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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 26 (1990), S. S71 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The objective of our clinical studies was to develop an effective combination chemotherapy regimen (CHT) with acceptable side effects, consisting of the two most potent drugs used as single agents in breast cancer. We tested the combination of an anthracycline, epirubicin (A) at 70 mg/m2 i.v. on day 1 or (B) at 120 mg/m2 i.v. on day 1 with an alkylating drug ifosfamide (IFO), (C) at 2.5 g/m2 in an i.v. infusion given over 4 h on days 1–3 or (D) at 5 g/m2 in a 24-h i.v. infusion given on day 1. Courses were repeated every 4 weeks. The combinations were given as first-line therapy as follows: CHT (A, C) in six cases and CHT (B, C) in five cases of advanced breast carcinoma, and CHT (B, D) in seven patients with primary inflammatory breast cancer. Due to side effects (e.g., stomatitis, mental disturbances) and applicability, CHT regimen (B, D) was preferred. Responses (12/18) occurred 1–3 cycles earlier than those previously achieved using the conventional epirubicin/cyclophosphamide CHT. We conclude that 5 g/m2 IFO given i.v. over 24 h with uroprotection (mesna) in a two-drug regimen is an effective dose with tolerable toxicity. Alopecia was seen in all cases. However, according to our experience, myelotoxicity is the dose-limiting factor for both of these drugs.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The object of the study was to evaluate the effectiveness of ifosfamide/etoposide and mesna therapy in advanced breast cancer. A total of 44 patients with breast cancer were included in the trial. Eligibility criteria included measurable, refractory disease; prior anthracycline therapy (or its contraindication); a life expectancy of at least 3 months; and adequate hepatic, renal, CNS and bone marrow function. All patients were≤70 years of age and had a Karnofsky performance status of≥50%. There were 36 evaluable cases. Sites of metastatic disease included bone (19), skin (18), liver (9), lung (14), lymph node (19), and miscellaneous (7). Treatment consisted of 1,500 mg/m2 ifosfamide given i.v. on days 1–5, 120 mg/m2 etoposide given i.v. on days 1–3, and 400 mg i.v. mesna given with and at 4 and 8 h after ifosfamide. Cycles were repeated every 28 days. Initial doses were reduced by 25% or 50% in patients who had previously undergone both chemotherapy and radiotherapy. A median of 4 cycles (range, 2–8) were given. The myelotoxicity was marked: WHO grades 3/4 leukopenia (n=37), grades 3/4 thrombocytopenia (n=12), and grades 2/3 anemia (n=13). Due to myelotoxicity, dose reduction or prolongation of treatment-free intervals was necessary in 28 cases. Alopecia was seen in 35 patients and CNS toxicity, in 8. Partial remission (PR) was obtained in five cases and complete remission (CR), in three. Sites of response included the lung (5), skin (4), lymph node (5), and peritoneum (1). The duration of response was 4 (n=2) and 8 (n=1) months for CR and 2 (n=2), 6 (n=2), and 10 (n=1) months for PR. We conclude that the ifosfamide/etoposide and mesna regimen is effective, but its myelotoxicity is treatment-limiting.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7276
    Keywords: metastasis ; microvessel density ; ovarian carcinoma ; proto-oncogenes ; resistance-related proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Relationships between the incidence of metastatic spread and microvessel density, expression of proto-oncogene products, or expression of resistance-related proteins were investigated in human ovarian carcinomas by immunohistochemistry. Ovarian carcinomas with a high microvessel density showed a significantly increased formation of metastases (P=0.005). Tumors with positive immunoreactivity of c-jun and c-myc products had a higher metastatic spread; however, these results were not statistically significant. A marginally significant correlation existed between the expression of erbB1 (EGFR) and metastatic spread (P=0.05). No significant relationship was found between the expression of the resistance-related proteins P-glycoprotein or glutathione S-transferase-π and the incidence of metastases. Furthermore, no correlation was detected between expression of the heat shock protein 70 and the occurrence of metastases.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: estrogen receptor ; estrogen response element (ERE) ; gel-shift assay ; human breast tumors ; immunoreactive ER
