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R Callies

Publications and source records attributed to R Callies.

At least 19 recordsLinked to original sources

Overexpression of cyclo-oxygenase-2 is an independent predictor of unfavourable outcome in node-negative breast cancer, but is not associated with protein kinase B (Akt) and mitogen-activated protein kinase (ERK1/2, p38) activation or with Her-2/neu signalling pathways.

BACKGROUND AND AIM: The production of prostaglandins is regulated by cyclo-oxygenases (COXs), which also have a role in tumour development and progression in various malignancies, including breast cancer. The mechanisms by which COX-2 contributes to unfavourable prognosis are still poorly understood. The association between expression of COX-2 and possible linked signalling pathways-namely, Akt, extracellular regulated kinases (ERK1/2), the stress-activated kinase p38 or Her-2/neu-is assessed in a series of 113 node-negative breast cancers. RESULTS: COX-2 was identified as an independent prognostic factor (p = 0.034) in node-negative breast cancer by survival analysis. The lack of a relationship between COX-2 expression and activated Akt, Erk1/2, p38 and Her-2/neu was indicated by statistical analysis. CONCLUSIONS: The prognostic effect of COX-2 expression on lymph node-negative breast cancer is confirmed-COX-2 is probably not regulated by HER-2, Akt, Erk1/2 or p38. Further studies are necessary for the elucidation of the signalling pathways responsible for the modification of COX-2 expression and the increased aggressiveness of breast cancers overexpressing COX-2.

Aged↗

[Antibiotic prophylaxis in cesarean section -- piperacillin versus piperacillin/tazobactam in 300 cesarean sections].

INTRODUCTION: Antibiotic prophylaxis is a standard procedure in obstetric surgery and has been discussed in various investigations. Use of treatment is judged by high efficacy and good tolerance. METHOD: In 300 patients undergoing cesarean sections we compared results of application of Piperacillin 4 g and Piperacillin/Tazobactam 4.5 g after cut of umbilical cord. Tazobactam/Piperacillin is a combination of a broad-spectrum penicillin and a beta-lactamase inhibitor with increased toxicity against staph. aureus, enterobacter, and other germs responsible for local and systemic infections in obstetric surgery. RESULTS: We did not observe any severe adverse effects. Rate of severe wound infections was 1.3 % (Tazobactam/Piperacillin) and 2 % (Piperacillin alone). The difference showed no statistic significance (p > 0.01). During postoperative course we found a higher increase of CRP (p < 0.01) in the Piperacillin group. CRP proved to be a useful objective parameter to distinguish between patients with or without postoperative infections. No differences were found in the number of leucocytes, time in hospital and other parameters.

Anti-Bacterial Agents↗

Relationship and prognostic significance of phospho-(serine 166)-murine double minute 2 and Akt activation in node-negative breast cancer with regard to p53 expression.

The Akt signalling pathway plays a central role in tumourigenesis. Activation of Akt is related to a more aggressive phenotype in various human cancers, including breast cancer. Its activation contributes to cancer progression via pleiotropic effects, including suppression of apoptosis and modulation of cell cycle regulation. Murine double minute 2 (MDM2) is an oncoprotein that inhibits the function of p53 tumour suppressor protein. Cell culture studies show that Akt-related phosphorylation of MDM2 at serine 166 allows MDM2 to gain nuclear entry and fulfil its p53 regulating function. This study was designed to analyse the relationship of phospho-MDM2 (pMDM2) expression with Akt activation to determine a possible prognostic relevance of pMDM2 in node-negative breast cancer with respect to Akt activation and p53 status. pMDM2, phospho-Akt (pAkt) and p53 protein expression status were analysed immunohistochemically in 121 paraffin-embedded breast cancer cases. Expression of pMDM2 correlated with Akt activation (P<0.001). Univariate analysis identified pMDM2 as a prognostic factor (P=0.0458) in node-negative breast cancers. The unfavourable prognostic significance was even more pronounced in tumours with a pMDM2(+)/pAkt(+) immunophenotype (P=0.0205). Stratification into a p53-negative subgroup further strengthened the adverse prognostic influence. These data confirm that MDM2 phosphorylation at serine 166 is mediated by Akt kinase. Besides the prognostic impact of pMDM2, our findings suggest that Akt-mediated modulation of the MDM2/p53 complex contributes to increased tumour aggressiveness especially in p53-negative breast cancers. However, due to the relatively small number of patients in this cohort, the results obtained need to be confirmed by larger cohorts.

