Philadelphia, U.S.A. – Researchers studying the molecular signals that drive a specific type of lymphoma have discovered a key biological pathway leading to this type of cancer. Cancerous cells have been described as being “addicted” to certain oncogenes (cancer-causing genes), and the new research may lay the groundwork for breaking that addiction and effectively treating aggressive types of B cell lymphoma.

B cell lymphomas, which occur both in children and adults, are cancers that attack B cells in the immune system.

“Our research suggests ways to devise more specific therapies to selectively kill tumor cells in a subset of lymphomas,” said study leader Andrei Thomas-Tikhonenko, Ph.D., an oncology researcher at The Children’s Hospital of Philadelphia.

The study, conducted in animal cells and human cell cultures, appeared May 1 in The Journal of Clinical Investigation.

An oncogene is a type of gene that normally produces a protein active in cell growth or regulation. However, when the gene is mutated or otherwise overproduced, it can cause cancer. One family of oncogenes is called MYC, and the current study focused on how the MYC oncogene drives B cell lymphoma. MYC codes for Myc, a type of protein called a transcription factor. At high levels, MYC causes the uncontrolled cell growth that is a hallmark of cancer.

The researchers focused on the crucial role of the cell surface receptor CD19, a protein residing on the surface of all B cells that normally recognizes foreign invaders. “We found that CD19 is absolutely required to stabilize the Myc protein,” said Thomas-Tikhonenko. “When Myc is stable and present in high levels, it fuels cancer.” Patients with high levels of the Myc protein are more likely to die of lymphoma.

Patients with high levels of Myc also had high levels of CD19, and the current study describes a previously unknown molecular pathway that depends on CD19. It also implicates CD19 as a molecular on-off switch on that pathway. Usually, said Thomas-Tikhonenko, when you inhibit one pathway, another pathway compensates to produce the same end result. But in this case, there is no such redundant pathway: “Without CD19, there is no Myc,” he added, “so controlling that on-off switch could represent a powerful tool against lymphoma.”

The findings are particularly relevant, said Thomas-Tikhonenko, to current oncology clinical trials that are testing antibodies that act broadly against the CD19 receptor. Such antibodies kill all B cells, and thus weaken the immune system. His study suggests that understanding the CD19 pathway could enable researchers to design a more specific therapy that selectively kills tumor cells while sparing healthy B cells.

Further studies in his lab, he added, will further investigate these molecular pathways and how to translate this knowledge into future anti-cancer treatments.

The National Institutes of Health, the V Foundation and the W.W. Smith Charitable Trust supported this study. In addition, a co-author, Elaine Y. Chung, Ph.D., was a fellow of the Leukemia and Lymphoma Society. Other co-authors, all from Children’s Hospital, were James N. Psathas, Ph.D., Duonan Yu, M.D., Ph.D., Yimei Li, Ph.D., and Mitchell J. Weiss, M.D., Ph.D.

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Cincinnati, OH, U.S.A.- Researchers have rejuvenated aged hematopoietic stem cells to be functionally younger, offering intriguing clues into how medicine might one day fend off some of the ailments of old age.

Scientists at Cincinnati Children‘s Hospital Medical Center and the Ulm University Medicine in Germany report their findings online May 3 in the journal Cell Stem Cell. The paper brings new perspective to what has been a life science controversy – countering what used to be broad consensus that the aging of hematopoietic stem cells (HSCs) was locked in by nature and not reversible by therapeutic intervention.

HSCs are stem cells that originate in the bone marrow and generate all of the body’s red and white blood cells and platelets. They are an essential support mechanism of blood cells and the immune system. As humans and other species age, HSCs become more numerous but less effective at regenerating blood cells and immune cells. This makes older people more susceptible to infections and disease, including leukemia.

Researchers in the current study determined a protein that regulates cell signaling – Cdc42 – also controls a molecular process that causes HSCs from mice to age. Pharmacologic inhibition of Cdc42 reversed HSC aging and restored function similar to that of younger stem cells, explained Hartmut Geiger, PhD, the study’s principal investigator and a researcher in the Division of Experimental Hematology/Cancer Biology at Cincinnati Children’s, and the Department of Dermatology and Allergic Diseases, Ulm University Medicine.

