Molecular alterations in oral carcinogenesis: significant risk predictors in malignant trasformation and tumor progression

2007 ◽  
Vol 22 (2) ◽  
pp. 132-143 ◽  
Author(s):  
N.G. Shah ◽  
T.I. Trivedi ◽  
R.A. Tankshali ◽  
J.A. Goswami ◽  
J.S. Shah ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Significant Risk ◽  
Molecular Alterations ◽  
Oral Carcinogenesis ◽  
Risk Predictors

Molecular Alterations in Oral Carcinogenesis: Significant Risk Predictors in Malignant Transformation and Tumor Progression

2007 ◽  
Vol 22 (2) ◽  
pp. 132-143 ◽  
Author(s):  
N.G. Shah ◽  
T.I. Trivedi ◽  
R.A. Tankshali ◽  
J.A. Goswami ◽  
J.S. Shah ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Progression ◽  
Early Stage ◽  
Significant Risk ◽  
Normal Mucosa ◽  
Ki 67 ◽  
Molecular Alterations ◽  
Oral Carcinogenesis ◽  
Risk Predictors ◽  
Early Stage Carcinoma

In this study an attempt was made to establish the significance of a battery of molecular alterations and thereby identify risk predictors in oral carcinogenesis. For this purpose, EGFR, Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb, Ki-67 and Bcl-2 were localized immunohistochemically in normal mucosa (n=12), hyperplasia (n=35), dysplasia (n=25), early stage carcinoma (n=65) and advanced stage carcinoma (n=70). Deregulation occurred at an early stage and the number of alterations increased with disease progression. Using multivariate logistic regression analysis, the significant risk predictor for hyperplasia from normal mucosa was Ki-67 (OR=5.75, p=0.021); the significant risk predictors for dysplasia from hyperplasia were EGFR (OR=12.96, p=0.002), Stat3 (OR=17.16, p=0.0001), p16 (OR=5.50, p=0.039) and c-myc (OR=5.99, p=0.052); the significant risk predictors for early stage carcinoma from dysplasia were p53 (OR=6.63, p=0.0001) and Rb (OR=3.81, p=0.056); and the significant risk predictors for further progression were EGFR (OR=5.50, p=0.0001), Stat3 (OR=4.49, p=0.0001), H-ras (OR=4.05, p=0.001) and c-myc (OR=2.99, p=0.015). Cyclin D1 holds a key position linking upstream signaling pathways to cell cycle regulation. Gene products of the mitogenic signaling pathway play an equally significant role as cell cycle regulatory proteins in the hyperplasia-dysplasia-early-advanced-carcinoma sequence and together may provide a reference panel of markers for use in defining premalignant lesions and predicting the risk of malignant transformation and tumor progression.

scholarly journals Incidence and risk predictors of acute kidney injury among HIV-positive patients presenting with sepsis in a low resource setting

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Davis Kimweri ◽  
Julian Ategeka ◽  
Faustine Ceasor ◽  
Winnie Muyindike ◽  
Edwin Nuwagira ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Significant Risk ◽  
Kidney Injury ◽  
Significant Risk Factor ◽  
Hiv Positive ◽  
Volume Depletion ◽  
Adjusted Risk ◽  
Adjusted Analysis ◽  
Resource Setting ◽  
Risk Predictors

Abstract Background Acute kidney injury (AKI) is a frequently encountered clinical condition in critically ill patients and is associated with increased morbidity and mortality. In our resource-limited setting (RLS), the most common cause of AKI is sepsis and volume depletion. Sepsis alone, accounts for up to 62 % of the AKI cases in HIV-positive patients. Objective The major goal of this study was to determine the incidence and risk predictors of AKI among HIV-infected patients admitted with sepsis at a tertiary hospital in Uganda. Methods In a prospective cohort study, we enrolled adult patients presenting with sepsis at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda between March and July 2020. Sepsis was determined using the qSOFA criteria. Patients presenting with CKD or AKI were excluded. Sociodemographic characteristics, physical examination findings, and baseline laboratory values were recorded in a data collection tool. The serum creatinine and urea were done at admission (0-hour) and at the 48-hour mark to determine the presence of AKI. We performed crude and multivariable binomial regression to establish the factors that predicted developing AKI in the first 48 h of admission. Variables with a p < 0.01 in the adjusted analysis were considered as significant predictors of AKI. Results Out of 384 patients screened, 73 (19 %) met our inclusion criteria. Their median age was 38 (IQR 29–46) years and 44 (60.3 %) were male. The median CD4 T-cell count was 67 (IQR 35–200) cells, median MUAC was 23 (IQR 21–27) cm and 54 (74.0 %) participants were on a regimen containing Tenofovir Disoproxil Fumarate (TDF). The incidence of AKI in 48 h was 19.2 % and in the adjusted analysis, thrombocytopenia (Platelet count < 150) (adjusted risk ratio 8.21: 95 % CI: 2.0–33.8, p = 0.004) was an independent predictor of AKI. Conclusions There is a high incidence of AKI among HIV-positive patients admitted with sepsis in Uganda. Thrombocytopenia at admission may be a significant risk factor for developing AKI. The association of thrombocytopenia in sepsis and AKI needs to be investigated.

