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Nigeria: FG and Cost of Cancer Screening

THE Federal Government’s recent directive to its hospitals to reduce the cost of cancer screening, though very commendable, is long overdue, considering that late diagnosis of the disease has resulted in the high rate of cancer related deaths in the country.

Cancer is one of the leading causes of deaths in the world, especially in developing countries, which carry about 80 per cent of the burden, globally. Unfortunately, in Nigeria with over 160 million people, going by the latest global report on population, detection of the killer non-communicable disease (NCD) is usually late.

Minister of Health, Prof. Onyebuchi Chukwu, who announced the reduction in the cost of screening for breast, cervical, prostate and colon cancers during the recent 17th Annual Conference of the Nigerian Association of Urological Surgeons (NAUS) in Abuja, said the directive to provide screening services at affordable prices is to ensure that the disease is detected early.

Other measures being taken by government to tackle the cancer scourge, he said, include equipping fully the University of Port Harcourt Teaching Hospital, the Federal Medical Centre, Gusau, Zamfara State and the Vesico Virginal Fistula (VVF) Centre, Abakaliki, Ebonyi State with mammography machines, cryoprobes, video culposcopes, ultrasound, loop electrosurgical excision procedure and enzyme-linked immunosorbent assay machines, so that these institutions can serve as referral centres for those who screen positive for pre-malignant lesions.

With the World Health Organisation (WHO) projecting that about 84 million people may die of cancer by 2015 if urgent steps are not taken to arrest the scourge, there is, indeed, need to facilitate a national policy on cancer management, starting with free or significantly reduced cost of cancer screening.

These moves by the Federal Government are steps in the right direction, considering that cancer is one disease that is no respecter of social status and one that has continued to deal devastating blows on the productive segments of the nation’s economy.

Among notable Nigerians whose lives were cut short by cancer are human rights activist and lawyer, Chief Gani Fawehinmi, who died in 2009 after a prolonged battle with lung cancer, Dr. Bekolari Ransome-Kuti, a medical doctor and human rights activist and Yemi Tella, coach of the Nigerian 2007 FIFA U-17 World Cup winning team.

Maryam, wife of former military president, Gen. Ibrahim Babangida, died of ovarian cancer on December 27, 2009 at California’s City Hope Hospital in the United States, aged 61, while the wife of Edo State Governor, Adams Oshiomhole, was swept away by cancer of the breast.

Presently, about two million cancer cases are said to be recorded in Nigeria with an estimated 350,000 new cases being diagnosed annually. Of the two million, only 10 per cent or about 200,000, have access to hospitals with radiotherapy facilities, while out of the number, only five per cent, about 10,000, have the resources to go abroad where they pay between $10,000 and $15,000 per patient for a three to five-weeks course of radiotherapy.

While about 27 per cent of the two million cases are suffering from breast cancer, about 25 per cent are cancer of the cervix cases. And of these two cancers that are devastating women in Nigeria, one has good prognosis, if detected early, while the other can be prevented. Yet they continue to cause untold hardships and deaths simply because of the dearth, and high cost, of facilities, especially for early detection, among other constraints.

Nigeria’s mortality and morbidity statistics for cancer are said to be high due to the late presentation syndrome involving 83-87 per cent of cancer patients, simply because the awareness level of Nigerians, especially women, is very low, even as this is dogged by superstition and cultural restraints.

As a matter of fact, some medical experts have argued that even the estimated 350,000 new cases of cancer diagnosed annually in Nigeria is far from the true figure of the cancer crisis in the country, insisting that a large number of cancers are not detected as majority of Nigerians are poor and live in rural areas, far removed from health facilities.

Lack of, or inadequate, research into this debilitating disease is also a major challenge. Nigeria, for instance, is said to contribute little or nothing to the global body of literature on cancers and most of these contributions are hospital based, perhaps representing the tip of the iceberg as majority of Nigerians live in rural areas, unable to access any health facilities.

As such, the cancer awareness efforts and screening methods to enhance early detection do not seem to have had much impact on the nation.

No doubt, the problems of lack of access to quality health care, ignorance, poverty and poor co-ordination of issues of health education complicate issues. For instance, facilities such as computerised tomography (CT) and Magnetic Resonance Imaging (MRI) are difficult to come by, and when available, the cost of accessing such facilities put them out of reach of the average citizen.

Of more concern is the fact that clinical services for cancer are grossly inadequate and poorly distributed. Only a few centers have functioning radiotherapy equipment, and though radiologic services are said to be generally available, access is seriously limited by high cost.

So, while the Federal Government’s move to reduce the cost of cancer screening in federal hospitals is commended, we call on the authorities to ensure that the screening equipment are available and more easily accessible, especially in the rural areas, while a more vigorous and better co-ordinated effort into cancer research must be encouraged in institutions across the country.

Source: http://allafrica.com/stories/201111241060.html

Research at A&M and Scripps finds HIV-killing compound

COLLEGE STATION - A powerful topical preventative for HIV, the virus that causes AIDS, could be a step closer to clinical trials, thanks to a newly discovered molecular compound that research at Texas A&M University and the Scripps Research Institute shows dissolves the virus on contact.

The ability of the synthetic compound known as “PD 404,182″ to break apart the AIDS-causing virus before it can infect cells was discovered by Zhilei Chen, assistant professor in the university’s Artie McFerrin Department of Chemical Engineering, and her team of researchers. Their findings appear in the November online edition of “Antimicrobial Agents and Chemotherapy,” a journal of the American Society for Microbiology.

“This is a virucidal small-molecule compound, meaning that it has the ability to kill a virus; in this case that virus is HIV,” Chen says.

“Basically, it acts by breaking the virus open. We found that when HIV comes in contact with this compound, it breaks open and loses its genetic material. In a sense, the virus ‘dissolves,’ and its RNA becomes exposed.

Since RNA is pretty unstable, once it is exposed it’s gone very quickly and the virus is rendered non-infectious.”

In other words, the compound works by quickly ripping open the virus before it can inject its genetic material into a human cell. What’s more – and perhaps even more important – the compound, Chen explains, achieves this by acting on something within the virus other than its viral envelope protein, meaning that the virus can’t alter its proteins to bolster its resistance – something that’s made HIV notoriously difficult to treat.

“We believe this compound is not working on the viral protein of the viruses but on something else common in all the viruses on which we tested it – some cellular material common in these viruses,” Chen notes. “Because this compound is acting on a component that is not encoded by the virus, it will be difficult for the virus to evolve resistance against this compound.”

While not a cure for HIV, the compound demonstrates significant potential for use as a preventative, specifically in the form of a topical gel that could be applied in the vaginal canal, Chen explains.

“We conducted a number of tests to demonstrate that this compound remains active in vaginal fluid and is not rendered ineffective,” Chen says. “In the form of a vaginal gel, the compound would serve as a barrier, acting almost instantaneously to destroy the virus before it could infect a cell, thereby preventing HIV transmission from one person to another.”

Surprisingly, Chen and her team did not set out to discover an HIV preventative. Instead, they were conducting screenings of molecules for use in potential drug therapies targeting hepatitis C virus, which causes the dangerous and often fatal disease of the liver. Employing a screening system developed by Chen, the team screened thousands of molecular compounds, in search of those that could block aspects of the HCV life cycle.

During the course of the screenings, the team made an interesting discovery

- not only was PD 404,182 an HCV inhibitor, it also worked on lentiviruses (the group’s negative control in its experimental procedures). Intrigued by that finding, Chen then tested PD 404,182 on HIV, which itself is a lentivirus and found the compound to be even more effective on HIV than on HCV.

“We believe PD 404,182 acts through a unique and important mechanism,” Chen notes. “Most of the known virucidal compounds interact with the virus membrane, but our compound does not appear to interact with the virus membrane. Instead, it bypasses interaction with the membrane and still compromises the structural integrity of the virus.”

The ability of the compound to avoid interaction with the virus membrane is important because human cells have similar membranes, Chen notes. If the compound were to disrupt the structure of the virus membrane, it could also disrupt and ultimately kill human cells. PD 404,182 doesn’t interact with these membranes and is therefore a more attractive option for clinical treatment, Chen says.

As is the case with any potential pharmaceutical, several key steps are still needed before it winds up on drug store shelves. In addition to several rounds of animal studies to ensure the compound is safe for humans, further collaborations with chemists are needed to continue to improve the efficiency of the compound. Chen says. What’s more, Chen also plans to further explore the mechanism by which PD 404,182 breaks apart HIV.

This work is collaboration between Chen’s team, consisting of graduate students Ana Maria Chamoun and Rudo Simeon, postdoctoral associate Karuppiah Chockalingam, and Professor Philippe Gallay’s team at the Scripps Research Institute.

