Gerald C O'Sullivan's research while affiliated with Energy Biosciences Institute and other places
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Publications (244)
Following publication of the original article [1], the authors reported an omission in the affiliations.
Purpose:
Electrochemotherapy (ECT) is the application of electric pulses to tumour tissue to render the cell membranes permeable to usually impermeant hydrophilic anti-cancer drugs, thereby enhancing cytotoxic effects. We sought to ascertain whether ECT can be an effective palliative treatment for cutaneous metastases of breast cancer.
Methods:...
Background and study aims:
Targeted delivery of specific chemotherapeutic drugs into tumors can be achieved by delivering electrical pulses directly to the tumor tissue. This causes a transient formation of pores in the cell membrane that enables passive diffusion of normally impermeant drugs. A novel device has been developed to enable the endosc...
Many epithelial cancers, particularly gastrointestinal tract cancers, remain poor prognosis diseases, due to resistance to cytotoxic therapy and local or metastatic recurrence. We have previously shown that apoptosis incompetent esophageal cancer cells induce autophagy in response to chemotherapeutic agents and this can facilitate their recovery. H...
Esophageal adenocarcinoma has the fastest growing incidence of any solid tumor in the Western world. Prognosis remains poor with overall five-year survival rates under 25 %. Only a limited number of patients benefit from chemotherapy and there are no biomarkers that can predict outcome. Previous studies have indicated that induction of autophagy ca...
We have previously reported that most patients with esophagogastric cancer (EGC) undergoing potentially curative resections have bone marrow micrometastases (BMM). We present 10-year outcome data of patients with EGC whose rib marrow was examined for micrometastases and correlate the findings with treatment and conventional pathologic tumor staging...
Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its...
Nonviral plasmid DNA gene therapy represents a promising approach for the treatment of many diseases including cancer. Intracellular delivery of DNA can be achieved with the application of electroporation, which facilitates the initial transport of exogenous DNA across the cell membrane into the cytoplasm. However, it does not guarantee further tra...
Changing work practices make it imperative that surgery selects candidates for training who demonstrate the spectrum of abilities that best facilitate learning and development of attributes that, by the end of their training, approximate the characteristics of a consultant surgeon.
The aim of our study was to determine the relative merits of compon...
Apparatus (20) for carrying out a prophylactic or treatment procedure on tissue comprises a device (21) having a chamber (22) and at least one active element such as an electrode (23) within the chamber (22). The chamber (22) has an opening (26) through which tissue is drawn into the chamber (22). Means for drawing the tissue into the chamber may c...
The invention is based on the surprising finding that treatment with a chemotherapeutic agent such as 5-fluorouracil (5-FU) and an autophagy inducer effectively inhibit the continued growth of, and prevent the recovery following drug withdrawal, of cancer cells. In vivo, drug resistance from a failure to adequately engage in apoptotic programmed ce...
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in both men and women, posing a serious demographic and economic burden worldwide. In the United Kingdom, CRC affects 1 in every 20 people and it is often detected once well established and after it has spread beyond the bowel (Stage IIA-C and Stage IIIA-C). A diagnosis at such a...
Background:
Colorectal cancer is the second leading cause of cancer-related mortality and frequently presents with locally advanced or metastatic disease. Adenovirus (Ad) vectors are important gene delivery agents because they offer efficient and broad tissue transduceability. However, their ability to penetrate through multicell layers in colorec...
Background:
The establishment of assessment reliability at the level of the individual trainee is an important attribute of assessment methodologies, particularly for doctors who have been failed. This issue is of particular importance for the process of competence assessment in the USA, UK, Australia and New Zealand.
Methods:
We use data from 1...
In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues.
Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Tempor...
Regulatory T cells (TRegs) constrain anti-tumour immunity and remain the most significant obstacle to successful immunotherapy of cancer. The immunosuppressive influence of these cells can be abrogated by depletion strategies, modulation of T cell plasticity and inhibition of function or migration. A novel and attractive strategy for inhibiting TRe...
Laparoscopic skills are difficult to learn. We, therefore, assessed the factors involved in skill acquisition, maintenance, and loss in 2 prospective, randomized studies.
