BACKGROUND: Electrochemotherapy(ECT) is a new and an efficient approach for the treatment of tumor. The technique is very easy to control and operate and is of little harm to normal tissue. Especially, it is very efficient in curing the superficial tumors. In the treatment process of ECT, the selection and constitute of electromagnetic impulse are the key factors.OBJECTIVE: To use the ECT as a therapeutic method for S-180 sarcomas in Kunming mice and obtain the optimal parameters of electromagnetic impulse in curing.SETTING: Department of Wireless Physics, College of Electronics-Information, Sichuan University DESIGN: Random grouping design and controlled experiment study MATERIALS: This experiment was conducted at the Laboratory of Cells, College of Life Sciences, Sichuan University from January 2003 to May 2004. Totally 106 Kunming mice were randomly divided into 12 groups: voltage 500 V, pulse number 5 and capacitance 6,10 and 14 μF, respectively in 3 groups, with 9 mice in each group;voltage 700 V, pulse number 5 and capacitance 6,10 and 14 μF, respectively in 3 groups, with 9 mice in each group; voltage 900 V, pulse number 5 and capacitance 6,10 and 14 μF, respectively in 3 groups,with 9 mice in each group; voltage 700 V, capacitance 10 μF, pulse number 7 and and 9 respectively in 2 groups , with 8 mice in each group , and control group with 9 mice in it.METHODS: The treatment includes injection of Bleomycin 0.04 mg per one (intraperitoneal injecting into tumors through multiple points), followed by application of electromagnetic impulse using the needles. The treatment was taken every three days andthree times in total. Mice were euthanized 18 days later. Tumor volume was measured before irradiation and 10 and 18 days after irradiation. Tumor volume (mm3)=3.141 59×length×width×height/6. Inhibitory rate(%)=(average tumor volume of the control group-average tumor volume after irradiation)/average tumor volume of control group×100%. The relative growth velocity=tumor volume after irradiation/Tumor volume before irradiation.MAIN OUTCOME MEASURES: Tumor volume; inhibitory rate; relative growth velocity RESULTS: Totally 106 animals were enrolled in the experiment and all of them entered the stage of result analysis. ①When the capacitance was 6 μF, the impulse numbers are 5, the voltage altered [for example the 10th day, when voltage was 500, 700, 900 V, the tumor volume was (66.99±91.17),(62.58±71.83),(78.43±73.91) mm3 , respectively]. The effect was the best when the voltage was 700 V, and was the worst when 900 V).②When the voltage and capacitance were fixed and the pulse numbers altered, for example voltage 700 V and capacitance 10 μF, taking the 10th day as the example , the pulse number was 5, 7 and 9, the tumor volume was (80.66±38.17),(41.33±36.40),(39.86±23.03) mm3, respectively. The inhibitory effect was better with the increase of pulse number, and the best when the pulse number was 9.CONCLUSION: According to experimental results, following parameters of electromagnetic impulse, can be concluded: ①The inhibitory effect is the best when the number of impulse is 5, voltage 700 V, capacitance 6 μF. ②The inhibitory effect increases with the increase of pulse number when the voltage is 700 V and capacitance is 10 μF, and is the best when the pulse number is 9.

Electrochemotherapy (ECT) is a novel cancer treatment in which electric pulses (EPs) inducing cell membrane pored (electroporation) are used as a means of delivering antitumor drugs to the cytoplasm of cancer cells. The minimal thresholds of electric field strength of in vitro tumor cell line and tumor tissue are 450-650 V/cm and 400-600 V/cm, respectively. The typical electrical requirement is 600-1300 V/cm, pulse width of 100 micros, 8 pulses, 1 Hz. More than 10 kinds of antitumor drugs have been applied to ECT, in which the most efficacious drug is Bleomycin, and then Cisplatin. Some exciting inhibitory effects on cells in vitro and on solid tumors in clinical trials have been noticed. The factors influencing ECT effects include the electric parameters, diameter of electrode, distribution of electric field lines, size of tumor, model of drugs injection and kinds of drugs. Some questions of ECT are still open, such as the dosages and kinds of drugs for clinical trials, model of drug injection, influence on normal tissues, therapeutic mechanism.
Antibiotics, Antineoplastic ; administration & dosage ; Antineoplastic Agents ; administration & dosage ; Bleomycin ; administration & dosage ; Cisplatin ; administration & dosage ; Electric Stimulation Therapy ; methods ; Electrochemistry ; Electroporation ; methods ; Humans ; Neoplasms ; therapy

