Archive for the ‘Research’ Category

Angiotensin-Receptor Blockades (ARBs) Found to Raise Risk of Cancer

July 9, 2010

Dr. Daniel Simon M.D., Division Chief of Cardiovascular Medicine and Director of HM-Heart and Vascular Institute at UHCMC; Dr. James Fang M.D., Section Chief of Heart Failure and Medical Director of Heart Transplantation at UHCMC; IIke Sipahi M.D., Associate Director of Heart Failure & Transplantation at UHCMC at the Harrington-McLaughlin Heart & Vascular Institute of UHCMC researched the effects of Angiotensin-Receptor Blockers (ARBs) on the risk of cancer.

ARBs are a widely utilized drug class used for treatment of hypertension, heart failure, diabetic nephropathy, and recently, for cardiovascular risk reduction.

Randomized controlled trials of ARBs with a follow-up of at least 1 year, and enrolling at least 100 patients were included in this meta-analysis. Information on new cancer development (first diagnosis) was available for 61,590 patients from five trials. Cancer data on common types of solid organ cancers such as lung and prostate cancer were available for 68,402 patients from five trials, and data on cancer deaths were available for 93,515 patients from eight trials.

The meta-analysis showed that patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%). Specifically, the risk of lung cancer was increased by 25%, which was also statistically significant.

“We have found the risk of new cancers was increased with these medications by 8-11 percent.  Most importantly, risk of lung cancer was increased by 25 percent,” said Dr. Sipahi. Although there was no statistically significant excess in cancer deaths (1.8% with ARBs vs 1.6% with control) the investigators pointed out that the average duration of follow-up of 4 years may be too short to capture cancer deaths.

“In medicine, physicians must balance the benefits and risks of all drug and device therapies.  We recommend that patients discuss the findings of this study with their physicians since ARBs are effective agents in the treatment of high blood pressure and heart failure,” said Dr. Simon.

They conclude that because of the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each individual ARB on the market, but they stated that their findings need further investigation.

In response to this publication from Case Western Reserve University, the European Medicines Agency (EMA) of the European Union announced that they started an investigation about the possible cancer risk of ARBs.

“This is the first time an association between ARBs and cancer development is suggested,” Dr. Sipahi continued. “While our findings are robust, they need to be replicated in other studies before they can be considered as definitive.”

The US Food and Drug Administration has not made any statement regarding this issue yet.

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Correlation Between Methicillin-Resistant Staphylococcus Aureus and Cystic Fibrosis Proven

July 9, 2010

Led by Dr. Elliott Dasenbrook MD MHS, Associate Director of The Adult Cystic Fibrosis Program, a UHCMC team in the Division of Pulmonary, Critical Care, and Sleep Medicine have published the findings from a major study about cystic fibrosis (CF) survival rates in the June 16 issue of JAMA.

Specifically, the study observed patients with CF who had methicillin-resistant Staphylococcus aureus (MRSA) detected in their respiratory tract.

The team composed a study with 19,833 CF patients across the nation between ages 6 and 45.  Times until death after diagnosis with MRSA were recorded in order to compare survival between CF patients with and without respiratory tract MRSA.

The unadjusted mortality rate was 18.3 deaths (95% confidence interval [CI], 17.5-19.1) per 1000 patient-years in patients without MRSA and 27.7 deaths (95% CI, 25.3-30.4) per 1000 patient-years in those with MRSA.  The team showed that there is a significantly higher rate of death in CF in people that have MRSA.

