to gather intelligence from Canadians detained overseas

20th Sunday, 2013  |   Uncategorized  |  no comments

spy service and Global Affairs made the sharing deal this year through the Security of Canada Information Sharing Act part of the omnibus security legislation known as C 51, says a secret May memo to Goodale from CSIS director Michel Coulombe.

The provisions, ushered in by the previous Conservative government, expanded the exchange of federally held information about activity that the security of Canada. collected by (Global Affairs Canada) through the provision of consular services can be directly relevant to investigations of threats to the security of Canada, says the heavily censored CSIS memo, obtained by The Canadian Press under the Access to Information Act.

However, it is often difficult for consular officials to determine when a detained Canadian has been tortured and what impact that has on the information they may be sharing,pandora rings uk said Alex Neve, secretary general of Amnesty International Canada.

That became glaringly evident in the case of Maher Arar, an Ottawa communications engineer who made false confessions of terrorist involvement while being tortured by his captors in a Syrian prison, Neve noted.

In general, the new arrangement seems based on an understanding that information obtained by consular officers while working with or interviewing Canadians detained abroad and will be shared with CSIS when relevant to national security, Neve said.

gives rise to very obvious concerns about the privacy rights of individuals receiving consular assistance. Dennis O who led a federal inquiry into the Arar case, recommended that consular officials clearly advise detainees in foreign countries of the circumstances under which information obtained from them may be shared with others outside the consular affairs bureau, before any such information is obtained.

Privacy commissioner Daniel Therrien warned last week the government hadn done enough to protect Canadians from exchanges under the Security of Canada Information Sharing Act.

In his annual report, Therrien said the law is broadly worded and leaves much discretion to agencies to define what sort of activities undermine security.

The sharing arrangement between CSIS and Global Affairs underscores the concerns raised by the privacy commissioner and reaffirms the NDP desire to see C 51 repealed, said Matthew Dube, the party public safety critic.

appropriate safeguards aren in place. Global Affairs Canada nor CSIS would discuss the sort of information the spy service hoped to obtain through the new sharing arrangement. http://www.pandoracharmuksale.com Both agencies say they carry out their duties in accordance with relevant legal and privacy obligations.

The C 51 provisions are intended to improve domestic information sharing for national security purposes while respecting the privacy rights of Canadians matter where they are, said Global Affairs spokeswoman Kristine Racicot.

Evolutionary theory of cancer overlooks genetic research

16th Wednesday, 2013  |   Cancer  |  no comments

SEA&SEA 1200HD

Author: Darren Saunders. Laboratory Head at Garvan Institute.  


It’s not difficult to see physics’ influence on biology. Erwin Schrödinger’s book What is Life?, for instance, is widely credited with providing a theoretical basis for the storage of genetic information.
James Watson cited it as inspiration for his work with Francis Crick and Rosalind Franklin deciphering the structure of DNA.
The DNA structure was solved using X-ray crystallography, a seminal technique pioneered by father and son physics Nobel laureates William and Lawrence Bragg.
In fact, walk into any modern biology lab and you’ll see researchers using instruments packed with lasers, precision optics, and radiation, and often talking to each other through Wi-Fi – all the fruits of physics.
So, in some ways, it’s a little surprising that more biologists haven’t taken notice of the Davies-Lineweaver theory.
It was first published two years ago in a physics journal and has received widespread press coverage. But it is yet to receive much attention in biology or oncology and has only been cited a few times.
While the theory hasn’t been getting much attention formally, perhaps tellingly, it has received some stinging criticism. I suspect a common response of many biologists, such as PZ Myers, is “they’re physicists, they must know something about this we don’t”.
Something old, something new?

