Duke Research Blog

Following the people and events that make up the research community at Duke.

Category: Cancer (Page 1 of 7)

A Summer Well-Spent In and Around Toxic Waste Sites

Edison, NJ is just 40 miles from Manhattan and 70 miles from Philadelphia. It’s also home to the US EPA’s Emergency Response Team (ERT), where I spent the summer as an intern.

Stella Wang and an EPA contractor used lifts to test oil being pumped out of these huge tanks. It was found to be contaminated with mercury, benzene and lead.

At the start of my internship, I had little idea of how ERT functioned. Unlike the 10 regional offices of the Environmental Protection Agency, ERT is a “headquarters” or Washington, DC-based group, which means it responds to incidents all over the country such as oil spills, train derailments, and natural disasters.

For example, my mentor, an air specialist who generally works from his cubicle in Edison, aided in the immediate aftermath of Hurricane Katrina by employing equipment to analyze air for hazardous pollutants. Other ERT team members have conducted sediment sampling to expedite the hazardous waste removal process, given consultation advice to other EPA members for long-term remedial site work, and led the innovation of new technology.

I was able to shadow and help my mentor and fellow ERT members with their Superfund site removal work. I created accurate maps showing injection well locations, learned how to use air monitoring instruments, and helped perform chemical lab experiments that will be employed for future site analysis.

Perhaps my favorite part of the internship was traveling to a myriad of active sites. At these sites, I not only got to see how ERT members worked with EPA’s on-scene coordinators, but also observed the physical removal and remediation processes. I was fortunate to visit a particular site multiple times — I witnessed the removal of contaminated oil from an abandoned lot as the summer progressed.

Stella Wang (left) and an EPA air specialist calibrating a air monitoring instrument before a public event.

At another site, I saw the beginning of an injection process intended to prevent the contamination of underground drinking water by hexavalent chromium. By pumping sodium lactate into underground wells, the hexavalent is converted into the insoluble and benign chromium-3 ion. If the injection process works, the community will no longer be threatened by this particular hazardous material.

ERT also acts in anticipation of possible contamination to protect the public. At largely attended events like the Democratic National Convention, a few ERT members will arrive with monitoring equipment. They pride themselves in their real-time data collection for a reason: throughout the event, they can detect whether a contaminant has been released and immediately instigate an emergency response to protect attendees.

Thanks to various ERT members, I felt accepted and welcome. They were open and patient with my never-ending questions about their career paths and other things. They’ve graciously taken me out to lunch so that they could get to know me better, ensuring my inclusion in their small community.

Of course, the experiences I had this summer, while brief, have taught me a tremendous amount and I have a clearer sense of how this division of the US federal government functions. But, it would be inaccurate and unjust to omit the impact that its people made on me.

Stella Wang, Duke 2019Guest post by Stella Wang, Class of 2019

If the Cancer Doesn’t Kill You, the Drug Prices Might

The medical community is growing alarmed about a creeping malady that can diminish the quality of life for patients in treatment and even shorten their lives.

It’s found everywhere in the United States, but not to the same degree in other developed countries. They’re calling it “Financial Toxicity.”

Yousuf Zafar is an oncologist and health policy researcher.

A cancer diagnosis more than doubles an American’s chance of declaring bankruptcy, Duke medical oncologist  Yousuf Zafar, MD, MHS,  told an audience of nursing faculty and students at a May 10 luncheon lecture sponsored by the Duke Center for Community and Population Health Improvement. And that bankruptcy, in turn, has been shown to decrease survival rates.

In addition to treating cancer patients, Zafar studies access to care and the cost of care at the Duke Cancer Institute, the Sanford School of Public Policy, and the Margolis Center for Health Policy.

Zafar told personal stories of two patients who waved off treatments because of the financial hardship they feared.

Gleevec (Imatinib) is an oral chemotherapy made by Novartis.

One of them had a job with health insurance, but no prescription drug coverage, which put him on the hook for $4,000 in medications to treat his rectal cancer for just a few weeks. Had either the patient or Dr. Zafar brought the topic up, the costs might have been avoided, but they never talked about money, he said.

