Cellular model systems to study the tumor biological role of kallikrein-related peptidases in ovarian and prostate cancer

Since the identification of the gene family of kallikrein related peptidases (KLKs), their function has been robustly studied at the biochemical level. In vitro biochemical studies have shown that KLK proteases are involved in a number of extracellular processes that initiate intracellular signaling pathways by hydrolysis, as reviewed in Chapters 8, 9, and 15, Volume 1. These events have been associated with more invasive phenotypes of ovarian, prostate, and other cancers. Concomitantly, aberrant expression of KLKs has been associated with poor prognosis of patients with ovarian and prostate cancer (Borgoño and Diamandis, 2004; Clements et al., 2004; Yousef and Diamandis, 2009), with prostate-specific antigen (PSA, KLK3) being a long standing, clinically employed biomarker for prostate cancer (Lilja et al., 2008). Data generated from patient samples in clinical studies, alongwith biochemical activity, suggests that KLKs function in the development and progression of these diseases. To bridge the gap between their function at the molecular level and the clinical need for efficacious treatment and prognostic biomarkers, functional assessment at the in vitro cellular level, using various culture models, is increasing, particularly in a three-dimensional (3D) context (Abbott, 2003; Bissell and Radisky, 2001; Pampaloni et al., 2007; Yamada and Cukierman, 2007).

Natural, engineered and synthetic inhibitors of kallikrein-related peptidases

There is a rapidly growing appreciation of the important physiological roles played by kallikreins and kallikrein-related peptidases (KLKs). Recent studies have revealed that these enzymes control key events in processes as diverse as inflammation and skin desquamation. Accordingly, there is considerable interest in developing tools to further dissect kallikrein activity, and a burgeoning effort aimed at producing lead inhibitors for therapeutic development. Indeed, several candidate inhibitors are already in clinical trials. This chapter surveys the naturally occurring kallikrein inhibitors, together with strategies for employing these molecules as bioscaffolds, as well as current progress in the development of small-molecule kallikrein inhibitors.

Bug reproduction : a collaborative practice within software maintenance activities

Software development settings provide a great opportunity for CSCW researchers to study collaborative work. In this paper, we explore a specific work practice called bug reproduction that is a part of the software bug-fixing process. Bug re-production is a highly collaborative process by which software developers attempt to locally replicate the ‘environment’ within which a bug was originally encountered. Customers, who encounter bugs in their everyday use of systems, play an important role in bug reproduction as they provide useful information to developers, in the form of steps for reproduction, software screenshots, trace logs, and other ways to describe a problem. Bug reproduction, however, poses major hurdles in software maintenance as it is often challenging to replicate the contextual aspects that are at play at the customers’ end. To study the bug reproduction process from a human-centered perspective, we carried out an ethnographic study at a multinational engineering company. Using semi-structured interviews, a questionnaire and half-a-day observation of sixteen software developers working on different software maintenance projects, we studied bug reproduction. In this pa-per, we present a holistic view of bug reproduction practices from a real-world set-ting and discuss implications for designing tools to address the challenges developers face during bug reproduction.