Source: http://www.kxxv.com/story/16095021/research-at-am-and-scripps-finds-hiv-killing-compound

First Clinical Trial of Autologous Cardiac Stem Cells Shows Positive Results

Initial data from the first ever trial to evaluate autologous cardiac stem cell (CSC) transplants in humans suggests that the treatment improves left ventricular (LV) systolic function by an average of 12% over one year, and reduces infarct size in patients with severe heart failure due to ischemic heart disease. The trial investigators say the results triple the 4% average improvement that they had projected and calls for the start of larger Phase II trials.

Stage A of the ongoing open-label Phase I SCIPIO (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy) study, by investigators at the University of Louisville and Brigham and Women’s Hospital, is evaluating CSC transplantation in patients with severe heart failure secondary to ischemic cardiomyopathy. The target population includes patients who underwent coronary artery bypass grafting (CABG), had LV ejection fraction (EF) of less than or equal to 40%, and a previous myocardial infarction.

Treated patients were administered with about a million autologous CSCs by intracoronary infusion, at a mean of 113 days after CABG. To generate the cardiac stem cells, tissue from the right atrial appendage was harvested from the patients at the time of CABG, and CSCs were isolated and expanded at the Brigham and Women’s Hospital.

Data from 14 of 16 patients assigned to the treatment group, and seven from the control group (best supportive care), have now been published in The Lancet to coincide with data presentation at the American Heart Association’s Scientific Sessions meeting in Orlando, FL. The reported data showed that autologous CSC transplantation led to an increase in LVEF from 30.3% before CSC infusion to 38.5% at four months after infusion. In contrast, the LVEF of seven control patients didn’t change over eight months. The benefits of CSC transplantation was even more pronounced at one year in eight evaluated patients, for whom LVEF increased by 12.3 ejection fraction units compared with baseline. In the seven treated patients evaluated using MRI, infarct size was also shown to have decreased by 24% at 4 months, and 30% at one year.

The trial has been led by Roberto Bolli, M.D., at the University of Louisville and Piero Anversa, Ph.D., at Brigham and Women’s Hospital/Harvard Medical School in Boston. “The results are striking,” Dr. Bolli states. “While we do not yet know why the improvement occurs, we have no doubt now that ejection fraction increased and scarring decreased. If these results hold up in future studies, I believe this could be the biggest revolution in cardiovascular medicine in my lifetime.”

The published paper in The Lancet is titled “Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised Phase I trial.”

Source: http://www.genengnews.com/gen-news-highlights/first-clinical-trial-of-autologous-cardiac-stem-cells-shows-positive-results/81245949/

FDA Clears Abbott’s Confirmatory Chagas Disease Assay

FDA approved Abbott’s in vitro enzyme strip assay for Chagas disease. The Abbott ESA Chagastest detects antibodies to the causative pathogen Trypanosoma cruzi in serum or plasma samples. It is indicated for use as an additional, more specific test on human samples that have been found to be repeatedly reactive using a licensed screening test.

The T. cruzi parasite is transmitted through contact with the feces of an infected triatomine bug, but infection can also occur congenitally, through transfusions of contaminated blood products, or through an organ transplant from an infected donor.

U.S. Centers for Disease Control and Prevention (CDC) estimates suggest that as many as 11 million people worldwide are infected with Chagas disease, including over 300,000 in the U.S. alone. Concerns about Chagas disease transmission through blood led FDA to implement mandatory Chagas disease screening of donated blood back in 2007. “The new Abbott ESA Chagas test provides organizations that screen blood with an approved testing method help the blood supply safe and enable them to confidently counsel infected donors,” remarks John Coulter, divisional vp for Abbott’s diagnostics business.

Source: http://www.genengnews.com/gen-news-highlights/fda-clears-abbott-s-confirmatory-chagas-disease-assay/81245981/

Vaccine for ovarian, breast cancer shows promise

(CBS) A new vaccine that targets ovarian and breast cancer has shown promise in early studies, giving scientists hope they may be closer to stopping the deadly diseases.

PICTURES: 25 breast cancer myths busted

Known as PANVAC, the vaccine triggers the immune system to attack tumor cells.

“With this vaccine, we can clearly generate immune responses that lead to clinical responses in some patients,” lead scientist Dr. James Gulley, director and deputy chief of the clinical trials group at the laboratory of tumor immunology and biology at the National Cancer Institute, said in a written statement.

For their research, published in the Nov. 8 issue of Clinical Cancer Research, scientists tested the vaccine on 26 patients, 12 of whom had breast cancer, 14 of whom ovarian. Most of the women had undergone prior chemotherapy treatment.

What did the scientists find? The vaccine caused women with breast cancer’s disease progression to stall for 2.5 months, and their median survival was 14 months. Four had stable disease, meaning the cancer didn’t grow nor shrink. Women with ovarian cancer reported a two month gap in disease progression, and survived for 15 months, and three had stable disease.

The cancer vaccine stalls cancer progression for only a couple of months? What’s the big deal?

“That time frame is not anything to write home about,” Gulley told WebMD. But he said that one of the women who had breast cancer currently shows evidence of cancer after undergoing the experimental vaccine – four years later.

“It gives us encouragement that we may be on to something here,” he said.

That 32-year-old woman was the youngest in the study, according to WebMD, but her cancer had spread to her liver and chest lymphnodes. At 18 months, there was no X-ray evidence of cancer. Gulley isn’t sure why her treatment was so successful, but the woman had only undergone chemotherapy once. That suggests her immune system might have been stronger than the other women’s.

But don’t expect the vaccine on the market anytime soon. This was only a small study, so more needs to be done.

Gulley said interest in a cancer vaccine is increasing among scientists, but said in the statement that “more studies in the appropriate patient populations are required” to ensure safety, and which patients would benefit most.

The National Cancer Institute has more on cancer vaccines in development.

Source: http://www.cbsnews.com/8301-504763_162-57321522-10391704/vaccine-for-ovarian-breast-cancer-shows-promise/

Coffee Drinking Linked To Lower Risk Of Common Skin Cancer

New research presented at a conference in the US on Monday finds that drinking coffee is linked to a lower risk of a common form of skin cancer known as basal cell carcinoma (BCC). Results of a prospective study that followed over 25,000 cases of skin cancer suggest coffee may be an important dietary option to prevent BCC.

The research is the work of Dr Fengju Song and colleagues. Song is a postdoctoral fellow in the department of dermatology at Brigham and Women’s Hospital and Harvard Medical School.

For the study, the researchers used data from the Nurses’ Health Study, covering 72,921 participants followed from June 1984 to June 2008, and the Health Professionals Follow-Up Study, covering 39,976 participants from June 1986 to June 2008. These studies gathered detailed information about diet and health, including consumption of beverages such as coffee.

From those cohorts, the researchers identified 25,480 cases of skin cancer, comprising 22,786 BCC cases, 1,953 squamous cell carcinoma (SCC) cases, and 741 cases of melanoma.

Song and colleagues found a 20% reduction in risk for BCC among women who drank more than three cups of coffee per day, while for men who drank more than three cups per day the risk was 9% lower. These reductions were in comparison to counterparts who only drank less than 1 cup of coffee a month.

The relationship between amount of coffee consumed and BCC was inverse: that is more coffee was linked to lower risk, so that when participants were ranked according to how much coffee they drank, those in the top 20% of consumption (upper quintile) had the lowest risk, with 18% reduction for women and 13% reduction for men, compared to those in the lowest 20% of consumption (bottom quintile).

Song told the press:

“Given the nearly 1 million new cases of BCC diagnosed each year in the United States, daily dietary factors with even small protective effects may have great public health impact. Our study indicates that coffee consumption may be an important option to help prevent BCC.”

The researchers were quite surprised at the finding, and that it only applied to BCC and not the other types of skin cancer.

Animal studies have pointed to links between skin cancer risk and coffee consumption, but epidemiological studies in human populations have not arrived at the same conclusions, they said.

Song explained that tests on mice have shown that consuming caffeine or applying it to the skin reduces the number of UV-damaged keratinocytes (the most common cell type in the outer skin layer or epidermis) via programmed cell death or apoptosis, and that this also markedly reduces the subsequent development of SCC.

“However, in our cohort analysis, we did not find any inverse association between coffee consumption and the risk for SCC,” said Song, who suggests there is a need for further research that specifically addresses the link between coffee intake and BCC and also explores the underlying biological mechanism.

