PubMed Health⌕ Search

Biomedical subjects

R Kreienberg

Publications and source records attributed to R Kreienberg.

At least 19 recordsLinked to original sources
PubMed2001

Adenoviral transduction efficiency of ovarian cancer cells can be limited by loss of integrin beta3 subunit expression and increased by reconstitution of integrin alphavbeta3.

Recombinant adenoviruses expressing a therapeutic gene are currently used in clinical studies for treatment of advanced ovarian cancer. We therefore tested whether the expression level of primary (CAR) and secondary adenovirus receptors (integrins) was predictive of the efficacy of adenoviral gene transfer in ovarian cancer cells. Adenoviral transduction efficiency (ATE) was determined with an E1-deleted adenovirus type 5 expressing beta-galactosidase under a CMV promoter (AdGal). ATE was studied in relationship to the expression level of both CAR (coxsackie and adenovirus receptor) and integrins. A representative sample of 25 permanent human cell lines established from advanced ovarian cancer in our laboratory and the OV-2774 cell line were tested. Overall, ATE increased with increasing titers of AdGal. At a given titer of 50 infectious units per cell, transduction efficiency varied from 6 to 94% among the individual cell lines. All cell lines expressed CAR and integrin alpha(v)beta(5), but no relation between ATE and expression level of CAR or alpha(v)beta(5) integrin was observed. In contrast, cell lines with poor ATE, despite expressing high levels of CAR, lacked expression of integrins alpha(v)beta(3) and alpha(5)beta(1). Reconstitution of alpha(v)beta(3) integrin by reexpressing the beta(3) subunit significantly enhanced ATE of ovarian cancer cells. In ovarian cancer, neither integrins nor CAR alone appear to be potentially useful predictive markers for ATE by serotype 5 adenovirus in clinical gene therapy. A minimum level of CAR necessary for binding of adenoviruses was observed in all tested ovarian cancer cell lines. Loss of alpha(v)beta(3) integrin is frequently associated with advanced stages of ovarian cancer and can significantly reduce ATE.

Adenoviridae↗
PubMed2001

Bladder carcinoma associated with cyclophosphamide therapy for ovarian cancer occurring with a latency of 20 years.

BACKGROUND: Cyclophosphamide-induced urothelium cancer of the bladder is a well-known entity. The risk for inducing such cancer grows with duration and dosage of cyclophosphamide therapy. The lag time between termination of treatment and development of urothelial cancer has been observed to be between 9 months and 11 years. Single cases have been reported 14, 16, 17, and 21 years after cyclophosphamide treatment. CASE: We report a case of a bladder cancer occurring after a lag time of 20 years after oral therapy with cyclophosphamide for ovarian cancer. The bladder cancer was detected due to gross hematuria. CONCLUSION: It is of great importance for gynecologists to continue to care for patients who have received long-term cyclophosphamide treatment, even if the treatment was completed decades ago. One possible early symptom of cyclophosphamide-induced bladder cancer is painless hematuria. This can easily be used to detect bladder cancer in women at risk, even after a very long latency period.

Adult↗
PubMed2001

Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures.

The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) with conventional staging techniques. The differentiation between malignant and benign lesions and the detection of multifocal disease, axillary and internal lymph node involvement, and distant metastases were evaluated. One hundred and seventeen female patients were prospectively examined using FDG-PET and conventional staging methods such as chest X-ray, ultrasonography of the breast and liver, mammography and bone scintigraphy. All patients were examined on a modern full-ring PET scanner. Histopathological analysis of resected specimens was employed as the reference method. The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour. The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93% and 75% respectively. FDG-PET was twofold more sensitive (sensitivity 63%, specificity 95%) in detecting multifocal lesions than the combination of mammography and ultrasonography (sensitivity 32%, specificity 93%). Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79% and 92% (41% and 96% for clinical evaluation). FDG-PET correctly indicated distant metastases in seven patients. False-positive or false-negative findings were not encountered with FDG-PET. Chest X-ray was false-negative in three of five patients with lung metastases. Bone scintigraphy was false-positive in four patients. Three patients were upstaged since FDG-PET detected distant metastases missed with the standard staging procedure. It is concluded that, compared with the imaging methods currently employed for initial staging, FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases. Due to a false-negative rate of 20% in detecting axillary lymph node metastases, FDG-PET cannot replace histological evaluation of axillary status.

