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Low Levels of Serum Bilirubin Spell Higher Lung Cancer Risk for Male Smokers

Elevated levels of bilirubin in the blood get attention in the clinic because they often indicate that something has gone wrong with the liver. Now researchers have found that male smokers with low levels of the yellow-tinged chemical are at higher risk for lung cancer and dying from the disease.

A team led by researchers at The University of Texas MD Anderson Cancer Center reported its findings in a late-breaking abstract at the AACR Annual Meeting 2013 in Washington, D.C.

“Our study indicates male smokers with low levels of bilirubin are a high-risk group that can be targeted with smoking cessation help, low-dose spiral CT screening of their lungs and other preventive measures,” said senior author Xifeng Wu, M.D., Ph.D., professor and chair of MD Anderson’s Department of Epidemiology and the Betty B. Marcus Chair in Cancer Prevention.

Lung cancer usually is diagnosed at a late stage, when tumors are inoperable and treatments largely ineffective. The overall five-year survival rate is 15 percent, but it falls to 5 percent for stage 3 lung cancer patients and 1 percent for those with stage 4 disease.

Spiral CT scans catch cancer early, biomarker could reduce false positives

The National Lung Screening Trial found that low-dose spiral computed tomography screening reduces mortality among heavy smokers by 20 percent. However, 95 percent of growths found by spiral CT are false positives, a barrier to large-scale screening.

“Validated biomarkers are urgently needed to improve risk prediction for lung cancer and to reduce false positives, shifting the balance toward more effective and efficient CT screening for cancer detection,” Wu said.

The researchers started with an objective analysis of levels of metabolites — substances produced during metabolism. Bilirubin is produced during the breakdown of old blood cells.

They analyzed 60 samples divided into three groups known as “trios” — normal controls, early stage and late stage non-small cell lung cancer patients. The top three metabolites were validated in two more groups of 50 and 123 trios.

When bilirubin emerged as the most significant metabolite, another validation study was done in a prospective cohort of 435,985 people with 208,233 men in Taiwan.

Men were divided into four groups according to their serum bilirubin levels. Lower bilirubin level was associated with significantly higher rates of both lung cancer incidence and mortality.

In the Taiwanese cohort, the incidence rate per 10,000 person-years in men was 7.02 for those in the lowest bilirubin quartile (.68 mg/dL or less), compared to 3.73 in the highest quartile of bilirubin level (1.12 mg/dL or more). The mortality rate per 10,000 person-years was 4.84 for the lowest level compared with 2.46 in the highest bilirubin quartile.

Next step: Establish a risk prediction model in heavy smokers

Bilirubin makes sense as a protective agent because of its anti-oxidant, anti-inflammatory and anti-proliferative effects. “It’s plausible that bilirubin protects against lung cancer by scavenging free radicals and carcinogens associated with smoking,” said study presenter Fanmao Zhang, a doctoral candidate in epidemiology.

Indeed, a Belgian study showed that bilirubin in the high normal range lowered cancer mortality in men. A study in the United Kingdom showed higher bilirubin levels in the normal range were associated with lower risks of chronic obstructive pulmonary disease, lung cancer and all-cause mortality. Neither of those studies stratified their analysis of bilirubin by smoking status.

“We expected that bilirubin might be protective, but our finding that bilirubin levels affect only smokers was somewhat of a surprise,” Wu said. “Our discovery that low levels increase lung cancer risk is unique.”

Smokers in the two middle cohorts of bilirubin levels also had higher lung cancer risk than those in the highest quartile. As an objective risk index for lung cancer and all-cause mortality, low levels of bilirubin should send an urgent message to quit smoking, said Chi Pang Wen, M.D., Ph.D., co-lead author from National Health Research Institutes, Taiwan.

The next step, Wu said, is to evaluate the predictive value of serum bilirubin in heavy smokers and to establish a risk prediction model that incorporates bilirubin and other biomarkers with clinical and epidemiological data to improve the efficiency of lung cancer risk prediction.

Source: EurekAlert!

Molecules Generated that Can Halt Metastasis of Colon Cancer

A Basque research consortium has managed to halt the progress of colon cancer and its metastasis in the liver in an experimental model with mice. This advance, that may open a new path for the future treatment of such pathologies, has been achieved by creating molecules which interfere with the adhesion of tumour cells to other cells of the organism. In this way, the molecules halt both the growth of the tumour and the dissemination of the tumour to and its proliferation in other organs.

The research, published in the prestigious North American Journal of Medicinal Chemistry, is based on a previous work by researchers at the University of the Basque Country (UPV-EHU) which had described a series of molecules which reduced the metastasis of melanoma (a serious variety of skin cancer) in mice. That research opened up the possibility of generating new molecules with this activity in other types of cancer and following a similar strategy, something which has been achieved in this, later research, applied to colon cancer and its metastasis of the liver.

