), and 450 current smokers (weighted percentage, 15.6%). Estimated exposure to court-ordered antismoking advertisements was 40.6% (95% CI, 37.5%-43.7%) among the full sample and 50.5% (95% CI, 41.4%-59.6%) among current smokers. Exposure was lowest among those aged 18 to 34 years (37.4%; 95% CI, 28.0%-46.8%), those with a high school education or less (34.5%; 95% CI, 29.3%-39.8%), and those with household annual income less than $35 000 (37.5%; 95% CI, 32.0%-42.9%). Among current smokers, Hispanic respondents had lower exposure rates (42.2%; 95% CI, 18.5%-65.9%) than non-Hispanic white respondents (51.7%; 95% CI, 40.4%-63.1%). As the advertising campaign's duration increased, exposure rates increased. Individuals with a high school education or less had lower odds of antismoking advertisement exposure than those with college or postgraduate degrees (adjusted odds ratio, 0.67; 95% CI, 0.48-0.94). Current smokers had higher odds of exposure than never smokers (adjusted odds ratio, 1.81; 95% CI, 1.17-2.80). Among those exposed to antismoking advertisements, 70.5% saw multiple antismoking messages.

Conclusions And Relevance: Approximately 1 of 2 smokers reported exposure to the federal court-ordered antismoking advertisements. However, exposure was relatively lower among several subgroups, including individuals aged 18 to 34 years, only one-third of whom reported exposure. Increasing the duration of antismoking advertisements as well as expanding their coverage to youth-oriented media may increase their potential public health impact.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.6935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628589PMC
July 2019

Differences in Sun Protection Behaviors Between Rural and Urban Communities in Texas.

J Rural Health 2019 03 4;35(2):155-166. Epub 2019 Mar 4.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: The increasing incidence of skin cancer is a global health issue. In order to identify at-risk populations in Texas, we compared sun protection behaviors and sunburn history across rural and urban counties.

Methods: An online health screening survey collected data from a nonprobability sample of Texas residents in 2018. Data were weighted by sex, age, race, and ethnicity. Multinomial multivariable logistic regression identified key factors associated with sun protection behaviors and sunscreen use. Weighted Pearson's χ  test identified differences between urban and rural respondents in strength of sunscreen used and sunburn history.

Findings: Rural residents in Texas were less likely to seek shade (OR = 0.58; P = .004) and less likely to use sunscreen lotion (OR = 0.65; P = .013) compared to their urban counterparts. Sunscreen use was also lower among current versus never smokers (OR = 0.67; P = .034) but higher in those with personal versus no cancer history (OR = 2.14; P = .004). Although rural versus urban residents were more likely to use higher SPF sunscreen (P < .002), they had more blistering sunburns over the course of their life (P < .001) and these injuries were more likely to occur at an earlier age, between 5 and 14 years old (P < .001).

Conclusions: Increased attention to sun protective behaviors among rural communities in Texas is vital to help reduce the high prevalence of sunburn injury and incidence of skin cancer.
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http://dx.doi.org/10.1111/jrh.12350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436991PMC
March 2019

Cancer-Related Risk Perceptions and Beliefs in Texas: Findings from a 2018 Population-Level Survey.

Cancer Epidemiol Biomarkers Prev 2019 03 30;28(3):486-494. Epub 2019 Jan 30.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Cancer beliefs and perceptions of cancer risk affect the cancer continuum. Identifying underlying factors associated with these beliefs and perceptions in Texas can help inform and target prevention efforts.

Methods: We developed a cancer-focused questionnaire and administered it online to a nonprobability sample of the Texas population. Weighted multivariable logistic regression analysis identified key factors associated with perceptions and beliefs about cancer.

Results: The study population comprised 2,034 respondents (median age, 44.4 years) of diverse ethnicity: 45.5% were non-Hispanic white, 10.6% non-Hispanic black, and 35.7% Hispanic. Self-reported depression was significantly associated with cancer risk perceptions and cancer beliefs. Those indicating frequent and infrequent depression versus no depression were more likely to believe that: (i) compared to other people their age, they were more likely to get cancer in their lifetime [OR, 2.92; 95% confidence interval (CI), 1.95-4.39 and OR, 1.79; 95% CI, 1.17-2.74, respectively]; and (ii) when they think about cancer, they automatically think about death (OR, 2.05; 95% CI, 1.56-2.69 and OR, 1.46; 95% CI, 1.11-1.92, respectively). Frequent depression versus no depression was also associated with agreement that (i) it seems like everything causes cancer (OR, 1.67; 95% CI, 1.26-2.22) and (ii) there is not much one can do to lower one's chance of getting cancer (OR, 1.44; 95% CI, 1.09-1.89). Other predictors for perceived cancer risk and/or cancer beliefs were sex, age, ethnicity/race, being born in the United States, marital status, income, body mass index, and smoking.

