The Wayne State University School of Medicine has secured a unique grant from the W.K. Kellogg Foundation that will expand research into maternal-fetal medicine with a focus on reducing high-risk pregnancies.

The grant, said Dr. Robert Sokol, M.D., the John M. Malone Jr., M.D., Endowed Chair and director of the C.S. Mott Center for Human Growth & Development at the School of Medicine, will complement research being conducted at the National Institutes of Health’s Perinatology Research Branch located at the Wayne State University School of Medicine and the Detroit Medical Center. Dr. Sokol serves as coordinator of the Kellogg grant.

The $750,000 grant will support research that WSU investigators will have to submit for consideration. A committee consisting of Dr. Sokol, Dean Valerie M. Parisi, M.D., M.P.H., M.B.A.; Bonita Stanton, M.D., vice dean of Research; Sonia Hassan, M.D., dean for Maternal, Perinatal and Child Health; and Hillary Ratner, WSU vice president of Research; and Gloria Heppner, WSU associate vice president of Research, will review applications for research projects under the grant. The group anticipates awarding three individual grants ranging from $90,000 to $125,000, followed by another round of like amounts during a 36-month period.

The Perinatal Virtual Discovery Grant is intended to encourage innovative, exploratory and evolving research projects, with the goal of attracting highly competent basic science and clinical researchers to apply their expertise to problems associated with high-risk pregnancy, perinatal research and other scientific endeavors related to improving pregnancy outcomes.

Dr. Sokol noted that another strategy behind the program is to provide funding for projects that could in turn attract additional research grants from other external agencies. Projects selected for funding will complement current research of the PRB and be best-positioned for external funding, with an eye toward exponential return on investment as success of the projects lead to greater external funding.

The Kellogg Foundation, Dr. Sokol said, rarely allows a grantee the leeway to determine how foundation funding will be further divided. “This is an indication of the great confidence they have in the research being conducted here,” he said.

Dr. Sokol said administrators of the grant hope to attract WSU researchers who might not normally believe their work relates to perinatal and maternal-fetal medicine, as well as faculty members already working in these areas. The grants, he said, should attract cross-disciplinary researchers.

“Wayne State University has been an international leader in this type of medicine and research since the 1960s,” Dr. Sokol said. “If you wanted to study in this area, you came here. This grant will expand research efforts that have a definitive impact on the area of maternal-fetal medicine and obstetrics and gynecology that will benefit our region and state, and will spread to the world.”

Premature birth is the leading cause of infant mortality in Michigan. The state’s rate of premature birth increased more than 10 percent between 1998 and 2008. One of every eight babies born in Michigan – 295 in an average week – is born prematurely. And Michigan’s rate of preterm birth (12.7 percent) exceeds the national average of 12.3 percent.

The Michigan Department of Community Health reports that for every 1,000 live births in the state, approximately eight infants die before their first birthday. Data compiled in 2009 by the Centers for Disease Control and Prevention and the MDCH indicate Michigan’s infant mortality rate consistently exceeds the national average. In addition, there is an alarming disparity in the access to care, quality of care and pregnancy outcome among ethnic groups in Michigan.

African-American mothers experience more birth complications, including more premature births, preeclampsia – a sudden and dangerous increase in blood pressure – and babies with low birth weight. Infants born to black mothers in Michigan are 70 percent more likely to be born prematurely than infants of other races, according to a 2010 report released by the Center for Healthcare Research & Transformation, a public policy and research organization based in Ann Arbor. Nineteen percent of babies born to black mothers in the state were born before 34 weeks of gestation, said the report, compared to 11 percent of white and Hispanic newborns. While the state’s rate of premature births held stable for births less than 34 weeks of gestation, the rate increased 20 percent among births between 24 to 27 weeks. In 2008, the city of Detroit alone experienced a premature birth rate of 17 percent.

Nationally, preterm birth is a $26 billion annual problem. The CDC reports that preterm births topped the list of the most expensive hospitalizations in Michigan in 2007. Each premature birth in the state costs an average of $102,103 at the time of discharge from the hospital, 14 times the cost of a normal birth.

It is problems such as these, Dr. Sokol said, that warrant this innovative pilot program.

