Feasibility and effectiveness of treatment strategy of tandem high-dose chemotherapy and autologous stem cell transplantation in combination with 131 I-MIBG therapy for high-risk neuroblastoma.

This study was performed to evaluate the safety and effectiveness of tandem HDCT/ASCT combined with targeted radiotherapy using 131 I-MIBG for high-risk neuroblastoma. Patients with high-risk neuroblastoma were treated with 8 to 10 cycles of induction chemotherapy before tandem HDCT/ASCT. Patients received 131 I-MIBG treatment before the second HDCT/ASCT. Local radiotherapy and maintenance therapy were performed after tandem HDCT/ASCT. Between 2012 and 2016, 19 patients were diagnosed with high-risk neuroblastoma in our institution and 18 of them received tandem HDCT/ASCT combined with 131 I-MIBG therapy. For the first HDCT/ASCT regimen, 12 patients received busulfan/melphalan and six patients received melphalan/etoposide/carboplatin. The second HDCT included ThioCy. The median dose of 131 I-MIBG was 17.2 mCi/kg for the first eight patients, while 12 patients in the latter period of the study received reduced dose of 10.7 mCi/kg. The 5-year OS and EFS rates were 79% and 61%, respectively, for all 19 patients with high-risk neuroblastoma, and 83% and 64%, respectively, for 18 patients who completed tandem HDCT/ASCT combined with 131 I-MIBG therapy. Six patients experienced disease relapse and five patients died. Treatment-related mortality was not observed. Among 15 evaluable patients, 11 patients (73%) developed hypothyroidism, six patients (40%) had CKD, and six patients (40%) had growth failure. Hypothyroidism and growth failure were less frequent in patients who received reduced doses of 131 I-MIBG therapy. Tandem HDCT/ASCT combined with HD 131 I-MIBG therapy could be feasible for patients with high-risk neuroblastoma with acceptable toxicity profiles and favorable outcomes.

MRI Monitoring of Tumor-Selective Anticancer Drug Delivery with Stable Thermosensitive Liposomes Triggered by High-Intensity Focused Ultrasound.

Monitoring of drug release from a heat-activated liposome carrier provides an opportunity for real-time control of drug delivery and allows prediction of the therapeutic effect. We have developed short-chain elastin-like polypeptide-incorporating thermosensitive liposomes (STLs). Here, we report the development of STL encapsulating gadobenate dimeglumine (Gd-BOPTA), a MRI contrast agent, and doxorubicin (Dox) (Gd-Dox-STL). The Dox release profile from Gd-Dox-STL was comparable to Gd-Dox-LTSL; however, the serum stability of Gd-Dox-STL was much higher than Gd-Dox-LTSL. MRI studies showed that the difference in T1 relaxation time between 37 and 42 °C for Gd-Dox-STL was larger than the difference for Gd-Dox-LTSL. Although relaxivity for both liposomes at 42 °C was similar, the relaxivity of Gd-Dox-STL at 37 °C was 2.5-fold lower than that of Gd-Dox-LTSL. This was likely due to Gd-BOPTA leakage from the LTSL because of low stability at 37 °C. Pharmacokinetic studies showed plasma half-lives of 4.85 and 1.95 h for Gd-Dox-STL and Gd-Dox-LTSL, respectively, consistent with in vitro stability data. In vivo MRI experiments demonstrated corelease of Dox and Gd-BOPTA from STL under mild hyperthermia induced by high-intensity focused ultrasound (HIFU), which suggests STL is a promising tumor selective formulation when coupled with MR-guided HIFU.

Red ginseng delays age-related hearing and vestibular dysfunction in C57BL/6 mice.

Since Korean red ginseng (KRG) has been proven to protect against gentamicin-induced vestibular and hearing dysfunction, the effects of KRG on age-related inner ear disorder in C57BL/6 mice were investigated. While age-related hearing loss was detected at the age of 6months (32kHz) and 9months (16kHz) in the control group, it was significantly delayed (p<0.05) in the 150mg/kg KRG-treated group. Vestibular dysfunction was observed in the tail-hanging and swimming tests, with significantly different severity scores and swimming times detected between the control and 150mg/kg KRG-treated group at the age of 12months (p<0.05). Mice treated with 500mg/kg KRG exhibited irritability and aggravated inner ear dysfunction. Histological observation supported the findings of hearing and vestibular function defects. In conclusion, C57BL/6 mice showed early-onset hearing loss and progressive vestibular dysfunction with aging, which were delayed by treatment with 150mg/kg KRG. However, 500mg/kg KRG treatment may induce aggressive behavior.

