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Biomedical subjects

W Böcker

Publications and source records attributed to W Böcker.

At least 19 recordsLinked to original sources
PubMed2006

[Papillary tumors of the breast].

The term papilloma applies to benign proliferative epithelial breast lesions with a papillary architecture. The papillae in such lesions contain an arborizing fibrovascular core, glandular surface epithelium and a basal myoepithelial layer. A basement membrane encloses these structures. Papilloma may occur at any site in the ductal lobular system and according to its localization is subdivided into two types: solitary (central) papilloma which are located in the major nipple/subareolar ducts or large segmental ducts and multiple (peripheral) papillomas in cystically dilated terminal ductal lobular units (TDLU). Stromal changes, epithelial metaplasia and/or proliferations and neoplasia may alter the prototypical architecture. In a significant number of papillomas atypia can be identified which have to be classified as atypical proliferates of the ductal type. These lesions must be distinguished from the papillary type of ductal carcinoma in situ. Some 17% of all papilloma are associated with (synchronous) intraductal or invasive carcinoma, but these also act as an indicator for subsequent (metachronous) carcinoma. As a consequence, in minimally invasive biopsy papilloma has to be classified as B3 and usually has to be followed by surgical excision.

Breast Neoplasms↗
PubMed2006

[The significance of "normal tissue" in the development of breast cancer: new concepts of early carcinogenesis].

Only little information on the primary molecularbiological events involved in early breast is available. In particular, the definition of postulated precursor lesions of invasive breast cancer, such as ductal hyperplasia or ductal carcinoma in situ, is under an intense, controversial discussion in terms of pathogenesis and tumor biology. The most recent research on biological regulation mechanisms and genetic alterations in morphologically normally appearing breast tissue give rise for a reinterpretation for the most common progression models of breast cancer. The detection of genetic alterations within normal breast tissue in particular challenges the commonly postulated relationship between invasive and in situ breast carcinomas on the one hand, and benign, proliferative breast lesions on the other. The concerns about these relationship are further supported by the description of different cellular compartments within the normal female breast, including a "progenitor cell compartment" with different cytokeratin expression patterns, which can be transferred towards well known or suspected precursor lesions of invasive and in situ breast cancer. The aim of this manuscript is to provide an overview of the most recent results and developments in breast pathology, and to describe the consequences of our changing understanding of breast carcinogenesis.

Breast↗
PubMed2006

A novel surgical technique for transverse sternal bone defects using flexible intramedullary nailing.

Transverse sternal bone defects as a result of surgery or trauma remain an important clinical condition with serious sequelae. Patients sometimes complain of local pain during movement and breathing. Usually, defects are filled with prosthetic materials which remain permanently IN SITU. Small defects can be treated with autogenous bone grafts, whereas large defects are difficult to stabilize with common osteosynthetic techniques. Here, we report a new surgical technique using flexible intramedullary nailing ("Elastic Stable Intramedullary Nailing"--ESIN or "Embrochage Centro-Medullaire Elastique Stable"--ECMES) to stabilize a sternal defect after surgical removal of an osteochondral lesion. The defect was bridged by two elastic titanium nails and an autogenous corticocancellous bone graft. This new surgical technique showed a good clinical and functional outcome.

Adult↗
PubMed2006

Hormones and progeny of breast tumor cells.

