Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions

Mallery, Susan R.; Zwick, Jared C.; Pei, Ping; Tong, Mingwei; Larsen, Peter E.; Shumway, Brian S.; Lü, Bo; Fields, Henry W.; Mumper, Russell J.; Stoner, Gary D.

doi:10.1158/0008-5472.can-08-0568

Cited by 106 publications

(138 citation statements)

References 43 publications

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“…Immunohistochemical analysis revealed over expression of COX-2 in oesophagus, stomach, breast, pancreas, lung, colon, skin, urinary bladder and prostate cancers (Mendes et al, 2009). Increased levels of COX-2 were shown in premalignant lesions of oral cavity (Mallery et al, 2008). A positive association between mutant p53 and over expression of COX-2 has been shown in oral carcinogenesis (Nishimura et al, 2004).…”

Section: Discussionmentioning

confidence: 93%

Proapoptotic, Anti-Cell Proliferative, Anti-Inflammatory And Antiangiogenic Potential Of Carnosic Acid During 7,12 Dimethylbenz[A]Anthracene-Induced Hamster Buccal Pouch Carcinogenesis

Rajasekaran¹,

Manoharan²,

Silvan³

et al. 2012

Afr. J. Trad. Compl. Alt. Med.

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The present study has investigated the modulating effect of carnosic acid on the expression pattern of cell proliferative (proliferating cell nuclear antigen (PCNA) cyclin D1 and a transcription factor c-fos), apoptotic (p53, Bcl-2, Bax caspase -3 and 9), inflammatory (Nuclear factor kappa B (NFκB) and cyclooxygenase-2 (COX-2) and angiogenic (vascular endothelial growth factor (VEGF) markers during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the hamsters buccal pouches by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Hundred per cent tumour formation (well-differentiated squamous cell carcinoma) accompanied by deregulation in the above mentioned molecular markers was noticed in hamsters treated with DMBA alone (tumour bearing hamsters). Oral administration of carnosic acid at dose of 10mg/kg bw to hamsters treated with DMBA not only completely prevented the tumour formation, but also corrected the abnormalities in the expression pattern of molecular markers. The present study suggests that carnosic acid might have inhibited the tumour formation by exerting anti-cell-proliferative, anti-inflammatory, anti-angiogenic and apoptotic potential during DMBA-induced hamster buccal pouch carcinogenesis.

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Section: Discussionmentioning

confidence: 93%

Proapoptotic, Anti-Cell Proliferative, Anti-Inflammatory And Antiangiogenic Potential Of Carnosic Acid During 7,12 Dimethylbenz[A]Anthracene-Induced Hamster Buccal Pouch Carcinogenesis

Rajasekaran¹,

Manoharan²,

Silvan³

et al. 2012

Afr. J. Trad. Compl. Alt. Med.

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“…Further, loss of keratin 4 and cornulin expression can be a valuable enrolment criterion for tertiary prevention trials in treated HNSCC patients. Several experimental approaches are being studied and showed promising initial results (50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

Differential Proteomics Identifies Protein Biomarkers That Predict Local Relapse of Head and Neck Squamous Cell Carcinomas

