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Local Biotech September 13, 2007

Posted by ramunas in media, personal.
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Slightly offtopic, but anyway: today I’ve attended some local biotechnology conference about the perspectives of this field in our country and will present some news. There were presentations of several quite known local manufacturers and some from start-ups.

The Fermentas, historically producer of restriction enzymes, but now offering wide range of molecular research/diagnostic tools with offices worldwide, impressed me with a nice NoLimits™ DNA fragments picture (source), which would fit on a T-shirt :)

Multiple fast digestion (5 minutes) with FastDigest™ Restriction Enzymes was also something new for me to hear.

Reverse terminator based sequencing ArraySBS (sequencing-by-sequencing) project, developed jointly with Estonian Asper Biotech and Swedish Oligovation may be useful addition for whole genome sampling/sequencing fewer.

Biopharmaceutics producer Sicor Biotech may soon present own chimeric/humanized antibodies for cancer treatment.

Biocentras produces specific microbial strains for remediation of soil polluted by oil and offers this type of cleaning service.

Sorpo diagnostics, mainly involved in viral/microbial disease diangostics, just created SORPOclean™ modules for rapid isolation of DNA or RNA from various clinical specimens and SORPOline™ kits are designed for highly specific and sensitive detection of pathogen DNA/RNA by end-point PCR/RT-PCR.

Still, I think this emerging biotech industry need put more efforts for government lobby, cause its importance is (strangely) underscored (what an ignorance).

3 Genomic Tests for Therapy Decisions | Breast Cancer September 11, 2007

Posted by ramunas in breast cancer, cancer genetics, genetic testing, research, sporadic cancer.
3 comments

During the first American Society of Clinical Oncology (ASCO) Breast Cancer Symposium researchers from The University of Texas M. D. Anderson Cancer Center presented two research updates on the genomic predictors in the breast cancer.

In one poster results from two studies involving 960 patients validating a Affymetrix U133 microarray-based 200-gene index test that predicts a patient’s response to hormone-suppressing therapy (sensitivity to endocrine therapy (SET index)) are presented. It was developed by M.D. Anderson in collaboration with Nuvera Biosciences Inc.
In these two studies, the Sensitivity to Endocrine Therapy (SET) Index score predicted distant relapse free survival (DRFL) among 453 patients who received tamoxifen, an anti-estrogen therapy, for five years, but revealed no prognostic information in the absence of endocrine therapy.

“We believe this is the first genomic test to predict sensitivity to hormone therapy independent of a patient’s prognosis if no post-surgical treatment is received,” (via)

Poster abstract here.

The other poster presents results from combined use of three genomic prognostic and treatment response predictors tests in lymph node-negative breast cancer.

The 3 clinical outcome predictors are;

  • A 30-gene predictor of the cancer’s sensitivity to chemotherapy developed by M.D. Anderson investigators.
  • The 200-gene index (SET) of sensitivity to hormone (endocrine) therapy developed by M.D. Anderson in collaboration with Nuvera Biosciences Inc.

The ASCO poster describes gene expression profiles analyzed from 198 patients with stage 1 or stage 2 breast cancer that had not spread to the lymph nodes and who had not been given chemotherapy or endocrine therapy after surgery.

Among the 198 patients, 55 were predicted to be at relatively low risk that the cancer would return. Of those low-risk patients, 21 were predicted to have cancer vulnerable to chemotherapy and 16 were predicted to have tumors susceptible to endocrine therapy. Two had cancers sensitive to both therapies.

Of the 143 patients predicted to have a high risk of recurrence, the analysis predicted 109 had cancer unlikely to respond to endocrine therapy, 64 were predicted to be insensitive to chemotherapy, and 38 were predicted to be unlikely to respond to both therapies (via).

Conclusion: A substantial proportion of low risk-patients appears to be highly sensitive to systemic treatment modalities, and many high-risk patients are predicted to be refractory to existing therapies. Simultaneous prediction of risk of recurrence and sensitivity to therapies may lead to more appropriate treatment decisions for individuals because the predicted sensitivity to chemotherapy and endocrine therapy could be weighed against the risk of relapse.

“Let’s say a new patient has a needle biopsy performed, and the microarray analysis of the tumor’s gene expression predicts she is at low risk of recurrence and also has cancer that is insensitive to both chemo- and endocrine therapies; in this cases the best option is relatively clear; surgery alone. However, it is important to know the sensitivity of the cancer to chemo- or endocrine therapies independent of the risk of recurrence alone. For example, a person even with low risk for cancer recurrence might elect to receive further therapy if her cancer is known to be highly susceptible to treatment.” , investigators explain.

