الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Oral squamous cell carcinoma (OSCC) is a prominent subset of head and neck cancers, which are the sixth most common cancer worldwide and the third most common cancer in developing nations. It remains one of the most difficult malignancies to control because of its high ability for local invasion and metastasis. Despite the advance in the therapeutic strategies, the prognosis and survival rates of OSCC patients is still poor.
The development of OSCC is a multi-step process comprised of initiation, promotion and progression. One of the theories regarding oral carcinogenesis is that the tumor growth is dependent on cancer stem cells (CSCs) that have the capacity of self-renewal and promote tumor initiation, progression and metastasis. Furthermore, there is a strong focus on CSCs and its role in cancer development. Specific markers for this cells as CD44 have been investigated in the hope of developing a deeper understanding of their role in the pathogenesis of OSCC and producing novel therapeutic strategies, as curative therapy available for oral cancer.
The anticancer drugs need to be tested for their efficacy in killing CSCs rather than the bulk population of cancer cells. Genistein, as a chemopreventive agent has been shown to suppress the growth of several types of cancer by decreasing the methylation of DNA. Oxaliplatin is a chemotherapeutic compound that has shown a wide range of anti-tumor activity by disrupting the replication and transcription of DNA structure.
The objective of the current work was to study and compare the effect of genistein and oxaliplatin (each alone and in combination) during experimentally 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch (HBP) carcinogenesis using CD44 antibody as CSCs marker.
A total of 100 adult golden Syrian hamsters were included in this experimental study. Four animals were examined for normal histological pattern. The remaining 96 animals were distributed into groups as follows: a control, group I, painted with paraffin oil only; group II, painted with DMBA mixed in a heavy mineral oil. Then the animals in group II randomly were divided into 4 subgroups as following: group IIA, was only painted with DMBA; group IIB, was given orally administrated genistein; group IIC, was injected with oxaliplatin once weekly; group IID, was given both genistein and oxaliplatin. Clinicopathological, histopathological and immunohistochemical evaluation of the animals’ tissues were done every 4 weeks.
The decrease in the proliferation and activity of CSCs as well as the reduction in carcinogenesis process were highly statistically significant in animals that received genistein orally (daily 20 mg/kg), as a chemopreventive agent, compared to the animals that were only treated by DMBA. Moreover, the oxaliplatin demonstrated effectiveness and tolerance in reducing the DMBA carcinogenesis process as well as in reducing the proliferation and activity of CSCs in a dose of 4 mg/kg once weekly.
Furthermore, the combined effect of a natural chemopreventive agent (as genistein) and a chemotherapeutic drug (as oxaliplatin), was more effective in reducing the proliferation and activity of CSCs as well as the carcinogenesis process of inducing OSCC, than using each one alone.