Small molecule reduce the spread of cancer

One small molecule that regulate gene expression plays a big role in keeping human safe from the machinations of cancer. In human lung cancer cells, low levels of the microRNA, miR-125a-5p, which enables the death of aberrant cells like cancer cells, correlates with high levels of the protein TIMP-1, which is already associated with a poor prognosis in patients with cancer.

Conversely, when they decrease TIMP-1 levels in these highly lethal cancer cells, tumor spread goes down while rates of cell death go up along with expression of miR-125a-5p, says Dr. Mumtaz V. Rojiani, cancer biologist in the Department of Medicine at the Medical College of Georgia and a member of the Molecular Oncology and Biomarkers Program at the Georgia Cancer Center at Augusta University.

While increasing microRNA levels is technically difficult, further delineating how cancer hijacks these normal body systems may help identify new treatment targets. TIMP-1 has a positive role in a healthy body to balance levels of enzymes the body makes to ease cell movement for things like wound healing or reproduction.

The healthy body and cancer make these enzymes, matrix metalloproteinases, or MMPs, to break down the surrounding matrix that helps keep cells stable. While it's critical to positives like wound healing, when the matrix breakdown is usurped by cancer, it also gives cancer cells this freedom to move.

In cancer, TIMP-1 levels rise dramatically and it has a distinctive role enabling both growth of new blood vessels and inhibition of apoptosis, a cell's natural inclination to die if something unfixable is wrong. In cancer, what the tumor cells do is start secreting a lot more of these enzymes so they can break down the matrix and start migrating and metastasizing.

Classically, TIMP-1 should be inhibiting MMPs but over the years it has been found to have other functions that actually increase tumor aggressiveness. In their studies of TIMP-1 expression in human lung cancer cells, they saw this aggressive response. It turned out that TIMP-1 is like a two-faced individual smiling at cancer sometimes and other times cutting it off.

Increased levels of two-faced TIMP-1 have been found in increased tumor spread and poor prognosis in breast, gastric and colorectal cancers as well as the non-small cell lung cancer the MCG scientists studied, which accounts for about 85 percent of all lung cancers and has a five-year survival rate of under 20 percent.

TIMP-1 overexpression also is associated with increased upregulation of Bcl-2, a protein which can prevent apoptosis, or cell death. To make bad matters worse, a key way chemotherapy works is by inducing apoptosis and TIMP-1 has been associated with potentially deadly drug resistance.
However, with high expression of miR-125a-5p, TIMP-1 becomes the target. One result is increased expression of the gene p53, a known tumor suppressor, which enables cell death.

When ressearchers knocked down TIMP-1 expression, it significantly increased expression of miR-125a-5p. Conversely, when they restored higher levels of TIMP-1, miR-125a-5p expression went down. The look of the cancer cells changed with the level of TIMP-1. At high levels they looked more like cells unshackled from their current location and able to migrate and invade. When they decreased TIMP-1 levels, the cells pretty much stayed put.

 Adding more synthetic miR-125a-5p to the cancer cells, and the lung cancer cells moved more toward a stationary normal look and cell death increased. When they inhibited miR-125a-5p, the cells were ready to roam. Looking at the biopsies of lung cancer patients, they found as expected TIMP-1 expression much higher in the lung cancer tissue than nearby healthy tissue. But they also saw an inverse relationship between high levels of TIMP-1 and miR-125a-5p levels. In fact, tumor cells had almost no miR-125a-5p.
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Bacteria obtain resistance from competitor

Bacteria not only develop resistance to antibiotics, they also can pick it up from their rivals. In a recent publication in Cell Reports, Researchers from the Biozentrum of the University of Basel have demonstrated that some bacteria inject a toxic cocktail into their competitors causing cell lysis and death. Then, by integrating the released genetic material, which may also carry drug resistance genes, the predator cell can acquire antibiotic resistance.

The frequent and sometimes careless use of antibiotics leads to an increasingly rapid spread of resistance. Hospitals are a particular hot spot for this. Patients not only introduce a wide variety of pathogens, which may already be resistant but also, due to the use of antibiotics to combat infections, hospitals may be a place where anti-microbial resistance can develop and be transferred from pathogen to pathogen. One of these typical hospital germs is the bacterium Acinetobacter baumannii. It is also known as the "Iraq bug" because multidrug-resistant bacteria of this species caused severe wound infections in American soldiers during the Iraq war.

The emergence and spread of multidrug resistance could be attributed, among other things, to the special skills of certain bacteria: Firstly, they combat their competitors by injecting them with a cocktail of toxic proteins, so-called effectors, using the type VI secretion system (T6SS), a poison syringe. They are able to uptake and reuse the released genetic material. In the model organism Acinetobacter baylyi, a close relative of the Iraq bug, Prof. Marek Basler's team at the Biozentrum of the University of Basel, has now identified five differently acting effectors. Some of these toxic proteins kill the bacterial competition very effectively, but do not destroy the cells.

The predator bacteria take up the released DNA fragments. If these fragments carry certain drug resistance genes, the specific resistance can be conferred upon the new owner. As a result, the antibiotic is no longer effective and the bacterium can reproduce largely undisturbed. Pathogens with such abilities are a major problem in hospitals, as through contact with other resistant bacteria they may accumulate resistance to many antibiotics -- the bacteria become multidrug-resistant. In the worst case, antibiotic treatments are no longer effective, thus nosocomial infections with multidrug-resistant pathogens become a deadly threat to patients.

The T6SS, as well as a set of different effectors, can also be found in other pathogens such as those which cause pneumonia or cholera. Interestingly, not all effectors are sufficient to kill the target cell, as many bacteria have developed or acquired antitoxins -- so-called immunity proteins. Antibiotics and anti-microbial resistance have existed for a long time. They developed through the coexistence of microorganisms and enabled bacteria to defend themselves against enemies or to eliminate competitors. This is one of the ways in which bacteria can conquer and colonize new environmental niches. With the use of antibiotics in medicine, however, the natural ability to develop resistance has become a problem. This faces researchers with the challenge of continually developing new antibiotics and slowing down the spread of drug resistance.
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New way of treating HIV

 HIV drugs target the virus, the virus is not stable; it always mutates because the virus can become resistant to effective drugs, directing the immune system to kill the disease is better than targeting the virus with drug.

Some people are okay with HIV suppressing treatment, but more people are experiencing drug resistance. HIV- 1 is the most widespread, HIV can be classified into R5 and X4 viruses.

R5 viruses are linked with primary infection while X4 viruses occur in later stages of HIV diseases in some HIV patients. Detection of X4 is an indication that the patient's HIV infection has progressed to dangerous state.

Immune system protein suppresses damaging HIV strains, X4, by preventing the virus from infecting cells can be improve on, strengthening the immune system to kill the virus will be more effective because viruses cannot escape the body's immune system.
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