VICC News & Publications Mon, 15 Dec 2014 16:30:28 +0000 en-US hourly 1 Visit unites stem cell transplant patient, donor Mon, 15 Dec 2014 16:29:27 +0000 stem cell patient, donor meeting

Darlena Clark hugs Jon Strong, who donated the stem cells that were transplanted into Clark to treat her blood disorder. (photo by Anne Rayner)

When Darlena Clark of Hendersonville, Tennessee, saw Jon Strong for the first time at Nashville International Airport she, “just grabbed him and hugged him and just held on.”

Strong, a U.S. Navy hospital corpsman based at Camp Pendleton, California, was the stranger from across the country who had volunteered to be a bone marrow donor, and it was his stem cells that saved Clark’s life.

Clark, 67, waited a year before learning the name of her donor — the time required under the rules of the stem cell donation program. But as soon as the deadline expired, and Strong agreed to be identified, the pair started talking, and soon Clark and her husband, Dennis, decided to fly Strong, his wife, Stephanie, and their two children to Nashville to celebrate Thanksgiving week together.

“It’s hard to imagine how grateful you could feel to someone you’ve never met,” said Clark. “You have someone’s blood and they’ve saved your life. How much more could anyone give? So, it’s an amazing experience to be in that position and to be able to meet the person.”

Clark had been diagnosed with myelodysplastic syndrome (MDS), the same blood disorder that ABC News anchor Robin Roberts has been battling. In MDS some of the cells in the bone marrow become damaged and the disease can progress to a form of cancer called acute myeloid leukemia (AML).

Years before Clark became a patient in the Stem Cell Transplant Clinic at Vanderbilt-Ingram Cancer Center, Strong, now 37, had helped lead a bone marrow donation registration drive at his naval base.

Strong was flown to Georgetown University Medical Center in Washington, D.C., and for five days he stayed at a local hotel, making daily visits to the Georgetown clinic, where he received shots to stimulate his stem cells.In June 2013, he received a call that his stem cells appeared to be a match for a patient in need.
“When asked, there was no question, at least in my mind, whether I was going to donate or not,” Strong said. “It was just ‘how soon do you need it done?’ That’s how I like to think the hospital corpsman field is anyway. As medical people we would always strive to do our best.”

“After the Navy, those shots were no big deal,” said Strong, with a grin. He took Tylenol and hung out in the hotel hot tub to manage the joint pain from the shots.

stem cell donor, patient

During a visit to the Vanderbilt-Ingram Cancer Center Stem Cell Transplant Clinic, Madan Jagasia, MBBS, center, talks with stem cell recipient Darlena Clark, second from left, her husband, Dennis, left, stem cell donor Jon Strong, second from right, and his wife, Stephanie. (photo by Anne Rayner)

After his stem cells were harvested, they were sent to VICC and on July 11, 2013, Clark received the infusion of stem cells. It was a significant date for patient and donor — transplant day for Clark and the 15th wedding anniversary for Jon and Stephanie Strong.

A year and a half later, Clark is doing well, and she wanted Strong and his family to tour the VICC Stem Cell Transplant Clinic and meet some of the medical professionals who made the transplant possible, including Madan Jagasia, MBBS, section chief of Hematology and Stem Cell Transplant and director of the Outpatient Stem Cell Transplant Unit.

“This is what we live for. This is the most rewarding experience for us because in what we do there are lots of wins and losses. So this is really rewarding for us to see a patient doing so well, to see a human save a human,” said Jagasia.

He pointed out that 70 percent of the stem cell transplants performed at Vanderbilt are done on an outpatient basis, and the program is growing every year.

More information on the donor registry is available at the National Marrow Donor Program, or visit

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Tindle to lead Tobacco Research and Treatment Fri, 21 Nov 2014 15:50:25 +0000 November is well-known as Lung Cancer Awareness Month. It is also the month that highlights awareness of less publicized forms of cancer including pancreatic cancer and stomach cancer.

All three of these diseases share a common risk factor — cigarette smoking.

“Smoking is the leading cause of preventable disease and death and it is claiming 480,000 people a year,” said Tindle, associate professor of Medicine. “The public may not realize that smokers die an average of 13 years earlier than non-smokers.”

Fifty years after the first U.S. Surgeon General’s historic report that linked tobacco products to lung cancer, Vanderbilt has recruited Hilary Tindle, M.D., MPH, as director of Tobacco Research and Treatment. Tindle is a well-known tobacco researcher who contributed to the 2014 50th anniversary Surgeon General’s report.

