DDMC-p53 gene therapy with or without cisplatin and microwave ablation

Abstract

Lung cancer remains the leading cause of death in cancer patients. Severe treatment side effects and late stage of disease at diagnosis continue to be an issue. We investigated whether local treatment using 2-diethylaminoethyl-dextran methyl methacrylate copolymer with p53 (DDMC-p53) with or without cisplatin and/or microwave ablation enhances disease control in BALBC mice. We used a Lewis lung carcinoma cell line to inoculate 140 BALBC mice, which were divided into the following seven groups; control, cisplatin, microwave ablation, DDMC-p53, DDMC-p53 plus cisplatin, DDMC-p53 plus microwave, and DDMC-p53 plus cisplatin plus microwave. Microwave ablation energy was administered at 20 W for 10 minutes. Cisplatin was administered as 1 mL/mg and the DDMC-p53 complex delivered was 0.5 mL. Increased toxicity was observed in the group receiving DDMC-p53 plus cisplatin plus microwave followed by the group receiving DDMC-p53 plus cisplatin. Infection after repeated treatment administration was a major issue. We conclude that a combination of gene therapy using DDMC-p53 with or without cisplatin and microwave is an alternative method for local disease control. However, more experiments are required in a larger model to identify the appropriate dosage profile.

Intratumoral Treatment with Chemotherapy and Immunotherapy for NSCLC with EBUS-TBNA 19G

“…According to the genome of the patients we have chemotherapy treatment, tyrosine kinase inhibitors and immunotherapy. Intratumoral chemotherapy and combination of this treatment modality have been investigated in the past twenty years both in animal models and patients 13 , 15 , 16 , 30 - 33 . There are several issues to address before starting such a study.…”

Intravascular Treatment Techniques for Locoregional Therapies of Lung Tumors

“…Dazu gehörten die lokale Injektion verschiedener Medikamente, z. B. DDMC-p53-Gentherapie oder Lipiodol [45], die versuchen, mit der Infusion einer NaCl-Lösung die Tumormikroumgebung zu verändern, um die Gewebeimpedanz zu verringern [46] oder die Bronchial-oder Pulmonalarterie zu verschließen, um den durch Ventilation und Perfusion verursachten Wärmeverlust zu reduzieren [47]. 2005 wurde in einer retrospektiven Studie bei Patienten mit Lungenmetastasen bei kolorektalem Karzinom die Behandlung mit Chemotherapie verglichen mit einer multimodalen Therapie (einschließlich modifizierter pharmakokinetisch-modulierender Chemotherapie, Bestrahlung und Radiofrequenzablation [RFA]).…”

“…Numerous animal studies examined various periprocedural techniques to improve the efficiency of thermoablation. These include local injection of various medications, e. g. DDMC-p53 gene therapy or lipiodol [45], that attempt to change the tumor microenvironment with the infusion of an NaCl solution in order to reduce the tissue impedance [46] or to close the bronchial or pulmonary artery to reduce heat loss caused by ventilation and perfusion [47]. In 2005, in a retrospective study in patients with lung metastases in colorectal cancer, treatment with chemotherapy was compared to multimodal treatment (including modified pharmacokinetic-modulating chemotherapy, radiation, and radiofrequency ablation (RFA)).…”

Producing the appropriate model and drug for intratumoural ablation

“… 1 , 2 Moreover, these systems have been used along with drugs and gene therapy in order to enhance their antenna treatment effect. 3 , 4 The application of the antenna can be done transthoracically, under CT guidance, inside an open surgery under ultrasound guidance, or even endoscopically. 1 , 2 , 5 Several experiments have been performed initially in animal models, in order to evaluate the tumour necrosis effect and drug absorption in pathology findings.…”

“…The addition of the drug lipiodol did not have any additional effect as a combination therapy with microwave ablation and/or cisplatin. In the study by Hohenforst-Schmidt et al, 3 a novel (at that time) non-viral vector 2-diethylaminoethyl-dextran methyl methacrylate (DDMC) was combined with p53 and administered locally with or without microwave ablation and cisplatin as a combination treatment. Again, on pathology specimens from the tumour after injection of the DDMC–p53 complex, thick concentrations could be observed in the injection sites.…”