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

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

Hospital-community interactions foster coexistence between methicillin-resistant strains of Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of morbidity and mortality in both hospitals and the community. Traditionally, MRSA was mainly hospital-associated (HA-MRSA), but in the past decade community-associated strains (CA-MRSA) have spread widely. CA-MRSA strains seem to have significantly lower biological costs of resistance, and hence it has been speculated that they may replace HA-MRSA strains in the hospital. Such a replacement could potentially have major consequences for public health, as there are differences in the resistance spectra of the two strains as well as possible differences in their clinical effects. Here we assess the impact of competition between HA- and CA-MRSA using epidemiological models which integrate realistic data on drug-usage frequencies, resistance profiles, contact, and age structures. By explicitly accounting for the differing antibiotic usage frequencies in the hospital and the community, we find that coexistence between the strains is a possible outcome, as selection favors CA-MRSA in the community, because of its lower cost of resistance, while it favors HA-MRSA in the hospital, because of its broader resistance spectrum. Incorporating realistic degrees of age- and treatment-structure into the model significantly increases the parameter ranges over which coexistence is possible. Thus, our results indicate that the large heterogeneities existing in human populations make coexistence between hospital- and community-associated strains of MRSA a likely outcome

Ceroplastes albolineatus, the first scale insect shown to sequester pyrrolizidine alkaloids from its host-plant Pittocaulon praecox

The occurrence of pyrrolizidine alkaloids (PAs) in Pittocaulon (ex Senecio) praecox (Asteraceae) a species endemic to Mexico was established. The aboveground plant organs contain the 1,2-saturated monoester 7-angeloyl-dihydroxyheliotridane together with a small proportion of its 9-angeloyl isomer as major alkaloid. The monoesters are accompanied by the macrocyclic otonecine derivative senkirkine. Roots contain only related macrocyclic PAs with senecionine, senkirkine and platyphylline as major component