Feeds:
Posts
Comments

Archive for the ‘Glycobiology: Biopharmaceutical Production, Pharmacodynamics and Pharmacokinetics’ Category


Glycobiology vs Proteomics: Glycobiologists Prespective in the effort to explain the origin, etiology and potential therapeutics for the Coronavirus Pandemic (COVID-19)

 Curator: Ofer Markman, PhD

 The sugars involved in a viral disease are unique in many ways when compared with the DNA/RNA or the proteins involved: they are almost totally dependent on the infected cells and thus are not affected by the viral mutation rate or by the virus at all. Nevertheless they are affected by the cells, their type and their sugar production mechanisms and in some respect to the production rate by which the virus is replicated in the infected cells. Mutations may have nevertheless major effect not on the structures of the glycans but rather on the existence of the glycosylation site, and thus the glycan at all, but not on its structures.

This may make the gycomolecule a good target for diagnostics as stability in the molecule may mean longer life shelve of diagnostics kits.

Unique sugars are already predicted/found in the virus from certain Chinese origin, in this case an o-linked glycan/s not previously detected.

  • The proximal origin of SARS-CoV-2

Kristian G. AndersenAndrew RambautW. Ian Lipkin, Edward C. Holmes & Robert F. Garry

Nature Medicine (2020)Cite this article

https://www.nature.com/articles/s41591-020-0820-9

  • The covid-19 coronavirus epidemic has a natural origin, scientists say

https://globalhealthnewswire.com/2020/03/17/the-covid-19-coronavirus-epidemic-has-a-natural-origin-scientists-say/

  • Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26

Naveen Vankadari & Jacqueline A. Wilce

https://www.tandfonline.com/doi/full/10.1080/22221751.2020.1739565

Nevertheless, if the virus can infect multiple cells once current cells are not going to be available for any reason those viruses may present other glycans.

Once one starts to treat the infected person via modulation of protein production or by other means the change in the dynamic of protein production vs. protein glycosylation may cause changes in protein glycosyation, including their structures, this is well known to biotechnologists producing glycoproteins in labs and production.

This may either be a problem in understanding the state of disease or an advantage as it may help following response to the treatment and help as a co-treatment diagnostics.

Early Studies include the following:

  • Carbohydrate-based Diagnostics: A New Approach to COVID-19 Testing?

Mar 19, 2020 | Original story from Iceni Diagnostics

https://www.technologynetworks.com/diagnostics/news/carbohydrate-based-diagnostics-a-new-approach-to-covid-19-testing-332313

Glycans may play a role in treatment as well. TAMIFLU a case in point. Tamiflu is directed to the flu enzyme Neuraminidaze that is part of the viral structures. This approach was also explored to develop treatments.

  • Pneumagen Ltd Leverages its Novel Glycan Approach to Target Coronavirus (COVID-19) Infections

March 17, 2020 PR-M03-20-NI-024

https://www.pharmasalmanac.com/articles/pneumagen-ltd-leverages-its-novel-glycan-approach-to-target-coronavirus-covid-19-infections

Glycans do not only effect their own involvement in treatment/diagnostics they also are effecting protein based diagnostics for this see statement by Dr. Michael Mercier of UAH

  • We’re dealing with COVID-19, but what’s a virus in the first place?

23-Mar-2020 8:45 AM EDT, by University of Alabama Huntsville

https://www.newswise.com/articles/we-re-dealing-with-covid-19-but-what-s-a-virus-in-the-first-place

 

Other related articles on this topic published on this topic in this Open Access Online Scientific Journal include the following: 

 

The Relevance of Glycans in the Viral Pathology of COVID-19

Reporter: Ofer Markman, PhD

https://pharmaceuticalintelligence.com/2020/03/23/glycans-in-the-viral-pathology-of-covid-19/

Read Full Post »


Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Obesity is a global concern that is associated with many chronic complications such as type 2 diabetes, insulin resistance (IR), cardiovascular diseases, and cancer. Growing evidence has implicated the digestive system, including its microbiota, gut-derived incretin hormones, and gut-associated lymphoid tissue in obesity and IR. During high fat diet (HFD) feeding and obesity, a significant shift occurs in the microbial populations within the gut, known as dysbiosis, which interacts with the intestinal immune system. Similar to other metabolic organs, including visceral adipose tissue (VAT) and liver, altered immune homeostasis has also been observed in the small and large intestines during obesity.

 

A link between the gut microbiota and the intestinal immune system is the immune-derived molecule immunoglobulin A (IgA). IgA is a B cell antibody primarily produced in dimeric form by plasma cells residing in the gut lamina propria (LP). Given the importance of IgA on intestinal–gut microbe immunoregulation, which is directly influenced by dietary changes, scientists hypothesized that IgA may be a key player in the pathogenesis of obesity and IR. Here, in this study it was demonstrate that IgA levels are reduced during obesity and the loss of IgA in mice worsens IR and increases intestinal permeability, microbiota encroachment, and downstream inflammation in metabolic tissues, including inside the VAT.

 

IgA deficiency alters the obese gut microbiota and its metabolic phenotype can be recapitulated into microbiota-depleted mice upon fecal matter transplantation. In addition, the researchers also demonstrated that commonly used therapies for diabetes such as metformin and bariatric surgery can alter cellular and stool IgA levels, respectively. These findings suggested a critical function for IgA in regulating metabolic disease and support the emerging role for intestinal immunity as an important modulator of systemic glucose metabolism.

 

Overall, the researchers demonstrated a critical role for IgA in regulating intestinal homeostasis, metabolic inflammation, and obesity-related IR. These findings identify intestinal IgA+ immune cells as mucosal mediators of whole-body glucose regulation in diet-induced metabolic disease. This research further emphasized the importance of the intestinal adaptive immune system and its interactions with the gut microbiota and innate immune system within the larger network of organs involved in the manifestation of metabolic disease.

 

Future investigation is required to determine the impact of IgA deficiency during obesity in humans and the role of metabolic disease in human populations with selective IgA deficiency, especially since human IgA deficiency is associated with an altered gut microbiota that cannot be fully compensated with IgM. However, the research identified IgA as a critical immunological molecule in the intestine that impacts systemic glucose homeostasis, and treatments targeting IgA-producing immune populations and SIgA may have therapeutic potential for metabolic disease.

