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Model for the signaling pathway leading to SCAR activation during S2 cell lamella formation. The con A-coated coverslip activates both Rac proteins and Nck by
Depth of carcinoma invasion: Smoothelin is a novel smooth muscle-specific marker expressed only in terminally differentiated smooth muscle cells as part of its contractile cytoskeletons. Unlike traditional smooth muscle markers (ie, SMA and MSA), smoothelin expression is absent or limited in noncontractile and proliferative smooth muscle cells or cells with smooth muscle-like features (ie, myofibroblasts). Smoothelin expression is detected in the muscularis propria (strong) of the urinary bladder and the gastrointestinal tract, but is weak or absent in the muscularis mucosae. This immunohistochemical staining pattern is very helpful in determining the depth of bladder carcinoma invasion since normal or hyperplastic muscularis mucosae may be easily misdiagnosed as muscularis propria in superficial bladder biopsy or transurethral resection specimens ...
Amoebae of the slime mould Dictyostelium discoideum form broad ultrathin cytoplasmic lamellae by a centripetal contractile process soon after they have spread on certain solid surfaces. We have investigated the surface requirements for initial triggering of this contact-mediated signalling system. The lamellar response is not normally evoked by glass, but is seen on glass covalently derivatized with paraffinic chains, as well as on glass covalently derivatized with amine groups and on glass bearing adsorbed polylysine. We have recorded the frequency of the lamellar response on these surfaces as a function of ionic strength and pH, and have measured the electrostatic potentials of the surfaces by the streaming potential method. Using these data we have concluded that the general trigger for the lamellar response is not a simple physical or chemical property of the substrata: it is not dependent on specific chemical groups, degree of hydrophobicity, electrostatic potential, or charge density, ...
Patients and specimens. Fifty-four patients who underwent resection for adenocarcinoma lung cancer at the National Taiwan University Hospital between September 1994 and December 1996 were studied. This study was approved by the institutional review board of National Taiwan University Hospital. Written informed consent was obtained from all patients. Specimens of lung cancer tissue obtained at surgery were immediately snap frozen in liquid nitrogen and stored until use.. The histologic classification of these tumors was based on the WHO criteria (20). Pathologic staging was done according to the tumor-node-metastasis system for lung cancer staging (21). The patients consisted of 24 men and 30 women (mean age, 60.2 ± 10.8 years). The surgicopathologic stage of disease was I in 19 patients, II in 7 patients, III in 20 patients, and stage IV in 8 patients. Tumor status was T1 in 12 patients, T2 in 26 patients, T3 in 13 patients, and T4 in 3 patients. Twenty-four patients had no lymph node ...
including screening analysis, studies of lamellae formation & data assessment. Glass delamination studies for pharmaceutical containers are necessary to mitigate risks associated with generation of lamellae (or small glass flakes) from the inner surface of a glass pharmaceutical container.. Glass delamination represents a serious quality issue, and several drugs have recently been recalled due to this problem and Regulatory Authorities such as the US Food and Drug Administration (FDA) have highlighted these product recalls. Small glass particles - when injected directly into a patient - may lead to serious health risks such as embolic, thrombotic and other vascular events.. Manufacturing process differences within the glass industry and the nature of drug product are reported to be the most dominant factors that enhance glass delamination. Manufacturing conditions such as the moulding process or formation from glass tubing under high temperatures, plus any additional treatments after formation, ...
Hypoxia plays a key role in tumour cell survival, invasion, and metastasis. An increasing number of studies have attemptedto characterize the tumour response to hypoxia and to identify predictive markers of disease. Here we show that hypoxiaincreases tumour cell invasion and migration by the modulation of Rab11, an important molecule for vesicular trafficking.In our study, we found that Rab11, together with the activation of Rac1, could stimulate invasion and migration of cervicalcancer cell lines HeLa/SiHa in hypoxia. Activation of Rac1 activity by hypoxia seems to be central to carcinoma invasion.We also found that these effects could be related to the integrin αvβ3. In addition, we studied the molecular pathway for thisprocess. Our results showed that in cervical cancer cell lines HeLa/SiHa, Rac1 activation in hypoxia could stimulateinvasion and migration, and this process was mediated by integrin αvβ3-mediated FAK and PI3K phosphorylation.Furthermore, hypoxia induced a dramatic increase ...
