Genomics and proteomics approaches to the study of cancer-stroma interactions

Background: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression. Methods: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells. Results: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR. Conclusions: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.

New approaches to underground systems in Brazilian Smilax species (Smilacaceae)

MARTINS, A. R. (Institute of Biology, State University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil), N. PUT, (Division of Biology and Education, University of Vechta, 49377 Vechta, Germany), A. N. SOARES, A.B BOMB, and B. APPEZZATO DA GLORIA (Biological Science Department, Escola Superior de Agricultura `Luiz de Queiroz`, University of Sao Paulo, 13418-900, Piracicaba, SP, Brazil). J. Torrey Bot. Soc. 137: 220-235. 2010.-New approaches to underground systems in Brazilian Smilax species (Smilacaceae). Scientific studies show that the watery extract of the thickened underground stem and its adventitious roots of the genus Smilax can act as a therapeutic agent in immunoinflammatory disorders, such as rheumatic arthritis. Brazilians have used this genus of plants in folk medicine, however it is very hard to identify these species, since the morphology of the underground systems is very similar in this group. For better identification of those systems, we studied six species of Smilax L. (S. brasiliensis, S. campestris, S. cissoides, S. goyazana, S. oblongifolia and S. rufescens), collected in different regions of Brazil with different physiognomies and soil characteristics. The main purpose is to describe the morpho-anatomy of the underground systems and to analyze if their structure depends on environmental conditions. The underground stem (rhizophore) is of brown color and it is knotty, massive, slender (S. rufescens) or tuberous (S. brasiliensis, S. campestris, S. cissoides, S. goyazana and S. oblongifolia). The tuberization is a result of primary thickened meristem (PTM) activity. The color and thickness of the adventitious roots change during development because the epidermis and outer cortex are disposed of, so the inner cortex becomes the new covering tissue with lignified and dark color cells. There are differences in starch grain shapes in mature roots. The chemical attributes of the soil are very similar in all studied environments and, even when soil characteristics varied, all the species` underground system was distributed close to the soil surface (10 to 15 cm deep). The species exhibited clonal growth hence their underground system functions as storage structures and the axillary buds can sprout into new stems. Only Smilax rufescens, collected in sandy soil of Restinga, has vegetative dispersal due to the runners.

Analysis of Approaches to Controllership in Mater`s Thesis from Post-graduate Programs in Accounting Sciences

The objective of the Study is to analyze approaches in master`s thesis in Brazilian Post-Graduate Programs in Accounting Sciences in relation to Controllership, in terms of their conceptual, procedural and organizational aspects, as proposed by Borinelli (2006). The research is descriptive and it uses a quantitative approach. The sample consists of 26 master`s thesis which have the word ""Controllership"" in their titles. Resulting from analysis, in Perspective I (conceptual aspects), in which the elements of definition, object of study and relationship with other sciences were referenced, consensus among authors of the master`s thesis was not verified. In Perspective II (procedural aspects), which deals with activities and functions of Controllership by means of how they materialize as areas of knowledge within organizations, it was observed that the approach in the master`s thesis is quite differentiated in terms of the scope of activities. In relation to Perspective III (organizational aspects), there is also no consensus about what constitutes typical Controllership activities, but master`s thesis do include in the definition of Controllership the idea that it is a service or function of information. It was concluded that the approach to controllership, in terms of its conceptual, procedural and organizational aspects is similar to the elements proposed by Borinelli (2006).

