Weill Cornell Medical College has announced that it is the recipient of $400 million, made up of several major gifts, bringing the prestigious Medical College to the halfway mark in just the first seven months of its $1.3 billion capital campaign — “Discoveries that Make a Difference” — launched in October 2006.

These gifts also bring Cornell University’s comprehensive campaign, Far Above, the Campaign for Cornell, to $1.653 million.

The largest of the gifts announced is $250 million — believed to be the single largest gift ever given to a medical college — from Joan and Sanford I. Weill, Chairman of the Board of Overseers of Weill Cornell Medical College. Additionally, Mr. & Mrs. Weill are making a $50 million gift to Cornell University — the largest gift ever to the Ithaca campus from an individual — to help fund its New Life Sciences Initiative, which aims to keep the University competitive in light of vast changes in genomics and interdisciplinary research. This initiative will help advance research and other collaborations between Ithaca-based and Weill Cornell faculty. The combined $300 million is the largest gift to the University from a single individual. To date, Mr. and Mrs. Weill and the Weill Family Foundation have given more than $500 million to Weill Cornell Medical College.

Maurice R. Greenberg, a member of the Board of Overseers of Weill Cornell Medical College and Chairman and CEO of C. V. Starr and Company, and his wife Corinne, are giving $25 million. Another $25 million comes from the Starr Foundation. The Greenbergs and the Starr Foundation have been generous and loyal benefactors of the Weill Cornell Medical College and NewYork-Presbyterian Hospital. Mr. Greenberg is also the Chairman Emeritus of NewYork-Presbyterian Hospital.

The final donation is a $100 million gift from long-time supporters of Weill Cornell who wish to remain anonymous.

The gifts will go toward the overall “Discoveries that Make a Difference” capital campaign that will fund a variety of projects, including:

* New translational and clinical research programs (bench-to-patient), focused on several areas — obesity, diabetes and metabolic disorders; cardiovascular diseases; neurodegenerative and neuropsychiatric disorders and aging; cancer; global health and infectious diseases; children’s health; molecular therapeutics; and reproductive and regenerative medicine. The goal is to translate the benefits of research advances immediately to patients, supporting Weill Cornell’s mission to provide the highest standards of patient care through less invasive procedures, reduced morbidity, shorter hospital stays, and speedier recovery times.

* Support for students, including student financial aid, international scholarship funds, graduate fellowships, and funds to enhance the living-learning experience.

* Support for education, including funding for faculty who are largely engaged in teaching medical students.

* Faculty and program support, including endowed faculty positions, endowed academic support positions and research and program enhancement. This program seeks to increase research faculty recruits, including full-time researchers, translational physician-scientists and clinical faculty recruits; and add new research centers and institutes.

* State-of-the-art facilities, including a proposed Biomedical Research Building, to be built on East 69th Street, giving researchers and scientists the cutting-edge tools and increased space for accelerated innovation and biomedical discovery. Labs will be designed in an open-floor layout, fostering communication and collaboration among scientists and creating synergies for translational research. As the first new research facility built on the Weill Cornell campus in two decades, it will keep New York City at the epicenter of biomedical research.

* Collaborative research between Weill Cornell Medical College and Cornell University in Ithaca: New translational research programs will promote scientific synergies by the world-renowned experts working on both campuses. Of Mr. and Mrs. Weill’s total gift, $25 million will fund research collaborations between the campuses in Ithaca and New York City, and will establish the Joan and Sanford I. Weill Institute for Cell and Molecular Biology at the University.

* Global collaborations and international education: Weill Cornell is deeply committed to making important contributions on a global scale. Education, training and research programs span the globe from our New York City campus to the Weill Cornell Medical College in Doha, Qatar, to training programs in Bugando, Tanzania and Salzburg, Austria, to research and clinical activities in Haiti and affiliated programs on The Methodist Hospital campus in Houston, Texas.

“This is an historic day for Weill Cornell Medical College, and my wife Joan and I are thrilled to be a part of the celebration,” said Mr. Weill. “Each of the gifts that we are announcing today is being made by donors who have contributed generously to Weill Cornell in the past. This speaks volumes of our national and global reach, and it strongly validates the job that our dean, Dr. Tony Gotto, is doing. He is a great partner and under his leadership, we have recruited 15 new department chairs, out of a total of 23 departments, and we have seen our National Institutes of Health funding nearly double. These gifts will also create new translational and clinical research programs that will directly impact our patients.”