Adult↗
PubMed2001

Impact of the axillary nodal status on sentinel node mapping in breast cancer and its relevance for technical proceeding.

OBJECTIVE: The aim of this study is to analyze whether the axillary status influences the lymphatic mapping procedure in malignant breast disease and whether clinically relevant consequences for the technique of Sentinel Node (SN) biopsy may be drawn from this information. MATERIALS AND METHODS: SN biopsy was performed in 150 consecutive patients using a combination of the radioguided and the blue-dye technique. Axillary status was compared with the number of detected nodes. In cases of numerous nodes with tracer uptake, the radioactivity of each radiolabeled node was measured separately in a dose calibrator. We analyzed whether an increased tracer uptake could possibly indicate a 'true' or 'dominant' SN. Blue dye uptake was registered and compared with radioactivity. The findings were related to the histologic results. RESULTS: In patients with a positive axillary status, significantly more radiolabeled nodes were detected than in node negative patients (median 3 vs. 2; p < 0.001). In 54/86 patients with numerous SNs a 'dominant' node with at least twice the radioactivity than other marked nodes could be identified (62.8%). From 26 cases with axillary involvement, 20 patients (76.9%) were identified by the 'dominant' and the remaining six women (23.1%) by others than the seemingly leading SN. CONCLUSION: Axillary lymph node involvement influences the drainage pattern in breast cancer. Patients with numerous SNs have an increased risk of axillary involvement. A high tracer uptake does not permit the identification of a 'true' SN. A lack of surgical accuracy may lead to pitfalls if the axilla is not screened carefully for all radioactive nodes.

Adult↗
PubMed2001

Endoscopic axillary surgery in breast cancer.

BACKGROUND: The aim was to provide an assessment of the current status of endoscopic axillary surgery in patients with breast cancer. METHODS: Fifty-three patients underwent endoscopic lymphadenectomy. The surgical efficiency (operating time, number of resected nodes, intraoperative and postoperative complications), short-term morbidity (duration of drainage, total lymph flow, seroma rate) and long-term outcome (pain, numbness, mobility, strength, oedema) were assessed. The incidence and severity of different arm symptoms were compared with the results of 396 patients treated with a conventional axillary procedure. Finally, all available data relating to endoscopic axillary surgery were reviewed. RESULTS: The operating time ranged from 60 to 150 min. A mean 17 (range 10-28) lymph nodes was resected. The extent of postoperative lymphorrhoea (mean 372 ml) and the seroma rate (eight of 34 patients) were not significantly reduced in comparison with conventional surgery. The assessment of long-term morbidity revealed fewer disturbances of sensitivity and a decreased rate of severe symptom intensity for pain, oedema and complaints related to mobility. CONCLUSION: Despite excellent visualization of anatomical landmarks and improved long-term morbidity, endoscopic lymph node dissection cannot be regarded as a suitable technique for routine axillary management in breast cancer because of long operating times.

Adult↗
PubMed2001

Preoperative diagnosis of ovarian tumors with MR imaging: comparison with transvaginal sonography, positron emission tomography, and histologic findings.

