Among U.S. women, an estimated 21,880 new cases and 13,850 deaths occurred in 2010 from epithelial ovarian cancer, one of the most common forms of ovarian cancer and the most lethal gynecologic cancer in women.
Previously, Kathleen M. Mulder, Ph.D., professor, biochemistry and molecular biology, along with members of her laboratory, learned that km23-1 -- a protein -- is defective in nearly half of all ovarian cancer patients. In the current study, researchers induced over-expression of km23-1 in human ovarian cancer cells placed in mice, causing the cells to produce large amounts of the normal protein.
km23-1 is a subunit of dynein, a motor protein that transports cargo along paths in the cell called microtubules. The dynein motor has many jobs in the cell, including major roles in cell division.
"Although microtubule-binding agents, such as the drug paclitaxel, are being used in the treatment of ovarian cancer, drug resistance has significantly limited their efficacy," Mulder said. "It is critical to develop novel, targeted therapeutics for ovarian cancer. Motor protein regulatory agents may offer promise for providing improved efficacies with reduced side effects in the treatment of ovarian cancer and other human malignancies."
Nageswara Pulipati, Ph.D., postdoctoral fellow in Mulder's lab, said, "We used a method to cause the tumors to express high levels of normal km23-1, but only in the experimental group of mice. Compared to the control group, the tumors were much smaller when km23-1 was over-expressed."
Findings were reported online (http://onlinelibrary.wiley.com/doi/10.1002/ijc.25954/abstract) and will appear in an upcoming edition of The International Journal of Cancer.
"The dynein motor protein is needed to transport checkpoint proteins along the microtubules during mitosis. However, when km23-1 levels are high, at least one checkpoint protein, BubR1, is not transferred properly," said Qunyan Jin, M.D., research associate in Mulder's lab.
During the cell division process, several checkpoints exist where specific proteins put a hold on cell division until proper completion of a specific step can be verified. When km23-1 is over-expressed, a checkpoint is stalled during mitosis -- the stage in the cell division process that normally facilitates equal splitting of the chromosomes into two identical groups before the mother cell splits into two daughter cells.
"Normally, if everything is correct at this checkpoint, the cell then goes on to divide," Mulder said. "However, with the over-expression of km23-1, the checkpoint stays on and cell division does not proceed normally, which leads to a slow cell death."
Mulder and her lab team will now look at how the over-expression of km23-1 may be mimicked to target km23-1, using nanotechnology to deliver a drug to the cancer cells, and how this approach may possibly be used in humans.
This National Institutes of Health and the Department of Defense supported this work. Also contributing to this research were Xin Liu, Ph.D., Yan Zhao, Ph.D., Baodong Sun, M.D., Manoj K. Pandey, Ph.D., Jonathan P. Huber, Ph.D. and Wei Ding, Ph.D.
Matt Solovey | EurekAlert!
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy