‘The overactive bladder syndrome has become an accepted way to simplify a complex array of symptoms and leads people to believe that an overactive bladder is an independent disease in itself. However, the truth is not as simple as this, as there are usually several factors at work explaining the symptoms. This is also one of the reasons why so called overactive bladder medications often do not bring the hoped result,’ says Kari Tikkinen, MD, PhD, from the HUCS Department of Urology.
The article on overactive bladder syndrome, which was co-written by Tikkinen, who currently holds a senior researcher post at the McMaster University in Canada, and Anssi Auvinen, Professor of Epidemiology from the University of Tampere, was recently published. For the article, the researchers systematically reviewed the studies on overactive bladder and the channels through which these studies have been funded.
The authors argue that the symptoms of an ‘overactive bladder’ ought to be studied individually and not as an ambiguous constellation of symptoms. This way the underlying causes of the symptoms can be better understood and more effective treatments can be developed.
The expression ‘overactive bladder’ was coined at an industry-sponsored symposium held in 1997. The following year, the FDA approved the first drug for the treatment of ‘symptoms of overactive bladder’, after which the pharmaceutical industry launched high-profile, worldwide promotional campaigns for drugs aimed at treatment of the syndrome.
According to the current definition, overactive bladder (OAB) syndrome is defined as the presence of urinary urgency with or without urgency incontinence, usually with increased daytime frequency and nocturia in the absence of infection or other obvious pathology.
‘The definition is vague and ambiguous because it includes unspecific terms, such as ‘usually’ and ‘with or without’, and the unclear expression ‘other obvious pathology’,’ Tikkinen says and continues, ‘For the pharmaceutical industry this definition is probably quite useful, as it is partly the reason why one medicine can be prescribed to a large number of patients.’
Research into overactive bladder has increased significantly over the past ten years and the pharmaceutical industry has invested heavily in it. ‘It has previously been shown that research funded by commercial actors often ends up unpublished if the results don’t serve the interests of the company,’ Tikkinen points out.
Tikkinen and Auvinen also bring to the fore that in many studies on prevalence of overactive bladder, very mild symptoms have been classified as abnormal.
‘More independent, non-commercially funded research on the subject is needed. There are, in the end, a huge number of people who suffer from urinary urgency and increased urinary frequency, and current treatments are not bringing sufficient relief,’ Tikkinen says. EurekAlert

New research from Queen Mary, University of London has uncovered a gene which plays a key role in the development of oesophageal cancer (cancer of the gullet).
The researchers studied families who suffer a rare inherited condition making them highly susceptible to the disease and found that a fault in a single gene was responsible. Initial studies suggest that the gene could play a role in the more common, non-inherited form of the disease, revealing a new target for treating this aggressive type of cancer.
Oesophageal cancer affects more than 8,000 people each year in the UK and rates are rising. It is more common in the UK than anywhere else in Europe.
Survival rates are poor compared to other types of cancer with only eight per cent of people alive five years after diagnosis. Scientists know little about how oesophageal cancer develops and very few drugs for targeting the disease are currently available.
The new study was led by Professor David Kelsell from Barts and the London Medical School, Queen Mary, University of London with collaborators from the University of Dundee and the University of Liverpool.
The research concentrated on three families with a hereditary condition called tylosis with oesophageal cancer. This condition affects the skin and mouth and sufferers have a 95 per cent chance of developing oesophageal cancer by the age of 65.
The research revealed that all three families carried a faulty version of a gene called RHBDF2.
Experiments showed that this gene plays an important role in how cells that line the oesophagus, and cells in the skin, respond to injury. When the gene is functioning normally it ensures that cells grow and divide in a controlled fashion to help heal a wound.
However, in tylosis patients’ cells, and in cells from oesophageal cancers, the gene malfunctions. This allows cells to divide and grow uncontrollably, causing cancer.
Professor Kelsell explains: ‘In studying this relatively rare condition, we have made an important discovery about a cancer that is all too common. Finding a genetic cause for this aggressive cancer, and understanding what that gene is doing, is an enormous step forward.
‘By analysing the complex biology which causes a particular type of cancer we begin to understand which treatments might be effective and also which treatments are unlikely to help.’ Queen Mary University of London

