This article titled “Human guinea pigs lend their courage to a golden era of cancer research” was written by Sarah Boseley, for The Guardian on Monday 22nd August 2011 17.06 UTC

David Cox is a human guinea pig. He is also a man with a cancer for whom there are no more conventional options and who reasonably believes that, at 56, it is too early to call it a day. So Cox is only too happy to be one of the first people to try out a new drug, fresh from the laboratory. It could come with a load of unpleasant and unexpected side-effects. But it just might save his life.

Cox was diagnosed with mesothelioma three years ago – the result of working as an engineer in a boiler room full of asbestos, he believes. It’s a cancer that doesn’t usually have a good outcome. Like many people with advanced cancers, he has been on one trial after another. The last was a phase 2 – the trial of a drug that has been shown to be safe and have some effect in some people already. It seemed to work for six months, he said, and then it stopped.

“I went for the results of some scans on the Tuesday,” he said. “They told me the results and the options I had. Within three days they’d got me on this trial.” This is a phase 1 trial – a drug that has never been tested in humans before.

Cox didn’t think twice about it. “I had nothing to lose,” he said. When he was warned about possible side-effects, he remarked that the side-effects of not trying another drug were death. “You can’t get much worse than that,” he told his doctor.

Both his trials were run by the Royal Marsden, the world-renowned cancer hospital. The first was at its Chelsea site in west London. The latest is taking place at the other site in Sutton, south London, where the Marsden’s cancer doctors work in close collaboration with scientists at the cutting edge of drug discovery and genomics in the adjoining building belonging to the Institute of Cancer Research.

When Harpal Kumar, chief executive of Cancer Research UK talks of a “golden era” of cancer research, these are some of the scientists and clinicians who are making it happen.

The Marsden uniquely has a drug development unit integrated into the hospital, allowing patients who have run out of options on conventional drugs to join trials where they can get the latest experimental medicines. Where those drugs were once aimed at a single cancer – breast or prostate or lung – these days they are targeted at particular mutations in the cancer. The old drugs worked in only up to a third of patients because each cancer is different. The new drugs aim to have a higher success rate – in a much smaller group of patients tested for the particular mutation.

Sarah Stapleton who runs the unit, said: “The patients have exhausted standard therapies and they are offered the option of a voluntary trial of targeted therapy.”

For the volunteers with advanced cancers, these experimental drugs are their last chance, but Stapleton and the doctors have to be careful what they say to them. “We have to be very honest about what we’re offering to our patients here. There are lots of ethical considerations for a patient entering a trial. These drugs are at a very early stage. They might not help and there is a fairly low chance of helping and they could cause them more problems in terms of side-effects than they are experiencing at the moment.

“The key is explaining it is not a miracle drug. Sometimes that is what people can expect, but it is not what we have got.”

A trial will last two or three years. Patients have to stay in hospital usually for the first month – though they go home at weekends. “It is a huge time commitment because they have to come every week. We are going to take some time that they may not get back,” said Stapleton. But many are philosophical and altruistic. They join the trial in the hope that it may help others, even if not themselves.

The exciting times are when they see particularly good and sometimes even dramatic results. It happened with a drug to prevent cancer returning in women with the BRCA genes that predispose them to breast and ovarian cancer. “We saw very good response rates from that,” said Stapleton.

If Kumar from Cancer Research is right, the unit could be seeing more and more good outcomes. The Marsden is involved in the tumour testing trial that is about to start – supplying patients and also one of the three labs that will design and interpret panels of genetic tests. Somehow, they have to do it within a tight budget – the plan is to find a relatively cheap and feasible way to offer these molecular diagnostic tests across the whole of the NHS.

Dr David Gonzalez de Castro, head of the Marsden’s molecular diagnostics laboratory, said the first two years, involving 9,000 tumour samples from patients in seven hospitals, was a bid to find out whether it was possible. “The question is can the NHS provide molecular diagnosis for all cancer types routinely and can this be linked not only to patient outcome but also research?” he said.

Each genetic test for lung, colorectal or breast cancer costs around £150 to £200. Cancer Research’s plan is to carry out a panel of five or six tests for each cancer type for maybe £300. Gonzalez de Castro shakes his head in a sort of wonder. “It’s a challenge,” he says with a laugh. If all goes well, after two years the tests will begin to be offered in a further 10 to 20 centres. Then before long, the testing will be available throughout the NHS. The government is behind the scheme – it committed to developing and funding a national testing structure in the last cancer plan in January.

