This Awesome Blood Labyrinth Is The Newest Method For Catching Cancer Cells

This Awesome Blood Labyrinth Is The Newest Method For Catching Cancer Cells

A new chip with a labyrinth design promises big improvements in detecting rare and aggressive cancer cells in the blood, helping doctors to anticipate tumour growth and plan customised treatments for their patients.
By controlling the flow of the blood through this micro-maze, the chip is able to separate out larger types of cells, including cancer cells and cancer stem cells known to be particularly malignant and resistant to drugs.
Such cancer cells can be one in a billion in a flow of normal white blood cells, and the new method is more effective and faster than current techniques at finding its targets, according to the team from the University of Michigan. “The markers for them are so complex, there is no one marker we could target for all these stages.”
The cells are also thought to sometimes transform into cancer stem cells (CSCs), types of cells that can grow and feed new tumours, which is another reason scientists are keen to keep a close eye on them.
Also crucial are the many corners the researchers have built into their maze: It creates a flow that puts the smaller white blood cells in the perfect position to get snagged.
What’s left at the other end is a much cleaner stream of cancer cells that scientists can then use for their analysis.
The new process is fast too, and by adding a second chip, the team was able to reduce the number of white blood cells in a sample by 10 in just five minutes.
In this case, once the cancer cells are caught and filtered out, scientists can study them to find ones on their way to and from stem-like states.
The new technique is also being used in a breast cancer clinical trial, investigating the effectiveness of a treatment that blocks an immune-signalling molecule called interleukin 6 – experts think interleukin 6 enables cancer stem cells, and this labyrinth-on-a-chip should help to prove it.

Ethanol-triggered Lipophagy Requires SQSTM1 in AML12 Hepatic Cells

Ethanol-triggered Lipophagy Requires SQSTM1 in AML12 Hepatic Cells

We found that both LC3 and SQSTM1 could colocalize with lipid droplets (LDs) following ethanol treatment. In addition, increased ubiquitin signals were found to colocalize with SQSTM1 on LDs in response to ethanol.
Hepatic triglycerides (TG) level in alcoholic fatty liver disease models was reduced by activating autophagy, and was elevated when autophagy was inhibited5,6.
The lipid content in AML12 cells as measured by the levels of TG and cholesterol was elevated in 24 hours after ethanol treatment (Fig.
SQSTM1 is important for LC3 to be associated with LDs and ethanol-induced lipophagy.
In addition, the SQSTM1 level was elevated significantly following PLIN knockdown, although the level of LC3 was only mildly affected (Supplementary Fig. Furthermore, the colocalization of SQSTM1 to the LDs was significantly reduced by the inhibition of PLIN expression in either ethanol alone (Fig. 7A and B) or ethanol plus CQ (Fig.
Using this model, we had the following findings: (1) Autophagy is activated by ethanol in AML12 cells, which requires ethanol to be oxidized; (2) Autophagy regulates the level of lipid content in ethanol-treated cells, consistent with previous in vivo studies that autophagy modulators affect hepatic lipid levels; (3) Autophagic degradation of lipid droplets is indicated by the colocalization of autophagosomes with the lipid droplets and the blockage of the degradation by lysosome inhibitors; (4) Recognition of lipid droplets by autophagosomes is mediated by SQSTM1, and involves ubiquitination signaling; and (5) PLIN could be a target recognized by SQSTM1 and serve as an anchor for autophagosomes on lipid droplets.

