Metformin treatment caused cancer stem cell death in pancreatic cancer cell lines

Public release date: 19-Jun-2012 [ | E-mail | Share ]

Contact: Jeremy Moore jeremy.moore@aacr.org 215-446-7109 American Association for Cancer Research

LAKE TAHOE, Nev. Results of some preclinical trials have shown that low doses of the antidiabetic drug metformin may effectively destroy cancer stem cells, a group of cells that are considered to be responsible for tumor initiation and, because they are resistant to standard chemotherapies, tumor relapse.

In addition, when metformin was combined with a standard chemotherapy used for pancreatic cancer, the combination treatment was able to efficiently eradicate both cancer stem cells and more differentiated cancer cells, which form the bulk of the tumor, according to data presented by Christopher Heeschen, M.D., Ph.D., at the American Association for Cancer Research's Pancreatic Cancer: Progress and Challenges conference, held in Lake Tahoe, Nev., from June 18-21, 2012. Heeschen is professor for experimental medicine at the Spanish National Cancer Research Centre in Madrid, Spain.

Most clinical trials of pancreatic cancer conducted during the last 15 years have failed to show marked improvement in median survival, suggesting that the selected approaches were not sufficient for several reasons, according to Heeschen. In recent years, researchers have identified cancer stem cells which, as opposed to the cancer cells that make up the bulk of the tumor, are a small subset of cells that are resistant to conventional therapy.

"Therefore, efficiently targeting these cells will be crucial for achieving higher cure rates in patients with pancreatic cancer," he said. "Our newly emerging data now indicate that metformin, a widely used and well-tolerated drug for the treatment of diabetes, is capable of efficiently eliminating these cells."

Specifically, the researchers found that metformin-pretreated cancer stem cells were particularly sensitive to alterations to their metabolism through the activation of AMPK. In fact, metformin treatment resulted in the death of cancer stem cells. In contrast, treatment of more differentiated cancer cells with metformin only arrested the cells' growth.

"As the cancer stem cells represent the root of pancreatic cancer, their extinction by reprogramming their metabolism with metformin in combination with the stalling of the proliferation of more differentiated cells should result in tumor regression and long-term, progression-free survival," Heeschen said.

The researchers generated data to support this idea when they treated immunocompromised mice implanted with a diverse set of patient-derived tumors with a combination of metformin and gemcitabine, the standard chemotherapeutic treatment for pancreatic cancer. They found that the treatment resulted in reduced tumor burden and the prevention of relapse as compared with treatment with either drug alone.

"Intriguingly, in all tumors treated with metformin to date, relapse of disease was efficiently prevented and there were no noticeable adverse effects," Heeschen said.

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Metformin treatment caused cancer stem cell death in pancreatic cancer cell lines

Pluristem Therapeutics' Cell Therapy Broadens Addressable Markets – Demonstrates Systemic Effectiveness of …

HAIFA, Israel, June 19, 2012 (GLOBE NEWSWIRE) -- Pluristem Therapeutics, Inc. (PSTI) (TASE:PLTR) announced today at the 2012 Bio International Convention the results of a pre clinical study it conducted measuring the effectiveness of its Placental eXpanded (PLX) cells when administered intramuscularly(IM). Cell therapies are traditionally delivered through intravenous (IV) injections for systemic effect. However, Pluristem's latest findings show that its PLX cells can be effective when injected by needle, into the muscle. Avoiding the use of an IV is simple and more cost-effective. This opens far larger markets for treatments in a wide range of potential outpatient settings and local clinics.

"The ability for IM injections of PLX cells has significant market implications that potentially broaden the indications and frequency with which our cell therapy can be used. We look forward to conducting additional testing of this very promising approach," said Zami Aberman, Chairman and CEO of Pluristem.

The study found that Intramuscularly administered PLX cells are safe, effective, easy to inject and provided systemic therapeutic benefits in a wide range of hematological disorders, as well as primary and secondary bone marrow failure, such as in radiation sickness and possibly for some complications from chemotherapy and radiotherapy.

