Volatile organic compounds in head and neck squamous cell carcinoma—An in vitro pilot study

Owing to the lack of specific symptoms, diagnosis of head and neck squamous cell carcinoma (HNSCC) may be delayed. We evaluated volatile organic compounds in tumor samples from patients suffering from HNSCC and tested the hypothesis that there is a characteristic altered composition in the headspace of HNSCC compared with control samples from the same patient with normal squamous epithelium. These results provide the basis for future noninvasive breath analysis in HNSCC. Headspace air of suspected tumor and contralateral control samples in 20 patients were analyzed using ion-mobility spectrometry. Squamous cell carcinoma was diagnosed in 16 patients. In total, we observed 93 different signals in headspace measurements. Squamous cell carcinomas revealed significantly higher levels of volatile cyclohexanol (0.54 ppb_v, 25th to 75th percentiles 0.35–0.86) compared with healthy squamous epithelium (0.24 ppb_v, 25th to 75th percentiles 0.12–0.3; p < 0.001). In conclusion, head and neck squamous cell carcinoma emitted significantly higher levels of volatile cyclohexanol in headspace compared with normal squamous epithelium. These findings form the basis for future breath analysis for diagnosis, therapy control and the follow-up of HNSSC to improve therapy and aftercare.     

Preparation and in vivo imaging of a novel potential αvβ3 targeting PET/MRI dual-modal imaging agent

Journal of Radioanalytical and Nuclear Chemistry - Multi-modal biomedical imaging has played an essential role in tumor diagnosis. However, constructing a multi-modal imaging contrast agent with...     

Radiosynthesis and evaluation of 188Re-c(RGDyK)-His as a novel radiotherapeutic agent for integrin αvβ3 targeting tumour

The successes of noninvasive methods to visualize and quantify integrin α_vβ₃ expression in vivo have paved the way for radiolabeling anti-integrin therapy in clinic. Arginine-glycine-aspartice (RGD) peptide and related derivatives labeled with radionuclides for radio-therapy, which specifically targeting integrin α_vβ₃-positive tumors, could be used to treat these tumors. We have labeled c(RGDyK)-His, a RGD derivative, with ¹⁸⁸Re and the radio-therapy efficiency has been evaluated in model nude mice. c(RGDyK)-His was labeled with ¹⁸⁸Re by chelating with [¹⁸⁸Re(CO)₃(H₂O)₃]⁺ under a slightly basic condition. The in vitro specific binding affinity to U87 MG cell lines and the biodistribution of ¹⁸⁸Re-c(RGDyK)-His in the animal tumor models was measured. The inhibitory effects of ¹⁸⁸Re-c(RGDyK)-His were observed more than 1 month, and evaluated by microPET/CT imaging with ¹⁸F-FDG. Results of in vivo, cell uptake demonstrated ¹⁸⁸Re-c(RGDyK)-His had a high specific binding affinity to receptor integrin α_vβ₃. In biodistribution experiment, ¹⁸⁸Re-c(RGDyK)-His was accumulated in the tumor and cleared fast from the normal tissues. In radiotherapy study, tumor growth inhibition was significantly higher in the treatment groups than in the control groups. These studies showed that ¹⁸⁸Re-c(RGDyK)-His could be effectively used for integrin α_vβ₃ targeting therapy. This may offer a potential therapeutic strategy for the treatment of integrin-positive tumors in clinic.     

A tripodal ruthenium-gadolinium metallostar as a potential α(v)β(3) integrin specific bimodal imaging contrast agent

Gd(III)-containing metallostar contrast agents are gaining increased attention, because their architecture allows for a slower tumbling rate, which, in turn, results in larger relaxivities. So far, these metallostars find possible applications as blood pool contrast agents. In this work, the first example of a tissue-selective metallostar contrast agent is described. This RGD-peptide decorated Ru(II)(Gd(III))(3)metallostar is synthesized as an α(v)β(3)-integrin specific contrast agent, with possible applications in the detection of atherosclerotic plaques and tumor angiogenesis. The contrast agent showed a relaxivity of 9.65 s(-1) mM(-1), which represents an increase of 170%, compared to a low-molecular-weight analogue, because of a decreased tumbling rate (τ(R) = 470 ps). The presence of the MLCT band (absorption 375-500 nm, emission 525-850 nm) of the central Ru(II)(Ph-Phen)(3)-based complex grants the metallostar attractive luminescent properties. The (3)MLCT emission is characterized by a quantum yield of 4.69% and a lifetime of 804 ns, which makes it an interesting candidate for time-gated luminescence imaging. The potential application as a selective MRI contrast agent for α(v)β(3)-integrin expressing tissues is shown by an in vitro relaxometric analysis, as well as an in vitroT(1)-weighted MR image.     