“The health challenges that confront the world today are far bigger than these gifts,” said Mr. Greenberg. “Our goal is to speed research discoveries from the bench to the bedside, where doctors can improve the quality of care for patients and the quality of life for all of us.”

“We are grateful and humbled to be the recipient of such immense generosity. It is almost overwhelming,” said Antonio M. Gotto, Jr., M.D., Dean of Weill Cornell Medical College. “Our doctors, researchers, students, patients and the people we serve will be the direct beneficiaries of these gifts, which will support and promote our educational programs, research, recruiting efforts and patient services. We are committed to producing the finest doctors, generating research to relieve human suffering, provide excellent patient care and sharing our experience in other parts of the world.”

“With this extraordinary and generous gift, Joan and Sandy Weill are not only securing the foundation of our great medical school at the cutting edge of research, they are also setting the course for unprecedented collaboration among scientists and researchers throughout Cornell University that is likely to contribute to the well being of generations to come of fellow Americans,” said Peter Meinig, Chairman of the Cornell University Board of Trustees.

“Those who dare to dream are the people who make a difference in this world. With this amazing gift, on top of an already extraordinary history of giving, Joan and Sandy Weill honor, reward, and inspire the dreams of a new generation of scientists and researchers at Weill Cornell Medical College and across Cornell University’s Ithaca campus,” said David Skorton, President of Cornell University. “By directing his immense generosity at our faculty’s collaborative efforts, Sandy and Joan Weill are setting the gold standard for all our efforts to secure the future of our great institution; in so doing, he and Joan are also making a qualitative difference in the lives of countless human beings across the globe.”

“These gifts to our campaign represent the best possible investment one can make in scientific progress — with benefits now and for generations to come,” said Robert J. Appel, Chairman, The Campaign for Weill Cornell Medical College. “As our capital campaign — Discoveries that Make a Difference — continues, so does our ability to support the doctors and scientists of today and tomorrow. We would urge those who believe in the Weill Cornell mission to join us in making that difference in the medical discoveries of tomorrow.”

About Weill Cornell Medical College

Weill Cornell Medical College — Cornell University’s Medical School located in New York City — is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, AIDS, obesity, cancer, psychiatry and public health — and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. The Medical College — in its commitment to global health and education — has a strong presence in such places as Qatar, Tanzania, Haiti, Brazil, Salzburg, and Turkey. With the historic Weill Cornell Medical College in Qatar, the Medical School is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the world’s first clinical trial for gene therapy for Parkinson’s disease, and, most recently, the first indication of bone marrow’s critical role in tumor growth. For more information, visit medrnell/.

About The Discoveries That Make A Difference Campaign

The Campaign for Weill Cornell Medical College, Discoveries that Make a Difference, will raise an unprecedented $1.3 billion in private philanthropy to translate the findings of basic science into the most advanced treatments for patients as quickly as possible. In the 21st century, the most profound discoveries in medical science will occur at the intersection of disciplines and through the collaboration of new ideas. Discoveries will fund a bold strategic plan including paradigm-shifting initiatives in biomedical research, medical education, and patient care to advance global health and well-being. The Discoveries Campaign leverages the synergies created by Weill Cornell’s partnerships with NewYork-Presbyterian Hospital, Memorial Sloan-Kettering Cancer Center, The Rockefeller University, The Methodist Hospital-Houston, as well as Weill Cornell Medical College in Doha, Qatar, and through our work in global health in Tanzania and Haiti. The Campaign will support the recruitment and retention of the very best faculty, doubling our existing research space with the construction of a new biomedical research building, and expanding programs in ten discrete areas: cancer; cardiovascular medicine; obesity, diabetes and metabolic disorders; neurodegenerative, neuropsychiatric diseases and aging; stem cell, developmental biology, regenerative and reproductive medicine; global health and infectious diseases; molecular therapeutics; children’s health; education; and collaborative opportunities with our Ithaca campus.

Contact: Jonathan Weil

New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College Continue reading →

MethylGene Inc. (TSX:MYG) reported preliminary Phase I data for MGCD265 in a poster session at the 2009 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference in Boston.

MGCD265 is an oral, small molecule multi-targeted kinase inhibitor for cancer that targets the Met, VEGF, Ron and Tie-2 receptor tyrosine kinases thereby inhibiting multiple pathways involved in tumor growth, metastasis and angiogenesis. The objective of this Phase I dose-escalation trial (Trial 265-102) is to evaluate the maximum-tolerated dose, safety, pharmacodynamics (PD) and pharmacokinetics (PK) of MGCD265 when administered orally to patients with advanced metastatic or unresectable solid tumors that were refractory to standard therapy. The starting dose for the trial was 24mg/m2 of MGCD265 administered daily every other week for a 28-day cycle. This trial is a companion to Trial 265-101 which is evaluating MGCD265 administered daily without interruption.

