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37th Annual J.P. Morgan HEALTHCARE CONFERENCE: News at #JPM2019 for Jan. 10, 2019: Deals and Announcements

Reporter: Stephen J. Williams, Ph.D.

From Biospace.com

 

JP Morgan Healthcare Conference Update: Sage, Mersana, Shutdown Woes and Babies

Speaker presenting to audience at a conference

With the J.P. Morgan Healthcare Conference winding down, companies remain busy striking deals and informing investors about pipeline advances. BioSpace snagged some of the interesting news bits to come out of the conference from Wednesday.

SAGE Therapeutics – Following a positive Phase III report that its postpartum depression treatment candidate SAGE-217 hit the mark in its late-stage clinical trial, Sage Therapeutics is eying the potential to have multiple treatment options available for patients. At the start of J.P. Morgan, Sage said that patients treated with SAGE-217 had a statistically significant improvement of 17.8 points in the Hamilton Rating Scale for Depression, compared to 13.6 for placebo. The company plans to seek approval for SAGE-2017, but before that, the FDA is expected to make a decision on Zulresso in March. Zulresso already passed muster from advisory committees in November, and if approved, would be the first drug specifically for postpartum depression. In an interview with the Business Journal, Chief Business Officer Mike Cloonan said the company believes there is room in the market for both medications, particularly since the medications address different patient populations.

 

Mersana Therapeutics – After a breakup with Takeda Pharmaceutical and the shelving of its lead product, Cambridge, Mass.-based Mersana is making a new path. Even though a partial clinical hold was lifted following the death of a patient the company opted to shelve development of XMT-1522. During a presentation at JPM, CEO Anna Protopapas noted that many other companies are developing therapies that target the HER2 protein, which led to the decision, according to the Boston Business Journal. Protopapas said the HER2 space is highly competitive and now the company will focus on its other asset, XMT-1536, an ADC targeting NaPi2b, an antigen highly expressed in the majority of non-squamous NSCLC and epithelial ovarian cancer. XMT-1536 is currently in Phase 1 clinical trials for NaPi2b-expressing cancers, including ovarian cancer, non-small cell lung cancer and other cancers. Data on XMT-1536 is expected in the first half of 2019.

Novavax – During a JPM presentation, Stan Erck, CEO of Novavax, pointed to the company’s RSV vaccine, which is in late-stage development. The vaccine is being developed for the mother, in order to protect an infant. The mother transfers the antibodies to the infant, which will provide the baby with protection from RSV in its first six months. Erck called the program historic. He said the Phase III program is in its fourth year and the company has vaccinated 4,636 women. He said they are tracking the women and the babies. Researchers call the mothers every week through the first six months of the baby’s life to acquire data. Erck said the company anticipates announcing trial data this quarter. If approved, Erck said the market for the vaccine could be a significant revenue driver.

“You have 3.9 million birth cohorts and we expect 80 percent to 90 percent of those mothers to be vaccinated as a pediatric vaccine and in the U.S. the market rate is somewhere between $750 million and a $1 billion and then double that for worldwide market. So it’s a large market and we will be first to market in this,” Erck said, according to a transcript of the presentation.

Denali Therapeutics – Denali forged a collaboration with Germany-based SIRION Biotech to develop gene therapies for central nervous disorders. The two companies plan to develop adeno-associated virus (AAV) vectors to enable therapeutics to cross the blood-brain barrier for clinical applications in neurodegenerative diseases including Parkinson’s, Alzheimer’s disease, ALS and certain other diseases of the CNS.

AstraZeneca – Pharma giant AstraZeneca reported that in 2019 net prices on average across the portfolio will decrease versus 2018. With a backdrop of intense public and government scrutiny over pricing, Market Access head Rick Suarez said the company is increasing its pricing transparency. Additionally, he said the company is looking at new ways to price drugs, such as value-based reimbursement agreements with payers, Pink Sheet reported.

Amarin Corporation – As the company eyes a potential label expansion approval for its cardiovascular disease treatment Vascepa, Amarin Corporation has been proactively hiring hundreds of sales reps. In the fourth quarter, the company hired 265 new sales reps, giving the company a sales team of more than 400, CEO John Thero said. Thero noted that is a label expansion is granted by the FDA, “revenues will increase at least 50 percent over what we did in the prior year, which would give us revenues of approximate $350 million in 2019.”

Government Woes – As the partial government shutdown in the United States continues into its third week, biotech leaders at JPM raised concern as the FDA’s carryover funds are dwindling. With no new funding coming in, reviews of New Drug Applications won’t be able to continue past February, Pink Sheet said. While reviews are currently ongoing, no New Drug Applications are being accepted by the FDA at this time. With the halt of NDA applications, that has also caused some companies to delay plans for an initial public offering. It’s hard to raise potential investor excitement without the regulatory support of a potential drug approval. During a panel discussion, Jonathan Leff, a partner at Deerfield Management, noted that the ongoing government shutdown is a reminder of how “overwhelmingly dependent the whole industry of biotech and drug development is on government,” Pink Sheet said.

Other posts on the JP Morgan 2019 Healthcare Conference on this Open Access Journal include:

#JPM19 Conference: Lilly Announces Agreement To Acquire Loxo Oncology

36th Annual J.P. Morgan HEALTHCARE CONFERENCE January 8 – 11, 2018

37th Annual J.P. Morgan HEALTHCARE CONFERENCE: #JPM2019 for Jan. 8, 2019; Opening Videos, Novartis expands Cell Therapies, January 7 – 10, 2019, Westin St. Francis Hotel | San Francisco, California

37th Annual J.P. Morgan HEALTHCARE CONFERENCE: News at #JPM2019 for Jan. 8, 2019: Deals and Announcements

 

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Open Access e-Scientific Publishing: Elected among 2018 Nature’s 10 Top Influencers – ROBERT-JAN SMITS: A bureaucrat launched a drive to transform science publishing

Curator: Aviva Lev-Ari, PhD, RN,

Editor-in-Chief, https://pharmaceuticalintelligence.com/

UPDATED by 1/15/2019

Entire editorial board resigns over open access

The editorial board of an influential scientometrics journal — the Journal of Informetrics — has resigned and launched a competing free-to-read journal. The board wanted Elsevier to offer free access to detailed citation data, among other things. “Elsevier needs to be able to continue investing in ways that add value to the research process, which it cannot do if it gives this value away for free,” said the publisher. The former editors have launched a competing free-to-read journal called Quantitative Science Studies.