High-intensity focused ultrasound-induced, localized mild hyperthermia to enhance anti-cancer efficacy of systemic doxorubicin: an experimental study.

The aim of this study was to evaluate the enhancement of the efficacy of systemic doxorubicin by pulsed high-intensity focused ultrasound (HIFU)-induced, localized mild hyperthermia. For the in vitro study, the intranuclear uptake of doxorubicin by squamous cell carcinoma (SCC)-7 cells incubated at different temperatures was compared. For the in vivo study, mice with SCC-7 tumors were assigned to either the control, conventional hyperthermia, HIFU hyperthermia, doxorubicin-alone, conventional hyperthermia + doxorubicin or HIFU hyperthermia + doxorubicin group. Conventional hyperthermia was induced by immersing the tumor in warm water (42.5°C), and HIFU hyperthermia was induced by HIFU after optimizing the parameters with direct temperature measurements (frequency = 1 MHz, pulse repetition frequency = 5 Hz, power = 12 W, duty cycle = 50%). In the in vitro study, fluorescence was more intense at 42°C than at 37°C and was time dependent. In the in vivo study, tumor growth in the HIFU hyperthermia + doxorubicin group was most prominently suppressed with the highest apoptotic index compared with all other groups (p < 0.05). Pulsed HIFU-induced localized mild hyperthermia enhanced the anti-cancer efficacy of systemic doxorubicin more than conventional mild hyperthermia.

In vitro and in vivo antioxidant activities of polysaccharide purified from aloe vera (Aloe barbadensis) gel.

The in vitro and in vivo antioxidant potentials of a polysaccharide isolated from aloe vera gel were investigated. Enzymatic extracts were prepared from aloe vera gel by using ten digestive enzymes including five carbohydrases and five proteases. Among them, the highest yield was obtained with the Viscozyme extract and the same extract showed the best radical scavenging activity. An active polysaccharide was purified from the Viscozyme extract using ethanol-added separation and anion exchange chromatography. Purified aloe vera polysaccharide (APS) strongly scavenged radicals including DPPH, hydroxyl and alkyl radicals. In addition, APS showed a protective effect against AAPH-induced oxidative stress and cell death in Vero cells as well as in the in vivo zebrafish model. In this study, it is proved that both the in vitro and in vivo antioxidant potentials of APS could be further utilized in relevant industrial applications.

Radiofrequency ablation for viable hepatocellular carcinoma around retained iodized oil after transcatheter arterial chemoembolization: usefulness of biplane fluoroscopy plus ultrasound guidance.

OBJECTIVE: To assess the technical feasibility and local efficacy of biplane fluoroscopy plus US-guided percutaneous radiofrequency ablation (RFA) for viable hepatocellular carcinoma (HCC) around retained iodized oil after transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Our prospective study was approved by our institutional review board and informed consent was obtained from all participating patients. For patients with viable HCC around retained iodized oil after TACE, biplane fluoroscopy plus US-guided RFA was performed. We evaluated the rate of technical success and major complications on a post-RFA CT examination and local tumor progression with a follow-up CT. RESULTS: Among 40 consecutive patients, 19 were excluded due to one of the following reasons: poorly visible HCC on fluoroscopy (n = 13), high risk location (n = 2), RFA performed under monoplane fluoroscopy and US guidance (n = 2), and poorly identifiable new HCCs on US (n = 2). The remaining 21 patients with 21 viable HCCs were included. The size of total tumors ranged from 1.4 to 5.0 cm (mean: 3.2 cm) in the longest diameter. Technical success was achieved for all 21 HCCs, and major complications were observed in none of the patients. During the follow-up period (mean, 20.3 months; range, 6.5-29.9 months), local tumor progression was found in two patients (2/21, 9.5%). Distant intrahepatic metastasis developed in 76.2% (16/21) of patients. CONCLUSION: When retained iodized oil around the tumor after TACE hampers the targeting of the viable tumor for RFA, biplane fluoroscopy plus US-guided RFA may be performed owing to its technical feasibility and effective treatment for viable HCCs.

[Clinicopathologic characteristics of superficial gastric cancer diagnosed at primary health care institutions in 2011].

