Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: A meta-analysis of clinical evidence

Background

Abnormal NF-??B2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-??B2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-??B2 mutant, and human multiple myeloma cell lines.

Methods

We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines.

Results

Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein) in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells.

Conclusions

These findings provide a mouse model for human multiple myeloma with aberrant NF-??B2 activation and suggest a molecular mechanism for NF-??B2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.     

The epidemiology of medically attended sport and recreational injuries in Queensland

The Queensland Sport and Recreation Injury Survey (QSRIS) is a retrospective study describing the annual incidence of injuries in the state of Queensland, Australia, resulting from sport and recreational activity involvement. Data were collected by means of a computer-assisted-telephone-interview (CATI) survey of a representative sample of Queenslanders in the spring of 2000. The sample produced a total of 1337 respondents aged 18 to 94 years. The survey asked information regarding medically attended, non-fatal injuries resulting from sport and recreational activities in the past 12 months. Of the 1337 individuals surveyed, 191 of the respondents reported one or more injuries that required medical attention resulting in a total of 222 Injuries. This represents an overall rate of 1,666 medically attended injuries per 10,000 people. Among those reporting a sport or recreational injury, the most common types of injuries were a strained/pulled muscle (30.9%), sprained/torn ligament (24.1%), and fracture (12.6%). The most common bodily locations of injuries were the shoulders (13.0%) and knees (12.5%). Results detail the nature and type of injury, medical professional attending to the injury and the nature of the sport or recreational activity that led to the reported injury, highlighting the number of injuries associated with general fitness activities achieved through high participation rates and low injury rates. This remains an area of much needed attention given the promotional push towards raising the levels of physical activity at a population level.     

Minimally invasive technology in the management of breast disease

Minimally invasive surgery is gaining popularity around the world because it achieves the same or even superior results when compared to standard surgery but with less morbidity. Minimally invasive breast surgery is a broad concept encompassing new developments in the field of breast surgery that work on this minimally invasive principle. In this regard, breast-conserving surgery and sentinel lymph node biopsy are good illustrations of this concept. There are three major areas of progress in the minimally invasive management of breast disease. First, percutaneous excisional devices are now available that can replace the surgical excision of breast mass lesions. Second, various ablative treatments are capable of destroying breast cancers in situ instead of surgical excision. Third, mammary ductoscopy provides a new approach to the investigation of mammary duct pathology. Clinical experience and potential applications of these new technologies are reviewed.     

Oncolytic Reovirus Effectively Targets Breast Cancer Stem Cells

Recent evidence suggests that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are resistant to current anticancer therapies. Hence, novel cancer therapies will need to be tested for both tumor regression and CSC targeting. Herein we show that oncolytic reovirus that induces regression of human breast cancer primary tumor samples xenografted in immunocompromised mice also effectively targets and kills CSCs in these tumors. CSCs were identified based on CD24⁻CD44⁺ cell surface expression and overexpression of aldehyde dehydrogenase. Upon reovirus treatment, the CSC population was reduced at the same rate as non-CSCs within the tumor. Immunofluorescence of breast tumor tissue samples from the reovirus- and mock-treated mice confirmed that both CSCs and non-CSCs were infectible by reovirus, and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay showed that both populations died by apoptosis. Ras, which has been shown to mediate reovirus oncolysis, was found to be present at similar levels in all cell types, and this is consistent with their comparable sensitivity to reovirus. These experiments indicate that oncolytic reovirus has the potential to induce tumor regression in breast cancer patients. More important, the CSC population was equally reduced and was as susceptible to reovirus treatment as the non-CSC population.     

Brain responses to stimuli mimicking dental treatment among non‐phobic individuals: A meta‐analysis

Numerous neuroimaging studies have attempted to identify how the brain responds to stimuli mimicking dental treatment in normal non‐phobic individuals. However, results were sometimes inconsistent due to small sample sizes and methodological variations. This meta‐analysis employs standardized procedures to summarize data from previous studies to identify brain regions that were consistently activated across studies, elicited by stimuli such as pictures, sounds, or audiovisual footage mimicking those encountered during dental treatments. A systematic literature search was carried out using PubMed and Scopus. The meta‐analysis analyzed data from 120 healthy subjects from seven neuroimaging studies. We assessed the risk of bias among the included studies with the Risk of Bias Assessment Tool for Nonrandomized Studies. One study appeared to have a high risk of selection bias, whereas the others were considered to have a low risk of bias. Results revealed three clusters of activation with cluster sizes ranging from 768 mm³ to 1,424 mm³. Stimuli mimicking dental treatment consistently activated the bilateral anterior insula; right dorsal anterior cingulate, putamen, and medial prefrontal cortex; and left claustrum. This study confirmed that audio and/or visual stimuli mimicking dental treatment consistently activated the fear‐related brain regions among healthy subjects, mostly consistent with activations from general anxiety but without the involvement of the amygdala.     

Mechanical model testing of rebreathing potential in infant bedding materials

Rebreathing of expired air may be a lethal hazard for prone sleeping infants. This paper describes a mechanical model to simulate infant breathing, and examines the effects of bedding on exhaled air retention. Under simulated rebreathing conditions, the model allows the monitoring of raised carbon dioxide (CO2) inside an artificial lung-trachea system. Resulting levels of CO2 (although probably exaggerated in the mechanical model compared with an infant, due to the model's fixed breathing rate and volume) suggest that common bedding materials vary widely in inherent rebreathing potential. In face down tests, maximum airway CO2 ranged from less than 5% on sheets and waterproof mattresses to over 25% on sheepskins, bean bag cushions, and some pillows and comforters. Concentrations of CO2 decreased with increasing head angle of the doll, away from the face down position. Recreations of 29 infant death scenes also showed large CO2 increases on some bedding materials, suggesting these infants could have died while rebreathing.