Calcium electroporation may offer a simple general tool for anticancer therapy. Transient permeabilization of cancer cell membranes created by applying short, high-voltage pulses in tumors enables high calcium influxes that trigger death. In this study, we compared the relative sensitivity different human tumor models and normal tissues to electroporation. Plasma membrane Ca2+-ATPase (PMCA) protein expression was confirmed vitro all lines primary dermal fibroblasts studied. types tested...

Electroporation is used in cancer treatment because of its ability to increase local cytotoxicity e.g. bleomycin (electrochemotherapy) and calcium (calcium electroporation). Calcium electroporation a novel anticancer that selectively kills cells by necrosis, cell death pathway stimulates the immune system due high release antigens "danger signals." In this exploratory study, we aimed investigate whether could initiate an response similar electrochemotherapy. To end, treated immunocompetent...

Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of (ICD) rely endoplasmic reticulum (ER) stress for trafficking danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality tumor ablation, cause activation ER-resident sensor PERK in both CT-26 colon carcinoma EL-4 lymphoma cells. correlates with sustained CRT exposure plasma membrane apoptosis induction...

The principal bioeffect of the nanosecond pulsed electric field (nsPEF) is a lasting cell membrane permeabilization, which often attributed to formation nanometer-sized pores. Such pores may be too small for detection by uptake fluorescent dyes. We tested if Ca2+, Cd2+, Zn2+, and Ba2+ ions can used as nanoporation markers. Time-lapse imaging was performed in CHO, BPAE, HEK cells loaded with Fluo-4, Calbryte, or Fluo-8 Ca2+ did not change fluorescence intact cells, whereas their entry after...

The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in cell membrane disrupted by nsEP (20 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for U937 human monocytes stably expressing Cas9 nuclease. extent permeabilization measured uptake Yo-Pro-1 (YP) dye and compared sham-exposed KOs control cells transduced with non-targeting (scrambled) gRNA. Only two KOs, SCNN1A...

Electric shocks, the only effective therapy for ventricular fibrillation, also electroporate cardiac cells and contribute to high-mortality post-cardiac arrest syndrome. Copolymers such as Poloxamer 188 (P188) are known preserve membrane integrity viability of electroporated cells, but their utility against injury from cardiopulmonary resuscitation (CPR) remains be established. We studied time course cell killing, mechanisms death, protection with P188 in AC16 human cardiomyocytes exposed...

Cancer ablation therapies aim to be efficient while minimizing damage healthy tissues. Nanosecond pulsed electric field (nsPEF) is a promising modality because of its selectivity against certain cell types and reduced neuromuscular effects. We compared killing efficiency by PEF (100 pulses, 200 ns-10 µs duration, 10 Hz) in panel human esophageal cells (normal pre-malignant epithelial smooth muscle). Normal were less sensitive than the ones unipolar (15-20% higher LD50, p < 0.05). Smooth...

&lt;div&gt;Abstract&lt;p&gt;Calcium electroporation may offer a simple general tool for anticancer therapy. Transient permeabilization of cancer cell membranes created by applying short, high-voltage pulses in tumors enables high calcium influxes that trigger death. In this study, we compared the relative sensitivity different human tumor models and normal tissues to electroporation. Plasma membrane Ca&lt;sup&gt;2+&lt;/sup&gt;-ATPase (PMCA) protein expression was confirmed &lt;i&gt;in...

&lt;p&gt;Supplementary Table 1. Overview of conductivities. An overview the conductivity used in simulation electric field distribution tumor, skin above, and muscle below treated with calcium electroporation. The system was constructed using three tissue (skin, muscle) domains overall geometry as an extruded 2D (Figure 4). references for each are also shown table.&lt;/p&gt;

&lt;p&gt;Figure S4. Effect on skin above tumors treated with calcium electroporation MDA-MB231 (human breast cancer) different doses of electroporation: 168 mM CaCl2 injected in a volume equivalent to 20% - 80% tumor and 100 500 half the volume. Skin was removed 2 days after treatment. EP = electroporation. Inflammation dermis/subcutis extravasation erythrocytes dermis were scored. Percent sections each scoring group linear regression mean dosing are shown, n 4-5 for 3 untreated/sham...

&lt;p&gt;Figure S2. Light microscope image of colon cancer tumor treated with calcium electroporation HT29 (human cancer) 168 mM and removed 6 days after treatment. HE section showing healing the replacement connective tissue in central/upper left area image, a small necrosis lower corner, vital right side image.&lt;/p&gt;

&lt;p&gt;Figure S3. Tumor necrosis after treatment with different doses of calcium electroporation MDA-MB231 (human breast cancer) tumors treated electroporation: 168 mM CaCl2 injected in a volume equivalent to 20% - 80% tumor and 100 500 half the volume. Calcium concentration is shown per Fraction was estimated by stereological point counting removed 2 days treatment. Each data together linear regression for or without electroporation. Data points controls are left panel grey symbols....

&lt;p&gt;Legends for supplementary figures S1-S7: Figure S1. Image of PVDF membrane showing total protein content in normal and cancer cell lines; S2. Light microscope image colon tumor treated with calcium electroporation; S3. Tumor necrosis after treatment different doses S4. Effect on skin above tumors S5. muscle below S6. tissue directly S7. Plasma ATPase (PMCA) mRNA level lines.&lt;/p&gt;

&lt;p&gt;Figure S1. Image of PVDF membrane showing total protein content in normal and cancer cell lines Total elicited by staining with SimplyBlue SafeStain (Invitrogen) performed after western blotting plasma calcium ATPase (PMCA) expression primary fibroblasts (HDF-n) four (H69, small lung cancer&lt;/p&gt;

&lt;p&gt;Figure S7. Plasma membrane calcium ATPase (PMCA) mRNA level in normal and cancer cell lines Total PMCA, isoform 1, isoform4 primary fibroblasts (HDF-n) four (H69, small lung cancer&lt;/p&gt;

&lt;p&gt;Figure S7. Plasma membrane calcium ATPase (PMCA) mRNA level in normal and cancer cell lines Total PMCA, isoform 1, isoform4 primary fibroblasts (HDF-n) four (H69, small lung cancer&lt;/p&gt;

&lt;p&gt;Figure S2. Light microscope image of colon cancer tumor treated with calcium electroporation HT29 (human cancer) 168 mM and removed 6 days after treatment. HE section showing healing the replacement connective tissue in central/upper left area image, a small necrosis lower corner, vital right side image.&lt;/p&gt;

&lt;p&gt;Figure S3. Tumor necrosis after treatment with different doses of calcium electroporation MDA-MB231 (human breast cancer) tumors treated electroporation: 168 mM CaCl2 injected in a volume equivalent to 20% - 80% tumor and 100 500 half the volume. Calcium concentration is shown per Fraction was estimated by stereological point counting removed 2 days treatment. Each data together linear regression for or without electroporation. Data points controls are left panel grey symbols....

&lt;p&gt;Legends for supplementary figures S1-S7: Figure S1. Image of PVDF membrane showing total protein content in normal and cancer cell lines; S2. Light microscope image colon tumor treated with calcium electroporation; S3. Tumor necrosis after treatment different doses S4. Effect on skin above tumors S5. muscle below S6. tissue directly S7. Plasma ATPase (PMCA) mRNA level lines.&lt;/p&gt;