Oncology Biomarkers

Afamin and apolipoprotein A-IV: novel protein markers for ovarian cancer.

2009-06-24T06:41:00.000-07:00

Comparative proteomics identified the vitamin E-binding plasma protein afamin as a potential novel tumor marker for ovarian cancer. In addition, we observed in a previous small study decreased plasma concentrations of apolipoprotein A-IV (apoA-IV) in preoperative patients with kidney cancer.
Afamin, but not apoA-IV, added independent diagnostic information to CA125 and age for differentiating ovarian cancer from benign and healthy samples; the odds ratio of ovarian cancer was reduced by 44% for each doubling of afamin (P = 0.032). The relatively low sensitivity, however, clearly indicates that afamin and apoA-IV alone are not sufficiently suitable as diagnostic markers for ovarian cancer. Afamin contributes, however, independent diagnostic information to CA125, thus establishing its potential as an adjunct marker to CA125.

Cancer Epidemiol Biomarkers Prev. 2009 Apr;18(4):1127-33.
Dieplinger H, Ankerst DP, Burges A, Lenhard M, Lingenhel A, Fineder L, Buchner H, Stieber P.

Pathways in cancer

2009-06-17T21:32:00.000-07:00

Source: http://www.genome.jp/kegg/pathway/hsa/hsa05200.html

Main genetic abnormalities of colorectal cancer

2009-06-10T01:59:00.000-07:00

The Pharmacogenomics Journal (2009) 9, 147–160;
Pharmacogenetics and biomarkers in colorectal cancer
A S Strimpakos, K N Syrigos and M W Saif

Proliferation of immature tumor vessels is a novel marker of clinical progression in prostate cancer.

2009-06-03T02:52:00.000-07:00

Nestin (neuroepithelial stem cell protein) is expressed in immature endothelial cells, and we here introduce coexpression of Nestin and Ki-67 as a novel angiogenesis marker on tissue sections. Including vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1alpha (HIF-1alpha) expression, we studied relation to disease progression in prostate cancer. Different patient series were included. Sections from 104 radical prostatectomies with long follow-up, 33 castration-resistant prostate cancers, 28 nonskeletal metastases, 13 skeletal metastases, and 41 benign prostatic hyperplasias were immunostained for Nestin/Ki-67, VEGF-A, and HIF-1alpha. Vascular proliferation by Nestin/Ki-67-positive vessels was counted within "hotspot" areas. Median vascular proliferation counts were 4- to 5-fold higher in castration-resistant prostate cancers and metastases versus localized cancers and prostatic hyperplasias (P < 0.0005). Among localized cancers, high vascular proliferation was significantly related to adverse clinicopathologic features and was a strong and independent predictor of biochemical failure (P < 0.005), clinical recurrence (P = 0.005), and skeletal metastasis (P = 0.025) in multivariate analysis. Castration-resistant cancers were characterized by reduced VEGF-A and increased HIF-1alpha expression, and vascular proliferation was associated with reduced patient survival in this group. Thus, vascular proliferation was of independent prognostic importance among prostate cancers. When compared with localized cancers, vascular proliferation was significantly increased in castration-resistant cases and metastatic lesions. The castration-resistant tumors exhibited weak VEGF-A but strong HIF-1alpha expression. These novel data might have an effect on clinical evaluation and treatment of prostate cancer patients.

Clin Cancer Res. 2009 Jun 1;15(11):3654-62. Epub 2009 May 26
Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA.

Prostate cancer oncology biomarkers

2009-05-22T04:49:00.000-07:00

PSA has been used for many years as a screening tool to detect the presence of PCa and to evaluate the treatment response.7 E. Canby-Hagino, J. Hernandez and T.C. Brand et al., Prostate cancer risk with positive family history, normal prostate examination findings, and PSA less than 4.0 ng/mL, Urology 70 (2007), pp. 748–752. Article | PDF (83 K) | View Record in Scopus | Cited By in Scopus (2)⁷ However, its role is evolving as a useful marker for assessing the risk of future PCa, although this concept has not yet been widely incorporated into clinical practice.⁸ A number of studies have evaluated PSA as an indicator of the risk of developing future PCa.

