The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Tag Archives: cancer stem cells

Friday Science Review: May 7, 2010

Amazing!  Three Nature papers this week…

Cracking the Code: The human body is much more complex than the 20,000 or so genes that are encoded in our DNA.  This multiplicity of genetic messages is enhanced by alternative gene splicing, a process where different segments of DNA exons are spliced together to create a different gene message.  It is possible to create hundreds of new messages from a single gene.  The so called “splicing code” or rules that determines how and where a particular part of a gene is spliced with another segment was deciphered by researchers at the University of Toronto.  They can now accurately predict how genetic messages are rearranged on a large scale.  Hundreds of different RNA features are taken into account including certain factors in specific tissues to give rise to tissue specific expression.  This is an amazing discovery by Drs. Brendan Frey and Benjamin Blencowe that garnered the cover story in this week’s Nature journal.

Stem Cells on Hormones: The ovarian hormone, progesterone, stimulates breast stem cells as its levels peak during the natural reproductive cycle.  Researchers observed up to a 14-fold expansion of breast stem cells at peak progesterone levels in a mouse model.  This is the first evidence of a direct link between hormones and breast stem cells.  Since cancers are thought to initiate from stem cells, if there are other oncogenic factors pushing the system this may be a critical point that ultimately drives the start of a cancer.  There are implications of this study to further understanding how reproductive history is a strong risk factor for breast cancer and may lead to therapeutic intervention.  The research team at Princess Margaret Hospital, University Health Network was led by Dr. Rama Khokha and describes their work in Nature.

Reversing HER2 Breast Cancer: Through genomic studies of HER2 positive breast cancer, it was noted that the 14-3-3sigma gene was frequently missing.  After several years of hard work focusing on this gene, researchers have demonstrated that the 14-3-3sigma gene does indeed play a specific role in the development and function of breast epithelial tissue.  In the absence of 14-3-3sigma, the normally organized and polarized sheets of epithelial cells clump together and lose polarity.  It is this loss of organization without 14-3-3sigma that likely contributes to breast cancer progression.  From a therapeutic standpoint, the reintroduction of 14-3-3sigma into HER2 positive breast cancer cells resulted in the restoration of cell polarity and opens a window for further studies as a pathway to target.  Dr. William Muller (my former mentor) and his team at McGill University describe their research in the early edition of Genes and Development.

Bionic Muscle: Artificial proteins were assembled together in a fashion that mimics the molecular spring structure of a muscle protein called Titin, which is a very large protein that gives muscle tissue its unique properties of strength, extensibility and resilience.  This is why muscle has superior elasticity.  The biomaterial looks like a string of beads and although it exhibits only some of the mechanical characteristics of muscle tissue, its structure can be adjusted to provide specific properties of different types of muscle.  There are obvious future applications of this technology in regenerative medicine and tissue engineering.  Drs. Hongbin Li and John Gosline at the University of British Columbia present their work in this week’s Nature journal.

Friday Science Review: March 26, 2010

Why Did the Duck Kill the Chicken? Well… a scientific explanation is RIG-I.  Ducks are resistant to influenza viruses but may by asymptomatic carriers.  One of the reasons for ducks’ resistance is because ducks express the RIG-I protein that senses the presence of the viruses.  Chickens, however, do not appear to express RIG-I or a similar protein and have no method to detect the presence of viruses to illicit an immune response.  This could have implications to the poultry industry who do not want to see their entire farm wiped out by a viral outbreak and may want to start breeding transgenic chickens expressing RIG-I.  The discovery was led by Dr. Katharine Magor and her team at the University of Alberta and is published in the early edition of the Proceedings of the National Academy of Sciences.

Promoting Cancer Cell Growth: The YB-1 (Y-box binding protein-1) transcription factor is a known oncogene that is expressed in a significant percentage of breast cancers.  In this study, scientists demonstrated that YB-1 induces the expression of CD44 and CD49f, which are associated with cancer stem cells and used as stem cell markers.  Although they do not make a direct link to breast cancer stem cells, they suggest that it is this link that explains why YB-1 expressing cancers are resistant to drugs such as paclitaxel and are associated with disease recurrence and poor outcome.  The principal investigator of the study was Dr. Sandra Dunn at the University of British Columbia. Details of the study were reported in Cancer Research.

Knock, knock… Let Me In: A transporter protein that is selectively expressed in blood cells can be manipulated to facilitate the entry of cancer drugs into the cell.  This is extremely important for new treatment regimes against blood cancers such as AML and other leukemias.  Researchers found that the Human Carnitine Transporter encoded by the SLC22A16 gene acts as a gateway and can mediate the uptake of the polyamine class of drugs such as the anti-cancer agent Bleomycin.  Dr. Dindial Ramotar, Université de Montréal, first demonstrated this in yeast cells and now in human cells as reported in the Journal of Biological Chemistry.

Please, No More Radiation: A genetic mutation in the p53 gene in children with a rare type of brain cancer – choroid plexus carcinoma (CPC) – is a new marker indicating a poor response to radiation therapy.  It is unfortunate that this signals a more aggressive disease, however, this finding would relieve the patient of having to suffer through the difficulties of radiation.  The inherited p53 mutation is associated with a condition called Li-Fraumeni syndrome and is found in about 50% of CPC cases.  Without the mutation, CPC patients treated by radiation have a good chance of recovery.  The study, led by Dr. David Malkin at the Hospital for Sick Children, Toronto, is published in the advance online issue of the Journal of Clinical Oncology.

