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Google’s Driverless Cars – The Competition is the Self Driving Vehicles: A New Generation of Unmanned Jeeps

June 3, 2014 by 2012pharmaceutical

Google’s Driverless Cars – The Competition is the Self Driving Vehicles: A New Generation of Unmanned Jeeps

Reporter: Aviva Lev-Ari, PhD, RN

As Google dreams of driverless cars, IDF deploys them

Self driving vehicles are not new for the Israeli army, and a new generation of unmanned jeeps is set to debut

BY DAVID SHAMAH June 3, 2014, 4:00 pm 

A Guardium UGV on patrol along the Gaza border fence (Photo credit: Courtesy IDF)

A Guardium UGV on patrol along the Gaza border fence (Photo credit: Courtesy IDF)

Google isn’t the only high-tech group working to produce driverless vehicles. While the Silicon Valley tech giant is still experimenting with driverless technology for use by civilians, the IDF has been using unmanned vehicles for at least five years to protect Israelis.

The army announced this week a program to upgrade its driverless fleet, to include vehicles that can scout areas before soldiers move in and warn of possible dangers before they arrive, and vehicles that will safely and autonomously transport weapons and equipment to soldiers already in the field.

It is unclear when the Google driverless cars will be on the market, with industry pundits believing it will be at least three years, if not longer. The IDF, using Israeli technology, much of it developed in the army itself, has deployed unmanned vehicles for some time now. “Vehicles without drivers are nothing new for the Israeli military,” according to the IDF spokesperson. “They have been used extensively in small devices that enter buildings and large cars equipped with 360-degree cameras.” Among the unmanned vehicles already in use is the Guardium Unmanned Ground Vehicle (UGV), which patrols the Gaza fence around the clock. According to the spokesperson, “the IDF’s ground forces plan to expand its use of these tools, as experts invent new vehicles based on creative and cutting-edge designs.”

Three new vehicles will enter into army service during the coming two years, among them the Loyal Partner, an armor patrol carrier (APC) Hummer-type vehicle that will carry weapons and devices to soldiers in the field. It is controlled from a nearby base station by joystick and mouse controls, making it capable of traversing rough terrain and able to remain stable while ascending or descending steep hills.

Loyal Partner “will be used as a line of defense for the forces at the front,” said Maj. Lior Trablisi, the head of the IDF’s robot and technology unit. “It will be able to move while identifying bombs and the source of gunfire, able to carry out missions without considerations of risks or manpower. It can remain in the field for long periods of time, carrying out missions precisely and providing a relative advantage to soldiers.”

The Carrier Robot is smaller than the Loyal Partner, but may be just as useful in saving lives, said Trablisi. The robot is lightweight, designed to be carried on the back by soldiers on patrol, and specially designed for exploring the interior of buildings or tunnels constructed by terrorists. The Carrier Robot can be sent into a tunnel to gather intelligence before soldiers enter. It is equipped with cameras, sensors, and a communications system capable of transmitting signals from underground. It is one of the few systems in the world that can do this, said Trablisi.

“The idea is to enter operations with lightweight, portable robots that can function for a number of hours,” said Trablisi. “The device will do things that no human can, such as mapping entire buildings and terror tunnels. The groundbreaking technology will allow soldiers to understand the exact appearance of any structure, helping them avoid the dangers of underground or urban combat.” The system is set to be active by the end of 2015, the army said.

A third system, the Border Protector, was developed specifically to patrol the Gaza border. The vehicle will be able to operate in any kind of weather, operating autonomously along the border fence and transmitting images and data back to headquarters. If anything seems amiss, a battalion of soldiers can be sent in to deal with the problem. Otherwise, soldiers could remain on alert, away from the danger zone.

The new vehicle is planned to replace the Guardium UGV, currently used along the Gaza border. The new system, said Trablisi, can operate for longer periods and contain more and better sensor and communication equipment. “It will be possible to guide the vehicle to all sorts of places without operation rooms nearby,” with operators directing the vehicle from kilometers away. Base stations for the UGV need to be within several hundred meters of the vehicle. The upgrade should enable more units to deploy vehicles more frequently, providing higher levels of security, said Trablisi.

Although IDF brass has been complaining about government budget cuts, which include cancelling exercises for soldiers and pilots for the time being, funds will continue to be pumped into programs for the development of robots, unmanned vehicles and other high-tech soldier substitutes. In the long run, said Trablisi, these technologies will save the army money, because it will be able to cut down on manned patrols.

Far more important, though, are the lives that will be saved by these technologies. Better to risk a robot than to risk a human life, said Trablisi. “A robot doesn’t deal with the same difficulties of lighting, gunfire or breathing [underground],” he said. Robots and unmanned vehicles, he noted, will become “indispensable tools for the surveillance of enemy activities, without putting Israeli forces in danger.”

Click below for a video of the Guardium UGV in action:

 

Read more: As Google dreams of driverless cars, IDF deploys them | The Times of Israel http://www.timesofisrael.com/as-google-dreams-of-driverless-cars-idf-deploys-them/#ixzz33alOWNBq
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Posted in Technology Transfer: Biotech and Pharmaceutical | Leave a Comment »

Endothelial Cell Dysfunction plays a role in the Pathogenesis of Alzheimer’s Disease, Atherosclerosis, Diabetes, and Pulmonary Hypertension: New Research @Cleveland Clinic

June 2, 2014 by 2012pharmaceutical

Endothelial Cell Dysfunction plays a role in the Pathogenesis of Alzheimer’s Disease, Atherosclerosis, Diabetes, and Pulmonary Hypertension: New Research @Cleveland Clinic

Reporter: Aviva Lev-Ari, PhD, RN

Cleveland Clinic: Improving Endothelial Cell Recovery
TAGS:
Cleveland Clinic, Life Sciences, Nature, Theoretical-IP Transfer
STATUS: Awarded  |  ACTIVE SOLVERS: 174  |  POSTED: 11/05/13

 

Endothelial cell dysfunction plays a role in the pathogenesis of Alzheimer’s disease, atherosclerosis, diabetes, and pulmonary hypertension. Research in these areas hinges upon successful isolation and growth of endothelial progenitor cells (EPC). These cells may be obtained directly from diseased tissue or isolated from peripheral blood samples. To maintain maximum viability, EPC must be processed and plated within two hours of a blood draw. The challenge is to identify a method that preserves EPC and allows processing to take place the next day while maintaining the yield and viability of the cells.

This Challenge requires only a written proposal.

 

Source: InnoCentive      Challenge ID: 9933159
Challenge Overview

Pulmonary arterial hypertension (PAH) is a chronic and currently incurable disease that affects the walls of the arteries that carry blood to the lungs. In PAH, these arteries constrict abnormally leading to increased blood pressure and extra strain on the heart. Some forms of PAH are hereditary and research at the Cleveland Clinic focuses on characterizing signaling defects resulting from genetic mutations. Experiments require endothelial progenitor cells (EPC) isolated from peripheral blood samples. The EPC are exquisitely sensitive and must be processed and cultured within two hours of a blood draw, thereby limiting the available patient pool. Cleveland Clinic is searching for a new method to preserve EPC in blood, so that samples can be shipped overnight for processing the next day.

Dr. Micheala Aldred of the Cleveland Clinic Genomic Medicine Institute is a translational genetics researcher with a specific interest in pulmonary arterial hypertension. Cleveland Clinic strives to make scientific advances that will benefit patient care and support outside relationships that promise public benefit.

This is a Theoretical Challenge that requires only a written proposal to be submitted.  The Challenge award will be contingent upon theoretical evaluation of the proposal by the Seeker.

