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Tag Archives: cancer

Friday Science Review: June 4, 2010

New fixes for spinal injury, Staph infection and cancers…

Spinal Cord Self-Repair: A natural repair mechanism in our bodies may be the key to treating spinal-cord injuries.  Following a spinal cord injury, there is an increase in expression of serotonin receptors and the receptors are spontaneously active even in the absence of serotonin.  This autoactivation is thought to be a response or repair mechanism that is initiated as a result of the injury.  Pharmacological agents may be used to try to enhance this receptor activity to promote recovery.  The caveat, however, is that the receptors remain “on” and may explain the spasms experienced by spinal injury patients.  In this case, inhibitory drugs may be beneficial to preventing these muscle spasms.  Dr. Karim Fouad and his team conducted the research at the University of Alberta (Edmonton) and present their work in Nature Medicine.

Super Bug’s Magic Revealed:  MRSA, or methicillin-resistant Staphylococcus aureus, is a strain of Staph that has become resistant to most types of antibiotics.  Scientists now know why and what makes a harmless bacteria become pathogenic Super Bugs.  A small chemical (aureusimines) made by MRSA bugs is the key factor that determines their virulence and ability to cause severe disease.  The researchers discovered how these chemicals are made in the bacterium and then tried to shut off the different pathways involved in the synthesis of these chemicals.   Blocking aureusimine production resulted in a much weaker and less virulent bug, which allowed the mouse model patients to recover from S. aureus infections.  This information comes at a crucial time when drug resistance is on the rise and new anti-bacterial targets are desperately needed.  McMaster University scientists led by Dr. Nathan Magarvey describe their breakthrough discovery in the latest Science magazine.

Controlling Cell Growth: The research of Dr. Nahaum Sonenberg and his McGill University team on the mechanisms controlling cell growth and proliferation have had significant impact in advancing the field.  They continue their key discoveries with the delineation of mTORC1 and the 4E-BP proteins.  Although mTORC1 is known to be involved in connecting growth and nutrient signals to control cell size and cell division, 4E-BPs are only involved in mediating the cell proliferation pathway and not cell growth.  This distinction is important because mTORC1 is implicated in a variety of diseases and these related pathways are targets for therapeutic drugs, so further refinements can be made accordingly.  The report is published here in Science magazine.

A Cancer Cure in Sponge? A peptide found in sea sponge can inhibit tumour cell metastasis.  The Neopetrosiamide A (NeoA) peptide prevents tumour cells from sticking to surfaces by decreasing cell surface proteins such as integrins and inducing the disassembly of structural complexes called focal adhesions.  Its mechanism of action is unknown but it somehow causes important “sticky” proteins to be kicked out of the cell rather than trafficking to their proper locations.  This is a developing story to keep an eye on.  The study is published in PLoS One by Dr. Calvin Roskelley’s team at the University of British Columbia.

Friday Science Review: February 19, 2010

Hunks and pigs highlight this week’s research wrap-up…

HUNKs Stop Cancer Metastasis: Researchers screening tumour cells found that expression of the enzyme HUNK (Hormonally Up-regulated Neu-associated Kinase) is significantly lower in cancers.  When they reconstituted HUNK into metastatic cancer cells, it decreased their metastastic potential when tested in mouse cancer models.  Its actions block the association of PP2A and cofilin-1 and prevent the formation of actin filaments, which are key skeletal proteins involved in the cell migration process.  Dr. Tak Mak led the research team at the Campbell Family Institute for Breast Cancer Research and published the study in the Proceedings of the National Academy of Sciences.

Malaria Research Gets Genomic Help: A genome-wide study on the parasite Plasmodium falciparum should help researchers in the hunt for new drugs against malaria.  The genome of 189 malaria samples from around the world were decoded and analyzed to try to identify key genes that are responsible for the parasite’s propensity to evolve and become resistant to currently available drug treatments.  These data are invaluable for the design of future therapeutic approaches.  An international team was co-led by Dr. Philip Awadalla at the Université de Montréal and reports their work in the current issue of Nature Genetics.

Genetic Clues to Diabetes: Using a genome-wide association approach, 13 SNPs concentrated in 4 genetic regions were identified to be strongly correlated with glycemic control in type 1 diabetes.  For example, SORCS1 is strongly associated with hypoglycemia (low blood glucose) and BNC2 is correlated with eye and kidney complications.  This study is a first for suggesting that there may be a genetic contribution to the individual’s ability to control blood glucose levels.  The Hospital for Sick Children’s Dr. Andrew Paterson led the study, which appears in the journal Diabetes.