“Aging is interesting, in part because we still don’t understand how we age,” Geiger said. “Our findings suggest a novel and important role for Cdc42 and identify its activity as a target for ameliorating natural HSC aging. We know the aging of HSCs reduces in part the response of the immune system response in older people, which contributes to diseases such as anemia, and may be the cause of tissue attrition in certain systems of the body.”

The findings are early and involve laboratory manipulation of mouse cells, so it remains to be seen what direct application they may have for humans. Still, the study expands what is known about the basic molecular and cellular mechanisms of aging – a necessary step to one day designing rational approaches to aiding a healthy aging process.

One reason the research team focused on Cdc42 is that previous studies have reported elevated activity of the protein in various tissue types of older mice – which have a natural life span of around two years. Also, elevated expression of Cdc42 has been found in immune system white blood cells in older humans.

In the current study, researchers found elevated activity of Cdc42 in the HSCs of older mice. They also were able to induce premature aging of HSCs in mice by genetically increasing Cdc42 activity in the cells. The aged cells lost structural organization and polarity, resulting in improper placement and spacing of components inside the cells. This disorganization contributed to the cells’ decreased functional efficiency.

The researchers then analyzed HSCs from older mice to see if inhibition of Cdc42 would reverse the aging process. They used a specific dose (5uM) of a pharmacologic inhibitor of Cdc42, CASIN, to reduce the protein’s activity in the cells – processing them for 16 hours ex vivo in laboratory cultures. This improved structural organization, increased polarity and restored functionality in the older cells to levels found in young cells.

To test the rejuvenated cells, the researchers used a process known as serial competitive transplantation. This included extracting HSCs from young (2-4 months) and aged (20-26 months) mice and processing them in laboratory cultures. Young and rejuvenated cells were then engrafted into recipient mice. This allowed scientists to compare how well young and rejuvenated aged HSCs started to repopulate and transform into different types of blood cells. It also confirmed that HSCs rejuvenated by targeting Cdc42 do function similarly to young stem cells.

Researchers next plan to test the Cdc42 inhibitor, CASIN, in mice to see how HSCs and various tissues in the laboratory models respond. In particular, they are testing red blood cell production, endurance and immune response in the mice. The research team is also acquiring samples of human HSCs to see how those cells respond in laboratory tests to Cdc42 expression.

The first author on the study was Maria Carolina Florian, PhD, from the University of Ulm. Also collaborating were Karin Doerr, Anja Niebel, Deidre Daria, Hubert Schrezenmeier, MD, PhD, Markus Rojewski and Karin Sharffetter-Kochanek, all from the University of Ulm, and Yi Zheng, PhD, and Marie-Dominique Filippi, PhD, of Cincinnati Children’s.

Funding support for the research came from the Deutsche Forschungsgemeinschaft and the National Institutes of Health.

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California, U.S.A. - Amgen announced that four individuals who have made a difference for others affected by cancer in their communities have been selected as Breakaway from Cancer Champions.

They will be honored at the seventh consecutive edition of the Amgen Tour of California as part of Amgen’s Breakaway from Cancer initiative. The Amgen Tour of California is America’s largest and most prestigious road cycling stage race, which will travel nearly 750 miles throughout California from May 13 – 20, 2012.

The four Breakaway from Cancer Champions were selected following a public call for nominations in four of this year’s host finish cities, followed by an online voting campaign that concluded in April. The 2012 Breakaway from Cancer Champions are:

Santa Rosa – Marc Van Riper for co-founding Kathy’s Camp for Kids, a nonprofit organization dedicated to meeting the needs of the children of cancer patients. Kathy’s Camp for Kids is a place where fear of cancer is replaced with fun, friendship and encouragement.

Livermore – Two-time testicular cancer survivor Bob Hammer for founding the “Have a Ball” Foundation, which has raised more than $1,000,000 since its start and benefits 20 cancer organizations, sends kids with cancer to camps and has established and granted scholarships for students.

Clovis – Susan Mott for acting as a tireless advocate for awareness and fundraising for blood cancers. Specifically, Susan has raised money and organized blood drives for her toddler granddaughter, Madyn, who was diagnosed with leukemia in June 2011.

Los Angeles – Cancer survivor Danielle McLaughlin for her work advocating for young adults with cancer and her extraordinary accomplishments as a paratriathlete. Danielle is currently the National and World Paratriathlon Champion for Female Below-Knee Amputees.

