Searching for magic bullet against cancer caused by asbestos: One step closer?

Jan. 17, 2014 — Mesothelioma is a very aggressive cancer associated with asbestos exposure, which is usually diagnosed in an advanced stage. So far no therapeutic strategy has proven effective against this deadly cancer and the prognosis remains very poor with only few exceptions.

In December, the research team of Antonio Giordano, a pathologist, Director and Founder of the Sbarro Health Research Organization in Philadelphia, PA, and Professor of Pathology and Oncology at the University of Siena, Italy, published two separate studies aiming to address the urgent need to identify possible new methods for mesothelioma treatment.

In the first study, published in the scientific journal Cell Cycle, Giordano's researchers tested on mesothelioma cells the effect of two drugs designed to reactivate the p53 protein, one of the most important 'tumor suppressors', which is turned off in most human cancers. "In mesothelioma, although p53 is rarely mutated, it is inactivated by alterations in its pathway," says Francesca Pentimalli of the National Cancer Institute of Naples, Italy, lead author of the study. Both of the drugs used in the study target p53, but with different mechanisms of action. One in particular, called RITA, proved to be very toxic. Specifically, RITA caused mesothelioma cells, and not 'healthy' cells, to undergo apoptosis -- a type of programmed cell death that occurs through the activation of a specific 'cascade' of events.

"The ability of RITA to induce apoptosis is remarkable considering that mesothelioma is very refractory to this process. In fact the most aggressive and rare variant, sarcomatoid mesothelioma, did not respond to the treatment probably because of its intrinsically high levels of molecules acting as inhibitors of this process" says Alfredo Budillon, Head of the Experimental Pharmacology Unit of the National Cancer Institute of Naples and coauthor of the study. "It remains to be seen whether the combination of RITA with other activators of apoptosis can achieve efficacy also against the more aggressive cases."

Furthermore, challenging mesothelioma cells with RITA worked in synergy with the chemotherapy drug cisplatin, which is the mainstay of treatment for this disease, suggesting that its use in a clinical setting could possibly help to reduce the required doses and the side effects of chemotherapy, thereby improving patients' quality of life.

The second study, published online in Cancer Biology and Therapy and led by Paola Indovina of the University of Siena and the Sbarro Institute for Cancer Research and Molecular Medicine, Temple University in Philadelphia, was designed along the same lines as the first study. In the second study, the authors tested, for the first time in mesothelioma, a new drug called MK-1775 in combination with cisplatin. MK-1775 is a selective inhibitor of WEE1, a protein that is crucial in activating a 'checkpoint' for the repair of damaged DNA before the cell starts its division process. The rationale for this strategy is based on the fact that many cancer cells, especially those with non-functional p53, rely on WEE1 to stall cell division and allow cells to repair the damage induced by genotoxic agents, such as many chemotherapeutic drugs, including cisplatin. WEE1 inhibition limits the time available for repair and, therefore, sensitizes cancer cells to DNA-damaging agents. Indeed, inhibiting WEE1 with MK-1775 selectively sensitized mesothelioma cells to the genotoxic action of cisplatin by preventing checkpoint activation and forcing the cells to divide despite the damage, thus triggering apoptosis.

"Overall our studies are aimed at identifying promising new molecular therapies against mesothelioma that hold the potential for clinical use in the near future. MK-1775, for example, is already being utilized in clinical trials for other types of tumors in the United States," Giordano concludes.

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WHO responding to health needs caused by Typhoon Haiyan (“Yolanda”)

11 November 2013 | MANILA, Philippines - WHO has activated an organization-wide mobilization to work closely with the Department of Health, Philippines (DoH) to organize relief efforts for the survivors of Typhoon Haiyan.

The typhoon – locally known as Yolanda – ravaged the central part of the archipelago Friday morning with winds reaching speeds of more than 250 km per hour causing storm surges of up to 5 metres. Many people living in these affected areas were injured and the devastating effects of this typhoon left already vulnerable health facilities damaged or completely destroyed. As a result of the breadth and severity of the storm, health services in the worst affected areas no longer exist or are severely stretched, with medical supplies in very short supply.

“We are working closely with the Philippine Government and local authorities to assess and rapidly address the life-saving needs of the people affected by this typhoon,” says Dr Julie Hall, WHO Representative to the Philippines. “WHO has an assessment team on the ground in Bohol, and we are sending teams to Cebu and Tacloban with the United Nations Disaster Assessment and Coordination (UNDAC) teams in support of national response efforts. WHO is flying in more than two dozen health emergency relief experts and emergency health kits for the initial response.”

The Government estimates that some 4.5 million people have been affected in the Central Philippines. WHO is mobilizing supplies to assist the Government in providing a coordinated, effective and rapid response:

• An initial shipment of four emergency kits with medicines and supplies to cover basic health needs of 120?000 persons during one month and supplies to perform 400 surgical interventions are being deployed. Four diarrhoeal disease kits with medicines and supplies to treat 3000 cases of acute diarrhoea are also being sent.
• WHO is also supporting the Department of Health (DoH) in strengthening its early warning alert and response network (EWARN) to rapidly detect disease outbreaks and other public health threats related to food and environmental hazards.
• The Government is receiving international assistance such as field hospitals and medical teams, and WHO is working closely with the Government to ensure those supplies and teams go where they are needed most.
• Medical storage spaces have also been damaged, and WHO is working to re-establish logistics bases for new supplies that are arriving.

