Curcumin-Induced Apoptosis in Human Hepatocellular Carcinoma J5 Cells: Critical Role of Ca+2-Dependent Pathway

The antitumor effects of curcumin, a natural biologically active compound extracted from rhizomes of Curcuma longa, have been studied in many cancer cell types including human hepatocellular carcinoma (HCC). Here, we investigated the effects of Ca2+ on curcumin-induced apoptosis in human HCC J5 cells. The abrogation of mitochondrial membrane potential (ΔΨm), the increase of reactive oxygen species (ROS) production, and calcium release were demonstrated with flow cytometry as early as 15 minutes after curcumin treatment. In addition, an increase level of cytochrome c in the cytoplasm which led to DNA fragmentation was observed. To verify the role of Ca2+ in curcumin-induced apoptosis, 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), an intracellular calcium chelator, was applied. Cell viability was increased, but ΔΨm, ROS production, activation of caspase 3, and cell death were decreased in J5 cells pretreated with BAPTA for 2 h followed by the treatment of 25 μM curcumin. These results suggest that the curcumin-induced apoptosis in human HCC J5 cells is via mitochondria-dependent pathway and is closely related to the level of intracellular accumulation of calcium

Molecular Imaging, Pharmacokinetics, and Dosimetry of 111In-AMBA in Human Prostate Tumor-Bearing Mice

Molecular imaging with promise of personalized medicine can provide patient-specific information noninvasively, thus enabling treatment to be tailored to the specific biological attributes of both the disease and the patient. This study was to investigate the characterization of DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA) in vitro, MicroSPECT/CT imaging, and biological activities of 111In-AMBA in PC-3 prostate tumor-bearing SCID mice. The uptake of 111In-AMBA reached highest with 3.87 ± 0.65% ID/g at 8 h. MicroSPECT/CT imaging studies suggested that the uptake of 111In-AMBA was clearly visualized between 8 and 48 h postinjection. The distribution half-life (t1/2α) and the elimination half-life (t1/2β) of 111In-AMBA in mice were 1.53 h and 30.7 h, respectively. The Cmax and AUC of 111In-AMBA were 7.57% ID/g and 66.39 h∗% ID/g, respectively. The effective dose appeared to be 0.11 mSv/MBq−1. We demonstrated a good uptake of 111In-AMBA in the GRPR-overexpressed PC-3 tumor-bearing SCID mice. 111In-AMBA is a safe, potential molecular image-guided diagnostic agent for human GRPR-positive tumors, ranging from simple and straightforward biodistribution studies to improve the efficacy of combined modality anticancer therapy

Double Beta-Decay of Tellurium-128 and Tellurium-130

The isotopic composition of xenon has been determined in the gas released by stepwise heating of two, geologically-old tellurium minerals - melonite, NiTe2, from the Robb-Montbray property in Quebec and altaite, PbTe, from the Mattagami Lake area of Quebec. We calculate values of 2540 ± 680 and 2550 ± 1300 for the ratio of the ββ-decay half-lives, T1 2 128/T1 2 130, from the amounts of radiogenic 128Xe and 130Xe in the melonite and the altaite, respectively, and a value of T1 2 128 = (1.8 ± 0.7) × 1024y. Lepton number violation is not required by these results

Double Beta-Decay of ⁸²Se and ¹³⁰Te

The isotopic compositions of xenon and krypton in the mineral kitkaite, NiTeSe, were measured to determine the amounts of radiogenic 82Kr and 130Xe produced by the double-beta decay of 82Se and 130Te, respectively. From the ratio of radiogenic 82Kr to radiogenic 130Xe in this mineral, it is concluded that the half-life of 130Te is larger than that of 82Se by a factor of 7.3 ± 0.9. If the age of the host rock, 2.00 × 109 y, is taken as an upper limit on the gas-retention age of the mineral, then values of (1.25 ± 0.08) × 1021y and (1.72 ± 0.19) × 1020y are obtained as upper limits on the half-lives of 130Te and 82Se respectively. A more realistic upper limit of T82 1 2 ≤ (1.4 ± 0.2) × 1020y is obtained from these results and those of a recent measurement here indicating T8130 1 2 ≤ 1 × 1021y

Geochemically Measured Half-Lives of ⁸²Se and ¹³⁰Te

We have repeated the measurement of radiogenic 82Kr and 130Xe in the mineral kitkaite, NiTeSe, and obtained half-life values of (1.2 ± 0.1) × 1020y for 82Se and (7.5 ± 0.3) × 1020y for 130Te based on the parent/daughter ratios in the kitkaite and the xenon retention age of associated uraninite. The mineralization age of the kitkaite is used to set upper limits of T1 2 82 ≤ 2 × 1020y and T1 2 130 ≤ 12.5 × 1020y

Tumor burden talks in cancer treatment with PEGylated liposomal drugs.

