Omics! Omics!: NGS Saves A Young Life

Omics! Omics!: NGS Saves A Young Life: One of the most electrifying talks at AGBT this year was given by Joe DeRisi of UCSF, who gave a brief intro on the difficulty of diagnosin...

Particle beam cancer therapy: The promise and challenges

http://www.sciencedaily.com/releases/2014/03/140303143251.htm

For some patients with advanced breast cancer, chemo may be enough and they can be spared from the ordeal of going through surgery and radiation

It’s not been much time when Angelina Jolie initiated a “to go for or not to go for mastectomy” debate after being found with mutation in one of those ‘breast cancer risk prone gene BRCA1’. Well before you decide to go under a knife of surgeon, this could be a worth considering study that just came up from a very experienced physician based in India, which you want to discuss with your team of doctors.  

In a very prestigious AACR meeting currently ongoing in San Antonio, namely “2013 San Antonio Breast Cancer Symposium, held Dec. 10–14” Dr. Rajendra Badwe from Tata Memorial Hospital, Mumbai, India raised many eyebrows when he presented his findings in which he and his team led a study of 350 women with widely spread breast cancers that had shrunk after initial chemotherapy. Almost 50% of these patients went through mastectomy (surgery to remove the breast or the lump plus any cancerous lymph nodes). Rest of them did not have surgery. After about two years, 40 % of both groups were alive, suggesting that just chemotherapy could be enough. Women diagnosed with advanced breast cancer who respond well to chemotherapy get no additional benefit from having surgery and radiation afterwards. However, Dr. Rajendra Badwe, went on saying that options for surgery and radiation can be reserved for patients who need it for palliative reasons.

http://www.aacr.org/home/public--media/aacr-press-releases.aspx?d=3236&utm_source=twitter&utm_medium=tweet&utm_content=newsrelease&utm_campaign=2013sabcs

Targeting a specific area of the body for surgery or radiation is called loco-regional treatment, or LRT. Conventional wisdom has been that women with advanced (Stage 4) breast cancer, in which the disease has metastasized (spread to other organs), are treated only with chemotherapy unless other health issues (among them the relief of pain or other symptoms; the prevention of bone fractures; the tumor causing an open wound) dictate otherwise. In last decade, however, research community divided on into two school of thought on whether or not to use other supplementary treatment modalities such as surgery and radiation so they realized severe need of trials to confirm their theories. To find which of the two treatment methods resulted in the best survival outcomes for patients, Badwe and his colleagues in India, conducted a prospective, randomized, controlled trial funded by Badwe's hospital and the Department of Atomic Energy Clinical Trial Center in India.

Between 2005 and 2013 the researchers enrolled 350 women with metastatic breast cancer whose tumor responded positively to six cycles of chemotherapy. One group of patients received LRT, while the other group did not receive LRT. Both groups were matched for age, tumor size and extent of the metastases, and hormone receptor and HER2 receptor status.

Patients in the LRT group had either a lumpectomy or mastectomy and surgical removal of lymph nodes, followed by radiation treatment. All patients whose breast cancers were hormone-related received standard hormone therapy, regardless of the group to which they had been assigned.While the cancer was well-controlled in women who underwent surgery, that didn't translate into a survival advantage over the women who did not have surgery, Badwe said.The researchers also found a 7 percent excess death rate in patients who received LRT. The finding was not statistically significant, they said, but it aligned with the previous such findings that suggest surgical removal of the primary tumor in patients with advanced breast cancer might trigger the metastases.

“From a clinical practice point of view, as a surgeon I might know when to operate,” Dr. Badwe said. “But most importantly, when not to operate is equally important. “We need to know what the tumor is sensitive to,” Badwe said. “That is of greater value than loco-regional treatment.”

The extra expense of surgery and radiation, and the impact of those treatments on a patient’s quality of life also contribute to the researchers’ position that LRT should be done only within the tenets of clinical trials, he said.

While given the genetic differences between various populations, findings from this study have to be analyzed in that perspective, however, these findings open the door for more research on this aspect and warrant for more efforts towards new targeted therapies. 

Silence please! New siRNA data provides powerful free tool for biomedical research community !

