Joo Heung Lee

Roles of AKT1 and AKT2 in non-small cell lung cancer cell survival, growth, and migration

Although AKT/protein kinase B is constitutively active in non‐small cell lung cancer (NSCLC) cells and is an attractive target for enhancing the cytotoxicity of therapeutic agents, the distinct roles of the AKT isoforms in NSCLC are largely unknown. In the present study, we investigated the roles of AKT1 and AKT2 in NSCLC cells using RNAi. The siRNA targeting of AKT1 or AKT2 effectively decreased protein levels of AKT1 and AKT2, respectively, in A549 and H460 cells. Cisplatin treatment of these cells increased apoptotic cell death compared with control. The siRNA‐induced knockdown of AKT1 in H460 cells significantly decreased basal MEK/ERK1/2 activity, resulting in nuclear factor‐κB activation, whereas knockdown of AKT2 resulted in anti‐apoptotic Bcl‐2 family protein MCL‐1 (MCL‐1) cleavage, the collapse of mitochondrial membrane potential, cytochrome c release, and activation of the caspase cascade. Consequently, both siRNA treatments enhanced the chemosensitivity of H460 cells to cisplatin. However, neither AKT1 nor AKT2 siRNA treatment had any effect of p27 expression, and although both treatments tended to induced G2/M phase arrest, the effect was not statistically significant. Treatment with AKT1 siRNA markedly decreased colony formation growth and migration, but AKT2 siRNA had no significant effects on these parameters. These data suggest that AKT1 and AKT2 both contribute to cell survival, albeit via different mechanisms, and that the effects on cell growth and migration are predominantly regulated by AKT1. These findings may aid in refining targeted strategies for the inhibition of AKT isoforms towards the sensitization of NSCLC cells to therapeutic agents. (Cancer Sci 2011; 102: 1822–1828)

Efficacy and safety of incobotulinum toxin A in periocular rhytides and masseteric hypertrophy: side-by-side comparison with onabotulinum toxin A

Background: Incobotulinum is a newly developed botulinum toxin A in which the complexing proteins had been removed. Objective: The aim was to compare the efficacy and safety of incobotulinum with onabotulinum in treating periocular rhytides and masseteric hypertrophy. Methods: A randomized, double-blind, split-face study was planned. Fifty-six patients were treated for periocular rhytides and the other 56 patients were treated for masseteric hypertrophy. Onabotulinum was injected on one side of the face and incobotulinum was injected on the other side of the face. The degree of periocular rhytides and masseteric hypertrophy was rated using Fitzpatrick Wrinkle Classification System (FWCS) and 10-point visual analogue scale (VAS) (0: the minimum to 10: the maximum). Objective and subjective rating was performed at pretreatment and every posttreatment follow-up visit by investigators and subjects. Result: The efficacy and safety of incobotulinum were not inferior to those of onabotulinum in treating periocular rhytides and masseteric hypertrophy up to 16 weeks after injection. There were no noteworthy differences in the onset time of effect between two botulinum toxins for periocular wrinkles and masseteric hypertrophy. No adverse event was reported. Conclusion: Incobotulinum provided non-inferior efficacy and safety for the treatment of periocular rhytides and masseteric hypertrophy compared with classic onabotulinum.

Dermatomyositis associated with generalized subcutaneous edema and Evans syndrome

Although periorbital edema is a common manifestation of dermatomyositis (DM), generalized subcutaneous edema associated with DM is extremely rare. Evans syndrome is an autoimmune disease in which an individuals antibodies attack ones own red blood cells and platelets. Evans syndrome is rarely a presenting feature of DM. DM has been rarely reported to be associated with either generalized edema or Evans syndrome. We report the case of a 52-year-old Korean woman who presented with generalized subcutaneous edema, an erythematous rash, dysphagia, and proximal muscle weakness, and subsequently developed features of Evans syndrome. Treatment with high-dose glucocorticoids and an immunosuppressive agent controlled the DM, the generalized subcutaneous edema, and the Evans syndrome.

