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Espaço de publicação e discussão sobre oncologia. GBM IMMUNOTHERAPY ONCO-VIRUS ONCOLOGY CANCER CHEMOTHERAPY RADIOTHERAPY


Quinta-feira, 23.07.15

Gold nanoparticles with functional surfaces regulate osteogenic differentiation of stem cells

 

Gold nanoparticles with functional surfaces regulate osteogenic differentiation of stem cells

Published on June 8, 2015 at 3:00 AM ·

Tissue Regeneration Materials Unit (Guoping Chen, Unit Director) at the International Center for Materials Nanoarchitectonics (MANA) (Masakazu Aono, Director General, MANA), NIMS (Sukekatsu Ushioda, President) successfully developed gold nanoparticles that have functional surfaces and act on osteogenic differentiation of stem cells.

In regenerative medicine, the technology to control stem cell functions such as differentiation and proliferation is indispensable. It has been reported that nanosized gold particles promote the differentiation of human mesenchymal stem cells into osteoblasts. Also, other studies suggested that various functional groups such as amino, carboxyl and hydroxyl groups promote or inhibit stem cell differentiation. Based on these reports, we assumed that gold nanoparticles with surface modified with functional groups is a promising candidate to control stem cell functions. However, specific effects of such particles on the differentiation of human mesenchymal stem cells was unknown.

We synthesized gold nanoparticles with surface modified with one of the following functional groups: a positively-charged amino group (-NH2), a negatively-charged carboxyl group (-COOH) or a neutral hydroxyl group (-OH), and identified how they affect the osteogenic differentiation of mesenchymal stem cells that were derived from human bone marrow. Among these three types of nanoparticles, those with the carboxyl groups were uptaken by cells and exhibited a strong bone differentiation-inhibitory effect compared to the other types of nanoparticles. Furthermore, we investigated the effect of gold nanoparticles with carboxyl groups on the gene expression profile of mesenchymal stem cell from human bone marrow. The results indicated that the nanoparticles inhibited several gene expressions related to osteogenic differentiation. Therefore, the influence of the gold nanoparticles on promoting or inhibiting osteogenic differentiation varied depending on the types of functional groups.

In view of regenerative medicine, it is essential to develop technology enabling controlling stem cell functions as well as safe and high-quality stem cells. In the present study, we attempted to control stem cell functions through material manipulation, and our findings will contribute to the creation of novel nanomaterials that facilitate the advancement of stem cell manipulation. We intend to build upon these results in our future endeavors in developing regenerative medicine.

Source:

International Center for Materials Nanoarchitectonics

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por cyto às 22:52

Terça-feira, 21.07.15

TSRI study reveals alternative approach to current anti-HIV strategies

 

TSRI study reveals alternative approach to current anti-HIV strategies

Published on July 9, 2015 at 8:49 AM 

AIDS Study Points to ‘Functional Cure’

HIV-infected patients remain on antiretroviral therapy for life because the virus survives over the long-term in infected dormant cells. Interruption of current types of antiretroviral therapy results in a rebound of the virus and clinical progression to AIDS.

But now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown that, unlike other antiretroviral therapies, a natural compound called Cortistatin A reduces residual levels of virus from these infected dormant cells, establishing a near-permanent state of latency and greatly diminishing the virus' capacity for reactivation.

"Our results highlight an alternative approach to current anti-HIV strategies," said Susana Valente, a TSRI associate professor who led the study. "Prior treatment with Cortistatin A significantly inhibits and delays viral rebound in the absence of any drug. Our results suggest current antiretroviral regimens could be supplemented with a Tat inhibitor such as Cortistatin A to achieve a functional HIV-1 cure, reducing levels of the virus and preventing reactivation from latent reservoirs."

The study was published this week in the journal mBio.

Cortistatin A was isolated from a marine sponge, Corticium simplex, in 2006, and in 2008, TSRI chemist Phil Baran won the global race to synthesize the compound. A configuration of the compound, didehydro-Cortistatin A, was shown in earlier studies to target the protein Tat, which exponentially increases viral production.

The new study shows that didehydro-Cortistatin A inhibits replication in HIV-infected cells by significantly reducing levels of viral messenger RNA - the blueprints for producing proteins and more infection.