The results of the study demonstrated a significant survival and recovery rate of bone marrow and peripheral blood counts in animals pre-irradiated by high lethal doses. These findings indicate that the IM route of administration of PLX cells stimulate the hematopoietic stem cells (HSCs) of the bone marrow to produce red and white blood cells as well as platelets crucial for the treatment of hematological disorders. The study was conducted in cooperation with the Sharett Institute of Oncology at Hadassah Hospital in Jerusalem.

"Pluristem is extremely pleased at how convincingly this study's data demonstrates that our PLX cells have the ability to stimulate the HSCs involved in rescuing bone marrow. With PLX cells, we may be able to reverse the traditional mindset that if you want to get a systemic effect, you need to inject the cells intravenously," said Liat Flaishon, MD. PhD. BD Director and the Head of the Radiation project at Pluristem.

"We had announced on May 9, 2012 the successful treatment of a pediatric patient whose bone marrow graft was rescued using our PLX cells. This data demonstrates the basis for the successful treatment. In the treatment conducted by Professor Reuven Or from the Bone Marrow Transplantation Unit at Hadassah, PLX cells were given to this patient intramuscularly as well," added Dr. Flaishon.

Prof. Raphael Gorodetsky, Head of the Laboratory of Biotechnology and Radiobiology in the Cancer Research Laboratories of Sharett Institute of Oncology at Hadassah Hospital, has been conducting the animal studies of Pluristem's PLX cells in the past several months. In these studies PLX cells and control medium were administered intramuscularly to C3H mice previously irradiated by a total body dose of 770cGy. The company previously reported initial results from these studies with respect to Acute Radiation Syndrome.

The key results of the Study include:

- After an initial sharp fall, a significant increase in the total number of bone marrow cells extracted from the major bones at 23 days was recorded: from~16million cells/mouse to ~32 million cells/mouse in the PLX treated (p<0.001). Non-irradiated animals had an average of 40 million cells.

- at 23 days a significant increase in the total number of red blood cells was recorded from 3.5 in the surviving controls to 6 million cells/microliter, in comparing the PLX (p<0.001). Non-irradiated animals had an average of 7 million cells/microliter.

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Pluristem Therapeutics' Cell Therapy Broadens Addressable Markets - Demonstrates Systemic Effectiveness of ...

State Awards $9.8 Million For Stem Cell Projects

Gov. Dannel P. Malloy Monday announced $9.8 million in grants to 19 stem cell research projects in the state. The Connecticut Stem Cell Research Advisory Committee had selected the recipients at its grant review meeting last Tuesday in Farmington.

"Connecticut's continued support of stem cell research has allowed for exciting and innovative research to take place right here in our state," Malloy said in a statement. "The research projects funded by these grants allow scientists to do revolutionary work that puts Connecticut at the forefront of bioscience industry."

Of the 19 grants, 13 grants totaling $7.25 million were awarded to Yale scientists, five went to University of Connecticut researchers, and one went to a collaboration between Wesleyan and UConn scientists.

The largest grant, $1.8 million, was awarded to D. Eugene Redmond of Yale. Redmond has focused on cellular repair in the nervous system and how it relates to Parkinson's disease.

UConn's Stormy Chamberlain, an assistant professor of genetics and developmental biology at the UConn Health Center, received a $450,000 grant to develop new therapies for Prader-Willi syndrome and Angelman Syndrome, both rare genetic disorders. Children born with Prader-Willi Syndrome have difficulty feeding and develop poor muscle tone, and starting about age 2, they develop an insatiable appetite that lasts for their lifetime. People with Angelman Syndrome suffer speech difficulties, seizures, problems with motor control and balance, and serious intellectual disabilities

Although Chamberlain generally focuses on Angelman Syndrome, the three-year project also will include Prader-Willi because the causes of the two disorders are similar. Angelman Syndrome is caused by the deletion of genes on a certain chromosome on the mother's side, while Prader-Willi Syndrome is caused by the deletion of genes in same chromosome on the father's side.

