Common cancer stem cell gene variants predict colon cancer recurrence

<p>PURPOSE: Recent evidence suggests that cancer stem cells (CSC) are responsible for key elements of colon cancer progression and recurrence. Germline variants in CSC genes may result in altered gene function and/or activity, thereby causing interindividual differences in a patient's tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of CSC genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II colon cancer.p><p>EXPERIMENTAL DESIGN: A total of 234 patients treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. Whole blood samples were analyzed for germline polymorphisms in genes that have been previously associated with colon CSC (CD44, Prominin-1, DPP4, EpCAM, ALCAM, Msi-1, ITGB1, CD24, LGR5, and ALDH1A1) by PCR-RFLP or direct DNA-sequencing.p><p>RESULTS: The minor alleles of CD44 rs8193 C>T, ALCAM rs1157 G>A, and LGR5 rs17109924 T>C were significantly associated with increased TTR (9.4 vs. 5.4 years; HR, 0.51; 95% CI: 0.35-0.93; P = 0.022; 11.3 vs. 5.7 years; HR, 0.56; 95% CI: 0.33-0.94; P = 0.024, and 10.7 vs. 5.7 years; HR, 0.33; 95% CI: 0.12-0.90; P = 0.023, respectively) and remained significant in the multivariate analysis stratified by ethnicity. In recursive partitioning, a specific gene variant profile including LGR5 rs17109924, CD44 rs8193, and ALDH1A1 rs1342024 represented a high-risk subgroup with a median TTR of 1.7 years (HR, 6.71, 95% CI: 2.71-16.63, P < 0.001).p><p>CONCLUSION: This is the first study identifying common germline variants in colon CSC genes as independent prognostic markers for stage III and high-risk stage II colon cancer patients.p>

Pharmacogenetic angiogenesis profiling for first-line Bevacizumab plus oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer

<p>PURPOSE: There is substantial germline genetic variability within angiogenesis pathway genes, thereby causing interindividual differences in angiogenic capacity and resistance to antiangiogenesis therapy. We investigated germline polymorphisms in genes involved in VEGF-dependent and -independent angiogenesis pathways to predict clinical outcome and tumor response in metastatic colorectal cancer (mCRC) patients treated with bevacizumab and oxaliplatin-based chemotherapy.p><p>EXPERIMENTAL DESIGN: A total of 132 patients treated with first-line bevacizumab and FOLFOX or XELOX were included in this study. Genomic DNA was isolated from whole-blood samples by PCR-RFLP or direct DNA sequencing. The endpoints of the study were progression-free survival (PFS), overall survival (OS), and response rate (RR).p><p>RESULTS: The minor alleles of EGF rs444903 A>G and IGF-1 rs6220 A>G were associated with increased OS and remained significant in multivariate Cox regression analysis (HR: 0.52; 95% CI: 0.31-0.87; adjusted P = 0.012 and HR: 0.60; 95% CI: 0.36-0.99; adjusted P = 0.046, respectively). The minor allele of HIF1α rs11549465 C>T was significantly associated with increased PFS but lost its significance in multivariate analysis. CXCR1 rs2234671 G>C, CXCR2 rs2230054 T>C, EGFR rs2227983 G>A, and VEGFR-2 rs2305948 C>T predicted tumor response, with CXCR1 rs2234671 G>C remaining significant in multiple testing (P(act) = 0.003).p><p>CONCLUSION: In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy.p>

Placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes: The effect of vitamin C and E supplementation

<p>AIM: In view of the increased rates of pre-eclampsia observed in diabetic pregnancy and the lack of ex vivo data on placental biomarkers of oxidative stress in T1 diabetic pregnancy, the aim of the current investigation was to examine placental antioxidant enzyme status and lipid peroxidation in pregnant women with type 1 diabetes. A further objective of the study was to investigate the putative impact of vitamin C and E supplementation on antioxidant enzyme activity and lipid peroxidation in type 1 diabetic placentae.p><p>METHODS: The current study measured levels of antioxidant enzyme [glutathione peroxidase (Gpx), glutathione reductase (Gred), superoxide dismutase (SOD) and catalase] activity and degree of lipid peroxidation (aqueous phase hydroperoxides and 8-iso-prostaglandin F2α) in matched central and peripheral samples from placentae of DAPIT (n=57) participants. Levels of vitamin C and E were assessed in placentae and cord blood.p><p>RESULTS: Peripheral placentae demonstrated significant increases in Gpx and Gred activities in pre-eclamptic in comparison to non-pre-eclamptic women. Vitamin C and E supplementation had no significant effect on cord blood or placental levels of these vitamins, nor on placental antioxidant enzyme activity or degree of lipid peroxidation in comparison to placebo-supplementation.p><p>CONCLUSION: The finding that maternal supplementation with vitamin C/E does not augment cord or placental levels of these vitamins is likely to explain the lack of effect of such supplementation on placental indices including antioxidant enzymes or markers of lipid peroxidation.p>

