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Femtosecond laser-assisted selective reduction of neovascularization in rat cornea
Sidhu, Mehra S.,Choi, Min-Yeong,Woo, Suk-Yi,Lee, Hyun-Kyu,Lee, Heung-Soon,Kim, Kyu-Jin,Jeoung, Sae Chae,Choi, Jun-Sub,Joo, Choun-Ki,Park, Il-Hong Springer London 2014 LASERS IN MEDICAL SCIENCE Vol.29 No.4
<P>Nonlinear multiphoton absorption induced by focusing near infrared (NIR) femtosecond (fs) laser pulses into a transparent cornea allows surgery on neovascular structures with minimal collateral damage. In this report, we introduce an fs laser-based microsurgery for selective treatment of rat corneal neovascularizations (in vivo). Contiguous tissue effects are achieved by scanning a focused laser pulse below the corneal surface with a fluence range of 2.2–8.6 J/cm<SUP>2</SUP>. The minimal visible laser lesion (MVL) threshold determined over the corneal neovascular structures was found to be 4.3 J/cm<SUP>2</SUP>. Histological and optical coherence tomography examinations of the anterior segment after laser irradiations show localized degeneration of neovascular structures without any unexpected change in adjacent tissues. Furthermore, an approximately 30 % reduction in corneal neovascularizations was observed after 5 days of fs laser exposure. The femtosecond laser is thus a promising tool for minimally invasive intrastromal surgery with the aid of a significantly smaller and more deterministic photodisruptive energy threshold for the interaction between the fs laser pulse and corneal neovascular structures.</P>
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Kwon, HyukIl,Lim, WonBong,Kim, JiSun,Jeon, SangMi,Kim, SangWoo,Karna, Sandeep,Cha, HyunRok,Kim, OkJoon,Choi, HongRan Baillière Tindall ; Springer London 2013 Lasers in medical science Vol.28 No.3
<P>Hyperglycemia occurs in patients with poorly controlled diabetes mellitus and contributes to bone resorption and increased susceptibility to bacterial infections. Hyperglycemia can incite low-grade inflammation that can contribute to the resorption of bone, especially the periodontal bone. The increased susceptibility to periodontal infections can contribute to bone resorption through the activation of osteoclasts. In this study, the osteoblastic, clonal cell line, MC3T3-E1, was used in an in vitro model of hyperglycemia and lipopolysaccharide-induced reactive oxygen species generation to determine the potential anti-inflammatory effect of 635 nm light-emitting diode (LED) irradiation or whether 635 nm LED irradiation can be a potential anti-inflammatory treatment. LED irradiation of MC3T3-E1 cells stimulated with lipopolysaccharide in a high glucose-containing medium decreased the level of cyclooxygenase gene and protein expression and reduced the level of prostaglandin E2 expression by decreasing the amount of reactive oxygen species generation. LED irradiation also inhibited the osteoclastogenesis in MC3T3-E1 cells by regulating the receptor activator of nuclear factor kappa-B ligand and osteoprotegerin. These findings reveal the mechanisms which are important in the pathogenesis of diabetic periodontitis and highlight the beneficial effects of 635 nm LED irradiation in reducing the adverse effects of diabetic periodontitis.</P>
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Therapeutic effects of systemic photodynamic therapy in a leukemia animal model using A20 cells.
