Cervical cancer is the second most frequently diagnosed cancer and the second leading cause of cancer related deaths in women worldwide. American Indian (AI) women living on the Northern Plains have a greater incidence of cervical cancer and suffer from a higher mortality rate. Our recent studies have shown that AI women have more than twice the incidence of HPV infection and that HPV positive AI women have a two times higher likelihood of having abnormal PAP tests than HPV positive Caucasian women; suggesting underlying causes which increase HPV pathology. One potential cofactor may be smoke exposure and its effects on the host immune response and HPV oncogenesis. Our data indicate that 4 times more AI women smoke as compared to Caucasian women and the majority of HPV positive AI women smoke. While smoking is a recognized risk factor for cervical cancer, the molecular interactions between HPV and smoke compounds are unknown. Our laboratory has recently shown that smoke carcinogen Benzo[a]Pyrene (BaP) increases the expression of HPV oncoproteins, suggesting a direct molecular link between HPV infection and exposure to smoke. We have also identified that curcumin, a natural anti-cancer compound, effectively inhibits the expression of HPV oncoproteins. Based on this compelling evidence, we hypothesize that exposure to tobacco smoke synergizes with HPV infection and increases the incidence and severity of cervical cancer in American Indian women by increasing the expression of HPV oncoproteins (E6/E7) and modulating cellular/humoral immune responses. Additionally, we hypothesize that curcumin or nanocurcumin may be effective methods for the repression of HPV infection in AI women. We propose to 1) investigate novel mechanisms of synergy between HPV infection, BaP and the development of cervical cancer, 2) evaluate the efficacy of curcumin/nanocurcumin to suppress HPV oncogene expression in preclinical and clinical settings, and 3) to investigate the effect of smoke exposure on cervical immune responses. The results of this study will provide information regarding underlying etiological factors that are responsible for cervical cancer health disparity in AI women and will ultimately reduce the burden of cervical cancer.
| Ganju, Aditya; Chauhan, Subhash C; Hafeez, Bilal Bin et al. (2018) Protein kinase D1 regulates subcellular localisation and metastatic function of metastasis-associated protein 1. Br J Cancer 118:587-599 |
| Khan, Sheema; Zafar, Nadeem; Khan, Shabia S et al. (2018) Clinical significance of MUC13 in pancreatic ductal adenocarcinoma. HPB (Oxford) 20:563-572 |
| Kumari, Sonam; Khan, Sheema; Gupta, Subash C et al. (2018) MUC13 contributes to rewiring of glucose metabolism in pancreatic cancer. Oncogenesis 7:19 |
| Karuri, Asok Ranjan; Kashyap, Vivek Kumar; Yallapu, Murali Mohan et al. (2017) Disparity in rates of HPV infection and cervical cancer in underserved US populations. Front Biosci (Schol Ed) 9:254-269 |
| Hafeez, Bilal Bin; Ganju, Aditya; Sikander, Mohammed et al. (2017) Ormeloxifene Suppresses Prostate Tumor Growth and Metastatic Phenotypes via Inhibition of Oncogenic ?-catenin Signaling and EMT Progression. Mol Cancer Ther 16:2267-2280 |
| Setua, Saini; Khan, Sheema; Yallapu, Murali M et al. (2017) Restitution of Tumor Suppressor MicroRNA-145 Using Magnetic Nanoformulation for Pancreatic Cancer Therapy. J Gastrointest Surg 21:94-105 |
| Khan, S; Sikander, M; Ebeling, M C et al. (2017) MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression. Oncogene 36:491-500 |
| Ganju, Aditya; Khan, Sheema; Hafeez, Bilal B et al. (2017) miRNA nanotherapeutics for cancer. Drug Discov Today 22:424-432 |
| Setua, Saini; Khan, Sheema; Doxtater, Kyle et al. (2017) miR-145: Revival of a Dragon in Pancreatic Cancer. J Nat Sci 3: |
| Boya, Vijayakumar N; Lovett, Renn; Setua, Saini et al. (2017) Probing mucin interaction behavior of magnetic nanoparticles. J Colloid Interface Sci 488:258-268 |
Showing the most recent 10 out of 31 publications