 

References:

 

https://www.nature.com/articles/s41467-019-11370-y?elqTrackId=dc86e0c60f574542b033227afd0fdc8e

 

https://www.jci.org/articles/view/88879

 

https://www.nature.com/articles/nm.2353

 

https://diabetes.diabetesjournals.org/content/57/6/1470

 

https://www.sciencedirect.com/science/article/pii/S1550413115001047?via%3Dihub

 

https://www.sciencedirect.com/science/article/pii/S1550413115002326?via%3Dihub

 

https://www.sciencedirect.com/science/article/pii/S1931312814004636?via%3Dihub

 

https://www.nature.com/articles/nature15766

 

https://www.sciencedirect.com/science/article/pii/S1550413116000371?via%3Dihub

 

https://www.nature.com/articles/nm.2001

 

https://www.sciencedirect.com/science/article/abs/pii/S1550413118305047?via%3Dihub

 

Read Full Post »


Larry H Bernstein, MD, FCAP, Curator

https://pharmaceuticalintelligence.com/6/7/2014/Health benefit of anthocyanins from apples and berries noted for men

After significant studies have been completed, particularly on a relationship between anthocyanins consumption and decreasd risk of Parkinson’s Disease in men, it is unclear why a comparable effect is not seen in women.  This would lead one to ask questions about predominant time course of development in relationship to androgen activity.  Pre- and postmenopausal status would seem to make no difference. It is reported that the anthocyanins cross the blood brain barrier.  There are other questions that need to be raised.  There is a decline in the production of transthyretin by the choroid plexus in the elderly – not sex related – with an elevation of homocysteine that is reciprocal to decline in transthyretin-RBP complex, that is related to AD.  This is mediated by cystathionine-beta synthase, and involves matrix metalloproteinases.  A mechanism for Parkinson’s Disease has been postulated to be related to Parkin gene expression, but how does this work, and why do we see the sex assymetry?

Eating flavonoids protects men against Parkinson’s disease

General DietMissed – Medical Breakthroughs • Tags: AnthocyaninFlavonoidHarvard University,HealthNeurologyParkinsonParkinson DiseaseUniversity of East Anglia

http://healthresearchreport.me/       07 Apr 2012

Men who eat flavonoid-rich foods such as berries, tea, apples and red wine significantly reduce their risk of developing Parkinson’s disease, according to new research by Harvard University and the University of East Anglia (UEA).

Published today in the journal Neurology ®, the findings add to the growing body of evidence that regular consumption of some flavonoids can have a marked effect on human health. Recent studies have shown that these compounds can offer protection against a wide range of diseases including heart disease, hypertension, some cancers and dementia.

This latest study is the first study in humans to show that flavonoids can protect neurons against diseases of the brain such as Parkinson’s.

Around 130,000 men and women took part in the research. More than 800 had developed Parkinson’s disease within 20 years of follow-up. After a detailed analysis of their diets and adjusting for age and lifestyle, male participants who ate the most flavonoids were shown to be 40 per cent less likely to develop the disease than those who ate the least. No similar link was found for total flavonoid intake in women.

The research was led by Dr Xiang Gao of Harvard School of Public Health in collaboration with Prof Aedin Cassidy of the Department of Nutrition, Norwich Medical School at UEA.

“These exciting findings provide further confirmation that regular consumption of flavonoids can have potential health benefits,” said Prof Cassidy.

“This is the first study in humans to look at the associations between the range of flavonoids in the diet and the risk of developing Parkinson’s disease and our findings suggest that a sub-class of flavonoids called anthocyanins may have neuroprotective effects.”

Prof Gao said: “Interestingly, anthocyanins and berry fruits, which are rich in anthocyanins, seem to be associated with a lower risk of Parkinson’s disease in pooled analyses. Participants who consumed one or more portions of berry fruits each week were around 25 per cent less likely to develop Parkinson’s disease, relative to those who did not eat berry fruits. Given the other potential health effects of berry fruits, such as lowering risk of hypertension as reported in our previous studies, it is good to regularly add these fruits to your diet.”

Flavonoids are a group of naturally occurring, bioactive compunds found in many plant-based foods and drinks. In this study the main protective effect was from higher intake of anthocyanins, which are present in berries and other fruits and vegetables including aubergines, blackcurrants and blackberries. Those who consumed the most anthocyanins had a 24 per cent reduction in risk of developing Parkinson’s disease and strawberries and blueberries were the top two sources in the US diet.

The findings must now be confirmed by other large epidemiological studies and clinical trials.

Parkinson’s disease is a progresssive neurological condition affecting one in 500 people, which equates to 127,000 people in the UK. There are few effective drug therapies available.  Dr Kieran Breen, director of research at Parkinson’s UK said: “This study raises lots of interesting questions about how diet may influence our risk of Parkinson’s…   there are still a lot of questions to answer and much more research to do before we really know how important diet might be for people with Parkinson’s.”

 

Eating berries may lower risk of Parkinson’s

Missed – Medical Breakthroughs • Tags: BerryDoctor of PhilosophyFlavonoidParkinson,Parkinson DiseaseXiang Gao

http://healthresearchreport.me/    Public release date: 13-Feb-2011

ST. PAUL, Minn. –New research shows men and women who regularly eat berries may have a lower risk of developing Parkinson’s disease, while men may also further lower their risk by regularly eating apples, oranges and other sources rich in dietary components called flavonoids. The study was released today and will be presented at the American Academy of Neurology’s 63rd Annual Meeting in Honolulu April 9 to April 16, 2011.

Flavonoids are found in plants and fruits and are also known collectively as vitamin P and citrin. They can also be found in berry fruits, chocolate, and citrus fruits such as grapefruit.

The study involved 49,281 men and 80,336 women. Researchers gave participants questionnaires and used a database to calculate intake amount of flavonoids. They then analyzed the association between flavonoid intakes and risk of developing Parkinson’s disease. They also analyzed consumption of five major sources of foods rich in flavonoids: tea, berries, apples, red wine and oranges or orange juice. The participants were followed for 20 to 22 years.

During that time, 805 people developed Parkinson’s disease. In men, the top 20 percent who consumed the most flavonoids were about 40 percent less likely to develop Parkinson’s disease than the bottom 20 percent of male participants who consumed the least amount of flavonoids. In women, there was no relationship between overall flavonoid consumption and developing Parkinson’s disease. However, when sub-classes of flavonoids were examined, regular consumption of anthocyanins, which are mainly obtained from berries, were found to be associated with a lower risk of Parkinson’s disease in both men and women.

“This is the first study in humans to examine the association between flavonoids and risk of developing Parkinson’s disease,” said study author Xiang Gao, MD, PhD, with the Harvard School of Public Health in Boston. “Our findings suggest that flavonoids, specifically a group called anthocyanins, may have neuroprotective effects. If confirmed, flavonoids may be a natural and healthy way to reduce your risk of developing Parkinson’s disease.”
May 10, 2013

Could eating peppers prevent Parkinson’s?

Missed – Medical Breakthroughs • Tags: American Neurological AssociationAnnals of Neurology,Group Health CooperativeNicotineParkinsonParkinson’s diseaseSolanaceaeUniversity of Washington

Contact: Dawn Peters sciencenewsroom@wiley.com 781-388-8408 Wiley

Dietary nicotine may hold protective key

New research reveals that Solanaceae—a flowering plant family with some species producing foods that are edible sources of nicotine—may provide a protective effect against Parkinson’s disease. The study appearing today inAnnals of Neurology, a journal of the American Neurological Association and Child Neurology Society, suggests that eating foods that contain even a small amount of nicotine, such as peppers and tomatoes, may reduce risk of developing Parkinson’s.