Biomarkers, Tumor↗

[Pros and cons of early cancer detection in breast carcinoma].

Mammography is an appropriate method for the detection of early forms of cancer of the breast, and for reducing mortality. Whether this actually succeeds depends upon the quality of the early detection strategies employed. Currently the data on reduction of mortality by mammographic screening remain ambivalent.

Adult↗

[Detection of endometriosis during cesarean section for HELLP syndrome in the 32nd week of pregnancy].

The rare case of a decidualized endometriosis of the appendix vermiformis is reported in a woman who developed HELLP syndrome during the 32nd week of a twin pregnancy. Cesarean section and simultaneous appendectomy were performed. An inspection of the appendix should always be carried out if an endometriosis-associated anamnesis is known. No pathophysiological correlations between the HELLP syndrome and the endometriosis of the appendix vermiformis could be found.

Adult↗

Expression of the cell adhesion molecules ICAM-1 and VCAM-1 in the cytosol of breast cancer tissue, benign breast tissue and corresponding sera.

OBJECTIVE: Cellular adhesion molecules ICAM-1 and VCAM-1 have been implicated in tumor progression and metastasis. As the sequential interaction of neoplastic cells with the endothelium of tumor neovascularisation is believed to be essential for tumor metastasizing processes, we analysed the concentration of ICAM-1 and VCAM-1 in the cytosol of patients with human breast cancers and their corresponding sera. We compared the obtained values with established prognostic parameters for breast cancer. Benign breast tissues were also analyzed. PATIENTS AND METHODS: Levels of ICAM-1 and VCAM-1 of 62 patients with invasive breast cancer and 17 patients with benign breast tissue were measured using commercially available sandwich enzyme-linked immunoassays with monoclonal antibodies. To establish a reference and control group, levels of ICAM-1 and VCAM-1 were measured in the sera of 66 women without breast tumors. RESULTS: The mean cytosol concentration of ICAM-1 and VCAM-1 was significantly higher in the breast cancer specimens than in the tissue of patients with benign breast diseases. This could be found not only in the tumor cytosol but also in the corresponding sera of the patients. No correlations between the ICAM-1 and VCAM-1 expressions and established prognostic parameters could be observed. CONCLUSIONS: Our findings suggest that malignant breast cancer cells could induce neovascularisation with subsequent high expressions of ICAM-1 and VCAM-1. These upregulations of adhesion molecules might contribute to changes in invasive phenotypes by promoting endothelial cell adhesion and angiogenesis, as well as being responsible for the recognition of tumor cells by the human immune system. Prognostic relevance for the development of breast cancer could not be established.

Adult↗

The role of age in the course of breast cancer.

UNLABELLED: BACKGROUND AND QUESTION: A retrospective study was performed. To check the hypothesis whether there is an inverse connection between age and prognosis. PATIENTS AND METHODS: We investigated a total group of 1000 cases with breast cancer primarily and consecutively treated between 1968 and 1986. After grouping the patients by tumor stage and median age various life table analyses were performed to calculate and compare the overall survival. Entry date was the date at diagnosis of a first breast cancer or date at first diagnosis of distant metastasis. RESULTS: Young patients with a tumor size T1 and T2 had a significantly better prognosis than older patients with the same tumor stage. Influence of age became significantly weaker in patients with a T3 and T4 tumor. At least in the patients with a primarily M1 stage hardy any more dependence of age could be demonstrated. Similar results were obtained for the 198 patients which presented a distant recurrence. CONCLUSION: Better general life expectancy of young patients is the cause of substantially better overall survival in curable stages. Advanced breast cancer is a strongly life-threatening factor. The fatal influence of large tumor mass is independent of age.

Aged↗

Expression of the CD44 variant isoforms 6 and 4/5 in breast cancer. Correlation with established prognostic parameters.