Poster abstract here.

A collection of posters from section “familial breast cancer/genetic testing” available here.

GeneGenie#15 | Carnival Release September 9, 2007

Posted by ramunas in cancer genetics.
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[Courtesy of Ricardo Vidal]

Foreword:

It is my pleasure to release #15 edition of blog carnival Gene-Genie, a carnival about genes and gene-related disorders.

So, let’s take a run.

Gene Scan

The hottest news is certainly that J. Craig Venter’s personal genome was sequenced – it resonated everywhere, from labs to blogosphere: the best collection of articles is here (by EyeOnDNA). Analysis of this the most comprehensive human genome to date revealed, that humans are more unique than it was thought. Some of the sequence in Venter’s genome is associated with wet earwax, increased risk of antisocial behaviour, Alzheimer’s and cardiovascular diseases (via). Good news for personalized medicine and good promo for 454 (thought I believe in nanopores future). Be ready for low cost-genomes ($1K) sooner than 2014 (a detailed explanation why it’s so expensive now is here (by DigitalBio) and sense your own genetic information while browsing at 23andme. What could we expect from Venter more now? Probably synthesized version of own genome at his Synthetic Genomics, Inc.

Hurry up, PGP’ers!

I think we will soon forget Sanger’s method of the ’70 ies like tend to forget Maxam-Gilbert’s, but still now, after automated fluorescent sequencing is done there’re lot of data to analyze visually or rely on Staden (my favourite), Chromas Lite, Phred, Mutation Surveyor or KB. The unexpected experience of DigitalBio with ABI’s KB is writen here.
There is dismaying news from an US Army about genetic discrimination covered by EyeOnDNA.

Be Healthy

Higlight Health warns, that smoking leads to changes in gene expression, some of which are reversible and some of which are permanent (more that 10yrs), according to a new study from BMC Cancer. Smoking is the single most important avoidable cancer risk factor. Don’t start smoking in the first place. If you do smoke, now is the time to quit (via).

Now, a 5-minute cigarette brake :]

Our sponsors??!

Avoid passive smoking too – it is even more harmful:

More stories about cancer:

My brief BRAF story about simple somatic oncogene mutation which is specific to sporadic colorectal cancer but not hereditary form and about a new immunohistochemical prognostic test for breast cancer.

A new important gene associated with aggressiveness of breast cancer – tumor suppresor acetyl-transferase TIP60 (story by GeneSherpa), which rather unusually needs only one copy malfunctioning to start enhancing tumor growth (because of haploinsufficiency).

Cotch dot net writes about the importance of DNA checkpoints in the tumour development from an evolutionary perspective.

Bonus: Funky guys from BayBlab just released the first blog carnival about cancer research.

If you still smoke and sooner or later develop a lung cancer – don’t worry – you can bank your DNA just before a funerals. A comprehensive list of labs providing this service is listed here (by Genetic Genealogist).

Letters from Editor to a Host.

I have received very informative letter from editor Bertalan – that list will fulfill you for sure (some of the links appear repeatedly, but it represents the way our genome is organized:):

And here are the others:

Well, now we have to slow down our speed and congratulate a new carnival host – Neurophilosophy ! Please further submit articles by filling in the carnival submission form.

Skinny Art | Make Your Own Bio-Sci-Dna Skin September 7, 2007

Posted by ramunas in media.
2 comments

Have you considered putting a DNA pic, sequence, bio-art or a whole personal genome on your laptop, PC, iPod or even fridge? Just make your own bio-sci-dna design and let the guys from Skins.lt do their best (and they offer free shipping till the end of month, btw) :)

[this is a nice picture of my native city Vilnius , listed in UNESCO] (source)

New Molecular Test For Postmenopausal Breast Cancer | Mammostrat September 6, 2007

Posted by ramunas in breast cancer, mammostrat, sporadic cancer, technology.
3 comments

The Molecular Profiling Institute, Inc. has just announced that they are now providing Mammostrat, a new molecular-targeted breast prognostic test, to breast cancer patients, nationwide in the USA. The Mammostrat prognostic test utilizes five immunohistochemical (IHC) biomarkers a diagnostic algorithm.to classify patients into high, moderate, or low-risk categories for disease recurrence.

