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UPMC First in Region to Use Next Generation Gamma Knife for Brain Tumors

UPMC is the first hospital in the region and the third institution in the United States to treat patients with the Leksell Gamma Knife Icon®. Using a stereotactic radio surgery system (SRS), a type of radiation therapy that condenses the Gamma Knife’s high-power energy on a small area, the machine enables physicians to perform non-invasive, computer-driven, bloodless brain surgery to destroy tumors and vascular malformations once considered inoperable. Despite the name, SRS does not require surgical incisions.

“UPMC’s history of innovation in radiosurgery began in 1987 when we installed North America’s first unit, which we have used to treat more than 14,000 patients,” said L. Dade Lunsford, MD, director of the Center for Image-Guided Neurosurgery. Dr. Lunsford trained in Sweden under Professor Lars Leksell, the inventor of SRS and the Gamma Knife.

“Each of the five previous generations of Gamma Knife units has improved efficiency and allows us to provide a highly effective option for the many patients who receive treatment each year at UPMC,” Dr. Lunsford said. “With the option of a frame-based or frameless approach for non-invasive cranial immobilization, Icon gives us a new way to treat a wide array of complex neurological conditions, including brain tumors, vascular disease, facial nerve pain and functional disorders.”

The Icon’s SRS uses MRI and other radiological images to identify and target precise locations within the brain to ensure dosage is appropriately distributed to the area, regardless of the position of the patient’s head. This minimizes side effects and enables treatment of larger tumors and those close to critical brain structures.

The Center for Image-Guided Neurosurgery began treating patients with the Leksell Gamma Knife Icon in May. The Center serves as an international training and outcomes analysis site, using the latest generation of radio-surgical technologies and treats more than 650 patients per year. UPMC has trained more than 2,000 surgeons, radiation oncologists, medical physicists and other health care providers in the use of brain radiosurgery during the past 20 years.

Dr. Lunsford is a consultant for and stockholder in Stockholm, Sweden-based Elekta AB, maker of the Gamma Knife Icon system.

Broccoli Sprout Extract May Protect Against Oral Cancer Recurrence

Potent doses of broccoli sprout extract activate a “detoxification” gene and may help prevent cancer recurrence in survivors of head and neck cancer, according to a trial by the University of Pittsburgh Cancer Institute, partner with UPMC CancerCenter, confirming preliminary results presented last year at the American Association for Cancer Research Annual Meeting.

It is the first study demonstrating that the extract protects against oral cancer, with the results of human, animal and laboratory tests reported today in the journal Cancer Prevention Research. This research is funded through Pitt’s Specialized Program of Research Excellence grant in head and neck cancer from the National Cancer Institute.

“With head and neck cancer, we often clear patients of cancer only to see it come back with deadly consequences a few years later,” said lead author Julie Bauman, MD, MPH, co-director of the UPMC Head and Neck Cancer Center of Excellence. “Unfortunately, previous efforts to develop a preventative drug to reduce this risk have been inefficient, intolerable in patients and expensive. That led us to ‘green chemoprevention’—the cost-effective development of treatments based upon whole plants or their extracts.”

Cruciferous vegetables, such as broccoli, cabbage and garden cress, have a high concentration of the naturally occurring molecular compound sulforaphane, which previously has been shown to protect people against environmental carcinogens.

Dr. Bauman and her colleagues treated human head and neck cancer cells in the laboratory with varying doses of sulforaphane and a control, and compared them to normal, healthy cells that line the throat and mouth. The sulforaphane induced both types of cells to increase their levels of a protein that turns on genes that promote detoxification of carcinogens, like those found in cigarettes, and protect cells from cancer.

In a small preclinical trial, 10 healthy volunteers drank or swished fruit juice mixed with broccoli sprout extract for several days. The volunteers had no significant problems tolerating the extract and the lining of their mouths showed that the same protective genetic pathway activated in the laboratory cell tests was activated in their mouths, meaning that the sulforaphane was absorbed and directed to at-risk tissue.

Dr. Bauman also collaborated with senior author Daniel E. Johnson, PhD, professor of medicine at Pitt and a senior scientist in the UPCI Head and Neck Cancer Program, to see how the extract performed in mice predisposed to head and neck cancer. The mice who received the sulforaphane developed far fewer tumors than their counterparts who did not receive the extract.

