Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease whose etiology remains largely unknown. The uncontrolled oxidative stress in SLE contributes to functional oxidative modifications of cellular protein, lipid and DNA and consequences of oxidative modification play a crucial role in immunomodulation and trigger autoimmunity. Measurements of oxidative modified protein, lipid and DNA in biological samples from SLE patients may assist in the elucidation of the pathophysiological mechanisms of the oxidative stress-related damage, the prediction of disease prognosis and the selection of adequate treatment in the early stage of disease. Application of these biomarkers in disease may indicate the early effectiveness of the therapy. This review is intended to provide an overview of various reactive oxygen species (ROS) formed during the state of disease and their biomarkers linking with disease. The first part of the review presents biochemistry and pathophysiology of ROS and antioxidant system in disease. The second part of the review discusses the recent development of oxidative stress biomarkers that relates pathogenesis in SLE patients and animal model. Finally, this review also describes the reported clinical trials of antioxidant in the disease that have evaluated the efficacy of antioxidant in the management of disease with ongoing conventional therapy.

Src family kinases (SFKs) integrate signal transduction for multiple receptors, regulating cellular proliferation invasion and metastasis in human cancer. Although Src is rarely mutated in human prostate cancer, SFK activity is increased in the majority of human prostate cancers. In order to determine the molecular mechanisms governing prostate cancer bone metastasis, FVB murine prostate epithelium was transduced with oncogenic v-Src. The prostate cancer cell lines metastasized in FVB mice to brain and bone. Gene expression profiling of the tumors identified activation of a CCR5 signaling module when the prostate epithelial cells (PEC) lines were grown in vivo vs. tissue cultures. The whole body, bone and brain metastatic prostate cancer burden was reduced by oral CCR5 antagonist. Clinical trials of CCR5 inhibitors may warrant consideration in patients with CCR5 activation in their tumors.

Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans.

Non-small cell lung carcinomas (NSCLC) overexpress the Her2/ /neu gene in approximately 59% of cases. Trastuzumab, a humanized monoclonal antibody, interferes with Her2 signaling and is approved for the treatment of Her2/ /neu overexpressing breast cancer. However, its therapeutic use in Her2/ /neu overexpressing NSCLC remains obscure. The present study aimed to determine the role of 64 Cu-labeled trastuzumab positron emission tomography (PET) for non-invasive imaging of Her2/ /neu expression in NSCLC. Trastuzumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with 64 Cu. The molecular specificity of DOTA-trastuzumab was determined in NSCLC cell lines with Her2/ /neu overexpression (NCI-H2170) and negative expression (NCI-H520). Imaging of Her2/ /neu expression was performed in NCI-H2170 tumor-bearing mice with L ung cancer is one of the world's leading causes of death, with a 5-year survival rate of less than 10%.(1) Activation of ras genes and human epidermal growth factor receptor 2 (Her2/neu) genes is encountered in subpopulations of non-small cell lung carcinoma (NSCLC) patients and has been linked to shortened survival. Overexpression of the Her2/neu gene is closely associated with intrinsic multiple drug resistance in NSCLC cell lines.(2) Her2/neu is a transmembrane tyrosine kinase belonging to the surface receptor family. It does not bind ligand but instead acts as a preferred heterodimerization partner for ligand-activated sibling members to amplify mitotic signaling. Trastuzumab, a humanized monoclonal antibody that targets Her2/neu, inhibits neoplastic cell proliferation both in vitro and in vivo.(4) In breast cancer, overexpression of Her2/neu is seen in 40% of cases, and its activation follows heterodimerization with a member of the EGFR family and triggers important biological effects such as proliferation, migration and differentiation.(5) Trastuzumab significantly increases the survival of patients with advanced metastatic breast cancer. Overexpression of Her2/neu is reported in up to 59% of cases of NSCLC and the 2+/3+ overexpression rate is 5-20% in adenocarcinomas.(8-10) As in breast cancer, studies have suggested that the overexpression of Her2/neu in NSCLC is associated with a worse prognosis than negative expression of Her2/ neu. (11,12) The role of trastuzumab targeting Her2/neu expression in the NSCLC has been largely marginalized. Even though NSCLC is usually chemoresistant, the synergistic effect between trastuzumab and chemotherapeutic agents was found to be greater in Her2/neu positive NSCLC than in breast cancer cell lines. (13,14) NSCLC patients with Her2/neu overexpression (3+) in immunohistochemistry (IHC) had better survival when treated with trastuzumab-based therapy than the overall population, but only a small percentage of patients benefited.(10) The marked variation in functional anatomy and pathophysiology within human tumors and within individual patients may account for the high va...

ABSTRACT. The purpose of this study is to evaluate the role of diffusion-weighted imaging (DWI) in combination with T 1 and T 2 weighted MRI for the characterisation of renal carcinoma. The institutional review board approved the study protocols and waived informed consent from all of the patients. 47 patients (32 male and 15 female; age range, 21-85 years; median age, 65 years) who had suspected renal lesions on abdominal CT underwent MRI for further evaluation and characterisation of the lesions from April 2005 to August 2007 in our university hospital. A region of interest was drawn around the tumour area on apparent diffusion coefficient (ADC) maps. Final diagnosis was confirmed by histological examination of surgical specimens from all patients. The ADC value was significantly higher in renal cell carcinoma (RCC) ; p50.0004), whereas intensity on T 1 and T 2 weighted imaging did not reach statistical significance. In conclusion, DWI has clinical value in the characterisation of renal carcinomas and could be applied in clinical practice for their management. Renal cell carcinoma (RCC) is the most common primary malignant tumour of the kidney; it accounts for 2-3% of all adult cancers and is the sixth cause of death by tumour throughout the world. More than 80% of renal cancers that arise in the renal parenchyma are RCC, whereas the majority of renal pelvis cancers are transitional cell carcinomas (TCCs) [1][2][3]. The three most common subtypes of RCC are (i) clear cell carcinoma, one of the most common types, accounting for 70-80% of cases; (ii) papillary renal cell carcinoma, accounting for about 10-15% of cases; and (iii) chromophobe renal carcinoma, which is the least common, accounting for 5% of all RCCs. The annual rate of RCC diagnosis is increasing as a result of incidental detection by crosssectional abdominal imaging of patients with suspected abdominal disorders. Increased detection rates carry a favourable prognosis; however, mortality from RCC has not decreased [2][3][4].Diffusion-weighted imaging (DWI) is frequently used in cranial MRI studies and has shown potential for the characterisation of lesions such as acute cerebral infarctions, intracranial tumours, various infectious diseases and metabolic disorders [5][6][7][8]. The role of DWI is limited outside the central nervous system, owing to its inherent extreme sensitivity to motion, such as that related to respiration, peristalsis and artefacts, thus resulting in a high signal to noise ratio. With the development of advanced MR technology and the use of faster robust sequences, better quality has been obtained in abdominal imaging [9]. DWI with high b-values has been reported to have a high sensitivity for depicting malignant disease. Apparent diffusion coefficient (ADC) values of malignant hepatic, ovarian, breast, prostatic, colonic and uterine cervical tumours were lower than those of benign lesions or normal tissue [10][11][12][13][14][15][16][17][18].Previous studies have suggested that patients with chromophobe and papillary RCC ha...