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Johannes Pammer

Publications and source records attributed to Johannes Pammer.

15 recordsLinked to original sources
PubMed2006

Interferon-alpha prevents apoptosis of endothelial cells after short-term exposure but induces replicative senescence after continuous stimulation.

Although the antiangiogenic activity of type I interferons (IFN) is well known, the mechanism by which it occurs is unclear. In the present study, we have investigated effects of short-term and long-term IFN-alpha exposure on different types of endothelial cells (EC). Short-term IFN-alpha treatment resulted in a distinct reduction of apoptosis of serum and growth factor starved HUVEC and HDMEC. This was accompanied by a strong upregulation of the IFN inducible guanylate binding protein-1 (GBP-1) whereas no consistent regulation of several known antiapoptotic proteins was evident. Stable transfection of HUVEC with an expression vector for GBP-1 mimicked the protective effect of IFN-alpha, suggesting that GBP-1 may contribute to the inhibition of apoptosis. When IFN-alpha, together with serum and EC growth factors, was present continuously a decrease of population doublings by more than 40% was observed in both HDMEC and HCAEC. In addition, the cells displayed a senescent phenotype significantly earlier than control cells and showed an increased adherence for monocytes. Our findings suggest that the antiangiogenic effect of IFN-alpha is mediated by inducing EC senescence rather than EC apoptosis. Furthermore IFN-alpha released in chronic inflammatory conditions might contribute via its prosenescent activity to the pathogenesis of atherosclerosis.

Apoptosis↗
PubMed2006

Hydroxymethylglutaryl-coenzyme A reductase inhibitors induce apoptosis in human cardiac myocytes in vitro.

Recent findings have implicated hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins, an established class of drugs for the treatment of hypercholesterolemia, in tissue remodeling in the heart. Statins induce apoptosis in different cell culture systems including rat neonatal cardiomyocytes. We investigated possible effects of different statins in vitro in human adult cardiac myocytes on the expression of proteins thought to be involved in the regulation of apoptosis such as Mcl-1, an inhibitor of apoptosis, Bax, an inducer of apoptosis, as well as on cytoplasmic histone-associated-DNA-fragments. Human adult cardiac myocytes (HACM) were treated with different statins at concentrations from 0.01 to 5 microM for up to 96 h. Whereas the lipophilic statin simvastatin at a concentration of 5 microM downregulated Mcl-1 mRNA by 49%, the hydrophilic pravastatin had no effect. Bax mRNA levels were not affected by neither of the statins. Simvastatin but not pravastatin reduced Mcl-1 protein expression whereas Bax protein was not detectable in HACM as determined by Western blotting. Simvastatin, atorvastatin and fluvastatin induced an up to seven-fold increase in histone-associated-DNA-fragments whereas pravastatin did not. Simvastatin up regulated histone-associated-DNA-fragments dose-dependently, and mevalonate and geranylgeranyl pyrophosphate reversed this effect to control levels. Our results show that lipophilic statins can induce a pro-apoptotic state in human adult cardiac myocytes in vitro. We speculate that, similar to findings in animal models, statins might be involved in the attenuation of cardiac hypertrophy and remodeling in humans by modulating the balance between cell survival and apoptosis.

Adult↗
PubMed2005

Mcl-1, vascular endothelial growth factor-R2, and 14-3-3sigma expression might predict primary response against radiotherapy and chemotherapy in patients with locally advanced squamous cell carcinomas of the head and neck.

PURPOSE: This study was done to explore whether the expression of a selected set of proteins could predict primary response to radiotherapy or concomitant radiotherapy and chemotherapy in patients with advanced head and neck cancer. EXPERIMENTAL DESIGN: Forty-three pretreatment tumor biopsies were taken during diagnostic panendoscopy and examined for Mcl-1, vascular endothelial growth factor (VEGF)-R2, CD9, and 14-3-3sigma expression by immunohistochemistry. Forty-three patients underwent primary radiotherapy, of which, 29 patients received concomitant chemotherapy (low dose daily cisplatin, mitomycin C bolus). The primary end-point was locoregional tumor control 6 months after completion of radiotherapy. Mcl-1, VEGF-R2, CD9, and 14-3-3sigma expression were correlated with patients' primary response to radiotherapy and chemotherapy and with established clinicopathologic variables. RESULTS: Thirty complete and 13 partial responses were observed in our patient group. High expression levels of Mcl-1 (P=0.021), VEGF-R2 (P=0.032), and 14-3-3sigma (P=0.013), but not of CD9, in tumor biopsies was correlated with complete response. Overexpression of at least two of the three aforementioned proteins in pretreatment biopsies predicted-with a likelihood of 80%-whether a patient would achieve complete response to radiotherapy and chemotherapy. However, if only one of these proteins is overexpressed, there is a likelihood of 84.6% that this patient would not completely respond to therapy. CONCLUSION: Determining the expression levels of Mcl-1, VEGF-R2, and 14-3-3sigma may be helpful in predicting the early clinical response in head and neck tumor patients receiving primary radiotherapy and chemotherapy and may further allow a pretherapeutic selection of patients.