"In latently infected primary T cells isolated from nine HIV-infected subjects being treated with antiretroviral drugs, didehydro-Cortistatin A reduced viral reactivation by an average of 92.3 percent," said Guillaume Mousseau, the first author of the study and a member of the Valente lab.

The results suggest an alternative to a widely studied strategy for latent HIV eradication known as "kick and kill," which tries to purge viral reservoirs by "kicking" them out of their latency with reversing agents and stopping new rounds of infection with an immunotherapy agent to boost the body's own immune system response while on antiretroviral treatment.

"In our proposed model, didehydro-Cortistatin A inhibits the viral transcriptional activator, Tat, far more completely, delaying or even halting viral replication, reactivation and replenishment of the latent viral reservoir," said Valente.

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por cyto às 18:25

Terça-feira, 21.07.15

Patients' own genetically engineered immune cells show significant success against multiple myeloma

 

Patients' own genetically engineered immune cells show significant success against multiple myeloma

Published on July 21, 2015 at 2:37 AM 

In recent years, immunotherapy has emerged as a promising treatment for certain cancers. Now this strategy, which uses patients' own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable. The results appeared in a study published online today in Nature Medicine.

Patients received an infusion of altered immune cells known as T-cells - roughly 2.4 billion of them - after undergoing a stem cell transplantation of their own stem cells. In 16 of 20 patients with advanced disease, there was a significant clinical response. The scientists found that the T-cell therapy was generally well-tolerated and that modified immune cells traveled to the bone marrow, where myeloma tumors typically are found, and showed a long-term ability to fight the tumors. Relapse was generally associated with a loss of the engineered T-cells.

"This study suggests that treatment with engineered T-cells is not only safe but of potential clinical benefit to patients with certain types of aggressive multiple myeloma," says first author Aaron P. Rapoport, MD, the Gary Jobson Professor in Medical Oncology at the University of Maryland School of Medicine. "Our findings provide a strong foundation for further research in the field of cellular immunotherapy for myeloma to help achieve even better results for our patients."

The trial is the first published use of genetically modified T-cells for treating patients with multiple myeloma. The approach has been used to treat leukemia as well as lymphoma, according to Dr. Rapoport, who is the Director of the Blood and Marrow Transplant Program at the University of Maryland Marlene and Stewart Greenebaum Cancer Center.

More than 77,000 people in the United States have multiple myeloma, with about 24,000 new cases diagnosed each year. Patients are treated with chemotherapy and in many cases an autologous stem cell transplant, but long-term response rates are low, and median survival is three to five years.

"The majority of patients who participated in this trial had a meaningful degree of clinical benefit," Dr. Rapoport notes. "Even patients who later relapsed after achieving a complete response to treatment or didn't have a complete response had periods of disease control that I believe they would not have otherwise experienced. Some patients are still in remission after nearly three years."

The research is a collaboration between the University of Maryland School of Medicine, the Perelman School of Medicine at the University of Pennsylvania and Adaptimmune, a clinical stage biopharmaceutical company which owns the core T-cell receptor technology and funded the study. Dr. Rapoport and co-authors Edward A. Stadtmauer, MD, of the University of Pennsylvania Abramson Cancer Center, and Gwendolyn K. Binder-Scholl, PhD, of Adaptimmune, contributed equally to the research. Dr. Rapoport is the study's principal investigator.

In the clinical study, patients' T-cells were engineered to express an affinity-enhanced T-cell receptor (TCR) specific for a type of tumor antigen, or protein, known as a cancer-testis antigen (CT antigen). The target CT antigens were NY-ESO-1 and LAGE-1. Up to 60 percent of advanced myelomas have been reported to express NY-ESO-1 and/or LAGE-1, which correlates to tumor proliferation and poorer outcomes. According to Adaptimmune, the trial is the first published study of lentiviral vector mediated TCR gene expression in humans.

Of the 20 patients treated, 14 (70 percent) had a near complete or complete response three months after treatment. Median progression-free survival was 19.1 months and overall survival was 32.1 months. Two patients had a very good partial response three months post treatment. Half the patients were treated at the University of Maryland Greenebaum Cancer Center and half at the University of Pennsylvania Abramson Cancer Center. Researchers note that the response rate was better than would be expected for a standard autologous stem cell transplant. In addition, patients did not experience side effects which have been associated with another type of genetically engineered T-cells (chimeric antigen receptors, or CARS) used to treat other cancers.

