Attachment of HeLa cells during early G1 phase

Both growth factor directed and integrin dependent signal transduction were shown to take place directly after completion of mitosis. The local activation of these signal transduction cascades was investigated in early G1 cells. Interestingly, various key signal transduction proteins were found in blebs at the cell membrane within 30 min after mitosis. These membrane blebs appeared in round, mitotic-like cells and disappeared rapidly during spreading of the cells in G1 phase. In addition to tyrosine-phosphorylated proteins, the blebs contained also phosphorylated FAK and phosphorylated MAP kinase. The formation of membrane blebs in round, mitotic cells before cell spreading is not specific for mitotic cells, because similar features were observed in trypsinized cells. Just before cell spreading also these cells exhibited membrane blebs containing active signal transduction proteins. Inhibition of signal transduction did not affect membrane bleb formation, suggesting that the membrane blebs were formed independent of signal transduction

Novel role of cPLA2α in membrane and actin dynamics

Actin-directed processes such as membrane ruffling and cell migration are regulated by specific signal transduction pathways that become activated by growth factor receptors. The same signaling pathways that lead to modifications in actin dynamics also activate cPLA2α. Moreover, arachidonic acid, the product of cPLA2α activity, is involved in regulation of actin dynamics. Therefore, it was investigated whether cPLA2α plays a role in actin dynamics, more specifically during growth factor-induced membrane ruffling and cell migration. Upon stimulation of ruffling and cell migration by growth factors, endogenous cPLA2α and its active phosphorylated form were shown to relocate at protrusions of the cell membrane involved in actin and membrane dynamics. Inhibition of cPLA2α activity with specific inhibitors blocked growth factor-induced membrane and actin dynamics, suggesting an important role for cPLA2α in these processes

Systemic Pharmacokinetics of Oxaliplatin After Intraperitoneal Administration by Electrostatic Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC) in Patients with Unresectable Colorectal Peritoneal Metastases in the CRC-PIPAC Trial

Background Electrostatic pressurized intraperitoneal aerosol chemotherapy (ePIPAC) is a palliative treatment for unresectable peritoneal metastases from various primary cancers. However, little is known about the systemic pharmacokinetics of oxaliplatin after ePIPAC. Methods Twenty patients with unresectable colorectal peritoneal metastases were treated with repetitive ePIPAC monotherapy with oxaliplatin (92 mg/m(2)) and a simultaneous intravenous bolus of leucovorin (20 mg/m(2)) and 5-fluorouracil (400 mg/m(2)). Samples were collected during each ePIPAC: whole blood att = 0,t = 5,t = 10,t = 20,t = 30,t = 60,t = 120,t = 240,t = 360 andt = 1080 min for plasma and plasma ultrafiltrate concentrations; urine att = 0,t = 1,t = 3,t = 5 andt = 7 days. Samples were analyzed using atomic absorption spectrometry. Pharmacokinetics were analyzed using nonlinear mixed-effects modeling. Results Four patients received one ePIPAC, three patients received two ePIPAC, and thirteen patients received >= 3 ePIPAC. The population pharmacokinetic models adequately described the pharmacokinetics of oxaliplatin after ePIPAC. The plasma ultrafiltrateC(max)of oxaliplatin reached 1.36-1.90 mu g/mL after 30 min with an AUC(0-24 h)of 9.6-11.7 mu g/mL * h. The plasmaC(max)reached 2.67-3.28 mu g/mL after 90 min with an AUC(0-24 h)of 49.0-59.5 mu g/mL * h. The absorption rate constant (Ka) was 1.13/h. Urine concentrations of oxaliplatin rapidly decreased to less than 3.60 mu g/mL in 90% of the samples at day 7. Discussion Systemic exposure to oxaliplatin after ePIPAC seemed comparable to that after systemic chemotherapy, as described in other literature. Since this is an indirect comparison, future research should focus on the direct comparison between the systemic exposure to oxaliplatin after ePIPAC and after systemic chemotherapy

Insertion patterns of CIS gene families.

<p>For each of five families the columns indicate which tumors contained an insertion for that specific member of a family. Rows indicate specific tumors.</p

A network of significant co-occurring and mutually exclusive common insertion sites (CISs).

<p>CISs are indicated by their manually curated target gene. Red edges indicate a co-occurrence relationship, while green edges indicate a mutually exclusive relationship. The number in parenthesis and the size of the nodes indicate the number of tumors with a viral insertion in the relevant CIS. The thickness of the edges is a measure of the significance of the relationship between the nodes.</p

Analysis of clonality between different families of genes.

<p><b>A.</b> A heatmap of all combinations of gene families and single genes not assigned to a family. Significant difference in clonality for each family are calculated using a binominal test for all samples that are co-inserted in that specific gene (family) pair. Blue squares indicate a significant clonal relation from the group indicated on the Y-axis to the group indicated on the X-axis. Yellow squares indicate a significant clonal relationship from the X-axis to the Y-axis. Black squares indicate no significant relation. <b>B.</b> A network view of the heatmap in A. showing only significant (P<0.05) clonality relationships. An edge points from the more clonal gene(family) to the lesser clonal gene(family). The thickness of an edge is a measure of the significance of the clonality relation. For the fraction displayed on the edges, the numerator represents the number of times the parent node had a higher clonality score while the denominator represents the number of times the child node had a higher clonality score, in a tumor that contained insertions in both nodes.</p

Significant known and novel common insertion sites.

<p>This table gives an overview of the significant CISs and their potential target genes.</p>1<p>Although Fgfr1 has not been found as a common insertion site in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062113#pone.0062113-Theodorou1" target="_blank">[11]</a>, the authors do mention finding one insertion near the gene.</p>2<p>The <i>Myb</i> CIS is a merge of two overlapping CISs (upstream and downstream of the <i>Myb</i> gene).</p

MMTV integrations in two novel CISs.

<p>The putative target gene is shown, with the arrow indicating the transcriptional direction. Arrowheads indicate the genomic location of the viral integrations, with the direction of the arrow indicating the viral transcription direction. Colors indicate the cohort from which the integrations were recovered.</p

Simulation of Microgravity by Magnetic Levitation and Random Positioning: Effect on Human A431 Cell Morphology

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