14-3-3 Proteins↗
PubMed2004

Loss of vascular endothelial growth factor a activity in murine epidermal keratinocytes delays wound healing and inhibits tumor formation.

The angiogenic cytokine vascular endothelial growth factor (VEGF)-A plays a central role in both wound healing and tumor growth. In the skin, epidermal keratinocytes are a major source of this growth factor. To study the contribution of keratinocyte-derived VEGF-A to these angiogenesis-dependent processes, we generated mice in which this cytokine was inactivated specifically in keratin 5-expressing tissues. The mutant mice were macroscopically normal, and the skin capillary system was well established, demonstrating that keratinocyte-derived VEGF-A is not essential for angiogenesis in the skin during embryonic development. However, healing of full-thickness wounds in adult animals was appreciably delayed compared with controls, with retarded crust shedding and the appearance of a blood vessel-free zone underneath the newly formed epidermis. When 9,12-dimethyl 1,2-benzanthracene was applied as both tumor initiator and promoter, a total of 143 papillomas developed in 20 of 23 (87%) of control mice. In contrast, only three papillomas arose in 2 of 17 (12%) of the mutant mice, whereas the rest merely displayed epidermal thickening and parakeratosis. Mutant mice also developed only 2 squamous cell carcinomas, whereas 11 carcinomas were found in seven of the control animals. These data demonstrate that whereas keratinocyte-derived VEGF-A is dispensable for skin vascularization under physiological conditions, it plays an important albeit nonessential role during epidermal wound healing and is crucial for the development of 9,12-dimethyl 1,2-benzanthracene-induced epithelial skin tumors.

Animals↗
PubMed2003

Motility-related protein-1/CD9 expression in head and neck squamous cell carcinoma.

INTRODUCTION: Motility-related protein (MRP)-1/CD9 is implicated in cell adhesion and motility and was shown to be clearly involved in tumor prognosis and angiogenesis. Elevated MRP-1/CD9 expression on tumor cells has been linked to a favorable prognosis in breast cancer, colon cancer, lung cancer, and HNSCC. Because MRP-1/CD9 is associated with angiogenesis, it might play a role in tumor angiogenesis as well. METHODS: We analyzed MRP-1/CD9 expression in HNSCC specimens and cell lines by real-time RT-PCR and in HNSCC biopsy specimens and stromal vessels by immunohistochemistry. Kruskal Wallis and Chi2 test, univariate and multivariate Cox regression, and Kaplan-Meier methods were used for statistical analysis. RESULTS: Real-time and PCR RT showed elevated expression of MRP-1/CD9 in one (SCC25) of four HNSCC cell lines and two of six HNSCC patients, whereas two cell lines (SCC9 and JPPA) and one HNSCC patient had lower MRP-1/CD9 levels compared with other specimens. Immunohistochemistry demonstrated strong MRP-1/CD9 IR expression on tumor cells in 13 patients (39%), whereas 21 patients (61%) had less to medium MRP-1/CD9 IR expression. Increased MRP-1/CD9 expression on tumor cells was correlated with prolonged patient survival (p =.02) and a longer disease-free interval (p =.004), a diminished recurrence rate (p =.02), and lower stages of neck lymph nodes (p =.04). MRP-1/CD9 IR was also found in a subpopulation of vessels that seem to be less in tumor specimens than in normal mucosa (p <.0001). MRP-1/CD9+ vessels are podoplanin+ and are therefore regarded as lymphatic vessels. CONCLUSIONS: Our results revealed that elevated MRP-1/CD9 expression on HNSCC is linked to a favorable clinical outcome and confirmed reports of MRP-1/CD9 expression in other carcinomas. MRP-1/CD9+ vessels were found to be lymphatic in nature. The number and staining intensity of these vessels is decreased in tumor tissue, which suggests a stabilizing role for this protein in lymphangiogenesis.

Adult↗
PubMed2003

Transient effect of topical treatment of cutaneous leishmaniasis with imiquimod.

BACKGROUND: Treatment of cutaneous leishmaniasis can be painful and protracted and cosmetic results are often unsatisfying. The immune modulator imiquimod has been reported to be suitable for the treatment of a variety of infectious skin diseases and neoplasias. OBJECTIVE: We investigated the efficacy of topical application of imiquimod in the treatment of old world leishmaniasis in a placebo-controlled prospective study. METHODS: Twelve patients were treated with imiquimod cream using a standard protocol, i.e. topical application three times a week, and a further three served as control group. RESULTS: Lesions of cutaneous leishmaniasis regressed within the first 2-4 weeks in 10 of the 12 patients, whereas in two patients no change was observed. However, after 8 weeks all lesions showed progression. CONCLUSION: Our results thus demonstrate that topical application of imiquimod alone is ineffective in treating old world cutaneous leishmaniasis. Further studies are required to demonstrate a possible benefit of imiquimod in combination with other, preferably orally administered medicines.

