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.

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.

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.

scholarly journals Addressing Barriers to Uptake of Breast Cancer Chemoprevention for Patients and Providers

2015 ◽  
pp. e50-e58 ◽  
Author(s):  
Katherine D. Crew
Keyword(s):  
Breast Cancer ◽  
Primary Prevention ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Chemoprevention ◽  
The United States ◽  
Cancer Risk Assessment ◽  
Breast Cancer Risk Assessment ◽  
Breast Cancer Chemoprevention

Breast cancer is the most common malignancy among women in the United States, and the primary prevention of this disease is a major public health issue. Because there are relatively few modifiable breast cancer risk factors, pharmacologic interventions with antiestrogens have the potential to significantly affect the primary prevention setting. Breast cancer chemoprevention with selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene, and with aromatase inhibitors (AIs) exemestane and anastrozole, is underutilized despite several randomized controlled trials demonstrating up to a 50% to 65% relative risk reduction in breast cancer incidence among women at high risk. An estimated 10 million women in the United States meet high-risk criteria for breast cancer and are potentially eligible for chemoprevention, but less than 5% of women at high risk who are offered antiestrogens for primary prevention agree to take it. Reasons for low chemoprevention uptake include lack of routine breast cancer risk assessment in primary care, inadequate time for counseling, insufficient knowledge about antiestrogens among patients and providers, and concerns about side effects. Interventions designed to increase chemoprevention uptake, such as decision aids and incorporating breast cancer risk assessment into clinical practice, have met with limited success. Clinicians can help women make informed decisions about chemoprevention by effectively communicating breast cancer risk and enhancing knowledge about the risks and benefits of antiestrogens. Widespread adoption of chemoprevention will require a major paradigm shift in clinical practice for primary care providers (PCPs). However, enhancing uptake and adherence to breast cancer chemoprevention holds promise for reducing the public health burden of this disease.

Abstract 1270: Potential metabolic and molecular mechanisms of black raspberry-mediated oral cancer chemoprevention

2018 ◽  
Author(s):  
Steve Oghumu ◽  
Thomas J. Knobloch ◽  
Logan C. Weghorst ◽  
Lei Bruschweiler-Li ◽  
Cheng Wang ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Molecular Mechanisms ◽  
Cancer Chemoprevention ◽  
Black Raspberry

scholarly journals New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals:In VitroandIn VivoStudies and the Underlying Mechanisms

2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Madhulika Singh ◽  
Shankar Suman ◽  
Yogeshwer Shukla
Keyword(s):  
Skin Cancer ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cancer Chemoprevention ◽  
Chemopreventive Agents ◽  
Novel Approach ◽  
Comprehensive Knowledge ◽  
Underlying Mechanisms

Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenicin vitroandin vivomodels and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer.

scholarly journals Cancer Chemoprevention: Current State of the Art

2014 ◽  
Vol 7 ◽  
pp. CGM.S11288 ◽  
Author(s):  
Kristin R. Landis-Piwowar ◽  
Neena R. Iyer
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Chemoprevention ◽  
Cancer Therapies ◽  
Metastatic Progression ◽  
Chemopreventive Agents ◽  
Mesenchymal Transition ◽  
Initiation Phase ◽  
Current State

The aim of cancer chemoprevention is disruption or delay of the molecular pathways that lead to carcinogenesis. Chemopreventive blocking and/or suppressing agents disrupt the molecular mechanisms that drive carcinogenesis such as DNA damage by reactive oxygen species, increased signal transduction to NF-κB, epigenomic deregulation, and the epithelial mesenchymal transition that leads to metastatic progression. Numerous dietary phytochemicals have been observed to inhibit the initiation phase of carcinogenesis, and therefore are useful in primary chemoprevention. Moreover, phytochemicals are capable of interfering with the molecular mechanisms of metastasis. Likewise, numerous synthetic compounds are relevant and clinically viable as chemopreventive agents during the fundamental stages of carcinogenesis. While molecularly targeted anti-cancer therapies are in constant stages of development, superior patient outcomes are observed if carcinogenic processes are prevented altogether. This article reviews the role of chemopreventive compounds in inhibition of cancer initiation and their ability to reduce cancer progression.

scholarly journals Metabolic Regulation of Glycolysis and AMP Activated Protein Kinase Pathways during Black Raspberry-Mediated Oral Cancer Chemoprevention

Metabolites ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 140 ◽  
Author(s):  
Thomas J. Knobloch ◽  
Nathan M. Ryan ◽  
Lei Bruschweiler-Li ◽  
Cheng Wang ◽  
Matthew C. Bernier ◽  
...  
Keyword(s):  
Drinking Water ◽  
Oral Cancer ◽  
Metabolic Pathways ◽  
Metabolic Regulation ◽  
Control Diet ◽  
Public Health Problem ◽  
Cancer Chemoprevention ◽  
Rat Urine ◽  
Oral Carcinogenesis ◽  
The Usa