In study 1, 24 laparoscopic novices were randomly assigned to a control condition who performed the laparoscopic assessment task; Massed condition who trained on virtual reality (...
The ability to track microbes in real time in vivo is of enormous value for preclinical investigations in infectious disease or gene therapy research. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumours following systemic administration. Bioluminescent Imaging (BLI) r...
3D Co-localisation of Tumour And Bacterial Bioluminescence. Movie providing tomographic detail of source signal distribution of B. breve lux (green) 10 days post IV administration to mice bearing HCT116 FLuc (orange) expressing tumours. B. breve lux is observed in multiple disparate ‘clusters’ within the tumour.
(MOV)
3D Intratumoural Optical and μCT Imaging. Combined μCT and luminescence imaging of subcutaneous HCT116-luc2 tumour colonised by B. breve. Viable tumour (FLuc green/blue), vasculature (contrast agent – red) and bacterial (orange/yellow) signals are visualised.
(MOV)
Tumour Vasculature Immunohistochemistry. Murine endothelial cells within U87 tumour were visualised by IHC staining specific for CD31. Sections were incubated with anti-PCAM-1 antibody, followed by secondary biotinylated polyclonal Rabbit anti-goat immunoglobulin, and HRP-labelled Polymer Anti-Rabbit and visualised with DAB counterstained with Harr...
Bacterial Bioluminescence in the GIT. Movie depicting rotational 3D optical tomography in combination with mouse anatomical atlas displaying luminescence in GIT of mice 27 days post oral administration of lux-labelled E. coli MG1655.
(AVI)
Fundamentals of Surgical Simulation explains in detail, from a behavioural science/human factors perspective, why modern image guided medicine such as surgery, interventional cardiology and interventional radiology are difficult to learn and practice. Medicine is currently at a tipping point in terms of how physicians in procedural based medicine a...
Gallagher et al¹ raise important questions for all medical practitioners in their article on the persistent next-day effects of excessive alcohol consumption on laparoscopic surgical performance. Although their 2 studies involved a small number of participants, the magnitude of measured effects was substantial. Significantly, the results were deriv...
Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-κB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy....
To a large extent, the increase in usage of laparoscopic surgery as an operative technique during the 1980s concealed many
of its problems. However, had it not been for the development of laparoscopic surgery, medicine and surgery may never have
taken account of ‘human factors’ as they relate to the practice of procedural medicine. As seen over the...
In the previous chapters we identified very specific human factor reasons why medical procedures such as image guided surgery
are difficult to learn and practice. They make unique perceptual, cognitive and psychomotor demands on the trainee and practitioner.
The same research that has allowed us to identify these difficulties also provides us with...
Mouret first performed laparoscopic cholecystectomy in the late 1980s. Previously, laparoscopic techniques were part of gynecological
practice and it was not until the development of a video computer chip allowed the magnification and projection of images
on to television screens that laparoscopic surgery became integrated into general surgery (Joh...
E-learning comprises all forms of electronically supported learning and teaching which are aimed at imparting or facilitating
the construction of knowledge. E-learning is perceived by many as made up of the computer and network-enabled transferor of
knowledge. Applications that facilitate this process include web-based learning, computer-based lear...
Change has been the order of the day in medicine, but particularly in disciplines such as surgery. Surgery has changed the
way it treats patients with interventions becoming less invasive but also becoming more difficult to learn and to practice.
Sometimes these changes were patient driven. One of these changes, minimally invasive surgery (MIS) was...
Computer-based simulation has several advantages when compared with conventional methods for surgical training. One major
advantage is that the same experience or sequence of events can be replicated repeatedly. This repetition allows the trainee
to learn from mistakes in a safe environment. Another benefit which is probably of equal if not more om...
While the art of simulation has been known for many centuries the science of simulation has only come to the fore in the late
twentieth and early twenty-first century. Simulation is the imitation of some real thing, state of affairs, or process. The
act of simulating something generally entails representing certain key characteristics or behaviors...
The use of simulators to train surgical skills was ushered in as a consequence of the difficulties in acquiring the skills
to practice minimally invasive surgery (Satava 1993). This revolution in surgical training forced the surgical community to
think about training in general. Haluck et al. (2007) has suggested that when the field of medical simu...