Wen, Lan Ying,Bae, Su-Mi,Chun, Heung-Jae,Park, Kye-Shin,Ahn, Woong Shick Baillière Tindall ; Springer London 2012 LASERS IN MEDICAL SCIENCE Vol.27 No.2
<P>Photodynamic therapy (PDT) is attracting attention because of its noticeable inhibitory effects on the growth of dermatological and other solid tumors. Here, we studied the use of PDT in systemic diseases such as leukemia, lymphoma, and metastatic cancer, for which tumor formation areas cannot be clearly compartmentalized. We developed a systemic PDT method and examined its effect in a leukemia mouse model. Growth inhibition of A20 cells (H-2(d), murine B-lymphoma/leukemia, and Balb/c origin) induced by PDT/Photodithazine was evaluated by EZ-Cytox assay. After PDT, changes in cell morphology were assessed by light microscopy. Induction of apoptosis, as well as changes in the cell cycle, were assessed by fluorescence-activated cell sorting (FACS) analysis. A20 cells were injected into Balb/c mice through the tail veins, and PDT was performed. A total of 10 mg kg(-1) body weight of Photodithazine concentration was injected intravenously. After 5 min, micro photofibers (diameter, 200 μm) were inserted into the tail veins and irradiated at 1,200 J with a laser. PDT inhibited growth of A20 cells and resulted in marked morphological changes. PDT also induced apoptosis and G1 arrest. In a leukemia mouse model, systemic PDT increased the survival rate (p < 0.01). This is the first report of the effects of systemic PDT in a leukemia animal model. PDT has been applied only locally in most cases, for example to solid tumors. This study provides experimental evidence that systemic PDT could effectively be applied to systemic and spread tumors, for which tumor formation areas cannot clearly be determined.</P>
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Ko, Chang-Yong,Kang, Heesung,Ryu, Yeonhang,Jung, Byungjo,Kim, Hyunsoo,Jeong, Daewon,Shin, Hong-In,Lim, Dohyung,Kim, Han Sung Baillière Tindall ; Springer London 2013 Lasers in medical science Vol.28 No.6
<P>This study was aimed to evaluate the effects of low-level laser therapy (LLLT) in the treatment of trabecular bone loss induced by skeletal unloading. Twelve mice have taken denervation operation. At 2 weeks after denervation, LLLT (wavelength, 660 nm; energy, 3 J) was applied to the right tibiae of 6 mice (LASER) for 5 days/week over 2 weeks by using a minimally invasive laser needle system (MILNS) which consists of a 100 μm optical fiber in a fine needle (diameter, 130 μm) [corrected]. Structural parameters and histograms of bone mineralization density distribution (BMDD) were obtained before LLLT and at 2 weeks after LLLT. In addition, osteocyte, osteoblast, and osteoclast populations were counted. Two weeks after LLLT, bone volume fraction, trabeculae number, and trabeculae thickness were significantly increased and trabecular separations, trabecular bone pattern factor, and structure model index were significantly decreased in LASER than SHAM (p?<?0.05). BMDD in LASER was maintained while that in SHAM was shifted to lower mineralization. Osteocyte and osteoblast populations were significantly increased but osteoclast population was significantly decreased in LASER when compared with those in SHAM (p?<?0.05). The results indicate that LLLT with the MILNS may enhance bone quality and bone homeostasis associated with enhancement of bone formation and suppression of bone resorption.</P>
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Ahn, Inhye E,Ju, Ji Hyeon,Park, Sung-Hwan,Kim, Ho-Youn Acta Medica Belgica ; Springer London 2010 CLINICAL RHEUMATOLOGY Vol.29 No.2
<P>Erosions of the bone and cartilage are considered as a cardinal feature of rheumatoid arthritis (RA) leading to joint destruction and functional limitations. This report is a radiologic observation of distinguishable bone erosion repair with concomitant increase of radio-opacity of trabecular bones after 15 months of antitumor necrosis factor (TNF) antibody adalimumab therapy in a 26-year-old woman with RA resistant to conventional therapy. Although the introduction of anti-TNF antibodies has contributed to the slowing and arrest of RA progression, destruction itself has been generally acknowledged as an irreversible process with little hope (only 1.8% of erosions) in resolution. Our patient's dramatic structural retrieval is a discrepant, yet notable case pivoting the previous belief on the skeletal restoration capacity of anti-TNF antibody into a circulating cytokine-dependent manner.</P>
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Zhang, Xianglan,Choi, Eun Joo,Zheng, Zhenlong,Zhu, Lianhua,Cho, Sung Bin,Kim, Ki-Yoel,Kim, Jin,Cha, In-Ho Baillière Tindall ; Springer London 2015 LASERS IN MEDICAL SCIENCE Vol.30 No.1