“Amgen is passionate about helping those with cancer and we are proud to honor individuals who make a positive difference in the fight against cancer,” said Stuart Arbuckle, vice president and general manager, Amgen Oncology. “Breakaway from Cancer was founded on the belief that it takes a team to overcome this disease and the Champions program exemplifies this commitment to helping others.”

Founded by Amgen in 2005, Breakaway from Cancer is a national initiative to increase awareness of the important resources available to people affected by cancer – from prevention through survivorship. Breakaway from Cancer represents collaboration between Amgen and four nonprofit organizations dedicated to empowering patients with education, resources and hope.

The Breakaway from Cancer Champions will lead the “Breakaway Mile,” an approximately one-mile march that celebrates cancer survivors and crosses the Amgen Tour of California finish line prior to the stage conclusion of the professional race. The Breakaway Mile will take place in four 2012 race host cities on race day: Santa Rosa, Livermore, Clovis and Los Angeles. Each Breakaway Mile will also feature an Amgen scientist who plays a crucial role in developing breakthrough medicines for patients affected by cancer and other serious illnesses.

At the conclusion of each stage of the Amgen Tour of California, the Breakaway from Cancer Champion or a local cancer survivor will present Amgen’s Breakaway from Cancer Most Courageous Rider jersey to the professional rider who best exemplifies the character of those engaged in the fight against cancer—courage, sacrifice, inspiration, determination and perseverance.

Also during the 2012 Amgen Tour of California, a local cancer survivor will officially start each day’s stage by firing the official start gun. He or she will also have the opportunity to meet the prior day’s recipient of Amgen’s Breakaway from Cancer Most Courageous Rider jersey.

All Breakaway from Cancer programs benefit the initiative’s four nonprofit partners – Prevent Cancer Foundation, Cancer Support Community, Patient Advocate Foundation and National Coalition for Cancer Survivorship. Representatives of these four organizations will travel with the Amgen Tour of California, hosting a Breakaway from Cancer information booth at the Lifestyle Festival held in each of the finish cities along the route.

Image Courtesy of   Amgen Tour of California

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Last year, as part of Propublica ongoing investigation into the troubled state of death investigation in America, PBS “Frontline,”ProPublica and NPR took a closer look at what can be the most troubling and difficult cases — suspicious deaths of young children.

Propublica discovered a growing awareness in the medical community of a variety of diseases that can mimic the symptoms of child abuse, including hereditary blood disorders, leukemia and vitamin K deficiency.

One doctor Propublica spoke to — Dr. Michael Laposata, a pathologist and blood-clotting expert at Vanderbilt University who co-published a 2005 study on diseases that can mimic abuse — is pioneering a new blood testing regimen to rule out these types of disorders.

“If you’re lucky, most places … do the three routine tests: PT, PTT [both blood-clotting tests] and a platelet count, and that’s it,” Dr. Laposata told FRONTLINE in a phone interview. “It turns out most of the kids that have a bleeding problem have something other than that.”

Laposata and his colleagues have devised a system to make blood testing as foolproof as possible for doctors in cases of potential abuse: They created a tiered series of blood tests, known as a “Non-Accidental Injury Coagulation Panel,” which can identify underlying disorders that are more common in children. The panel can be performed with a small amount of blood, which is key when the patient is a baby.

“I think it’s the most comprehensive evaluation for a bleeding disorder that anybody has put forth to date,” Laposata said.

The panel is expected to be introduced soon at Vanderbilt and Dr. Laposata hopes to study its efficacy and to follow cases through the system over the years.

Because blood tests like these can only be performed on living patients whose blood is still flowing, a gap remains in diagnosing underlying conditions from autopsies. Laposata hopes that advances in genome testing could someday help close it, allowing for hereditary disorders to be better identified.

He said he also hopes his coagulation panel “will spur doctors to invent similar panels to evaluate bone injuries and skin changes that are also misdiagnosed as child abuse.”

Laposata was one of a number of doctors and other experts to offer testimony during the appeals process of Ernie Lopez, a Texas man convicted in 2003 of sexually assaulting 6-month-old Isis Vas. Isis, who had bruising and bleeding in the brain and vagina, later died. Lopez was sentenced to 60 years in prison.

