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  • 11
    ISSN: 1573-7217
    Keywords: breast cancer ; Cox regression ; histologic tumor grading ; node negative ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prognostic effect of histological tumor grade was evaluated in 1036 patients with early breast cancer (pT1 pN0 M0) entered into a trial comparing mastectomy and breast preserving treatment. All analyses were adjusted for the factors treatment, patients' age, and tumor size. Tumor grade was defined according to Bloom and Richardson based on the sum of scores assigned to each of three histological features: 1) degree of differentiation, 2) pleomorphism, and 3) mitotic index. The relative importance of these factors with regard to disease-free survival was evaluated. In univariate as well as in multivariate analyses the pleomorphism was the only factor showing a significant effect (univariate: p=0.0024, multivariate: p=0.015). It was investigated how the factors should be combined to define a histological grading score which yields the best possible classification of the patients with respect to prognosis. A new grading system was defined splitting the patients into three groups: 1) pleomorphism 1; 2) pleomorphism 2 or pleomorphism 3 and mitotic index 1; 3) pleomorphism 3 and mitotic index 2 or 3. This yields a good classification of the patients with respect to prognosis (p=0.0004). The prognostic effect of this score was compared with the effects of the grading systems proposed in the literature. According to Bloom and Richardson and in the modified version by Schauer and Weiss, grading is based on the sum of scores of the various histological factors. Therefore, the strong effect of the pleomorphism was diluted in these grading definitions (Bloom and Richardson: p=0.03, Schauer and Weiss: p=0.028). The grading system proposed by Le Doussalet al. consists only of the scores of pleomorphism and mitotic index (p=0.014). In summary, the factor pleomorphism showed a stronger effect on disease-free survival by itself than the grading systems proposed in the literature.
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  • 12
    ISSN: 1432-1335
    Keywords: NSCLC ; Vindesine ; Etoposide ; Dexverapamil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine whether the chemotherapy resistance of non-small cell lung cancer could be modified by oral dexverapamil, the D-isomer of verapamil, 54 patients were entered into a randomised phase II study of oral dexverapamil plus chemotherapy (vindesine/etoposide) (arm B) versus chemotherapy (arm A) alone in January 1994. Chemotherapy consisted of intravenous vindesine 3 mg/m2 bolus on days one and five and etoposide 140 mg/m2 on days two and four. Dexverapamil was given for six days, 1500 mg a day divided into six doses of 250 mg every four hours starting 24 h prior to chemotherapy. According to the individual tolerability, the single dose could be increased up to a maximum of 400 mg. Cycles were repeated 3 weekly up to four courses. At this stage of the analysis, 34 patients (18 in arm A and 16 in arm B) are evaluable for toxicity and response. Cardiovascular side effects were more marked in the patient group with dexverapamil. On average, the dose of dexverapamil was 1800 mg a day. There were 5 partial remissions (31.3%) and 9 no changes (56.3%) in the group with dexverapamil as opposed to 2 partial remissions (11.1%) and 6 no changes (33.3%) in the group without dexverapamil. As far as the preliminary results show, the addition of dexverapamil to vindesine/etoposide chemotherapy in this study seems to be associated with improved outcome.
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  • 13
    ISSN: 1432-1335
    Keywords: Lung cancer ; Genetic predisposition ; Familial cancer ; Benzo[a]pyrene, DNA adducts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The in vitro formation of benzo[a]pyrene-DNA adducts was determined in peripheral blood monocytes of 22 lung cancer patients with at least one first-degree relative with lung cancer and compared to results obtained in 30 healthy controls. In patients, the mean (SEM) adduct formation was 2.8 (0.3) fmol/μg DNA as compared to 2.1 (0.1) fmol/μg in controls (p〈0.05), and it was independent of age and smoking habits. These findings support the hypothesis that carcinogen-DNA adduct formation may be one factor of a constitutionally enhanced lung cancer risk.
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  • 14
    ISSN: 1432-1335
    Keywords: Key words RT/PCR ; PTHrP ; Metastasis ; Blood ; Bone marrow ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor cell dissemination in the bone marrow is an independent prognostic marker for relapse and survival for patients with primary breast cancer. Parathyroid-hormone-related protein (PTHrP) is expressed in most primary tumors and bone metastases of patients with breast cancer. PTHrP acts as an autocrine growth factor for breast cancer cells in vitro and there is evidence that it is especially important for osseous metastasis. For a sensitive detection of PTHrP-positive disseminated tumor cells a reverse transcriptase/polymerase chain reaction (RT/PCR) assay for PTHrP transcripts in the peripheral blood (PB) and in the bone marrow (BM) has been established. In mixing studies, the sensitivity of the reverse transcriptase/polymerase chain reaction (RT/PCR) for PTHrP was one tumor cell in 1 × 106 mononuclear cells. At this level of sensitivity, transcripts of PTHrP were detected in none of 30 PB samples and in 3 of 25 BM samples of healthy volunteers; there were also no transcripts of PTHrP in the PB and BM of 6 patients with benign breast lesions. The PB samples of 31 patients and the BM samples of 34 patients with predominantly early-stage breast cancer were tested for PTHrP expression along with immunocytology against cytokeratin 18 (CK18) as a standard immunological detection technique. PTHrP expression was shown in 9 of 31 patients in the PB and in 9 of 34 patients in the BM. In 30 patients, PB and BM samples were available simultaneously. There were cases of combined positive findings in the PB and the BM (4/30) and of isolated positivity in the PB (5/30) or in the BM (4/30). Compared to immunocytology, RT/PCR assay of PTHrP assay was significantly more sensitive in the peripheral blood (8/30 by RT/PCR compared to 1/30 by immunocytology). In the bone marrow there were cases of positivity for both markers (2/34), cases of isolated positivity by immunocytology for CK18 (3/34) and cases of isolated positivity for PTHrP transcripts (7/34). In conclusion the RT/PCR assay for PTHrP transcripts is a feasible and very sensitive technique for the detection of tumor cell dissemination in the PB, even in patients with early-stage breast cancer. The specificity of detection of PTHrP transcripts in the bone marrow is limited, possibly because of autochthonous expression of PTHrP in osteoblastic cells. The clinical follow-up of the subgroups of patients at risk, as defined by this assay, will show its prognostic significance for patients with breast cancer.