Parkinson’s disease is a movement disorder caused by a loss of brain cells that produce dopamine. Symptoms include facial, hand, arm, and leg tremors, stiffness in the limbs, loss of balance, and slower overall movement. Nearly one million Americans have Parkinson’s, with 60,000 new cases diagnosed in the U.S. each year, and up to ten million individuals worldwide live with this disease according to the Parkinson’s Disease Foundation. Currently, there is no cure for Parkinson’s, but symptoms are treated with medications and procedures such as deep brain stimulation.

Previous studies have found that cigarette smoking and other forms of tobacco, also a Solanaceae plant, reduced relative risk of Parkinson’s disease. However, experts have not confirmed if nicotine or other components in tobacco provide a protective effect, or if people who develop Parkinson’s disease are simply less apt to use tobacco because of differences in the brain that occur early in the disease process, long before diagnosis.

For the present population-based study Dr. Susan Searles Nielsen and colleagues from the University of Washington in Seattle recruited 490 patients newly diagnosed with Parkinson’s disease at the university’s Neurology Clinic or a regional health maintenance organization, Group Health Cooperative. Another 644 unrelated individuals without neurological conditions were used as controls. Questionnaires were used to assess participants’ lifetime diets and tobacco use, which researchers defined as ever smoking more than 100 cigarettes or regularly using cigars, pipes or smokeless tobacco.

Vegetable consumption in general did not affect Parkinson’s disease risk, but as consumption of edible Solanaceae increased, Parkinson’s disease risk decreased, with peppers displaying the strongest association. Researchers noted that the apparent protection from Parkinson’s occurred mainly in men and women with little or no prior use of tobacco, which contains much more nicotine than the foods studied.

“Our study is the first to investigate dietary nicotine and risk of developing Parkinson’s disease,” said Dr. Searles Nielsen. “Similar to the many studies that indicate tobacco use might reduce risk of Parkinson’s, our findings also suggest a protective effect from nicotine, or perhaps a similar but less toxic chemical in peppers and tobacco.” The authors recommend further studies to confirm and extend their findings, which could lead to possible interventions that prevent Parkinson’s disease.

###

This study is published in Annals of Neurology. Media wishing to receive a PDF of this article may contact sciencenewsroom@wiley.com.

Full citation: “Nicotine from Edible Solanaceae and Risk of Parkinson Disease.” Susan Searles Nielsen, Gary M. Franklin, W.T. Longstreth Jr, Phillip D. Swanson and Harvey Checkoway. Annals of Neurology; Published May 9, 2013 (DOI:10.1002/ana.23884).

URL Upon Publication: http://doi.wiley.com/10.1002/ana.23884

Author Contact: To arrange an interview with Dr. Susan Searles Nielsen, please contact Leila Gray with the University of Washington Health Sciences News Office at +1 206-685-0381 or at leilag@uw.edu.

About the Journal

Annals of Neurology, the official journal of the American Neurological Association and the Child Neurology Society, publishes articles of broad interest with potential for high impact in understanding the mechanisms and treatment of diseases of the human nervous system. All areas of clinical and basic neuroscience, including new technologies, cellular and molecular neurobiology, population sciences, and studies of behavior, addiction, and psychiatric diseases are of interest to the journal. The journal is published by Wiley on behalf of the
American Neurological Association and Child Neurology Society. For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/ana.

Flavonoids from berries shown to protect men against Parkinson’s disease

December 19, 2013 · by MrT

by: John Phillip, John is a Certified Nutritional Consultant and Health Researcher

(NaturalNews) Past research bodies have confirmed the health-protective effect of a natural diet rich in flavonoids to protect against a wide range of diseases including heart disease, hypertension, some cancers, and dementia. Researchers from Harvard University and the University of East Anglia have published the result of a study in the journalNeurology that demonstrates how these plant-based phytonutrients can significantly lower the risk of developing Parkinson’s disease, especially in men.

Flavonoids from healthy foods such as berries, tea, apples, and red wine cross the delicate blood-brain barrier to protect neurons against neurologic diseases such as Parkinson’s. This large scale study included more than 130,000 men and women participants that were followed for a period of twenty years. During this time, more than 800 individuals developed Parkinson’s disease.

A diet high in flavonoids from berries lowers Parkinson’s disease risk by forty percent

After a detailed analysis of their diets and adjusting for age and lifestyle, male participants who ate the most flavonoids were shown to be forty percent  less likely to develop the disease than those who ate the least. No similar link was found for total flavonoid intake in women.

This was the first study to examine the connection between flavonoid consumption and the development of Parkinson’s disease. The findings suggest that a sub-class of flavonoids called anthocyanins may exhibit neuroprotective effects. Participants consuming one or more portions of berry fruits each week were around twenty-five percent less likely to develop Parkinson’s disease, relative to those who did not eat berry fruits.

Flavonoids are the bioactive, naturally occurring chemical compounds found in many plant-based foods and drinks.

This study demonstrated the main protective effect was from the consumption of anthocyanins, which are present in berries and other fruits and vegetables including aubergines, blackcurrants, and blackberries. Strawberries and blueberries are the two most common sources of flavonoids in the US diet, contributing to a twenty-four percent lowered risk in this research.

Parkinson’s disease is among a group of chronic diseases presently affecting one in 500 people, with new cases on the rise. Drug therapies are ineffective and bear significant side effects.

Nutrition experts recommend adding a minimum of three to five servings of flavonoids to your diet each week. Include all varieties of berries, apples, and green tea to guard against Parkinson’s disease and other neurodegenerative illnesses.

 

Read Full Post »


Larry Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/6-19-3014/larryhbern/Activation of Efficient and Multiple Site-specific Nonstandard Amino Acid Incorporation

 

Cell-free Protein Synthesis from a Release Factor 1 Deficient Escherichia coli Activates Efficient and Multiple Site-specific Nonstandard Amino Acid Incorporation

Seok Hoon Hong Ioanna Ntai §Adrian D. Haimovich #, Neil L. Kelleher §Farren J. Isaacs #, and Michael C. Jewett *

Department of Chemical and Biological Engineering,Chemistry of Life Processes Institute, §Department of Chemistry, and Department of Molecular Biosciences,Northwestern University, Evanston, Illinois 60208,United States of America

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, United States of America

# Systems Biology Institute, Yale University, West Haven, Connecticut 06516, United States of America

Member, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, United States of America

Institute of Bionanotechnology in Medicine, Northwestern University, Chicago, Illinois 60611, United States of America

ACS Synth. Biol.20143 (6), pp 398–409

DOI: 10.1021/sb400140t

Publication Date (Web): December 13, 2013

Copyright © 2013 American Chemical Society

*Tel: +1 847 467 5007. Fax (+1) 847 491 3728. E-mail: m-jewett@northwestern.edu

Site-specific incorporation of nonstandard amino acids (NSAAs) into proteins

Site-specific incorporation of nonstandard amino acids (NSAAs) into proteins

 

 

 

 

 

 

 

 

 