The results of the mouse, human and lab studies have been so successful that Dr. Bauman has started a larger clinical trial in volunteers previously cured of head and neck cancer. These participants are taking capsules containing broccoli seed powder, which is more convenient to take regularly than the extract mixed with juice.

“Head and neck cancers account for approximately 3 percent of all cancers in the US, but that burden is far greater in many developing countries,” said Dr. Bauman. “A preventative drug created from whole plants or their extracts may ease the costs of production and distribution, and ultimately have a huge positive impact on mortality and quality of life in people around the world.”

Additional authors on this research are Yan Zang, PhD, Malabika Sen, PhD, Changyou Li, PhD, Lin Wang, MD, Daniel P. Normolle, PhD, and Thomas W. Kensler, PhD, all of Pitt; Patricia A. Egner, MS, and Jed W. Fahey, ScD, both of Johns Hopkins University; and Jennifer R. Grandis, MD, FACS, of the University of California at San Francisco.

This work was supported by National Institutes of Health grants P50CA097, R01CA190610, and P30 CA4747904; and by the Lewis B. and Dorothy Cullman Foundation.

Early Detection, Smaller Cancer Among Benefits of Skin Cancer Screening at Primary Care Visits

Skin cancer screenings performed by primary care physicians (PCPs) during routine office visits improve the detection of potentially deadly melanomas and find them in earlier stages, according to new research from the University of Pittsburgh School of Medicine.

The results will be presented today at the 52nd annual American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

“Our findings suggest that PCP screening is an effective way to improve early detection of melanoma, which could potentially save lives,” said lead author Laura Ferris, MD, PhD, associate professor, Department of Dermatology, Pitt School of Medicine and member of the Melanoma Program, University of Pittsburgh Cancer Institute.

Rates of melanoma, the most dangerous form of skin cancer, are on the rise, and skin cancer screenings are one of the most important steps for early detection and treatment, said Dr. Ferris. Typically, patients receive skin checks by setting up an appointment with a dermatologist.

The goal of the new UPMC screening initiative, which was modeled after a promising German program, was to improve the detection of melanomas by making it easier for patients to get screened during routine office visits with their PCPs, explained Dr. Ferris.

PCPs completed training on how to recognize melanomas and were asked to offer annual screening during office visits to all patients aged 35 and older. In 2014, during the first year of the program, 15 percent of the 333,788 eligible UPMC patients were screened in this fashion.

On average, the melanomas detected in the group who received a screening at a primary care visit were nearly twice as thin as those detected in the group that was not screened by a PCP. Thinner melanomas have a better prognosis than thicker ones that are more advanced, so the new findings suggest PCP screening is able to find melanomas at an earlier, more treatable stage, said Dr. Ferris.

In addition, only 5 percent of people in the screening group had especially worrisome melanomas that were thicker than 1 millimeter—which are more likely to metastasize and require a biopsy of a nearby lymph node—while 20 percent of the unscreened group did.

“The PCP screenings prevented a lot of people from needing more aggressive therapy. Additionally, we did not see a high rate of false positive biopsies, in which no skin cancer was present, nor did we see a high rate of unnecessary dermatology referrals or skin surgeries, all of which suggest that the program did not simply drive up health care costs needlessly,” Dr. Ferris said.

Another important finding was that nearly half of the screened patients were men, who are more likely to get and die from melanoma than women but have been underrepresented in other skin cancer screenings published to date. “It’s exciting that our approach improves detection in this especially vulnerable population,” said Dr. Ferris.

Funding for this study was provided by a National Cancer Institute Specialized Program of Research Excellence (SPORE) grant in skin cancer (5P50CA121973-08).

Additional members of the research team included Melissa Saul, MS, Francis Solano, MD, Erica Neuren, BA, Jian-Min Yuan, MD, PhD, and John Kirkwood, MD, all of UPMC; Martin Weinstock, MD, PhD, of Brown University; and Allan Geller, MPH, RN, of Harvard University.