Mooooooooo: Scientists have finished sequencing the genome of two different types of cows – one beef and one dairy – using Life Technologies’ next generation SOLiD™ 3 System.  It cost $130K and took only seven months to complete.  In comparison, it cost $50M and four years, finishing in 2009, to sequence the first cow.  The genomic information is important to the industry for making breeding decisions and to identify genetic markers of specific desirable traits.  So that T-bone steak waiting for you to grill up this summer will be even juicier and tastier.  The Bovine Genomics Program at the University of Alberta led by Dr. Stephen Moore performed the sequencing study.

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Friday Science Review: October 30, 2009

Regenerative medicine and Cross-border awards…

Gene Therapy Saves Donor Lungs: A technique using gene therapy on donor lungs before transplantation may be used to repair and save damaged lungs, making them potentially suitable for transplantation into patients.  The procedure involves first preserving the lungs at normal body temperature in a protective chamber called the Toronto XVIVO Lung Perfusion System, which continuously pumps a solution of oxygen, proteins and nutrients.  Next, adenovirus gene therapy is used to introduce the IL-10 cytokine gene into the lungs.  IL-10 helps to decrease inflammation, which would lead to improved health and function of the donor lungs and better outcome for the patient.

Dr. Shaf Keshavjee, the project leader at the McEwen Centre for Regenerative Medicine, describes the rationale:

“It’s as if gene therapy turbocharges each individual cell to manufacture many more proteins in its own IL-10 factory.”

“This protein down-regulates or decreases the inflammatory potential of cells injured before and during the transplant process. It also has the capacity to turn down the recipient’s immune system which rejects the transplanted organ.”

The research study is reported in this week’s issue of Science, Translational Medicine.

A Platform to Test Cardiac Cell Therapy:  A model system for evaluating stem cell transplant in cardiac cell therapy to repair damaged heart tissue is described in this study by Drs. Peter Zandstra and Milica Radisic’s team at the University of Toronto.  Using their engineered heart tissue (EHT) as the analytical platform, they applied stem-cell derived cardiac cells and measured molecular and electrophysiological parameters of the EHT.  The system was verified as a predictive strategy to interrogate different cell transplantation conditions for the capacity to survive and functionally integrate into heart tissue.  This tool should help researchers accelerate development of cardiac cell therapy strategies and it can also provide mechanistic insight into the challenges of a successful transplant.  On a personalized medicine theme, an advantage of the system is that the EHTs are customizable and can be derived from individuals for patient specific testing prior to the actual treatment.  The study appears in this week’s edition of the Proceedings of the National Academy of Sciences.

“Cross-border” Cancer Stem Cell Therapy Award: The Collaborative Partnership Program between the California Institute for Regenerative Medicine (CIRM) and the Cancer Stem Cell Consortium (CSCC) in Canada have awarded two internationally recognized Canadian researchers with support to lead their respective cancer stem cell based therapy projects.

One project will develop agents to directly target leukemic stem cells that are resistant to current therapies.  This will be co-led by Dr. John Dick, Princess Margaret Hospital and Dr. Dennis Carson, University of California San Diego.

The other project will develop small molecules targeting cancer-initiating cells within solid tumor cancers and will be co-led by Dr. Tak Mak, Princess Margaret Hospital and Dr. Dennis Slamon, University of California, Los Angeles.

The awards offer each project up to $40 million (USD) over four years, with funding for the Canadian investigators contributed by Genome Canada and Canadian Institutes of Health Research through the CSCC and funding for the Californian investigators contributed by CIRM.

Congratulations to Drs. John Dick and Tak Mak!

Top 10The Scientist magazine ranked Dalhousie University in Halifax and the University of Toronto in the top 10 best places to work in academia outside of the U.S. Based on a web survey of scientists regarding job satisfaction, pay, research resources and relationships with their peers and management, Dalhousie ranked 5th and U of T came in at 10th place.  It is very nice to see Canadian institutions and our great research environment recognized by peers around the world.

Friday Science Review: First Time for Everything Edition

First time for blood stem cell factors:  Dr. Guy Sauvageau of the University of Montreal produced a large number of blood stem cells in the lab from a smaller sample taken from bone marrow using a novel screening technique to identify mediators of the stem cell repopulating activity.  The study was published in this week’s Cell.  Dr. Sauvageau said that “[i]t could be possible to envision transplants for all adults from existing umbilical cord blood banks.”

First time for viral destruction of cancer stem cells:  A group out of Dalhousie used reovirus on fresh breast cancer tissue removed from a patient, while most cancer studies use cancer cell lines developed for laboratory use.  Not only does reovirus kill the cancer stem cells and cancer cells, it also stimulates the body’s anti-cancer immune system.

First time for a dual axis rotational cardiac X-ray:  The University of Ottawa Heart Institute (UOHI) has the first one of these X-ray machines for clinical use in North America.  It produces better images in less time with less dye and less radiation.

First time for driving into space:  The headlines said “Calgary scientists determine outer space only an hour’s drive away.”  Apparently all the debate about where the atmosphere stops and space begins could have been solved if the scientists involved had gotten out of the lab and into their cars a bit sooner.

First time for a meta-diet:  A group at McMaster conducted a meta-study of the effects of various diets on coronary heart disease and concluded that the Mediterranean diet is meta-good, and that trans-fats are meta-bad.  The WSJ Health blog said:  “So [the analysis] is a useful, if not particularly surprising, guide.”

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