After embolization, patients were monitored in the hospital and discharged Epigenetics inhibitor only after their liver enzymes had peaked. All patients were prophylactically administered antibiotics for one week in order to prevent abscess formation. Intravenous narcotics were typically administered for pain control. In case of recurrence or progression, TAE procedure can be performed several times [39]. When proximal embolization of tumor-feeding arteries in hepatic metastases was performed

major effectiveness is remarked. Individual embolizations were spaced approximately 4 weeks apart and the majority of patients completed their embolizations in 2 or 3 times [9, 40, 41]. Efficacy Many learn more reviews have been published on loco-regional ablative treatments of liver metastases of NENs. Several studies have been reported on TACE, while only Barasertib mouse few studies on TAE. This review focuses on TAE performance and safety in patients with liver metastases of NENs. It has to be highlighted that many authors did not report data on clinical response to TAE or reported these data as indirect consequence of decrease of tumour markers. As a whole, 896 patients with NEN and liver metastases have been treated for a total of 979 TAE procedures. Median survival rates ranged from 10 to 80 months [9, 21, 35, 39, 42–52], but in the most of studies it

was between 35 and 60 months (Table  1). Survival was reported to be correlated to objective tumor response. Progression free survival ranged from 0 to 60 months. Objective tumour response, including partial and complete response, was 50% as average (range, 2-100%). If we consider both tumour response and stabilization of tumor growth, the rate of patients who received a benefit from TAE was about 40% [9, 21, 35, 39, 42–52] (Table  1). Clinical response was about 56% (range, 9-100%). As far as biochemical response is concerned, TAE was reported to be effective in reducing biochemical markers in >50%

of patients with NEN. In NEN patients with carcinoid syndrome, major decreases in 5-HIAA levels (>50% decrease as compared to baseline) occured in a range of 11-100% [9, 35, 39, 42–44, 51, 53–57] (Table  2). Table 1 Tumour response and survival rate in patients treated with Transarterial Embolization (TAE) Paper Number and type of NEN Number of TAEs TR OS Loewe et al. 2003[7] 23 carcinoids 75 TAE 4 (18%) CR, Montelukast Sodium 12 (55%) PR, 6 (27%) PD 69 months   (22 pts evaluable)   Gupta et al. 2003[18] 69 carcinoids Carcinoids: Carcinoids: 46 (67%) PR, 6 (8.5%) MR, 11 (16%) SD, 6 (8.5%) PD 18 months   54 PNENs 42 TAE/27 TACE PNEN: 19 (35%) PR, 1 (2%) MR, 32 (59%) SD, 2 (4%) PD     PNENs:     32 TAE/22 TACE   Carrasco et al. 1986[32] 25 carcinoids 25 TAE 20 (87%) CR, 1 (5%) PD 11 months   (23 evaluable)   Strosberg et al. 2006[36] 59 carcinoids 161 TAE 23 pts evaluable: 11 (48%) PR, 12 (52%) SD 36 months   20 PNENs     5 unspecified NENs   Hanssen et al. 1989[39] 19 carcinoids (7 evaluable) 7 TAE 7 (100%) PR 12 months Wangberg et al.

Briefly, it was found that c-myc in both SBT and NSBT

was SB202190 research buy inversely correlated with p16, r = -0.74 and r = -0.68 respectively, and Rb, r = -0.83 and r = -0.89 respectively (P < 0.05). p53 was positively correlated with bcl-2, r = +0.72, in SBT (P < 0.05) but not in NSBT. EGFR was positively correlated with c-myc in both SBT, r = +0.57, and NSBT, r = +0.61 (P < 0.05). And p16 was inversely correlated with p53 in SBT, r = -0.59, and NSBT, r = -0.64 (P < 0.05). Discussion This study confirmed that the Middle East is greatly affected by schistomiasis. In this study, SBT was 53.57% of the involved cases of bladder cancer. In addition, the mean age of SC and SBT patients was lower than in NSC and NSBT respectively with significant male predominance in SBT and SC cases. This indicated that

schistomal infection speeds up the incidence of SC and SBT. This finding was supported by another report which revealed that the development of SBT occurs in younger age group, 49.4 years [7] and Ro 61-8048 molecular weight 51.4 years [19] where it affects males predominantly. SBT was associated significantly with SCC, high grade, and invasive tumors while NSBT was associated with TCC, a bit lower grade, and less invasive tumors. This provided evidence that the molecular basis and the underlying mechanisms of cancer development in SBT and NSBT might be different. Regarding the association of SBT with SCC, this study was congruous with other reports [6, 19] but this study showed that SBT is associated more with high grade tumors and disagreed with other studies [19, 20] conducted in Egypt which revealed that

