Objective: Melanoma differentiation associated gene-7 [mda-7/Interleukin (IL)-24] has been identified as a novel anti-cancer agent, which specifically induces apoptosis in cancer cells but not in normal epithelial, endothelial and fibroblast cells. The objective of this study was to evaluate the anti-tumor effect of adenovirus-mediated mda-7/IL-24 (Ad.mda-7) gene therapy in ovarian carcinoma and further improve anti-tumor effect by enhancing infectivity of Ad.mda-7.
Methods: A panel of human ovarian carcinoma cells, OV-4, HEY, SKOV3, SKOV3.ip1 and control normal human mesothelial cells, were infected by a replication deficient recombinant adenovirus encoding mda-7/IL-24 and control virus Ad.CMV.Luc. After 72 h, apoptosis was evaluated by TUNEL and Hoechst staining and further quantified by fluorescent activated cell sorter (FACS) analysis. Infectivity of Ad.mda-7 was enhanced by retargeting it to CD40 or EGF receptors overexpressed on ovarian cancer cells. Subsequently, enhancement in apoptosis of CD40- or epidermal growth factor receptor (EGFR)-retargeted Ad.mda-7 was evaluated.
Results: Adenoviral-mediated delivery of mda-7 induces apoptosis ranging from 10-23% in human ovarian cancer cells tested with the highest percentage of apoptosis noted in SKOV3 cells. Minimal apoptosis was noted in normal mesothelial cells. CD40- or EGFR-retargeted Ad.mda-7 increased apoptosis by 10-32% when compared to that achieved with untargeted Ad.mda-7.
Conclusion: Ad.mda-7 exhibits ovarian cancer-specific apoptosis, but does not affect normal human mesothelial cells. Infectivity enhanced CD40- and EGFR-retargeted Ad.mda-7 augments apoptosis induction, thus increasing the therapeutic index and translational potential of Ad.mda-7 gene therapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ygyno.2004.04.028 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Rare dual MYH9-ROS1 fusion variants in a patient with lung adenocarcinoma: A case report.
Medicine (Baltimore)
January 2025
Department of Respiratory and Critical Care Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong Province, China.
Rationale: ROS proto-oncogene 1 (ROS1) fusion is a rare but important driver mutation in non-small cell lung cancer, which usually shows significant sensitivity to small molecule tyrosine kinase inhibitors. With the widespread application of next-generation sequencing (NGS), more fusions and co-mutations of ROS1 have been discovered. Non-muscle myosin heavy chain 9 (MYH9) is a rare fusion partner of ROS1 gene as reported.
View Article and Find Full Text PDFThree cases of hemoglobin M disease in a family lineage: Case report and literature review.
Medicine (Baltimore)
January 2025
Department of Pediatric Hematology, Children's Medical Center, The First Hospital of Jilin University, Changchun, China.
Rationale: This study presents a case of hemoglobin M disease (HMD), a rare inherited disorder characterized by persistent cyanosis and hypoxemia, observed across 3 generations within a single family. The diagnosis of HMD poses significant challenges, particularly in asymptomatic individuals, due to its rarity and the subtlety of its symptoms. Notably, there is a scarcity of reports on methemoglobinemia in pediatric populations, which further complicates early detection and intervention.
View Article and Find Full Text PDFOne hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.
Blood
January 2025
Division of Immunology and Allergy, Children's Hospital of Philadelphia; Department of Pediatrics, Perelman School of Medicine; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.
View Article and Find Full Text PDFBioprinted optoelectronically active cardiac tissues.
Sci Adv
January 2025
Department of Electrical and Computer Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Electrical stimulation of existing three-dimensional bioprinted tissues to alter tissue activities is typically associated with wired delivery, invasive electrode placement, and potential cell damage, minimizing its efficacy in cardiac modulation. Here, we report an optoelectronically active scaffold based on printed gelatin methacryloyl embedded with micro-solar cells, seeded with cardiomyocytes to form light-stimulable tissues. This enables untethered, noninvasive, and damage-free optoelectronic stimulation-induced modulation of cardiac beating behaviors without needing wires or genetic modifications to the tissue solely with light.
View Article and Find Full Text PDFChemopreventive role of β-caryophyllene in DMBA-induced skin cancer: Modulation of apoptotic pathways and PI3K/Akt signaling in Swiss albino mice.
Adv Clin Exp Med
January 2025
Department of Dermatology, The Affiliated Hospital to Changchun University of Chinese Medicine, China.
Background: The skin, with its robust structural integrity and advanced immune defense system, serves as a critical protective barrier against environmental toxins and carcinogenic compounds. Despite this, it remains vulnerable to the harmful effects of certain hazardous agents.
Objectives: This study aimed to investigate the chemopreventive potential of β-caryophyllene (BCP) in mitigating 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis, focusing on the modulation of apoptosis and PI3K/AKT signaling pathways.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!