Immunotherapy Improves Survival, Quality of Life in Rapidly Progressing Head and Neck Cancer

Immunotherapy doubles overall survival and improves quality of life, with fewer side effects, in a treatment-resistant and rapidly progressing form of head and neck carcinoma, reports a large, randomized international trial co-led by investigators at the University of Pittsburgh Cancer Institute (UPCI). The new trial was considered so successful that it was stopped early to allow patients in the comparison group to receive the new drug.

Findings from the international CheckMate-141 phase III clinical trial were presented today at the 52nd annual American Society of Clinical Oncology (ASCO) meeting in Chicago. A subset of the results were previously presented at the American Association for Cancer Research meeting in April of this year.

“These exciting results indicate that there is a new standard of care option for a population of head and neck cancer patients with no other treatment options,” said the trial’s international co-chair Robert Ferris, MD, PhD, UPMC Endowed Professor, and chief of the Division of Head and Neck Surgery and co-leader of the Cancer Immunology Program at UPCI.

The new drug, nivolumab, which belongs to a class of drugs known as immunotherapeutics, enables the body’s immune system to destroy cancer cells. It currently is approved to treat certain types of cancers, including melanoma and lung cancer.

The trial enrolled 361 patients with recurrent or metastatic head and neck squamous cell carcinoma who had not responded to platinum-based chemotherapy, a rapidly progressing form of the disease with an especially poor prognosis, said Dr. Ferris. Patients were randomized to receive either nivolumab or a single type of standard chemotherapy until tumor progression was observed.

The nivolumab group achieved better outcomes than the standard chemotherapy group by all accounts. After 12 months, 36 percent of the nivolumab group was alive, compared to just 17 percent of the standard chemotherapy group.

Nivolumab treatment also doubled the number of patients whose tumors shrunk, and the number whose disease had not progressed after six months of treatment. Importantly, these benefits were achieved with just one-third the rate of serious adverse events reported in the standard chemotherapy group.

In addition, on average, patients receiving nivolumab reported that their quality of life remained stable or improved throughout the study, while those in the chemotherapy group reported a decline.

While nivolumab improved survival rates in the overall study population, it appeared to be most successful in patients whose tumors were positive for the human papillomavirus (HPV). This is important because the fraction of head and neck cancers attributable to HPV infection has increased by 250 percent over the past several decades, Dr. Ferris explained.

“Unfortunately, most patients in this trial still experienced a progression of their cancer, demonstrating that we still have a lot of work to do. But, the future appears brighter than ever before because there is a new class of agents, immunotherapies, which we now know can prolong survival and improve quality of life, with few side effects, in head and neck cancer,” said Dr. Ferris.

The research team currently is working to identify new biomarkers that will allow them to develop a better understanding of how drug resistance develops, and how to best design effective combinations of medications that may improve patient responses.

The trial’s other co-chair is Maura Gillison, MD, PhD, from Ohio State University. Additional U.S. institutions that participated in the trial include University of Texas MD Anderson Cancer Center, Stanford Cancer Institute, University of Chicago, University of Michigan, and Dana-Farber Cancer Institute. International collaborators are located at Centre Leon Berard, Centre Antoine Lacassagne, and Institut Gustave Roussy, all in France; Fondazione IRCCS Istituto Nazionale Tumori, in Italy; The Institute of Cancer Research, in the United Kingdom; University Hospital Essen, in Germany; and National Cancer Center Hospital East and Kobe University Hospital, both in Japan.

The trial was funded by the drug manufacturer, Bristol-Myers Squibb, who is now seeking FDA approval for the use of nivolumab in head and neck carcinoma.

Immunotherapy Effective Against Some Types of Sarcoma

An existing cancer immunotherapy drug reduces tumor size in some types of rare connective tissue cancers, called sarcomas, report researchers at the University of Pittsburgh Cancer Institute (UPCI). Additional analyses of tumor biopsies and blood samples, which will help the researchers better understand which sarcoma subtypes will benefit most from the new treatment, are underway.

Interim results from the phase II clinical trial were presented today at the 52nd annual American Society of Clinical Oncology (ASCO) annual meeting in Chicago by principal investigator Hussein Abdul-Hassan Tawbi, MD, PhD, formerly of UPCI and current associate professor, University of Texas MD Anderson Cancer Center.