After reviewing lab tests performed on Isis before her death, Laposata concluded that they contained ”clear abnormalities” and suggested that Vas suffered from a bleeding disorder known as disseminated intravascular coagulation (DIC). He gave an affidavit in the case in 2010. Last month, the Texas Criminal Court of Appeals voided Ernie Lopez’s conviction, saying Lopez received ineffective counsel because his attorneys did not adequately challenge the prosecution’s medical evidence.

Potter County District Attorney Randall Sims says he will retry Lopez. Take a look at Dr. Laposata’s PowerPoint presentation highlighting the difficulty in diagnosing abuse cases. On one side is a photo of a child with bruises from a bleeding disorder; on the other, a photo of a child who was abused.

“I’ve been looking at patients with bleeding problems for years, more than two decades,” he said. “And if you show me the two children with the bruises on their legs, I couldn’t tell you that that one is the bleeding disorder. I’d have to do the blood test to find out.”

by Gretchen Gavett, Special to ProPublica, Feb. 21, 2012, 3:16 p.m.

Gretchen Gavett is a digital associate producer for Frontline. “The Child Cases,” Propublica’s film on questionable convictions in child death cases, can be watched anytime online.

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Researchers have discovered that a subtype of leukemia characterized by a poor prognosis is fueled by mutations in pathways distinctly different from a seemingly similar leukemia associated with a much better outcome. The findings from the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project highlight a possible new strategy for treating patients with this more aggressive cancer.

The work provides the first details of the genetic alterations fueling a subtype of acute lymphoblastic leukemia (ALL) known as early T-cell precursor ALL (ETP-ALL). The results suggest ETP-ALL has more in common with acute myeloid leukemia than with other subtypes of ALL. The study appears in the January 12 edition of the journal ‘Nature’.

ALL is the most common childhood cancer and about 12 percent of patients have T-ALL. T-ALL arises from T-lineage white blood cells that make up one branch of the immune system. ETP-ALL was discovered by St. Jude researchers and accounts for about 12 percent of T-cell ALL. Many ETP-ALL patients fail to respond to current therapy and never enter remission. Only 30 to 40 percent of these patients become long-term survivors, compared to about 80 percent of children battling other T-ALL subtypes.

“The mutations and gene expression profile we identified in this study suggest that patients with ETP-ALL might benefit from treatment that includes drugs developed for treatment of acute myeloid leukemia,” said Charles Mullighan, M.D., Ph.D., an associate member of the St. Jude Department of Pathology and one of the study’s corresponding authors.

Mullighan said ETP-ALL was selected for inclusion in the pediatric cancer genome project due to the poor outcome and the lack of information on the genetic lesions that underlie this aggressive subtype of leukemia. “St. Jude is a pioneer in increasing overall ALL survival rates, which today exceed 90 percent for St. Jude patients. Now, we are working toward similar progress against this rare form of the disease,” he said.

The human genome is the complete set of instructions needed to assemble and sustain human life. Leukemia and other cancers develop when normal cells accumulate mutations in the genome that cause the unchecked cell growth that is a hallmark of cancer. The three-year Pediatric Cancer Genome Project is sequencing the genomes of tumor cells and matched normal DNA samples of 600 children with some of the most poorly understood and aggressive cancers. Investigators believe the findings will be the foundation for the next generation of clinical tools.

For this study, researchers sequenced and analyzed the normal and cancer genomes of 12 St. Jude patients with ETP-ALL. Investigators then checked for some of the same mutations in an additional 94 young leukemia patients with either ETP-ALL or other types of T-cell ALL.

“We found mutations unique to ETP-ALL that are not seen in other forms of ALL,” said co-author Richard Wilson, Ph.D., director of The Genome Institute at Washington University. “The results provide new targets for therapy and a way to use genetic tests to identify ETP-ALL patients early and earmark them for more aggressive therapy.”

The pattern of mutations identified in ETP-ALL was reminiscent of changes associated with AML, Mullighan said. The alterations were concentrated in genes in the cytokine receptor and RAS signaling pathways that are involved in the type of cell regulation disrupted in cancer. The mutations, which included NRAS, FLT3, JAK3, IL7R, and other genes, were found in about 67 percent of patients with ETP-ALL, but in only 19 percent of other T-ALL patients.