Nature | 4 min read

2018 Nature’s 10

  • Yuan Cao, Graphene wrangler
  • Viviane Slon, Humanity’s historian
  • He Jiankui, CRISPR rogue
  • Jess Wade, Diversity champion
  • Valérie Masson-Delmotte, Earth monitor
  • Anthony Brown, Star mapper
  • Bee Yin Yeo, Force for the environment
  • Barbara Rae-Venter, DNA detective
  • Robert-Jan Smits, Open-access leader
  • Makoto Yoshikawa, Asteroid hunter

Ones to watch 2019

About Nature’s 10

About the Nature’s 10 image

 

ROBERT-JAN SMITS: Open-access leader: A bureaucrat launched a drive to transform science publishing.

BY HOLLY ELSE

Credit: Artur Eranosian/European Commission

The architect of this year’s bold push to get rid of paywalls in science publishing says he got his ideas from an unlikely source: the publishers themselves.

In March, Robert-Jan Smits was tasked by the European Union’s research commissioner, Carlos Moedas, with a special one-year mission: to get more research papers published outside journal paywalls, and fast. A veteran science-policy bureaucrat, Smits decided to go to the source: he asked big publishers how he could do it. They told him that if the organizations that pay for research insisted the findings had to be published openly, journals would have to adapt.

So that’s what Smits set out to persuade research funders to do — in a plan launched in September that has sent shock waves through science publishing.

Smits has spent decades pulling the science-policy strings at the European Commission, and, until his current assignment, had served eight years as the director-general of research. He was ideally connected to begin rallying Europe’s agencies with the idea, dubbed Plan S for ‘science, speed, solution, shock’, as he puts it. As Nature went to press, 16 funders had signed the plan; they require that the results of work they support be made freely available at the time of publication, starting in 2020.

Publishers have been dictating how research is published for decades, Smits says. “Now it is the funders calling the shots, and we will do things differently.”

It’s too early to know what the ultimate impact of Plan S on research publishing will be. Its details are open for consultation, and much might depend on how many other funders adopt the idea — but it will at least improve access to research, says Peter Suber, director of the Harvard Open Access Project and the Harvard Office for Scholarly Communication in Cambridge, Massachusetts. Smits has been overwhelmed with messages of support. But the initiative has also met with resistance: several publishers have said it could put them out of business, and some researchers have said that they don’t want their choice of where to publish to be restricted.

Smits is no stranger to disrupting the status quo in European science. In 2007, he was instrumental in setting up the excellence-focused European Research Council (ERC) funding agency — when, he says, very few member states wanted it. “We had to go country by country to convince people that we needed it,” he says.

Those who have worked with Smits are not surprised by his ability to get consensus on controversial policies. “Robert-Jan has a fantastic memory, of people, events, documents, policies. His networking capacity is spectacular,” says Helga Nowotny, a former president of the ERC.

Smits’ short tenure as open-access tsar is almost over. Next year, he will leave to become chair of the Eindhoven University of Technology in his native Netherlands. “It’s time for me to leave the commission at what I consider my height,” he says.

SOURCE

https://www.nature.com/immersive/d41586-018-07683-5/index.html?utm_source=Nature+Briefing&utm_campaign=2c80f8d674-briefing-dy-20181218&utm_medium=email&utm_term=0_c9dfd39373-2c80f8d674-43323101

Other Related articles published in this Open Access Online Journal include the following:

University of California accounts for nearly 10% of all published research in the United States. It’s also a significant partner of Elsevier, which publishes about 18% of all UC output and collects more than 25% of the university’s $40-million overall subscription budget.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/12/09/university-of-california-accounts-for-nearly-10-of-all-published-research-in-the-united-states-its-also-a-significant-partner-of-elsevier-which-publishes-about-18-of-all-uc-o/

‘Plan S’ of Eleven research funders in Europe will make all scientific works free to read as soon as they are published – New policy if adopted could determine the Future of Global Journal Subscription as doomed

 

 

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/10/01/plan-s-of-eleven-research-funders-in-europe-will-make-all-scientific-works-free-to-read-as-soon-as-they-are-published-new-policy-if-adopted-could-determine-the-future-of-global-jou/

 

https://pharmaceuticalintelligence.com/open-access-scientific-journal/

Three Genres in e-Scientific Publishing AND Three Scientists’ Dilemmas

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/06/28/three-genres-in-e-scientific-publishing-and-three-scientists-dilemmas/

e-Scientific Publishing: The Competitive Advantage of a Powerhouse for Curation of Scientific Findings and Methodology Development for e-Scientific Publishing – LPBI Group, A Case in Point

Author and Editor-in-Chief: Aviva Lev-Ari, PhD RN

https://pharmaceuticalintelligence.com/2017/06/20/e-scientific-publishing-the-competitive-advantage-of-a-powerhouse-for-curation-of-scientific-findings-and-methodology-development-for-e-scientific-publishing-lpbi-group-a-case-in-point/

Innovations in electronic Scientific Publishing (eSP): Case Studies in Marketing eContent, Curation Methodology, Categories of Research Functions, Interdisciplinary conceptual innovations by Cross Section of Categories, Exposure to Frontiers of Science by Real Time Press coverage of Scientific Conferences

Editor-in-Chief http://pharmaceuticalintelligence.comAviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/05/06/case-studies-of-innovations-in-electronic-scientific-publishing-esp-marketing-econtent-curation-methodology-categories-of-research-functions-interdisciplinary-conceptual-innovations-by-cross-sec/

FIVE years of e-Scientific Publishing @pharmaceuticalintellicence.com, Top Articles by Author and by e-Views >1,000, 4/27/2012 to 1/29/2018

Editor-in-Chief: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/04/28/five-years-of-e-scientific-publishing-pharmaceuticalintellicence-com-top-articles-by-author-and-by-e-views-1000-4272012-to-4272017/

 

e-Recognition via Friction-free Collaboration over the Internet: “Open Access to Curation of Scientific Research”

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/03/17/e-recognition-via-friction-free-collaboration-over-the-internet-open-access-to-curation-of-scientific-research/

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Live 2:30-4:30 PM  Mediterranean Diet and Lifestyle: A Symposium on Diet and Human Health:  October 19, 2018

Reporter: Stephen J. Williams, Ph.D.

 

2:30 Mediterranean Diet, Intangible Heritage and Sustainable Tourism?

Prof. Fabio Parasecoli, PhD.

 

 

Nutrition and Food Department, New York University

We focus on more of the cultural aspects and the relevance of this diet to tourism in Italy where there is a high rate of unemployment.  The diet is interesting from a touristic standpoint as the diet have the perspective of the different ingredients inherent in Italy.  The mediterranean diet food pyramid totally different than US.  How do we explain to consumers these medical concepts; for example in China, Germany they are using different ways to explain the benefits of this diet.

