University Times

Proteins provide cell protection against nitric oxide injury Pitt scientists have reported the first laboratory evidence that metallothionein proteins protect cells against injury from nitric oxide (NO).

Metallothionein proteins are small, metal-binding proteins thought to normally protect cells from injury due to exposure to heavy metals, mutagens, anti-cancer agents and free radicals.

"Although investigators have suspected that these proteins protect cells against NO-induced damage, there has been no clear evidence for this effect until now," said lead investigator Bruce Pitt, a professor of pharmacology in the School of Medicine.

Nitric oxide has received attention in recent years because it appears in many parts of the body and participates in many essential functions, including regulating blood pressure, transmitting nerve signals and defending the body against disease. However, the properties that make NO superb at killing cancer cells and micro-organisms also can threaten healthy cells.

Two engineering profs get Central RDF grants The University of Pittsburgh Central Research and Development Fund has granted funds to two assistant professors of electrical engineering.

Ilan Grave received a $13,970 grant for "Generation and Control of Field Domain Patterns Along a GaAs/A1GaAs Superlattice for a Quantum Well Spatial Light Modulator." Patrick J. Loughlin received $13,400 for research on "Time-Frequency Methods for Machine Monitoring." Both grants are for two years, beginning July 1.

Faculty members receive NSF equipment grants Two faculty members in the Department of Chemical and Petroleum Engineering have received engineering equipment grants from the National Science Foundation.

The foundation granted $56,945 to associate professor Eric Beckman, principal investigator, "Research Series FT-IR Spectrometer." Co-PIs are fellow Pitt engineering faculty members Alan Russell, James Goodwin Jr., Julie d'Itri and Sindee Simon.

Simon also was awarded $23,000 for "Thermal Analysis System Upgrade." Simon's grant will permit acquisition of a new differential scanning calorimeter.

Engineering school awarded contract from DOE The U.S. Department of Energy has awarded a contract to the Pitt School of Engineering Center for Energy Research to evaluate the use of by-products from advanced sulfur removal systems in treating metal-laden characteristic hazardous wastes.

New therapy aids cancer patients An outpatient therapy for malignant pleural effusions can improve a cancer patient's quality of life while reducing hospital costs, according to a researcher at the University of Pittsburgh Cancer Institute (UPCI).

The presence of effusion signifies that the space between the lungs and ribs (pleural space) has filled with fluid, thus impeding lung expansion. Malignancy is the most common cause of pleural effusions in adults over 60, with 50 percent of breast cancer patients and 25 percent of lung cancer patients experiencing this condition.

"Until now, doctors have treated this condition by inserting large-bore tubes through the chest wall and hospitalizing patients for 5-10 days at a time," said Chandra Belani, principal investigator of the research, co-director of UPCI's Experimental Therapeutics Program and a Pitt associate professor of medicine. "This alternative therapy could save costs related to hospitalization and allow patients to spend more time at home." IL-2 treatment improves survival rates for ovarian cancer patients Findings from a clinical trial conducted by Magee-Womens Hospital and the University of Pittsburgh Cancer Institute using the drug interleukin-2 (IL-2) to treat end-stage ovarian cancer patients indicate a long-term survival rate of 26.4 percent, which is significantly higher than survival rates associated with standard treatment. IL-2 stimulates the immune system to fight cancer.

Law firm endows chair in bioethics The Pittsburgh-area law firm of Dickie, McCamey & Chilcote will donate $1.5 million to Pitt's Center for Medical Ethics to endow a chair in bioethics.

Income from the endowment will support research and education in medical ethics. n UPCI tests vaccine on patients with melanoma In a University of Pittsburgh Cancer Institute (UPCI) study, investigators are vaccinating people with advanced cases of the deadly skin cancer melanoma using molecules that are overexpressed in melanoma cells.

Unlike a vaccine that is given to prevent disease or the recurrence of cancer, this vaccine is being used against established cancer in the hope that it will stimulate the patient's immune system to better detect and kill melanoma cells.

"Melanoma is one of the few cancers known to be immunogenic, meaning that its cells bear molecular markers that are well recognized by cells of the immune system. In this trial, we hope to capitalize on this recognition and strengthen it," said Walter Storkus, laboratory principal investigator of the study and associate professor in Pitt's departments of surgery and molecular genetics and biochemistry.

John Kirkwood, who is a clinical co-principal investigator of the study, professor of medicine and chief of medical oncology at the University of Pittsburgh Medical Center and director of UPCI's Melanoma Center, said: "This trial differs from the vast majority of other vaccine trials for melanoma because we are vaccinating individuals with part of a specific melanoma protein, or peptide, rather than with whole melanoma cells. This precision will allow us to learn which of these marker peptides best triggers an immune response against the disease." This year an estimated 34,000 people will develop melanoma in the United States and 7,000 will die from the disease. No therapy has been documented that significantly prolongs survival, according to the investigators.

Grant made for development of anti-cancer drugs The National Cancer Institute has granted $2.5 million to Pitt researchers to develop a class of promising new anti-cancer drugs.

This National Cooperative Drug Discovery Grant is one of only four awarded this year in the United States. It will enable Pitt investigators to develop drugs that selectively inhibit ras, a gene that in its mutant form is estimated to account for more than 30 percent of all human cancers.

Like a home thermostat that senses temperature changes and triggers the furnace to maintain a cozy 70 degrees, the body of an HIV-infected person senses the decline in certain immune cells (T cells) and adjusts their production to maintain a healthy number. This finding, made by investigators at Pitt and four other U.S. institutions, is reported in the July issue of Nature Medicine.

According to the researchers, when this homeostasis fails, the effect is chilling. The T cell number plummets, signaling that 1.5 years later the affected person will develop AIDS.

During the course of HIV infection, the virus constantly invades and destroys CD4 T cells, their primary target, but does not ravage CD8 T cells, another group of immune cells.

"We found that the immune system responds to CD4 cell depletion by 'blindly' producing both more CD4 cells and more CD8 cells, thus preserving an overall T cell count," said Albert Donnenberg, associate professor of hematology at UPMC and co-principal investigator on the research, which is part of the federally funded Multicenter AIDS Cohort Study (MACS). "Our evidence strongly suggests that breakdown of homeostatis is mechanistically linked to AIDS. It could be the event that causes the body to become vulnerable to infections that characterize AIDS." Among the other researchers involved in the study is Charles Rinaldo, head of the Pitt Men's Study, the branch of MACS at Pitt.

Investigators at Pitt and the Dana Farber Cancer Institute have successfully vaccinated laboratory animals against cancer by harnessing an important, hitherto unexploited cellular pathway that induces the creation of potent anti-cancer immune cells (killer T cells), according to a report in the July issue of Nature Medicine.

"This vaccine successfully stimulates the production in mice of killer T cells that can destroy cultured cancer cells, in addition to protecting the animals against future injections with live tumor cells," said Louis Falo, Pitt assistant professor of dermatology and investigator with the University of Pittsburgh Cancer Institute. "Our findings have the potential to improve clinical cancer vaccines by effectively stimulating killer T cells, which are known to be important in attacking human cancers. The application of this type of vaccine to human cancers is at least several years away. Our next immediate step is to attempt to use this vaccine to cure mice which already have tumors." Also collaborating in the research was Kenneth Rock and M. Kovacsovics-Bankowski, both at the Dana Farber Cancer Institute in Boston, and Kathleen Thompson at Pitt.