BACKGROUND/AIMS: Stomach cancer is prevalent in Korea. The purpose of this study was to evaluate the characteristics of superficial gastric cancers detected at SOK Sokpeynhan Internal Medical Network, the nationwide primary health care institutions. METHODS: We prospectively analysed the clinicopathologic and endoscopic characteristics of 218 superficial gastric cancer patients diagnosed using gastric endoscopy at SOK network from January 2011 through December 2011. RESULTS: The mean age was 58.5 years old and male to female ratio was 1.7 : 1. Asymptomatic patients were most common (45.0%). The macroscopic classification revealed that simple types (63.8%) were more common than complex types (36.2%). The most common type was IIc (28.4%) and other types were as follows; IIb (16.1%), IIb+IIc (13.3%), IIa (10.6%), III (9.2%), IIa+IIc (7.3%), IIc+IIa (6.0%), IIc+IIb (5.0%). The most commonly involved sites were the body (53.1%) and greater curvature (32.6%) of the stomach. The size of lesion was less than 1 cm (69.3%) and less than 5 mm (33.5%) in diameter. The most common pathologic type was tubular adenocarcinoma (75.7%). Helicobacter pylori infection rate was 50.2%. Fifty five percent of the cases were diagnosed via endoscopy of National Health Insurance Corporation screenings. CONCLUSIONS: Superficial gastric cancers in 2011 at primary health care SOK network were different from those of previous reports. Type IIc was most common but type IIb was more prevalent and the body and greater curvature of the stomach were the most commonly involved sites. Therefore, careful observation of the proximal gastric mucosa and mucosal color change is needed.

Gas-filled phospholipid nanoparticles conjugated with gadolinium play a role as a potential theragnostics for MR-guided HIFU ablation.

To develop a long-circulating theragnostics, meaning therapeutics and diagnostics for MR-guided HIFU ablation, we designed and prepared Gd-C(5)F(12)-phospholipid nanobubbles (PLNs) 30-100 nm in diameter. The biochemical and physical characterization of Gd-C(5)F(12)-PLNs were performed. Since Gd-C(5)F(12)-PLN-50 (Φ = 50 nm) and Gd-C(5)F(12)-PLN-100 (Φ = 100 nm) enhanced the hyperthermal effect of HIFU size- and concentration-dependently in a tissue-mimicking phantom, its circulation, distribution, tumor accumulation and tumor ablation were examined in tumor-bearing mice. The plasma-half life of Gd-C(5)F(12)-PLNs was longer than 1.5 hrs. Gd-C(5)F(12)-PLNs mainly accumulated in the liver and the spleen, suggesting that they are slowly secreted through the hepatobiliary pathway. Monitored by the T1 signal intensity of MR, Gd-C(5)F(12)-PLNs accumulated in tumor tissues for 8 hours in mice. HIFU with Gd-C(5)F(12)-PLN-100 showed the increased tumor ablation area as compared with HIFU alone. The results suggest that Gd-C(5)F(12)-PLNs exhibit a potential theragnostics for MR-guided HIFU ablation.

Pattern and chronological change of iodized oil retention in radiofrequency ablation-induced vascular injury area: differentiation from iodized oil retention in recurrent hepatocellular carcinoma on computed tomography.

PURPOSE: The purpose of this study was to evaluate the pattern and the chronological change of iodized oil retention in a radiofrequency ablation (RFA)-induced vascular injury area as compared with that in recurrent hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Informed consents from all the patients and approval from the institutional review board were obtained. The computed tomographic scans of 226 patients who underwent both RFA and subsequent transcatheter arterial chemoembolization for recurrence were retrospectively reviewed. The RFA-induced vascular injury area that did not have HCC recurrence in it were examined and assessed whether iodized oil was retained after transcatheter arterial chemoembolization. We evaluated the incidence, the shape, and the duration of the iodized oil retention in the RFA-induced vascular injury area and compared them with those found in recurrent HCC from the same patient. The rate of misinterpretation was calculated. RESULTS: Of 59 RFA-induced vascular injury areas that were within the range of segmental embolization, 33 RFA-induced vascular injury areas (55.9%) in 31 patients retained iodized oil. The shapes of the iodized oil in the RFA-induced vascular injury area were diffuse-dense (n = 13), diffuse-faint (n = 8), nodular-dense (n = 8), or nodular-faint (n = 4). In 29 (93.5%) of 31 patients, at least one recurrent HCC retained iodized oil, and they were all nodular-dense in shape. The duration of the retention in RFA-induced vascular injury area (mean [SD], 3.3 [3.2] months) was significantly shorter than that in recurrent tumors (21.2 [12.5] months, P < 0.001). In 21.2% (7/33) of the cases, the iodized oil density in the RFA-induced vascular injury area was clinically misinterpreted as recurrent HCC. CONCLUSIONS: The RFA-induced vascular injury area frequently retains iodized oil, which could mimic recurrent HCC. However, we determined that iodized oil in the RFA-induced vascular injury area differs from that in HCC in variety in shape and shorter duration of retention.