BACKGROUND: The objective of this study was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) as a local salvage treatment after incomplete transarterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC). METHODS: The main eligibility criteria were a greatest tumor dimension (LD sum) <10 cm, inoperable HCC, and incomplete response after TACE. Prescribed SBRT doses were up to 60 gray (Gy) in 3 fractions, but doses were reduced until normal tissue constraints were allowed. RESULTS: Between May 2008 and February 2011, 50 patients were enrolled in this phase 2 trial, of which 47 patients were evaluable. Forty‐one patients had Child‐Pugh class A disease (A5/A6 were 32/9), 6 patients had class B7 disease, and 5 patients had portal vein tumor thrombosis. All patients underwent TACE 1 to 5 times before SBRT. SBRT doses ranged from 42 to 60 Gy in 3 fractions (median dose, 57 Gy), and the median LD sum was 29 mm (range, 13‐78 mm). Eighteen patients (38.3%) achieved complete remission within 6 months of completing of SBRT, and 18 patients (38.3%) had a partial response. The 2‐year local control rate was 94.6%, the overall survival rate was 68.7%, and the progression‐free survival rate was 33.8%. Three patients (6.4%) experienced grade 3 gastrointestinal toxicity, and 2 patients (4.3%) experienced grade 4 gastric ulcer perforation. CONCLUSIONS: This trial demonstrated that SBRT after incomplete TACE for inoperable HCC achieves promising rates of response and local control. On the basis of these study results, a modified, multi‐institutional, phase 2 trial to reduce gastrointestinal toxicity is recommended. Cancer 2012. © 2012 American Cancer Society.

BackgroundRecent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC.MethodsBetween 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0–7.0 cm), and the median dose was 51 Gy (range, 33–60 Gy).ResultsLC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45–54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT.ConclusionsThis study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.

The structures and functions of the cellular acidic compartments are strongly dependent on the pH gradients across vesicular membranes. Measurement and imaging of the vesicular pH require fluorophores with appropriate pK(a) values. In this report, we characterized the pH-dependent lifetime responses of a family of acidotropic probes, LysoSensors, to evaluate their usefulness to low-pH lifetime imaging. LysoSensors are cell-permeable weak bases that selectively accumulate in acidic vesicles after being protonated. They have higher quantum yields at lower pH ranges to allow visualization of the lysosomes. For LysoSensors DND-167, DND-189, and DND-153, raising the buffer pH increased the quenching effects of their basic side chains and substantially reduced their steady-state fluorescence and lifetimes. The apparent pK(a) values determined from their lifetime responses were shifted to near neutral values because of the dominant intensity contribution from their protonated species. One unique property of LysoSensor DND-189 is its nonmonotonic lifetime responses of the maxima occurring between pH 4 and 5. LysoSensor DND-192 did not show significant lifetime changes over a wide pH range. LysoSensor DND-160, which was the only excitation and emission ratiometric probe, showed significant pH-dependent lifetime changes as well as its spectral shifts. Its apparent pK(a) values determined from the lifetime responses were comparable to the lysosomal pH because of its bright basic form. Because of the pH-dependent absorption spectra, the apparent pK(a) values could be manipulated between 3 and 5 by changing the excitation and/or emission wavelengths. These results indicate that LysoSensor DND-160 is a promising probe for lifetime imaging to determine lysosomal pH.

SBRT using CyberKnife for localized prostate cancer is safe and well tolerated. We obtained promising results with 34 Gy in a 4-fraction regimen especially for the high-risk patients.

High dose SBRT for colorectal oligometastases was found to produce results comparable with surgical series. To improve local control, dose higher than 48 Gy are recommend when possible, but further study will be required to define the optimal normal tissue constraints and acceptable toxicity.