SBT is associated more with low grade tumors. Unfortunately no studies were conducted in the same region of our study in order to compare. Nevertheless, the possible explanation of this variation might be attributed to the geographical variation between the Nile river valley Exoribonuclease in Egypt and that in Jordan, Syria and Iraq. Alterations in cell cycle, oncogenic, and apoptotic proteins are the key events in determining the biological behavior of bladder cancer [21]. This study provided evidence that the biological behavior between SBT and NSBT and between SC/NSC and CTL groups was different. However, no remarkable differences were found between SC and NSC groups. The expression level of the all studied markers, except for p16 and ki-67 proteins, was different between SBT and NSBT. p53, bcl-2, c-myc, Rb, and EGFR proteins were significantly higher in SBT than in NSBT. This could highlight the important targets of anticancer therapy in SBT and NSBT. Surprisingly, the cystitis patients, who were confirmed free of any premalignant Tideglusib ic50 lesions, showed higher expression of p53, bcl-2, ki-67, and EGFR but not c-myc, p16, and Rb proteins than in CTL group. This provided a clue that both SC and NSC might act as an intermediate stage between normal and tumorous tissues indicating the danger of the long-lasing inflammation of the bladder.

28 log (47%) reduction in total viable cells compared to the control samples (bacteria only). THCPSi NPs that were not loaded with NO applied at the same concentration

produced a negligible reduction in the biofilm density, indicating that the NO released from the prepared NO/THCPSi NPs was the primary cause of any antimicrobial action. In comparison with the high doses of NO donor silica NPs reportedly required for the treatment of S. epidermidis selleck chemical biofilms [22], the sugar-mediated NO/THCPSi NPs showed effective biofilm reduction at a fractional dose. Cytotoxicity of NO/THCPSi NPs to NIH/3T3 fibroblast cells The biocompatibility of THCPSi NPs has been previously reported by Santos and co-workers [25, 28], where cytotoxicity, oxidative, and inflammatory responses were studied for a variety of mammalian cell lines. The toxicity

of NO/THCPSi NPs, glucose/THCPSi NPs, and THCPSi NPs at different concentrations (0.05 to 0.2 mg/mL) over 48 h was evaluated using the NIH/3T3 cell line, which is one of the most commonly used fibroblast cell lines and often used as a model for skin cells. Two viability assays were used for toxicity studies: LDH and fluorescein NU7441 mw diacetate-propidium iodide (FDA-PI). As shown in Figure 6, the Alvocidib results from the LDH assay showed well over 90% viability for all NP types up to 0.1 mg/mL. However, increasing the concentration of NO/THCPSi NPs to 0.2 mg/mL reduced the viability of NIH/3T3 cells to 92%. In contrast, the viability of fibroblast cells incubated with glucose/THCPSi NPs and THCPSi NPs at 0.15 and 0.2 mg/mL remained over 95%. The results of the FDA-PI assay (Additional file 1: Figure S3) were consistent with those obtained using the LDH assay. Figure 6 Toxicity of the NPs to NIH/3T3 fibroblasts using the LDH assay after 48-h incubationc NO/THCPSi NPs (red bars), glucose/THCPSi NPs (blue bars), and THCPSi NPs (yellow bars). Viability measures normalized to no NP control samples (n = 3; mean ± standard deviation shown). The cytotoxicity

of THCPSi NPs has been reported to be concentration dependent [25, 27], and increased very concentrations of NO/THCPSi NPs did raise cytotoxicity. However, the cytotoxicity of THCPSi NPs on fibroblast cells is much less than observed for silica NPs, silver NPs, and other clinical antiseptic wound treatments [3, 11, 44, 45]. We note that dosage optimization (e.g., concentration of 0.1 mg/mL) enables a balance between high antibacterial efficacy and low toxicity towards mammalian cells present in a wound environment to be achieved. Conclusions The present work demonstrates the capacity of THCPSi NPs to be loaded with NO by utilizing the sugar-mediated thermal reduction of nitrite. These NO/THCPSi NPs possess the capacity to deliver NO at therapeutic levels in a more sustained manner than previously demonstrated using NO-releasing NPs. NO delivered from the NPs was effective at killing pathogenic P. aeruginosa, E. coli, and S. aureus after only 2 h of incubation.

