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Biomedical subjects

E Steiner

Publications and source records attributed to E Steiner.

At least 19 recordsLinked to original sources
PubMed2007

Role of the progesterone receptor for paclitaxel resistance in primary breast cancer.

Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) mRNA expression was also determined by quantitative RT-PCR. We observed a clear association of the PR status with chemosensitivity to paclitaxel. Higher levels of immunohistochemically detected PR expression correlated with decreased chemosensitivity (P=0.008). Similarly, high levels of PR mRNA expression were associated with decreased paclitaxel chemosensitivity (P=0.007). Cells from carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2 (P=0.013). Multiple regression analysis identified PR receptor status and T-stage as independent predictors of paclitaxel chemosensitivity, whereas the ER, N-stage, grading and age were not influential. In conclusion, in vitro sensitivity to paclitaxel was higher for PR-negative compared with PR-positive breast carcinoma cells. Thus, PR status should be considered as a possible factor of influence when designing new trials and chemotherapy protocols.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Full spectral decomposition of ring currents.

Within the ipsocentric method for calculation of molecular magnetic response, projection of perturbed orbitals onto the virtual orbital space allows partition of induced current density into contributions from individual virtual excitations between occupied and unoccupied orbitals, enabling detailed assignment of the origin of currents in, e.g., benzene, cyclooctatetraene, borazine, coronene, and corannulene. Whereas delocalized currents in benzene and planar cyclooctatetraene are described by transitions within the valence space, localized currents in the borazine pi system involve excitations outside the valence space.

Journal Article↗
PubMed2006

Phase II study of weekly docetaxel in patients with recurrent or metastatic endometrial cancer: AGO Uterus-4.

OBJECTIVE: The aim of this phase II multicenter study was to evaluate the safety, toxicity and efficacy of docetaxel administered weekly as first line chemotherapy in patients with recurrent or metastatic endometrial cancer. PATIENTS AND METHODS: Thirty five patients with recurrent or metastatic endometrial cancer without previous chemotherapy were enrolled to receive three 6-week cycles of docetaxel 35 mg/m(2)/week with 2-week breaks between the cycles. Therapy response was evaluated after every 6-week cycle, and therapy was continued in case of at least stable disease. Final therapy response was evaluated after three 6-week cycles of docetaxel. RESULTS: Thirty five patients with a median age of 65 years (range, 37-80 years) were evaluable for toxicity assessment, one patient presented with severe anaphylactic reaction during the second application of docetaxel and therapy was discontinued. Subsequently, this patient received doxorubicin-cisplatin combination chemotherapy. Another patient was initially documented with uterine papillary serous cancer but secondarily confirmed as uterine carcinosarcoma. Thus, 33 patients were assessable for response. Overall response rate was 21% (3 PR and 4 CR). Three patients showed stable disease. Median TTP and OAS were 12 weeks and 43 weeks, respectively. Therapy with weekly docetaxel was well tolerated; in particular, no grade 3 or 4 hematological toxicities occurred. CONCLUSION: Docetaxel weekly has a favorable toxicity profile, is well tolerated and shows encouraging activity in patients with advanced endometrial cancer.

Adult↗
PubMed2006

[Plastic reconstructive procedures of vulvar carcinoma: results and complications].

PURPOSE: This study describes the results of the plastic reconstructive measures in 207 patients with a primary or a recurrent vulvar cancer. These procedures were analysed in sight of surgical excision, previous therapy, and detailed postoperative results. METHODS: All procedures and clinical parameters were recorded standardized in a data bank and analysed using statistical methods. RESULTS: In 123 local (cutaneous or fasciocutaneous) and 84 regional (myocutaneous) flaps we found a primary healing in about 2/3 of the cases. Local flaps exhibited secondary healing in 31 %, regional flaps in 20 %. This often involved the donor sites and generally did not present any permanent problems. Pronounced healing disturbances (necrosis of more than 10 %) was not achieved in local flaps, in regional flaps it aroused in 5.9 %. Gluteal femoral flaps were used most frequently and showing the best results of all myocutaneous flaps. They were comparable with the local reconstructions by a high degree of reliability and healing. In 15 cases a tissue-loss was observed. In these patients, elevated risk factors, certain oncological characteristics and technical problems could be demonstrated. CONCLUSION: Plastic surgery enlarges the spectrum of operative therapy of vulvar cancer, especially in extensive or recurrent tumors, leading to a favourable oncological outcome and good cosmetic results. Severe healing disturbances are rare and can be controlled.