A Cultural Formation

  • a way of life, for tourism there is the way of life people want to adopt (easiest way to do this is go to the Mediterranean and learn the lifestyle)
  • so for example Olive Garden for marketing purposes sent a few chefs for half a day training so the image of learning to cook in the mediterranean diet style can be very powerful communicative tool
  • 2003 UNESCO Convention for Safeguarding the Culturing Heritage: protecting landscapes but then decided to protect other intangible heritage like oral, language, oral traditions like transmitting recipes, social and festive events (how do we cook how do we grow tomatoes, wheat etc)
  • UNESCO: promoted France Gastronomic, Mediterranean Diet, and traditional Mexican Cuisine (Mayan)
  • defined Greece, Italy, Morroco then included Cyprus Crotia and Portugal in the Mediterranean diet
  • has it been used for promotion: no UNESCO did not use this since does not safeguard the culture
  • (gastrodiplomacy); like Korea and kimchie; included in the list of cultural cuisine but can create tourist bubbles as you tourism places like hotels don’t always use; for reasons of economy or safety or accessibility , local food
  • Centrality of Territorio:  food consumed from tourist should come from the area

Sustainable Tourism: a form of tourism where have the intention to get to know the place;

have to think in three ways

  1. environmental
  2. social
  3. cultural

how do we make a circular economy so no waste; for example certain companies using food waste to make other products

Tourism clusters made of many groups; he is working on a way to jump start these networks in Nigeria;

Sustainable Food Supply Chain Tourism can be used as way to engage people and promote the diet

Question: are there regions where people are not adopting the diet because of taste, preferences

Yes there is always a problem with accessibility, affordability, trade issues and regional acceptance. For instance in Australia a big push back against the Mediterranean diet.  Medical professionals need to work with communication experts and media experts in developing ways to communicate the benefits since “no one wants to be preached at” and “as economies get richer people want to be more modern and try new things”

In Nigeria we are working with many different industries like transportation, engineers, the IT industry and chefs to build a scalable model

 

3.00 Italy as a Case Study: Increasing Students’ Level of Awareness of the Historical, Cultural, Political and Culinary Significance of Food

Prof. Lisa Sasson

Nutrition and Food Department, New York University

Started a program at NYU to understand food  from a nutritionist and historical point of view as a cultural heritage in Italy, but when students came back students mentioned it changed their food shopping habits

they described diet as wine, pasta, and olive oil

Artisional Production:  understanding the taste and flavor; she wanted them to learn about the food culture and educate their tastes

Food Memories: how we pass on recipes and food aromas, food tastes.  The students were experienced food in a unique way for the first time, experiencing what cheese, quality oil other foods when fresh tastes like.  Artisional foods may be expensive but need only a little of it because the tastes and flavors are so potent due to the phytochemicals

Within six months students:

  1. increased consumption of weekly wine consumption with meals
  2. increased consuming satisfying meals
  3. increased time consuming meals

In the womb the fetus is actually acquiring sense of taste (amniotic fluid changes with mother diet; can detect flavor chemicals)

Student Perceptions after a study Abroad Program

  • eating foods local and seasonal
  • replacing butter with quality olive oil
  • using herbs
  • very little sugar
  • unsweetened beverages
  • limiting red meats
  • fish a couple of times a week
  • dairy in moderation
  • no processed foods

Eating and Dining for Americans is a Challenge:  The students ate well and satisfying meals but ate alot but did not gain weight

3:30 Italian Migration and Global Diaspora

Dr. Vincenzo Milione, PhD

Director of Demographics Studies, Calandra Institute, City University of New York

for a PDF of this presentation please click heresbarro handout.

Dr. Millione used the U.S. Census Bureau Data to estimate the growth of the Italian diaspora descendants in host countries in the Americas and to determine the mixed global ancestry of Italian descendants.

  • Italian emigration to the US happened in two waves
  1.            Wave 1: early 1900 peaking between 1901 and 1911 (turn of century)
  2.            Wave 2: 1951-1971 (post WWII)

This pattern was similar between North and South America although South American had first Italian immigration; in 1860 we got rid of slavery so many jobs not filled new orleans

Developing a mathematical model of Italian diaspora: the model is centered on the host country population dynamics but descendants are separated into first generation and multi generation

Model dependent on:

  • birth and death rates
  • first generation population growth
  • multi generational population growth
  • emigration from host country over time

He was able to calculate an indices he termed Year of Italianization Change (YIC): the year the growth of the multi generation supercedes the first generation immigrant population 

Country Year of Italianlization Change (YIC)
Brazil 1911
Uruguay 1915
Argentina 1918
USA 1936
Venezuela 1963
Canada 1968
Australia 1988

 

note: as a result there is an increasing loss of language and traditional customs with host country cultural adaptation among the native born descendants

In addition, over the last 20 years Italian-American population growth demonstrates that Italian-American self-identity in the United States has increased.  The census data identified two ancestries of the respondent.  In mixed ancestry Italian-American respondents to the extent they identify Italian first demonstrating the strong Italian-American identity.

The foreign born Italian Americans mirror the immigration pattern of Italian immigration from Italy until 1980 where more Italian Americans self identify as foreign born in other countries and not in Italy

Summary

  • over 5 million Italians have emigrated from Italy from 1980 to present
  • most went to North and South America but many went to other global countries
  • the Italian immigration to the different countries in the Americas varies over the period of mass emigration when the growth of multi generational Italian descendants is greater then first generation Italians (Year of Italianization Change) goes from 1911 in Brazil to 1988 in Australia
  • Immigrants to the USA was not just from Italy but from almost all nations globally over all geographical continents
  • Italina immigrants descendants greatly grew after 1930 with appreciable increase with other ethnicities such that 61% of Italian Americans are mixed ancestry in 2014: to date mixed ancestry represents 98% of Italian Americans
  • younger italian americans more likely to have mixed ancestry with Central and South America, Asian and African ethnicities

over time during immigration eating habits has changed but more research is needed if and how the italian recipes and diet has changed as well

 

4:15 Conclusions

Prof. Antonio Giordano, MD, PhD.

To follow or Tweet on Twitter please use the following handles (@) and hashtags (#):

@ handles


@S_H_R_O 

@SbarroHealth

@Pharma_BI 

@ItalyinPhilly

@WHO_Europe

@nutritionorg

# hashtags


#healthydiet

#MediterraneanDiet

#health

#nutrition

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Announcement 11AM- 5PM: Live Conference Coverage  from Mediterranean Diet and Lifestyle: A Symposium on Diet and Human Health @S.H.R.O. and Temple University October 19, 2018

Reporter: Stephen J. Williams, Ph.D.

 

 The Sbarro Health Research Organization, in collaboration with the Consulate General of Italy in Philadelphia will sponsor a symposium on the Mediterranean Diet and Human Health on October 19, 2018 at Temple University in Philadelphia, PA.  This symposium will discuss recent finding concerning the health benefits derived from a Mediterranean-style diet discussed by the leaders in this field of research.

