Phil Sang Chung

Intratumoral hypericin and KTP laser therapy for transplanted squamous cell carcinoma.

Objectives/Hypothesis To test intratumoral photodynamic therapy (IPDT) as a new treatment for squamous cell carcinoma in a preclinical tumor model.

Role of surgery in the management of anaplastic thyroid carcinoma: Korean nationwide multicenter study of 329 patients with anaplastic thyroid carcinoma, 2000 to 2012

The Korean Society of Thyroid Head and Neck Surgery established a nationwide multicenter registry of anaplastic thyroid carcinoma (ATC) and evaluated the prognostic factors and treatment outcomes of ATC.

Oxidative stress induced by carboplatin promotes apoptosis and inhibits migration of HN‑3 cells

Laryngeal squamous cell carcinoma (LSCC) is currently a serious public health problem in China; thus, it is urgent to identify effective treatment strategies for this disease. Previous studies demonstrated that reactive oxygen species (ROS) serve important roles in the apoptosis of LSCC cells. It has also been indicated that carboplatin (CBDCA), a second-generation platinum compound with broad antineoplastic properties, is able to induce oxidative stress to produce ROS, which in turn promotes apoptosis. Thus, the present study investigated if CBDCA is cytotoxic in LSCC cells due to the oxidative stress caused by ROS. Therefore, an MTT assay was performed to determine the cell viability of HN-3 LSCC cells following treatment with different doses of CBDCA. Subsequently, the expression levels of ROS and the rate of apoptosis/necrosis were evaluated in the cells. Following this, the HN-3 cells were co-treated with CBDCA and glutathione (GSH) or H2O2, followed by an MTT assay, a cell migration assay and western blot analysis. The results demonstrated that CBDCA reduced the viability of HN-3 cells in a time- and dose-dependent manner and promoted the production of ROS and apoptosis at certain doses. Additionally, the combination treatment of CBDCA and H2O2 enhanced the inhibitory effects of CBDCA on cell viability and migration ability, and promoted apoptosis in HN-3 cells; whereas the combined treatment of CBDCA and GSH exerted opposite effects. The results of the present study demonstrated that CBDCA promotes the apoptosis of HN-3 cells through accumulation of ROS, which may provide a novel treatment strategy for treating LSCC.

Mechanism of HN‑3 cell apoptosis induced by carboplatin: Combination of mitochondrial pathway associated with Ca2+ and the nucleus pathways

Laryngeal carcinomas have been recognized as a serious health threat worldwide. In the present study, the mechanism of apoptosis in HN-3 cells induced by carboplatin (CBCDA), a widely used anti-cancer drug, was investigated. The pro-apoptotic effect of CBCDA in HN-3 cells was demonstrated to be time- and dose-dependent. Therefore, the stages of apoptosis were investigated in chronological order. The results demonstrated that excessive generation of cytosolic Ca2+ in HN-3 cells was initially triggered when cells were exposed to CBCDA, followed by the appearance of mitochondrial depolarization and oxidative stress, leading to the release of apoptosis-inducing factor. At later stages, expression of caspase-8 was increased due to the apoptotic signals originating from CBCDA-induced DNA damage, as well as caspase-9 and poly ADP ribose polymerase (PARP) expression upregulation. Glutathione decreased the available CBDCA concentration, decreased apoptosis and alleviating oxidative stress, thus reducing the actual effective concentration. Mechanistic research may benefit the rational design of more efficient therapeutic strategies as well as development of novel platinum-based agents.

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.

Photosensitizer effect of 9-hydroxypheophorbide α on diode laser-irradiated laryngeal cancer cells: Oxidative stress-directed cell death and migration suppression

The present study aimed to investigate the effect, and elucidate the potential mechanisms, of 9-hydroxypheophorbide α-based photodynamic therapy (9-HPbD-PDT) on apoptosis and necrosis induction, and migration suppression of laryngeal cancer AMC-HN-3 (HN-3) cells. Phototoxicity initiated by 9-HPbD-PDT on HN-3 cells was observed in a photosensitizer dose-dependent pattern. There was an initial increase of apoptotic cells coupled with gradual enhancement of reactive oxygen series (ROS) generation at lower doses of 9-HPbD. By contrast, at a higher dose of 9-HPbD, there was a clear increase of necrotic cells with a gradual decrease of ROS generation. Following PDT, an elevated percentage of apoptotic cells with shrinkage or condensing nuclei was observed using Hoechst 33342/propidium iodide double staining, and an upregulated expression of poly ADP-ribose polymerase was detected through western blotting. A disruption of the mitochondrial membrane potential was detected 2 h following PDT. Significant suppression of cell migration and downregulation of epidermal growth factor receptor (EGFR) expression were recorded following PDT. These results indicate that the distribution of photosensitizer leads to differences in the generation of ROS, which subsequently determines the type of cell death. Overall, mitochondrial activation under oxidative stress is important in the 9-HPbD-PDT-induced apoptosis of HN-3 cells. Migration suppression of HN-3 cells following PDT may be associated with the inhibited expression of EGFR, due to oxidative stress.

Photodynamic Therapy of otitis media in-vitro and in-vivo using gerbil

The aim of this study was to evaluate antibacterial effects of PDT on common bacteria causing otitis media with effusion (OME). In vitro study was carried out using a hematoporphyrin derivative sensitizer (photogem) and 632 nm diode laser on H. influenzae, M. catarrhalis, and S. pneumoniae. One ml of each bacterial suspension was incubated for 3 hours and various concentrations of photogem were administered into the suspension. The suspensions were irradiated with 632 diode laser (15 J/cm2). The presence of colony forming units of the bacteria was examined, microscopic structures of bacteria were examined by TEM, and cytometry of bacteria was performed. The PDT was effective in killing all 3 kinds of bacteria. TEM showed damaged bacterial cell membrane and cytoplasmic structures and the flow cytometry showed lower number of viable bacteria in PDT group comparing to the control group. In vivo PDT study was performed using gerbil. S. pneumoniae or H. influenzae was injected into bullae. Photogem was injected into bullae in 2 days by when OME was developed and transcanal irradiation of 632 nm diode laser (90 J) was performed with a fiber perforated through an ear drum into a middle ear cavity and bulla. Four days after PDT, middle ear and bulla were washed with DPBS and the washed DPBS was cultured. The presence of bacterial colonies was examined. PDT was effective in killing S. pneumoniae in 87 % of the infected bullae with OME while it was effective to eradicate H. influenzae in 50 % of the infected bullae with OME. The results of these studies demonstrated that PDT may be effective to treat otitis media. It may have clinical implication to treat otitis media that is resistant to antibiotic therapy.