A fiber-optic sensor created by a team of Purdue University researchers that is capable of measuring oxygen intake rates could have broad applications ranging from plant root development to assessing the effectiveness of chemotherapy drugs.

The self-referencing optrode, developed in the lab of Marshall Porterfield, an associate professor of agricultural and biological engineering, is non-invasive, can deliver real-time data, holds a calibration for the sensor’s lifetime and doesn’t consume oxygen like traditional sensors that can compete with the sample being measured. A paper on the device was released on the early online version of the journal The Analyst this week.

“It’s very sensitive in terms of the biological specimens we can monitor,” Porterfield said. “We don’t only measure oxygen concentration, we measure the flux. That’s what’s important for biologists.”

Mohammad Rameez Chatni, a doctoral student in Porterfield’s lab, said the sensor could be used broadly across disciplines. Testing included tumor cells, fish eggs, spinal cord material and plant roots.

Cancerous cells typically intake oxygen at higher rates than healthy cells, Chatni said. Measuring how a chemotherapy drug affects oxygen intake in both kinds of cells would tell a researcher whether the treatment was effective in killing tumors while leaving healthy cells unaffected.

Plant biologists might be interested in the sensor to measure oxygen intake of a genetically engineered plant’s roots to determine its ability to survive in different types of soil.

“This tool could have applications in biomedical science, agriculture, material science. It’s going across all disciplines,” Chatni said.

The sensor is created by heating an optical fiber and pulling it apart to create two pointed optrodes about 15 microns in diameter, about one-tenth the size of a human hair. A membrane containing a fluorescent dye is placed on the tip of an optrode.

Oxygen binds to the fluorescent dye. When a blue light is passed through the optrode, the dye emits red light back. The complex analysis of that red light reveals the concentration of oxygen present at the tip of the optrode.

The optrode is oscillated between two points, one just above the surface of the sample and another a short distance away. Based on the difference in the oxygen concentrations, called flux, the amount of oxygen being taken in by the sample is calculated.

It’s the intake, or oxygen transportation, that Porterfield said is important to understand.

“Just knowing the oxygen concentration in or around a sample will not necessarily correlate to the underlying biological processes going on,” he said.

Porterfield said future work will focus on altering the device to measure things such as sodium and potassium intake as well. The National Science Foundation funded the research.

Writer:
Brian Wallheimer

Source:
Brian Wallheimer

Purdue University

Minerva Biotechnologies, a leading cancer and stem cell development company, announced a major breakthrough in the treatment of cancers. In an article published this month in the Journal of Breast Cancer Research and Treatment, “MUC1* is a Determinant of Trastuzumab (Breast Cancer Cells” , Minerva researchers reported that tumor cells that had grown resistant to anti-cancer drugs do so by over-expressing a growth factor receptor that they named MUC1*. Researchers reversed the drug resistance by treating the cancer cells with the original drug plus one of Minerva’s proprietary MUC1* inhibitors. The therapeutic effect of several anti-cancer drugs, including Genentech’s blockbuster drug Herceptin, was restored when the drugs were co-administered with a MUC1* antagonist.

Acquired drug resistance is a major problem for cancer therapy. In the United States, 211,000 women are diagnosed each year with breast cancer. About 20% of those women overexpress a specific growth factor receptor that Herceptin targets and thus are eligible for treatment with that drug. Women treated with Herceptin are three-times more likely to survive for at least five years and two-times more likely to survive without a cancer recurrence. Unfortunately, up to 25% of the patients who begin Herceptin treatment become resistant to the drug within the first year. The results of Minerva’s study imply that Herceptin resistance could be prevented or reversed by treating patients with a combination therapy that includes a MUC1*-targeting drug. In addition to Herceptin, the study showed that MUC1* inhibitors reversed acquired resistance to other chemotherapy drugs including Taxol, Doxorubicin and Cylcophosphamide.