Written by Catharine Paddock PhD
Copyright: Medical News Today

Source: http://www.medicalnewstoday.com/articles/236557.php

XXI Century Database of Traditional Chinese Medicine Released

October 18, 2011

A comprehensive database developed by King’s College London researchers that features the chemical components found in traditional Chinese medicines has been released to market this month, allowing researchers to explore age-old remedies in the search for tomorrow’s new drugs.

Provided under licence to Tim Tec LLC, a US-based life science supplier company, the ‘Chem-TCM’ database is the most comprehensive of its kind. Featuring over 12,000 chemicals found in plants used in Chinese medicine, the database provides a valuable research tool for the pharmaceutical and biotechnology industries, academic researchers, and the medical profession (including the complementary health sector).

Part-funded by Innovation China UK (ICUK), the database has been developed through collaboration between researchers in the Institute of Pharmaceutical Science at King’s, Dr David Barlow, Dr Thomas Ehrman and Professor Peter Hylands, and the Shanghai Institute of Materia Medica (SIMM).

To create the Chem-TCM database, the King’s researchers analysed patterns in the known and predicted biological activities of 12,000 chemicals from over 300 Chinese herbs in relation to their usage in traditional Chinese medicine. Their results reveal that many categories in Chinese medicine are translatable into Western terminology. Dr David Barlow said: ‘Traditional Chinese medicine has undergone a remarkable renaissance in recent years. However, the unique language used to describe categories of medicines has hindered effective understanding of one of the most developed and mature systems of alternative medicine in existence.

‘With the Chem-TCM database, future researchers will now be better able to understand the chemical basis of remedies that have been in use for thousands of years. This is likely to be of benefit both in the search for new drugs and, equally significantly, in understanding how Chinese medicine works.’

Chem-TCM features four major parts: chemical identification, botanical information, predicted activity against Western therapeutic targets, and estimated molecular activity according to traditional Chinese medicine categories.

Dr. Marat Niazoff, CEO of TimTec LLC, said: ‘This database is a comprehensive attempt to link Chinese and Western medicine on the molecular level. It is a great contribution to the further study of natural products and their pharmacological potential. The database gathers diverse structural material and a wealth of phytochemical information, opening new possibilities for virtual screening in particular.’ With over 15 years of experience in serving life-science R&D and established global customer base TimTec is well positioned to assume product development and distribution role. Chem-TCM commercial license is the protected adaptation of ChemDBsoft, TimTec chemical records and database managements software. TimTec welcomes this unique database product to its offerings.

Manyi Cristofoli, Director of ICUK, said: ‘I am pleased another ICUK-funded proof-of-concept project has now been commercialised in the pharmaceutical industry – this is a very good example of how academia and industry can successfully collaborate for innovation at a truly international level. The partnership with TimTec opens up a new global channel to jointly realise the wide potential in traditional Chinese medicine.’

King’s College London

King’s College London is one of the top 30 universities in the world (2011/12 QS international world rankings), and was The Sunday Times ‘University of the Year 2010/11′, and the fourth oldest in England. A research-led university based in the heart of London, King’s has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.

King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.

King’s College London and Guy’s and St Thomas’, King’s College Hospital and South London and Maudsley NHS Foundation Trusts are part of King’s Health Partners. King’s Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: www.kingshealthpartners.org.

The College is in the midst of a five-year, £500 million fundraising campaign – World questions|King’s answers – created to address some of the most pressing challenges facing humanity as quickly as feasible. The campaign’s three priority areas are neuroscience and mental health, leadership and society, and cancer. For more information, please visit www.kcl.ac.uk

TimTec

TimTec LLC is a privately held company located in Newark, Delaware, USA. It was founded in 1995 to begin its work in the areas of acquisition and distribution of synthetic organic and natural compounds, custom synthesis, scientific software and laboratory equipment to become a full service partner for drug discovery.

TimTec has developed strong in-house expertise in the design of screening products to offer a full line of libraries and compound sets of various specialisation for different assays. In addition, the company provides compound management, custom formatting and computational services.

www.chemtcm.com , www.timtec.net, or info@timtec.net


Innovation China UK

Funded by HEIF3 and BIS Global Partnership Fund, the Innovation China UK (ICUK) is a collaboration programme supporting joint innovation and knowledge transfer between the UK and China. Based at Queen Mary Innovation Limited – a wholly-owned subsidiary company of Queen Mary University of London, ICUK provides a full range of services to UK companies and HEIs seeking to develop and commercialise their research and technology in the Chinese market. www.icukonline.org

X-Body BioSciences and Tanabe Research Labs Team Up to Develop mAbs for Autoimmune Diseases

X-Body Biosciences entered a partnership with Tanabe Research Laboratories (TRL) to identify therapeutic target epitopes and develop monospecific and/or bispecific antibodies against those targets. TRL is focussed on discovery and development of biologicals for autoimmune diseases.

Under terms of the deal, X-Body will be responsible for screening, and TRL will fund the work. TRL has the option to negotiate rights to the antibodies discovered in the collaboration for further preclinical research, clinical development, and commercialization.

X-Body will leverage its human antibody library and Protein Chain Reaction™ screening technology. The platform reportedly allows for screening against cell surface targets in their native state on live cells or purified target proteins.

This selection system employs next-generation sequencing to analyze thousands of hits to obtain high-quality leads. The modular leads generated can be incorporated into V(H) domain, scFv, IgG, and bispecific antibody formats.

“X-Body’s technology represents a major step forward in the ability to rapidly generate thousands of human antibodies against functionally relevant targets,” according to Roland Newman, Ph.D., CSO of TRL. “The power and versatility of X-Body’s platform in generating antibodies against targets that are inaccessible by conventional techniques offers new and exciting prospects.”

Source: http://www.genengnews.com/gen-news-highlights/x-body-biosciences-and-tanabe-research-labs-team-up-to-develop-mabs-for-autoimmune-diseases/81245774/

Body & Mind – HEALTH U.S. Doctor Cautious About HIV Vaccine

A New York City-based infectious disease specialist said a new vaccine developed by Spanish scientists, which could turn HIV into minor infection status, is reason to be cautiously optimistic.

Dr. Joseph Rahimian said Thursday news of an HIV vaccine is certainly exciting, but questions remain.

“An HIV vaccine has been the holy grail for infectious disease doctors for a very long time,” Rahimian said. “ There are a lot of people interested in creating one and obviously a lot of demand for it, so there would be a lot of excitement if this research is accurate.”

The vaccine, developed by scientists at the Spanish Superior Scientific Research Council (CSIC) in Madrid, works by training the immune system to detect HIV and learn how to combat the virus.

In a trial involving 30 healthy volunteers, scientists found that 90 percent of those who were given the MVA-B vaccine developed an immunity against the virus and 85 percent maintained this for a year.

Professor Mariano Esteban, from CSIC, said, “MVA-B vaccine has proven to be as powerful as any other vaccine currently being studied, or even more.”

He said the vaccine was like showing the body a picture of the HIV, “so that it is able to recognize it if it sees it again in the future.”

“If the virus enters the body and tries to develop in a cell, the immune system is ready to inactivate the virus and destroy the infected cell,” he added. Scientists hope that if bigger trials are successful, HIV would no longer cause AIDS and would be much less contagious.

‘”If this genetic cocktail passes Phase II and Phase III future clinic trials, and makes it into production, in the future HIV could be compared to herpes virus nowadays,” according to the study.

However, Rahimian said this study needs much more room to grow.

“The population that they used is very small, and they followed them out to one year. So one important question is how long does this last for? A vaccine that has to be given repeatedly every year is less exciting than a vaccine that can give long-term immunity,” he said.

On the other hand, Rahimian pointed out there are some vaccines given every year, which are successful, like the flu shot.

“I would say many people have tried to create vaccines, and it is a very difficult task, so any enthusiasm for a successful vaccine is guarded,” he said.

Source: http://www.foxnews.com/health/2011/09/29/new-vaccine-could-turn-hiv-into-minor-infection/

Study: Shark Chemical May Protect Humans Against Viruses

A chemical derived from sharks could help protect humans against viral infections such as hepatitis, American research out Tuesday showed.

Scientists found that a chemical called squalamine demonstrated effective antiviral activity against a range of human viruses from yellow fever to hepatitis B, C and D, in both lab and animal experiments.

As the chemical has already been used in human clinical trials for the treatment of cancer and eye disorders, it means it could quickly be tested as a new drug treatment for viral diseases, researchers at Georgetown University Medical Center, Washington, said.

“To realize that squalamine potentially has broad antiviral properties is immensely exciting, especially since we already know so much from ongoing studies about its behavior in people,” lead researcher Professor Michael Zasloff, said.

“Squalamine appears to protect against viruses that attack the liver and blood tissues, and other similar compounds that we know exist in the shark likely protect against respiratory viral infections, and so on,” he added.

