Folic acid supplementation increases survival and modulates high risk HPV-induced phenotypes in oral squamous cell carcinoma cells and correlates with p53 mRNA transcriptional down-regulation

<p>Abstract</p> <p>Background</p> <p>Although the primary risk factors for developing oral cancers are well understood, less is known about the relationship among the secondary factors that may modulate the progression of oral cancers, such as high-risk human papillomavirus (HPV) infection and folic acid (FA) supplementation. This study examined high-risk HPV and FA supplementation effects, both singly and in combination, to modulate the proliferative phenotypes of the oral cancer cell lines CAL27, SCC25 and SCC15.</p> <p>Results</p> <p>Using a comprehensive series of integrated <it>in vitro </it>assays, distinct effects of HPV infection and FA supplementation were observed. Both high-risk HPV strains 16 and 18 induced robust growth-stimulating effects in CAL27 and normal HGF-1 cells, although strain-specific responses were observed in SCC25 and SCC15 cells. Differential effects were also observed with FA administration, which significantly altered the growth rate of the oral cancer cell lines CAL27, SCC15, and SCC25, but not HGF-1 cells. Unlike HPV, FA administration induced broad, general increases in cell viability among all cell lines that were associated with <it>p53 </it>mRNA transcriptional down-regulation. None of these cell lines were found to harbor the common C677T mutation in methylenetetrahydrofolate reductase (<it>MTHFR</it>), which can reduce FA availability and may increase oral cancer risk.</p> <p>Conclusion</p> <p>Increased FA utilization and DNA hypermethylation are common features of oral cancers, and in these cell lines, specifically. The results of this study provide further evidence that FA antimetabolites, such as Fluorouracil (f5U or 5-FU) and Raltitrexed, may be alternative therapies for tumors resistant to other therapies. Moreover, since the incidence of oral HPV infection has been increasing, and can influence oral cancer growth, the relationship between FA bioavailability and concomitant HPV infection must be elucidated. This study is among the first pre-clinical studies to evaluate FA- and HPV-induced effects in oral cancers, both separately and in combination, which provides additional rationale for clinical screening of HPV infection prior to treatment.</p

A Rutile Chevron Modulation in Delafossite-Like Ga 3– x In 3 Ti x O 9+ x /2

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A Rutile Chevron Modulation in Delafossite-Like Ga 3– x In 3 Ti x O 9+ x /2

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A Rutile Chevron Modulation in Delafossite-Like Ga 3– x In 3 Ti x O 9+ x /2

International audienceThe structure solution of the modulated, delafossite-related, orthorhombic Ga3–xIn3TixO9+x/2 for x = 1.5 is reported here in conjunction with a model describing the modulation as a function of x for the entire system. Previously reported structures in the related A3–xIn3TixO9+x/2 (A = Al, Cr, or Fe) systems use X-ray diffraction to determine that the anion lattice is the source of modulation. Neutron diffraction, with its enhanced sensitivity to light atoms, offers a route to solving the modulation and is used here, in combination with precession electron diffraction tomography (PEDT), to solve the structure of Ga1.5In3Ti1.5O9.75. We construct a model that describes the anion modulation through the formation of rutile chevrons as a function of x. This model accommodates the orthorhombic phase (1.5 ≤ x ≤ 2.1) in the Ga3–xIn3TixO9+x/2 system, which transitions to a biphasic mixture (2.2 ≤ x ≤ 2.3) with a monoclinic, delafossite-related phase (2.4 ≤ x ≤ 2.5). The optical band gaps of this system are determined, and are stable at ∼3.4 eV before a ∼0.4 eV decrease between x = 1.9 and 2.0. After this decrease, stability resumes at ∼3.0 eV. Resistance to oxidation and reduction is also presented

Tris(3,5-di-<i>tert</i>-butylcatecholato)molybdenum(VI): Lewis Acidity and Nonclassical Oxygen Atom Transfer Reactions

In the solid state, tris­(3,5-di-<i>tert</i>-butylcatecholato)­molybdenum­(VI) forms a dimer with seven-coordinate molybdenum and bridging catecholates. NMR spectroscopy indicates that the dimeric structure is retained in solution. The molybdenum center has a high affinity for Lewis bases such as pyridine or pyridine-<i>N</i>-oxide, forming seven-coordinate monomers with a capped octahedral geometry, as illustrated by the solid-state structure of (3,5-^<i>t</i>Bu₂Cat)₃Mo­(py). Structural data indicate that the complexes are best considered as Mo­(VI) with substantial π donation from the nonbridging catecholates to molybdenum. Both the dimeric and the monomeric tris­(catecholates) react rapidly with water to form free catechol and oxomolybdenum bis­(catecholate) complexes. Monooxomolybdenum complexes are also obtained, more slowly, on reaction with dioxygen, with organic products consisting mostly of 3,5-di-<i>tert</i>-butyl-1,2-benzoquinone with minor amounts of the extradiol oxidation product 4,6-di-<i>tert</i>-butyl-1-oxacyclohepta-4,6-diene-2,3-dione. The pyridine-<i>N</i>-oxide complex reacts on heating (with excess pyO) to form initially (3,5-^<i>t</i>Bu₂Cat)₂MoO­(Opy) and ultimately MoO₃(Opy), with quinone and free pyridine as the only organic products. The decay of (3,5-^<i>t</i>Bu₂Cat)₃Mo­(Opy) shows an accelerated, autocatalytic profile because the oxidation of its product, (3,5-^<i>t</i>Bu₂Cat)₂MoO­(Opy), produces an oxo-rich, catecholate-poor intermediate which rapidly conproportionates with (3,5-^<i>t</i>Bu₂Cat)₃Mo­(Opy), providing an additional pathway for its conversion to the mono-oxo product. The tris­(catecholate) fragment Mo­(3,5-^<i>t</i>Bu₂Cat)₃ deoxygenates Opy in this nonclassical oxygen atom transfer reaction slightly less rapidly than does its oxidized product, MoO­(3,5-^<i>t</i>Bu₂Cat)₂