To receive an award, the Solvers must transfer to the Seeker their exclusive Intellectual Property (IP) rights to the solution.  However, the Seeker may be willing to consider a licensing agreement for a partial award if exclusive IP cannot be transferred by the Solver.

SOURCE

 

Posted in Alzheimer's Disease, Atherogenic Processes & Pathology, Cell Biology, Signaling & Cell Circuits, Diabetes Mellitus, Frontiers in Cardiology and Cardiovascular Disorders, Origins of Cardiovascular Disease | Leave a Comment »

CardioMEMS sold to St. Jude Medical: Boston Millennia Partners announced that St. Jude Medical (NYSE: STJ) is acquiring the remaining 81 percent of CardioMEMS, Inc. it does not own for $375 million

June 2, 2014 by 2012pharmaceutical

CardioMEMS sold to St. Jude Medical: Boston Millennia Partners announced that St. Jude Medical (NYSE: STJ) is acquiring the remaining 81 percent of CardioMEMS, Inc. it does not own for $375 million

Reporter: Aviva Lev-Ari,  PhD, RN

 

UPDATED on 6/3/2014

 

Boston Millennia Partners announces the sale of its portfolio company CardioMEMS to St. Jude Medical

Boston, MA – June 3, 2014

Boston Millennia Partners is pleased to announce that St. Jude Medical (NYSE: STJ) is acquiring the remaining 81 percent of CardioMEMS, Inc. it does not own for $375 million.

Dana Callow, Managing General Partner at Boston Millennia Partners, said, “We congratulate the management team of CardioMEMS for the recent FDA approval of the company’s remote heart monitoring device. We agree with the belief of many cardiology experts that the CardioMEMS HF System represents the most significant advancement in the treatment of congestive heart failure in the past twenty years. With the subsequently announced acquisition of CardioMEMS by St. Jude Medical, this device will receive broad distribution and improve the lives of patients worldwide.

The CardioMEMS HF System uses a miniaturized, wireless monitoring sensor that is implanted in the pulmonary artery (PA) during a minimally invasive procedure to directly measure PA pressure. Directly measuring PA pressure via a procedure called a right-heart catheterization is a standard-of-care practice for managing worsening HF in patients who have been hospitalized. The CardioMEMS HF System allows patients to transmit the same information from their homes to their health care providers, allowing for personalized and proactive management to reduce the likelihood of hospitalization. “The approval of the CHAMPION Heart Failure Monitoring System is a significant event for both patients and for those who pay for healthcare. Avoiding unnecessary hospitalizations and reducing the risk of acute decompensation in patients with this chronic disease benefits everyone”, said Pat Fortune, Venture Partner at Boston Millennia Partners.

About CardioMEMS

Headquartered in Atlanta, CardioMEMS is a medical device company that has developed a proprietary wireless sensing and communication technology for the human body. The company’s technology platform is designed to improve the management of severe chronic cardiovascular diseases such as heart failure, aneurysms, and hypertension. The sensors can be permanently implanted into the heart and blood vessels due to their small size, durability and lack of wires and batteries. CardioMEMS developed this technology based on the belief that frequent, on-demand, real-time monitoring of vital information enables proactive patient management leading to fewer hospitalizations, improved patient quality of life, and more efficient and cost-effective health care. CardioMEMS was founded by Jay Yadav, M.D., an interventional cardiologist and entrepreneur. Lead investors in CardioMEMS include Arcapita Ventures, Boston Millennia Partners and Foundation Medical Partners. For more information, please visit http://www.cardiomems.com.

About St. Jude Medical

St. Jude Medical is a global medical device manufacturer dedicated to transforming the treatment of some of the world’s most expensive, epidemic diseases. The company does this by developing cost-effective medical technologies that save and improve lives of patients around the world. Headquartered in St. Paul, Minn., St. Jude Medical has four major clinical focus areas that include cardiac rhythm management, atrial fibrillation, cardiovascular and neuromodulation. For more information, please visit sjm.com.

SOURCE

http://campaign.r20.constantcontact.com/render?ca=a5d4772f-7673-449c-9b09-2bb48d802dc6&c=6407cc90-31f8-11e3-946e-d4ae527b895a&ch=64ad3450-31f8-11e3-959c-d4ae527b895a

FDA News Release

FDA approves first implantable wireless device with remote monitoring to measure pulmonary artery pressure in certain heart failure patients

For Immediate Release

May 28, 2014

Release

The U.S. Food and Drug Administration today approved the CardioMEMS HF System that measures the pulmonary artery (PA) pressures and heart rates of patients with New York Heart Association (NYHA) Class III heart failure who have been hospitalized for heart failure in the previous year. The device allows health care professionals to monitor the condition of their patients remotely.

About 5.8 million people in the United States have heart failure, a condition in which the heart cannot pump enough blood to meet the body’s needs. With proper treatment and lifestyle changes, people with heart failure can live longer and more active lives. The NYHA Functional Classification further defines the extent of heart failure in patients. Patients with Class III heart failure experience marked limitation in physical activity, even during less-than-ordinary activity such as walking short distances.

The CardioMEMS HF System is used by the patient in the home or other remote location. This is the first permanently implantable wireless system intended to provide PA pressure measurements, including systolic, diastolic and mean PA pressures. The PA pressure data are reviewed by physicians who can make decisions regarding the status of the patient and, if necessary, initiate changes in medical therapy, with the goal of  reducing hospitalization due to heart failure.

The system consists of three parts:

  • A battery-free Implantable Sensor/Monitor implanted permanently in the PA;
  • Delivery System, a transvenous catheter designed to deploy the Implantable Sensor, within the distal PA; and
  • CardioMEMS Hospital and Patient Electronics Systems where the Electronics System acquires and processes signals from the Implantable Sensor/Monitor and transfers PA pressure measurements to a secure database.

“Heart failure is one of the most common reasons for hospitalizations for people aged 65 and older,” said Christy Foreman, director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health. “The goal of this first-of-its-kind implantable wireless device with remote monitoring of pulmonary artery pressure is to reduce heart failure-related hospitalizations.”

To support the approval, the company submitted data from its pivotal clinical study. Concerns about the clinical study were discussed at the December 8, 2011 meeting of the Circulatory System Devices Panel of FDA’s Medical Devices Advisory Committee. The company provided additional follow-up data and analyses that were discussed at the October 9, 2013 meeting of the Circulatory System Devices Panel to address these concerns.

The clinical study, in which 550 participants had the device implanted and were randomized into either the control group or investigational group, showed a clinically and statistically significant reduction in heart failure-related hospitalizations for the participants whose doctors had access to pulmonary artery pressure data. Of the participants who had the device implanted (or in whom there was an attempt to implant the device), 98.6 percent were free from device/system-related complications at six months. Of the devices implanted, 100 percent were operational at 6 months, and there were no device explants or repeat implants during this time period.

The FDA believes that there is reasonable assurance that the device is safe and effective for heart failure management with the goal of reducing the rate of heart failure-related hospitalizations in certain patients. The FDA is requiring a thorough Post-Approval Study to continue to learn about the device’s performance when used outside the context of a clinical study.

The CardioMEMS HF System is manufactured by CardioMEMS, Inc., located in Atlanta, Ga.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

SOURCE

 

 

cardiomems

The FDA recent approval of a heart failure monitoring device will allow physicians to check up on patients’ health remotely. Intel Free Press, CC BY-SA 2.0

The Food and Drug Administration (FDA) announced Thursday its approval for the first wireless implantable device, known as CardioMEMS HF System, designed to monitor the health of heart failure patients remotely.