A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease

A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease

All four Traj18-partial deletion mouse lines harbored similar Traj gene segments as WT B6 mice, except for Traj18 (Fig.
(a) TCRα repertoire diversity analyzed by next generation sequencing.
Frequencies of iNKT cells in the spleen and liver from WT B6 and Traj18−/− (1-1 L) mice were analyzed by flow cytometry, which revealed iNKT cell-deficiency in Traj18−/− (1-1 L) mice (Fig. Analysis of developmental stages of thymocytes revealed no difference between Traj18−/− (1-1 L) and WT B6 mice (Supplemental Fig. We also analyzed the frequencies of T cells with specific functions such as type 2 NKT cells, regulatory T cells (Treg) and mucosal-associated invariant T (MAIT) cells in the thymus, resulting in no differences between Traj18−/− (1-1 L) and WT B6 mice (Supplemental Fig.
Because some functional studies on iNKT cells require animals on a genetic background distinct from the B6 strain, we also generated a Traj18−/− (1-1 L) BALB/c mouse line by backcrossing, and confirmed the absence of iNKT cells and cytokine production in response to α-GalCer stimulation (Supplemental Fig.
However, divergent findings for the metabolic role of iNKT cells have been reported in studies using the previously generated Traj18−/− mouse strain.
Among the experimental groups on HFD, both Traj18−/− (1-1 L) and Cd1d−/− mice gained less weight than WT B6 mice, whereas there was no significant difference in the weight gain between Traj18−/− (1-1 L) and Cd1d−/− mice (Fig.
Another new Traj18−/− mouse line generated by Dashtsoodol et al. also contained similar Trav1-Traj33 expression levels as WT B6 mice13, indicating normal MAIT cell development and cell number.

Quantitative proteomic Analysis Reveals up-regulation of caveolin-1 in FOXP3-overexpressed human gastric cancer cells

Quantitative proteomic Analysis Reveals up-regulation of caveolin-1 in FOXP3-overexpressed human gastric cancer cells

We have recently reported that FOXP3 inhibited proliferation of gastric cancer (GC) cells through activating the apoptotic signaling pathway.
Then, the label-free quantitative proteomic approach was employed to further investigating the down-stream proteins regulated by FOXP3, resulting in a total of 3,978 proteins quantified, including 186 significantly changed proteins.
Then label-free proteomic experiments were performed to analyze the FOXP3-overexpressed AGS cells and vector cells, resulting in a total of 3978 proteins identified, of which 186 proteins were significantly changed (fold change >1.5, students’ t test p value <0.01) between these two types of cells. FOXP3 was over-expressed in GC cells with lentivirus transfection (AF cells), and the empty vector was also transfected into GC as control cells (ANC cells). The migration of GC cells was also significantly inhibited in FOXP3-overexpressing groups in the transwell migration assay (Fig. The number of migrated cells was lower for AF when compared with ANC, suggesting that FOXP3 inhibited GC cell migration. AF: FOXP3-overexpressing AGS cells; ANC: vector controls. Full size image Box plot analysis was applied to comparing the Log2 transformed LFQ intensity of the AF and ANC cell samples. Collectively, 186 proteins were significantly changed between AF and ANC cells; among them, 67 proteins were down-regulated and 119 proteins were up-regulated in the AF cells (Fig. According to our results, CAV1 were up-regulated in FOXP3-overexpressing cells comparing to control cells, and these results were consistent with the tumor suppresser role of CAV1 in primary tumors as reported.

‘Cell of origin’ for Barrett’s esophagus identified

‘Cell of origin’ for Barrett’s esophagus identified

Researchers have discovered that Barrett’s esophagus starts in a previously unknown area of unique cells in the lining of the food pipe. They hope that the discovery will lead to better screening and treatment of the condition, which can lead to esophageal cancer.
This can be felt as heartburn and difficulty swallowing food.
In a small proportion of cases, Barrett’s esophagus can develop into a rare cancer called esophageal adenocarcinoma.
As with other cancers, early detection is the key to prolonging survival in esophageal cancer.
Here, at the gastroesophageal junction, the tissue that lines the digestive tract, or the epithelium, changes gradually — as it nears the stomach — from that of the food pipe to that of the intestines.
Much like stem cells, they still have the potential to become different types of cell, but they have already started down the path that will lead to a particular tissue type.
The researchers also replicated these findings in “organoids” grown from unique basal progenitor cells sampled from the gastroesophageal junctions of mice and humans.