Drug delivery directly into muscle using an autoinjector is faster and may be more effective in stopping prolonged seizures, according to a study sponsored by the National Institutes of Health and conducted by a Wayne State University School of Medicine researcher.

The Department of Emergency Medicine at Wayne State University School of Medicine was one of a number of sites that conducted a trial comparing the effectiveness of two Federal Drug Administration-approved anti-seizure medications and how they are administered to patients suffering prolonged seizures before they arrive at hospitals.

The Rapid Anticonvulsant Medication Prior to Arrival Trial, or RAMPART, was designed to determine whether midazolam or lorazepam are safer and more effective when paramedics are called to treat patients whose seizures aren’t stopping. The study was funded by the National Institute of Neurological Disorders and Stroke, part of the NIH.

The prolonged seizures, called status epilepticus, create an emergency situation, said Robert Welch, M.D., associate professor of the WSU Department of Emergency Medicine, who oversaw the Detroit portion of the study. Estimates indicate that between 120,000 and 200,000 such cases take place each year in the United States. As many as 55,000 people die from the seizures.

Complications of prolonged seizures, Dr. Welch explained, include impaired ventilation and aspiration into the lungs, which can result in pneumonia. Other issues include heart rhythm problems and direct injury to the nervous system. “Optimal outcomes in patients therefore depend on treatments that lead to rapid cessation of seizure,” Dr. Welch said. “In the pre-hospital setting, it can be difficult to treat this group of patients, particularly since starting an IV to administer medications can be very difficult.”

Emergency Medical Services crews generally administer anticonvulsant drugs at the scene intravenously as a first-line treatment for seizures. However, starting an IV in a patient experiencing seizures can pose a challenge for paramedics and waste precious time. Applying an intramuscular injection using a device similar to the EpiPen used to treat severe allergic reactions is easier, faster and more reliable, especially in patients having convulsions. The researchers sought to determine whether an intramuscular injection, which quickly delivers anticonvulsant medicine into a patient’s thigh muscle, is as safe and effective as giving medicine directly into a vein. The study, which was carried out by paramedics, compared how well delivery by each method stopped patients’ seizures by the time the ambulance arrived at the emergency department.
Midazolam and lorazepam are benzodiazepines, a class of sedating anticonvulsant drugs. Midazolam was a candidate for injection because it is rapidly absorbed from muscle. Lorazepam must be given by IV.

The study, published in the Feb. 16 issue of The New England Journal of Medicine, found that 73 percent of patients in the group receiving midazolam via direct injection into the thigh muscle were seizure-free upon arrival at the hospital, compared to 63 percent of patients who received IV treatment with lorazepam. Patients treated with midazolam also were less likely to require hospitalization than those receiving IV lorazepam. Among those admitted, both groups had similarly low rates of recurrent seizures.

“This study demonstrated that giving an intramuscular dose of medication is just as effective in stopping the prolonged seizure as is giving an intravenous medication,” said Dr. Welch, who also serves as Director of Clinical Research for the department, as well as principal investigator of the Wayne State University hub of the Neurological Emergencies Treatment Trials Network. “Since it can be very difficult to establish an IV in a patient who is seizing, giving a medication intramuscularly is easier, and may lead to better outcomes. In order to reduce the potential for brain damage, stopping the seizure as soon as possible is the goal of treating status epilepticus. This method is as good, and maybe better, than trying to start an IV and administer medication.”

The study involved 1,024 patients nationwide. The WSU portion of the study consisted of 178 enrolled patients, the largest group of patients in the study. Paramedics treated patients in the study who were transported to Detroit Receiving Hospital, Sinai Grace Hospital and St. John Hospital.

Paramedics involved in RAMPART used study boxes with a time-stamped voice recorder. This tool allowed them to make quick decisions, indicate the time treatment began and the time the convulsions stopped, all without having to interrupt patient care to record data. The goal of the study was to control seizures within 10 minutes without having to deliver a second dose of medicine.

Since the study involved patients who were severely affected and could not make decisions for themselves, the research was given exception from informed consent parameters. If patients were unconscious after they were transported to the hospital and the seizure had subsided, a member of the study team attempted to contact a family member. If patients later determined that they no longer wished to continue participating in the study after initial treatment, they could opt out. Community consultation was held in advance of the study to raise awareness, ensure transparency and gain input from residents.