Conclusions: Depression and other predictors are associated with cancer risk perceptions and beliefs in Texas.

Impact: Increased attention to reducing depression may improve cancer risk perceptions and beliefs.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-0846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401259PMC
March 2019

Distinct epidemiological profiles associated with inflammatory breast cancer (IBC): A comprehensive analysis of the IBC registry at The University of Texas MD Anderson Cancer Center.

PLoS One 2018 24;13(9):e0204372. Epub 2018 Sep 24.

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.

Background: To date, studies on inflammatory breast cancer (IBC) lack comprehensive epidemiological data. We analyzed detailed prospectively collected clinical and epidemiological data from the IBC Registry at The University of Texas MD Anderson Cancer Center.

Methods: Patients with IBC (n = 248) were consecutively diagnosed and prospectively enrolled between November 2006 and April 2013. All patients were newly diagnosed and at least 18 years old. Secondary IBC was excluded. Overall 160 variables were collected and evaluated including sociodemographics, anthropometrics, tobacco and alcohol consumption, reproductive variables, and family history data.

Results: Mean age at diagnosis was 51.6 (±11.5 SD) years, and the majority of patients were White (77.8%). A mean BMI ≥ 25 kg/m2, irrespective of menopausal status, was observed in 80.2% of all patients, with 82.6% of African Americans being obese. Approximately 42.2% of patients were ever smokers, and 91% reported ever being pregnant. A history of breastfeeding was reported in 54% of patients, with significant differences between ethnic groups in favor of White women (P<0.0001). Other reproductive factors such as use of birth control pills & hormone replacement therapy were also more frequently associated with White women compare to other ethnic groups (P < 0.05). In the multivariate Cox proportional hazard analysis, African American or Hispanic ethnicity, not having breastfed, higher clinical stage, and TNBC subtype were associated with shorter survival.

Conclusion: Our data suggest that IBC is associated with distinct epidemiological profiles. This information could assist in targeting patients with specific preventive strategies based on their modifiable behavioral patterns.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204372PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152950PMC
March 2019

Genome-wide association study identifies genes associated with neuropathy in patients with head and neck cancer.

Sci Rep 2018 06 8;8(1):8789. Epub 2018 Jun 8.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.

Neuropathic pain (NP), defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system, is a debilitating chronic pain condition often resulting from cancer treatment. Among cancer patients, neuropathy during cancer treatment is a predisposing event for NP. To identify genetic variants influencing the development of NP, we conducted a genome-wide association study in 1,043 patients with squamous cell carcinoma of the head and neck, based on 714,494 tagging single-nucleotide polymorphisms (SNPs) (130 cases, 913 controls). About 12.5% of the patients, who previously had cancer treatment, had neuropathy-associated diagnoses, as defined using the ICD-9/ICD-10 codes. We identified four common SNPs representing four genomic regions: 7q22.3 (rs10950641; SNX8; P = 3.39 × 10), 19p13.2 (rs4804217; PCP2; P = 2.95 × 10), 3q27.3 (rs6796803; KNG1; P = 6.42 × 10) and 15q22.2 (rs4775319; RORA; P = 1.02 × 10), suggesting SNX8, PCP2, KNG1 and RORA might be novel target genes for NP in patients with head and neck cancer. Future experimental validation to explore physiological effects of the identified SNPs will provide a better understanding of the biological mechanisms underlying NP and may provide insights into novel therapeutic targets for treatment and management of NP.
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http://dx.doi.org/10.1038/s41598-018-27070-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993794PMC
June 2018

Gangliosides in Nerve Cell Specification.

Prog Mol Biol Transl Sci 2018 17;156:241-263. Epub 2018 Jan 17.

Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, United States; Charlie Norwood VA Medical Center, Augusta, GA, United States. Electronic address:

The central nervous system is generated from progenitor cells that are recognized as neural stem cells (NSCs). NSCs are defined as undifferentiated neural cells that are characterized by the capacity for self-renewal and multipotency. Throughout neural development, NSCs undergo proliferation, migration, and cellular differentiation, and dynamic changes are observed in the composition of carbohydrate-rich molecules, including gangliosides. Gangliosides are sialic acid-containing glycosphingolipids with essential and multifaceted functions in brain development and NSC maintenance, which reflects the complexity of brain development. Our group has pioneered research on the importance of gangliosides for growth factor receptor signaling and epigenetic regulation of ganglioside biosynthesis in NSCs. We found that GD3 is the predominant ganglioside species in NSCs (>80%) and modulates NSC proliferation by interacting with epidermal growth factor receptor signaling. In postnatal brain, GD3 is required for long-term maintenance of NSCs. Deficiency in GD3 leads to developmental and behavioral deficits, such as depression. The synthesis of GD3 is switched to the synthesis of complex, brain-type gangliosides, namely, GM1, GD1a, GD1b, and GT1b, resulting in terminal differentiation and loss of "stemness" of NSCs. In this process, GM1 is augmented by a novel GM1-modulated epigenetic gene regulation mechanism of glycosyltransferases at a later differentiation stage. Consequently, our research suggests that stage-specific gangliosides play specific roles in maintaining NSC activities and in cell fate determination.
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http://dx.doi.org/10.1016/bs.pmbts.2017.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261283PMC
February 2019

Special issue: Glycobiology on stem cells ---editorial.

Glycoconj J 2017 12;34(6):691

Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.

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http://dx.doi.org/10.1007/s10719-017-9803-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261276PMC
December 2017

Prins Reaction of Homoallenyl Alcohols: Access to Substituted Pyrans in the Halichondrin Series.

Org Lett 2017 11 27;19(22):6092-6095. Epub 2017 Oct 27.

Integrated Chemistry Engine, Eisai AiM Institute , 4 Corporate Drive, Andover, Massachusetts 01810, United States.

Prins reaction of homoallenyl alcohols with aldehyde dimethylacetals in the presence of methoxyacetic acid directly affords tetrasubstituted pyrans relevant to halichondrins with complete control of the C27 stereogenic center. Regioselective Tsuji reduction of the resultant allylic acetates stereoselectively establishes the C25 stereogenic center and C26 exocyclic olefin. Building upon these findings, we achieved concise access to the halichondrin C14-C38 and eribulin C14-C35 fragments.
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http://dx.doi.org/10.1021/acs.orglett.7b02934DOI Listing
November 2017

Identification of Small and Non-Small Cell Lung Cancer Markers in Peripheral Blood Using Cytokinesis-Blocked Micronucleus and Spectral Karyotyping Assays.

Cytogenet Genome Res 2017 13;152(3):122-131. Epub 2017 Sep 13.

Department of Radiology, Houston Methodist Research Institute, Houston, TX, USA.

Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer. There is an urgent need to develop tools to identify individuals at high risk of developing SCLC. We have previously reported that the cytokinesis-blocked micronucleus (CBMN) assay is a strong predictor of non-small cell lung cancer (NSCLC). Here, we investigate the sensitivity of the CBMN endpoints as predictors of SCLC risk. We conducted the CBMN assay on SCLC patients (n = 216), NSCLC patients (n = 173), and healthy controls (n = 204). Per sample, 1,000 binucleated cells (BN) were scored, and 3 endpoints, micronuclei (BN-MN), nucleoplasmic bridges (BN-NPB), and nuclear buds(BN-BUD), were recorded. Spectral karyotyping was also conducted on SCLC patients (n = 116) and NSCLC patients (n = 137) to identify genomic regions unique to each disease. Significantly higher levels of CBMN endpoints were observed in both cancer groups compared to controls. BN-NPBs were significantly higher among SCLC patients compared to NSCLC patients (p < 0.001). Chromosomes 5 and 17 were associated with BN-MN, and chromosomes 5, 18, 20, and 22 were associated with BN-NPBs in SCLC patients. Given the high frequency of chromosome aberrations observed in SCLC, events such as reinsertion of the micronucleus and chromothripsis may be potential mechanisms for the genetic instability in these patients.
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http://dx.doi.org/10.1159/000479809DOI Listing
October 2017

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

PLoS One 2017 5;12(7):e0180396. Epub 2017 Jul 5.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA), a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive) and thymine degradation pathways (p = 1.06-08) were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis). The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67). In conclusion, gene network analysis identified novel molecules and biological processes, including pathways related to inflammation and oxidative stress, that are relevant to mucositis development, thus providing the basis for future studies to improve the management and treatment of mucositis in patients with cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180396PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498049PMC
October 2017

Anti-Sulfoglucuronosyl Paragloboside Antibody: A Potential Serologic Marker of Amyotrophic Lateral Sclerosis.

ASN Neuro 2016 Oct 28;8(5). Epub 2016 Sep 28.

Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, GA, USA Department of Neurology, ALS Clinic, Medical College of Georgia, Augusta University, GA, USA

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. Although the etiology of ALS is obscure, genetic studies of familiar ALS suggest a multifactorial etiology for this condition. Similarly, there probably are multiple causes for sporadic ALS. Autoimmune-mediated motor neuron dysfunction is one proposed etiology for sporadic ALS. In the present study, anti-glycolipid antibodies including GM1, GD1b, GD3, and sulfoglucuronosyl paragloboside (SGPG) were investigated in the sera of a large number of patient samples, including 113 ALS patients and 50 healthy controls, by means of enzyme-linked immunosorbent assay with affinity parametric complex criterion evaluation and thin-layer chromatography immunooverlay (immuno-TLC). Anti-SGPG antibodies were found in the sera of 13.3% ALS patients (15 out of 113). The highest titer reached 1:1600. The presence of anti-SGPG antibodies in the serum samples was also confirmed by immuno-TLC. Importantly, a multiple logistic regression analysis showed that the presence of anti-SGPG antibody was positively correlated with age (p < .01) and negatively correlated with ALS Functional Rating Scale score (p < .05). Moreover, the localization of SGPG-immunoreactivity on the motor neurons of rat spinal cord and a mouse motor neuronal cell line, NSC-34 was observed by an immunofluorescence method. These data suggest that SGPG could represent a specific pathogenic antigen in those ALS patients. The presence of anti-SGPG antibodies in the serum of ALS patients should represent a diagnostic biomarker of ALS, and it could reflect the severity of the disease.
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http://dx.doi.org/10.1177/1759091416669619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043593PMC
October 2016

Genome-wide association study suggests common variants within RP11-634B7.4 gene influencing severe pre-treatment pain in head and neck cancer patients.

Sci Rep 2016 Sep 27;6:34206. Epub 2016 Sep 27.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Pain is often one of the first signs of squamous cell carcinoma of the head and neck (HNSCC). Pain at diagnosis is an important prognostic marker for the development of chronic pain, and importantly, for the overall survival time. To identify variants influencing severe pre-treatment pain in 1,368 patients newly diagnosed with HNSCC, we conducted a genome-wide association study based on 730,525 tagging SNPs. The patients were all previously untreated for cancer. About 15% of the patients had severe pre-treatment pain, defined as pain score ≥7 (0 = "no pain" and 10 = "worst pain"). We identified 3 common genetic variants in high linkage disequilibrium for severe pre-treatment pain, representing one genomic region at 1q44 (rs3862188, P = 3.45 × 10; rs880143, P = 3.45 × 10; and rs7526880, P = 4.92 × 10), which maps to the RP11-634B7.4 gene, a novel antisense gene to three olfactory receptor genes. Olfactory receptor genes, upstream effectors of the MAPK signaling cascade, might be novel target genes for pain in HNSCC patients. Future experimental validation to explore biological mechanisms will be key to defining the role of the intronic variants and non-coding RNA for pain in patients with HNSCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037456PMC
http://dx.doi.org/10.1038/srep34206DOI Listing
September 2016

Epigenetic regulation of ganglioside expression in neural stem cells and neuronal cells.

Glycoconj J 2017 12 19;34(6):749-756. Epub 2016 Aug 19.

Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA.

The structural diversity and localization of cell surface glycosphingolipids (GSLs), including gangliosides, in glycolipid-enriched microdomains (GEMs, also known as lipid rafts) render them ideally suited to play important roles in mediating intercellular recognition, interactions, adhesion, receptor function, and signaling. Gangliosides, sialic acid-containing GSLs, are most abundant in the nerve tissues. The quantity and expression pattern of gangliosides in brain change drastically throughout development and these changes are mainly regulated through stage-specific expression of glycosyltransferase genes. We previously demonstrated for the first time that efficient histone acetylation of the glycosyltransferase genes in mouse brain contributes to the developmental alteration of ganglioside expression. We further demonstrated that acetylation of histones H3 and H4 on the N-acetylgalactosaminyltransferase I (GalNAcT, GA2/GM2/GD2/GT2-synthase; B4galnt1) gene promoter resulted in recruitment of trans-activation factors. In addition, we showed that epigenetic activation of the GalNAcT gene was detected and accompanied by an apparent induction of neuronal differentiation of neural stem cells (NSCs) responding to an exogenous supplement of ganglioside GM1. Most recently, we found that nuclear GM1 binds with acetylated histones on the promoters of the GalNAcT as well as on the NeuroD1 genes in differentiated neurons. Here, we will introduce epigenetic regulation of ganglioside synthase genes in neural development and neuronal differentiation of NSCs.
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http://dx.doi.org/10.1007/s10719-016-9719-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260978PMC
December 2017