The study was originally developed by Carl H. June, MD, of the University of Pennsylvania Abramson Cancer Center, and Dr. Rapoport, who have been research collaborators for 18 years.

"Multiple myeloma is a treatable but largely incurable cancer. This study reveals the promise that immunotherapy with genetically engineered T-cells holds for boosting the body's ability to attack the cancer and provide patients with better treatments and control of their disease," says E. Albert Reece, MD., PhD, MBA, vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. "This trial is also an excellent example of significant scientific advances that result from collaborations between academic medical institutions and private industry."

Source:

University of Maryland Medical Center

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por cyto às 18:10

Terça-feira, 21.07.15

Single molecule appears to be central regulator driving cancer metastasis

 

Single molecule appears to be central regulator driving cancer metastasis

Published on July 14, 2015 at 6:21 AM · 

Cancer is a disease of cell growth, but most tumors only become lethal once they metastasize or spread from their first location to sites throughout the body. For the first time, researchers at Thomas Jefferson University in Philadelphia report a single molecule that appears to be the central regulator driving metastasis in prostate cancer. The study, published online July 13th in Cancer Cell, offers a target for the development of a drug that could prevent metastasis in prostate cancer, and possibly other cancers as well.

"Finding a way to halt or prevent cancer metastasis has proven elusive. We discovered that a molecule called DNA-PKcs could give us a means of knocking out major pathways that control metastasis before it begins," says Karen Knudsen, Ph.D., Director of the Sidney Kimmel Cancer Center at Thomas Jefferson University, the Hilary Koprowski Professor and Chair of Cancer Biology, Professor of Urology, Radiation Oncology, and Medical Oncology at Jefferson.

Metastasis is thought of as the last stage of cancer. The tumor undergoes a number of changes to its DNA - mutations - that make the cells more mobile, able to enter the bloodstream, and then also sticky enough to anchor down in a new location, such as the bone, the lungs, the liver or other organs, where new tumors start to grow. Although these processes are fairly well characterized, there appeared to be many non-overlapping pathways that ultimately lead to these traits.

Now, Dr. Knudsen and colleagues have shown that one molecule appears to be central to many of the processes required for a cancer to spread. That molecule is a DNA repair kinase called DNA-PKcs. The kinase rejoins broken or mutated DNA strands in a cancer cell, acting as a glue to the many broken pieces of DNA and keeping alive a cell that should normally self-destruct. In fact, previous studies had shown that DNA-PKcs was linked to treatment resistance in prostate cancer, in part because it would repair the usually lethal damage to tumors caused by radiation therapy and other treatments. Importantly, Dr. Knudsen's work showed that DNA-PKcs has other, far-reaching roles in cancer.

The researchers showed that DNA-PKcs also appears act as a master regulator of signaling networks that turn on the entire program of metastatic processes. Specifically, the DNA-PKcs modulates the Rho/Rac enzyme, which allows many cancer cell types to become mobile, as well as a number of other gene networks involved in other steps in the metastatic cascade, such as cell migration and invasion.

In addition to experiments in prostate cancer cell lines, Dr. Knudsen and colleagues also showed that in mice carrying human models of prostate cancer, they could block the development of metastases by using agents that suppress DNA-PKcs production or function. And in mice with aggressive human tumors, an inhibitor of DNA-PKcs reduced overall tumor burden in metastatic sites.

In a final analysis that demonstrated the importance of DNA-PKcs in human disease, the researchers analyzed 232 samples from prostate cancer patients for the amount of DNA-PKcs those cells contained and compared those levels to the patients' medical records. They saw that a spike in the kinase levels was a strong predictor of developing metastases and poor outcomes in prostate cancer. They also showed that DNA-PKcs was much more active in human samples of castrate-resistant prostate cancer, an aggressive and treatment-resistant form of the disease.

"These results strongly suggest that DNA-PKcs is a master regulator of the pathways and signals that lead to the development of metastases in prostate cancer, and that high levels of DNA-PKcs could predict which early stage tumors may go on to metastasize," says Dr. Knudsen.