Davies and Lineweaver’s theory says cancer represents an evolutionary throwback or “atavism”. They suggest that cancer cells are under the control of an ancient genetic program linked to the earliest multicellular organisms, or metazoans.
Organisms such as sea sponges and jellyfish are probably the closest living examples of primitive metazoa.
The idea that cancer represents some kind of devolutionary state is not new. All the way back to Theodore Boveri early last century, researchers have recognised that tumour cells resemble those seen early in embryonic development.
And more recent molecular evidence tells us that many of the genetic pathways controlling early development are re-activated in tumours.
This line of thinking on the evolutionary basis of cancer has already driven the development of several classes of drugs aimed at remodelling the genetic program of cancer cells.
Indeed, the genomic revolution has given new life to our understanding of cancer’s evolution, with important insights into mechanisms of disease progression and drug resistance.
So, the most perplexing aspect of the Davies-Lineweaver theory is that it’s not particularly new. Indeed, it seems hauntingly reminiscent of the infamous example of a medical student “rediscovering” calculus.
Another limitation of the theory is the idea that early metazoa represent tumour-like growths. There’s simply no evidence for this premise.
Cancer cells are dysfunctional by definition, and we can see evidence of this at many levels. Early metazoa do not possess these “hallmarks” of a tumour.

Testing the waters
The basis of any scientific theory is to provide testable predictions based on evidence. And the atavism theory also falls short on this measure.
If cancers are running some kind of primitive genetic program, we should be able to see evidence of this program in both tumour cells and primitive metazoans. While we are drowning in a flood of information about tumour genomes, we don’t yet have much genomic data on early metazoa to compare against.
Indeed, testable predictions are pretty hard to find in the theory, but there has been a cheeky suggestion that an obvious one would be to take a tumour and drop it in the ocean.
If it really is a throw-back to some early metazoan life-form such as jellyfish or sea sponge, it should have no problem surviving.
Anyone who has ever spent time trying to keep tumour cells alive in a lab to study them will tell you it’s not that simple.

Not quite there yet
Many researchers probably still hold on to somewhat romantic notions of a universal basis for treating cancer, as hinted at by Davies and Lineweaver. But the avalanche of genomic and functional evidence is taking us in the opposite direction.
Genomics is providing ever deeper insights into tumour biology, and the deeper we look, the more complicated the picture appears.
Each patient’s disease is different, and everyone responds differently to treatment. Cancer treatment is embracing this heterogeneity, with ever-more personalised treatments.
The contribution of physics to understanding and treatment of cancer is already immeasurable. As outsiders, Davies and Lineweaver have arrived very quickly at a theoretical understanding of cancer built on decades of research.
Davies even jokes that his main qualification for cancer research is that he is unencumbered by any prior knowledge of the subject. It brings Isaac Newton’s famous words about seeing further by standing on the shoulders of giants to mind.
If Davies and Lineweaver can fully exploit their unencumbered position and provide a truly disruptive insight into cancer, their next leap of logic could be worth watching out for. But the evidence will need to be extraordinary.
Source:

The Conversation 6 October 2013. http://theconversation.com/evolutionary-theory-of-cancer-overlooks-genetic-research-16837?utm_medium=email&utm_campaign=Latest+from+The+Conversation+for+16+October+2013&utm_content=

Latest+from+The+Conversation+for+16+October+2013+CID_c08edb6ef3a6d3f82c1432a2d0921cc4&utm_

source=campaign_monitor&utm_term=Evolutionary%20theory%20of%20cancer%20overlooks%20genetic%20research