There is also a variation in the distribution and prevalence of the various Nutlin-3a mouse SCCmec types in MRCoNS in different countries [26]. SCCmec type III has been found to

be the most prevalent in southern Brazil (52%), SCCmec type IV in the United Kingdom (36%), type IVa in Japan (40.8%), and type II in China. Some authors have recently reported type V and untypable elements in two S. haemolyticus isolates www.selleckchem.com/products/pci-32765.html from Nigeria [27]. Our data add on to this latter study providing information for CoNS other than S. haemolyticus circulating in Nigeria. SCCmec could not be classified in two of the MRCoNS isolates. They may belong to other SCCmec types not considered in the present investigation or may be among those that cannot be assigned to by currently-available PCR-based methods. Nevertheless the design and validation of a comprehensive SCCmec typing classification scheme

for MRCoNS is heavily challenged selleckchem by the frequent isolation of strains possessing “non-typeable” elements or even positive to more than one SCCmec-type [16, 25]. In our study, SCCmec types were assigned by PCR protocols originally developed for SCCmec in MRSA [14, 15], supporting the general conclusion that the scheme is still suitable as a first screening of SCCmec types in MRCoNS. Our results also indicate a large diversity in the J1 region in type IV of SCCmec and a large diversity and heterogenous reservoir of SCCmec among the MRCoNS isolated from faecal samples of humans. This may be a risk for interspecies horizontal transfer of new SCCmec types between CoNS and S. aureus[28]. The hypothesis of the particular case of SCCmec transfer between

S. epidermidis and S. aureus has also been reported [11]. Although direct proof of transfer was not obtained in this study, SCCmec type IVd was present in 8 MRCoNS of various species indicating the possibility Thiamine-diphosphate kinase of interspecies transfer of SCCmec elements in CoNS strains in the gastrointestinal tracts. Conclusion In conclusion, our study indicated that CoNS colonising the gastrointestinal tracts of healthy individuals may represent a reservoir of different antibiotic resistance genes and SCCmec elements. Acknowledgements This work was supported by the Italian Ministry of Education, University, and Research (MIUR, grant PRIN, number 200929YFMK_003 to M. P.) and from the University of Camerino (code FPA00057 to L.A.V.) References 1. Piette A, Verschraegen G: Role of coagulase-negative staphylococci in human disease. Vet Microbiol 2009,134(1):45–54.PubMedCrossRef 2. Akinkunmi E, Lamikanra A: Species distribution and antibiotic resistance in coagulase-negative staphylococci colonizing the gastrointestinal tract of children in Ile-Ife, Nigeria. Trop J Pharm Res 2010,9(1):35–43.CrossRef 3. Archer GL, Climo MW: Antimicrobial susceptibility of coagulase-negative staphylococci. Antimicrob Agents Chemother 1994, 38:2231–2237.PubMedCentralPubMedCrossRef 4.

J Mater Sci 2013, 48:3334–3340.CrossRef 21. Ghadimkhania G, Tacconi NR, Chanmanee W, Janaky C, Rajeshwar K: Efficient

solar photoelectrocheck details synthesis of methanol from carbon dioxide using hybrid CuO-Cu 2 O semiconductor nanorod arrays. Chem Commun 2013, 49:1297–1299.CrossRef 22. Yu XJ, Zhang AM, Zhang J, Zhao J, Yao BH, Liu GJ: Preparation and characterization of Cu 2 O thin films by electrodeposition. Adv Mater Res 2011, 413:371–374.CrossRef 23. Bijani S, Martıínez L, Gabás M, Dalchiele EA, Ramos-Barrado JR: Low-temperature electrodeposition of Cu LEE011 2 O thin films: modulation of micro-nanostructure by modifying the applied potential and electrolytic bath pH. J Phys Chem C 2009, 113:19482–19487.CrossRef 24. Yao HC, Zeng XY, Zhang DJ, Liu L, Yuan BQ: Shape-controlled synthesis of Cu 2 O microstructures at glassy carbon electrode by electrochemical method for non-enzymatic glucose sensor. Int J Electrochem Sci 2013, 8:12184–12191. 25. Jiang P, Prendergast D, Borondics F, Porsgaard S, Giovanetti L, Pach E, Newberg J, Bluhm H, Besenbacher F, Salmeron M: Experimental and theoretical investigation of the electronic structure of Cu 2 O and CuO thin films on Cu(110) using X-ray photoelectron