Sarcoma is a rare disease, encompassing less than 1 percent of adult cancers, and the available treatments are limited, so the need for new therapies is high, explained the current lead investigator for the Pittsburgh site, Melissa Burgess, MD, assistant professor of medicine at UPCI.

“This is a pivotal trial for sarcoma, the first and largest trial to be conducted using this specific immunotherapeutic approach. What makes this trial special is that we collected biopsies and blood samples to really study how the treatment is working or not working in these patients. These immune monitoring studies will offer unique insights into the biology of immunotherapy in sarcoma,” Dr. Burgess said.

Immunotherapies work by using a patient’s own immune cells to target cancer cells. The new trial examined the safety and effect of pembrolizumab, which currently is approved for use in advanced melanoma and certain types of advanced lung cancer, on tumor size in four types of soft tissue sarcomas and three types of bone sarcomas.

UPCI, the first of 12 sites to enroll subjects, contributed approximately one quarter of the 80 total patients. Patients received the drug every three weeks. Tumor assessments began at eight weeks and were conducted every 12 weeks thereafter. The trial enrolled on a rolling basis, and is still in progress, so in these results, not all patients have received the drug for the same amount of time.

About 20 percent of patients in the combined soft tissue sarcoma group showed a reduction in tumor size during at least one time point. However, when the researchers looked at the sarcoma subtypes individually, they found one with especially promising results: 44 percent of patients with undifferentiated pleomorphic sarcoma experienced a reduction in tumor size. Encouraging improvements in tumor size also were found in two subtypes of bone sarcomas, osteosarcoma and chondrosarcoma, Dr. Burgess noted.

“Unfortunately, these early results suggest that there is limited efficacy of pembrolizumab in the patient population as a whole. However, it’s promising that the drug seems to be beneficial in specific sarcoma subtypes. Our ongoing immune monitoring studies will allow us to better characterize the patients who will most benefit from this therapy for future clinical trials,” said Dr. Burgess.

Additional co-authors of the trial trial include Denise K. Reinke, MS, NP, MBA, of SARC, which coordinated the trial; John Crowley, PhD, of Cancer Research and Biostatistics; Brian Van Tine, MD, PhD, of Washington University in St. Louis; James Hu, MD, of University of Southern California Norris Comprehensive Cancer Center; Scott Schuetze, MD, and Laurence Baker, DO, of University of Michigan; Sandra D’Angelo, MD, of Memorial Sloan Kettering Cancer Center; Steven Attia, DO, of Mayo Clinic Jacksonville, Dennis Priebat, MD, of MedStar Washington Hospital Center; Scott Okuno, MD, of Mayo Clinic, Rochester; Richard Riedel, MD, of Duke University Medical Center, Lara Davis, MD, of Oregon Health and Sciences University; Sujana Movva, MD, of Fox Chase Cancer Center; Damon Reed, MD, of Moffitt Cancer Center; Robert Maki, MD, PhD, of Tisch Cancer Institute; and Shreyaskumar Patel, MD, of University of Texas MD Anderson Cancer Center.

Funding for the trial was provided by Merck & Co., the maker of pembrolizumab, Sarcoma Alliance for Research Through Collaboration, Sarcoma Foundation of America and QuadW Foundation. Funding for the ongoing studies was partially provided by local philanthropic support group Pittsburgh Cure Sarcoma.

UPCI-Led International Trial Changing Standard of Care for Advanced Breast Cancer

Surgery to remove the primary tumor in women diagnosed with stage IV breast cancer, followed by the standard combination of therapies, adds months to the patients’ lives, compared with standard therapy alone, an international clinical trial led by a University of Pittsburgh Cancer Institute (UPCI) professor revealed.

The results of the phase III randomized, controlled trial will be presented Saturday at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. The study was selected for the society’s “Best of ASCO,” an effort to condense the research “most relevant and significant to oncology” into a two-day program to increase global access to cutting-edge science.

“Our findings will change the standard of care for women newly diagnosed with stage IV breast cancer,” said principal investigator Atilla Soran, MD, MPH, clinical professor of surgery, University of Pittsburgh School of Medicine, and breast surgical oncologist with UPMC CancerCenter. “We’ve shown that surgery to remove the primary tumor—either through lumpectomy or mastectomy—followed by standard therapy, is beneficial over no surgery.”

