Related Articles

Circulating tumor cells (CTCs) are responsible for metastases in distant organs via hematogenous dissemination. Fundamental studies in the past decade have suggested that neutralization of CTCs in circulation could represent an effective strategy to prevent metastasis. Current paradigms of targeted drug delivery into a solid tumor largely fall into two main categories: unique cancer markers (e.g. overexpression of surface receptors) and tumor-specific microenvironment (e.g. low pH, hypoxia, etc.). While relying on a surface receptor to target CTCs can be greatly challenged by cancer heterogeneity, targeting of tumor microenvironments has the advantage of recognizing a broader spectrum of cancer cells regardless of genetic differences or tumor types. The blood circulation, however, where CTCs transit through, lacks the same tumor microenvironment as that found in a solid tumor. In this study, a unique "microenvironment" was confirmed upon introduction of cancer cells of different types into circulation where activated platelets and fibrin were physically associated with blood-borne cancer cells. Inspired by this observation, synthetic silica particles were functionalized with activated platelet membrane along with surface conjugation of tumor-specific apoptosis-inducing ligand cytokine, TRAIL. Biomimetic synthetic particles incorporated into CTC-associated micro-thrombi in lung vasculature and dramatically decreased lung metastases in a mouse breast cancer metastasis model. Our results demonstrate a "Trojan Horse" strategy of neutralizing CTCs to attenuate metastasis.

Lire la suite...

Small-cell lung cancer (SCLC) comprises 13-20% of all lung cancers but is the fifth leading cause of cancer death worldwide. SCLC prognosis remains poor despite improvements in diagnosis and therapy over the last 30 years. Current treatment is systemic chemotherapy, flanked by thoracic irradiation for limited stage disease; however, about two-thirds of patients are diagnosed with extensive stage disease when thoracic irradiation is not worthwhile. Randomized trials on surgical resection in patients with limited stage disease conducted in the pre-PET era, when both staging and treatment were inadequate, did not support a role for surgery in disease management. However recent retrospective and population-based studies indicate that outcomes after surgery in patients with very early SCLC are comparable to those in patients with non-SCLC, and that survival is better than in SCLC patients not given surgery. CT screening identifies SCLC at an earlier stage - with better survival - than usual care, and offers the hope that more SCLC patients may become long-term survivors. However, cases must be exhaustively staged to identify those likely to benefit from surgery. Finding a specific SCLC marker to facilitate early diagnosis remains a priority.

Lire la suite...

Patients with chronic obstructive pulmonary diseases (COPD) often experience comorbid conditions. The most common comorbidities that have been associated with COPD include cardiovascular diseases, lung cancer, metabolic disorder, osteoporosis, anxiety and depression, skeletal muscle dysfunction, cachexia, gastrointestinal diseases, and other respiratory conditions. Not only are comorbidities common but they also considerably influence disease prognosis and patients׳ health status, and are associated with poor clinical outcomes. However, perusal of literature indicates that little has been done so far to effectively assess, manage, and treat comorbidities in patients with COPD.
The aim of this review is to comprehensively narrate the comorbid conditions that often coexist with COPD, along with their reported prevalence and their significant impacts in the disease management of COPD. A perspective on integrated disease management approaches for COPD is also discussed.

BACKGROUND: For oncological evaluations, quantitative radiology gives clinicians significant insight into patients' response to therapy. In regard to the Response Evaluation Criteria in Solid Tumours (RECIST), the classification of disease evolution partly consists in applying thresholds to the measurement of the relative change of tumour. In the case of tumour volumetry, response thresholds have not yet been established. This study proposes and validates a model for calculating thresholds for the detection of minimal tumour change when using the volume of pulmonary lesions on CT as imaging biomarker. METHODS: Our work is based on the reliability analysis of tumour volume measurements documented by the Quantitative Imaging Biomarker Alliance. Statistics of measurements were entered into a multi-parametric mathematical model of the relative changes derived from the Geary-Hinkley transformation. The consistency of the model was tested by comparing modelled thresholds against Monte Carlo simulations of tumour volume measurements with additive random error. The model has been validated by repeating measurements on real patient follow ups. RESULTS: For unchanged tumour volume, relying on a normal distribution of error, the agreement between model and simulations featured a type I error of 5.25 %. Thus, we established that a threshold of 35 % of volume reduction corresponds to a partial response (PR) and a 55 % volume increase corresponds to progressive disease (PD). Changes between -35 and +55 % are categorized as stable disease (SD). Tested on real clinical data, 97.1 % [95.7; 98.0] of assessments fall into the range of variability predicted by our model of confidence interval. CONCLUSIONS: Our study indicates that the Geary Hinkley model, using published statistics, is appropriate to predict response thresholds for the volume of pulmonary lesions on CT.