The rudimentary human glandular breast, with the approach of puberty, starts to grow both at glandular and stromal sites. Full differentiation is a gradual process and takes many years, and is only fully attained by pregnancy. The risk of breast cancer is inversely related to parity. Women during adolescence have the highest susceptibility to breast cancer development. This appears to be the period when the mammary gland has the highest number of stem cells. Stem cells may represent important targets for transformational events. Immunohistochemistry allows for identification of the lineage-specific precursor glandular and myoepithelial cells and their differentiated progeny. Both estrogen receptor subtypes are found in epithelial cells of alveoli and ducts as well as in stromal cells. Immunophenotypia of benign proliferative breast disease favors a fundamentally different epithelial composition from that of most malignant epithelial proliferations such as atypical ductal hyperplasia, ductal carcinoma in situ, lobular neoplasia and invasive breast carcinoma. Immunophenotypical characterization of these lesions assists in distinguishing benign from malignant disease. Based on the observation of bilateral risks and frequent multifocality with atypical ductal hyperplasia, atypical lobular hyperplasia and lobular carcinoma in situ, it is suggested that these may represent risk factors as well as precursors. One should, however, realize that ductal as well as lobular premalignant breast lesions ultimately arise from stem cells in the terminal duct lobular units. Estrogen receptor-beta (ERbeta)-positive and ERalpha-negative expression characterizes the highest levels of proliferative cancer cell activity. Point mutations and alterations of co-activators and co-repressors will also determine hormone sensitivity. There is evidence for different genetic pathways in the development of ductal carcinoma in situ and lobular carcinoma in situ. While they share recurrent 16q losses, a second hit in the E-cadherin gene explains the advent of lobular lesions and their common existence with the primary ductal type. Based on our immunocytochemical observations, the most likely target cell of malignant transformation is the Ck18/18-positive and ER-negative transient cell of normal breast epithelium. Pregnancy confers a different genomic imprint to breast epithelial stem cells. Further elucidation of this mechanism may assist in developing appropriate means of breast cancer prevention. This paper is the Pieter van Keep Memorial Lecture given by Professor Hermann Schneider at the 11th World Congress on the Menopause, October 18-22, 2005, in Buenos Aires, Argentina.

Breast Neoplasms↗
PubMed2005

Expression patterns of angiogenic and lymphangiogenic factors in ductal breast carcinoma in situ.

The objective of this study was to investigate expression of various growth factors associated with angiogenesis and lymphangiogenesis and of their receptors in ductal carcinomas in situ of the breast (DCIS). We studied protein expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF)-A, endothelin (ET)-1, and VEGF-C, and their receptors bFGF-R1, Flt-1, KDR, ET(A)R, ET(B)R, and Flt-4 immunohistochemically in 200 DCIS (pure DCIS: n=96; DCIS adjacent to an invasive component: n=104) using self-constructed tissue microarrays. Basic fibroblast growth factor-R1, VEGF-C, Flt-4, and ET(A)R were expressed in the tumour cells in the majority of cases, whereas bFGF and Flt-1 expression was rarely observed. VEGF-A, KDR, ET-1, and ET(B)R were variably expressed. The findings of VEGF-C and its receptor Flt-4 as lymphangiogenic factors being expressed in tumour cells of nearly all DCIS lesions and the observed expression of various angiogenic growth factors in most DCIS suggest that in situ carcinomas are capable of inducing angiogenesis and lymphangiogenesis. Moreover, we found a higher angiogenic activity in pure DCIS as compared to DCIS with concomitant invasive carcinoma. This association of angiogenic factors with pure DCIS was considerably more pronounced in the subgroup of non-high-grade DCIS (n=103) as compared with high-grade DCIS (n=94). Determination of these angiogenic markers may therefore facilitate discrimination between biologically different subgroups of DCIS and could help to identify a particularly angiogenic subset with a potentially higher probability of recurrence or of progression to invasiveness. For these DCIS, targeting angiogenesis may represent a feasible therapeutic approach for prevention of progression of DCIS to invasion.

Adolescent↗
PubMed2005

Targeting of Rad51-dependent homologous recombination: implications for the radiation sensitivity of human lung cancer cell lines.

The aim of the present work was to study the role of Rad51-dependent homologous recombination in the radiation response of non-small-cell lung cancer (NSCLC) cell lines. A dose- and time-dependent increase in the formation of Rad51 and gamma-H2AX foci with a maximum at about 4 and 1 h after irradiation, followed by a decrease, has been found. The relative fraction of cells with persisting Rad51 foci was 20-30% in radioresistant and 60-80% in radiosensitive cell lines. In comparison, a higher fraction of residual Dsb was evident in cell lines with nonfunctional p53. Transfection with As-Rad51 significantly downregulates radiation-induced formation of Rad51 foci and increases apoptosis, but did not influence the rejoining of DNA double-strand breaks. Interestingly, wortmannin, a well-known inhibitor of nonhomologous end-joining, also inhibits Rad51 foci formation. In general, there was no correlation between the clonogenic survival at 2 Gy and the percentage of initial Rad51 or gamma-H2AX foci after ionising radiation (IR). The most reliable predictive factor for radiosensitivity of NSCLC cell lines was the relative fraction of Rad51 foci remaining at 24 h after IR. Although most of the Rad51 foci are co-localised with gamma-H2AX foci, no correlation of the relative fraction of persisting gamma-H2AX foci and SF2 is evident.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

[Outcome quality in terms of product safety in preoperative autologous blood donation].