OBJECTIVE:To investigate the inhibitory effect of siRNA expression vector inhibiting human insulin-like growth factor 2(IGF2)gene on the proliferation of hepatoma cell line Huh-7. METHODS:siRNA expression vector pGL3-hAFP-hTERT-siRNA3(“siRNA3”)which inhibited IGF2 gene by dual promoter regulation of recombinant human alpha-foetoprotein(hAFP)and human telomerase reverse transcriptase(hTERT)was transfected into the Huh-7 cell and normal hepatocyte L-02,and then a nega-tive control group(vector pGL3-hAFP-hTERT)and a blank control group were set up. IGF2 mRNA expression was detected by re-al-time fluorescent quantitative polymerase chain reaction 48 h after transfection into the cells in all groups;the activity of the cells by the microplate reader 0,24,48 and 72 h thereafter;and the cell cycle and apoptosis by the flow cytometer 48 h thereafter,and the changes in the protein levels of IGF2,PCNA,Cyclin E2,Cyclin D2,Cdc2 and Bcl-2 in the cell were detected by Western blot. RESULTS:Compared with the negative control group and blank control group,IGF2 mRNA expression in the Huh-7 cell transfected with siRNA3 was obviously weaker;at 48 and 72 h after transfection,the activity of Huh-7 cell signigicantly reduced, Huh-7 cells at G1 phase obviously increased and those at S phase markedly decreased;the occurrence of early,late and total apopto-sis in Huh-7 cells apparently increased,and the protein expression of IGF2,PCNA,Cyclin E2,Cyclin D2,Cdc2 and Bcl-2 in cells significantly weakened,with statistically significance(P<0.01 or P<0.05). No obvious change in the above-mentioned index-es could be found in L-02 cells transfected with siRNA3 expression vector (P>0.05). CONCLUSIONS:siRNA which inhibited IGF2 gene by dual promoter regulation of recombinant hAFP and hTERT can specially inhibit IGF2 gene expression and the prolifer-ation of Huh-7 cells,which may be involved with down-regulated protein expression of cell proliferation-associated gene PCNA, cell cycle control-associated genes Cyclin E2,Cyclin D2 and Cdc2 and apoptosis regulation-associated gene Bcl-2 as a result of down-regulated IGF2 mRNA expression and protein expres-sion.

This study evaluated the effects of electric pulses combined with antitumor drugs on S180 tumor cells. It was found that the growth of S180 sarcoma was inhibited with a maximum inhibition ratio of 95.5% after the use of electric pulses in combination with the injection of bleomycin (BLM), and the blood vessels of tumor were obviously fewer than those of the untreated tumor in vivo. The mitochondria of S180 tumor cells were swollen after the use of electric pulses in combination with adriamycin. The results showed that electrochemotherapy has evident inhibitory effect on the growth of S180 sarcoma and the mechanism may involve the suppression of tumor angiogenesis and changes in the ultrastructures of tumor cells.
Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; Bleomycin ; administration & dosage ; Combined Modality Therapy ; Electric Stimulation Therapy ; methods ; Electrochemistry ; Mice ; Neovascularization, Pathologic ; prevention & control ; Sarcoma 180 ; blood supply ; therapy

Purpose: Combinations of immune checkpoint inhibitors (ICIs) and chemotherapy have become the standard first-line treatment for human epidermal growth factor receptor 2 (HER-2)-negative advanced gastric cancer. However, primary resistance remains a challenge, with no effective biomarkers available for its prediction. This retrospective study explores the relationship between the baseline inflammatory burden index (IBI) and primary resistance in such context. Materials and Methods: We analyzed 62 patients with HER-2-negative advanced gastric cancer who received ICIs and chemotherapy as their first-line treatment. The IBI was calculated as follows: C-reactive protein (mg/L) × neutrophil count (10 3 /mm 3 )/lymphocyte count (10 3 /mm 3 ). Based on disease progression within 6 months, patients were categorized into the primary resistant or the control group. We compared baseline characteristics and IBI scores between the groups and assessed the predictive value of the IBI using the receiver operating characteristic curve. Both univariate and multivariate binary logistic regression analyses were conducted to identify factors influencing primary resistance. Results: Nineteen patients were included in the primary resistance group, and forty-three patients were included in the control group. The IBI was significantly higher in the resistant group compared to the control group (P<0.01). The area under the curve for the IBI was 0.82, indicating a strong predictive value. Multivariate analysis identified the IBI as an independent predictor of primary resistance (P=0.014). Conclusions The baseline IBI holds promise as a predictor of primary resistance to combined ICIs and chemotherapy in patients with HER-2-negative advanced gastric cancer.