Zasloff believes the research, published in the “Proceedings of the National Academy of Sciences” journal, also explains the mystery of how sharks, which have a very primitive immune system, can so effectively fight the viruses that plague other living creatures.

He continued, “We may be able to harness the shark’s novel immune system to turn all of these antiviral compounds into agents that protect humans against a wide variety of viruses. That would be revolutionary. While many antibacterial agents exist, doctors have few antiviral drugs to help their patients, and few of those are broadly active.”

Source: http://www.foxnews.com/health/2011/09/20/study-shark-chemical-may-protect-humans-against-viruses/

Insulin May Help Treat Alzheimer’s

Researchers are investigating insulin as a possible treatment for Alzheimer’s disease, and in a preliminary study, the results look promising.A study in the journal Archives of Neurology suggests that intranasal insulin – that is, delivered through the nose – may help with cognition and functioning in patients who have both mild and more severe dementia.It’s premature to think of this as a treatment; the study only looked at 104 people, and needs to be repeated in much larger groups before it can be deemed effective. But it sets the stage for broader clinical trials.Recent research has suggested that insulin plays an important role in a number of brain functions, in addition to regulating blood sugar. Insulin promotes cell repair and cell genesis, so the thinking is that it could actually modify the course of Alzheimer’s disease, says lead study author Suzanne Craft, professor of psychiatry at VA Puget Sound and University of Washington.It also appears to protect against the toxic effects of beta-amyloid, the protein involved in the brain plaques associated with dementia. Insulin also prevents the formation of the toxic form of tau, a biomarker found in the cerebrospinal fluid of Alzheimers’ patients, Craft said.”What we saw was that for the insulin-treated patients, the ones who had improvement in memory and function had improvement in spinal fluid biomarkers,” she said.The goal of this study was to supplement and normalize the insulin levels in the brain without affecting levels in the rest of the body. This was done with a device that was designed to deliver insulin through the nose to the brain without getting too much into the blood.Researchers tested patients who had either early Alzheimer’s or mild cognitive impairment, a team for the early stages of dementia.Patients treated with insulin were able to remember information over a period of time better than those who got placebo; in fact, performance improved 20%. They also showed an enhancement in brain glucose metabolism in some areas; those who received placebo tended to show a decline.Alzheimer’s patients in the insulin group benefited more in terms of daily function than those with mild cognitive impairment, but by definition mild cognitive impairment does not greatly impair daily functioning.The treatment had the mild side effects of occasional mild headache and runny nose, but had a good safety profile generally, Craft said.In patients with mild cognitive impairment, researchers observed improvement in daily function and general cognitive abilities.But researchers don’t know what would be the optimal dosing and schedule of intranasal insulin for treating dementia; that is still an open question.So what does this mean for diabetics who already give themselves daily injections of insulin to manage their condition? Researchers don’t yet understand how much of that insulin is actually getting into the brain, Craft said; and if you’re not diabetic, having high levels of insulin in the blood is probably not good in the long run, so no one should experiment with this at home. Diabetes is a known risk factor for Alzheimer’s, but there are a lot of unanswered questions about that connection.

Source: http://www.kxly.com/health/29172695/detail.html

Ark to Manufacture PsiOxus’ IV-Administered Oncolytic Virus for Clinical Trials

    Ark Therapeutics negotiated a manufacturing partnership with PsiOxus Therapeutics for the latter’s ColoAd1 candidate for the treatment of colorectal cancer. Under terms of the agreement Ark will work with PsiOxus to generate an IV formulation of the adenovirus-based oncolytic product using its suspension-based single-use system (ATOSUS) for toxicological and Phase I/II clinical studies.

    ColoAd1 is an Ad3/Ad11p hybrid, designed as a broad-spectrum anticancer therapeutic capable of destroying tumor cells at minute concentrations, but with minimal damage to healthy tissue. The oncolytic virus has been generated using the evolutionary principle of natural selection, to generate a candidate that PsiOxus claims demonstrates anticancer potency at 0.1–10 femtomolar concentration, including activity against drug-resistant cancers. The initial target indications for ColoAd1 will be metastatic colorectal cancer and primary hepatic cellular carcinoma.

    The evolutionary approach used to generate ColoAd1 involves generating a chimeric adenovirus library by homologous recombination under atypical conditions of super-infection, PsiOxus explains. Multiple rounds of selection are subsequently carried out to identify strains with a tumor-dependent phenotype that also rapidly killed tumor cells. Candidate oncolytic viruses are then screened on normal cells to select a candidate with optimal therapeutic index.

    PsiOxus was established in December 2010 through the merger of Myotec Therapeutics and Hybrid BioSystems. The ColoAd1 candidate originated at Hybrid Biosystems, a firm initially established to exploit viruses as therapeutics. The candidate was developed by Hybrid in collaboration with Bayer Schering. Hybrid Biosystems also developed the PolyStar vaccine vector system, and PolyMap adjuvant/immunotherapeutics platform, both of which PsiOxus inherited when it was formed last year.

    PsiOxus’ lead clinical-stage compound, MT-102, is a small-molecule anabolic catabolic transforming agent, which is currently undergoing a placebo-controlled Phase II trial as a treatment for disease-related cachexia. MT-102 was originally developed by Myotec, itself an Imperial College London spin-out established to progress work by university scientists on the underlying mechanisms of cachexia. PsiOxus says promising preclinical results from in vivo studies evaluating MT-102 against age-related sarcopenia will also be followed up through future clinical studies.

    Source: http://www.genengnews.com/gen-news-highlights/ark-to-manufacture-psioxus-iv-administered-oncolytic-virus-for-clinical-trials/81245663/

Clinical Successes and New Technologies Revive Gene Therapy

    The prospect of curing human diseases by replacing a disease-related gene with a normal version remains the ultimate goal of gene therapy. But in its early days, attempts at gene therapy met with unpredictable and occasionally fatal outcomes. The field sustained a serious setback in 2000 following the death of 18-year old Jesse Gelsinger after receiving gene therapy to treat orinthine trascarbamlase deficiency (OTCD), a rare metabolic disorder that prevents the body from breaking down ammonia.

    Gene therapy took another blow in September 2003, when the FDA placed a temporary halt on all gene therapy trials using retroviral vectors in blood stem cells. The agency was responding to the development of a leukemia-like disorder that developed in a three-year-old boy following successful gene therapy for to X-linked severe combined immunodeficiency disease (X-SCID). Subsequently, the disease developed in three children, one of whom died from it.

    Now, bolstered by the development of enabling technologies and recent clinical successes, gene therapy is making a significant comeback. Effective gene delivery has been established in multiple formats including direct DNA delivery, genetically engineered autologous cells, and specifically targeted gene modification or insertion.

    Adrenoleukodystrophy

    In 2009, international teams of researchers reported the successful treatment of two children suffering from adrenoleukodystrophy (ALD). ALD is a severe hereditary condition caused by mutations in ABCD1 gene, which encodes the adrenoleukodystrophy protein (ALDP), a protein involved in fatty acid degradation.

    Over the course of the disease, afflicted individuals steadily lose the myelin sheath that surrounds nerve cells. Myelin loss results in loss of nerve function, leading to increasing physical and mental disability. X-linked ALD, the most common form of the disease, affects boys as early as age six, with death usually occurring before the patients reach adolescence.

    While ALD progression can be halted by allogeneic hematopoietic cell transplantation (HCT), finding correctly matched donors and the inherent dangers in the procedure present problems.

    Investigators in France reported successful treatment of two ALD patients for whom there were no matched donors. They first removed CD34+ cells, then transfected the cells ex vivo with a lentiviral vector encoding the wild-type correct form of the gene encoding ALDP, and finally re-infusing them into the patients after they had received myeloablative treatment.

    Over a span of 24 to 30 months of follow-up, the authors said, they could detect polyclonal reconstitution, with 9 to 14% of granulocytes, monocytes, and T and B lymphocytes expressing the ALD protein.

    Beginning 14 to 16 months after infusion of the genetically corrected cells, progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT. Thus, the authors said, lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD.

    Leber Congenital Amaurosis

    Another successful area for gene therapy has been Leber congenital amaurosis (LCA), a heritable form of progressive blindness. LCA, the result of a mutation in the RPE65 gene, may be treatable by introducing a normal copy of the mutated gene directly into the retinas of affected individuals.

    Normally, the RPE65 protein converts dietary vitamin A into a retina-specific form of vitamin A needed for rhodopsin formation. Rhodopsin is a visual pigment that absorbs light after it enters the eye, and it requires the RPE65 protein to regenerate after light exposure. Therefore, mutations in the RPE65 gene seen in LCA disrupt the visual cycle and prevent normal vision.