Dr. Soran began the trial in 2007, ultimately recruiting a total of 274 women newly diagnosed with stage IV breast cancer from 25 institutions. Half the women received standard therapy, which avoids surgery and consists of a combination of chemotherapy, hormonal therapy and targeted therapy, while the other half first had surgery to remove their primary breast tumor, followed by the standard therapy.

At about 40 months after diagnosis, the women who received the surgery plus standard therapy lived an average of nine months longer than their counterparts who received standard therapy alone. Nearly 42 percent of the women who received surgery lived to five years after diagnosis, compared with less than 25 percent of the women who did not receive surgery.

The trial also showed that surgery in younger women with less aggressive cancers resulted in longer average survival than in women with more aggressive cancers that had spread to the liver or lungs.

“Our thinking is similar to how you might approach a battle against two enemies,” said Dr. Soran. “First you quickly dispatch one army—the primary tumor—leaving you to concentrate all your efforts on battling the second army—any remaining cancer.”

This research was primarily funded by the Turkish Federation of Societies for Breast Diseases. The study received scientific advisement from UPMC and assistance with statistical analysis from epidemiologists at the University of Pittsburgh Graduate School of Public Health.

3D Bioprinted Model for the Study of Precancerous Breast Disease Aims to Reduce Unnecessary Treatment

Researchers at the University of Pittsburgh Cancer Institute (UPCI) and materials and biomedical engineers at Carnegie Mellon University (CMU) will address the overdiagnosis and overtreatment of a non-invasive precancerous breast tumor by creating the first-ever 3D bioprinted breast ductal structure to identify markers for low-risk premalignant disease.

The scientists were awarded nearly $800,000 in a two-year grant from the U.S. Congressionally Directed Medical Research Program of the Department of Defense.

Improvements in mammography screening have resulted in earlier detection of invasive breast cancer, and this is also associated with an increase in the detection of non-invasive breast cancer, such as ductal carcinoma in situ (DCIS) – the earliest form of breast cancer where the disease has not spread out of the milk duct.  Over 60,000 women are diagnosed with DCIS each year, and the majority of non-invasive lesions will not progress to invasive diseases if left untreated. However, the majority of these women undergo unnecessary surgeries, treatments and therapy.

“More research is required to identify the minority of DCIS lesions that will progress to invasive disease and thus require treatment,” explained Adrian Lee, PhD, professor of pharmacology and chemical biology at UPCI. “Our hope is that our research will reveal novel biomarkers that will be useful for predicting which DCIS are likely to progress. We can then offer personalized therapy to those who require intervention, while reducing the overtreatment of DCIS in those who don’t. This could have a major impact upon thousands of women each year.”

UPCI researchers will collaborate with materials and biomedical engineers at CMU and use 3D bioprinting to print a breast ductal system in the laboratory. They will then grow DCIS cells in the printed duct. By printing a replica of a mouse ductal system, experts will be able to create a unique model to study why some DCIS progress to invasion while others remain indolent. Genes involved in progression may serve as biomarkers indicating the need to treat DCIS.

“3D bioprinting is transforming how we can build tissues. By allowing us to use medical imaging data to accurately recreate complex biology, this has the potential to revolutionize bioengineering and tissue regeneration,” said Adam Feinberg, PhD, associate professor in CMU’s departments of Materials Science and Engineering and Biomedical Engineering. “Printing of cells and organs has been challenging because these are soft materials. Our novel technology solves this, and we are excited by the opportunity to collaborate with our colleagues at UPCI to advance our understanding of DCIS and invasion.”

The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program, under Award No. W81XWH-16-1-0017 & W81XWH-16-1-0018.

Easy Ways to Improve Patient Comfort During Skin Cancer Screenings

New research from the University of Pittsburgh School of Medicine suggests two simple ways dermatologists can make patients more comfortable during full-body skin cancer checks: respect patient preferences for the physician’s gender as well as whether, and how, they prefer to have their genitals examined. The findings are published online today in JAMA Dermatology.

“This study identifies barriers to getting skin checks. Giving patients choices that reduce embarrassment during an exam may make a person more likely to get regular skin checks, leading to higher rates of skin cancer detection,” said lead author Laura Ferris, MD, PhD, associate professor, Department of Dermatology, Pitt School of Medicine and member of the Melanoma Program, University of Pittsburgh Cancer Institute.