Chamberlain estimates that she's one of 30 researchers in the U.S. who studies Angelman Syndrome.

"The state funding really helps rare diseases because the foundations that typically fund their research are limited," she said, adding that support often is limited to fundraisers organized by families of those with the conditions.

A stem cell education outreach program, run by Laura Grabel, a professor of biology at Wesleyan, and Ren-He Xu, a professor of genetics at UConn, received $500,000. Grabel said the program, which has been in operation since 2006, holds workshops and retreats for stem cell researchers and educates the general public by sending speakers to schools and various organizations. The program also has representatives speak to high school science teachers about incorporating stem cell science in their curricula.

Although the program was started partly because of the controversy over the use of stem cells, Grabel said "we've seen very little pushback it's been very positive."

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State Awards $9.8 Million For Stem Cell Projects

Chicago woman cured of sickle cell disease

ScienceDaily (June 18, 2012) Chicagoan Ieshea Thomas is the first Midwest patient to receive a successful stem cell transplant to cure her sickle cell disease without chemotherapy in preparation for the transplant.

University of Illinois Hospital & Health Sciences System physicians performed the procedure using medication to suppress her immune system and one small dose of total body radiation right before the transplant.

The transplant technique is relatively uncommon and is a much more tolerable treatment for patients with aggressive sickle cell disease who often have underlying organ disease and other complications, says Dr. Damiano Rondelli, professor of medicine at UIC, who performed Thomas's transplant.

The procedure initially allows a patient's own bone marrow to coexist with that of the donor. Since the patient's bone marrow is not completely destroyed by chemotherapy or radiation prior to transplant, part of the immune defense survives, lessening the risk of infection. The goal is for the transplanted stem cells to gradually take over the bone marrow's role to produce red blood cells -- normal, healthy ones.

Thomas, 33, had her first sickle cell crisis when she was just 8 months old. Her disease became progressively worse as an adult, particularly after the birth of her daughter. She has spent most of her adult life in and out of hospitals with severe pain and has relied on repeated red blood cell transfusions. Her sickle cell disease also caused bone damage requiring two hip replacements.

"I just want to be at home with my daughter every day and every night," said Thomas, who depends on family to help care for her daughter during her frequent hospitalizations.

This type of stem cell transplant is only possible for patients who have a healthy sibling who is a compatible donor.

Thomas' sister was a match and agreed to donate blood stem cells through a process called leukapheresis. Several days prior to leukapheresis, Thomas' sister was given drugs to increase the number of stem cells released into the bloodstream. Her blood was then processed through a machine that collects white cells, including stem cells. The stem cells were frozen until the transplant.

Last Nov. 23, four bags of frozen stem cells were delivered to the hospital's blood and marrow transplant unit. One by one, the bags were thawed and hung on an IV pole for infusion into Thomas. The procedure took approximately one hour. Her 13-year-old daughter, Miayatha, was at her bedside.

Six months after the transplant, Thomas is cured of sickle cell disease and no longer requires blood transfusions.

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Chicago woman cured of sickle cell disease

Stemtech: Stem cell nutrition could eclipse antioxidant supplement market

The emerging field of stem cell nutrition has the potential to eclipse the massive antioxidant supplement business according to the boss of the Californian firm responsible for creating a completely new category in nutritional supplements.

Ray Carter Jr, CEO of Stemtech International, was speaking to NutraIngredients-USA after signing a multi-million dollar deal with Australian biotech firm Marinova to include its proprietary Fucoidan ingredients in Stemtechs new SE2 supplement.

The next generation of Stemtechs best-selling StemEnhance supplement, SE2 also includes a concentrate of blue-green algae Aphanizomenon flos-aquae (AFA), the herb Polygonum multiflorum and the fungus Cordyceps sinensis.