Schaaij-Visser

Graveland

Gauci

et al. 2009

Clinical Cancer Research

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Purpose: The 5-year survival rates of head and neck squamous cell carcinomas (HNSCC) remain disappointing. HNSCCs develop in precursor fields of genetically altered cells that are often not completely resected when the tumor is excised, causing local relapse. These precursor fields are mostly recognized as dysplasia, but histologic grading cannot reliably predict malignant transformation. Our aim was to discover and validate protein biomarkers that can detect precursor fields and predict local relapse in HNSCC using immunostaining of surgical margins. Experimental Design: We compared paired and genetically characterized normal, precursor, and tumor tissues of eight patients by proteome analysis to identify differentially expressed proteins. The prognostic value of candidate protein biomarkers was evaluated by immunohistochemical analysis of 222 surgical margins of 46 HNSCC patients who developed local relapse or remained disease free. Significant associations were determined by Kaplan-Meier survival analysis and Cox-proportional hazards models. Results: Forty proteins showed significant differential expression (false discovery ratecorrected P < 0.05). Most discriminative markers suited for immunostaining were keratin 4 and cornulin. Low expression in the surgical margins of keratin 4 (hazard ratio, 3.8; P = 0.002), cornulin (hazard ratio, 2.7; P = 0.025), and their combination (hazard ratio, 8.8; P = 0.0005) showed a highly significant association with the development of local relapse. Dysplasia grading had no prognostic relevance. Conclusions: Immunohistochemical assessment of keratin 4 and cornulin expression in surgical margins of HNSCC patients outperforms histopathologic grading in predicting the risk for local relapse. These markers can be used to initiate more frequent and lifelong surveillance of patients at high risk of local relapse, and enable selection for adjuvant treatment or tertiary prevention trials. (Clin Cancer Res 2009;15(24):7666-75) Head and neck squamous cell carcinoma (HNSCC) develops in the mucosal linings of the upper aerodigestive tract and is the sixth most common cancer worldwide (1). The 5-year survival rates of HNSCC are approximately 60% (1) and have only moderately improved the last decades (2) mainly because 20% to 40% of all patients develop a local relapse in the same or adjacent anatomic region even when the surgical margins are histologically tumor free (3, 4). Clinically these relapses at the primary and adjacent anatomic sites are assigned as local recurrences when they develop within three years and at <2 cm distance of the primary tumor. Relapses not fulfilling these criteria are clinically classified as second primary tumors. Despite the difference in clinical assignment, many local relapses have in fact the same pathobiological origin (3-8).It has been well established that HNSCC is the result of a multistep process characterized by the accumulation of genetic and epigenetic alterations (9). Genetic analysis of surgical margins has shown that HNSCC frequent...

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“…In addition, dietary administration of BRBs has been shown to inhibit esophageal, oral cavity, and mammary tumorigenesis in animal models (11). In humans, BRBs have been shown to be well tolerated and exert protective effects in multiple phase I human clinical trials in patients with colorectal cancer (14), Barrett's esophagus (15), and oral dysplasia (16,17).…”

Section: Introductionmentioning

confidence: 99%

A Phase Ib Study of the Effects of Black Raspberries on Rectal Polyps in Patients with Familial Adenomatous Polyposis

Wang¹,

Burke

Hasson

et al. 2014

Cancer Prevention Research

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Familial adenomatous polyposis (FAP) is characterized by the early onset of colonic polyposis and a high risk for colorectal cancer. FAP is treated by colectomy followed by lifelong removal of rectal polyps. This study determined whether black raspberries (BRBs) might regress rectal polyps in patients with FAP. Fourteen patients with FAP were treated with BRBs daily for 9 months. Seven patients received BRB powder orally plus two BRB suppositories inserted into the rectum at bedtime. The other 7 received an oral placebo plus the suppositories. Rectal polyp counts and polyp sizes were obtained at time zero and after 9 months of BRB treatment. Polyps and adjacent normal tissue were collected at both time points. The burden (P ¼ 0.036) but not number (P ¼ 0.069) of rectal polyps was significantly decreased. No benefit was noted with the addition of oral BRBs. Three patients were nonresponders. BRBs significantly decreased cellular proliferation, DNA methylation methyl transferase 1 protein expression, and p16 promoter methylation, but not promoter methylation of the Wnt pathway antagonists, SFRP2 and WIF1, in rectal polyps (adenomas) from responders but not from nonresponders. The MBD-seq assay revealed more demethylated transcription start sites (TSS), including those for miRNAs, in BRB-treated adenomas from the responders. In conclusion, BRB suppositories seem sufficient for regressing rectal polyps in patients with FAP. Cancer Prev Res; 7(7); 666-74. Ó2014 AACR.

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Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions

Cited by 106 publications

References 43 publications

Proapoptotic, Anti-Cell Proliferative, Anti-Inflammatory And Antiangiogenic Potential Of Carnosic Acid During 7,12 Dimethylbenz[A]Anthracene-Induced Hamster Buccal Pouch Carcinogenesis

Proapoptotic, Anti-Cell Proliferative, Anti-Inflammatory And Antiangiogenic Potential Of Carnosic Acid During 7,12 Dimethylbenz[A]Anthracene-Induced Hamster Buccal Pouch Carcinogenesis

Differential Proteomics Identifies Protein Biomarkers That Predict Local Relapse of Head and Neck Squamous Cell Carcinomas

A Phase Ib Study of the Effects of Black Raspberries on Rectal Polyps in Patients with Familial Adenomatous Polyposis

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