Mediterranean Diet

The description of the Mediterranean Diet stems from the nutritionist Ancel Keys, who in 1945, in the wake of the US Fifth Army, landed in Southern Italy, where he observed one of the highest concentrations of centenarians in the world. He also noticed that cardiovascular diseases, widespread in the USA, were less frequent there. In particular, among the Southern Italians, the prevalence of “wellness” diseases such as hypertension and diabetes mellitus, was particularly associated with fat consumption, suggesting that the main factor responsible for the observations was the type of diet traditionally consumed among people facing the Mediterranean Sea, which is low in animal fat, as opposed to the Anglo-Saxon diet. The link between serum cholesterol and coronary heart disease mortality was subsequently demonstrated by the Seven Countries Study. Later, the concept of Mediterranean Diet was extended to a diet rich in fruits, vegetables, legumes, whole grains, fish and olive oil as the main source of lipid, shared among people living in Spain, Greece, Southern Italy and other countries facing the Mediterranean basin …

Prof. Antonino De Lorenzo, MD, PhD.

   

 

The Symposium will be held at:

Biolife Science Building, Room 234

Temple University, 1900 North 12th street

Philadelphia, PA 19122

 

For further information, please contact:

Ms. Marinela Dedaj – Sbarro Institute,  Office #: 215-204-9521

 

11:00 Welcome

Prof. Antonio Giordano, MD, PhD.

Director and President of the Sbarro Health Research Organization, College of Science and Technology, Temple University

 

Greetings

Fucsia Nissoli Fitzgerald

Deputy elected in the Foreign Circumscription – North and Central America Division

 

Consul General, Honorable Pier Attinio Forlano

General Consul of Italy in Philadelphia

 

11:30 The Impact of Environment and Life Style in Human Disease

Prof. Antonio Giordano MD, PhD.

 

12.00 The Italian Mediterranean Diet as a Model of Identity of a People with a Universal Good to Safeguard Health?

Prof. Antonino De Lorenzo, MD, PhD.

Director of the School of Specialization in Clinical Nutrition, University of Rome “Tor Vergata”

 

12:30 Environment and Health

Dr. Iris Maria Forte, PhD.

National Cancer Institute “Pascale” Foundation | IRCCS · Department of Research, Naples, Italy

 

13:00 Lunch

 

2:30 Mediterranean Diet, Intangible Heritage and Sustainable Tourism?

Prof. Fabio Parasecoli, PhD.

Nutrition and Food Department, New York University

 

3.00 Italy as a Case Study: Increasing Students’ Level of Awareness of the Historical, Cultural, Political and Culinary Significance of Food

Prof. Lisa Sasson

Nutrition and Food Department, New York University

 

3:30 Italian Migration and Global Diaspora

Dr. Vincenzo Milione, PhD

Director of Demographics Studies, Calandra Institute, City University of New York

 

4:00 Pasta Arte: New Model of Circular Agricultural Economy: When an Innovated Tradition Takes Care of You and of the Environment

Dr. Massimo Borrelli

CEO and Founder of Arte

 

4:15 Conclusions

Prof. Antonio Giordano, MD, PhD.

 

Coordinator of the Symposium, Dr. Alessandra Moia, PhD.

 

Prof. Antonio Giordano, MD, PhD.

Professor of Molecular Biology at Temple University in Philadelphia, PA where he is also Director of the Sbarro Institute for Cancer Research and Molecular Medicine. He is also Professor of Pathology at the University of Siena, Italy. He has published over 500 articles, received over 40 awards for his contributions to cancer research and is the holder of 17 patents.

 

Prof. Antonino De Lorenzo, MD, PhD.

Full Professor of Human Nutrition and Director of the Specialization School in Food Science at the University of Rome “Tor Vergata”. He is the Coordinator of the Specialization Schools in Food Science at the National University Council and Coordinator of the PhD. School of “Applied Medical-Surgical Sciences” Director of UOSD “Service of Clinical Nutrition, Parenteral Therapy and Anorexia”. He also serves as President of “Istituto Nazionale per la Dieta Mediterranea e la Nutrigenomica”.

 

Dr. Iris Maria Forte, PhD.

Iris Maria Forte is an oncology researcher of INT G. Pascale Foundation of Naples, Italy. She majored in Medical Biotechnology at the “Federico II” University of Naples, earned a PhD. in “Oncology and Genetics” at the University of Siena in 2012 and a Master of II level in “Environment and Cancer” in 2014. Iris Maria Forte has worked with Antonio Giordano’s group since 2008 and her research interests include both molecular and translational cancer research. She published 21 articles mostly focused in understanding the molecular basis of human cancer. She worked on different kinds of human solid tumors but her research principally focused on pleural mesothelioma and on cell cycle deregulation in cancer.

 

Prof. Fabio Parasecoli, PhD.

Professor in the Department of Nutrition and Food Studies. He has a Doctorate in Agricultural Sciences (Dr.sc.agr.) from Hohenheim University, Stuttgart (Germany), MA in Political Sciences from the Istituto Universitario Orientale, Naples (Italy), BA/MA in Modern Foreign Languages and Literature from the Università La Sapienza, Rome (Italy). His research explores the intersections among food, media, and politics. His most recent projects focus on Food Design and the synergies between Food Studies and design.

 

Prof. Lisa Sasson, MS

Dietetic Internship Director and a Clinical Associate Professor in the department. She has interests in dietetic education, weight and behavior management, and problem-based learning. She also is a private practice nutritionist with a focus on weight management. She serves as co-director of the Food, Nutrition and Culture program in Florence Italy, the New York State Dietetic Association and the Greater New York Dietetic Association (past president and treasurer).

 

Dr. Vincenzo Milione, PhD.

Director of Demographic Studies for The John D. Calandra Italian American Institute, Queens College, City University of New York. He has conducted social science research on Italian Americans. His research has included the educational and occupational achievements; Italian language studies at the elementary and secondary levels, high school non-completion rates; negative media portrayals of ethnic populations including migration studies and global diaspora.

 

Dr. Massimo Borrelli

Agricultural entrepreneur, Manager of the Italian Consortium for Biogas (CIB) and delegate for the Bioeconomy National Department of Confagricoltura. He developed A.R.T.E based on a model of agricultural circular economy, beginning and ending in the ground. He constructed the first biogas plant in the territory creating a new way to make agriculture, investing in research and development, experimentation and most of all, in people. In a few short years, he succeeded to close the production chain producing goods characterized by their high quality and usage of renewable energy.

 

Dr. Alessandra Moia, PhD.

Vice-President for Institutional and International Relations of the Istituto Nazionale per la Dieta Mediterranea e la Nutrigenomica (I.N.D.I.M.). Has managed relations with the academic institutions to increase awareness and develops projects for the diffusion of the Mediterranean Diet. She served as Director of Finance for the National Institute of Nutrition, for the Ministry of Agriculture and Forestry.