Acctually, it is not a true genetic test. Mammostrat is a five-antibody immunohistochemistry (IHC) prognostic test for postmenopausal, estrogen receptor-expressing, hormone receptor-treated (tamoxifen) breast cancer patients with node-negative disease who will receive hormonal therapy and are considering adjuvant chemotherapy. It utilizes standard paraffin-embedded tissue (via and via) .

The five markers are as follows:

  • p 53 , which is known to play a central role in cell cycle regulation and mutations in p53 contribute to tumor formation (aka “the Guardian of Genome”)
  • HTF9C , which is co-expressed with proteins that are involved in DNA replication, implicating HTF9C in DNA replication and cell cycle control.
  • CEACAM5 , which is normally expressed in embryonic tissue and is aberrantly expressed in some cancers.
  • NDRG1, which is expressed under conditions of hypoxia and other stresses. It may have a role in helping tumors survive under the hypoxic, stressful environment confronting aggressive tumors.
  • SLC7A5, which is involved in nutrient transport. Over-expression of SLC7A5 could help sustain the high growth rate of cancer cells by increasing a cell’s ability to consume nutrients.

Mammostrat testing is performed by staining the supplied sections and appropriate control tissue with the five Mammostrat antibodies. A trained pathologist will then score the stained slides according to established criteria. A “0″ for negative staining or a “1″ for positive staining for each antibody will be entered into the AGI algorithm to calculate a “Risk Index.” The Risk Index value will be used to classify the patient as low, moderate, or high likelihood of breast cancer recurrence. The ordering pathologist will receive a report similar to the sample report shown here. The Mammostrat report will list the staining result for each antibody, the Risk Index category (i.e. low, medium, or high) and an interpretation of what the score means for the patient.

Pathologists, oncologists and patients should use the Mammostrat test results in conjunction with other clinical information to help select amongst treatment options (via).

Because Mammostrat uses traditional immunohistochemistry technology, the test is expected to be significantly less expensive than existing molecular-based, prognostic tests for breast cancer and is typically covered by insurance.

“Mammostrat’s cost-effective, molecular-targeted analysis enables MPI to provide the test at a significant discount compared to our competitors. Moreover, test results will be available quickly — an average of seven business days — versus two weeks for alternative, comparable tests.” , says Todd Maney, Ph.D., Vice President of New Product Development.

The test was developed by Applied Genomics, Inc (AGI). who rigorously translated recent genomic insights in cancer into a novel immunohistochemistry test. Mammostrat test results have been validated using over a thousand patient samples in North America.

AGI also has developed PulmoType and PulmoStrat IHC based antibody tests for lung cancer.

The standard of care for most of postmenopausal women with estrogen receptor expressing, node negative breast cancer is surgery to remove tumor followed by hormone signaling targeted therapy (e.g. tamoxifen or aromatase inhibitors) (ref.).

The prognosis for this group of early stage, estrogen receptor positive breast cancer patients is considered favorable with approximately 90% or more of these patients surviving five years and longer. However, several studies have demonstrated that outcomes can be further improved by treatment with cytotoxic chemotherapy. Since it is clear that most patients will remain disease free in the absence of additional therapy it is likely that cytotoxic therapy is only important for a small subset of these early-stage cancers. Since chemotherapy comes with difficult side effects (e.g. nausea, hair loss, severe fatigue) and long term risk of cardiovascular complications and secondary tumors, the decision whether to use adjuvant chemotherapy is difficult and controversial. The potential benefit of using Mammostrat testing is to identify those patients at high risk of cancer recurrence and therefore more likely to benefit from additional chemotherapy as opposed to those patients at low risk of recurrence who may choose to forgot chemotherapy.

I think it would be of interest to include these protein encoding genes into some gene expression profiling test as well.

A BRAF Story | Colorectal, Thyroid CA and Melanoma September 6, 2007

Posted by ramunas in cancer genetics, colon cancer, colorectal cancer, genetic testing, hereditary cancer, HNPCC, sporadic cancer.
4 comments

For the first time I’ve read about BRAF oncogene in a poster presented during one of the European Society of Human Genetics conference, probably in Amsterdam, Holland. It appeared that a single amino acid substitution (p.V600E), a hotspot point mutation, is an useful marker to exclude HNPCC (hereditary non-polyposis colorectal cancer). Interestinlgy, this somatic mutation of BRAF gene, which belongs to the RAF family of protein kinases from the RAS/RAF/MAPK pathway, is more than 90% present in sporadic colorectal cancers with methylated hMLH1 gene. Therefore, if you have access to a tumor DNA after simple PCR test you can exclude or suspect hereditary form of this cancer. The detection of a positive BRAF-V600E mutation in a colorectal cancer suggests a sporadic origin of the disease and the absence of germline alterations of MLH1, MSH2 and also of MSH6. These findings have a potential impact in the genetic testing for HNPCC diagnostics and suggest a potential use of BRAF as exclusion criteria for HNPCC or as a molecular marker of sporadic cancer (via).

