Julita Kulbacka - Academia.edu (original) (raw)

Papers by Julita Kulbacka

International Journal of Molecular Sciences

Pancreatic cancer has no symptoms until the disease has advanced and is aggressive cancer with ea... more Pancreatic cancer has no symptoms until the disease has advanced and is aggressive cancer with early metastasis. Up to now, the only curative treatment is surgical resection, which is possible in the early stages of the disease. Irreversible electroporation treatment offers new hope for patients with unresectable tumors. Irreversible electroporation (IRE) is a type of ablation therapy that has been explored as a potential treatment for pancreatic cancer. Ablation therapies involve the use of energy to destroy or damage cancer cells. IRE involves using high-voltage, low-energy electrical pulses to create resealing in the cell membrane, causing the cell to die. This review summarizes experiential and clinical findings in terms of the IRE applications. As was described, IRE can be a non-pharmacological approach (electroporation) or combined with anticancer drugs or standard treatment methods. The efficacy of irreversible electroporation (IRE) in eliminating pancreatic cancer cells has ...

Folia Histochemica et Cytobiologica, 2011

Melanoma is the most severe of all skin cancers as it may grow rapidly and metastasize. The appli... more Melanoma is the most severe of all skin cancers as it may grow rapidly and metastasize. The application of photodynamic therapy (PDT) opens new perspectives in treatment of this cancer. Numerous studies suggest that the exposure of tumor cells to PDT can lead to cell death via two separate processes: apoptosis or necrosis. The aim of this study was to assess in vitro photodynamic therapy which induces apoptosis in the human Beidegröm Melanoma (BM) cell line, using neutral comet assay. The cells were incubated with Photofrin II (15 μg/ml and 30 μg/ml) 4 h before and 3 h after irradiation for 5 or 10 min with the light intensity of 10 mW/cm2, using a lamp with red filter (632.8 nm). The percentage of apoptotic cells was significantly higher after PDT comparing to control cells. We observed 25% and 70% of apoptotic cells after shorter irradiation and treatment with 15 μg/ml and 30 μg/ml of Ph II, respectively. After longer ir...

Cancers, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Molecules, 2020

Electroporation, applied as a non-thermal ablation method has proven to be effective for focal pr... more Electroporation, applied as a non-thermal ablation method has proven to be effective for focal prostate treatment. In this study, we performed pre-clinical research, which aims at exploring the specific impact of this so-called calcium electroporation on prostate cancer. First, in an in-vitro study of DU 145 cell lines, microsecond electroporation (μsEP) parameters were optimized. We determined hence the voltage that provides both high permeability and viability of these prostate cancer cells. Subsequently, we compared the effect of μsEP on cells’ viability with and without calcium administration. For high-voltage pulses, the cell death’s mechanism was evaluated using flow-cytometry and confocal laser microscopy. For lower-voltage pulses, the influence of electroporation on prostate cancer cell mobility was studied using scratch assays. Additionally, we applied calcium-binding fluorescence dye (Fluo-8) to observe the calcium uptake dynamic with the fluorescence microscopy. Moreover,...

Oncology in Clinical Practice, 2008

W Polsce rak jelita grubego nalezy do grupy nowotworow o najgorszym rokowaniu. Mozliwośc wyleczen... more W Polsce rak jelita grubego nalezy do grupy nowotworow o najgorszym rokowaniu. Mozliwośc wyleczenia jest przede wszystkim uzalezniona od stopnia zaawansowania choroby w chwili jej rozpoznania. Podstawową metodą jest chemioterapia, ktora jest skuteczna tylko u cześci chorych z powodu oporności na zastosowane leki cytotoksyczne. Chemioterapia jest zazwyczaj cześcią skojarzonego postepowania, ktore sklada sie dodatkowo z chirurgicznego leczenia i radioterapii oraz wprowadzonych ostatnio modulatorow oporności wielolekowej i lekow celowanych. Zadaniem nowoczesnych przeciwnowotworowych lekow celowanych jest hamowanie molekularnych szlakow onkogenezy oraz selektywne wprowadzanie aktywnych substancji do komorek nowotworowych. Do nowoczesnych lekow nalezą miedzy innymi: modulatory aktywności cząsteczek biorących udzial w przekazywaniu sygnalow, regulatory cyklu komorkowego, czynniki kontrolujące angiogeneze i aktywnośc procesow przerzutowania, mechanizmy warunkujące lekoopornośc oraz onkogen...

