Posts Tagged ‘cancer’

Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL

Friday, March 27th, 2015

RUNX1 is most connected in TLX1 & 3 expr. net. It’s a tumor suppressor disabled by LOF mutations.

Rev. engineering…identifies RUNX1 as tumor suppressor in T-ALL http://www.nature.com/nm/journal/v18/n3/full/nm.2610.html It’s the most connected TF in the expression network

Nat Med. Author manuscript; available in PMC 2012 Sep 1.
Nat Med. 2012 Feb 26; 18(3): 436–440.
Published online 2012 Feb 26. doi: 10.1038/nm.2610

Giusy Della Gatta,1 Teresa Palomero,1,2 Arianne Perez-Garcia,1 Alberto Ambesi-Impiombato,1 Mukesh Bansal,3Zachary W. Carpenter,1 Kim De Keersmaecker,4,5 Xavier Sole,6,7 Luyao Xu,1 Elisabeth Paietta,8,9 Janis Racevskis,8,9Peter H Wiernik,8,9 Jacob M Rowe,10 Jules P Meijerink,11 Andrea Califano,1,3 and Adolfo A. Ferrando1,2,12

The Trip Treatment – The New Yorker

Saturday, February 21st, 2015

Annals of Medicine
FEBRUARY 9, 2015 ISSUE
The Trip Treatment
Research into psychedelics, shut down for decades, is now yielding exciting results.
BY MICHAEL POLLAN

The Trip Treatment
http://www.newyorker.com/magazine/2015/02/09/trip-treatment A new idea to relieve cancer suffering & depression, revisiting #psychedelics banned for >40 years

QT:{{”

After the screening, Mettes was assigned to a therapist named Anthony Bossis, a bearded, bearish psychologist in his mid-fifties, with a specialty in palliative care. Bossis is a co-principal investigator for the N.Y.U. trial.

After four meetings with Bossis, Mettes was scheduled for two dosings—one of them an “active” placebo (in this case, a high dose of niacin, which can produce a tingling sensation), and the other a pill containing the psilocybin.

“I felt a little like an archeologist unearthing a completely buried body of knowledge,” he said. Beginning in the nineteen-fifties, psychedelics had been used to treat a wide variety of conditions, including alcoholism and end-of-life anxiety. The American Psychiatric Association held meetings centered on LSD. “Some of the best minds in psychiatry had seriously studied these compounds in therapeutic models, with government funding,” Ross said.

“I’m personally biased in favor of these type of studies,” Thomas R. Insel, the director of the National Institute of Mental Health (N.I.M.H.) and a neuroscientist, told me. “If it proves useful to people who are really suffering, we should look at it. Just because it is a psychedelic doesn’t disqualify it in our eyes.”

I was struck by how the descriptions of psychedelic journeys differed from the typical accounts of dreams. For one thing, most people’s recall of their journey is not just vivid but comprehensive, the narratives they reconstruct seamless and fully accessible, even years later.

This might help explain why so many cancer patients in the trials reported that their fear of death had lifted or at least abated: they had stared directly at death and come to know something about it, in a kind of dress rehearsal.

The default-mode network was first described in 2001, in a landmark paper by Marcus Raichle, a neurologist at Washington University, in St. Louis, and it has since become the focus of much discussion in neuroscience. The network comprises a critical and centrally situated hub of brain activity that links parts of the cerebral cortex to deeper, older structures in the brain, such as the limbic system and the hippocampus.

The network, which consumes a significant portion of the brain’s energy, appears to be most active when we are least engaged in attending to the world or to a task. It lights up when we are daydreaming, removed from sensory processing, and engaging in higher-level “meta-cognitive” processes such as self-reflection, mental time travel, rumination, and “theory of mind”—the ability to attribute mental states to others. Carhart-Harris describes the default-mode network variously as the brain’s “orchestra conductor” or “corporate executive” or “capital city,” charged with managing and “holding the entire system together.” It is thought to be the physical counterpart of the autobiographical self, or ego.

“The brain is a hierarchical system,” Carhart-Harris said. “The highest-level parts”—such as the default-mode network—“have an inhibitory influence on the lower-level parts, like emotion and memory.” He discovered that blood flow and electrical activity in the default-mode network dropped off precipitously under the influence of psychedelics, a finding that may help to explain the loss of the sense of self that volunteers reported….Just before Carhart-Harris published his results, in
a 2012 paper in Proceedings of the National Academy of Sciences, a researcher at Yale named Judson Brewer, who was using fMRI to study the brains of experienced meditators, noticed that their default-mode networks had also been quieted relative to those of novice meditators. It appears that, with the ego temporarily out of commission, the boundaries between self and world, subject and object, all dissolve. These are hallmarks of the mystical experience.


Carhart-Harris doesn’t romanticize psychedelics, and he has little patience for the sort of “magical thinking” and “metaphysics” they promote. In his view, the forms of consciousness that psychedelics unleash are regressions to a more “primitive style of cognition.” Following Freud, he says that the mystical experience—whatever its source—returns us to the psychological condition of the infant, who has yet to develop a sense of himself as a bounded individual. The pinnacle of human development is the achievement of the ego, which imposes order on the anarchy of a primitive mind buffeted by magical thinking. (The developmental psychologist Alison Gopnik has speculated that the way young children perceive the world has much in common with the psychedelic experience. As she puts it, “They’re basically tripping all the time.”) The psychoanalytic value of psychedelics, in his view, is that they allow us to bring the workings of the unconscious mind “into an observable space.”

