The inaugural Canadian Consortium for LABC (locally advanced breast cancer) conference was held at Langdon Hall, Cambridge, Ontario, April 11–12, 2010. The meeting focused on current and future directions in labc treatment and research, the specific benefits of labc as a model for clinical and translational research, strategies for increased national and international collaboration, and ongoing clinical trials. Exciting Canadian initiatives in labc research are underway, focusing on identifying molecular signatures that will allow for the development of new tailored therapies. The challenge of identifying patient subgroups for accrual is being addressed through strategies to foster and improve national collaboration. This meeting report includes highlights from each presentation at the conference.
Breast neoplasms; cancer treatment; clinical research; translational research; neoadjuvant therapy; biomarkers
An epidemiologic shift in esophageal and gastric carcinomas has occurred in recent years in the Western world. Adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ) is now the predominant esophageal carcinoma, and proximal gastric cancers now account for nearly half of gastric carcinomas. Tumors involving the GEJ appear to be a distinct clinical entity that presents a challenge to oncologists due to issues in staging and classification and uncertainties regarding optimal treatment approach. Beyond surgical resection as the primary treatment modality, the roles of neoadjuvant or adjuvant therapies in GEJ cancers are not clearly defined. This article reviews the major randomized trials of combined-modality treatment in populations with esophageal and gastric cancers that included patients with GEJ carcinomas and discusses how the findings relate to and inform the management of GEJ tumors. In general, preoperative or perioperative chemotherapy appears to improve survival, and the addition of neoadjuvant or adjuvant chemoradiotherapy increases locoregional control and appears to improve survival. Although GEJ tumors account for only 20% to 35% of cancers in the most relevant randomized trials, the available data suggest that trimodality therapy with chemotherapy, radiation, and surgery is a reasonable treatment approach for GEJ tumors. Further clinical trials are needed to define the optimal sequencing and combinations of surgery, radiotherapy, and chemotherapy. These trials should include appropriate definitions and stratification of GEJ tumors in order to facilitate translation of findings to treatment practice.
The larynx sits at the crossroads between gastrointestinal and respiratory tracts. Besides its intrinsic importance in breathing, swallowing and voice production, the larynx is also exposed to unique immunological challenges. Given the propensity of chronic inflammatory conditions such as chronic laryngitis, which affects up to 20% of Western populations, it is perhaps surprising that our understanding of the immunology of this organ remains relatively limited. However, recent work on the immunological architecture of the laryngeal mucosa, and its changes that result from external challenges and inflammatory conditions, provided valuable insight into the fascinating immunology of this organ. The lessons learnt from these investigations may go beyond devising improved therapy for chronic laryngeal inflammation. Establishing whether and how the laryngeal mucosa may be involved in the modulation of wider mucosal responses may provide novel routes to the treatment of other inflammatory diseases of the respiratory and alimentary tracts such as asthma and inflammatory bowel disease.
The presence of the cellular prion protein (PrPC) on the cell surface is critical for the neurotoxicity of prions. Although a number of biological activities have been attributed to PrPC, a definitive demonstration of its physiological function remains elusive. In this review, we will discuss some of the proposed functions of PrPC, focusing on recently suggested roles in cell adhesion, regulation of ionic currents at the cell membrane, and neuroprotection. We will also discuss recent evidence supporting the idea that PrPC may function as a receptor for soluble oligomers of the amyloid β peptide and possibly other toxic protein aggregates. These data suggest surprising new connections between the physiological function of PrPC and its role in neurodegenerative diseases beyond those caused by prions.
