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Biomedical subjects

A Orbo

Publications and source records attributed to A Orbo.

At least 19 recordsLinked to original sources
PubMed2004

Genetic derangements in the tumor suppressor gene PTEN in endometrial precancers as prognostic markers for cancer development: a population-based study from northern Norway with long-term follow-up.

OBJECTIVES: The purpose of the current study was to characterize the role of PTEN in malignant transformation and to evaluate the significance of mutated PTEN exons as prognostic markers in the carcinogenesis of endometrial hyperplasia. A comparison of PTEN mutations as prognostic markers with former investigated prognosticators was also intended. METHODS: Histological material from 68 patients with endometrial hyperplasia and 10-20 years of follow-up of whom 18 later developed cancer was examined. PCR amplification and DNA sequencing were performed, screening the most frequently mutated exons 5a-8b of the PTEN gene. RESULTS: Mutations were demonstrated in 13.2% of the patients. Of the patients with cancer development, five showed to have PTEN mutations corresponding to 28%. Of the patients remaining without carcinoma, only 8% had PTEN mutations (P = 0.04). In total, there were three missense, three nonsense, and four frameshift mutations, and twice as many mutations leading to a truncated protein (six) than mutations altering one amino acid in the entire protein (three). Mutations were distributed in the following manner: three in exon 5a, two in exon 5b, two in exon 6, two in exon 7, and one in exon 8b. Only mutations in exons 6, 7, and 8a were connected with cancer development or coexisting cancer and six out of seven mutations within these exons were frameshift or nonsense mutations. CONCLUSIONS: Our results showed that mutations in the PTEN gene were statistically more frequent in cases with cancer development or coexisting cancer. Although the specificity was acceptable, the sensitivity of PTEN mutations was too low to make it suitable as a tumor marker (sensitivity of 27% and specificity of 91%) in clinical practice.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Loss of expression of MLH1, MSH2, MSH6, and PTEN related to endometrial cancer in 68 patients with endometrial hyperplasia.

Derangements in the tumor suppressor gene PTEN and the mismatch-repair genes, hMLH1, hMSH2, and hMSH6, have an important role in endometrial carcinogenesis. The purpose of this study was to assess immunohistochemically the pattern of protein expression for these genes in 68 patients with endometrial hyperplasia and to determine the relation of protein expression to cancer development or coexistence of cancers. Loss of expression of these genes also was evaluated as potential tumor markers for clinical use. PTEN and hMLH1 both showed loss of expression in 55% of specimens from 18 patients with subsequent or coexisting carcinoma. D&C specimens from 50 patients who did not develop cancer (10 patients underwent hysterectomy within 2 years; 40 had no hysterectomy; follow-up of 10-20 years), expressed protein at a much higher frequency (92% for PTEN and 98% for hMLH1). The parameter with the strongest independent relation to subsequent or coexisting carcinoma in a stepwise multiple logistic regression analysis was hMLH1. Evaluation of the investigated factors as prognostic markers for tumor development showed high specificity (92% for PTEN, 98% for MLH1) at the expense of sensitivity (56% for PTEN, 56% for MLH1). The results were compared with the results of the computerized image analysis algorithm, the D-score.

Adaptor Proteins, Signal Transducing↗
PubMed2000

[Computer-based morphometric image analysis of endometrial hyperplasia].

Former studies have shown that only 20% of endometrial hyperplasias progress to carcinoma. Objective criteria for predicting the outcome of hyperplasias have been lacking. Because hysterectomy has been the therapy of choice to avoid malignant development, overtreatment of these patients is still a clinical problem. A computer-based morphometric image analysis system has proved to be a considerable improvement for the pathologist in assessing which patients will develop cancer. The system is based on ten nuclear and twelve glandular architectural features. The three parameters with the best statistical power of discriminating between patients developing malignancy and those remaining healthy were combined into a morphometric classification rule (D-score or discriminating score). We give a brief description of this method and its background.

Endometrial Hyperplasia↗
PubMed2000

Computerised morphometrical analysis in endometrial hyperplasia for the prediction of cancer development. A long-term retrospective study from northern Norway.

AIMS: To evaluate and compare the long term prognostic value of the WHO classification and the computerised multivariate morphometrical D score in endometrial hyperplasia. To test the reproducibility of the D score in two different centres. METHODS: Histopathological WHO classification and computerised morphometrical analysis using the D score (< 0, high risk; > 1, low risk; 0-1, uncertain) in a population based study from northern Norway of archival dilatation and curettage material from 68 women with 10-20 years of follow up. RESULTS: Of the 68 patients included in the study, 18 developed cancer. The sensitivity and specificity of the D score (< 0 v > 1) were 100% and 78%, respectively, which was better than the WHO classification (89% and 60%, respectively). The negative and positive predictive values for the D score were 100% and 58% and of the WHO classification 94% and 44%, respectively. This study found a slightly higher specificity for the D score than former retrospective studies, but otherwise the results were comparable. The D score results were reproducible between the two centres (R = 0.91; slope = 0.98; intercept = 0.3). CONCLUSIONS: D score assessment is a reproducible and more accurate predictor of outcome of endometrial hyperplasia than the WHO classification assessed by an experienced gynaecological pathologist. Routine application of the D score might reduce over and undertreatment of endometrial hyperplasia.