OBJECTIVE: Our study evaluated the diagnostic performance of MR imaging compared with that of transvaginal sonography and positron emission tomography (PET) in patients with clinically asymptomatic adnexal findings. An additional goal was to determine whether the combination of the three methods enhanced their diagnostic accuracy. SUBJECTS AND METHODS: Included in the study were 103 women with suspicious adnexal findings on sonography. Patients underwent transvaginal sonography, MR imaging, and PET within 3 weeks of the initial sonography. For MR imaging, axial and sagittal T1-weighted gradient-echo sequences (unenhanced and enhanced) and T2-weighted turbo-spin-echo sequences were acquired. Transvaginal sonography was performed with a 7.5-MHz transducer head. For PET, a modern full-ring scanner was used. The results of diagnostic imaging techniques were first evaluated separately, and reviewers were blinded to the results of other methods. Finally, a second session resulted in a consensus diagnosis based on the findings of all three methods. Results of histology were considered the gold standard. RESULTS: Histology revealed 12 malignant and 91 benign ovarian tumors. The following data were calculated for MR imaging, transvaginal sonography, PET, and consensus diagnosis: sensitivities, 83%, 92%, 58%, 92%; specificities, 84%, 59%, 78%, 84%; diagnostic accuracies, 83%, 63%, 76%, 85%, respectively. MR imaging, particularly with contrast-enhanced fat-saturated T1-weighted sequences, was found to correctly reveal dermoid and endometrial cysts. All three methods had false-negative findings with borderline tumors. CONCLUSION: Transvaginal sonography is the diagnostic method of choice as a screening technique for ovarian processes. Suspicious findings on transvaginal sonography should be confirmed on MR imaging. If MR imaging confirms a dermoid or endometrial cyst, further diagnostic procedures may be unnecessary. In all other cases, a surgical evaluation must be considered.

Adolescent↗
PubMed2001

Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. See The biology behind: K. A. Foon and M. Bhattacharya-Chatterjee, Are solid tumor anti-idiotype vaccines ready for prime time? Clin. Cancer Res., 7:1112-1115, 2001.

The aim of the present study was to assess whether the induction of specific immune responses by vaccination with the murine monoclonal anti-idiotypic antibody ACA125, which imitates the tumor-associated antigen CA125, has a positive influence on the survival of patients with recurrent ovarian carcinoma. Forty-two patients with platinum-pretreated recurrences were included in a clinical Phase I/II trial of consolidation in third-line therapy. Patients initially received four immunizations with 2 mg of alum-precipitated anti-idiotype ACA125 every 2 weeks and then monthly applications. No serious allergic reactions could be detected within a maximal control period of 56 months. Hyperimmune sera of 27 of 42 patients (64.2%) showed increased concentrations of human antimouse antibodies. Specific anti-anti-idiotypic antibodies as a marker for induced immunity were detected in 28 of 42 patients (66.7%). The survival of the whole ACA125-treated collective of patients after a mean of 12.6 antibody applications was 14.9 +/- 12.9 months. The survival of patients with a positive immune response was 19.9 +/- 13.1 months in contrast with 5.3 +/- 4.3 months in those patients without detectable anti-CA125 immunity (P < 0.0001). According to these results, vaccination with a suitable anti-idiotypic antibody offers an effective way to induce specific immunity against a primarily nonimmunogenic tumor antigen such as CA125 and is associated with a positive impact on the survival of patients with recurrent ovarian cancer with few side effects, which warrants a Phase III trial for ovarian cancer patients after primary therapy.

Antibodies, Anti-Idiotypic↗
PubMed2001

Correlation of p53 mutations with resistance to platinum-based chemotherapy and shortened survival in ovarian cancer.

PURPOSE: The p53 tumor suppressor gene plays a central role in cell cycle regulation and induction of apoptosis. We analyzed p53 alterations and their impact on response to chemotherapy and clinical outcome in ovarian cancer patients. EXPERIMENTAL DESIGN: One hundred seventy-eight ovarian carcinomas, snap frozen and stored at -80 degrees C, were analyzed for mutations of the p53 gene (exons 2-11) by single-strand conformation polymorphism and DNA sequencing and for p53 overexpression by immunohistochemistry (monoclonal antibody DO7). RESULTS: p53 mutations were found in 56% (99 of 178) of the tumors, and 62% of these were located in evolutionary highly conserved domains of the gene. Time to progression and overall survival were significantly shortened in patients with p53 mutations compared with wild-type p53 (P = 0.029 and P = 0.014) and patients with mutations in highly conserved domains as opposed to nonconserved domains or wild-type p53 (P = 0.010 and P = 0.007). p53 protein overexpression (>10% positively stained nuclei) was found in 62% (110 of 178). Time to progression and overall survival were shorter in cases with p53 overexpression (cutpoint, 10%: P = 0.071 and P = 0.056) but only marginally significant. Resistance to adjuvant cisplatin or carboplatin chemotherapy was significantly more frequent in patients with p53 overexpression (P = 0.001) or p53 missense mutations (P = 0.008) than patients with normal p53. CONCLUSIONS: p53 alterations correlate significantly with resistance to platinum-based chemotherapy, early relapse, and shortened overall survival in ovarian cancer patients in univariate analysis. In multivariable analysis though, p53 was not an independent prognostic factor.

