Biological monitoring of cancer chemoprevention

Pillai, Radhakrishna; Garewal, Harinder S.; Wood, Steven; Watson, Ronald R.

doi:10.1002/jso.2930510314

Cited by 9 publications

(7 citation statements)

References 48 publications

(33 reference statements)

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“…These changes are grouped as genomic, proliferation and differentiation markers. Changes in multiple markers are more likely to represent histological transition of precancer to cancer [10, 11]. The goal of the present study is to evaluate the expression of epidermal growth factor receptor (EGFR) and its ligand transforming growth factor-α (TGF-α) in OL with dysplasia and OSMF as intermediate markers of malignancy.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of TGF-α and EGFR Expression in Oral Leukoplakia and Oral Submucous Fibrosis by Quantitative Immunohistochemistry

Srinivasan

Jewell

2001

Oncology

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Objective: Oral leukoplakia (OL) and oral submucous fibrosis (OSMF) are clinically distinct preneoplastic states that precede the development of oral squamous cell carcinoma. Recently, attempts are being made to identify specific molecular event(s) as prognostic markers to identify oral precancerous lesions with higher malignant potential. The goal of the present study was to evaluate the expression of EGFR and its ligand TGF-α in OL with dysplasia and OSMF as intermediate markers of malignancy by quantitative immunohistochemistry. Methods: Oral tissues were stained with monoclonal antibodies to TGF-α and EGFR. The results were analyzed with Photoquant image analysis software. Results: The expression of TGF-α and EGFR was upregulated in OL, OSMF and oral squamous cell carcinomas relative to normal oral mucosa. The area and intensity of staining of TGF-α in the proliferative layers (stratum germinativum) increased linearly in OL with mild, moderate and severe dysplasia as compared to control mucosa (p < 0.05). EGFR levels increased linearly in the stratum spinosum in OL with increasing degrees of dysplasia (p < 0.05). In general, the expression of both proteins in OSMF was similar to that in OL with moderate dysplasia. Conclusions: EGFR and TGF-α represent early markers of malignancy in OL with dysplasia. Quantitative measurement of these proteins may provide intermediate endpoints in prospective chemopreventive trials.

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Section: Introductionmentioning

confidence: 99%

Evaluation of TGF-α and EGFR Expression in Oral Leukoplakia and Oral Submucous Fibrosis by Quantitative Immunohistochemistry

Srinivasan

Jewell

2001

Oncology

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“…In this era of ''Animal Conservation Rights'' animal models have there own set of ethical and political problems, apart from professional difficulties. Several putative biomarkers have also been proposed to evaluate the role of antioxidants: however, none has been proven to be fully validated [33]. Assessment by ''Carter's criteria'' is a two dimensional measurement of the lesion which can be misleading and has a marked subjective observational bias.…”

Section: Does Antioxidant Therapy Influence Lipid Peroxidase?mentioning

confidence: 99%

Role of Measurement of Antioxidant Enzymes in Evaluation of Antioxidant Therapy in Tobacco Abusers with Oral Leukoplakia

Jain

Singh

et al. 2011

Indian J Otolaryngol Head Neck Surg

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Antioxidants are widely used in chemoprevention of malignancy. Numerous studies in medical literature have reported the evaluation of this treatment protocol by indirect methodology-epidemiology, invitro studies, pharmacology and animal models etc. However, there is a paucity of literature on the measurement of antioxidant enzymes as a parameter for assessing the outcome of antioxidant therapy. This study explores the efficacy and outcome of antioxidant enzyme assay in relation to antioxidant therapy in tobacco abusers, hitherto unreported in medical literature. A prospective cohort study with control in 50 patients carried out at a tertiary care teaching Institution (Institute of Medical Sciences, Banaras Hindu University, Varanasi, India). Out of these patients, 10 patients acted as control, rest 40 patients-all tobacco users in some form, were divided into three groups on the basis of histopathological grading of dysplasia-no dysplasia, mild or moderate dysplasia. The levels of Lipid peroxidase (LPO), Superoxide dismutase (SOD) and Catalase (CAT) in mucosa and serum were assayed in each group, and re-evaluated at the end of 3 months after intervention with antioxidant treatment. To detect any alteration in degree of dysplasia a repeat biopsy was also done at the end of 3 months. The results were statistically analysed using paired t test. A statistically significant decrease in level of LPO and SOD, and an increase in CAT levels were recorded both in mucosa and serum. However, no change in dysplasia and no new case of dysplasia were observed. Further, antioxidant treatment was continued for a year and the final out come of the lesion was assessed by ''Carter's criteria''. A final success rate of 74.19% was recorded in terms of partial or complete regression of the lesion. This study confirms the therapeutic efficacy of antioxidants in oral leukoplakia, and cites the importance of LPO, SOD and CAT in evaluating the efficacy of antioxidant treatment. However, the study failed to elucidate any relationship between enzyme measurement and the final outcome of the lesion.

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“…51 Specific markers can serve as surrogate or intermediate endpoints for cancer, that is, they represent changes in the continuum of events between the initiation of carcinogenesis and the final expression of clinically evident disease. 52 This biomarker concept is used in the management of other diseases as well. For example, cholesterol quantitation is used to indicate the progression of atherosclerosis as a surrogate in determining the risk of myocardial infarction.…”

Section: Biomarkersmentioning

confidence: 99%

“…[54][55][56] Identification and validation of such markers is important in the design of large-scale studies because fewer trial subjects are required to achieve statistical power and more agents can be evaluated over less time than by using cancer as the endpoint. 52,54,57 Examples of potential prevention biomarkers identified include genetic markers (e.g., nuclear aberrations, such as micronuclei; gene amplification; and mutation); cellular markers (e.g., differentiation markers and measures of proliferation, such as thymidine labeling index); histologic markers (e.g., premalignant lesions, such as leukoplakia and colonic polyps); and biochemical and pharmacologic markers (e.g., ornithine decarboxylase activity). 52 Despite the identification and investigation of several potential biomarkers (Table 6), [58][59][60] none of these surrogates has yet been validated as an accurate predictor of future cancer incidence.…”

Section: Biomarkersmentioning

confidence: 99%

“…52,54,57 Examples of potential prevention biomarkers identified include genetic markers (e.g., nuclear aberrations, such as micronuclei; gene amplification; and mutation); cellular markers (e.g., differentiation markers and measures of proliferation, such as thymidine labeling index); histologic markers (e.g., premalignant lesions, such as leukoplakia and colonic polyps); and biochemical and pharmacologic markers (e.g., ornithine decarboxylase activity). 52 Despite the identification and investigation of several potential biomarkers (Table 6), [58][59][60] none of these surrogates has yet been validated as an accurate predictor of future cancer incidence. The development of standardized biomarkers of intermediate endpoints that can reveal very early or specific stages of carcinogenesis and that are sensitive, specific, quantitative, and reproducible is critical to the design of effective chemoprevention trials.…”

Section: Biomarkersmentioning

confidence: 99%

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