Blastic Plasmacytoid Dendritic Cell Neoplasm: Analysis of Clinicopathological Feature and Treatment Outcome of Seven Cases

Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN), which is derived from the precursor of plasmacytoid dendritic cells, is a rare and highly aggressive hematologic malignancy. It has only recently been recognized as a distinct entity. BPDCN characteristically has a predilection for cutaneous involvement. Objective The aim of this study was to describe the clinical and pathological features of BPDCN, and to review the treatment courses to analyze the prognosis and the optimal therapeutic approach. Methods We retrospectively reviewed seven BPDCN cases registered in the Samsung Medical Center database between January 2010 and December 2014. Results The median age of the patients was 52 years (range, 18~79 years), and six patients were male. The clinical staging was as follows: skin (n=5), lymph node (n=6), bone marrow (n=4), and peripheral blood (n=2). The skin manifestations were bruise-like tumefaction (n=4), erythematous nodule (n=4), or multiple erythematous papules (n=1). The pathological evaluation revealed dense diffuse or nodular infiltration of neoplastic cells, which were positive for CD4, CD56, and CD123 in the immunohistochemical analysis. Six patients received multiagent chemotherapy as the first-line treatment, alone (n=4), or followed by stem cell transplantation (SCT, n=1) or concurrent radiotherapy (n=1). The median progression-free survival after the first-line treatment was 6 months (range, 2~12 months). Conclusion Three different skin manifestations were observed, with pathological features analogous to each other. All patients who received chemotherapy without SCT achieved partial or complete response but experienced relapse. Furthermore, they showed various clinical courses irrelevant to the cutaneous involvement.

Cutaneous Mycobacterium massiliense Infection of the Sole of the Feet.

Mycobacterium massiliense which is recognized as a separate species from M. abscessus is little known regarding its clinical patterns and the response to treatment. We present a case of a localized cutaneous infection due to M. massiliense of the sole associated with acupuncture. M. massiliense was identified via polymerase chain reaction-hybridization analysis. We treated the patient with single-drug therapy consisting of clarithromycin for 4 months and the patient showed a significant response to this treatment.

Photodynamic therapy using a new formulation of 5-aminolevulinic acid for wrinkles in Asian skin: A randomized controlled split face study

Abstract Background: Photodynamic therapy (PDT) with intense pulsed light (IPL) was proven effective for photorejuvenation. Recently, a new formulation of 0.5% 5-aminolevulinic acid (ALA) liposomal spray has been available. We designed a randomized split face study to evaluate usefulness and safety of IPL-PDT using a liposomal spray for periorbital wrinkles in Asians. Methods: Patients received three treatments every 3 weeks. The half of the face was treated with IPL-PDT and the other half with long pulsed Nd:YAG laser (LPNY). Skin fluorescence was measured using a spectrophotometer for the guidance of PDT treatment. Wrinkle score was marked by two-blinded independent dermatologists. Results: One patient dropped out due to 3-d lasting erythema on PDT side. The difference of mean reduction in lower and lateral periorbital wrinkle score on PDT side between the first and the last visit was statistically significant (p = 0.008 and p = 0.001, respectively). Lateral periorbital wrinkles treated with PDT showed better results than LPNY-treated sides. Twenty-five percent of patients reported good to excellent outcomes. Conclusion: This study demonstrated that PDT with a liposomal spray provided modest wrinkle reduction without serious adverse effect and it might be a promising treatment modality for wrinkle treatment in Asians.

A Case of Reticulate Acropigmentation of Kitamura Treated with 532-nm Q-Switched Nd:YAG Laser: 10 Years of Follow-Up Observation

