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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 175-180 
    ISSN: 1432-2307
    Keywords: Flow cytometry ; Adrenal neoplasms ; Parathyroid neoplasms ; Pancreatic neoplasms ; DNA content ; Multiploidy ; Stemline heterogeneity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The co-existence of 2 or more aneuploid stemlines (DNA multiploidy) has been described in malignant human neoplasms and such cancers have often been found to be associated with a poor prognosis. Here 3 benign human adenomas with 2 co-existing aneuploid stemlines are described. Despite DNA stemline heterogeneity and large DNA indices up to 2.8 none of the adenomas recurred or gave rise to metastases after a simple excision during the follow-up of 8, 10 and 11 years. Two adenomas were hormonally active. Marked cellular atypia and frequent mitoses were seen in 1 of the adenomas but the other 2 tumours had little atypia. The present cases indicate that DNA stemline heterogeneity may occur in benign adenomas, and not even the presence of 2 aneuploid stemlines with greatly increased nuclear DNA content can be regarded as a conclusive sign of malignancy.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 17 (1990), S. 59-61 
    ISSN: 1573-7217
    Keywords: aneuploidy ; breast cancer ; flow cytometry ; proliferative rate ; quality control ; S-phase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Consecutive sections from 33 paraffin-embedded human breast carcinomas without intratumor heterogeneity were sent for flow cytometric (FCM) DNA analysis in two experienced laboratories. FCM instruments, run conditions, and tumor disaggregation procedures were different in the two laboratories. In four cases (12%) the laboratories reported a different DNA ploidy and DNA index (DI). These variations were due to analytical reasons, differences in the detection rates of near-diploid and tetraploid DIs, not due to interpretation of data or the criteria used for aneuploidy. There was a significant correlation between S-phase fractions (SPF) obtained in the two laboratories (r = 0.90, p〈0.0001) if only cases with concordant DI were included. Discordant DI usually led to very different SPF values.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nuclear medicine 13 (1988), S. 502-506 
    ISSN: 1619-7089
    Keywords: Thyroid neoplasms ; Thyroid imaging ; Fluorodeoxyglucose ; Flow cytometry ; DNA aneuploidy ; Differential diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fourteen human thyroid tumors were studied with 18F-fluorodeoxyglucose (FDG) imaging. The proliferative activity and DNA ploidy of the tumors was assessed by DNA flow cytometry. FDG accumulated in a Hürthle cell carcinoma, an anaplastic carcinoma and a thyroid lymphoma, but only slightly or not at all in the three papillary carcinomas studied. Three of the eight benign tumors also accumulated FDG, but two of these were selected for imaging because of a large number of proliferating cells in DNA flow cytometry. Two carcinomas with increased nuclear DNA content retained FDG, but a histologically benign follicular adenoma with DNA aneuploidy did not. We conclude that in addition to malignant thyroid tumors, histologically benign tumors may also accumulate FDG, and therefore the value of FDG scanning in the preoperative diagnosis of thyroid malignancy is limited.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2307
    Keywords: Islet-cell neoplasms ; Insulinoma ; Gastrinoma ; Glucagonoma ; DNA index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Eighteen pancreatic neuroendocrine (NE) tumours were analysed for nuclear DNA content by image cytometry (ICM) and flow cytometry (FCM). The DNA indices (DIs) obtained by ICM were somewhat higher than those obtained by FCM, but a major disagreement was present only in 1 case. Thirteen patients had been followed up at least for 6 years after the diagnosis or until death. At 6 years of follow-up all 4 patients with a tumour with a DI≥1.8 by ICM had died from their NE tumour or had metastatic disease, whereas all 9 patients with a smaller DI had no evidence of the disease (P=0.001). The DIs calculated from the FCM data also correlated well with the final outcome (P=0.01). A high incidence of DNA aneuploidy was found by both methods in histologically and clinically benign NE tumours; 12 (67%) were DNA aneuploid by FCM and 16 (89%) by ICM. It is concluded that pancreatic NE tumours are frequently DNA aneuploid, and both cytometric DNA methods give prognostic information in these tumours. The presence of DNA aneuploidy should not be considered as a sign of malignant behaviour in pancreatic NE tumours, whereas a large DI is associated with poor prognosis.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1335
    Keywords: Melanoma ; Interferon ; Chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was conducted to evaluate the efficacy and the tolerability of a four-drug chemotherapy regimen combined with interferon α(IFN) in metastatic melanoma. Between March 1991 and August 1993, 55 patients with advanced melanoma were enrolled for the present multicentre phase II study. Fortynine patients were eligible and evaluable for toxicity; 48 patients were evaluable for response. The treatment schedule consisted of a 5-day regimen of dacarbazine, vincristine, bleomycin and lomustine, plus 6×106 IU IFNα three times weekly subcutaneously for 2 weeks starting on day 8. The cycle was repeated on day 29. Among the 48 assessable patients, 16 objective responses were seen, yielding a response rate of 33% (95% confidence interval 20%–46%). Seven patients achieved a complete response (CR) of a median of 6 + months (range 1 + to 21 + months) and 9 patients achieved a partial response (PR) of a median of 9 months (range 4–13 months). The median overall survival was 12 + months (range 6+ to 23 + months) for the patients with CR and 15 + months (range 8–20 months) for the patients with PR. Even the survival of the 7 patients with stable disease was fairly long (median 12, range 7–17 months), appearing to be significantly longer than the survival of the 25 patients with progressive disease (median 5, range 1–24 + months). The treatment was moderately well tolerated, although all patients experienced some mild form of toxicity, mostly gastrointestinal symptoms, neurotoxicity and haematotoxicity. Grade 3–4 adverse effects were noted in 39% of the patients. No toxic deaths occurred. It can be concluded that the present regimen produces meaningful responses for patients with metastatic melanoma. A randomised study is needed to determine the effect on survival.