Estimates suggest that one in five people will develop skin cancer over the course of a lifetime. Rates of melanoma, which account for less than one percent of skin cancer cases but the vast majority of skin cancer deaths, have tripled over the last 40 years.

The best way to prevent skin cancer is to use adequate protective measures during sun exposure, perform regular self-examinations, and, for those patients at increased risk of developing skin cancer, obtain annual full-body screenings from a dermatologist, said Ferris.

The current study was born out of an observation from Ferris’ own dermatology practice: many women wanted female physicians and were uncomfortable having male students in the room during their exams. While a strong preference for a same gender physician has been documented among patients undergoing colonoscopies, there wasn’t much data available about dermatology, Ferris explained.

In the new study, the researchers at three institutions, including UPMC, administered an anonymous survey to 443 adults undergoing a full-body screening for skin cancer.

Overall, people generally preferred a physician who shared their gender. Breaking the data down by gender, one third of women and nearly one fifth of men expressed a gender preference. Among this group, nearly all (99 percent) of the women preferred a female physician, and almost two thirds of the men preferred a male physician.

The biggest predictor of preferring a female physician among women was being under age 30. Young women have one of the fastest growing rates of melanoma, so taking physician gender preference into account in this group may have an especially large impact, Ferris noted.

Typically, patients are asked to completely disrobe for a skin cancer screening. When asked about clothing preferences, nearly half of women and 40 percent of men preferred to leave their undergarments in place during the exam.

“What we learned is that a substantial number of people preferred to leave their undergarments on and have us work around them,” said Ferris.

Less than 1 percent of melanomas are found in the genital region, so with 31 percent of women and 13 percent of men preferring not to have their genitals examined at all, another important message from the study is that physicians need to balance the benefit of occasionally finding a genital melanoma with causing a lot of people discomfort or anxiety, she added.

The researchers are now focused on putting their findings into practice. “When we think about the relative risks and benefits of cancer screening, if we’re causing people discomfort, then we need to think of that as doing harm. Our study provides some easy ways to reduce that harm,” Ferris said. “In the age of personalized medicine, taking simple steps, such as offering a choice of physician gender and degree of disrobement during an examination, can allow us to personalize the skin cancer screening examination to minimize discomfort.”

Co-authors of the study include Neil Houston, BA, and Westley Mori, BA, both of Pitt School of Medicine; Aaron Secrest, MD, PhD, and Mark Eliason, MD, both of University of Utah; and Ryan Harris, MD, and Charles Phillips, MD, both of East Carolina University.

The study was funded by National Institutes of Health grants UL1-TR-000005 and P50CA121973.

Watercress Extract Detoxifies Carcinogens in Smokers, Clinical Trial Demonstrates

Watercress extract taken multiple times a day significantly inhibits the activation of a tobacco-derived carcinogen in cigarette smokers, researchers at the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter, demonstrated in a phase II clinical trial presented today at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans.

The trial also showed that the extract detoxifies environmental carcinogens and toxicants found in cigarette smoke, and that the effect is stronger in people who lack certain genes involved in processing carcinogens. This trial was supported by a grant from the National Cancer Institute (NCI).

“Cigarette smokers are at far greater risk than the general public for developing lung cancer, and helping smokers quit should be our top cancer prevention priority in these people,” said Jian-Min Yuan, MD, PhD, associate director of the UPCI’s Division of Cancer Control and Population Science and an epidemiologist with Pitt’s Graduate School of Public Health. “But nicotine is very addictive, and quitting can take time and multiple relapses. Having a tolerable, nontoxic treatment, like watercress extract, that can protect smokers against cancer would be an incredibly valuable tool in our cancer-fighting arsenal.”

Dr. Yuan, who also is Pitt’s Arnold Palmer Endowed Chair in Cancer Prevention, and his colleagues enrolled 82 cigarette smokers in the randomized clinical trial. The participants either took 10 milligrams of watercress extract mixed in 1 milliliter of olive oil four times a day for a week or they took a placebo. Each group of participants then had a one week “wash-out” period where they didn’t take anything and then switched so that those getting the placebo now received the extract. They all continued their regular smoking habits throughout the trial.