 

About the Sbarro Health Research Organization

The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org

To follow or Tweet on Twitter please use the following handles (@) and hashtags (#):

@ handles


@S_H_R_O 

@SbarroHealth

@Pharma_BI 

@ItalyinPhilly

@WHO_Europe

@nutritionorg

# hashtags


#healthydiet

#MediterraneanDiet

#health

#nutrition

Please see related articles on Live Coverage of Previous Meetings on this Open Access Journal

Real Time Conference Coverage for Scientific and Business Media: Unique Twitter Hashtags and Handles per Conference Presentation/Session

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Tweets Impression Analytics, Re-Tweets, Tweets and Likes by @AVIVA1950 and @pharma_BI for 2018 BioIT, Boston, 5/15 – 5/17, 2018

BIO 2018! June 4-7, 2018 at Boston Convention & Exhibition Center

LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

HUBweek 2018, October 8-14, 2018, Greater Boston – “We The Future” – coming together, of breaking down barriers, of convening across disciplinary lines to shape our future

 

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Thriving at the Survival Calls during Careers in the Digital Age – An AGE like no Other, also known as, DIGITAL

Author and Curator: Aviva Lev-Ari, PhD, RN

 

The source for the inspiration to write this curation is described in

Survival Calls during Careers in the Digital Age

https://pharmaceuticalintelligence.com/2018/06/13/survival-calls-during-careers-in-the-digital-age/

 

In this curation, I present the following concepts in three parts:

  1. Part 1: Authenticity of Careers in the Digital Age: In Focus, the BioTechnology Sector
  2. Part 2: Top 10 books to help you survive the Digital Age

  3. Part 3: A case study on Thriving at the Survival Calls during Careers in the Digital Age: Aviva Lev-Ari, UCB, PhD’83; HUJI, MA’76 

 

Part 1: Authenticity of Careers in the Digital Age: 

In Focus, the BioTechnology Sector

 

Lisa LaMotta, Senior Editor, BioPharma Dive wrote in Conference edition | June 11, 2018

Unlike that little cancer conference in Chicago last week, the BIO International convention is not about data, but about the people who make up the biopharma industry.

The meeting brings together scientists, board members, business development heads and salespeople, from the smallest virtual biotechs to the largest of pharmas. It allows executives at fledgling biotechs to sit at the same tables as major decision-makers in the industry — even if it does look a little bit like speed dating.

But it’s not just a partnering meeting.

This year’s BIO also sought to shine a light on pressing issues facing the industry. Among those tackled included elevating the discussion on gender diversity and how to bring more women to the board level; raising awareness around suicide and the need for more mental health treatments; giving a voice to patient advocacy groups; and highlighting the need for access to treatments in developing nations.

Four days of meetings and panel discussions are unlikely to move the needle for many of these challenges, but debate can be the first step toward progress.

I attended the meetings on June 4,5,6, 2018 and covered in Real Time the sessions I attended. On the link below, Tweets, Re-Tweets and Likes mirrors the feelings and the opinions of the attendees as expressed in real time using the Twitter.com platform. This BioTechnology events manifested the AUTHENTICITY of Careers in the Digital Age – An AGE like no Other, also known as, DIGITAL.

The entire event is covered on twitter.com by the following hash tag and two handles:

 

I covered the events on two tracks via two Twitter handles, each handle has its own followers:

The official LPBI Group Twitter.com account

The Aviva Lev-Ari, PhD, RN Twitter.com account

Track A:

  • Original Tweets by @Pharma_BI and by @AVIVA1950 for #BIO2018 @IAmBiotech @BIOConvention – BIO 2018, Boston, June 4-7, 2018, BCEC

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/06/11/original-tweets-by-pharma_bi-and-by-aviva1950-from-bio2018-iambiotech-bioconvention-bio-2018-boston-june-4-7-2018-bcec/

 

  • Reactions to Original Tweets by @Pharma_BI and by @AVIVA1950 from #BIO2018

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/06/12/reactions-to-original-tweets-by-pharma_bi-and-by-aviva1950-from-bio2018/

Track B:

  • Re-Tweets and Likes by @Pharma_BI and by @AVIVA1950 from #BIO2018 @IAmBiotech @BIOConvention – BIO 2018, Boston, June 4-7, 2018, BCEC

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/06/11/re-tweets-and-likes-by-pharma_bi-aviva1950-from-bio2018-iambiotech-bioconvention-bio-2018-boston-june-4-7-2018-bcec/

Part 2: Top 10 books to help you survive the digital age

From Philip K Dick’s obtuse robots to Mark O’Connell’s guide to transhumanism, novelist Julian Gough picks essential reading for a helter skelter world

Here are 10 of the books that did help me [novelist Julian Gough]: they might also help you understand, and survive, our complicated, stressful, digital age.