The hygiene hypothesis states that childhood asthma develops as a result of decreased exposure to infectious agents during infancy and early childhood. This results in the persistence of the neonatal T helper lymphocyte 2 immunophenotype, thereby predisposing the child to atopic disease. While multiple studies support the hygiene hypothesis in asthma ontogeny, the evidence remains inconclusive; multiple other environmental exposures in early childhood also alter predisposition to asthma. Moreover, the current paradigm for asthma development extends far beyond simple childhood environmental exposures to include fetal development, genetic predisposition, and interactions of the developmental state and genetics with the environment.
asthma; child; fetal programming; gene by environment; infection
Insulin like growth factor receptor (IGF-1R) targeting became one of the most investigated areas in anticancer drug development during the last decade. Strategies aiming to block IGF-1R activity include monoclonal antibodies, tyrosine kinase inhibitors and anti-ligands antibodies. Initial enthusiasm quickly encountered challenges. Unfortunately the validation of the efficacy of IGF-1R targeted agents in large clinical trials failed, however anecdotal single agent activity was seen in early studies. Consequently, questions regarding the selection of right target population and the appropriate trial design are arising. Despite the plethora of clinical trials conducted no predictive biomarker has been validated so far and resistance mechanisms to IGF-1R inhibitors remain unclear. The other issue to be addressed is how to best combine IGF-1R inhibitors with other therapeutic approaches. This review highlights the most relevant clinical data emphasizing the main tumor types where IGF-1R inhibition showed potential interest. We also tried to extract based on clinical and translational data some candidate biomarkers that could help better to select patient population who potentially could benefit most from this therapeutic approach.
IGF-1R inhibitors; Monoclonal antibodies; Tyrosine kinase inhibitors; Predictive biomarker
Cancer control researchers seek to reduce the burden of cancer by studying interventions, their impact in defined populations, and the means by which they can be better used. The first step in cancer control is identifying where the cancer burden is elevated, which suggests locations where interventions are needed. Geographic information systems (GIS) and other spatial analytic methods provide such a solution and thus can play a major role in cancer control. This report presents findings from a workshop held June 16–17, 2005, to bring together experts and stakeholders to address current issues in GIScience and cancer control. A broad range of areas of expertise and interest was represented, including epidemiology, geography, statistics, environmental health, social science, cancer control, cancer registry operations, and cancer advocacy. The goals of this workshop were to build consensus on important policy and research questions, identify roadblocks to future progress in this field, and provide recommendations to overcome these roadblocks.
To analyse economic aspects of tobacco control policy issues in China.
Published and collected survey data were used to analyse economic consequences of smoking. Economic analysis was used to address the role of tobacco farmers and the cigarette industry in the Chinese economy.
In the agricultural sector, tobacco has the lowest economic rate of return of all cash crops. At the same time, the tobacco industry's tax contribution to the central government has been declining.
Economic gains become less important as the negative health impact of smoking on the population garners more awareness. China stands at a crossroads to implement the economic promises of the World Health Organization's Framework Convention on Tobacco Control and promote the health of its population.
economics; tobacco control; China
Since the observation of the blood oxygenation level dependent (BOLD) effect on measured MR signal in the brain, functional magnetic resonance imaging (fMRI) has rapidly become the tool of choice for exploring brain function in cognitive neuroscience. Although fMRI is an exciting and powerful means to examining the brain in vivo, the field has sometimes permitted itself to believe that patterns of BOLD activity reveal more than it is possible to measure given the method’s spatial and temporal sampling, while concurrently not fully exploring the amount of information it provides. In this article, we examine some of the constraints on the kinds of inferences that can be supported by fMRI. We critique the concept of reverse inference that is often employed to say some cognitive function must be present given activity in a specific region. We review the consideration of functional and effective connectivity that remain infrequently applied in cognitive neuroimaging, highlighting recent thinking on the ways in which functional imaging can be used to characterize inter-regional communication. Recent advances in neuroimaging that make it possible to assess anatomical connectivity using diffusion tensor imaging (DTI) and we discuss how these may inform interpretation of fMRI results. Descriptions of fMRI studies in the media, in some instances, serve to misrepresent fMRI’s capabilities. We comment on how researchers need to faithfully represent fMRI’s promise and limitations in dealing with the media. Finally, as we stand at the crossroads of fMRI research, where one pathway leads toward a rigorous understanding of cognitive operations using fMRI and another leads us to a predictable collection of observations absent of clear insight, we offer our impressions of a fruitful path for future functional imaging research.