scholarly journals Understanding Carcinogenesis for Fighting Oral Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Takuji Tanaka ◽  
Rikako Ishigamori
Keyword(s):  
High Risk ◽  
Oral Cancer ◽  
Cancer Risk ◽  
Molecular Mechanisms ◽  
Field Cancerization ◽  
Targeted Prevention ◽  
Chemopreventive Agents ◽  
Oral Cancers ◽  
Risk Patients ◽  
Oral Malignancy

Oral cancer is one of the major global threats to public health. Oral cancer development is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are able to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will give us important advances for detecting high-risk patients, monitoring preventive interventions, assessing cancer risk, and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from research using appropriate animal carcinogenesis models. New approaches, such as interventions with molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

scholarly journals Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Takuji Tanaka ◽  
Mayu Tanaka ◽  
Takahiro Tanaka
Keyword(s):  
High Risk ◽  
Oral Cancer ◽  
Cancer Risk ◽  
Molecular Mechanisms ◽  
Cancer Chemoprevention ◽  
Field Cancerization ◽  
Targeted Prevention ◽  
Chemopreventive Agents ◽  
Oral Cancers ◽  
Oral Carcinogenesis

Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

Oral Cancer Prevention and the Evolution of Molecular-Targeted Drug Development

2005 ◽  
Vol 23 (2) ◽  
pp. 346-356 ◽  
Author(s):  
Scott M. Lippman ◽  
Jon Sudbø ◽  
Waun Ki Hong
Keyword(s):  
High Risk ◽  
Oral Cancer ◽  
Cancer Risk ◽  
Molecular Mechanisms ◽  
Retinoic Acid Receptor ◽  
Intraepithelial Neoplasia ◽  
Complete Resection ◽  
Premalignant Lesions ◽  
Targeted Prevention ◽  
Molecular Targeted Drug

The multifaceted rationale for molecular-targeted prevention of oral cancer is strong. Oral cancer is a major global threat to public health, causing great morbidity and mortality rates that have not improved in decades. Oral cancer development is a tobacco-related multistep and multifocal process involving field carcinogenesis and intraepithelial clonal spread. Biomarkers of genomic instability, such as aneuploidy and allelic imbalance, can accurately measure the cancer risk of oral premalignant lesions, or intraepithelial neoplasia (IEN). Retinoid–oral IEN studies (eg, of retinoic acid receptor-beta, p53, genetic instability, loss of heterozygosity, and cyclin D1) have advanced the overall understanding of the biology of intraepithelial carcinogenesis and of preventive agent molecular mechanisms and targets—important advances for monitoring preventive interventions and assessing cancer risk and pharmacogenomics. Clinical management of oral IEN varies from watchful waiting to complete resection, although complete resection does not prevent oral cancer in high-risk patients. New approaches, such as interventions with molecular-targeted agents and agent combinations in molecularly defined high-risk oral IEN patients, are urgently needed to reduce the devastating worldwide consequences of oral cancer.

Neuroblastoma: An Updated Review on Biology and Treatment

2020 ◽  
Vol 20 (13) ◽  
pp. 1014-1022 ◽  
Author(s):  
Suresh Mallepalli ◽  
Manoj Kumar Gupta ◽  
Ramakrishna Vadde
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Molecular Mechanisms ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Mycn Amplification ◽  
Dependent Manner ◽  
High Risk Patients ◽  
Treatment And Prevention ◽  
Risk Patients

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. Conclusions: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery &radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.

Global tissue stiffness on breast MR elastography: High-risk dense breast patients have higher stiffness compared to average-risk dense breast patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10541-10541
Author(s):  
Bhavika K. Patel ◽  
Kay Pepin ◽  
Kathy R Brandt ◽  
Gina L. Mazza ◽  
Barbara A. Pockaj ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Risk ◽  
Menopausal Status ◽  
Risk Groups ◽  
Average Risk ◽  
Tissue Stiffness ◽  
Tissue Properties ◽  
Dense Breasts ◽  
Risk Patients

