Minor Assignment

           My research question is the following; what are the impacts of mesenchymal stem cells (MSCs) on tumor proliferation and tumor angiogenesis in cervical cancer cells-transplanted into nude mice. Nowadays, a number of clinical trials on MSCs therapy have been rising since 2004, especially tissue repair because MSCs can possess self-renewal and can be differentiated into ectoderm, mesoderm, and endoderm and also can home to inflammatory sites such as wound. Tumor environment is characterized by the presence of inflammatory cells as well as wound. However, the impact of MSCs on tumor environment remains controversial.

           Researchers who have looked at this subject are Huang and co-worker, and Kéramidas and co-worker. Both of studies focused on the impact of MSCs on tumor growth and tumor angiogenesis, although they did experiments in the different cancer models. These results were interesting evidences for research in this filed as well.

         Huang and co-worker (2013) argue that MSCs increased the tumor growth and tumor angiogenesis through interleukin-6/endothelin-1/alternatively protein B (IL-6/ET-1/Akt) pathway by activating MSCs-secreted IL-6 in human colorectal cancer cells-transplanted nude mice.

     In contrast, Kéramidas and co-worker (2013) investigate the impact of MSCs in adenocarcinoma cells-transplanted nude mice model. They found MSCs decreased tumor growth. Although they could not decrease tumor angiogenesis, they could normalize tumor vasculature.

         The results of both studies were controversial. Therefore, my study aims to clarify this issue in cervical cancer cell-transplanted nude mice model.

        My work will be closer to Huang’s and Kéramidas’ because both studies demonstrated the impact of MSCs on colorectal cancer and adenocarcinoma cancer, respectively. My study will investigate the impact of MSCs on tumor growth, tumor angiogenesis, and involved mechanisms in cervical cancer-transplanted nude mice model.

       The findings of my study may be a new knowledge for further experiments or cancer therapies.

References:

1. Huang, W.H., Chang, M.C., Tsa, K.S., Hung, M.C., Chen, H.L., & Hung, S.C. (2013). Mesenchymal stem cells promote growth and angiogenesis of tumors in mice. Oncogene, 12;32(37):4343-54.

2. Kéramidas, M., Fraipont, F., Karageorgis, A., Moisan, A., Persoons, V., Richard, M., & et al. (2013). The dual effect of mesenchymal stem cells on tumour growth and tumour angiogenesis. Stem Cell Research & Therapy, 4:41. 

Assignment2 (Introduction)

The anti-tumor effect of curcumin on pRb degradation and plasma protein extravasation releasing in cervical cancer-implanted nude mice model

Natchaya Wongeakin

Stage1: Almost all cases of cervical cancer which are attributed by HPV infection is the fourth most common cancer in women worldwide. It is also the fourth most common cause of cancer death (266,000 deaths in 2012); almost 70% of cases are in areas with lower levels of development (WHO, 2013). Nowadays, ICO HPV Information Centre estimates that every year 8,184 Thai women are diagnosed with cervical cancer and 4,513 Thai women die from the disease. Cervical cancer ranks as the 2nd most common cancer in Thai women, especially women between 15 and 44 years of age (ICO Information Centre on HPV and Cancer, 2014).

Satge2: The major oncogenic HPV protein E7 is involved in the immortalization of target cells by inactivation of cellular tumor suppressor retinoblastoma protein (pRb), leading to the release of activation of E2f (Huh et al, 2007). The pRb degradation can enhance angiogenic factors through HIF pathway leading to cancer cell proliferation and differentiation, and cancer nrovascularization (Duxbury and Whang, 2007; Wang et al 2014). In addition to angiogenic factors, HIF pathway is also associated with endothelial progenitor cell (EPC) migration to mediate cancer neovascularization (Matsui et al, 2004; Litz et al, 2006) by motivating of plasma protein extravasation releasing such as SDF-1 (Ceradini et al, 2004; kioi et al, 2010). In recently, plants contain numerous bioactive molecules such as polyphenols are used for prevention and treatment in various diseases. Curcumin is the one of polyphenols which several researches indicated the anti-tumorigenic property (Basu et al, 2013; Dai et al, 2013; Yin et al, 2013).
 

Stage3: However, it is unclear whether curcumin could decrease cervical cancer progression by inhibiting pRb degradation and plasma protein extravasation releasing in cervical cancer.

Stage4: In the present study aim to investigate the anti-tumor effects of curcumin on pRb and SDF-1 expressions in cervical cancer-implanted nude mice model.

Stage5: These findings would identify a novel treatment to decrease cervical cancer progression.