Preliminary results from Trial 265-102

MGCD265 capsules are well tolerated with signs of activity and pharmacodynamic effect.

To date, 20 patients have been enrolled in Trial 265-102 and have received doses of MGCD265 ranging from 24 mg/m2 to 340 mg/m2 with the maximum tolerated dose still to be determined. No dose-limiting toxicities have been observed. The Company has also introduced a tablet form, which will provide improved manufacturing of MGCD265 finished form.

Preliminary efficacy data indicate six patients with stable disease (30 percent of patients enrolled) per RECIST criteria, including one patient with a rare and aggressive form of bladder cancer, classified histologically as sarcomatoid, who was treated with MGCD265 for 12 cycles (approximately one year). This patient’s cancer had previously progressed after three different courses of chemotherapy (chemo-resistant). Sarcomatoid tumors exhibit features of EMT (epithelial to mesenchymal transition), a process in which Met is known to play a role. An archived tumor biopsy obtained from this patient prior to MGCD265 treatment demonstrated Met expression and phosphorylation, and FISH analysis showed polysomy of chromosome 7 resulting in multiple copies of the Met gene. In a post-treatment tumor sample, a decrease in the level of phospho-Met was seen as well as a decrease in intact vascular structures using endothelial cell labeling with anti-CD31. These data suggest that treatment with MGCD265 resulted in long-term stable disease (10 cycles) and that the compound is inhibiting its targets in this patient. Also of note, a patient with medullary thyroid cancer experienced tumor shrinkage of 10 percent.

Across the study, MGCD265 appears to have a good safety profile at the doses administered with only grade two or less drug-related adverse events reported in the 20 treated patients. The most frequently reported drug-related grade two adverse event was diarrhea which occurred in two patients. This favorable safety profile may provide an opportunity to further investigate MGCD265 in combination with chemotherapy and as maintenance therapy.

“We continue to be encouraged by the activity, safety and pharmacodynamic characteristics of MGCD265,” said Donald F. Corcoran, President and Chief Executive Officer of MethylGene. “We have not yet identified the maximum tolerated dose and we continue to evaluate MGCD265 in our Phase I trials while progressing the compound into Phase II trials including our ongoing trial in combination with Tarceva® and docetaxel.”

MethylGene will continue its two ongoing Phase I trials and has initiated its Phase II program with MGCD265 in combination with Tarceva® (erlotinib) and docetaxel, focused on non-small cell lung cancer (NSCLC) patients. MethylGene has demonstrated good preclinical in vivo efficacy and tolerability of MGCD265 in combination with both agents. The Tarceva® combination may be of particular interest, as it has been shown that Met and EGFR functionally cooperate. The simultaneous inhibition of Met and EGFR has demonstrated enhanced anti-tumor activities in multiple in vivo models. Importantly, Met amplification has been described as a mechanism of resistance to EGFR inhibitors in NSCLC patients; therefore, blocking Met offers a compelling rationale to overcome resistance to EGFR inhibitors, such as Tarceva®, in the clinic. The Company also expects to commence another Phase II trial in breast cancer or bladder cancer.

Source
MethylGene Inc.

View drug information on Tarceva. Continue reading →

Radiation Medical Group, Inc. is the first center in the nation to use a new version of the SAVI applicator for radiation treatment of breast cancer, potentially expanding the number of women who will qualify for breast brachytherapy.

RMG is the first center to use the SAVI™ 6-1Mini applicator, which is designed for the delivery of radiation to small or hard-to-treat lumpectomy cavities. The new device makes a shorter, more convenient form of radiation therapy available to more women.

“We are proud to be the first center to offer this new SAVI applicator option,” said Gina Mansy, M.D., a radiation oncologist at RMG. “We are committed to providing women with state-of-the-art technology and the latest treatment breakthroughs, to arm them in the fight against breast cancer.”

Devices like the SAVI applicator provide a form of radiation known as breast brachytherapy, which targets the tumor site from inside the breast. Breast brachytherapy typically involves two treatments per day for just five days. The traditional form of therapy, whole breast radiation, requires five treatments a week for a period of six weeks, which can be inconvenient for women.