Manufactured by CardioMEMS Inc., located in Atlanta, Ga., the device is meant to give health care professionals an early look at pulmonary artery (PA) pressure data, which they can use to change medication dosage or treatment method before the need for hospitalization. In the clinical study leading up to the FDA’s approval, 98.6 percent of subjects using the device saw no device-related complications within six months, and, of the devices implanted, 100 percent were operational within the same timeframe.

“Heart failure is one of the most common reasons for hospitalizations for people aged 65 and older,” said Christy Foreman, director in the FDA’s Center for Devices and Radiological Health, in the news release. According to the Centers for Disease Control and Prevention, roughly half of all people who develop heart failure die within five years of diagnosis, straining the national economy to the tune of $32 billion annually.

Heart failure occurs when the heart is no longer able to pump enough blood and oxygen to the surrounding parts of the body. While this doesn’t mean the heart necessarily stops beating altogether, the pulse it sends is too weak to replenish major organs. In typical cases, the blood that would normally leave the heart through the aorta never exits the muscle, recycling back into the heart and pooling in the surrounding valves. In congestive heart failure cases, blood may pool in other major organs as well.

The new device is intended to monitor the pressure of this outgoing blood. If the data shows the pressure is too low, physicians located remotely can check up on patients to gauge their health. Not all heart failure patients qualify for the device, the FDA explains. Only people with New York Heart Association (NYHA) Class III heart failure, who have been hospitalized for heart failure in the previous year, are eligible.

SOURCE

 

Posted in Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Congenital Heart Disease, Ecosystems & Industrial Concentration in the Medical Device Sector, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Origins of Cardiovascular Disease | Leave a Comment »

2014 Physician Appointment Wait Times and Medicaid and Medicare Acceptance Rates

June 2, 2014 by 2012pharmaceutical

2014 Physician Appointment Wait Times and Medicaid and Medicare Acceptance Rates

Reporter: Aviva Lev-Ari, PhD, RN

 

 

2014 Survey

Merritt Hawkins, An AMN Healthcare Company

 

Physician Appointment Wait Times and Medicaid and Medicare Acceptance Rates

A survey examining the time needed to schedule a new patient appointment

with a physician in 15 major metropolitan markets and the rates of physician

Medicaid and Medicare acceptance in these markets. Based on 2013 data.

SOURCE

Click to access mha2014waitsurvPDF.pdf

 

Posted in Healthcare Reform | Leave a Comment »

Bridging the Gap in Medical Innovations – Elazer Edelman @ TEDMED 2013

June 1, 2014 by 2012pharmaceutical

Bridging the Gap in Medical Innovations – Elazer Edelman @ TEDMED 2013

 

Reporter: Aviva Lev-Ari, PhD, RN

Article ID #141: Bridging the Gap in Medical Innovations – Elazer Edelman @ TEDMED 2013. Published on 6/1/2014

WordCloud Image Produced by Adam Tubman

 

WATCH VIDEO

http://www.tedmed.com/talks/show?id=17771&videoId=233708&ref=about-this-talk

Q&A with Elazer Edelman  @ TEDMED 2013

WATCH VIDEO

http://www.tedmed.com/talks/show?id=17771&videoId=233708&ref=about-this-talk

Posted in Frontiers in Cardiology and Cardiovascular Disorders, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, Interviews with Scientific Leaders | Tagged | Leave a Comment »

Development of a Pancreatobiliary Chemotherapy Eluting Stent for Pancreatic Ductal Adenocarcinoma PIs: Jeffrey Clark (MGH), Robert Langer (Koch), Elazer Edelman (Harvard:MIT HST Program)

June 1, 2014 by 2012pharmaceutical

Development of a Pancreatobiliary Chemotherapy Eluting Stent for Pancreatic Ductal Adenocarcinoma PIs: Jeffrey Clark (MGH), Robert Langer (Koch), Elazer Edelman (Harvard:MIT HST Program)

Reporter: Aviva Lev-Ari, PhD, RN

New research teams funded in pancreatic cancer, glioblastoma

New research teams funded in pancreatic cancer, glioblastoma

Dana-Farber/Harvard Cancer Center and the David H. Koch Institute for Integrative Cancer Research at MIT announced this week that they have funded four research teams in a joint collaboration aimed at solving the most intractable challenges in cancer.

The Koch Institute-Dana-Farber/Harvard Cancer Center Bridge Project is designed to help bring the expertise of these two Centers to bear on complex translational problems in cancer research. A particular emphasis is placed on fostering joint approaches by engineers and cancer scientists, both basic and clinical/translational. This application round called for collaborative research projects that focus on critical problems in glioblastoma and pancreatic cancer.

Awards are for $325,000 (total costs) per team project per year for up to two years. Congratulations to the following teams who will receive funding in this first round:

Single-cell functional, genomic, and transcriptomic analysis in Glioblastoma
PIs: Keith Ligon (DFCI), J. Christopher Love (Koch), Matthew Meyerson (DFCI/Broad)

Nano-ARBs: A novel approach to improve drug delivery in PDACs
PIs: Rakesh Jain (MGH), Robert Langer (Koch)

Development of a Pancreatobiliary Chemotherapy Eluting Stent for Pancreatic Ductal Adenocarcinoma
PIs: Jeffrey Clark (MGH), Robert Langer (Koch), Elazer Edelman (Harvard:MIT HST Program)

A Coordinated Effort for Advancing Immunotherapies Against Pancreatic Cancer
PIs: Hidde Ploegh (Whitehead/Koch), Kai W. Wucherpfennig (DFCI), J. Christopher Love (Koch)

 

SOURCE

http://www.dfhcc.harvard.edu/news/news/article/4571/

 

Elazer Edelman – Harvard Cancer Center announce launch of ‘Bridge Project’ to attack most-lethal forms of cancer

Institutions, research teams, non-profit organizations join forces in novel approaches targeting pancreatic cancer, glioblastoma.

March 6, 2012

The David H. Koch Institute for Integrative Cancer Research at MIT and Dana-Farber/Harvard Cancer Center (DF/HCC) announced today that they have funded several research teams in a joint collaboration aimed at solving the most intractable challenges in cancer.

The Bridge Project — an unprecedented clinical research collaboration between MIT and DF/HCC — has awarded grants to four interdisciplinary teams made up of biologists, bioengineers and clinical researchers representing both cancer centers. Each joint team is focused on improving the prognosis facing patients affected by two of the most-lethal cancers today: pancreatic cancer and a form of brain cancer, glioblastoma.

The Bridge Project grants represent the most extensive collaboration of its kind between Boston’s two National Cancer Institute (NCI)-designated cancer centers. In addition to individual philanthropists Arthur Gelb and Thomas Peterson, key support for the initiative comes from two leading innovative non-profit cancer research organizations: The Lustgarten Foundation, the nation’s largest private foundation dedicated solely to funding pancreatic cancer research, and the National Brain Tumor Society.

“We have made tremendous advances in many cancers in recent decades, but pancreatic cancer and glioblastoma remain exceedingly difficult to treat,” said David Livingston, deputy director of Dana-Farber/Harvard Cancer Center. “From a clinical perspective, we are eager to gain a more sophisticated understanding of the underlying biology that’s driving these diseases, and to work with leading scientists and engineers to design fresh approaches for how we might intervene.”

“We believe that success against cancer will come if we apply the same creativity and innovation to the research enterprise that we do to the research itself,” said Tyler Jacks, director of the Koch Institute. “New kinds of interdisciplinary collaboration are absolutely essential in order to rapidly translate research discoveries into clinical strategies that will benefit patients in the near-term. We are very excited to work with Dana-Farber/Harvard Cancer Center, with the help of visionary philanthropists and support of two leading research organizations, to make this program a reality.”