A number of potential biomarkers have been identified that might provide additional predictive value in determining the risk of future PCa. Transforming growth factor-β1, interleukin-6, the urokinase plasminogen activation system, chromogranin A, and prostate-specific membrane antigen have all demonstrated some degree of predictive value in PCa, but all are unproved to date.³⁶ In the case of transforming growth factor-β1, the data from some studies have shown it to be valuable in predicting tumor progression, metastasis, and biochemical progression, but other studies failed to confirm these data.^[37]^,^[38]^and^[39] Some limited data have also pointed to the value of interleukin-6 as a predictor of disease progression and patient survival.^[40]^and^[41]

Few of these newer biomarker candidates are likely to eventually play an important role in future PCa prediction. From the data from several recent studies, only PCa gene 3 (PCA3), BRCA, and early PCa antigen 2 (EPCA-2) show considerable promise.

Risk of developing prostate cancer in the future: overview of prognostic biomarkers.
Fleshner NE, Lawrentschuk N.
Urology. 2009 May;73(5 Suppl):S21-7.

Protein-based biomarkers in detection of lung cancer: currently available

2009-05-08T05:01:00.000-07:00

BMB Rep. 2008 Sep 30;41(9):615-25.
Biomarkers for the lung cancer diagnosis and their advances in proteomics.
Sung HJ, Cho JY.

Protein-based biomarkers for the detection of lung cancer: potential

2009-05-08T04:57:00.000-07:00

BMB Rep. 2008 Sep 30;41(9):615-25.
Biomarkers for the lung cancer diagnosis and their advances in proteomics.
Sung HJ, Cho JY.

Schematic workflow of lung cancer biomarker discovery.

2009-05-08T04:50:00.000-07:00

Biomaterials from three for protein biomarker discovery,lung tissues, sputum, and body fluids, are usually used. In sputum, cancer cells apart from cancer sites are supposed to be detected. In biopsied lung tissues, not only cancer cells but also other molecules involved in self-defense mechanism of human body such as, immune cells, cytokines and derivatives from immune or inflammation responses can be found. In body fluids, although pleural fluids, ascite, urine etc can be used, blood is most commonly used in biomarker studies for its advantages of easy access and routine blood chemistry measurements in the patients. In blood, however, more potential biomarkers exist and this includes many biomarkers found in biopsied cancer tissues and many circulating protein fragments generated in the diseased tissue microenvironment or by circulating proteins derived from the diseased tissues. After proper preparation each protein can be analyzed by similar procedures of the identification, verification, and validation. For protein identification, prepared samples are analyzed by mass spectrometry. LC-ESI-MS/MS and MALDI-TOF/MS are most commonly used platforms. Potential biomarkers, elevated or decreased in their expression levels, are confirmed by Western blot, ELISA or by recent development of multiple reaction monitoring.

BMB Rep. 2008 Sep 30;41(9):615-25.
Biomarkers for the lung cancer diagnosis and their advances in proteomics.
Sung HJ, Cho JY.

Biomarkers in Prostate Cancer Diagnosis and Prognosis

2009-05-05T02:13:00.000-07:00

To review the most recent advances in genetic testing for prostate cancer risk and of new molecular diagnostic assays to improve diagnostic accuracy and treatment decision beyond prostate-specific antigen (PSA) testing.

Multiple independent studies had demonstrated evidence that genetic variations in three regions of chromosome 8q24 and one each at 17q12 and 17q24.3 are independent predictors of prostate cancer risk in addition to family history and serum PSA levels. The small percentage of individuals with several anomalies can have up to 10 times the risk of prostate cancer. Novel molecular urine tests have been studied, and the prostate cancer antigen 3 RNA detection has been studied most extensively and is now commercially available. It provides an independent and synergistic information to predict a higher or lower risk of prostate cancer at given PSA level and can further help predict the tumor volume and Gleason grade found on the prostatectomy specimen. Sensitivity of the prostate cancer antigen 3 test could be improved by the detection of the fusion gene transcripts transmembrane protease serine 2-E26 transformation specific-related gene and serine peptidase inhibitor Kazal type 1 who may in addition allow the identification of prostate cancer patients at higher risk of life-threatening disease.