Dr. Welch said that when the autoinjectors are available they should become standard equipment in EMS units and ambulances. Until that time, he recommended that paramedics administer midazolam intramuscularly in the thigh using a traditional syringe.

RAMPART investigators said that while autoinjectors might someday be available for use by epilepsy patients and their family members, more research is required. Because of the strong sedative effect of midazolam, on-site medical supervision is now required for patient safety.

The Neurological Emergencies Treatment Trials Network, funded by the NIH, includes more than 100 emergency departments and EMS agencies in 17 major metropolitan areas. The organization was formed to conduct large trials to reduce the burden of injuries and illnesses affecting the brain, spinal cord and peripheral nervous system. The network, Dr. Welch said, explores the narrow window of opportunity that seems to exist in treating neurologic damage from a variety of conditions, ranging from stroke and traumatic brain injury to seizures and meningitis. The study of rapid interventions by NETT requires the assistance of paramedics treating patients in the field.

A Wayne State University School of Medicine post-doctoral researcher has secured a significant grant to study the signaling process that triggers a type of breast cancer to transform into an invasive state.

Kingsley Osuala, Ph.D., a post-doctoral trainee in the Department of Pharmacology, has secured a three-year, $450,000 grant from the Department of Defense Breast Cancer Research Program for his study, “Paracrine Cytokine/Chemokine Pathways in Progression of Ductal Carcinoma in Situ to Invasive Ductal Carcinoma."

“This is especially exciting as only 22 grants nationally were issued in this category for this fiscal year,” said Osuala, who received his doctorate degree in Biomedical Science from the University of Central Florida. “This is a major milestone for me since it will be the first grant that I am listed as principal investigator.”

Dr. Osuala is investigating the process by which breast cancer moves from a pre-invasive state to an invasive state. Ductal carcinoma in situ, a pre-invasive breast cancer, was the fourth-leading cause of cancer diagnosed in women worldwide in 2010. Communication between the DCIS cells and other surrounding cells is known to accelerate movement to an invasive cancer, but the molecules responsible for the process have not been identified, he said.

The objective of the study, Dr. Osuala said, is to evaluate the potential roles of two small proteins that communicate between cells -- the chemokine CCL20 and the cytokine IL-6 -- in the progression of ductal carcinoma in situ to an invasive state. Recent data has uncovered a previously unknown mechanism by which cancer cells increase expression of CCL20 and IL-6 to manipulate their environment, rendering them invasive. Thus, CCL20 and IL-6 may be potential targets for new drugs as well as markers that might allow us to accurately predict which patients with DCIS are likely to have their DCIS progress to invasive tumors, he said.

“By identifying chemokine/cytokine signaling pathways that are critical to breast cancer progression, we should be able to slow or even halt the invasion of breast cancers,” he said. “Such an advantage would give clinicians more time to treat and remove breast cancer before it can travel to various other organs. This study is unique in that we are evaluating the tumor and other cells in the tumor’s microenvironment rather than just the tumor cells alone. This novel approach will provide answers about the way tumors interact with their neighboring cells.”

The study, Dr. Osuala said, will provide technical insight for future studies in the discovery of biomarkers for early-stage breast cancers and in breast cancer in general.

“Defining new drug targets should give clinicians a new tool for the treatment of breast cancer, potentially increasing the post-diagnosis life expectancy of patients,” he said. “Additional benefits of this study include decreased reliance on toxic therapies such as radiotherapy and conventional chemotherapy, and reductions in overtreatment.”

Dr. Osuala said he owes thanks to his mentor, Bonnie Sloane, Ph.D., Chair of Pharmacology, and Ambika Mathur, Ph.D., professor of Pediatrics, associate dean of the Wayne State University Graduate School and director of the School of Medicine’s M.D./Ph.D. program, for encouraging him to apply for the grant.

Zhuo-Hua Pan, Ph.D., professor of Anatomy/Cell Biology for the Wayne State University School of Medicine, was appointed scientific director of the Ligon Research Center of Vision at the Kresge Eye Institute and named the Edward T. and Ellen K. Dryer Endowed Professor in Vision and Blindness Research for the WSU Department of Ophthalmology and Kresge Eye Institute.