International Journal of Molecular Sciences, 2021

Electroporation is influenced by the features of the targeted cell membranes, e.g., the cholester... more Electroporation is influenced by the features of the targeted cell membranes, e.g., the cholesterol content and the surface tension of the membrane. The latter is eventually affected by the organization of actin fibers. Atorvastatin is a statin known to influence both the cholesterol content and the organization of actin. This work analyzes the effects of the latter on the efficacy of electroporation of cancer cells. In addition, herein, electroporation was combined with calcium chloride (CaEP) to assess as well the effects of the statin on the efficacy of electrochemotherapy. Cholesterol-rich cell lines MDA-MB231, DU 145, and A375 underwent (1) 48 h preincubation or (2) direct treatment with 50 nM atorvastatin. We studied the impact of the statin on cholesterol and actin fiber organization and analyzed the cells’ membrane permeability. The viability of cells subjected to PEF (pulsed electric field) treatments and CaEP with 5 mM CaCl2 was examined. Finally, to assess the safety of t...

Polymers in Medicine, 2021

Natural polymers have been commonly applied in medicine and pharmacy. Their primary function is t... more Natural polymers have been commonly applied in medicine and pharmacy. Their primary function is to enhance drug delivery, tissue regeneration or wound healing, and diagnostics. Natural polymers appear promising for photodynamic protocols, including photodiagnosis (PDD) and photodynamic therapy (PDT). Currently, the most challenging issue with natural polymers is to appropriately select the most effective material regarding the type of cancer treated. The technological achievements enable functionalization of natural polymers by specific antibodies, or enhancement using fluorescent or quantum dot markers for diagnostic applications. This review will discuss the types and properties of natural polymers and available applications of PDD and PDT which seem to be promising in cancer treatment. Treatment of neoplastic diseases is still a challenge for both physicians and scientists, so the search for alternative methods of treatment and diagnosis based on natural materials is relevant.

Pharmaceutics, 2020

Estrogens (Es) play a significant role in the carcinogenesis and progression of ovarian malignanc... more Estrogens (Es) play a significant role in the carcinogenesis and progression of ovarian malignancies. Depending on the concentration, Es may have a protective or toxic effect on cells. Moreover, they can directly or indirectly affect the activity of membrane ion channels. In the presented study, we investigated in vitro the effectiveness of the ovarian cancer cells (MDAH-2774) pre-incubation with 17β-estradiol (E2; 10 µM) in the conventional chemotherapy (CT) and electrochemotherapy (ECT) with cisplatin or calcium chloride. We used three different protocols of electroporation including microseconds (µsEP) and nanoseconds (nsEP) range. The cytotoxic effect of the applied treatment was examined by the MTT assay. We used fluorescent staining and holotomographic imaging to observe morphological changes. The immunocytochemical staining evaluated the expression of the caspase-12. The electroporation process’s effectiveness was analyzed by a flow cytometer using the Yo-Pro™-1 dye absorptio...

Molecules, 2021

Modifications of the composition or organization of the cancer cell membrane seem to be a promisi... more Modifications of the composition or organization of the cancer cell membrane seem to be a promising targeted therapy. This approach can significantly enhance drug uptake or intensify the response of cancer cells to chemotherapeutics. There are several methods enabling lipid bilayer modifications, e.g., pharmacological, physical, and mechanical. It is crucial to keep in mind the significance of drug resistance phenomenon, ion channel and specific receptor impact, and lipid bilayer organization in planning the cell membrane-targeted treatment. In this review, strategies based on cell membrane modulation or reorganization are presented as an alternative tool for future therapeutic protocols.

Surgical Oncology, 2021

In this study, irreversible electroporation (IRE), electrochemotherapy (ECT), and calcium electro... more In this study, irreversible electroporation (IRE), electrochemotherapy (ECT), and calcium electroporation (CaEP) techniques were investigated as new strategies for human pancreatic cancer. Qualification of the patients, best "therapeutic moment" for each patient, safety, and complications after procedures were examined. In this pilot study were included 13 patients in this study, which were operated on in different pancreatic cancer stages. Patients underwent IRE or ECT with intravenous admission of cisplatin or electroporation with calcium intratumoral administration. The IRE procedure was safe for the patients. Medium overall survival for IRE, IRE + CTH, and IRE + CaCl 2 was respectively: 16, 29.5, and 19 months comparing to 10 months in control chemotherapy (CTH) group. Thus, IRE, ECT, and CaEP can be effective strategies for pancreatic cancer treatment.

