Development of an Orthotopic Human Pancreatic Cancer Xenograft Model Using Ultrasound Guided Injection of Cells

Mice have been employed as models of cancer for over a century, providing significant advances in our understanding of this multifaceted family of diseases. In particular, orthotopic tumor xenograft mouse models are emerging as the preference for cancer research due to increased clinical relevance over subcutaneous mouse models. In the current study, we developed orthotopic pancreatic cancer xenograft models in mice by a minimally invasive method, ultrasound guided injection (USGI) comparable to highly invasive surgical orthotopic injection (SOI) methods. This optimized method prevented injection complications such as recoil of cells through the injection canal or leakage of cells out of the pancreas into the peritoneal cavity. Tumor growth was monitored in vivo and quantified by ultrasound imaging weekly, tumors were also detected by in vivo fluorescence imaging using a tumor targeted molecular probe. The mean tumor volumes for the USGI and SOI models after 2 weeks of tumor growth were 205 mm3 and 178 mm3 respectively. By USGI of human pancreatic cancer cell lines, human orthotopic pancreatic cancer xenografts were established. Based on ultrasound imaging, the orthotopic human pancreatic cancer xenograft take rate was 100% for both human pancreatic cancer cell lines used, MiaPaCa-2 and Su86.86, with mean tumor volumes of 28 mm3and 30 mm3. We demonstrated that this USGI method is feasible, reproducible, facile, minimally invasive and improved compared to the highly-invasive SOI method for establishing orthotopic pancreatic tumor xenograft models suitable for molecular imaging

Development of an Orthotopic Human Pancreatic Cancer Xenograft Model Using Ultrasound Guided Injection of Cells

Mice have been employed as models of cancer for over a century, providing significant advances in our understanding of this multifaceted family of diseases. In particular, orthotopic tumor xenograft mouse models are emerging as the preference for cancer research due to increased clinical relevance over subcutaneous mouse models. In the current study, we developed orthotopic pancreatic cancer xenograft models in mice by a minimally invasive method, ultrasound guided injection (USGI) comparable to highly invasive surgical orthotopic injection (SOI) methods. This optimized method prevented injection complications such as recoil of cells through the injection canal or leakage of cells out of the pancreas into the peritoneal cavity. Tumor growth was monitored in vivo and quantified by ultrasound imaging weekly, tumors were also detected by in vivo fluorescence imaging using a tumor targeted molecular probe. The mean tumor volumes for the USGI and SOI models after 2 weeks of tumor growth were 205 mm3 and 178 mm3 respectively. By USGI of human pancreatic cancer cell lines, human orthotopic pancreatic cancer xenografts were established. Based on ultrasound imaging, the orthotopic human pancreatic cancer xenograft take rate was 100% for both human pancreatic cancer cell lines used, MiaPaCa-2 and Su86.86, with mean tumor volumes of 28 mm3and 30 mm3. We demonstrated that this USGI method is feasible, reproducible, facile, minimally invasive and improved compared to the highly-invasive SOI method for establishing orthotopic pancreatic tumor xenograft models suitable for molecular imaging

Multi-Directional Growth of Aligned Carbon Nanotubes Over Catalyst Film Prepared by Atomic Layer Deposition

The structure of vertically aligned carbon nanotubes (CNTs) severely depends on the properties of pre-prepared catalyst films. Aiming for the preparation of precisely controlled catalyst film, atomic layer deposition (ALD) was employed to deposit uniform Fe2O3 film for the growth of CNT arrays on planar substrate surfaces as well as the curved ones. Iron acetylacetonate and ozone were introduced into the reactor alternately as precursors to realize the formation of catalyst films. By varying the deposition cycles, uniform and smooth Fe2O3 catalyst films with different thicknesses were obtained on Si/SiO2 substrate, which supported the growth of highly oriented few-walled CNT arrays. Utilizing the advantage of ALD process in coating non-planar surfaces, uniform catalyst films can also be successfully deposited onto quartz fibers. Aligned few-walled CNTs can be grafted on the quartz fibers, and they self-organized into a leaf-shaped structure due to the curved surface morphology. The growth of aligned CNTs on non-planar surfaces holds promise in constructing hierarchical CNT architectures in future