Describing the first case, Dr. Mansy said: “The patient wanted to have an accelerated course of therapy, but with her small breasts and small tumor cavity,
other breast brachytherapy devices simply would not have fit. Without SAVI, she would have had to undergo six weeks of standard radiation instead of just five days of therapy with this device.”

In addition to shortening the therapy time, the new applicator minimizes radiation exposure of healthy tissue. This approach reduces damage to critical structures such as the skin, heart, lungs and ribs.

SAVI is the only single-entry device that enables physicians to sculpt the radiation dose specifically to the patient’s specific anatomy. The ability to control the dose provides several advantages over other, balloon brachytherapy devices.

“I’ve used the balloon on several occasions, but there were many cases where I either had to remove the device or decline treatment because the tumor bed was too close to the skin,” said Dr. Mansy. “This newer device uses multiple catheters, which allows you to manipulate the dose and direct it away from healthy structures, regardless of the size or shape of the cavity.”

RMG expects the device to increase the number of women who can choose a five-day course of treatment.

“The SAVI 6-1Mini applicator will benefit many women who are interested in breast brachytherapy, particularly those who are not candidates for other devices,” said Julie Barone, M.D., a breast surgeon with Oncology Associates of San Diego. “This new device provides the option of an accelerated form of radiation to women with small breasts or those with lumpectomy cavities close to the skin.”

Post-operative radiotherapy to the breast is part of the routine care of patients who choose to have lumpectomy surgery. Lumpectomy, combined with radiation, is an appropriate treatment for most women with early-stage breast cancer. It provides equivalent survival to that of mastectomy and is often preferred by many women because it allows preservation of the breast.

RMG also offers Intensity Modulated Radiotherapy (IMRT) for breast cancer treatment. IMRT is the most technologically advanced treatment available in external beam radiation therapy. It involves directing a high dose radiation beam to a specific target on the body such as a tumor.

About Radiation Medical Group, Inc.

Radiation Medical Group has become San Diego’s leading expert on radiation therapy by using the most advanced techniques and the latest equipment. With its multi-disciplinary approach to cancer care, RMG offers an expert team of specially trained physicians, physicists, therapists, nurses, and complementary therapists, who work with patients to design a customized plan of care that aims to effectively and comfortably treat cancer while preserving healthy tissue and minimizing side effects. RMG has three locations in the San Diego area.

Radiation Medical Group, Inc. Continue reading →

The NHS Technology Adoption Centre has launched the How To Why To Guide on Insulin Pump Therapy and believes that this tool can help redress the inequities which currently exist in the treatment of type 1 diabetes. The Guide, which is the result of an intensive two-year project, provides practice guidance to enable the successful implementation of the therapy. The unique tool provides:

– clinical evidence enabling hospitals to better understand insulin pump therapy;

– support to put together a business case which guides the commissioning process;

– a roadmap to pump service implementation and the necessary supporting policies.

Commenting on the Guide, Dr Rowan Hillson MBE, National Clinical Director for Diabetes said: “People with diabetes should have access to the most appropriate insulin therapy for their needs. This includes insulin pumps where they are indicated. I believe that the How To Why To Guide will be a valuable tool to facilitate the wider adoption of insulin pump therapy and I encourage people to use it in their clinical settings.”

Three NHS Trusts have been involved in the development of the Guide; each having successfully implemented an insulin pump therapy service.

– Birmingham Children’s Hospital NHS Foundation Trust

– Whittington Hospital NHS Trust

– East Lancashire Hospitals NHS Trust

It is estimated that, in the UK, 1 in 200 adults have type 1 diabetes with the current prevalence in children approximately 1 in 700-1000.

In order to avoid complications it is important that those with type 1 diabetes manage their blood glucose levels carefully. An internationally accepted measure of good diabetes control is the glycated haemoglobin (HbA1c). The NICE guidance for diabetes care and the Quality and Outcomes Framework advocate a treatment target of HbA1c < 7.5%. However, the National Diabetes Audit has recently shown that 85% of children with diabetes do not meet this target putting them at substantially greater risk of complications.

The majority of patients control their insulin levels through multiple daily injections (MDI). However, in many cases this leads to poor control of diabetes and can also negatively affect an individual’s quality of life.

An alternative to MDI is insulin pump therapy. This portable pump provides precise dosing of insulin with controlled and steady delivery controlling the infusion of insulin in a more flexible manner than conventional insulin injections. NICE recommends the use of insulin pump therapy for some people with type 1 diabetes and estimates that it is likely to benefit 8-15 per cent of adults and up to 50 per cent of children under the age of 12.