Porky Pig to the Rescue: Scientists revealed a significant advantage to transplanting porcine pancreatic islet cells as a therapeutic for diabetes.  In contrast to using human islet cells, porcine derived cells do not result in the formation of islet amyloids, which allows them to continue functioning properly for the long term.  They attribute this porcine advantage to differences in the sequences of islet amyloid polypeptide (IAPP).  Dr. Bruce Verchere’s team at the University of British Columbia describes their work in the Proceedings of the National Academy of Sciences.

In (un)related news, Guelph University’s genetically engineered pigs or “Enviropigs” were given the OK by Environment Canada as being non-toxic to the environment.  Now they await Health Canada’s nod before they appear in your local supermarket.

Stem Cells Don’t Mind DNA Damage: Canadian scientists have discovered that stem cells intentionally damage their own DNA in order to regulate development… continue reading the rest of the story here at the Stem Cell Network Blog.

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Friday Science Review: January 8, 2010

I am starting the new year and decade by recognizing the accomplishments of two distinguished scientists…

Two outstanding Canadian scientists were recognized for their valuable contributions to the global research community.

Dr. Andras Nagy’s innovative technique to reprogram mature body cells into stem cells – called induced pluripotent stem cells or iPS cells – was named Method of the Year by the prestigious journal Nature Methods.  Earlier in the year, Dr. Nagy was selected as one of Scientific American magazine’s top 10 – Guiding Science for Humanity.

Dr. Tony Pawson was honoured as one of ten “Nation Builders of the Decade” by the Globe and Mail.  His breakthrough research over the past decade and beyond has propelled our understanding of the intricate communication that goes on within a cell and between cells.  Dr. Pawson was also awarded the Kyoto Prize this year.

Bypassing PTEN Mutants in Cancer Cells: The discovery of a novel link between the proteins PTEN and PKR may lead to new approaches forncer treatments.  Dr. Antonis Koromilas’ research at McGill University identified that the tumour suppressor function of PTEN requires it to activate the PKR-eIF2alpha pathway, which applies an inhibitory control on protein synthesis.  In a cancer cell where PTEN is mutated, PKR also loses its ability to control protein synthesis and the cell continues growing into a tumour.  The significance of this is that they can now try to bypass the PTEN mutation and find alternate ways to activate PKR and regain control of cell growth.  The research is reported in the journal Science Signaling.

Distinguishing Sister Chromatids: In studying cell division, scientists have long desired to follow the fate of sister chromatids – the identical chromosome copies that is distributed to each cell during the process of cell division.  Researchers used the CO-FISH (chromosome orientation fluorescence in situ hybridization) technique with unidirectional probes.  When they observed the process in different cell types, they found that the chromatids segregated randomly in some cell types but not in others.  The non-randomness may be a mechanism to direct cells to be slightly different from its sister cell and is one of many layers of complexity in developing higher organisms.  The solution to this biological phenomenon by Dr. Peter Lansdorp at the BC Cancer Agency deserves the recognition in the prestigious journal Nature.

Prognostic Marker for Bone Cancer Survival: Genetic deletion mutations in a specific chromosome region called osteo3q13.31 may be predictive of a poor prognosis for osteosarcoma patients.  The copy number alteration (CNA) marker was identified in subsets (80%) of osteosarcoma patients where their bone cancers appeared to be more difficult to treat.  With this genetic marker, patients may be screened to identify candidates who should be treated more aggressively from the onset of diagnosis.  Furthermore, the osteo3q13.31 region contains 3 genes that were not previously associated with the disease and requires further investigation that may lead to additional therapeutic options.  The study was conducted by Dr. David Malkin’s team at The Hospital for Sick Children and is published in Cancer Research.

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Friday Science Review: December 4, 2009

Universal Cancer Signalling Pathway: This is an interesting new twist on cancer signalling that may make scientists rethink how to tackle the disease.  It is thought that there is no single cure for cancer as the hetergenous disease may arise from mutations in a number of different pathways.  In this report, however, researchers demonstrate that many of the cancers converge on HIF-2a, part of the oxygen-sensing system that is required for tumours to grow.  By inhibiting HIF-2a, they could attenuate the growth of a diverse number of aggressive cancers including glioblastomas, colorectal tumours, and non-small cell lung carcinomas.  This universal cancer axis converging on HIF-2a could turn out to be a silver-bullet for cancer therapy.   Dr. Stephen Lee at the University of Ottawa led the team and describes the research in the online edition of the Proceedings of the National Academy of Sciences.

