A5061936570- Microbial Inactivation Methods
- CRISPR and Genetic Engineering
- Transgenic Plants and Applications
- Microfluidic and Bio-sensing Technologies
- Cancer Cells and Metastasis
- Cancer-related molecular mechanisms research
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Bacillus and Francisella bacterial research
- Cancer Genomics and Diagnostics
- Ultrasound and Hyperthermia Applications
- RNA Interference and Gene Delivery
- Viral Infectious Diseases and Gene Expression in Insects
- Toxin Mechanisms and Immunotoxins
- Viral gastroenteritis research and epidemiology
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- 3D Printing in Biomedical Research
- interferon and immune responses
- Plasma Applications and Diagnostics
- Metastasis and carcinoma case studies
- Pregnancy and Medication Impact
- MRI in cancer diagnosis
- Knee injuries and reconstruction techniques
- Hematopoietic Stem Cell Transplantation
Institute of Oncology Ljubljana
2018-2025
University of Ljubljana
2020-2025
In the treatment of cancer, immunomodulatory approaches are developed to support organism in fighting cancer or enhance effects local ablative techniques. To this end, we conducted an interventional, open-label, single-arm Phase I trial evaluate safety and tolerability intratumoral phIL12 plasmid DNA gene electrotransfer as primary objectives. The study was dose-escalating with 3 consecutive cohorts patients per dose level (0.5 mg/ml, 1 mg/ml 2 mg/ml) according a matched + design....
Abstract Calcium electroporation (CaEP) is a novel anti-tumour treatment that induces cell death by internalization of large quantities calcium. The effectiveness CaEP has been demonstrated in vitro , vivo and preliminary clinical trials; however, its effects on the vasculature have not previously investigated. Using dorsal window chamber tumour model, we observed affected to same degree normal blood vessels as it disrupted caused eradication necrosis. In all cases, effect was more...
ABSTRACT Vitamin A (VitA) is an essential nutrient, affecting many cell functions, such as proliferation, apoptosis, and differentiation, all of which are important for the regeneration various tissues. In this study, we investigated effects a VitA‐enriched diet on urothelium urinary bladder in mice after cyclophosphamide (CP)‐induced injury. Female were fed normal 1 week before receiving intraperitoneal injection CP (150 mg/kg). Urinary bladders removed 3 days CP. On Day 1, RNA sequencing...
Immune therapies are currently under intensive investigation providing in many cases excellent responses different tumors. Other possible approach for immunotherapy is a targeted intratumoral delivery of interleukin 12 (IL-12), cytokine with anti-tumor effectiveness. Due to its immunomodulatory action, it can be used as an imunostimulating component situ vaccinating effect local ablative therapies. We have developed phIL12 plasmid devoid antibiotic resistance marker transgene human IL-12 p70...
Electrochemotherapy (ECT) is a clinically acknowledged method that combines the use of anticancer drugs and electrical pulses. with bleomycin (BLM) can induce immunogenic cell death (ICD) in certain settings. However, whether this ubiquitous over different cancer types for other relevant chemotherapeutics used electrochemotherapy unknown. Here, we evaluated vitro B16-F10, 4T1 CT26 murine tumor lines, triggered changes ICD-associated damage-associated molecular patterns (DAMPs): Calreticulin...
Several studies have shown that different control plasmids may cause antitumor action in murine tumor models after gene electrotransfer (GET). Due to the differences GET protocols, plasmid vectors, and experimental models, observed effects were incomparable. Therefore, current study was conducted comparing effectiveness of three using same parameters. We followed cytotoxicity vitro effect vivo pControl, pENTR/U6 scr pVAX1 B16.F10 melanoma cells tumors. Types cell death upregulation selected...
Circulating tumor cell count is an independent prognostic factor in early breast cancer. CTCs can be found the blood of 20% patients prior to neoadjuvant therapy. We aimed assess suitability magnetic-activated separation (MACS) technology for isolation and cytological characterization CTCs. In preclinical part study, lines were spiked into buffy coat samples derived from healthy donors, isolated using MACS. Breast cancer cells with preserved morphology successfully isolated. clinical part,...
