Monday, November 26, 2012

This low-fat lunch can help fight cancer

I love egg salad sandwiches, but don’t have them as often as I would like, as eggs are high in cholesterol and saturated fat  Still, I eat no meat and watch my fats, so I feel OK with an egg or two a day, especially if they are boiled or poached.  And eggs can be healthy, primarily because of their high content of vitamins B2 and B12, which has been shown in some studies to reduce the risk of breast cancer.  They also include selenium, an antioxidant.

This lunch added up to 231 calories and also included doses of vitamin A (red pepper and Spring mix), vitamin C (strawberries), and whole grains (bread), which can also reduce breast cancer risk.   To be really effective, you would need at least a half of a red pepper, 6-8 strawberries, and a hefty handful of spring mix.  (I took the photo midway through lunch, so I had already eaten half of it. Sorry, but it was good.)

BUT: Peppers, strawberries and lettuce are all on the Environmental Working Group’s Dirty Dozen, a list of produce with high amounts of pesticides (numbers 3, 5, and 9 respectively), so go organic if you can afford it.   If your budget can’t handle the extra cost, still eat your fruits and veggies—the EWG says that the benefits of a diet rich in fruits and vegetables is healthy enough to outweigh the risks of pesticides.  And wash them well.

Calorie Counts:
1 boiled egg: 78 calories
Organic spring mix:: 5 calories
Organic red pepper:  12 calories
Organic strawberries: 6 calories


Biomedical engineering research to focus on personalized therapies to inhibit breast cancer metastasis

The following is from a news release from the City College of New York.   What I love is that the person getting this grant to study breast cancer therapies is a biomedical engineering professor and she is looking at the problem from a different perspective that most other researchers.  

For some time, researchers have known about disparities in diagnoses and outcomes among breast cancer patients based on race and age. However, they have been challenged to develop a set of criteria that can be used to reliably target drug delivery mechanisms based on an individual patient's tumor.

Dr. Debra Auguste, associate professor of biomedical engineering in the Grove School of Engineering at The City College of New York, will investigate personalized therapies to inhibit breast cancer metastasis supported by the National Institutes of Health Director's New Innovator Award. The grant, which provides $1.5 million over five years, funds "exceptionally creative new investigators who propose highly innovative projects that have the potential for unusually high impact."

"By applying our knowledge and experience in chemical engineering, materials science and nanotechnology, we hope to develop therapeutics that will increase breast cancer patient survival by inhibiting tumor progression and metastasis," said Professor Auguste, who joined the Grove School faculty in September from the Harvard University School of Engineering and Applied Science.

"Our goal is to use biological information to design new drug delivery vehicles that can target tumors. We have been studying what the cell surface looks like, how proteins relate to one another, how they are organized and what their ratios are."

The strategy marks a departure from other investigations that have focused on the role of messenger RNA, which is transcribed into proteins. "People often think if you have a large amount of messenger RNA you have a large amount of protein, but we don't necessarily know how much protein is being produced," she said.

Current breast cancer treatments are regulated by cell surface presentation. For example, breast cancer cells that express estrogen receptor and human epidermal growth receptor-2 on their surface are treated with hormone (anti-estrogen or aromatase inhibitors) or targeted therapies such as the monoclonal antibody trastuzamab (Herceptin), respectively.

Professor Auguste plans to develop personalized treatment approaches for four metastatic breast cancer populations: black women, white women, women over 40 and women under 40. Epidemiological studies have found that white women are more likely than black women to be diagnosed with breast cancer, however black women are more likely to die from it. In addition, women under 40 are more prone to aggressive forms of the disease.

She expects to characterize the surface density and proximity of two receptors that govern cell recruitment: CXC chemokine receptor type 4 (CXCR4) and CC chemokine receptor type 7 (CCR7). This information will then be used to synthesize complementary engineered liposomes (CELs) that cooperatively bind CXCR4 and CCR7 and deliver short interfering RNA (siRNA) to knock down lipocalin-2 (Lcn2), which has been shown to induce the epithelial to mesenchymal transition (EMT).

Lipocalins are a family of proteins that transport small, hydrophobic molecules such as steroids, retinoids and lipids. A growing body of evidence points to the EMT playing a role in metastasis of cancers.

