Glioblastoma cells: A heterogeneous and fatal tumor interacting with the parenchyma

AbstractGlioblastomas (GBMs) are considered to be one of the deadliest human cancers, characterized by a high proliferative rate, aggressive invasiveness and insensitivity to radio- and chemotherapy, as well as a short patient survival period. Moreover, GBMs are among the most vascularized and invasive cancers in humans. Angiogenesis in GBMs is correlated with the grade of malignancy and is inversely correlated with patient survival. One of the first steps in tumor invasions is migration. GBM cells have the ability to infiltrate and disrupt physical barriers such as basement membranes, extracellular matrix and cell junctions. The invasion process includes the overexpression of several members of a super-family of zinc-based proteinases, the Metzincin, in particular a sub-group, metalloproteinases. Another interesting aspect is that, inside the GBM tissue, there are up to 30% of microglia or macrophages. However, little is known about the immune performance and interactions of the microglia with GBMs. These singular properties of GBMs will be described here. A sub-population of cells with stem-like properties may be the source of tumors since, apparently, GBM stem cells (GSCs) are highly resistant to current cancer treatments. These cancer therapies, while killing the majority of tumor cells, ultimately fail in GBM treatment because they do not eliminate GSCs, which survive to regenerate new tumors. Finally, GBM patient prognostic has shown little improvement in decades. In this context, we will discuss how the membrane-acting toxins called cytolysins can be a potential new tool for GBM treatment

Cardiomiopatia de Takotsubo: características clínicas e fisiopatologia: revisão sistemática: Takotsubo cardiomyopathy: clinical features and pathophysiology: a systematic review

A cardiomiopatia de Takotsubo diz respeito a uma forma aguda e reversível da insuficiência cardíaca em que muitas das vezes está correlacionada com a síndrome coronariana aguda. Essa pesquisa tem como objetivo evidenciar as características clínicas e a fisiopatologia da cardiomiopatia de Takotsubo. Trata-se de uma Revisão Integrativa da Literatura. Foram encontrados 4 artigos, sendo 3 desses relatos de caso. Após análise e interpretação dos dados, concluiu-se que a cardiomiopatia de Takotsubo apresenta características clínicas que podem se confundir a outras doenças coronarianas, por isso é essencial o diagnóstico diferencial. Percebe-se a necessidade de mais estudos referentes à temática da cardiomiopatia de Takotsubo

Detection of mice colorectal tumors by endoluminal ultrasound biomicroscopic images and quantification of image augmented gray values following injection of VEGFR-2 targeted contrast agent

Rationale and Objectives: Ultrasound biomicroscopy (UBM) is a noninvasive imaging technique that can be applied in detecting colonic tumors and, once associated with an ultrasound contrast agent (UCA), can identify the molecular expression of cancer-related biomarkers, such as the vascular endothelial growth factor receptor 2 (VEGFR-2). The present work aimed to detect colonic tumors and quantify augmented gray values of endoluminal UBM (eUBM) images from colonic tumors following the injection of VEGFR-2 targeted UCA (VEGFR2-UCA) into a mouse model of colorectal cancer. Material and Methods: A 40 MHz miniprobe catheter inserted through the biopsy channel of a pediatric flexible bronchofiberscope was used to obtain colonoscopic and B-mode eUBM images simultaneously. Seventeen tumor-bearing mice had their colons inspected and six of them were subjected to a VEGFR2-UCA injection to predict VEGFR-2 expression. Results: All animals developed distal colon tumors and eUBM was able to detect all of them and also to characterize the tumors, with 71.4% being in situ lesions and 28.6% being tumors invading the mucosa + muscularis mucosae + submucosa layers, as confirmed by histopathology. After VEGFR2-UCA injection, gray values from the eUBM tumoral images increased significantly (p < 0.01). Tumor sites with increased eUBM image gray values corresponded to areas with increased VEGFR-2 expression, as confirmed by immunohistochemistry. Conclusion: The results confirm eUBM as a powerful noninvasive and real-time tool for detecting colon tumor and its invasiveness and once associated with VEGFR2-UCA may become a tool for the detection of VEGFR-2 expression in colonic tumors

The iterative process of plant species inventorying for obtaining reliable biodiversity patterns ADDITIONAL KEYWORDS: beta diversity -hornworts -laurel forests -Linnaean shortfall -liverworts - Macaronesia -mosses -spore-producing plants -Wallacean shortf

We require representative data of species occurrence to explain plant diversity patterns, but most of the available information is incomplete and biased. To improve our knowledge, we suggest that species inventorying should be an iterative process encompassing the following: (1) the detection of taxonomic and geographical gaps; (2) the planning of a survey design to reduce such gaps; and (3) the evaluation of field sampling results. Here, we focus on the latter phase for the bryophytes of Terceira Island (Azores) for which we have previously estimated &lt; 1% of the area as well surveyed based on historical collections. To examine the performance of our stratified survey based on two factors (land use and environmental regions), we used rarefaction curves, ANOVA tests and bootstrap sampling. We recorded 40% of all the species known for the island and presented eight new citations. The species assemblages remained similar between historical and current inventories. Most localities had completeness values &gt; 85%, but we always exceeded the optimal sampling effort. Land uses and environmental regions affected species diversity, but, unexpectedly, to a different degree. Our study illustrates the difficulties of planning field surveys to obtain reliable biodiversity patterns, even when prior information and standardized sampling protocols are explicitly considered