“Dr. Pan will bring novel gene-therapy approaches for treating blindness to the institute,” said Mark Juzych, M.D., M.H.S.A., director of the Kresge Eye Institute and professor and Chair of the School of Medicine’s Department of Ophthalmology. “Dr. Pan’s technology is a perfect example of the type of translational research that we are interested in developing, going from the lab bench to new therapies for patients.”

Dr. Pan now holds a joint appointment with the departments of Ophthalmology and Anatomy/Cell Biology for the WSU School of Medicine.

“I am very excited about the new appointment,” said Dr. Pan, who introduced the concept of inserting a light-sensitive protein into the retina to restore vision in patients. “This is a great honor for me and also a unique opportunity to partner with the Department of Ophthalmology and the Department of Anatomy and Cell Biology to advance the research aimed at restoring vision in the blind.”

The Dryer Endowed Professorship was established in 2010 through a $1 million gift from the Edward T. and Ellen K. Dryer Foundation to the Ligon Research Center of Vision at the Kresge Eye Institute. The professorship is awarded to a researcher making significant contributions to artificial vision and the restoration of vision to the blind. The endowment allows for the expansion of current research and the exploration of new research that shows the potential to fight eye diseases and potentially cure blindness.

An executive in the banking industry, Edward Dryer and his wife, Ellen, were lifelong residents of Detroit. While traveling on business in New York, Mr. Dryer suddenly lost his sight and as a result, his job. He continued to follow the market by having his wife read to him daily from The Wall Street Journal and other financial publications. Mr. Dryer began investing in the stock market, and through a combination of savvy investment strategies and a modest lifestyle, his investments grew.
Twelve years ago, the Dryers died within four months of each other. The Dryer Charitable Foundation was established in their name through their estate plan, with a mission to aid people who have limited sight and to aid research for the prevention of blindness.

“We have been searching for a nationally prominent leader in vision restoration research for the past year,” said Gary Abrams, M.D., professor of Ophthalmology and founding director of the Ligon Research Center of Vision. “Dr. Pan has developed the most promising avenue of research in the world at this time, and we feel he is the perfect match for this position.”

RetroSense Therapeutics LLC, a Michigan-based company, announced in October that it executed its exclusive, worldwide option and signed a license agreement for Dr. Pan’s novel gene-therapy approaches for treating blindness.

Dr. Pan, along with colleagues at Salus University in Pennsylvania, developed the breakthrough therapy and follow-on approaches that offer promise to people suffering with blindness caused by age-related macular degeneration and retinitis pigmentosa -- retinal degenerative disorders that are currently incurable.

Age-related macular degeneration is the leading cause of blindness in people older than 60, affecting more than 8 million people in the United States alone. Worldwide, 500,000 individuals lose their eyesight annually to AMD, which is the result of progressive deterioration of photoreceptor cells in the central portion of the retina.

Retinitis pigmentosa is a genetically-determined eye disease caused by mutations in more than 100 different genes. An estimated 100,000 people in the U.S. have RP, which typically manifests as night blindness and progresses to tunnel vision and sometimes complete blindness.

Dr. Pan’s novel strategy focused on genetically converting light-insensitive inner retinal neurons into photosensitive cells, thus restoring light-sensitivity to retinas that lack photoreceptors. Using a virus that delivers a photoreceptor gene from green algae called channelrhodopsin-2 (ChR2), he found that ChR2 made the inner retinal neurons become light sensitive, and that it persisted for long periods in the neurons, ultimately leading to restored responses to light in the brain’s visual cortex.

With this technology, combined with the business and drug development expertise of RetroSense, Dr. Pan is hopeful his breakthrough treatment is on the fast track to restoring a vital part of the human experience to people suffering from retinal degeneration worldwide.

“We are delighted to enhance our position in this space by licensing these novel approaches to vision restoration,” said Sean Ainsworth, founder and CEO of RetroSense. “Channelrhodopsin-based approaches to vision restoration are garnering a great deal of attention from academia and industry right now. It’s a very hot field and we are quite pleased to be aligned with Dr. Pan and his colleagues who pioneered the approach.”

Ainsworth licensed the technology from Wayne State University in an effort to eventually test the technology in humans. Phase I clinical trials could begin in early 2013.

The Ligon Research Center of Vision is a multidisciplinary center and one of only a few in the world exploring the possibility of artificial vision for the blind. The center is dedicated to restoring vision in patients who are losing their sight or have become blind from retinal degenerations.

