Human antibodies targeting cell surface antigens overexpressed by the hormone refractory metastatic prostate cancer cells: ICAM-1 is a tumor antigen that mediates prostate cancer cell invasion

Transition from hormone-sensitive to hormone-refractory metastatic tumor types poses a major challenge for prostate cancer treatment. Tumor antigens that are differentially expressed during this transition are likely to play important roles in imparting prostate cancer cells with the ability to grow in a hormone-deprived environment and to metastasize to distal sites such as the bone and thus, are likely targets for therapeutic intervention. To identify those molecules and particularly cell surface antigens that accompany this transition, we studied the changes in cell surface antigenic profiles between a hormone-sensitive prostate cancer line LNCaP and its hormone-refractory derivative C4-2B, using an antibody library-based affinity proteomic approach. We selected a naïve phage antibody display library to identify human single-chain antibodies that bind specifically to C4-2B but not LNCaP. Using mass spectrometry, we identified one of the antibody-targeted antigens as the ICAM-1/CD54/human rhinovirus receptor. Recombinant IgG1 derived from this single-chain antibody binds to a neutralizing epitope of ICAM-1 and blocks C4-2B cell invasion through extracellular matrix in vitro. ICAM-1 is thus differentially expressed during the transition of the hormone-sensitive prostate cancer cell line LNCaP to its hormone-refractory derivative C4-2B, plays an important role in imparting the C4-2B line with the ability to invade, and may therefore be a target for therapeutic intervention

Engineered Models of Metastasis with Application to Study Cancer Biomechanics

Three-dimensional complex biomechanical interactions occur from the initial steps of tumor formation to the later phases of cancer metastasis. Conventional monolayer cultures cannot recapitulate the complex microenvironment and chemical and mechanical cues that tumor cells experience during their metastatic journey, nor the complexity of their interactions with other, noncancerous cells. As alternative approaches, various engineered models have been developed to recapitulate specific features of each step of metastasis with tunable microenvironments to test a variety of mechanistic hypotheses. Here the main recent advances in the technologies that provide deeper insight into the process of cancer dissemination are discussed, with an emphasis on three-dimensional and mechanical factors as well as interactions between multiple cell types

Facilitating students’ reflections on community practice:A new approach

In Australia, the nurses’ registration board necessitates nurses to be competent reflective practitioners. Consequently, student nurses require opportunities to develop those capacities. This chapter discusses the challenges of engaging nursing students in a novel pedagogical approach aimed to enhance their critical reflectivity. The example is community health practicum experience. Aside from the students’ assessment requirement to submit a clinical portfolio, there was no post-practicum follow-up to augment their learning of their community health placements. At the time this study was undertaken, the graduate-entry students only spent 1 week on their community health practicum and third-year undergraduate students 2 weeks. However, previous research has clearly identified that student nurses spend their first week assimilating into a new clinical setting before they are able to focus and reflect on their learning needs. The community health facilities students attend are quite varied in what they might offer in terms of opportunities and engagement. To augment learning a discussion forum was created on a project-specific, web-based learning interface, ‘Critical reflection on Community Practice’. Students were requested to upload a short video clip to share their learning experience of their community health placements. The videos were analysed for both evidence of reflectivity using The Reflective Writing Framework and knowledge content through content analysis. Findings illustrate a richer depth of knowledge, heightened awareness, and enhanced reflectivity. An examination on the benefits and limitations of video as a pedagogical approach for facilitating post-practicum critical reflection is presented.</p

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