Jeong Hwan Moon

Chlorin e6 Derivative Radachlorin Mainly Accumulates in Mitochondria, Lysosome and Endoplasmic Reticulum and Shows High Affinity toward Tumors in Nude Mice in Photodynamic Therapy

The efficacy of photodynamic therapy (PDT) depends upon the amount of photosensitizer accumulated in the malignant tissues. Radachlorin is a popular photosensitizer used in photodynamic therapy to treat various types of cancer. In this study, we have studied the main organelles responsible for the accumulation of radachlorin in human anaplastic thyroid cancer in vitro and in vivo. The optimal time window for uptake and clearance of radachlorin also was studied. Confocal microscopic images confirmed that the radachlorin is mainly acquired by mitochondria and partially by lysosome and endoplasmic reticulum. Studies also showed that the maximum amount of radachlorin was accumulated within 3–6 h after the treatment. Radachlorin also showed a higher affinity toward malignant tumors compared to the other organs in mice xenograft model. Uptake of radachlorin reached an optimum amount within 6 h and most of the radachlorins were also cleared from the body in next 48 h. Therefore, detailed information regarding exact accumulation sites and a time window in which maximum amount of drug is accumulated and cleared were obtained by this study. Hence, not only the efficacy of the treatment can be increased but the phototoxicity after the treatment also can be controlled.

Carboplatin synergistically triggers the efficacy of photodynamic therapy via caspase 3-, 8-, and 12-dependent pathways in human anaplastic thyroid cancer cells

Anaplastic thyroid cancer is one of the most aggressive forms of malignancies which grow very rapidly. Several conventional methods have been applied for the treatment of anaplastic thyroid cancer, but most of them were not successful in complete recovery of the patients. Therefore, a combination of two or more conventional modalities is being applied nowadays for the treatment of this type of cancer. In this present study, the combination of photodynamic therapy (PDT) and chemotherapy has been studied in anaplastic thyroid cancer. Human anaplastic thyroid cancer cells FRO were treated with a chemotherapy drug, carboplatin (cis-diammine-1,1-cyclobutanedicarboxyl-ateplatinum II (CBDCA)), and radachlorin-mediated PDT individually and in combination. Several parameters like cytotoxicity assay by MTT, apoptosis study by annexin V and propidium iodide, cell cycle analysis by flow cytometry, confocal microscopic study, and Western blot analysis for different apoptosis-related proteins like Bax, cytochrome c, caspases 3, 9, 8, and 12, etc. were studied to check the efficacy of the combination treatment as well as to find out the mechanism of this enhanced efficacy. Results showed that both PDT and CBDCA can induce apoptosis in FRO cells. However, a synergistic efficacy was observed when the cells were treated with CBDCA and PDT in combination. Changes in mitochondrial membrane potential and an increase in reactive oxygen species generation were observed in combination treatments. The enhanced expression of different apoptotic pathway-related proteins like Bax, cytochrome c, caspase 3, caspase 8, caspase 12, etc. also confirmed the higher efficacy of combination treatment. Therefore, with this combination treatment, not only a higher efficacy can be achieved but also the effective dose of the chemotherapy drug can be reduced, and hence, the adverse side effects of the chemotherapy drugs can also be controlled.

Enhanced survival of ischemic skin flap by combined treatment with bone marrow-derived stem cells and low-level light irradiation

The aim of this study is to examine the enhanced survival effect of ischemic skin flap by combined treatment with bone marrow-derived stem cells (BMSCs) and low-level light irradiation (LLLI). The neovasculogenic effect of BMSCs induced by LLLI was detected using a wound healing and tube formation assay. ICR mice were divided into four groups: control group, LLLI group, BMSCs group, and combine-treated group. The percentage of skin flap necrosis area was calculated on the seventh post-operative day. Specimens were harvested for histologic analyses. LLLI promoted BMSC migration and tube formation. The flap survival rate of combined treated group was significantly higher than that of the control group. Histologic results demonstrated a significant increase in neovascularization in the combined treatment group. This study demonstrates that combination treatment of BMSCs and LLLI could enhance the survival of ischemic skin flap in a mouse model.