Adult stem cells, tissue maintenance and repair

SE2 helps increase the number of adult stem cells or master cells that are released into the bloodstream before migrating into tissues where they reproduce and become new healthy cells, effectively helping the body renew and repair itself, claimed Carter.

Stemtech products have already generated more than $200m in sales since 2005, he added: Stem cell nutrition addresses a brand new way to support health [and]has the potential to eclipse the massive antioxidant supplement business.

When consumers first heard the words stem cell, they were inundated with media reports about the controversy and promise of embryonic stem cell (ESC) research.

Fast forward to today, and they are beginning to learn that adult stem cells actually show much more clinical promise without the ethical and moral controversy surrounding ESCs.

The bodys natural renewal system

Adult stem cellshave been shown to be the bodys natural renewal system, he claimed.

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Stemtech: Stem cell nutrition could eclipse antioxidant supplement market

Stem Cell Scientist Shinya Yamanaka Receives Millennium Technology Award

By Anne Holden on June 18, 2012

Gladstone Institutes Senior Investigator Shinya Yamanaka, MD, PhD, a professor of anatomy at UCSF, has won the Millennium Technology Award Grand Prize, the worlds largest and most prominent technology award.

Shinya Yamanaka, MD, PhD

This award recognizes Yamanakas discovery of a way to turn adult skin cells into cells that act like embryonic stem cells. This discovery has since altered the fields of cell biology and stem cell research, offering new hope for the future of both personalized and regenerative medicine.

Yamanaka and Linus Torvalds, creator of Linux, were named laureates or finalists for the 2012 prize in April. For the first time in the awards history, both laureates were named joint Grand Prize winners today by the President of the Republic of Finland. Yamanaka and Torvalds will share 1.2 million Euros.

Six years ago, Yamanaka discovered that altering the genes of adult skin cells in mice allowed him to induce the cells into becoming like embryonic stem cells. He called them induced pluripotent stem cells, or iPS cells. In 2007, he announced that he had done the same with human adult skin cells.

Scientists all over the world are using Yamanakas method to create stem cells and making great strides in research, said Ainomaija Haarla, president of Technology Academy Finland. His achievement has had a great impact on research in medicine and biotechnology as pluripotent stem cells are already being used for medical drug testing and the growth of implant tissues. Yamanaka is unquestionably the father of this innovation.

Many see iPS cell technology as an entirely new platform for fundamental studies of human disease. Rather than using disease models made in yeast, flies or mice for research, iPS technology lets scientists create human stem cells from the skin cells of patients with a specific disease. As a result, the iPS cells contain a complete set of the genes that resulted in that disease representing the potential of a far-superior human model for studying disease development, new drugs and treatments. In the future, iPS cells could be used to test both drug safety and efficacy for an individual patient.

The Millennium Technology Prize is Finlands tribute to technological innovation that significantly improves the quality of human life today and for future generations. Notable past recipients include Tim Berners-Lee, inventor of the World Wide Web, Professor Shuji Nakamura, inventor of revolutionary light sources, Professor Robert Langer, inventor of biomaterials for controlled drug release and tissue regeneration and Professor Michael Grtzel, inventor of dye-sensitized solar cells.

as researchers and physicians we must continue to innovate new solutions that will help improve the lives of millions worldwide affected by these and many other diseases.

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Stem Cell Scientist Shinya Yamanaka Receives Millennium Technology Award

Sistemic to Moderate Regenerative Medicine Panel at 2012 Bio International Convention

BOSTON--(BUSINESS WIRE)--

Sistemic Ltd., a leading provider of microRNA-based problem-solving services and kit-based products to the Cell Therapy community, announced today that chairman and CEO Jim Reid is moderating a panel discussion at the 2012 Bio International Convention on Wednesday, June 20, in Boston. Featuring leaders from the regenerative medicine space, the panel is titled Stem Cell Therapies Fact or Fiction, and will share the lessons learned to-date from Scottish, European and American perspectives on the path to successfulcommercialization of stem cell therapies.