Site-specific incorporation of nonstandard amino acids (NSAAs) into proteins enables the creation of biopolymers, proteins, and enzymes with new chemical properties, new structures, and new functions. To achieve this, amber (TAG codon) suppression has been widely applied. However, the suppression efficiency is limited due to the competition with translation termination by release factor 1 (RF1), which leads to truncated products. Recently, we constructed a genomically recoded Escherichia coli strain lacking RF1 where 13 occurrences of the amber stop codon have been reassigned to the synonymous TAA codon (rEc.E13.ΔprfA). Here, we assessed and characterized cell-free protein synthesis (CFPS) in crude S30 cell lysates derived from this strain. We observed the synthesis of 190 ± 20 μg/mL of modified soluble superfolder green fluorescent protein (sfGFP) containing a single p-propargyloxy-l-phenylalanine (pPaF) or p-acetyl-l-phenylalanine. As compared to the parentrEc.E13 strain with RF1, this results in a modified sfGFP synthesis improvement of more than 250%. Beyond introducing a single NSAA, we further demonstrated benefits of CFPS from the RF1-deficient strains for incorporating pPaF at two- and five-sites per sfGFP protein. Finally, we compared our crude S30 extract system to the PURE translation system lacking RF1. We observed that our S30 extract based approach is more cost-effective and high yielding than the PURE translation system lacking RF1, 1000 times on a milligram protein produced/$ basis. Looking forward, using RF1-deficient strains for extract-based CFPS will aid in the synthesis of proteins and biopolymers with site-specifically incorporated NSAAs.

Keywords: 

cell-free protein synthesisPURE translationnonstandard amino acid;release factor 1genomically recoded organisms

 

 

 

 

Read Full Post »


Larry H Bernstein, MD, Writer, Curator
http://pharmaceutical intelligence.com/2013/06/22/ Demythologizing sharks, cancer, and shark fins/lhbern

 

Sharks have survived some 400 million years on Earth. Could their longevity be due in part to an extraordinary resistance to cancer and other diseases? If so, humans might someday benefit from the shark’s secrets—but leading researchers caution that today’s popular shark cartilage “cancer cures” aren’t part of the solution.

 

The belief that sharks do not get cancer is not supported in fact, but it is the basis for decimating a significant part of the shark population for shark fins, and for medicinal use.  The unfortunate result is that there is no benefit.

 

A basis for this thinking is that going back to the late 1800s, sharks have been fished commercially and there have been few reports of anything out of the ordinary when removing internal organs or preparing meat for the marketplace.  In addition, pre-medical students may have dissected dogfish sharks in comparative anatomy, but you don’t see reports of cancerous tumors.

 

Carl Luer of the MOTE Marine Laboratory’s Center for Shark Research in Sarasota, Florida, has been studying sharks’ cancer resistance for some 25 years.  Systematic surveys of sharks are difficult to conduct, as capturing the animals in large numbers is time-consuming, and cancer tests would likely require the deaths of large numbers of sharks. Of the thousands of fish tumors in the collections of the Smithsonian Institution, only about 15 are from elasmobranchs, and only two of these are thought to have been malignant.

 

Scientists have been studying cancerous tumors in sharks for 150 years.

 

The first chondrichthyes’ (cartilaginous fishes, including sharks) tumor was found on a skate and recorded by Dislonghamcps in 1853. The first shark tumor was recorded in 1908. Scientists have since discovered benign and cancerous tumors in 18 of the 1,168 species of sharks. Scarcity of studies on shark physiology has perhaps allowed this myth to be accepted as fact for so many years.

 

In April 2000, John Harshbarger and Gary Ostrander countered this shark myth with a presentation on 40 benign and cancerous tumors known to be found in sharks, and soon after a blue shark was found with cancerous tumors in both its liver and testes. Several years later a cancerous gingival tumor was removed from the mouth of a captive sand tiger shark, Carcharias Taurus. Advances in shark research continue to produce studies on types of cancer found in various species of shark.  Sharks, like fish, encounter and take in large quantities of environmental pollutants, which may actually make them more susceptible to tumorous growth. Despite recorded cases of shark cancer and evidence that shark cartilage has no curative powers against cancer sharks continue to be harvested for their cartilage.

 

Sharks and their relatives, the skates and rays, have enjoyed tremendous success during their nearly 400 million years of existence on earth, according to Dr. Luer. He points out that one reason for this certainly is their uncanny ability to resist disease. Sharks do get sick, but their incidence of disease is much lower than among the other fishes. While statistics are not available on most diseases in fishes, reptiles, amphibians, and invertebrates, tumor incidence in these animals is carefully monitored by the Smithsonian Institution in Washington, D.C.

 

The Smithsonian’s enormous database, called the Registry of Tumors in Lower Animals, catalogs tissues suspected of being tumorous, including cancers, from all possible sources throughout the world. Of the thousands of tissues in the Registry, most of them are from fish but only a few are from elasmobranchs. Only 8 to 10 legitimate tumors are among all the shark and ray tissues examined, and only two of these are thought to have been malignant.

 

An observation by Gary Ostrander, a Professor at Johns Hopkins University, is that there may be fundamental differences in shark immune systems so that they aren’t as prone to cancer.  The major thrust of the Motes research focuses on the immunity of sharks and their relatives the skates and rays. While skates aren’t as interesting to the public as their shark relatives, their similar biochemical immunology and their ability to breed in captivity make them perhaps more vital to Luer’s lab work.   The result is to study the differences and similarities to the higher animals, and what might possibly be the role of the immune system in their low incidence of disease.

 

This low incidence of tumors among the sharks and their relatives has prompted biochemists and immunologists at Mote Marine Laboratory (MML) to explore the mechanisms that may explain the unusual disease resistance of these animals. To do this, they established the nurse shark and clearnose skate as laboratory animals. They designed experiments to see whether tumors could be induced in the sharks and skates by exposing them to potent carcinogenic (cancer-causing) chemicals, and then monitored pathways of metabolism or detoxification of the carcinogens in the test animals. While there were similarities and differences in the responses when compared with mammals, no changes in the target tissues or their genetic material ever resulted in cancerous tumor formation in the sharks or skates.

 

The chemical exposure studies led to investigations of the shark immune system. As with mammals, including humans, the immune system of sharks probably plays a vital role in the overall health of these animals. But there are some important differences between the immune arsenals of mammals and sharks. The immune system of mammals typically consists of two parts which utilize a variety of immune cells as well as several classes of proteins called immunoglobulins (antibodies).

 

Compared to the mammalian system, which is quite specialized, the shark immune system appears primitive but remarkably effective. Sharks apparently possess immune cells with the same functions as those of mammals, but the shark cells appear to be produced and stimulated differently. Furthermore, in contrast to the variety of immunoglobulins produced in the mammalian immune system, sharks have only one class of immunoglobulin (termed IgM). This Immunoglobulin normally circulates in shark blood at very high levels and appears to be ready to attack invading substances at all times.