Materials, 2021

Traditional chemo-mechanical retraction/displacement materials can impact the gingival margin tis... more Traditional chemo-mechanical retraction/displacement materials can impact the gingival margin tissues. This study was undertaken to analyze biological responses induced in human gingival fibroblasts (HGFs) upon application of injectable astringent-based agents used in the cordless retraction technique. HGFs were exposed to hemostatic agents (five gels, three pastes, and one foam) based on aluminium chloride, aluminium sulphate and ferric sulphate. Changes in cell viability and proliferation were evaluated using an MTT assay and a BrdU assay. The cytoskeleton structure organization (zyxin and F-actin) was visualized by confocal laser scanning microscopy. Oxidative stress was determined using the Griess Reagent System. The RNA expression levels of antioxidant enzymes were quantified by real-time RT-PCR. The statistical significance was evaluated using Student’s t-test and one-way ANOVA with post-hoc Tukey HSD test. The evaluated agents did not downregulate fibroblast viability or prol...

Cancers, 2020

The observation that an application of a pulsed electric field (PEF) resulted in an increased per... more The observation that an application of a pulsed electric field (PEF) resulted in an increased permeability of the cell membrane has led to the discovery of the phenomenon called electroporation (EP). Depending on the parameters of the electric current and cell features, electroporation can be either reversible or irreversible. The irreversible electroporation (IRE) found its use in urology as a non-thermal ablative method of prostate and renal cancer. As its mechanism is based on the permeabilization of cell membrane phospholipids, IRE (as well as other treatments based on EP) provides selectivity sparing extracellular proteins and matrix. Reversible EP enables the transfer of genes, drugs, and small exogenous proteins. In clinical practice, reversible EP can locally increase the uptake of cytotoxic drugs such as cisplatin and bleomycin. This approach is known as electrochemotherapy (ECT). Few in vivo and in vitro trials of ECT have been performed on urological cancers. EP provides ...

Molecules, 2020

Ovarian cancer is the leading cause of death from gynecologic malignancies. Some estrogens, as we... more Ovarian cancer is the leading cause of death from gynecologic malignancies. Some estrogens, as well as xenoestrogens, such as chromium (VI) (Cr(VI)), are indicated as important pathogenic agents. The objective of this study was to evaluate the role of estradiol and some its metabolites upon exposure to the metalloestrogen Cr(VI) in an in vitro model. The changes in cell viability of malignant ovarian cancer cells (SKOV-3 resistant to cisplatin) exposed to 17β-estradiol (E2) and its two metabolites, 2-methoxyestradiol (2-MeOE2) and 16α-hydroxyestrone (16α-OHE1), upon exposure to potassium chromate (VI) and its interactions were examined. The single and mixed models of action, during short and long times of incubation with estrogens, were applied. The different effects (synergism and antagonism) of estrogens on cell viability in the presence of Cr(VI) was observed. E2 and 16α-OHE1 caused a synergistic effect after exposure to Cr(VI). 2-MeOE2 showed an antagonistic effect on Cr(VI). Th...