Synthesis of [64Cu]DOTA-ADIBON3-Ala-PEG28-A20FMDV2 via copper-free click chemistry for PET imaging of integrin αvβ6

Catalyst-free click reactions are effective chemical tools for synthesis of radiometal-based radiopharmaceuticals offering advantages towards preparation of non-toxic agents with high specific activity. In the present study the radiotracer [⁶⁴Cu]DOTA-ADIBON₃-Ala-PEG₂₈-A20FMDV2, [⁶⁴Cu]3, was synthesized for positron emission tomography imaging of integrin α_vβ₆ expressing tumors via a strain-promoted click reaction using both a “pre-click” and “post-click” approaches. The radiotracer, prepared in >99 % radiochemical yield, was evaluated in vitro (64.6 ± 2.8 % binding to α_vβ₆-positive cells vs. <5 % to α_vβ₆-negative cells) and in vivo (α_vβ₆-positive tumor uptake: 1.52 ± 0.16 % ID/g, 24 h p.i.). While the high initial renal uptake (76.2 ± 10.7 % ID/g at 1 h p.i.) was comparable to a previously reported radiotracer, [⁶⁴Cu]DOTA-PEG₂₈-A20FMDV2, [⁶⁴Cu]3 showed notably improved renal clearance (11.3 ± 2.5 % ID/g at 24 h p.i.). Thus, the introduction of a chelator-strained alkyne system resulted in improved pharmacokinetics for the present radiotracer, highlighting the attractive prospects of strain-promoted click-based preparations in the construction of radiometalated bioconjugates for targeted molecular imaging and therapy.     

Tetrameric RGD induces clustering of integrin αvβ3 on the melanoma cell surface and decreases cell viability

The recombinant hybrid protein SR15 composed of streptavidin fused with RGD peptide is obtained. The ability of this protein to recognize human melanoma cells (MeWo line) is demonstrated. Types of expressed RGD-binding integrins in the cells of this line are identified. It is found that the recombinant hybrid protein SR15 binds to integrin αvβ3 on the surface of human melanoma cells. The binding to the protein SR15 results in clustering of αvβ3 receptors on the surface of MeWo cells, internalization of the recombinant protein, and an almost twofold decrease in cell viability.     

Collision induced absorption in the a1Δ(v = 2) ← X3Σg(-)(v = 0) band of molecular oxygen

Using cavity ring-down spectroscopy we measured the collision induced absorption spectrum associated with the a(1)Δ(v = 2) ←X(3)Σ(g)(-)(v = 0) band of oxygen near 922 nm both in pure oxygen and in mixtures of oxygen and nitrogen. For pure oxygen, we report for this band an integrated absorption of (1.56 - 0.04/+0.40) × 10(-5) cm(-2) amg(-2). We find that collisions between oxygen and nitrogen do not result in any measurable CIA signal. At 1 bar of oxygen, this collision induced transition is much stronger than the allowed magnetic dipole and electric quadrupole transitions.     

Renner-Teller and Fermi resonance interactions for the v3=1 and v7=2 vibronic levels in the A2Πu and X2Πg electronic states of HC4H+