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Evidence to date indicates that structurally abnormal estrogen receptor (variant ER) can be detected in some human breast tumors. Based onin vitro ability to bind DNA sequences containing the cognate estrogen response element (ERE), these variant receptors may be categorized into DNA-binding ER (Type-1 variants) and non-DNA-binding ER (Type-2 variants). To look for Type-2 variants of normal size (67 kDa ER) that lack the ability to form immunoreactive ER-ERE complexes, a panel of 40 cryopreserved primary breast tumors were extracted and analyzed by enzyme immunoassay (ER-EIA), gel-shift, and Western blot techniques. For the 33 tumor extracts containing ≥10 fmol/mg ER (by ER-EIA), the amount of 67 kDa ER detectable by D75 anti-ER monoclonal antibody under fully denatured and reduced assay conditions (Western blotting) did not correlate well with the presence or intensity of D75 immunoreactive ER-ERE bands seen under native conditions by gel-shift assay. Overall, 30% (10 of 33) of these extracts containing 67 kDa ER failed to produce immunoreactive ER-ERE complexes, with this frequency varying from over 40% in tumor samples with lower ER content (10-49 fmol/mg) to 11% in tumor samples with the highest ER content (〉100 fmol/mg). These results indicate that Type-2 variant receptors characterized as non-DNA-binding 67 kDa ER may be present in a significant fraction of ER-positive primary breast tumors; preliminary evidence suggests that further study of abnormalities in ER tertiary or quaternary structure, such as those produced by intracellular oxidation of ER thiol groups, is warranted.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7217
    Keywords: breast cancer ; CD44 variants ; metastasis ; tumor progression marker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Splice variants of CD44 expressed in a metastasizing cell line derived from a rat pancreatic adenocarcinoma have been shown recently to confer metastatic potential onto non-metastasizing rat pancreatic carcinoma and sarcoma cell lines. Homologues of these variants have also been detected in a variety of human malignancies. Using antibodies raised against a bacterially expressed fusion protein containing variant CD44 sequences, we have explored the expression of variant CD44 glycoproteins on tumors of the female breast. The material examined included normal tissue, hyperplastic lesions, 103 primary invasive mammary carcinomas, 10in situ carcinomas, 12 local recurrences and 18 lymph node metastases. Using a polyclonal serum directed against several variant CD44 epitopes, normal mammary epithelia as well as ductal hyperplasias were negative for these splice variants, while the variant CD44 epitopes were detectable in all but six of the primary invasive carcinomas. From the reaction with various monoclonal antibodies and polyclonal sera specific for individual epitopes it is obvious that the tumors predominantly express CD44 variants encoded by exons v5 to v7. Interestingly, all investigated lymph node metastases reacted positively with the variant-specific antibodies, in contrast to primary tumors which reacted in 54% to 86% of the cases, depending on the antibody used. Statistical analysis revealed a significant correlation between expression of variant exons v3/v4 and v6 and increased tumor grade (p = 0.001 and p 〈 0.05, respectively; Fisher's exact test). Exon v6 is carried by the variants which confer metastatic capability in the rat. These results indicate that the expression of the CD44 variants is upregulated in mammary carcinomas and is closely linked to tumor anaplasia.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-0646
    Keywords: oxazaphosphorines ; chemotherapeutic activity ; myelotoxicity ; DNA-damage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This study compares the two oxazaphosphorine compounds ASTA Z 7557 (AZ) and cyclophosphamide (CP) in their therapeutic activity as well as in their myelotoxicity and DNA damage being induced after a single intraperitoneal injection. Therapeutic activity was determined towards methylnitrosourea-induced rat mammary carcinomas in vivo and in vitro, resulting in comparable efficacy of both compounds at their optimal doses, respectively, with the sensitivity of individual tumors being reflected by the degree of inhibition of 3H-thymidine uptake of these cells in vitro. Myelotoxicity was measured as inhibition of pluripotent (CFU-S) and macrophage-granulocyte committed (CFU-C) stem cells together with the extent of single strand breaks and DNA-DNA interstrand crosslinks in murine bone marrow. At equimolar base AZ was found to induce a higher level of DNA damage than CP in the bone marrow of mice 16 hours after a single intraperitoneal injection. Both compounds depressed the pluripotent stem cell compartment of the bone marrow to a similar extent, whereas AZ was significantly less toxic to the granulocyte cell lineage.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-7217
    Keywords: breast cancer ; gonadotropin-releasing hormone-analog ; GnRH ; receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gonadotropin-releasing hormone analogs (GnRH-A) have been added to the armentarium in the therapy of hormone-dependent breast cancer in premenopausal women. The effect of chronic GnRH-A-treatment in premenopausal women is based on the suppression of the hypothalamus-pituitary-ovarian axis and the reduction of sex-steroid serum levels. In addition, a number of experimental and clinical data have been accumulated indicating a direct action of GnRH-A on breast cancer cells and tissue. In this study we analyzed 235 human breast cancer biopsies for specific GnRH-A-binding. We demonstrate high affinity GnRH-A binding sites in human breast cancer tissues. The evaluation of clinical data showed no correlation of the level of GnRH-A-binding with classical tumor parameters.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 18 (1991), S. 43-48 
