ACR-368, a CHK1/2 Kinase Inhibitor, in Patients With Relapsed or Refractory Desmoplastic Small Round Cell Tumor: Phase I/II Trial Results.

Purpose: We hypothesized that ACR-368 (prexasertib) would be active in desmoplastic small round cell tumor (DSRCT) because of favorable responses in preclinical models.

Methods: Preclinical work identified ACR-368 activity in DSRCT, and a phase I/II trial of ACR-368 and irinotecan in patients 12 months and older with relapsed/refractory DSRCT was conducted. The primary objectives were determination of recommended phase II dose (RP2D) and best overall response rate (ORR) at the RP2D in DSRCT, with ≥3 of 16 responses considered promising.

Evaluation and Utilization of Flow Artifacts at CT.

Flow artifacts are commonly encountered at contrast-enhanced CT and can be difficult to discern from true pathologic conditions. Therefore, radiologists must be comfortable distinguishing flow artifacts from true pathologic conditions. This is of particular importance when evaluating the pulmonary arteries and aorta, as a flow artifact may be mistaken for a pulmonary embolism or dissection flap.

Don't skip a beat! Critical findings in imaging studies performed in adults with congenital heart disease.

With ongoing advances in both medical and surgical management, the population of adults with congenital heart disease (CHD) continues to grow each year and has surpassed the number of pediatric cases. These adult patients will present to adult emergency departments with increasing frequency. Adults with CHD are at increased risk of developing not only cardiovascular complications, such as aortic dissection and thromboemboli, but also abdominopelvic and neurologic processes at younger ages.

Subclavian Artery: Anatomic Review and Imaging Evaluation of Abnormalities.

The subclavian artery is an important structure that may be overlooked at CT of the chest and neck, in part because of its anatomic location at the periphery of the field of view but also because the clinical indication for CT examinations infrequently directs attention specifically to evaluation of the subclavian artery. As with all arteries, the subclavian artery has the potential to be involved in a variety of abnormalities, including pseudoaneurysms, dissections, stenosis or thrombosis, and vasculopathies. In addition, the subclavian artery can be secondarily involved as a collateral pathway because of an abnormality elsewhere.

Impact of Pretransplantation CT on Liver Donation in Potential Deceased Organ Donors.

Background: Computed tomography (CT) is routinely used to determine the suitability of potential living donor liver transplants, providing important information about liver size, vascular anatomy, and the presence of other diseases that would preclude it from safe donation. CT is not routinely used, however, when evaluating eligible deceased organ donors after brain death, a group which comprises most orthotopic liver transplants. After the installation of a CT scanner at a local procurement facility, CTs have been performed on potential deceased organ donors and used, in conjunction with other evaluative protocols, to help direct donation decisions and assist in procurement procedures.

CT Appearance of Pulmonary Arteriovenous Malformations and Mimics.

A pulmonary arteriovenous malformation (PAVM) is a fistulous connection between a pulmonary artery and a pulmonary vein that bypasses the normal pulmonary capillary bed resulting in a right-to-left shunt. Because of the potential for paradoxical emboli, PAVMs are treated when their feeding arteries exceed 3 mm or patients are symptomatic. PAVMs are often encountered in patients with suspected hereditary hemorrhagic telangiectasia (HHT).

Correction: Characterization of CDK(5) inhibitor, 20-223 (aka CP668863) for colorectal cancer therapy.

[This corrects the article DOI: 10.18632/oncotarget.23749.

Symbiotic prodrugs (SymProDs) dual targeting of NFkappaB and CDK.

The release of an active drug from the prodrug generates a pro-fragment that typically has no biological activity and could result in adverse effects. By combining two drugs, wherein each drug acts as a pro-fragment of the other drug will eliminate the pro-fragment in the prodrug. As they are prodrugs of each other and are symbiotic, we termed these as symbiotic prodrugs (SymProDs).

CDK5 Inhibitor Downregulates Mcl-1 and Sensitizes Pancreatic Cancer Cell Lines to Navitoclax.

Developing small molecules that indirectly regulate Mcl-1 function has attracted a lot of attention in recent years. Here, we report the discovery of an aminopyrazole, 2-([1,1'-biphenyl]-4-yl)--(5-cyclobutyl-1-pyrazol-3-yl)acetamide (analog 24), which selectively inhibited cyclin-dependent kinase (CDK) 5 over CDK2 in cancer cell lines. We also show that analog 24 reduced Mcl-1 levels in a concentration-dependent manner in cancer cell lines.

Tumor Staging of Lung Cancer: Essential Concepts for the Radiologist.

Several important modifications have been proposed for the tumor (T) descriptor for lung cancers. New size cutoffs have been determined and there are new T descriptors for adenocarcinoma in situ, minimally invasive adenocarcinoma, and part-solid adenocarcinomas with a solid component > 0.5 cm to 3 cm (T1a, T1b, T1c).

Chemical Genetic Screens Identify Kinase Inhibitor Combinations that Target Anti-Apoptotic Proteins for Cancer Therapy.

The study presented here provides a framework for the discovery of unique inhibitor combinations that target the apoptosis network for cancer therapy. A pair of doxycycline (Dox)-inducible cell lines that specifically report on the ability of an inhibitor to induce apoptosis by targeting either the Mcl-1 arm or the Bcl-2/Bcl-xL/Bcl-w arm were used. Cell-based assays were optimized for high throughput screening (HTS) with caspase 3/7 as a read out.

Characterization of CDK(5) inhibitor, 20-223 (aka CP668863) for colorectal cancer therapy.

Colorectal cancer (CRC) remains one of the leading causes of cancer related deaths in the United States. Currently, there are limited therapeutic options for patients suffering from CRC, none of which focus on the cell signaling mechanisms controlled by the popular kinase family, cyclin dependent kinases (CDKs). Here we evaluate a Pfizer developed compound, CP668863, that inhibits cyclin-dependent kinase 5 (CDK5) in neurodegenerative disorders.

Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC).

Cyclin-dependent kinase 9 (CDK9), a member of the cyclin-dependent protein kinase (CDK) family, is involved in transcriptional elongation of several target genes. CDK9 is ubiquitously expressed and has been shown to contribute to a variety of malignancies such as pancreatic, prostate and breast cancers. Here we report the development of a heterobifunctional small molecule proteolysis targeting chimera (PROTAC) capable of cereblon (CRBN) mediated proteasomal degradation of CDK9.

Ewing sarcoma EWS protein regulates midzone formation by recruiting Aurora B kinase to the midzone.

Ewing sarcoma is a malignant bone cancer that primarily occurs in children and adolescents. Eighty-five percent of Ewing sarcoma is characterized by the presence of the aberrant chimeric EWS/FLI1 fusion gene. Previously, we demonstrated that an interaction between EWS/FLI1 and wild-type EWS led to the inhibition of EWS activity and mitotic dysfunction.