Dear Editor: Reticulate acropigmentation of Kitamura (RAPK) is an uncommon pigmentary disorder that was first reported in Japan1. Since then, similar cases have been described worldwide; nevertheless, most were still in Japanese patients2. RAPK shows reticulate hyperpigmentation of the dorsum of the acral areas without hypopigmented macules. Despite the report of using 20% azelaic acid to treat RAPK, there has been no certain treatment guaranteeing a clinical effect for more than half a century3. Herein, we present a patient with RAPK who was successfully treated with 532-nm Q-switched Nd:YAG laser (532-nm QSND; MedLite IV Nd:YAG laser; HOYA ConBio, Fremont, CA, USA). A 29-year-old Korean woman visited our dermatologic clinic for childhood-onset acral hyperpigmentation in March 2002. Reticulate acral hyperpigmentation was recognized but no interspersed hypopigmentation was detected. She had no family history of pigmentary disorder. She neither had taken medication known to induce hyperpigmentation nor had a history of contact to any chemical agent that can cause pigmentary changes. She underwent skin biopsies for the hyperpigmented confluent patch on the dorsum of the hand and discrete hyperpigmented macule on the dorsum of the foot. Histologically, lentiginous melanocytic hyperplasia and some dermal melanophages were observed with mild epidermal atrophy (Fig. 1). On the basis of the findings, we made a diagnosis of RAPK. Considering the histologic findings of superficially situated melanocytic hyperplasia, we used 532-nm QSND. We tested the laser to evaluate its efficacy and safety. A small area of the left arm was selected as the test area. Topical anesthetic agent was applied on the area before treatment. Treatment with parameters of 4-mm spot size, 2 J/cm2 was applied. Some pain was present during treatment but it was tolerable, and significant clinical improvement was observed in the area without any complication. We gradually expanded the treatment area. During the sessions, mild blisters developed after treatment with 2.7 J/cm2 or higher; however, they disappeared without leaving hyper- or hypopigmentation. A total of seven sessions of laser treatment, with energy between 2.0 and 2.7 J/cm2, were successfully made from March 2002 to November 2007 (Fig. 2), and the interval between treatments was several months to 2 years. Thereafter, she was lost to follow-up for 4 years because of personal reasons. In March 2012, she visited our clinic for treatment of the remaining lesions. There was neither a recurrence of RAPK nor treatment-related adverse effects on the previously treated area. We treated the residual lesions with same parameters as previously used, and the clinical effect was also good. Fig. 1 (A) Lentiginous melanocytic hyperplasia and dermal melanophages with some degree of epidermal atrophy (H&E, ×100). (B) Lentiginous hyperplasia of the basal melanocytes (Fontana Masson, ×100). Fig. 2 (A) Reticulated brownish patches on the dorsum of both hands before treatment. (B) Significant improvement of hyperpigmentation after seven sessions of treatment

A case of cutaneous metastatic cholangiocarcinoma on the percutaneous transhepatic biliary drainage catheter insertion site.

Dear Editor: Cutaneous metastasis of cholangiocellular carcinoma (CCC) is a rare occurrence and the majority of such cases develop after the placement of a percutaneous transhepatic biliary drainage (PTBD) catheter1. Most cases of PTBD catheter-related cutaneous metastatic CCC that have been reported in the literature to date have rarely included a dermatologic manifestation2. Herein, we report a case of cutaneous metastatic CCC that developed after PTBD catheter insertion. A 74-year-old male patient who had an unresectable CCC visited our dermatology clinic for evaluation of a firm, 2 cm-sized, erythematous and hyperpigmented nodule on his right abdomen. The nodule had developed on the exit site of a former indwelling PTBD catheter. The catheter had been inserted one year prior and was removed after 5 months. A percutaneous transhepatic gallbladder drainage catheter had then been inserted near the exit site of the former PTBD catheter. The nodule had appeared 6 months after the removal of the PTBD catheter and it had gradually increased in size (Fig. 1). The patient had a medical history of malignancies associated with percutaneous indwelling catheters; therefore, we performed a skin biopsy on the nodule to determine if it was a possible skin metastasis or a hypertrophic scar. The histopathology results identified well-developed glands composed of atypical tumor cells between the sclerotic scar tissues (Fig. 2). Based on the clinical and histologic findings, we made a diagnosis of metastatic CCC resulting from PTBD catheter insertion. PTBD is commonly used in the treatment of malignant biliary obstruction and catheter-related cutaneous metastasis on the PTBD exit site has been only rarely reported since the 1980s3. Catheter-related metastasis can develop at all sites along the catheter tract, from the insertion site to the exit site4. Recently, Takahashi et al.5 suggested that the incidence of cutaneous metastasis related to PTBD has been rather underestimated. They reported that catheter site metastasis may recur metachronously or synchronously, and the mean time interval between catheter insertion and the onset of recurrence was 14.4 months. Fig. 1 Brownish firm nodule on the site of right flank which is exit site of the prior percutaneous transhepatic biliary drainage catheter. Current percutaneous transhepatic gallbladder drainage catheter is indwelled beside the tumor. Fig. 2 Metastatic tumor cells intervening sclerotic dense collagen fibers in the dermis (H&E, ×40) and atypical cells form gland like structures (inset: H&E, ×100). As in this case, catheter-related skin metastasis usually occurs at the catheter insertion site and evolves rapidly. It can be difficult to differentiate between this metastasis and a hypertrophic scar. Therefore, clinicians should make careful observations and meticulously evaluate, by histopathology, any suspicious skin lesion associated with a PTBD catheter.