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

Nutritional supplement can slow cancer growth and enhance effects of chemotherapy

Mannose sugar, a nutritional supplement, can both slow tumor growth and enhance the effects of chemotherapy in mice with multiple types of cancer.

This lab study is a step towards understanding how mannose could be used to help treat cancer.

The results of the study, which was funded by Cancer Research UK and Worldwide Cancer Research, are published in Nature.

Tumors use more glucose than normal, healthy tissues. However, it is very hard to control the amount of glucose in your body through diet alone. In this study, the researchers found that mannose can interfere with glucose to reduce how much sugar cancer cells can use.

Professor Kevin Ryan, lead author from the Cancer Research UK Beatson Institute, said: "Tumors need a lot of glucose to grow, so limiting the amount they can use should slow cancer progression. The problem is that normal tissues need glucose as well, so we can’t completely remove it from the body. In our study, we found a dosage of mannose that could block enough glucose to slow tumor growth in mice, but not so much that normal tissues were affected. This is early research, but it is hoped that finding this perfect balance means that, in the future, mannose could be given to cancer patients to enhance chemotherapy without damaging their overall health.”

The researchers first examined how mice with pancreatic, lung or skin cancer responded when mannose was added to their drinking water and given as an oral treatment. They found that adding the supplement significantly slowed the growth of tumors and did not cause any obvious side effects.

To test how mannose could also affect cancer treatment, mice were treated with cisplatin and doxorubicin - two of the most widely used chemotherapy drugs. They found that mannose enhanced the effects of chemotherapy, slowing tumor growth, reducing the size of tumors and even increasing the lifespan of some mice.

Several other cancer types, including leukemia, osteosarcoma, ovarian and bowel cancer, were also investigated. Researchers grew cancer cells in the lab and then treated them with mannose to see whether their growth was affected. Some cells responded well to the treatment, while others did not. It was also found that the presence of an enzyme that breaks down mannose in cells was a good indicator of how effective treatment was.

Professor Kevin Ryan added:"Our next step is investigating why treatment only works in some cells, so that we can work out which patients might benefit the most from this approach. We hope to start clinical trials with mannose in people as soon as possible to determine its true potential as a new cancer therapy.”

Mannose is sometimes used for short periods to treat urinary tract infections, but its long-term effects have not been investigated. It’s important that more research is conducted before mannose can be used in cancer patients.

Martin Ledwick, Cancer Research UK’s head nurse, said:"Although these results are very promising for the future of some cancer treatments, this is very early research and has not yet been tested in humans. Patients should not self-prescribe mannose as there is a real risk of negative side effects that haven’t been tested for yet. It’s important to consult with a doctor before drastically changing your diet or taking new supplements.”

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 : 8.Advancement in Cancer Treatment

Better chemo drug adsorption onto targeted delivery capsules

The efficacy of chemotherapy treatment depends on how effectively it reaches cancerous cells. Increasing targeted delivery could mean decreasing side effects. Scientists are enhancing methods of selectively transmitting active chemotherapy agents and reducing their toxicity by encapsulating chemo drugs into active carbon used as the targeted delivery device.

In a new study, Gabriel Román, National University of the South,Argentina, and colleagues have demonstrated that adding minute amounts of aluminium atoms onto activated carbon atoms helps increase the adsorption onto the delivery carbon capsule of a standard chemotherapy drug, called 5-Fluorouracil (5-FU). This drug is typically used for stomach, colorectal, neck and head cancer treatments. This model could lead to more effective and convenient cancer treatments with fewer side effects by encapsulating the chemo drug into the active carbon, so that it can be taken orally.

In this study its examined that the adsorption of 5-FU on test surfaces made up of activated carbon alone and a version containing a minute dispersion of aluminium within the activated carbon structure. They relied on molecular modelling simulation to predict and display adsorption configuration and energy changes in the two scenarios.

They also found that aluminium inclusion increases the adsorption capacity of active carbon. This is because the addition of the metal increases the interactions of the drug with the atoms of the encapsulation material in areas where it is polarised. The electric charges present in some areas of the surface of the drug interact with the charges of the aluminium atoms on the surface of the capsule material. This means they contribute to improving its adsorption properties as less energy is required for the adsorption and the drug is at a shorter distance from the encapsulation material.

We encourage researchers all around the globe 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” . For more info visit :Cell Tissue Science 2019

New discovery on T cell behavior has major implications for cancer immunotherapy

Scientists at the University of Colorado Anschutz Medical Campus have discovered that disease-fighting T cells, elicited from vaccines, do not require glucose for their rapid reproduction, a finding with major implications for the development of immunotherapies for cancer patients.