Voravit Ratanatharathorn, M.D., F.A.C.P., professor of the Wayne State University School of Medicine Department of Internal Medicine’s Division of Hematology/Oncology and the Barbara Ann Karmanos Cancer Center, was cited as a Health Care Hero Award honorable mention by Crain’s Detroit Business.

Dr. Ratanatharathorn, a member of the Wayne State University Physician Group, serves as co-director of the Blood and Marrow Stem Cell Transplant Program, Department of Internal Medicine, Division of Hematology/Oncology at Karmanos and the School of Medicine. He also is director of the J.P. McCarthy Cord Bank at Karmanos, the state’s only non-profit cord stem cell bank.

Crain’s named him the honorable mention in its Advancement of Health Care category, recognizing his contributions to new medical discoveries and for improving quality and access to care.

He is featured in the Sept. 12 edition of Crain’s Detroit Business and will be honored at a special Health Care Heroes luncheon Oct. 20 at the Motor City Casino in Detroit. The luncheon is part of Crain’s Health Care Leadership Summit.

Dr. Ratanatharathorn brought stem cell transplantation to Michigan and provided curative therapy to thousands of patients dealing with hematologic malignancies. He established the first transplant center in the state in the early 1980s and was the first to perform autologous, allogeneic and unrelated transplantation on patients at a time when there were few centers in the United States performing those procedures.

Over the years, he has mentored countless health care professionals in the subspecialty of stem cell transplantation. He is a leader in the management of post-transplant complications, making transplants feasible for more high-risk individuals. He also has researched and formulated several therapies to assist bone marrow transplant patients in their recovery.

“Dr. Ratanatharathorn makes it a priority to know his patients as people in addition to understanding the complexities of their diagnosis and treatment plan,” said George Yoo, M.D., F.A.C.S., associate professor and vice chair of the Department of Otolaryngology-Head & Neck Surgery and Oncology for the School of Medicine and chief medical officer at the Karmanos Cancer Center. “He has relentless energy, is truly compassionate, has an excellent bedside manner and uses humor to promote healing. Dr. Ratanatharathorn truly leads by example as a dedicated physician, teacher, father and friend. Those who know him know he is the best!”

While millions of mothers have cajoled their children to dig into the veggies on the basis of good nutrition, a Wayne State University School of Medicine researcher is taking that advice more than a few steps further by developing compounds from them to make the fight against cancer more efficacious.

Fazlul H. Sarkar, Ph.D., professor of Pathology and Oncology, for the School of Medicine and the Karmanos Cancer Institute, studies natural agents found in a variety of vegetables and a spice that can decrease tumor growth and greatly enhance the effectiveness of chemotherapy or radiation therapy treatments. Dr. Sarkar’s research stemmed from many years of research on the development of active agents against cancer discovered from the bounties of nature. However, what nature can offer in terms of novel chemotherapeutic agents has not been fully exploited.

The National Cancer Institute, National Institutes of Health - Natural Products Repository houses some 170,000 extracts from samples of more than 70,000 plant and 10,000 marine organisms collected from more than 25 countries, as well as more than 30,000 extracts of diverse bacteria and fungi. This repository is considered to be the source of novel compounds to add to the 500,000 compounds envisaged for the NIH Roadmap Molecular Library.

After more than 40 years of screening these extracts, a critical arsenal of cancer drugs has been developed. That arsenal was led by the flagship drug Taxol, which has been approved by the Federal Drug Administration for the treatment of several human malignancies. Many other drugs originally discovered from nature have also been approved by the FDA, including camptothecin and its analogs (topotecan and irinotecan), vinblastine and vincristine, and microbial-derived anthracyclines such as doxorubicin and the bleomycins. Several other promising compounds are in testing in clinical trials against cancer and other deadly diseases such as AIDS. Interestingly, it has been estimated that more than 60 percent of approved anti-cancer drugs are derived in one way or another from natural sources, and thus far, natural products chemistry has proved superior to that of combinatorial chemistry, Dr. Sarkar said.

