Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many immunotherapeutic approaches, but little data are available about Ep-CAM expression in major human malignancies with respect to level, frequency, tumour stage, grade, histologic tumour type and impact on survival. We analysed by immunohistochemical staining tissue microarrays with 4046 primary human carcinoma samples from colon, stomach, prostate and lung cancers for both frequency and intensity of Ep-CAM expression under highly standardised conditions. A total of 3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7% (n=1186) of colon, 90.7% of gastric (n=473), and 87.2% of prostate cancers (n=414), and in 63.9% of lung cancers (n=1287). No detectable Ep-CAM staining was found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and 13.5% of lung cancers. The only significant correlation of Ep-CAM expression with tumour grading was observed in colon cancer where high-level Ep-CAM expression on grade 3 tumours was down to 92.1% (P<0.0001). Adenosquamous and squamous carcinomas of the lung had a lower percentage of high-level Ep-CAM expression compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and 17.3% of tumours being Ep-CAM negative. With the exception of moderately differentiated colon carcinoma, where patients not expressing Ep-CAM on their tumours showed an inferior survival (P=0.0014), correlation of Ep-CAM expression with survival did not reach statistical significance for any of the other cancer indications and subgroups. In conclusion, the data strongly support the notion that Ep-CAM is a prime target for immunotherapies in major human malignancies. This is because the most common human cancers show (i) a low frequency of Ep-CAM-negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given tumour, and (iii) for most cancers, an insignificant influence of tumour staging, grading and histology on Ep-CAM expression

Delivering goods in urban areas. How to deal with urban policy restrictions and the environment?

Time-access regulations and vehicle restrictions are increasingly used, especially in western Europe, to improve social sustainability in urban areas. These regulations considerably affect the distribution process of retail chain organizations as well as the environmental burden. This paper studies the impact of governmental time windows, vehicle restrictions, and different retailers' logistical concepts on the financial and environmental performance of retailers. We use a case study with two cases that differ in their drop sizes as input for an experiment. The retailers provided all organizational, flow, and cost data of the distribution process between their distribution centers and their stores. We use these data to calculate the impacts of different scenarios on the retailers' financial and environmental performances based on a fractional factorial design in which urban policies and the retailers' logistical concepts are varied, using vehicle routing software. We test the propositions with a third case. We show that the cost impact of time windows is the largest for retailers who combine many deliveries in one vehicle round-trip. The cost increase due to vehicle restrictions is the largest for retailers whose round-trip lengths are restricted by vehicle capacity. Vehicle restrictions and time windows together do not increase a retailer's cost more than individually. Variations in delivery volume and store dispersion hardly influence the impact of urban policy and the retailer's logistical concept decisions. [ABSTRACT FROM AUTHOR