Asymmetric cell division (ACD) is a physiologic process during development and tissue homeostasis. ACD produces two unequal daughter cells: one has stem/progenitor cell activity and the other has potential for differentiation. Recent studies showed that misregulation of the balance between self-renewal and differentiation by ACD may lead to tumorigenesis in Drosophila neuroblasts. However, it is still largely unknown whether human cancer stem–like cells exhibit ACD or not. Here, using human neuroblastoma cells as an ACD model, we found that MYCN accumulates at spindle poles by GSK-3β phosphorylation during mitosis. In parallel, the ACD-related ubiquitin ligase Trim32 was recruited to spindle poles by CDK1/cyclin B–mediated phosphorylation. Trim32 interacted with MYCN at spindle poles during mitosis, facilitating proteasomal degradation of MYCN at spindle poles and inducing ACD. Trim32 also suppressed sphere formation of neuroblastoma-initiating cells, suggesting that the mechanisms of ACD produce differentiated neuroblastoma cells that will eventually die. Thus, Trim32 is a positive regulator of ACD that acts against MYCN and should be considered as a tumor-suppressor candidate. Our findings offer novel insights into the mechanisms of ACD and clarify its contributions to human tumorigenesis. Cancer Res; 74(19); 1–11. ©2014 AACR.
Molecular Response to Letrozole in ILC
Invasive lobular carcinoma (ILC) accounts for approximately 10% to 15% of breast carcinomas, and although it responds poorly to neoadjuvant chemotherapy, it appears to respond well to endocrine therapy. Pre- and on-treatment (after 2 weeks and 3 months) biopsies and surgical samples were obtained from 14 postmenopausal women with estrogen receptor–positive (ER+) histologically confirmed ILC who responded to 3 months of neoadjuvant letrozole and were compared with a cohort of 14 responding invasive ductal carcinomas (IDC) matched on clinicopathologic features. RNA was extracted and processed for whole human genome expression microarray. Dynamic clinical response was assessed using periodic three-dimensional ultrasound measurements performed during treatment and defined as a reduction of >70% in tumor volume by 3 months. Pretreatment profiles of ILC and IDC tumors showed distinctive expression of genes associated with E-cadherin signaling, epithelial adhesion, and stromal rearrangement. The changes in gene expression in response to letrozole were highly similar between responding ILC and IDC tumors; genes involved in proliferation were downregulated and those involved with immune function and extracellular matrix remodeling were upregulated. However, molecular differences between the histologic subtypes were maintained upon treatment. This is the first study of molecular changes in ILC in response to endocrine therapy to date. The genes that change on letrozole are highly consistent between ILC and IDC. Differences in gene expression between ILC and IDC at diagnosis are maintained at each time point on treatment. Cancer Res; 74(19); 1–6. ©2014 AACR.
Can sugar consumption cause breast cancer?
A recent study stated that drinking three sugar sweetened drinks a week would increase the risk of having breast cancer. The study had 776 pre-menopausal women and 779 post-menopausal women. Each women’s breast density was assessed by examining their mammograms. The women were told to make a note of sweet they consumed such as chocolates, cakes, ice cream or any sweet drinks. Also they were asked to make a note of how much of spoonful of sugar they add to the drinks.
It was then found out that post-menopausal women who consumed more of sugar, an increase in the density of breast. While the pre-menopausal women observed an increase in breast density when they consumed sugar food. These women, in a week were just consuming three sugar sweetened drinks. The study then further stated that sugar tends to increase the migration of breast cells together. This explains the fact that the premenopausal women who consumed sugar-sweetened drinks were 3 percent more likely to have dense breasts than those who didn’t consume the drinks. And having dense breasts increases your risk of breast cancer by making it difficult to see tumors on mammograms.
However, there is more to be studied on this matter. But until then there is still a link between the sugar consumption and breast density. About 40% of women in the US have dense breast and they are totally unaware of it. Doctors say that women with a dense breast are five time more likely to have a breast cancer and 10 times more likely to miss the tumor in the mammogram test.
Does vitamin D reduce the chances of having bowel cancer?
Medically known as colorectal cancer or colon cancer, is a type of cancer that affects the larger bowel and rectum. The growth of it is very slow. Its takes a period of 10 years to grow and then it starts to spread and affect the other parts of the body. This is the second most common cancer in Europe. Around 447,000 cases of bowel cancer were seen in the year 2012.