 

Another difference lies in the fact that sharks, skates, and rays lack a bony skeleton, and so do not have bone marrow. In mammals, immune cells are produced and mature in the bone marrow and other sites, and, after a brief lag time, these cells are mobilized to the bloodstream to fight invading substances. In sharks, the immune cells are produced in the spleen, thymus and unique tissues associated with the gonads (epigonal organ) and esophagus (Leydig organ). Some maturation of these immune cells occurs at the sites of cell production, as with mammals. But a significant number of immune cells in these animals actually mature as they circulate in the bloodstream. Like the ever-present IgM molecule, immune cells already in the shark’s blood may be available to respond without a lag period, resulting in a more efficient immune response.

 

Research was being carried out during the 1980’s at the Massachusetts Institute of Technology (MIT) and at Mote Marine Laboratory designed to understand how cartilage is naturally able to resist penetration by blood capillaries. If the basis for this inhibition could be identified, it was reasoned, it might lead to the development of a new drug therapy. Such a drug could control the spread of blood vessels feeding a cancerous tumor, or the inflammation associated with arthritis.

 

The results of the research showed only that a very small amount of an active material, with limited ability to control blood vessel growth, can be obtained from large amounts of raw cartilage. The cartilage must be subjected to several weeks of harsh chemical procedures to extract and concentrate the active ingredients. Once this is done, the resulting material is able to inhibit blood vessel growth in laboratory tests on animal models, when the concentrated extract is directly applied near the growing blood vessels.  One cannot assume that comparable material in sufficient amount and strength is released passively from cartilage when still in the animal to inhibit blood vessel growth anywhere in the body.

 

Tumors release chemicals stimulating the capillary growth so a nutrient-rich blood supply is created to feed the tumorous cells. This process is called angiogenesis. If scientists can control angiogenesis, they could limit tumor growth. Cartilage lacks capillaries running through it. Why should this be a surprise?  Cartilage cells are called chondrocytes, and they fuction to produce a acellular interstitial matrix consisting of hyaluronan (complex carbohydrate formed from hyaluronic acid and chondroitin sulfate) which is protective of interlaced collagen.   Early research into the anti-angiogenesis properties of cartilage revealed that tiny amounts of proteins could be extracted from cartilage, and, when applied in concentration to animal tumors, the formation of capillaries and the spread of tumors was inhibited.

 

Henry Brem and Judah Folkman from the Johns Hopkins School of Medicine first noted that cartilage prevented the growth of new blood vessels into tissues in the 1970s. The creation of a blood supply, called angiogenesis, is a characteristic of malignant tumors, as the rapidly dividing cells need lots of nutrients to continue growing.  It is valuable to consider that these neovascular generating cells are not of epithelial derivation, but are endothelial and mesenchymal. To support their very high metabolism, tumors secrete a hormone called ‘angiogenin’ which causes nearby blood vessels to grow new branches that surround the tumor, bringing in nutrients and carrying away waste products

 

Brem and Folkman began studying cartilage to search for anti-angiogenic compounds. They reasoned that since all cartilage lacks blood vessels, it must contain some signaling molecules or enzymes that prevent capillaries from forming. They found that inserting cartilage from baby rabbits alongside tumors in experimental animals completely prevented the tumors from growing. Further research showed calf cartilage, too, had anti-angiogenic properties.

 

 

 

A young researcher by the name of Robert Langer repeated the initial rabbit cartilage experiments, except this time using shark cartilage. Indeed, shark cartilage, like calf and rabbit cartilage, inhibited blood vessels from growing toward tumors. Research by Dr. Robert Langer of M.I.T. and other workers revealed a promising anti-tumor agent obtainable in quantity from shark cartilage. The compound antagonistic to the effects of angiogenin, called ‘angiogenin inhibitor’, inhibits the formation of new blood vessels, neovascularization, that is essential for supporting cancer growth.

 

The consequence of the”shark myth” is not surprising. An inhabitant of the open ocean, the Silky Shark is ‘hit’ hard by the shark fin and shark cartilage industries – away from the prying eyes of a mostly land bound public. As a consequence of this ‘invisibility’, mortality of Silkies is difficult to estimate or regulate.  North American populations of sharks have decreased by up to 80% in the past decade, as cartilage companies harvest up to 200,000 sharks every month in US waters to create their products. One American-owned shark cartilage plant in Costa Rica is estimated to destroy 2.8 million sharks per year. Sharks are slow growing species compared to other fish, and simply cannot reproduce fast enough to survive such sustained, intense fishing pressure. Unless fishing is dramatically decreased worldwide, a number of species of sharks will go extinct before we even notice.

 

Sources:
1.  National Geographic News: NATIONALGEOGRAPHIC.COM/NEWS

 

2. Do Sharks Hold Secret to Human Cancer Fight?
by Brian Handwerk for National Geographic News.  August 20, 2003

 

3. Busting Marine Myths: Sharks DO Get Cancer!
by Christie Wilcox   November 9th 2009

 

 

 

 

 

Sand tiger shark (Carcharias taurus) at the Ne...

Sand tiger shark (Carcharias taurus) at the Newport Aquarium. (Photo credit: Wikipedia)

 

Angiogenesis

Angiogenesis (Photo credit: Wikipedia)

 

 

 

 

 

 

 

 

 

 

 

The immune response

The immune response (Photo credit: Wikipedia)

 

Read Full Post »


Larry H. Bernstein, MD, Reviewer and Curator
Leaders in Pharmaceutical Intelligence
https://pharmaceuticalintelligence.com/2013/06/20/Naked Mole Rats Cancer-Free/lhbern

This discussion is a novel piece of investigations now and earlier  published in the Proceedings of the National Academy of Sciences, and another in Nature pertaining to aging, longevity, and cancer.  The blind mole rat has an unexpected lifespan compared to other rodents.  There are also findings of a related naked mole rat that comes into the picture.  They are related, but not exactly the same. In both cases, the moles are cold-blooded, live underground with a queen and workers and they don’t develop cancer. The naked mold rates don’t develop cancer because of the presence of an imbalance in the intercellular matrix caused by abundant naturally produced, sticky complex carbohydrate also found in human joints that repels the cells at their interstices.

This is fascinating because it is also an important aspect of joint mobility.  In the situation of chondomalacia before erosion of the articular cartilage, the movement and shearing stresses initially induced production of more chondrocytes and with that, a thickened cartilage that becomes taxed until it loses matrix fluid, followed by loss of matrix and loss of collagen by shearing stress.  This type of motion and shear stress plays no part in the life of the naked mole rat, which has a rough skin.  The property of the cellular matrix seems to be characterized by both the production of the intercellular goo…called hyalurenan (like hyaluronic acid) and sparse hyaluronidase to remove and remodel the cell architecture.  How this is related to extreme aging and no loss of cellular growth control, having sparce ubiqitination that is involve in cell death and repair is unclear.

