Permanent inflation of detachable balloons with a low-viscosity, hydrophilic polymerizing system

A polymer system was developed for use in permanent inflation of detachable balloons, to avoid long-term reliance on the integrity of balloon shells or valve mechanisms. This system is based on 2-hydroxy-ethyl methacrylate (HEMA) as the monomer, in combination with a cross-linking agent and a water-soluble curing system. The low-viscosity, hydrophilic mixture can be exchanged through a small-bore catheter into a detachable balloon and polymerizes in 40-60 minutes at body temperature. Partially polymerized HEMA can cause vascular occlusion; hence, careful timing of balloon detachment is required. The evolution of the radiographic appearance of HEMA-filled balloons is predictable. The balloons remain radiopaque on plain radiographs as long as the balloon shell and valve mechanisms are competent. After rupture of the shell or failure of the valve mechanism, the balloons become invisible on plain radiographs but remain hyperattenuating on computed tomography scans.     

Carcinoma of the breast: detection with MR imaging versus xeromammography

Detectability of breast cancer with magnetic resonance (MR) imaging versus xeromammography was quantitatively compared. MR images were obtained of breasts of 120 women who underwent xeromammography. T1 values were determined for masses larger than 2 cm. Cancer was histologically confirmed in 39 breasts and was considered excluded from 81 due to results of biopsy, cyst aspiration, or sonography or absence of change in xeromammographic findings over time. Images were blindly interpreted by three observers, and results were expressed as receiver operating characteristic curves. Detectability of breast cancer was substantially better with xeromammography than with MR imaging for all observers (P less than .03, 10(-6), and .001). On MR images, spiculation of a mass, distorted architecture, skin thickening, and nipple or skin retraction were specific but relatively insensitive indicators of cancer. Masses with smooth, distinct margins and signal intensity greater than that of fat on T2-weighted images were always benign. Other findings and T1 values were not diagnostically useful. The authors conclude that xeromammography is superior to MR imaging in detection of breast cancer.     

The larger bronchi in cryptogenic fibrosing alveolitis: a morphometric study

In a morphometric study of the main, lobar, and segmental bronchi of the left lung in nine cases of cryptogenic fibrosing alveolitis the quantity of gland was found to be significantly greater than in a group of normal controls, and similar to that of a group of patients with chronic bronchitis. The quantity of muscle was also increased, amounts in the segmental bronchi being higher than in the bronchitic patients. The cause of these changes is uncertain, but they seem likely to be due to proximal extension of repeated and persistent infection of the lung parenchyma.     

Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy

The tumor microenvironment, in particular, the tumor vasculature, as an important target for the cytotoxic effects of radiation therapy is an established paradigm for cancer therapy. We review the evidence that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated in endothelial cells exposed to ionizing radiation (IR) and is a molecular target for the development of novel radiation sensitizing agents. On the basis of this premise, several promising preclinical studies that targeted the inhibition of the PI3K/Akt activation as a potential method of sensitizing the tumor vasculature to the cytotoxic effects of IR have been conducted. An innovative strategy to guide cytotoxic therapy in tumors treated with radiation and PI3K/Akt inhibitors is presented. The evidence supports a need for further investigation of combined-modality therapy that involves radiation therapy and inhibitors of PI3K/Akt pathway as a promising strategy for improving the treatment of patients with cancer.     

Integrin alpha v beta 3 antagonist Cilengitide enhances efficacy of radiotherapy in endothelial cell and non-small-cell lung cancer models

PURPOSE: Integrins alpha v beta 3 and alpha v beta 5 are important in tumor growth and angiogenesis and have been recently explored as targets for cancer therapy. Radiotherapy also inhibits tumor growth and affects vasculature. We explored the combination of integrin antagonist Cilengitide (EMD 121974) and ionizing radiation. METHODS AND MATERIALS: Levels of alpha v beta 3 were determined for human umbilical vein endothelial cells (HUVEC), as well as H157 and H460 human non-small-cell lung cancer cells, using FACS analysis and immunofluorescence imaging. Clonogenic assays, Western immunoblots probed for cleaved caspase 3, and Annexin-V probing were used to evaluate cell survival and apoptosis. A cell detachment assay and matrigel assay were used to further examine the effects of treatment. RESULTS: Human umbilical vein endothelial cells had the highest alpha v beta 3 level, followed by H157, and H460. Interestingly, we found that 5 Gy irradiation induced expression of alpha v beta 3 in all cell lines. Clonogenic assays showed a radiosensitizing effect with Cilengitide, and calculation of the dose enhancement ratio showed that the effect was highest in HUVECs (1.38), followed by H157 (1.19), and H460 (1.10), corresponding to the levels of target expression. There was an increase in apoptotic cells after combination treatment with Cilengitide and radiation, and there was an increase in detached cells after treatment with Cilengitide. Additionally, there was decreased endothelial tubule formation after combination treatment. CONCLUSIONS: We conclude that radiation induces expression of alpha v beta 3 integrin in endothelial and non-small-cell lung cancer models, and that integrin antagonist Cilengitide is a radiosensitizer in proportion to the levels of target integrin expression.     

Radiation-guided gene therapy of cancer

Gene therapy has been proposed as a means to combat cancer. However, systemic toxicity observed in preclinical trials suggested the importance of selectively targeted delivery and inducible gene expression in tumor tissues. Discovery of radiation-inducible promoter sequences provides one way to minimize inadvertent toxicity from gene therapy in normal tissues. Radiation is administered to selectively induce cytotoxic gene expression in the targeted tumor tissues. With promising results from phase II clinical trials using TNF-expressing adenovirus, it is possible to have radiation-guided gene therapy regimes once the tumor-targeted delivery has been achieved. Tumor endothelium is an attractive biological target for gene therapy, because it has the advantage of stability, accessibility, and bioavailability for therapeutic agents. Technological development of DNA microarray, proteomic profiling, and phage-displayed libraries accelerates the identification of tumor-specific endothelial biomarkers and discovery of its relevant affinity reagents for targeted delivery. The application of radiation-guided gene delivery, its amplification, as well as expression of gene therapy presents great opportunities to be employed as an alternative cancer treatment.     

Lithium treatment prevents neurocognitive deficit resulting from cranial irradiation

Curative cancer treatment regimens often require cranial irradiation, resulting in lifelong neurocognitive deficiency in cancer survivors. This deficiency is in part related to radiation-induced apoptosis and decreased neurogenesis in the subgranular zone of the hippocampus. We show that lithium treatment protects irradiated hippocampal neurons from apoptosis and improves cognitive performance of irradiated mice. The molecular mechanism of this effect is mediated through multiple pathways, including Akt/glycogen synthase kinase-3beta (GSK-3beta) and Bcl-2/Bax. Lithium treatment of the cultured mouse hippocampal neurons HT-22 induced activation of Akt (1.5-fold), inhibition of GSK-3beta (2.2-fold), and an increase in Bcl-2 protein expression (2-fold). These effects were sustained when cells were treated with lithium in combination with ionizing radiation. In addition, this combined treatment led to decreased expression (40%) of the apoptotic protein Bax. The additional genes regulated by lithium were identified by microarray, such as decorin and Birc1f. In summary, we propose lithium treatment as a novel therapy for prevention of deleterious neurocognitive consequences of cranial irradiation.