Source
Minerva Biotechnologies

View drug information on Taxol.

Researchers have found links between an individual’s genetics and their response to treatment with chemotherapy. The findings, by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues, show how a genetic variation, located in the SOD2 gene, may affect how a person responds to the chemotherapy drug cyclophosphamide. Cyclophosphamide is used in the treatment of breast and other cancers.

The SOD2 gene produces a key protein that protects cells from damage by molecules known as reactive oxygen species, or free radicals. Reactive oxygen species are produced by normal cellular processes and the action of some chemotherapy drugs. The findings represent the first preliminary evidence pointing toward a mechanism and a potential biomarker for cyclophosphamide resistance in breast cancer patients. The study appeared online June 9, 2009, in Clinical Cancer Research.

“This study shows how, with the progress of individualized medicine, a diagnostic test may be developed that determines whether a patient has certain genetic variations that may modify the effect of certain chemotherapies,” said study author Sharon Glynn, Ph.D., of NCI’s Center for Cancer Research.

“In the future, such tests may be used to guide the treatment of patients with the SOD2 variation, ensuring that they receive a therapy that is more effective than cyclophosphamide-based therapies,” added senior author Stefan Ambs, Ph.D., also of the Center for Cancer Research.

Most genes in human cells are present in two copies-one inherited from the mother and the other inherited from the father. These gene copies can vary from one another. Some variations in genes play an important role in how a gene is expressed or how its protein product functions.

The variant identified by the researchers in the SOD2 gene affects both the structure and the function of the encoded protein, an enzyme known as manganese superoxide dismutase (MnSOD) and affects the ability of MnSOD to reach its proper location in the cell and its activity level. MnSOD normally functions inside cellular compartments known as mitochondria and helps protect cells from damage caused by reactive oxygen species formed during cellular metabolism. Excessive levels of reactive oxygen species can be toxic to cells. Indeed, some anticancer drugs depend on increased production of reactive oxygen species to kill cancer cells. Furthermore, some studies have indicated that, because MnSOD neutralizes reactive oxygen species, it can modify the effects of chemotherapy drugs. For example, in laboratory and animal models, increased activity of MnSOD protects cells against the toxic effects of doxorubicin, which is a widely used anticancer drug.

In the new study, the research team investigated whether the variation affected survival in two separate groups of women with breast cancer: 248 women in the United States and 340 women in Norway. Some of the women received chemotherapy, and some did not receive chemotherapy. The team first analyzed DNA from the women to determine their genotype, meaning which types of the SOD2 gene they had. The researchers found that, among patients who received chemotherapy, those who had one form had decreased survival and those with another form had the poorest survival. In contrast, the genotype of SOD2 did not affect survival among those who did not receive chemotherapy.

Next, the team looked at the relationship between SOD2 genotype and the type of chemotherapy the women received. The data were analyzed according to which of three types of commonly used chemotherapy drugs were administered: doxorubicin, 5-fluorouracil, or cyclophosphamide. Both doxorubicin and cyclophosphamide generate reactive oxygen species in cancer cells during treatment. The researchers determined that the presence of a particular variant was associated with decreased survival of patients treated with chemotherapy regimens that contained any of the three drugs. However, the most significant effects were found with the drug cyclophosphamide. Women with a distinct variant form of SOD2 and who received cyclophosphamide-containing chemotherapy had the poorest survival.

The research team says more work is necessary to confirm these findings and to examine the precise mechanism by which a genotype influences the response of cancer cells to cyclophosphamide. The team plans to examine the influence of several variations on the resistance to other chemotherapies.

For more information on Dr. Ambs’ research, please go here.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Reference: Glynn SA, Boersma BJ, Howe TM, et al. A Mitochondrial Target Sequence Polymorphism in MnSOD Predicts Inferior Survival in Breast Cancer Patients Treated with Cyclophosphamide. Online June 9, 2009. Clinical Cancer Res.

Source
National Cancer Institute