Defects in muscarinic receptor-coupled signal transduction in isolated parotid gland cells after in vivo irradiation: evidence for a non-DNA target of radiation

Radiation-induced dysfunction of normal tissue, an unwanted side effect of radiotherapeutic treatment of cancer, is usually considered to be caused by impaired loss of cell renewal due to sterilisation of stem cells. This implies that the onset of normal tissue damage is usually determined by tissue turnover rate. Salivary glands are a clear exception to this rule: they have slow turnover rates (>60 days), yet develop radiation-induced dysfunction within hours to days. We showed that this could not be explained by a hypersensitivity to radiation-induced apoptosis or necrosis of the differentiated cells. In fact, salivary cells are still capable of amylase secretion shortly after irradiation while at the same time water secretion seems specifically and severely impaired. Here, we demonstrate that salivary gland cells isolated after in vivo irradiation are impaired in their ability to mobilise calcium from intracellular stores (Ca2+i), the driving force for water secretion, after exposure to muscarinic acetylcholine receptor agonists. Using radioligand-receptor-binding assays it is shown that radiation caused no changes in receptor density, receptor affinity nor in receptor-G-protein coupling. However, muscarinic acetylcholine agonist-induced activation of protein kinase C alpha (PKCα), measured as translocation to the plasma membrane, was severely affected in irradiated cells. Also, the phorbol ester PMA could no longer induce PKCα translocation in irradiated cells. Our data hence indicate that irradiation specifically interferes with PKCα association with membranes, leading to impairment of intracellular signalling. To the best of our knowledge, these data for the first time suggest that, the cells' capacity to respond to a receptor agonist is impaired after irradiation

Characteristics of Patients Who Survived < 3 Months or > 2 Years After Surgery for Spinal Metastases: Can We Avoid Inappropriate Patient Selection?

PURPOSE: Survival after metastatic cancer has improved at the cost of increased presentation with metastatic spinal disease. For patients with pathologic spinal fractures and/or spinal cord compression, surgical intervention may relieve pain and improve quality of life. Surgery is generally considered to be inappropriate if anticipated survival is < 3 months. The aim of this international multicenter study was to analyze data from patients who died within 3 months or 2 years after surgery, to identify preoperative factors associated with poor or good survival, and to avoid inappropriate selection of patients for surgery in the future. PATIENTS AND METHODS: A total of 1,266 patients underwent surgery for impending pathologic fractures and/or neurologic deficits and were prospectively observed. Data collected included tumor characteristics, preoperative fitness (American Society of Anesthesiologists advisory [ASA]), neurologic status (Frankel scale), performance (Karnofsky performance score [KPS]), and quality of life (EuroQol five-dimensions questionnaire [EQ-5D]). Outcomes were survival at 3 months and 2 years postsurgery. Univariable and multivariable logistic regression analyses were used to find preoperative factors associated with short-term and long-term survival. RESULTS: In univariable analysis, age, emergency surgery, KPS, EQ-5D, ASA, Frankel, and Tokuhashi/Tomita scores were significantly associated with short survival. In multivariable analysis, KPS and age were significantly associated with short survival (odds ratio [OR], 1.36; 95% CI, 1.15 to 1.62; and OR, 1.14; 95% CI, 1.02 to 1.27, respectively). Associated with longer survival in univariable analysis were age, number of levels included in surgery, KPS, EQ-5D, Frankel, and Tokuhashi/Tomita scores. In multivariable analysis, the number of levels included in surgery (OR, 1.21; 95% CI, 1.06 to 1.38) and primary tumor type were significantly associated with longer survival. CONCLUSION: Poor performance status at presentation is the strongest indicator of poor short-term survival, whereas low disease load and favorable tumor histology are associated with longer-term survival

Dysregulation of Gene Expression in the Artificial Human Trisomy Cells of Chromosome 8 Associated with Transformed Cell Phenotypes

A change in chromosome number, known as aneuploidy, is a common characteristic of cancer. Aneuploidy disrupts gene expression in human cancer cells and immortalized human epithelial cells, but not in normal human cells. However, the relationship between aneuploidy and cancer remains unclear. To study the effects of aneuploidy in normal human cells, we generated artificial cells of human primary fibroblast having three chromosome 8 (trisomy 8 cells) by using microcell-mediated chromosome transfer technique. In addition to decreased proliferation, the trisomy 8 cells lost contact inhibition and reproliferated after exhibiting senescence-like characteristics that are typical of transformed cells. Furthermore, the trisomy 8 cells exhibited chromosome instability, and the overall gene expression profile based on microarray analyses was significantly different from that of diploid human primary fibroblasts. Our data suggest that aneuploidy, even a single chromosome gain, can be introduced into normal human cells and causes, in some cases, a partial cancer phenotype due to a disruption in overall gene expression