Activity patterns of urban red foxes (Vulpes vulpes) reduce the risk of traffic-induced mortality

Traffic collisions can be a major source of mortality in wild populations, and animals may be expected to exhibit behavioral mechanisms that reduce the risk associated with crossing roads. Animals living in urban areas in particular have to negotiate very dense road networks, often with high levels of traffic flow. We examined traffic-related mortality of red foxes (Vulpes vulpes) in the city of Bristol, UK, and the extent to which roads affected fox activity by comparing real and randomly generated patterns of movement. There were significant seasonal differences in the number of traffic-related fox deaths for different age and sex classes; peaks were associated with periods when individuals were likely to be moving through unfamiliar terrain and would have had to cross major roads. Mortality rates per unit road length increased with road magnitude. The number of roads crossed by foxes and the rate at which roads were crossed per hour of activity increased after midnight when traffic flow was lower. Adults and juveniles crossed 17% and 30% fewer roads, respectively, than expected from randomly generated movement. This highly mobile species appeared to reduce the mortality risk of minor category roads by changing its activity patterns, but it remained vulnerable to the effects of larger roads with higher traffic flows during periods associated with extraterritorial movements.

Incorporation of cis-9, trans-11 or trans-10, cis-12 conjugated linoleic acid into human erythrocytes in vivo

The purpose of this study was to determine the incorporation into erythrocytes of cis (c)-9,trans (t)-11 conjugated linoleic acid (CLA) and t10,c12 CLA consumed as supplements highly enriched in these isomers. Healthy men (31 8 years) consumed 1, 2, and 4 capsules containing approximately 80 g/100 g of either c9,t11 CLA or t10,c12 CLA for sequential 8-week periods. Fatty acid concentrations in erythrocyte total lipids were determined at baseline and after consumption of the highest dose. The increase in c9,t11 CLA concentration (0.31 g/100 g) was significantly greater than that in t10,c12 CLA (0.19 g/100 g). This was associated with minor changes in concentrations of some fatty acids of chain length greater than 20 carbons. These data suggest selective assimilation of individual CLA isomers into erythrocyte lipids and partial substitution for specific saturated and polyunsaturated fatty acids. (C) 2005 Elsevier Inc. All rights reserved.

Proportions of A1, A2, B and C β-casein protein variants in retail milk in the UK

The A1 variant protein of the β-casein family has been implicated in various disease states although much evidence is weak or contradictory. The primary objective was to measure, for the first time, the proportions of the key β-casein variant proteins in UK retail milk over the course of one year. In total, 55 samples of semi-skimmed milk were purchased from five supermarkets over the course of a year and the proportions of the A1, A2, B and C casein variant proteins were measured, using high resolution HPLC-MS. The results showed that β-casein in UK retail milk comprises approximately 0.58, 0.31, 0.07 and 0.03 A2, A1, B and C protein variants, respectively. The proportion of A2 is higher than some early studies would predict although the reasons for this and any implications for health are unclear

Dependence of the product on the P-P ligand in reactions of [RuCl(3)(NO)(P-P)] complexes (P-P = aromatic diphosphines) with 2-mercaptopyridine

This study presents the syntheses and characterization of 2-mercaptopyridine (pyS(-)) complexes containing ruthenium(II) with the following general formula [Ru(pyS)(2)(P-P)], P-P = (c-dppen) = cis-1,2-bis(diphenylphosphino)ethylene) (1); (dppe)=1,2-bis(diphenylphosphino)ethane (2); (dppp)=1,3-bis(diphenylphosphino)propane (3) and (dppb) = 1,4-bis(diphenylphosphino)butane (4). The complexes were synthesized from the mer- or fac-[RuCl(3)(NO)(P-P)] precursors in the presence of triethylamine in methanol solution with dependence of the product on the P-P ligand. The reaction of pyS- with a ruthenium complex containing a bulky aromatic diphosphine dppb disclosed a major product with a dangling coordinated dppbO-P, the [Ru(pyS)(2)(NO)(eta(1)-dppbO-P)]PF(6) (5). In addition, this work also presents and discusses the spectroscopic and electrochemical behavior of 1-5. and report the X-ray structures for I and S. (C) 2009 Elsevier Ltd. All rights reserved.

A group topology on the free abelian group of cardinality c that makes its square countably compact

Under p = c, we prove that it is possible to endow the free abelian group of cardinality c with a group topology that makes its square countably compact. This answers a question posed by Madariaga-Garcia and Tomita and by Tkachenko. We also prove that there exists a Wallace semigroup (i.e., a countably compact both-sided cancellative topological semigroup which is not a topological group) whose square is countably compact. This answers a question posed by Grant.

