The new mechanism of the body against harmful bacteria

Bacterial infection can cause the body’s problems, when the patient often has weakened immune function. But complicates the problem is, given after antibiotic therapy, can reduce or prevent infection, to life in the body mainly in the gut health promoting bacteria produce negative influence. If the microflora balance is broken, can cause harmful bacteria dominated, and antibiotic resistant strains.

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In view of this, scientists are more interested in, clear body is how against pathogens, but not eliminate benign bacteria. The researchers believe that to understand this point may lead to new ways to enhance the body’s natural defense against bacterial infection ability. Now researchers have identified an unusual mechanism of human body, using its mechanism can sense the presence of pathogenic bacteria and destroy them. Its mechanism is not the direct detection of microorganism,  but each cell can monitor interference with mitochondrial bacteria.

Some intestinal bacteria causing mitochondrial dysfunction may contribute to infection. MSK cell biologist Cole Haynes said: as a response to the perceived some time when cells mitochondria function is disturbed, they open the promoter on bacterial attack. Haynes explained that this mechanism may have evolved to enable cells to detect harmful bacteria from the beneficial bacteria.

The Haynes team is the main research stress response, stress response is a natural mechanism of cell protection and maintenance of mitochondria. Mitochondria provide energy, allowing the cells to perform its normal function. Mitochondrial dysfunction seems to play a role in cancer and aging process. In recent years, Dr Haynes and his colleagues have focused on a protein called ATFS-1 protection. When cells are under stress, accumulation of ATFS-1 in the nucleus and the opening of a series of genes that contribute to restoring mitochondrial function. But the researchers found that ATFS-1 also opened related to fight bacterial genes. The researchers assume that maybe this stress response and innate immunity together, help the body to detect disrupted mitochondrial bacteria, and eliminate pathogens.

EGFR Blockade Enriches for Lung Cancer Stem–like Cells

Erlotinib can be effective in the treatment of special gene changes in patients with advanced lung cancer , but when the same drugs  for the treatment of early stage lung cancer patients, treatment effect was not effective. Recently, published a report in the l Journal Cancer Research, researchers from Ohio State University Cancer Center, it has carried on the analysis to the reasons of the occurrence of the above results.

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Oncologists use of erlotinib for epidermal growth factor receptor(EGFR) mutation in patients with lung cancer. Gene mutation which patients are often will accelerate the deterioration, and erlotinib can block the molecular activities of the body excessive. The study revealed, when erlotinib promote tumor atrophy smaller at the same time, the drug also increased invasion tumor therapy. Therefore, termination cancer growth could accelerate, leading to an unknown secondary effect the reason may because by inhibition of EGFR.

 Professor David Carbone says,  erlotinib blocking EGFR could activate the expression of a sub signal molecule Notch3, the activation of pathways will lead to cancer stem cell development, and accelerate the growth of tumor. This study may explain why clinical erlotinib can make patients with early-stage lung cancer survival rate decreases dramatically.

This study in the use of non small cell lung cancer cell lines were studied to reveal whether the inhibition of EGFR molecules can enhance the activity of the Notch signaling pathway. The results show that once the Notch signal activation, mutant EGFR will direct inhibition of the Notch signal, and the use of erlotinib inhibits EGFR will remove the restrictions on the Notch signal to activate the Notch pathway. This result show that the bidirectional target special role may overcome the negative effects on the body.

The key point of this study are as follows: 1) in two non small cell lung cancer cell lines, erlotinib therapy can be respectively killed 84% and 75% cells, in the survival of the cells, 23% and 70% of all the cells become a stem cell like cells; 2) erlotinib therapy can increase the growth potential of survival of lung cancer cells  by activating Notch3 receptors and increase the number of stem cell like cells.

Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations

Scientists from the University of Sheffield reveals the effect of common gene targeting role reversal induced Parkinson disease mutations related research, published in the International Journal of Nature Communications. The name is a mutation in the LRRK2 gene causes the individual with the risk of Parkinson disease, however, the mechanism is not clear.

In this paper, the researchers Kurt De and Professor Vos through carrying the LRRK2 Roc-COR mutation of Drosophila melanogaster were found, a special kind of drug can be completely restored movement problems because of the Drosophila gene mutation caused. These drugs are inhibitors of histone deacetylase, its function can be lack of transportation system target neurons into the role to carry error LRRK2 gene and reversal of the nervous system. The scientists say, this study reveals the lack of internal transportation system of nerve cells and LRRK2 Parkinson mutations directly the association between exercise caused problems; but deletion mutation of LRRK2 neurons caused by transport can be completely reversed.