DNA hypermethylation markers of poor outcome in laryngeal cancer

This study examined molecular (DNA hypermethylation), clinical, histopathological, demographical, smoking, and alcohol variables to assess diagnosis (early versus late stage) and prognosis (survival) outcomes in a retrospective primary laryngeal squamous cell carcinoma (LSCC) cohort. The study cohort of 79 primary LSCC was drawn from a multi-ethnic (37% African American), primary care patient population, diagnosed by surgical biopsies in the Henry Ford Health System from 1991 to 2004 and followed from 5 to 18 years (through 2009). Of the 41 variables, univariate risk factors of p < 0.10 were tested in multivariate models (logistic regression (diagnosis) and Cox (survival) models (p < 0.05)). Aberrant methylation of estrogen receptor 1 (ESR1; p = 0.01), race as African American (p = 0.04), and tumor necrosis (extensive; p = 0.02) were independent predictors of late stage LSCC. Independent predictors of poor survival included presence of vascular invasion (p = 0.0009), late stage disease (p = 0.03), and methylation of the hypermethylated in cancer 1 (HIC1) gene (p = 0.0002). Aberrant methylation of ESR1 and HIC1 signified independent markers of poorer outcome. In this multi-ethnic, primary LSCC cohort, race remained a predictor of late stage disease supporting disparate diagnosis outcomes for African American patients with LSCC

Recurrence in oral and pharyngeal cancer is associated with quantitative MGMT promoter methylation

<p>Abstract</p> <p>Background</p> <p>Biomarkers that predict clinical response, tumor recurrence or patient survival are severely lacking for most cancers, particularly for oral and pharyngeal cancer. This study examines whether gene-promoter methylation of tumor DNA correlates with survival and recurrence rates in a population of patients with oral or pharyngeal cancer.</p> <p>Methods</p> <p>The promoter methylation status of the DNA repair gene <it>MGMT </it>and the tumor suppressor genes <it>CDKN2A and RASSF1 </it>were evaluated by methylation-specific PCR in 88 primary oral and pharyngeal tumors and correlated with survival and tumor recurrence. Quantitative <it>MGMT </it>methylation was also assessed.</p> <p>Results</p> <p>29.6% of the tumors presented with <it>MGMT </it>methylation, 11.5% with <it>CDKN2A </it>methylation and 12.1% with <it>RASSF1 </it>methylation. <it>MGMT </it>promoter methylation was significantly associated with poorer overall and disease-free survival. No differences in methylation status of <it>MGMT </it>and <it>RASSF1 </it>with HPV infection, smoking or drinking habits were observed. A significant inverse trend with the amount of <it>MGMT </it>methylation and overall and disease-free survival was observed (p_trend= 0.002 and 0.001 respectively).</p> <p>Conclusion</p> <p>These results implicate <it>MGMT </it>promoter methylation as a possible biomarker for oral and pharyngeal cancer prognosis. The critical role of MGMT in DNA repair suggests that defective DNA repair may be correlative in the observed association between <it>MGMT </it>promoter methylation and tumor recurrence. Follow-up studies should include further quantitative MSP-PCR measurement, global methylation profiling and detailed analysis of downstream DNA repair genes regulated by promoter methylation.</p

Vitamin D status is inversely associated with markers of risk for type 2 diabetes: A population based study in Victoria, Australia