Purpose: Combinations of immune checkpoint inhibitors (ICIs) and chemotherapy have become the standard first-line treatment for human epidermal growth factor receptor 2 (HER-2)-negative advanced gastric cancer. However, primary resistance remains a challenge, with no effective biomarkers available for its prediction. This retrospective study explores the relationship between the baseline inflammatory burden index (IBI) and primary resistance in such context. Materials and Methods: We analyzed 62 patients with HER-2-negative advanced gastric cancer who received ICIs and chemotherapy as their first-line treatment. The IBI was calculated as follows: C-reactive protein (mg/L) × neutrophil count (10 3 /mm 3 )/lymphocyte count (10 3 /mm 3 ). Based on disease progression within 6 months, patients were categorized into the primary resistant or the control group. We compared baseline characteristics and IBI scores between the groups and assessed the predictive value of the IBI using the receiver operating characteristic curve. Both univariate and multivariate binary logistic regression analyses were conducted to identify factors influencing primary resistance. Results: Nineteen patients were included in the primary resistance group, and forty-three patients were included in the control group. The IBI was significantly higher in the resistant group compared to the control group (P<0.01). The area under the curve for the IBI was 0.82, indicating a strong predictive value. Multivariate analysis identified the IBI as an independent predictor of primary resistance (P=0.014). Conclusions The baseline IBI holds promise as a predictor of primary resistance to combined ICIs and chemotherapy in patients with HER-2-negative advanced gastric cancer.

Purpose: Combinations of immune checkpoint inhibitors (ICIs) and chemotherapy have become the standard first-line treatment for human epidermal growth factor receptor 2 (HER-2)-negative advanced gastric cancer. However, primary resistance remains a challenge, with no effective biomarkers available for its prediction. This retrospective study explores the relationship between the baseline inflammatory burden index (IBI) and primary resistance in such context. Materials and Methods: We analyzed 62 patients with HER-2-negative advanced gastric cancer who received ICIs and chemotherapy as their first-line treatment. The IBI was calculated as follows: C-reactive protein (mg/L) × neutrophil count (10 3 /mm 3 )/lymphocyte count (10 3 /mm 3 ). Based on disease progression within 6 months, patients were categorized into the primary resistant or the control group. We compared baseline characteristics and IBI scores between the groups and assessed the predictive value of the IBI using the receiver operating characteristic curve. Both univariate and multivariate binary logistic regression analyses were conducted to identify factors influencing primary resistance. Results: Nineteen patients were included in the primary resistance group, and forty-three patients were included in the control group. The IBI was significantly higher in the resistant group compared to the control group (P<0.01). The area under the curve for the IBI was 0.82, indicating a strong predictive value. Multivariate analysis identified the IBI as an independent predictor of primary resistance (P=0.014). Conclusions The baseline IBI holds promise as a predictor of primary resistance to combined ICIs and chemotherapy in patients with HER-2-negative advanced gastric cancer.

In this paper are analyzed the effect of electrochemotherapy and its mechanism. The favorable parameter of electric pulses (EP) was studied in vitro using the S-180 cells exposed to various EP. After the tumor model was copied, the tumor-bearing mice were randomly divided into four groups: control, chemotherapy, electrotherapy, and electrochemotherapy. The tumor inhibitory ratio, the cure ratio and the level of oxygen free radicals (OFR) were determined. The inhibitory ratio and cure ratio of electrochemotherapy group were significantly higher than those in the chemotherapy, electrotherapy and control groups (P < 0.05). The injury of OFR was decreased while the immunological competence was increased. The mechanism of electrochemotherapy may be related with the enhancement of cell membranepermeability, the depression of drug resistance, the improvement of immunological competence, and so on.
Animals ; Antineoplastic Agents ; administration & dosage ; Bleomycin ; administration & dosage ; Drug Delivery Systems ; methods ; Electric Stimulation Therapy ; methods ; Electrochemistry ; Electroporation ; methods ; Mice ; Random Allocation ; Sarcoma 180 ; therapy

In this paper is reported a new approach for the treatment of sarcoma--electroporation therapy. Electroporation can accelerate pharmacal molecules into cytoplasm by transient electromagnetic pulses. We have utilized the phenomenon of electroporation treating the S-180 sarcomas in the hind legs of the Kunming mice by intratumoral injection of anti-tumor agent at low dose. From the experiment, we learned that this approach can bring about remarkable effect. The technical procedure is easy to do and easy to control. Especially, it is useful in curing the flat tumor and has little untoward side effect. It deserves to be recommended as a new approach to treating the tumor in clinics.
Animals ; Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cyclophosphamide ; therapeutic use ; Electrochemotherapy ; methods ; Mice ; Neoplasm Transplantation ; Sarcoma 180 ; drug therapy ; pathology

This article reports the experiment studies on treating the S-180 sarcomas of KM mice with high-intensity electric pulse and antitumor drug (cyclophosphamide). The results showed that the experimental group of electric field combined with drug has the best effect on tumor, compared with the control group. In addition, electric field can inhibit the formation of vas Capillaries and decrease the supply of nutrition for tumor cell. In conclusion, electric field has inhibited the growth of tumor.
Animals ; Antineoplastic Agents ; therapeutic use ; Combined Modality Therapy ; Cyclophosphamide ; administration & dosage ; Electric Stimulation Therapy ; methods ; Injections, Intralesional ; Mice ; Sarcoma 180 ; pathology ; therapy ; Treatment Outcome