scholarly journals Edoxaban versus warfarin on stroke risk in patients with atrial fibrillation: a territory-wide cohort study

2021 ◽  
Author(s):  
Dicken Kong ◽  
Jiandong Zhou ◽  
Sharen Lee ◽  
Keith Sai Kit Leung ◽  
Tong Liu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cohort Study ◽  
Ischemic Stroke ◽  
Propensity Score ◽  
Ischaemic Stroke ◽  
Propensity Score Matching ◽  
Lower Risk ◽  
Cox Regression ◽  
Significant Risk ◽  
Risk Predictors

AbstractBackgroundIn this territory-wide, observational, propensity score-matched cohort study, we evaluate the development of transient ischaemic attack and ischaemic stroke (TIA/Ischaemic stroke) in patients with AF treated with edoxaban or warfarin.MethodsThis was an observational, territory-wide cohort study of patients between January 1st, 2016 and December 31st, 2019, in Hong Kong. The inclusion were patients with i) atrial fibrillation, and ii) edoxaban or warfarin prescription. 1:2 propensity score matching was performed between edoxaban and warfarin users. Univariate Cox regression identifies significant risk predictors of the primary, secondary and safety outcomes. Hazard ratios (HRs) with corresponding 95% confidence interval [CI] and p values were reported.ResultsThis cohort included 3464 patients (54.18% males, median baseline age: 72 years old, IQR: 63-80, max: 100 years old), 664 (19.17%) with edoxaban use and 2800 (80.83%) with warfarin use. After a median follow-up of 606 days (IQR: 306-1044, max: 1520 days), 91(incidence rate: 2.62%) developed TIA/ischaemic stroke: 1.51% (10/664) in the edoxaban group and 2.89% (81/2800) in the warfarin group. Edoxaban was associated with a lower risk of TIA or ischemic stroke when compared to warfarin.ConclusionsEdoxaban use was associated with a lower risk of TIA or ischemic stroke after propensity score matching for demographics, comorbidities and medication use.

scholarly journals The Impact of Age and Sex in DLBCL: Systems Biology Analyses Identify Distinct Molecular Changes and Signaling Networks

2015 ◽  
Vol 14 ◽  
pp. CIN.S34144 ◽  
Author(s):  
Afshin Beheshti ◽  
Donna Neuberg ◽  
J. Tyson Mcdonald ◽  
Charles R. Vanderburg ◽  
Andrew M. Evens
Keyword(s):  
Systems Biology ◽  
Tumor Progression ◽  
B Cell Lymphoma ◽  
The Cancer Genome Atlas ◽  
Young Females ◽  
Molecular Alterations ◽  
Cancer Genome Atlas ◽  
Male Patients ◽  
The Impact ◽  
Age And Sex

Potential molecular alterations based on age and sex are not well defined in diffuse large B-cell lymphoma (DLBCL). We examined global transcriptome DLBCL data from The Cancer Genome Atlas (TCGA) via a systems biology approach to determine the molecular differences associated with age and sex. Collectively, sex and age revealed striking transcriptional differences with older age associated with decreased metabolism and telomere functions and female sex was associated with decreased interferon signaling, transcription, cell cycle, and PD-1 signaling. We discovered that the key genes for most groups strongly regulated immune function activity. Furthermore, older females were predicted to have less DLBCL progression versus older males and young females. Finally, analyses in systems biology revealed that JUN and CYCS signaling were the most critical factors associated with tumor progression in older and male patients. We identified important molecular perturbations in DLBCL that were strongly associated with age and sex and were predicted to strongly influence tumor progression.