By targeting drug transport system function of nerve cells, researchers can not only inhibit the movement of individual flies, but also can restore the body damage of Drosophila melanogaster. LRRK2 gene can produce an effect of cell of many biochemical processes of protein, which can bind to microtubules in cells (cells in transport). Lack of transport system in cells tend to induce Parkinson disease, the researchers said, mutation of specific LRRK2 may influence neuronal function of transportation, causing motion problem to observe in Drosophila in the body.
Then the researchers use a variety of ways to reveal the association between mutation, inhibit the LRRK2 protein and microtubule transport system may supplement the lack of nerve cells transport and Drosophila body motion missing. Researcher De Vos said, they successfully use the deacetylase inhibitors increased acetylation of alpha tubulin microtubules form carrying, then they found increased microtubule acetylation has a direct effect on cell axonal transport.

New finding for Melanoma Cells and LPA

Recently, cancer researchers from the University of Glasgow through research found that melanoma cells may be “follow” the body a naturally occurring molecule trajectory, and this naturally occurring molecules can directly cause diffusion occurs malignant skin cancer, the related research published in the International Journal of PLOS Biology.

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At present, the number of patients diagnosed with melanoma is 5 times than 40 years ago. In the UK, every year around 13000 people are diagnosed with the disease, and every year about 2200 people died because of the disease. The development of an effective therapy to inhibit melanoma cell proliferation for effective control of melanoma and treatment of the disease is the key. We can use the clothes in time from the sun or avoid direct sunlight to effectively protect the skin from sunburn, thereby reducing the risk of melanoma.

In this paper, the researchers found that melanoma cells perhaps through a called lysophosphatidic acid (LPA) molecules to give itself a green light to diffusion, LPA molecules can promote melanoma cell movement in the body diffusion. Through the study of cancer cells and mice, the researchers found that tumor cells can be decomposed by LPA molecules near the environment to open it in the body of the “travel”. Once the LPA molecules in the environment surrounding the level drops, the tumor cells will leave the tumor matrix to find contains higher levels of LPA environment.

Unlike other cancers, melanoma cells can spread from the beginning, so once the LPA molecule to give a melanoma cell diffusion direction, they will start in the body diffusion, which means that melanoma is hard to deal with, because its diffusion and deteriorating quickly. Robert Insall said skin cancer cells can open their own light to cause cancer cells to spread. The next step is to reveal how the melanoma cell crushing LPA molecules to open the spread of cancer journey, researchers are still in the beginning of the study, they hope to through further research to help doctors make the reasonable therapy for the treatment of melanoma patients.

Bristol-Myers Squibb Announces Multiple Regulatory Milestones for Opdivo (nivolumab)

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease, and occurs when cancer spreads beyond the surface of the skin to the other organs, such as the lymph nodes, lungs, brain or other areas of the body.

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Melanoma is less common than other skin cancers. However, it is much more dangerous if it is not found in the early stages. It causes the majority (75%) of deaths related to skin cancer. Globally, in 2012, melanoma occurred in 232,000 people and resulted in 55,000 deaths. Australia and New Zealand have the highest rates of melanoma in the world. It has become more common in the last 20 years in areas that are mostly Caucasian.

These days, Bristol-Myers Squibb Company announced multiple regulatory milestones for Opdivo (nivolumab), an investigational PD-1 immune checkpoint inhibitor. In the U.S., the Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application (BLA) for previously treated advanced melanoma and the Prescription Drug User Fee Act (PDUFA) goal date for a decision is March 30, 2015. The FDA also granted Opdivo Breakthrough Therapy status for this indication. In the European Union, the European Medicines Agency (EMA) has validated for review the Marketing Authorization Application (MAA) for Opdivo in advanced melanoma. The application has also been granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use (CHMP).

Blood: blocking special protein, STAT3 in cells, enhances NK cell–dependent tumor surveillance

STAT transcription factor involved in many kinds of cancers. STAT3 is usually in a state of activation in tumor cells, therefore drug targeting effect of STAT3 is often used in cancer treatment.  However STAT3 on the development of the immune system is very important. Recently, researchers from Austria public university through the study revealed, blocking the immune system cells in the STAT3 may lead to enhanced efficacy of anti tumor immunity, new cancer therapy which anti STAT3 development offers new hope, related research published in the International Journal of Blood.