  1. Marshall McLuhan Unbound by Marshall McLuhan (2005)
    The visionary Canadian media analyst predicted the internet, and coined the phrase the Global Village, in the early 1960s. His dense, complex, intriguing books explore how changes in technology change us. This book presents his most important essays as 20 slim pamphlets in a handsome, profoundly physical, defiantly non-digital slipcase.
  2. Ubik by Philip K Dick (1969)
    Pure pulp SF pleasure; a deep book disguised as a dumb one. Dick shows us, not a dystopia, but a believably shabby, amusingly human future. The everyman hero, Joe Chip, wakes up and argues with his robot toaster, which refuses to toast until he sticks a coin in the slot. Joe can’t do this, because he’s broke. He then has a stand-up row with his robot front door, which won’t open, because he owes it money too … Technology changes: being human, and broke, doesn’t. Warning: Dick wrote Ubik at speed, on speed. But embedded in the pulpy prose are diamonds of imagery that will stay with you for ever.
  3. The Singularity Is Near by Ray Kurzweil (2005)
    This book is what Silicon Valley has instead of a bible. It’s a visionary work that predicts a technological transformation of the world in our lifetime. Kurzweil argues that computer intelligence will soon outperform human thought. We will then encode our minds, upload them, and become one with our technology, achieving the Singularity. At which point, the curve of technological progress starts to go straight up. Ultimately – omnipotent, no longer mortal, no longer flesh – we transform all the matter in the universe into consciousness; into us.
  4. To Be a Machine by Mark O’Connell (2017)
    This response to Kurzweil won this year’s Wellcome prize. It’s a short, punchy tour of transhumanism: the attempt to meld our minds with machines, to transcend biology and escape death. He meets some of the main players, and many on the fringes, and listens to them, quizzically. It is a deliberately, defiantly human book, operating in that very modern zone between sarcasm and irony, where humans thrive and computers crash.
  5. A Visit from the Goon Squad by Jennifer Egan (2011)
    This intricately structured, incredibly clever novel moves from the 60s right through to a future maybe 15 years from now. It steps so lightly into that future you hardly notice the transition. It has sex and drugs and rock’n’roll, solar farms, social media scams and a stunningly moving chapter written as a PowerPoint presentation. It’s a masterpiece. Life will be like this.
  6. What Technology Wants by Kevin Kelly (2010)
    Kelly argues that we scruffy biological humans are no longer driving technological progress. Instead, the technium, “the greater, global, massively interconnected system of technology vibrating around us”, is now driving its own progress, faster and faster, and we are just caught up in its slipstream. As we accelerate down the technological waterslide, there is no stopping now … Kelly’s vision of the future is scary, but it’s fun, and there is still a place for us in it.
  7. The Meme Machine by Susan Blackmore (1999)
    Blackmore expands powerfully and convincingly on Richard Dawkins’s original concept of the meme. She makes a forceful case that technology, religion, fashion, art and even our personalities are made of memes – ideas that replicate, mutate and thus evolve over time. We are their replicators (if you buy my novel, you’ve replicated its memes); but memes drive our behaviour just as we drive theirs. It’s a fascinating book that will flip your world upside down.
  8. Neuromancer by William Gibson (1984)
    In the early 1980s, Gibson watched kids leaning into the screens as they played arcade games. They wanted to be inside the machines, he realised, and they preferred the games to reality. In this novel, Gibson invented the term cyberspace; sparked the cyberpunk movement (to his chagrin); and vividly imagined the jittery, multi-screened, anxious, technological reality that his book would help call into being.
  9. You Are Not a Gadget: A Manifesto by Jaron Lanier (2010)
    Lanier, an intense, brilliant, dreadlocked artist, musician and computer scientist, helped to develop virtual reality. His influential essay Digital Maoism described early the downsides of online collective action. And he is deeply aware that design choices made by (mainly white, young, male) software engineers can shape human behaviour globally. He argues, urgently, that we need to question those choices, now, because once they are locked in, all of humanity must move along those tracks, and we may not like where they take us. Events since 2010 have proved him right. His manifesto is a passionate argument in favour of the individual voice, the individual gesture.
  10. All About Love: New Visions by bell hooks (2000)
    Not, perhaps, an immediately obvious influence on a near-future techno-thriller in which military drones chase a woman and her son through Las Vegas. But hooks’s magnificent exploration and celebration of love, first published 18 years ago, will be far more useful to us, in our alienated digital future, than the 10,000 books of technobabble published this year. All About Love is an intensely practical roadmap, from where we are now to where we could be. When Naomi and Colt find themselves on the run through a militarised American wilderness of spirit, when GPS fails them, bell hooks is their secret guide.

SOURCE

https://www.theguardian.com/books/2018/may/30/top-10-books-to-help-you-survive-the-digital-age?utm_source=esp&utm_medium=Email&utm_campaign=Bookmarks+-+Collections+2017&utm_term=277690&subid=25658468&CMP=bookmarks_collection

Part 3: A case study on Thriving at the Survival Calls during Careers in the Digital Age:  Aviva Lev-Ari, UCB, PhD’83; HUJI, MA’76

 

On June 10, 2018

 

Following, is a case study about an alumna of HUJI and UC, Berkeley as an inspirational role model. An alumna’s profile in context of dynamic careers in the digital age. It has great timeliness and relevance to graduate students, PhD level at UC Berkeley and beyond, to all other top tier universities in the US and Europe. As presented in the following curations:

Professional Self Re-Invention: From Academia to Industry – Opportunities for PhDs in the Business Sector of the Economy

https://pharmaceuticalintelligence.com/2018/05/22/professional-self-re-invention-from-academia-to-industry-opportunities-for-phds-in-the-business-sector-of-the-economy/

 

Pioneering implementations of analytics to business decision making: contributions to domain knowledge conceptualization, research design, methodology development, data modeling and statistical data analysis: Aviva Lev-Ari, UCB, PhD’83; HUJI, MA’76 

https://pharmaceuticalintelligence.com/2018/05/28/pioneering-implementations-of-analytics-to-business-decision-making-contributions-to-domain-knowledge-conceptualization-research-design-methodology-development-data-modeling-and-statistical-data-a/

 

This alumna is Editor-in-Chief of a Journal that has other 173 articles on Scientist: Career Considerations 

https://pharmaceuticalintelligence.com/category/scientist-career-considerations/

 

In a 5/22/2018 article, Ways to Pursue Science Careers in Business After a PhD by Ankita Gurao,

https://bitesizebio.com/38498/ways-to-pursue-the-business-of-science-after-a-ph-d/?utm_source=facebook&utm_medium=social&utm_campaign=SocialWarfare

Unemployment figures of PhDs by field of science are included, Ankita Gurao identifies the following four alternative careers for PhDs in the non-academic world:

  1. Science Writer/Journalist/Communicator
  2. Science Management
  3. Science Administration
  4. Science Entrepreneurship

My career, as presented in Reflections on a Four-phase Career: Aviva Lev-Ari, PhD, RN, March 2018

https://pharmaceuticalintelligence.com/2018/03/06/reflections-on-a-four-phase-career-aviva-lev-ari-phd-rn-march-2018/

has the following phases:

  • Phase 1: Research, 1973 – 1983
  • Phase 2: Corporate Applied Research in the US, 1985 – 2005
  • Phase 3: Career Reinvention in Health Care, 2005 – 2012
  • Phase 4: Electronic Scientific Publishing, 4/2012 to present

These four phases are easily mapped to the four alternative careers for PhDs in the non-academic world. One can draw parallel lines between the four career opportunities A,B,C,D, above, and each one of the four phases in my own career.

Namely, I have identified A,B,C,D as early as 1985, and pursued each of them in several institutional settings, as follows:

A. Science Writer/Journalist/Communicator – see link above for Phase 4: Electronic Scientific Publishing, 4/2012 to present 

B. Science Management – see link above for Phase 2: Corporate Applied Research in the US, 1985 – 2005 and Phase 3: Career Reinvention in Health Care, 2005 – 2012 

C. Science Administration – see link above for Phase 2: Corporate Applied Research in the US, 1985 – 2005and Phase 4: Electronic Scientific Publishing, 4/2012 to present 

D. Science Entrepreneurship – see link above for Phase 4: Electronic Scientific Publishing, 4/2012 to present  

Impressions of My Days at Berkeley in Recollections: Part 1 and 2, below.