The excitation of the v(3) = 1 (σ(g)(+) C-C stretch) and the v(7) = 2 (π(g)(2) C≡C-C bend) modes in the A(2)Π(u) electronic state of diacetylene cations results in Renner-Teller (R-T) and Fermi interactions. The 3(0)(1) and 7(0)(2) vibronic bands in the A(2)Π(u)-X(2)Π(g) transition of HC(4)H(+) have been measured with rotational resolution using cavity ringdown spectroscopy in a supersonic slit jet discharge. The analysis yields T(00) = 20520.828(4) cm(-1), B' = 0.14047(2) cm(-1), and A' = -17.95(1) cm(-1) for the v(3) = 1 and T(00) = 20573.659(4) cm(-1), B' = 0.14018(3) cm(-1), and A' = -11.55(1) cm(-1) for the v(7) = 2 level in the A(2)Π(u) electronic state. A vibronic analysis has been carried out taking into consideration the R-T, spin-orbit, and Fermi resonance interactions between the ν(3) and ν(7) modes. The levels are fitted to the eigenvalues of an appropriate Hamiltonian matrix. This yields the vibrational frequencies ω(3)′ = 811.8 cm(-1) and ω(7)′ = 403.2 cm(-1), Renner parameter ε(7)′ = 0.065, Fermi coefficients W(1)′ = 10.3 cm(-1) and W(2)′ = 5.1 cm(-1), and spin-orbit interaction constant A(SO)′ = -31.1 cm(-1). A corresponding R-T analysis has been carried out for the X(2)Π(g) ground state of HC(4)H(+) using data available in the literature [Callomon, J. H. Can. J. Phys. 1956, 34, 1046]. This gives ω(3)" = 956.2 cm(-1), ω(7)" = 435.4 cm(-1), ε(7)" = 0.028, W(1)" = 7.2 cm(-1), W(2)" = 10.9 cm(-1), and A(SO)" = -33.3 cm(-1).     

Synthesis and evaluation of a phenylbenzothiazole-based 99mTc(CO)3-radiotracer for possible application in imaging of β-amyloid plaques in Alzheimer’s disease

The 2-phenyl benzothiazole pharmacophore is known to have high affinity for amyloid beta (Aβ) and is therefore derivatized, to [N-(4′-benzothiazol-pyridin-2-yl-methyl-amino)-acetic acid (BTPAA)] for radiolabeling with [^99mTc(CO)₃(H₂O)₃]⁺ precursor. The radiotracer, ^99mTc(CO)₃–BTPAA is evaluated in vitro and in vivo to determine its binding with the Aβ and ability to cross the blood brain barrier. The radiotracer prepared in >95 % radiochemical yield, showed ~25 % inhibition in presence of thioflavin-T, indicating its specificity towards aggregated Aβ protein. The radiotracer also showed brain uptake of 0.25 ± 0.04 % injected dose/g at 2 min post injection, indicating its ability to cross the blood brain barrier.     

Microwave Spectrum and Dipole Moment of 1,3‐dioxolane in the Hindered‐Pseudorotation States v = 0, 1, 2, and 3

The microwave spectrum of 1,3dioxolane (C₃H₆O₂) in the ground and first three excited states of hindered pseudorotation was studied. The transitions corresponding to the _b, _c, and _a components of the dipole moment were identified. The spectrum was analyzed using numerical diagonalization of the effective rotational Hamiltonian for four interacting states of hindered pseudorotation. The rotational constants, centrifugal distortion constants, the constants of interaction between general rotation and hindered pseudorotation, and the distances between the quasidegenerate vibrational levels ₀₁ = 64840.5, ₁₂ = 122231.7 and ₂₃ = 119732.7 MHz are determined. From the Stark effect of microwave transitions, the dipole moment components (in Debye units) in the hinderedpseudorotation states v = 0, 1, 2, and 3 are determined: 0|_b|0 = 1|_b|1 = 1.22, 2|_b|2 = 1.20, 3|_b|3 = 1.21, 0|_c|1 = 0.77, 2|_c3 = 0.66, and 1|_a|2 = 0.19.     