Obviously, the confirmation should be done by testing for germline mutations mismatch repair (MMR) genes (mostly MLH1, MSH2, MSH6). Also, immunohistochemistry may point you which protein is missing. The Bethesda guidelines , original (1997) and revised (2003), are designed to select cases for analysis of microsatelite instability (MSI) features of tumor, but testing for BRAF mutation can yield additional and faster information.

Conventional strategy for genetic testing of affected individuals from families with suspected hereditary non-polyposis colorectal cancer (source):

However,

Screening of mismatch repair (MMR) genes can be avoided in cases positive for V600E if no other significant evidence, such as fulfilment of the strict Amsterdam criteria, suggests MMR associated HNPCC. In this context, mutation analysis of the BRAF hotspot is a reliable, fast, and low cost strategy which simplifies genetic testing for HNPCC, one article states.

That is a story about colorectal cancer, but it was interesting for me to find out, that the same mutation of BRAF oncogene can be present in thyroid cancer. That may be useful in predicting the level of aggression of thyroid cancer and help guide treatment options and follow-up care, says the new research paper published in the September issue of the “Annals of Surgery”.

Researchers concluded, that BRAF V600E mutation is primarily present in conventional papillary thyroid cancer. It is associated with an aggressive tumor phenotype and higher risk of recurrent and persistent disease in patients with conventional papillary thyroid cancer. Testing for this mutation may be useful for selecting initial therapy and for follow-up monitoring.

Study author, Kebebew E, explained that identification of the mutation in patients with thyroid cancer could be very useful in a variety of ways. For example, patients with the mutation may be candidates for a more aggressive approach to surgery, such as removing the central lymph node along with the diseased thyroid, to avoid the possibility of metastasis following surgery. BRAF V600E testing could also be useful for deciding between low- or high-dose radioiodine ablation therapy.

Other BRAF mutations are found in melanoma and BRAF possitive tumors may be more sensitive to a new class of drugs – protein MEK inhibitors (such as PD0325901, developed by Pfizer Research and Development).

Update on Research | CIMBA & BRCA Trial September 5, 2007

Posted by ramunas in BRCA, breast cancer, cancer genetics, genetic testing, hereditary cancer, research.
1 comment so far

Just let you know about some updates in Research section (all in UK):

  • CIMBA (from Cambridge Genetic Epidemiology Unit and stands for “Consortium of Investigators of Modifiers of BRCA1/2″) is an international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers. The aim of CIMBA is to provide sufficient sample sizes to allow large scale studies in order to evaluate reliably the effects of genetic modifiers. It is sure, that identification of genetic modifiers of breast cancer risk for BRCA1 and BRCA2 mutation carriers will lead to an improved understanding of breast cancer. This knowledge may prove useful for the determination of individualized risk of cancer amongst carriers, who have significantly increased, but variable, risk for breast, ovarian and some other cancers.
    Any group can contribute to research if can provide at least 92 BRCA1 and BRCA2 mutation carriers genotype and risk factors data. Currently there is a list of 27 international groups contributing to research.
    Recently there was the first report published in Cancer Epidemiology Biomarkers & Prevention , where the F31I polymorphism in AURKA oncogene, which previously has been associated with breast cancer risk in the homozygous state, was not found to be associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations were genotyped for F31I.
    A review of CIMBA is available at Breast Cancer Research.
  • The BRCA Trial (an international trial supported by Breakthrough & Cancer Research UK), which is interested in developing and improving individualized treatments for a specific type of hereditary breast cancer (again for BRCA1 and BRCA2 carriers).

The cancer research is an important field to gain a new knowledge not only in cancer genetics. And if somebody would like to support it, should consider buying pinky Nokia’s phone or Belkin’s Apple iPod :)

Stay Connected September 3, 2007

Posted by ramunas in media.
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Could not resist touching TouchGraph Browser after EyeOnDNA and ScienceRoll posts :) Some colorful caleidoscope of connections which Google sorts out for name. Makes some sense, though.

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