Immunotherapy for Glioblastoma: Current State, Challenges, and Future Perspectives.

Glioblastoma is the most lethal intracranial primary malignancy by no optimal treatment option. Cancer immunotherapy has achieved remarkable survival benefits against various advanced tumors, such as melanoma and non-small-cell lung cancer, thus triggering great interest as a new therapeutic strategy for glioblastoma. Moreover, the central nervous system has been rediscovered recently as a region for active immunosurveillance. There are vibrant investigations for successful glioblastoma immunotherapy despite the fact that initial clinical trial results are somewhat disappointing with unique challenges including T-cell dysfunction in the patients. This review will explore the potential of current immunotherapy modalities for glioblastoma treatment, especially focusing on major immune checkpoint inhibitors and the future strategies with novel targets and combo therapies. Immune-related adverse events and clinical challenges in glioblastoma immunotherapy are also summarized. Glioblastoma provides persistent difficulties for immunotherapy with a complex state of patients' immune dysfunction and a variety of constraints in drug delivery to the central nervous system. However, rational design of combinational regimens and new focuses on myeloid cells and novel targets to circumvent current limitations hold promise to advent truly viable immunotherapy for glioblastoma.

Therapeutic Effects of Mesenchymal Stem Cells on a Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Model.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are the most severe cutaneous drug hypersensitivity reactions, which are unpredictable adverse drug reactions. SJS/TEN is associated with significant mortality and morbidity; however, effective treatment is difficult. Mesenchymal stem cells (MSCs) are well-known for their anti-inflammatory and tissue regeneration properties. The purpose of the present study was to verify whether MSCs could be applied for the treatment of SJS/TEN. We developed an SJS/TEN mouse model using peripheral blood mononuclear cells from a lamotrigine-induced SJS patient. MSCs were injected into the model to verify the treatment effect. In SJS model mice treated with MSCs, ocular damage rarely occurred, and apoptosis rate was significantly lower. We demonstrated a therapeutic effect of MSCs on SJS/TEN, with these cells presenting a potential novel therapy for the management of this disorder.

Gallic acid regulates body weight and glucose homeostasis through AMPK activation.

Gallic acid [3,4,5-trihydroxybenzoic acid (GA)], a natural phytochemical, is known to have a variety of cellular functions including beneficial effects on metabolic syndromes. However, the molecular mechanism by which GA exerts its beneficial effects is not known. Here we report that GA plays its role through the activation of AMP-activated protein kinase (AMPK) and by regulating mitochondrial function via the activation of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Sirtuin 1 (Sirt1) knockdown significantly blunted GA's effect on PGC1α activation and downstream genes, suggesting a critical role of the AMPK/Sirt1/PGC1α pathway in GA's action. Moreover, diet-induced obese mice treated with GA showed significantly improved glucose and insulin homeostasis. In addition, the administration of GA protected diet-induced body weight gain without a change in food intake. Biochemical analyses revealed a marked activation of AMPK in the liver, muscle, and interscapular brown adipose tissue of the GA-treated mice. Moreover, uncoupling protein 1 together with other genes related to energy expenditure was significantly elevated in the interscapular brown adipose tissue. Taken together, these results indicate that GA plays its beneficial metabolic roles by activating the AMPK/Sirt1/PGC1α pathway and by changing the interscapular brown adipose tissue genes related to thermogenesis. Our study points out that targeting the activation of the AMPK/Sirt1/PGC1α pathway by GA or its derivatives might be a potential therapeutic intervention for insulin resistance in metabolic diseases.

Appropriate timing for thyroidectomy scar treatment using a 1,550-nm fractional erbium-glass laser.

BACKGROUND: Surgical scarring is a common cosmetic problem that occurs in various surgical fields, including dermatology. Many trials have been conducted to determine how to prevent this distressing scar formation. A 1,550-nm fractional erbium-glass laser has been used to improve the appearance of surgical scars, but an appropriate treatment time has not been established. OBJECTIVES: To determine the appropriate time to apply 1,550-nm fractional erbium-glass laser treatment for thyroidectomy scars. MATERIALS AND METHODS: Korean patients with linear surgical suture lines after thyroidectomy (N = 65) were treated using a 1,550-nm fractional erbium-glass laser. Patients were divided into three groups according to postoperative treatment time. Laser treatment was started in 40, 15, and 10 patients 3 weeks, 3 months, and 6 months postoperatively, respectively. Each patient was treated three times at 1-month intervals using the same parameters (14 mJ, 100 spots/cm(2) , 2 passes). RESULTS: Mean Vancouver Scar Scale scores were significantly lower after laser treatment (p < .01), with the greatest difference in the group that began treatment 3 weeks postoperatively. Global assessment also indicated better cosmetic outcomes in the 3-week postoperative treatment group. CONCLUSION: Early postoperative 1,550-nm fractional erbium-glass laser treatment of thyroidectomy scars is more effective than later treatment.