Fibroblasts, cells that play a role in the structural framework of tissues, play an apparent role in melanoma tumour growth. Fibroblasts also contribute to melanoma drug resistance and may also facilitate the ‘flare’ response when a tumour’s metabolism is enhanced following a patient being removed from a targeted therapy, said researchers at Moffitt Cancer Center in Tampa.
Alexander R. Anderson, Ph.D., co-director of Integrative Mathematical Oncology at Moffitt, and Moffitt Comprehensive Melanoma Research Center member Keiran S. Smalley, Ph.D., along with colleagues from the Wistar Institute in Philadelphia, investigated the role of fibroblasts in melanoma progression.
‘A role for fibroblasts in cancer progression has long been suspected,’ explained Anderson, who works with mathematical models of cancer to investigate tumour cell- microenvironment interactions. ‘In this study, we used an integrated mathematical and experimental approach to investigate whether melanoma cells recruit, activate and stimulate fibroblasts to deposit certain proteins known to be pro-survival for melanoma cells.’
Fibroblasts are the most common of connective tissues, and they function to synthesise the ‘extra cellular matrix’ of cells and collagen, the structural framework – also called ‘stroma’ – for tissues.
The researchers knew that fibroblasts were drawn to cancer cells and that they became activated by cancer cells. They also knew that different cancer cell lines have varying capabilities for recruiting and stimulating fibroblasts. An expectation has been that aggressive cancers stimulate fibroblasts more than do less aggressive cancers.
When they investigated the relationship between fibroblasts and tumours using mathematical models, the research team came up with some unexpected findings.
Anderson and Smalley expected the fibroblast-derived ‘extra cellular matrix’ that supports the tumour structure to have ‘direct effects on tumour behaviour.’ However, once they ran their theoretical models they came up with a number of unexpected conclusions with potentially far-reaching implications about drug resistance and tumour growth.
‘Our finding that the fibroblast population might facilitate the ‘flare response’ – a period during which a tumour has enhanced metabolism and increases it progression trajectory after patients are removed from targeted therapy – was a surprise,’ said Smalley, whose research aims at developing new therapies for melanoma and getting them into clinical practice.
The researchers knew that a targeted therapy would kill only the tumour population, not the fibroblasts in the tumour structure. However, the finding that fibroblasts contribute to melanoma drug resistance was unexpected.
‘Targeted therapies may actually hasten tumour progression when they are stopped due to resistance to the targeted drug,’ said Smalley. ‘We found in our models that fibroblasts appear to facilitate the flare response after targeted therapy ends.’
Their conclusions about the relationship between fibroblasts and cancer tumours were not predicted or expected, but revealed though the use of mathematical models.
‘If these conclusions are confirmed experimentally, we may gain important new insights into how drug resistance can be managed clinically,’ concluded Anderson. H. Lee Moffitt Cancer Center & Research Institute

