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Scientists uncover new way to defeat therapy-resistant prostate cancer

Posted by star on 2016-12-29 18:22:09
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A new study led by scientists from the Florida campus of The Scripps Research Institute (TSRI) sheds light on a signaling circuit in cells that drives therapy resistance in prostate cancer. The researchers found that targeting the components of this circuit suppresses advanced prostate cancer development.

 

The study, led by TSRI Associate Professor Jun-Li Luo, was published online ahead of print in the journal Molecular Cell.

A New Strategy to Fight Prostate Cancer

Prostate cancer—which, according to the American Cancer Society, affects one in six American men—is the second-leading cause of death after lung cancer in American men.

Currently, the most effective treatment of advanced prostate canceris to deprive the cancer of what feeds it—androgen hormones such as testosterone. Unfortunately, almost all patients eventually develop resistance to this therapy, leaving doctors with no options to counteract the inevitable.

The new study shows that a "constitutively active" signaling circuit can trigger cells to grow into tumors and drive therapy resistance in advanced prostate cancer. A cell signal pathway with constitutive activity requires no binding partner (ligand) to activate; instead, the signaling circuit continually activates itself.

This signaling circuit, which is composed of the protein complex IκBα/NF-κB (p65) and several other molecules, controls the expression of stem cell transcription factors (proteins that guide the conversion of genetic information from DNA to RNA) that fuel the aggressive growth of these resistant cancer cells.

"The fact that the constitutive activation of NF-kB in the circuit is independent of traditional activation opens the door for potential treatment options," said Luo.

Targeti......

Hot Pepper Compound Inhibits Growth of Breast Cancer Cells

Posted by star on 2016-12-29 18:07:27
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Capsaicin, a compound found in peppers of the genus Capsicum, inhibits the growth of breast cancer cells, according to a team of researchers in Germany.

The team’s experiments were carried out with the SUM149PT cell culture, a model system for a particularly aggressive type of breast cancer, i.e. the triple-negative type.

In the cultivated cells, the researchers detected a number of typical olfactory receptors.

“One receptor occurred very frequently; it is usually found in the fifth cranial nerve. It belongs to the so-called transient receptor potential channels and is named TRPV1 (transient receptor potential vanilloid receptor),” they explained.

“That receptor is activated by the spicy molecule capsaicin as well as by helional, a scent of fresh sea breeze.”

The authors confirmed the existence of TRPV1 in tumor cells in nine different samples from patients suffering from breast cancer.

They activated the TRPV1 receptor in the cell culture with capsaicin or helional, by adding the substances to the culture for a period of several hours or days. As a result, the cancer cells divided more slowly.

Moreover, the treatment caused tumor cells to die in larger numbers.

The surviving cells were no longer able to move as quickly as heretofore; this implies that their ability to form metastases in the body was impeded.

“If we could switch on the TRPV1 receptor with specific drugs, this might constitute a new treatment approach for this type of cancer,” said Prof. Hanns Hatt, from the Department of Cell Physiology at the Ruhr-University Bochum.

“An intake......


Artemisinin occurs naturally in the leaves of the sweet wormwood, a sweetly aromatic herb with small, yellow flower heads and the source of the Traditional Chinese Medicine ‘Qing Hao.’

The compound is a potent anti-malarial agent, and can kill highly drug-resistant strains.

In the new study, artemisinin stopped the ability of Mycobacterium tuberculosis(Mtb), the causative agent of tuberculosis, to become dormant. This stage of the disease often makes the use of antibiotics ineffective.

“When Mtb are dormant, they become highly tolerant to antibiotics. Blocking dormancy makes the bacteria more sensitive to these drugs and could shorten treatment times,” Dr. Abramovitch said.

Mtb needs oxygen to thrive in the body. The immune system starves this bacterium of oxygen to control the infection.

Dr. Abramovitch and co-authors found that artemisinin attacks a molecule called heme, which is found in the Mtb oxygen sensor.

By disrupting this sensor and essentially turning it off, artemisinin stopped the disease’s ability to sense how much oxygen it was getting.

“When the Mtb is starved of oxygen, it goes into a dormant state, which protects it from the stress of low-oxygen environments. If Mtb can’t sense low oxygen, then it can’t become dormant and will die,” Dr. Abramovitch said.

The researchers indicated that dormant Mtb can remain inactive for decades in the body. But if the immune system weakens at some point, it can wake back up and spread. Whether it wakes up or stays ‘asleep’ though, Mtb can take up to six months to treat and is one of the main reasons the disease is so difficult to control.

After screening 540,000 different compounds, the authors also found five other possible chemical inh......


Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine in immuno-inflammatory diseases.

MIF expressions have been detected in the head kidney, spleen, liver, brain, intestine, gill, heart, stomach, and muscle of E. awoara infected with Vibrio parahaemolyticus. The mRNA levels observed in infected groupers were higher than those in healthy groupers. MIF, tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1) tissue levels have been measured by ELISA.

A significant increase in MIF, TNF-α, and IL-1 tissue levels have been found in the treatment groups compared with those in controls. MIF, TNF-α and IL-1 tissue levels in the spleen, head kidney, intestine, and liver of E. awoara during the challenge trial with V. parahaemolyticus were significantly higher than those in controls. There was evidence of functions of MIF in a positive feedback loop with TNF-α and IL-1 that could perpetuate the inflammatory process in grouper infected with V. parahaemolyticus.

In conclusion, these results indicated that MIF was related to pathogen-induced immune response.



Only Half of Chromosome is DNA

Posted by star on 2016-12-28 18:56:38
Hits:186

DNA makes up only half of the material inside chromosomes, according to a new study published in the journal Molecular Cell. Up to 47% of their structure is a mysterious sheath that surrounds the genetic material.

A research team headed by University of Edinburgh scientists developed a precise microscopy method that allows them to study the structure of chromosomes in detail.

The method, called 3D-CLEM, combines light and scanning electron microscopy with computational modeling software to produce high-resolution 3D images of chromosomes.

“3D-CLEM has allowed us to determine the length, width, surface area, volume, and DNA packing density of all normal human chromosomes and to determine the DNA content of a small synthetic artificial chromosome,” the authors explained.

“The imaging technique we have developed to study chromosomes is truly groundbreaking,” added study co-lead author Dr. Daniel Booth, of the University of Edinburgh’s School of Biological Sciences.

“Defining the structure of all 46 human chromosomes for the first time has forced us to reconsider the idea that they are composed almost exclusively of chromatin, an assumption that has gone largely unchallenged for almost 100 years.”

Analysis of the images reveals that material containing DNA and supporting proteins — known as chromatin — accounts for between 53 and 70% of the total contents of chromosomes.

The remaining 30 to 47% is composed of the chromosome periphery.

While the precise function of this sheath is unknown, Dr. Booth and co-authors suggest it may keep chromosomes isolated from one another during the key process of cell division.

“This so-called chromosome periphery could help to prevent errors from occurring when cells divide — a hallmark of some forms of cancer and diseases associated with birth defects,” they said.......

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