The testing is essential even now to find out whether, for instance, a woman with breast cancer is HER2 positive and needs Herceptin or a man with bowel cancer has a K-RAS gene mutation and should be given another cancer drug called cetuximab. Yet, according to a recent study by the Royal College of Pathologists, not everybody who needs a test is getting one.

But the new trial has a second and equally important and exciting purpose beyond securing equal access to tumour testing. All the patients who join will be asked if their results can be stored, along with details of their treatment and the outcomes. Cancer Research will be working with the cancer registries who already collect anonymised data on patients, said James Peach, its director of stratified medicine who is in charge of the project.

It is exciting, says Peach, because researchers will be able to find out what works, not just in terms of drugs but also surgery and radiotherapy, for people with cancers caused by specific genetic mutations. It opens the way to much better, more accurate treatment. “We will find out which drugs we should not be using and discover combinations we did not know about,” he said. There will also be significant benefits in surgery and radiotherapy, because scientists may discover which sorts of tumours are likely to be more aggressive than others.

guardian.co.uk © Guardian News & Media Limited 2010

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This article titled “Asbestos: the hidden health hazard in millions of homes” was written by Andrew Don, for The Observer on Saturday 30th April 2011 23.01 UTC

Your home has a 50% chance of harbouring asbestos, which could be lethal if disturbed.

The use of asbestos has been common in the industrialised world since the mid-19th century and it was not until 1999 that a total ban was imposed. Lee Carter, principal director of the consultants WSP Environment & Energy, says that it has been widely used in residential property: “Among private homes, more than 50% are likely to include some asbestos-containing materials.”

While this may sound alarming, asbestos is likely to be dangerous only if it is released into the air and you breathe it in. Then you could be at long-term risk of developing lung cancer, asbestosis or mesothelioma (a cancer that forms in the lining of the chest or abdomen). Experts say that there should be little or no risk if the asbestos is enclosed and left undisturbed but it must be regularly checked for signs of deterioration.

But accidents happen and the previously dormant devil within could be released when “improvement” work is being carried out, for example, or when a burst pipe causes damage to ceilings.

This is what happened to Brian Fitzpatrick, 49, from South Darenth, Kent, who endured the Christmas from hell when he discovered water damage in his house on 22 December. Pipes had burst in the loft and contractors alerted him to the threat of asbestos in the Artex coating on his ceilings. Before the sample results came back, one of the ceilings collapsed and the industrial dryer blew asbestos around the house. Fitzpatrick and his family have had to relocate while repairs and decontamination take place, a process that could continue for several more months.

Although the results of sampling tests indicated a low number of asbestos particles in the air, the family remain concerned for the future. Fitzpatrick, a partner at the building consultancy EC Harris, said: “It’s a nightmare. No one expected asbestos. Emotionally, the experience has been traumatic for all the family but especially for my wife and daughter.”

Fitzpatrick says that his insurer is picking up the £10,000 cost of replacing all 13 ceilings, as well as the cost of air-quality and material sampling tests, and is paying up to £30,000 for the family’s emergency accommodation. The soft furnishings in the house will have to be disposed of under controlled conditions.

But the Association of British Insurers points out that policies will cover removal of asbestos only as part of a householder’s damage claim, and not simply because asbestos happens to have been identified.

In older homes, asbestos is often present in ceilings decorated using Artex textured coating. This is because, until the mid-1980s, Artex was made with white asbestos to strengthen it. However, Joe Oakins, a surveyor at Vintec Environmental Management, says: “We find asbestos products used in the strangest places and sometimes apparently for no reason. Often builders used whatever they had lying around, so you often find off-cuts of asbestos boards used as packing and filler.”

Peter Coling, technical director at Kinleigh Folkard & Hayward Chartered Surveyors, estimates that 30% of asbestos is found in ceiling coatings, 15% in boiler flue pipes and ducts, and 15% in floor tiles. A further 15% is found in areas such as cold water storage tanks, insulation materials, eaves, gutters and rainwater pipes, while 10% is in cement panel ceilings, 10% in outbuildings and 5% in fire protection materials, for example on the underside of integral garage roofs and in cupboards enclosing boilers.

Phil Wright, chief engineer at the inspection and insurance service Allianz Engineering, says: “It is difficult to establish how much asbestos is present in a home without employing a specialist to undertake a full inspection.” Samples need to be taken for analysis at a laboratory approved by the United Kingdom Accreditation Service.