Aged↗
PubMed2000

Induced micronucleus frequencies in peripheral lymphocytes as a screening test for carriers of a BRCA1 mutation in breast cancer families.

Enhanced sensitivity to the chromosome-damaging effects of ionizing radiation is a feature of many cancer-predisposing conditions. It has been suggested that women with breast cancer are deficient in the repair of radiation-induced DNA damage. We have now investigated whether mutagen sensitivity is related to mutations in the breast cancer gene BRCA1. We studied the induction and repair of DNA damage in lymphocytes of women from families with familial breast cancer and breast and ovarian cancer. The mutagens used were gamma-irradiation and hydrogen peroxide and the DNA effects were determined with the micronucleus test and the comet assay. Women with a BRCA1 mutation (n = 12) and relatives without the familial mutation (n = 10) were compared to controls (i.e., healthy women without family history of breast or ovarian cancer; n = 17). Our results indicate a close relationship between the presence of a BRCA1 mutation and sensitivity for the induction of micronuclei. Compared to a concurrent control, 10 of 11 women with a BRCA1 mutation showed elevated radiation sensitivity. Of the 10 related women without the familial mutation, only 2 had clearly enhanced micronucleus frequencies. In addition to the sensitivity toward gamma-irradiation, hypersensitivity toward hydrogen peroxide was also observed, indicating that the mutagen sensitivity is not solely due to a defect in the repair of DNA double strand breaks. In contrast to the results with the micronucleus assay, we found no significant difference between women with and without a BRCA1 mutation with respect to the induction and repair of DNA damage in the comet assay. This finding suggests a normal rate of damage removal and points to a disturbed fidelity of DNA repair as a direct or indirect consequence of a BRCA1 mutation. Our results support the usefulness of induced micronucleus frequencies as a biomarker for cancer predisposition and suggest its application as a screening test for carriers of a BRCA1 mutation in breast cancer families.

Adult↗
PubMed2000

Classification of asymptomatic adnexal masses by ultrasound, magnetic resonance imaging, and positron emission tomography.

OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of sonography versus magnetic resonance imaging (MRI) and positron emission tomography (PET) in the characterization of adnexal masses. METHODS: One hundred and one patients with asymptomatic adnexal masses, which were scheduled for laparoscopy, underwent preoperative transvaginal ultrasound, MRI, and 2-[(18)F]fluoro-2-deoxy-d-glucose PET. Two different sonomorphological scoring systems were used to distinguish malignant from benign lesions. In addition, transvaginal Doppler flow velocimetry was performed and the resistance index (RI) of ovarian blood vessels was calculated. RI values below 0.45 were considered to indicate malignancy. MRI was evaluated on the basis of signal intensity and morphologic features such as wall thickness, septations, fluid or solid components, and vascularity. PET imaging was used to determine 2-[(18)F]fluoro-2-deoxy-D-glucose uptake. Malignancy was suspected if radiotracer uptake equaled or exceeded that of the liver. Based on histologic findings, sensitivity, specificity, positive and negative predictive values, and accuracy were first calculated independently for each imaging technique. Finally, a second session resulted in a consensus diagnosis being made based on the findings of all three modalities. RESULTS: Sonographic evaluation of adnexal masses resulted in correct classification of 11 of 12 ovarian malignancies (sensitivity 92%) but with a specificity of only 60%. With MRI and PET, specificities improved to 84 and 80% respectively, but sensitivities decreased. When all imaging modalities were combined, sensitivity and specificity were 92 and 85%, respectively, and accuracy was 86%. CONCLUSION: Combination of ultrasound with MRI and PET may improve accuracy in differentiation of benign from malignant ovarian lesions. However, negative MRI or PET results do not rule out early-stage ovarian cancer or borderline malignancies.