Professor Auguste hopes to produce CEL therapies that will enhance cooperative binding to each cell type and reduce cell migration and invasion. Homogeneous and biphasic CELs are designed to complement the relative surface density and organization of receptors on breast cancer cells. They do so by allowing conjugated antibodies to rearrange on the surface or by clustering antibodies within gel-phase lipid domains.

"The binding event is regulated by multiple receptors. We need to understand how multiple proteins work together to engineer adhesion," she explained. "If we can understand that, we can hopefully go from a non-adhesive vehicle to one that is adhesive in order to trigger a favorable response. The key is adhesion of the drug delivery vehicle to tumor cells."

In previous research targeting cytokine-activated endothelial cells, Professor Auguste reported evidence that vehicles that complement the cell surface enhance binding.

Professor Auguste plans to encapsulate cancer drugs inside a lipid shell that will be very similar to a cell membrane and decorate the shell with one or more antibodies arranged in different ratios. She also intends to "play around" with the molecules' surface mobility and organization. "We'll test lots of different engineering parameters in order to achieve optimal efficacy."

To assess the effect of CEL on cell migration, activation survival and the EMT process, she will conduct mechanistic studies involving the expression of various proteins and enzymes.  

Professor Auguste intends to demonstrate similarities and differences among six different breast cancer cell lines and deliver a platform technology designed to address tumor metastasis. The cell lines chosen represent the most metastatic and invasive forms of breast cancer with the poorest prognoses for survival. "We want to learn what is different about these breast cancers and whether we can develop a better treatment that can more effectively target the tumor and control it," she said.

NIH established the Director's New Innovator Award to address two important goals: stimulating highly innovative research and supporting promising new investigators. It differs from traditional NIH grants in that it is designed specifically to support unusually creative new investigators with highly innovative research ideas at an early stage of their career when they may lack the preliminary data required for an R01 grant. In 2012, 51 such awards were granted nationally.

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Study Hints of New Therapy for TNBC with p53 Mutation

A preclinical study shows oral Aurora A/angiogenic kinase inhibitor, ENMD-2076 can be effective against triple-negative breast cancer.  Published in Clinical Cancer Research, the research  also identified predictive biomarkers that may be useful in selecting patients that are particularly sensitive to ENMD-2076. Tumors with the p53 mutation and increased p53 expression were especially sensitive to this treatment. 
The study analyzed twenty-nine breast cancer cell lines representative of the wide variety of clinically defined breast cancer subtypes that were exposed to ENMD-2076.  Results indicated that  ENMD-2076 was effective against the cell lines of the TNBC subtype  and much less effective against luminal and HER2-amplified subtypes.  Within TNBC tumors, cell lines with a p53 mutation and increased p53 expression were more sensitive to the the effects of ENMD-2076 exposure than those with decreased p53 expression.  This means that future clinical trials with ENMD-2076 may focus specifically on TNBC tumors with the p53 mutation.
According to Jennifer R. Diamond MD of the University of Colorado School of Medicine, who led the research, "Through this study, we show that ENMD-2076 has activity against preclinical models of breast cancer with more robust activity against TNBC.  The study also supports further clinical investigation of ENMD-2076 in patients with metastatic TNBC with an emphasis on the continued development of p53-based predictive biomarkers."
Ken Ren, Ph.D.,  Chief Executive Officer of EntreMed, which produces ENMD-2076, said, "One of the major challenges for the development of a target therapy for cancer is the identification of a responsive subtype with a predictive biomarker. In our previous Phase 1 study, we observed a patient with TNBC who had failed multiple chemotherapy regimens then had clinically significant stabilization of disease for 41 weeks after ENMD-2076 treatment.  The benchmark of median duration after first line therapy in such patients with metastasis is just 12 weeks. This pre-clinical study illustrated scientific insight into the selective sensitivity of TNBC to ENMD-2076 with direct correlation to p53 mutation and over expression. It provides strong support for the rational of our ongoing Phase 2 TNBC trial. Upon further confirmation clinically, it may also provide guidance on future trials for patient selection, and may increase the probability of success. We are continuing to enroll patients in the ongoing Phase 2 trial and anticipate the initiation of a second site for this trial soon. We remain on track with our clinical development activities and expect our progress to accelerate in the coming months and year."
From EntreMed: ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases which have been shown to play important roles in the pathology of several cancers. ENMD-2076 has shown promising activity in Phase 1 clinical trials in solid tumor cancers, leukemia, and multiple myeloma. ENMD-2076 is currently completing a Phase 2 trial for ovarian cancer.  EntreMed, Inc. recently initiated a Phase 2 study of ENMD-2076 in triple-negative breast cancer.
SOURCE: " "Predictive Biomarkers of Sensitivity to the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Preclinical Breast Cancer Models," Clinical Cancer Research, November 7, 2012.
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Friday, November 23, 2012