Long-Term Alterations of Cytokines and Growth Factors Expression in Irradiated Tissues and Relation with Histological Severity Scoring

PURPOSE: Beside its efficacy in cancer treatment, radiotherapy induces degeneration of healthy tissues within the irradiated area. The aim of this study was to analyze the variations of proinflammatory (IL-1α, IL-2, IL-6, TNF-α, IFN-γ), profibrotic (TGF-β1), proangiogneic (VEGF) and stem cell mobilizing (GM-CSF) cytokines and growth factors in an animal model of radiation-induced tissue degeneration. MATERIALS AND METHODS: 24 rats were irradiated unilaterally on the hindlimb at a monodose of 30 Gy. Six weeks (n=8), 6 months (n=8) and 1 year (n=8) after irradiation the mediators expression in skin and muscle were analyzed using Western blot and the Bio-Plex® protein array (BPA) technology. Additional histological severity for fibrosis, inflammation, vascularity and cellularity alterations scoring was defined from histology and immnunohistochemistry analyses. RESULTS: A significant increase of histological severity scoring was found in irradiated tissue. Skin tissues were more radio-sensitive than muscle. A high level of TGF-β1 expression was found throughout the study and a significant relation was evidenced between TGF-β1 expression and fibrosis scoring. Irradiated tissue showed a chronic inflammation (IL-2 and TNF-α significantly increased). Moreover a persistent expression of GM-CSF and VEGF was found in all irradiated tissues. The vascular score was related to TGF-β1 expression and the cellular alterations score was significantly related with the level of IL-2, VEGF and GM-CSF. CONCLUSION: The results achieved in the present study underline the complexity and multiplicity of radio-induced alterations of cytokine network. It offers many perspectives of development, for the comprehension of the mechanisms of late injuries or for the histological and molecular evaluation of the mode of action and the efficacy of rehabilitation techniques

Choroid plexus tumours

Choroid plexus tumours are rare epithelial brain tumours and limited information is available regarding their biology and the best treatment. A meta-analysis was done to determine prognostic factors and the influence of various treatment modalities. A thorough review of the medical literature (1966–1998) revealed 566 well-documented choroid plexus tumours. These were entered into a database, which was analysed to determine prognostic factors and treatment modalities. Most patients with a supratentorial tumour were children, while the most common sites in adults were the fourth ventricle and the cerebellar pontine angle. Cerebellar pontine angle tumours were more frequently benign. Histology was the most important prognostic factor, as one, five, and 10-year projected survival rates were 90, 81, and 77% in choroid plexus-papilloma (n=353) compared to only 71, 41, and 35% in choroid plexus-carcinoma respectively (P<0.0005). Surgery was prognostically relevant for both choroid plexus-papilloma (P=0.0005) and choroid plexus-carcinoma (P=0.0001). Radiotherapy was associated with significantly better survival in choroid plexus-carcinomas. Eight of 22 documented choroid plexus-carcinomas responded to chemotherapy. Relapse after primary treatment was a poor prognostic factor in choroid plexus-carcinoma patients but not in choroid plexus-papilloma patients. Treatment of choroid plexus tumours should start with radical surgical resection. This should be followed by adjuvant treatment in case of choroid plexus-carcinoma, and a ‘wait and see’ approach in choroid plexus-papilloma

Internet of Things for Sustainable Forestry

Forests and grasslands play an important role in water and air purification, prevention of the soil erosion, and in provision of habitat to wildlife. Internet of Things has a tremendous potential to play a vital role in the forest ecosystem management and stability. The conservation of species and habitats, timber production, prevention of forest soil degradation, forest fire prediction, mitigation, and control can be attained through forest management using Internet of Things. The use and adoption of IoT in forest ecosystem management is challenging due to many factors. Vast geographical areas and limited resources in terms of budget and equipment are some of the limiting factors. In digital forestry, IoT deployment offers effective operations, control, and forecasts for soil erosion, fires, and undesirable depositions. In this chapter, IoT sensing and communication applications are presented for digital forestry systems. Different IoT systems for digital forest monitoring applications are also discussed

Neurenteric cyst - a case report of this rare disorder

Neurenteric cysts are rare congenital lesions that are believed to be the result of the split notochord syndrome. We report the clinical case of a 5-year-old boy presenting with vague gastrointestinal symptoms and fatigue, who had undergone resection of a small intestine duplication cyst as a newborn. Computed tomography revealed a mediastinal neurenteric cyst with partial destruction of several thoracic vertebrae. Resection of the tumor proved effective. Recognition of this disorder is important because of its benign nature, the prognosis after surgical resection can be good. If the diagnosis is made in an early stage, unnecessary progressive destruction of surrounding structures may be prevented. (C) 2007 Elsevier Inc. All rights reserved