“Our study findings may prompt many doctors to reconsider how they care for CF patients,” says Dr. Dasenbrook. He adds, “Until now, some CF doctors weren’t aggressively treating patients with MRSA.  Doctors often viewed MRSA to not be as important as other respiratory-tract infections. With our study findings, treatment patterns may changes as the risk of death is 1.3 times greater for CF patients with MRSA.”

hematology oncology publications :: Q2 | 2010

July 8, 2010

Inhibition of Lck enhances glucocorticoid sensitivity and apoptosis in lymphoid cell lines and in chronic lymphocytic leukemia
Harr M, Caimi P, McColl K, Zhong F, Patel S, Barr P, Distelhorst C.
Cell Death Differ. 2010 Mar

Non-Hodgkin’s lymphoma in the elderly
Caimi PF, Barr PM, Berger NA, Lazarus HM.
Drugs Aging. 2010 Mar

Correlation between ZAP-70, phospho-ZAP-70, and phospho-Syk expression in leukemic cells from patients with CLL
Kaplan D, Meyerson HJ, Li X, Drasny C, Liu F, Costaldi M, Barr P, Lazarus HM.
Cytometry B Clin Cytom. 2010 Mar

Toxicity of sunitinib plus bevacizumab in renal cell carcinoma
Rini BI, Garcia JA, Cooney MM, Elson P, Tyler A, Beatty K, Bokar J, Ivy P, Chen HX, Dowlati A, Dreicer R.
J Clin Oncol. 2010 Jun

Variability of pulse oximetry measurement over 1 year in children with sickle cell disease depends on initial oxygen saturation measurement
Mullin JE, Cooper B, Seicean S, Strunk R, Rosen C, Redline S, Kemp J, DeBaun MR.
Pediatr Blood Cancer. 2010 Jul

Inhibition of Lck enhances glucocorticoid sensitivity and apoptosis in lymphoid cell lines and in chronic lymphocytic leukemia
Harr MW, Caimi P, McColl K, Zhong F, Patel S, Barr P, Distelhorst C.
Cell Death Differ. 2010 Mar

O-fucose modulates notch-controlled blood lineage commitment
Yan Q, Yao D, Wei LL, Huang Y, Myers J, Zhang L, Xin W, Shim J, Man Y, Petryniak B, Gerson S, Lowe JB, Zhou L.
Am J Pathol. 2010 Jun

Umbilical cord blood-selected CD133(+) cells exhibit vasculogenic functionality in vitro and in vivo
Finney MR, Fanning LR, Joseph ME, Goldberg JL, Greco NJ, Bhakta S, Winter DG, Forster M, Scheid PE, Sabe M, Pompili VJ, Laughlin MJ.
Cytotherapy. 2010

Correlation between ZAP-70, phospho-ZAP-70, and phospho-Syk expression in leukemic cells from patients with CLL
Kaplan D, Meyerson HJ, Li X, Drasny C, Liu F, Costaldi M, Barr P, Lazarus HM.
Cytometry B Clin Cytom. 2010 Mar

Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis
Kang Z, Altuntas CZ, Gulen MF, Liu C, Giltiay N, Qin H, Liu L, Qian W, Ransohoff RM, Bergmann C, Stohlman S, Tuohy VK, Li X.
Immunity. 2010 Mar

CXCR2-positive neutrophils are essential for cuprizone-induced demyelination: relevance to multiple sclerosis
Liu L, Belkadi A, Darnall L, Hu T, Drescher C, Cotleur AC, Padovani-Claudio D, He T, Choi K, Lane TE, Miller RH, Ransohoff RM.
Nat Neurosci. 2010 Mar

ARQ-197, an oral small-molecule inhibitor of c-Met for the treatment of solid tumors
Bagai R, Fan W, Ma PC.
IDrugs. 2010 Jun

A segregation analysis of Barrett’s esophagus and associated adenocarcinomas
Sun X, Elston R, Barnholtz-Sloan J, Falk G, Grady WM, Kinnard M, Mittal SK, Willis JE, Markowitz S, Brock W, Chak A.
Cancer Epidemiol Biomarkers Prev. 2010 Mar

Confirmation of Linkage to and Localization of Familial Colon Cancer Risk Haplotype on Chromosome 9q22
Gray-McGuire C, Guda K, Adrianto I, Lin CP, Natale L, Potter JD, Newcomb P, Poole EM, Ulrich CM, Lindor N, Goode EL, Fridley BL, Jenkins R, Le Marchand L, Casey G, Haile R, Hopper J, Jenkins M, Young J, Buchanan D, Gallinger S, Adams M, Lewis S, Willis J, Elston R, Markowitz SD, Wiesner GL.
Cancer Res. 2010 Jul