The large proportion of natural products in drug discovery has stemmed from the diverse structures and the intricate carbon skeletons of natural products, especially flavonoids, coumarins and indoles, and increasing evidence suggests that natural compounds are superior for further drug development. Agents derived from natural sources could be very useful for the treatment of human malignancies either alone or such agents could be useful as an adjunct to conventional therapeutics, both chemotherapy and radiation therapy. Keeping abreast of emerging and rapid advances in the synthesis, characterization and testing of many such agents that are coming through the drug pipeline through exploitation of natural sources became important for Dr. Sarkar’s focused research on specific and novel classes of compounds derived from both natural resources as well as from the tables of synthetic medicinal chemists, which could become newer arsenals for fighting the battle against human malignancies.

The compounds so far examined by Dr. Sarkar -- found in soy, leafy vegetables, cruciferous vegetables like broccoli and Brussels sprouts, hot peppers and curcumin, an ingredient in the spice turmeric -- work by making cancerous tumors more sensitive to the attacks of chemotherapy and radiotherapy and in most cases cause cancer cell death while protecting normal cells.

Dr. Sarkar, whose research is currently funded by five NIH-RO1 grants, has demonstrated that combining genistein (isoflavones), a component of soy, with the chemotherapy drug oxaliplatin causes pancreatic cancer cells to react more sensitively to chemotherapy. The finding is exciting because pancreatic cancer, a malignant tumor within the pancreatic gland, is often considered the most deadly form of cancer. Depending on the extent of the tumor at the time of diagnosis, the prognosis is generally regarded as poor. Few victims are still alive five years after diagnosis, and complete remission remains extremely rare.

According to the NCI, 43,140 Americans were diagnosed with pancreatic cancer, and 36,800 died from the disease in 2010. Pancreatic cancer remains the fourth leading cause of cancer deaths in men and the third leading cause of cancer deaths in women in the United States. Only 15 percent of pancreatic tumors are surgically removable. About 15 percent to 20 percent of patients who undergo surgery survive five years after the treatment. The average survival of patients with a more advanced stage of the disease is only six months.

The rates of incidence and mortality related to pancreatic cancer have remained relatively constant over the last 30 years. The NCI says that one in every 71 Americans born today will be diagnosed with cancer of the pancreas. Only about 4 percent of those diagnosed survive. Chemotherapy remains a standard of treatment despite the dire outcomes.

Dr. Sarkar’s research with genistein (isoflavones), however, shows promise in making chemotherapy more effective in combating the tumors, and not just in pancreatic cancer -- breast, prostate and other types of cancer cells have also demonstrated sensitivity to the compound.

The soy derivative, he explained, works by limiting the cancer cell’s ability to mutate in an attempt to battle chemotherapy drugs. In effect, it weakens the cancer cell’s defensive mechanisms. In an animal model, pre-treating pancreatic cancer cells with genistein and then with oxaliplatin increased cancer cell death and reduced the spread of the cancer into lymph nodes.

Dr. Sarkar does not claim these naturally occurring compounds and their synthetic variations have the ability to cure cancers. Instead, they appear to have an adjuvant characteristic that assists chemotherapy treatments by inhibiting a cancer cell’s ability to mutate to fight treatment. Similar observations on isoflavones have also been made with radiotherapy in prostate and renal cancer models.

“Think of it in terms of a flood,” he said. “The chemotherapy is the water and it seeks to flood the cancer cells. The cells, in reaction, throw up sandbags (mutate) to block the flow, and they are very good at setting up those sandbags. Water, however, will continue to seek openings in the sandbag wall, and if these compounds can knock down enough sandbags, then the chemotherapy chemicals can become more effective.”

He has tested soy isoflavones in sensitizing prostate cancer cells to radiation therapy. The isoflavones works by inhibiting cell survival pathways activated in response to the attack by radiation. Simultaneously, the isoflavones from soy showed antioxidant and anti-inflammatory characteristics, which can help prevent or diminish the adverse side effects of radiation therapy on normal cells.

In a clinical study, 42 patients with localized prostate cancer were selected to randomly receive 200 milligrams of soy isoflavones or a placebo daily for six months starting on their first day of radiation therapy. At each point during the study, the men who received the isoflavones reported decreased urinary, bowel and incontinence side effects, and better erectile function, than their counterparts who received the placebo.

“I really think that we are only scratching the surface as to the potential compounds in plants that can assist us in winning the battle against cancers,” said Dr. Sarkar, who has been engaged in this field of research for more than 20 years.