In one week, the watercress extract reduced activation of the carcinogen known as nicotine-derived nitrosamine ketone in the smokers by an average of 7.7 percent. It increased detoxification of benzene by 24.6 percent and acrolein by 15.1 percent, but had no effect on crotonaldehyde. All the substances are found in cigarette smoke.

Participants who lacked two genes involved in a genetic pathway that helps the antioxidant glutathione remove carcinogens and toxicants from the body saw an even bigger benefit to taking the watercress extract, which increased their detoxification of benzene by 95.4 percent, acrolein by 32.7 percent and crotonaldehyde by 29.8 percent.

A phase III clinical trial in hundreds of people must be performed before the treatment could be recommended for smokers, and Dr. Yuan warned that while eating cruciferous vegetables, such as watercress and broccoli, is good for people, they are unlikely to have the same pronounced effect as the extract.

Additional researchers on this project are Irina Stepanov, PhD, Sharon E. Murphy, PhD, Steven G. Carmella, BA, Heather H. Nelson, PhD, Dorothy Hatsukami, PhD, and Stephen S. Hecht, PhD, all of the University of Minnesota.

This research was funded by NCI grant R01CA122244.

Four Young Researchers from the Same UPCI Lab Receive AACR Scholar-in-Training Awards

Four young investigators from the same laboratory at the University of Pittsburgh Cancer Institute, partner with UPMC CancerCenter,  have been recognized with American Association for Cancer Research (AACR) scholar-in-training awards for AACR’s annual meeting in New Orleans, April 16 to 20.

“I am delighted the efforts of my students have been so successful and look forward to the next steps they take in their promising research careers,” said lab leader Shivendra Singh, PhD, professor of pharmacology and chemical biology, and UPMC Chair in Cancer Prevention Research, Pitt School of Medicine. His lab focuses on examining enzymes that play a role in drug metabolism and cellular defenses against environmental toxins, as well as exploring the anti-carcinogenic effects of certain natural agents found in edible plants.

Three researchers received scholar-in training awards in memory of Dr. Lee W. Wattenberg, a pioneer in cancer prevention research, who served as AACR president in 1992. According to AACR, these awards are presented to young investigators presenting high-quality papers relating to cancer prevention research.

Those awardees are:

Su Hyeong Kim, PhD: “Role of c-Myc in prostate cancer stem-like cell inhibition by sulforaphane” (Abstract 822).

In this project, Dr. Kim showed that sulforaphane, which naturally occurs in broccoli and other cruciferous vegetables, can inhibit prostate cancer in lab tests because it blocks the effects of c-Myc, a gene that regulates cancer growth. This investigation was supported by grant CA115498 of the National Cancer Institute (NCI), part of the National Institutes of Health.

Subrata K. Pore, PhD: “Benzyl isothiocyanate inhibits breast cancer-induced osteoclastogenesis” (Abstract 826).

Dr. Pore and colleagues built on previous work showing that benzyl isothiocyanate (BITC), found in edible cruciferous vegetables such as garden cress, inhibits breast cancer in a mouse model of the disease. In advanced breast cancer, bone loss can occur, which can be deadly with spreading disease. In this project, the team showed that BITC can limit bone breakdown by reducing the production of bone-resorbing cells called osteoclasts. This study was supported by NCI grant CA129347.

Krishna Beer Singh, PhD: “c-Myc is a novel target of prostate cancer cell growth inhibition by honokiol” (Abstract 831).

Dr. Singh led a project that showed honokiol, a naturally occurring agent derived from magnolia trees, suppressed activity of c-Myc and other genes that play key roles in prostate cancer growth. This study was supported by NCI grants CA101753 and CA115498.

In addition, a fourth researcher from the Singh Lab received a $1,500 AACR-Triple Negative Breast Cancer Foundation scholar-in-training award.

Ruchi Roy, PhD: “Benzyl isothiocyanate mediates glucose uptake through AKT activation in breast cancer cells” (Abstract 833).

Dr. Roy showed in animal models that BITC’s effects in suppressing Her-2-driven breast tumors could be enhanced with the addition of an agent that inhibits the protein AKT. This study was supported by NCI grant CA129347.

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