In “The Doors of Perception,” Aldous Huxley concluded from his psychedelic experience that the conscious mind is less a window on reality than a furious editor of it. The mind is a “reducing valve,” he wrote, eliminating far more reality than it admits to our conscious awareness, lest we be overwhelmed. “What comes out at the other end is a measly trickle of the kind of consciousness which will help us to stay alive.” Psychedelics open the valve wide, removing the filter that hides much of reality, as well as dimensions of our own minds, from ordinary consciousness.
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Emerging landscape of oncogenic signatures across human cancers

Saturday, January 17th, 2015

Landscape of oncogenic signatures across human #cancers
http://www.nature.com/ng/journal/v45/n10/full/ng.2762.html Disjoint types dominated by copy number changes or mutations

pp1127 – 1133

Giovanni Ciriello, Martin L Miller, Bülent Arman Aksoy, Yasin Senbabaoglu, Nikolaus Schultz & Chris Sander

doi:10.1038/ng.2762

Chris Sander and colleagues have extracted significant functional events from 12 tumor types. Tumors can be classified as being driven largely by either mutation or copy number changes, and, within this division, subclasses of cross-tissue patterns of events are discerned that suggest sets of combinatorial therapies.

Variation in cancer risk among tissues can be explained by the number of stem cell divisions

Monday, January 12th, 2015

Tomasetti & Volgenstein

Science 2 January 2015:
Vol. 347 no. 6217 pp. 78-81
DOI: 10.1126/science.1260825

It’s a correlation between aggressiveness, mutations and cell division http://www.sciencemag.org/content/347/6217/78

Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types : Nature Genetics : Nature Publishing Group

Thursday, January 8th, 2015

Analysis of noncoding somatic mutations &…expression alterations http://www.nature.com/ng/journal/v46/n12/full/ng.3141.html 505 WGS variants w. RNAseq, #TCGA as of Mar ’14

all of what’s in TCGA as of spring ’14

505 TCGA WGS Somatic mutations, Expression Calls, CNA
via
https://www.synapse.org/#!Synapse:syn2882200

Orthogonal to PCAWG-607 (Alexandrov et al + 100 "public" stomach cancers)

Cereal killer: Are you eating too much iron? – health – 04 December 2014 – Test – New Scientist

Wednesday, December 31st, 2014

Cereal killer: Are you eating too much iron? http://www.newscientist.com/article/mg22429980.500-cereal-killer-are-you-eating-too-much-iron.html Too much from vitamins is potentially linked to heart disease, cancer &c

Can AIDS Be Cured? | The New Yorker

Wednesday, December 24th, 2014

Can #AIDS Be Cured? http://www.newyorker.com/magazine/2014/12/22/can-aids-cured Now a chronic disease, treatable w/ HAART cocktails? Parallels w/ cancer evolution & resistance

MEDICAL DISPATCH DECEMBER 22, 2014 ISSUE
CAN AIDS BE CURED?
Researchers get closer to outwitting a killer.
BY JEROME GROOPMAN

BMC Bioinformatics | Abstract | Sensitive detection of pathway perturbations in cancers

Tuesday, December 23rd, 2014

Sensitive detection of pathway perturbations in #cancers
http://www.biomedcentral.com/1471-2105/13/S3/S9/abstract Differential expression of #pathways (in toto or a sub-part)

** Sensitive detection of pathway perturbations in cancers. Rivera et al. BMC Bioinfo (2014)

In this paper, the authors introduce a new computational method that identifies subsets of pathways that exhibit differential gene expression between cancer and normal tissue. Some previous methods only considered differential expression in sets of genes without considering the structure of interactions between the genes or their protein products. Other previous methods looked at pathway
perturbations, but required all members of a pathway to exhibit differential gene expression in order for the pathway to appear significant. The authors demonstrate the general superiority of their method to these previous methods, as well as the robustness of their method to missing data. The authors also consider future enhancements, such as taking into account the direction of differential expression, using more information on the nature of each gene interaction involved, and using universal protein interaction networks to incorporate data beyond what is found in curated pathway databases.

interesting article

Monday, December 15th, 2014

Bioinformatics. Sep 15, 2013; 29(18): 2223–2230.
Published online Jul 9, 2013. doi: 10.1093/bioinformatics/btt375 PMCID: PMC3753564

A comparative analysis of algorithms for somatic SNV detection in cancer

Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer

Thursday, November 20th, 2014

Dataset of 100 freely available STAD T/N pairs

http://www.nature.com/ng/journal/v46/n6/full/ng.2983.html#affil-auth

Kai Wang,
Siu Tsan Yuen,
Jiangchun Xu,
Siu Po Lee,
Helen H N Yan,
Stephanie T Shi,
Hoi Cheong Siu,
Shibing Deng,
Kent Man Chu,
Simon Law,
Kok Hoe Chan,
Annie S Y Chan,
Wai Yin Tsui,
Siu Lun Ho,
Anthony K W Chan,
Jonathan L K Man,
Valentina Foglizzo,
Man Kin Ng,
April S Chan,
Yick Pang Ching,
Grace H W Cheng,
Tao Xie,
Julio Fernandez,
Vivian S W Li,
Hans Clevers,
Paul A Rejto,
Mao Mao
& Suet Yi Leung

Nature Genetics 46, 573–582 (2014) doi:10.1038/ng.2983Received 01 August 2013 Accepted 18 April 2014 Published online 11 May 2014