    Several groups have reported progress in treating the disease in individuals with the specific mutation. In 2008, these researchers administered subretinal injections of recombinant adeno-associated virus (AAV) vector expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter.

    Investigators concluded that the safety, extent, and stability of improvement in vision in all patients support the use of AAV-mediated gene therapy for treatment of inherited retinal diseases, with early intervention resulting in the best potential gain.

    HIV/AIDS

    Apart from advancements in DNA delivery and in vectors for gene delivery into patients’ cells, zinc finger nuclease technology may prove truly transformative to gene therapy in general. Zinc finger nucleases (ZFNs) are synthetic proteins consisting of an engineered zinc finger DNA-binding domain fused to the cleavage domain of a restriction endonuclease. These engineered molecules allow cellular DNA to be cut at specific points, with gene modification then occurring via the cell’s own natural repair mechanisms. They may also allow the insertion of entire genes at desired cleavage sites to replace missing or mutated genes.

    Sangamo and colleagues from the University of Pennsylvania announced positive preliminary data from their Phase I trial being conducted in HIV-infected immunologic nonresponders. The patients enrolled in this study were HIV-infected individuals on highly active antiretroviral therapy with undetectable levels of virus but low T-cell counts.

    The investigators used zinc fingers custom-designed to bind to specific DNA sequences in the CCR5 gene in HIV-infected patients’ T cells. The zinc finger proteins act as molecular scissors, bringing a DNA enzyme to the CCR5 gene to cut its sequence. During the repair process, a new mutation arises in the CCR5 protein, rendering it nonfunctional. Since the HIV virus uses the normal, unmodified version of CCR5 to gain access to T cells, the engineered cells became completely resistant to infection.

    The data showed that a single infusion of the engineered cells was well tolerated, and the CCR5-modified cells successfully engrafted in all of the patients. The treatment also resulted in a durable improvement in total CD4+ T-cell counts in five of six patients analyzed.

    The ZFN-CCR5-modified cells also exhibited normal T-cell growth kinetics and trafficking and underwent selective expansion in the gut mucosa, a major reservoir of virus in the body, suggesting, as predicted, that the cells were resistant to HIV infection.

    Sangamo’s Philip Gregory, CSO and vp, research, told GEN that the goal of developing the company’s zinc finger nuclease program “has been to give investigators the ability to perform precision engineering directly on the genome itself.”

    In the HIV application, he pointed out, no new DNA is being introduced. “We are really introducing a mutation ourselves just with the nucleases. We were able to do this because DNA repair mechanisms themselves are error prone. When the cells repair the break generated by the ZFN, the process occurs without error checking and mutations are introduced specifically at the site of the break. We can use this to achieve one desired outcome, knockout of the gene that’s been cleaved by the nuclease—in this case, the CCR5 gene. When the cell repairs it, it will create mutations.”

    In explaining the production process for the autologous cells carrying the mutated CCR5 gene, Gregory said that the cells are collected from patients and sent to a processing facility, where they are exposed to the ZFN. The cells are expanded, and then re-infused into the patient, where they engraft, expand in the patients, and get trafficked to the normal place in the body.

    “These cells are noninfectable by HIV,” Gregory said. He further explained that “just by protecting T cells, we aimed to create a reservoir of these cells that couldn’t be infected. These cells protect against loss of cells in HIV-infected patients.”

    Gregory emphasized that CCR5 itself as a target “is one of the few situations in which we know the biology of the protein from the situation that exists in the natural population of patients. Patients with the Delta 32 CCR5 mutation don’t have the receptor on their cells and are completely normal but are resistant to infection.

    “It turns out,” he said, “that an important feature of that mutation is that it eliminates CCR5 completely, giving rise to cells with no receptor on their surfaces.”

    Sangamo says it is testing its product across a full range of HIV patients including those for whom current drug regimens are failing. “We are making good progress and are letting the data tell us where to focus our further clinical trials.”

    All this progress, investigators point out, represents the culmination of years of experience, encompassing multiple disciplines from molecular biology through clinical science. And hopefully as positive clinical results continue to emerge, effective gene therapy, in whatever format, will become a real therapeutic option for intractable human diseases.

    Source: http://www.genengnews.com/analysis-and-insight/clinical-successes-and-new-technologies-revive-gene-therapy/77899451/

Genetic Link Predisposes to Mesothelioma

An investigation led by scientists at the University of Hawaii Cancer Center, Honolulu, and Fox Chase Cancer Center, Philadelphia has identified germline mutations in the BAP1 gene that predispose individuals to malignant mesothelioma. The research, published online yesterday in Nature Genetics, describes two U.S. families with a high incidence of mesothelioma, as well as other cancers, associated with mutations of the gene BAP1 [1].

Scientists have discovered that individuals who carry a mutation in a gene called BRCA1-associated protein 1 (BAP1) are susceptible to developing two forms of cancer — mesothelioma and melanoma of the eye. When these individuals are exposed to asbestos or similar mineral fibers, their risk of developing mesothelioma, an aggressive cancer of the lining of the chest and abdomen, may be markedly increased.

Mesothelioma tumors are typically associated with asbestos and erionite exposure. Erionite is a naturally occurring mineral fiber similar to asbestos that is found in rock formations and volcanic ash. Deposits have been located in at least 12 states. However, unlike asbestos, erionite is not currently regulated by the U.S. Environmental Protection Agency as one of the six asbestos fibers [2]. Only a small percentage of people exposed to asbestos or erionite actually develop mesothelioma.

Mesothelioma is one of the deadliest forms of cancer, killing approximately 3,000 people each year in the United States, with half of those diagnosed dying within one year. Moreover, rates of new cases of mesothelioma in parts of the world, including Europe and China, have risen steadily over the past decade.

Michele Carbone, M.D., Ph.D., study co-leader and director of the University of Hawaii Cancer Center, said [3]:

This discovery is a first step in understanding the role of the BAP1 gene and its potential utility when screening for mutations in those at high risk. Identifying people at greatest risk for developing mesothelioma, especially those exposed to dangerous levels of asbestos and erionite worldwide, is a task made easier by virtue of this discovery.

Joseph R. Testa, Ph.D., study co-leader and Carol and Kenneth E. Weg chair in Human Genetics at Fox Chase Cancer Center, added [3]:

This is the first study to demonstrate that individual genetic makeup can greatly influence susceptibility to mesothelioma. People exposed to dangerous levels of asbestos or erionite, those with a strong family history of mesothelioma, or those who have been previously diagnosed with a rare tumor of the eye known as uveal melanoma, may benefit from this new discovery.

The researchers focused on two US mesothelioma families — one in Wisconsin and one in Louisiana — in which members were not exposed to asbestos or erionite. Family members developed a number of malignancies, including breast, ovarian, pancreatic and renal cancers, although mesothelioma predominated.

The scientists suspected that mutations in the BAP1 gene might underlie mesothelioma in people with a strong family history of the disease after noticing genetic changes in or near other stretches of DNA where the BAP1 gene is located. Looking more closely at two families with unusually high rates of mesothelioma, they saw that every person who had provided a sample and had developed mesothelioma or melanoma of the eye also carried mutations in the BAP1 gene. Further study led to sequencing the gene in 26 individuals who had developed mesothelioma but did not have a family history of the disease. Tumors from about 25 percent of this group carried mutations in the BAP1 gene, and in two cases the mutations were inherited. Both of the individuals with inherited mutations had previously developed melanoma of the eye.

The researchers hypothesize that when individuals with BAP1 mutations are exposed to asbestos, mesothelioma predominates over melanoma of the eye. Alternatively, the BAP1 mutation alone may be sufficient to cause mesothelioma, providing a cause for tumors that arise spontaneously without previous environmental exposure.

Source: http://www.highlighthealth.com/research/genetic-link-predisposes-to-mesothelioma/

Combining Gene and Cell Therapy Is Arming Researchers with More Options for Cancer

    A few years ago most pharma and biotech companies ran away from autologous therapies, especially complex cell-based treatments. Following Dendreon’s introduction of its autologous dendritic cell therapy to treat prostate cancer, however, researchers are venturing into one-off treatments for difficult to treat diseases.

    In a huge scientific boost to the entire field of cell-based adoptive immunotherapy, scientists from the University of Pennsylvania announced on August 10 that they had used autologous, genetically engineered T cells to rid three patients of chronic lymphoid leukemia (CLL). The researchers said that it took them 20 years to achieve this breakthrough and that their work may provide a roadmap for treating other cancers.