Eighty one invasive breast cancers were analysed immunohistochemically to detect if they expressed the adhesion molecules CD44 v6 and v4/5, and the results were evaluated using the semiquantitative IR-score. The results were further divided into four groups: negative, weak positive, moderate positive and strong positive. Fifteen benign breast tumors were also analysed. Sixty eight breast cancers were CD44v6 and v4/5 positive. T3 and T4 cancers showed statistically significant higher positive CD44 rates than T1 and T2 cancers (P < 0.05). We also found a statistically significant correlation between the estrogen receptor and the CD44 status and between the CD44 status and the cathepsin-D status, whereas no correlation between CD44 and the lymph node status, the M status, the grading of the tumors, the progesterone receptor and the menopausal status could be found. Eleven benign tumors were CD44v6 and v4/5 positive. We could not establish any correlation between the expression of CD44 and the metastasizing capacity of breast cancer.

Breast↗

Detection of p53 auto-antibodies in the sera of breast cancer patients with a new recurrence using an ELISA assay. Does a correlation with the recurrence free interval exist?

INTRODUCTION: Mutations of the tumor suppressor gene p53 are common in multiple cancer forms, including breast cancer. Data are available that suggest, that the loss of the wild type form of p53 and the appearance of the mutant forms of p53 are correlated with a poorer overall survival rate in patients with breast cancer. The accumulation of the mutant forms of p53 in the cytoplasmatic rooms of the tumor cells leads to the production of human auto-antibodies against these mutant p53 proteins. Therefore, the aim of this study was to analyse and quantify the levels of serum auto-antibodies against p53 protein in patients with an intact immunological system having an active and new recurrence of breast cancer and to compare the obtained results with the recurrence free interval and with established prognostic parameters at the time of first diagnosis, to see if patients with a positive p53 auto-antibody status had a poorer prognosis than those who were p53 auto-antibody positive. MATERIALS AND METHODS: The ser of 61 patients with breast cancer, who experienced a new, clinical and biophysically identified local or distant recurrence and that showed an intact immunological system were analysed with an ELISA assay of Dianova to determine the concentration of auto-antibodies against mutant p53. RESULTS: 14.5% of the patients showed a positive p53 auto-antibody serum status. The recurrence free interval between the p53 auto-antibody positive and negative patients was almost the same: 4.12 years for the p53 auto-antibody positive patients versus 3.72 years for the p53 auto-antibody negative patients (independent t-test value = 0.224 and p value = 0.824; statistically not a significant difference). When comparing the p53 auto-antibody status with established prognostic parameters we could only find a statistically significant correlation with tumor size. No correlations were obtained when comparing the p53 auto-antibody status with the N- and M status, the ER- and PR status, the menopausal status and the cathepsin-D status. DISCUSSION: We were able to demonstrate that the expression of serum auto-antibodies against mutant p53 can not be used as a prognostic parameter in patients with breast cancer as the recurrence free interval between the p53 auto-antibody positive and negative patients did not differ. The determination of the auto-antibodies against p53, though easy to perform, is therefore not a test that helps clinicians in their treatment options, but it remains a useful test for the description of the biological mechanisms of breast cancer.

Autoantibodies↗

Estrogen and progesterone receptor content of GnRH analogue pretreated and untreated uterine leiomyomata.

OBJECTIVES: The steroid receptor concentration and the histological morphology of uterine leiomyomata in premenopausal patients undergoing myomectomy therapy with and without a preoperative GnRH analogue, was analysed to evaluate whether the GnRH analogue therapy leads to important hormonal receptor changes, histomorphological changes and a significant shrinkage of the leiomyomata. STUDY DESIGN: Sixty-one GnRH analogue pretreated leiomyomata and 28 untreated leiomyomata were analysed. To determine the estrogen and progesterone receptor concentrations, immunohistochemical techniques were used and quantified with the immuno-reactive score (IRS-score). The leiomyomata were divided into cellular rich, normal, hyaline or cystic degenerated and necrotic according to their histology. RESULTS: The GnRH analogue pretreated leiomyomata group showed higher levels of estrogen and progesterone receptors than the untreated group (37.7% of the GnRH analogue group had a high positive and 29.5% a moderate positive estrogen receptor status whereas high levels of estrogen receptor could be found in only 14.3% of the untreated group). The leiomyomata of both groups with the exception of the necrotic ones, were estrogen and progesterone receptor positive. CONCLUSIONS: Our study suggests that pretreatment of uterine leiomyomata leads to a significant increase in the hormonal receptor concentration of these benign tumors. If pretreated leiomyomata are not removed surgically immediately after the therapy, a rapid regrowth can occur and again cause clinical symptoms.

