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Biomedical subjects

Thomas Bogenrieder

Publications and source records attributed to Thomas Bogenrieder.

14 recordsLinked to original sources
PubMed2003

[Detection of lymph node metastases of malignant melanoma by palpation and ultrasound].

BACKGROUND AND PURPOSE: Early detection of metastases of malignant melanoma has therapeutic implications. The aim of this study was to evaluate palpation and ultrasound examination in the diagnostics of lymph node metastases in locally advanced melanoma. PATIENTS AND METHODS: 83 patients suffering from melanoma (Clark level IV or V) were examined for lymph node metastases by palpation and sonography. Findings were compared to histopathologic results after lymph node extirpation if available or the findings at the next follow-up visit. RESULTS: Lymph node metastases were confirmed histopathologically in 14 patients at the first study visit, in three others at the control visit. Sensitivity, specificity, positive and negative predictive values of palpation for the detection of metastases or suspicious nodes with increasing volume at follow-up in this population were 65%, 81%, 48%, and 89%, and of ultrasound 100%, 66%, 45%, and 100%, respectively. CONCLUSION: Sonography of lymph nodes should be included as a standard procedure in the detection of metastases of locally advanced malignant melanoma.

Adult↗
PubMed2003

Reciprocal regulation of MelCAM and AKT in human melanoma.

Alteration in the expression of invasion/metastasis-related melanoma cell adhesion molecule (MelCAM) is strongly associated with the acquisition of malignancy by human melanoma. However, little is known about the molecular and biochemical mechanisms that regulate the expression and function of MelCAM, or its downstream signaling transduction. In this study, we show that there is a reciprocal regulation loop between AKT and MelCAM. Pharmacological inhibition of AKT in human melanoma cell lines substantially reduced the expression of MelCAM. Overexpression of constitutively active AKT upregulated the levels of MelCAM in melanoma cell lines, whereas expression of a dominant-negative PI-3 kinase downregulated MelCAM. On the other hand, overexpression of MelCAM activated endogenous AKT and inhibited proapoptotic protein BAD in melanoma cells, leading to increased survival under stress conditions. Constitutive activation of AKT was observed in most melanoma cell lines and tumor samples of different progression stages. These data link AKT activation with MelCAM expression, and implicate that intervention of MelCAM-AKT signaling axis in melanoma is a potential therapeutical approach.

Adenoviridae↗
PubMed2003

Axis of evil: molecular mechanisms of cancer metastasis.

Although the genetic basis of tumorigenesis may vary greatly between different cancer types, the cellular and molecular steps required for metastasis are similar for all cancer cells. Not surprisingly, the molecular mechanisms that propel invasive growth and metastasis are also found in embryonic development, and to a less perpetual extent, in adult tissue repair processes. It is increasingly apparent that the stromal microenvironment, in which neoplastic cells develop, profoundly influences many steps of cancer progression, including the ability of tumor cells to metastasize. In carcinomas, the influences of the microenvironment are mediated, in large part, by bidirectional interactions (adhesion, survival, proteolysis, migration, immune escape mechanisms lymph-/angiogenesis, and homing on target organs) between epithelial tumor cells and neighboring stromal cells, such as fibroblasts as well as endothelial and immune cells. In this review, we summarize recent advances in understanding the molecular mechanisms that govern this frequently lethal metastatic progression along an axis from primary tumor to regional lymph nodes to distant organ sites. Affected proteins include growth factor signaling molecules, chemokines, cell-cell adhesion molecules (cadherins, integrins) as well as extracellular proteases (matrix metalloproteinases). We then discuss promising new therapeutic approaches targeting the microenvironment. We note, however, that there is still too little knowledge of how the many events are coordinated and integrated by the cancer cell, with conspiratorial help by the stromal component of the host. Before drug development can proceed with a legitimate chance of success, significant gaps in basic knowledge need to be filled.

Cell Adhesion Molecules↗
PubMed2003

Function and regulation of melanoma-stromal fibroblast interactions: when seeds meet soil.

Melanoma development and progression not only involve genetic and epigenetic changes that take place within the melanocytic cells, but also involve processes that are determined collectively by contextual factors including intercellular adhesions and communications. In this review, we focus on melanoma-stromal fibroblast crosstalk by direct cell-cell contact and by growth factors/cytokines/chemokines interacting with their respective receptors. The interactions between melanoma cells and stromal fibroblasts create a context that promotes tumor growth, migration/invasion, and angiogenesis. An understanding of this process and developing new experimental and screening models are of great importance for the development of effective therapeutical strategies to treat melanoma.

Animals↗
PubMed2003

Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8.

