Advances in oncologic imaging

Imaging has become a pivotal component throughout a patient's encounter with cancer, from initial disease detection and characterization through treatment response assessment and posttreatment follow‐up. Recent progress in imaging technology has presented new opportunities for improving clinical care. This article provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, and colorectal cancers, and lymphoma. CA Cancer J Clin 2012. © 2012 American Cancer Society.     

Receptor‐interacting protein (RIP) and Sirtuin‐3 (SIRT3) are on opposite sides of anoikis and tumorigenesis

BACKGROUND:

Regulating cross‐talk between anoikis and survival signaling pathways is crucial to regulating tissue processes and mitigating diseases like cancer. Previously, the authors demonstrated that anoikis activates a signaling pathway involving the CD95/Fas‐mediated signaling pathway that is regulated by receptor‐interacting protein (RIP), a kinase that shuttles between Fas‐mediated cell death and integrin/focal adhesion kinase (FAK)‐mediated survival pathways. Because it is known that sirtuin‐3 (SIRT3), a nicotinamide adenine dinucleotide‐dependent deacetylase, regulates cell survival, metabolism, and tumorigenesis, the authors hypothesized that SIRT3 may engage in cross‐talk with Fas/RIP/integrin/FAK survival‐death pathways in cancer cell systems.

METHODS:

Using immunohistochemical staining, immunoblotting, human tissue microarrays, and overexpression and suppression approaches in vitro and in vivo, the roles of RIP and SIRT3 were examined in oral squamous cell carcinoma (OSCC) anoikis resistance and tumorigenesis.

RESULTS:

RIP and SIRT3 had opposite expression profiles in OSCC cells and tissues. Stable suppression of RIP enhanced SIRT3 levels, whereas stable suppression of SIRT3 did not impact RIP levels in OSCC cells. The authors observed that, as OSCC cells became anoikis‐resistant, they formed multicellular aggregates or oraspheres in suspension conditions, and their expression of SIRT3 increased as their RIP expression decreased. Also, anoikis‐resistant OSCC cells with higher SIRT3 and low RIP expression induced an increased tumor burden and incidence in mice, unlike their adherent OSCC cell counterparts. Furthermore, stable suppression of SIRT3 inhibited anoikis resistance and reduced tumor incidence.

CONCLUSIONS:

The current results indicted that RIP is a likely upstream, negative regulator of SIRT3 in anoikis resistance, and an anoikis‐resistant orasphere phenotype defined by higher SIRT3 and low RIP expression contributes to a more aggressive phenotype in OSCC development. Cancer 2012. © 2012 American Cancer Society.     

Effects of lipopolysaccharide (LPS) and peptidoglycan (PGN) on estradiol production in bovine granulosa cells from small and large follicles

In cows, postpartum uterine infection due to bacteria that produce lipopolysaccharide (LPS) or peptidoglycan (PGN) leads to ovarian dysfunction. The aim of this study was to determine the effect of LPS and/or PGN on estradiol production from granulosa cells from small and large follicles in the bovine ovary. Granulosa cells from small and large ovarian follicles were exposed to LPS and/or PGN in vitro. LPS inhibited the expression of TLR4, CD14, MD2 and NOD1 genes in FSH-treated granulosa cells from small follicles. LPS suppressed estradiol (E2) production in granulosa cells from small and large follicles, while PGN inhibited E2 production in granulosa cells from large follicles. LPS or PGN did not affect granulosa cell survival. Although LPS alone suppressed E2 production in granulosa cells from small and large follicles, E2 production was not further suppressed when PGN was added to culture medium with LPS alone. Our data demonstrated that susceptibility to LPS or PGN in granulosa cells depends on the follicle developmental stage. The results of the present study suggest that ovarian dysfunction in cows with postpartum uterine infection may be caused by inhibitory effects of LPS and PGN on E2 production in granulosa cells.