OHSU Knight Cancer Institute study results suggest that more patients than initially thought could potentially be treated with a new class of drugs, PARP inhibitors
A constellation of defective proteins suspected in causing a malfunction in the body’s ability to repair its own DNA could be the link scientists need to prove a new class of drugs will be effective in treating a broad range of ovarian cancer patients, an Oregon Health & Science University Knight Cancer Institute study found.
These research results have prompted additional exploration into whether the patient population included in clinical trials for drugs that target the enzyme poly ADP ribose polymerase (PARP) should be expanded. Several forms of cancer are more dependent on PARP for their growth than regular cells, which means that targeting these enzymes when they go haywire is a potentially effective way to treat ovarian cancer. Currently PARP inhibitors are being tested with patients who have two types of malfunctioning proteins, BRCA1 or BRCA2. But, the OHSU Knight Cancer Institute study of additional proteins, beyond BRCA proteins, suggests that they too are playing a role in driving ovarian cancer.
Tapping into the potential of PARP inhibitors could change the dynamics of ovarian cancer treatment. There has not been a substantial increase in treatment options for ovarian cancer in the past two decades, said Tanja Pejovic, M.D., Ph.D., gynaecologic oncologist at the OHSU Knight Cancer Institute. Pejovic, who led the study of these additional defective proteins, added that the results provide evidence that further research into the role of multiple proteins is warranted.
Only about 10 to 15 percent of women with ovarian cancer have BRCA 1 or BRCA 2 mutations. Pejovic’s study of 186 patients with nonhereditary cancer found that 41 percent who had an early recurrence of the disease also had abnormal levels of the other proteins tracked. In contrast, only 19.5 percent of patients who hadn’t yet had a recurrence of the disease in three years had abnormal levels of these proteins.
‘If we are able to identify the proteins that differentiate these patients at risk for early recurrence, this would open up a new direction in ovarian cancer treatment,’ Pejovic said.
The study — which was supported by the Sherie Hildreth Ovarian Cancer (SHOC) Foundation — focused on proteins that are supposed to assist cells in repairing harmful breaks in DNA strands, a process called homologous recombination (HR). The malfunctioning of HR is not well understood in ovarian cancers where there is no family history of the disease. However, there is evidence that these proteins influence a patient’s ability to respond to drugs and their survival rates after treatment. Oregon Health & Science University

A recent analysis of clinical trial results performed by the Radiation Therapy Oncology Group (RTOG) demonstrate that a chromosomal abnormality—specifically, the absence (co-deletion) of chromosomes 1p and 19q—have definitive prognostic and predictive value for managing the treatment of adult patients with pure and mixed anaplastic oligodendrogliomas. The presence of the chromosomal abnormality was associated with a substantially better prognosis and near-doubling of median survival time when treatment with combined chemotherapy and radiation therapy was compared to treatment with radiation therapy alone.
Oligodendrogliomas are uncommon tumours that represent approximately 4.0% of all brain tumours. Mixed oliogdendrogliomas (those also containing astrocytic elements) account for 1.0% of all brain tumours. Pure and mixed oligodendrogliomas that contain anaplastic (malignant) cells typically grow more rapidly than non-anaplastic tumours.

The RTOG 9402 trial A Phase III Intergroup Randomized Comparison of Radiation Alone vs. Pre-Radiation Chemotherapy for Pure and Mixed Anaplastic Oligodendrogliomas was conducted with four other National Cancer Institute (NCI)-supported co-operative groups. Trial participants had a pathologically confirmed pure or mixed anaplastic oligodendroglioma and were randomly assigned into one of two treatment arms. The 148 participants randomised to Arm 1 were treated with PCV (procarbazine, CCNU [lomustine] and vincristine) chemotherapy and radiation therapy (RT), and the 143 participants randomised to Arm 2 were treated with RT alone.

RTOG 9402 study results showed no survival benefit for patients treated with early PVC chemotherapy plus RT over RT alone. Although a significant impact on median progression-free survival time was realised (2.6 years versus 1.7 years for RT alone), the regimen was associated with significantly more adverse side effects. The study authors also reported that study participants in both arms whose tumour lacked chromosomes 1p and 19q had longer median survival times as compared with participants without these deletions (> 7 vs. 2.8 years, respectively). This led the study authors to conclude that ‘tumours with 1p and 19q co-deletion are less aggressive or more responsive to PCV chemotherapy or both.’

A recent analysis undertaken of the RTOG 9402 data (at a median study participant follow-up time of 11 years) is planned for submission to the 2012 American Society of Clinical Oncology Annual Meeting. However, due to the finding’s significance for patient care, results are reported here in advance of submission. Radiation Therapy Oncology Group