<P>Pheophorbide a (Pa) is a chlorine-based photosensitizer, and Pa-mediated photodynamic therapy (PDT) reportedly exhibits antitumor activity against various malignancies. The aim of our study was to investigate the therapeutic effect of Pa-mediated PDT on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorobol-13-acetate (TPA)-induced mouse papillomas. Thirty mice received a topical application of DMBA/TPA on their backs to induce mouse papillomas. One week after two sessions of Pa-mediated PDT, immunohistochemical stains and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate the apoptotic effects thereof on the papillomas. Among 63 mouse papillomas treated with Pa-mediated PDT, 17.5% of the lesions were completely removed 1 week after the first treatment, while 31.7% disappeared 1 week after the second treatment. Statistical analyses revealed significant differences in therapeutic outcomes for the Pa-mediated PDT group in comparison to a solvent-PDT group and a Pa group. Additionally, a marked downregulation of proliferating cell nuclear antigen expression, as well as upregulation of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerase expression, was noted in the Pa-PDT group, compared to the solvent-PDT group and Pa group. TUNEL assay revealed higher apoptotic cell counts in the Pa-PDT group, although the difference was not statistically significant. Our data demonstrated that Pa-mediated PDT is effective in treating DMBA/TPA-induced mouse papillomas.</P>
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Moon, Sook,Bae, Jung Yoon,Son, Hwa-Kyung,Lee, Doo Young,Park, Gyeongju,You, Hyun,Ko, Hyojin,Kim, Yong-Chul,Kim, Jin Baillière Tindall ; Springer London 2015 LASERS IN MEDICAL SCIENCE Vol.30 No.2
<P>Photodynamic therapy (PDT) with photosensitizer is one of the promising modalities for cancer treatment. For clinical use of PDT, screening process should be preceded to enhance sensitivity to PDT. Thus, we investigated a molecular biomarker to determine the sensitivity to pheophorbide a (Pa)-PDT in immortalized human oral keratinocytes (IHOK) and oral squamous cell carcinoma (OSCC) cell lines. Two IHOK and several OSCC cell lines were used. After Pa-PDT, cell viability was reduced by more than 50%, and reactive oxygen species were generated in IHOK and OSCC cell lines. Additionally, apoptosis occurred in PDT-treated cells. IHOK(S) and IHOK(P), the two IHOK cell lines derived from the same source, showed a difference in cytotoxicity after Pa-PDT. To explain this difference in cytotoxicity, we looked at the expression of Wnt signaling-related genes in these two cell lines, for the morphology of IHOK(S) which was spindle like and elongated and distinct from IHOK(P) and the parent cell. Among the relevant genes, runt-related transcription factor 3 (RUNX3), an apoptosis-related gene, was selected as a potential marker that confers sensitivity to PDT. We found that the cytotoxicity by Pa-PDT was proportional to RUNX3 expression in OSCC cell lines. Additionally, knockdown of RUNX3 expression reduced cytotoxicity by Pa-PDT, suggesting that RUNX3 might be a biomarker to determine sensitivity to Pa-PDT. This was the first study to find a new target molecule that enhances Pa-PDT effects in IHOK and OSCC cell lines. Hence, the development of a PDT-dependent biomarker could provide a novel approach to improve the effects of PDT on oral precancerous and cancerous lesions.</P>
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Kim, Hye Won,Park, Jin Kyun,Yang, Ji-Ae,Yoon, Young Im,Lee, Eun Young,Song, Yeong Wook,Kim, Hang Rae,Lee, Eun Bong Acta Medica Belgica ; Springer London 2014 CLINICAL RHEUMATOLOGY Vol.33 No.9
<P>Clinical characteristics of antitumor necrosis factor (TNF) agents-related tuberculosis (TB) in ankylosing spondylitis (AS) are not well described. The aim was to compare the incidences and the characteristics of TB in AS and rheumatoid arthritis (RA) during TNF inhibitor treatment. AS (n?=?1,322) and RA (n?=?3,154) patients who received medical care between January 2001 and August 2011 were enrolled. The incidence of TB in patients treated, or not, with TNF inhibitors and the clinical features associated with TB were explored. Seven patients with AS and seven with RA developed TB while receiving TNF inhibitor therapy, resulting in an incidence rate of 600.2/100,000 person-years (PYs) (95 % confidence interval (CI), 241.3-1236.3) for those with AS and 771.6/100,000 PYs (95 % CI, 310.2-1589.9) for those with RA. Incidence rate ratios for TNF inhibitor-treated vs. untreated patients were 4.87 for AS (95 % CI, 1.50-15.39; p?<?0.001) and 3.61 for RA (95 % CI, 1.38-8.07; p?<?0.001). Low body mass index was identified as a significant risk factor for TB in the AS group (odds ratio (OR), 13.0; p?=?0.002). Extrapulmonary TB was predominant at 85.7 % during TNF inhibitor treatment. Three (42.8 %) of the AS patients, but none of the RA patients, developed TB with concomitant isoniazid. All AS patients recovered from TB whereas two of seven RA patients died. Treatment with TNF inhibitors significantly increases the risk of extrapulmonary TB in AS. Symptoms of infection should warrant clinicians to evaluate for TB during TNF inhibitor therapy in AS patients.</P>
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