Free Books for Your Book Club

One  in eight U.S. women will develop invasive breast cancer over the course of her lifetime. What if there were something you could do to reduce that risk?  It could be something as simple as sitting down and chatting with a group of friends? Surviving Triple-Negative Breast Cancer offers the opportunity for you to do just that.

Oxford University Press is happy to provide free books for the first official group that incorporates Surviving Triple-Negative Breast Cancer into its club reading list. And I  will contribute to the discussion via a Skype session.  

Why read about such a specialized disease?  Because reducing your risk of TNBC can mean reducing your risk of other forms of cancer, as well as diseases such as type II diabetes, heart disease, even Alzheimer’s. 

The book educates all readers on the fact that breast cancer is not a one-size-fits-all disease—something I wish I had known before I was diagnosed. It demonstrates how diet and exercise can help reduce risk of recurrence of TNBC and other diseases.  It shows the heart of a survivor, with the 11 profiles of amazing women who went on to live full lives after diagnosis. So, while its focus is on TNBC, its approach reaches far beyond. 

Reviews of the book have been quite positive—all five stars on Amazon, and a starred review with a “highly recommended” from the Library Journal.  One thing I especially love is that readers appreciate my occasional humor.

Interested in getting your book club on board?  Here is what you need to know:

Send me a note about your book group—how many are in it, who they are, and why you want to talk about Surviving Triple-Negative Breast Cancer.  And tell me a bit about you—who you are, and if you have any experience with breast cancer.  You can do this as a comment on my Positives About Negative blog or as a response on my Facebook page.  A few sentences will do. We ask for a minimum of three members in any club that wishes to be considered. 

If you’re currently not a member of a book club, but are interested in starting one to discuss this book, check out the following book club organizations:

Feel free to email me with questions or ideas.  I always love to hear your thoughts.

Wednesday, November 21, 2012

Is miR-200c therapy the future of TNBC treatment?

NEWS RELEASE from the University of Colorado-Denver

Epithelial cells are homebodies – they like to attach to things and becoming detached initiates a form of cell suicide known as anoikis (literally "homeless" in Latin). But in order for cancer cells to metastasize they have to leave their homes and to survive while traveling they must resist anoikis – like a third-grader at sleep-away camp. Cancer cells do this by taking a page from the neuron playbook. Neurons are by nature unbound – they grow and link to each other and not to a substrate. Neurons have a protein called TrkB that allows them to survive anoikis; healthy epithelial cells don't have TrkB and so are susceptible to anoikis.

Carcinoma cells are epithelial cells gone bad and have learned to act like neurons, inappropriately activating TrkB signaling to escape anoikis. They do it by a mutation that nixes production of a microRNA called miR-200c.

When researchers at the University of Colorado Cancer Center reintroduced miR-200c to aggressive, triple-negative breast cancer cells, these cells regained sensitivity to anoikis and self-destructed.

"The reason this is attractive is that we're restoring something that healthy cells make normally. We foresee that miR-200c therapy will be a lot less toxic than chemotherapeutic drugs," says Jennifer Richer, PhD, co-director of the CU Cancer Center Tissue Processing and Procurement Core and senior author of two papers on miR-200c, one published today in the journalPLOS ONE and another published October 16 in the journal Molecular Cancer Therapeutics.

In the PLOS ONE paper, Richer and colleagues including first author Erin Howe, PhD, cultured triple-negative breast cancer cells in forced suspension – detached from a substrate. This most aggressive form of breast cancer didn't care – it had learned to be anoikis-resistant. But then the group reintroduced miR-200c, which had been lost in these cells. MicroRNAs regulate genes, turning them on or off, and sure enough in this case, the group saw that miR-200c directly turned off the neuronal protein TrkB. With miR-200c added, TrkB turned off the cells died of homesickness.

