ALK pERKs up MYCN in neuroblastoma.

The gene expressing the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) is mutated and aberrantly expressed in several cancers. The clinical efficacy of the ALK inhibitor, crizotinib, lags behind expectations for treating MYCN-amplified, ALK-mutant neuroblastoma, a deadly childhood cancer. In this issue of Science Signaling, Umapathy et al.

Does imaging αvβ3 integrin expression with PET detect changes in angiogenesis during bevacizumab therapy?

Unlabelled: In recent years, there has been a growing interest in molecular imaging markers of tumor-induced angiogenesis. Several radiolabeled RGD (arginine, glycine, aspartate) peptides have been developed for PET imaging of αvβ3 integrins in the tumor vasculature, but there are only limited data on how angiogenesis inhibitors affect the tumor uptake of these peptides.

Methods: Changes in (68)Ga-NODAGA-c(RGDfK) peptide uptake were measured using PET during bevacizumab therapy of 2 αvβ3-negative squamous cell carcinoma cell lines (A-431 and FaDu) that induce αvβ3-positive neovasculature when transplanted into nude mice.

Renal sulfatides: sphingoid base-dependent localization and region-specific compensation of CerS2-dysfunction.

Mammalian kidneys are rich in sulfatides. Papillary sulfatides, especially, contribute to renal adaptation to chronic metabolic acidosis. Due to differences in their cer-amide (Cer) anchors, the structural diversity of renal sulfatides is large.

AP4 is required for mitogen- and c-MYC-induced cell cycle progression.

AP4 represents a c-MYC-inducible bHLH-LZ transcription factor, which displays elevated expression in many types of tumors. We found that serum-starved AP4-deficient mouse embryo fibroblasts (MEFs) were unable to resume proliferation and showed a delayed S-phase entry after restimulation. Furthermore, they accumulated as tetraploid cells due to a cytokinesis defect.

N-terminal modifications improve the receptor affinity and pharmacokinetics of radiolabeled peptidic gastrin-releasing peptide receptor antagonists: examples of 68Ga- and 64Cu-labeled peptides for PET imaging.

Unlabelled: Gastrin-releasing peptide receptors (GRPrs) are overexpressed on a variety of human cancers, providing the opportunity for peptide receptor targeting via radiolabeled bombesin-based peptides. As part of our ongoing investigations into the development of improved GRPr antagonists, this study aimed at verifying whether and how N-terminal modulations improve the affinity and pharmacokinetics of radiolabeled GRPr antagonists.

Methods: The potent GRPr antagonist MJ9, Pip-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH(2) (Pip, 4-amino-1-carboxymethyl-piperidine), was conjugated to 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA), and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and radiolabeled with (68)Ga and (64)Cu.

An inducible hepatocellular carcinoma model for preclinical evaluation of antiangiogenic therapy in adult mice.

The limited availability of experimental tumor models that faithfully mimic the progression of human tumors and their response to therapy remains a major bottleneck to the clinical translation and application of novel therapeutic principles. To address this challenge in hepatocellular carcinoma (HCC), one of the deadliest and most common cancers in the world, we developed and validated an inducible model of hepatocarcinogenesis in adult mice. Tumorigenesis was triggered by intravenous adenoviral delivery of Cre recombinase in transgenic mice expressing the hepatocyte-specific albumin promoter, a loxP-flanked stop cassette, and the SV40 large T-antigen (iAST).

PET/MR in Oncology: Non-18F-FDG Tracers for Routine Applications.

PET/MR is a new multimodal imaging technique that is expected to improve diagnostic performance, especially in oncologic patients in certain indications. Apart from the clinical relevance of PET with F-FDG, various other tracers exist and are increasingly used, which allow insights into multiple physiologic and biologic processes. In this review, we discuss the current and potential future applications of hybrid PET/MR, focusing on non-F-FDG tracers.

The p53/miR-34 axis in development and disease.

The tumor suppressor p53 is one of the most frequently mutated genes in human cancers. MicroRNAs (miRNAs) are small non-protein coding RNAs that regulate gene expression on the post-transcriptional level. Recently, it was shown that p53 regulates the expression of several miRNAs, thereby representing an important mechanism of p53 signaling.

The glucose-dependent insulinotropic polypeptide receptor: a novel target for neuroendocrine tumor imaging—first preclinical studies.

Unlabelled: A new family of peptide receptors, the incretin receptor family, overexpressed on many neuroendocrine tumors (NETs) is of great importance because it may enable the in vivo peptide-based receptor targeting of a category of NETs that does not express the somatostatin receptor. Impressive in vivo diagnostic data were published for glucagonlike peptide 1 receptor-targeting radiopeptides. Recently, promising in vitro data have appeared for the second member of the incretin family, the glucose-dependent insulinotropic polypeptide (GIP) receptor.

Heterogeneous Antibody-Based Activity Assay for Lysine Specific Demethylase 1 (LSD1) on a Histone Peptide Substrate.

Posttranslational modifications of histone tails are very important for epigenetic gene regulation. The lysine-specific demethylase LSD1 (KDM1A/AOF2) demethylates in vitro predominantly mono- and dimethylated lysine 4 on histone 3 (H3K4) and is a promising target for drug discovery. We report a heterogeneous antibody-based assay, using dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) for the detection of LSD1 activity.