IL-8 is a strong chemoattractant for neutrophils, and it is constitutively produced by many tumors, including human melanomas. To determine the biologic importance of IL-8 for melanoma cells from primary and metastatic lesions, we transduced selected cell lines constitutively producing low levels of IL-8 with IL-8 cDNA using a replication-deficient adenoviral vector. Nontumorigenic SBcl2 primary melanoma cells formed tumors when transduced with increasing plaque-forming units of IL-8 per cell. However, at high IL-8 transduction levels (100 ng/ml/10(5) cells in 48 hr), tumor growth was impaired due to massive neutrophil infiltration. A similar biphasic response was observed in WM115 primary melanomas, which are tumorigenic but not metastatic. Depletion of neutrophils with an antibody that blocks the accumulation of granulocytes at the site of inflammation enabled transduced primary melanomas secreting high levels of IL-8 to survive and grow. In contrast, highly tumorigenic and metastatic 451Lu cells showed marked increases in tumor growth and number of metastatic foci in the lungs depending on the expression levels of IL-8. Cytotoxicity assays with isolated neutrophils confirmed the preferential killing of primary over metastatic melanoma cells. SBcl2 cells stimulated by IL-8 to form tumors in immunodeficient mice were induced to produce VEGF, suggesting that the angiogenic response is enhanced due to increased growth factor production. Our results demonstrate that nontumorigenic primary melanomas depend on IL-8 stimulation in vivo for growth and that tumor growth depends on the level of neutrophil infiltration. Metastatic melanomas proliferate in vivo independently of infiltrating neutrophils.

Adenoviridae↗
PubMed2003

Stroma formation and angiogenesis by overexpression of growth factors, cytokines, and proteolytic enzymes in human skin grafted to SCID mice.

Reorganization of skin during wound healing, inflammatory disorders, or cancer growth is the result of expression changes of multiple genes associated with tissue morphogenesis. We wanted to identify proteins involved in skin remodeling and select those that may be targeted for agonistic or antagonist therapeutic approaches in various disease processes. Full-thickness human skin was grafted to severe combined immunodeficient mice and injected intradermally with 38 different adenoviral vectors inserted with 37 different genes coding for growth factors, cytokines, proteolytic enzymes and their inhibitors, adhesion receptors, oncogenes, and tumor suppressor genes. Responses were characterized for infiltration of inflammatory cells, vascular density, matrix formation, fibroblast-like cell proliferation, and epidermal hyperplasia. Of the 17 growth factor vectors, 16 induced histological changes in human skin. Members of the VEGF and angiopoietin families induced neovascularization. PDGFs and TGF-betas stimulated connective tissue formation, and the chemokines IL-8 and MCP-1 attracted inflammatory neutrophils and monocytes, respectively. The serine protease uPA induced a vascular response similar to that of VEGF. Vectors with adhesion receptors, oncogenes and tumor suppressor genes had, with few exceptions, little effects on skin architecture. The overall results suggest that adenoviral vectors can effectively remodel the architecture of human skin for studies in morphogenesis, inflammatory skin disorders, wound healing, and cancer development.

Adenoviridae↗
PubMed2003

Treatment of Old World cutaneous leishmaniasis with intralesionally injected meglumine antimoniate using a Dermojet device.

Pentavalent antimonial compounds, the mainstay in the treatment of the various forms of leishmaniasis, have considerable toxicity, are difficult to administer and expensive. We describe a safe and efficient therapeutic modality using a spring-loaded and air-powered device for the intralesional injection of a high-velocity meglumine antimoniate microspray in a patient with cutaneous leishmaniasis.

Adolescent↗
PubMed2003

Orofacial granulomatosis as the initial presentation of Crohn's disease in an adolescent.

Orofacial granulomatosis (OFG) is a rare and heterogeneous clinical condition that presents with chronic swelling of the oral or facial tissues due to granulomatous inflammation. It is histologically characterized by noncaseating giant cell granulomata and epithelioid histiocytes. OFG includes the previously recognized clinical entities of Melkersson-Rosenthal syndrome and cheilitis granulomatosa (Miescher's cheilitis). A consistently effective medical treatment is not currently available. We describe an adolescent patient with a history of recurrent orofacial swelling preceding gastrointestinal symptoms by several years. He exhibited clinical and histological changes consistent with the diagnosis of OFG. It was resistant to standard therapies such as topical corticosteroids. Thorough history taking and clinical examination suggested Crohn's disease (CD), and further tests confirmed the diagnosis. The patient improved promptly after initiating oral treatment for CD with mesalazine and prednisolone. We conclude that OFG may be under- or misdiagnosed since the clinical manifestation may be misleading and its course is independent of or even preceding CD. Thus, patients with OFG should be asked about gastrointestinal symptoms consistent with CD. Those with suspicious symptoms should undergo a careful gastrointestinal evaluation, possibly including enteroclysis and complete gastrointestinal endoscopic examination, especially when the patient's history is conspicuous.