Inhibitory effects of Saururi chinensis extracts on melanin biosynthesis in B16F10 melanoma cells.

Saururus chinensis has been used in folk medicine in Korea for the treatment of edema, jaundice, gonorrhea, and several inflammatory diseases. Saururi chinensis extracts (SCE) have demonstrated anti-inflammatory and anti-oxidant activities, as well as anti-asthmatic, antihypertensive, anti-angiogenic, and therapeutic activities for atopic dermatitis. However, the inhibitory activity of SCE on the melanogenesis signaling pathway is not completely understood. This study examined the effects of SCE on the melanogenesis signaling pathway activated by α-melanocyte-stimulating hormone (α-MSH). We found that SCE inhibited melanin production in a dose-dependent manner without causing cytotoxicity in B16F10 cells. Interestingly, SCE decreased α-MSH-induced tyrosinase activity in B16F10 cells but did not inhibit tyrosinase activity under cell-free conditions. The results of this study indicate that SCE may reduce pigmentation by way of an indirect, nonenzymatic mechanism. We also found that SCE decreased α-MSH-induced microphthalmia-associated transcription factor (MITF) and tyrosinase expression and induced the activation of extracellular signal-regulated kinase (ERK). These results suggest that the depigmenting effect of SCE may result from downregulation of MITF and tyrosinase expression due to increased ERK activity. Thus, our results provide evidence that SCE might be useful as a potential skin-whitening agent.

Treatment of infraorbital dark circles in atopic dermatitis with a 2790-nm erbium: yttrium scandium gallium garnet laser: a pilot study.

BACKGROUND: Although many Asian atopic patients have orbital darkening symptom and the demand to treat this condition is increasing, little has been reported in the literature on the treatment of infraorbital dark circles in atopic dermatitis. OBJECTIVE: To evaluate the clinical efficacy and safety of 2790-nm erbium:yttrium scandium gallium garnet (Er:YSGG) laser therapy for reducing infraorbital dark circles in atopic dermatitis patients. MATERIALS AND METHODS: Ten Korean patients over 21 year with mild atopic dermatitis and infraorbital dark circles were enrolled in this study. Patients who need active atopic dermatitis treatments are excluded because of the possibility of aggravation after laser treatment. They were treated for dark circles using a 2790-nm Er:YSGG laser. The treatment parameters were 1.8-2.2 J/cm² fluence, 6-mm spot size, and 0.3-ms pulse width with 10% overlap over the infraorbital areas once with a 4-week interval between treatments. Efficacy was assessed with a quartile grading score ranging from 0 to 5 by a blinded investigator, and the patients also documented their degree of satisfaction with the same grading score. All possible side effects were evaluated. RESULTS: The clinical assessment showed 74.5% (2.7) and 72.5% (2.5) improvements, and the patient satisfaction scale scores improved an average of 74% (2.4) and 71.5% (2.3) at 2 months and 4 months after treatment, respectively. There were no severe side effects or aggravation of atopic dermatitis. CONCLUSION: Our study suggests that 2790-nm Er:YSGG laser therapy can be effectively and safely used in the treatment of infraorbital dark circles in atopic dermatitis patients.

Acute dystonia by droperidol during intravenous patient-controlled analgesia in young patients.

Patient-controlled analgesia (PCA) is an important means for postoperative analgesia with parenteral opioid. However, postoperative nausea and vomiting (PONV) remains a major problem with a PCA system. Droperidol is used in PCA to prevent PONV. Extrapyramidal reactions by droperidol are, however, occasionally induced. We describe two cases of severe extrapyramidal hypertonic syndrome with an intravenous administration of droperidol in PCA in young patients, following orthopedic surgery.