Adult↗
PubMed1998

Urinary levels of cyclic guanosine monophosphate (cGMP) in patients with cancer of the uterine cervix: a valuable prognostic factor of clinical outcome?

Changes in urinary cyclic nucleotide levels have been reported in patients with various types of cancers. The present study was conducted to relate changes in urinary levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) to the clinical outcome of 11 patients treated for cancer of the uterine cervix. Urine was sampled for 24 h before and 3 months after primary treatment. The levels of cGMP increased in all the patients (n = 5) who relapsed within the observation period of 39 months. 4 of these patients showed an increased cGMP/cAMP ratio. In the patients without relapse (n = 6), the cGMP levels decreased, whereas the cGMP/cAMP ratios were unchanged. No marked changes in the levels of cAMP were observed for either of the groups. The measurement of urinary cGMP levels seems to be a valuable tool in the follow-up of patients with cancer of the uterine cervix.

Adult↗
PubMed1997

[How hazardous is the use of female steroid hormones?].

The development of female steroid hormone-related neoplasms such as gynaecologic and mammary cancers is influenced by hormones administered exogenously. Hormonal contraceptives and hormone replacement therapy both affect the risk of developing cancers in the endometrium, cervix, ovarium, and mammary glands. The authors refer to the recent literature and discuss the findings for the different types of cancers individually. Oestrogens promote development of cancers of the uterine corpus, but women who take progestins combined with oestrogens run no greater risk than women who do not take hormones. Female steroid hormones appear to increase the risk of developing cancer of the uterine cervix slightly, but protect against the development of ovarian cancer. An higher risk of developing mammary cancer is seen after taking oral contraceptive pills.

Breast Neoplasms↗
PubMed1996

[Tumor markers in gynecological cancer].

Tumour markers can be defined as biological changes indicating the existence of malignancy in the organism. After the development of monoclonal antibodies, an array of new tumor markers have been discovered over the last two decades. General guidelines are given for the use of tumour markers in practice. Finally, the markers of special relevance for gynecological oncology, and some other recently discovered markers are described.

Biomarkers, Tumor↗
PubMed1996

[Tamoxifen and endometrial cancer. A case report].

Tamoxifen is an oestrogen antagonist with partial agonistic effects that is used extensively in the treatment of mammary carcinoma. We report a case of an 80 year old woman who was operated on for carcinoma of the mammary gland and developed endometrial carcinoma after ten years of tamoxifen treatment. Tamoxifen has been noted for its reportedly low incidence of side effects. Since 1985, however, several reports have associated tamoxifen with higher risk of endometrial carcinoma. We also review the relevant literature published during the last decade.

Adenocarcinoma↗
PubMed1996

Export of guanosine 3',5'-cyclic monophosphate (cGMP) from human erythrocytes characterized by inside-out membrane vesicles.

The present study was undertaken to characterize the export of cGMP from human erythrocytes at 37 degrees C. Inside-out membrane vesicles were exposed to cGMP and [3H]-cGMP in the presence and absence of 2 mmol l-1 ATP. In the absence of ATP, an equilibrium was reached within 15 min for the lowest tested concentration (0.65 mumol l-1), and the amount of cGMP in the vesicles was linearly correlated to the cGMP concentrations in the incubate. These observations suggest that the ATP-independent process represents passive diffusion or non-saturated binding to membrane components. In the presence of ATP, cGMP accumulated linearly during the test period (up to 120 min) and the transport into the inside-out vesicles was dependent on both low- and high-Km transport. The kinetic parameters for the low-Km process were determined after 5 and 120 min, the Km values being 4.6 (SD 1.9) and 4.7 (SD 1.1) mumol l-1 (n = 3), respectively. The corresponding Vmax values were 400 (SD 50) and 440 (SD 70) fmol mg-1 min-1. The high-Km process was characterized by Km = 170 (SD 50) mumol-1 and Vmax = 1610 (SD 280) fmol mg-1 min-1 (n = 5). The present data demonstrate an ATP-requiring saturable transport system for cGMP in human erythrocytes.