  • Recollections: Part 1 – My days at Berkeley, 9/1978 – 12/1983 –About my doctoral advisor, Allan Pred, other professors and other peers

https://pharmaceuticalintelligence.com/2018/03/15/recollections-my-days-at-berkeley-9-1978-12-1983-about-my-doctoral-advisor-allan-pred-other-professors-and-other-peer/

  • Recollections: Part 2 – “While Rolling” is preceded by “While Enrolling” Autobiographical Alumna Recollections of Berkeley – Aviva Lev-Ari, PhD’83

https://pharmaceuticalintelligence.com/2018/05/24/recollections-part-2-while-rolling-is-preceded-by-while-enrolling-autobiographical-alumna-recollections-of-berkeley-aviva-lev-ari-phd83/

The topic of Careers in the Digital Age is closely related to my profile, see chiefly: Four-phase Career, Reflections, Recollections Parts 1 & 2 and information from other biographical sources, below.

Other sources for my biography

 

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Curation of selected topics and articles on Role of G-Protein Coupled Receptors in Chronic Disease as supplemental information for #TUBiol3373

Curator: Stephen J. Williams, PhD 

Below is a series of posts and articles related to the role of G protein coupled receptors (GPCR) in various chronic diseases.  This is only a cursory collection and by no means represents the complete extensive literature on pathogenesis related to G protein function or alteration thereof.  However it is important to note that, although we think of G protein signaling as rather short lived, quick, their chronic activation may lead to progression of various disease. As to whether disease onset, via GPCR, is a result of sustained signal, loss of desensitization mechanisms, or alterations of transduction systems is an area to be investigated.

From:

Molecular Pathogenesis of Progressive Lung Diseases

Author: Larry H. Bernstein, MD, FCAP

 

Chronic Obstructive Lung Disease (COPD)

Inflammatory and infectious factors are present in diseased airways that interact with G-protein coupled receptors (GPCRs), such as purinergic receptors and bradykinin (BK) receptors, to stimulate phospholipase C [PLC]. This is followed by the activation of inositol 1,4,5-trisphosphate (IP3)-dependent activation of IP3 channel receptors in the ER, which results in channel opening and release of stored Ca2+ into the cytoplasm. When ER Ca2+ stores are depleted a pathway for Ca2+ influx across the plasma membrane is activated. This has been referred to as “capacitative Ca2+ entry”, and “store-operated calcium entry” (3). In the next step PLC mediated Ca2+ i is mobilized as a result of GPCR activation by inflammatory mediators, which triggers cytokine production by Ca2+ i-dependent activation of the transcription factor nuclear factor kB (NF-kB) in airway epithelia.

 

 

 

In Alzheimer’s Disease

Important Lead in Alzheimer’s Disease Model

Larry H. Bernstein, MD, FCAP, Curator discusses findings from a research team at University of California at San Diego (UCSD) which the neuropeptide hormone corticotropin-releasing factor (CRF) as having an important role in the etiology of Alzheimer’s Disease (AD). CRF activates the CRF receptor (a G stimulatory receptor).  It was found inhibition of the CRF receptor prevented cognitive impairment in a mouse model of AD.  Furthermore researchers at the Flanders Interuniversity Institute for Biotechnology found the loss of a protein called G protein-coupled receptor 3 (GPR3) may lower the amyloid plaque aggregation, resulting in improved cognitive function.  Additionally inhibition of several G-protein coupled receptors alter amyloid precursor processing, providing a further mechanism of the role of GPCR in AD (see references in The role of G protein-coupled receptors in the pathology of Alzheimer’s disease by Amantha Thathiah and Bart De Strooper Nature Reviews Feb 2011; 12: 73-87 and read post).

 

In Cardiovascular and Thrombotic Disease

 

Adenosine Receptor Agonist Increases Plasma Homocysteine

 

and read related articles in curation on effects of hormones on the cardiovascular system at

Action of Hormones on the Circulation

 

In Cancer

A Curated History of the Science Behind the Ovarian Cancer β-Blocker Trial

 

Further curations and references of G proteins and chronic disease can be found at the Open Access journal https://pharmaceuticalintelligence.com using the search terms “GCPR” and “disease” in the Search box in the upper right of the home page.

 

 

 

 

 

 

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Lesson 9 Cell Signaling:  Curations and Articles of reference as supplemental information for lecture section on WNTs: #TUBiol3373

Stephen J. Wiilliams, Ph.D: Curator

The following contain curations of scientific articles from the site https://pharmaceuticalintelligence.com  intended as additional reference material  to supplement material presented in the lecture.

Wnts are a family of lipid-modified secreted glycoproteins which are involved in:

Normal physiological processes including

A. Development:

– Osteogenesis and adipogenesis (Loss of wnt/β‐catenin signaling causes cell fate shift of preosteoblasts from osteoblasts to adipocytes)

  – embryogenesis including body axis patterning, cell fate specification, cell proliferation and cell migration

B. tissue regeneration in adult tissue

read: Wnt signaling in the intestinal epithelium: from endoderm to cancer

And in pathologic processes such as oncogenesis (refer to Wnt/β-catenin Signaling [7.10]) and to your Powerpoint presentation

 

The curation Wnt/β-catenin Signaling is a comprehensive review of canonical and noncanonical Wnt signaling pathways

 

To review:

 

 

 

 

 

 

 

 

 

 

 

Activating the canonical Wnt pathway frees B-catenin from the degradation complex, resulting in B-catenin translocating to the nucleus and resultant transcription of B-catenin/TCF/LEF target genes.

Fig. 1 Canonical Wnt/FZD signaling pathway. (A) In the absence of Wnt signaling, soluble β-catenin is phosphorylated by a degradation complex consisting of the kinases GSK3β and CK1α and the scaffolding proteins APC and Axin1. Phosphorylated β-catenin is targeted for proteasomal degradation after ubiquitination by the SCF protein complex. In the nucleus and in the absence of β-catenin, TCF/LEF transcription factor activity is repressed by TLE-1; (B) activation of the canonical Wnt/FZD signaling leads to phosphorylation of Dvl/Dsh, which in turn recruits Axin1 and GSK3β adjacent to the plasma membrane, thus preventing the formation of the degradation complex. As a result, β-catenin accumulates in the cytoplasm and translocates into the nucleus, where it promotes the expression of target genes via interaction with TCF/LEF transcription factors and other proteins such as CBP, Bcl9, and Pygo.

NOTE: In the canonical signaling, the Wnt signal is transmitted via the Frizzled/LRP5/6 activated receptor to INACTIVATE the degradation complex thus allowing free B-catenin to act as the ultimate transducer of the signal.

Remember, as we discussed, the most frequent cancer-related mutations of WNT pathway constituents is in APC.

This shows how important the degradation complex is in controlling canonical WNT signaling.