    Additionally, researchers from Memorial Sloan-Kettering Cancer Center are reporting positive results in leukemia and ovarian cancer. Their treatment approach is similar to the Penn study but uses a different target.

    Finally, Genesis Biopharma is also in the adoptive cell immunotherapy game. It signed a CRADA with NCI to develop treatments to destroy metastatic melanoma cells using a patient’s tumor infiltrating lymphocytes (TILs).

    Leveraging TILS

    Under the terms of Genesis’ five-year agreement, the company will work with Steven A. Rosenberg, M.D., Ph.D., chief of the NCI’s Surgery Branch. It has been independently developing its Contego™ autologous cell therapy product candidate for the treatment of stage IV metastatic melanoma.

    This June, the company reported entering into a process development and scale-up agreement with Lonza. Genesis Biopharma will develop Contego as a ready-to-infuse autologous cell therapy product containing TILs obtained from an individual patient’s metastatic melanoma tumors.

    Contego is made by isolating TILs from an individual patient’s resected tumor, then expanded in vitro to several hundred million cells. The expanded TILs are then infused into the patient, where they subsequently attack melanoma tumors throughout the body. Contego is based on the TIL adoptive cell therapy being used at the NCI, MD Anderson Cancer Center, and the H. Lee Moffitt Cancer & Research Institute.

    In 2006, Dr. Rosenberg reported on studies using genetically engineered autologous T lymphocytes from melanoma patients. The authors commented that although objective cancer regression could be achieved in metastatic melanoma patients with TILs following patient immunodepletion, generation of tumor-specific T cells in this mode of immunotherapy often proved limiting.

    The authors reported that they could specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encoded a T-cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least two months after the infusion.

    The authors said that although the response rate (2 out of 15 patients, or 13%) is lower than that achieved by the infusion of unmodified autologous TILs (50%), the injected cells thrived and made up at least 10% of the patients’ total T cells weeks later. Two men who had even higher levels of the modified T cells experienced a dramatic recovery, remaining healthy 18 months following treatment.

    While Dr. Rosenberg said the success rate was low, he noted that “this is just a start.” Dr. Rosenberg’s group is working on improving the treatment including engineering other molecules into the cells to improve their tumor-finding capabilities and long-term persistence in patients.

    Souped-Up T Cells

    The University of Pennsylvania team that reported the stunning results in leukemia this month seem to have overcome some of the challenges previous TIL therapies faced, such as persistence in patients as Dr. Rosenberg pointed out. The Penn investigators reported that in their trial, which included three advanced chronic lymphocytic leukemia (CLL) patients, genetically modified versions of their own T cells behaved like “serial killers” and hunted down and obliterated tumors, resulting in sustained remissions of up to a year.

    “Within three weeks the tumors had been blown away in a way that was much more violent that we expected,” said senior author Carl June, M.D., director of Translation Research and a professor at Penn’s Abramson Cancer Center. His team published their results in simultaneously in The New England Journal of Medicine and Science Translational Medicine.

    The treatment protocol involved removing patients’ cells, genetically modifying them in Penn’s vaccine production facility, and then infusing the new cells back into the patient’s body following chemotherapy. T cells extracted from patients were genetically customized to trigger an attack on cancer cells. Of the three patients treated with the T cells, two remained free of leukemia for more than a year, and the third patient remained in remission for seven months.

    Investigators said that the treatment may potentially offer a replacement for risky bone marrow transplants as well as allow a personalized approach useful in other cancers. For the three patients in the study, the only potential curative therapy would have involved a bone marrow transplant. The procedure carries at least a 20% mortality risk and has only about a 50% chance of a cure.

    Key hurdles that had to be overcome, according to the Penn scientists, included robust expansion of the cells after delivery to the patient, prolonged persistence of the cells in the patient, and ongoing functional expression of the chimeric antigen receptors (CARs) post-infusion.

    Their technique for producing the CAR cells and the combination of genetic elements introduced into the cells overcame these problems. The scientists genetically modified patient T cells to express desired proteins, introducing genes into the cells via a nonreplicating lentivirus. The T cells were engineered to express CARs on their surfaces, recognizing a protein, CD19, expressed on the surface of normal and cancerous B cells.

    Particularly ingenious was engineering cells that could provoke a T-cell response to CD19 antigen in the absence of a major histocompatibility (MHC) restriction, allowing for much broader cellular targeting than can be obtained with normal T cells. The CAR T cells also expanded over 1,000-fold in the patients and persisted for over six months.

    It takes between 10 and 12 days to produce the genetically engineered T cells, including isolation of cells from the patient, selection of the appropriate cells, transfection with the lentiviral construct, and expansion in culture. Each infused CAR-expressing T cell, the investigators said, eradicates about 1,000 CLL cells and, they said, some of the infused cells persist as memory CAR T cells, retaining anti-CD19 functionality.

    Also reporting encouraging results with TIL therapy, Alena Chekmasova, Ph.D., and Renier Brentjens, M.D., Ph.D., investigators at the Department of Medicine at Memorial Sloan-Kettering Cancer Center, reported the generation of several CARs targeted to the retained extracellular domain of MUC16, termed MUC-CD, an antigen expressed on most ovarian carcinomas.

    “Our approach doesn’t differ particularly from the Penn group’s approach. Only the target is different,” Dr. Brentjens told GEN. “However, the dynamics of how a therapy works in a liquid tumor like leukemia may differ from how it works against a solid tumor.” He explained that his laboratory is using “mouse models to study how the cells will function when we translate the therapy to a clinical setting.” Dr. Brentjens noted that his group’s research with engineering T cells from leukemia patients will appear online in the journal Blood later this month.

    In his ovarian cancer work, Dr. Brentjens’ team studied the in vitro biology of human T cells retrovirally transduced to express CARs by co-culture assays on artificial antigen-presenting cells as well as by cytotoxicity and cytokine-release assays using human MUC-CD(+) ovarian tumor cell lines and primary patient tumor cells. They also assessed the in vivo antitumor efficacy of MUC-CD-targeted T cells in SCID-Beige mice bearing peritoneal human MUC-CD(+) tumor cell lines.

    They reported that the CAR-modified, MUC-CD-targeted T cells showed efficient MUC-CD-specific antitumor cell activity against both human ovarian cell lines and primary ovarian carcinoma cells in vitro. In mice bearing human MUC-CD(+) tumors, infusion of the engineered cells either delayed progression or eradicated the disease. The authors concluded that the preclinical study results justify further clinical investigation in patients with high-risk, MC16-bearing ovarian cancers.

    Dr. Brentjens said that his laboratory collaborates with Dr. June’s group at Penn and also runs CD19 trials. “Going forward we have a collaboration with Carl June at Penn wherein we will treat patients with a 50-50 mix of T cells modified to express either our receptor or their receptor. While both receptors target CD19, we use a different co-signaling domain, CD28, and they use 4-1BB. The question, he says, for the field in general, centers on which type of receptor design works best so we can move forward on how to further optimize this technology.”

    GEN asked Dr. Brentjens whether and how this cell-based therapy will be marketed. “It depends on what the product is,” he said. “Will it be the virus that contains the artificial receptor gene or will the modified T cells themselves be the product?” If the cells are the product, it requires GMP facilities where they can generate the cells. Each patient will be an individual customer, similar to the Dendreon model.

    Tumors have evolved many different multiple strategies to evade the immune system, including reduced antigen presentation and inhibition of effector lymphocyte function as well as the maintenance of tumor microenvironments hostile to immune function.

    Scientists however continue to hope that genetic modifications of adoptively transferred cells may eventually overcome these challenges and improve clinical outcomes for intractable cancers. As researchers translate basic research into clinical results, all eyes are on proving safety and efficacy in patients in Phase II and III studies.

    Source: http://genengnews.com/analysis-and-insight/combining-gene-and-cell-therapy-is-arming-researchers-with-more-options-for-cancer/77899448/

Scientists Claim Differentiated Cancer Cells Can Convert to Stem-Like Cells to Maintain Equilibrium

    Cells in individual tumors can interconvert into different cell types including reverting into cancer stem cells in order to maintain equilibria in terms of the proportion of cells existing in different states within the cancer, researchers claim.They found that rather than existing as a hierarchical society in which all cells are derived from cancer stem cells, cancers exist as a decentralized society of different cell types that can sense when one type of cell has been depleted and generate new cells of the relevant type to take their place.

    The group included scientists at the Massachusetts of Institute of Technology Broad Institute, Tufts University, and Harvard Medical School. Details are published in Cell in a paper titled “Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells.” Results could have significant implications for cancer cell therapy, claim lead researchers Eric S. Lander, Ph.D., and Piyush B. Gupta, Ph.D., because removing cancer stem cells will just prompt other cell types in the tumor to convert into stem cells to top up the population.