The Basque research consortium is made up of the CIC bioGUNE biociences research centre, the UPV/EHU, the Institute of Genetics and a Molecular and Cell Biology (IGBMC) in Strasbourg (France), and the Ikerchem spin-off Enterprise. Moreover, researchers from the Rocasolano Chemical-Physical Institute, from the CSIC (the Spanish Council for Scientific Research) and from the Novartis Institute for Biomedical Research took part.

“In this project we first designed inhibitors to cell adhesion involved in the metastasis of murine melanomas, and then undertook the chemical synthesis of these molecules, testing their biological potential and activity. What was surprising was that our calculations predicted that, by introducing relatively small changes, we would be able to generate new molecules with the capacity to inhibit cell adhesion involved in another type of cancer. This prediction was confirmed by the experiments, suggesting that these techniques of chemical design and synthesis could be extended to other related therapeutic targets”, stated Dr. Fernando Cossío, UPV/EHU professor and co-founder of Ikerchem S. L., as well as President of the Executive Committee of Ikerbasque.

“Besides its relevance in the control of cancer and metastasis, this research highlights that, in the Basque Country, there are research teams at academic centres and in companies with the necessary experience and skill to tackle multidisciplinary projects of biomedical relevance, combining synthetic and computational chemistry with the structural analysis of the mechanism and the biological validation of the molecules generated”, stated Dr. Francisco Blanco, Ikerbasque lecturer and researcher at CIC bioGUNE.

Impact of cancer and metastasis

Cancer is the second cause of human mortality and its incidence increases with age. Thanks to progress in the early diagnosis and control of detected tumours, enhancing the rate of survival has been achieved and, in this sense, it is believed that further progress can be made in these two aspects of the disease.

Currently 90 % of deaths from cancer are produced by the reappearance of the original tumour in another part of the body, a process known as metastasis. This process consists of a cancerous cell of the original tumour passing through the body of the patient and lodging in another organ, generating a new tumour.

The colon is not the organ with the greatest cancer mortality rate, but it gives rise to metastasis of the liver, which is. In fact the liver is the organ where metastasis of tumours originatng in other parts of the body is more frequent. This is because the liver acts as a filter for the blood and the lymph and so cancerous cells flowing in these fluids can be trapped therein.
The lethal danger arising from the migration of cancerous cells throughout the body is what drives researchers in the quest for therapies to halt metastasis.

Study: Design, Synthesis, and Functional Evaluation of Leukocyte Function Associated Antigen-1 Antagonists in Early and Late Stages of Cancer Development

Source: Basque

Rosetta Genomics Reports Study Comparing microRNA Profiles of Cancer of Unknown Primary and Metastases of Known Primary Tumors Published in Clinical Experimental Metastasis

Rosetta Genomics Ltd. (NASDAQ: ROSG), a leading developer and provider of microRNA-based molecular diagnostics, announced last week that data from a study assessing the differences between cancer of unknown primary (CUP) and metastatic solid tumors of known primary metastases (KPM) by profiling microRNA expression were recently published in Clinical Experimental Metastasis, in an article entitled “Global microRNA profiling in favorable prognosis subgroups of cancer of unknown primary (CUP) demonstrates no significant expression differences with metastases of matched known primary tumors.”

Breakthrough Research in DNA Mutation Analysis Could Lead to Earlier Diagnosis and More Tools for Personalized Treatment for Cancer Patients

Because all cancers occur due to abnormalities in DNA, scientists are able to use DNA sequencing to analyze the mutations in each patient’s DNA. Once this sequencing is complete, doctors can match each patient to the best available drug for his or her particular cancer, thus personalizing the treatment for each patient and improving health outcomes. In the past, DNA sequencing has required tumor tissue, which could only be obtained by biopsying the tissue – an invasive procedure not ideal for the patient. In this study, Chan et al. explored the use of shotgun massively parallel sequencing of plasma DNA from cancer patients to scan a cancer genome without surgery.

The researchers extracted DNA from the tumor tissues of 4 liver patients and 1 breast and ovarian cancer patient, and then analyzed the preoperative and postoperative plasma samples of these patients. Through the use of multiregional sequencing of tumor tissues and shotgun sequencing of plasma DNA, the researchers have shown that plasma DNA sequencing is a powerful tool for cancer detection, monitoring, and research.

“This ground-breaking study uses brand new technology–the multiregional sequencing research tool will lead to routine practice leading to lower cost,” said Eleftherios P. Diamandis, MD, PhD, FRCP(C), FRSC, Head of Clinical Biochemistry at Mount Sinai Hospital and Editor of this special issue of Clinical Chemistry. “This is the first time analysis has been done non-invasively instead of performing a biopsy on human tissue. The proof of principle is demonstrated and will be more readily available and cost effective in the future.”

Study: Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing

Source: PR Newswire

Thomas Jefferson University Researchers Discover New Pathways that Drive Metastatic Prostate Cancer

Elevated levels of Cyclin D1b could function as a novel biomarker of lethal metastatic disease in prostate cancer patients, according to a pre-clinical study published ahead of print on December 21 in the Journal of Clinical Investigation by researchers at the Kimmel Cancer Center at Jefferson.