Microsurgical anatomy and approaches to the cavernous sinus

OBJECTIVE: The aim of this article is to describe the anatomy of the cavernous sinus and to provide a guide for use when performing surgery in this complex area. Clinical cases are used to illustrate routes to the cavernous sinus and its contents and to demonstrate how the cavernous sinus can be used as a pathway for exposure of deeper structures. METHODS: Thirty cadaveric cavernous sinuses were examined using X3 to X40 magnification after the arteries and veins were injected with colored silicone. Distances between the entrance of the oculomotor and trochlear nerves and the posterior clinoid process were recorded. Stepwise dissections (if the cavernous sinuses, performed to demonstrate the intradural and extradural routes, are accompanied by intraoperative photographs of those approaches. RESULTS: The anatomy of the cavernous sinus is complex because of the high density of critically important neural and vascular structures. Selective cases demonstrate how a detailed knowledge of cavernous sinus anatomy can provide for safer surgery with low morbidity. CONCLUSION: A precise understanding of the bony relationships and neurovascular contents of the cavernous sinus, together with the use of cranial base and microsurgical techniques, has allowed neurosurgeons to approach the cavernous sinus with reduced morbidity and mortality, changing the natural history of selected lesions in this region. Complete resection of cavernous sinus meningiomas has proven to be difficult and, in many cases, impossible without causing significant morbidity. However, surgical reduction of such lesions enhances the chances for success of subsequent therapy.

Clinical Approaches to Preserve beta-Cell Function in Diabetes

In type 2 diabetes (DM2) there is progressive deterioration in beta-cell function and mass. It was found that islet function was about 50% of normal at the time of diagnosis and reduction in beta-cell mass of about 60% at necropsy (accelerated apoptosis). Among the interventions to preserve the beta-cells, those to lead to short-term improvement of beta-cell secretion are weight loss, metformin, sulfonylureas, and insulin. The long-term improvement was demonstrated with short-term intensive insulin therapy of newly diagnosed DM2, the use of antiapoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase 4 and/or to inhibit that enzyme (GLP-1 enhancers). The incretin hormones are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and overall maintenance of glucose homeostasis. From the two major incretins, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), only the first one or its mimetics or enhancers can be used for treatment. The GLP-1 mimetics exenatide and liraglutide as well as the DPP4 inhibitors (sitagliptin and vildagliptin) were approved for treatment of DM2.

The implications of microsurgical anatomy for surgical approaches to the sellar region

The knowledge of the normal anatomy and variations regarding the management of tumors of the sellar region is paramount to perform safe surgical procedures. The sellar region is located in the center of the middle cranial fossa; it contains complex anatomical structures, and is the site of various pathological processes: tumor, vascular, developmental, and neuroendocrine. We review the microsurgical anatomy (microscopic and endoscopic) of this region and discuss the surgical nuances regarding this topic, based on anatomical concepts.

Nonoperative Approaches to Rectal Cancer: A Critical Evaluation

A neoadjuvant multimodality approach with chemoradiation therapy (CRT) is the preferred treatment strategy for most distal rectal cancers. Significant downstaging and complete pathologic response may develop after this strategy, and there is still controversy regarding the management of these patients. In this setting, a nonoperative approach has been suggested in select patients with complete clinical response after thorough clinical, endoscopic, and radiologic assessment. However, the assessment of these patients is not straightforward and remains complex. Available data regarding this approach are limited to a single institution`s experience from retrospective analyses. Standardization of the assessment of tumor response and the development of radiological/molecular tools may clarify the role of no immediate surgery in patients with complete clinical response after neoadjuvant CRT. Advances in radiation and medical oncology could potentially lead to significant improvements in complete tumor regression rates, leading to an increase in importance of a minimally invasive approach in patients with rectal cancer. Semin Radiat Oncol 21:234-239 (C) 2011 Elsevier Inc. All rights reserved.

Microsurgical anatomy of the safe entry zones on the anterolateral brainstem related to surgical approaches to cavernous malformations

