Heterogeneity for IGF-II production maintained by public goods dynamics in neuroendocrine pancreatic cancer

The extensive intratumor heterogeneity revealed by sequencing cancer genomes is an essential determinant of tumor progression, diagnosis, and treatment. What maintains heterogeneity remains an open question because competition within a tumor leads to a strong selection for the fittest subclone. Cancer cells also cooperate by sharing molecules with paracrine effects, such as growth factors, and heterogeneity can be maintained if subclones depend on each other for survival. Without strict interdependence between subclones, however, nonproducer cells can free-ride on the growth factors produced by neighboring producer cells, a collective action problem known in game theory as the “tragedy of the commons,” which has been observed in microbial cell populations. Here, we report that similar dynamics occur in cancer cell populations. Neuroendocrine pancreatic cancer (insulinoma) cells that do not produce insulin-like growth factor II (IGF-II) grow slowly in pure cultures but have a proliferation advantage in mixed cultures, where they can use the IGF-II provided by producer cells. We show that, as predicted by evolutionary game theory, producer cells do not go extinct because IGF-II acts as a nonlinear public good, creating negative frequency-dependent selection that leads to a stable coexistence of the two cell types. Intratumor cell heterogeneity can therefore be maintained even without strict interdependence between cell subclones. Reducing the amount of growth factors available within a tumor may lead to a reduction in growth followed by a new equilibrium, which may explain relapse in therapies that target growth factors

EMT, the cytoskeleton, and cancer cell invasion

The metastatic process, i.e. the dissemination of cancer cells throughout the body to seed secondary tumors at distant sites, requires cancer cells to leave the primary tumor and to acquire migratory and invasive capabilities. In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. The molecular processes underlying such cellular changes are still only poorly understood, and the various migratory organelles, including lamellipodia, filopodia, invadopodia and podosomes, still require a better functional and molecular characterization. Notably, direct experimental evidence linking the formation of migratory membrane protrusions and the process of EMT and tumor metastasis is still lacking. In this review, we have summarized recent novel insights into the molecular processes and players underlying EMT on one side and the formation of invasive membrane protrusions on the other sid

Sprouty proteins, masterminds of receptor tyrosine kinase signaling

Angiogenesis relies on endothelial cells properly processing signals from growth factors provided in both an autocrine and a paracrine manner. These mitogens bind to their cognate receptor tyrosine kinases (RTKs) on the cell surface, thereby activating a myriad of complex intracellular signaling pathways whose outputs include cell growth, migration, and morphogenesis. Understanding how these cascades are precisely controlled will provide insight into physiological and pathological angiogenesis. The Sprouty (Spry) family of proteins is a highly conserved group of negative feedback loop modulators of growth factor-mediated mitogen-activated protein kinase (MAPK) activation originally described in Drosophila. There are four mammalian orthologs (Spry1-4) whose modulation of RTK-induced signaling pathways is growth factor- and cell context-dependant. Endothelial cells are a group of highly differentiated cell types necessary for defining the mammalian vasculature. These cells respond to a plethora of growth factors and express all four Spry isoforms, thus highlighting the complexity that is required to form and maintain vessels in mammals. This review describes Spry functions in the context of endothelial biology and angiogenesis, and provides an update on Spry-interacting proteins and Spry mechanisms of actio

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

Abstract.: The fatality of cancer predominantly results from the dissemination of primary tumor cells to distant sites and the subsequent formation of metastases. During tumor progression, some of the primary tumor cells as well as the tumor microenvironment undergo characteristic molecular changes, which are essential for the metastatic dissemination of tumor cells. In this review, we will discuss recent insights into pro-metastatic events occurring in tumor cells themselves and in the tumor stroma. Tumor cell-intrinsic alterations include the loss of cell polarity and alterations in cell-cell and cell-matrix adhesion as well as deregulated receptor kinase signaling, which together support detachment, migration and invasion of tumor cells. On the other hand, the tumor stroma, including endothelial cells, fibroblasts and cells of the immune system, is engaged in an active molecular crosstalk within the tumor microenvironment. Subsequent activation of blood vessel and lymph vessel angiogenesis together with inflammatory and immune-suppressive responses further promotes cancer cell migration and invasion, as well as initiation of the metastatic proces

Development and evaluation of polymeric nanoparticle formulations for triamcinolone acetonide delivery

The aims of this study were to develop polymeric NP formulations for triamcinolone acetonide (TA) delivery, from biodegradable and biocompatible hydrophobic polymers, which provide sustained release, prolonged stability and low toxicity, and to assess the toxicity of TA NPs (TA-NPs) compared to TA alone upon BALB/c 3T3 and ARPE 19 cell culture models.The study involved investigation of three different types of polymers: poly(D,L,lactide) (PDLLA), poly(D,L,lactide-co-glycolide)(PLGA) and methoxypolyethyleneglycol poly(D,L,lactide-co-glycolide)(mPEG PLGA). Two different methods were studied in the TA-NPs preparation: spontaneous emulsification solvent diffusion and emulsification solvent evaporation methods.The results show that emulsification-solvent evaporation method was superior to spontaneous emulsification solvent diffusion in terms of yield, loading and entrapment efficiency. TA-NPs synthesised of mPEG PLGA exhibited the smallest particle size, highest efficiency and fastest release of TA, whereas PDLLA produced large TA-NPs with the slowest TA release. The toxicity study revealed that BALB/c 3T3 was more sensitive than ARPE 19 and was concentration dependent in response to 24 hour exposure of either TA or TA-NPs, while ARPE 19 appeared to be less sensitive to the exposure. All NPs were less toxic than TA in all concentrations, in both cell models