However, despite positive NICE guidance insulin pump therapy is poor with considerable inequities in both provision and access being found across the UK with many areas having less than 1 percent take up. The UK also significantly lags behind many other parts of the world where, in some countries, uptake is nearing 40 percent.

In order to overcome these issues NTAC developed the How To Why To Guide on Insulin Pump Therapy. The IPT Guide is one of a series designed to address the issues of poor technology adoption across the NHS.

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Older patients battling pneumonia spent less time in the hospital when treated using osteopathic manipulative medicine – a drug-free form of hands-on medical care focusing on increasing muscle motion – in addition to conventional care, recently published research shows.

Kari Hortos, a Michigan State University professor in the College of Osteopathic Medicine’s Department of Internal Medicine, was one of seven site investigators as part of the five-state Multicenter Osteopathic Pneumonia Study in the Elderly.

The study revealed patients being treated additionally with osteopathic manipulative medicine stayed in the hospital one day less compared to patients receiving conventional care only.

“The results suggest a role for osteopathic manipulative medicine to support conventional therapy in the treatment of pneumonia, which is the fourth most common hospital diagnosis in the country,” Hortos said. “Besides the obvious benefit of getting people home quicker, the cost savings could be enormous. Further study is needed with these treatments.”

The randomized, controlled clinical trial worked with seven hospitals to assess the impact of osteopathic manipulative treatment in patients 50 and older. The study, done between March 2004 and February 2007, was recently published in the journal Osteopathic Medicine and Primary Care.

In addition to the reduced length of hospital stay, manipulative medicine also showed a slight decrease in both the amount of intravenous antibiotics needed and respiratory failure, according to the study findings.

Osteopathic manipulative treatments have been used throughout the United States since the late 1800s. The techniques can be used to alleviate pain, restore range of motion and enhance the immune system.

Another form of treatment called light touch – a light form of massage – also was used as a comparative group in the MOPSE study; while patients receiving it did respond favorably, the results were not as significant as for those receiving osteopathic treatments in addition to conventional care.

Hortos said the fact even light-touch treatments showed some benefit emphasizes the possible role human touch may play in helping patients heal.

“Human contact, both from a physical and emotional aspect, seems to help patients heal faster,” she said.

The MOPSE study was funded by a group of foundations led by a $1.5 million grant from the Osteopathic Heritage Foundation and the Foundation for Osteopathic Health Services.

The study involvement of the MSU College of Osteopathic Medicine also was notable because of the coordination with the college’s Statewide Campus System, which is made up of 31 member hospitals providing postdoctoral training to graduates, Hortos said. Lori Dillard, a professor at the college’s Macomb County campus, was the lead specialist and worked with Mt. Clemens Regional Medical Center as part of the MOPSE study. Hortos also serves as associate dean of the college’s Macomb County campus.

“The coordination with Mt. Clemens Regional Medical Center is a great example of how the college can work with the Statewide Campus System to recruit patients for community-based research,” Hortos said. “The college has the structure in place to conduct both site-specific and general research in an efficient manner.”

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CARDIOVASCULAR DISEASE: Flushing out key limitations to a drug that protects against heart attack

The drug niacin is used to modulate fat levels in the blood and thereby reduce the risk of a heart attack. However, noxious effects on the skin that have been termed ‘flushing’ limit its use in the clinic. Understanding the mechanisms underlying flushing might identify therapeutic targets that could suppress flushing and enable wider use of niacin. Insight into this has now been provided by a team of researchers, led by Stefan Offermanns, at the Max-Planck-Institute for Heart and Lung Research, Germany, that studied in mice the mechanisms underlying flushing caused by niacin, which targets the protein GPR109A.

Specifically, the team found that different molecular pathways in different cell types in the skin mediated the two phases of niacin-induced flushing. The early phase of flushing was mediated via GPR109A on Langerhans cells and involved the protein COX-1, while the late phase was mediated via GPR109A on skin cells (keratinocytes) and involved COX-2. Inhibitors of COX-1 and COX-2 selectively blocked the anticipated phases of flushing. The authors hope that these data will lead to the development of new approaches to mitigate the skin toxicity that limits the use of niacin in the clinic.

In an accompanying commentary, Richard Dunbar and Joel Gelfand, at the University of Pennsylvania, Philadelphia, note that these data bring us closer to understanding the noxious skin effects of niacin. However, they caution that the readouts of flushing assessed in mouse models (redness) might not correlate with some of the other noxious skin effects (such as pain and itching) that niacin induces.