Organic synthesis and biological evaluation of novel “3 + 1” mixed ligands of technetium-99m Gabapentin as receptor imaging agents

This work focuses on the “3 + 1” mixed ligands of ^99mTc labeled Gabapentin as α2δ receptor imaging agents in the brain. Gabapentin 1-(aminomethyl)cyclohexanacetic acid as monodentate and two tridentates: tridentate A; 3-(2-imino-thiozolidin-4-one)-quinozoline-4-(3H)-one and tridentate B; N-(4-chlorophenyl)-2-imino-2H-chromene-3-Carbothioamide which were synthesized and characterized by infrared analysis (IR), ¹H nuclear magnetic resonance (NMR), and mass spectrum. ^99mTc-complexes were prepared by the “3 + 1” mixed ligand approach. The labeling conditions were optimized and the complexes was extracted by chloroform and purified by high performance liquid chromatography. ^99mTc-complexs were lipophilic and stable for at least 8–12 h at room temperature. The biodistribution of the ^99mTc-complexes was evaluated in mice. The brain uptake was 4.5% and 3.5% ID/g (percentage of the injected dose per gram) at 5 min, and the retention was 1.5% and 1.7% ID/g at 120 min for ^99mTc-complex A and ^99mTc-complex B, respectively.     

209Bi NQR in Mixed Oxides 2Bi2O3· B2O3, 3Bi2O3· 5B2O3, and Bi2O3· 3B2O3

It was earlier found from nuclear quadrupole resonance (NQR) measurements and computer modeling that -Bi₂O₃, Bi₃O₄Br and mixed oxides Bi₂O₃· 2Al₂O₃, Bi₂O₃· 2Ga₂O₃, Bi₂O₃· 3GeO₂, and 2Bi₂O₃· 3GeO₂exhibit local ordered magnetic fields from 30 to 200 G. It thus follows that these compounds are not diamagnets in a conventional sence of the word. With the aim of revealing previously unknown magnetic properties in bismuth(III) oxide-based Main Group element compounds, the mixed bismuth–boron oxides 2Bi₂O₃· B₂O₃, 3Bi₂O₃· 5B₂O₃, and Bi₂O₃· 3B₂O₃were prepared and studied using ²⁰⁹Bi NQR. The quadrupole interactions of the ²⁰⁹Bi nuclei and their electronic environment were studied, the crystallochemical features of the compounds were discussed, and the conformity of the ²⁰⁹Bi results to the X-ray structure data was verified. The preliminary tests in the field of a permanent magnet showed that the resonance intensities increase in external magnetic fields, indicating that a magnetism of unknown nature develops in the titled compounds. It was found reasonable to continue studies of the magnetic properties of these compounds using single-crystal ²⁰⁹Bi NQR in external magnetic fields.     

Bond functions in molecular excited states: MRD CI calculations for the A3Σ+u,B3Πg and W3Δu states of N2

Using double-zeta plus polarization (DZP) basis sets systematically augmented with a variety of bond functions, the term dissociation energies are calculated for the A³Σ⁺_u, B³Π_g and W³Δ_u states of N₂. It is found that the best agreement with literature values is generally with a basis set composition of DZP augmented by a set of s, p and d orbitals at the bond midpoint. The excited state potential energy curves and spectroscopic constants for the B³Π_g state are calculated from this basis and compared with experimental values. Good agreement was obtained, considering the small basis set size, with the spectroscopic constants ω_e, ω_eχ_e, ω_ey_e, B_e and α_e and the dissociation energy D_e (e.g., D_e = 3.38 (3.681, exp.), 4.75 (4.897) and 4.77(4.873) eV for the A, B and W stages, respectively). Poorer agreement was obtained for the term energy T′₀ (7.92 versus 7.35 eV, exp., for the B state). The error in term energy arises largely from an error in the calculated ⁴S → ²D splitting (2.705 versus 2.383 eV, exp.), and shifting the potential curve for the B state by a constant amount leads to much improved agreement relative to the ground state. The counterpoise correction applied to the potential curve of the B state causes a drastic deterioration of the results and shows qualitatively incorrect behaviour, and is therefore not recommended for calculations of this type.     

Synthesis of Ag_2S nano-sized clusters and their chemical sensitizations in AgCl cubic and {100} tabular microcrystal imaging systems

1 Introduction Since the 1990s, silver chloride {100} tabular grain emulsion has attracted much attention from research-ers working in different enterprises all over the world, such as Eastman Kodak[1―5], Agfa-Gavaert[6,7] and the Lucky Group Company in …     

Does the molecular structure of CaH2 affect the dihydrogen bonding in CaH2 … HY (Y = CH3, C2H3, C2H, CN, and NC) complexes? A quantum chemistry study using MP2 and B3LYP methods

