[(18)F]-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography of LAPC4-CR Castration-Resistant Prostate Cancer Xenograft Model in Soft Tissue Compartments.

Preclinical xenograft models have contributed to advancing our understanding of the molecular basis of prostate cancer and to the development of targeted therapy. However, traditional preclinical in vivo techniques using caliper measurements and survival analysis evaluate the macroscopic tumor behavior, whereas tissue sampling disrupts the microenvironment and cannot be used for longitudinal studies in the same animal. Herein, we present an in vivo study of [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) designed to evaluate the metabolism within the microenvironment of LAPC4-CR, a unique murine model of castration-resistant prostate cancer.

Using glow stick chemistry for biological imaging.

Purpose: This study describes an imaging strategy based on glow stick chemistry to non-invasively image oxidative stress and reactive oxygen species (ROS) production in living animals.

Procedures: Upon stimulation, phagocytes produce toxic levels of ROS to kill engulfed microorganisms. The mitochondrial respiratory chain continually generates low levels of superoxide (O2·(-)) that serve as a source for generation of downstream ROS, which function as regulatory signaling intermediaries.

Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance.

Purpose: To extend the results of a phase III trial in patients with non-small cell lung cancer with adenocarcinomas harboring EML4-ALK fusion.

Experimental Design: We conducted a co-clinical trial in a mouse model comparing the ALK inhibitor crizotinib to the standard-of-care cytotoxic agents docetaxel or pemetrexed.

Results: Concordant with the clinical outcome in humans, crizotinib produced a substantially higher response rate compared with chemotherapy, associated with significantly longer progression-free survival.

Targeted imaging of Ewing sarcoma in preclinical models using a 64Cu-labeled anti-CD99 antibody.

Purpose: Ewing sarcoma is a tumor of the bone and soft tissue characterized by diffuse cell membrane expression of CD99 (MIC2). Single-site, surgically resectable disease is associated with an excellent 5-year event-free survival; conversely, patients with distant metastases have a poor prognosis. Noninvasive imaging is the standard approach to identifying sites of metastatic disease.

Characterization of Torin2, an ATP-competitive inhibitor of mTOR, ATM, and ATR.

mTOR is a highly conserved serine/threonine protein kinase that serves as a central regulator of cell growth, survival, and autophagy. Deregulation of the PI3K/Akt/mTOR signaling pathway occurs commonly in cancer and numerous inhibitors targeting the ATP-binding site of these kinases are currently undergoing clinical evaluation. Here, we report the characterization of Torin2, a second-generation ATP-competitive inhibitor that is potent and selective for mTOR with a superior pharmacokinetic profile to previous inhibitors.

A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response.

Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored.

Prevention of diabetes development in those with the metabolic syndrome.

Metabolic syndrome is characterized by abnormal glucose levels, central obesity, hypertension, elevated triglycerides, and low HDL cholesterol. This article reviews available data regarding the impact of lifestyle modification and drug therapies on the progression to diabetes in high risk individuals, such as those with hypertension, dyslipidemia, obesity, and prediabetes. Lifestyle and pharmacological interventions may alter metabolic parameters and impact progression to diabetes.

Skeletal anomalies of the upper cervical spine in children with Down syndrome.

This study showed that a significantly greater number of children with Down syndrome (45 to 78) have cervical spine anomalies than an age- and sex-matched group of normal children (3 of 38). Moreover, children with Down syndrome who had atlantoaxial instability had an increased frequency of cervical spine anomalies (31 of 39) as compared with an age- and sex-matched group of children with this chromosome disorder who did not have atlantoaxial instability (14 of 39).

Occult pulmonary embolism: a common occurrence in deep venous thrombosis.

Ventilation-perfusion scans were used in a prospective study to determine the prevalence of occult pulmonary embolus in proven deep venous thrombosis. Fifty-eight patients without symptoms of pulmonary embolism, but with venographically proven deep venous thrombosis, were subjected to chest radiographs, 99mTc macroaggregated-albumin perfusion scans, and 133Xe ventilation scans. Of the 49 patients with deep venous thrombosis proximal to the calf veins, 17 (35%) had high-probability scans.

Renal abscess: a complication of ethanol embolization.

The authors describe a previously unreported complication of ethanol ablation of a renal tumor in one case. A renal abscess developed in a patient with preexisting silent urosepsis 5 weeks following ablation. Routine urinalysis, Gram stain, and urine culture are recommended as preprocedure tests to avoid such complications.