Title: Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice

Accompanying Commentary
Title: Seeing red: flushing out instigators of niacin-associated skin toxicity

IMMUNOLOGY: Function of rare immune cell uncovered

Basophils are immune cells that are found in very small numbers in the blood. We currently have very little understanding of their function, but such information could be obtained by the development of a basophil-deficient mouse. A team of researchers, led by Hajime Karasuyama, at Tokyo Medical and Dental University Graduate School, Japan, has now generated mice in which basophils can be selectively deleted by administration of diptheria toxin. Furthermore, using these mice, they identified an essential and nonredundant role for basophils in the immune response to ticks that mediate babesiosis, Q fever, and Russian encephalitis in humans. The authors suggest that their data might open new avenues of research for the development of strategies for controlling tick-borne diseases and that their mice will be useful in determining the functions of basophils in health and disease, a sentiment echoed in an accompanying commentary by Booki Min, at the Cleveland Clinic Foundation, Cleveland.

Title: Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks

Accompanying Commentary
Title: Mice that “conditionally” lack basophils, AT LAST

ONCOLOGY: The protein Sema3E: the black sheep in the Sema3 family

Sema3 proteins are traditionally considered to be inhibitors of tumor growth and spread (metastasis). However, a team of researchers, led by Luca Tamagnone, at the University of Torino Medical School, Italy, and Massimiliano Mazzone, at Flanders Institute for Biotechnology, Belgium, has now determined that although the Sema3 protein Sema3E inhibits the growth of human tumor cells after transplantation into mice, it actually promotes their invasiveness and metastasis to distant sites. Consistent with this, expression of Sema3E and the protein to which it binds (Plexin D1) correlated with metastatic progression of human tumors. The authors therefore suggest that targeting Sema3E and the molecules to which it binds to mediate its effects might provide a way to block tumor metastasis. However, in an accompanying commentary, Michael Klagsbrun and Akio Shimizu, at Children’s Hospital Boston, Boston, caution that more clinical data are needed to confirm that Sema3E has a central role in tumor metastasis in humans.

Title: Sema3E-Plexin D1 signaling drives human cancer cell invasiveness and metastatic spreading in mice

Accompanying Commentary
Title: Semaphorin 3E, an exception to the rule

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During the 85th General Session of the International Association for Dental Research, scientists are reporting that they have developed a method for the effective healing of, and relief of pain associated with, canker sores.

Canker sores (scientifically known as aphthous ulcers) are painful recurring ulcers inside the mouth that afflict 60 million Americans. They are not viral or contagious. The most common form, called minor aphthous ulcers, are less than 10 mm in diameter and typically heal within 10-14 days. The direct cause of canker sores is unknown, but studies have shown that stress, family history, and cuts in the mouth (like those caused by braces or accidental bites) are indirect causes. Diet may be a factor for some people as well, though specific triggering foods have not been identified. There are no significant complications caused by unhealed canker sores, but the acute mouth pain can interfere with the ability to eat, drink, or speak and impair the sufferer’s quality of life.

Licorice has been used for over 4000 years as a healing agent. The medicinal capabilities of licorice root (Glycyrrhiza) extract (GX) have been established by long-term clinical use and, most recently, by scientific research. GX has been identified to have anti-inflammatory, soothing, and coating abilities and provides proven, rapid relief for canker sores.

The researchers reported on a study of a new, patented dissolving oral patch with this traditional herbal medicine. In randomized, controlled trials conducted by researchers at the University of Washington and Orahealth Corporation, 8 out of 10 people using an oral GX patch (CankerMelts®) had no more base pain after 3 days of use. Further, the canker sores treated with the oral GX patch shrank to one-tenth their original size after 7 days, while untreated canker sores grew larger. In a separate prior study, 26 out of 27 canker sores (96%) that were treated with the CankerMelts oral patch healed in 3 or fewer days.

The gels and mouthwashes used for years by canker sore sufferers are designed to numb the pain or cover the ulcer in a protective coating to protect against irritation. To many people, this is simply inadequate: A numb mouth and days or weeks of excruciating pain can make it tough to enjoy your favorite foods and drinks or talk comfortably with friends and family. The CankerMelts oral patch technology allows the disc to stick inside the mouth, in contact with the sore and usually covering the sore to protect it from irritation. Pain relief (not numbing of the mouth) is achieved in roughly 10 minutes, and the all-natural disc dissolves slowly in the mouth, providing 2-6 hours of time-released medication exactly in the needed spot.