and absorption spectroscopy. J Chem Phys 2013, 138:024704. 1–6CrossRef 26. Zhang L, Wang H: Interior structural tailoring of Cu 2 O shell-in-shell nanostructures through multistep Ostwald ripening. J Phys Chem C 2011, 115:18479–18485.CrossRef 27. Zhao WY, Fu WY, Yang HB, Tian CJ, Li MH, Li YX, Zhang LN, Sui YM, Zhou XM, Chen H, Zou GT: Electrodeposition of Cu 2 O films and their photoelectrochemical Niraparib cost properties. Cryst Eng Comm 2011, 13:2871–2877.CrossRef 28. Laidoudi S, Bioud AY, Azizi A, Schmerber G, Bartringer J, Barre S, Dinia A: Growth and characterization of electrodeposited Cu 2 O thin films. Semicond Sci Tech 2013, 28:115005. Ribonucleotide reductase 1–7CrossRef 29. Grez P, Herrera F, Riveros G, Ramírez A, Henríquez R, Dalchiele E, Schrebler R: Morphological, structural,

and photoelectrochemical characterization of n-type Cu 2 O thin films obtained by electrodeposition. Phys Status Solidi A 2012, 209:2470–2475.CrossRef 30. Shinde SL, Nanda KK: Facile synthesis of large area porous Cu 2 O as super hydrophobic yellow-red phosphors. RSC Adv 2012, 2:3647–3650.CrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions XSJ and MZ prepared the films and tested the surface topography. X-ray diffraction was investigated by SWS and XPS. The surface morphology and optical properties were measured by GH and ZQS. The calculations were carried out by XSJ who also wrote the manuscript. Besides, MZ helped to draft the manuscript. All authors read and approved the final manuscript.”
“Background Organic optoelectronic devices provide interesting features as they can be applied on inexpensive and flexible large-area substrates [1–3].

Specimens of Ae. albopictus were anaesthetised with ether and surface-disinfected this website as previously described [12], then crushed individually in 150 μl of sterile 0.8% NaCl with sterile piston pellets. After a brief vortexing, the homogenate was used in different isolation procedures using various media, from generalist to selective. All solid media were FRAX597 ic50 supplemented with 2.5 μg ml-1 amphotericin B to prevent the growth of fungi. An aliquot of the homogenate (10 μl) was streaked onto a modified rich solid Luria-Bertani medium (LBm, LB with 5 mg ml-1 NaCl) and incubated

at 28°C for 24 to 48 h. Another aliquot (20 μl) was inoculated into 1 ml of selective enrichment medium I (0.2% KNO3, 0.02% MgSO4.7H2O, 0.2% sodium acetate, 0.04 M KH2PO4, pH 6), a medium which is suitable for the isolation of Acinetobacter species [29]. Cultures were incubated at 30°C for 24 to 48 h with shaking. When microbial

growth occurred, an aliquot (10 μl) of the culture was streaked onto Herellea agar plates (Biolife, Italy), a medium suitable for the isolation of Gram-negative bacteria especially members of the Acinetobacter genus and the Enterobacteriaceae family [30]. These cultures were further incubated at 37°C for 24 to 48 h. In parallel, 1 ml of pre-enrichment liquid medium (pH 3.5), which is suitable for the isolation of acetic acid bacteria [31], was inoculated with an aliquot of homogenate (20 μl). These cultures were incubated with shaking at 30°C for 3 days. When microbial growth occurred, an aliquot (10 μl) was streaked onto CaCO3 agar plates see more (pH 6.8), a medium suitable for the isolation of members of the genus Asaia, and the plate was incubated at 30°C for 3 days as previously described [32]. Colonies were selected according to various characteristics including colour,

shape, or size. Individual colonies were then re-inoculated onto fresh agar plates of the appropriate isolation Ureohydrolase medium. Newly formed colonies were streaked again to check for purity and stored in 25% glycerol at -20°C for two weeks before they were transported to the laboratory in Lyon, France. Isolates were re-streaked and new glycerol stocks were made and stored at -80°C. Brief morphological descriptions of colony size, shape and colour were recorded for each isolate. PCR and amplified ribosomal DNA restriction analysis (ARDRA) For PCR, a sterile toothpick was used to transfer bacteria from a single colony freshly grown on appropriate medium into 20 μl sterile water in a 0.5 ml Eppendorf tube. The homogenate was placed on a heating block at 95°C for 2 min followed by 2 min on ice. This step was repeated and the tube was centrifuged at 16,000 g for 5 min. The supernatant (2 μl) was used as template in a 50-μl PCR reaction.