Debbie Hales, director of Asbestos First, one of 450 licensed removal firms in the UK, says: “With textured coatings you have to take [samples] from different locations. It can be free of asbestos in one part and not in the next because of the way it was manufactured.”

Hales says that the cost of a sampling visit should be about £150 plus VAT. If any additional samples are required during the visit, expect to pay about £20 plus VAT per sample. To remove an area of textured coating, such as Artex, containing asbestos costs about £1,200 plus VAT for up to 20sq m, including disposal and air-quality tests.

guardian.co.uk © Guardian News & Media Limited 2010

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The fluid or liquid that is found in the chest will eventually be replaced by a solid growing tumour. This can lead to breathing difficluties, pnuemonia, or decreased heart function with arrhythmias (funny heartbeats). This increase in solid mass can also lead to severe pain in the chest wall, requiring narcotic medications.

Loss of weight due to poor appetite can also occur. The disease may spread to other parts of the body, but this usually occurs late in the course of the disease. The most frequently involved organs are the liver, the adrenal gland, the kidney, and the opposite lung that is affected.

What is my prognosis?

This depends on several factors – your age, whether you are male or female (as women tend to do better than men), the size of the tumour when diagnosed and the type, i.e. patients who are diagnosed with the epithelial type of mesothelioma as opposed to the 2 other types tend to have a better advantage. 

Also ther are certain blood values that tend to indicate who will have a worse prognosis. For example- if the platelet cell count ( cells that are responsible for making blood clot) is elevated, the hemoglobin (cells that carry oxygen) is low, and the white blood cells (cells that fight infection) are high, these can indicate a poorer prognosis.

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Although wedge biopsies – and even open biopsy via thoractomy – are sometimes required to establish a diagnosis for mesothelioma, there are several less invasive forms of sampling which may be diagnostic in some settings.

These latter samples are discussed as below:

Effusion Fluid

When a serous effusion is present an adequate sample (preferably over 50ml of fluid) should be collected and sent to the cytology laboratory; this will enable smears and a cell block to be prepared. In addition, som of the cell deposit can be set aside for ultrastructural examination. A definate diagnosis of malignant mesothelioma can be made on cytology of effusions in the majority of cases.

Closed Needle Biopsy

Although taking a close needle biopsy (of the Abrahams’ type) at the time of tapping the effusion was the standard practice in the past, there has been a reduction in this form of sampling related to a significant proportion of inadequate or inconclusive biopsies. The high diagnostic yield from effusion cytology has probably also influenced this decline.

Fine Needle Aspiration (FNA)

Over the past years – there has been an increase in thin core sampling for plueral-based lesions, especially where there is no accompanying serous effusion. This procedure is well tolerated by patients who require only a simple local anaesthetic.

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It has been estimated that 49% of cancerpatients reported dyspnea as one of their symptoms. Dyspnea is particularly a common complaint among individuals with lung cancer and mesothelioma but can  also be a manifestation of other illnesses such as asthma and COPD.

What is Dyspnea?

Dyspnea is a breathing condition that is caused by labored breathing. The patient with dyspnea may feel like he or she is suffocating or fighting for air. Dyspnea often requires emergency treatment but the intensity and the level of laboured breathing can vary in intensity. Mesothelioma patients are more likely to experience a pleural effusion (a build of fluid in the lungs)  and the evacuation of any fluid build up will alleviate symptoms but may the fluid may re-cur.

Causes of Shortness of breath can come from various places in the lung due to the following complaints:

1. Channels disease Breath -> asthma, emphysema Adult respiratory distress syndrome (ARDS)

2. Parenchyma Disease

3. Pulmonary Vascular Disease -> Primary Pulmonary Hypertension

4. Pleural diseases -> Pneumothorax, Disease Wall lunktrauma,

5. Chronic bronchitis, CHF, Cor pulmonary, pleural effusion, bone abnormalities

6. Pneumonia, pulmonary embolism, hemotoraks, neurologic

7. Laryngeal obstruction, pulmonary infiltrates with eosinophilia (PIE). Venooklusi lung disease, fibrosis.

8. Lung cancer, Mesothelioma.

Severity of Dyspnea is usually determined by Hugh-Jones classification that is classified as follows:

- First Degree: work looks the same as those who have the same age, walking, climbing stairs may be like other healthy people.

