Increased viable osteoblast density in the presence of nanophase compared to conventional alumina and titania particles

In the present in vitro study, osteoblast (bone-forming cells) viability and cell density were investigated when cultured in the presence of nanophase compared to conventional (i.e. micron) alumina and titania particles at various concentrations (from 10,000 to 100 microg/ml of cell culture media) for up to 6h. Results confirmed previous studies of the detrimental influences of all ceramic particulates on osteoblast viability and cell densities. For the first time, however, results provided evidence of increased apoptotic cell death when cultured in the presence of conventional compared to nanophase alumina and titania particles. Moreover, since material characterization studies revealed that the only difference between respective ceramic particles was nanometer- and conventional-dimensions (specifically, phase and chemical properties were similar between respective nanophase and conventional alumina as well as titania particles), these results indicated that osteoblast viability and densities were influenced solely by particle size. Such nanometer particulate wear debris may result from friction between articulating components of orthopedic implants composed of novel nanophase ceramic materials. Results of a less detrimental effect of nanometer--as compared to conventional-dimensioned particles on the functions of osteoblasts provide additional evidence that nanophase ceramics may become the next generation of bone prosthetic materials with increased efficacy and, thus, deserve further testing.     

The promise of nanotechnology for solving clinical problems in breast cancer

Approaches for breast cancer treatment are invasive, disfiguring, have significant side-effects, and are not always curative. Nanotechnology is an emerging area which is focused on engineering of materials <100 × 10(-9) m. There is significant promise for advancing nanotechnology to improve breast cancer diagnosis and treatment including non-invasive therapy, monitoring response to therapy, advanced imaging, treatment of metastatic disease, and improved nodal staging. Current approaches and important future directions are discussed.     

The transcription factor PAX2 regulates ADAM10 expression in renal cell carcinoma

ADAM10 is a metalloprotease that plays an important role in the progression and metastasis of various cancers. In the present study, we present compelling evidence that PAX2 can bind to the promotor of ADAM10 and regulate ADAM10 protein expression in renal cancer cells. We further show that ADAM10 is the major sheddase for the constitutive cleavage of L1-CAM and c-Met, two important proteins involved in the progression of renal cancer. The downregulation of ADAM10 led to a more scattered cell phenotype, which was accompanied by the induction of Slug and the loss of E-cadherin, which is observed during epithelial-to-mesenchymal transition (EMT). In addition, the downregulation of ADAM10 reduced the proliferation but induced the migration of renal cancer cells. Notably, the downregulation of PAX2 led to an increased L1-CAM expression, which was accompanied by a massive metalloprotease-mediated release of soluble L1-CAM. Importantly, soluble L1-CAM induced the proliferation of endothelial cells and the migration of renal cancer cells. Finally, we can demonstrate that the silencing of PAX2 led to an L1-CAM-dependent activation of the PI3K/Akt pathway, one important pathway mediating cancer cell survival. In summary, we identified PAX2 as a regulator of L1-CAM and ADAM10, which play crucial roles in the progression of various cancers including renal cell carcinoma and the downregulation of ADAM10 maybe an earlier step in renal cancer development as it seems to be involved in processes of EMT.     

Characterization of CXCL16 and ADAM10 in the normal and transplanted kidney

The chemokine CXCL16 plays an important role in the recruitment of leukocytes to sites of inflammation influencing the course of experimental glomerulonephritis. Here we show that human kidneys highly express CXCL16 in the distal tubule, connecting tubule and principal cells of the collecting duct with weak expression in the thick ascending limb of Henle. Beside the membrane localization, a soluble form of CXCL16 can be proteolytically released which acts as a chemotactic factor. In human renal tissue the expression pattern of the disintegrin-like metalloproteinase ADAM10 is similar to that of CXCL16, suggesting ADAM10 can potentially cleave CXCL16 in vivo. When we tested this in primary tubular cells we found that blockade of ADAM10 activity inhibited the IFN-gamma induced release of soluble CXCL16. Acute tubular damage in renal allografts was associated with elevated urinary CXCL16 and this correlated with focally increased apical CXCL16 expression in the distal tubules and collecting ducts. Renal allograft biopsies, with a histopathological diagnosis of acute interstitial rejection, showed increased basolateral ADAM10 expression together with high numbers of infiltrating T cells. Our results suggest that CXCL16 and ADAM10 are involved in the recruitment of T cells to the kidney and play an important role in inflammatory kidney diseases.     

Radiation therapy of mesothelioma: the Heidelberg experience and future aspects

Pleural mesothelioma is a rare but fatal tumour. Numerous attempts to find effective treatment approaches have, in general, been disappointing. To date, the most promising treatment is surgery, or surgery in combination with radio and chemotherapy as a part of a multidisciplinary approach. Preliminary results from clinical trials evaluating intensity modulated radiotherapy are encouraging. Further randomised trials are proposed.     