Hilary Tindle, M.D., MPH

Hilary Tindle, M.D., MPH

In addition to cancer, smoking also leads to cardiac diseases by hastening plaque buildup in blood vessels, or atherosclerosis.

Tobacco use is costing the U.S. $300 billion annually in health care costs and lost productivity. These societal costs are not geographically uniform. States like Tennessee and Kentucky still have some of the highest percentages of smokers, which may contribute to the region’s designation as the Stroke Belt and the Cancer Belt.

Tindle said eight in 10 smokers see a doctor annually and seven in 10 want to quit smoking. Over half of smokers actually try to quit every year. But most don’t use quit aids like nicotine replacement products, prescription medications or counseling programs and, as a result, 95 percent of unaided quit attempts fail.

“We need to track and treat smokers in order to have an impact,” explained Tindle. “We can leverage the Electronic Health Record to track and treat tobacco users. We can proactively treat people over time and if they are not motivated to quit smoking, we can help get them motivated.”

Over the next year, VUMC will create and implement the new patient-centered tobacco control program which will include education for providers and staff.

The program will include assistance to patients while they are hospitalized.

“We can manage their nicotine withdrawal symptoms while they are in the hospital, regardless of the reason that brought them there,” said Tindle. “We will visit the patient at the bedside, talk to them about their tobacco use and discuss the relationship of smoking to their illness.”

At the time of discharge, VUMC will arrange for medication and counseling and provide an e-Referral to the Tennessee Tobacco Quit Line, a free telephone support program available at (800) QUIT-NOW (800-784-8669.)

Tindle said there are already compelling signs that Americans are willing to make lifestyle changes regarding tobacco use.

“There are now more former smokers than smokers. We can do it. We can’t afford to be pessimistic about changing smoking habits.”

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Gene linked to breast cancer therapy response Fri, 21 Nov 2014 15:34:34 +0000 A group of Vanderbilt-led investigators has identified a new gene mutation that may explain why some breast cancer patients do not respond to anti-hormone therapy.

Carlos Arteaga and colleagues

Carlos L. Arteaga, M.D., left, Justin Balko, Pharm.D., Ph.D., Luis Schwarz, M.D., and colleagues are studying a gene mutation that may shed light on why some breast cancer patients don’t respond to anti-hormone therapy. (photo by Joe Howell)

The study was published online in the Journal of Clinical Investigation. Luis Schwarz, M.D., and Emily Fox, Ph.D., served as co-first authors of the study, led by senior author Carlos L. Arteaga, M.D., director of the Breast Cancer Program and the Center for Cancer Targeted Therapies at Vanderbilt-Ingram Cancer Center, along with colleagues at the University of Texas M.D. Anderson Cancer Center, Houston, and Emory University, Atlanta.

Many breast cancer patients have tumors that are fueled by hormones such as estrogen, which binds to estrogen receptors (ER) in tumor cells. The receptors activate ER-dependent genes that, in turn, help ER-positive (ER+) cancers grow.

ER+ tumors often respond to anti-estrogen agents like tamoxifen, fulvestrant or aromatase inhibitors such as letrozole, anastrazole or exemestane. These drugs, referred to as endocrine therapy, are widely used by patients with early and advanced breast cancer.

However, a significant fraction of patients with ER+ metastatic breast cancer don’t respond to endocrine therapy because their tumors are initially resistant or acquire drug resistance after an initial response to anti-estrogens. To identify genetic alterations that help explain this resistance, the investigators profiled ER+ breast tumors from four patients who were treated with the aromatase inhibitor letrozole prior to their mastectomies. These tumors did not respond to the letrozole as measured by markers of proliferation in the mastectomy specimens.

The investigators performed deep sequencing on the tumors and identified a novel mutation (D189Y) in a gene of the Src family of kinases called LYN.

“Src family kinases like LYN are known to be associated with carcinogenesis, cancer cell invasion and metastatic progression,” said Schwarz, a postdoctoral research fellow at VICC.

The investigators also identified other LYN mutations in breast tumors in the Cancer Genome Atlas. Like D189Y, these mutations increase the activity of the LYN protein.