Malignant T cells in cutaneous T-cell lymphoma lesions contain decreased levels of the antiapoptotic protein Ku70
Ferenczi K, Ohtola J, Aubert P, Kessler M, Sugiyama H, Somani AK, Gilliam AC, Chen JZ, Yeh I, Matsuyama S, McCormick TS, Cooper KD.
Br J Dermatol. 2010 Apr

Securinine induces p73-dependent apoptosis preferentially in p53-deficient colon cancer cells
Rana S, Gupta K, Gomez J, Matsuyama S, Chakrabarti A, Agarwal ML, Agarwal A, Agarwal MK, Wald DN.
FASEB J. 2010 Jun

Factor XII stimulates ERK1/2 and Akt through uPAR, integrins, and the EGFR to initiate angiogenesis
LaRusch GA, Mahdi F, Shariat-Madar Z, Adams G, Sitrin RG, Zhang WM, McCrae KR, Schmaier AH.
Blood. 2010 Jun

Comorbidities, functional limitations, and geriatric syndromes in relation to treatment and survival patterns among elders with colorectal cancer
Koroukian SM, Xu F, Bakaki PM, Diaz-Insua M, Towe TP, Owusu C.
J Gerontol A Biol Sci Med Sci. 2010 Mar

Factor XII: what does it contribute to our understanding of the physiology and pathophysiology of hemostasis & thrombosis
Stavrou E, Schmaier AH.
Thromb Res. 2010 Mar

Research on the effects of intensive treatment on hyperglycemia on type 2 diabetes

July 8, 2010

Dr. Faramarz Ismail-Beigi M.D., PhD., the previous Division Chief of Endocrinology, and a team of internationally renowned UHCMC diabetes specialists researched the effects of intensive treatment of hyperglycemia (or high blood sugar, a condition in which an excessive amount of glucose circulates in the blood plasma) on microvascular outcomes in type 2 diabetes in analyzing the ACCORD randomized trial.

Hyperglycemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes.

The team set out to find out if reducing the blood glucose concentration to normal levels in people with established type 2 diabetes decreases the rate of microvascular complications. 10,251 patients were randomly assigned, 5,128 to the intensive glycemia control group and 5,123 to standard group. Intensive therapy was stopped before study end because of higher mortality in the glycemia group, and patients were transitioned to standard therapy. After reviewing the results, it was clear that intensive therapy did not reduce the risk of advanced measures of microvascular outcomes (such as kidney failure requiring dialysis, or advanced disease of the retina requiring surgery), but delayed the onset of albuminuria and some measures of eye complications and neuropathy.

The conclusion was made that microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycemia.

Dr. Ismail-Beigi suggests that “In elderly people with established type 2 diabetes of many years’ duration and a history of prior cardiovascular disease (such as a heart attack), or risk factors for cardiovascular disease, the benefits and risks associated with intensive blood sugar control needs to be carefully assessed on an individual basis.  The best approach is for patients to have a discussion with their health-care provider to set an appropriate blood sugar goal.”

The Prophetic Protein :: Who is at risk for heart attack?

June 25, 2010

Tense hours in the emergency room while tests confirm a heart attack may be rolled back to mere minutes, thanks to a telltale protein marker identified by Case Western Reserve University School of Medicine researchers. Better yet, a routine blood test for the nefarious protein could serve as an early warning to people at high risk :: Take steps now, and you may dodge the dangerous attack altogether.

When the proverbial elephant takes a seat on one’s chest, it is a decided hint: That person might be having a heart attack, or myocardial infarction (MI). Every 25 seconds, someone in the United States has one, according to the American Heart Association, but the oft-reported sensation of chest tightening or pain is just that-a clue. Even in the hospital, it can take eight to 12 hours for current tests to conclusively rule a heart attack in or out. Common alternative culprits in chest pain are intense heartburn or a gallstone attack.