Electrochemotherapy has good local effectiveness in the treatment of vulvar cancer. Most studies have reported safety and electrochemotherapy for palliative gynecological cancers mostly squamous cell carcinoma. Some tumors, however, fail to respond electrochemotherapy. The biological features/determinants nonresponsiveness are not determined yet.A recurrence carcinoma was treated by using intravenous administration bleomycin. performed hexagonal electrodes according standard operating...
Skin, the largest organ in body, provides a passive physical barrier against infection and contains elements of innate adaptive immune systems. Skin consists various cells, including keratinocytes, fibroblasts, endothelial cells cells. This diversity cell types could be important to gene therapies because DNA transfection elicit different responses types. Previously, we observed upregulation activation cytosolic sensing pathways several non-tumor tumor as well tumors after electroporation...
Irradiation of tumors generates danger signals and inflammatory cytokines that promote the off-target bystander abscopal effects, evident especially when radiotherapy is administered in combination with immune checkpoint inhibitors (ICI). The underlying mechanisms are not fully understood; however, cGAS-STING pathway was recognized as main mediator. In our study, we demonstrate by immunofluorescent staining tumor cells well macrophages, cell types abundant microenvironmeent (TME) accumulate...
Interleukin 12 (IL-12) is a key cytokine that mediates antitumor activity of immune cells. To fulfill its clinical potential, the development focused on localized delivery systems, such as gene electrotransfer, which can provide IL-12 to tumor microenvironment. Gene electrotransfer plasmid encoding human already in trials USA, demonstrating positive results treatment melanoma patients. comply with EU regulatory requirements for application, recommend use antibiotic resistance gene-free...
One of the new treatment options for unresectable locally advanced pancreatic cancer is electrochemotherapy (ECT), a local ablative therapy that potentiates entry chemotherapeutic drugs into cells, by application an electric field to tumor. Its feasibility and safety were demonstrated in preclinical clinical studies; however, there lack studies assessing actions different used ECT, their mechanisms interactions with other target are practice.The aim study was determine cytotoxicity two...
Gene electrotransfer (GET) of plasmids encoding interleukin 12 (IL-12) has already been used for the treatment various types tumors in human oncology and as an adjuvant DNA vaccines. In recent years, we have developed a plasmid IL-12 (phIL12) that is currently phase I clinical study. The aim was to confirm results non-clinical study mice on pharmacokinetic characteristics safety porcine model better resembled skin. GET phIL12 skin performed nine pigs using different concentrations invasive...
Infection with high-risk human papillomavirus (HPV) strains is one of the risk factors for development oral squamous cell carcinoma (OSCC). Some patients HPV-positive OSCC have a better prognosis and respond to various treatment modalities, including radiotherapy or immunotherapy. However, since HPV can only infect cells, there are few immunocompetent mouse models available that enable immunological studies. Therefore, aim our study was develop transplantable model characterize it in vitro...
Liquid biopsy is becoming an important source of new biomarkers during the treatment metastatic cancer patients. Using size-based microfluid technology, we isolated circulating tumor cells (CTCs) from breast patients to evaluate their presence and cluster formation, as well megakaryocytes immune-inflammatory blood cells, correlate with clinicopathological data overall survival (OS). In total, 59 (median age 60.4 years) were included in study: 62.7% luminal A/B-like, 20.3% HER2-positive, 17%...
Electrochemotherapy (ECT1) is used for treatment of unresectable abdominal malignancies. This study aims to show that ECT porcine portal vein anastomosis safe and feasible in order extend the indications margin attenuation after resection locally advanced pancreatic carcinoma. No marked differences were found between control group treated groups. Electroporation thus caused irreversible damage vascular smooth muscle cells tunica media could bedue narrow electroporation zone may occur near...
Abstract Background Circulating tumor cells (CTCs) have become an important biomarker in breast cancer. Different isolation tech-niques based on their biological or physical features were established. Currently, the most widely used methods for visualization after separation are immunofluorescent staining, which does not provide information morphology. Materials and The aim of this study was to evaluate how two different techniques affect cell morphology analyse with routine cytopathological...