"The finding that DNA-PKcs is a likely driver of lethal disease states was unexpected, and the discovery was made possible by key collaborations across academia and industry," explains Dr. Knudsen. Key collaborators on the study, in addition to leaders of the Sidney Kimmel Cancer Center's Prostate Program, included the laboratories of Felix Feng (University of Michigan), Scott Tomlins (University of Michigan), Owen Witte (UCLA), Cory Abate-Shen (Columbia University), Nima Sharifi (Cleveland Clinic) and Jeffrey Karnes (Mayo Clinic), and contributions from GenomeDx.

Although not all molecules are easily turned into drugs, at least one pharma company has already developed a drug that inhibits DNA-PKcs, and is currently testing it in a phase 1 study (NCT01353625). "We are enthusiastic about the next step of clinical assessment for testing DNA-PKcs inhibitors in the clinic. A new trial will commence shortly using the Celgene CC-115 DNA-PKcs inhibitor. This new trial will be for patients advancing on standard of care therapies, and will be available at multiple centers connected through the Prostate Cancer Clinical Trials Consortium, of which we are a member," explained Dr. Knudsen.

"Although the pathway to drug approval can take many years, this new trial will provide some insight into the effect of DNAP-PKcs inhibitors as anti-tumor agents. In parallel, using this kinase as a marker of severe disease may also help identify patients whose tumors will develop into aggressive metastatic disease, so that we can treat them with more aggressive therapy earlier," says Dr. Knudsen. "Given the role of DNA-PKcs in DNA repair as well as control of tumor metastasis, there will be challenges in clinical implementation, but this discovery unveils new opportunities for preventing or treating advanced disease."

Source:

Thomas Jefferson University

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por cyto às 18:05

Sábado, 04.07.15

gene mutation linked to anaplastic oligodendroglioma

Scientists identify gene mutation linked to anaplastic oligodendroglioma

Published on June 12, 2015 at 9:23 AM · 

Scientists have identified a gene mutation linked to the development of an aggressive form of brain cancer.

Researchers found that errors in a gene known as TCF12 - which plays a key role in the formation of the embryonic brain are associated with more aggressive forms of a disease called anaplastic oligodendroglioma.

The new research is the largest ever genetic study of oligodendrogliomas, and provides important insights into their causes - and how they might be treated.

Oligodendrogliomas are fast-growing cancers that account for around 5-10 per cent of all tumours of the brain and central nervous system, and typically have a very poor prognosis.

Researchers at The Institute of Cancer Research, London, in collaboration with laboratories in France and Canada, compared the genetic sequence of 134 of these brain tumours with the DNA of healthy cells.

The study was largely funded by Investissements d'avenir and Génome Québec, with support from Cancer Research UK, and was published in the journal Nature Communications.

Researchers identified mutations in the TCF12 gene in 7.5 per cent of anaplastic oligodendrogliomas. They found that this subset of cancers grew more rapidly, and in other ways seemed more aggressive, than those where the gene was intact.

TCF12 is the genetic code for a protein that binds to DNA and controls the activity of other genes. The researchers found that mutations in TCF12 rendered the protein less able to bind to DNA, and this in turn led to a reduction in activity of other key genes - including one already associated with cancer spread, known as CHD1.

The researchers initially read the DNA sequence of 51 tumours and went on to look for TCF12 mutations in an additional group of 83.

The researchers also discovered errors in the gene IDH1 in 78 per cent of the tumours, confirming the findings of an initial scan of the data.

Finding out more about what genetic faults cause anaplastic oligodendrogliomas will allow scientists and clinicians to develop new personalised therapies that target a range of the mutations driving the disease.

Professor Richard Houlston, Professor of Molecular and Population Genetics at The Institute of Cancer Research, London, said:

"Our in-depth study has set out many of the genetic defects that cause this rare but highly aggressive form of brain cancer - including identifying a gene mutation that appears in particularly fast-growing forms.

"Anaplastic oligodendrogliomas are difficult to remove by surgery and don't respond well to other forms of treatment. We hope this new information might be used to discover new targeted therapies, offering patients a better chance at survival from this aggressive cancer."

Source:

Institute of Cancer Research

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por cyto às 11:46

Sábado, 04.07.15

way to stop growth of cancer cells by targeting the Warburg Effect

SLU researchers find way to stop growth of cancer cells by targeting the Warburg Effect

Published on June 26, 2015 at 10:55 PM 

In research published in Cancer Cell, Thomas Burris, Ph.D., chair of pharmacology and physiology at Saint Louis University, has, for the first time, found a way to stop cancer cell growth by targeting the Warburg Effect, a trait of cancer cell metabolism that scientists have been eager to exploit.