“When present in ER+ breast cancer cells, these mutations induce an advantage in proliferation of cells as well as resistance to anti-estrogen therapies,” said Schwarz. “To the best of our knowledge, no one had previously described how these LYN mutations work.”

The authors tested assays in three cell lines and in a mouse model to identify potential therapies for ER+ breast cancers harboring D189Y LYN. They tested two Src inhibitors and identified the drug dasatinib as the most effective. Since dasatinib is already approved for another form of cancer, it could be adapted for testing in breast cancer.

The authors note that the agent is not an ideal drug because it is not a pure LYN inhibitor. However, they hope that their identification of the new LYN mutation will spur development of a LYN inhibitor for testing in patients with breast cancer.

“Our findings suggest that a LYN inhibitor could be an effective treatment when combined with endocrine therapies in patients with breast cancer,” said Arteaga, also the Donna S. Hall Professor of Breast Cancer Research.

The authors include Justin Balko, Pharm.D., Ph.D., Joan Garrett, Ph.D., Maria Gabriela Kuba, M.D., Monica Valeria Estrada, M.D., Monica Red-Brewer, Ph.D., Ingrid Mayer, M.D., Vandana Abramson, M.D., Mark Kelley, M.D., Ingrid Meszoely, M.D., Vanderbilt; Ana María González-Angulo, M.D., Gordon Mills, M.D., Ph.D., M.D. Anderson Cancer Center; and Monica Rizzo, M.D., Emory University.

Support for the study included funding from the National Cancer Institute, a division of the National Institutes of Health (P50 CA098131, P30 CA68485, P30 CA016672), Susan G. Komen for the Cure, the Breast Cancer Research Foundation, the American Cancer Society and the Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú.

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More breast cancer patients choose mastectomy Fri, 21 Nov 2014 15:22:03 +0000 20100114JH010mammo

Far more breast cancer patients are choosing to undergo mastectomy, including removal of both breasts, instead of choosing breast conservation surgery even when they have early stage disease that is confined to one breast, a Vanderbilt study shows. In the past decade, there have also been marked trends toward higher proportions of women opting for breast reconstruction.

The rates of increase were steepest among women with lymph node-negative and in situ (contained) disease.

This is a reversal of trends seen since the 1990s when breast conservation surgery (BCS) was found to produce equivalent cancer outcomes and was endorsed as a standard of excellence by a National Institutes of Health Consensus Conference.

The Vanderbilt University study, led by Kristy Kummerow, M.D., and Mary Hooks, M.D., MBA, was published online in the Nov. 19 edition of JAMA Surgery.

Using the National Cancer Data Base, the investigators studied records of more than 1.2 million adult women treated at centers accredited by the American Cancer Society and the American College of Surgeons Commission on Cancer from Jan. 1, 1998, to Dec. 31, 2011.

During that time, a total of 35.5 percent of those women underwent mastectomy. The adjusted odds of mastectomy in BCS-eligible women increased 34 percent during the most recent eight years of the study period. Rates of bilateral mastectomy (removal of both breasts) for cancer in one breast increased from 1.9 to 11.2 percent from 1998 to 2011.

In women undergoing mastectomy, rates of breast reconstruction increased from 11.6 to 36.4 percent in the same time period.

The rise in mastectomy rates in the U.S. was most pronounced among younger women with noninvasive disease, those with smaller tumors, and those with node-negative disease, indicating the cancer was less likely to spread beyond the initial tumor. This suggests that factors unrelated to disease burden or cancer control are influencing women, especially younger patients.

“Our findings of still-increasing rates of mastectomy, breast reconstruction and bilateral mastectomy in women with early-stage breast cancer has implications for physician and patient decision making, as well as quality measurement,” said Kummerow.

The authors note that the trend toward breast reconstruction may be explained by multiple factors. The National Accreditation Program for Breast Centers expects that all women undergoing mastectomy be offered reconstruction. And the Women’s Health and Cancer Rights Act, passed in 1998, mandated insurance coverage of postmastectomy reconstruction. Prior research found that this law significantly increased the proportion of women insured by Medicare and Medicaid who underwent reconstructive procedures.

The study could not determine the number of patients who have tested positive for mutations in the BRCA gene which greatly increases the risk of developing breast cancer, and may influence women to remove both breasts. The research also could not determine the number of patients whose tumors have been identified as triple-negative. These hormone receptor negative tumors are more aggressive and difficult to treat.

The authors note that further research is needed to understand patient, provider, policy and social factors associated with these trends.