OBJECTIVE OF THE STUDY: The most common form of autologous blood transfusion is where blood is donated in anticipation of elective surgery. The aim of this study is to critically evaluate the product safety of autologous blood units. METHODS: The results are based on an analysis of the documented data and records of 22,630 cases with 21,553 patients and 49,650 autologous blood donations, blood processing and testing protocols, and reported transfusion reactions following autologous transfusions. RESULTS AND CONCLUSIONS: Autologous blood components are prepared individually, and an established system of quality assurance with controls of processes and products is particularly important to meet quality standards. The red cell content of autologous units cannot be standardized as in allogeneic components. Due to the differences between the laboratory screening programmes for patients and donors, the risk of transmission of virus infections is different from that of allogeneic blood components. The quality of stored autologous red cells is comparable to that of allogeneic products. Results of systematic sterility monitoring lead to the conclusion that under the conditions practised the risk of transfusion-associated sepsis is not higher to that of allogeneic products. Soluble biological response modifiers which accumulate during storage, are assumed to be the cause of reactions that occur in one of 4,500 autologous transfusions. Incorrect allocation and handling errors continue to be a serious problem in autologous transfusions.

Blood Component Transfusion↗
PubMed2003

Influence of local complications on capsule formation around model implants in a rat model.

We studied the capsule formation around various filled breast implants and other related changes in distant organs (e.g., liver, spleen, lymph nodes) in a rat model 3 and 6 months after implantation. Model implants, one per rat, (filled with saline, n = 19; silicone, n = 14; cohesive silicone, n = 17; and hydrogel, n = 19) were implanted subcutaneous in the lower back of rats. The animals were sacrificed regularly after 3 and 6 months of implantation or when wound defects occurred. The capsules and organs were examined histologically, and immunohistology of the capsules was performed. A monoclonal antibody specific for AIF-1 (allograft inflammatory factor 1) was used to detect activated macrophages. Wound defects occurred most frequently after implantation of saline and hydrogel implants. Increased capsule thickness was associated with increased grade of inflammation, fibrosis, and the type of implant filling. There was a significant positive correlation between capsule thickness, presence of chronic inflammation, and AIF-1-positive macrophages (p < 0.0001), indicating that inflammation plays an important role in capsule formation. Remarkably, saline and silicone implants (in absence of local complications) cause only a blande slight fibrosis in capsules after 6 months of implantation, whereas capsules around cohesive silicone implants exhibited a more severe fibrosis with an increased capsule thickness. Most importantly, hydrogel seems to be most potent to induce an inflammatory infiltrate with AIF-1 expressing macrophages at the implantation site, independent of implantation time, and capsules also produced a significant increase in thickness after 6 months.

Animals↗
PubMed2003

Interdisciplinary consensus on the use and technique of vacuum-assisted stereotactic breast biopsy.

PURPOSE: Quality assurance of stereotactic vacuum-assisted breast biopsy (VB). METHOD: A consensus was achieved based on the existing literature and the experience of VB users (Ethicon Endosurgery, Norderstedt). RESULTS: The imaging work-up must be completed according to existing standards before an indication for stereotactic VB is established. Indications include microcalcifications and small non-palpable masses; for the time being lesions very close to the skin and architectural distortions (radial scar) are considered less suitable. Acquisition of >20 cores (11 Gauge) should be routinely attempted (goals: as complete a removal of small lesions as possible, thereby increasing diagnostic confidence and reducing so-called 'underestimates'). The pre/post-fire and post-biopsy stereotactic images and a post-biopsy orthogonal mammogram must be documented. All cases with no or uncertain histopathological correlation require discussion in a regular interdisciplinary conference and a documented consensus concerning further work-up or therapy. Standardised documentation of the primary findings and follow-up mammography after approximately 6 months is requested. CONCLUSION: This consensus includes protocols for the establishment of an indication, performance indicators, interdisciplinary interpretation and therapeutic recommendation, documentation and follow-up. It does not replace official recommendations for percutaneous biopsy.