The hyaluronidases (EC 3.2.1.35) are a family of enzymes that degrade hyaluronic acid.  In humans, there are six associated genes, including HYAL1, HYAL2, HYAL3, and PH-20/SPAM1. By catalyzing the hydrolysis of hyaluronan, a constituent of the extracellular matrix (ECM), hyaluronidase lowers the viscosity of hyaluronan.  http://upload.wikimedia.org/wikipedia/commons/2/2f/Hyaluronidase-1OJN.png

The blind mole rat is closely related, but it differs in that it has a mechanism by which the cells have limited proliferation and don’t proliferate to the point of getting out of control.  This is because after several generations of cellular proliferation they produce a protein,  IFN-β.  This protein induces massive apoptosis, limiting the size of the sell population. There are findings in these investigations that might be relevant to understanding cancer resistance, and perhaps it could provide clues to treatment approaches.  If that is too much to ask for, it gives us great insight into how cells organize.

Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism

Gorbunovaa V, Hinea C, Tiana X, Ablaevaa J, Gudkovb AV, Nevoc E, and Seluanova A.
Contributed by Eviatar Nevo, October 3, 2012 (sent for review August 28, 2012)

Abstract

Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle East. BMR is distinguished by its adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 y), and resistance to cancer. Spontaneous tumors have never been observed in spalacids. To understand the mechanisms responsible for this resistance, we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani. BMR cells proliferated actively for 7–20 population doublings, after which the cells began secreting IFN-β, and the cultures underwent massive necrotic cell death within 3 d. The necrotic cell death phenomenon was independent of culture conditions or telomere shortening. Interestingly, this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat, Heterocephalus glaber, the naked mole rat in which cells display hypersensitivity to contact inhibition. Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death. Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways, and triggered by the release of IFN-β. Thus, we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground.

Source:

1To whom correspondence may be addressed. E-mail:  vera.gorbunova@rochester.edu, nevo@research.haifa.ac.il, or andrei.seluanov@rochester.edu.

2Present address: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115.

http://www.pnas.org/content/early/2012/10/31/1217211109

naked mole rat

Image: Greg Goebel/Flickr


Long-Lived Rat May Hold Clues to Combating Aging

BY BRANDON KEIM02.17.09

The extraordinarily durable proteins in the world’s longest-lived rodent may contain a vital piece of the puzzle of aging.

  • Like short-lived mice, the cells of naked mole rats are suffused with free-floating, cell-damaging oxygen free radicals. 
  • Unlike the mice — and every other species that appears compromised by oxidative deterioration, including humans — they’ve found a way to live with it.

“When we compare the lab mouse with the naked mole rat, we find a striking difference in their systems,” said study co-author Asish Chaudhuri, a University of Texas Health Science Center biochemist. “Their proteins are still working. Even when damaged, the functions are maintained.”

The findings, published Monday in the Proceedings of the National Academy of Sciences, represent a new wrinkle in the oxidative-stress theory of aging. According to the theory, mitochondria — cellular machines that produce our bodies’ energy — pump out highly reactive oxygen molecules during respiration. Called free radicals, these molecules bind easily with other molecules, including DNA. Over time, DNA breaks down, compromising cellular function. Eventually whole tissues and organs no longer function.  Multiple studies have found evidence of mitochondrial malfunction in a range of diseases that become more common with age, from heart disease to neurodegeneration to cancer. Drugs designed to rejuvenate mitochondria have shown promise in treating diabetes, and are celebrated as possible therapies for other conditions.

DNA repair rate is an important determinant of...

DNA repair rate is an important determinant of cell pathology (Photo credit: Wikipedia)

Chaudhuri’s team’s findings don’t contradict the role of mitochondria, but expand the theory to include cellular proteins other than DNA. They also explain a condundrum: some long-lived species display plenty of oxidative damage. “We’ve studied a dozen species, half short-lived and the others long-lived. One long-lived species would have lots of oxidative damage, and another would have little. The one thing that seemed to be consistent was protein stability,” said University of Texas Health Sciences Center gerontologist Steven Austad, who was not involved in the current study. “Until recently I’ve focused on DNA damage and repair, but this strikes me as even more fundamental. For DNA repair to work, you need all the repair proteins to work properly.”  Mole rats caught the researchers’ attention because they can live for 30 years, or ten times longer than lab mice, even though the two are similarly sized.

They found that mole rats do have efficient mitochondria that release fewer free radicals than expected. But their mitochondria aren’t perfect. Free radicals still gather and cause damage. Two-year-old mole rats show just as much oxidative stress two-year-old mice — and then live for another quarter-century.  The key appears to be their proteins, which continue to function despite damage. Study co-author Rochelle Buffenstein, a University of Texas Health Sciences Center physiologist, likened the phenomena to rusting cars: in other species, the axles rust, but in naked mole rats, it’s just the doors.  With heat and urea — both of which typically cause complex protein spools to unfold — the researchers tried to break down the proteins, but to no avail.  “You can basically hit them with a sledgehammer, and the proteins don’t unfold,” said Buffenstein. “Something makes them inherently more stable. There might be small molecules that tack on to proteins and help them retain structure in the face of cellular stress.”

Mole rats also appear to delay protein repair until the last possible moment, thus saving energy and resources. When proteins finally do break down, mole rats do an especially efficient job of cleaning them up. Only a tiny bit of ubiquitin — the chemical tag used to label damaged proteins for disposal — is required.  Finally, specialized protein-disposal structures, called proteosomes (tied to ubiqitination), don’t appear to break down with age in mole rats.

English: Damaraland mole-rat (Fukomys damarensis)

English: Damaraland mole-rat (Fukomys damarensis) (Photo credit: Wikipedia)

The researchers will next try to determine what maintains the mole rat’s proteins and proteosome. If, as Buffenstein suspects, it turns out to be an as-yet-unidentified protein protectant, scientists could apply the findings to people. “If we can identify those proteins, we can use them to study aging and age-related diseases. These animals don’t have any symptoms of neurodegeneration, even in old age,” said Chaudhuri. “Then we can design peptides that act like the protein, and take it as a drug.”

Citation:

Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat.

By Viviana I. Perez, Rochelle Buffenstein, Venkata Masamsetti, Shanique Leonard, Adam B. Salmon, James Meleb, Blazej Andziak, Ting Yang, Yael Edrey, Bertrand Friguet, Walter Ward, Arlan Richardson and Asish Chaudhuri. Proceedings of the National Academy of Sciences, Vol. 106 No. 7, Feb. 16, 2009.

Why Blind Mole Rats Don’t Get Cancer

By Ian Steadman, Wired UK

Blind mole rats don’t get cancer. in 2011 it was found they have a gene that stops cancerous cells from forming. The same team thought that two other cancer-proof mole rat species might have similar genes, but instead it turns out that they do develop cancerous cells. It’s just that those cells are programmed to destroy themselves if they become dangerous.

The blind mole rat (Spalax typhlus) has tiny e...

The blind mole rat (Spalax typhlus) has tiny eyes completely covered by a layer of skin. (Photo credit: Wikipedia)

Mole rats, which live in underground burrows throughout Southern and Eastern Africa, and the Middle East, are fascinating creatures. The naked mole rat, in particular, is the only cold-blooded mammal known to man, doesn’t experience pain, and is also arguably the only mammal (along with the Damaraland mole rat) to demonstrate eusociality — that is, they live in large hierarchical communities with a queen and workers, like ants or bees.

