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R Kreienberg

Publications and source records attributed to R Kreienberg.

At least 37 records · Page 2Linked to original sources
PubMed2002

Adjuvant endocrine treatment with medroxyprogesterone acetate or tamoxifen in stage I and II endometrial cancer--a multicentre, open, controlled, prospectively randomised trial.

Endometrial cancer is a hormone-dependent disease and therefore an adjuvant hormonal therapy might improve the outcome in the early stages of the disease. Between 1983 and 1989, we conducted a randomised trial of 388 patients who received either medroxyprogesterone acetate (MPA) (n=133) or tamoxifen (n=121) orally for 2 years, or were observed only (n=134) after surgical therapy. The aim was to evaluate whether an adjuvant treatment can improve disease-free and overall survival rates. After a median follow-up period of 56 months (range 3-199 months), we observed no differences in the disease-free and overall survival rates for the tamoxifen group compared with the control or the MPA group. Side-effects were more frequent and severe in the MPA-group than in the tamoxifen group. In patients with early endometrial cancer, adjuvant endocrine treatment did not significantly improve the outcome. However, tamoxifen did have some beneficial effects on coexisting morbidity.

Adult↗
PubMed2002

Shoulder-arm morbidity following axillary dissection and sentinel node only biopsy for breast cancer.

AIMS: The purpose of this study was to examine the outcome of shoulder-arm morbidity in patients with breast cancer after various axillary staging procedures. We used a new specific summation score to compare conventional axillary node dissection (AD) and sentinel node only biopsy for postoperative shoulder-arm morbidity. METHODS: Eighty-five patients undergoing conventional AD and 66 patients undergoing sentinel node biopsy were evaluated both subjectively (questionnaire) and objectively (clinical examination) for reduced muscle strength, limited range of motion, lymphedema and pain, dysesthesias and loss of sensitivity. The symptoms elicited were rated by their severity with a single summation score describing all symptoms reported. RESULTS: Subjective evaluation of patients undergoing breast conserving surgery showed a highly significant difference in favor of SNB only (P< or =0.002). On clinical examination the outcome of patients with SNB only was also significantly or highly significantly better (difference in arm volume:P =0.007; difference in arm muscle strength: P=0.016; loss of sensitivity: P<0.001). Of a total score of 100 (=no symptoms), the mean for AD patients was 80.2 vs 92.8 for SNB patients (P=0.001). In patients undergoing total mastectomy the difference was only significant for pain sensations and total scores. CONCLUSIONS: SNB appears to reduce morbidity. Summation scores are a suitable and practicable tool for describing the symptoms associated with axillary surgery.

Arm Injuries↗
PubMed2002

Pre-operative staging of invasive breast cancer with MR mammography and/or PET: boon or bunk?

This study compared pre-operative staging with MR mammography (MRM) and positron emission tomography (PET) in patients with clinically suspected breast cancer according to the Breast Imaging Reporting and Data System, category 5. A total of 43 patients with breast cancer were examined. MRM included both T(2) weighted turbo spin echo sequences and T(1) weighted gradient echo sequences (three-dimensional fast low angle shot) before and after application of gadolinium-DPTA. All patients then underwent examination with a modern full-ring PET scanner following injection of fluorodeoxyglucose. We evaluated the efficacy of these methods in the diagnosis of primary tumour, contralateral carcinomas, bifocal, trifocal or multifocal disease, as well as non-invasive cancer portions and tumour size. Determination of patients' N-status was only attempted using PET. All findings were validated by histological examination. MRM was slightly superior to PET in several areas, such as in the respective methods' sensitivity and specificity. Sensitivities for MRM and PET were: 100% vs 93.0% in diagnosis of the primary tumour; 100% vs 100% in diagnosis of contralateral carcinomas; and 95.2% vs 92.5% in diagnosis of bifocal, trifocal or multifocal disease. Specificities for MRM and PET were: 100% vs 97.5% in diagnosis of contralateral carcinomas; and 96.8% vs 90.3% in diagnosis of bifocal, trifocal or multifocal disease. Non-invasive cancer portions and tumour sizes were equally well determined with both methods. The sensitivity of PET for detection of lymph node involvement was 80% and specificity 95%. MRM and PET were superior to conventional methods in nearly all areas studied; the findings of one or both of the methods impacted positively on patients' surgical treatment in 12.5-15% of cases. Pre-operative MRM and/or PET can have a positive influence on surgical treatment planning. Therefore, it appears useful to perform pre-operative staging with MRM or PET in these patients.

Adult↗
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

Characterization of a human carcinosarcoma cell line of the ovary established after in vivo change of histologic differentiation.