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1335
    Keywords: Apoptosis ; Paclitaxel ; Squamous-cell carcinoma cell line ; Time-lapse video microscopy ; Head and neck cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Paclitaxel (Taxol) is a potent chemotherapeutic drug for squamous-cell carcinoma (SCC) of the head and neckin vitro with microtubule-stabilizing activity that arrests cells in G2-M. To study the mechanism of its cytotoxic effect on SCCin vitro, we exposed five laryngeal SCC cell lines to 10 nM paclitaxel. The cell lines were studied by time-lapse video microscopy for 96 h, and by agarose gel electrophoresis. Paclitaxel blocked the cells in the premitotic phase for 6–24 h, after which the cells died morphologically by apoptosis. Mitotically arrested cells were seen within a few minutes after exposure to paclitaxel. No mitoses were seen in the paclitaxel-treated cells. A few apoptoses were also seen in the control cultures grown without paclitaxel, but they represented only 6%–20% of the frequency of apoptoses seen in the paclitaxel-treated group. In some paclitaxel-treated cultures the cells escaped the mitotic arrest without cytokinesis and formed multinucleated cells that eventually died. Agarose gel electrophoresis showed oligonucleosomal DNA fragmentation characteristic of apoptosis. We conclude that time-lapse video microscopy is an efficient method of observing drug-induced morphological changes in cell culture. Paclitaxel at a 10 nM concentration rapidly induces a premitotic block, which usually leads to apoptotic cell death. In some cases multinucleated cells are formed that morphologically also eventually die by apoptosis.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 53 (1999), S. 161-166 
    ISSN: 1573-7217
    Keywords: vascular endothelial growth factor (VEGF) ; angiogenesis ; serum markers ; tumor progression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability. Many types of malignant human tumors have been shown to produce VEGF. Recently, increased serum concentrations of VEGF (S-VEGF) have been reported in patients with various types of cancer, and high S-VEGF levels have also been associated with unfavorable prognosis. We have now measured S-VEGF in sera taken from 105 patients with a benign breast tumor or breast cancer. None of the women with a benign breast tumor had S-VEGF higher than 328 pg/ml (median, 57 pg/ml) whereas S-VEGF levels in metastatic breast cancer ranged from 7 to 1347 pg/ml (median, 186 pg/ml P=0.0018), and in locoregional breast cancer from 11 to 539 pg/ml (median, 104 pg/ml P=0.13). S-VEGF was higher in patients with locoregional ductal cancer (median, 107 pg/ml) than in those with locoregional lobular cancer (median, 44 pg/ml; P=0.029) or in patients with benign breast tumor (median, 57 pg/ml; P=0.033). Patients with metastatic cancer undergoing therapy had lower S-VEGF than those who had symptomatic treatment only (P=0.021). The results indicate that dissemination of breast cancer may be accompanied by an elevation of circulating VEGF and that primary ductal cancers are associated with higher S-VEGF levels than lobular cancers or benign breast lesions.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 63 (2000), S. 225-234 
    ISSN: 1573-7217
    Keywords: breast cancer ; cholesterol ; triglycerides ; tamoxifen ; toremifene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tamoxifen decreases serum cholesterol (S-cholesterol) level about 10% and low-density lipoprotein cholesterol (S-LDL) 15–20%, but in most studies it has increased serum triglyceride levels and had little effect on serum high-density cholesterol (S-HDL). The effect of another antiestrogen, toremifene, on the serum lipid profile has not been completely studied. We monitored serum lipid levels longitudinally in 141 axillary node-positive postmenopausal breast cancer patients who received randomly either 40 mg toremifene or 20 mg tamoxifen as adjuvant therapy for 36 months, and in 34 postmenopausal women who received no adjuvant systemic therapy after surgery for axillary node-negative breast cancer. No significant differences were found between the drugs in their effects on S-cholesterol, LDL, HDL, or triglyceride levels, or on the cholesterol-to-HDL or LDL-to-HDL ratios. For both drugs the S-cholesterol and S-LDL absolute lowering effect was the greater the higher the pretreatment level. For a patient with a median pretreatment value, toremifene decreased S-cholesterol 6% and tamoxifen 13%, and S-LDL decreased by 13% and 23%, respectively, at 6 months of therapy. Six months after stopping three-year antiestrogen therapy S- cholesterol and S-LDL levels had returned to the pretreatment levels. In conclusion, we found no major differences between 40 mg toremifene and 20 mg of tamoxifen in their effect on the serum lipid levels, which return to the pretreatment levels within 6 months after cessation of therapy.
    Type of Medium: Electronic Resource
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