In addition, mutations in genes known or predicted to disrupt normal development of blood stem cells or lymphocytes were identified in 58 percent of ETP-ALL patients, but in just 17 percent of other T-ALL patients. The affected genes included ETV6, RUNX1, IKZF1, and GATA3. GATA3 helps regulate the early stages of T cell development, and mutations in the gene were found exclusively in ETP-ALL patients.

Epigenetic mutations, which are alterations affecting genes that indirectly influence the activity of other genes, were also more common in ETP-ALL patients. These genes, including EZH2 and SUZ12, were mutated or deleted in 45 percent of ETP-ALL patients, but in just 11 percent of the comparison group. The targeted genes modify proteins known as histones, which control gene activity through DNA binding.

Researchers also showed that ETP-ALL includes recurring mutations in about a half-dozen genes not previously linked to blood cancers. The list includes the genes RELN and DNM2. “The pattern of mutations we found in those genes suggests they function as tumor suppressors and their loss contributes to the malignant transformation of developing blood cells,” Mullighan said.

Mullighan said work is underway to develop laboratory models of human ETP-ALL and to use these models to identify AML drugs that are most likely to benefit ETP-ALL patients. The list of possible drugs includes high-dose cytarabine and targeted chemotherapy agents that inhibit activity in the cytokine receptor and JAK signaling pathways found in this study to be disrupted in ETP-ALL patients, researchers said. Those pathways help regulate cell division and normal development of the blood system.

“This is the first of a series of important discoveries on the genomic basis of childhood cancers that are emerging from the Pediatric Cancer Genome Project, which is on schedule to fully sequence 600 pediatric cancer genomes by 2013,” said Dr. William E. Evans, St. Jude director and CEO.

James Downing, M.D., St. Jude scientific director, St. Jude PCGP site leader and a corresponding author of the study, added, “This study highlights how the genome project is generating new insights into the genetic alterations that underlie some of the most aggressive childhood cancers and in turn is pointing us toward new therapeutic options that may increase the survival rates for children with these cancers.”

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Naples is an ancient city in Italy, one of the oldest in the world, famous for its history, its beauties, its art and its gastronomical specialities. Born as a Greek colony 2,800 years ago during its all history was the scene of many events that left their mark , characterizing the Italian history playing an important role in promoting the unification of the country and the Italian culture spread all over the world.

The beautiful gulf, the view of the volcano Vesuvius, the architectural and artistic treasures are the characteristics that make Naples the wonderful city that Italians know and foreigners dream.

Its historical center, which is the largest of Europe, has been listed as a World Heritage Site by UNESCO in 1995 thanks to its immense artistic and cultural value.

Nowadays all these beauties are in a real grip of garbage. The latest news reported that currently almost 2,000 tons of garbage lie on the streets of the city.

Residents say the smell is unbearable. In many cases it is even difficult for them going out from their houses because the waste bags are left outside the doors and sometime the piles reach the windows of buildings first floors.

A situation almost unimaginable in a big city of a Western European country, but that for Naples residents is the sad and not new reality.

In fact the garbage issue is a recurring issue for Naples. Since the middle of 1990 the city and its surroundings have suffered from waste management problems. The incapacity of the local administration and the infiltration of the Camorra – the local mafia organization that import waste from all over Europe – in the municipal garbage disposal business have led to the strong crisis which broke out in 2008, and still weigh heavily on this area.

The solution of the crisis promised by the Prime Minister Silvio Berlusconi since starting his mandate – that was also the point on which he built up his electoral campaign – didn’t solve the problem.

The center of the city and some other area were cleaned, but this situation of apparent calm lasted just for a while. In 2010 the government proposed to open new landfills in the region to face the problem – for example inside the Vesuvius National Park – but in the residents of the designed areas tried to block this action.

Cashes with the police, garbage trucks blocked by people stuck in the middle of the streets, rubbish skip committed to the flames, real scenes of urban guerrilla warfare that made Naples famous all over the world not for its beauties but for its garbage.

Until now all the government’s measures turned out totally useless and definitely not appropriate, and the emergency goes on.

Meanwhile the worries about the population’s health rise. Leukemia, throat cancer, and respiratory illnesses rates are higher day after day due to air and water pollution. A very high price to pay for the residents which watch with impotence the decay of their city and risk to compromise their state of health.

There is still a possibility for Naples to be free from the garbage and to be famous just for its beauties again?

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