Adenosine Triphosphate↗
PubMed1995

Effect of probenecid, verapamil and progesterone on the concentration-dependent and temperature-sensitive human erythrocyte uptake and export of guanosine 3',5' cyclic monophosphate (cGMP).

Elevated extracellular cGMP levels have been observed in various clinical conditions, and the analyte has been proposed as a diagnostic marker of cardiovascular as well as malignant diseases. However, the use of extracellular cGMP as a pathophysiological marker requires detailed knowledge about the cellular biokinetics of cGMP (synthesis, metabolic conversion and export). In the present study the transport of cGMP in human erythrocytes has been further characterized. The uptake of cGMP was dependent on a concentration gradient and was temperature-sensitive, compatible with passive diffusion. The cGMP export was temperature-sensitive, saturable (Km = 3.4 +/- 1.0 mu mol l-1), inhibited by probenecid and verapamil and stimulated by progesterone. The results show that human erythrocytes possess a cGMP transport system similar to that found in other cells and that extracellular levels of cGMP are dependent on intracellular levels, membrane transport and influenced by physiological factors and pharmacological agents.

Biological Transport↗
PubMed1994

Cell density dependence of cAMP and cGMP levels in four human cell lines derived from carcinomas of the uterine cervix.

Several studies have shown altered biokinetics of cyclic nucleotides in human cancer. In order to mimic the growing tumor bulk in carcinomas of the uterine cervix, four human cell lines (C4-I, C33A, ME-180, and SiHa) were expanded in serum-supplemented cell cultures. The extra- and intracellular levels of cAMP and cGMP were determined at increasing cell densities. In all of the cell lines, a cell density-dependent increase in the extracellular cGMP/cAMP ratio was observed. cAMP was distributed to the extracellular compartment against a concentration gradient at low cell densities but was retained in the intracellular compartment at high cell densities. In contrast, cGMP was distributed to the extracellular compartment against a concentration gradient for the whole range of cell densities. This study suggests that the cell density-dependent increase in the extracellular cGMP/cAMP ratio in cell lines derived from carcinomas of the uterine cervix is a result of changes occurring in both intracellular levels and cellular excretion of cyclic nucleotides.

Cell Count↗
PubMed1993

Effect of serum and cell density on transmembrane distribution of cAMP and cGMP in transformed (C4-I) and non-transformed (WI-38) human cells.

The ratio between cGMP and cAMP in plasma/urine is elevated in several types of malignancies. The present in vitro study showed that the ratio between extracellular cGMP and cAMP increased during the proliferation of C4-I cells (derived from a carcinoma of the uterine cervix), whereas this ratio decreased in WI-38 cells (normal lung fibroblasts). These results can be explained by differences between the transformed and non-transformed cells in the cell-density-dependent transmembrane distribution and intracellular levels of cyclic nucleotides. In the serum-deprived cultures, no profound effects were seen on the cell-density-dependent biokinetics of cAMP and cGMP. In the absence of serum, growth of C4-I cells was markedly retarded, whereas WI-38 cells were unable to expand at all.

Cell Count↗
PubMed1990

Topographic criteria in the diagnosis of tumor emboli in intramammary lymphatics.

Topographic relationships to adjacent structures were used as criteria to identify intramammary lymphatics with tumor emboli in breast cancer patients, in addition to conventional morphologic criteria. Patterns of relationship to blood vessels, non-neoplastic lobules and ducts, and empty lymphatics were defined. Ninety-five cases were independently reviewed by two observers. Interobserver reproducibility of the diagnosis of lymphatic vessel invasion (LVI) was 82% (kappa 0.60). The observers agreed on the presence of LVI in 23 patients (24%), of whom 21 (91%) had positive lymph nodes. Only among patients in whom more than ten emboli were identified was the frequency of positive lymph nodes markedly higher than in the total material. The location of tumor emboli relative to the invasive tumor was of little significance. LVI was a more powerful predictor of lymph node status than tumor size, margin contour, histologic grade and histologic type, and was highly significant also when controlled for these features.

Breast↗
PubMed1989

Mechanism of death in avalanche victims.

The autopsies of 12 victims from two snow avalanches in North-Norway are reported. Supportive evidence from non-autopsied and surviving victims is included. Consistent autopsy findings were prominent lung oedema, moderate cerebral oedema, extreme contraction of the left ventricle, petechiae in the superior vena cava drainage area, and acute congestion in lungs and kidneys. In four cases in whom no resuscitation was attempted, aortic oxygen pressure was in the range expected in pure asphyxial-type deaths in one and in pure cardiac-type deaths in three. No air pocket was seen in front of the mouth and nose in any of the fatal cases. Three fatal cases had fractures. It is concluded that the immediate cause of death in most cases was general body compression with acute respiratory and circulatory failure.

Adolescent↗