Cleavage of L1 in exosomes and apoptotic membrane vesicles released from ovarian carcinoma cells.

PURPOSE: The L1 adhesion molecule (CD171) is overexpressed in human ovarian and endometrial carcinomas and is associated with bad prognosis. Although expressed as a transmembrane molecule, L1 is released from carcinoma cells in a soluble form. Soluble L1 is present in serum and ascites of ovarian carcinoma patients. We investigated the mode of L1 cleavage and the function of soluble L1. EXPERIMENTAL DESIGN: We used ovarian carcinoma cell lines and ascites from ovarian carcinoma patients to analyze soluble L1 and L1 cleavage by Western blot analysis and ELISA. RESULTS: We find that in ovarian carcinoma cells the constitutive cleavage of L1 proceeds in secretory vesicles. We show that apoptotic stimuli like C2-ceramide, staurosporine, UV irradiation, and hypoxic conditions enhance L1-vesicle release resulting in elevated levels of soluble L1. Constitutive cleavage of L1 is mediated by a disintegrin and metalloproteinase 10, but under apoptotic conditions multiple metalloproteinases are involved. L1 cleavage occurs in two types of vesicles with distinct density features: constitutively released vesicles with similarity to exosomes and apoptotic vesicles. Both types of L1-containing vesicles are present in the ascites fluids of ovarian carcinoma patients. Soluble L1 from ascites is a potent inducer of cell migration and can trigger extracellular signal-regulated kinase phosphorylation. CONCLUSIONS: We suggest that tumor-derived vesicles may be an important source for soluble L1 that could regulate tumor cell function in an autocrine/paracrine fashion.     

Temozolomide Combined with Irradiation as Postoperative Treatment of Primary Glioblastoma Multiforme

BACKGROUND AND PURPOSE: The role of radiochemotherapy in the treatment of primary glioblastoma multiforme is still discussed controversially. To evaluate the feasibility and toxicity of irradiation and concomitant administration of 50 mg/m(2) temozolomide in patients with primary malignant glioma, this phase I/II study was conducted. PATIENTS AND METHODS: 53 Patients with histologically confirmed WHO grade IV malignant glioma were enrolled into the study. All patients were treated with radiation therapy up to a total dose of 60 Gy using conventional fractionation of 5 x 2.0 Gy/week. Temozolomide was administered orally each therapy day at a dose of 50 mg/m(2). RESULTS: Prior to radiochemotherapy, complete resection (n = 14), subtotal resection (n = 22) or a biopsy (n = 17) of the tumor was performed. The median time interval between surgery and radiochemotherapy was 21 days. Treatment-related toxicity was very mild. Acute toxicity > grade 2 was observed in one patient who developed grade 4 hemotoxicity. Minor side effects of chemotherapy included nausea and vomiting. No severe late effects were observed. Median progression-free and overall survival were 8 and 19 months, respectively. The overall survival rate was 72% at 1 and 26% at 2 years. Age and extent of surgery significantly influenced survival. CONCLUSION: The combination of temozolomide plus radiation therapy is feasible and safe in terms of toxicity. Overall survival times were relatively long compared to survival times reported for radiotherapy alone. The application of 50 mg/m(2) of temozolomide can be performed throughout the whole time course without interruption due to side effects and might largely contribute to the prolonged overall survival. Further evaluation is warranted as to which dose of temozolomide is optimal with regard to tumor response and toxicity.     

The disintegrin-metalloproteinases ADAM 10, 12 and 17 are upregulated in invading peripheral tumor cells of basal cell carcinomas

Background:  Members of the a disintegrin and metalloproteinase (ADAM) family are expressed in malignant tumors and participate in the pathogenesis of cancer. However, the presence of ADAM 10, 12, 17 and their role in basal cell carcinoma (BCC) have not been described. The purpose of this study was to investigate expression of ADAM 10, 12 and 17 in BCC.
Methods:  Expression of ADAM 10, 12 and 17 was analyzed by immunohistochemistry in skin tissues obtained from 25 patients with different types of BCC.
Results:  Immunoreactivity of ADAM 10, 12 and 17 was increased at the peripheral tumor margin compared with central areas of BCC tumor cell nests. Immunoreactivity of ADAM 10 and 12 was increased in the deep margin of invading tumor cell nests in mixed BCC. Focally increased expression of ADAM 12 was detected in squamous differentiated tumor cells of nodular BCC. In addition, immunoreactivity of ADAM 17 was increased in superficial BCC.
Conclusions:  ADAM 10, 12 and 17 showed different expression pattern in BCC histologic subtypes, indicating their different role in the BCC pathogenesis. Overexpression of ADAM 10, 12 and 17 immunoreactivity in deep invasion area of BCC indicates that these three proteases may play an important role in the locally invasive and highly destructive growth behavior of BCC. Additionally, we suggest that ADAM 17 may play an important role in early development of BCC.     

L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas

Ovarian and uterine carcinomas are the most common cause of cancer-related deaths in gynecological malignant diseases. We aimed to assess whether the L1 adhesion molecule, an important mediator for cell migration for neural and tumour cells, is expressed in these carcinomas.     

Microbial barriers

Barrier wound therapy is commonplace in the health care environment and functions to limit bacterial colonization and infection in both acute wounds and recalcitrant chronic wounds. This article reviews the nature of acute and chronic wounds and their available adjunctive barrier therapies.     

Sphenoid sinusitis caused by Clostridium perfringens.

Anaerobic bacterial infections in chronic sinusitis are well described in literature. We present what is believed to be the first reported case of Clostridium perfringens presenting as the causative pathogen in paranasal sinusitis. This patient presented with severe headaches and, with CT and MRI findings of unilateral sphenoid sinus opacification, with bone demineralization and intrasinus calcification. This patient responded to endoscopic debridement and long-term antibiotics without sequelae.     

Development of learning and memory in mice after brief paradoxical sleep deprivation.

The effects of three hour paradoxical sleep deprivation (3 hr PSD) via the water tank procedure to produce retrograde amnesia of active avoidance and inhibitory avoidance learning was examined in mice. Results indicated no memory impairment in experimentally treated groups. An attempt was then made to induce amnesia by administering ECS immediately after 3 hr PSD thereby increasing the susceptibility of the memory trace to disruption. This procedure, however, also results in good retention. We conclude that the paradoxical sleep (PS) phase immediately after aversively motivated training is not essential for subsequent development of learning and memory. These results do not, however, detract from previously reported protracted PSD effects on memory storage processes.