Posts Tagged ‘cancer’

ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma: Cancer Cell

May 22, 2015

ALK Mutations Confer Differential Oncogenic Activation
http://www.cell.com/cancer-cell/abstract/S1535-6108%2814%2900393-6 MD modeling better assessing #SNV impact than stats, ie sift

ALK Mutations Confer Differential Oncogenic Activation and Sensitivity to ALK Inhibition Therapy in Neuroblastoma

Scott C. Bresler
Daniel A. Weiser
Peter J. Huwe

Ravi Radhakrishnan
Mark A. Lemmon
Yaël P. Mossé

DOI: http://dx.doi.org/10.1016/j.ccell.2014.09.019

The evolutionary history of lethal metastatic prostate cancer : Nature : Nature Publishing Group

May 2, 2015

The evolutionary history of…metastatic prostate #cancer http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14347.html Unexpected: polyclonal "seeding" w/ much met-to-met spread

Transmissible Dog Cancer Genome Reveals the Origin and History of an Ancient Cell Lineage

May 2, 2015

Transmissible Dog #Cancer #Genome Reveals…History of…Cell Lineage http://www.sciencemag.org/content/343/6169/437.abstract 1.9M somatic mutations from origin ~11K yrs ago

Summarizing 4 conferences last week: AACR ’15, ISEV ’15, BioIT ’15 & ICEBEM 2015

April 28, 2015

AACR 2015
http://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=25#.VT8JXa1Viko https://linkstream2.gerstein.info/tag/i0pcawg15/

ISEV/ERCC Education Day – ISEV – International Society for
Extracellular Vesicles
http://www.isevmeeting.org/isevercc-education-day.html
https://linkstream2.gerstein.info/tag/i0isev/

2015 Bio-IT World Conference & Expo
http://www.bio-itworldexpo.com/
https://linkstream2.gerstein.info/tag/i0bioit15/
http://lectures.gersteinlab.org/summary/Progressive-summarization-large-scale-data-interpret-cancer–20150423-i0bioIT15/

8th International Conference on Ethics in Biology, Engineering & Medicine (ICEBEM 2015)
http://www.downstate.edu/orthopaedics/bioethics/
http://lectures.gersteinlab.org/summary/Soc-n-Tech-Soln-to-Privacy-in-Personal-Genomics–20150424-i0icebem15/

Tweets for all of them
https://storify.com/markgerstein/favorite-tweets-from-bioit-15-aacr-15-and-isev-15-16

“The Race” to Clone BRCA1

April 25, 2015

The Race to Clone #BRCA1 http://www.sciencemag.org/content/343/6178/1462.abstract
Lessons on #LOF mutations, synthetic lethality, silly gene names & the 2-hit hypothesis

synthetic lethality (PARP inhibitors), gene names (RING fingers)

Health: Make precision medicine work for cancer care

April 20, 2015

Make #precisionmedicine work for cancer http://www.nature.com/news/health-make-precision-medicine-work-for-cancer-care-1.17301 @MarkARubin1: >90% of…patients carry a mutation that may be drug-responsive

QT:{{"
“Hugely complicated genomic reports are rarely available in electronic form and are seldom tied to basic information about the patient. Whole-genome sequencing on tumour samples from nearly 14,000 people by the International Cancer Genome Consortium (ICGC), for instance, has revealed nearly 13 million mutations across the genome.


Since 2013, working with a team of computational biologists from Weill Cornell and the Centre for Integrative Biology at the University of Trento in Italy, my colleagues and I have conducted a pilot programme to determine the feasibility of tying genomic to clinical data in real time. So far, we have created easy-to-read reports for 250 people with cancer.

We have discovered that more than

"more than 90% of our patients carry a mutation that may be responsive to a known drug — although less than 10% of the patients may be eligible for a clinical trial either for logistical reasons or because there is insufficient evidence to warrant trying a non-approved drug.”
"}}

BRAF pseudogene and cancer development

April 17, 2015

BRAF #Pseudogene Functions as a Competitive Endogenous RNA; [Shows it] induces Lymphoma [after alteration, in mice]
http://www.cell.com/cell/abstract/S0092-8674(15)00244-5

Cell. 2015 Apr 9;161(2):319-32. doi: 10.1016/j.cell.2015.02.043. Epub 2015 Apr 2.

Karreth FA1, Reschke M1, Ruocco A1, Ng C1, Chapuy B2, Léopold V1, Sjoberg M3, Keane TM3, Verma A4, Ala U1, Tay Y1, Wu D5, Seitzer N1, Velasco-Herrera Mdel C3, Bothmer A1, Fung J1, Langellotto F6, Rodig SJ7, Elemento O4, Shipp MA2, Adams DJ3, Chiarle R8, Pandolfi PP9.

Abstract
Research over the past decade has suggested important roles for pseudogenes in physiology and disease. In vitro experiments
demonstrated that pseudogenes contribute….

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

March 27, 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

February 21, 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.
“}}

Emerging landscape of oncogenic signatures across human cancers

January 17, 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.