Antitumor Activity Of Irradiated Riboflavin On Human Renal Carcinoma Cell Line 786-o.

Riboflavin (vitamin B2) is a precursor for coenzymes involved in energy production, biosynthesis, detoxification, and electron scavenging. Previously, we demonstrated that irradiated riboflavin (IR) has potential antitumoral effects against human leukemia cells (HL60), human prostate cancer cells (PC3), and mouse melanoma cells (B16F10) through a common mechanism that leads to apoptosis. Hence, we here investigated the effect of IR on 786-O cells, a known model cell line for clear cell renal cell carcinoma (CCRCC), which is characterized by high-risk metastasis and chemotherapy resistance. IR also induced cell death in 786-O cells by apoptosis, which was not prevented by antioxidant agents. IR treatment was characterized by downregulation of Fas ligand (TNF superfamily, member 6)/Fas (TNF receptor superfamily member 6) (FasL/Fas) and tumor necrosis factor receptor superfamily, member 1a (TNFR1)/TNFRSF1A-associated via death domain (TRADD)/TNF receptor-associated factor 2 (TRAF) signaling pathways (the extrinsic apoptosis pathway), while the intrinsic apoptotic pathway was upregulated, as observed by an elevated Bcl-2 associated x protein/B-cell CLL/lymphoma 2 (Bax/Bcl-2) ratio, reduced cellular inhibitor of apoptosis 1 (c-IAP1) expression, and increased expression of apoptosis-inducing factor (AIF). The observed cell death was caspase-dependent as proven by caspase 3 activation and poly(ADP-ribose) polymerase-1 (PARP) cleavage. IR-induced cell death was also associated with downregulation of v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homologue (avian)/protein serine/threonine kinase B/extracellular signal-regulated protein kinase 1/2 (Src/AKT/ERK1/2) pathway and activation of p38 MAP kinase (p38) and Jun-amino-terminal kinase (JNK). Interestingly, IR treatment leads to inhibition of matrix metalloproteinase-2 (MMP-2) activity and reduced expression of renal cancer aggressiveness markers caveolin-1, low molecular weight phosphotyrosine protein phosphatase (LMWPTP), and kinase insert domain receptor (a type III receptor tyrosine kinase) (VEGFR-2). Together, these results show the potential of IR for treating cancer.

Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice

The N-acylhydrazone (NAH) analogues N-methyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-785) and N-benzyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-786) were prepared from 2-thienylidene 3,4-methylenedioxybenzoylhydrazine (LASSBio-294). The ability of LASSBio-785 and LASSBio-786 to decrease central nervous system activity was investigated in male Swiss mice. LASSBio-785 or LASSBio-786 (30 mg/kg, ip) reduced locomotor activity from 209 ± 26 (control) to 140 ± 18 (P < 0.05) or 146 ± 15 crossings/min (P < 0.05), respectively. LASSBio-785 (15 or 30 mg/kg, iv) also reduced locomotor activity from 200 ± 15 to 116 ± 29 (P < 0.05) or 60 ± 16 crossings/min (P < 0.01), respectively. Likewise, LASSBio-786 (15 or 30 mg/kg, iv) reduced locomotor activity from 200 ± 15 to 127 ± 10 (P < 0.01) or 96 ± 14 crossings/min (P < 0.01), respectively. Pretreatment with flumazenil (20 mg/kg,ip) prevented the locomotor impairment induced by NAH analogues (15 mg/kg, iv), providing evidence that the benzodiazepine (BDZ) receptor is involved. This finding was supported by the structural similarity of NAH analogues to midazolam. However, LASSBio-785 showed weak binding to the BDZ receptor. LASSBio-785 or LASSBio-786 (30 mg/kg,ip, n = 10) increased pentobarbital-induced sleeping time from 42 ± 5 (DMSO) to 66 ± 6 (P < 0.05) or 75 ± 4 min (P < 0.05), respectively. The dose required to achieve 50% hypnosis (HD50) following iv injection of LASSBio-785 or LASSBio-786 was 15.8 or 9.5 mg/kg, respectively. These data suggest that both NAH analogues might be useful for the development of new neuroactive drugs for the treatment of insomnia or for use in conjunction with general anesthesia.