In the aftermath of the typhoon, reaching the affected areas and people has proven to be a sizeable logistical challenge. The true extent of the death and destruction has yet to be quantified. The super typhoon ripped roofs off houses and uprooted trees, interrupting telecommunications and electricity supplies. Many air- and sea-ports in the affected areas are closed. Until roads are cleared, movement will be difficult in these areas, posing significant logistical challenges to emergency relief operations.

Adding to the complexity of this response, another tropical storm is expected to hit the Philippines later this week. Foreign governments and international aid agencies have already pledged support in the form of air transportation and equipment, but more help is urgently needed to save the lives of the survivors.

WHO’s rapid deployment of health experts and supplies to the Philippines has been possible thanks to the financial support for surge capacity provided by numerous international partners, including the European Commission. Due to the magnitude of the disaster, WHO is seeking immediate financial contributions to cover initial response operations. A joint appeal by United Nations and non-governmental organizations will be issued in the coming days.

For more information, or for an interview with Dr Julie Hall, WHO Representative, please contact:

Ms Christine “Tiffany” Domingo-Cool
Event Response operations/Risk communications
Telephone: +639 15 710 4361
E-mail: domingoc@wpro.who.int

Christy Feig
Director of Communications
Telephone: +41 79 251 7055
E-mail: feigc@who.int

Gregory Hartl
Coordinator, News and Social Media
Telephone: +41 79 203 6715
E-mail: hartlg@who.int

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'Cascade of events' caused sudden explosion of animal life

Sep. 19, 2013 — The explosion of animal life on Earth around 520 million years ago was the result of a combination of interlinked factors rather than a single underlying cause, according to a new study.

Dozens of individual theories have been put forward over the past few decades for this rapid diversification of animal species in the early Cambrian period of geological time.

But a paper by Professor Paul Smith of Oxford University and Professor David Harper of Durham University suggests a more holistic approach is required to discover the reasons behind what has become known as the Cambrian Explosion.

Theories for the Cambrian Explosion fall into three main categories -- geological, geochemical and biological -- and most have been claimed as standalone processes that were the main cause of the explosion.

Whatever the cause, this major evolutionary event led to a wide range of biological innovation, including the origin of modern ecosystems, a rapid increase in animal diversity, the origin of skeletons and the first appearance of specialist modes of life such as burrowing and swimming.

Among the weird and wonderful creatures to emerge in the early Cambrian was Anomalocaris, the free-swimming, metre-long top predator of the time with a mouth composed of 32 overlapping plates that could constrict to crush prey. It is distantly related to modern arthropods, including crabs and lobsters.

Vertebrate animals also made their first appearance in the Cambrian Explosion, the distant ancestors of modern fish, reptiles, birds and mammals.

Professor Smith, Professor Harper and a team of scientists have spent four years working on data from a site in northernmost Greenland, facing the Arctic Ocean.

The site, at Siriuspasset, is located at 83°N, just 500 miles from the North Pole in a remote part of north Greenland. Although logistically very difficult to reach, Siriuspasset attracted the team because of the high quality of its fossil material and the insights it provides.

Professor Smith and Professor Harper's findings are published in the latest edition of the journal Science.

Professor Smith, lead author of the report and Director of the Oxford University Museum of Natural History, said: 'This is a period of time that has attracted a lot of attention because it is when animals appear very abruptly in the fossil record, and in great diversity. Out of this event came nearly all of the major groups of animals that we recognise today.

'Because it is such a major biological event, it has attracted much opinion and speculation about its cause.'

Described by the researchers as a 'cascade of events', the interacting causes behind the explosion in animal life are likely to have begun with an early Cambrian sea level rise. This generated a large increase in the area of habitable seafloor, which in turn drove an increase in animal diversity. These early events then translate into the complex interaction of biological, geochemical and geological processes described in individual hypotheses.

Professor Harper, Professor of Palaeontology in the Department of Earth Sciences at Durham University, said: 'The Cambrian Explosion is one of the most important events in the history of life on our planet, establishing animals as the most visible part of the planet's marine ecosystems.

'It would be naive to think that any one cause ignited this phenomenal explosion of animal life. Rather, a chain reaction involving a number of biological and geological drivers kicked into gear, escalating the planet's diversity during a relatively short interval of deep time.

'The Cambrian Explosion set the scene for much of the subsequent marine life that built on cascading and nested feedback loops, linking the organisms and their environment, that first developed some 520 million years ago.'

Professor Smith said: 'Work at the Siriuspasset site in north Greenland has cemented our thinking that it wasn't a matter of saying one hypothesis is right and one is wrong. Rather than focusing on one single cause, we should be looking at the interaction of a number of different mechanisms.

'Most of the hypotheses have at least a kernel of truth, but each is insufficient to have been the single cause of the Cambrian explosion. What we need to do now is focus on the sequence of interconnected events and the way they related to each other -- the initial geological triggers that led to the geochemical effects, followed by a range of biological processes.'

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