-  Second Degree: even if obstruction is not obtained, the patient is unable to walk like other people the same age.

- Third degree: although not able to walk like a healthy person in normal levels, patients can still walk a mile or more to pace yourself.

- Fourth Degree: people walk 50 m or more in need of a break or not to continue it.

- Fith degree: shortness of breath occurs when changing clothes or rest, and the person is usually unable to leave home.

 Sudden onset of  dyspnea (over several hours) in otherwise healthy patients diagnosis:

• Channel respiratory (acute asthma attack),

• Parenchymal lung (acute pulmonary edema or acute infectious processes such as bacterial pneumonia),

• Pleural cavity (pneumothorax)

• Vascularization lungs (pulmonary embolism)

Presentation of sub acute (over several days to weeks) diagnosis:

• Exacerbation of existing respiratory disease before (asthma or chronic bronchitis)

• Infection parenkimal running slow (Pneumocystis carinii pneumonia in AIDS patients, mycobacterium or fungal pneumonia)

• Non-infectious inflammatory processes that run relatively slow (Wegener’s granulomatosis, eosinophilic pneumonia, bronchiolitis obliterans with organizing pneumonia, etc.)

• Neuro muscular disease (Guillain-Barre ‘syndrome, myasthenia gravis),

• Pleural disease (pleural effusions with various causes of heart disease or chronic)

 A chronic presentation (i.e. months to years) is often indicated for chronic obstructive pulmonary disease, chronic interstitial lung disease, or heart disease.

Dyspnea Treatment:

Surgery

Surgical removal of  Tumour, obstruction

Pleural Effusion

Drainage of fluid build-up in the lung

Oxygen Therapy

O2 Therapy is one of the respiratory therapies to maintain adequate tissue oxygenation. The main objective of O2 is (1) to overcome the state of hypoxemia in accordance with the results of Blood Gas Analysis, (2) to reduce the work of breath and reduce myocardial work.

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There are also several consultant-led clinics and hospitals in Germany, Austria, Switzerland and The Netherlands that specialise in this therapy.

Mistletoe therapy improves and strengthens the natural defenses of the body through a supportive effect on the immune system, and has been shown to ease the side-effects of chemotherapy and radiotherapy. Mistletoe therapy can also help cancer patients cope with symptoms like fatigue, nausea, digestive problems and weight loss, sleeplessness, low mood, recurring infections and pain.

Woman uses Mistletoe therapy to treat non-hodgkins Lyphoma.

Joan van Holsteijn, age 53 (above) refused chemotherapy and believes that she fought the cancer by using Mistletoe instead. She had a large tumour in her leg and has since had the all-clear since her Mistletoe treatment. In a statement she said that she owes her life to Mistletoe and is grateful for such treatment.

In the UK   – Mistletoe therapy is available via private Homoeopathic Hospitals and clinics, such as ‘Park Attwood’ a non-profit charitable organisation, and up until recently – UK cancer patients – who cannot afford the Mistletoe Therapy have had their treatment funded by the NHS.   

However – such funding is being withdrawn by the UK Government along side other complimentary therapies. This means that it will be no longer available for funding on the NHS – leaving cancer patients who have faith in and draw strength from complimentary medicine like Mistletoe treatment – to try and pay for the treatment themselves.

Debbie Brewer –  (below) A UK resident who was diagnosed with Mesothelioma (a rare lung cancer caused by asbestos inhalation) in 2006, received Mistletoe Therapy at the ‘Park Atwood’ Clinic  in 2008. She had the treatment along side a pioneering treatment called Chemoembolization.

Debbie has a lot of faith in Mistletoe Therapy and she knows from her own experience with the treatment how important it will be to other cancer sufferers like her self. She has currently set up a government petition asking that funding for Mistletoe Therapy will continue to be available on the NHS. An excerpt from her petition reads:

“We hope that the government can look into supporting patients who have found their treatment works, even in a psychological way, please don’t remove what little hope and faith patients have. Mesothelioma has very little open to it that helps patients, taking mistletoe away from these patients is cruel and heartless”

Please support and sign Debbie’s Petition here:

http://www.gopetition.co.uk/petitions/mistletoe.html

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The results of the Phase I trial suggest that pemetrexed, (unlike some other newly developed chemotherapy drugs) is safely tolerated to allow it to be administered at a high dose with concurrent radiotherapy, increasing the  potentialityof the treatment.

