ObjectiveTo determine the DNA replication error (RER) status in young patients with colorectal cancer (CRC), and to compare the clinical and pathologic characteristics of RER-positive and RER-negative cases. Summary Background DataRecent studies suggest that patients with RER-positive CRC have an improved prognosis. Further data are required to confirm this observation in young CRC patients. MethodsAll patients 40 years of age and younger with CRC admitted to the National Naval Medical Center between 1970 and 1992 were considered for inclusion in the study. After review, 36 patients for whom the original archived pathology specimen could be retrieved served as the study population. The RER status was determined using a previously described polymerase chain reaction-based assay. The clinical and pathologic features and survival data were compared to RER status.

Justifications for punishment are generally grounded in retribution or consequentialism. Retribution is rooted in and legitimized by common sense notions of free will, claiming that offenders freely and rationally choose to commit a criminal act, and are therefore deserving of punishment. Consequen-

TME), comprises not only primary tumor cells, but also vasculature, immune cells, stromal cells, and transformed extracellular matrix (ECM). [4] ECM density and composition are known to participate in a positive feedback loop in tumor progression; as neoplastic cells proliferate, they deposit more matrix, which results in increased stiffness of the tissue, enhanced pathways for migration, interference with cell-cell adhesion, and upregulation of growth factor signaling. [5] Despite matrix density being used as a helpful diagnostic tool in diseases like breast and testicular cancer, the roles that specific types of matrix-cell interactions associated with increased matrix density play in tumor cell behavior have yet to be fully characterized.Efforts have been made to study the effect of cancerous ECM using in vitro models via 2D cancer cell cultures on and 3D cancer cell cultures in naturally derived biomaterials, like Matrigel and collagen. [6] The advent of 3D cell cultures for tumor models was particularly important because cells have been shown to behave differently in 2D from 3D, with 3D culture often more accurately recapitulating behavior in situ. [7,8] These in vitro studies have provided great insight to the roles of secreted factors, 3D paracrine signaling, and matrix proteins in TME development. Unfortunately, these naturally derived systems have a few key disadvantages that make using them to independently examine cancer cell responses to biomechanical and biochemical cues challenging. First, the limited information provided on composition and the batch-to-batch variability of Matrigel can limit the ability to draw insightful conclusions or compare results from different studies. Second, the mechanical strength of these materials, with elastic moduli ranging from 0.044 to 10 kPa, [9] is more comparable to healthy soft tissue than to soft tissue neoplasia, which have clinically reported elastic moduli of up to 100 kPa. [6,10] Furthermore, tumor cell responses to increased matrix density are a result of not only the change in mechanical properties, such as elastic modulus, but also the change in bioactivity, such as number of cell adhesion sites. These materials contain bioactive sites, such as integrin-binding regions, within their structure. Typically, to increase the stiffness of the matrix, the density of the material is increased, which means the density of the bioactive sites increases as well. Because these properties are intrinsically linked, it is difficult to assess the impacts of bioactivity and mechanical properties independently. [11][12][13] Thus, in order to Increased extracellular matrix (ECM) density in the tumor microenvironment has been shown to influence aspects of tumor progression such as proliferation and invasion. Increased matrix density means cells experience not only increased mechanical properties, but also a higher density of bioactive sites. Traditional in vitro ECM models like Matrigel and collagen do not allow these properties to be investigated independently. In this work...

The tumor microenvironment (TME) plays a determining role in everything from disease progression to drug resistance. As such, in vitro models which can recapitulate the cell–cell and cell–matrix interactions that occur in situ are key to the investigation of tumor behavior and selecting effective therapeutic drugs. While naturally derived matrices can retain the dimensionality of the native TME, they lack tunability and batch-to-batch consistency. As such, many synthetic polymer systems have been employed to create physiologically relevant TME cultures. In this review, we discussed the common semi-synthetic and synthetic polymers used as hydrogel matrices for tumor models. We reviewed studies in synthetic hydrogels which investigated tumor cell interactions with vasculature and immune cells. Finally, we reviewed the utility of these models as chemotherapeutic drug-screening platforms, as well as the future directions of the field.