The challenge in the years to come will be to introduce these new gene-based diagnostic and prognostic tests in algorithms integrating the other known risk factors of age, ethnicity, family history and PSA level to better tailor diagnostic and therapeutic strategies.

Written by:
Fradet Y.
Curr Opin Urol. 2009 May;19(3):243-6.

http://www.urotoday.com/

Genetic Variants Linked with Risk of Breast Cancer

2009-04-15T07:14:00.000-07:00

Breast cancer is the second leading cause of cancer death in women. In order to better understand how breast cancer develops, researchers continue to search for genetic variants that increase risk for the disease. Two well known genes that influence the risk of breast and ovarian cancer are BRCA1 and BRCA2. Mutations in these genes account for a relatively small proportion of all cases of breast cancer, however, and researchers hypothesize that many other genetic variants may also be important. These other variants may not be as strongly linked with breast cancer risk as BRCA1 and BRCA2, but they may be more common and, in combination, may account for the majority of cases of inherited breast cancer.

Identification of genetic variants linked with breast cancer would contribute to our understanding of breast cancer biology, which in turn could lead to more effective treatments. In addition, it may eventually be possible to use information about a broad range of genetic variants in order to predict a woman’s risk of breast cancer and to individualize breast cancer prevention efforts.

Researchers involved in the current study analyzed more than 500,000 gene variants using blood samples from roughly 1,100 women with breast cancer and 1,100 women without breast cancer. The gene variants that appeared to be linked with breast cancer during this initial step were further evaluated in additional groups of women with and without breast cancer.

The end result was the identification of two previously unidentified genetic variants, 1p11.2 and 14q24.1 (RAD51L1), which significantly increased the risk the breast cancer. The first variant is located on a part of chromosome 1 that has an unknown function. The second variant is located within a gene on chromosome 14 that is involved with DNA repair.

Reference: Thomas G, Jacobs KB, Kraft P et al. A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). Nature Genetics. Online publication March 29, 2009.

Technologies for characterizing tumours

2009-04-08T02:54:00.001-07:00

Molecular alterations in tumours can be uncovered by using
technologies that assess changes in the content or sequence of DNA,
its transcription into messenger RNA or microRNA, the production
of proteins or the synthesis of various metabolic products. Below is
a partial list of the various types of information that can be obtained
about tumours and some of the technologies that are used to make
those assessments.
DNA copy-number assessment
• Comparative genome hybridization to DNA microarrays
Mutation screening
• DNA sequencing
• Mass-spectrometry-based genotyping
• Mutation-specific PCR
Gene-expression profiling
• DNA microarrays
• Multiplex PCR
MicroRNA-expression profiling
• DNA microarrays
• Multiplex PCR
Proteomic profiling
• Mass spectrometry
Phosphoproteomic profiling
• Mass spectrometry after immunoprecipitation with phosphotyrosinespecific
antibodies
Metabolomic profiling
• Mass spectrometry

nature.com

Estimating the Risk of McCain's Deadly Cancer Relapse

2008-10-24T05:36:00.000-07:00

Interesting article in "The Lancet" followed by a piece in "New Scientist" on McCain's risk of melanoma recurrence within the four-year term.
Even though McCain's risk of recurrence is lower than his chances of becoming president elect, the numbers are striking...

"John Alam, a Cambridge, Massachusetts, physician with 17-years in clinical research who now works as a biotechnology consultant, estimates that Senator John McCain has a 6% risk of dying of a melanoma recurrence each year – or about 22% over four years. "There is a one-in-four to one-in-five chance that he would not survive a first term," he told New Scientist.