    ISSN: 1573-7217
    Keywords: breast cancer ; debrisoquine ; genetic pharmacology ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary There may exist an association between the genetically determined oxidation status of the antihypertensive agent debrisoquine (DEB) and the propensity to develop tumours. The metabolism of DEB is extensive in 90% of healthy subjects (metabolic ratio=MR=0–12.6; MR=% DEB excreted divided by % 4-hydroxy-DEB excreted) and poor in 10% (MR 〉12.6). In patients with cancer of the lung, urinary bladder, and gastrointestinum, the percentage of high metabolizers is increased to 〉98%. The poor metabolizer mode is almost devoid of cancer patients. It was investigated whether breast cancer patients show a similar association with respect to the oxidative status of DEB. 108 breast cancer patients and 123 women with benign gynecologic disorders received 1 tablet of 10 mg DEB orally in the evening. Urine was collected for the subsequent 8 hrs and analysed for its content of DEB and its main urinary metabolite 4-OH-DEB by means of HPLC. No decreased amount of poor metabolizers was seen in the cancer group.
    Type of Medium: Electronic Resource
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  • 9
    Publication Date: 2015-09-29
    Description: This paper presents new data sets relating to the abundance of atomic oxygen in the upper mesosphere and lower thermosphere, which were derived from the nighttime green line emission measurements of the SCIAMACHY (Scanning Imaging Absorption Spectrometer for Atmospheric CHartographY) instrument on the European Environmental Satellite (Envisat). These are compared to recently published data sets from the same SCIAMACHY green line measurements through the application of a different photochemical model and to data collected by the SABER (Sounding of the Atmosphere using Broadband Emission Radiometry) instrument. We find that the retrieved atomic oxygen concentration depends on the choice of the underlying photochemical model. These dependencies explain a large proportion of the differences between recently published data sets. The impact of the 11-year solar cycle on volume emission rates and atomic oxygen abundances was analyzed for various data sets, with the finding that the solar cycle effect varies with the atomic oxygen data set used. The solar cycle impact on the SCIAMACHY data increases with altitude. Above 96 km, it is significantly larger than predicted by HAMMONIA (Hamburg Model of the Neutral and Ionized Atmosphere). Investigations indicate that these variations are primarily driven by total density compression/expansion variations during the solar cycle, rather than different photolysis rates.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
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  • 10
    Publication Date: 2015-10-27
    Description: Cancer is a large class of diseases that are characterized by a common set of features, known as the Hallmarks of Cancer . One of these hallmarks is the acquisition of genome instability and mutations. This, combined with high proliferation rates and failure of repair mechanisms, leads to clonal evolution as well as a high genotypic and phenotypic diversity within the tumor. As a consequence, treatment and therapy of malignant tumors is still a grand challenge. Moreover, under selective pressure, e.g. caused by chemotherapy, resistant subpopulations can emerge that then may lead to relapse. In order to minimize the risk of developing multi-drug resistant tumor cell populations, optimal (combination) therapies have to be determined on the basis of an in-depth characterization of the tumor's genetic and phenotypic makeup, a process which is an important aspect of stratified medicine and precision medicine. We present DrugTargetInspector (DTI), an interactive assistance tool for treatment stratification. DTI analyzes genomic, transcriptomic and proteomic datasets and provides information on deregulated drug targets, enriched biological pathways and deregulated subnetworks, as well as mutations and their potential effects on putative drug targets and genes of interest. To demonstrate DTI's broad scope of applicability, we present case studies on several cancer types and different types of input -omics data. DTI's integrative approach allows users to characterize the tumor under investigation based on various -omics datasets and to elucidate putative treatment options based on clinical decision guidelines, but also proposing additional points of intervention that might be neglected otherwise. DTI can be freely accessed at http://dti.bioinf.uni-sb.de . This article is protected by copyright. All rights reserved.
    Print ISSN: 0020-7136
    Electronic ISSN: 1097-0215
    Topics: Biology , Medicine
    Published by Wiley-Blackwell
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