10541 Background: Biomechanical tissue properties may vary in the breasts of patients at elevated risk for breast cancer. We aim to quantify in vivo biomechanical tissue properties in various breast densities and in both normal risk and high risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association of biomechanical properties of the breast with cancer risk. Methods: In this IRB–approved prospective single-institution study, we recruited two groups of women differing by breast cancer risk to undergo a 3.0 T dynamic contrast enhanced MRI/MRE of the breast. Low-average risk women were defined as having no personal or significant family history of breast cancer, no prior high risk breast biopsies and a negative mammography within 12 months. High-risk breast cancer patients were recruited from those patients who underwent standard of care breast MR. Within each breast density group (non-dense versus dense), two-sample t-tests were used to compare breast stiffness, elasticity, and viscosity across risk groups (low-average vs high). Results: There were 50 low-average risk and 86 high-risk patients recruited to the study. The risk groups were similar on age (mean age = 55.6 and 53.6 years), density (68% vs. 64% dense breasts) and menopausal status (66.0% vs. 69.8%). Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high risk patients ( N = 55) compared to low-average risk patients ( N = 34; all p < 0.001). In the multivariate logistic regression model, breast stiffness remained a significant predictor of risk status (OR=4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, MRI BPE, age, and menopausal status. Similar results were seen for breast elasticity (OR=4.88, 95% CI [2.08, 11.43]) and viscosity (OR=11.49, 95% CI [1.15, 114.89]). Conclusions: Structurally-based, quantitative biomarker of tissue stiffness obtained from global 3D breast MRE is associated with differences in breast cancer risk in dense breasts. As such, tissue stiffness could provide a novel prognostic marker to help identify the subset of high-risk women with dense breasts who would benefit from increased surveillance.[Table: see text]

A Randomized Trial of Broad Area ALA–PDT for Field Cancerization Mitigation in High-Risk Patients

2020 ◽  
Vol 19 (5) ◽  
pp. 452-458
Author(s):  
Daniel Piacquadio ◽  
Anna Houlihan ◽  
Mary Beth Ferdon ◽  
James Berg ◽  
Stuart Marcus
Keyword(s):  
High Risk ◽  
Randomized Trial ◽  
Field Cancerization ◽  
Broad Area ◽  
High Risk Patients ◽  
Risk Patients

Cell-based breast cancer risk stratification based on DNA methylation in fine needle aspiration samples

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1508-1508
Author(s):  
D. Euhus ◽  
D. Bu ◽  
S. Milchgrub ◽  
A. M. Leitch ◽  
C. M. Lewis
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Lower Risk ◽  
Breast Tissue ◽  
Needle Aspiration ◽  
Gail Model ◽  
Rassf1a Methylation ◽  
Risk Patients

1508 Background: Tumor suppressor gene (TSG) methylation is identified in nearly all breast cancers, but rarely in histologically normal breast tissue from wonen unaffected with breast cancer. Its occurrence in high risk preneoplasia and in benign breast tissue adjacent to breast cancer suggests that it may represent a high risk field change that could be exploited for cell-based breast cancer risk stratification. Methods: TSG methylation was measured by quantitative methylation-specific real time PCR in 53 breast tumor fine needle aspiration (FNA) biopsies, 84 cellular random periareolar FNAs (RP-FNA) ipsilateral or contralateral to these cancers, 36 cellular RP- FNAs from unaffected women at high risk for breast cancer by the Gail model, and 95 cellular RP-FNAs from unaffected women at lower risk by the Gail model. Results: The breast tumors showed a high frequency of TSG methylation: RASSF1A 80%, HIN-1 65%, Cyclin D2 60%, RAR-β2 53%, and APC 47%. In general, RP-FNA samples from cancer patients and Gail high risk patients showed a greater frequency of methylation than samples from Gail lower risk patients: RASSF1A 43% vs. 21%, P = 0.001, HIN-1 32% vs. 20%, P = 0.05; Cyclin D2 18% vs. 9%, P = 0.10; RAR-β2 21% vs. 18%, P = 0.68; and APC 25% vs. 16%, P = 0.17. Twelve of 215 RP-FNA samples (5%) showed very high levels of methylation (>10% methylation for two or more genes). Only two of these samples were from women classified as lower risk by the Gail model. Methylation frequencies were entirely independent of cell yields but the frequency of RASSF1A methylation increased with increasing Masood scores (P = 0.05). Methylation of RASSF1A in one breast was highly predictive of RASSF1A methylation in the opposite breast (P < 0.0001). Conclusions: TSG methylation appears to be a breast cancer risk-associated field change that can be quantified in RP-FNA samples. RASSF1A methylation occurs frequently in benign breast epithelium, provides reasonable discrimination between high and lower risk breasts (O.R. = 2.0), is related to cytological atypia, and may be an early marker of a methylator phenotype. Quantification of TSG methylation in RP-FNA samples may provide a valuable surrogate endpoint biomarker for Phase II prevention trials. No significant financial relationships to disclose.

scholarly journals Prostate cancer risk group is associated with other-cause mortality in men with localized prostate cancer