The initial grant recipients were selected by an external advisory team that provided rigorous, expert review of more than a dozen proposals submitted by faculty from both institutions for consideration in this round of funding. The external advisers selected those projects that they believe have the greatest potential of generating high-impact clinical outcomes in the future.

The Bridge Project aims to raise and deploy $50 million over the next three to five years into additional research teams focused on potentially transformative initiatives.

The teams receiving grant funding in this first round include:

  • Keith L. Ligon (Dana-Farber), J. Christopher Love (Koch Institute at MIT), Matthew Meyerson (Dana-Farber and Broad Institute) working on single-cell functional, genomic and transcriptonic analysis in glioblastoma;
  • Rakesh K. Jain (Mass General Hospital) and Robert S. Langer (Koch Institute at MIT) working on angiotensin receptor blockers (ARBs) as a novel approach to improve drug delivery in the treatment of pancreatic cancer;
  • Jeffrey W. Clark (MGH), Robert S. Langer (Koch Institute at MIT), Elazer Edelman (Harvard:MIT HST Program) working on the development of a pancreatobiliary chemotherapy eluting stent for pancreatic ductal adenocarcinomas;
  • Hidde Ploegh (Whitehead and Koch Institutes), Kai W. Wucherpfennig (Dana-Farber), and J. Christopher Love (Koch Institute at MIT) working on novel immunotherapies against pancreatic cancer.

 

SOURCE

http://csbi.mit.edu/news_2012/2012_edelman2.html

 

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy | Tagged , , | Leave a Comment »

Locally Advanced Pancreatic Cancer: Efficacy of FOLFIRINOX

June 1, 2014 by 2012pharmaceutical

Locally Advanced Pancreatic Cancer: Efficacy of FOLFIRINOX

Reporter: Aviva Lev-Ari, PhD, RN

 

Oncologist. 2013;18(5):543-8. doi: 10.1634/theoncologist.2012-0435. Epub 2013 May 8.

FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience.

Faris JE1, Blaszkowsky LS, McDermott S, Guimaraes AR, Szymonifka J, Huynh MA, Ferrone CR, Wargo JA, Allen JN, Dias LE, Kwak EL, Lillemoe KD, Thayer SP, Murphy JE, Zhu AX, Sahani DV, Wo JY, Clark JW, Fernandez-del Castillo C, Ryan DP, Hong TS.

Author information

Abstract

The objective of our retrospective institutional experience is to report the overall response rate, R0 resection rate, progression-free survival, and safety/toxicity of neoadjuvant FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and chemoradiation in patients with locally advanced pancreatic cancer (LAPC). Patients with LAPC treated with FOLFIRINOX were identified via the Massachusetts General Hospital Cancer Center pharmacy database. Demographic information, clinical characteristics, and safety/tolerability data were compiled. Formal radiographic review was performed to determine overall response rates (ORRs). Twenty-two patients with LAPC began treatment with FOLFIRINOX between July 2010 and February 2012. The ORR was 27.3%, and the median progression-free survival was 11.7 months. Five of 22 patients were able to undergo R0 resections following neoadjuvant FOLFIRINOX and chemoradiation. Three of the five patients have experienced distant recurrence within 5 months. Thirty-two percent of patients required at least one emergency department visit or hospitalization while being treated with FOLFIRINOX. FOLFIRINOX possesses substantial activity in patients with LAPC. The use of FOLFIRINOX was associated with conversion to resectability in >20% of patients. However, the recurrences following R0 resection in three of five patients and the toxicities observed with the use of this regimen raise important questions about how to best treat patients with LAPC.

KEYWORDS:

Chemoradiation; FOLFIRINOX; Locally advanced pancreatic cancer; Neoadjuvant; R0 resection

Comment in

PMID:

 23657686

[PubMed – indexed for MEDLINE] PMCID:

PMC3662845

 

Free PMC Article

SOURCE
http://www.ncbi.nlm.nih.gov/pubmed/23657686?dopt=Abstract
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662845/
This article has been cited by other articles in PMC.

Results

Twenty-two patients with locally advanced pancreatic cancer received FOLFIRINOX at the MGH Cancer Center in the 20-month period spanning July 2010 to February 2012. Baseline demographic and clinical characteristics are listed in Table 1. The median age of patients was 63 years (range: 49–78 years), including 13 men and 9 women. All patients except one were chemotherapy näive. Fifty-eight percent of patients had pancreatic head/uncinate lesions and 42% had body/tail lesions. Ten of the 22 patients had a biliary stent in place at the start of FOLFIRINOX. All patients with a recorded status in clinic notes had an Eastern Cooperative Oncology Group performance status of 0 or 1. Median follow-up for patients was 19.3 months.

Table 1.

Demographic and clinical characteristics (n = 22)

A total of 178 cycles of chemotherapy were given to the 22 patients, of which 156 cycles contained all three active drugs (5-FU, irinotecan, and oxaliplatin). Sixty-six cycles were with full doses of FOLFIRINOX. Five patients were started on FOLFOX during the initial cycle(s) of chemotherapy, with addition of irinotecan to later cycles. An additional five patients were started on FOLFIRINOX, with eventual discontinuation of oxaliplatin or irinotecan. Patients received a median of 8 cycles of FOLFIRINOX, and 7.5 cycles in which all three active drugs were included (Table 2). Patients received a median of 2.5 full-dose FOLFIRINOX cycles. Of the 17 patients who received 5-FU, irinotecan, and oxaliplatin on the first cycle, 13 received full doses of each drug, including the 5-FU bolus of 400mg/m2. Following FOLFIRINOX, all but two patients received fluoropyrimidine-based chemoradiation (Table 2). In the five patients undergoing surgical resections, a median of 8 cycles of FOLFIRINOX were delivered (range 6–8), with a median of 4 full-dose cycles of FOLFIRINOX (range 3–8).

Table 2.

Treatment: FOLFIRINOX and chemoradiation

Overall, six nonconfirmed partial responses (PR) were observed in 22 evaluable patients (ORR 27.3%) while on FOLFIRINOX (Table 3). One additional patient had a nonconfirmed partial response following chemoradiation, and another had a nonconfirmed partial response following chemoradiation and intraoperative IORT, for a total of 8 of 22 evaluable patients (ORR 36.4%). In all, 19 of 22 patients had decreases in CA19–9 by 30% or more, and 17 of the 22 had decreases of 50% or more from baseline CA19–9 prior to starting FOLFIRINOX. A total of 13 of 22 patients had ≥20% reductions in target lesion measurements as indicated by the waterfall plot in Figure 1. Following neoadjuvant FOLFIRINOX, 12 patients were taken to the operating room for exploration. Five patients underwent R0 resections (Fig. 2), of whom one patient had no remaining evidence of tumor. Seven patients had surgically unresectable disease and six of these patients had intraoperative radiation therapy (IORT) administered, with or without palliative hepaticojejunostomy and/or gastrojejunostomy; of the six undergoing IORT, only one patient has experienced progressive disease. Our decision to proceed with IORT was based on the experience of Willett et al. [14], in which the retrospective experience with IORT for unresectable pancreatic cancer at MGH was characterized. The 3-year survival was 7%, with five patients surviving more than 5 years.

Table 3.

Objective response rate
Figure 1.

Progression-free survival.
Figure 2.

Waterfall plot of maximum percent change from baseline scans during FOLFIRINOX treatment.