SKP’ing Stem Cells: A special type of cell called SKPs (skin-derived precursors) may be the elusive adult dermal stem cell involved in regenerating skin, wound-healing, and keeping hair healthy and growing.  In the study, researchers characterized the specialized population of cells and determined that SKPs can self-renew, maintain their ability to transform into other cells types, and regenerate hair follicles or other dermal cell types when grafted.  These properties are suggestive that SKPs are indeed THE dermal stem cells and may have important future applications such as in hair restoration and wound-healing.  Dr. Jeffrey Biernaskie completed the research in the lab of Dr. Freda Miller at Sickkids Hospital and recently started his own group at the University of Calgary.  The report appears in this latest edition of Cell Stem Cell.

Comparative Genomics Links Autism and Schizophrenia: A new study comparing the genomes of autistic patients and schizophrenic patients proved the connection between the two disorders that were previously thought to share behavioural similarities.  Both illnesses are associated with anomalies in the same region of the genome but differ substantially in the nature of the genetic changes.  Part of the genomic region is missing in autistic patients whereas extra copies of the genome are present in schizophrenic patients.  The affected genes appear to control head size and brain growth with overdevelopment of the brain in autistic patients and underdevelopment in schizophrenics.  By knowing that the two disorders are genetically linked, research on one disorder immediately provides clues for the other and will aid in advancing treatment options for both.  The study was conducted by Dr. Bernard Crespi’s group at Simon Fraser University and is reported in the Proceedings of the National Academy of Sciences.

Signalling Links in Neurological Disorders: Perturbations in either Dopamine or BDNF (brain-derived nerutrophic factor) pathways are implicated in neurological disorders.  Researchers have now defined the molecular relationship linking the two pathways to similar disorders.  The calcium signalling cascade is the key intermediate between dopamine receptor activation and BDNF production leading to neuronal growth.  With this new understanding of the pathways associated with schizophrenia, depression, and drug addiction, additional molecular targets are available for potential therapeutic intervention.  The study was led by Dr. Susan George at the Centre for Addiction and Mental Health (Toronto) and is reported in the early online edition of the Proceedings of the National Academy of Sciences.

Small Molecule Pathway Database: SMPDB (www.smpdb.ca) is an interactive, visual database containing more than 350 small-molecule pathways found in humans.  It is designed to support drug discovery research and pathway elucidation by employing clinical metabolomics, transcriptomics, proteomics and systems biology information.  The pathways describe relevant organs, organelles, subcellular compartments, protein cofactors, protein locations, metabolite locations, chemical structures and protein quaternary structures.  SMPBP is a very useful tool that was put together by Dr. David Wishart’s group at the University of Alberta and is described in detail in Nucleic Acids Research.

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Friday (the 13th) Science Review: November 13, 2009

No bad luck here in unraveling new genetic and proteomic links in disease…

Gene Variants Linked to Hearing LossA genetic link to hearing loss in children who are being treated with the chemotherapy drug, cisplatin, has been identified.  Cisplatin is a widely used anti-cancer drug but one of the harmful side effects is hearing loss experienced by over 60% of young cancer patients.  In the study by Dr. Michael Hayden’s team (Child & Family Research Institute, Vancouver), they analyzed 220 drug metabolism genes and found variants in two particular genes that are associated to hearing loss in children – one gene is called TPMT (thiopurine methyltransferase) and the other is COMT (catechol-O-methyltransferase).  With this information, doctors can perform genetic tests to determine the patient’s susceptibility to developing hearing loss and seek alternative treatment if necessary.  Further studies investigating how these enzymes contribute to cisplatin-induced hearing loss could lead to drugs to counteract these effects while receiving the benefits of cisplatin therapy.  The study appears in this week’s Nature Genetics.

The Missing Links in 5q- Syndrome: In patients with 5q- syndrome, a portion of chromosome 5 is deleted and the result is abnormal function of bone marrow cells leading to severe anemia.  We now know what is missing in this region of chromosome 5 that have key roles in maintaining the integrity of bone marrow cells.  In the investigation reported in Nature Medicine, Dr. Aly Karsan at the University of British Columbia and BC Cancer Agency discovered that two microRNAs (miRNAs), miR-145 and miR-146a, are lost in 5q- syndrome. MicroRNAs are short, single-stranded RNA that act to down regulate expression of specific target genes.  The targets of miR-145 and miR-146a are two proteins called TIRAP and TRAF6, which play important roles in immune signalling but should be turned off in hematopoietic stem/progenitor cells during blood cell development.  In support of their hypothesis, the researchers demonstrated in mice that forced expression of TRAF6 results in a condition that is similar to human 5q- syndrome.