Other investigators for the study include Liping Du, Ph.D., David Penson, M.D., MPH, and Yu Shyr, Ph.D.

The research was supported by the U.S. Department of Veterans Affairs, the Veterans Affairs Office of Academic Affiliations, the Veterans Affairs National Quality Scholars Program, and with use of facilities at Veterans Affairs Tennessee Valley Healthcare System in Nashville.

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New insight on oral cancer culprits Wed, 12 Nov 2014 16:13:52 +0000 Oral squamous cell carcinoma (OSCC) treatments have been slow to advance despite the aggressive nature of these tumors that commonly metastasize.

Models for the development of improved OSCC therapeutics have also been scarce. Thomas Andl, Ph.D., Claudia Andl, Ph.D., and colleagues previously observed coordinated loss of connective molecules (E-cadherin) and growth factor (TGFbeta) signaling in human OSCC.

Now, in the November issue of Carcinogenesis, the investigators describe a new mouse model based on the errant signaling in these human cancers and demonstrate that loss of E-cadherin and TGFbeta signaling is sufficient to cause OSCC.

Though TGFbeta signaling and E-cadherin both pose a challenge for drug targeting in tumor cells, this novel mouse cancer model provides an in vivo paradigm to test therapeutics targeting different pathways impacting OSCC. This work not only addresses the complex role that TGFbeta signaling plays in OSCC formation and progression, but also provides new insight regarding how TGFbeta signaling controls oral squamous cell turnover.

This work was supported by grants from the National Institutes of Health (DK075379, DK094900, DK058404).

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Bone Cancer Image Featured in Contest Tue, 11 Nov 2014 21:29:00 +0000 osteosarcoma (bone cancer) cell

Osteosarcoma (bone cancer) cell at 8000X magnification. Image courtesy Dylan Burnette, Ph.D.

An image by Dylan Burnette, Ph.D., an assistant professor of Cell and Developmental Biology and Vanderbilt-Ingram Cancer Center member, was chosen as a winning entry in the 2014 Nikon Small World Photomicrography Competition. Burnette’s image shows an osteosarcoma (bone cancer) cell at 8000X magnification.

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Protein “pockets” help ID cancer genes Tue, 11 Nov 2014 16:30:29 +0000 Somatic mutations, which can occur in any cell except sperm or egg, are not inheritable.

Several recent studies have demonstrated that disease-causing mutations commonly alter protein folding, protein stability and protein-protein interactions. It has been difficult, however, to determine which somatic mutations identified in tumor samples “drive” the cancer development and which are just “along for the ride.”


Using a computational approach they developed, Zhongming Zhao, Ph.D., and colleagues systematically investigated somatic mutations located in protein “pocket” regions that, among other functions, bind small molecules, enzymes and nucleic acids.

Reporting last month in Genome Medicine, they found that somatic mutations in protein pocket regions tend to be functionally important during tumorigenesis and sensitive to anticancer drug responses. They identified four putative cancer genes that are associated with overall poor survival rates in patients with melanoma, lung or colorectal cancer.

Protein pocket-based prioritization of somatic mutations thus provides a promising approach to uncover putative cancer drivers and biomarkers of anticancer drug response.

The study was supported in part by National Institutes of Health grants LM011177, LM007450, CA095103, CA098131 and CA068485.

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Immune cell activity and melanoma Thu, 06 Nov 2014 16:32:58 +0000 Melanoma, the most lethal form of skin cancer, spreads aggressively and is often resistant to therapy. Melanoma tumor formation is driven in part by nuclear factor-kappa B (NF-kappaB)-mediated gene transcription, and loss of NF-kappaB activity can block melanoma tumor formation. However, NF-kappaB also plays a crucial role in immune cells.

In an October online edition of Cancer Research, first author Jinming Yang, Ph.D., corresponding authors Fiona Yull, D.Phil., and Ann Richmond, Ph.D., and colleagues detailed effects of blocking NF-kappaB activity in myeloid cells on “anti-tumor” immune responses. Disappointingly, mice with myeloid specific inhibition of NF-kappaB exhibited enhanced melanoma growth and metastasis. In contrast, enhancing NF-kappaB activity in myeloid cells resulted in impaired tumor growth and metastasis.