One patient did not receive IORT due to the discovery of peritoneal and omental implants. Of the five patients who had R0 resections, three have experienced distant recurrence, at a median of 81 days (range: 74–144 days). One patient is now more than 500 days since resection and has no evidence of recurrence. Median progression-free survival for the entire cohort was 11.7 months (95% confidence interval: 8.3–21.8 months; Fig. 2), with 14 of the 22 patients demonstrating local or distant progression thus far. Overall survival was not calculated because only five patients have died since starting FOLFIRINOX.

With regard to tolerability, only events that could be captured and appropriately graded from the medical record were included (Table 4). A total of 7 of the 22 (32%) required hospitalization or emergency department visits during FOLFIRINOX, >50% of which were for non-neutropenic fevers or dehydration/diarrhea. Because three patients were admitted multiple times, there were 12 hospitalization events. Although there were four patients who developed grade 3 or 4 neutropenia, there were no cases of febrile neutropenia. Only two patients discontinued FOLFIRINOX for toxicities related to treatment. In the five patients who underwent R0 resections, the median length of stay was 7 days (range 5–35). Two of the five patients had no postsurgical complications. Two patients had postoperative infections. One patient was readmitted 10 days after discharge with fevers and leukocytosis, although cultures and workup was negative. One of the patients who had a postoperative infection also had to undergo permanent transhepatic drain placement due to multiple biliary strictures after neoadjuvant FOLFIRINOX and chemoradiation (transhepatic drains placed during Whipple surgery).

Table 4.

Hospitalization and selected toxicities

Discussion

This is the largest published series of patients with locally advanced pancreatic cancer treated with FOLFIRINOX. Recently, the activity of FOLFIRINOX in patients with borderline or locally advanced pancreatic cancer was reported [15], which included a total of 18 patients, of whom 14 had locally advanced disease. In these 14 patients, four patients proceeded directly to surgery after 3–12 cycles of FOLFIRINOX, and two of these 14 had an R0 resection. An additional three patients underwent R0 resections after completing chemoradiation treatment. Thus, the R0 resection rate in this case series, excluding the patients with borderline resectable disease, was 36% (5 of 14 patients). Our R0 resection rate of 23% (5 of 22 patients) is in the range reported by Hosein et al. [15] and may reflect a new era of converting locally advanced pancreatic cancer into resectable pancreatic cancer with the use of FOLFIRINOX.

Given the superior activity of FOLFIRINOX in comparison with gemcitabine, it is extremely important to establish the activity and toxicity of FOLFIRINOX in patients with locally advanced pancreatic cancer. Our experience raises at least four important issues. The first major issue involves the subjective definition of locally advanced and borderline pancreatic cancer. The R0 resection rates range from 8%–64% in 510 patients from 13 studies employing various neoadjuvant chemoradiation protocols for unresectable pancreatic cancer [16]. Despite the large discrepancy in R0 resection rates, overall survival is similar between the studies, suggesting that the extreme heterogeneity in resection rates observed in this meta-analysis is due more to the subjective definition of borderline and locally advanced disease. Our series is restricted to patients with locally advanced pancreatic cancer as determined by an experienced pancreatic surgery group. It is critical that future studies separate patients with locally advanced and borderline resectable disease. In addition to evaluating these two categories separately, establishing formal consensus criteria for locally advanced and borderline disease is of critical importance. At present, one institution’s locally advanced pancreatic cancer may be considered a borderline resectable patient in another institution. The uneven definition and application of criteria used to assign categories to the radiographic presentation of patients with pancreatic cancer probably introduces the greatest amount of variability in the percentage of patients who can undergo a potential curative resection. There are criteria to define locally advanced and borderline pancreatic cancer, which are defined by NCCN guidelines specifically by location in the pancreatic head, body, or tail [12]. As of yet, however, there has not been complete acceptance of and adoption of these criteria. At MGH, we have a multidisciplinary meeting with radiology, surgery, radiation oncology, and medical oncology, during which the imaging, consisting of a pancreatic-protocol CT, is reviewed in detail to assign a stage based on NCCN criteria. A major criticism of the current study is the lack of an independent review board assessing our adherence to these criteria.

A second important issue involves the contribution and sequencing of chemoradiation following neoadjuvant FOLFIRINOX. In our study, with the exception of one patient with progressive disease and another who declined chemoradiation, all patients proceeded to chemoradiation after FOLFIRINOX. In the Hosein et al. study [15], a subset of patients were brought directly to the operating room for attempted resection following maximal response to FOLFIRINOX; interestingly, only half of these patients (two of four patients) were able to have R0 resections. Although chemoradiation may ultimately prove essential for R0 resections, critics argue that this window of time could allow for micrometastatic disease, previously controlled via FOLFIRINOX, to develop. Importantly, our experience suggests that this is an uncommon event. The timing and sequencing of neoadjuvant chemotherapy and chemoradiation is an active debate at all cooperative group meetings.

Third, it is critical to assess the tolerability of FOLFIRINOX specifically in patients with locally advanced disease who often have compromised biliary drainage prior to embarking on a multi-institutional study. With more than 30% of patients requiring an emergency department visit or admission during FOLFIRINOX treatment, this regimen is quite toxic in a patient population that is considered technically incurable. Although a third of these hospitalizations were brief admissions for diarrhea/dehydration, there were two admissions for non-neutropenic bacteremia. Reassuringly, with the use of prophylactic growth factor with all cycles of FOLFIRINOX in this series, there were no cases of febrile neutropenia. Given our experience, upfront dose modification of the FOLFIRINOX regimen might be necessary, particularly in less well-selected populations of patients. Currently, the impact on dose reductions, such as elimination of the 5-FU bolus, is unknown, both in terms of efficacy and toxicity. The reason for the large discrepancy in full-dose FOLFIRINOX cycles in our study (37% of cycles) and the Hosein et al. study (83% of cycles) [15] is unknown, but it may relate to differences in patient selection, including age and performance status. In addition, approximately one-third of patients had borderline disease in the Hosein et al. study, whereas all patients in our study had locally advanced disease. A limitation of this retrospective analysis is that we cannot accurately grade subjective complaints such as peripheral neuropathy, fatigue, and diarrhea from the medical record. Retrospective data on subjective toxicities is inherently incomplete and unreliable and, thus, was not included. Although of clear importance to a discussion of tolerability of a newer chemotherapy regimen such as FOLFIRINOX, an accurate assessment of the frequency and severity of these side effects must be assessed prospectively.

A final and more basic question is whether a patient with initially unresectable disease who achieves an R0 resection after neoadjuvant FOLFIRINOX is really curable. Would palliative systemic chemotherapy and/or chemoradiation achieve the same outcome, avoiding the known morbidity and potential mortality of surgical resection? In our series, three of the five patients with an R0 resection developed distance recurrence at a median of 81 days after surgery. Although we share the enthusiasm that neoadjuvant therapy may permit resection for patients with initially unresectable disease, these early results remind us that the vast majority of patients with pancreatic cancer have systemic disease.

Investigation of biomarkers that may allow for prediction of local versus systemic recurrence could prove helpful in decisions regarding chemoradiation for these patients. For example, an autopsy series found a strong association between local recurrence and an intact DPC4 gene [17]. If this finding is corroborated in other larger studies, chemoradiation could be reserved for patients with intact DPC4. Searching for additional biomarkers that might allow for prediction of response to and toxicity from FOLFIRINOX, as well as benefit from chemoradiation, would be helpful in personalizing therapies with ample potential to both improve response and reduce harm.