In the Molecular Cancer Therapeutics paper with Diana Cittelly, PhD as first author, the group showed that reintroducing miR-200c to ovarian cancer cells in animal models not only restarted anoikis, but also sensitized these cells to the widely used chemotherapy paclitaxel. This preclinical work takes the important first steps toward a human clinical trial of miR-200c, likely in combination with existing chemotherapies.

"But you can't just introduce microRNAs into the bloodstream," Richer says, "because they end up trapped in the liver." Richer points out that for this reason the only existing clinical trial of microRNA-based therapy is for hepatitis C – which, of course, targets the liver. The other option is applying microRNA directly to tumor cells, "Which seems very possible in the case of metastatic ovarian cancer, which tends to metastasize in the peritoneal cavity and is often directly targeted in this cavity by chemotherapy in the clinic," Richer says.
Unbound cancer cells that are immune to anoikis are most dangerous – they can travel away from their home to invade other tissues. Unbound cancer cells sensitized to anoikis by the reintroduction of miR-200c aren't dangerous at all. They're dead.

I Want and Want. But I Don't Need. Thanksgiving 2012

Somewhere close to my cozy home, a child is hungry.  As my husband and I plan our Thanksgiving Day—we are without family for the first time in many years—a mother nearby tries to stretch her income through the end of the month and still give the kids at least a small treat for this day of thanksgiving.

In a special report on hungry kids in Iowa, The Des Moines Register reported that 15 percent of the children in this food-producing state lived in poverty and hunger in 2010.  Citing statistics from Feeding America, the paper noted that, “At least once during the year, about one out of five Iowa children doesn’t know where his or her next meal will come from.”

One out of five children are uncertain of their next meal in this state with farms and silos full of food, with an economy healthier than that of most other states.  One out of five.   That statistic just throws me, and I can’t forget the images of the beautiful children who are hungry. I grew up without much money, but I have never, ever in my life, faced real hunger.

So, this year instead of shopping for our turkey and dressing and cranberries and pies and then gorging ourselves and regretting it later, we’re filling our shopping cart with canned tuna and chicken, soups, oatmeal, cereal, boxed milk, peanut butter, and crackers, plus personal items like toilet paper and toothpaste.  And we’re taking it to the Food Bank of Iowa.  

Our own Thanksgiving will be a simple meal at home and then a long walk in the woods.  And doesn’t that sound lovely?  Lucky, lucky us.

I need this reminder because, like many Americans, I stew ridiculously about what I don’t have, what I think I need, what I know I want.  Our stove and refrigerator are living way beyond their expected lifetimes.  Our carpet needs to be replaced.  Our countertops are Formica, for heavens sake.  Oh, what would the Property Brothers say about our house?  Not a lick of granite in it. 

So I stew and stew and stew.  I want, I want, I want.   

And then I remember the hungry kids and give myself a metaphorical whap in the face.  Our biggest worry is what we are going to eat—not if.  And our stove and refrigerator sill work and we use them daily to make blessedly wonderful meals.  I never have to worry if we can pay the utilities or get the roof fixed if it needs it.

And I have healthcare.  If I need to go to the doctor, I go. 

Our few boxes of food will not solve the problem of hungry Iowa children, but it will make at least a small dent.  And it is money better spent than on our own excesses.  Through the process I have gained something incredibly important to me—a perspective that helps me curb my advertising-and-Facebook-and HGTV-driven desires to do and have and consume it all.

I am lucky.  I have to work hard to remember that., but I am much saner for doing it.  Paying it forward works both ways.

Monday, November 12, 2012

SABSC Here I Come

I am heading to San Antonio for my first-ever breast cancer conference, the San Antonio Breast Cancer Symposium, December 3-8.  I hope to visit with researchers, practitioners, other advocates, and media outlets.  I plan to blog regularly from San Antonio.

I am pretty pleased that the conference organizers consider this blog an official media outlet and offered me a press pass representing Positives About Negative.  Whooheee.  I am a media mogul.  As if.

I am looking forward to offering you a bit of an expansion of my little media operation here.  There are a few sessions specifically on TNBC.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Tuesday, November 6, 2012

P53 May Be Protective Protein for TNBC

Expression of the p53 protein was associated with better prognosis in patients with estrogen-negative tumors but with a worse prognosis for estrogen-positive tumors, according to a study published in the November 5 edition of Breast Cancer Research.  The protective value of p53 applies to both triple-negative and Her2-positive breast cancer.