Thus, myeloid cell NF-kappaB activity is essential for mounting the optimal “anti-tumor” immune response, emphasizing the need to consider effects of anti-cancer therapies not only on tumor cells, but also on the immune cells in the tumor microenvironment.

This research was supported by grants from the TVHS Department of Veterans Affairs and from the National Institutes of Health (CA116021, CA068485).

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Courage Unmasked Fri, 31 Oct 2014 21:43:25 +0000 Radiation masks donated by head and neck cancer patients and decorated by Nashville-area artists were displayed during the recent Courage Unmasked event at Vanderbilt’s Sarratt Gallery. More than 60 masks visible on the back wall were decorated by Nashville area artists to raise funds for Vanderbilt-Ingram Cancer Center head and neck cancer patients.

Radiation masks donated by head and neck cancer patients and decorated by Nashville-area artists were displayed during the recent Courage Unmasked event at Vanderbilt’s Sarratt Gallery. More than 60 masks visible on the back wall were decorated by Nashville area artists to raise funds for Vanderbilt-Ingram Cancer Center head and neck cancer patients.

Read more about the project here.

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New Insights on Postpartum Breast Cancer Fri, 31 Oct 2014 21:34:24 +0000 Nearly 25 percent of all breast cancers among premenopausal women occur within two to five years following a pregnancy.

These postpartum tumors are more likely to spread or metastasize to other parts of the body, leading to an increased risk of death.

A new study led by Cook and published recently in the Journal of Clinical Investigation helps explain the cellular activity that leads to breast tumor metastasis among women who have recently given birth. Other contributors include first author Jamie Stanford, Ph.D., a former VICC postdoctoral fellow now working for the Susan G. Komen Foundation, and collaborators at the University of North Carolina and the University of Illinois.

Rebecca Cook, Ph.D.

Rebecca Cook, Ph.D.

“Unfortunately, these are young women who have just had children. All breast cancer deaths are tragic, but the loss of a young woman who is also a mother is so devastating for families and has a profoundly negative societal impact,” said Rebecca Cook, Ph.D., assistant professor of Cancer Biology.

Breast tissues undergo massive transformations during pregnancy in preparation for nursing the new infant. After milk production has ended, there is a cascade of cell death.

“This cell death removes about 90 percent of breast epithelial cells during a very short window of time, which triggers widespread remodeling and repair of breast tissue by the immune system,” explained Cook.

During this remodeling, immune cells called macrophages operate like tiny Pac-Man arcade game characters, gobbling up the dying cells before the dying cells can release intracellular contents which can provoke immune attack. As another safeguard against immune attack, macrophages that ‘eat’ dying cells also secrete immune suppressive factors. Macrophages use one molecule — MerTK — to control both of those processes.

Using a mouse model, Cook and her colleagues found that immune suppression in the postpartum breast triggered by MerTK mistakenly protects tumors, increasing their ability to spread.

“This is similar to an amplified wound healing response that is orchestrated and amplified by MerTK, and that drives tumor malignancy,” said Cook.

The investigators treated mice harboring postpartum tumors with an investigational drug labeled BMS-777607, designed to inhibit MerTK. Following treatment, investigators saw decreased clean-up of dying breast cells in the postpartum breast, decreased immune suppression and decreased metastasis. The drug, which is in clinical testing for other forms of cancer, was used for just seven days to avoid disrupting the immune response and creating autoimmunity.

While more research is needed, Cook said the results suggest that using a MerTK inhibitor in conjunction with other therapies could be helpful.

“MerTK-directed therapies may prevent the accelerated rate of tumor spread caused by the postpartum remodeling processes. This would be a short window of treatment in the postpartum period but with the long-term benefit of preventing tumor recurrence at distant sites,” said Cook.

In the meantime, Cook said women who have recently given birth need to be vigilant about breast health.

Other investigators who contributed to the study include Christian Young, Ph.D., Donna Hicks, Philip Owens, Ph.D., Andrew Williams, David Vaught, Ph.D., Meghan Morrison, Jiyeon Lim, Michelle Williams, Dana Brantley-Sieders, Ph.D., Justin Balko, Pharm.D., Ph.D., Vanderbilt; Debra Tonetti, M.D., University of Illinois; and H. Shelton Earp III, M.D., University of North Carolina.

Funding for the study was provided by the National Cancer Institute, a division of the National Institutes of Health, (CA143126, CA009592), the Department of Defense (BC120793), and the Susan G. Komen Foundation.

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