Adult↗
PubMed2006

Cellular functions of vaults and their involvement in multidrug resistance.

Vaults are evolutionary highly conserved ribonucleoprotein (RNP) particles with a hollow barrel-like structure. They are 41 x 73 nm in size and are composed of multiple copies of three proteins and small untranslated RNA (vRNA). The main component of vaults represents the 110 kDa major vault protein (MVP), whereas the two minor vault proteins comprise the 193 kDa vault poly(ADP-ribose) polymerase (VPARP) and the 240 kDa telomerase-associated protein-1 (TEP1). Vaults are abundantly present in the cytoplasm of eukaryotic cells and they were found to be associated with cytoskeletal elements as well as occasionally with the nuclear envelope. Vaults and MVP have been associated with several cellular processes which are also involved in cancer development like cell motility and differentiation. Due to the over-expression of MVP (also termed lung resistance-related protein or LRP) in several P-glycoprotein (P-gp)-negative chemoresistant cancer cell lines, vaults have been linked to multidrug resistance (MDR). Accordingly, high levels of MVP were found in tissues chronically exposed to xenobiotics. In addition, the expression of MVP correlated with the degree of malignancy in certain cancer types, suggesting a direct involvement in tumor development and/or progression. Based on the finding that MVP binds several phosphatases and kinases including PTEN, SHP-2 as well as Erk, evidence is accumulating that MVP might be involved in the regulation of important cell signalling pathways including the PI3K/Akt and the MAPK pathways. In this review we summarize the current knowledge concerning the vault particle and discuss its possible cellular functions, focusing on the role of vaults in chemotherapy resistance.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Influence of diabetes mellitus and nodal distribution in endometrial cancer and correlation to clinico-pathological prognostic factors.

OBJECTIVE: The aim of this study was to describe the relationships between the distribution of nodal disease, clinico-pathological patterns and recurrence and survival in surgically staged cases of endometrial cancer. METHODS: Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence and survival were collected. The chi square test was used to test associations between variables. The Kaplan-Meier method was used for survival analysis and Cox's proportional hazards model for multiple regression analysis. RESULTS: Sixty-nine out of 181 patients underwent lymph node dissection. Twenty-three had pelvic lymph node dissection, 23 underwent pelvic and paraaortic lymph node dissection and 20 patients had lymph node sampling. The median count of removed lymph nodes was 22.4. Fifty-four lymph node dissections showed negative lymph nodes and in 15 cases there was a minimum of one positive lymph node. Overall survival was in correlation to nodal involvement with a p value of 0.0017. Patients with lymph node involvement showed significantly more recurrence than patients with negative lymph nodes (p = 0.003). The depth of myometrial invasion correlated with lymph node metastasis (p = 0.01) and patients with additional diabetes mellitus showed significantly more nodal involvement (p = 0.02). CONCLUSION: Endometrial cancer showed pelvic lymph node (PLN) and paraaortic lymph node (PALN) involvement. Under-diagnosis of the disease might result if there was only a PLN, but with or without PALN involvement there was no significant difference in overall survival or recurrence. There was an univariate correlation between lymph node involvement and diabetes.

Acanthoma↗
PubMed2005

Reconstructive surgery following resection of primary vulvar cancers.

OBJECTIVE: This study describes the surgical treatment and follow-up of 213 patients with primary vulvar cancer; particular attention is given to reconstructive surgical procedures. METHODS: The clinical and pathological parameters of the patients were recorded according to standardized procedures, and the data concerning type of operation, surgical reconstruction and postoperative course of disease (recurrence-free and overall survival) were analyzed. RESULTS: In about one-third of the cases, plastic surgery reconstruction involving skin-flaps was performed. In the present group of patients, plastic surgery procedures led to an elevated degree of operability as well as to more satisfactory results in terms of wound healing. For minor cosmetic defects, local (fasciocutaneous) skin-flaps resulted in excellent wound healing and short periods of in-patient treatment, even in patients with larger tumors. In cases exhibiting more severe wounds extending over larger areas of the vulva and its surrounding regions, similarly encouraging results were achieved using regional (myocutaneous) skin-flaps. CONCLUSION: The present study shows that reconstructive surgery of the vulva leads to good results in patients with vulvar cancer. Plastic surgery enlarges the spectrum of available operative therapy in vulvar cancer, especially in large tumors, and its application leads to a favorable oncological outcome as well as excellent cosmetic results in patients with vulvar cancer.