In countries such as the UK and Ireland, high profile medical error cases had profound implications for the process under
which doctors were deemed qualified to practice medicine. It also brought to the fore once again the debate about competency.
In the previous chapters, we discussed the reasons why certain types of surgical skills such as those for laparoscopic surgery
are difficult to learn. The processes of skill acquisition for laparoscopic surgery, are precisely the same processes involved
in skill acquisition per se. Skill acquisition can occur coincidently (but not necessarily effi...
The induction of systemic immune responses against antigenic targets that are over expressed by cancer cells represents a powerful therapeutic strategy to target metastatic cancer. We generated specific antitumor immune responses in a murine model of prostate cancer by oral administration of an attenuated strain of Salmonella typhimurium containing...
Background:
Von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-α (HIF-α), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnR...
We investigated the cell-death mechanisms induced in esophageal cancer cells in response to the chemotherapeutic drugs, 5-fluorouracil (5-FU) and cisplatin. Chemosensitive cell lines exhibited apoptosis whereas chemoresistant populations exhibited autophagy and a morphology resembling type II programmed cell death (PCD). Cell populations that respo...
Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression.
We investigated use of the C-X-C chemokine receptor type 4 (CXCR4) promoter to restrict AAV expression to tumour cells, in subcutaneous MCF-7 xenograft mouse mod...
Electrochemotherapy, utilizing bleomycin and cisplatin as chemotherapeutic drugs along with electric pulses locally delivered
to the treated tumors, plays an important role in the local control of cancers. The treatment is easy to perform, on an outpatient
basis, for the treatment of skin melanoma, breast cancer, or other tumor skin metastases. An...
Surgery is the standard modality for the removal of tumors, either alone or in combination
with other therapies such as radiotherapy and chemotherapy. These treatment adjuncts can be associated with significant toxicity, may not be appropriate at the time of diagnosis, and do not necessarily reduce the risk of metastasis. Consequently, a considerab...
Preclinical results with various gene therapy strategies indicate significant potential for new cancer treatments. However, many therapeutics fail at clinical trial, often due to differences in tissue physiology between animal models and humans, and tumor phenotype variation. Clinical data relevant to treatment strategies may be generated prior to...
The human gastrointestinal (GI) tract represents a vast microbial ecosystem with a high degree of complexity and inter-individual
diversity. The large intestine contains an estimated 1011–1012 bacteria per gram of contents and it is thought that total bacterial cells outnumber human cells by at least an order of
magnitude (O’Sullivan 2005; O’Hara a...
Although Imatinib has transformed the treatment of chronic myeloid leukemia (CML), it is not curative due to the persistence of resistant cells that can regenerate the disease. We have examined how Bcr-Abl-expressing cells respond to two mechanistically different therapeutic agents, etoposide and Imatinib. We also examined Bcr-Abl expression at low...
Many strategies have been adopted to unleash the potential of gene therapy for cancer, involving a wide range of therapeutic genes delivered by various methods. Immune therapy has become one of the major strategies adopted for cancer gene therapy and seeks to stimulate the immune system to target tumour antigens. In this study, the feasibility of A...
This video describes the use of patient tissue as an ex vivo model for the study of gene delivery. Fresh patient tissue obtained at the time of surgery is sliced and maintained in culture. The ex vivo model system allows for the physical delivery of genes into intact patient tissue and gene expression is analysed by bioluminescence imaging using th...
Anti-cancer therapy faces major challenges, particularly in terms of specificity of treatment. The ideal therapy would eradicate tumor cells selectively with minimum side effects on normal tissue. Gene or cell therapies have emerged as realistic prospects for the treatment of cancer, and involve the delivery of genetic information to a tumor to fac...
von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-α (HIF-α), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 and...
This video describes the establishment of liver metastases in a mouse model that can be subsequently analysed by bioluminescent imaging. Tumour cells are administered specifically to the liver to induce a localised liver tumour, via mobilisation of the spleen and splitting into two, leaving intact the vascular pedicle for each half of the spleen. L...
Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers...