Oral cancer is a public health problem with an incidence of almost 50,000 and a mortality of 10,000 each year in the USA alone. Black raspberries (BRBs) have been shown to inhibit oral carcinogenesis in several preclinical models, but our understanding of how BRB phytochemicals affect the metabolic pathways during oral carcinogenesis remains incomplete. We used a well-established rat oral cancer model to determine potential metabolic pathways impacted by BRBs during oral carcinogenesis. F344 rats were exposed to the oral carcinogen 4-nitroquinoline-1-oxide in drinking water for 14 weeks, then regular drinking water for six weeks. Carcinogen exposed rats were fed a 5% or 10% BRB supplemented diet or control diet for six weeks after carcinogen exposure. RNA-Seq transcriptome analysis on rat tongue, and mass spectrometry and NMR metabolomics analysis on rat urine were performed. We tentatively identified 57 differentially or uniquely expressed metabolites and over 662 modulated genes in rats being fed with BRB. Glycolysis and AMPK pathways were modulated during BRB-mediated oral cancer chemoprevention. Glycolytic enzymes Aldoa, Hk2, Tpi1, Pgam2, Pfkl, and Pkm2 as well as the PKA-AMPK pathway genes Prkaa2, Pde4a, Pde10a, Ywhag, and Crebbp were downregulated by BRBs during oral cancer chemoprevention. Furthermore, the glycolysis metabolite glucose-6-phosphate decreased in BRB-administered rats. Our data reveal the novel metabolic pathways modulated by BRB phytochemicals that can be targeted during the chemoprevention of oral cancer.

scholarly journals Public support for healthcare-mediated disclosure of hereditary cancer risk information: Results from a population-based survey in Sweden

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Andreas Andersson ◽  
Carolina Hawranek ◽  
Anna Öfverholm ◽  
Hans Ehrencrona ◽  
Kalle Grill ◽  
...  
Keyword(s):  
At Risk ◽  
High Risk ◽  
Cancer Risk ◽  
Hereditary Cancer ◽  
Healthcare Professionals ◽  
Risk Information ◽  
Lifetime Risk ◽  
Targeted Prevention ◽  
Hereditary Risk ◽  
Risk Scenarios

Abstract Background Targeted surveillance of at-risk individuals in families with increased risk of hereditary cancer is an effective prevention strategy if relatives are identified, informed and enrolled in screening programs. Despite the potential benefits, many eligible at-risk relatives remain uninformed of their cancer risk. This study describes the general public’s opinion on disclosure of hereditary colorectal cancer (CRC) risk information, as well as preferences on the source and the mode of information. Methods A random sample of the general public was assessed through a Swedish citizen web-panel. Respondents were presented with scenarios of being an at-risk relative in a family that had an estimated increased hereditary risk of CRC; either 10% (moderate) or 70% (high) lifetime risk. A colonoscopy was presented as a preventive measure. Results were analysed to identify significant differences between groups using the Pearson’s chi-square (χ2) test. Results Of 1800 invited participants, 977 completed the survey (54%). In the moderate and high-risk scenarios, 89.2 and 90.6% respectively, would like to receive information about a potential hereditary risk of CRC (χ2, p = .755). The desire to be informed was higher among women (91.5%) than men (87.0%, χ2, p = .044). No significant differences were found when comparing different age groups, educational levels, place of residence and having children or not. The preferred source of risk information was a healthcare professional in both moderate and high-risk scenarios (80.1 and 75.5%). However, 18.1 and 20.1% respectively would prefer to be informed by a family member. Assuming that healthcare professionals disclosed the information, the favoured mode of information was letter and phone (38.4 and 33.2%). Conclusions In this study a majority of respondents wanted to be informed about a potential hereditary risk of CRC and preferred healthcare professionals to communicate this information. The two presented levels of CRC lifetime risk did not significantly affect the interest in being informed. Our data offer insights into the needs and preferences of the Swedish population, providing a rationale for developing complementary healthcare-assisted communication pathways to realise the full potential of targeted prevention of hereditary CRC.

Conversion of Normal To Malignant Phenotype: Telomere Shortening, Telomerase Activation, and Genomic Instability During Immortalization of Human Oral Keratinocytes

2001 ◽  
Vol 12 (1) ◽  
pp. 38-54 ◽  
Author(s):  
M.K. Kang ◽  
M.-H. Park
Keyword(s):  
High Risk ◽  
Oral Cancer ◽  
Environmental Factors ◽  
Genomic Instability ◽  
Hpv Infection ◽  
Oral Keratinocytes ◽  
Chemical Carcinogens ◽  
Oral Carcinogenesis ◽  
High Risk Hpv

Normal somatic cells terminate their replicative life span through a pathway leading to cellular senescence, which is triggered by activation of p53 and/or pRb in response to critically shortened telomere DNA. Potentially neoplastic cells must first overcome the senescence checkpoint mechanisms and subsequently activate telomerase to propagate indefinitely. Although telomerase activation is closely associated with cellular immortality, telomerase alone is not sufficient to warrant tumorigenicity. Environmental factors, including chemical carcinogens and viral infection, often contribute to aberrant changes leading to tumorigenic conversion of normal cells. Of particular importance in oral cancer development are tobacco-related chemical carcinogens and human papillomavirus (HPV) infection. To describe the molecular mechanisms by which these environmental factors facilitate the genesis of oral cancer, we first established an in vitro multistep oral carcinogenesis model by sequential exposure of normal human oral keratinocytes (NHOK) to "high risk" HPV and chemical carcinogens. Upon introduction of the HPV genome, the cells bypassed the senescence checkpoint and entered into an extended, but not immortal, life span during which telomere DNA continued to shorten. In a few immortal clones surviving beyond the crisis, we found a marked elevation of telomerase activity and stabilization of telomere length. Furthermore, the E6 and E7 oncoproteins of "high risk" HPV disrupted the cell cycle control and DNA repair in immortalized HOK, and enhanced mutation frequency resulting from genomic instability. However, HPV infection alone failed to give rise to a tumorigenic cell population, which required further exposure to chemical carcinogens in addition to HPV infection. Analysis of the data presented suggests that oral carcinogenesis is a series of discrete genetic alterations that result from a continued genotoxic challenge by environmental risk factors. Our in vitro model may be useful for investigators with interest in furthering our understanding of oral carcinogenesis.

Sign in / Sign up

Export Citation Format

Share Document