Adjuvants, Immunologic↗
PubMed2003

Differential expression pattern of cyclooxygenase-1 and -2 in head and neck squamous cell carcinoma.

OBJECTIVE: The enzyme cyclooxygenase catalyzes the first step of the synthesis of prostanoids Cyclooxygenase has been shown to exist in two distinct isoforms: cyclooxygenase-1 is constitutively expressed as a housekeeping enzyme in most tissues whereas the inducible cyclooxygenase-2 has been reported to be involved in inflammatory processes and in the carcinogenesis of squamous cell carcinoma. The aim of this study was to investigate the distribution patterns of cyclooxygenase-1 and -2 in peritumoral lymphocytic infiltrates and tumor cells of head and neck carcinoma. MATERIAL AND METHODS: Immunohistochemical analysis was performed using paraffin-embedded tumor specimens from 24 patients suffering from oropharyngeal, hypopharyngeal and oral squamous cell carcinomas. RESULTS: We observed that cyclooxygenase-2 immunoreactivity, compared to that of cyclooxygenase-1, was significantly increased in peritumoral lymphocytic infiltrates as well as in tumor cells. CONCLUSION: The expression of cyclooxygenase-2 in both tumor specimens and the surrounding peritumoral lymphocytic infiltrates supports the hypothesis that cyclooxygenase may be one of several important links between chronic inflammation and carcinogenesis.

Carcinoma, Squamous Cell↗
PubMed2003

Heterogeneous expression and regulation of CD40 in human hepatocellular carcinoma.

OBJECTIVE: CD40, a member of the tumour necrosis factor receptor family, plays a major role in adaptive immune responses and contributes to cancer surveillance. Conflicting results have been reported recently on the expression and function of CD40 in carcinomas. The aim of the present study was to investigate the role of CD40 in human hepatoma. DESIGN/METHODS: CD40 expression was examined in hepatomas and derived cell lines by immunohistochemistry, flow cytometry and reverse transcriptase polymerase chain reaction. We investigated in hepatoma cell lines the regulation of CD40 by pro-inflammatory cytokines and the effects of its ligation with soluble CD40L on the expression of co-stimulatory and pro-apoptotic cell-surface molecules and survival. RESULTS: CD40 was detected with a similar frequency of about 40% in hepatoma specimens and derived cell lines but not in normal hepatocytes. Tumour necrosis factor alpha and its combination with interferon gamma upregulated CD40 only in intrinsically positive cell lines. CD40 ligation had no effect on cell viability or surface expression of CD54, CD80, CD86 or CD95. CONCLUSIONS: CD40 is expressed variably in human hepatoma and enhanced by distinct pro-inflammatory cytokines. The lack of detectable effects of CD40 ligation does not support a major role of this molecule in hepatocellular carcinoma biology.

Adult↗
PubMed2003

CD9 expression on lymphatic vessels in head and neck mucosa.

CD9, a member of the transmembrane 4 superfamily, is involved in cell adhesion, migration, and tumor metastasis. Little is known about its vascular expression pattern. In this study, we investigated CD9 expression on endothelial cells in the mucosa of the head and neck and compared it with vascular tumors. Using immunohistochemistry, expression of CD9 was studied in 17 samples of head and neck mucosa and skin (laryngeal mucosa: n = 2, oral: n = 6, and epidermis: n = 9) and a variety of vascular tumors (lymphangiomas: n = 9, juvenile nasopharyngeal angiofibromas: n = 4, hemangiomas: n = 7, angiosarcomas: n = 5, and Kaposi's sarcomas: n = 7) and compared with the expression of CD34 and PAL-E (blood vessel markers) and the lymphatic marker podoplanin. Regular lymphatic endothelium and lymphangiomas were strongly positive for CD9 and podoplanin but were mostly negative for PAL-E and CD34. By contrast, blood vessel endothelium and hemangiomas were strongly positive for PAL-E and CD34 but were mostly negative for CD9 and podoplanin. Weak to moderate CD9 reactivity was also observed on EC of juvenile nasopharyngeal angiofibromas, angiosarcomas, and Kaposi's sarcomas. Expression of CD9 by lymphatic EC was confirmed by reverse-transcriptase PCR and Western blot analyses. CD9 may be useful as a marker for lymphatic EC. It could promote the adherence of inflammatory and tumor cells to lymphatic EC and participate in the growth and maintenance of the lymphatic capillary net.