Bacteria-mediated transfer of plasmid DNA to mammalian cells (bactofection) has been shown to have significant potential as an approach to express heterologous proteins in various cell types. This is achieved through entry of the entire bacterium into cells, followed by release of plasmid DNA. In a murine model, we show that Listeria monocytogenes...
Certain bacteria have emerged as biological gene vectors with natural tumor specificity, capable of specifically delivering genes or gene products to the tumor environment when intravenously (i.v.) administered to rodent models. We show for the first time that oral administration of bacteria to mice resulted in their translocation from the gastroin...
Development of gene-based therapies for the treatment of inherited and acquired diseases, including cancer, has seen renewed interest in the use of nonviral vectors coupled to physical delivery modalities. Low-frequency ultrasound (US), with a well-established record in a clinical setting, has the potential to deliver DNA efficiently, accurately an...
Immunological therapies enhance the ability of the immune system to recognise and destroy cancer cells via selective killing mechanisms. DNA vaccines have potential to activate the immune system against specific antigens, with accompanying potent immunological adjuvant effects from unmethylated CpG motifs as on prokaryotic DNA. We investigated an e...
The International Society for Cell and Gene Therapy (ISCGT) of Cancer annual meeting was held from September 2 through September 4, 2009, in Cork, Ireland ( www.iscgt2009.com ). The conference was held in conjunction with the Irish Society for Gene and Cell Therapy third annual meeting, and brought together scientists and clinicians from around the...
Treatment of recurrent or in-transit unresectable melanoma continues to be a major therapeutic challenge. Electrochemotherapy (ECT) is a therapeutic option for those patients whose lesions are not suitable for surgical resection and who have exhausted all other treatment modalities. ECT combines electroporation of tumor cells with the administratio...
Electroporation is the application of high-voltage short-duration pulses to transiently permeabilize cells, permitting the cellular uptake of macromolecules, including nucleic acid. Although much attention has been focused on DNA vaccines, antigen-encoding RNA molecules may also stimulate immunity. Several methods are being examined in an effort to...
In a pilot-scale, open-label study to determine the ability of well-characterized probiotic Lactobacillus salivarius UCC118 cells to adhere to human epithelial cells in situ, the bacterial strain was administered to ulcerative colitis patients at approximately 109 CFU/day for 12 days. Microbiological analysis of biopsy specimens demonstrated that t...
In several intestinal disease states, altered microflora, impaired gut barrier and/or intestinal inflammation offer a rationale for the effective therapeutic use of probiotic microorganisms. However, for most candidate probiotic organisms there is a lack of evidence detailing their characterisation and effects on host flora and immunity. We have pr...
The most common cause of death of cancer sufferers is through the occurrence of metastases. The metastatic behaviour of tumour cells is regulated by extracellular growth factors such as hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, and aberrant expression/activation of the c-Met receptor is closely associated with...
Prostate stem cell antigen (PSCA) is a cell surface antigen expressed in normal human prostate and over expressed in prostate cancer. Elevated levels of PSCA protein in prostate cancer correlate with increased tumor stage/grade, with androgen independence and have higher expression in bone metastases. In this study, the PSCA gene was isolated from...
Metastatic disease is dependent on tumor cell migration through the venous and lymphatic systems and requires dynamic rearrangement of adherens junctions. Endocytosis of cadherins is a key mechanism to dynamically arrange adherens junctions, signaling, and motility in tumor cells; however, the role of shear in regulating this process in metastatic...
Challenges for oncology practitioners and researchers include specific treatment and detection of tumours. The ideal anti-cancer therapy would selectively eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria have emerged as biological gene vectors with natural tumour specificity, capable of homing to tumours and replica...
The VHL (von Hippel-Lindau) tumour-suppressor gene is inactivated in VHL disease and in sporadic cases of CCRCC [clear-cell RCC (renal cell carcinoma)]. pVHL (VHL protein) functions as part of an E3 ubiquitin ligase complex that targets proteins for proteasomal degradation. The best-characterized substrate is HIF-alpha (hypoxia-inducible factor-alp...
The aim of this review article is to provide a concise overview of the pre-clinical development of electrochemotherapy (ECT), its present utility in clinical practice and to examine its potential application to therapeutic modalities in the future.