Biopsy, Needle↗
PubMed2002

[WHO classification of breast tumors and tumors of the female genital organs: pathology and genetics].

Under the supervision of P. Kleihues and L. H. Sobin, the "World Health Organisation Classification of Tumours" with its numerous volumes is currently being re-edited. Following the first three volumes on "Central Nervous System", "Digestive System" and "Haematopoetic System", the volume on "Tumours of the Breast and Female Genital Organs" will be published this autumn. This volume will be edited by F. Tavassoli and P. Devilee. The new WHO books serve a double function of text books and atlases of tumour pathology. The first part of the new volume includes the genetics and pathology of the entire spectrum of malignant tumours and their precursor lesions. The following part is devoted to benign proliferative lesions.

Breast Neoplasms↗
PubMed2001

Cytogenetic analysis of multifocal bladder cancer supports a monoclonal origin and intraepithelial spread of tumor cells.

Bladder cancer is often characterized by a multifocal growth pattern. This observation has given rise to the hypothesis of "field cancerization," predicting a polyclonal origin of multiple tumors rising from an area of independently transformed mucosa cells. On the other hand, genetic studies suggested a monoclonal origin. To address these contradictory hypotheses, we performed comparative genomic hybridization (CGH) on 32 tumors originating from six bladder cystectomy specimens. All tumors derived from the same patient showed a set of 7-13 identical chromosomal aberrations and additional individual alterations. Most striking were the findings of 17p losses in all (32 of 32) tumors of the six cystectomy specimens and 20p gains in all tumors of four bladders, as well as an unexpected high number of chromosomal changes (20.4 alterations per tumor on average). To clarify a possible role of the TP53 tumor suppressor gene on 17p13, we applied immunohistochemistry and sequence analysis on the tumors and additional 52 mucosa samples. Identical TP53 mutations and protein overexpression was found in individual tumors only as well as in mucosa samples from continuous areas. Our results not only provide further evidence for a monoclonal origin of multifocal bladder cancer but also point at intraepithelial migration of tumor cells carrying specific chromosomal aberrations.

Cell Movement↗
PubMed2001

[Endometrial metastasis of a "balloon" cell melanoma mimicking a "xanthomatous endometritis"].

Xanthomatous changes are unusual lesions of the corpus endometrium that may mask endometrial carcinoma. The term "xanthomatous endometritis" refers to morphological changes frequently induced by estrogen stimulation. We report for the first time a case of uterine metastasis of balloon-cell melanoma mimicking xanthomatous endometritis. Light microscopic, immunohistological, and ultrastructural results are presented and discussed in connection with our ideas on the pathogenesis of this peculiar tumor. The findings favor the hypothesis of a regressive phenomenon in the balloon-cell transformation of melanoma cells. The melan-A immunohistology seems to be more important in the diagnosis of balloon cell melanoma than the classic melanoma antibody HMB 45.

Diagnosis, Differential↗
PubMed2001

[Keratin 5-positive cells in the breast are progenitor cells of glandular and myoepithelial differentiation. A cell biological model as a basis of breast pathology].

In the present computer-assisted labelling study we demonstrate for the first time that in normal breast tissue keratin (K) 5+ progenitor cells give rise to either glandular (K 8/18+) or to myoepithelial cells (sm-actin = SMA+) via intermediary cells (either K 5/6+; K 8/18+ or K 5/6+; SMA+). Furthermore we have conclusive evidence that benign proliferative breast disease lesions are progenitor cell-derived lesions. In contrast, most breast cancers appear to evolve from glandularly differentiated cells. Western blotting experiments which show large amounts of K 5 in benign proliferative breast lesions, but not in ductal carcinoma in situ confirm the immunofluorescence data. Our results pave the way towards a new cell biological model of breast regeneration, benign proliferative breast disease and breast cancer.