Sugiura A, Nakashima K, Tanaka K, Mizuno T: Clarification of the structural and functional features of the osmoregulated kdp operon of Escherichia coli. Mol Microbiol 1992, 6:1769–1776.CrossRefPubMed 6. Jung K, AG-120 clinical trial Altendorf K: Towards an understanding of the molecular

mechanisms of stimulus perception and signal transduction by the KdpD/KdpE system of Escherichia coli. J Mol Microbiol Biotechnol 2002, 4:223–228.PubMed 7. Zimmann P, Puppe W, Altendorf K: Membrane topology analysis of the sensor kinase KdpD of Escherichia coli. J Biol Chem 1995, Pexidartinib in vitro 270:28282–28288.CrossRefPubMed 8. Heermann R, Fohrmann A, Altendorf K, Jung K: The transmembrane domains of the sensor kinase KdpD of Escherichia coli are not essential for sensing K + limitation. Mol Microbiol 2003, 47:839–848.CrossRefPubMed 9. Heermann R, Altendorf K, Jung K: The hydrophilic N-terminal domain complements the membrane-anchored Raf inhibitor C-terminal domain of the sensor kinase KdpD of Escherichia coli. J Biol Chem 2000, 275:17080–17085.CrossRefPubMed 10. Jung K, Altendorf

K: Individual substitutions of clustered arginine residues of the sensor kinase KdpD of Escherichia coli modulate the ratio of kinase to phosphatase activity. J Biol Chem 1998, 273:26415–26420.CrossRefPubMed 11. Zimmann P, Steinbrügge A, Schniederberend M, Jung K, Altendorf K: The extension of the fourth transmembrane helix of the sensor kinase KdpD of Escherichia coli is involved in sensing. J Bacteriol 2007, 189:7326–7334.CrossRefPubMed 12. Sugiura A, Hirokawa K, Nakashima K, Mizuno T: Signal-sensing mechanisms of the putative osmosensor KdpD in Escherichia coli. Mol Microbiol 1994, 14:929–938.CrossRefPubMed 13. Brandon L, Dorus S, Epstein W, Altendorf K, Jung

K: Modulation of KdpD phosphatase implicated in the physiological expression of the Kdp-ATPase of Escherichia coli. Mol Microbiol 2000, 38:1086–1092.CrossRefPubMed 14. Rothenbücher MC, Facey SJ, Kiefer D, Kossmann M, Kuhn A: The cytoplasmic C-terminal domain of the Escherichia coli KdpD protein functions as a K + sensor. J Bacteriol 2006, 188:1950–1958.CrossRefPubMed acetylcholine 15. Puppe W, Zimmann P, Jung K, Lucassen M, Altendorf K: Characterization of truncated forms of the KdpD protein, the sensor kinase of the K + -translocating Kdp system of Escherichia coli. J Biol Chem 1996, 271:25027–25034.CrossRefPubMed 16. Jung K, Altendorf K: Truncation of amino acids 12–128 causes deregulation of the phosphatase activity of the sensor kinase KdpD of Escherichia coli. J Biol Chem 1998, 273:17406–17410.CrossRefPubMed 17. Ohwada T, Sagisaka S: An immediate and steep increase in ATP concentration in response to reduced turgor pressure in Escherichia coli B. Arch Biochem Biophys 1987, 259:157–163.CrossRefPubMed 18. Siegele DA: Universal stress proteins in Escherichia coli. J Bacteriol 2005, 187:6253–6254.CrossRefPubMed 19.

Cells were then plated on LB agar containing kanamycin for selection of mutants whose wild-type genes were replaced by allelic exchange via double crossover recombination. Gene replacement in candidate clones was verified by PCR with upFW and dwRV primers (Figure Angiogenesis inhibitor 6). Allelic replacement in candidate clones was further confirmed by sequencing the CH5424802 cost mutant region in the resulting mutants. Figure 6 Gene replacement. (a) Schematic representation of the strategy used to construct mutants by gene replacement. Small, red and shaded arrows represent the primers, the target

gene, and the kanamycin (Km) resistance cassette, respectively. The three PCR products obtained (PCR1, PCR2, and PCR3) were mixed at equimolar concentrations and subjected to a