    One of the puzzling features of cancer cell populations is their ability to retain phenotypic equilibrium over extended periods of time, the team writes. Populations of cancer cells often harbor subpopulations with specific cell-surface marker profiles, which are stably maintained across many cell divisions in culture.

    To investigate the basis of this equilibrium-maintaining phenomenon further, the researchers isolated and separately cultured three cell types—stem-like, basal, and luminal—from two different human breast cancer lines derived from primary tumors. Each of the three cell types was confirmed to display specific morphological and cell surface marker characteristics.

    These relatively pure subpopulations of cells, which each represented a given differentiation state, were then allowed to expand in culture, and  relevant population dynamics monitored over time. Surprising, the researchers found that when they assessed the relative proportions of stem-like, basal, and luminal cells in each originally ‘pure’ population after expansion, there had been an evident rapid progression back to equilibrium proportions.

    Two lines of evidence indicated that this progression was due to interconversion between states, rather than as a result of differential growth rates of cells in the basal, stem-like, or luminal states, they claim. Firstly, there was no difference in the proliferation rates of the stem-like, basal, or luminal subpopulations sorted from either of the two stem cell lines: they all replicated at about the same rate.

    Secondly, given the purity of the original sorted populations and the rapid rate of return to equilibrium proportions, some minority subpopulations would need to have been dividing at more than three times per day to achieve the observed proportions through differential growth rate alone. “Such a high proliferation rate is implausible because even the most rapidly dividing human cells— embryonic stem cells—require at least 24 hours to complete a proliferation cycle,” they claim.

    Based on the notion that interconversion between cell states was therefore occurring, the team used data from their expanded breast cancer cell populations to developed a Markov model, in which the cell type transition probabilities depend only on a cell’s current state, not on its prior state. The inferred Markov transition probabilities thus make it possible to quantitatively predict how a population of cells evolves over time, given the initial proportions of cells in different states.

    The resulting model made several predictions about how the cell populations would develop, and these were confirmed in the cultured breast cancer populations, the researchers note. However, a number of unexpected predictions also emerged. One of these was that basal and luminal cells can transition back into a stem-like state: “that is, cancer stem-like cells can arise from non-stem-like cells.” This essentially contradicts current concepts relating to normal tissues, which assume a rigid lineage-hierarchy in which stem cells can give rise to nonstem cells, but not vice versa, they write.

    They tested this particular prediction by implanting either freshly sorted, or sorted and then cultured subpopulations of tumor cells in mice. As expected according to traditional dogma, only the stem-like fraction could efficiently seed tumors, and neither the luminal nor basal fraction was capable of doing so.

    However, because the lack of tumor-seeding ability displayed by the basal and luminals could have been due to their inability to survive after transplantation, the researchers repeated the exercise by co-inoculating the cells with GFP-labeled, irradiated parental carrier cells from one of the breast cancer lines. Under these conditions, all three fractions (stem-like, basal, and luminal) were equally capable of efficiently seeding tumors.

    Moreover, examination of the tumors arising from basal and luminal subpopulations mixed with irradiated carrier cells revealed the presence of significant numbers of stem-like cells. The proportions of basal, stem-like, and luminal cells contained in the resulting tumors were comparable irrespective of the sorted subpopulation initially used to seed the tumor.

    “Collectively, these results demonstrated that the luminal and basal fractions can indeed regenerate functional stem-like cells in vivo and suggested that convergence toward equilibrium cell-state proportions could be occurring due to cell-state interconversion within tumors,” the authors write. “A specific prediction of this quantitative model is that any subpopulation of cancer cells will return to a fixed equilibrium of cell-state proportions over time, provided that it is possible through one or more interconversions to transition between any two states.”

    The de novo generation of cancer stem cells has implications for the effectiveness of anticancer therapies focused on killing this cell type, because of the ability of other cancer cell types to regenerate cancer stem cells after cessation of therapy and lead to renewed tumor growth, they add. “Therefore, in order to be effective, cancer therapies will need to combine agents that are selectively toxic to cancer stem cells with agents that either target the bulk noncancer stem cell populations within tumors or inhibit transitions from noncancer stem cell to cancer stem cell states.”

    The team claims their model could also be extended to other biological settings in which stochastic state transitions occur, either in normal or diseased contexts.

    Source: http://www.genengnews.com/gen-news-highlights/scientists-claim-differentiated-cancer-cells-can-convert-to-stem-like-cells-to-maintain-equilibrium/81245572/

Adding caffeine to sunscreen could guard against skin cancer

Scientists have worked out how caffeine might protect against certain skin cancers – a finding that could lead to better sunscreens.

The research, conducted in mice, suggests that caffeine changes the activity of a gene involved in the destruction of cells that have DNA damage and are therefore more likely to become cancerous. The scientists said this may lead to new ways of preventing skin cancer, though other experts cautioned that it did not mean coffee lovers were better protected against the disease.

Skin cancer is a common disease. According to Cancer Research UK, around 100,000 cases of non-melanoma were registered in the UK in 2008, and just under 12,000 cases of the more dangerous malignant melanoma. These cancers can be caused by over-exposure to ultraviolet light from the sun, which can damage the DNA of skin cells, leading to errors when the cells divide.

The overall protective role of caffeine against cancers has been noted in previous studies, but Allan Conney of the department of chemical biology at Rutgers University in New Jersey wanted to find the specific molecular mechanisms behind it. He suspected that the response might involve a gene called ATR, which is suppressed when caffeine molecules are around. This suppression encourages the death of DNA-damaged cells.

Conney tested the idea by creating genetically modified mice whose ATR genes were deficient and exposing them to ultraviolet light until they developed skin cancer. After 19 weeks of UV exposure, he found that these mice developed 69% fewer tumours than those that had fully functioning ATR genes. In addition, tumours in the GM mice developed three weeks later than in standard mice.

After 34 weeks of UV exposure, all the mice had developed tumours, mainly a type of non-melanoma cancer called squamous cell carcinoma (SCC). The results were published on Monday in the Proceedings of the National Academy of Sciences.

“All of this suggests the possibility that caffeine, possibly [applied to the skin], would have an inhibitory effect on sunlight-induced skin cancer,” said Conney. “In addition to the effects on the ATR pathway, caffeine also has sunscreening properties.”

SCCs are less common than the other type of non-melanoma cancer, called basal cell carcinomas, but it’s the former that are more dangerous. “People rarely die from basal cell carcinomas, but you need more invasive cutting to get it out,” said Conney. “There’s more disfiguration with basal cell than squamous cell. It’s the squamous cell cancers that can metastasise and are more dangerous.”

Jessica Harris, a health information manager at Cancer Research UK, pointed out that Conney’s study examined how caffeine affected genes when it was directly applied to the skin, rather than ingested. “It didn’t look at the effects of drinking coffee, so doesn’t tell us whether or not this could reduce the risk of skin cancer,” she said.

Studies looking at coffee consumption and cancer in large groups of people have provided mixed results, she added. “Some have found that coffee drinking may slightly reduce the risk of certain types of cancer, but the evidence is not yet strong enough to be certain, and these effects tend to be seen among people who drink very large amounts.”

The best way to reduce the risk of skin cancer, said Harris, “is to enjoy the sun safely, taking care not to burn by using a combination of shade, clothing and sunscreen.”

Dot Bennett, a professor of cell biology at St George’s, University of London, said that any move to add caffeine or related molecules to sunscreens should be undertaken with care. “First one might want to check there is no adverse effect of caffeine on the incidence of other cancers, especially melanoma (pigmented skin cancer), which kills over four times as many people as [squamous cell carcinoma]. But caffeine lotion might promote tanning a little, since this family of molecules stimulates pigment cells to make more pigment.”

Source: http://www.guardian.co.uk/science/2011/aug/15/adding-caffeine-sunscreen-skin-cancer

Blood Antibody May Signal Start of Ovarian Cancer

WEDNESDAY, Aug. 17 (HealthDay News) — Researchers have found an antibody that might someday be useful in identifying women who have a higher risk of ovarian cancer, or possibly diagnosing early ovarian cancer.

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This particular antibody, which was detected in blood, develops as an immune system response to a protein called mesothelin. This protein is present in advanced ovarian cancer. Although mesothelin is found in normal tissue, it’s found in abundance in ovarian cancer cells.

The current study found that infertile women, who are known to have an increased risk of ovarian cancer, were more likely to have the mesothelin antibody. The researchers also found that women with ovarian cancer were more likely to have this antibody.