Biomarkers↗
PubMed2000

[Establishing a cytogenetic and morphological progression models of invasive breast cancer. Comparative genomic hybridization (CGH) in malignant and premalignant tumors of the female breast].

Ductal carcinoma in situ of the female breast and lobular carcinoma in situ are regarded as precursor lesions of invasive breast cancer. We used comparative genomic hybridization to analyze the genetic relationship between these two types of lesion and invasive breast cancer. The series included 166 patients with ductal or lobular carcinoma in situ and invasive breast cancer. Our results reflect the broad heterogeneity of morphologically different subtypes of invasive and noninvasive breast cancer. The data also provide evidence of multiple genetic pathways of invasive breast cancer associated with different morphological subtypes. In conclusion, we propose a combined model of morphological-genetic progression with various parallel pathways in the pathogenesis of invasive breast cancer.

Breast Neoplasms↗
PubMed2000

Clinical relevance of immunohistochemical expression of p53-targeted gene products mdm-2, p21 and bcl-2 in breast carcinoma.

The present study was designed to investigate the clinical/prognostic relevance of immunohistochemical expression of p53-targeted genes mdm-2, p21WAF1 and bcl-2 alone and in combination with p53 for the indirect assessment of p53 gene status in breast cancer. 141 archival breast carcinomas were immunostained, and the putative mutational status of the p53 gene was defined in 21 of them, as a control for immunohistochemistry, using the polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis. Genetic changes of p53 correlated significantly with p53 protein overexpression (p = 0.01) but did not do so with any of the related molecules. Immunohistochemical p53 status was directly correlated with mdm-2 (p = 0.0001), p21 (p = 0.0004) and inversely with bcl-2 (p = 0.005) expression. bcl-2 proved to be an independent marker of prognosis, p53 only in the group of node-positive carcinomas, whereas bcl-2-/p53+ tumours revealed the worst prognosis. Mdm-2 and p21 expression was of prognostic significance neither alone nor in combination. We conclude that the detection of down-stream regulators of p53 does not increase the efficacy of immunohistochemistry in assessing the functional status of p53 in breast cancer; however, their combined analysis may help to select subgroups of patients at the extremes of risk for recurrence, or those with greater chances for survival.

Adult↗
PubMed2000

Effects of indapamide in rats with pressure overload left ventricular hypertrophy.

We studied the in vivo effects of the antihypertensive diuretic agent indapamide on left ventricular (LV) morphology in chronically pressure-overloaded rat hearts. LV pressure and subsequently LV mass were increased by banding the ascending aorta over a period of 6 weeks. Thereafter, animals were treated with low-dose (1 mg/kg/day, n = 9) or high-dose (10 mg/kg/day, n = 9) indapamide for another 6 weeks. Low-dose indapamide treatment reduced LV weights as compared with vehicle-treated controls (n = 9; -12%; p = 0.008). Furthermore, low-dose indapamide treatment resulted in a decrease of myocyte volume (59.0 +/- 10.6 vs. 79.0 +/- 9.8 m3 x 10(-27); p < 0.05) and an improvement of molecular markers of hypertrophy: a reduction of LV atrial natriuretic factor mRNA expression (-37%; p < 0.05), and an increase of the V1/V3 myosin ratio (+121%; p < 0.05). Low-dose indapamide also reduced significantly plasma (-65%) and LV angiotensin-converting enzyme (ACE) activities (-74%) as well as LV mRNA levels (-24%). These changes were observed despite continued pressure overload of the LV and despite a lack of significant changes in sodium excretion with the prolonged administration of low-dose indapamide. High-dose indapamide treatment showed no significant effects on LV mass, structure, and gene expression. Furthermore, high-dose indapamide increased plasma renin activity substantially, whereas low-dose treatment was without effect on circulating renin. In conclusion, in rats with continuous LV pressure-overload low-dose treatment with indapamide leads to mild regression of cardiac hypertrophy, accompanied by a downregulation of components of the cardiac renin-angiotensin system. These effects may be mediated by mechanisms apart from the known diuretic and antihypertensive actions of indapamide, because sodium excretion and blood pressure were stable with long-term treatment and are unlikely to be related to LVH regression in this model.

Animals↗