Adnexal Diseases↗
PubMed2000

Growth suppression of human ovarian carcinoma OV-MZ-2a and OV-MZ-32 cells mediated by gene transfer of wild-type p53 enhanced by chemotherapy in vitro.

PURPOSE: The aim of this work was to observe the growth and chemosensitivity of human ovarian cancer OV-MZ-2a and OV-MZ-32 cells following adenovirus-based wild-type p53 (Ad-p53) gene transfer alone or combined with chemotherapeutic agents. METHODS: Transduction efficiency was determined with a reporter construct of adenovirus galactosidase by staining with 5-bromo-4-chloro-3-indolyl beta-D-galactoside. For growth inhibition, OV-MZ-2a or OV-MZ-32 cells were infected with Ad-p53 particles at a multiplicity of infection (m.o.i.) of 0.2-20, alone or combined with the chemotherapeutic agents taxol, cisplatin, doxorubicin or mitomycin C. Growth inhibition (assayed by trypan blue exclusion), target gene expression (by Western blotting) and clonogenicity (by soft-agar assay) were determined following Ad-p53 transfer. RESULTS: High transduction efficiency was observed following adenovirus galactosidase gene transfer; 94% of OV-MZ-2a cells and 69% of OV-MZ-32 cells expressed the transgene. Following transfer of Ad-p53 into the two cell lines, a high level of p53 expression was detected after 12, 24, 48, 72 and 96 h in OV-MZ-2a cells. At a m.o.i of 20, 96% and 90% growth inhibition were achieved in OV-MZ-2a cells and OV-MZ-32 cells respectively. Clonogenicity was lost completely in both cell lines following wild-type p53 transfer. Meanwhile, Ad-p53 gene transfer combined with taxol, cisplatin, doxorubicin or mitomycin C was shown to be even more effective in suppressing growth in the two cell lines. CONCLUSIONS: Our results may suggest that wild-type p53 gene transfer mediated by an adenoviral vector is a potential strategy for treating ovarian cancer, and a combination of Ad-p53 gene transfer and chemotherapeutic agents may be an even better treatment of the cancer.

Adenocarcinoma↗
PubMed2000

Axilloscopy and endoscopic sentinel node detection in breast cancer patients.

BACKGROUND: Sentinel node biopsy is a promising technique that allows the axillary status of breast cancer patients to be predicted with high accuracy. Reducing false negative results remains a major challenge for the improvement of this procedure. Furthermore, new techniques are required to achieve axillary clearing with less morbidity in cases of unsuccessful mapping or multicentric carcinoma. We analyzed whether axilloscopy and endoscopic sentinel node biopsy is a feasible procedure for visualization of the axillary space and resection of the sentinel node using endoscopic techniques. METHODS: Following blue dye-guided lymphography and liposuction of the axillary fat, endoscopic axillary sentinel node biopsy was performed in 35 breast cancer patients. We then assessed the exposure of anatomical landmarks, the detection rate of the sentinel node, the false negative rate, and the accuracy of consecutive axillary clearing. RESULTS: In almost every case, an excellent anatomical orientation was achieved. The detection rate for the sentinel node was 83.3%. In one case, the sentinel node did not reflect the status of the residual axilla. A mean number of 17.1 lymph nodes was harvested at consecutive axillary clearing. CONCLUSIONS: Axilloscopy and endoscopic sentinel node biopsy, following liposuction of the axillary fat, is a feasible procedure that allows identification and minimally invasive resection of the sentinel node with high accuracy. The endoscopic approach might help to minimize the pitfalls of sentinel node biopsy by visualizing the axillary space. In future, it may become a technique that enables minimally invasive axillary clearing when complete lymphadenectomy is required.