Our institutional experience with FOLFIRINOX should serve as a template for future clinical trials designed to definitively address the utility of FOLFIRINOX for patients with both locally advanced and borderline resectable pancreatic cancer. Currently, we have separate protocols at our institution for patients with clearly resectable disease, borderline resectable disease, and locally advanced disease. The issues regarding integration of FOLFIRINOX into these different stages of disease are critically important in the pancreatic cancer community.

Conclusion

For patients with locally advanced pancreatic cancer, FOLFIRINOX possesses substantial activity, and its use was associated with conversion to resectable status in more than 20% of patients. However, recurrent disease was discovered in three of the five patients. There was a significant toxicity signal, with nearly a third of patients requiring at least one emergency department visit or hospitalization. The optimal strategy for treating patients with locally advanced pancreatic cancer requires further study.

Acknowledgments

These data were presented in part at the ASCO Gastrointestinal Cancer Symposium 2012, San Francisco, California.

SOURCE
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662845/

 

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, FDA Regulatory Affairs | Tagged | Leave a Comment »

Bristol-Myers Squibb ($BMY): Leading Risk Taker on a estimated $1.3 Billion Committed to Fund 78 currently known Clinical Trials which will enroll 19,000 Cancer Patients

May 29, 2014 by 2012pharmaceutical

Bristol-Myers Squibb ($BMY): Leading Risk Taker on a estimated $1.3 Billion Committed to Fund 78 currently known Clinical Trials which will enroll 19,000 Cancer Patients

Reporter: Aviva Lev-Ari, PhD, RN

 

 

http://www.asco.org/

http://www.asco.org/meetings

American Society of Clinical Oncology — History

ASCO 50th Annual Meeting: Science & Society

VIEW VIDEO

http://am.asco.org/

May 30-June 3, 2014

McCormick Place
Chicago, Illinois

ASCO was founded in 1964 by a small group of physician members of the American Association of Cancer Research (AACR) who recognized the need for the creation of a separate society dedicated to issues unique to clinical oncology.

Below, explore highlights of ASCO’s past through a series of in-depth articles. You can also experience the history of the Society through video vignettes from the people who believed in ASCO from the beginning and learn about ASCO’s Founders and Past Presidents.

History Article Series

SOURCE

http://www.asco.org/about-asco/society-history

 

Citigroup last year put a $35 billion figure on the market potential for these drugs, the oft-cited megablockbuster number helps explain why these companies are so interested in being among the first to the market.

Bristol-Myers Squibb (($BMY), Naomi Kresge and Robert Langreth report, is devoting an estimated $649 million to its immuno-oncology work, which is primarily devoted to getting nivolumab through the clinic and into the market.

Merck ($MRK), which is furiously at work on MK-3475 as many of the rest of its projects struggle, at one point recently described its immuno-oncology program as a pipeline unto itself. But the pharma giant is actually a distant second at this stage of the race, at least in terms of spending, with an estimated commitment of $327 million. Then

Roche ($RHHBY) – programs costing an estimated $189 million – hasn’t enjoyed as much attention for its PD-L1 program for MPDL3280A, but new data from a small study on bladder cancer looked promising and its Genentech unit is looking to make a splash in Chicago.

AstraZeneca ($AZN) bring up the rear, with $145 million on immuno-oncology – prospects with its immuno-oncology program for the PD-L1 therapy MEDI4736

Cancer vaccines were once the darlings of the R&D field for immunotherapies, but as Emily Mullin reports in FierceVaccines, a string of failures has seriously dimmed the prospects for the one-time leaders in the field. Still, some new biotechs are coming along. And as I reported in a separate story today, big players like J&J are looking to find some new ways to better apply some old, and failed, technologies.

SOURCE
From: FierceBiotech <editors@fiercebiotech.com>
Reply-To: <editors@fiercebiotech.com>
Date: Thu, 29 May 2014 16:50:54 +0000 (GMT)
To: <avivalev-ari@alum.berkeley.edu>
Subject: | 05.29.14 | ASCO: Top R&D bets crest $1B in immuno-oncology; J&J bags new prostate cancer tech

J&J expands prostate cancer program with cancer vax tech from Aduro

May 29, 2014 | By 

Johnson & Johnson’s ($JNJ) busy deal team in California has nailed down another development pact–this time zeroing in on new technology at a Berkeley biotech that will be used to expand its considerable efforts on prostate cancer R&D. And the deal includes rights to a failed cancer vaccine program which has recently sparked some positive trial results in a follow-up effort aimed at salvaging the work.

Aduro CEO Stephen Isaacs

This new deal from the J&J Innovation center zeroes in on a pact to license therapeutic candidates from Aduro BioTech’s drug development platform, which is focused on kicking up an immune response. The platform tech involves the use of live-attenuated double deleted Listeria monocytogenes strains to spawn the antigens needed to provoke an immune system attack on cancer.

Aduro didn’t break down the dollars in the deal, but the whole package of milestones and an upfront tallies up to $365 million, most of which is likely back ended.

SOURCE

J&J expands prostate cancer program with cancer vax tech from Aduro – FierceBiotech http://www.fiercebiotech.com/story/jj-expands-prostate-cancer-program-cancer-vax-tech-aduro/2014-05-29#ixzz3388xfcqU

Like Merck and AstraZeneca, Bristol-Myers is fascinated by the therapeutic potential of marrying an immune checkpoint drug with a therapy–INCB24360–that is designed to spur an immune system attack on cancer cells. Their Phase I/II study, which will explore the combos impact on multiple tumor types, is being co-funded by the two companies with Incyte taking the lead on the work.

“Given the encouraging data for Incyte’s IDO1 inhibitor and our current understanding of nivolumab’s anti-tumor immune response, we see this as an important area of study to add to our broad clinical development program,” said Bristol’s Michael Giordano in a statement.

CytomX, meanwhile, is gaining a $50 million upfront, unspecified preclinical development milestones and up to $298 million in additional milestones for each of up to 4 new “Probodies,” or new drug candidates. The targets include CTLA-4, a well-validated target in the field.

The biotech is a 2013 Fierce 15 company which was spun out from the labs of the University of California, Santa Barbara. Their next-level antibodies come with a peptide that blocks the antibody’s ability to bind to an antigen until it’s clipped off by a disease-associated enzyme.

– here’s the release on the Incyte deal
– see the release on the CytomX partnership

Related Articles:
AstraZeneca, Bristol-Myers add immuno-oncology collaborations for pipeline stars
A Phase III win puts Incyte’s cancer drug in line for blockbuster status
Incyte’s new CEO says his pipeline is underrated–and undervalued

SOURCE
Bristol-Myers adds $1.24B deal plus a partnership in immuno-oncology deal frenzy – FierceBiotech http://www.fiercebiotech.com/story/bristol-myers-adds-348m-deal-plus-partnership-immuno-oncology-deal-frenzy/2014-05-27#ixzz3389rRiFZ

Bristol-Myers Squibb: It’s all about the ‘breakthrough’ drug nivolumab now

May 15, 2014 | By 

Bristol-Myers ($BMY) has one of the best drug development track records in the industry, and the big biotech is devoting major resources to its immuno-oncology lead. Bristol-Myers issued 5 new releases on nivolumab last night, and they all followed an early-morning statement on a new nivo combo study being mounted with Celldex.

The FDA helped make Bristol-Myers’ case for the PD-1 drug by giving nivolumab breakthrough status for Hodgkin’s lymphoma after failure of autologous stem cell transplant and brentuximab. But the analysts were hungry for more data, not bragging rights to a drug they had assigned blockbuster expectations to long ago.

They got a taste of that with promising results for nivolumab combined with Yervoy in previously treated renal cancer.

