High unmet medical need for tumor markers
CEPA has prioritized its clinical development program in terms clinical utility and unmet medical need for tumor markers. The projects outlined below are based on RT-PCR analyses of HMGA expression that allow for quantitation of the transcripts.
(1) HMGA expression in peripheral blood of breast cancer patients
Background - Breast cancer is one of the most common human malignancies. In Europe and the United States it affects about one in ten women once in her life. Both an increased incidence and reduced mortality from the disease have generated a large patient population requiring medical follow-up. Despite some available tumor markers there is still a need to have better markers for monitoring these patients (locoregional recurrence, metastases).
Aims - To use HMGA gene expressing breast cancer cells circulating in the peripheral blood of cancer patients for monitoring of patients. To determine the sensitivity and specificity of this marker and the marker lead-times.
Samples/Methods - Blood samples from breast cancer patients and controls. Isolating RNA from the samples, preparing cDNA thereof and amplification of specific transcript(s) by quantitative RT-PCR. Clinical follow-up.
Selected references:
- Mol Carcinog. 1997 Jul;19(3):153-6.
Expression of HMGI-C, a member of the high mobility group protein family, in a subset of breast cancers: relationship to histologic grade.
Rogalla P, Drechsler K, Kazmierczak B, Rippe V, Bonk U, Bullerdiek J. - Br J Cancer. 2003 May 6;88(9):1406-10.
Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer.
Langelotz C, Schmid P, Jakob C, Heider U, Wernecke KD, Possinger K, Sezer O. - Histol Histopathol. 2003 Oct;18(4):999-1004.
High mobility group protein HMGA1 expression in breast cancer reveals a positive correlation with tumour grade.
Flohr AM, Rogalla P, Bonk U, Puettmann B, Buerger H, Gohla G, Packeisen J, Wosniok W, Loeschke S, Bullerdiek J.
(2) Characterization of thyroid nodules by HMGA expression patterns
Background - Thyroid nodules are common tumors in the general population and only a small proportion of them are malignant. Nevertheless, it is well known that initially benign tumors can become malignant. Biopsy by fine-needle aspiration is one of the first line investigations of solitary nodules but there are difficulties in objectively identifying those thyroid nodules that are malignant or are at risk to become malignant, respectively. Tumor markers and prognostic indicators will help to avoid unnecessary surgery and to find the best therapeutic options in those patients who have thyroid carcinoma.
Aims - To check a larger series of samples obtained by fine-needle aspiration for expression of HMGA genes. To correlate the findings with the results of cytopathology and follow-up.
Samples/Methods - Samples obtained by fine-needle aspiration and matching blood samples. Isolating RNA from the samples, preparing cDNA thereof and amplification of specific transcript(s) by quantitative RT-PCR. Conventional cytology/histology.
Selected references:
- Cancer Res. 1998 Sep 15;58(18):4193-8.
Detection of high mobility group I HMGI(Y) protein in the diagnosis of thyroid tumors: HMGI(Y) expression represents a potential diagnostic indicator of carcinoma.
Chiappetta G, Tallini G, De Biasio MC, Manfioletti G, Martinez-Tello FJ, Pentimalli F, de Nigris F, Mastro A, Botti G, Fedele M, Berger N, Santoro M, Giancotti V, Fusco A. - Korean J Intern Med. 2000 Jan;15(1):71-5.
The expression of the high mobility group I(Y) mRNA in thyroid cancers: useful tool of differential diagnosis of thyroid nodules.
Kim SJ, Ryu JW, Choi DS. - Langenbecks Arch Surg. 2004 Jun;389(3):193-7. Epub 2004 Apr 24.
HMGI(Y) gene expression as a potential marker of thyroid follicular carcinoma.
Czy W, Balcerczak E, Jakubiak M, Pasieka Z, Kuzdak K, Mirowski M.
(3) Molecular urine cytology based on HMGA expression analyses
Background - Transitional bladder cancer is the most common bladder tumor and at initial diagnosis about 90% of these tumors are superficial. Even despite correct clinical management the tumors recur in approximately 70% of cases. Despite major research into other methods for early detection of recurrences urine cytology so far remains the gold standard.
Aims - To use urine samples for non-invasive detection of bladder cancer and its recurrences by determining the expression level of HMGA genes.
Samples/Methods - Taking an urine sample. Isolating the urothelial cells by centrifugation. Isolation of RNA thereof and preparing of cDNA. Determining the expression level of HMGA genes by quantitative RT-PCR. Correlation to clinical data.
(4) Screening of high risk patients for endometrial cancer
Background - Endometrial cancer is a malignant tumor of the lining of the uterus. Mainly occurring in postmenopausal women, there is an estimated number of about 35,000 newly diagnosed cases per year in the United States. The use of Tamoxifen in the treatment of breast cancer increases the risk of developing endometrial cancer. Transvaginal ultrasound (endometrial thickness) is often used to detect endometrial cancer in women taking Tamoxifen.
Aims - To develop a new non-invasive method for the early detection of endometrial cancer for example using cells obtained by uterine washings.
Samples/Methods - Endometrial cells obtained by non-invasive methods. Isolation of RNA thereof and preparing of cDNA. Determining the expression level of HMGA genes by quantitative RT-PCR. Correlation to follow-up and histopathology, respectively.