nested overlap-extension PCR to generate the desired linear DNA (see Materials and Methods for details). (b) Diagram showing the integration of the linear DNA via two recombination events. (c) Representation of the original genetic material replaced by the recombinant DNA on the A. baumannii chromosome. Knockout construction by gene disruption Plasmid insertion in the omp33 gene (Table 1) was carried out as previously described [10], with slight modifications. Briefly, kanamycin- and zeocin-resistant plasmid pCR-BluntII-TOPO, unable to replicate in A. baumannii, was used as a suicide vector. An internal fragment (387 bp) of the omp33 gene was amplified by PCR with 33intUP and 33intDW primers (Table 2) and genomic DNA buy LY3039478 from A. baumannii ATCC 17978 as a template. The PCR product was cloned into the pCR-BluntII-TOPO vector and electroporated in E. coli to yield the pTOPO33int plasmid (Table 3). Recombinant plasmid (0.1 μg) was then introduced in the kanamycin- and zeocin-susceptible A. baumannii ATCC 17978 strain by electroporation. Mutants were selected on kanamycin-containing plates. Inactivation of the omp33 gene by insertion of the plasmid via single crossover recombination was confirmed by sequencing the amplified PCR products with

the SP6 + 33extUP and T7 + 33extDW primer pairs (Table 2). Construction of pET-RA plasmid for gene expression in A. baumannii In order to complement mutant phenotypes, the pET-RA plasmid [Genbank: HM219006] was constructed, and carried a rifampicin resistance Immune system cassette, a gene coding for a green fluorescent protein (GFP), and the A. baumannii replication origin, which is a plasmid origin of replication (Figure 7). The pET-RA vector was used to express promoterless genes under control of the CTX-M14 β-lactamase gene promoter, previously cloned upstream of the GFP gene (Figure 7). For pET-RA construction, the pMW82 vector [Genbank: EF363313] was amplified by PCR, excluding the coding region of the ampicillin resistance cassette. The rifampicin resistance cassette was then amplified from the pAT-RA vector [Genbank: HM219005] and introduced into the pMW82 vector.

We noted that numerous cell lines showed protection from apoptotic stimuli, staurosporine or etoposide, when exposed to long-term INCB28060 datasheet hypoxia (72 hours). In addition, these cells had unusually enlarged mitochondria. selleck chemicals llc Here we reveal that mitochondria of hypoxia-induced chemotherapy-resistant cells undergo a hypoxia-inducible factor-dependent and mitofusin 1-mediated change in morphology from a tubular network to an enlarged phenotype. An imbalance in mitochondrial fusion/fission occurs since silencing of the mitochondrial

fusion protein mitofusin 1 reestablished a tubular morphology. Enlarged mitochondria conserved their transmembrane potential and ATP production, and contained an as yet undetected short isoform of the voltage-dependent anion channel VDAC3. Hypoxic cells were insensitive to staurosporine- and etoposide-induced cell death, but the silencing of VDAC3 restored sensitivity. Our results demonstrate

that hypoxia, by inducing mitochondrial fusion, confers selective protection from apoptosis through expression of a short isoform of VDAC3 that allows maintenance of ATP and cell survival in hypoxia. O60 Biomechanical Model of Stress-Dependent Formation of Tissue Organizing Structures (TOS) Associated with Solid Tumor Formation, Invasion and Metastasis Sarah Crawford 1 1 Cancer Biology P505-15 Research Laboratory, Department of Biology, Southern Connecticut State Sorafenib clinical trial University, New Haven, CT, USA Research studies on early stage solid tumor formation in our laboratory led to the identification of a novel class of cell derived vesicles released by cell budding

or fission that play a critical role in this process, termed “tissue organizing structures” (TOS). These trypsin-resistant, membrane-delimited particles, approximately 2 micron diameter, are produced by diverse cell types, both normal and malignant, and contain genetic material. Documented activities include a critical role in orchestrating solid tumor formation in vitro and the induction of cell morphogenesis following fusion with neighboring cells. Proposed mechanisms of cell transformation include horizontal gene transfer and a novel mechanism termed “insertional membrane editing”. Recent studies in this laboratory have focused on the biophysical components of the cell microenvironment that may contribute to the formation of these novel structures. This research extends previously elaborated biomechanical models of malignant transformation by implicating a specific biological/structural response with direct physiological consequences to biophysical forces initiated by tissue structure interactions.