Second-order M ller-Plesset(MP2) and density functional theory(DFT) calculations have been carried out in order to investigate the structures and properties of dihydrogen-bonded CaH 2 HY(Y = CH 3,C 2 H 3,C 2 H,CN,and NC) complexes.Our calculations revealed two possible structures for CaH 2 in CaH 2 HY complexes:linear(I) and bent(II).The bond lengths,interaction energies,and strengths for H H interactions obtained by both MP2 and B3LYP methods are quite close to each other.It was found that the interaction energy decreases with increasing electron density at the Ca-H bond critical point.Atom-in-molecule(AIM) results show that for all of Ca-H H-Y interactions considered here,the Laplacian of the electron density at the H H bond critical point is positive,indicating the electrostatic nature of these Ca-H H-Y dihydrogen bonded systems.     

Fixation and reduction of molecular nitrogen by [WH4(PC2H5Ph2)4] and [WH4(PCH3Ph2)4] in a γ-radiation field

Hydride complexes of W(IV) with dpep (diphenylethylphosphine) and dpmp (diphenylmethylphosphine) were irradiated in thf+C₆H₁₂(11) solutions, saturated with N₂+H₂(13). Radiation yields of hydrazine, ammonia and amines were evaluated. The mechanism of reduction of molecular nitrogen is discussed.     

Chemical composition of the essential oil from basil (Ocimum basilicum Linn.) and its in vitro cytotoxicity against HeLa and HEp-2 human cancer cell lines and NIH 3T3 mouse embryonic fibroblasts

This study examines the chemical composition and in?vitro anticancer activity of the essential oil from Ocimum basilicum Linn. (Lamiaceae), cultivated in the Western Ghats of South India. The chemical compositions of basil fresh leaves were identified by GC-MS: 11 components were identified. The major constituents were found to be methyl cinnamate (70.1%), linalool (17.5%), β-elemene (2.6%) and camphor (1.52%). The results revealed that this plant may belong to the methyl cinnamate and linalool chemotype. A methyl thiazol tetrazolium assay was used for in?vitro cytotoxicity screening against the human cervical cancer cell line (HeLa), human laryngeal epithelial carcinoma cell line (HEp-2) and NIH 3T3 mouse embryonic fibroblasts. The IC(50) values obtained were 90.5 and 96.3?μg?mL(-1), respectively, and the results revealed that basil oil has potent cytotoxicity.     

A functional comparison between the HER2(high)/HER3 and the HER2(low)/HER3 dimers on heregulin-β1-induced MMP-1 and MMP-9 expression in breast cancer cells

Overexpression of HER2 correlates with more aggressive tumors and increased resistance to cancer chemotherapy. However, a functional comparison between the HER2(high)/HER3 and the HER2(low)/HER3 dimers on tumor metastasis has not been conducted. Herein we examined the regulation mechanism of heregulin- β1 (HRG)-induced MMP-1 and -9 expression in breast cancer cell lines. Our results showed that the basal levels of MMP-1 and -9 mRNA and protein expression were increased by HRG treatment. In addition, HRG-induced MMP-1 and -9 expression was significantly decreased by MEK1/2 inhibitor, U0126 but not by phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294002. To confirm the role of MEK/ERK pathway on HRG-induced MMP-1 and -9 expression, MCF7 cells were transfected with constitutively active adenoviral- MEK (CA-MEK). The level of MMP-1 and -9 expressions was increased by CA-MEK. MMP-1 and -9 mRNA and protein expressions in response to HRG were higher in HER2 overexpressed cells than in vector alone. The phosphorylation of HER2, HER3, ERK, Akt, and JNK were also significantly increased in HER2 overexpressed MCF7 cells compared with vector alone. HRG-induced MMP-1 and -9 expressions were significantly decreased by lapatinib, which inhibits HER1 and HER2 activity, in both vector alone and HER2 overexpressed MCF7 cells. Finally, HRG-induced MMP-1 and MMP-9 expression was decreased by HER3 siRNA overexpression. Taken together, we suggested that HRG-induced MMP-1 and MMP-9 expression is mediated through HER3 dependent pathway and highly expressed HER2 may be associated with more aggressive metastasis than the low expressed HER2 in breast cancer cells.