AKTIVITAS ANTIBAKTERI LOTION MINYAK KAYU MANIS TERHADAP Staphylococcus epidermidis PENYEBAB BAU KAKI

Abstract: Trans-cinnamaldehyde is the major chemical compound of cinnamon oil which is potential as anantibacterial agent. Due to this activity, Cinnamon oil can be formulated into a lotion for practical use.This study aimed to determine the antibacterial activity of cinnamon oil and cinnamon oil lotion againstStaphylococcus epidermidis, which causes unacceptable foot odor. This study was a pure experimentalstudy. Stages of this study were starting from the obsevation of antibacterial activity of Cinnamon oilagainst Staphylococcus epidermidis which was done by using diffusion method to determine theconcentrations used in the formulation. Cinnamon oil was then formulated into lotions with variation ofconcentrations of 12; 18; and 24% (w/w) respectively. Furthermore, the quality of lotion based on itsphysical properties such as viscosity and spread-ability, and the antibacterial activity of lotion weredetermined. The inhibition zones then were statistically analyzed by using the Kruskal-Wallis test withassistance of R 2.14.1software. The result showed that cinnamon oil lotion had good physical properties ata concentration of 12% (w/w). Cinnamon oil itself and the formulations had significant activity againstStaphylococcus epidermidis. Moreover, cinnamon oil and its formulation showed similar antibacterialactivity against Staphylococcus epidermidis.Keywords : antibacterial activity, cinnamon oil, lotion, Staphylococcus epidermidi

Aktivitas Antibakteri Lotion Minyak Kayu Manis Terhadap Staphylococcus Epidermidis Penyebab Bau Kaki

Trans-cinnamaldehyde is the major chemical compound of cinnamon oil which is potential as an antibacterial agent. Due to this activity, Cinnamon oil can be formulated into a lotion for practical use.This study aimed to determine the antibacterial activity of cinnamon oil and cinnamon oil lotion against Staphylococcus epidermidis, which causes unacceptable foot odor. This study was a pure experimentalstudy. Stages of this study were starting from the obsevation of antibacterial activity of Cinnamon oil against Staphylococcus epidermidis which was done by using diffusion method to determine the concentrations used in the formulation. Cinnamon oil was then formulated into lotions with variation of concentrations of 12; 18; and 24% (w/w) respectively. Furthermore, the quality of lotion based on itsphysical properties such as viscosity and spread-ability, and the antibacterial activity of lotion were determined. The inhibition zones then were statistically analyzed by using the Kruskal-Wallis test withassistance of R 2.14.1software. The result showed that cinnamon oil lotion had good physical properties at a concentration of 12% (w/w). Cinnamon oil itself and the formulations had significant activity againstStaphylococcus epidermidis. Moreover, cinnamon oil and its formulation showed similar antibacterial activity against Staphylococcus epidermidis

Softsensors: New approach for process monitoring cell growth in small scale fermentation systems

Process development and in particular the use of high throughput systems required sampling for controlling. One of the most important parameter is the cell growth, but sampling, sample dilution and analyzing is time consuming and generates high efforts in the case of high throughput fermentation systems. Sampling allows also only a look in the culture status at a certain time point, the information between two sample points is missing. Therefore we develop a new softsensor, which takes online signals of the bioreactor, which are correlated to cell growth to estimate the cell growth. The new approach based on multiple linear regression and on artificial neural network processed the common online signals of the bioreactors to estimate the cell growth as online signal during cultivation time. The cell growth estimated by softsensor was successful implemented in the multiple small scale bioreactor system and resulted estimated values with high confidence and low root mean squared error below 15 %

PEMERIKSAAN PROFIL LIPID PADA JEMAAT LANSIA SALAH SATU GEREJA KRISTEN DI YOGYAKARTA

Lipid profile examination including total cholesterol level, triglycerides level and high-density lipoprotein cholesterol reduction is essential to be done as a routine activity quinquennially to prevent someone from the risk of cardiovascular diseases, diabetes and obesity. This kind of examination is mandatory for the elderly people to maintain their quality of life. In order to support the government program on the prevention of the cardiovascular diseases, a team of social service of Faculty of Pharmacy Universitas Sanata Dharma (FFUSD) was organizing an event of lipid profile examination in one of Christian church located in Kalasan, Yogyakarta. As many as 35 elderly people were enthusiastically participating on the event. A nurse from Poliklinik Sanata Dharma was appointed to take the blood samples, which were further taken to the Biochemistry Laboratory in FFUSD to get analysed. The results were sent to the participants in private. The overall blood lipid profiles of most participants showed good level of quality, indicating that they have been trying to manage their life healthily. However, as much as 62. 8% of participants showed a low level of the high-density lipoprotein cholesterol.  This was believed due to the food intake which was still rich in oil and fat.  The event was very succesful and the responses were very positive. The participants felt assisted with a fast and accurate results sent