A new diketopiperazine alkaloid, golmaenone (1) and related alkaloids, neoechinulin A (2) and L-alanyl-L-tryptophan anhydride (3), have been isolated from the culture broth of the marine-derived fungus Aspergillus sp. The structure and absolute stereochemistry of the new compound (1) was assigned by spectroscopic methods and the advanced Marfey's method. Compounds 1 and 2 exhibited a significant radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC 50 values of 20 and 24 m mM, respectively, which are similar to the positive control, ascorbic acid (IC 50 , 20 m mM). Compounds 1 and 2 also showed an ultraviolet-A (UV-A) (320-390 nm) protecting activity with ED 50 values of 90 and 170 m mM, respectively, which are more active than oxybenzone (ED 50 , 350 m mM) currently being used as sunscreen.Key words diketopiperazine alkaloid; golmaenone; neoechinulin A; L-alanyl-L-tryptophan anhydride; marine-derived fungus; Aspergillus sp.Diketopiperazines are widespread microbial products commonly found in nutrient rich cultures of both terrestrial 1) and marine fungi.2,3) Diketopiperazines are of interest because of their activity in various pharmacological assay systems. 4)As part of a program to explore the bioactive metabolites produced by the fungi isolated from marine habitats, 5) we investigated the bioactive constituents of the marine algicolous fungus and isolated a new golmaenone (1) in addition to neoechinulin A (2) and L-alanyl-L-tryptophan anhydride (3).A fungal strain (culture # MFA 212) was isolated from the surface of the marine red alga Lomentaria catenata collected at Golmae Village, Ulsan City, Korea in 2002, and it was identified by fatty acid methyl ester anlaysis (FAME) as a Aspergillus sp.6) The fungus was cultured (10 l) in a seawaterbased medium. 7)The culture broth and mycelium were separated, and the broth was extracted with ethyl acetate to provide a crude extract (1.5 g), which was subjected to a combination of column chromatography on silica gel (n-hexane/EtOAc) and octadesyl silica (ODS) gel (H 2 O/MeOH) to furnish three fractions containing diketopiperazines 1 (20 mg), 2 (120 mg), and 3 (35 mg). Further purifications of each fraction by HPLC (YMC ODS-A, MeOH) yielded a new golmaenone (1) (12 mg), as well as neoechinulin A (2) (95 mg) and Lalanyl-L-tryptophan anhydride (3) (7 mg).Golmaenone (1) Table 1).The connection of the functional groups in 1, which led to the planar structure, was achieved on the basis of HMQC and HMBC correlations. Key HMBC correlations between H-15 and C-2, C-6 and C-16; between H-3 and C-7; between H-8 and C-7 and C-10; between H 3 -20/21 and C-16 and C-18; and between H-14 and C-8, C-10 and C-12, clearly estab- Fig. 1 lished the planar structure of 1.The geometry of C-8/C-9 double bond in compound 1 was determined to be (Z) configuration on the basis of the chemical shifts of H-8 [d 7.22 (1H, s)] and H-14 [d 11.57 (1H, s)], which were shifted to the low field by the deshielding effect of the carbonyl group on b-vinyl proton 9) and by the hydr...

We describe an approach to creating a new class of luminophores which display both long wavelength emissions exceeding 600 nm and long lifetimes. These luminophores are based on resonance energy transfer (RET) from a long lifetime donor to a short lifetime but long wavelength acceptor. We demonstrated the possibility of obtaining these desirable spectral properties using donors and acceptors noncovalently bound to DNA. The donor was a ruthenium (Ru) metal-ligand complex in which one of the diimine ligands intercalated into double-helix DNA. The acceptors were either nile blue, TOTO-3, or TO-PRO-3. Upon binding of the acceptor to donor-labeled DNA, we found that the acceptor quantum yield was remarkably enhanced so that the wavelength-integrated intensities of the donor and acceptor bound to DNA were many-fold greater than the intensity of the donor and acceptor alone when separately bound to DNA. The origin of this effect is efficient energy transfer from the donor. Under these conditions the effective overall quantum yield approaches that of the acceptor. Importantly, the increased quantum yield can be obtained while maintaining usefully long apparent acceptor lifetimes of 30 to 80 ns. The effect of an increased quantum yield from a low quantum yield donor may find use in assays to detect macromolecular binding interactions. These results suggest the synthesis of covalently linked donor-acceptor pairs with the desirable spectral properties of long wavelength emission, high quantum yield, and moderately long lifetimes for gated detection.

This study aimed to determine whether there are regional influences on attitudes toward olfaction. A total of 1082 participants aged 21-50 years from 4 different regions (Mexican, Korean, Czech, and German) were asked to rate general attitudes toward olfaction in everyday life. To examine affective attitudes to odors (i.e., pleasantness), participants were also asked to list 3 odors as being the most pleasant or unpleasant, respectively. Next, the mentioned odor names were attributed to 1 of 4 main categories: "Food & Drink," "Social relationship," "Nature," and "Civilization" and the distribution of these categories was compared across regions. Mexicans were significantly different to the other regions in their general attitudes toward olfaction. In addition, in all regions, in comparison with men, women indicated a higher interest in the sense of smell. Moreover, a significant positive correlation was present between individuals' self-rating of olfactory sensitivity and general attitudes toward olfaction. Finally, there were significant cross-regional differences in affective attitudes toward specific categories of odors. In conclusion, our findings support and extend the notion that regions affect attitudes toward the olfactory world.