p53 Signaling on Microenvironment and Its Contribution to Tissue Chemoresistance

Chemoresistance persists as a significant, unresolved clinical challenge in many cancer types. The tumor microenvironment, in which cancer cells reside and interact with non-cancer cells and tissue structures, has a known role in promoting every aspect of tumor progression, including chemoresistance. However, the molecular determinants of microenvironment-driven chemoresistance are mainly unknown. In this review, we propose that the TP53 tumor suppressor, found mutant in over half of human cancers, is a crucial regulator of cancer cell-microenvironment crosstalk and a prime candidate for the investigation of microenvironment-specific modulators of chemoresistance. Wild-type p53 controls the secretion of factors that inhibit the tumor microenvironment, whereas altered secretion or mutant p53 interfere with p53 function to promote chemoresistance. We highlight resistance mechanisms promoted by mutant p53 and enforced by the microenvironment, such as extracellular matrix remodeling and adaptation to hypoxia. Alterations of wild-type p53 extracellular function may create a cascade of spatial amplification loops in the tumor tissue that can influence cellular behavior far from the initial oncogenic mutation. We discuss the concept of chemoresistance as a multicellular/tissue-level process rather than intrinsically cellular. Targeting p53-dependent crosstalk mechanisms between cancer cells and components of the tumor environment might disrupt the waves of chemoresistance that spread across the tumor tissue, increasing the efficacy of chemotherapeutic agents

Immunohistochemical analysis of retinoblastoma and β-catenin as an assistant tool in the differential diagnosis between Crohn's disease and ulcerative colitis.

In about 10-15% of patients with inflammatory bowel diseases (IBD) there is no clear definitive differential diagnosis between Crohn's disease (CD) and ulcerative colitis (UC) and the disease is classified as indeterminate colitis. Since pharmacological and surgical treatments differ in CD and UC, establishing a correct diagnosis is critical. The aim of this work was to access the expression profile of proteins involved in colonic inflammation and cancer in samples from CD and UC. For that, colon samples from 24 CD, 21 UC and 10 control patients were processed for immunohistochemistry using anti-phosphorylated RB at Ser(807/811) and anti-β-catenin. Crypts were blinded, analyzed and counted for phosphorylated RB-positive (phospho-RB) cells or scored for positive β-catenin staining. Western blot was used for confirming immuhistochemical results: RB phosphorylation was significantly greater in colon samples from patients with CD compared with UC (p<0.005). In contrast, the expression of β-catenin was significantly increased in UC compared with CD (p<0.005) samples. Phospho-RB and β-catenin are negatively correlated (CC: -0.573; p = 0.001). A positive phospho-RB test yielded high levels of sensitivity, specificity, negative and positive predictive values, and accuracy for the diagnosis of CD against UC. This work indicates that RB phosphorylation and β-catenin nuclear translocation are differently expressed in CD and UC, and provide novel insights into the pathogenic mechanisms of IBD. In particular, rates of phospho-RB-positive cells in mucosal samples emerge as a promising tool for the differential diagnosis of patients with IBD

Immunofluorescence staining for phosphorylated RB is increased in colon biopsies from CD patients.

<p>A. RB phosphorylation was detected in colon biopsies from control (non inflamed; n = 5), CD (n = 7) and UC patients (n = 6) by immunofluorescence staining using phosphorylated RB Ser^807/811 and phosphorylated RB Thr^821/826 antibodies. Nuclei were stained with 4′,6-diamidino-2-phenylindole (DAPI). Scale bar = 50 µm. B. Histogram showing RB fluorescence staining intensity in Ser^807/811 (white bars) and Thr^821/826 (black bars) residues. *p<0.05 when compared with percentage of phosphorylated RB Ser^807/811-positive cells in UC samples and ^##p<0.01 when compared with percentage of phosphorylated RB Thr^821/826 -positive cells in UC samples.</p

Scatter-plot showing the correlation between phospho-RB and b-catenin among patients with CD and UC.

<p>ROC curves determined thresholds for establishing positive test values. Phospho-RB is expressed as percentages, while β-catenin is expressed as intensity scores.</p

Diagnostic capability of phospho-RB and β-catenin immunhistochemical tests in differentiating Crohn's disease from ulcerative colitis.

<p>All values are presented as percentages. Cut-off values were determined by ROC curves, establishing as positive tests: phospho-RB-positive cells ≥24%; and β-catenin score ≤1.4. The positive endpoint was arbitrarily considered for the diagnosis of Crohn's disease. NPV, negative predictive value; PPV, positive predictive value.</p

Phospho-RB and β-catenin staining pattern helps the differential diagnose of IBDU cases.

<p>A. Low phospho-RB ser^807/811and high β-catenin staining in a 50-year old woman patient lately diagnosed with UC (Patient A). B. High phospho-RB ser^807/811and low β-catenin staining in a 28-year old woman lately diagnosed with CD (Patient B). Slides were counterstained with methyl green. Scale bar = 50 µm.</p