Antineoplastic Agents, Hormonal↗

[ROC analysis of image quality in digital luminescence radiography in comparison with current film-screen systems in mammography].

AIM: To compare in mammography the image quality of digital luminescence radiography (DLR) to that of usual film screen mammography and xeromammography. MATERIALS AND METHODS: Three single emulsion film-screen combinations, one double coated high resolution film and xeroradiography, were tested for this purpose. In our phantom study the detectability of microcalcifications, fibrils and low contrast details were first of all studied separately. Image processing techniques were, for example, contrast variation by grey scale level windowing, "unsharp mask" filtering and regulatable edge enhancement. Phantom images were made and then the image quality was evaluated by observer performance study using a receiver operating characteristic (ROC analysis). RESULTS: Best results in respect of detection of microcalcifications and fibrils were found in xeroradiography, luminescent image plate and double-coated film-screen combination. These systems showed more favourable ROC curves than the single emulsion film-screen combinations. CONCLUSIONS: Our results indicate that image quality of digital images in the field of image processing is equal to that of conventional mammographic techniques and partially superior to detection of low contrast details.

Breast Neoplasms↗

Level of c-erbB-2 oncoprotein in the homogenate of malignant and benign breast tumor samples.

The concentration of c-erbB-2 oncoprotein (HER-2/neu) was examined in the membrane fraction of 196 breast cancer and 39 benign breast specimens using a recently introduced ELISA-assay. The results were compared with established clinical and laboratory prognostic factors, 19% of all breast cancer specimens showed a c-erbB-2 protein level above 10 HNU/micrograms extract protein and were so classified as positive. Considering only the samples of primary tumors the rate was 21%. Surprisingly the rate was only 13.5% in the tissue samples of recurrent disease. Significant correlations were found between high c-erbB-2 protein levels and the tumor diameter, the axillary lymph node status and the progesterone receptor status. In contrast no correlation was found with estrogen receptor or menopausal status. All specimens of benign tumors showed levels < 10 HNU/micrograms extract protein and were classified as negative. The measurement of the c-erbB-2 protein using this ELISA assay was simple to perform and revealed reliable results. Nevertheless the prognostic power of the c-erbB-2 protein seems to be of minor relevance in comparison with established clinical and laboratory parameters, as the positive rates are too small in regard to the much higher recurrence rates of breast cancer. Probably the serum levels of this oncoprotein will be of greater clinical interest in the course of breast cancer.

Breast Diseases↗

The appearance of neutral lipid signals in the 1H NMR spectra of a myeloma cell line correlates with the induced formation of cytoplasmic lipid droplets.

The appearance of high resolution neutral lipid signals in the 1H NMR spectra of myeloma cells grown in the presence of oleate was shown to correlate with the appearance of cytoplasmic lipid droplets observable by electron microscopy. The spin-spin relaxation times of these lipid signals were similar to those measured previously for lipid resonances in other cell types. These data suggest that cytoplasmic lipid droplets could make a significant contribution to the neutral lipid signals observed in the 1H NMR spectra of some cells.

Animals↗

In situ nuclear magnetic resonance of N pulse labels monitors different routes for nitrogen assimilation.

Nuclear magnetic resonance offers the possibility of noninvasive in situ observation of (15)N pulse labeling in the presence of light. In vivo, exclusively the delta-nitrogen of Gln is labeled in the cyanobacterium Microcystis firma when glutamate synthase is inhibited by azaserine. In contrast, the green alga Chlorella fusca is additionally capable of incorporating nitrogen into Glu, thus providing evidence for an anabolic function of glutamate dehydrogenase in this organism.

Journal Article↗

Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study.

Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4-hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer.

Adult↗