OBJECTIVES: Cell lines are valuable in vitro models for clinical and basic research. Most ovarian cancer cell lines described are serous cystadenocarcinomas or poorly differentiated adenocarcinomas. The establishment of ovarian cancer cell lines with rare histologic differentiation is especially of interest. We describe the establishment of a carcinosarcoma cell line of the ovary after in vivo selection. METHODS: The cell line OV-MZ-22 was established from a solid tumor mass in the upper abdomen. At the time of establishment, the patient underwent secondary debulking and was pretreated with six cycles of cis-platinum/epirubicin/cyclophosphamide. Features of the cell line studied included morphology, ultrastructure, heterotransplantation, chromosome analysis, and analysis of intermediate filament proteins and actins by immunocytochemistry. RESULTS: The first histologic report of the patient described a papillary cystadenocarcinoma, which changed to a carcinosarcoma with predominantly sarcomatous differentiation at secondary debulking. This cell line is aneuploid and shows no expression of the tumor-associated antigens CA-125 and CEA, but an overexpression of MDR-1, lung resistance protein, p53, and topoisomerase I and II, but not of multidrug-resistance-associated protein. The cell line did not give rise to transplant tumors in nude mice. The histologic and immunocytochemical comparison of the primary and the relapsed tumor proved evidence of an in vivo change of differentiation from predominantly papillary cystadenocarcinoma to carcinosarcoma. Morphological characteristics and intermediate filament pattern underlined the sarcomatous differentiation and origin of this cell line. The differentiation phenotype of OV-MZ-22 cells is that of smooth-muscle cells. CONCLUSION: The change of histologic differentiation was apparently due to a selection process caused by platinum-containing chemotherapy. The origin of the cell line and its rarity make this new line an appropriate tool for further investigation.

Actins↗
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

Cytogenetic analysis of human zygotes displaying three pronuclei and one polar body after intracytoplasmic sperm injection.

BACKGROUND: Digynic zygotes with three pronuclei and one polar body obtained after intracytoplasmic sperm injection (ICSI) were studied cytogenetically to elucidate the frequency and origin of chromosomal abnormalities at the earliest stage of conception. METHODS: Uncleaved, single-cell zygotes were incubated with podophyllotoxin and vinblastine and fixed by a gradual fixation air drying method. The chromosomes were stained with Giemsa. RESULTS: Twenty-two (50%) out of 44 informative zygotes revealed cytogenetic alterations, including aneuploidy (six cells, 13.6%), structural aberrations (10 cells, 22.7%) and combinations of numerical and structural abnormalities (two cells, 4.5%). In one case (2.3%), double aneuploidy or an effect of chromosomal translocation could not be distinguished and one zygote (2.3%) turned out tetraploid due to injection of a diploid spermatozoon. Two zygotes (4.5%) showed an irregular chromatid segregation between the two maternal complements. In completely analysable cells, the sex chromosome ratio XXX:XXY was 17:15. CONCLUSIONS: Digynic ICSI zygotes carry a high rate of cytogenetic abnormalities that obviously have been transmitted by the participating oocytes and spermatozoa. We also confirmed the previously reported, possibly ICSI-induced irregular oocyte chromatid segregation. The results suggest that aneuploidy in the oocytes must have been caused by predivision instead of non-disjunction.

Cell Nucleus↗
PubMed2001

Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives.

Oral contraceptives have been shown to be protective against hereditary ovarian cancer. The variant progesterone receptor allele named PROGINS is characterized by an Alu insertion into intron G and two additional mutations in exons 4 and 5. The PROGINS allele codes for a progesterone receptor with increased stability and increased hormone-induced transcriptional activity. We studied the role of the PROGINS allele as a modifying gene in hereditary breast and ovarian cancer. The study included 195 BRCA1 and BRCA2 carriers with a prior diagnosis of ovarian cancer, 392 carriers with a diagnosis of breast cancer and 249 carriers with neither cancer. Fifty-eight women had both forms of cancer. Five hundred and ninety-five women had a BRCA1 mutation and 183 women had a BRCA2 mutation. Overall, there was no association between disease status and the presence of the PROGINS allele. Information on oral contraception use was available for 663 of the 778 carriers of BRCA1 or BRCA2 mutations. Among the 449 subjects with a history of oral contraceptive use (74 cases and 365 controls), no modifying effect of PROGINS was observed [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.5-1.3]. Among the 214 carriers with no past exposure to oral contraceptives, the presence of one or more PROGINS alleles was associated with an OR of 2.4 for ovarian cancer, compared to women without ovarian cancer and with no PROGINS allele (P = 0.004; 95% CI 1.4-4.3). The association was present after adjustment for ethnic group and for year of birth.

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↗