An astrobiological view of cancer’s evolutionary origin

16th Wednesday, 2013  |   Cancer  |  no comments

yvpn6g2y-1355355723 Author: Charley Lineweaver. Researcher at Research School of Astronomy and Astrophysics at Australian National University. Sponges and hydra, which are made of colonies of cells with a small number of cell types, have some similarities with cancer. Biodiversity Heritage Library Life originated on Earth about four billion years ago. Death, sex and multicellularity came along about a billion years later. According to our new atavistic model, cancer came with multicellularity. About ten years ago, Paul Davies and I, who had both trained as astrophysicists, became interested in astrobiology and the question “Are we alone?”. Astrobiologists study the big picture of the evolution of life. We study macro-evolution on time scales of billions of years. The origin of multicellularity in terrestrial life is one of the important things we need to know about if we want to make guesstimates about multicellular life forms on other planets. We studied the evolution of the cellular differentiation that led to the different organs in a multicellular body. As new students of cancer, we were taught that cancer is a genetic disease of multicellular life forms. Cancer is predominantly a disease of old age in which the body’s cells de-differentiate and proliferate without regulation. It seemed natural to us that since cancer involves the reversal of the pathways of differentiation, it must depend on the suppression of the genes that evolved hundreds of millions years ago that led to cell differentiation. Using these observations, we developed a new model for the origin and evolution of cancer. The central concept of our model is that the complex adaptive behaviours of cancer don’t come from Darwinian evolution during the several decades in which cancer progresses inside a human body. Rather, these behaviours originate from the destruction of the relatively recently evolved genes that control cell propagation, and the reactivation of ancient genes that were in control a billion years ago – before the evolution of highly differentiated cell types in multicellular organisms. Our model conceptualises cancer as a genetic and physiological atavism, not as mysteriously resilient and adaptive rogue cells. Genomes have a complicated history, like a canvas that has been painted on over and over again with different scenes in each layer. When the top surface of this palimpsest gets old and cracks and peels off, you don’t get random mutations of colour – you get glimpses of the underlying scenes that were painted years earlier. Those underlying scenes are the ancient genes that used to rule the roost. And those ancient scenes don’t contain the genes to regulate cell proliferation. So cells can proliferate without knowing where they are in the body, and cancer emerges. Our model gives hope to cancer researchers because it predicts that the number of adaptive behaviours available to cancer is not open-ended. If cancer evolved like bacteria or viruses, by passing on genetic variations to an uninterrupted line of descendants, then its evolution would be open-ended like the evolution of bacteria becoming increasingly resistant to antibiotics. But cancer dies with its victim. And subsequent cases of cancer know nothing about previous cases. As a result, the strategies and weapons cancer uses to stay alive are ancient and limited in variety. As we do more genetic profiling of cancer progression, our model predicts that we will find a limited number of patterns of gene expression. Understanding the genetic patterns of cancer progression is the key to managing cancer most efficiently. We could potentially overcome cancer if its progression were predictable, just as a battle can be more easily won if an enemy is predictable. There’s a strong body of evidence to support our theory, including cancer’s many abilities that can’t be explained by only a few decades of trial-and-error evolution inside an ageing body. These abilities have to have evolved. To accurately de-differentiate and still remain viable, as cancer cells do, requires a degree of navigation through an adaptive landscape that has to be regulated by genes that know their way around. The first animals to evolve (think sponges and hydra) were made of colonies of cells with a small number of cell types. These have some similarities with cancer. Cancer is a genetic disease of cells of our own body. As the differences between cancer genomes and normal genomes emerge from the mutational noise, our model predicts that the “driver” genes of cancer will be found to be old friends who helped us become multicellular creatures more than a billion years ago. Our new cancer model shines evolutionary light on cancer’s origin and gives cancer researchers reasons for optimism. Source: The Conversation 18 December 2012. http://theconversation.com/an-astrobiological-view-of-cancers-evolutionary-origin-1334

Immunobiology and conflicting roles of the human NKG2D lymphocyte receptor and its ligands in cancer

8th Tuesday, 2013  |   Others  |  no comments

nri1995-f3

El-Gazzar A, GrohV, Spies T.  Journal of Immunology, 2013;191(4):1509-1515. 

Cancers adopt diverse strategies to safeguard their survival, which often involve blinding or incapacitating the immune response, thereby gaining battleground advantage against the host. In immune responses against cancer, an important stimulatory lymphocyte receptor is NKG2D because the tumor-associated expression of its ligands promotes destruction of malignant cells. However, with advanced human cancers profound changes unfold wherein NKG2D and its ligands are targeted or exploited for immune evasion and suppression. This negative imprinting on the immune system may be accompanied by another functional state wherein cancer cells co-opt expression of NKG2D to complement the presence of its ligands for self-stimulation of tumor growth and presumably malignant progression. 


This review emphasizes these conflicting functional dynamics at the immunity-cancer biology interface in humans, within an overview of the immunobiology of NKG2D and mechanisms underlying the regulation of its ligands in cancer, with reference to instructive clinical observations and translational approaches.