Unlike recent advances in personalized medicine that focus on specific genetic mutations associated with different types of cancer, this research targets a broad principle that applies to almost every kind of cancer: its energy source.

The Saint Louis University study, which was conducted in animal models and in human tumor cells in the lab, showed that a drug developed by Burris and colleagues at Scripps Research Institute can stop cancer cells without causing damage to healthy cells or leading to other severe side effects.

The Warburg Effect

Metabolism -- the ability to use energy -- is a feature of all living things. Cancer cells aggressively ramp up this process, allowing mutated cells to grow unchecked at the expense of surrounding tissue.

"Targeting cancer metabolism has become a hot area over the past few years, though the idea is not new," Burris said.

Since the early 1900s, scientists have known that cancer cells prefer to use glucose as fuel even if they have plenty of other resources available. In fact, this is how doctors use PET (positron emission tomography) scan images to spot tumors. PET scans highlight the glucose that cancer cells have accumulated.

This preference for using glucose as fuel is called the Warburg effect, or glycolysis.

In his paper, Burris reports that the Warburg effect is the metabolic foundation of oncogenic (cancer gene) growth, tumor progression and metastasis as well as tumor resistance to treatment.

Cancer's goal: to grow and divide

Cancer cells have one goal: to grow and divide as quickly as possible. And, while there are a number of possible molecular pathways a cell could use to find food, cancer cells have a set of preferred pathways.

"In fact, they are addicted to certain pathways," Burris said. "They need tools to grow fast and that means they need to have all of the parts for new cells and they need new energy."

"Cancer cells look for metabolic pathways to find the parts to grow and divide. If they don't have the parts, they just die," said Burris. "The Warburg effect ramps up energy use in the form of glucose to make chemicals required for rapid growth and cancer cells also ramp up another process, lipogenesis, that lets them make their own fats that they need to rapidly grow."

If the Warburg effect and lipogenesis are key metabolic pathways that drive cancer progression, growth, survival, immune evasion, resistance to treatment and disease recurrence, then, Burris hypothesizes, targeting glycolysis and lipogenesis could offer a way to stop a broad range of cancers.

Cutting off the energy supply

Burris and his colleagues created a class of compounds that affect a receptor that regulates fat synthesis. The new compound, SR9243, which started as an anti-cholesterol drug candidate, turns down fat synthesis so that cells can't produce their own fat. This also impacts the Warburg pathway, turning cancer cells into more normal cells. SR9243 suppresses abnormal glucose consumption and cuts off cancer cells' energy supply.

When cancer cells don't get the parts they need to reproduce through glucose or fat, they simply die.

Because the Warburg effect is not a feature of normal cells and because most normal cells can acquire fat from outside, SR9243 only kills cancer cells and remains non-toxic to healthy cells.

The drug also has a good safety profile; it is effective without causing weight loss, liver toxicity, or inflammation.

Promising Results So far, SR9243 has been tested in cultured cancer cells and in human tumor cells grown in animal models. Because the Warburg pathway is a feature of almost every kind of cancer, researchers are testing it on a number of different cancer models.

"It works in a wide range of cancers both in culture and in human tumors developing in animal models," Burris said. "Some are more sensitive to it than others. In several of these pathways, cells had been reprogramed by cancer to support cancer cell growth. This returns the metabolism to that of more normal cells."

In human tumors grown in animal models, Burris said, "It worked very well on lung, prostate, and colorectal cancers, and it worked to a lesser degree in ovarian and pancreatic cancers."

It also seems to work on glioblastoma, an extremely difficult to treat form of brain cancer, though it isn't able to cross the brain/blood barrier very effectively. The challenge for researchers in this scenario will be to find a way to allow the drug to cross this barrier, the body's natural protection for the brain, which can make it difficult for drug treatments to reach their target.

And, in even more promising news, it appears that when SR9243 is used in combination with existing chemotherapy drugs, it increases their effectiveness, in a mechanism apart from SR9243's own cancer fighting ability.