Adolescent↗
PubMed2002

Cell-surface proteolysis, growth factor activation and intercellular communication in the progression of melanoma.

Normal skin architecture and melanocyte function is maintained by a dynamic interplay between the melanocytes themselves, the epithelial cells between which they are interspersed, and their microenvironment. The microenvironment consists of the extracellular matrix, fibroblasts, migratory immune cells, and neural elements supported by a vascular network, all within a milieu of cytokines, growth factors, and bioactive peptides as well as proteolytic enzymes. Cells interact with the microenvironment via complex autocrine and paracrine mechanisms. Proteolytic enzymes in melanoma may activate or release growth factors from the microenvironment or act directly on the microenvironment itself, thereby facilitating angiogenesis or tumor cell migration. This review summarizes recent findings regarding the expression, structure and function of proteolytic enzymes at or near the cell surface in cell-cell and cell-stroma interactions during melanoma progression. Cell-surface (membrane) peptidases are a multi-functional group of ectoenzymes that have been implicated in the control of growth and differentiation of many cellular systems. The potential, but yet speculative, role of other membrane-bound molecules, such as multifunctional surface proteins with adhesion and protease activity (ADAM gene family) or the ephrin/Eph receptor protein kinases in the pathogenesis of melanoma are discussed.

Animals↗
PubMed2002

Melanoma-stroma interactions: structural and functional aspects.

Cutaneous melanomas are notorious for their tendency to metastasise. Because the tumour microenvironment plays an important part in tumour development and progression, we review the structural and functional aspects of interactions between melanoma and the stroma. We emphasise fibrovascular patterns (both in uveal and cutaneous melanoma), cellular and extracellular composition of the stroma, and the molecules involved. Also, we discuss functional interactions, focusing on melanoma-fibroblast cross-talk by soluble factors and by direct cell-cell contact. On the basis of recent findings we propose that involvement of fibroblasts in melanoma-stromagenesis occurs through different stages: recruitment, activation, and conversion to myofibroblasts, or differentiation to fibrocytes. We reason that this involvement is topographically linked to different areas in and around the tumour, and hypothesise that stromal activation, as seen in tumor ulceration or immunological regression in melanoma, stimulates tumour progression.

Cell Communication↗
PubMed2002

Benign Degos' disease developing during pregnancy and followed for 10 years.

Degos' disease, or malignant atrophic papulosis, is a rare and often fatal multisystem vasculopathy of unknown etiology. The cutaneous manifestations comprise erythematous papules, which heal to leave scars with a pathognomonic central porcelain-white atrophic area and a peripheral telangiectatic rim. Involvement of the gastrointestinal tract is observed in 50% of cases, with intestinal perforation being the most common cause of death. Other organ systems can also be affected; 20% of cases involve the central nervous system. Systemic manifestations usually develop from weeks to years after onset of skin lesions or, in rare instances, may precede skin lesions. In the patient with Degos' disease reported in this article, the characteristic skin lesions developed during pregnancy, a precipitating event not previously reported. She has survived an unusually long time (10 years) without visceral or neurological involvement, despite florid cutaneous lesions. Moreover, we could detect the presence of antiphospholipid antibodies, the significance of which are currently unclear. These observations therefore confirm that there may be a strictly cutaneous form of Degos' disease with a favourable prognosis.

Antibodies, Antiphospholipid↗
PubMed2002

Eruptive multiple lentigo-maligna-like lesions in a patient undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing colorectal carcinoma: a lesson for the pathogenesis of malignant melanoma?

Induction of multiple eruptive dermal and atypical melanocytic naevi has frequently been reported in children with malignant haematological diseases and chemotherapy-induced immunosuppression. This is the first report of an adult patient to develop multiple eruptive melanocytic skin lesions while undergoing chemotherapy with an oral 5-fluorouracil prodrug for metastasizing cancer. Our observation adds further evidence to the link between systemic (iatrogenic or intrinsic) immunosuppression and the induction of melanocyte proliferation and transformation.

Administration, Oral↗
PubMedDate not supplied

Multiple, bilateral and painful ear nodules of the anthelices: a variant of chondrodermatitis nodularis?

A case of a distinctive clinicopathologic condition of the ear cartilage is presented, characterized by multiple, bilateral and painful nodules of the anthelices without epidermal involvement. Histologically, there was a peri-chondrial lymphohistiocytic infiltrate and a small focus of degenerate, basophilic cartilage as well as cystic chondromalacia containing an amorphous mass. This condition is both clinically and histopathologically distinct from other causes of ear nodules, although the lesions seen in our patient exhibit features of chondrodermatitis nodularis helices and therefore could well be a variant of the latter.

Adult↗