Results from the ESOPE trial demonstrate an 85% objective response rate (ORR) in solid cutaneous and...
Gene therapy involves the transfer of genetic information to a target cell to facilitate the production of therapeutic proteins and is now a realistic prospect as a cancer treatment. Gene transfer may be achieved through the use of both viral and non-viral delivery methods and the role of this method in the gene therapy of cancer has been demonstra...
Bleomycin is a nonpermeant, hydrophilic macromolecule with a high intrinsic anticancer cytotoxicity. However, the cytotoxic potential of the drug is restricted by its low membrane permeability. Application of low-intensity ultrasound to growing tumors enhances intracellular delivery of bleomycin after IP or intratumoral administration, thereby pote...
A role for the intestinal microbiota is routinely cited as a potential aetiological factor in colorectal cancer initiation and progression. As the majority of bacteria in the gut are refractory to culture we investigated this ecosystem in subjects with colorectal cancer and with adenomatous polyposis who are at high risk of developing colorectal ca...
When there is massive intestinal edema after laparotomy for abdominal trauma or infection, the wound is often difficult to close. We describe the use of a simple-to-use Velcro-like fascia prosthesis (Wittmann Patch; STARSURGICAL Inc., Burlington, Wisc.) designed specifically to provide temporary closure until swelling subsides and the wound can be...
The p21-activated kinase 1 (Pak1) is a serine/threonine kinase whose activity is regulated by both Rho GTPases and AGC kinase family members. It plays a role in cytoskeletal remodeling and cell motility as well as cell proliferation, angiogenesis, tumorigenesis and metastasis. An involvement of Pak1 in renal cell carcinoma (RCC), which remains high...
In rectal cancer variation in lymph node recovery influences the detection of nodal metastases and prognosis among Dukes B (Stage II) cases. However, the possible prognostic importance of node size and inherent patient/tumor characteristics in determining node recovery has not been studied.
We examined 269 Dukes B (Stage II) rectal tumors, with a m...
Animal studies suggest that prebiotics and probiotics exert protective effects against tumor development in the colon, but human data supporting this suggestion are weak.
The objective was to verify whether the prebiotic concept (selective interaction with colonic flora of nondigested carbohydrates) as induced by a synbiotic preparation-oligofructo...
To develop an optimized, reproducible system of electrochemotherapy, and to investigate its clinical application in patients with cutaneous or subcutaneous recurrences of inoperable or progressive disease recalcitrant to current anticancer treatments.
Electrochemotherapy is the application of electric pulses to tumor tissue, rendering the cell memb...
An improved system for luciferase tagging Listeria monocytogenes was developed by constructing a highly active, constitutive promoter. This construct gave 100-fold-higher activity in broth
than any native promoter tested and allowed for imaging of lux-tagged L. monocytogenes in food products, during murine infections, and in tumor targeting studies...
An epiphrenic diverticulum is a herniation of a pouch of esophageal mucosa through the musculature of the distal thoracic esophagus within 10cm of the oesophago-gastric junction. The pathological process is thought to be due to the application of pulsion forces to the mucosa above a functionally obstructing region of abnormal esophageal motility.
To metastasize, tumor cells must adopt different morphological responses to resist shear forces encountered in circulating blood and invade through basement membranes. The Rho and Ras GTPases play a critical role in regulating this dynamic behavior. Recently, we demonstrated shear-induced activation of adherent esophageal metastatic cells, characte...
The application of combined chemotherapy and cancer cell permeabilising electric pulses (electrochemotherapy) has been demonstrated here to be clinically effective in the treatment and control of extensive breast cancer. In this case study the application has proven to be successful in the palliative treatment of a patient with recurrent breast wal...
Renal cell carcinoma (RCC) is the most common malignancy of the kidney. Unfortunately, RCCs are highly refractory to conventional chemotherapy, radiation therapy, and even immunotherapy. Thus, novel therapeutic targets need to be sought for the successful treatment of RCCs. We now report that 6-anilino-5,8-quinolinequinone (LY83583), an inhibitor o...