[Orahealth, based in Bellevue, WA, is a privately held company founded in 2002 by CankerMelts inventor Jeff Haley and is dedicated to developing better oral health through medical science. For more information, visit orahealth/.]

This is a summary of abstract #1207, “CankerMelts Patches Reduce Pain and Speed Resolution of Aphthous Ulcers”, by J. Haley et al., of the University of Washington and Orahealth Corporation, presented during the 85th General Session of the International Association for Dental Research.

Contact: Linda Hemphill

International & American Association for Dental Research Continue reading →

Argenta Discovery Limited, the respiratory drug discovery and development company, announces a major milestone in its joint programme with AstraZeneca aimed at identifying improved inhaled bronchodilators to treat chronic obstructive pulmonary disease (COPD).

This important milestone marks the first candidate drug from the collaboration to enter Phase I safety and tolerability studies. This drug candidate is on track to enter Phase II ‘proof-of-concept’ trials later this year.

The original agreement between the two companies was announced in January 2007. Scientists from the two companies are collaborating to identify long-acting muscarinic (M3) antagonist (LAMA) and dual-acting muscarinic antagonist-??2 agonist (MABA) candidate drugs. These compounds will be developed as once-daily, inhaled mono or combination therapies. AstraZeneca will be responsible for the development and worldwide commercialisation of products arising out of the collaboration. Dependent upon success, Argenta is eligible for further development, regulatory and sales milestone payments. Royalties will also be payable to Argenta.

Commenting on the progress, Dr. Christopher Ashton, Argenta Discovery’s CEO, said, “The programme continues to deliver beyond the expectations of both parties and we are firmly on track to achieve our joint strategic goals for the programme.”

Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow obstruction that is progressive and current therapies, including inhaled corticosteroids, fail to treat disease progression. COPD is a leading cause of morbidity and mortality worldwide with an overall prevalence in adults over 40 years currently estimated at between 9 and 10%. Unlike many other major diseases, deaths due to COPD are increasing and the World Health Organisation (WHO) estimates by 2030 that COPD will be the third leading cause of mortality and fifth leading cause of morbidity in the world. Thus there is a high level of unmet medical need for this progressive and debilitating disease.

About Argenta Discovery

Argenta Discovery was founded in August 2000. Argenta has expertise in chronic respiratory diseases, including Chronic Obstructive Pulmonary Disease (COPD) and severe asthma. The company has generated a portfolio of pre-clinical bronchodilator and anti-inflammatory programmes with the goal of demonstrating clinical proof-of-concept. In 2009, Argenta completed its first Phase II clinical trial with ADC4022, an investigational medicine for the treatment of Chronic Obstructive Pulmonary Disease (COPD) and severe asthma.

Argenta also has a contract research division that provides integrated drug discovery services to a range of leading pharmaceutical and biotechnology companies worldwide. Argenta employs approximately 160 people and is based in Harlow, Welwyn Garden City and Slough, UK. For more information about Argenta Discovery, please visit argentadiscovery

Source
AstraZeneca
Continue reading →

Because insufficient evidence was provided by the manufacturers, NICE is unable to recommend the use the following treatments in the NHS:

– bevacizumab in combination with paclitaxel for the first-line treatment of metastatic breast cancer

– bevacizumab in addition to platinum-based chemotherapy for the first-line treatment of patients with inoperable advanced, metastatic or recurrent non-small-cell lung cancer (other than predominantly squamous cell histology)

– carmustine implants as an adjunct to surgery in patients with recurrent glioblastoma multiforme (a type of brain cancer) for whom surgery is appropriate

– cetuximab for the treatment of colorectal cancer following failure of oxaliplatin-containing chemotherapy

Andrew Dillon, NICE Chief Executive said:

“NICE is committed to producing timely guidance to the NHS using our fast-track single technology appraisal process. This process relies on the manufacturer to submit evidence so that we can appraise the treatment. Occasionally, manufactures either fail to make a submission or the submission is inadequate. Where this happens we work with the company to try and resolve the problem. If the problem cannot be resolved we will have to bring an appraisal to a conclusion without undertaking a full evaluation.

“In these circumstances, we will issue advice to the NHS which will say that ‘NICE is unable to recommend the use of the technology’. The advice will explain why we have come to the conclusion to terminate the appraisal and will offer advice to the NHS on what to do next. Normally, this will be that the NHS should be cautious in considering use of the treatment. Of course, if sufficient evidence does become available in the future, we may take the opportunity to review and to revise our advice to the NHS.”