Applied Sciences, 2020

(1) Background: In the last two decades, anticancer treatment has been extensively developed base... more (1) Background: In the last two decades, anticancer treatment has been extensively developed based on various physical methods, including electroporation (EP). On the basis of many in vitro and in vivo studies, electroporation and further electrochemotherapy (ECT) have been established as a treatment method for cutaneous and subcutaneous lesions. In this procedure, after placing electrodes in the tumor mass and the generation of electrical pulses, a reversible or irreversible rearrangement of the cell membrane occurs. Calcium electroporation has already been applied to treat skin tumors and subcutaneous tissue tumors. Here, we demonstrate the first application of irreversible electroporation (IRE) in combination with calcium ions and chemotherapy for patients with cancer. (2) Methods: This study aimed to present and compare the findings and outcomes of patients with locally advanced pancreatic adenocarcinoma who were qualified for the procedure. Two patients were treated with IRE with calcium ions after chemotherapy (paclitaxel + Gemcitabine (GCB) or FOLOX) or only FOLFOX (folinic acid calcium folinate, fluorouracil, and oxaliplatin). The clinicopathological data, overall survival, and the safety of the procedure were analyzed. (3) Results: Two patients were treated with calcium electroporation. One of the patients developed pancreatitis and the second developed pancreatic fistula, but both of them continued standard systemic treatment. Overall survival was 9 months in the first case and 21 months in the second case (and the patient is still alive). Calcium electroporation had a good impact on QOL (Quality of Life). (4) Conclusions: IRE accompanied chemotherapy, and intratumoral calcium ions administration might represent an additional therapy to surgery and chemotherapy in patients with locally advanced pancreatic cancer (LAPC), particularly in unresectable cases. However, further studies of randomized trials should be undertaken to elucidate the role of chemotherapy in IRE protocols.

Pharmaceutics, 2020

Melanoma is one of the most serious skin cancers. The incidence of this malignant skin lesion is ... more Melanoma is one of the most serious skin cancers. The incidence of this malignant skin lesion is continuing to increase worldwide. Melanoma is resistant to chemotherapeutic drugs and highly metastatic. Surgical resection can only be used to treat melanoma in the early stages, while chemotherapy is limited due to melanoma multi-drug resistance. The overexpression of glutathione S-transferase (GST) may have a critical role in this resistance. Caffeic acid phenethyl ester (CAPE) is a natural phenolic compound, which occurs in many plants. Previous studies demonstrated that CAPE suppresses the growth of melanoma cells and induces reactive oxygen species generation. It is also known that bioactivation of CAPE to its corresponding quinone metabolite by tyrosinase would lead to GST inhibition and selective melanoma cell death. We investigated the biochemical toxicity of CAPE in combination with microsecond electropermeabilization in two human melanoma cell lines. Our results indicate that ...

Applied Sciences, 2020

Electroporation increases the transmembrane transport of molecules. The combination of electric p... more Electroporation increases the transmembrane transport of molecules. The combination of electric pulses with cytostatic compounds is beneficial for cancer treatment. Doxorubicin (DOX) is a commonly used chemotherapeutic anticancer drug. Its fluorescence properties enable the investigation of drug distribution and metabolism. In this study, doxorubicin was enhanced by electroporation to eliminate cancer cells more effectively. The influence of electroporation on the drug uptake was evaluated in two cell lines: MCF-7/WT and MCF-7/DOX. The intracellular localization of doxorubicin and its impact on the intracellular structure organization were examined under a confocal microscope. Cellular effects were examined with the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test that estimates the rate of metabolism in viable cells. The ultrastructure (TEM) of tumor cells subjected to the electric field was analyzed. An enhanced doxorubicin efficacy was observed in MCF-7/DOX ...

Animals, 2020

Background: The aim of this study was to present the first domestic animal trial of nanosecond el... more Background: The aim of this study was to present the first domestic animal trial of nanosecond electroporation with chemotherapy and CO2 laser surgery. Methods: sixteen-year-old domestic cat with diagnosed melanoma on oral cavity was the case used in the study. Firstly, CO2 laser surgery was used for the removal of most of tumor mass. Then nanoelectrochemotherapy with bleomycin was applied including appropriate margin of healthy tissue. A 15 ± 4 kV/cm × 15 ns pulsing protocol was employed with a total of 800 ± 100 pulses. Only one session of nanoelectrochemotherapy (nanoECT) was performed. Results and conclusions: during the next two weeks areas of focal necrosis were replaced by the granulation tissue. Complete wound healing was observed four weeks after initial treatment. After 15 weeks post treatment, no local recurrence was apparent.

Nutrients, 2019

Cancers are one of the leading causes of deaths affecting millions of people around the world, th... more Cancers are one of the leading causes of deaths affecting millions of people around the world, therefore they are currently a major public health problem. The treatment of cancer is based on surgical resection, radiotherapy, chemotherapy or immunotherapy, much of which is often insufficient and cause serious, burdensome and undesirable side effects. For many years, assorted secondary metabolites derived from plants have been used as antitumor agents. Recently, researchers have discovered a large number of new natural substances which can effectively interfere with cancer cells’ metabolism. The most famous groups of these compounds are topoisomerase and mitotic inhibitors. The aim of the latest research is to characterize natural compounds found in many common foods, especially by means of their abilities to regulate cell cycle, growth and differentiation, as well as epigenetic modulation. In this paper, we focus on a review of recent discoveries regarding nature-derived anticancer a...