The other patient passed up another round of treatment for his pancreatic cancer, for fear of the bills his family would be saddled with when he died.

Chemotherapy for cancer would typically cost $100/month in the 1970s, Zafar said. But today that figure can be “ten, or tens, of thousands per month.” (Inflation would make that 1970 dollar about $6, not $600.)

“Pricing in the European Union and the rest of the world is a completely different picture,” he said.  In the US, pricing “simply reflects what the market will bear.”

Another source of the steep climb is the advent of biologic drugs, which are expensive to develop, use and store, but offer more targeted therapy for individual patients. One of the most successful of these is Gleevec (Imatinib) an oral chemotherapy that became 158 percent more expensive from 2007 to 2014, Zafar said.

If you do a Google search for Gleevec, the first thing you find is a Novartis page with the headline “Understand Your Out-Of-Pocket Costs For Gleevec” that includes a link to financial assistance resources.

In the face of outrageous costs and questionable benefits, a treatment team in many cases can help patients find other means of support or alternative treatments to achieve the same end with less financial damage. But they have to have the conversation, Zafar said. He’d like to see Duke’s Cancer Center become the first in the country to be totally transparent about costs, but he acknowledged that it may be a difficult quest.

To help enable those conversations, Zafar developed a mobile app called Pathlight to help patients make more informed decisions and plan better for the financial burden of treatment. For some of the technology used in the project, Zafar has partnered with a software company called Vivor, which has found innovative ways to help patients navigate to financial assistance programs. That part of the project is supported by the NIH’s National Cancer Institute.

Even for people not in treatment, drugs have become more costly. Healthcare premiums rose 182 percent from 1999 to 2013, with workers paying an increasing share of the cost of their own employee health plans.

Is this any way to run a health system?

“I don’t have all the answers – I don’t think anybody does,” Zafar said. “But I think we need to move toward a single-payer system.”

Post by Karl Leif Bates

 

Cells Need Their Personal Space

One of the body’s first lines of defense against harmful pathogens is the skin. The constant maintenance of this epithelial cell layer which serves as a barrier to infection  is essential to fighting off disease.

Jody Rosenblatt, an Associate Professor in the Department of Oncological Sciences at the University of Utah School of Medicine, has made it her lab’s mission to study the function of epithelia as a barrier, how this barrier is maintained, and what happens when it goes awry.

Jody Rosenblatt, PhD is an investigator for the Huntsman Cancer Institute at the University of Utah School of Medicine and a Howard Hughes Medical Institute Faculty Scholar

Rosenblatt recently spoke at Duke’s Developmental & Stem Cell Biology Colloquium where she presented some extraordinary findings about how epithelia can squeeze out  both healthy and dying cells  to preserve the protective barrier.

Some c cells commit suicide via programed cell death and are forced out of the cell layer because they are no longer functional. But in the case of forcing out living cells, “cell extrusion is more like a homicide” said Rosenblatt. The fact that perfectly functional living cells are pushed out of a cell layer perplexed her group until they discovered it was happening as a response to cell overcrowding.

Rosenblatt explained that like people, cells tend to like their personal space, so when this is compromised, live cells are actively pushed out of the cell layer, restoring balanced cell numbers.

Rosenblatt’s lab took this discovery a step farther and pinpointed the pathway that likely induces the extrusion of live cells.

Piezo1, a stretch-activated calcium ion channel present in epithelial cells, senses crowding and activates sphingosine-1-phosphate (S1P), the driver of epithelial cell extrusion. When Piezo1 channels are inhibited and don’t sense stretching, cells cannot extrude.

Using zebrafish, Rosenblatt showed that when extrusion was blocked by compromising the S1P2 pathway, epidermal cells form masses that are resistant to chemotherapy drugs and signals for programmed cell death.

Rosenblatt explains the importance of regulating cell extrusion in the epithelium to maintain the tissue’s function as a protective barrier for our organs. Misregulation of this function can result in diseases such as metastatic cancers.

