Apoptotic mechanism induced by 9-HPbD-PDT in AMC-HN-3 cellsSkin phototoxicity is one of the main side effects of photodynamic therapy (PDT). To overcome this problem, some new photosensitizers have been developed with longer absorbance wavelengths and shorter half-life in the body. In this study, we investigated the mechanism of PDT mediated by a new chlorophyll derivative photosensitizer, 9-hydroxypheophorbide α (9-HPbD), on AMC-HN-3 cancer cells. Phototoxicity and apoptosis on AMC-HN-3 cells induced by 9-HPbD was exhibited in a time-and dose-dependent manner. Mitochondria and endoplasmic reticulum (ER) were observed as preferential sites of 9-HPbD accumulation. Photoactivation of 9-HPbD-loaded AMC-HN-3 cells led to a rapid generation of reactive oxygen species (ROS) at 30 min, followed by a loss of mitochondrial membrane potential (MMP) at 2 h, translocation of apoptosisinducing factor (AIF) at 2 h, and the release of cytochrome c at 3 h following PDT. Caspase-12, an important caspase involved in ER-induced apoptosis, and C/EBP homologous protein (CHOP), an ER stress inducible transcription factor, were also upregulated after PDT (3-12 h and 6-12 h, respectively). Subsequently, activation of caspase-9 at 6 h, caspase-3 and PARP at 12 h also occurred in PDT-treated AMC-HN-3 cells.The above observations demonstrate that both mitochondria and ER serve not only as the sites of sensitizer binding, but also the subcellular targets of 9-HPbD-PDT, effective activation of which is responsible for 9-HPbD PDT-induced apoptosis in AMC-HN-3 cells.

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.

Background: The aim of study is to investigate the role of transient receptor potential cation channel subfamily V member 1 (TRPV1) on xerostomia-induced inflammatory response in vivo. Methods: Parotid, submandibular, and lingual gland were removed for xerostomia induction. The expression of inflammatory cytokines, TRPV1, NFkB, and MAPK in xerostomia was evaluated and compared in both TRPV1 wild and knockout mice. Results: The level of interleukin-6 (IL-6) and IL-17, neutrophil/CD4 T-cell infiltration, phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N terminal kinase, TRPV1, and the localization of NFkB were elevated in xerostomia-induced TRPV1 wild-type mice. In contrast, inflammatory cytokines and MAPK were decreased in xerostomia-induced TRPV1 knockout mice. TRPV1 antagonist treatment also reduced tongue ulceration, neutrophil/CD4 + T-cell expression, IL-6, and IL-17 in TRPV1 wild-type mice. Conclusion: TRPV1 had a crucial role in modulating inflammation in xerostomia and targeting TRPV1 might be a promising therapeutic strategy for xerostomia.

Objective: Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV) types 6 and 11 and is potentially preventable through vaccination. This study estimated incidence of juvenile-onset RRP before the implementation of the national HPV vaccination program in South Korea. Methods: We conducted a cohort study using claims data provided by a mandatory insurance program to estimate the incidence of RRP and associated healthcare use. Patients with juvenile RRP were defined as those aged ≤12 years with ≥2 admission or ≥2 outpatient visits during which they received the International Classification of Diseases code of benign neoplasms of the larynx (D14.1). Results: During 2002-2014, 123 children (74 boys and 49 girls) were diagnosed with RRP. The patients had a mean of 6.5 person-years of follow-up. The incidence was estimated at 0.30/100,000 person-year. The median age at diagnosis was 4 (mean, 4.3) years. Thirty-six (29.3%) patients underwent surgery, including 23 patients (18.7%) who underwent 2 or more surgeries. Severe disease, measured by more frequent surgeries and shorter time intervals between consecutive surgeries, was associated with a younger age at diagnosis. Conclusion: The estimated incidence of juvenile-onset RRP in South Korea was similar to that reported in other countries. The RRP burden should continue to be monitored using the National Health Insurance Service claims data.

Background and ObjectivesAnaplastic thyroid carcinoma (ATC) is one of the lethal human neoplasms. Photodynamic therapy (PDT) is based on the interaction of a photosensitizer and light with a specific wavelength, and induces destruction of cancer cells. The purpose of this study is to evaluate the effect of the PDT with photofrin on SNU-80 anaplastic thyroid cancer cells. Materials and MethodsAfter PDT, cell viability was measured by MTT assay. The experiments were done at photofrin concentration of 1.6 to 3.2 μg/ml. Subcellular localization of photofrin were observed by ER-Tracker TM and Mito-Tracker ® . Hoechst and propidium iodide (PI) double stained cells were analyzed to measure the cellular apoptosis and necrosis using confocal microscope at 4, 8, and 24 hours after laser irradiation. Caspase activation was measured by western blot analysis. ResultsCytotoxicity was increased accordingly to increasing photofrin concentration in MTT assay. The photofrin was localized at cytoplasm and mitochondria inside SNU-80 cells. Apoptosis and necrosis cells were increased on confocal microscope, as time after irradiation was progressed. The expression of caspase-3, -9 and poly (ADP-ribose) polymerase (PARP) were detected by Western blot analysis indicating that Photoprin-PDT showed cytotoxicity to anaplastic thyroid cancer cells in dose-dependent pattern. ConclusionPhotofrin-PDT led to in vitro cell death of SNU-80 cells through mitochondrial mediated apoptosis. PDT could be used as a part of multimodal treatment for ATC.