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This so-called signaling proteins and transcription activator STAT is a key group of many different signal paths, many types of cancer are directly related to STAT protein.STAT3 is a kind of “arch-criminal” common, usually in the activated state of expression in tumor cells, the researchers spent a lot of efforts to effect of STAT3 in the field of target in the development, but still can not determine whether the targeted STAT3 therapy is suitable for the treatment of cancer patients.

At present,  the most important problem in STAT3 is a transcription factor essential for healthy individuals play many key functions, especially the development of the immune system is crucial for many immune cells, especially a called natural killer cells, which is the first line of defense to help the body against viruses and cancer invasion. Ability of mouse natural killer  cells in the STAT3 decreased will enhance the body against melanoma and leukemia cells, and transfer ability of melanoma cells will decrease, so the researchers said, natural killer cell deletion of STAT3 may be effective “killer tumor cells”.

Finally, the researchers noted, loss of STAT3 will promote the natural killer cells become lost vitality, on the contrary it will enhance natural killer cell killing tumor cell potential; the inhibition of STAT3 may help in the treatment of cancer patients through two ways, one of which is a block cancer cell division, another is to enhance natural killer cells of the patients with the body to more effectively the end of cancer cells.

Reference: Loss of STAT3 in murine NK cells enhances NK celldependent tumor surveillance

Vaccine Protection Against Human Papillomavirus

Recent studies show that, in Germany every year there are about 11.2/100 000 of women will get cervical cancer. Persistent infection with high-risk human papillomavirus(HPV) is a poor and cervical neoplasia cervical development a necessary prerequisite.

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Human papillomavirus vaccination is a controversial and the topic of discussion,because in 2007. It was incorporated into the German Standing Committee recommended vaccination (STIKO). The researchers conducted a systematic review showed protection against type 16 and type 18 HPV vaccine for more than 5 years.

The German market authorization are vaccines for type 16 and type 18 HPV virus, because these two viruses are the most common type of risk in Germany. Before the two type HPV virus infection to human vaccination can provide protection, so do the prevention of foundation of HPV infection of cervical cancer.

Sexual contact is the main way to the spread of the HPV virus, in 12 to 17 years old girls and young women without sexual contact in vaccination is the most effective way to prevent HPV. The researchers investigated the HPV vaccine for girls and women to the effect of vaccination through short-term and long-term follow-up.  However, the number of small research and participants can show the vaccine long-term protection of the quality of evidence is lower than the short-term protection of the quality of evidence.

In order to improve the quality of vaccine of long-term protection of evidence, the researchers decided to continue the randomized controlled trial was conducted in order to further determine the duration of protectionof HPV vaccine, and observational study to evaluate the efficacy of the vaccine.

Cell fate regulation by gelsolin in human gynecologic cancers

Ovarian cancer is the most deadly cancer in female gynecological diseases, studies have shown that a woman’s chance of about 50% in the period of their life will suffer from the disease, researchers in Ottawa and Taiwan. the article about why the ovary cancer is usually on the chemical therapy with this view resistance provides new insights, and to improve the diagnosis and treatment of the method provides a possibility.

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According to the “Canadian” Journal of ovarian cancer related data to estimate, in 2014 about 2700 Canadian women diagnosed with ovarian cancer, about 1750 women were killed. The disease is usually can be diagnosed in the late stage, while the ovarian cancer chemotherapy has produced resistance to.

These findings are better able to help clinicians to diagnose ovarian cancer patients, the key is to understand the role of calcium binding actin protein. The formation of growth in the protein level and ovarian cancer related, which is likely to cause ovarian cancer resistant to chemical therapy.

The researchers showed the process of calcium binding microfilament protein for the protection of how cancer cells at the molecular level. The discovery is very important, because it will help clinicians according to the amount of actin binding proteins calcium to determine the most effective treatment scheme. But the work is needed to determine the very precise microfilament protein amount of calcium binding, because the amount of determination can be explicitly formulate specific solutions for cancer chemotherapy resistance held etc..

In addition, the ovarian cancer cell of a same protein are resistant to chemical therapy can overcome obstacles on this treatment. By cutting off the calcium binding actinprotein to divided into special fragment, and the fragment will be embedded into the chemotherapy resistance in cancer cells, the team found that these cells are very sensitive to the chemotherapy drug cisplatin with tumor killing effect becomes.