{NCI pa: Exploratory Studies in Cancer Detection, Prognosis and Prediction (similarity to NCI-PA98-022); revised R21 application. Cervical cancer is a leading gynecologic malignancy with 14,500 new cases and 400 deaths yearly. Eighty to 90% of women with cervical cancer are infected with human papillomavirus (HPV). Cervical intra- epithelial neoplasia (CIN) markers the pre-cancerous stage. Ten to 20% of women develop cervical cancer. Paper smears and HPV testing have limitations in identifying women progressing to cancer, not helpful in the patients with ASCUS/AGUS (atypical squamous/glandular cells of undetermined significance) and for monitoring therapy efficacy (paucity of tissue after therapy) in recurrence. Our data-supported hypothesis is that progression of squamous cell cervical cancer from CIN is related to up-regulation of EGF-R and insulin-like growth factor-II (IGF-II) proteins in cervical epithelium, followed by significant increases in serum IGF-II levels (specific to cervical cancer; levels decrease after therapy. Our latter finding provides us with an excellent opportunity to develop a non-invasive screening test that gives an added value to pap smear and HPV testing. We propose that: Serum IGF-II levels can be used to identify patients who are at risk of developing cervical cancer and, more importantly, to monitor therapy efficacy in the patients with cervical cancer. We shall obtain serum levels of IGF-II (ELISA) in women with: 1. Normal Pap smear; 2. Abnormal Pap smear with no CIN; 3. Endometrial or ovarian cancer; 4. CIN-I, II or III pre-treatment; 5. CIN-I, II or III, post-treatment; 6. Invasive cervical cancer pre- treatment or at a time of hysterectomy; and, 7. Invasive cervical cancer (6 months and a year) post-treatment. We shall correlate the levels of IGF-II with clinical diagnosis of CIN or cervical cancer, size of neoplasm and resolution or recurrence of the disease and the smoking history. We believe that serum IGF-II test could compliment the Pap test to reduce deaths by cervical cancer.
| Lane, Derrick; Gray, Elizabeth A; Mathur, Rajesh S et al. (2005) Up-regulation of vascular endothelial growth factor-C by nicotine in cervical cancer cell lines. Am J Reprod Immunol 53:153-8 |
| Mathur, Subbi P; Mathur, Rajesh S; Creasman, Willaim T et al. (2005) Early non-invasive diagnosis of cervical cancer: beyond Pap smears and human papilloma virus (HPV) testing. Cancer Biomark 1:183-91 |
| Mathur, Rajesh S; Mathur, Subbi P (2003) In vitro downregulation of growth factors by insulin-like growth factor binding protein-3 in cervical cancer. Gynecol Oncol 91:410-5 |
| Mathur, Subbi P; Landen, Charles P; Datta, Susan M et al. (2003) Insulin-like growth factor II in gynecological cancers: a preliminary study. Am J Reprod Immunol 49:113-9 |
| Mathur, Subbi P; Mathur, Rajesh S; Underwood, Paul B et al. (2003) Circulating levels of insulin-like growth factor-II and IGF-binding protein 3 in cervical cancer. Gynecol Oncol 91:486-93 |