The two species examined by the University of Rochester’s Vera Gorbunova and her team were the Judean Mountains blind mole rat (Spalax judaei) and the Golan Heights blind mole rat (Spalax golani), which live within small regions of Israel. The team took cells from the rodents and put them in a culture that would force them to multiply beyond what would happen within the animals’ bodies. For the first seven to 20 multiplications, things looked fine, but beyond 20 multiplications the cells started rapidly dying off.  Examining the cells as they died revealed that they had started to produce a protein, IFN-β, that caused them to undergo “massive necrotic cell death within three days”. In effect, once the cells had detected that they had multiplied beyond a certain point, they killed themselves. The cells of naked mole rats have a self-preservation mechanism tied to a hypersensitivity to overcrowding, which stops them from multiplying too much.  On the one hand (blind mole rat) you have self-destruction at a point at which there is crowding due to IFN-β.  On the other hand, you find an aversion to overcrowding (naked mole rat).

In the Proceedings of the National Academy of Sciences, Gorbunova hypothesizes that the blind mole rats’ unique habitat — almost entirely underground — might mean that they “could perhaps afford to evolve a long lifespan, which includes developing efficient anti-cancer defences”. Blind mole rats have extremely long lifespans by rodent standards, often living beyond 20 years at a time.

The reasons why this is, though, are still all hypothetical, as the precise mechanism that triggers the production of the IFN-β is still unknown. The hope is that this research could eventually lead to new therapies for cancer in humans.

Super Sugar Keeps Naked Mole Rats Cancer-Free

BY ELIZABETH PENNISI, SCIENCENOW 06.20.13

Although they are quite ugly and confined to a life underground, naked mole rats have at least one attribute that other animals, even humans, might aspire to: They don’t get cancer. Now, researchers have discovered that the secret to this rodent’s good health is a complex sugar that helps keeps cells from clumping together and forming tumors.  It exists in the spaces between cells called the extracellular matrix, “the work underlines the very important regulatory role of [the] extracellular matrix in cancer,” says Bryan Toole, a cancer biologist at the Medical University of South Carolina in Charleston who was not involved with the study. Molecular and cell biologist Vera Gorbunova of the University of Rochester in New York wanted to take a different tack and focus on animals that seem protected from tumors. So she tracked down the lifespans of 20 different rodents, looking for the ones that live a long time. Beavers and gray squirrels last a couple of decades, but naked mole rats outlive those larger animals by 10 years.  Furthermore, naked mole rats have a unique social structure, with one queen that produces all the young for an underground colony full of helpers. Thanks to these studies, scientists know for sure that this species doesn’t get cancer. Given that naked mole rats live long and are resistant to cancer, “we fell in love with them right away,” Gorbunova says.

At first, she and her colleagues did not know where to look for the source of animals’ cancer resistance. But when they grew naked mole rat cells in a lab dish, they noticed that cells wouldn’t get too close together. Furthermore, the dish contents got very gooey, and when they eliminated the goo, the cells would clump together. The researchers tracked the stickiness to a complex sugar called hyaluronan, which cells make and release into the extracellular matrix.  Hyaluronan exists in all animals, helping lubricate joints and serving as an essential component in skin and cartilage. However, naked mole rat hyaluronan is unusual in that each molecule is about 5 times the size of hyaluronan molecules from mice, rats, and humans. In addition, the researchers discovered that the enzyme that breaks down this sugar (hyaluronidase) is not very active in naked mole rats, allowing the compound to accumulate to higher concentrations than it does in other animals. The researchers think that this sugar evolved to make naked mole rat skin more elastic and able to cope with the tight squeeze of the narrow underground tunnels.

But does it prevent cancer? Gorbunova and her colleagues tried to stimulate naked mole rat cells to form tumors by exposing them to viral proteins that in mice lead to tumor growth. These proteins inactivate genes that suppress cancer, yet still naked mole rat cells did not show uncontrolled growth. However, when the researchers interfered with the production of hyaluronan or revved up the activity of the enzyme that breaks the sugar down, thereby reducing its concentrations, tumors did form in live animals, they report online today in Nature.

The work is “very thought-provoking [and] adds an interesting wrinkle to the role of the extracellular matrix in cancer,” says Roy Zent, a cell biologist at Vanderbilt University Medical Center in Nashville. Toole agrees. “It pushes our thoughts forward [about hyaluronan] in a very dramatic way,” he notes. “It establishes hyaluronan as an important player in cancer.”  “If we could alter our [hyaluronan] or stabilize it somehow, we may be able to suppress cancers,” suggests Carlo Maley, an evolutionary cancer biologist at the University of California, San Francisco, who was not involved with the work. The next step, he adds, is to “put the naked mole rat [hyaluronan] gene into mice and test if they are cancer resistant.”

English: Naked mole rats. Cropped version of F...

English: Naked mole rats. Cropped version of File:Naked Mole Rats.jpg. (Photo credit: Wikipedia)

Naked Mole rat baby

Naked Mole rat baby (Photo credit: Wikipedia)

English: Spalax leucodon, syn. Nannospalax leu...

English: Spalax leucodon, syn. Nannospalax leucodon Magyar: Földikutya (Photo credit: Wikipedia)

Read Full Post »


Cardio-Metabolic Drug Targets, Inaugural, September 25 – 26, 2013, Westin Waterfront | Boston, Massachusetts  

 

Reporter: Aviva Lev-Ari, PhD, RN

                                 

ABOUT THIS CONFERENCE

Cardiovascular disease, diabetes, obesity and dyslipidemia, though traditionally treated as separate entities, are often conditions that appear together in individuals because of defects in underlying metabolic processes. Researchers are therefore now seeking compounds that target biological points of intersection of these related diseases in the hopes of ‘killing more birds with one stone.’ Or they are approaching drug development of a compound for a specific disease with a greater awareness of the backdrop of related conditions.

Join fellow biomedical researchers from academia and industry at our day and a half conference, Cardio-Metabolic Drug Targets to discuss the impact of this paradigm change in the way drugs are discovered and developed in the cardio-metabolic arena and to stay abreast of the latest targets and drug development candidates in the pipeline.