This is higher than the estimate of McCain's physician at the Mayo Clinic, who previously told reporters that he had a less than 10% chance of deadly relapse. On the other end of the scale, a group of physicians – and Obama supporters – has called on McCain to release more health records, claiming that his risk of relapse could be higher than 60%.

Alam's estimate is based on studies of the survival rates of others with melanoma, where the patients were grouped by the size and location of their tumour, their gender and age. His estimate – which is no more than an educated guess, of course – falls between the previous estimates of 10 and 60% for one important reason.

Many of the prognostic models that others have cited are based on patient studies that did not perform a sentinel lymph node (SLN) biopsy, a relatively new procedure that attempts to determine whether a tumour has spread to lymph nodes that serve as a cellular superhighway for aggressive tumours.

If the biopsy turns up no melanoma after surgery, patients are at a far lower risk of relapse and mortality than patients who are SLN-positive, according to two recent clinical studies.

However, some dermatologists worry that failing to detect melanoma in the biopsy can lead to false negatives and an underestimate of relapse risk. However, the procedure has become routine in patients with more advanced melanomas, such as McCain's, Alam says.

McCain, according to records posted on his campaign website, was SLN-negative when doctors performed the biopsy in August 2000, Alam writes in a short letter to The Lancet.

Alam says he performed the analysis independent of the Obama campaign. "Because the analysis is an objective, evidence-based analysis, I believe my having contributed has no bearing on the results of the analysis," he adds.

For comparison, a quick web search reveals the odds of dying in the US of other causes, natural and unnatural:

* Heart disease (lifetime) 1 in 5
* Poisoning (lifetime): 1 in 180
* Firearm (lifetime): 1 in 324
* Car accident (lifetime): 1 in 247
* Bicycle accident (lifetime): 1 in 4,472
* Defenestration (lifetime): 1 in 6,422
* Venomous plants and animals (lifetime): 1 in 46,539
* Legal execution (lifetime): 1 in 72,494
* Lightning (lifetime): 1 in 81,949
* Fireworks (lifetime): 1 in 1,884,832
* Shark (annual): 1 in 8,000,000

Journal reference: The Lancet (vol 371, p 1462)

From: http://www.newscientist.com/channel/health/dn15026-doctor-estimates-mccains-cancer-death-risk.html?feedId=online-news_rss20

Colby Pharmaceutical Company to treat metastatic prostate cancer after the prostate is removed

2008-06-15T17:24:00.000-07:00

One of the most unhappy groups of men is a group with a prostate cancer biomarker(PSA) in peripheral blood after their prostate has been removed. If the disease is metastasized in the bone, the prognosis for these men is very poor.

However, Colby Pharmaceutical Company (www.colbypharma.com), is working on bringing highly potent oxidative stress modulating drugs to market that show efficacy in pre-clinical trials.

What is PSA:
Prostate specific antigen (PSA) is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of normal men, and is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is the most effective test currently available for the early detection of prostate cancer. Rising levels of PSA over time are associated with both localized and metastatic prostate cancer (CaP).

Upcoming Prostate Cancer Diagnostics

2008-01-29T13:11:00.000-08:00

One interesting startup company I came across is Aureon, which developed a biomarker diagnostic, which predicts PSA recurrence and clinical disease progression in patients who have undergone radical prostatectomy. Samples are collected using needle biopsy.

The first diagnostic is Prostate Px, which looks at a set of seven protein prostate cancer biomarkers to fairly accurately predict PSA recurrence.

Among Aureon's founders are leading scientists at Memorial Sloan-Kettering Cancer Center, Yale Cancer Center, and Albert Einstein College of Medicine. he company is well financed and is rapidly moving ahead with its proastata diagnostic.

ww.aureon.com

Oncology Biomarkers Meeting Complete

2008-01-18T20:05:00.000-08:00

I attended GTCbio's Oncology Biomarkers conference held in San Francisco's hotel Whitcomb last week. The biotech calendar has many biomarker conferences this year, but this event was definitely one of the best out there.

The level of delegates was striking and presentations were top notch!