Led by top physician-researcher Daniel I. Simon, MD, investigators at the School of Medicine, however, have discovered a marker of heart attack that promises to cuthours off the time for definitive MI diagnosis-to the tune of confirmation within 10 to 15 minutes of arriving at the emergency room. What’s more, a simple blood test for the novel myeloid-related protein-8/14 (MRP-8/14) marker could give long-used cholesterol screening a run for its money as a signal of MI in the making, years ahead of the cardiac attack.

“Though we gain great insight into patients’ potential risk for cardiovascular disease using conventional biomarkers, we are limited in identifying some people at risk,” says Douglas Vaughan, MD, professor of cardiology at Northwestern University’s Feinberg School of Medicine and chair of its Department of Medicine. “An additional marker measured in people’s blood could valuably refine our ability to take care of patients with coronary artery disease.”

To hone in on the up-and-coming predictive protein MRP- 8/14, researchers applied an unprecedented scientific approach that scoured entire human genomes for cardiac warning signs. “We were on the hunt. We wanted to know what genes turn on or off in heart attack patients,” explains Dr. Simon, the Herman K. Hellerstein Professor of Cardiovascular Research at the School of Medicine and director of University Hospitals Harrington-McLaughlin Heart & Vascular Institute. Dr. Simon and his team of researchers identified MRP-8/14 as their best-bet marker for heart attack for use in emergency settings and as a potential companion to routine cholesterol screening in the doctor’s office.

Dr. Simon’s account is a tale of finding a little molecule with big potential-a project born in a lab in New England that has grown on a campus in Cleveland.

Read the full story at Medicus.

Cardiologists discover cancer risks in group of blood pressure medications

June 24, 2010

University Hospitals Case Medical Center cardiologists have uncovered new research showing an increased risk of cancer with a group of blood pressure medications known as angiotensin-receptor blockers (ARBs).

This class of drugs is used by millions of patients not only for high blood pressure but also for heart failure, cardiovascular risk reduction and diabetic kidney disease.

University Hospitals Harrington-McLaughlin Heart & Vascular Institute’s Drs. Ilke Sipahi, Daniel I. Simon and James C. Fang recently completed a meta-analysis of over 60,000 patients randomly assigned to take either an ARB or a control medication. Their findings are published online today at The Lancet Oncology.

The researchers found that patients randomized to ARBs has “significantly increased risk of new cancer” compared to control patients.

“We have found the risk of new cancers was increased with these medications by 8-11 percent,” said Dr. Ilke Sipahi, associate director of heart failure and transplantation and assistant professor at Case Western Reserve University School of Medicine. “Most importantly, risk of lung cancer was increased by 25 percent.”

However, the research did not establish any link between ARBs and other types of cancer such breast cancer.

“This is the first time an association between ARBs and cancer development is suggested,” Dr. Sipahi continued. “While our findings are robust, they need to be replicated in other studies before they can be considered as definitive.”

Before this study, there were no major safety concerns with ARBs except for their use in pregnancy and in patients with chronic kidney or blockages of kidney arteries. Interestingly, previous animal studies with ARBs have been negative for cancer development.

“In medicine, physicians must balance the benefits and risks of all drug and device therapies,” said Dr. Daniel Simon, director of the Harrington-McLaughlin Heart & Vascular Institute at University Hospitals Case Medical Center and professor at Case Western Reserve University School of Medicine. “We recommend that patients discuss the findings of this study with their physicians since ARBs are effective agents in the treatment of high blood pressure and heart failure. Meta-analyses are a powerful tool to look at low frequency safety signals, but require confirmation with other approaches, such as large national health and managed care registries.”

Prostate Cancer at CWRUmedicine

June 20, 2010

Worldwide, prostate cancer is one of the most common types of cancer found in men. Learning more about prostate cancer and treatment options can help you and your loved ones take an active part in making choices about care.

* Click here to read about new research conducted by the Division of Hematology Oncology at Case Western Reserve University.

The prostate is a chestnut-sized gland below the bladder, which contributes most of the fluid that combines with a man’s sperm to make semen.

