What makes macrophages to protect glioblastoma cells?

The median survival of glioblastoma patients is about 12 to 15 months, and only 5% of patients can survive for 5 years. One third of all glioblastomas patients have PTEN deficiency.
Researchers at MD Anderson Cancer Center in the University of Texas said: “a common genetic defect causes glioblastoma to transmit molecular information to the wrong type of immune cell, convening macrophages to protect and cultivate brain tumors rather than to attacking them. As many as one third of the viable cells found in glioblastoma are macrophages. The researchers point out that they are the main components of the tumor microenvironment.
Their study identified pathways for macrophages to enter glioblastoma and also identified growth factors secreted by macrophages that protect cancer cells from programmed cell death and promote the growth of new blood vessels.
After a series of experiments, through the PTEN knockout cell line, and later in the mouse model of glioblastoma, they found: 1. With the down-regulation of PTEN, a gene called YAP1 is activated, which is a transcription factor that increases the expression of LOX, a novel macrophage attractor; 2. LOX is linked to the β1 integrin-PYK2 pathway on macrophages, causing them to migrate into the tumor microenvironment; 3. Macrophages directly help glioma cells by secreting growth factor SPP1, which increases cancer cell survival and angiogenesis to protect tumors.
The researchers developed a human xenograft mouse model of glioblastoma with high expression of LOX, YAP1 and macrophage markers. Elimination of LOX in these models by small molecule LOX inhibitors (BAPN) or anti-LOX antibodies, impairs tumor growth and significantly reduces macrophage infiltration. They found that blocking LOX had no effect on glioma cell proliferation, but it did increase programmed cell death in cancer cells and reduced the formation of blood vessels that support tumors. However, this only recruited tumors with PTEN ......

To reveal the mechanism of intestinal microbial destruction in patients with enteritis

Researchers at Duke University's medical research institute have recently discovered molecular links to microbial destruction during the onset of inflammatory bowel disease, such as triggering inflammatory bowel disease (IBD).
This research is dedicated to a unique biotechnology toolkit to understand why the microbiome changes during enteritis and how it triggers unhealthy inflammatory responses. These tools allow them to measure chemical changes in microbes, opening the door to new treatments in the future.
The intestinal microbiome is a community of trillions of microbes, including bacteria, viruses and fungi. Each person has their own unique microbiome, which studies have shown to play an important role in many diseases, including IBD.IBD affects more than 3 million people worldwide, and its incidence is rising. IBD is a chronic disease characterized by periods of remission followed by sudden onset during which the disease becomes active.
In the study, 100 participants were followed for a year and IBD patients were compared with a control group without the disease. The participants provided faecal samples once a week, blood samples once a quarter, and a set of colon biopsies for analysis at the start of the study. The samples were analyzed using molecular, cellular, and clinical tools to understand the detailed biochemical characteristics of the disease.
First, these detailed measurements make it easy to observe and confirm research findings, such as the loss of overall intestinal biodiversity, and the
What's more, IBD patients have fewer microbial-derived chemicals during disease activity, which they speculate may be the result of a combination of factors, including less metabolism of beneficial microorganisms, less absorption of nutrients, higher levels of water or blood in the gut, and more rapid bowel movement. These factors reduce the overall stability of the intestinal microbial ecosystem, leading to more improper immune response......

Research has found that certain genes allow cancer cells to remain dormant

Researchers at Harvard University have identified key genes that allow certain cancer cells to become dormant, as well as the microenvironment in which they live, a development that could help prevent cancer metastasis and recurrence in the future.
Dormant cancer cells are a risk factor for cancer metastasis and recurrence because they are difficult for the body's immune system to recognize and attack, and for chemotherapy drugs to work against them. The medical community has been trying to figure out how cancer cells go into hibernation, which could help develop targeted drugs that identify and kill cancer cells.
Using a two-photon microscope, researchers at duke university medical research center and their team identified dormant myeloma cells in laboratory animals, they report in the new issue of cell.
The researchers analyzed the genome of dormant hemangioma cells to find the genes that were activated, and found that certain genes were not normally activated in dormant cancer cells. Further research showed that these specific genes caused dormant cancer cells to release genetic markers similar to those of human immune cells, to ward off attacks from the immune system and drugs, and to be released only when cancer cells approached osteoblasts. The researchers concluded tentatively that the microenvironment in which cancer cells live has a key effect on whether they go into hibernation or not.
The approach is different in that it looks at cancer cells and the tissues they are in as a whole. It's not just the cancer cells themselves, but also their microenvironment that determines whether they're dormant or not.
The researchers said the next step would be to use the results to try to identify the genetic markers that cancer cells release when they go into hibernation, in the hope of identifying common features that could lead to the development of targeted therapies that specifically target dormant cancer cells.

Modulation of Transcription Factor Activity

Regulation of transcription initiation is of fundamental importance in controlling gene expression. In many cases, the availability of factors that bind to specific sites in promoters is the switch that turns a gene on. Various strategies to control the binding of specific factors have been discovered. One of the most straight forward is de novo synthesis of the specific factor. This requires an additional level of transcription regulation and translation of the mRNA that encodes the specific factor. All of these steps take some time; therefore, this regulatory scheme is not used in situations in which rapid responses are required. Instead, it is used more commonly in regulating developmental pathways.
Several mechanisms are used for rapid regulation of the activity of existing transcription factors. One mechanism involves the formation of an active factor from two inactive subunits. This association can be regulated through synthesis or by modification of preexisting subunits, leading to their association. Binding of small-molecule ligands is another means of controlling transcription factor activity. In this case, the binding of the ligand induces a .conformational change that leads to DNA binding and transcription activation Interaction of transcription factors with inhibitory subunits is also used to regulate factor activity. In this case, the binding of the ligand induces a conformational change that leads to DNA binding and transcription activation. Interaction of transcription factors with inhibitory subunits is also used to regulate factor activity. The DNA binding or activation potential is held in check until the appropriate signal leads to dissociation of the inhibitory factor. Covalent modification for example, by phosphorylation is also used to convert inactive transcription factors to a functional form. Finally, the ability of transcription factors to bind DNA may be regulated by restricting their localization to the cytoplasm. These regulatory......

Novel molecular mechanisms by which cancer cells migrate to tumor sites

The study found that metastatic cancer cells can leave tumors and spread in large groups, rather than acting alone. Scientists from the University of California studied the key processes this behavior helps. When a cancer metastasizes, the host cell (the front end) expends more energy and blocks the cell from moving forward, creating a new tumor site.
The research is important for advancing the field of metabolomics, which is a new field in the fight against cancer. Researchers using metabolomics to slow down the production of cancer cells may shed light on the molecular mechanisms involved in cancer cell metastasis.
In this study, the researchers said, they found that in addition to proliferation, cancer cells also require energy to migrate, which means that scientists can use cancer cells' metabolism to guide their migration. The researchers used lung cancer cells to study and further elucidate the mechanisms by which these cancer cells metastasize, which is crucial to the development of new anticancer therapies.
Researchers study of lung cancer cells, they have developed a new way of computing simulation, confirmed the front and rear cancer cells in the process of cancer metastasis are energy demand, and front cells need to be as much as 60% of energy, mainly due to the density of the through the organization, and metastasis of cancer cells every 5 hours will convert a cell role to promote effective cancer metastasis.
The researchers say the development of fluorescent biosensors could help track energy-releasing molecules in cancer cells. They will also conduct further research to elucidate new molecular mechanisms of cancer cell metastasis and develop new therapies to inhibit cancer metastasis.