Other cell signaling systems are controlled by protein degradation:

A.  The Forkhead family of transcription factors

Read: Regulation of FoxO protein stability via ubiquitination and proteasome degradation

B. Tumor necrosis factor α/NF κB signaling

Read: NF-κB, the first quarter-century: remarkable progress and outstanding questions

1.            Question: In cell involving G-proteins, the signal can be terminated by desensitization mechanisms.  How is both the canonical and noncanonical Wnt signal eventually terminated/desensitized?

We also discussed the noncanonical Wnt signaling pathway (independent of B-catenin induced transcriptional activity).  Note that the canonical and noncanonical involve different transducers of the signal.

Noncanonical WNT Signaling

Note: In noncanonical signaling the transducer is a G-protein and second messenger system is IP3/DAG/Ca++ and/or kinases such as MAPK, JNK.

Depending on the different combinations of WNT ligands and the receptors, WNT signaling activates several different intracellular pathways  (i.e. canonical versus noncanonical)

 

In addition different Wnt ligands are expressed at different times (temporally) and different cell types in development and in the process of oncogenesis. 

The following paper on Wnt signaling in ovarian oncogenesis shows how certain Wnt ligands are expressed in normal epithelial cells but the Wnt expression pattern changes upon transformation and ovarian oncogenesis. In addition, differential expression of canonical versus noncanonical WNT ligands occur during the process of oncogenesis (for example below the authors describe the noncanonical WNT5a is expressed in normal ovarian  epithelia yet WNT5a expression in ovarian cancer is lower than the underlying normal epithelium. However the canonical WNT10a, overexpressed in ovarian cancer cells, serves as an oncogene, promoting oncogenesis and tumor growth.

Wnt5a Suppresses Epithelial Ovarian Cancer by Promoting Cellular Senescence

Benjamin G. Bitler,1 Jasmine P. Nicodemus,1 Hua Li,1 Qi Cai,2 Hong Wu,3 Xiang Hua,4 Tianyu Li,5 Michael J. Birrer,6Andrew K. Godwin,7 Paul Cairns,8 and Rugang Zhang1,*

A.           Abstract

Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy in the US. Thus, there is an urgent need to develop novel therapeutics for this disease. Cellular senescence is an important tumor suppression mechanism that has recently been suggested as a novel mechanism to target for developing cancer therapeutics. Wnt5a is a non-canonical Wnt ligand that plays a context-dependent role in human cancers. Here, we investigate the role of Wnt5a in regulating senescence of EOC cells. We demonstrate that Wnt5a is expressed at significantly lower levels in human EOC cell lines and in primary human EOCs (n = 130) compared with either normal ovarian surface epithelium (n = 31; p = 0.039) or fallopian tube epithelium (n = 28; p < 0.001). Notably, a lower level of Wnt5a expression correlates with tumor stage (p = 0.003) and predicts shorter overall survival in EOC patients (p = 0.003). Significantly, restoration of Wnt5a expression inhibits the proliferation of human EOC cells both in vitro and in vivo in an orthotopic EOC mouse model. Mechanistically, Wnt5a antagonizes canonical Wnt/β-catenin signaling and induces cellular senescence by activating the histone repressor A (HIRA)/promyelocytic leukemia (PML) senescence pathway. In summary, we show that loss of Wnt5a predicts poor outcome in EOC patients and Wnt5a suppresses the growth of EOC cells by triggering cellular senescence. We suggest that strategies to drive senescence in EOC cells by reconstituting Wnt5a signaling may offer an effective new strategy for EOC therapy.

Oncol Lett. 2017 Dec;14(6):6611-6617. doi: 10.3892/ol.2017.7062. Epub 2017 Sep 26.

Clinical significance and biological role of Wnt10a in ovarian cancer. 

Li P1Liu W1Xu Q1Wang C1.

Ovarian cancer is one of the five most malignant types of cancer in females, and the only currently effective therapy is surgical resection combined with chemotherapy. Wnt family member 10A (Wnt10a) has previously been identified to serve an oncogenic function in several tumor types, and was revealed to have clinical significance in renal cell carcinoma; however, there is still only limited information regarding the function of Wnt10a in the carcinogenesis of ovarian cancer. The present study identified increased expression levels of Wnt10a in two cell lines, SKOV3 and A2780, using reverse transcription-polymerase chain reaction. Functional analysis indicated that the viability rate and migratory ability of SKOV3 cells was significantly inhibited following Wnt10a knockdown using short interfering RNA (siRNA) technology. The viability rate of SKOV3 cells decreased by ~60% compared with the control and the migratory ability was only ~30% of that in the control. Furthermore, the expression levels of β-catenin, transcription factor 4, lymphoid enhancer binding factor 1 and cyclin D1 were significantly downregulated in SKOV3 cells treated with Wnt10a-siRNA3 or LGK-974, a specific inhibitor of the canonical Wnt signaling pathway. However, there were no synergistic effects observed between Wnt10a siRNA3 and LGK-974, which indicated that Wnt10a activated the Wnt/β-catenin signaling pathway in SKOV3 cells. In addition, using quantitative PCR, Wnt10a was overexpressed in the tumor tissue samples obtained from 86 patients with ovarian cancer when compared with matching paratumoral tissues. Clinicopathological association analysis revealed that Wnt10a was significantly associated with high-grade (grade III, P=0.031) and late-stage (T4, P=0.008) ovarian cancer. Furthermore, the estimated 5-year survival rate was 18.4% for patients with low Wnt10a expression levels (n=38), whereas for patients with high Wnt10a expression (n=48) the rate was 6.3%. The results of the present study suggested that Wnt10a serves an oncogenic role during the carcinogenesis and progression of ovarian cancer via the Wnt/β-catenin signaling pathway.

Targeting the Wnt Pathway includes curations of articles related to the clinical development of Wnt signaling inhibitors as a therapeutic target in various cancers including hepatocellular carcinoma, colon, breast and potentially ovarian cancer.

 

2.         Question: Given that different Wnt ligands and receptors activate different signaling pathways, AND  WNT ligands  can be deferentially and temporally expressed  in various tumor types and the process of oncogenesis, how would you approach a personalized therapy targeting the WNT signaling pathway?

3.         Question: What are the potential mechanisms of either intrinsic or acquired resistance to Wnt ligand antagonists being developed?

 

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

Targeting the Wnt Pathway [7.11]

Wnt/β-catenin Signaling [7.10]

Cancer Signaling Pathways and Tumor Progression: Images of Biological Processes in the Voice of a Pathologist Cancer Expert

e-Scientific Publishing: The Competitive Advantage of a Powerhouse for Curation of Scientific Findings and Methodology Development for e-Scientific Publishing – LPBI Group, A Case in Point 

Electronic Scientific AGORA: Comment Exchanges by Global Scientists on Articles published in the Open Access Journal @pharmaceuticalintelligence.com – Four Case Studies

 

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