8047
Background: By applying brief, electric pulses, cell membranes can be transiently permeabilised (electroporation). This can be applied focally to tumors, enhancing the uptake of certain chemotherapeutic agents dramatically (electrochemotherapy). Methods: From 2003 to 2005, patients with cancer of any histological diagnosis and symptomatic meta...
Citations
... We subjected the samples to a PEF protocol according to the ESOPE guidelines. 34 The repetition rate was set to 5 kHz. Each sample was subjected to a PEF protocol and then replaced. ...
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... In a previous study, we analysed LC3B staining patterns in oesophageal adenocarcinoma tissue. A distinctive globular staining pattern of LC3B was identified as a novel prognostic marker for resectable oesophageal adenocarcinoma [25]. In this study, we examine the value of active/cleaved caspase-3 (CC3) as an apoptosis indicator and two staining patterns of LC3B, as a reflection of autophagy in a chemotherapytreated cohort. ...
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... During a mentor-apprenticeship learning process, instructors can adjust the difficulty of the training task based on the progress of trainees to maximize the learning rate. Several proficiency-based learning approaches were presented for minimally invasive surgery skills training [55], [56]. For instance, a training curriculum was proposed to consider proficiency using FLS tasks [57]. ...
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... The efficacy of ECT as a treatment has been well demonstrated following the publication of outcome analyses collated from cancer centres across Europe, all demonstrating good response rates [1,9,10]. Furthermore, outcome analysis with regards to cutaneous malignancy histiotypes demonstrates the efficacy of ECT across multiple tumour types, including melanoma [11,12], breast cancer [13,14], and basal cell carcinomas (BCCs) [15,16], establishing ECT as a recognised treatment option contributing to the multi-disciplinary management of a variety of cutaneous malignancies. ...
... Although, until now, internal organ ECT is still at a research stage and medical devices approved for ECT do not support this treatment modality, there is a high potential in that approach, supported by earlier reports, e.g. for a liver cancer [22]. An advanced endosope for electrochemotherapy of internal organs has been recently developed [23], which could be applied for tumors of lung, oesophagus, colon, bladder, stomach, kidney, liver, pancreas, fibrosarcoma, breast, prostate, glioma, rectum, spleen, and ovary. The endoscope includes electrodes and applicators delivering drug locally. ...
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... *p-value < 0.05, **p-value < 0.01 and ***p-value < 0.0001 compared to the control. breast cancer cell and investigate whether ternary combination excess the effects or not (McKenna et al. 2013). ...
... [17][18][19] Here, it was hypothesized that a vacuum chamber could serve to isolate a controlled volume of skin tissue and perform noninvasive EP to induce transfection and immunogenicity following intradermal injection of a DNA vaccine. Combined vacuum + energy delivery systems have previously been developed for a variety of applications, including cosmetics applications for targeted destruction of subcutaneous fat, 20,21 facilitation of endoscopic chemotherapy delivery, 22,23 and even organ-targeted uptake of circulating nucleic acids. 24,25 In this research, the compatibility of such a system with skin delivery of nucleic acids was investigated. ...
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... Electroporation has been exploited in cancer treatment for increasing transport of chemotherapy drugs through the plasma membrane of cancer or malignant cells. The applied electric field in electrochemotherapy increases the uptake and accumulation of anti-tumour drugs into the malignant cells, thereby increasing the cytotoxic effect of the drugs [8]. Furthermore, a number of effects of applied external electric field have revealed to include altering the cellular functions and also cell surface redistribution and cytoskeletal reorganization [9]. ...
... In a previous study, we showed LC3A silencing in CCHE-45 cells, which was attributed to intergenic CpG island methylation (29). The inactivation of LC3A expression has been reported in various tumors, including lung, breast, and colon cancers (24,30). Notably, this inactivation is associated with aggresome formation, specifically in multiple myeloma (24,31). ...
... Among the key proteins studied, the conversion of LC3-I to LC3-II was signifcant as elucidated by the increase in LC3-II/LC3-I ratio and the expression of LC3-II increased across increasing time durations as per the outcomes. Tis outcome is supported by the results of the studies published previously [146,147]. It is also critical to note that the activation of LC3-I to LC3-II is not a major issue to consider for an autophagic ...
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