Silencing of perilipin by short hairpin RNA inhibits proliferation and induces apoptosis in liposarcoma cells.

Previous studies have identified that perilipin-1 (PLIN1) is a highly specific marker for liposarcoma. However, its functions have yet to be fully elucidated. The aim of the present study was to investigate the potential role of PLIN1 in the proliferation, migration and apoptosis of liposarcoma cells. Short hairpin RNA was designed to inhibit PLIN1 levels. Cell proliferation was monitored by Cell Counting Kit­8 assay and cell migration determined by wound healing assay. Flow cytometry was performed to assess the cell cycle distributions and apoptosis in liposarcoma cells. The results demonstrated that the expression of PLIN1 was significantly upregulated in liposarcoma tumor tissues compared with normal adipose tissues. Silencing of PLIN1 by short hairpin RNA significantly inhibited proliferation and migration and induced G1 phase cell cycle arrest and apoptosis in liposarcoma cell lines. It was identified that PLIN1 serves a crucial role in the pathogenesis and progression of liposarcoma and may be a potential therapeutic target for its clinical management.

Trastuzumab modified silica nanoparticles loaded with doxorubicin for targeted and synergic therapy of breast cancer.

Untargeted delivery as well as low efficacy are two main obstacles for effective breast cancer therapy. Here in this study, we surface modified silica nanoparticles (SLN) with Trastuzumab (Tra) to construct a tumor-targeting carrier (Tra-SLN) for specific drug delivery to human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells. In addition, Tra-SLN could also loaded with broad-spectrum anticancer drug doxorubicin (DOX) to finally construct a drug delivery system (DDS) capable of co-delivering Tra and DOX (Tra-SLN/DOX). Our results demonstrated that the as-prepared Tra-SLN/DOX was nanoscale particles with spheroid appearance which showed preferable stability in physiological environments. In addition, the Tra-SLN/DOX could specifically target to HER2 overexpressed MCF-7 cells. Both in vitro and in vivo experiments revealed that the Tra-SLN/DOX exerted enhanced anticancer efficacy when compared with Tra or DOX alone. It was suggested that Tra-SLN/DOX might be a promising platform for enhanced therapy of breast cancer.

Microbubbles: A Novel Strategy for Chemotherapy.

BACKGROUND: Ultrasound microbubbles have conventionally been used for diagnostic purposes. In recent years, however, new types of microbubbles have emerged as important carriers for drug delivery. Moreover, studies have shown that ultrasound microbubbles can serve as valuable and noninvasive tools in cancer therapy; thus the use of ultrasound microbubbles to deliver chemotherapeutic drugs to malignant tissues is a promising possibility. METHODS: In this review, we briefly describe the status of ultrasound microbubbles in clinical practice and then discuss the development of targeted microbubbles. Finally, we consider novel strategies for the use of microbubbles in cancer therapy. RESULTS: Many different kinds of microbubbles are emerged. Novel strategies of ultrasound microbubble have been shown to be effective in cancer therapy. CONCLUSION: Although many problems need to be solved in the future, the ultrasound drugs loaded microbubbles still have strong potential for the use in clinical cancer therapy.

Application of molecular imaging technologies in antitumor drug development and therapy.

Molecular imaging enables noninvasive characterization, quantification and visualization of biological and pathological processes in vivo at cellular and molecular level. It plays an important role in drug discovery and development. The skillful use of molecular imaging can provide unique insights into disease processes, which greatly aid in identifications of target. Importantly, molecular imaging is widely applied in the pharmacodynamics study to provide earlier endpoints during the preclinical drug development process, since it can be applied to monitor the effects of treatment in vivo with the use of biomarkers. Herein, we reviewed the application of molecular imaging technologies in antitumor drug development process ranging from identification of targets to evaluation of therapeutic effect.

Recurrent inflammatory myofibroblastic tumors harboring PIK3CA and KIT mutations.

Inflammatory myofibroblastic tumour (IMT) is a relatively rare soft tissue malignancy. It exhibits locally aggressive behavior with a tendency for local recurrence and rare metastasis, and rare recurrent IMTs may show histological progression. The genetic hallmark of IMT is ALK rearrangement from chromosome arm 2p, but gene mutations involved in IMT remain poorly understood. The aim of the present study was to perform a pairwise comparison of the gene mutations occurring in primary and recurrent IMT from the same patient. We conducted a high-throughput analysis of 238 known mutations of 19 oncogenes in pairwise comparison primary and recurrent samples from 2 patients of IMT using Sequenom MassARRAY technology. Our results revealed 2 mutations in 2 recurrent lesion samples, including one in exon 11 of the KIT gene, resulting in a T-C substitution at position 1727 (L576P), the recurrent sample underwent histologic progression with "pleomorphic undifferentiated sarcoma-like" transformation; the other mutation was in exon 19 of the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene, resulting in a G-A substitution at position 1624 (E542K). Moreover, no any mutation was found in the primary lesion samples from 2 patients. Our findings suggest that variable genome changes might be present in IMT, especially during the progression from a primary tumour to recurrence. To the best of our knowledge, no such longitudinal study of IMT has been undertaken previously.