Browsing by Author "Chiang, Hsin-Chien"

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Modulated electro-hyperthermia-enhanced liposomal drug uptake by cancer cells
(2019-01-01)
Tsang, Yuk-Wah
;
Chi, Kwan-Hwa
;
Huang, Cheng-Chung
;
Chi, Mau-Shin
;
Chiang, Hsin-Chien
Purpose: Modulated electro-hyperthermia (mEHT) stands to be a significant technological advancement in the hyperthermia field, utilizing autofocusing electromagnetic power on the cell membrane to create massive apoptosis. Since mEHT possesses the unique ability to excite cell membranes, we hypothesized that mEHT could enhance the uptake of liposomal drugs by enhancing phagocytic activity. Materials and methods: Water bath control and mEHT were used to compare the enhancement of liposome-encapsulated doxorubicin (Lipodox (R)) uptake by cancer cells. Cancer cells were made visible by doxorubicin fluorescence to investigate drug uptake. Viable cell yield was determined via the Trypan Blue exclusion method. Various substrates were used to investigate the mechanism of drug-uptake enhancement. The murine colon carcinoma model, CT26, was used to confirm the tissue infiltration of Lipodox (R) and its therapeutic effect. Results: mEHT treatment showed a significant enhancement of Lipodox (R) uptake of doxorubicin fluorescence compared with 37 degrees C or 42 degrees C water bath treatment. Tumor tissue sections also confirmed that mEHT treatment achieved the highest doxorubicin concentration in vivo (1.44 +/- 0.32 mu g/g in mEHT group and 0.79 +/- 0.32 mu g/g in 42 degrees C water bath). Wortmannin was used to inhibit the macropinocytosis effect and 70 kDa dextran-FITC served as uptake substance. The uptake of dextran-FITC by cancer cells significantly increased after mEHT treatment whereas such enhancement was significantly inhibited by wortmannin. Conclusion: The result showed mEHT-induced particle-uptake through macropinocytosis. mEHT-enhanced uptake of Lipodox (R) may amplify the therapeutic effect of liposomal drugs. This novel finding warrants further clinical investigation.
Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia
(2020-06-29)
Kuo, I-Ming
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Lee, Jih-Jong
;
Wang, Yu-Shan
;
Chiang, Hsin-Chien
;
Huang, Cheng-Chung
BackgroundModulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment.MethodsThis purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment.ResultsThe results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages.ConclusionsThe results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.
Relationship between Energy Dosage and Apoptotic Cell Death by Modulated Electro-Hyperthermia
(2020-06-02)
Kao, Patrick Hung-Ju
;
Chen, Chia-Hung
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Tsang, Yuk-Wah
;
Lin, Chen-Si
;
Chiang, Hsin-Chien
Modulated electro-hyperthermia (mEHT) is a form of mild hyperthermia (HT) used for cancer treatment. The principle utility of HT is the ability not only to increase cell temperature, but also to increase blood flow and associated pO(2) to the microenvironment. While investigational evidence has shown the unique ability of mEHT to elicit apoptosis in cancer cells, in vivo and in vitro, the same trait has not been observed with conventional HT. There is dissension as to what allows mEHT to elicit apoptosis despite heating to only mild temperatures, with the predominant opinion in favor of increased temperature at a cellular level as the driving force. For this study, we hypothesized that in addition to temperature, the amount of electrical energy delivered is a major factor in induction of apoptosis by mEHT. To evaluate the impact of electrical energy on apoptosis, we divided generally practiced mEHT treatment into 3 phases: Phase I (treatment start to 10min. mark): escalation from 25 degrees C to 37 degrees C Phase II (10min. mark to 15min. mark): escalation from 37 degrees C to 42 degrees C Phase III (15min. mark to 45min. mark): maintenance at 42 degrees C Combinations of mEHT at 18W power, mEHT at 7.5W power, water bath, and incubator were applied to each of the three phases. Power output was recorded per second and calculated as average power per second. Total number of corresponding Joules emitted per each experiment was also recorded. The biological effect of apoptotic cell death was assayed by annexin-V assay. In group where mEHT was applied for all three phases, apoptosis rate was measured at 31.18 +/- 1.47%. In group where mEHT was only applied in Phases II and III, apoptosis rate dropped to 20.2 +/- 2.1%. Where mEHT was only applied in Phase III, apoptosis was 6.4 +/- 1.7%. Interestingly, when mEHT was applied in Phases I and II, whether Phase III was conducted in either water bath at 42 degrees C or incubator at 37 degrees C, resulted in nearly identical apoptosis rates, 26 +/- 4.4% and 25.9 +/- 3.1%, respectively. These results showed that accumulation of mEHT at high-powered setting (18W/sec) during temperature escalation (Phase I and Phase II), significantly increased apoptosis of tested cancer cells. The data also showed that whereas apoptosis rate was significantly increased during temperature escalation by higher power (18W/sec), apoptosis was limited during temperature maintenance with lower power (7.5W/sec). This presents that neither maintenance of 42 degrees C nor accumulation of Joules by mEHT has immediate correlating effect on apoptosis rate. These findings may offer a basis for direction of clinical application of mEHT treatment.