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  • 15
    ISSN: 1432-1335
    Keywords: RT/PCR ; PTHrP ; Metastasis ; Blood ; Bone marrow ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tumor cell dissemination in the bone marrow is an independent prognostic marker for relapse and survival for patients with primary breast cancer. Parathyroid-hormone-related protein (PTHrP) is expressed in most primary tumors and bone metastases of patients with breast cancer. PTHrP acts as an autocrine growth factor for breast cancer cells in vitro and there is evidence that it is especially important for osseous metastasis. For a sensitive detection of PTHrP-positive disseminated tumor cells a reverse transcriptase/polymerase chain reaction (RT/PCR) assay for PTHrP transcripts in the peripheral blood (PB) and in the bone marrow (BM) has been established. In mixing studies, the sensitivity of the reverse transcriptase/polymerase chain reaction (RT/PCR) for PTHrP was one tumor cell in 1×106 mononuclear cells. At this level of sensitivity, transcripts of PTHrP were detected in none of 30 PB samples and in 3 of 25 BM samples of healthy volunteers: there were also no transcripts of PTHrP in the PB and BM of 6 patients with benign breast lesions. The PB samples of 31 patients and the BM samples of 34 patients with predominantly early-stage breast cancer were tested for PTHrP expression along with immunocytology against cytokeratin 18 (CK18) as a standard immunological detection technique. PTHrP expression was shown in 9 of 31 patients in the PB and in 9 of 34 patients in the BM. In 30 patients, PB and BM samples were available simultaneously. There were cases of combined positive findings in the PB and the BM (4/30) and of isolated positivity in the PB (5/30) or in the BM (4/30). Compared to immunocytology, RT/PCR assay of PTHrP assay was significantly more sensitive in the peripheral blood (8/30 by RT/PCR compared to 1/30 by immunocytology). In the bone marrow there were cases of positivity for both markers (2/34), cases of isolated positivity by immunocytology for CK18 (3/34) and cases of isolated positivity for PTHrP transcripts (7/34). In conclusion the RT/PCR assay for PTHrP transcripts is a feasible and very sensitive technique for the detection of tumor cell dissemination in the PB, even in patients with early-stage breast cancer. The specificity of detection of PTHrP transcripts in the bone marrow is limited, possibly because of autochthonous expression of PTHrP in osteoblastic cells. The clinical follow-up of the subgroups of patients at risk, as defined by this assay, will show its prognostic significance for patients with breast cancer.
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  • 16
    ISSN: 1569-8041
    Keywords: cisplatin ; MTA ; non-small-cell lung cancer (NSCLC) ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:To evaluate the activity of MTA plus cisplatin inchemotherapy-naïve patients with non-small cell lung cancer (NSCLC). Patients and methods:Thirty-six chemotherapy-naïve patientswith NSCLC received 500 mg/m2 MTA plus 75 mg/m2cisplatin every 21 days, with 4 mg dexamethasone orally twice daily on the daybefore, of, and after MTA administration. Results:Median age was 58 years. WHO performance status was0–2. Eighteen patients each had stage IIIB and IV disease. Seventeenpatients each had squamous-cell and adenocarcinoma; two had undifferentiateddisease. Fourteen patients (39%; 95% confidence interval:23%–57%) showed partial response; seventeen (47%)had stable disease. Median survival was 10.9 months. Twenty-one patients(59%) experienced grade 3 or 4 granulocytopenia without fever orinfection. Five (14%) and six (17%) patients experienced grade3 anemia and grade 3 or 4 thrombocytopenia, respectively. Nonhematologicaltoxicities included grade 3 nausea in two patients (6%), and grade 3and 4 diarrhea in one patient (3%) each. One patient each experiencedgrade 4 ALT and grade 3 bilirubin and AST elevations. Conclusions:MTA plus cisplatin is well tolerated and activeagainst NSCLC. Further studies of this combination are warranted.
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  • 17
    ISSN: 1432-1750
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 18
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Chemie Ingenieur Technik - CIT 63 (1991), S. 378-379 
    ISSN: 0009-286X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 2 Ill.
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