Français 786

Contient : 1° Calendrier en français ; 2° « Li Roumans del roi Alixandre », par [LAMBERT LE TORT et] « ALEXANDRE de Berri » ; 3° La Signification de la mort d'Alexandre, de « PIERE DE SAINT CLOOT » ; 4° La Vengeance d'Alexandre, de « GUI de Cambrai » ; 5° « Li Roumans dou Chevalier au Chisne et de Godefroit de Buillon », par « RAINAUT » ; 6° Chanson de Jérusalem, renouvelée par « GRAINDOR de Douai »

Evaluation of the effects of nicorandil and its molecular precursor (without radical NO) on proliferation and apoptosis of 786-cell

Nicorandil is a nitric oxide (NO) donor used in the treatment of angina symptoms. It has also been reported to protect cells and affect the proliferation and death of cells in some tissues. The molecules that interfere with these processes can cause dysfunction in healthy tissues but can also assist in the therapy of some disorders. In this study we examined the effect of nicorandil and of the molecular precursor that does not have the NO radical (N-(beta-hydroxyethyl) nicotinamide) on the cell proliferation and death of human renal carcinoma cells (786-O) under normal oxygenation conditions. The molecular precursor was used in order to analyze the effects independents of NO. In the cytotoxicity test, nicorandil was shown to be cytotoxic at very high concentrations and it was more cytotoxic than its precursor (cytotoxic at concentrations of 2,000 and 3,000 μg/mL, respectively). We propose that the lower cytotoxicity of the precursor is due to the absence of the NO radical. In this study, the cells exposed to nicorandil showed neither statistically significant changes in cell proliferation nor increases in apoptosis or genotoxicity. The precursor generated similar results to those of nicorandil. We conclude that nicorandil causes no changes in the proliferation or apoptosis of the cell 786-O in normal oxygenation conditions. Moreover, the lack of NO radical in the precursor molecule did not show a different result, except in the cell cytotoxicity. © 2013 Springer Science+Business Media Dordrecht.

Antitumor activity of irradiated riboflavin on human renal carcinoma cell line 786-O

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 786 - Weiterleitung des Schreibens von Daniel Friedrichsen

u.a. Pacht in Ohra; Immobilien in Ohra; Mühle; verweigerte Einsichtnahme in Geschäfstpapiere;

(Table 2) Trace element composition of seleceted clast and matrix materials from ODP Site 125-786

Shipboard examination of volcanic and sedimentary strata at Site 786 suggested that at least four types of breccias are present: flow-top breccias, associated with cooling and breakup on the upper surface of lava flows; autobreccias, formed by in-situ alteration at the base of flows; fault-gouge breccias; and true sedimentary breccias derived from weathering and erosion of underlying flows. It is virtually impossible to assess the origin of breccia matrix by textural and mineralogical analyses alone. However, it is fundamental for our understanding of breccia provenance to determine the source component of the matrix material. Whether the matrix is uniquely clastderived can be determined by geochemical fingerprinting. Trace elements that are immobile during weathering and alteration do not change their relative abundances. A contribution to the matrix from any source with an immobile trace element signature different from that of the clasts would appear as a perturbation of the trace element signature of the matrix. Trace element analysis of bulk samples from clasts and matrix material in individual breccia units was undertaken in a fashion similar to that used by Brimhall and Dietrich (1987, doi:10.1016/0016-7037(87)90070-6) in analyzing soil provenance: (1) to help distinguish between sedimentary and volcanic breccias, (2) to determine the degree of mixing and depth of erosion in sedimentary breccias, and (3) to analyze the local provenance of the individual breccia components (matrix and clasts). The following elements were analyzed by X-ray fluorescence (XRF): Rb, Sr, Ba, U, Zr, Cu, Zn, Ti, Cr, and V. Of these elements, Zr and Ti probably exhibit truly immobile behavior (Humphris and Thompson, 1978, doi:10.1016/0016-7037(78)90222-3 ). The remaining elements are useful as a reference for the extent of compositional change during the formation of matrix material (Brimhall and Dietrich, 1987, doi:10.1016/0016-7037(87)90070-6).

