A compound being developed to treat eye disease also kills leukemia cells

An active ingredient in eye drops that were being developed for the treatment of a form of eye disease has shown promise for treating an aggressive form of blood cancer. Scientists at the Wellcome Sanger Institute, University of Cambridge, University of Nottingham and their collaborators have found that this compound, which targets an essential cancer gene, could kill leukemia cells without harming non-leukemic blood cells.

The results was published in Nature Communications reveal a potential new treatment approach for an aggressive blood cancer with a poor prognosis.

Acute myeloid leukemia (AML) is a form of blood cancer that affects people of all ages, often requiring months of intensive chemotherapy and prolonged hospital admissions. It develops in cells in the bone marrow crowding out the healthy cells, in turn leading to life-threatening infections and bleeding.

Mainstream AML treatments have remained unchanged for over thirty years, with the current treatment being chemotherapy, and the majority of people's cancer cannot be cured. A subtype of AML, driven by rearrangements in the MLL gene has a particularly bad prognosis.

In a previous study, researchers at the Sanger Institute developed an approach, based on CRISPR gene editing technology, which helped them identify more than 400 genes as possible therapeutic targets for different subtypes of AML. One of the genes, SRPK1, was found to be essential for the growth of MLL-rearranged AML. SRPK1 is involved in a process called RNA splicing, which prepares RNA for translation into proteins, the molecules that conduct the majority of normal cellular processes, including growth and proliferation.

In a new study, Sanger Institute researchers and their collaborators set out to work out how inhibition of SRPK1 can kill AML cells and whether it has therapeutic potential in this disease. They first showed that genetic disruption of SRPK1 stopped the growth of MLL-rearranged AML cells and then went on to study the compound SPHINX31, an inhibitor of SRPK1, which was being used to develop an eye drop treatment for retinal neovascular disease -- the growth of new blood vessels on the retinal surface that bleed spontaneously and cause vision loss.

The team found that the compound strongly inhibited the growth of several MLL-rearranged AML cell lines, but did not inhibit the growth of normal blood stem cells. They then transplanted patient-derived human AML cells into immunocompromised mice and treated them with the compound. Strikingly, the growth of AML cells was strongly inhibited and the mice did not show any noticeable side effects.

Dr George Vassiliou, Wellcome Sanger Institute and the Wellcome-MRC Cambridge Stem Cell Institute, said: "We have discovered that inhibiting a key gene with a compound being developed for an eye condition can stop the growth of an aggressive form of acute myeloid leukemia without harming healthy cells. This shows promise as a potential approach for treating this aggressive leukemia in humans."

SRPK1 controls the splicing* of RNA in the production of new proteins. An example of a gene that is affected when SRPK1 is blocked is BRD4, a well-known gene that maintains AML. Inhibiting SRPK1 causes the main form of BRD4 to switch to another form, a change that is detrimental to AML growth.

Dr Konstantinos Tzelepis, the Wellcome Sanger Institute and University of Cambridge, said: "Our study describes a novel mechanism required for leukemia cell survival and highlights the therapeutic potential of SRPK1 inhibition in an aggressive type of AML. Targeting this mechanism may be effective in other cancers where BRD4 and SRPK1 play a role, such as metastatic breast cancer."

Professor David Bates, University of Nottingham and co-founder of biotech company Exonate, which develops eye drops for retinal diseases, said: "When Dr Vassiliou told me that SRPK1 was required for the survival of a form of AML, I immediately wanted to work with him to find out if our inhibitors could actually stop the leukemia cells growing. The fact that the compound worked so effectively bodes well for its potential development as a new therapy for leukemia. It will take some time, but there is real promise for a new treatment on the horizon for patients with this aggressive cancer."

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology,Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . 

You can submit your abstract on Session or Track : 09. Stem Cells and its Applications

Failed DNA repair triggers chromosomal chaos in cancer cells

Researchers at the German Cancer Research Center (Deutsches Krebsforschungszentrum , DKFZ) have established the trigger for catastrophic events that occur within the chromosomes of cancer cells.

They found that failure of DNA repair systems promotes fragmentation and disrupted assembly of chromosomes. However, the researchers say these DNA repair defects could potentially be treated with certain drugs.

Only a few years ago, scientists at the same research center reported that in a particularly aggressive form of childhood brain tumor, unprecedented chaos occurred in the cell nuclei.

Sections of chromosomes were broken at multiple points and incorrectly reassembled, while other sections were incorrectly copied or incorporated.

These events, which scientists refer to as “chromothripsis,” had not been seen before and differed from previously established genetic defects.