Effect of Topical Propolis on Wound Healing Process After Tonsillectomy: Randomized Controlled Study

Objectives The post-tonsillectomy pain and post-tonsillectomy hemorrhage are the two main problems after tonsillectomy. The aim of this study was to investigate the beneficial effects of water soluble ethanol extract propolis on post-tonsillectomy patient. Methods One hundred and thirty patients who underwent tonsillectomy or adenotonsillectomy were randomly divided into the control and propolis groups, each including 65 patients. The propolis group was applied with propolis orally immediately after surgery and by gargle. The pain scores were assessed on post-tonsillectomy 0, 1st, 2nd, 3rd, and 7th–10th day using a visual analogue scale score. Postoperative wound healing was evaluated by scoring pinkish membrane of tonsillar fossae on postoperative days 3 and 7–10. The incidence of post-tonsillectomy bleeding was examined in each group. Results Post-tonsillectomy pain was significantly less in propolis group compared to control group on postoperative days 3 and 7–10. Post-tonsillectomy hemorrhage was significantly less in the propolis group compared to the control group (P<0.05). The wound healing was significantly better in the propolis group compared to the control group on postoperative day 7–10 (P=0.002). Conclusion Applying the propolis to post-tonsillectomy wound showed beneficial effect of reducing postoperative pain, preventing hemorrhage, and accelerating of wound healing of tonsillar fossae.

Low-level laser therapy with 850 nm recovers salivary function via membrane redistribution of aquaporin 5 by reducing intracellular Ca 2+ overload and ER stress during hyperglycemia

The overall goal is to study the effect of low-level laser therapy (LLLT) on membrane distribution of major water channel protein aquaporin 5 (AQP5) in salivary gland during hyperglycemia. Par C10 cells treated with high glucose (50 mM) showed a reduced membrane distribution of AQP5. The functional expression of AQP5 was downregulated due to intracellular Ca2+ overload and ER stress. This reduction in AQP5 expression impairs water permeability and therefore results in hypo-salivation. A reduced salivary flow was also observed in streptozotocin (STZ)-induced diabetic mice model and the expression of AQP5 and phospho-AQP5 was downregulated. Low-level laser treatment with 850 nm (30 mW, 10 min = 18 J/cm2) reduced ER stress and recovered AQP5 membrane distribution via serine phosphorylation in the cells. In the STZ-induced diabetic mouse, LLLT with 850 nm (60 J/cm2) increased salivary flow and upregulated of AQP5 and p-AQP5. ER stress was also reduced via downregulation of caspase 12 and CHOP. In silico analysis confirmed that the serine 156 is one of the most favorable phosphorylation sites of AQP5 and may contribute to the stability of the protein. Therefore, this study suggests high glucose inhibits phosphorylation-dependent AQP5 membrane distribution. High glucose induces intracellular Ca2+ overload and ER stress that disrupt AQP5 functional expression. Low-level laser therapy with 850 nm improves salivary function by increasing AQP5 membrane distribution in hyperglycemia-induced hyposalivation.

Interstitial Laser Photocoagulation Using 980 nm Diode Laser in Benign Thyroid Nodule: A Feasibility Study

The aim of this study was to investigate the feasibility of using 980 nm diode laser for interstitial laser photocoagulation (ILP) before clinical application in benign thyroid nodule treatment. The bovine livers were cut into blocks to irradiate with 980 nm laser through the lumen of a 20-gauge spinal needle using a fiber optic guide. Laser irradiation was performed with the output power of 2 W and 3 W for 60, 120 and 180 seconds respectively. The liver blocks containing lesions were dissected along the axis of the fiber optic tracts and then cut transversely into slices. The thermal effect was evaluated by measuring the dimensions of the zone of coagulation necrosis. We present a case treated with 980 nm diode laser for the benign large thyroid nodule. All the irradiated areas zone measured in the gross specimens were 5.5 mm ± 1.4 mm (2 W, 60 s), 6.9 mm ± 1.4 mm (2 W, 120 s), 7.3 mm ± 0.5 mm (2 W, 180 s), 8.8 mm ± 2.2 mm (3 W, 60 s), 9.2 mm ± 0.8 mm (3 W, 120 s), 12.5 mm ± 4.1 mm (3 W, 180 s) respectively. The transverse diameter was as 5.1 mm ± 0.5 mm (2 W, 60 s), 6.1 mm ± 0.2 mm (2 W, 120 s), 9.9 mm ± 2.5 mm (2 W, 180 s), 6.2 mm ± 1.8 mm (3 W, 60 s), 7.7 mm ± 1.2 mm (3 W, 120 s), 8.8 mm ± 0.7 mm (3 W, 180 s) respectively. ILP was well tolerated and there was no complication. Interstitial laser photocoagulation with 980 nm diode laser induces well-defined tissue ablation correlated with energy parameters in bovine liver tissue and therefore, could be an efficient therapeutic tool in benign thyroid nodular disease.