Adult↗
PubMed2000

Long-term morbidity following axillary dissection in breast cancer patients--clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors.

OBJECTIVE: This study describes in detail the surgery-related symptoms following axillary lymph node dissection in breast cancer patients and considers both their significance for long term quality of life and the impact of possible influencing factors. MATERIAL AND METHODS: Three hundred and ninety six patients were studied retrospectively using a self-report questionnaire and a clinical examination. The symptoms, numbness, pain, edema, arm strength and mobility were evaluated. The subjective assessment of the degree of symptom intensity was compared with objective measurements. The extent of surgery (number of resected nodes, level of dissection) as well as the influence of demographic, oncologic and adjuvant measures (age, time interval, number of involved nodes, chemotherapy) were evaluated. RESULTS: Shoulder-arm morbidity and fear of cancer recurrence were the most important long-term sources of distress following breast cancer surgery in our study population. Demographic, oncologic and therapeutic measures including the extent of surgery had no influence on long-term morbidity. The intensity of all evaluated symptoms was reported to be more severe in patients' subjective statements than in the results of clinical assessment. CONCLUSION: Shoulder-arm morbidity following axillary dissection is a frustrating polysymptomatic disease that seems to be relatively unaffected by therapeutic measures. The surgical trauma necessary for adequate tumor staging (removal of 10 lymph nodes) seems decisive for the postsurgery syndrome following axillary dissection. For node-positive patients complete axillary clearing may improve tumor control without worsening long-termmorbidity. New techniques, such as the sentinel-node-biopsy, that selects patients with negative axillary status while preserving the integrity of axillary structures, may improve the overall morbidity.

Adult↗
PubMed2000

Effects of low-dose aspirin on uterine and fetal blood flow during pregnancy: results of a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: This study was conducted to evaluate uteroplacental and fetal hemodynamics in fetuses exposed to low-dose aspirin (100 mg/d). DESIGN: Randomized, placebo-controlled, double-blind trial. SUBJECTS: The study protocol included singleton pregnancies of less than 20 gestational weeks at risk for pre-eclampsia or fetal growth restriction. Exclusion criteria were diabetes mellitus, pre-existing proteinuric hypertension or fetal malformations. Forty-three pregnant women were randomly allocated to daily treatment with 100 mg aspirin (n = 22) or placebo (n = 21). METHODS: Pulsed Doppler measurements of the uterine artery, fetal middle cerebral artery, fetal aorta, ductus arteriosus and atrioventricular valves were performed longitudinally at 14 day intervals starting from 18 gestational weeks until delivery. Results were expressed as group medians (aspirin vs. placebo) and were analyzed by Mann-Whitney U-test. RESULTS: There was no difference in uterine, umbilical, aortic, middle cerebral and ductus arteriosus blood flow between the aspirin group and controls. Median ductal peak flow velocities increased with gestational age in both groups, but differences between groups did not reach significance. In the third trimester of pregnancy, ductal peak velocities > 140 cm/s were occasionally observed in both groups. However, end diastolic velocities > 35 cm/s or atrioventricular valve regurgitation never occurred. CONCLUSIONS: Daily administration of low-dose aspirin during the second and third trimesters of pregnancy does not alter uteroplacental or fetoplacental hemodynamics and does not cause moderate or severe constriction of the ductus arteriosus.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Autoimmunity against p53 predicts invasive cancer with poor survival in patients with an ovarian mass.