Source:

Saint Louis University

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por cyto às 11:25

Quinta-feira, 25.06.15

Acute Lymphoblastic Leukemia, Blood, Blood Cancer, Blood Disorder, Bone, Bone Marrow, Cancer, Cardiology, Cell, DNA, Education, Gene, Genetic, Genetics, Hematology, Hospital, Leukemia, Neurology, Neurosurgery, Oncology, Pediatrics, Platelets, Thrombocytop

Researchers track down key gene mutation responsible for causing acute lymphoblastic leukemia

Published on June 18, 2015 at 8:52 AM ·

After collecting data on a leukemia-affected family for nearly a decade, Children's Hospital of Michigan, Detroit Medical Center (DMC), Hematologist and Wayne State University School of Medicine Professor of Pediatrics Madhvi Rajpurkar, M.D., joined an international team of genetic researchers in an effort to track down a mutation partly responsible for causing the disease. Their findings, recently published in one of the world's leading science journals, have "major implications" for better understanding the genetic basis of several types of cancer, including leukemia.

Says Children's Hospital of Michigan Hematology/Oncology Researcher and Wayne State University Assistant Professor of Pediatrics Michael Callaghan, M.D., an investigator who co-authored the recently published study in Nature Genetics: "This is a very exciting new finding in cancer research - and I think a lot of the credit has to go to Dr. Rajpurkar for identifying the family (with the genetic mutation). This is a great example of how an astute clinician can help accomplish a breakthrough in research by paying careful attention to patients and then thinking long and hard about what she is seeing in the treatment room."

Two medical researchers from the Children's Hospital of Michigan and the Wayne State University School of Medicine have published the results of a nearly 10-year investigation that identified a key gene mutation that can trigger acute lymphoblastic leukemia, or ALL, and several other types of cancer.

Recently published in Nature Genetics, the findings assembled by the Children's Hospital of Michigan and Wayne State University School of Medicine duo and a team of international investigators have for the first time pinpointed a mutation that allows a lymphoblastic leukemia "precursor" to set the biochemical stage for the blood disorder.

ALL is a blood cancer that attacks an early version of white blood cells manufactured in bone marrow. Investigators have long suspected that it is caused in part by a mutation in a gene that is supposed to "turn off" excessive blood-cell growth. When the mutation suppresses the controlling mechanism that regulates the runaway growth, leukemia is often the result.

The study, "Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia," began nearly a decade ago when Dr. Rajpurkar treated a child at the Children's Hospital of Michigan for low blood platelets, known medically as "congenital thrombocytopenia." When both the child and an aunt later developed ALL - even as several other family members were diagnosed with thrombocytopenia - Dr. Rajpurkar began to suspect that there might be a genetic mutation at work in the family.

What followed was a 10-year journey through the labyrinth of the Human Genome, as the researchers worked with a growing number of genetic investigators to isolate and identify the mutation in a gene (ETV6) that regulates growth rates in bone marrow.

A key breakthrough in the quest for the genetic culprit took place when a nationally recognized expert in gene mutation - University of Colorado physician-researcher Jorge DiPaola, M.D. - joined Drs. Rajpurkar and Callaghan, and other investigators from Italy and Canada, in the effort to solve the DNA puzzle by uncovering the flaw in ETV6. The mutation discovery occurred in a core facility where the gene-sequencing took place.

While noting that "our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition," the study's authors concluded that the mutation occurs through "aberrant cellular localization" of the gene, which can result in "decreased transcriptional repression" during white blood cell formation.

"What we think that means," Dr. Callaghan said, "is that ETV6's job is to 'turn off' growth, but when you have this mutation, it can't turn it off because it's in the wrong place. It's usually supposed to sit on the DNA and keep things (including cancer) from getting made, but when you have this mutation, instead of sitting on the DNA it's sitting in a different part of the cell.... And that predisposes you to getting a (blood) cancer."

Dr. Rajpurkar, who is also the division chief of Hematology at the Children's Hospital of Michigan and an associate professor of Pediatrics at the Wayne State University School of Medicine, said she was "greatly pleased" that her decade of treating the Detroit family with the mutation eventually led to the breakthrough. "I told them that I didn't know what the family had," she said, "but that I would do my best to find out. Sometimes one has to accept uncertainty in the field of medicine, but (persistence in clinical research) pays off!"

The Children's Hospital of Michigan Pediatrician-in-Chief and chair of the Wayne State University School of Medicine Department of Pediatrics Steven E. Lipshultz, M.D., said the breakthrough was "hugely important" because it resulted in "a new association (between a genetic mutation and leukemia) that can now be scanned for.