Genetic and Epigenetic Biomarkers of Molecular Alterations in Oral Carcinogenesis

2015 ◽  
Vol 61 (10/2015) ◽  
Author(s):  
Raluca Dumache ◽  
Alexandru Rogobete ◽  
Nicoleta Andreescu ◽  
Maria Puiu
Keyword(s):  
Molecular Alterations ◽  
Oral Carcinogenesis ◽  
Epigenetic Biomarkers

scholarly journals Development and internal validation of a multivariable prediction model for 6-year risk of stroke: a cohort study in middle-aged and elderly Chinese population

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e048734
Author(s):  
Qi Yu ◽  
Yuanzhe Wu ◽  
Qingdong Jin ◽  
Yanqing Chen ◽  
Qingying Lin ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prediction Model ◽  
Ischaemic Stroke ◽  
Chinese Population ◽  
Significant Risk ◽  
Density Lipoprotein ◽  
Haemorrhagic Stroke ◽  
Middle Aged ◽  
Elderly Chinese ◽  
Risk Predictors

ObjectiveTo develop and internally validate a prediction model for 6-year risk of stroke and its primary subtypes in middle-aged and elderly Chinese population.DesignThis is a retrospective cohort study from a prospectively collected database.ParticipantsWe included a total 3124 adults aged 45–80 years, free of stroke or myocardial infarction at baseline in the 2009–2015 cohort of China Health and Nutrition Survey.Primary and secondary outcome measuresThe outcome of the prediction model was stroke. Investigated predictors were: age, gender, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), hypertension (HBP), drinking status, smoking status, diabetes and site. Stepwise multiple Cox regression was applied to identify independent predictors. A nomogram was constructed to predict 6-year risk of stroke based on the multiple analysis results. Bootstraps with 1000 resamples were applied to both C-index and calibration curve.ResultThe overall incidence of overall stroke was 2.98%. Age, gender, HBP and TC were found as significant risk predictors for overall stroke; age, gender, HBP and LDL-C were found as significant risk predictors for ischaemic stroke; age, gender, HBP, BMI and HDL-C were found as significant risk predictors for haemorrhagic stroke. The nomogram was constructed using significant variables included in the model, with a C-index of 0.74 (95% CI: 0.72 to 0.76), 0.74 (95% CI: 0.71 to 0.77), and 0.81 (95% CI: 0.78 to 0.84) for overall stroke, ischaemic stroke, and haemorrhagic stroke model, respectively. The calibration curves demonstrated the good agreements between predicted and observed 6-year risk probability.ConclusionOur nomogram could be convenient, easy to use and effective prognoses for predicting 6-year risk of stroke in middle-aged and elderly Chinese population.

scholarly journals Pineal gland protects against chemically induced oral carcinogenesis and inhibits tumor progression in rats

Oncotarget ◽  
2020 ◽  
Vol 11 (20) ◽  
pp. 1816-1831 ◽  
Author(s):  
Giseli Mitsuy Kayahara ◽  
Vitor Bonetti Valente ◽  
Rosani Belzunces Pereira ◽  
Felipe Yudi Kabeya Lopes ◽  
Marcelo Macedo Crivelini ◽  
...  
Keyword(s):  
Pineal Gland ◽  
Tumor Progression ◽  
Oral Carcinogenesis ◽  
Chemically Induced

scholarly journals Cell Cycle Dysregulation in Oral Cancer

2002 ◽  
Vol 13 (1) ◽  
pp. 51-61 ◽  
Author(s):  
R. Todd ◽  
P.W. Hinds ◽  
K. Munger ◽  
A.K. Rustgi ◽  
O.G. Opitz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Metabolic Stress ◽  
Regulatory Proteins ◽  
Regulatory Pathways ◽  
Oral Cancers ◽  
Molecular Alterations ◽  
Oral Carcinogenesis ◽  
Retinoblastoma Tumor

The dysregulation of the molecular events governing cell cycle control is emerging as a central theme of oral carcinogenesis. Regulatory pathways responding to extracellular signaling or intracellular stress and DNA damage converge on the cell cycle apparatus. Abrogation of mitogenic and anti-mitogenic response regulatory proteins, such as the retinoblastoma tumor suppressor protein (pRB), cyclin D1, cyclin-dependent kinase (CDK) 6, and CDK inhibitors (p21WAF1/CIP1, p27KIP1, and p16INK4a), occur frequently in human oral cancers. Cellular responses to metabolic stress or genomic damage through p53 and related pathways that block cell cycle progression are also altered during oral carcinogenesis. In addition, new pathways and cell cycle regulatory proteins, such as p12DOC-1, are being discovered. The multistep process of oral carcinogenesis likely involves functional alteration of cell cycle regulatory members combined with escape from cellular senescence and apoptotic signaling pathways. Detailing the molecular alterations and understanding the functional consequences of the dysregulation of the cell cycle apparatus in the malignant oral keratinocyte will uncover novel diagnostic and therapeutic approaches.

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