This finding lead them to examine samples of human pancreatic, lung, colon, and breast tumors. They found that in all of these cancers, S1P2 is significantly reduced. But if they restored S1P2 activity in cell lines of these cancers, the extrusion pathway was rescued and tumor size and metastases were greatly decreased!

Rosenblatt and her colleagues have shown that the importance of cell extrusion cannot be overstated. If extrusion is compromised, cells can begin to pile up and move beneath the cell layer, which can lead to invasion of the tissues beneath the epithelium and metastasis to other sites in the body.

Now that we are uncovering more of the pathways involved in tumor formation and metastasis, we can develop new drugs that may be the key to fighting these devastating diseases.

Guest Post by Amanda Cox, PhD candidate in biology

 

José Jerónimo – Innovations in Cervical Cancer Screening

José Jerónimo and his team are transforming the face of cervical cancer screening. Jerónimo is a physician and senior advisor for the women’s cancers branch of PATH, an international nonprofit organization that uses innovative technologies to improve health outcomes in developing countries. Jerónimo, who’s work at PATH has facilitated the prevention and treatment of cervical cancer for thousands in the developing world, spoke at the Duke Institute for Global Health on Dec. 2.

Cervical cancer testing has been a point of conflict in the medical community for quite some time now, for the pap smear — for many years, the only test available to detect cervical cancer — is not very sensitive to abnormal tissue. Since skepticism with the pap smear arose a few decades ago, doctors like Jerónimo have been working tirelessly to find more effective screening strategies.

José Gerónimo, Peruvian physician and public health advocate, received his specialty training in gynecologic oncology at the National Cancer Institute in Peru.

José Jerónimo, Peruvian physician and public health advocate, received his specialty training in gynecologic oncology at the National Cancer Institute in Peru.

Cervical cancer can be acquired through the presence of HPV (human papilloma virus). Chronic infections of HPV have been proven to increase the likelihood of contracting cervical cancer, so developing primary prevention initiatives to avoid developing HPV to begin with are essential to decrease the prevalence of cervical cancer. HPV testing, unlike the pap smear, can be self-collected and does not require the complex, expensive machinery that the pap smear does. Initial self-sampling studies in India, Uganda, and Nicaragua indicated a willingness by the female community to self-test, so long as sanitary and private conditions were provided.

Studies in the Jujuy province of Argentina indicated that community health workers played a key role in facilitating the self-sampling process. When the health workers differed locals to clinics or sent them to facilities for testing, only 20 percent actually went. But, when they brought the self-sampling tests to locals’ homes directly, testing was above 80 percent. The easy accessibility of self-sampling, along with encouragement by local health volunteers, clearly showed that self-sampling was much more effective.

A group of female community health workers in Lima, Peru, educating the community about HPV testing.

Jerónimo’s current work focuses on strengthening government screening systems for HPV that are already in place. By helping ministries introduce and scale up the testing, he and others at PATH hope to decrease HPV and cervical cancer rates.

But, it goes beyond testing. Jerónimo emphasizes the need for evaluation and follow-up mechanisms after testing positive. Although testing efforts have improved significantly, the treatment provided after for those who have tested positive is still lagging. Jerónimo claims that much of this is due to minimal efforts by the local governments to really follow through beyond the testing phase.

PATH is looking for innovative ways to treat HPV that are inexpensive and effective. They recently developed their own version of the thermal coagulator, a probe that treats infected tissue using heat. Their design runs on a battery, rather than needing constant electricity, and uses a progressive heating mechanism that is only activated upon touching the cervix. There is still progress to be made, in both testing and treatment of HPV and cervical cancer, but through efforts by both local and international communities, Jerónimo shows us that is possible.

lola_sanchez_carrion_100hedPost by Lola Sanchez-Carrion

Fostering a Collaborative Research Environment in Peru

We are told time and time again that Duke is a global university, one that transcends borders and takes interdisciplinary education to the next level.

On Monday, I was able to experience this international mindset firsthand at the Peru Health Symposium, a conference that celebrated a decade of culminating research efforts by Duke in Peru.