Pemetrexed is predominantly used for the treatment of pleural mesothelioma and already has a respected role in treating metastatic non-small-cell lung cancer. It has a chemical structure similar to folic acid, and prohibits the development of DNA and RNA by preventing the formation of the nucleotide bases.

Prof Françoise Mornex, head of the ‘Department of Radiotherapy Oncology at Centre Hospitalier Lyon Sud’ and colleagues carried out the first trial of the drug in combination with radiotherapy and cisplatin chemotherapy in cancer patients with stage three lung cancer (locally advanced, and not where the cancer had spread ‘metastatic’).

The trial consisted of 9 patients with no surgical intervention but stage 3 non-small-cell lung cancer. Firstly – they were administered two cyclesof chemotherapy, 3 weeks apart, with 500 mg/m2 of pemetrexed and 75 mg/m2 of cisplatin. This was proceeded by two cycles of combined chemotherapy and radiotherapy, where doses of pemetrexed began at 400 mg/m2 and were then escalated to 500mg/m2 and 600 mg/m2. Cisplatin and radiotherapy at 66 Gy/33 Gy fractions over 7 weeks stayed constant.’

Out of ten patients that commenced treatment, one was omitted from the trial before dose accumulation as a result of disease progression. Out of the remaining 9 however, seven participants completed all 4 phases of chemotherapy, and 8 completed radiotherapy treatment.

Only one patient experienced toxicity on the highest dose of pemetrexed, which was recorded as a grade 4 septic shock.

These particular doses of Pemetrexed were considered to be well-tolerated when given along side  with cisplatin and radiotherapy.It seems to be the only 3rd generation agent that can be favourably recommended safely at the maximumtrials with concurrent radiotherapy.

According to Professor Mornex who led the trial, these findings are important as most of the time, when combining radiation and chemotherapy concurrently, the dose of chemotherapy must be minimised somewhat due to excessive toxicity. The potential problem this presents though – is that by decreasing the chemotherapy dose, one reduces the capability of the chemotherapy on micro metastases and on the primary tumor. However – concerning pemetrexed, the tolerance is acceptable and allows for high cytotoxic doses during radiation, thus improving the chance of destroying cancerous cells.

Professor Mornex added – “This trial will have a positive impact on clinical practice in the near future,and this regimen is already being studied in several ongoing clinical trials around the world; it may become the treatment of choice in the future, for concurrent chemo-radiation schemes.”

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What is pawpaw?

The pawpaw is a large shrub that can be found in many areas of North America. The fruit looks like a large yellowish/green berry and is approximately between 5 and15 centimeters in length, and contains brown coloured seeds embedded in its soft fruit pulp. According to many who have eaten the fruit – it tastes really delicious like a creamy coconut banana flavour. The fruit is not viable commercially as it rapidly spoils once harvested. It also contains high nutrients, healthy fats, and complex carbohydrates.

People tend to think that the fruit is related to papaya fruit as it is similar in appearance but the two fruits are not at all related. Pawpaw consists of approximately 8 different varieties and one of them in particular – ‘Asimina triloba’ has been scientifically researched for its potential medicinal properties. Dr. J. Mclaughen a Professor of ‘Pharmacognosy’ at Purdue University, and who has studied this particular species for the past 20 years found it to contain a special compound called ‘annonaceous acetogenins’. Acetogenin is a natural fatty acid and possesses some very unique properties. In laboratory trials – the special compound was found to exhibit powerful properties in fighting cancer cells.

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Amphibole

Studies have been carried out concerning the asbestos fibre and its interaction with the mesothelial cell, but it is still unclear what exactly determines asbestos disease, particularly pleural mesothelioma (most common type). Theory suggests several factors: Asbestos fibres tend to accumulate in the pleural space by lodging in the parietal pleura around the draining lymphatic somata. Mesothelial cells are more sensitive to the toxic effects of asbestos than any other cells, and appear to be more sensitive than other cells to oxidant-induced DNA damage.

Asbestos is both a fibrogenic and carcinogenic fibre. Some of its biological toxicity relates to its fibrous shape, and yet fibres of a similar shape are not considered harmful. For instance – ‘amphibole’ asbestos fibres (crocidolite and amosite, blue and brown) are more predominantly associated with mesothelioma than chrysotile fibres, this is because amphibole fibres contain more iron, and their needle-like shape is more brittle.

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