OBJECTIVE: To study the microanatomy of the brainstem related to the different safe entry zones used to approach intrinsic brainstem lesions. METHODS: Ten formalin-fixed and frozen brainstem specimens (20 sides) were analyzed. The white fiber dissection technique was used to study the intrinsic microsurgical anatomy as related to safe entry zones on the brainstem surface. Three anatomic landmarks on the anterolateral brainstem surface were selected: lateral mesencephalic sulcus, peritrigeminal area, and olivary body. Ten other specimens were used to study the axial sections of the inferior olivary nucleus. The clinical application of these anatomic nuances is presented. RESULTS: The lateral mesencephalic sulcus has a length of 7.4 to 13.3 mm (mean, 9.6 mm) and can be dissected safely in depths up to 4.9 to 11.7 mm (mean, 8.02 mm). In the peritrigeminal area, the distance of the fifth cranial nerve to the pyramidal tract is 3.1 to 5.7 mm (mean, 4.64 mm). The dissection may be performed 9.5 to 13.1 mm (mean, 11.2 mm) deeper, to the nucleus of the fifth cranial nerve. The inferior olivary nucleus provides safe access to lesions located up to 4.7 to 6.9 mm (mean, 5.52 mm) in the anterolateral aspect of the medulla. Clinical results confirm that these entry zones constitute surgical routes through which the brainstem may be safely approached. CONCLUSION: The white fiber dissection technique is a valuable tool for understanding the three-dimensional disposition of the anatomic structures. The lateral mesencephalic sulcus, the peritrigeminal area, and the inferior olivary nucleus provide surgical spaces and delineate the relatively safe alleys where the brainstem can be approached without injuring important neural structures.

A geometrical approach of 3-D FEA for educational purposes applied to electrostatic fields

A geometrical approach of the finite-element analysis applied to electrostatic fields is presented. This approach is particularly well adapted to teaching Finite Elements in Electrical Engineering courses at undergraduate level. The procedure leads to the same system of algebraic equations as that derived by classical approaches, such as variational principle or weighted residuals for nodal elements with plane symmetry. It is shown that the extension of the original procedure to three dimensions is straightforward, provided the domain be meshed in first-order tetrahedral elements. The element matrices are derived by applying Maxwell`s equations in integral form to suitably chosen surfaces in the finite-element mesh.

Development Resource Planning: Complexity of Product Development and the Capacity to Launch New Products

Overcommitment of development capacity or development resource deficiencies are important problems in new product development (NPD). Existing approaches to development resource planning have largely neglected the issue of resource magnitude required for NPD. This research aims to fill the void by developing a simple higher-level aggregate model based on an intuitive idea: The number of new product families that a firm can effectively undertake is bound by the complexity of its products or systems and the total amount of resources allocated to NPD. This study examines three manufacturing companies to verify the proposed model. The empirical results confirm the study`s initial hypothesis: The more complex the product family, the smaller the number of product families that are launched per unit of revenue. Several suggestions and implications for managing NPD resources are discussed, such as how this study`s model can establish an upper limit for the capacity to develop and launch new product families.

An investigation into feature construction to assist word sense disambiguation

Identifying the correct sense of a word in context is crucial for many tasks in natural language processing (machine translation is an example). State-of-the art methods for Word Sense Disambiguation (WSD) build models using hand-crafted features that usually capturing shallow linguistic information. Complex background knowledge, such as semantic relationships, are typically either not used, or used in specialised manner, due to the limitations of the feature-based modelling techniques used. On the other hand, empirical results from the use of Inductive Logic Programming (ILP) systems have repeatedly shown that they can use diverse sources of background knowledge when constructing models. In this paper, we investigate whether this ability of ILP systems could be used to improve the predictive accuracy of models for WSD. Specifically, we examine the use of a general-purpose ILP system as a method to construct a set of features using semantic, syntactic and lexical information. This feature-set is then used by a common modelling technique in the field (a support vector machine) to construct a classifier for predicting the sense of a word. In our investigation we examine one-shot and incremental approaches to feature-set construction applied to monolingual and bilingual WSD tasks. The monolingual tasks use 32 verbs and 85 verbs and nouns (in English) from the SENSEVAL-3 and SemEval-2007 benchmarks; while the bilingual WSD task consists of 7 highly ambiguous verbs in translating from English to Portuguese. The results are encouraging: the ILP-assisted models show substantial improvements over those that simply use shallow features. In addition, incremental feature-set construction appears to identify smaller and better sets of features. Taken together, the results suggest that the use of ILP with diverse sources of background knowledge provide a way for making substantial progress in the field of WSD.