Jim Reid, Sistemic CEO, commented, "Sistemic is very active in the CellTherapyarena and aremembersof Alliance for Advanced Therapies (AAT) and the Alliance for Regenerative Medicine (ARM). We see the ability to raise this topic at the leading world event, BIO 2012, as animportantstep on the path to commercialization of these products which will be transformational in healthcare, and bring hope and cures to many people around the globe."

More information on the panel at BIO 2012:

What: Panel Discussion Featuring Leaders in the Regenerative Medicine Space

When: Wednesday, June 20, 3:00PM EDT

Where: Boston Convention Center, Room 254A

Who: Leaders of the Regenerative Medicine space:

Panel objectives include evaluating lessons learned and best practice including from the Scotland Roadmap for the commercialization of stem cell therapies; identifying global (US and EU) examples of progress in stem cell therapy commercialization; and facilitating a debate on the need for a global, multi-disciplinary approach to successful commercialization of stem cell therapies.

About Sistemic Ltd

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Sistemic to Moderate Regenerative Medicine Panel at 2012 Bio International Convention

Royal Oak Veterinarian Dr. Simon First in Michigan to Offer In-House Adult Pet Stem Cell Therapy

ROYAL OAK, Mich., June 17, 2012 (GLOBE NEWSWIRE) -- Woodside Animal Hospital announced they have added both stem cell therapy and cold laser therapy to their suite of services. These two cutting edge treatments are done entirely in-house, no third-party lab work is required. Royal Oak veterinarian Dr. John Simon is the first Michigan veterinarian to provide pets with in-house adult stem cell therapy. The stem cells are derived from the pet's fat deposits and absolutely no embryonic tissue is used.

"As a holistic veterinarian, I am committed to providing high quality, cutting-edge care that combines traditional veterinary care with advanced holistic treatments," said Dr. Simon. "Our in-house stem cell therapy and cold laser therapy procedures alleviate pain in limping dogs and promote internal healing following an injury. I also recommend these procedures for pets with osteoarthritis."

Cold laser therapy is a non-surgical approach to pain management. Holistic equine veterinarians have used the procedure for over 20 years to treat injuries and joint pain. Today, veterinarians are using cold laser therapy to provide natural pain relief for injured pets.

According to Dr. Simon, cold laser therapy works by using a low-level energy beam to penetrate just below the skin's surface. Injured cells use the laser's energy to repair cellular damage. This provides relief for pain and swelling following a soft tissue injury, such as a ligament, tendon or muscle strain.

"Cold laser therapy is a revolutionary treatment for natural pain management in animals," said the Royal Oak veterinarian. "Laser therapy allows for advanced pain management, especially for pets suffering from chronic conditions or soft tissue injuries."

Woodside Animal Hospital also provides in-house pet stem cell therapy. This treatment uses adult stem cells collected from a dog's fat deposits to promote the growth of new soft tissue and cartilage. By performing the whole procedure in the clinic, the stem cells can be harvested and re-injected on the same day.

"Our in-house pet stem cell therapy is an affordable, same-day treatment that helps dogs suffering from joint pain, osteoarthritis, soft tissue injuries and hip dysplasia," said Dr. Simon. "As pets age, it's natural that their range of movement becomes restricted. While oral joint care supplements and prescription painkillers can help, medication alone cannot restore a full range of movement. Our treatments help restore activity and movement."

In addition to cold laser therapy and stem cell therapy, Dr. Simon also provides holistic treatments for cancer in dogs, cat and dog rashes, and dietary needs. The Royal Oak practice is a full-service animal hospital with wellness care, vaccinations and surgical procedures.

Dr. Simon is active in the greater Detroit veterinary community, serving as the past president of the Oakland County Veterinary Medical Association and as a board member for the Southeastern Michigan Veterinary Medical Association (SEMVMA).

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Royal Oak Veterinarian Dr. Simon First in Michigan to Offer In-House Adult Pet Stem Cell Therapy