Adult↗
PubMed2004

Intrinsic and acquired forms of resistance against the anticancer ruthenium compound KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A).

KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A) is a metal complex with promising anticancer activity. Since chemoresistance is a major obstacle in chemotherapy, this study investigated the influence of several drug resistance mechanisms on the anticancer activity of KP1019. Here we demonstrate that the cytotoxic effects of KP1019 are neither substantially hampered by overexpression of the drug resistance proteins multidrug resistance-related protein 1, breast cancer resistance protein, and lung resistance protein nor the transferrin receptor and only marginally by the cellular p53 status. In contrast, P-glycoprotein overexpression weakly but significantly (up to 2-fold) reduced KP1019 activity. P-glycoprotein-related resistance was based on reduced intracellular KP1019 accumulation and reversible by known P-glycoprotein modulators. KP1019 dose dependently inhibited ATPase activity of P-glycoprotein with a K(i) of approximately 31 microM. Furthermore, it potently blocked P-glycoprotein-mediated rhodamine 123 efflux under serum-free conditions (EC(50), approximately 8 microM), however, with reduced activity at increased serum concentrations (EC(50) at 10% serum, approximately 35 microM). Moreover, P-glycoprotein-mediated daunomycin resistance could only be marginally restored by KP1019 in serum-containing medium, also indicating an influence of serum proteins on the interaction between KP1019 and P-glycoprotein. Acquired KP1019 resistance was investigated by selecting KB-3-1 cells against KP1019 for more than 1 year. Only an approximately 2-fold KP1019 resistance could be induced, which unexpectedly was not due to overexpression of P-glycoprotein or other efflux pumps. Accordingly, KP1019-resistant cells did not display reduced drug accumulation. Their unique cross-resistance pattern confirmed an ABC transporter-independent resistance phenotype. In summary, the likeliness of acquiring insensitivity to KP1019 during therapy is expected to be low, and resistance should not be based on overexpression of drug efflux transporters.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Current density, chemical shifts and aromaticity.

The intimate link between chemical shifts and magnetic criteria for aromaticity prompts a search for detailed understanding of patterns of current density induced in pi systems by external magnetic fields. Conceptual and practical advantages of calculation of current densities with a specific method of distribution of origin of vector potential, the ipsocentric choice, where the induced current density at each point is calculated with that point as origin, are outlined. This choice leads uniquely to canonical molecular orbital contributions that are free of unphysical occupied-occupied mixing. Characteristic magnetic response of delocalized pi systems is then effectively restricted to the activity of a small number of frontier electrons, governed by simple symmetry and node-counting rules, and readily visualized in current density maps. Localized orbitals for sigma systems can also be used, again eliminating occupied-occupied mixing. For integrated properties (magnetizability and nuclear shieldings), the ipsocentric method gives, in a well-defined sense, the orbital contributions that are best for purposes of interpretation. The general theory is illustrated by maps for a set of annelated pentalenes; the known benzopentalene (1) and 1,2:4,5-dibenzopentalene (2), the still unknown isomer of 2, 1,2:5,6-dibenzopentalene (3), and cyclopent[b,c]acenaphthylene (4), an unknown isomer of pyracylene, all of which consist of fusions of formally aromatic and anti-aromatic pi-conjugated systems.

Journal Article↗
PubMed2004

[Stereotactic vacuum-assisted breast biopsy - analysis of 166 cases].

OBJECTIVE: Screening mammography (as planned in Germany) will lead to an increasing number of breast biopsies. The purpose of this study was to determine the promise of directional large core biopsy as a patient-protecting therapeutic method. MATERIAL AND METHODS: 166 vacuum assisted, X-ray-guided biopsy procedures were analysed. RESULTS: Histopathologic examination resulted in 75.8 % benign lesions. Atypical proliferation and noninvasive neoplasia was found in 18.6 %, invasive carcinoma in 5.4 % of the biopsies. Complications were few. Neither skin- or chestwall injuries, nor pain or intraoperative bleeding caused an abortion. Postoperative we found four cases of bleeding, further on in 28.3 % a superficial, in 3 % a larger and deep hematoma, but in total without any operative revision. No infection was diagnosed. In the average 17.2 (8-31) specimens were removed. After excision of 18 probes the definitive histopathologic diagnosis was clear in all cases, also, the microcalcifications were found. The underestimation rate amounted to 3 of 35 cases. CONCLUSIONS: This clinical study proves stereotactic vacuum-assisted biopsy as a relieable method for analysing indeterminate mammographically detected breast lesions, which shows lower rates of complications than conventional surgical procedures.

