Searching for targets for the systemic therapy of mesothelioma

Increasing knowledge about the molecular characteristics of mesothelioma had led to the identification of novel potential targets for systemic therapy. This review elaborates on the rationale behind targeted approaches that have been and are undergoing exploration in mesothelioma and summarizes available clinical results and ongoing efforts to improve the systemic therapy of mesotheliom

Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma

Background: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. Patients and methods: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. Results: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). Conclusions: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distres

The PAX5 oncogene is expressed in N-type neuroblastoma cells and increases tumorigenicity of a S-type cell line

Neuroblastoma is a neural crest-derived neoplasm of infancy with poor outcome in patients with advanced disease. The oncogenic transcription factor PAX5 is an important developmental regulator and is implicated in the pathogenesis of several malignancies. Screening of neuroblastoma cell lines revealed PAX5 expression in a malignant subset of neuroblastoma cells, so-called ‘N-type' cells, but not in the more benign ‘S-type' neuroblastoma cells. PAX5 expression was also detected in small cell lung cancer, an aggressive tumor of neural crest origin. Based on this observation we hypothesized that there could be a relationship between PAX5 expression and the more malignant phenotype of N-type cells. Stable PAX5 expression was established in several clones of the S-type cell line CA-2E. A noticeable difference in morphology of these transfectants was observed and there was also a significant increase in the proliferation rate. Moreover, PAX5 expressing clones gained the ability to form colonies in a soft agar assay, a marker of tumorigenicity. Down-regulation of PAX5 in several N-type cell lines and one small cell lung cancer cell line utilizing small interfering RNA resulted in a significant decrease in growth rate. Taken together we propose PAX5 as an important factor for the maintenance of the proliferative and tumorigenic phenotype of neuroblastoma. Our data, together with a recent study on the role of PAX genes in cancer suggest that PAX5 and other PAX transcription factors might be valuable targets for cancer therap

Moving from a Product-Based Economy to a Service-Based Economy for a More Sustainable Future

Traditionally, economic growth and prosperity have been linked with the availability, production and distribution of tangible goods as well as the ability of consumers to acquire such goods. Early evidence regarding this connection dates back to Adam Smith's Wealth of Nations (1776), in which any activity not resulting in the production of a tangible good is characterized as unproductive of any value." Since then, this coupling of economic value and material production has been prevalent in both developed and developing economies throughout the world. One unintended consequence of this coupling has been the exponential increase in the amount of solid waste being generated. The reason is that any production and consumption of material goods eventually generates the equivalent amount of (or even more) waste. Exacerbating this problem is the fact that, with today's manufacturing and supply chain management technologies, it has become cheaper to dispose and replace most products rather than to repair and reuse them. This has given rise to what some call a disposable society." To put things in perspective: In 2012 households in the U.K. generated approximately 22 thousand tons of waste, which amounted to 411 kg of waste generated per person (Department for Environment, Food & Rural Affairs, 2015). During the same time period, households in the U.S. generated 251 million tons of waste, which is equivalent to a person generating approximately 2 kg of waste every day (U.S. Environmental Protection Agency, 2012). Out of these 251 million tons of total waste generated, approximately 20% of the discarded items were categorized as durable goods. The disposal of durable goods is particularly worrisome because they are typically produced using material from non- renewable resources such as iron, minerals, and petroleum-based raw materials