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Biomedical subjects

Ole Mogensen

Publications and source records attributed to Ole Mogensen.

7 recordsLinked to original sources

Expression of the epidermal growth factor system in endometrioid endometrial cancer.

OBJECTIVE: The Epidermal Growth Factor (EGF) system is expressed in healthy premenopausal endometrium. We describe the expression of the four receptors, HER1, HER2, HER3, HER4 and the six ligands amphiregulin, transforming growth factor alpha (TGF-alpha), heparin binding EGF like growth factor (HB-EGF), betacellulin, epiregulin and EGF in endometrioid endometrial cancer. METHODS: We have uterine samples from 45 women with endometrioid endometrial cancer. As normal counterparts, endometrial samples from thirteen postmenopausal women, and previous data on fourteen premenopausal women were employed. Extracted RNA was analyzed by real-time PCR; the receptors and ligands were localized by immunohistochemistry. RESULTS: Three receptors (HER1, HER2 and HER4) and two detectable ligands (TGF-alpha and HB-EGF) are expressed significantly higher in endometrial cancer than in healthy postmenopausal endometrium. Cancer tissue show significantly lower expression of HER1 and HER3, and higher expression of HER4, amphiregulin, TGF-alpha and HB-EGF compared to premenopausal endometrium; no difference is seen in HER2. EGF is undetectable in all of the samples. Immunohistochemically the receptors locate to the epithelium and/or glands while the ligands locate to the stroma (amphiregulin), the stroma and the epithelium (TGF-alpha, epiregulin), the epithelium (betacellulin) or are not detectable (HB-EGF, EGF). CONCLUSIONS: mRNA of all receptors and five ligands are present in endometrioid endometrial cancer, and the protein of all receptors and four ligands are identified by immunohistochemistry. The expression pattern in endometrioid endometrial cancer differs from the pattern in pre- and postmenopausal endometrium. The most remarkable finding is an increased level of HER4, a receptor which correlates to a favorable prognosis in other types of cancers.

Adult↗

RNA quality and gene expression analysis of ovarian tumor tissue undergoing repeated thaw-freezing.

Gene expression profiles evaluated by microarray-based quantization of RNA are used in studies of differential diagnosis and prognosis in cancer. RNA of good quality is mandatory for this evaluation. The RNA most often comes from tumor banks with limited amount of tissue, and the tissue often undergoes repeated thawing and freezing. We evaluated the influence of repeated division of tumor samples at room temperature, on RNA quality and quantity, in addition to the gene expression profile. Sixteen ovarian tumor samples were divided in three aliquots each, undergoing respectively one, two, and three thaw-freeze cycles. RNA from each aliquot was extracted on the day of division, and quantity and quality were evaluated. RNA from all three aliquots of four tumor samples underwent microarray analysis on Affymetrix Human Genome U133A 2.0 arrays. Microarray data were evaluated using both unsupervised, and supervised multivariate statistical methods, reliability analysis, as well as verification using published gene lists in ovarian cancer studies. RNA quality and quantity did not change during the division procedure and microarray data showed insignificant difference in gene expression. Tumor samples from tumor banks can be frozen and thawed at least three times without compromising the RNA integrity and genetic expression profile.

Cryopreservation↗

Carcinoma in situ cervicis uteri and inheritance--a Danish twin study.

OBJECTIVE: To determine the relative environmental and genetic influence in the development of carcinoma in situ (CIS) cervicis uteri. METHODS: Retrospective follow-up study with record linkage between The Danish Twin Register and The Danish Cancer Register. The study base comprises 27,004 female twins from 13,502 same-sex twin pairs. 5,258 were monozygotic and 8,244 dizygotic twin pairs. The statistic measurements are the coincidence ratio and the probandwise concordance rate in the two groups of twins with different zygosity. RESULTS: 750 twins were diagnosed with CIS cervicis uteri. 291 monozygotic twins came from 275 pairs and 459 dizygotic twins came from 435 pairs. There were 16 concordant monozygotic twin pairs and 24 concordant dizygotic pairs. The probandwise concordance rate was 0.11 (0.06-0.16) in monozygotic twins and 0.10 (0.06-0.14) in dizygotic twins. CONCLUSION: A family clustering of CIS was demonstrated in both groups of zygosity. The probandwise concordance rate was equal in the monozygotic and the dizygotic groups, which means that genetic factors are not important in the development of the disease. However, a shared environment among twins plays a role in the development of CIS cervicis uteri.

Adult↗

Serum protein profiling by miniaturized solid-phase extraction and matrix-assisted laser desorption/ionization mass spectrometry.