Adult↗
PubMed2003

p53 expression and resistance against paclitaxel in patients with metastatic breast cancer.

PURPOSE: Paclitaxel is an important agent in the pharmacological treatment of metastatic breast cancer. Despite its efficacy in selected patients, the majority of patients have a resistance against paclitaxel. The aim of this study was to identify the responding patients and hence prevent the other patients from ineffective treatment. Identifying these patients could spare them an ineffective treatment and could in turn characterize a subgroup of patients with a higher response rate. MATERIAL AND METHODS: Thirty-three patients with metastatic breast cancer received paclitaxel 175 mg/m(2 )either as first- (15 patients) or as second-line (18 patients) treatment. Immunohistochemistry was performed on the blocks of the primary tumors with monoclonal antibodies against p53, HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II. The expression of those factors was then correlated with the objective response to paclitaxel. RESULTS: Ten of 33 patients had an objective response to treatment. A significant correlation with the objective response was found for the expression of p53. None of the tumors with p53 expression ( n=11) responded to paclitaxel. In contrast, 10 of the 22 patients without p53 expression showed an objective response ( P=0.013). Expression of HER-2/ neu, P-glycoprotein, Glutathione-S-Transferase-pi, and beta-tubulin II did not show a correlation with the response to paclitaxel. CONCLUSION: The immunohistochemical detection of p53 characterizes patients with metastatic breast cancer unlikely to respond to paclitaxel.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Predictors of treatment discontinuity in outpatient mental health care.

BACKGROUND: Discontinuity of service utilisation among newly referred community outpatients is a common concern. However, knowledge about factors associated with service utilisation is inconsistent. METHOD: This study examined service utilisation of 323 newly referred patients in three community mental health centres (CMHCs) in Vienna, Austria over a 4-month period. Of this original cohort, 111 patients were interviewed at treatment start to identify factors associated with treatment discontinuity. RESULTS: After 4 months, one-third of the 323 newly referred patients had dropped out of CMHC treatment; one-third discontinued treatment at the CMHCs because of referrals or mutual agreement on treatment termination, and one-third was still in CMHC treatment. Multivariate analyses yielded a negative association between treatment discontinuity and the diagnosis of schizophrenia, availability of home care, living alone, and a high quality of life in the domains living situation and family/significant others. A positive association was found with unemployment, previous psychiatric admissions, low patient satisfaction with staff competence, and high self-assessment in global functioning. CONCLUSION: In treatment, differing perceptions of a patient's health status by the patient and by the psychiatrist should be addressed. Professionals should be aware that patients' difficulties in private social relations might affect both treatment alliance and service utilisation.

Adult↗
PubMed2002

[Valence of immunohistochemical analysis of endometrial carcinoma biopsy specimen].

OBJECTIVE: We compared immunohistological examination of endometrium biopsy specimen with the results of the immunohistological examination of tumor specimen to analyse the valence of this preoperative examination according to the clinico-pathological findings and overall-survival. MATERIAL AND METHOD: Between 1985 and 1995 193 women were treated of an endometrial carcinoma at the University hospital Mainz. In this group we evaluated 41 patients with enough preoperative endometrial biopsy material for a retrospective immunohistochemical analysis and complete follow-up data. The materials from diagnostic curettage were stained and analysed for oestrogen and progesterone receptor status and for MiB-1. The results were statistically analysed using Logrank-test for overall survival. RESULTS: The mean follow-up time was 49 months. We found a significant correlation between staining results of oestrogen (p-value = 0.0005) and progesterone (p-value=0.0003) receptor status with overall survival as well as for MiB-1 (p-value=0.05). The correlation of staining results between biopsy specimen results and tumor material from hysterectomy was 84-85 %. CONCLUSION: These well known prognostic factors are measurable on biopsy specimen material in same quality and high valence as on hysterectomy material.