Paeonol, a major compound of moutan cortex, attenuates cisplatin-induced nephrotoxicity in mice

27th Friday, 2013  |   Herb or Compound  |  no comments

Lee Hj, Lee Gy, Kim Hs, Bae Hs. Evidence-Based Complementary and Alternative Medicine. Volume 2013 (2013), http://dx.doi.org/10.1155/2013/310989


PastedGraphic-3


Cisplatin is an effective chemotherapeutic agent that is used for the treatment of a variety of cancers; however, its nephrotoxicity limits the use of this drug. In the present study, we examined whether paeonol, a major compound of Moutan Cortex, has protective effects on cisplatin-induced acute renal failure in mice. 


To accomplish this, Balb/c mice (6 to 8?wk of age, weighing 20 to 25?g) were administered, Moutan Cortex (300?mg/kg) or paeonol (20?mg/kg) once a day. 


At day 4, mice received cisplatin (30, 20, or 10?mg/kg) intraperitoneally. The paeonol-treated group showed marked attenuation of serum creatine and blood urea nitrogen levels as well as reduced levels of proinflammatory cytokines and nitric oxide when compared to the control group. In addition, the paeonol-treated group showed prolonged survival and marked attenuation of renal tissue injury. 

Taken together, these results demonstrated that paeonol can prevent the renal toxic effects of cisplatin.

Moutan Cortex, the root bark of Paeonia suffruticosa Andrews, has been used extensively as a traditional medicine for treatment of various diseases such as atherosclerosis, infection, and inflammation. Previous studies have revealed that the extracts of Moutan Cortex can inhibit nitric oxide and TNF-? in activated mouse peritoneal macrophages (Chung et al, 2007). 

A variety of compounds including paeonoside, paeonolide, apiopaeonoside, paeoniflorin, oxypaeoniflorin, benzoyloxypaeoniflorin, benzoylpaeoniflorin, paeonol, and sugars have been identified in Moutan Cortex (Chen et al, 2006). Paeonol, a major phenolic component of Moutan Cortex, has various biological activities such as antiaggregatory, antioxidant, anxiolytic-like, and anti-inflammatory functions (Ishiguro et al, 2006). In this study, paeonol treatment significantly reduced the elevated levels of serum creatinine and BUN. 

In addition, the role of proinflammatory cytokines in cisplatin-induced acute renal failure has been well documented (Faubel et al, 2007; Ramesh & Reeves, 2002), and elevation of the proinflammatory cytokines TNF-? and IL-1? as well as that of IL-6 has been demonstrated in humans with acute renal failure (Simmons et al, 2004). 

References
Chen G, L. Zhang, and Y. Zhu, “Determination of glycosides and sugars in moutan cortex by capillary electrophoresis with electrochemical detection,” Journal of Pharmaceutical and Biomedical Analysis, vol. 41, no. 1, pp. 129–134, 2006.
Chung HS, M. Kang, C. Cho et al., “Inhibition of nitric oxide and tumor necrosis factor-alpha by moutan cortex in activated mouse peritoneal macrophages,” Biological and Pharmaceutical Bulletin, vol. 30, no. 5, pp. 912–916, 2007.
Faubel F, E. C. Lewis, L. Reznikov et al., “Cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin (IL)-1?, IL-18, IL-6, and neutrophil infiltration in the kidney,” Journal of Pharmacology and Experimental Therapeutics, vol. 322, no. 1, pp. 8–15, 2007.
Ishiguro K, T. Ando, O. Maeda et al., “Paeonol attenuates TNBS-induced colitis by inhibiting NF-?B and STAT1 transactivation,” Toxicology and Applied Pharmacology, vol. 217, no. 1, pp. 35–42, 2006.
Ramesh G and W. B. Reeves, “TNF-? mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity,” Journal of Clinical Investigation, vol. 110, no. 6, pp. 835–842, 2002.
Simmons EM, J. Himmelfarb, M. T. Sezer et al., “Plasma cytokine levels predict mortality in patients with acute renal failure,” Kidney International, vol. 65, no. 4, pp. 1357–1365, 2004.