Serum autoantibodies against the p53 protein (p53 AAb) were analysed with a newly developed enzyme-linked immunosorbent assay (ELISA) based on highly purified and renatured p53. In a hospital-based cohort study, preoperative sera from 113 patients with ovarian cancer, 15 patients with borderline tumours and 117 patients with benign tumours of the ovaries were studied. The prevalence of p53 AAb in patients with invasive cancer was 19% (21/113). No p53 AAb were found in patients with borderline lesions or benign tumours. The ELISA had a specificity for malignancy of 99% (1 of 117; false-positive from a patient with severe diabetes mellitus) and a likelihood ratio (LR+) for a positive test result of 21.7 (elevated CA125 and malignancy: LR+ 3.7). p53 AAb were only detectable in patients with immunohistochemical staining of nuclear p53 in the tumour (P = 0.006). Presence of p53 AAb positively correlated with tumour stage (P = 0.034) and grade (P = 0.009). Kaplan-Meier analysis showed both a shortened overall survival (P = 0.0016, log-rank) and relapse-free survival (P = 0.055) for p53 AAb-positive patients (median follow-up 22 months). High titres related to even worse prognosis. p53 AAb independently related to poor survival adjusting for stage (P = 0.026), grade (P = 0.029) and residual disease after surgery (P = 0.005). Preoperative findings of adnexal mass with serum p53 AAb are strongly suggestive of an aggressive invasive ovarian cancer.

Adolescent↗
PubMed2000

Altered subcellular distribution of cadherin-5 in endothelial cells caused by the serum of pre-eclamptic patients.

The main clinical features of pre-eclampsia are oedema and vascular leakage. Cadherin-5 mediates endothelial cell-cell contact in the vascular endothelium and may regulate permeability as a vascular function. Therefore, we addressed the question of whether pre-eclampsia alters cadherin-5 expression and intracellular distribution. Confluent human umbilical vein endothelial cells (HUVEC) were incubated with 20% serum from patients with pre-eclampsia (n = 18), haemolysis-elevated liver enzymes-low platelet syndrome (HELLP) (n = 12), pregnancy-induced hypertension (PIH) (n = 18) or normal pregnancy (n = 10). After incubation with sera from patients with pre-eclampsia, immunostaining analyses showed cadherin-5 accumulation in vesicular and tubular structures of the Golgi apparatus. Immunoblot analyses of HUVEC after pre-eclampsia serum incubation showed an increase of the stable form of cadherin-5 while degradation products decreased. Degradation of cadherin-5 takes place at the cell membrane, so this decrease may be due to a decrease of cadherin-5 in the cell membrane. The accumulation of cadherin-5 in the vesicular and tubular structures of the Golgi apparatus indicates that targeting of cadherin-5 to the plasma membrane could be disrupted. We suggest that intracellular retention of cadherin-5 caused by serum factors in patients with pre-eclampsia may decrease the number of adhesion complexes in the cell membrane, thereby contributing to endothelial dysfunction.

Adult↗
PubMed2000

Soluble CD44 splice variants and pelvic lymph node metastasis in ovarian cancer patients.

Alternative splicing of CD44 and aberrant levels of soluble CD44 protein in the serum of cancer patients has been correlated to tumor progression and metastasis. To examine the clinical value of CD44 serum levels (sCD44) in ovarian cancer we determined concentrations of the soluble, variable isoforms sCD44std, sCD44v5 and sCD44v6 with a sensitive ELISA. Pre-operative serum samples from 66 patients with histologically diagnosed invasive disease as well as sera taken from 40 healthy blood donors were analyzed. In sera of ovarian cancer patients we detected elevated concentrations of overall CD44 serum levels represented by sCD44std (p=0.001), but decreased levels of the specific isoforms CD44v5 (p=0.0002) and v6 (p=0.0001). This is the first report demonstrating that ovarian cancer patients with pelvic lymph node metastasis at the time of diagnosis showed specifically elevated sCD44v6 (p=0.073) serum concentrations in comparison to patients without lymph node involvement, whereas overall sCD44 serum levels did not differ. Decreased serum levels of sCD44v5 were found in progesterone receptor-positive tumors (p=0. 059) and postmenopausal patients (p=0.032). Increased concentrations of sCD44v6 were detectable in estrogen receptor-positive tumors but not significantly (p=0.138). Serum CD44v5 levels were associated with shortened relapse-free survival time. No association was found between serum CD44 isoforms and the classical clinicopathological parameters stage and grading or overall survival. CD44 splice variants are possibly involved in a complex interaction with the hormonal environment during tumorigenesis and metastasis of ovarian cancer.

Alternative Splicing↗