Prostate cancer is the most common cancer other than skin cancer in American men and is the second leading cause of cancer death in men.

The American Cancer Society estimates that more than 234,000 men will be diagnosed with prostate cancer in 2006. Incidence rates for the disease are higher for African-American men than for white men.

Other Prostate Cancer Survivors ::

Harry Belafonte
Musician, actor and social activist Harry Belafonte

Robert De Niro
Actor Robert De Niro

Rudy Giuliani
Former New York City Mayor Rudy Giuliani

John Kerry
U.S. Senator & 2004 Presidential candidate John Kerry

Nelson Mandela
Former President of South Africa Nelson Mandela

Philips Healthcare, State of Ohio Announce Global Advanced Imaging Innovation Center

June 4, 2010

A $33.5 million commitment by Philips Healthcare and a $5 million Third Frontier grant from the state of Ohio will provide researchers at Case Western Reserve University, University Hospitals Case Medical Center, and Philips an opportunity to create medical imaging systems that will detect disease far earlier and be safer for patients than current methods.

The company and state announced the creation of the Global Advanced Imaging Innovation Center, to be housed at the University Hospitals Case Medical Center campus, at the same press conference where Gov. Ted Strickland designated Cleveland’s Health-Tech Corridor a state Hub of Innovation and Opportunity yesterday.

The corridor, created by the non-profit BioEnterprise and the economic-development corporation MidTown Cleveland, runs from downtown to University Circle. It includes Case Western Reserve, University Hospitals Case Medical Center (UHCMC), the Cleveland Clinic, Cleveland State University, Louis Stokes Cleveland VA Medical Center, and St. Vincent Charity Medical Center along with 75 biomedical companies, 45 technology companies and seven business incubators.

“We are pleased that the State of Ohio has awarded Ohio Third Frontier funding to our project,” said Jay Mazelsky, Senior Vice President and General Manager for Computed Tomography and Nuclear Medicine at Philips Healthcare. The company, which employs 1,100 in Highland Heights, has committed more than $6 million annually for five years, to the project.

“The goals of this center will be to provide strategic research, development and clinical validation for advanced imaging technologies, further developing our presence in northeast Ohio and building on our existing partnerships with Case Western Reserve University and University Hospitals.”

Using Phillip’s latest imagers, physicians and researchers from CWRU will help develop a variety of medical imaging technologies expected to enable doctors to see into the body’s molecules and atoms, revealing anatomical and functional information currently unattainable. They will test and improve imagers to provide for earlier diagnostics and better tracking of disease progression while increasing safety and comfort to patients.

Case Western Reserve is the lead agency for the state’s $5 million grant supporting the effort.

“This award is emblematic of the way that members of this corridor work together to achieve more than any organization could alone,” Case Western Reserve President Barbara R. Snyder said of the Third Frontier grant.

Snyder recounted the success CWRU has had in generating business and collaborating with hospitals and industry. As a result of professors’ research, the university has launched 24 companies since 2001; reaped $16.3 million in licensing revenue last year alone; and won an average of $385 million in state, federal and other grants during the last five years. In 2007, Case Western Reserve became lead agency, partnering with University Hospitals and Cleveland Clinic, on a $64 million Clinical and Translational Science Award – the largest single grant the National Institutes of Health has made in Northeast Ohio.

The announcements were made at the BioEnterprise building, in a room packed with Health-Tech Corridor boosters and members, including Cleveland Mayor Frank Jackson, Cuyahoga County Commissioner Tim Hagan, Cleveland Foundation President Ronn Richard and officials from UHCMC, Cleveland State University, the Cleveland Clinic and media.

The hub overlays the corridor. The new state designation comes with a $250,000 grant and gives research and development within the hub priority for future state grants.

Baiju Shah, president of BioEnterprise, said the Dutch-owned Philips could have chosen any location worldwide, but, “Their decision to locate their Center within the Cleveland Health-Tech Corridor is an example of what can happen when public entities led by the State of Ohio, private institutions, philanthropy and nonprofits collaborate.”