"Because of this finding," he added, "families will eventually be counseled regarding their risk for some kinds of cancer and targeted interventions will be devised and tested."

Dr. Lipshultz also noted that the new findings in "what many physicians and researchers regard as the leading journal in the world on the molecular genetic basis of human disease" also provide "an exciting and extremely encouraging example of how research that takes place in the clinical setting can greatly improve care for patients.

"Our goal at the Children's Hospital of Michigan is to do everything we can to help achieve better outcomes for the patients we serve. This latest publication by two CHM physician-researchers and their colleagues underlines the vitally important links between treatment and research, and to see them demonstrated so compellingly inNature Genetics is quite thrilling for all of us who spend our days trying to help kids at the Children's Hospital of Michigan!"

Source:

Wayne State University - Office of the Vice President for Research

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por cyto às 11:49

Segunda-feira, 18.05.15

way for noninvasive detection of early stage liver cancer

Research leads way for noninvasive detection of early stage liver cancer

Published on May 15, 2015 at 9:02 AM ·

Led by Georgia State University, researchers have developed the first robust and noninvasive detection of early stage liver cancer and liver metastases, in addition to other liver diseases, such as cirrhosis and liver fibrosis.

Their findings were published Wednesday (May 13) in Proceedings of the National Academy of Sciences.

More than 700,000 people are diagnosed with liver cancer each year. It is the leading cause of cancer deaths worldwide, accounting for more than 600,000 deaths annually, according to the American Cancer Society. The rate of liver cancer in the U.S. has sharply increased because of several factors, including chronic alcohol abuse, obesity and insulin resistance.

"Liver cancers associated with high mortality rates and poor treatment responses are often diagnosed in the late stages because there is not a reliable way to detect primary liver cancer and metastasis at a size smaller than one centimeter," said Jenny Yang, lead author on the paper, Distinguished University Professor and associate director of the Center for Diagnostics and Therapeutics at Georgia State.

The liver is a common site for a variety of cancers, including melanoma, breast, pancreatic and colon cancers. Magnetic resonance imaging (MRI) is the leading imaging technique to detect disease without using radiation. MRI contrast or imaging agents aid MRI techniques to obtain tissue-specific images.

As reported by Yang, the applications of MRI contrast agents are not effective for early detection of cancerous tumors because they are hampered by uncontrolled blood circulation time, low relaxation rate or sensitivity, and low specificity. Most contrast agents, she said, are rapidly excreted from the liver, not allowing sufficient time to obtain quality imaging.

To more effectively detect cancerous tumors at an early stage, researchers from Georgia State, in collaboration with researchers from Emory University, Georgia Tech, the University of Georgia and the University of Virginia, have developed a new class of protein-based contrast agents (PRCAs) and an imaging methodology that provides robust results for the early detection of liver cancer and other liver diseases.

ProCA32, the researchers' newly developed contrast agent, allows for imaging liver tumors that measure less than 0.25 millimeters. The agent is more than 40 times more sensitive than today's commonly used and clinically approved agents used to detect tumors in the liver.

ProCA32 widens the MRI detection window and is found to be essential for obtaining high-resolution quality images of the liver. This application has important medical implications for imaging various liver diseases, the origin of cancer metastasis, monitoring cancer treatment and guiding therapeutic interventions, such as drug delivery.

"Our new agents can obtain both positive and negative contrast images within one application, providing double the accuracy and confidence of locating cancerous tumors," Yang said. "These agents are also expected to be much safer with reduced metal toxicity."

The researchers have shown proof-of-concept that ProCA32 can be used to detect cancerous liver tumors at an early stage with high sensitivity. They have also demonstrated that these new agents better aid the imaging of multiple organs, including the kidney and blood vessels, in addition to the liver and tumors.

"ProCA32 may have far-reaching implications in the diagnosis of other malignancies, which in turn would facilitate development of targeted treatment along with effective monitoring of reduction of tumor burden," Yang said. "Our agent and methodology can also be applied to study the brain and monitor treatment outcomes in a number of disorders, including stroke and recovery after stroke, Alzheimer's disease, brain tumors and gliomas,"

Source:

Georgia State University

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por cyto às 14:03


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