Chromothripsis occurs in around 20 to 30% of all cancers, but until now, it has been largely unknown what triggers this genetic disaster.

As reported in the journal Nature Communications, Aurélie Ernst and team identified the failure of certain genetic repair systems as one of the causes.

The team studied a mouse model where the tools used by neural precursor cells to repair broken DNA had been genetically switched off. As a result, the animals developed malignant brain tumors that exhibited a high frequency of chromothripsis.

In addition, the chromothripsis almost always occurred in conjunction with extra copies of the cancer-promoting Myc oncogene.

If the DNA repair is defective and Myc nevertheless stimulates the division of these damaged cells, the risk of chaos in the genome is particularly high.”

Dr. Aurélie Ernst, Lead Author

The team confirmed that the failed genome repair and resulting catastrophic chromosomal events also apply to melanoma, brain tumors and breast cancer in humans and that the Myc oncogene is again involved.

Ernst says that although the chromosome chaos caused by failed DNA repair seem frightening, there are ways to specifically target cancer cells with such defects:

We can use drugs to switch off additionally another important DNA repair system. This leads to so much genetic damage that the cell is unable to survive. Healthy cells, on the other hand, which have all their repair systems, don't mind these drugs."

Dr. Aurélie Ernst, Lead Author

Drugs called PARP inhibitors are already clinically approved agents that block a key DNA repair system and Ernst says that if the genetic material of a tumor exhibits chromothripsis, it may be possible to treat them with PARP inhibitors in the future, although this would require confirmation in preclinical and clinical tests.

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” .  You can submit your abstract on Session or Track :12.Epigenetics and Epigenome

Scientists uncover hidden estrogen receptors in epithelial breast cells

Estrogens are hormones that play central roles in the development and the physiology of the breast, but also are involved in breast cancer. Like all hormones, estrogens exert their biological effects by binding to dedicated receptors in the target cell.

Scientists led by Cathrin Brisken at EPFL have now uncovered that half of the luminal epithelial breast cells that appear not to express the estrogen receptor actually express it at low levels. Publishing in Nature Communications, they show that different parts of the estrogen receptor play different roles in the luminal breast cells that give rise to cancer. Depending on whether a cell has low or high levels of the estrogen receptor, the hormone-dependent or the hormone-independent activities are more or less important for its function.

In addition, the researchers found that the action of the estrogen receptor is biphasic: it stimulates the expansion and growth of breast cells in young mice but inhibits it during pregnancy.

The discovery has immediate implications for the role of ERα in the development of breast cancer. "This begs the question whether these ER-pseudo-negative breast cells will ultimately turn into estrogen receptor-positive or -negative breast cancers," says Cathrin Brisken.

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatmentand many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . 

You can submit your abstract on Session or Track :1.Cell Biology

Advance stem cell therapy with biodegradable scaffold

Rutgers scientists have created a tiny, biodegradable scaffold to transplant stem cells and deliver drugs, which may help treat Alzheimer's and Parkinson's diseases, aging brain degeneration, spinal cord injuries and traumatic brain injuries.

A biodegradable inorganic nano-scaffold, consisting of stem cells, proteins and drugs, for advanced stem cell therapy and drug delivery.

Credit: KiBum Lee, Letao Yang and Sy-Tsong Dean Chueng

Stem cell transplantation, which shows promise as a treatment for central nervous system diseases, has been hampered by low cell survival rates, incomplete differentiation of cells and limited growth of neural connections.

So, Rutgers scientists designed bio-scaffolds that mimic natural tissue and got good results in test tubes and mice, according to a study in Nature Communications. These nano-size scaffolds hold promise for advanced stem cell transplantation and neural tissue engineering. Stem cell therapy leads to stem cells becoming neurons and can restore neural circuits.

"It's been a major challenge to develop a reliable therapeutic method for treating central nervous system diseases and injuries," said study senior author KiBum Lee, Department of Chemistry and Chemical Biology at Rutgers University-New Brunswick. "Our enhanced stem cell transplantation approach is an innovative potential solution."

The researchers, in cooperation with neuroscientists and clinicians, plan to test the nano-scaffolds in larger animals and eventually move to clinical trials for treating spinal cord injury. The scaffold-based technology also shows promise for regenerative medicine.

We welcome researchers from different part of the world to submit your latest research at our upcoming conference “12th World Congress on Cell & Tissue Science” scheduled on March 11-12,2019 in Singapore which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment and many more. For more info visit our conference website:Cell Tissue Science 2019