2020 ◽  
Vol 14 (10) ◽  
Author(s):  
Rehana Rasul ◽  
Anne Golden ◽  
Michael A. Feuerstein
Keyword(s):  
Prostate Cancer ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Cancer Risk ◽  
Risk Group ◽  
Prostate Cancer Risk ◽  
Initial Therapy ◽  
Localized Prostate Cancer ◽  
Treatment Type ◽  
Risk Patients

Introduction: Informed decision-making in localized prostate cancer must consider the natural history of the disease, risks of treatment, and the competing risks from other causes. Other-cause mortality has often been associated with comorbidity or treatment-related side effects. We aimed to examine the association between prostate cancer aggressiveness and other cause mortality. Methods: Using the Surveillance, Epidemiology, and End Results’ (SEER)18 registries, patients diagnosed with localized prostate cancer between 2004 and 2015 were identified. Patients were categorized into low-, intermediate- and high-risk groups. Vital status, death due to prostate cancer and death due to other causes were based on death certificate information. Survival analyses were performed to assess the association between prostate cancer risk group and mortality while adjusting for demographic variables, year of diagnosis, and initial therapy. Results: A total of 464 653 patients were identified with a median followup of 5.4 years. Cardiovascular disease was the most common cause of mortality during the study period. Compared to low-risk patients, intermediate- and high-risk patients had a higher risk of mortality from other cancers, from cardiovascular disease, and from other causes of death regardless of initial treatment. Men who underwent surgery as initial therapy had lower cumulative mortality rates compared to those with radiation as their initial therapy. Conclusions: Intermediate- and high-risk prostate cancers are associated with higher risk of other-cause mortality. This appears to be independent of treatment type and may not be solely explained by comorbidity status. Further studies controlling for comorbidity and treatment burden should be explored.

scholarly journals Evaluation of global and intragenic hypomethylation in colorectal adenomas improves patient stratification and colorectal cancer risk prediction

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Carla Debernardi ◽  
Laura Libera ◽  
Enrico Berrino ◽  
Nora Sahnane ◽  
Anna Maria Chiaravalli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Cancer Risk ◽  
Risk Prediction ◽  
Methylation Status ◽  
Low Risk ◽  
Colorectal Adenomas ◽  
Dna Hypomethylation ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Aberrant DNA hypomethylation of the long interspersed nuclear elements (LINE-1 or L1) has been recognized as an early event of colorectal transformation. Simultaneous genetic and epigenetic analysis of colorectal adenomas may be an effective and rapid strategy to identify key biological features leading to accelerated colorectal tumorigenesis. In particular, global and/or intragenic LINE-1 hypomethylation of adenomas may represent a helpful tool for improving colorectal cancer (CRC) risk stratification of patients after surgical removal of polyps. To verify this hypothesis, we analyzed a cohort of 102 adenomas derived from 40 high-risk patients (who developed CRC in a post-polypectomy of at least one year) and 43 low-risk patients (who did not develop CRC in a post-polypectomy of at least 5 years) for their main pathological features, the presence of hotspot variants in driver oncogenes (KRAS, NRAS, BRAF and PIK3CA), global (LINE-1) and intragenic (L1-MET) methylation status. Results In addition to a significantly higher adenoma size and an older patients’ age, adenomas from high-risk patients were more hypomethylated than those from low-risk patients for both global and intragenic LINE-1 assays. DNA hypomethylation, measured by pyrosequencing, was independent from other parameters, including the presence of oncogenic hotspot variants detected by mass spectrometry. Combining LINE-1 and L1-MET analyses and profiling the samples according to the presence of at least one hypomethylated assay improved the discrimination between high and low risk lesions (p = 0.005). Remarkably, adenomas with at least one hypomethylated assay identified the patients with a significantly (p < 0.001) higher risk of developing CRC. Multivariable analysis and logistic regression evaluated by the ROC curves proved that methylation status was an independent variable improving cancer risk prediction (p = 0.02). Conclusions LINE-1 and L1-MET hypomethylation in colorectal adenomas are associated with a higher risk of developing CRC. DNA global and intragenic hypomethylation are independent markers that could be used in combination to successfully improve the stratification of patients who enter a colonoscopy surveillance program. Graphic abstract

A Randomized Trial of Broad Area ALA–PDT for Field Cancerization Mitigation in High-Risk Patients

2020 ◽  
Vol 19 (5) ◽  
pp. 452-458
Author(s):  
Daniel Piacquadio ◽  
Anna Houlihan ◽  
Mary Beth Ferdon ◽  
James Berg ◽  
Stuart Marcus
Keyword(s):  
High Risk ◽  
Randomized Trial ◽  
Field Cancerization ◽  
Broad Area ◽  
High Risk Patients ◽  
Risk Patients
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