Cancer Genes Now Linked: Researchers at Queen’s University studying C. elegans worms identified a connection between two genes involved in cancer.  PTEN is a tumour suppressor and loss of function mutations are known to be involved in a number of cancers.  Eph receptor signalling is required in developmental pathways and its expression level is elevated in some cancers.  New evidence now connects PTEN and Eph receptors in development and cancer.  The research led by Dr. Ian Chin-Sang’s team demonstrated an inverse relationship where Eph receptors can phosphorylate and downregulate PTEN.  Conversely, PTEN activity can modulate Eph receptor signaling.  If there is an imbalance in this relationship, then the (negative) effects may be amplified quickly.  The study report appears in the current issue of Developmental Cell.

Determining Thryoid Hormone Receptor Complexes in Yeast: This is a neat genetic array assay using yeast as a simple model system to unravel co-regulators in thyroid hormone receptor (TR) activity.  A yeast strain expressing TR was systematically crossed with each of 384 yeast strains bearing deletions of known genes.  From this unbiased assay, researchers identified four genes that are deemed essential for thyroid hormone function and are also conserved in humans.  Dr. Paul Walfish (Toronto Mount Sinai Hospital) and his team focused on one of these genes, CCR4.  They validated its role in thyroid hormone receptor action by performing a series of CCR4 expression and deletion analyses in cultured human cells and proved its association with TR in response to thyroid hormone.  Details of their findings appear in the early online edition of The Proceedings of the National Academy of Sciences.

FGFR3 Phosphorylation Network in Disease: An emerging field in proteomic studies is large-scale phospho-proteomic analyses using mass spectrometry to map signalling pathways.  This technique was applied to define the FGFR3 phosphorylation network in multiple myeloma and other cancers.  The researchers also demonstrated in their work the ability to quantitatively detect the upregulation or downregulation of over 60 phosphorylation sites on proteins that either responded to growth factor stimulation or inhibition by the pharmacologic drug PD173074.  One could apply this general method for pharmacodynamic monitoring of any drug inhibitor to fully understand its implications in the cell.  Dr. Michael Moran’s research team at the Hospital for Sick Children and University of Toronto published their report in this week’s Proceedings of the National Academy of Sciences.

Friday Science Review: November 6, 2009

Just two stories this week – a cancer pathway and innovative dipsticks…

New Relationship between Tumour Suppressor Genes: Knocking out genes in mice believed to play a tumour inhibiting role would intuitively result in rapid cancer development.  However, it was a surprise to McGill researchers that mice lacking the tumour suppressors 4E-BP1 and 4E-BP2 were refractory to cancer growth.  When they deleted another well known tumour suppressor, p53, then they observed enhanced tumour growth more aggressive than knocking out p53 alone.  These results demonstrate for the first time a cooperative effect between 4E-BPs and p53 and highlight the advantages of indentifying individual molecular profiles to predict responsiveness to therapeutic strategies.  Dr. Nahum Sonenberg, who led the research team at McGill University remarks “this is another fine example how basic research, which intends to provide answers to fundamental questions about molecular mechanisms of cell proliferation, leads to unexpected findings that advance our ability to understand and cure human disease.”  The study appears in this week’s issue of Cancer Cell.

Bioactive Paper Sensors: A simple and rapid method to detect pesticides or toxins in food using innovative test strips was recently developed at McMaster University.  These “dipsticks” can sense the presence of small amounts of pesticides in food and within five minutes, a colour change indicates the level of the contaminant.  Future applications of this technology, with a few tweaks,  include detecting for the presence of food borne bacteria such as E.coli, Listeria, or Salmonella.  The practicality, ease of use without the need for large equipment, and the ability to get almost immediate results are huge advantages of the dipsticks to provide rapid screening and could play a role in curbing future outbreaks.  Dr. John Brennan’s team describes their research in the latest issue of Analytical Chemistry.

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Friday Science Review: August 28, 2009

A Montreal flavour this week…

Critical link between EGFR and Src oncogenes: On the heels of last week’s Friday Science Review post on Stat3 in breast cancer, Dr. William Muller’s research team at McGill University has published another significant find linking well known oncogenes, Src and EGFR/ErbB2.  Among their results, they demonstrated how Src can interact with some mutant EGFR receptors (identified in lung cancers) but not with wild type EGFR.  When a Src inhibitor was applied to cells expressing mutant EGFR, it attenuated the cancer-inducing potential of these EGFR mutants.  This suggests that Src is an important enzyme in the EGFR mutant signaling pathway and may present an alternate pathway to combat cancer cell resistance to EGFR inhibitors.