Oncology Reports, 2019

Betulinic acid (BTA) is naturally occurring triterpene that has received interest as a novel ther... more Betulinic acid (BTA) is naturally occurring triterpene that has received interest as a novel therapeutic substance with cytotoxicity towards a number of cancer cell lines. Despite the wide spectrum of biological and pharmacological effects, its effect may be limited its lipophobic properties. Therefore, strategies to improve the access of BTA to the cells are required to enhance the anticancer effects. Electroporation (EP) enables increased inflow of drugs into cancer cells, even at low doses, which may reduce the side effects caused by high doses of chemotherapy. The potential application of BTA in electrochemotherapy (ECT) in metastatic type of cancers was investigated in the present study. The efficacy of BTA with EP was estimated using a cell survival assay (MTT assay), microscopical morphology analysis and the immunocytochemical expression of heat shock proteins (HSPs). HSPs are molecules that protect the cell from harmful environmental, chemical and physical stresses, and ensure cell survival, recovery and proper functioning. HSP expression is induced various stress factors. Therefore, the expression of HSP27 and HSP70 was evaluated after cells were exposed to an external pulsed electric field and anticancer drugs. Facilitated drug delivery and the anticancer effect on metastatic tumor cells were evaluated in vitro. The effect of BTA was compared with cisplatin (CP), a standard cytostatic agent. Two different metastatic cancer cell lines were used, an ovary adenocarcinoma cell line (SW626) and melanoma cell line (Me45). BTA combined with EP exhibited similar efficacy to CP with EP after 24 and 48 h in SW626 and Me45 cancer cells. Me45 cells also had high HSP27 and low HSP70 immunosignals post-ECT treatment. ECT caused increased expression of HSP27 and HSP70 proteins in SW626 cells, which were less sensitive to ECT than the Me45 melanoma cell line. The results indicate that BTA may be efficiently applied instead of CP in ECT approaches, but its activity differs between tumor cell lines.

$Research paper thumbnail of {"__content__"=>"Electroporation with Cisplatin against Metastatic Pancreatic Cancer: Study on Human Primary Cell Culture.", "i"=>{"__content__"=>"In Vitro"}}$

BioMed research international, 2018

Despite the rapid progression of cancer pharmacotherapy, the high drug resistance of pancreatic d... more Despite the rapid progression of cancer pharmacotherapy, the high drug resistance of pancreatic ductal adenocarcinoma (PDA) makes it one of the most lethal malignancies. Therefore, there are high expectations associated with experimental therapies, such as electrochemotherapy (ECT). This technique involves the application of short electric pulses to induce transitional permeabilization of the cellular membrane, thus enhancing drug molecules influx. The aim of the study was to investigate the influence of electroporation with cisplatin (CisEP) on the primary culture of human PDA cells from lung metastases-their survival and stress response. Considering the growing importance of various research models, two established human PDA cell lines, EPP85-181P (sensitive to daunorubicin) and EPP85-181RDB (resistant to daunorubicin), were utilized as a reference control. Cisplatin revealed higher cytotoxicity towards established cell lines. Following CisEP application, we observed a significant...

International Journal of Molecular Sciences

Folia Histochemica et Cytobiologica, 2011

Cancers, 2021

Molecules, 2020

Oncology in Clinical Practice, 2008

International Journal of Molecular Sciences, 2021

Polymers in Medicine, 2021

Pharmaceutics, 2020

Molecules, 2021

Surgical Oncology, 2021

Materials, 2021

Cancers, 2020

Molecules, 2020

Applied Sciences, 2020

Pharmaceutics, 2020

Applied Sciences, 2020

Animals, 2020

Nutrients, 2019

Oncology Reports, 2019

$Research paper thumbnail of {"__content__"=>"Electroporation with Cisplatin against Metastatic Pancreatic Cancer: Study on Human Primary Cell Culture.", "i"=>{"__content__"=>"In Vitro"}}$

BioMed research international, 2018