Oral carcinoma

Yamamoto, T. et al. Role of EGCG-targeted p57/KIP2 in reducing tumorigenicity of oral carcinoma cells and blocking c-jun N-terminal kinase-mediated apoptosis. Toxicol. Appl. Pharmacol. 224, 318, 2007. 

The mitomycins are a family of aziridine-containing antibiotics isolated from Streptomyces lavendulae. One of these antibiotics, mitomycin C (MMC), is an antitumor antibiotic frequently used for the treatment of breast, lung, stomach, intestinal, testicular, cholioepithelial, seminal and oral carcinoma [18-20]. When human oral squamous cell carcinoma cell lines (HSC-2, HSC-4) were treated with MMC, the viable cell number was dose-dependently reduced (CC50 of MMC against HSC-2, HSC-3 and HSC-4 cells 3.5, 9.7 and 18 xM, respectively, determined 24 hours after treatment). The rapid decline of polyamines (measured at 3 hours after MMC treatment) was observed prior to the expression of early apoptosis markers such as the production of annexin-positive cells and caspase activation (Table 1) [21]. The interactions... 

In an investigation of the antitumor activities of ot-tocopherol acid succinate and acetate, the acid succinate form inhibited the growth of oral carcinoma cells, while stimulating the growth and differentiation of normal keratinocytes. The acetate form increased thymidine incorporation and mutant p53 expression in cancer cells, thereby increasing proliferation and... 

Vitamin K2 (menaquinone) represents a series of compounds in which the phytyl side chain of phytonadione has been replaced by a side chain built up of 1-14 isoprenyl units. It has been reported that vitamin K2 with four isoprenyl units (4) induced the monocytic differentiation of human myeloid leukemia cell lines [58], or apoptosis in isolated osteoclast [59] and human ovary cancer cells [60]. We have recently found that vitamin K2 derivatives (1-3) induced some tumor-specific cytotoxicity and non-apoptotic cell death in oral carcinoma [61]. As an extension of the search for tumor-specific substances targeted against human oral squamous, hepatocellular carcinoma, and promyelocytic leukemia cell lines, we investigated the QSAR of seven vitamin K2 derivatives (1-7) (Fig. 18), by conventional and recent techniques of computation chemistry, such as the concept of absolute hardness [ 16-18]. 

Pan XQ, Wang H, Lee RJ (2003) Antitumor activity of folate receptor-targeted liposomal doxorubicin in a KB oral carcinoma murine xenograft model. Pharm Res 20 417-422... 

Koyama K, Uobe K, Tanaka A. Highly sensitive detection of HPV-DNA in paraffin sections of human oral carcinomas. J Oral Pathol Med. 2007 36(l) 18-24. 

A-431 (epidermoid carcinoma) OKK (maxillary gland carcinoma) KATO-III (stomach carcinoma) KB (oral carcinoma) WiDr (colon adenocarcinoma) 1-407 (normal embryonic intestine) A-22 (arachnoid) NY (osteosarcoma) T-2346 (meningeoma) T-24 (bladder carcinoma) HLEC-1 (liver carcinoma)... 

Einhom J. and Wersall, J., Incidence of oral carcinoma in patients with leukoplakia of the oral mucosa, Cancer, 20, 2189,1967. 

Gonzalez de Mejia, E., Y.S. Song, M.V. Ramirez-Mares, and H. Kobayashi. 2005. Effect of yerba mate (Ilex paraguariensis) tea on topoisomerase inhibition and oral carcinoma cell proliferation. J. Agric. Food Chem. 53(6) 1966-1973. 

Zhuo X, Zhao H, Chang A, Ye H, Zhou Y, Song Y Tan Y (2012) Cytochrome P450 lAlIle462Val polymorphism and oral carcinoma risk an updated meta-analysis including 1515 cases and 2233 controls. Tumour Biol 33 2079-2089... 

Lymphoscintigraphy and sentinel node biopsy is a minimally invasive technique that samples first echelon lymph nodes and predicts the need of more extensive neck dissection. The accuracy has been assessed on oral cancers undergoing preoperative PET/CT followed by sentinel node biopsy (Civantos et al. 2003). Gross tumour replacement of lymph nodes and redirection of lymphatic flow represented a significant technical issue in oral carcinomas (Civantos et al. 2006). 

Tumour necrosis factor-a (TNF-a) transiently increased intracellular superoxide and other reactive oxygen species production in human fibroblasts (Meier et al. 1989) and human oral carcinoma SCC-25 cells (Liu et al. 2000). 

In a recent report by Tsai et al. [168], the cytotoxicity of DOX-loaded chitosan/ chondroitin (CHT/CHO) PEC particles to human oral carcinoma and lung carcinoma cells was studied with methacrylate modification and/or crosslinking as... 

Newly synthesized proteins were observed in oral carcinoma cells after treatment with ascorbic acid and other antioxidant nutrients. The treatment of the oral cancer cells with ascorbic acid produced a unique protein profile compared to untreated tumor control cells. Specifically, proteins at about 100 kDa and 80-60 kDa were noted following ascorbic acid treatment. This was similar to protein changes induced by reduced glutathione, an intracellular antioxidant. 

An immunoblot indicated that the level of the protein Bcl-2 was depressed when ascorbic acid was applied to tumor cells at a concentration of 70 p,M. Additional studies indicated that ascorbic acid at concentrations as low as 20 xM-1.25 p,M produced nucleosome formation (DNA fragmentation) of some of the tumor cells in a dose-dependent manner (Figs. 8 and 9). Subsequently, a determination of reduced levels of total mercaptans and intracellular levels of glutathione further suggested a prooxidant characteristic to the ascorbic acid treatment of the oral carcinoma cells (Figs. 10 and 11). 

FIGURE 8. Nucleosome formation in a human oral carcinoma cell line (SCC-25) was observed following treatment with ascorbic acid (20 xM, 3hr) (A), in comparison to untreated tumor cells (B). 

FIGURE 10. The total mercaptan concentration was ascertained following various treatments. The treatment with ascorbic acid (70 jxM, 6 hr) produced a significant reduction of mercaptans in a hamster oral carcinoma cell line (HCPC-1). The treatments were as follows 1) untreated, 2) p-carotene, 3) a-tocopherol acid succinate, 4) canthaxanthin, 5) reduced glutathione, 6) retinyl palmitate, 7) ascorbic acid. 

Noble, P.B. and Bentley, K.C., Locomotory characteristics of human lymphocytes undergoing negative chemotaxis to oral carcinomas. Exp. Cell Res., 1981,133 457-461. 

It is important to state here that these compounds have not been found to increase communication between established tumor cells and normal cells [5] this would be consistent with their inability in the lOTl/2 system to inhibit expression of the transformed phenotype i.e. growth of tumor cells in a background of normal cells, and with the experimental animal data showing that these compounds are active in the post-initiation phase of carcinogenesis prior to the establishment of tumors. These observations would also be consistent with the lack of ability of retinoic acid to inhibit solid tumor growth in clinical trials in head and neck cancer [16]. Thus, in general, the actions of carotenoids and retinoids are considered to be preventive and not therapeutic. In a recent study of dysplastic regions of the oral cavity in patients with a prior history of oral carcinoma, we discovered that even in these pre-cancerous lesions major reductions in connexin 43 expression had occurred [17]. Studies are underway to determine if retinoids can counter this decrease. 

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