Tumor metastasis to bone

Establishment of skeletal metastasis involves bidirectional interactions between the tumor cell and the cellular elements in the bone microenvironment. A better understanding of the pathophysiology of bone metastasis will be critical in developing the means to prevent bone metastasis or inhibit its progression. The receptor activator of nuclear factor-κB (RANK)/RANK ligand pathway has emerged as the key pathway regulating osteolysis in skeletal metastasis. A number of candidate factors, including the Wnt (wingless int) proteins, endothelin-1, and bone morphogenetic proteins, have been implicated in the establishment of osteoblastic metastasis. The complex nature of tumor-bone microenvironment interactions and the presence of multiple pathways that lead to bone metastasis suggests that simultaneous targeting of these pathways in the metastatic cascade are required for effective treatment. This review discusses current understanding of the pathophysiologic mechanisms that underlie the establishment of bone metastasis and potential molecular therapeutic strategies for prevention and treatment of bone metastasis

In vitro evaluation of a double-stranded self-complementary adeno-associated virus type2 vector in bone marrow stromal cells for bone healing

Background: Both adenoviral and lentiviral vectors have been successfully used to induce bone repair by over-expression of human bone morphogenetic protein 2 (BMP-2) in primary rat bone marrow stromal cells in pre-clinical models of ex vivo regional gene therapy. Despite being a very efficient means of gene delivery, there are potential safety concerns that may limit the adaptation of these viral vectors for clinical use in humans. Recombinant adeno-associated viral (rAAV) vector is a promising viral vector without known pathogenicity in humans and has the potential to be an effective gene delivery vehicle to enhance bone repair. In this study, we investigated gene transfer in rat and human bone marrow stromal cells in order to evaluate the effectiveness of the self-complementary AAV vector (scAAV) system, which has higher efficiency than the single-stranded AAV vector (ssAAV) due to its unique viral genome that bypasses the rate-limiting conversion step necessary in ssAAV.Methods: Self-complementaryAAV2 encoding GFP and BMP-2 (scAAV2-GFP and scAAV2-BMP-2) were used to transduce human and rat bone marrow stromal cells in vitro, and subsequently the levels of GFP and BMP-2 expression were assessed 48 hours after treatment. In parallel experiments, adenoviral and lentiviral vector mediated over-expression of GFP and BMP-2 were used for comparison.Results: Our results demonstrate that the scAAV2 is not capable of inducing significant transgene expression in human and rat bone marrow stromal cells, which may be associated with its unique tropism.Conclusions: In developing ex vivo gene therapy regimens, the ability of a vector to induce the appropriate level of transgene expression needs to be evaluated for each cell type and vector used. © 2011 Alaee et al; licensee BioMed Central Ltd

Prophylactic and Therapeutic Role of Human Breast Milk Proteins and Bioactive Peptides against Neonatal Bacterial Infections

Breast milk represents nature’s best mechanism to provide complete nourishment and protection to the newborn. Human breast milk acts as a store house of an array of bioactive factors, which includes antimicrobial proteins and antimicrobial peptides that confer early protection while lowering the incidence of developing various infections and exhibiting immune modulation property to activate the immune cells to fight against the invading pathogens. Among the bioactive peptides, endogenous peptides present in breast milk have opened a new window of research on studying their unique mechanisms of action. This will help in incorporating these peptides in formula milk for meeting special needs where breastfeeding is not possible. The present chapter aims to give a deep insight into the various antimicrobial peptides and the newly reported endogenous peptides in human breast milk with emphasis on their levels and activity in preterm milk as data related to this is lacking and preterm newborns are highly vulnerable to acquire infections. Further, the chapter focuses on highlighting the antibacterial mechanisms adopted by the bioactive peptides for protection against the neonatal bacterial pathogens with special emphasis on the infections caused by resistant bacterial strains in hospital settings (neonatal wards) and their future implications

The Evolution of Reverse Total Shoulder Arthroplasty and Its Current Use in the Treatment of Proximal Humerus Fractures in the Older Population

Proximal humerus fracture (PHF) is a common injury in the older population. While the majority of these fractures are treated non-operatively, a small subset of patients may benefit from surgical treatment. However, there continues to be an ongoing debate regarding the indications and ideal surgical treatment strategy. The use of reverse total shoulder arthroplasty (RTSA) has resulted in a paradigm shift in the treatment of PHFs in the older population. Unique biomechanical principles and design features of RTSA make it a suitable treatment option for PHFs in the older population. RTSA has distinct advantages over hemiarthroplasty and internal fixation and provides good pain relief and a reliable and reproducible improvement in functional outcomes. As a result, there has been an exponential increase in the volume of RTSA in the older population in last decade. The aim of this paper is to review the current concepts, outcomes and controversies regarding the use of RTSA for the treatment of PHFs in the older population

Multicentric giant cell tumor involving the same foot: A case report and review of literature

Multicentric giant cell tumour (GCT) is extremely rare; no case has been previously reported where two lesions occurred in the same foot at different sites. We report a case involving the calcaneus and subsequently the 3rd toe of the same foot and review the reported literature. In established cases of multicentricity, the histopathology has to be properly reviewed and the patient has to be followed up for a longer time with serial whole body assessment to pick up any subsquent lesions. The treatment of the local disease does not differ from a standard GCT

A Multimodal Feature Fusion Framework for Sleep-Deprived Fatigue Detection to Prevent Accidents

Sleep-deprived fatigued person is likely to commit more errors that may even prove to be fatal. Thus, it is necessary to recognize this fatigue. The novelty of the proposed research work for the detection of this fatigue is that it is nonintrusive and based on multimodal feature fusion. In the proposed methodology, fatigue is detected by obtaining features from four domains: visual images, thermal images, keystroke dynamics, and voice features. In the proposed methodology, the samples of a volunteer (subject) are obtained from all four domains for feature extraction, and empirical weights are assigned to the four different domains. Young, healthy volunteers (n = 60) between the age group of 20 to 30 years participated in the experimental study. Further, they abstained from the consumption of alcohol, caffeine, or other drugs impacting their sleep pattern during the study. Through this multimodal technique, appropriate weights are given to the features obtained from the four domains. The results are compared with k-nearest neighbors (kNN), support vector machines (SVM), random tree, random forest, and multilayer perceptron classifiers. The proposed nonintrusive technique has obtained an average detection accuracy of 93.33% in 3-fold cross-validation