A Rutile Chevron Modulation in Delafossite-Like Ga_3–<i>x</i>In₃Ti_<i>x</i>O_9+<i>x</i>/2

The structure solution of the modulated, delafossite-related, orthorhombic Ga_3–<i>x</i>In₃Ti_<i>x</i>O_9+<i>x</i>/2 for <i>x</i> = 1.5 is reported here in conjunction with a model describing the modulation as a function of <i>x</i> for the entire system. Previously reported structures in the related A_3–<i>x</i>In₃Ti_<i>x</i>O_9+<i>x</i>/2 (A = Al, Cr, or Fe) systems use X-ray diffraction to determine that the anion lattice is the source of modulation. Neutron diffraction, with its enhanced sensitivity to light atoms, offers a route to solving the modulation and is used here, in combination with precession electron diffraction tomography (PEDT), to solve the structure of Ga_1.5In₃Ti_1.5O_9.75. We construct a model that describes the anion modulation through the formation of rutile chevrons as a function of <i>x</i>. This model accommodates the orthorhombic phase (1.5 ≤ <i>x</i> ≤ 2.1) in the Ga_3–<i>x</i>In₃Ti_<i>x</i>O_9+<i>x</i>/2 system, which transitions to a biphasic mixture (2.2 ≤ <i>x</i> ≤ 2.3) with a monoclinic, delafossite-related phase (2.4 ≤ <i>x</i> ≤ 2.5). The optical band gaps of this system are determined, and are stable at ∼3.4 eV before a ∼0.4 eV decrease between <i>x</i> = 1.9 and 2.0. After this decrease, stability resumes at ∼3.0 eV. Resistance to oxidation and reduction is also presented

Structural, Electrical, and Optical Properties of the Tetragonal, Fluorite-Related Zn_0.456In_1.084Ge_0.460O₃

We report the discovery of Zn_0.456In_1.084­Ge_0.460O₃, a material closely related to bixbyite. In contrast, however, the oxygen atoms in this new phase occupy 4 Wyckoff positions, which result in 4 four-coordinate, 24 six-coordinate (2 different Wyckoff positions), and 4 eight-coordinate sites as compared to the 32 six-coordinate (also 2 different Wyckoff positions) sites of bixbyite. This highly ordered material is related to fluorite, Ag₆GeSO₈, and γ-UO₃ and is n-type with a bulk carrier concentration of 4.772 × 10¹⁴ cm^–3. The reduced form displays an average room temperature conductivity of 99(11) S·cm^–1 and an average optical band gap of 2.88(1) eV. These properties are comparable to those of In₂O₃, which is the host material for the current leading transparent conducting oxides. The structure of Zn_0.456In_1.084­Ge_0.460O₃ is solved from a combined refinement of synchrotron X-ray powder diffraction and time-of-flight neutron powder diffraction and confirmed with electron diffraction. The solution is a new, layered, tetragonal structure in the <i>I</i>4₁/<i>amd</i> space group with <i>a</i> = 7.033986(19) Å and <i>c</i> = 19.74961(8) Å. The complex cationic topological network adopted by Zn_0.456In_1.084­Ge_0.460O₃ offers the potential for future studies to further understand carrier generation in ∼3 eV oxide semiconductors

Selective Crystal Growth and Structural, Optical, and Electronic Studies of Mn₃Ta₂O₈

Mn3Ta2O8, a stable targeted material with an unusual and complex cation topology in the complicated Mn-Ta-O phase space, has been grown as a ≈3-cm-long single crystal via the optical floating-zone technique. Single-crystal absorbance studies determine the band gap as 1.89 eV, which agrees with the value obtained from density functional theory electronic-band-structure calculations. The valence band consists of the hybridized Mn d-O p states, whereas the bottom of the conduction band is formed by the Ta d states. Furthermore, out of the three crystallographically distinct Mn atoms that are four-, seven-, or eight-coordinate, only the former two contribute their states near the top of the valence band and hence govern the electronic transitions across the band gap. (Graph Presented)

When precession electron diffraction tomography goes dynamical

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