“In the Phase Ib CheckMate-016 trial, which evaluated the safety and tolerability of nivolumab at different doses and schedules as part of a regimen with other agents, (the overall response rate) for the investigational combination regimen of nivolumab and Yervoy (ipilimumab) ranged from 43-48% with a 24-week progression free survival rate that ranged from 64-65% in previously treated and treatment-naïve patients,” Bristol reported.

“These data are quite good, but perhaps not as ‘mind blowing’ as the combo data were in melanoma at last year’s ASCO,” says ISI’s Mark Schoenebaum.

Schoenebaum was more enthusiastic about nivo plus chemo in first-line lung cancer. “The one-year landmark (overall survival rates) in the abstract are stellar at 59%-87% (depending on chemo regimen and histology) which is above what you would expect historically (historical rates are 40%-50%).” But with serious signs of toxicity and a muted response among patients, expectations of Yervoy plus nivolumab in first-line lung cancer are plunging.

That’s the point that a lot of investors seized on Thursday morning, particularly after BMO Capital downgraded the stock after considerable speculation regarding the potential of Yervoy and nivo in lung cancer. Shares of Bristol-Myers slid 6% this morning.

There’s plenty more coming up on nivolumab at ASCO, so stay tuned.

– here’s the release from Bristol-Myers on the renal cell results
– here’s the release on lung cancer

Related Articles:
AstraZeneca, Bristol-Myers add immuno-oncology collaborations for pipeline stars
Bristol-Myers heads to FDA with nivolumab, but not fast enough
Is Bristol-Myers fading back in its hot race with Merck for PD-1 lead?

SOURCE

Bristol-Myers Squibb: It’s all about the ‘breakthrough’ drug nivolumab now – FierceBiotech http://www.fiercebiotech.com/story/bristol-myers-squibb-its-all-about-breakthrough-drug-nivolumab-now/2014-05-15#ixzz338AGBggx

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Human Immune System in Health and in Disease, Innovation in Immunology Diagnostics | Leave a Comment »

Two new possible Drug Targets for Triple Negative Breast Cancer: The genes, MLF2 (myeloid leukemia factor 2) and RPL39 (a ribosomal protein) have roles in Angiogenesis

May 29, 2014 by 2012pharmaceutical

Two new possible Drug Targets for Triple Negative Breast Cancer: The genes, MLF2 (myeloid leukemia factor 2) and RPL39 (a ribosomal protein) have roles in Angiogenesis

Reporter: Aviva Lev-Ari, PhD,RN

Cornell University Scientists discover two new possible drug targets for triple negative breast cancer

Thursday 29 May 2014 – 1am PST

The suppression of two genes reduce breast cancer tumor formation and metastasis by interfering with blood vessel formation and recruitment, report scientists from Houston Methodist and five other institutions in the Proceedings of the National Academy of Sciences (now online). The findings may help medical researchers identify effective drug targets for triple negative breast cancer, or TNBC.

The genes, MLF2 (myeloid leukemia factor 2) and RPL39 (a ribosomal protein), were found to most profoundly impact the production of nitric oxide synthase, which helps regulate blood vessel behavior and could be crucial to the recruitment of new blood vessels to growing tumors. These genes impact the spread of TNBC throughout the body, and have not so far been linked with breast cancer.

“We have found two unique genes that may affect the most lethal type of breast cancer” said principal investigator and Houston Methodist Cancer Center Director Jenny Chang, M.D., “Most importantly, by knowing how these genes function, we have drugs that can block nitric oxide signaling and will begin a clinical trial in the Cancer Center in the near future”

About 42,000 new cases of triple negative breast cancer (TNBC) are diagnosed in the United States each year, about 20 percent of all breast cancer diagnoses. Patients typically relapse within one to three years of being treated. TNBC is distinguished from other breast cancers in that it does not express the genes for estrogen receptor, progesterone receptor, and Her2/neu and is frequently harder to treat.

By suppressing close to five hundred TNBC-related genes, Chang’s group found interference was strongest with MLF2 and RPL39 in triple negative breast cancer model tissue. The scientists also learned that mutations in these genes in human patients were associated with worse survival in (human) triple negative breast cancer patients.

The researchers went a step further, determining which configurations of small inhibitory RNA (siRNA) were most efficient at shutting down MLF2 and RPL39 in breast cancer stem cell lines. siRNA molecules interfere with the cell’s ability to express genes and have proven to be effective drug tools for a wide variety of diseases, including some cancers.

In preliminary studies, the combination of siRNA and chemotherapy agent docetaxel significantly reducedtumor volume relative to chemotherapy alone and also appeared to prolong survival. Separate analyses showed suppression with siRNA appeared to yield fewer metastases to lung tissue.

Earlier this year, Chang, Weill Cornell Medical College Dean Laurie Glimcher, M.D., and colleagues reported to Nature another possible drug target for TNBC patients called XBP1, another gene previously unassociated with breast cancer.

“Together with our colleagues in Weill Cornell, we are launching clinical trials that affect these unique novel pathways that may cause TNBC to spread. These trials have potential to significantly impact this highly aggressive form of breast cancer.”

 

Chang has a secondary affiliation with Weill Cornell Medical College as a professor of medicine. Also contributing to the PNAS paper were Bhuvanesh Dave, Sergio Granados-Principal, Rui Zhu, Haifa Shen, Xuewu Liu, Mauro Ferrari, Ming Zhan, Stephen T.C. Wong, and Muthiah Kumaraswami (Houston Methodist), Stephen Benz (Five3 Genomics), Shahrooz Rabizadeh and Patrick Soon-Shiong (Chan Soon-Shiong Institute for Advanced Health), Ke-Da Yu and Zhimin Shao (Shanghai Cancer Center and Cancer Institute of Fudan University), Xiaoxian Li and Michael Gilcrease (University of Texas M.D. Anderson Cancer Center), and Vivek Mittal, Xi Chen, and Steven S. Gross (Weill Cornell Medical College). The work was funded by grants from the National Cancer Institute (R01 CA138197, U54 CA149196), Golfers against Cancer, the Breast Cancer Research Foundation, Causes for a Cure, Team Tiara, the Emily W. Herrman Cancer Research Laboratory, the U.S. Department of Defense Innovator Expansion Award (BC104158), the Susan G. Komen for the Cure (KG 081694), and Fundacion Alfonso Martin Escudero (SGP)

SOURCE

http://www.medicalnewstoday.com/releases/277410.php

Learn which HER2-positive breast cancer treatment may be right for you

http://www.her2treatment.com/?cid=per_DI_MBPTUA8059&c=MBPTUA8059&moc=MBPTUA8059&utm_source=google&utm_medium=cpc&utm_term=her2%20survival&utm_campaign=2012%20Perjeta.com%20HCP%20Content%20(Jun12)%20HER2Lander&gclid=CLaG0qWl0b4CFStk7AodfSQA3A

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

Cardiovascular Diseases, Volume One: Perspectives on Nitric Oxide in Disease Mechanisms

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Nitric Oxide in Health and Disease | Leave a Comment »

ipilimumab, a Drug that blocks CTLA-4 Freeing T cells to Attack Tumors @DM Anderson Cancer Center

May 28, 2014 by 2012pharmaceutical

ipilimumab, a Drug that blocks CTLA-4 Freeing T cells to Attack Tumors @DM Anderson Cancer Center

Reporter: Aviva Lev-Ari, PhD, RN

Article ID #140: ipilimumab, a Drug that blocks CTLA-4 Freeing T cells to Attack Tumors @DM Anderson Cancer Center. Published on 5/28/2014

WordCloud Image Produced by Adam Tubman

 

The immune system connection


To understand the cause of the swift progression, the team conducted gene expression profiling and RNA sequence analysis comparing control tumors to myofibroblast-depleted tumors.