In this study, they examined T cells that arose in the body's immune system after they received a subunit vaccination—a vaccine that uses just part of a disease-causing virus.

They found that these critical white blood cells, which attack and kill infection, did not rely on glucose to fuel their rapid division which occurs every two to four hours. Instead, they used another cellular engine, the mitochondria, to support their expansion.

"The knowledge that this magnitude of cell division can be supported by mitochondrial function has a number of potential practical implications for the development of future vaccines," said Ross Kedl, Ph.D., Professor of Immunology and Microbiology, University of Colorado School of Medicine.

Kedl continued by saying"T cells responding to infection usually depend on glucose for fuel. So do cancerous tumors. When T cells come up against tumors, they end up competing for glucose and the T cells often lose".

But when a T cell doesn't need glucose, he noted, it has a better chance of defeating tumor cells.

"T cells generated by subunit vaccination are ideally suited for use against cancer in conjunction with drugs that block aerobic glycolysis, a metabolic pathway to which the cancer is addicted, Tumor growth can be inhibited while the T cells are free to attack the tumor instead of competing against it for access to glucose."" Kedl said. 

Jared Klarquist, Ph.D., explained that scientists have historically studied T cell responses to infection with the idea that if they could understand how the cells respond, they could create better vaccines. Kedl and colleagues had already discovered a non-infectious vaccine method that could induce the same level of T cell immunity as those using infection.

Since then, researchers in Kedl's lab have found that the rules governing T cell responses to an infectious agent are very different from the cell's response to a subunit vaccine. And the fact that T cells derived from subunit vaccines don't require glucose to reproduce is a major finding.

"Prior to these findings, it was generally thought that whereas the mitochondria are good at making energy, T cells need glucose to produce the raw materials like proteins, fats and nucleic acids (like DNA) required to turn one cell into two," said Klarquist. "Knowing how the immune response is fueled after vaccination provides potential opportunities for metabolic or nutritional interventions for boosting a vaccine-elicited immune response."

Kedl agreed and says "Perhaps most intriguing, however, is the application of this knowledge to cancer immunotherapy,"

 

We encourage researchers all around the globe 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” . For more info visit :Cell Tissue Science 2019

New type of lung cancer

Researchers have discovered a new kind of small-cell lung cancer (SCLC). The discovery paves the way for developing personalized medicine approaches to target this previously unnoticed form of the disease.

"Cancer is not one thing, it's actually hundreds of distinct diseases." This common refrain helps explain the frustrating experience oncologists have in testing a promising new drug only to find that it works well in some patients but fails for the majority. Such experiences have led researchers to believe that the more they can distinguish tumor types based on meaningful biological signatures, the better chance they have of finding subsets of patients that will respond to specific drug candidates.

One type of cancer in desperate need of new drug is SCLC, a cancer without a specific treatment that often spreads early. Chemotherapy, radiotherapy, and surgery enable only 6% of patients to survive 5 years from the time of their diagnosis. About 10%-15% of all lung cancers are SCLC.

Fresh insight comes from an analysis of gene activity in human SCLC tumors. It reveals an unexpected activity pattern in around 20% of samples. The research team, led by Dr. Christopher Vakoc, Cold Spring Harbor Laboratory (CSHL) found a paucity of neuroendocrine markers in pulmonary neuroendocrine cells, a cell type thought to be the source of SCLC.

They used a method that was developed in 2015 that employs the gene-editing tool CRISPR to screen for specific proteins that are critical to the growth of various human cancer cell lines, including SCLC lines. Using this "CRISPR screen," the team found that a transcription factor called POU2F3 is expressed exclusively in the minority of SCLC tumors with low levels of neuroendocrine markers. It turns out that this variant form of SCLC tumors are derived from a separate class of rare cells called tuft cells.

"We were using the CRISPR screen to discover new vulnerabilities in this disease that we didn't know about before."The surprise is that in the process, we discovered a new form of lung cancer. " says Dr.Vakoc

Developing drugs that specifically target the function of POU2F3 may be particularly effective in the subset of patients with tumors that express high levels of this transcription factor.

"In the past, we've lumped the different forms of SCLC together because they look similar on a microscope slide, but we now have some molecular tests that can easily discriminate these malignancies. Our findings suggest that we should be designing clinical studies for them separately, to find therapies that might cater to the different types of tumor. " says Dr.Yu-Han Huang

Researchers is currently looking for collaborators to do preclinical tests in mice to test compounds that target POU2F3. They also plan to use their CRISPR-based stress test to look for variant types of pancreas cancer which they hope might provide similarly specific targets for treatments.

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