Potassium and argon concentrations and age determination of ODP Site 125-782 and 125-786

K-Ar whole-rock ages have been obtained for 30 samples from Sites 782 and 786, Ocean Drilling Program Leg 125 in the Izu-Bonin (Ogasawara) forearc region. They form a trimodal spread of ages between 9 Ma and 44 Ma and are, with a few exceptions, consistent with the inferred lithostratigraphy. The ages have been interpreted in terms of at least two distinct episodes of magmatic and/or hydrothermal activity. A group of ten samples, including the lava flows, gave an isochron age of 41.3 ± 0.5 Ma (middle-late Eocene). This is thought to represent the age of the principal magmatic development of the volcanic forearc basement, and is comparable to published ages on equivalent rocks from other parts of the forearc basement high (e.g., the Ogasawara Islands). It may be significant that this age is slightly younger than the timing of major plate reorganization in the Western Pacific at about 43 Ma. This was followed by a minor episode of intrusive magmatism at 34.6 ± 0.7 Ma (early Oligocene) which appears to have reset the ages of some of the earlier units. This event probably corresponds to the initiation of rifting of the "proto-arc" to form the Parece Vela Basin. Boninitic samples were erupted during both episodes of magmatism, the earlier being of low-Ca boninite type and the later being of medium- and high-Ca types. It is also possible that a third episode of intrusive magmatism affected the Izu-Bonin forearc region at both Sites 782 and 786 at about 17 Ma. This would be consistent with magmatic activity elsewhere in the region during the Miocene, associated with the end of active spreading in the Parece Vela Basin and the start of arc activity in the West Mariana Ridge.

Geochemistry of igneous rock samples of ODP Site 125-786

A morphologically complex igneous basement was penetrated at Leg 125 Site 786 beneath approximately 100 m of Eocene-Pleistocene sediments at 31°52.45 'N, 141°13.59'E in a 3082-m water depth. The site is located on the forearc basement high (FBH) of the Izu-Bonin (Ogasawara) Arc. In the broadest terms, the sequence in Hole 786B consists of a basal sheeted dike complex, heavily mineralized in places, with overlying pillow lavas giving way to a complex and repeated sequence of interlayered volcanic breccias and lava flows with some thin sedimentary intervals. The sequence has been further cut by dikes or sills, particularly of high-Ca and intermediate-Ca boninite, and is locally strongly sheared by faulting. The whole basement has been covered with middle Eocene-early Pleistocene sediments. A monomict breccia forms the shallowest portion of Hole 786B and a polymict breccia having Mn-oxide-rich clast coatings and matrix forms the deepest part of Hole 786A (-100-160 mbsf). The basement is tectonized in some places, and a mineralized stockwork is present in the deepest part of Hole 786B. A wide variety of rock types form this basement, ranging from mafic to silicic in character and including high-, intermediate-, and low-Ca boninites, intermediate- and low-Ca bronzite andesites, andesite, dacite, and rhyolite groups. Intragroup and intergroup relationships are complicated in detail, and several different upper mantle source(s) probably were involved. A significant role for orthopyroxene-clinopyroxene-plagioclase fractionation is indicated in the mafic-intermediate groups, and the most probable complementary cumulates should be noritic gabbros. Many overall similarities but some subtle differences are noted between the igneous basement at Site 786 and the subaerial outcrops of the FBH to the south in the type boninite locality of Chichijima. Both suites were derived by hydrous melting of a relatively shallow, refractory (harzburgitic) upper mantle source. These Bonin forearc basement rocks are similar in many respects to those of Eocene-Oligocene age now forming the forearc of the Marianas at Leg 60 Site 458 and on Guam. In sharp distinction, the geochemistry of the Eocene-Pleistocene ash sequences overlying the Bonin FBH must have been derived from a very different upper mantle source, implying considerable across-strike differences in sub-arc mantle composition.