“We’re taking a novel approach to try to identify earlier biomarkers of ovarian cancer by looking at high-risk women,” said study author Judith Luborsky, a professor of pharmacology, obstetrics and gynecology, and preventive medicine at Rush University Medical Center in Chicago.

“This study found that there are antibodies to mesothelin circulating in women that have infertility,” noted Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. Exactly what these findings mean isn’t yet clear, however. “Are these women who will develop ovarian cancer? Are these antibodies related to infertility? This research gives us some clues, and leads to many more questions,” he said.

As for an individual woman who’s currently concerned about ovarian cancer, Lichtenfeld said, “I would be very cautious about drawing any conclusion about the meaning of an elevated antibody level in an individual woman.”

Results of the study will be published Aug. 17 in the online version of the journal Cancer Epidemiology, Biomarkers & Prevention.

Almost 22,000 American women are diagnosed with ovarian cancer each year, and more than 15,000 women die each year as a result of this disease, reports the American Cancer Society.

Most women who develop ovarian cancer aren’t diagnosed until the disease is advanced. If it’s found early, ovarian cancer has a five-year survival rate of 94 percent, according to the cancer society. Two tests that experts hoped would help change that — a combination of transvaginal ultrasound and a blood test for CA-125, a marker associated with ovarian cancer — haven’t reduced a woman’s risk of dying from ovarian cancer, according to a recent study in the Journal of the American Medical Association.

Luborsky and her colleagues wanted to try to find a way to detect early cancer or a screening test for who’s at high risk for ovarian cancer before the cancer develops. Testing for mesothelin wouldn’t work, because it isn’t found at high levels until the cancer is advanced.

So, instead of looking for mesothelin, the researchers looked at a group of 109 infertile women, 28 women with ovarian cancer, and 24 women with benign ovarian cysts or tumors to see if these groups had antibodies to mesothelin. They also compared the three groups of women to healthy women to see if mesothelin antibodies were present.

Significant levels of mesothelin antibodies were found in women with ovarian cancer and in women with unexplained infertility or women who were infertile due to premature ovarian failure or ovulation problems. Women who were infertile due to endometriosis didn’t have significant levels of mesothelin antibodies, according to the study. Healthy women, and women with benign ovarian growths also didn’t have significant levels of mesothelin antibodies, the investigators found.

“There’s a lot more we have to learn, but our aim would be for a screening test that could improve detection,” said Luborsky.

Source: http://health.usnews.com/health-news/family-health/cancer/articles/2011/08/17/blood-antibody-may-signal-start-of-ovarian-cancer

Five Genes May Be Tied to Lethal Prostate Cancer

TUESDAY, Aug. 16 (HealthDay News) — In what may be a diagnostic advance, U.S. and Swedish researchers have linked five inherited genetic mutations to the development of a particularly aggressive and deadly form of prostate cancer.

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The findings could someday lead to development of an easy-to-administer blood test to screen for such mutations to help physicians assess the long-term risk faced by newly diagnosed prostate cancer patients, the researchers suggested.

“The ability to distinguish patients at elevated risk for having aggressive, life-threatening prostate cancer at the time of diagnosis could improve care for the subset of cases most likely to benefit from aggressive therapy and help avoid over-treatment of patients whose tumors are likely to remain indolent,” the study team, led by Janet L. Stanford, co-director of the Fred Hutchinson Cancer Research Center’s program in prostate cancer research, reported in the Aug. 16 online edition of Cancer Epidemiology, Biomarkers and Prevention.

At issue are longstanding concerns about unnecessary over-treatment of many prostate cancer patients who actually face a relatively low risk for fast disease progression and death. Because treatment can bring about undesirable side effects, such as sexual impotence and urinary incontinence, an effort has been under way to achieve a more personalized assessment of a patient’s particular prognosis after diagnosis.

“Biomarkers that could distinguish between patients with indolent vs. more aggressive tumors are urgently needed,” Stanford said in a journal news release. “The panel of markers we’ve identified provides the first validated evidence that inherited genetic variants play a role in prostate cancer progression and mortality. Ultimately these markers could be used in the clinic, along with other known predictors that are used to assess tumor aggressiveness, such as a high Gleason score, to identify men with a high-risk profile.”

The authors, looking for genetic differences that could highlight risk differences, gathered blood samples from more than 1,300 prostate cancer patients living in the Seattle region. All were between the ages of 35 and 74 when diagnosed.

DNA analyses of the samples were compiled with those of nearly 2,900 Swedish prostate cancer patients.

The result: Five single-letter mutations (or SNPs) were isolated among the patients’ “DNA alphabet” as having a significant bearing on prostate cancer progression in terms of affecting cell death, tumor growth, inflammation, androgen hormone levels, blood-vessel development and bone density.

Patients found to have at least four out of the five cited SNP mutations appeared to face a 50 percent higher risk for dying from their disease compared with those who carried two or fewer of the mutations.

William Phelps, program director of translational and preclinical cancer research at the American Cancer Society, said the push to develop more revealing diagnostic tools is driven by an acknowledgement that current treatment options can debilitate patients.

“If the treatments we had for prostate cancer were very tolerable or very safe you would probably treat everybody,” he explained. “But the treatments we have available today are less than ideal.”

“So certainly we can try to improve treatment,” Phelps noted. “But at the same time we can also try to improve ways to identify patients who are more likely to progress rapidly from those likely to be very slow going, so we can reserve treatment for only those instances when it’s really necessary.”

If there are markers that better define the men whose cancer is most likely to progress, “that would certainly prove very useful in the current climate,” he said.

Source: http://health.usnews.com/health-news/family-health/cancer/articles/2011/08/16/five-genes-may-be-tied-to-lethal-prostate-cancer

Suicide-Bombing Bacteria Could Fight Infections

Like any good military unit, infectious bacteria have access to numerous weapons and efficient communication systems. But like soldiers in the field, they’re also susceptible to suicide bombers. Researchers have used the tools of synthetic biology to create an Escherichia coli cell that can infiltrate foreign bacteria and explode, killing off the pathogens along with itself.

The project, says bioengineer Chueh Loo Poh of Nanyang Technological University in Singapore, was “inspired by nature,” particularly by quorum sensing, the ability of some bacteria to detect the number of microorganisms—either of their own species or others—in their environment. When pathogenic Pseudomonas aeruginosa sense other species impeding on their space and nutrients, they communicate with members of their own species using chemical signals and collectively start releasing a bacterial toxin called pyocin that kills off the competition. Together, these communication and defense capabilities allow P. aeruginosa to form tightly packed layers called biofilms, which can cause respiratory tract infections in humans and are particularly dangerous to cystic fibrosis patients.

Poh and chemical engineer Matthew Wook Chang, also at Nanyang Technological University, decided to turn P. aeruginosa‘s weapon system against itself, using E. coli as the carrier. The researchers tweaked the genes that allow P. aeruginosa to detect other members of its species and put this synthetic genetic code into E. coli‘s genome. They also gave E. coli a gene for making a modified pyocin that is toxic to P. aeruginosa. By linking the pyocin gene to the sensing genes, the researchers ensured that when the E. coli detected P. aeruginosa in the vicinity, it would fill itself with large amounts of pyocin and become a biological time bomb.

The researchers gave E. coli one last synthetic component: a “suicide gene” that is activated once the pyocin has had some time to build up, causing the cells to burst open and release their toxin. When Chang and Poh grew these synthetic E. coli in a dish with P. aeruginosa, the suicide bomber was able to kill 99% of the P. aeruginosa cells, the researchers report today in Molecular Systems Biology.

Justin Gallivan, a synthetic biologist at Emory University in Atlanta, says in an e-mail that the study “nicely illustrates” how synthetic bacteria can perform complex tasks. But he worries they may not be able to finish the job, because 1% of the infectious bacteria remained after the treatment—even when the researchers put four times as many E. coli as P. aeruginosa into the mix.

The system would also have to undergo a lot of work before it can be considered for use in humans—including, perhaps, replacing E. coli with another delivery system, says Richard Kitney, a synthetic biologist at Imperial College London. “Exposing people to E. coli is not a good thing,” Kitney says, as the bacteria are toxic outside the gut. He adds that the team would also have to show that pyocin is effective at killing P. aeruginosa that have already formed a biofilm.

For their part, Chang and Poh say that they plan to test the suicidal bacteria in mice infected with P. aeruginosa. It’s not clear, they say, whether pyocin is harmful to mammals, although some other natural bacterial toxins are currently approved for use as food preservatives. They also hope to tweak the synthetic system so that it can sense and respond to signaling molecules released by other species of pathogenic bacteria, such as those responsible for cholera.

Source: http://news.sciencemag.org/sciencenow/2011/08/suicide-bombing-bacteria-could-f.html