ITS som stöd för funktionshindrade bilförare : med fokus på förarstöd och säkerhet

Denna rapport presenterar ett examensarbete på C-nivå där uppdragsgivaren har varit Hedemora Anpassning som bygger om och anpassar bilar för människor med olika funktionshinder. Företaget vill i framtiden ha möjlighet att erbjuda sina kunder ITS-tjänster. Målet med arbetet har varit att undersöka hur ITS skulle kunna stödja de funktionshindrade i deras bilkörning. Syftet delades upp i två delsyften, dels kartläggning av vilka tjänster som finns och är under utveckling inom området ITS – förarstöd och säkerhet samt hur de skulle kunna användas/anpassas för funktionshindrade dels att göra en undersökning av vilka behov de funktionshindrade har av ITS. De metoder som använts har varit kvalitativa intervjuer samt litteraturstudier. De senare har använts för att få inblick i ämnet ITS och tjänster som finns eller är under utveckling inom området. Intervjuerna gjordes med personer som endera arbetar med forskning inom ITS eller är verksamma inom området samt med funktionshindrade bilförare. En kartläggning av tjänster har skett och resultatet av intervjuerna pekar på att det finns ett behov av ITS-tjänster för funktionshindrade bilförare. Delvis finns behov av tjänster som redan finns i dag, till exempel navigationssystem. Det finns även behov av andra tjänster som är under utveckling. Gemensamt för dessa tjänster är att de i vissa fall skulle behöva anpassas till de funktionshindrade med röstanpassning eller andra specifika anpassningar.

Funding was obtained from a Capes Fellowship to NM, grants CNPq Universal 481351/ 2011-6, CNPq PQ 306604/2012-4, FAPERN/CNPq Pronem 003/2011, Capes SticAmSud, and FAPESP/CEPID/Neuromat to S.R. CNPq Universal 473554/2011-9 and 480053/ 2013-8, CNPq PQ 308558/2011-1, FACEPE/CNPq-PRONEX APQ- 0203-1.05/08, FACEPE/CNPq-PRONEM APQ-1415-1.05/10, and CNAIPS to M.C

Funding was obtained from a Capes Fellowship to NM, grants CNPq Universal 481351/ 2011-6, CNPq PQ 306604/2012-4, FAPERN/CNPq Pronem 003/2011, Capes SticAmSud, and FAPESP/CEPID/Neuromat to S.R. CNPq Universal 473554/2011-9 and 480053/ 2013-8, CNPq PQ 308558/2011-1, FACEPE/CNPq-PRONEX APQ- 0203-1.05/08, FACEPE/CNPq-PRONEM APQ-1415-1.05/10, and CNAIPS to M.C

Anthrone and oxanthrone C,O-diglycosides from Picramnia teapensis

Two C,O-diglycosylated compounds, the anthrone picramnioside F, and the oxanthrone mayoside C, were isolated from the stem bark of Picramnia teapensis, along with the previously reported anthraquinones, 1-O-beta -D- and 8-O-beta -D-glucopyranosyl emodin. The compounds were separated by recycling-HPLC, and their structures were determined on the basis of spectroscopic analysis. CD measurements were used to establish the absolute configuration of the anthrone and oxanthrone. The antifungal activity of 1-O-beta -D- and 8-O--D-glucopyranosyl emodin against Leucoagaricus gongilophorus was shown to be similar to that of the lignan sesamin. (C) 2000 Elsevier B.V. Ltd. All rights reserved.

Doses reduzidas de fluazifop-p-butil + fomesafen no controle de plantas daninhas na cultura de soja

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

Avaliação de alguns tratamentos na intoxicação por amônia em bovinos

Para avaliar tratamentos na intoxicação por amônia, 15 novilhos, infundidos com solução de cloreto de amônio, foram distribuídos em três grupos de cinco animais cada e tratados, como: 1 - grupo-controle (C), infundido com solução salina fisiológica (H); 2 - grupo O+H, medicado com aminoácidos do ciclo da ureia (O) e H; 3 - grupo O+F+H, o mesmo protocolo do grupo 2 acrescido de furosemida (F). Os animais foram monitorados, colhendo-se amostras sanguíneas e todo volume urinário. Os tratamentos O+F+H e O+H promoveram melhora clínica pronunciada, em relação ao grupo H, isto é, permaneceram em estação, retornaram o movimento de rúmen e o apetite e recuperaram-se do edema pulmonar mais rapidamente. Observaram-se, nos grupos O+F+H e O+H, teores plasmáticos mais baixos de amônia e lactato-L, urina mais abundante, excreção pela urina de maior quantidade de amônio e ureia, depuração mais intensa de amônia do sangue e pH urinário mais baixo. Concluiu-se que os tratamentos propostos apresentaram ação efetiva principalmente por diminuírem a hiperamonemia, por meio da maior excreção renal de amônio e maior transformação hepática de amônia em ureia

Poultry offal meal in chicken: Traceability using the technique of carbon (C-13/C-12)- and nitrogen (N-15/N-14)-stable isotopes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)