Genes associated with tumor immunity were suppressed and fewer T cells and B cells infiltrated the myofibroblast-depleted tumors. The proportion of regulatory T cells, which suppress immune response, increased. They found greater expression of the immune checkpoint CTLA-4, which shuts down immune response.

The researchers then set up a new experiment using ipilimumab, a drug developed by co-author Jim Allison, Ph.D., chair of Immunology, that blocks CTLA-4, freeing T cells to attack tumors.

Jim Allison, Ph.D.

Mice with depleted myofibroblasts who were treated with ipilimumab to stifle CTLA-4 had an average survival increase of 60% compared to untreated control mice and those with either depleted myofibroblasts or treated with ipilimumab alone.

These findings suggest that

  • ipilimumab might work for patients with low levels of fibrosis in their tumors, Kalluri noted.
  • Combining ipilimumab with a hedgehog inhibitor is likely to work better for those with high-fibrosis.

The Kalluri laboratory is exploring these issues.

Co-authors with Kalluri, Maitra and Allison are first author Berna Özdemir, M.D., Ph.D., Julienne Carstens, Ph.D., Xiaofeng Zheng, Ph.D., Hikaru Sugimoto, Ph.D., Christoph Kahlert, Ph.D., and Valerie LeBleu, Ph.D. of Cancer Biology; Tsvetelina Pentcheva-Hoang,  Ph.D., Tyler Simpson, Ph.D., and Padmanee Sharma, M.D., Ph.D., of Immunology;  Chia-Chin Wu, Ph.D.,  and Lynda Chin, M.D., of Genomic Medicine; Hanane Laklai, Ph.D., and Valerie Weaver, Ph.D., of University of California, San Francisco; Sergey Novitskiy, M.D., Ph.D., and Harold Moses, M.D., of Vanderbilt University School of Medicine, Nashville, Tenn.; Ana De jesus-Acosta, M.D., Johns Hopkins Hospital, Baltimore; and Pedram Heidari, M.D., and Umar Mahmood, M.D., Ph.D., of Massachusetts General Hospital, Boston.

Ozdemir, Sigumoto, LeBleu, and Kahlert also were affiliated with Beth Deaconess Medical Center and Harvard Medical School during this research.

Kalluri holds the Rebecca Meyer Brown and Joseph Mellinger Brown Chair in Basic Science Research at MD Anderson.  Maitra holds the Sheikh Khalifa Bin Zayed Al Nahyan Distinguished University Chair in Cancer Research and Allison the Vivian L. Smith Distinguished Chair in Immunology.

This research was funded by grants from the National Cancer Institute of the National Institutes of Health (UO1 CA151925, CA113669, CA125550, CA155370 and CA163191, DK55001), the Cancer Prevention and Research Institute of Texas; MD Anderson’s Metastasis Research Center; the OncoSuisse M.D./Ph.D. Scholarship, the Swiss National Science Foundation Fellowship and a research fellowship from Deutsche Forschungsgemeinschaft.

 

SOURCE

http://www.mdanderson.org/newsroom/news-releases/2014/tissue-surrounding-cancer-cells-hinders-pancreatic-cancer.html?elq=99d9769b143a4d8fa5797a8dffe4ca67&elqCampaignId=11

Study results consistent with failed clinical trial


Kalluri and colleagues used genetically engineered mouse models that allowed depletion of tissue-repair cells called myofibroblasts in pancreatic cancer. Myofibroblasts compose a major portion of supportive tissue called stroma and also produce collagen, which serves as a scaffold for wound-healing and tissue regeneration.  Up to 90 percent of a pancreas tumor can consist of fibrotic support tissue.

When the scientists depleted myofibroblast production in mice with either early or later-stage pancreatic ductal adenocarcinoma their tumors became much more invasive, aggressive and lethal.

“We did these experiments thinking that we would show the importance of myofibroblasts and fibrosis in pancreas cancer progression, but the results went completely against that hypothesis,” Kalluri said.

Since myofibroblasts and collagen are thought to block chemotherapy, the team treated their myofibroblast-depleted mice with gemcitabine, the standard treatment for pancreas cancer.  The drug did not have any effect on the disease course or improve survival.

These results track those of a major clinical trial that combined a myofibroblast-depleting drug called a hedgehog inhibitor with gemcitabine to treat pancreatic cancer patients.  The trial was stopped in 2012 when an interim analysis showed the patients taking the combination had faster disease progression than the control group that took only gemcitabine, a surprising result.

“This paradigm-shifting study identifies the reason why the hedgehog-inhibitor trials failed,” said co-author Anirban Maitra, M.D., professor of Pathology and scientific director of the Sheikh Ahmed Bin Zayed Al Nahyan Center for Pancreatic Cancer Research.

Anirban Maitra, M.D.

All solid tumors include some degree of fibrosis, Maitra said, but not as much as pancreas cancer.

The team’s analysis of pancreatic tumors from 53 patients showed low levels of tumor myofibroblasts are associated with decreased survival.

Study findings are consistent with pathologic evidence that tumors with more fibrotic tissue more closely resemble normal pancreas tissue, indicating a better prognosis for patients, even though lab experiments indicated those tumors should be more aggressive, Maitra said.

“These findings also are likely to account for rather modest results in a phase I clinical trial of immunotherapy alone for pancreas cancer,” Maitra said. “But it’s not just a negative study, because it suggests what might work for these patients.”

And what might work hinges on immune checkpoint blockade.

 

SOURCE

http://www.mdanderson.org/newsroom/news-releases/2014/tissue-surrounding-cancer-cells-hinders-pancreatic-cancer.html?elq=99d9769b143a4d8fa5797a8dffe4ca67&elqCampaignId=11

 

Supportive tumor tissue surrounding cancer cells hinders, rather than helps, pancreatic cancer

Study shows fibrosis summons an immune attack, challenges theory that it blocks chemotherapy

MD Anderson News Release 05/22/14

Fibrous tissue long suspected of making pancreatic cancer worse actually supports an immune attack that slows tumor progression but cannot overcome it, scientists at The University of Texas MD Anderson Cancer Center report in the journal Cancer Cell.

“This supportive tissue that’s abundant in pancreatic cancer tumors is not a traitor as we thought but rather an ally that is fighting to the end. It’s a losing battle with cancer cells, but progression is much faster without their constant resistance,” said study senior author Raghu Kalluri, Ph.D., M.D., chair of Cancer

Raghu Kalluri, Ph.D., M.D.

 Biology. “It’s like having a car with weak yet functioning brakes vs. having one with no brakes.”

The team’s findings point to a potential new avenue for guiding treatment, including immunotherapy, and offer an explanation for the failure of a promising combination drug approach in clinical trials.

“Cancer is one form of tissue injury.  When our defense system detects damaged cells it sends soldiers to contain and repair the damage,” Kalluri said. “When it cannot remove the damaged cells and repair the injured area, our defensive fibrotic response tries to put a boundary around it, to contain it and prevent it from spreading.”

Pancreas cancer is resistant to treatment and only about 7 percent of patients survive for five years. An estimated 46,420 new U.S. cases will be diagnosed in 2014 and 39,590 people will die of the disease.

SOURCE

 

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, FDA Regulatory Affairs, Human Immune System in Health and in Disease, Innovation in Immunology Diagnostics, Interviews with Scientific Leaders, Translational Science | Leave a Comment »

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