Angiogenesis in Malignant Gliomas and Bevacizumab Resistance

Standard therapy for malignant gliomas includes maximal resection followed by radiotherapy and temozolomide. The increase in neovascularization in high-grade gliomas serves the increased metabolic demands of these fast-growing tumors and the main pathway mediating this process involves vascular endothelial growth factor (VEGF) and its receptor. This pathway is targeted by bevacizumab (BEV), an anti-VEGF monoclonal antibody. Though preclinical trials with BEV were promising, clinical trials failed to show improvement in overall survival, and ultimately GBM become resistant to BEV. By better understanding the molecular mechanisms involved in angiogenesis, new targets may be identified and by elucidating the mechanism behind BEV resistance, new treatment modalities may be developed to treat these aggressive tumors

Patient expectations for placebo treatments commonly used in osteopathic manipulative treatment (OMT) clinical trials: a pilot study

BACKGROUND: Placebo treatments should be believable to ensure expectation of benefit, yet not provide a true treatment effect. One obstacle to conducting clinical trials with osteopathic manipulative treatment (OMT) is choosing an appropriate placebo. Various placebo treatments have been used in OMT clinical trials. The purpose of this study was to determine expectations of 3 treatments (HVLA, placebo light touch, placebo sub-therapeutic ultrasound) commonly used in OMT clinical research trials. METHODS: A randomized, cross-over design was utilized. Subjects were recruited from the Family Medicine Clinic, Texas College of Osteopathic Medicine. Participants watched a video with 2 minute demonstrations of a High Velocity Low Amplitude (HVLA), placebo light touch (LT), and placebo sub-therapeutic ultrasound (ULTRA) treatment for low back pain. The order of presentations was randomized to control for order effect bias. Subjects indicated the extent of their agreement (using a 4 point Likert scale) with 4 statements that were presented after each treatment was viewed: 1)I believe this treatment would allow me to get better quicker; 2)I believe this treatment would decrease my low back pain; 3)I believe this treatment would make me more able to do the things I want to do; 4)This seems like a logical way to treat low back pain. Repeated measures analysis of variance was performed, and a partial Eta squared was calculated for each statement. Effect sizes (Cohen's d) were calculated where appropriate. RESULTS: Thirty of 40 eligible subjects participated. Twenty-two (73%) were female, 16 (53%) were Caucasian, and 11 (37%) had completed college. The mean age was 43 (SD = 15.). Repeated measures ANOVA revealed no significant differences for statements 2 and 4. For both statements 1 (p = 0.025) and 3 (p = 0.039), post hoc analysis revealed a difference between HVLA and LT. The partial Eta squared (η(p)(2)) was 0.105, 0.072, 0.107, and 0.024 for each statement, respectively. CONCLUSION: There is a difference in treatment expectation between HVLA and LT for statements 1 and 3. Participants responded more positively after viewing the HVLA treatment than the LT treatment. This suggests that sub-therapeutic ultrasound is the better placebo because the expectations were similar to those for HVLA

Mechanisms of Glioma Cell Invasion

Malignant gliomas are the most aggressive primary brain tumors. Although current treatment includes surgery and chemo/radiation therapy, life expectancy remains on the order of 2 years. One of the features, which make these tumors incurable, is their infiltration into normal brain tissue. This process is incompletely understood at a molecular level and appropriate targets need to be developed. This review discusses (1) the unique structure of the neural extracellular matrix (ECM), (2) the basis of the proliferation to migration transition that initiates the infiltrative process, (3) the remodeling of the ECM by degradation and synthesis of new components, and (4) trophic factors that act as chemoattractants and chemorepellents for migrating cells. Finally we briefly discuss the challenges facing the study of this complex process and future directions in attacking this important problem in neuro-oncology

Phakomatoses and Their Tumors: Genetics and New Treatment Options

In addition to sporadic primary neoplasms of the central nervous system, several genetic syndromes associated with CNS tumors have been identified. Tuberous sclerosis, neurofibromatosis-1 and -2, and von Hippel–Lindau syndrome belong to a collection of disorders called phakomatoses, which include both CNS tumors and cutaneous manifestations. The underlying genetics of these disorders are being elucidated and offer novel therapies for intervention

Evaluation of exercises designed to improve children's use of descriptive words in oral language

Thesis (Ed.M.)--Boston Universit

Detectability of low energy X-ray spectral components in type 1 AGN

In this paper we examine the percentage of type 1 AGN which require the inclusion of a soft excess component and/or significant cold absorption in the modelling of their X-ray spectra obtained by XMM-Newton. We do this by simulating spectra which mimic typical spectral shapes in order to find the maximum detectability expected at different count levels. We then apply a correction to the observed percentages found for the Scott et al. (2011) sample of 761 sources. We estimate the true percentage of AGN with a soft excess component to be 75+/-23%, suggesting that soft excesses are ubiquitous in the X-ray spectra of type 1 AGN. By carrying out joint fits on groups of low count spectra in narrow z bins in which additional spectral components were not originally detected, we show that the soft excess feature is recovered with a mean temperature kT and blackbody to power-law normalisation ratio consistent with those of components detected in individual high count spectra. Cold absorption with nH values broadly consistent with those reported in individual spectra are also recovered. We suggest such intrinsic cold absorption is found in a minimum of ~5% of type 1 AGN and may be present in up to ~10%.Comment: 10 pages, 6 figures, 4 tables. Accepted for publication in MNRA

Probing Unstable Massive Neutrinos with Current Cosmic Microwave Background Observations

The pattern of anisotropies in the Cosmic Microwave Background depends upon the masses and lifetimes of the three neutrino species. A neutrino species of mass greater than 10 eV with lifetime between 10^{13} sec and 10^{17} sec leaves a very distinct signature (due to the integrated Sachs-Wolfe effect): the anisotropies at large angles are predicted to be comparable to those on degree scales. Present data exclude such a possibility and hence this region of parameter space. For $m_\nu \simeq 30$ eV, $\tau \simeq 10^{13}$ sec, we find an interesting possibility: the Integrated Sachs Wolfe peak produced by the decaying neutrino in low-$\Omega$ models mimics the acoustic peak expected in an $\Omega = 1$ model.Comment: 5 pages, 4 figure

Spiritual Rituals of Chinese Ink Painting: The Suggestions of Shitao

Ritual has an essential connection with art. This article suggests that the study on Shitao has significance in proposing a ritual theory of art for two reasons. First, textual analysis on his treatise on ink painting, Hua-pu, demonstrates that an artist is/should be involved in the interconnectedness of what he or she depicts. This involvement requires penetration into the primordial intuition towards what he or she perceives and has an ethical imperative to use the artist’s talent conferred by heaven. Second, Shitao’s artistic practice is interpreted as a form of rites that are a reaction to the sociopolitical changes during the Ming-Qing dynastic transition. The elaboration on Shitao’s identity and Hua-pu‘s relevance to Daoism will further support the argument. And it is in this sense that Shitao’s case reveals the claim that “art is ritual,” which is metaphorical as it appeals to an ideal form of art

Current Trends in High-Grade Gliomas

This is an overview of the current trends in the management of high-grade gliomas based on the current evidence available at the time of compiling this chapter in the first quarter of 2016, by a dedicated, high-volume Neurosurgical Oncology team of clinical and surgical Neuro-Oncologists based in central Pennsylvania