Details of this study are described in this week’s Molecular and Cellular Biology.

MET oncogene in breast cancer: Next door to the Muller Lab at the new Goodman Cancer Centre in Montreal is Dr. Morag Park and her research team who recently generated a mouse model to mimic and study the Met oncogene in breast cancer.  The results were a complex cancer phenotype where gene expression and histological profiles demonstrated similarities to aggressive human breast cancers expressing Met.  Whereas prior to their study, Met was only correlated with poor outcome in breast cancer patients, this mouse model provides the specific link and identifies clinical cases where anti-Met therapy may be beneficial.

You can read more about it here in Proceedings of the National Academy of Sciences.

Key proteins in Natural Killer Cells: Also this week, Dr. André Veillette’s lab at the Institut de recherches cliniques de Montréal (IRCM) generated new insight into how Natural Killer Cells combat cancers of the blood, such as leukemias and lymphomas, or virus-infected blood cells.  As part of our immune system, the defense function of Natural Killer Cells requires three small proteins named SAP, EAT-2 and ERT that are unique to immune cells.  The proteins relay information from the cell surface SLAM family receptors to direct immune activities.  These data may eventually lead to pharmacological methods to increase the activity of Natural Killer Cells in destroying blood cancer cells or virus-infected cells.

Veillette’s lab generated knock-out mice missing all three proteins, which led to their findings, which are published in the latest edition of Nature Immunology.

p53 is regulated by JNK: p53 is a tumor suppressor protein that plays an important role in regulating cell growth and survival.  Its critical functions in the cell require p53 to be highly regulated through multiple layers of control, both to turn on and to turn off the protein’s activities.  One such method recently described in Proceedings of the National Academy of Sciences is through phosphorylation by the enzyme JNK.  This phosphorylation protects p53 from being targeted for destruction, thereby allowing p53 complexes to form and continue with their gene activating activities.

This research project was a collaboration between the Burnam Institute in San Diego and Dr. Katherine Borden’s team at the Université de Montréal.

Jurassic Park (for real?): Can you convert a chicken embryo to develop into a dinosaur?  No, this is not the makings of a movie but the idea of paleontologist Hans Larsson of McGill University who is proposing to try to make it work.  The theory is that by manipulating or swapping certain “switch” genes during the chicken embryo’s development, he can reproduce some features of a dinosaur.  He does not actually intend to hatch live prehistoric animals – for obvious reasons:

“It’s a demonstration of evolution,” said Larsson, who has studied bird evolution for the last 10 years.

“If I can demonstrate clearly that the potential for dinosaur anatomical development exists in birds, then it again proves that birds are direct descendants of dinosaurs.”

“We’re not going to hatch a T. rex or something,” Larsson chuckles.

The idea came to him after meeting Jack Horner, author of the book “How to Build A Dinosaur” and the technical advisor behind the Hollywood version of Jurassic Park.

Come back to the Friday Science Review (perhaps in a few years) for an update on the “chickensaurus” experiment…

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Trends Update — Personalized Medicine: DxS’ Latest Companion Diagnostics Deal

B&W_DNA_sequenceAs personalized medicine inches toward becoming the standard of care for cancer, the question of who pays for the genotyping becomes more important.  A deal announced Friday between DxS, a molecular diagnostics company, and Boehringer Ingelheim suggests that pharma companies will end up footing at least part of the bill by paying for the development (and marketing?) of companion diagnostics.

As noted by IVB in their Deals of the Week this week, the Boehringer Ingelheim deal is only one of several that DxS has done recently:

Last December, DxS signed a US-centered deal with Amgen to provide a companion diagnostic for the Big Biotech’s colorectal therapeutic Vectibix. The test maker’s so-called TheraScreen K-RAS test is already on the market in the EU and is used to help doctors determine which patients are unlikely to respond well to anti-EGFR therapies such as Bristol-Myers Squibb/ImClone’s Erbitux (cetuximab) and Amgen’s Vectibix. Moreover, DxS and Amgen have collaborated since last year on selling TheraScreen K-RAS alongside Vectibix in Europe, where the drug is cleared for patients with refractory metastatic colorectal cancer in which there is no K-RAS mutation.

Also notable: this statement in the press release attributed to Dr. Manfred Haehl, Corporate Senior Vice President Medicine of Boehringer Ingelheim…

As this year’s theme at ASCO highlights, it is very likely that personalised medicine will play an important role in selecting the most effective treatment for patients with cancer.

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Friday Science Review: January 23, 2009

Interesting science developments in and from Canada this week:

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