System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenicity

Many fibroblast-secreted proteins promote tumorigenicity, and several factors secreted by cancer cells have in turn been proposed to induce these proteins. It is not clear whether there are single dominant pathways underlying these interactions or whether they involve multiple pathways acting in parallel. Here, we identified 42 fibroblast-secreted factors induced by breast cancer cells using comparative genomic analysis. To determine what fraction was active in promoting tumorigenicity, we chose five representative fibroblast-secreted factors for in vivo analysis. We found that the majority (three out of five) played equally major roles in promoting tumorigenicity, and intriguingly, each one had distinct effects on the tumor microenvironment. Specifically, fibroblast-secreted amphiregulin promoted breast cancer cell survival, whereas the chemokine CCL7 stimulated tumor cell proliferation while CCL2 promoted innate immune cell infiltration and angiogenesis. The other two factors tested had minor (CCL8) or minimally (STC1) significant effects on the ability of fibroblasts to promote tumor growth. The importance of parallel interactions between fibroblasts and cancer cells was tested by simultaneously targeting fibroblast-secreted amphiregulin and the CCL7 receptor on cancer cells, and this was significantly more efficacious than blocking either pathway alone. We further explored the concept of parallel interactions by testing the extent to which induction of critical fibroblast-secreted proteins could be achieved by single, previously identified, factors produced by breast cancer cells. We found that although single factors could induce a subset of genes, even combinations of factors failed to induce the full repertoire of functionally important fibroblast-secreted proteins. Together, these results delineate a complex network of tumor-fibroblast interactions that act in parallel to promote tumorigenicity and suggest that effective anti-stromal therapeutic strategies will need to be multi-targeted

Globalization and International R&D Flows into Emerging Markets: Nomothetic Evidence

In this paper we analyze the impact of some determinants of international R&D expenditures made by overseas affiliates of MNCs. We also examine whether globalization has expedited international R&D investment flows since 1995, the year that internet access was opened up to mass usage and trade barriers began to concertedly decrease worldwide, following the emergence of the World Trade Organization (WTO). We find evidence that ethnic diversity, political stability, and patent rights enforcement promotes international flows of R&D investments. Increased workers’ educational levels appear to have contradicting effects on international R&D investment flows. When we isolated the effects of globalization into its component forces of technological advancement and trade liberalization, we found some notable interaction effects, especially involving trade barriers. Increased globalization since 1995 has increased international R&D flows in the face of diminishing tariff barriers. A dataset containing more countries and more recent time horizons should help to unravel some of the counter-intuitive and confounding results that our study has unearthed

Translational diffusion of fluorescent probes on a sphere: monte carlo simulations, theory, and fluorescence anisotropy experiment

Translational diffusion of fluorescent molecules on curved surfaces (micelles, vesicles, and proteins) depolarizes the fluorescence. A Monte Carlo simulation method was developed to obtain the fluorescence anisotropy decays for the general case of molecular dipoles tilted at an angle a to the surface normal. The method is used to obtain fluorescence anisotropy decay due to diffusion of tilted dipoles on a spherical surface, which matched well with the exact solution for the sphere. The anisotropy decay is a single exponential for α = 0° , a double exponential for α = 90° , and three exponentials for intermediate angles. The slower decay component(s) for α ≠ 0 arise due to the geometric phase factor. Although the anisotropy decay equation contains three exponentials, there are only two parameters, namely a and the rate constant, Dtr/R2, where Dtr is the translational diffusion coefficient and R is the radius of the sphere. It is therefore possible to determine the orientation angle and translational diffusion coefficient from the experimental fluorescence anisotropy data. This method was applied in interpreting the fluorescence anisotropy decay of Nile red in SDS micelles. It is necessary, however, to include two other independent mechanisms of fluorescence depolarization for molecules intercalated in micelles. These are the wobbling dynamics of the molecule about the molecular long axis, and the rotation of the spherical micelle as a whole. The fitting of the fluorescence anisotropy decay to the full equation gave the tilt angle of the molecular dipoles to be 1± 2° and the translational diffusion coefficient to be 1.3± 0.1×10-10 m2/s

Organizational Control Systems: Matching Controls with Organizational Levels

Companies today face a number of risks, such as environmental liabilities, losses from misuse of derivatives or harassment suits, which underscore the need for better control systems. Clearly, there is a tradeoff between having too much versus too little control. However, in addition to the amount of control, the mix of controls is important in maintaining the right balance within an organization. A framework is proposed that should help managers determine the appropriate matching of control types and control levels in their organizations. The matching is discussed for both traditional companies and modern, information-age companies

Transportation of lymph node biopsy specimens in selective Kirchner’s liquid medium for culture of tubercle bacilli

Lymph node biopsy specimens, obtained from 297 paediatric and adult patients with tuberculous lymphadenitis at Madurai, were transported in selective Kirchner’s liquid medium (KL-T) to the Tuberculosis Research Centre, Madras and processed for culture. Mycobucterium tuberculosis was isolated from 201 (68%) specimens. Of the 192 specimens received within 4 days of resection, 134 (69.8%) yielded M. tuberculosis on culture and of the 105 specimens received after 5 days, 67 (63.8%) were culture positive; the difference was not statistically significant. By incubating KL-T alone further, after removing the gland for processing, it was found that mere contact with the excised node during transportation was enough to retrieve 77 (38.3%) of the total of 201 positive isolates obtained, the delay did not affect the culture positivity rate. Thus, lymph node specimens for culture of tubercle bacilli can be stored in the refrigerator for up to 15 days and transported in KL-T at ambient temperature for 18-20 h without any loss in culture positivity

Tuberculosis awareness among educated public in two cities in Tamil Nadu

A questionnaire on source of information regarding tuberculosis, signs and symptoms, diagnostic methods, treatment duration and personal and community hygiene relating to tuberculosis, was administered to 446 students and employees with an educational status of high school certificate and above. The main source of information were books and magazines and 86% were aware that the Tuberculosis germ was the causative agent. Symptoms of Tuberculosis such as cough (85%) and loss of weight (74%) were well known. Other symptoms suchchest pain (29%), fever (27%) were less known. Sputum examination as a diagnostic tool was known to 68% while 80% knew about radiograph being used to diagnose the disease. Cough as a method of spread was known to 91%. In this questionnaire the duration of treatment was the least known fact. 28% felt that treatment could be stopped if symptoms disappeared. 16% were aware that the method of sputum disposal was by incineration. The implications are discussed