Antibodies, Monoclonal↗
PubMed2002

Dysphagia due to a large schwannoma of the oropharynx: case report and review of the literature.

Schwannoma is a benign, encapsulated tumor that is derived from Schwann cells. Approximately 25% to 45% of schwannomas occur in the head and neck. The most common site is the parapharyngeal space of the neck; intrapharyngeal occurrence is extremely rare. To our knowledge, this is the first report of a pedunculated schwannoma in the supraglottic oropharynx. Because of the location and mass of the tumor, the main symptom was dysphagia. The tumor was excised via direct microlaryngoscopy, and no recurrence was seen after 2 years of follow-up. When schwannomas are located in the pharynx, they may cause dyspnea and dysphagia or impair phonation. Therefore, when dysphagia is present, a thorough diagnostic procedure should be performed to evaluate the morphology and function of the upper aerodigestive tract.

Aged↗
PubMed2002

A possible role of keratinocytes of skin and mucous membranes in prion propagation and transmission.

Prion diseases or transmissible spongiform encephalopathies are lethal neurodegenerative diseases caused by proteinaceous agents that consist of an abnormal form of a host protein designated PrP and are devoid of nucleic acids. In laboratory settings these diseases are usually transmitted by intracerebral or peripheral inoculation. In the field they have been shown to be transmitted by uptake of contaminated food but in most instances the route of transmission remains obscure. Both nervous and lymphatic tissues in peripheral organs have been implicated in the spread and propagation of prions. The exact sites of uptake and initial propagation of the infectious agents have not yet been determined, however. As the expression of PrPc is required for the propagation of the infectious agent the search for peripheral cells positive for PrPc may reveal potential routes of entry and transmission. Recently epidermal and mucosal keratinocytes have been found to express PrPc. These data together with the recent finding that epithelial cells are able to support prion replication in vitro suggest that keratinocytes might play a role in the pathogenesis and/or transmission of prion diseases.

Animals↗
PubMed2002

Histopathologic correlation of high-resolution magnetic resonance imaging of human cervical tissue samples at 3 tesla: validation of a technique.

RATIONALE AND OBJECTIVES: High-resolution magnetic resonance (HR-MR) images of human cervical tissue samples were correlated with low magnification histology to investigate the MR presentation of normal and pathologic anatomic structures in cervical tissue samples at 3T. METHODS: Tissue samples were obtained from five large loop excision of the transformation zone (LLETZ) cone biopsies and one surgical specimen. HR-MR images (3D-Spin Echo sequence: TR/TE: 1500/60 milliseconds, voxel size of 117 x 208 x 234 microm) and low magnification (5x) histology sections were acquired in the same anatomical planes and correlated. RESULTS: In vitro HR-MR imaging of cervical tissue samples correlated well with low magnification microscopic histology, demonstrating normal anatomy (epithelium and its mucus layer, connective tissue of the stroma, glands, blood vessels). In vitro HR-MR imaging adds information about tumor content and margins. CONCLUSIONS: High resolution MR imaging of cervical tissue samples assists in the identification of both normal structures and pathologic changes.

Biopsy↗
PubMedDate not supplied

Selective alterations in mast cell subsets and eosinophil infiltration in two complementary types of intestinal inflammation: ascariasis and Crohn's disease.

OBJECTIVE: Numbers of mast cells (MCs) of different subpopulations and the extent of eosinophil infiltration were compared in Crohn's disease and ascariasis. These two types of intestinal inflammation are complementary with regard to T cell response (TH1 versus TH2), prevalence and environmental factors. METHODS: Histochemical, immunohistochemical and ultrastructural tools were applied to biopsies of morphologically uninvolved colon, ileum and duodenum from Crohn's and ascariasis patients, as well as resection margins and tissues from an experimental porcine ascariasis model. MC subsets were defined by their dye-binding properties, and their chymase content was analysed using biochemical tools. RESULTS: The TH2 (IgE-mediated) response in ascariasis was characterised by a dramatic increase in mucosal- type MCs (MMCs) and eosinophils in both the mucosa and the deeper layers of the intestinal wall and a simultaneous decrease of connective tissue-type MCs (CTMCs). Uninvolved intestine of Crohn's patients showed moderate proliferation of CTMCs in the deeper layers of the intestinal wall, but a significant decrease of the MMCs, associated with moderate eosinophilia in all layers of the gut. Similar changes were present in the uninvolved duodenum of Crohn's patients. Comparable amounts of chymase could be extracted from mucosal and submucosal duodenum, with similar proportions of its two principal isoforms in each. CONCLUSIONS: Our results indicate that T cell responses (TH1 or TH2) are associated with different MC subsets in intestinal inflammation. Changes remote from the focus of inflammation point to the systemic nature of the different MC responses.

Adult↗