A growing body of evidence suggests a protective role of Vitamin D on the risk of type 2 diabetes mellitus (T2DM). We investigated this relationship in a population sample from one Australian state. The data of 3,393 Australian adults aged 18±75 years who participated in the 2009±2010 Victorian Health Monitor survey was analyzed. Socio-demographic information, biomedical variables, and dietary intakes were collected and fasting blood samples were analyzed for 25, hydroxycholecalciferol (25OHD), HbA1c, fasting plasma glucose (FPG), and lipid profiles. Logistic regression analyses were used to evaluate the association between tertiles of serum 25OHD and categories of FPG (&lt;5.6 mmol/L vs. 5.6±6.9 mmol/L), and HbA1c (&lt;5.7% vs. 5.7±6.4%). After adjusting for social, dietary, biomedical and metabolic syndrome (MetS) components (waist circumference, HDL cholesterol, triglycerides, and blood pressure), every 10 nmol/L increment in serum 25OHD significantly reduced the adjusted odds ratio (AOR) of a higher FPG [AOR 0.91, (0.86, 0.97); p = 0.002] and a higher HbA1c [AOR 0.94, (0.90, 0.98); p = 0.009]. Analysis by tertiles of 25OHD indicated that after adjustment for socio-demographic and dietary variables, those with high 25OHD (65±204 nmol/L) had reduced odds of a higher FPG [AOR 0.60, (0.43, 0.83); p = 0.008] as well as higher HbA1c [AOR 0.67, (0.53, 0.85); p = 0.005] compared to the lowest 25OHD (10±44 nmol/L) tertile. On final adjustment for other components of MetS, those in the highest tertile of 25OHD had significantly reduced odds of higher FPG [AOR 0.61, (0.44, 0.84); p = 0.011] and of higher HbA1c [AOR 0.74, (0.58, 0.93); p = 0.041] vs. low 25OHD tertile. Overall, the data support a direct, protective effect of higher 25OHD on FPG and HbA1c; two criteria for assessment of risk of T2DM

Volatile compounds from plants. Origin, emission, effects, analysis and agro applications

Plants produce and emit large amounts of volatile organic compounds. The smell produced by plants has always been recognized for its commercial and aesthetic value and it is emitted not only from flowers and fruits, but also from vegetative tissues. Since approximately two decades, the influence of these scents in a vast array of interactions has been established carrying out physiological, ecological and more recently atmospheric functions. Generally these mixtures consist of terpenes, fatty acid derivatives and aromatic compounds. One of the major volatile's role is their involvement as signals to other organisms, and even for the same plant. Furthermore, they can be exported to modify the environment of the releaser species and influence the behavior of neighbors and enemies. Chemical volatiles have so many functions: in plant reproduction, attracting pollinators or seed disperser

Pensteminoside, an unusual catalpol-type iridoid from Penstemon gentianoides HBK (Plantaginaceae)

From the MeOH and ethyl acetate extracts of aerial parts of Penstemon gentianoides HBK (Plantaginaceae) an unusual iridoid of the catalpol-type, was isolated and characterized as pensteminoside: (8-O-trans-cinnamoyl, 6-hydroxy, 1-[beta-D-glucopyranoside-6'-O-((4"hydroxy)-cinnamoyl)]-catalpol) was isolated, along with the known iridoids: plantarelanoside and globularisicin, the flavone: luteolin and diosmetin, as well the phenylpropanoids, verbascoside and martynoside. Their structures were established by 1 D and 2D NMR spectroscopic analyses. (c) 2007 Elsevier Ltd. All rights reserved

Comparative study of ovatifolin antioxidant and growth inhibition activities

A comparative study on the effect of arturin (1), ovatifolin (3), deacetylovatifolin (5), and their 1-acetoxyarturin (2), 8-acetoxyovatifolin (4), 1,10-epoxyovatifolin (6), and 11,13-dihydroovatifolin (7)derivatives, isolated from Podanthus ovatifolius and Podanthus mitiqui, on the seedling growth, germination, and respiration of several monocot and dicot weedy target species was carried out. In addition to the inhibitory activity on the bleaching of crocin induced by alkoxyl radicals, these compounds also displayed scavenging properties toward DPPH in TLC autographic and spectrophotometric assays. The results indicate that ovatifolin (3), deacetylovatifolin (5), epoxyovatifolin (6), dihydroovatifolin (7), and the CH2Cl2 extract interfere with pre-emergence of seedlings at the level of respiration. These compounds appear to have selective effects on the radicle and shoot growth of Physalis ixocarpa and Trifolium pratense. Their allelopathic effects are comparable to those of parthenolide, a know natural growth inhibitor