Serum profiling by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) holds promise as a clinical tool for early diagnosis of cancer and other human diseases. Sample preparation is key to achieving reproducible and well-resolved signals in MALDI-MS; a prerequisite for translation of MALDI-MS based diagnostic methods to clinical applications. We have investigated a number of MALDI matrices and several miniaturized solid-phase extraction (SPE) methods for serum protein concentration and desalting with the aim of generating reproducible, high-quality protein profiles by MALDI-MS. We developed a simple protocol for serum profiling that combines a matrix mixture of 2,5-dihydroxybenzoic acid and alpha-cyano-4-hydroxycinnamic acid with miniaturized SPE and MALDI-MS. Functionalized membrane discs with hydrophobic, ion-exchange or chelating properties allowed reproducible MALDI mass spectra (m/z 1000-12,000) to be obtained from serum. In a proof-of-principle application, SPE with chelating material and MALDI-MS identified protein peaks in serum that had been previously reported for distinguishing a person diagnosed with breast cancer from a control. These preliminary results indicate that this simple SPE/MALDI-MS method for serum profiling provides a versatile and scalable platform for clinical proteomics.

Blood Proteins↗

Chemotherapy-induced changes of CA 125 in patients with epithelial ovarian cancer.

OBJECTIVES: CA 125 is a tumor marker widely used to diagnose, monitor, and follow-up women with epithelial ovarian cancer, as the marker is well related to the amount of vital tumor cells. However, CA 125 before the operation or during the first 2 courses of chemotherapy does not provide enough information concerning survival to serve as a prognostic marker. The present investigation was inspired by studies describing a paradoxical increase of tumor markers (CEA, CA 125, and CA 15-3) in the days after chemotherapy of women with breast cancer. If CA 125 increases within days after chemotherapy, the increase may be caused by death of the cancer cells. It was therefore speculated if a CA 125 spike may serve as an early prognostic parameter. The aim of the present investigation was to evaluate if CA 125 increases within days after the first course of chemotherapy of women with ovarian cancer. PATIENTS: Twenty women with epithelial ovarian cancer were included in the study. CA 125 was measured in each woman on day 0 (the day of, but before initiation of chemotherapy) and 1, 3, 5, 7, 9, and 14 days after chemotherapy. RESULTS: One woman was excluded due to normal CA 125 values. The remaining 19 patients displayed a significant decrease in CA 125 during the 14-day period after chemotherapy. CONCLUSION: In the present study, no chemotherapy-induced increase of CA 125 within the first 14 days after chemotherapy could be demonstrated.

Adult↗

Management of ovarian cysts.

BACKGROUND: The treatment of an ovarian cyst relies on its nature, and accurate preoperative discrimination of benign and malignant cysts is therefore of crucial importance. This study was undertaken to review the literature concerning the preoperative diagnosis and treatment of ovarian cysts. METHODS: Articles concerning ovarian cysts from a medline literature search during the period 1985-2003 were included in addition to articles found as references in the initial publications. RESULTS: Different methods for discriminating between benign and malignant ovarian cysts are discussed. The diagnosis and the treatment are assessed in relation to age, menopausal status, pregnancy, and whether the cyst is presumed to be benign or malignant. In general, expectant management is the choice in premenopausal and pregnant women with non-suspicious cysts and normal levels of CA-125. In postmenopausal women, unilocular, anechoic cysts less than 5 cm in diameter together with a normal CA-125 may be followed up. Operation is recommended in women with cysts larger than 5 cm and/or elevated levels of CA-125. Women with symptoms should be operated regardless of age, menopausal status, or ultrasound findings. CONCLUSIONS: The preoperative discrimination between benign and malignant ovarian cysts is a challenge. Multimodal methods improve the results of single modalities, but we still need improved preoperative diagnostic tools. Furthermore, these methods should be validated in consecutive patient populations large enough to give a reliable estimate of the method's sensitivity and specificity.

CA-125 Antigen↗

The prognostic value of pre-operative serum tetranectin, CA-125 and a combined index in women with primary ovarian cancer.

OBJECTIVE: To study the prognostic value of pre-operative serum tetranectin (TN), CA125 levels and a mathematical formula (Index1) in primary ovarian cancer. MATERIALS AND METHODS: The study group consisted of sixty-six patients with varying FIGO stages I-IV. The end-point was death from ovarian cancer. Evaluation was by univariate life-tables analyses and the multivariate Cox analysis. In the Cox analyses, the variables were tested respectively in actual values and as dichotomy variables with different cut-off levels: 6.7, 7.3 and 8.2 mg/l for TN, 35, 65, 100 and 165 U/ml for CA125. RESULTS: In stages I+II only CA125 was found to be significantly prognostic, whereas TN was of no prognostic value by univariate statistics. For stages III+IV patients significantly better survivals were found for patients with TN levels above the respective cut-offs compared to patients with low TN levels, whereas no significant value was found for CA125 by univariate statistics. In the Cox analyses, FIGO stage was the strongest and TN the second most prognostic variable, followed by age. CA125, Index1 and tumor types were of no prognostic value. The strongest prognostic value for TN was found at the cut-off level 8.2 mg/l (relative hazard for FIGO stages = 3.3 and for TN = 2.6). CONCLUSION: TN was a strong prognostic variable in patients with advanced ovarian cancer. To the contrary, CA125 was a strong prognostic factor in patients with a localised ovarian cancer and of no prognostic value in patients with advanced cancer. The variables may be useful in the selection of patients with a poor outcome for new treatment strategies.

Adult↗