SUGGESTED EVENT PACKAGE:

September 23: Allosteric Modulators of GPCRs Short Course 
September 24 – 25: Novel Strategies for Kinase Inhibitors Conference
September 25: Setting Up Effective Functional Screens Using 3D Cell Cultures Dinner Short Course
September 25 – 26: Cardio-Metabolic Drug Targets Conference

Scientific Advisory Board:

Jerome J. Schentag, Pharm.D., Professor of Pharmaceutical Sciences, University at Buffalo

Rebecca Taub, M.D., Ph.D., CEO, Madrigal Pharmaceuticals

Preliminary Agenda

BEYOND STATINS: NEW APPROACHES FOR REGULATING LIPID METABOLISM AND ATHEROSCLEROSIS

Macrophage ABC Transporters: Novel Targets to Promote Atherosclerotic Plaque Regression by Inducing Reverse Cholesterol Transport (RCT) Mechanism

Eralp “Al” Bellibas, M.D., Senior Director, Head, Clinical Pharmacology, The Medicines Company

Targeting PCSK9 for Hypercholesterolemia and Atherosclerosis

Hong Liang, Ph.D., Associate Research Fellow, Rinat Research Unit, Pfizer

Novel Treatment for Dyslipidemia: Liver-Directed Thyroid Hormone Receptor-ß Agonist

Rebecca Taub, M.D., Ph.D., CEO, Madrigal Pharmaceuticals

CARDIO-METABOLIC THERAPEUTIC CANDIDATES

Oral Mimetics of RYGB and GLP-1 in Metabolic Syndromes

Jerome J. Schentag, Pharm.D., Professor of Pharmaceutical Sciences, University at Buffalo

FGF21-Mimetic Antibodies for Type 2 Diabetes

Jun Sonoda, Ph.D., Group Leader, Scientist, Molecular Biology, Genentech

NEW CARDIO-METABOLIC TARGETS

Blockade of Delta-Like Ligand 4 (Dll4)-Notch Signaling Reduces Macrophage Activation and Attenuates Atherosclerotic Vascular Diseases and Metabolic Disorders

Masanori Aikawa, Ph.D., Assistant Professor, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical

Modulating Glycerolipid Metabolism in Myeloid Cells for Cardiometabolic Benefit

Suneil K. Koliwad, M.D., Ph.D., Assistant Professor, Diabetes Center/Department of Medicine, University of California San Francisco

AMPK as a Target in Lipid and Carbohydrate Metabolism

Ajit Srivastava, Ph.D., Adjunct Professor, Pharmacology, Drexel University; Independent Consultant, Integrated Pharma Solutions, LLC

 http://www.discoveryontarget.com/Cardio-Drug-Targets

Inaugural n September 25 – 26, 2013

Cardio-Metabolic Drug Targets

Targeting One, Treating More

»»Suggested Event Package

September 23: Allosteric Modulators of GPCRs Short Course 4

September 24-25: Novel Strategies for Kinase Inhibitors

Conference

September 25: Setting Up Effective Functional Screens Using 3D

Cell Cultures Dinner Short Course 9

September 25-26: Cardio-Metabolic Drug Targets Conference

Wednesday, September 25

11:50 am Registration

BEYOND STATINS: NEW APPRO ACHES FOR

REGULATING LIPID METABOLISM AND

ATHERO SCLERO SIS

1:30 pm Chairperson’s Opening Remarks

1:40 PLENARY KEYNOTE PRESENTATION: Towards a Patient-

Based Drug Discovery

Stuart L. Schreiber, Ph.D., Director, Chemical Biology and Founding Member, Broad

Institute of Harvard and MIT; Howard Hughes Medical Institute Investigator; Morris

Loeb Professor of Chemistry and Chemical Biology, Harvard University

3:10 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 FEATURED SPEAKER: Atherosclerosis and Cardio-

Metabolism Research Overview: Promising Targets

Margrit Schwarz, Ph.D., MBA, formerly Director of Research, Dyslipidemia and

Atherosclerosis, Amgen; currently President, MS Consulting, LLC

4:30 Sponsored Presentations (Opportunities Available)

5:00 Novel Treatment for Dyslipidemia: Liver-Directed Thyroid

Hormone Receptor-ß Agonist

Rebecca Taub, M.D., Ph.D., CEO, Madrigal Pharmaceuticals

5:30 Modulating Glycerolipid Metabolism in Myeloid Cells for

Cardiometabolic Benefit

Suneil K. Koliwad, MD., Ph.D. Assistant Professor, Diabetes Center/Department

of Medicine, University of California San Francisco (UCSF)

6:00 Targeting PCSK9 for Hypercholesterolemia and

Atherosclerosis

Hong Liang, Ph.D., Associate Research Fellow, Rinat Research Unit, Pfizer

6:30 Close of Day

Thursday, September 26

7:30 am Registration

NEW ARTHERO /LIPID/CARDIO-METABOLIC

DRUG TARGETS

8:00 Breakfast Interactive Breakout Discussion Groups

9:05 Chairperson’s Opening Remarks

9:10 ApoE derived ABCA1 agonists for the Treatment of

Cardiovascular Disease

Jan Johansson, M.D., Ph.D., CEO, Artery Therapeutics, Inc.

9:40 Blockade of Delta-Like Ligand 4 (Dll4)-Notch Signaling

Reduces Macrophage Activation and Attenuates Atherosclerotic

Vascular Diseases and Metabolic Disorders

Masanori Aikawa, Ph.D., Assistant Professor, Department of Medicine,

Brigham and Women’s Hospital and Harvard Medical

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

10:55 AMPK as a Target in Lipid and Carbohydrate Metabolism

Ajit Srivastava, Ph.D., Adjunct Professor, Department of Pharmacology, Drexel

University; Independent Consultant, Integrated Pharma Solutions, LLC

11:25 Macrophage ABC Transporters: Novel Targets to Promote

Atherosclerotic Plaque Regression by Inducing Reverse

Cholesterol Transport (RCT) Mechanism

Eralp “Al” Bellibas, M.D., Senior Director, Head, Clinical Pharmacology, The

Medicines Company

11:55 Targeting Ubiquitin Signaling Mediated Disease Pathology

of LDL Receptors

Udo Maier, Ph.D., Head of Target Discovery Research, Boehringer Ingelheim

Pharma

12:25 pm Sponsored Presentation (Opportunity Available)

12:55 Luncheon Presentation (Sponsorship Opportunity Available) or

Lunch on Your Own

Cardio-Metab olic Mimetics

2:25 Chairperson’s Opening Remarks

2:30 Oral Mimetics of RYGB and GLP-1 in Metabolic Syndromes

Jerome J. Schentag, PharmD, Professor of Pharmaceutical Sciences, University

at Buffalo

3:00 FGF21-Mimetic Antibodies for Type 2 Diabetes

Jun Sonoda, Ph.D., Group Leader, Scientist, Molecular Biology, Genentech

3:30 Ice Cream Refreshment Break in the Exhibit Hall with Poster

Viewing

gpCrS IN METABOLIC DISEASES

4:00 Targeting the Ghrelin Receptor with an Oral, Macrocyclic

Agonist

Helmut Thomas, Ph.D., Senior Vice President, Research and Preclinical

Development, Tranzyme Pharma

4:30 Presentation to be Announced

5:00 Lactate Receptor, GPR81/HCA1, as a Novel Target for

Metabolic Disorders

Changlu Liu, Ph.D., Scientific Director, Janssen Fellow, Head of Molecular

Innovation, Neuroscience, Janssen Research & Development, LLC

5:30 Targeting GPR55 in Cancer and Diabetes

Marco Falasca, Ph.D., Professor of Molecular Pharmacology, Queen Mary

University of London

6:00 Close of Conference

Read Full Post »

Older Posts »