His research using compounds derived from green leafy vegetables called Indole-3-Carbinol (I3C), which is readily converted to its self-dimerized compound, 3.3’-diindolylmethane (DIM) in the stomach, showed dramatic effects in preclinical studies. Since then, Dr. Sarkar, in collaboration with BioResponce LLC and Elisabeth Heath, M.D., associate professor of Oncology for the Wayne State University School of Medicine and director of Prostate Cancer Research at the Barbara Ann Karmanos Cancer Institute, has developed an improved formulation of DIM, which he has tested in a Phase I clinical trial in prostate cancer patients. Based on non-toxic dose calculation, he also has initiated a Phase II clinical trial at Karmanos Cancer Institute in collaboration with the Urology Department at Henry Ford Health System in patients diagnosed with prostate cancer. The preliminary results are “very encouraging,” Dr. Sarkar said.

He and his research colleagues have also tested extracts from a number of peppers and found that capsaicin too induced significant growth arrest and cell death in human breast and leukemia cancer cell lines, with no significant effect on normal cells. Capsaicin, the active component of peppers such as jalapenos and habaneros, is found mainly in the white pith that surrounds the internal seeds of such peppers. The compound can irritate and burn the skin, mucous membranes and eyes – hence its use in pepper sprays used by police departments. The rate of cancer cell inhibition and death, Dr. Sarkar found, correlated with the capsaicin content, based on the Scoville scale – a measurement of the hotness of peppers. The hotter the pepper from which the capsaicin is extracted, the more potent in knocking down the defensive mechanisms of the cancer cells. The results, he said, warrant additional research into the potential use of pepper extracts as anti-cancer agents.

Another compound showing promise in the fight against cancer can commonly be found in Indian cuisine. Curcumin, the major active ingredient in the spice turmeric, Dr. Sarkar has found, arrests the growth of cancer cells and promotes cancer cell death. However, the compound in its natural state is rapidly processed by the body, so its ability to remain and engage in the fight is relatively weak.

To overcome that weakness, Dr. Sarkar’s lab synthesized a novel curcumin analogue called CDF, which remains in the body longer, is absorbed more readily into the blood stream, and demonstrates a greater efficacy in diminishing the defensive mechanisms of cancer cells and causing cancer cell death when used in conjunction with chemotherapy treatments. He is now working to have CDF further synthesized into a drug to be taken in conjunction with chemotherapy for pancreatic, prostate and colon cancer. His research on CDF has been published in many high-impact journals, and he secured a five-year NIH-R01 grant which began July 1.

Dr. Sarkar, in collaboration with Adhip Majumdar, Ph.D., professor of Internal Medicine at the School of Medicine and the Karmanos Cancer Institute, and senior research career scientist at the Veterans Administration Medical Center, recently published in the journal Translational Oncology and Pharmaceutical Research findings that show the use of curcumin or CDF, either alone or in combination with standard chemotherapy in chemotherapy-resistant colon cancer cells, resulted in the killing of cancer cells that have a cancer stem-like cell quality. The findings are similar to those he published using pancreatic cancer cells. The colon cancer cells resist conventional chemotherapy and have the ability to renew themselves. They also provide a path for malignant cells to propagate and spread. Knocking out the stem-like cancer cells with a curcumin analogue, however, requires developing a compound that remains in the blood stream longer. He said that while curcumin has good absorption rates in the gastrointestinal system, it has very low absorption rates in the blood stream, with levels peaking and then disappearing within 30 minutes to an hour. His newly developed CDF compound raises hope in the fight against human malignancies.

While the produce aisle appears to hold plenty of promise for combating cancer -- Dr. Sarkar said he and his wife have added to their own diet some of the vegetables that are the originators of the compounds he studies -- he cautioned that fighting cancer isn’t as simple as ingesting massive amounts of soy, spinach and tumeric.

“You’d have a very difficult time eating as much curcumin in your diet as the amounts we synthesize for the compounds we are testing to facilitate the development of natural agents or their synthetic derivative as newer drugs that could be used alone as chemotherapy or could be an adjunct to other conventional therapeutics,” he said.

But adding more vegetables to your diet can’t hurt and definitely has its benefits. Just ask Mom – and Dr. Sarkar.