A great example of public-private scientific collaboration between the NIH’s National Center for Advancing Translational Sciences (NCATS) and Life Technologies Corporation, we all now have access to a plethora of   information about how turning off a gene in laboratory by small interfering RNAs (which in my opinion is one of the most powerful tool used in the first decade of 21st Century biomedical research),  one at a time, could help us figure out their exact functions and learn more about how our health is affected when those functions are disrupted. Here is what NIH Director Dr. Francis Collins has to say about this collaborative project outcomes: 

http://directorsblog.nih.gov/2013/12/11/sirnas-small-molecules-that-pack-a-big-punch/#more-2362 

Silence please! New siRNA data provides powerful free tool for biomedical research

Wonderful work by researchers from NIH’s National Center for Advancing Translational Sciences (NCATS) and Life Technologies Corporation, researchers...

http://directorsblog.nih.gov/2013/12/11/sirnas-small-molecules-that-pack-a-big-punch/#more-2362

Wow, Three Americans Win Joint Nobel Prize in Medicine.

Congratulations to Drs. James E. Rothman, Randy W. Schekman and Thomas C. Südhof!! 

• The 2013 Nobel Prize in Physiology or Medicine is awarded for discoveries of machinery regulating vesicle traffic, a major transport system in our cells.
• Through their discoveries, Rothman, Schekman and Südhof have revealed the exquisitely precise control system for the transport and delivery of cellular cargo.
• Disturbances in this transport system have deleterious effects and contribute to conditions such as neurological diseases, diabetes, and immunological disorders.

http://www.nobelprize.org/nobel_prizes/medicine/laureates/2013/press.html

http://www.npr.org/2013/10/07/230036563/2013-nobel-prize-in-medicine-awarded

Each Scientist's contribution in brief:

i)  Schekman discovered a set of genes that were required for vesicle traffic. 

ii) Rothman unraveled protein machinery that allows vesicles to fuse with their targets to permit transfer of cargo. 

iii) Südhof revealed how signals instruct vesicles to release their cargo with precision.

How important their work is could simply be understood by one example. We are well aware about Diabetes as a disease as it affects so many people on the earth, we also are aware that insulin is the key protein that gets defective in Diabetes.  However, most of us do not know how Insulin, which controls blood sugar levels, is made and released into the blood at the right place at the right time, and how it gets outside of the beta cells of the pancreas (in case of healthy people). Modern antidepressants only work because they prevent neurons from re-uptake of the neurotransmitter serotonin. But how was that serotonin released in the first place? Answer to such questions that deal with trafficking of biological molecules is studied in the field of "vascular trafficking" in cell biology.  This field is all about cellular structures called "vesicles". These bubble-like bags of cellular goodies are one common way that the cells gets things from the inside to the outside, sending off their chemical messages from a few micrometers away to a couple of meters. Some brain disorders such as Huntington's 

and Alzheimer's diseases have also been attributed at least in part to defects in the vesicle transport systems.

It is interesting to note that Randy Schekman, who is actually a St. Paul (Minnesota) native, a place currently I live and work, who has been at the University of California at Berkeley for 35 years, did most of his work using simple organism called yeast. It proves again that non-human model systems  have given us crucial insights to how  human bodies function in healthy state and diseases.

It is also interesting fact that 2 of 3 laureates were trained with previous Nobel laureates. Scheckman did his graduate work with legendary molecular biologist Arthur Kornberg (Physiology or Medicine 1959) while Südhof was a postdoctoral fellow with the cholesterol biology pioneers at the University of Texas Southwestern Medical School, Michael Brown and Joseph Goldstein (Physiology or Medicine 1985). So like teacher like disciple. 

Dr. Jeremy Berg, director of the Institute for Personalized Medicine at the University of Pittsburgh who for years also worked as director of the National Institute of General Medical Sciences, a part of the National Institutes of Health, aptly summarized the importance of the field pioneered by these laureates:-

"It's one of the prizes for which there is not a treatment that came out of it directly, but there are probably literally thousands of laboratories around the world whose work would not be taking place the way it is without their work," 

I do not need to mention that even my area of interest (cancer biology with emphasis to adhesion signaling and receptor tyrosine kinase signaling) could not have been as exciting and promising if there were no such pioneering work done by these scientists trio. 

Why Steve Jobs' Magic Doesn't Work In Medicine

A very beautiful article that explains why medicine does not work the way technology works.

http://www.forbes.com/sites/matthewherper/2011/10/31/why-steve-jobs-magic-doesnt-work-in-medicine/