Ex vivo assessment of targeted therapies in a rare metastatic epithelial–myoepithelial carcinoma

Epithelial–myoepithelial carcinoma (EMC) is a rare subtype of salivary gland neoplasms. Since the initial description of the cancer, just over 300 cases have been reported. EMCs occupy a biphasic cellular differentiation-state defined by the constitution of two cell types representing epithelial and myoepithelial lineages, yet the functional consequence of the differentiation-state heterogeneity with respect to therapy resistance of the tumors remains unclear. The reported local recurrence rate of the cases is approximately 30%, and while distant metastases are rare, a significant fraction of these cases are reported to receive no survival benefit from radio- or chemotherapy given in addition to surgery. Moreover, no targeted therapies have been reported for these neoplasms. We report here the first use and application of ex vivo drug screening together with next generation sequencing to assess targeted treatment strategies for a rare metastatic epithelial–myoepithelial carcinoma. Results of the ex vivo drug screen demonstrate significant differential therapeutic sensitivity between the epithelial and myoepithelial intra-tumor cell lineages suggesting that differentiation-state heterogeneity within epithelial–myoepithelial carcinomas may present an outlet to partial therapeutic responses to targeted therapies including MEK and mTOR inhibitors. These results suggest that the intra-tumor lineage composition of EMC could be an important factor to be assessed when novel treatments are being evaluated for management of metastatic EMC

Ex vivo modelling of drug efficacy in a rare metastatic urachal carcinoma

Background Ex vivo drug screening refers to the out-of-body assessment of drug efficacy in patient derived vital tumor cells. The purpose of these methods is to enable functional testing of patient specific efficacy of anti-cancer therapeutics and personalized treatment strategies. Such approaches could prove powerful especially in context of rare cancers for which demonstration of novel therapies is difficult due to the low numbers of patients. Here, we report comparison of different ex vivo drug screening methods in a metastatic urachal adenocarcinoma, a rare and aggressive non-urothelial bladder malignancy that arises from the remnant embryologic urachus in adults. Methods To compare the feasibility and results obtained with alternative ex vivo drug screening techniques, we used three different approaches; enzymatic cell viability assay of 2D cell cultures and image-based cytometry of 2D and 3D cell cultures in parallel. Vital tumor cells isolated from a biopsy obtained in context of a surgical debulking procedure were used for screening of 1160 drugs with the aim to evaluate patterns of efficacy in the urachal cancer cells. Results Dose response data from the enzymatic cell viability assay and the image-based assay of 2D cell cultures showed the best consistency. With 3D cell culture conditions, the proliferation rate of the tumor cells was slower and potency of several drugs was reduced even following growth rate normalization of the responses. MEK, mTOR, and MET inhibitors were identified as the most cytotoxic targeted drugs. Secondary validation analyses confirmed the efficacy of these drugs also with the new human urachal adenocarcinoma cell line (MISB18) established from the patient’s tumor. Conclusions All the tested ex vivo drug screening methods captured the patient’s tumor cells’ sensitivity to drugs that could be associated with the oncogenic KRASG12V mutation found in the patient’s tumor cells. Specific drug classes however resulted in differential dose response profiles dependent on the used cell culture method indicating that the choice of assay could bias results from ex vivo drug screening assays for selected drug classes

Dialogues on culture(s) of inclusion between African and Finnish educators

This chapter aims to respond to the important question of the difference between culturally responsive education and inclusive education, by analysing dialogues on inclusive education from different cultures, and to discuss how inclusion is and could be embedded in culturally responsive education. It explores the cross-cultural collaboration and implementation of inclusive education through the culturally responsive education lens. The chapter analyses the dialogues of teachers and students from five African and two Finnish universities. The African–Finnish network for inclusive teacher education (AFNITE) project has focused on reduction of inequality in lifelong learning and promoted 'inclusive education' as defined by UNESCO. The AFNITE project, as the project title states, has focused on inclusive teacher education. The chapter also analyses qualitative material that comprises dialogues conducted throughout the project activities. Usually equity, equality, and human rights are approached as so-called 'crosscutting' issues in educational development and too often it is assumed that they are realized

Cognitive radio systems evaluation: measurement, modeling, and emulation approach

No abstract available.publishe

Improving primary statistics prediction under imperfect spectrum sensing

Abstract Dynamic Spectrum Access (DSA) / Cognitive Radio (CR) systems utilize spectrum sensing to monitor spectrum status and decide transmission time in an opportunistic manner. This results in an increase in wireless spectrum efficiency. Spectrum sensing can also be used to monitor the statistics of primary users to gain information on occupation patterns and estimate the statistics of the primary traffic activity, a useful knowledge that can be exploited in many ways. In this research, three novel algorithms are proposed to enhance the estimation of primary user activity statistics under imperfect spectrum sensing given the knowledge of minimum transmission time. Simulation results show that the proposed methods enable accurate estimation for the primary user statistics. Moreover, the proposed methods are compared to previously proposed methods and it is shown they provide a significantly better estimation accuracy