Hepatocellular carcinoma (HCC) is one of the most common cancer types worldwide, particularly in China [1, 2]. HCCs that undergo early vascular invasion are highly resistant to existing therapies, such as chemotherapy [3]. Although current advances have been made in the diagnosis of HCC, the overall survival rate of the HCC patients is disappointingly low due to recurrence and metastasis [4, 5]. Extensive studies have identified that many risk factors such as hepatitis B (HBV) and hepatitis C (HCV), and dysregulation of signaling pathway and molecules, are implicated in HCC development [6, 7]. However, little is known about how HCC undergoes metastasis. Therefore, identifying potential molecular mechanisms contributing to the metastasis of HCC is one of the most critical issues.. Metastasis, a complex biological process that involves tumor cells detaching from the primary tumor, migrating and locating in distant organs, is the principal cause leading to death in all types of cancer including HCC ...
The locomotion of single epidermis cells, grown out from Xenopus laevis tadpole tails has been investigated by time-lapse cinemicrography using phase-contrast and reflection-contrast optics. The cells develop a large, mostly 200-250 nm thick, lamella, which adheres homogeneously to the supporting coverglass and exceeds the projection area of the cell body. From the comparison of RIC-pictures taken at high (1.06) and low (0.62) numerical aperture of illumination (I.N.A.) we deduce that at low I.N.A. the embossment of the medium-facing side of the lamella is visualized. By this method microcolliculi are demonstrated, which form at the edge of the lamellipodium and move backward. They resemble ruffles, but are flatter and no membrane flow towards the perinuclear region is observed. Indirect immunofluorescence reveals an enhanced staining for actin and alpha-actinin in the lamellipodium and in the transition region of cell body and lamella. Tonofilaments do not participate in lamella formation, the
The integrin α6β4 is upregulated in pancreatic carcinoma and signaling from this integrin promotes metastatic properties, including cancer cell invasion. We have previously shown that the integrin α6β4 promotes such properties by dramatically altering the transcriptome toward an invasive phenotype. Furthermore, we have found that transcriptome alterations can be accomplished through targeted DNA demethylation of specific promoters, as we have shown with the pro-metastatic gene S100A4. In this study, we find that signaling from the integrin α6β4 dramatically upregulates expression of amphiregulin (Areg) and epiregulin (Ereg), ligands for the epidermal growth factor receptor (EGFR), and that these ligands promote pancreatic carcinoma invasion. To determine if Areg and Ereg are regulated by DNA methylation, pancreatic cancer cells with low expression of the integrin α6β4 were treated with the DNA methyltransferase inhibitor 5-aza-2-deoxycytidine (DAC), which resulted in stable over ...
Laminin 5 regulates anchorage and motility of epithelial cells through integrins alpha6beta4 and alpha3beta1, respectively. We used targeted disruption of the LAMA3 gene, which encodes the alpha3 subunit of laminin 5 and other isoforms, to examine developmental functions that are regulated by adhesion to the basement membrane (BM). In homozygous null animals, profound epithelial abnormalities were detected that resulted in neonatal lethality, consistent with removal of all alpha3-laminin isoforms from epithelial BMs. Alterations in three different cellular functions were identified. First, using a novel tissue adhesion assay, we found that the mutant BM could not induce stable adhesion by integrin alpha6beta4, consistent with the presence of junctional blisters and abnormal hemidesmosomes. In the absence of laminin 5 function, we were able to detect a new ligand for integrin alpha3beta1 in the epidermal BM, suggesting that basal keratinocytes can utilize integrin alpha3beta1 to interact with an ...
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Control of integrin activation and signaling plays crucial roles in cell adhesion, spreading and migration. Here, we report that selective breakage of two conserved disulfide bonds located at the knees of integrin alpha(4)C589-C594 and beta(7)C494-C526 activated alpha(4)beta(7). This activated integrin had a unique structure that was different from the typical extended conformation of active integrin. In addition, these activated alpha(4)beta(7) integrins spontaneously clustered on the cell membrane and triggered integrin downstream signaling independent of ligand binding. Although these disulfide bonds were not broken during alpha(4)beta(7) activation by inside-out signaling or Mn2+, they could be specifically reduced by 0.1 mM dithiothreitol, a reducing strength that could be produced in vivo under certain conditions. Our findings reveal a novel mechanism of integrin activation under specific reducing conditions by which integrin can signal and promote cell spreading in the absence of ligand ...
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A new PocketMine-MP Beta Build has been released! Alpha_1.4dev-599 beta8, for Minecraft: PE v0.9.5 alpha Will plugins break? The API version has not been...
khangman-3.4.0_beta2.ebuild: Ebuild for 3.4.0_beta2. Note that beta2 has NOT been released as of this date. This ebuild is for inside testing by the KDE team, and is of course package.masked. *khangman-3.4.0_beta1 (15 Jan 2005) 15 Jan 2005; Dan Armak ...