The symposium was organized by Dr. William Pan, a professor of Global Environmental Health at Duke who has worked on many research projects in Peru ranging from reproductive health to tuberculosis. In his opening remarks, Pan said the trademark interdisciplinary nature of Duke has allowed it to succeed as a research institution in Peru, along with its affiliation to pioneers in Peruvian health/environmental research, like John Terborgh.

“We are standing on the shoulders of giants,” said Pan. During the first panel, several research projects were presented.

Field Work in Peru

Helena Frischtak conducting research with Peruvian children in the field.

Helena Frischtak, a 4th year medical student at UVA and former Doris Duke Fellow spent a year studying the neurological effects of mercury exposure on children. She performed basic neurological exams, along with cognitive tests amongst 5-11 year-old children, and preliminary data suggests potential impacts of mercury exposure on cognitive development.

Marlee Krieger of the Center for Global Women’s Health Technologies presented a cervical cancer treatment that brings colposcopy into the primary care setting. When one is screened for cervical cancer, a pap smear is first conducted and if abnormalities are detected, a colposcopy is performed and tissue is biopsied from the cervix. This multiple-step process is tedious, and the number of patients that return for the colposcopy often declines. By combining the steps into one visit and performing it with a simpler and cheaper device, testing efficiency has increased.

Maria Lazo Porras of Cayetano Heredia University (Lima’s prominent medical university) presented findings on the effects of migration from rural to urban regions on chronic disease. Her findings suggest a correlation between urbanization and obesity, but provided surprising results that indicate higher rates of hypertension and diabetes in rural communities.

Peru amazon

Illegal mining scars the Amazon’s lush forests and flushes mercury runoff into streams.

Students doing research in the Amazon presented posters of their findings to faculty members of the Nicolas School and DGHI.

The main theme resonating throughout the conference was the need for collaboration not only to address public/environmental health concerns, but to organize symposiums like this one. The culmination of efforts by the Center for Latin American and Caribbean Studies (CLACS), DGHI, and the Nicholas School have fueled the Peru project’s palpable success.

Below is the link to the documentary shown at the symposium:

http://www.daughterofthelake.pe/ – “Hija de la Laguna” (Daughter of the Lake), 2015. The documentary tells the story of how a Peruvian woman used her powers to stop illegal mining from destroying the lake in her community; a lake that to her, represents her mother’s spirit.

lola_sanchez_carrion_100hedPost by Lola Sanchez-Carrion

In Sync

DiTalia2The dividing red spots in this time-lapse video belong to a busily developing fruit fly embryo. A fruit fly egg can divide into some 6,000 cells in just two hours —  faster division than cancer tumors. To watch them action, graduate student Victoria Deneke and assistant professor Stefano Di Talia tagged the nuclei with a protein that glows red. In a recent study, they show that the cells coordinate their rapid divisions via waves of protein activity that spread across the embryo. The waves help ensure that all the cells enter the next stage of development at the same time.

Duke graduate student Victoria Deneke has been awarded an international student research fellowship from the Howard Hughes Medical Institute.

Duke graduate student Victoria Deneke has been awarded an international student research fellowship from the Howard Hughes Medical Institute.

Starting September 2016, Deneke became one of 20 graduate students from 14 countries selected for an international student research fellowship from the Howard Hughes Medical Institute.

Three-year fellowship is designed to support outstanding international graduate students studying in the United States who are ineligible for fellowships or training grants through U.S. federal agencies.

Born in El Salvador, Deneke earned her undergraduate degree in chemical engineering from the University of Notre Dame before joining Stefano Di Talia’s at Duke in 2013.

Fellows must be nominated by their institution; participation is by invitation only. Deneke is only the second student at Duke to receive an HHMI International Student Research Fellowship since the program was established in 2011.

CITATION:  “Waves of Cdk1 Activity in S Phase Synchronize the Cell Cycle in Drosophila Embryos,” Victoria Deneke, Anna Melbinger, Massimo Vergassola and Stefano Di Talia. Developmental Cell, August 2016. http://dx.doi.org/10.1016/j.devcel.2016.07.023

Page 1 of 7

Powered by WordPress & Theme by Anders Norén