Biopsy↗
PubMed2001

High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study.

BACKGROUND: Apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I) are thought to be better predictors of acute myocardial infarction than total cholesterol and LDL-cholesterol. We investigated whether apoB and apoA-I are predictors of risk of fatal myocardial infarction. We also aimed to establish whether apoB and apoA-I add further information about risk of fatal myocardial infarction to that obtained with total cholesterol, triglycerides, and LDL-cholesterol. METHODS: We recruited 175553 individuals mainly from screening programmes. We measured concentrations of apoB, apoA-I, total cholesterol, and triglycerides, and calculated apoB/apoA-I ratio and concentrations of LDL-cholesterol and HDL-cholesterol. The relation between death from acute myocardial infarction and initial values for apoB, apoA-I, and the other lipids was examined. FINDINGS: Mean follow-up was 66.8 months (SD 41.3) for 98722 men and 64.4 months (41.4) for 76831 women. 864 men and 359 women had fatal myocardial infarction. In univariate analyses adjusted for age and in multivariate analyses adjusted for age, total cholesterol, and triglycerides, the values for apoB and apoB/apoA-I ratio were strongly and positively related to increased risk of fatal myocardial infarction in men and in women. ApoA-I was noted to be protective. In multivariate analysis, apoB was a stronger predictor of risk than LDL-cholesterol in both sexes. INTERPRETATION: Although LDL-cholesterol and HDL-cholesterol are known risk factors, we suggest that apoB, apoB/apoA-I, and apoA-I should also be regarded as highly predictive in evaluation of cardiac risk. Although increased throughout the range of values of LDL-cholesterol, apoB and apoA-I might be of greatest value in diagnosis and treatment in men and women who have common lipid abnormalities, but have normal or low concentrations of LDL-cholesterol.

Adult↗
PubMed2001

Survival and extinction of delocalized ring currents in clamped benzenes.

Direct visualisation of induced current density in clamped benzenes 1-4 distinguishes between saturated clamping groups, for which the central benzene ring retains a conventional diamagnetic ring current, and strongly interacting, unsaturated clamps, for which the central ring supports only the localised circulations expected of a 1,3,5-cyclohexatriene with fully fixed double bonds.

Journal Article↗
PubMed2001

Yeast Mps1p phosphorylates the spindle pole component Spc110p in the N-terminal domain.

The yeast spindle pole body (SPB) component Spc110p (Nuf1p) undergoes specific serine/threonine phosphorylation as the mitotic spindle apparatus forms, and this phosphorylation persists until cells enter anaphase. We demonstrate that the dual-specificity kinase Mps1p is essential for the mitosis-specific phosphorylation of Spc110p in vivo and that Mps1p phosphorylates Spc110p in vitro. Phosphopeptides generated by proteolytic cleavage were identified and sequenced by mass spectrometry. Ser(60), Thr(64), and Thr(68) are the major sites in Spc110p phosphorylated by Mps1p in vitro, and alanine substitution at these sites abolishes the mitosis-specific isoform in vivo. This is the first time that phosphorylation sites of an SPB component have been determined, and these are the first sites of Mps1p phosphorylation identified. Alanine substitution for any one of these phosphorylated residues, in conjunction with an alanine substitution at residue Ser(36), is lethal in combination with alleles of SPC97, which encodes a component of the Tub4p complex. Consistent with a specific dysfunction for the alanine substitution mutations, simultaneous mutation of all four serine/threonine residues to aspartate does not confer any defect. Sites of Mps1p phosphorylation and Ser(36) are located within the N-terminal globular domain of Spc110p, which resides at the inner plaque of the SPB and binds the Tub4p complex.

Calmodulin-Binding Proteins↗
PubMed2001

Perineal excision of a large angiomyxoma in a young woman following magnetic resonance and angiographic imaging.

BACKGROUND: Aggressive angiomyxomas are rare, arise from connective tissue of the perineum or the lower pelvis, and affect predominantly young women. CASE: We describe an unusual case of aggressive angiomyxoma in which the perineal approach was possible owing to MRI scanning and selective angiography indications. CONCLUSION: In cases of large aggressive angiomyxomas these diagnostic procedures should make it possible to decide which operative route might be best for the patient.

Adult↗