PURPOSE: PEGylated liposomes are important drug carriers that can passively target tumor by enhanced permeability and retention (EPR) effect in neoplasm lesions. This study demonstrated that tumor burden determines the tumor uptake, and also the tumor response, in cancer treatment with PEGylated liposomal drugs in a C26/tk-luc colon carcinoma-bearing mouse model. METHODS: Empty PEGylated liposomes (NanoX) and those encapsulated with VNB (NanoVNB) were labeled with In-111 to obtain InNanoX and InVNBL in high labeling yield and radiochemical purity (all >90%). BALB/c mice bearing either small (58.4±8.0 mm(3)) or large (102.4±22.0 mm(3)) C26/tk-luc tumors in the right dorsal flank were intravenously administered with NanoVNB, InNanoX, InVNBL, or NanoX as a control, every 7 days for 3 times. The therapeutic efficacy was evaluated by body weight loss, tumor growth inhibition (using calipers and bioluminescence imaging) and survival fraction. The scintigraphic imaging of tumor mouse was performed during and after treatment. RESULTS: The biodistribution study of InVNBL revealed a clear inverse correlation (r (2) = 0.9336) between the tumor uptake and the tumor mass ranged from 27.6 to 623.9 mg. All three liposomal drugs showed better therapeutic efficacy in small-tumor mice than in large-tumor mice. Tumor-bearing mice treated with InVNBL (a combination drug) showed the highest tumor growth inhibition rate and survival fraction compared to those treated with NanoVNB (chemodrug only) and InNanoX (radionuclide only). Specific tumor targeting and significantly increased tumor uptake after periodical treatment with InVNBL were evidenced by scintigraphic imaging, especially in mice bearing small tumors. CONCLUSION: The significant differences in the outcomes of cancer treatment and molecular imaging between animals bearing small and large tumors revealed that tumor burden is a critical and discriminative factor in cancer therapy using PEGylated liposomal drugs

Synthesis and Preclinical Characterization of [18F]FPBZA: A Novel PET Probe for Melanoma

Introduction. Benzamide can specifically bind to melanoma cells. A 18F-labeled benzamide derivative, [18F]N-(2-diethylaminoethyl)-4-[2-(2-(2-fluoroethoxy) ethoxy)ethoxy]benzamide ([18F]FPBZA), was developed as a promising PET probe for primary and metastatic melanoma. Methods. [18F]FPBZA was synthesized via a one-step radiofluorination in this study. The specific uptake of [18F]FPBZA was studied in B16F0 melanoma cells, A375 amelanotic melanoma cells, and NB-DNJ-pretreated B16F0 melanoma cells. The biological characterization of [18F]FPBZA was performed on mice bearing B16F0 melanoma, A375 amelanotic melanoma, or inflammation lesion. Results. [18F]FPBZA can be prepared efficiently with a yield of 40–50%. The uptake of [18F]FPBZA by B16F0 melanoma cells was significantly higher than those by A375 tumor cells and NB-DNJ-pretreated B16F0 melanoma cells. B16F0 melanoma displayed prominent uptake of [18F]FPBZA at 2 h (7.81±0.82 %ID/g), compared with A375 tumor and inflammation lesion (3.00±0.71 and 1.67±0.56 %ID/g, resp.). [18F]FPBZA microPET scan clearly delineated B16F0 melanoma but not A375 tumor and inflammation lesion. In mice bearing pulmonary metastases, the lung radioactivity reached 4.77±0.36 %ID/g at 2 h (versus 1.16±0.23 %ID/g in normal mice). Conclusions. Our results suggested that [18F]FPBZA PET would provide a promising and specific approach for the detection of primary and metastatic melanoma lesions

Surface/structural characteristics and band alignments of thin Ga 2 O 3 films grown on sapphire by pulse laser deposition

Comprehensive structural, electrical and optical studies are performed on a series of gallium oxide (Ga 2 O 3 ) ultrathin films grown on sapphire with different growth temperatures (400–1000 °C) by pulsed laser deposition, via X-ray absorption spectroscopy (XAS), Raman scattering (RS) and X-ray photoelectron spectroscopy (XPS). For samples grown at different temperatures, the XAS results showed the coordination numbers of the materials varying, while their bond lengths remained nearly similar value. The RS revealed a low frequency vibration translation tetrahedral-octahedral mode (202 cm −1 ) of GaO 4 and a mid-frequency deformation octahedral mode (346 cm −1 ) of GaO 6 for films grown at higher temperatures. XPS analyses suggested the surface of samples composed of Ga[sbnd]O bonds with binding energy decreasing as the growth temperature increased. The β-Ga 2 O 3 /sapphire heterojunction is identified with the staggered-gap (type II) structure, and the valence-band offset (VBO) is found between (−0.52)–(−0.74) eV while conduction-band offset (CBO) from (−2.32)–(−3.32) eV. The band gap of the β-Ga 2 O 3 was deduced from the energy loss signals for O 1s photoelectrons. With the increase of the growth temperature, the band gap increases and both the VBO and CBO decrease. The identification of band alignment for heterojunction may facilitate interests in designing advanced opto-electronic devices

Body weight loss of the C26/tk-luc colon carcinoma-bearing mice after treatment with various liposomal drugs.

<p>The mice bearing large tumor (<i>n</i> = 9 for each group, A) and those bearing small tumor (<i>n</i> = 6 for each group, B) were injected intravenously with NanoX (•), InNanoX (▽), NanoVNB (▪) or InVNBL (◊) at 0, 7, and 14 days after first injection (arrow; three injections total). The zero time point indicates the initiation of therapy. Data were expressed as mean ± S.E.M.</p