Plasmocytoma of the urethra

CASE HISTORY AND FINDINGS: A 35-year-old male patient presented with a 1-year history of hesitancy in voiding. An urethrogram revealed urethral stricture, therefore an urethrotomy with biopsies was performed. Histologic results suggested the diagnosis of extramedullary mature plasmocytoma. TREATMENT AND OUTCOME: After external beam radiotherapy with a total dose of 45 Gy the patient is disease-free without any therapy-related late effects after a follow-up of 36 months. CONCLUSION: Primary localization of extramedullar plasmocytomas in the genitourinary tract is very rare. This case report discusses a case of a male patient suffering from plasmocytoma of the urethra, who could be treated successfully by primary external beam radiotherapy.     

L1 augments cell migration and tumor growth but not beta3 integrin expression in ovarian carcinomas

L1 is a neural cell adhesion molecule involved in cell migration, axon growth and guidance. Recent data have shown that L1 is overexpressed in ovarian and endometrial tumors and is associated with bad prognosis. How L1 promotes tumor progression is presently unknown. Here we show that L1 expression is predominantly confined to the invasive front of ovarian carcinomas. Overexpression of L1 in carcinoma cell lines by adenovirus-mediated gene transfer enhanced the haptotactic cell migration on extracellular matrix proteins. Expression of L1 augmented tumor growth of carcinomas xenografted in nonobese diabetic/severe combined immunodeficient mice (NOD/SCID). A recent report has demonstrated L1-dependent upregulation of beta3 integrin involving activation of the extracellular signal-regulated kinase (erk) pathway. We find that L1 and beta3 integrin are not coexpressed in ovarian carcinoma tissues. Overexpression of L1 did not upregulate beta3 integrin in ovarian carcinoma cell lines but could do so in HEK293 cells. Our results suggest that L1 could drive progression by enhancing cell migration and tumor growth but that L1 dependent and erk-regulated gene expression requires cell-type specific elements.     

L1 adhesion molecule (CD 171) in development and progression of human malignant melanoma

The L1 adhesion molecule (CD171) plays an important role in axon guidance and cell migration in the nervous system. In the human, L1 is expressed on tumors derived from neurocrest and on certain carcinomas. We have analyzed immunohistochemically L1 expression on paraffin embedded specimens of acquired melanocytic nevi, primary cutaneous melanomas, and cutaneous and lymph node metastases of malignant melanomas. We found an increase in L1 immunoreactivity in malignant melanomas and metastases of malignant melanomas as compared to acquired melanocytic nevi that was statistically significant (P<0.05). Additionally, a correlation of L1 immunoreactivity with histological data of prognostic value such as Clark level and the expression of alphav-integrins was found. We detected soluble L1 in the conditioned medium of cultivated melanoma cells but only in 1/40 serum samples from a panel of melanoma patients representing various stages of disease. Our findings suggest that the presence of L1 might contribute to tumor progression by promoting cell adhesion and migration.     

Sonographie von Tumoren des Bewegungsapparats

Sonography is an integral part of primary tumor diagnosis and follow-up for the great majority of organ systems. However, its value in the field of space-occupying processes of the locomotor system, especially of malignant bone tumors, has mostly been underestimated. The sonographic examination has to investigate the whole tumor region and the corresponding lymph nodes statically and dynamically. The examination procedure should be standardized and the documentation reliable. Evaluation criteria are the localization, dimensions, and volume of the tumors, echogenicity and homogeneity, peri- and intratumoral vascularization (vessel density and architecture), borders of the tumor, and neighboring structures. Pathologic changes not only of the soft tissues but also of the bones can be evaluated sonographically. Even subtle analysis does not permit definitive assessment of tumor status. Taking its physical limitations into consideration, high-resolution sonography, enhanced by color/PowerDoppler and three-dimensional techniques, is a valuable adjunct to improve diagnosis, therapy planning, monitoring, and posttherapeutic care of tumors of the locomotor system.     

Die Venenverschlusskrankheit der Leber nach infradiaphragmaler total lymphatischer Bestrahlung Eine seltene Nebenwirkung

BACKGROUND: Radiotherapy is potentially curative in early stages of follicle center lymphoma. Frequent side effects are pancytopenia, nausea and abdominal discomfort. A radiation-induced liver injury with serious clinical symptoms and changes in liver function is a rare complication. CASE REPORT: Whole abdomen was irradiated in a 49-year-old patient with a centrocytic-centroblastic lymphoma, stage IA (localization: left inguinal region). A total dose of 30 Gy was delivered in a weekly fractionation of five times 1.5 Gy. Kidneys were protected by shielding after a dose of 13.5 Gy, liver blocks were positioned after 25 Gy. During the last 2 days of therapy the patient presented with weight gain, ascites, dyspnoea and elevated liver enzymes. Diagnostics revealed hepatosplenomegaly, ascites and an increased portosystemic pressure gradient. Liver biopsy specimen showed a veno-occlusive disease. Complete relief of symptomatology was achieved within 7 days following placement of a transjugular intrahepatic portosystemic stent-shunt (TIPSS), heparinization and diuretics. Liver enzymes are in the normal range. CONCLUSION: Veno-occlusive disease of the liver (VOD) is a very rare side effect of primary abdominal irradiation of follicle center lymphoma. This complication should be taken into consideration if a patient presents with upper right quadrant pain, ascites and elevation of liver enzymes especially within 4 months following radiotherapy. Genesis of veno-occlusive disease, diagnostics, therapy and a review of the literature are presented.