Recent study has shown that people who suffer from bowel cancer, if consume vitamin D, then they are more likely to survive the cancer. The study was confirmed after researching about 1600 patients who had a bowel cancer surgery. The study showed that the patients who had a good level of vitamin D have half the risk of dying of this diseases than those who just had a minimal amount of vitamin D. The study is the first to correlate the long-term survival prospects of bowel cancer patients after diagnosis with total blood levels of vitamin D. The research team tested the blood samples of the patients after surgery. They found out that patients who had a good amount of vitamin D, in stage two cancer, the tumor was not seeing much spread. And 2/3rd of the patients with low vitamin D did not survive beyond 5 years.
Vitamin D is also known as the sunshine vitamin. Vitamin D is made in the body when the skin is exposed to sunlight. Also consumption of certain food like fish liver oil, eggs and other fishes like salmon, herring and mackerel. Vitamin D is known to boost the activity of calcium in the body and therefore, forming the bone function.
Some studies have also stated that in case there is low of vitamin D in a person, it is likely that he maybe at a risk of having chronic diseases. So doctors advice patients with bowel cancer to have a good level of vitamin D.
The research team is now planning on trying out for a clinical trial to test whether taking vitamin D tablets in combination with chemotherapy can improve bowel cancer survival rates.
Back in the Saddle with Team Penn Vet for the Ride to Conquer Cancer
When we think of cancer, we don’t always think of cancer in animals. But, for Sarah Rauers, administrative assistant, for the animal biology department at the University of Pennsylvania School of Veterinary Medicine, cancer in animals – and people – is always in her thoughts.
“At this point, I don’t think there is anyone who doesn’t know someone with, or who has had cancer,” says Sarah. “I’ve had family members, as well as pets, I’ve watched suffer through the disease.”
And that, says Sarah, is one of the things that has motivated her to join the Philadelphia Ride to Conquer Cancer this October.
“I went to an information session with my co-workers, and we decided to start a team together,” says Sarah. “There was so much energy and hope we saw within the ride and the research happening at Penn, we wanted to support the cause.”
Cancer Research at Penn Vet
Within the faculty at Penn Vet, there is a lot of research that focuses on cancer. “Penn Vet studies cancer biology in mice, dogs and larger animals – all part of a mission to pursue translational medicine,” says Sarah. “Breakthroughs in cancer research today made in research could someday can one day help conquer cancer in all species.”
The other motivation behind Sarah’s decision was a very personal one.
“A couple of years ago I was hit by a car while commuting on my bike to work,” she says. “I suffered a great deal of physical and emotional trauma from that experience. Getting back on my bike and participating in The Ride is a big milestone for me.”
As for her fundraising efforts, Sarah has been pleasantly surprised at the support she’s gotten from family and friends.
“Fundraising has been so much easier than I thought it would be. Shocked by the generosity of my friends and family, and ‘Facebook friends,’” she says. “If you are considering joining, just do it. For about three days after my team signed up we were concerned about what we got ourselves into but it’s going to be easier and more rewarding than any of us think!”
Check out more from Team Penn Vet here.
The Ride to Conquer Cancer®
Join Penn Medicine’s Abramson Cancer Center (ACC) on October 11 to 12, 2014 in the Ride to Conquer Cancer (RTCC)—an unforgettable and epic bike ride through Pennsylvania’s picturesque landscape -towards one life-changing destination: to cure cancer. The ride isn’t just for cyclists, it’s for anyone who wants to see a cure for cancer.
At two-days and 150+ miles the RTCC will be a physical challenge—and an emotional and inspirational weekend—that will give you a chance to ride side by side with physicians, patients and families–raising serious funds and awareness in the ACC’s fight to cure cancer.
The funds raised through the ride will be put to use immediately, powering the ACC’s vision to eradicate cancer as a cause of human disease and suffering through precision medicine, novel research, next-generation therapies, and compassionate care.
Join Today
This event will be remarkable, bringing together communities of cancer survivors, cyclists, and their supporters with a common goal to conquer this disease. Join the ride in October by registering today at www.ridetovictory.org or by calling (844) 777-7433.
Before the ride, you will have access to:
- Expert coaching
- Training rides in your area
- Personal web page for fundraising
- Helpful manual
- 2014 ride commemorative item
During the ride, participants will have access to:
- Event-day ride jersey
- Support along the route
- Catered meals
- Entertainment at camp
- Massage and medical care