About NICE

The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.

NICE produces guidance in three areas of health:

– public health – guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector

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In the work defended at the University of the Basque Country (UPV/EHU), an in vitro culture model of human colon cancer was created in order to reproduce the gene regulation that is expressed in these cancer cells during their growth as metastasis in the liver of patients. This in vitro culture model provides a simple tool for the study and identification of the origin of the factors regulating this expression, as well as a simple form of the therapeutic evaluation for new pharmaceutical drugs that block this route.

Cancer of the colon is the third most common kind of cancer in our society. And, in many cases, the first symptoms usually appear when the disease is already in quite an advanced state. Of those colon cancer patients who suffer metastasis, approximately 45 % will develop hepatic metastasis.

It is this theme that the Gipuzkoan biologist, Ms Amaya del Villar, deals with in her PhD, recently defended at the Faculty of Medicine and Odontology at the University of the Basque Country (UPV/EHU). It is research work in which colon cancer generated hepatic metastasis is analysed, a disease which may be propitiated by genes that are regulated by the very microenvironment or environment of the liver.

The PhD entitled “Study of the genes involved in hepatic metastasis of colon cancer and which are regulated by microenvironmental factors of the liver” was led by Fernando Vidal-Vanaclocha of the Department of Cell Biology and Histology at the UPV/EHU and obtained excellent cum laude. Cooperating in drawing up the doctoral thesis was the Pharmakine company and the Hepatic Surgery Unit at the Cruces Hospital in Bilbao.

Ms Amaya del Villar ??lvarez is a graduate in Biological Sciences from the University of Navarra and currently works for the Pharmakine company, continuing her research into cancer and metastasis.

This study aimed, on the one hand, to create an in vitro culture model of human colon cancer that would enable reproducing the gene regulation expressed by colon cancer cells during their growth as metastasis in the liver of patients with hepatic metastasis. On the other, it was aimed at identifying the origin of the factors regulating the expression of those genes. An in vitro model based on crops in the presence of conditional media

The in vitro model developed in this PhD thesis differs from current models in which the cell line from the human colon cancer is cultured in the presence of conditioned media of primary cells from the liver after being stimulated with tumour cell conditioned media. With in vitro conditioned media, the aim is to imitate the environment of the tumour cell during its implantation in an organ at a distance. This would be the simplest form to see the changes and responses produced with this kind of metastasis, and subsequently being able to develop new pharmaceutical drugs or therapeutic targets to combat it.

To this end, liver cells – hepatocytes and myofibroblasts – are isolated, and both cultured separately in the presence of conditioned media of a cell line of colon cancer. In each case, the media are collected in such a way that all the segregated soluble factors of these liver cells, responding to the tumour, are in the media. On the other hand, tumoural cells from the human colon cancer cell line were cultured for 24 hours in the presence of this conditioned media, in order to see the response that these produce in each case and compare it with both the hepatocytes and myofibroblasts.
More than 44,000 genes

To check the responses of the colon cancer tumoural cells in the conditioned media, a study of the genes was carried out and the origin of the factors regulating this expression identified. Once the 24 hours in the presence of conditioned media had passed, the nucleic acid of these cells was extracted and this subsequently subjected to the microarrays technique enabling the study of more than 44,000 genes at the same time. It was observed that one group of genes is regulated in the same way by both hepatocytes and myofibroblasts, but there are other groups that are regulated in a specific manner way by either hepatocytes or myofibroblasts. That is to say, genes regulated in the presence of conditioned media are different, depending on the cells. The biologist also observed that the hepatocytes regulate a significantly greater amount of genes than do the myofibroblasts.

“This study is only at its beginnings” stated the researcher. “Although we have possibly identified certain genes, further studies have to be undertaken. And, undoubtedly this is a field which will widen. The results so far obtained have to be corroborated with much wider studies, with a much larger number of patients, and so on”, she added.

“But, basically, I think it important to demonstrate the influence of the microenvironment in the process of metastasis”, she argued. “When studying cancer, it is good to have a more global, overall perspective, not solely focusing on the tumour or malignant cells”.

“If we manage to find out the process of regulation in the tumour cell during metastasis, we will have achieved the possibility of developing therapeutic targets in order to try and avoid, as it were, the metastasis occurring”.

ELHUYAR FUNDAZIOA
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