Posts Tagged ‘surgery’

Rare stem cells hold potential for infertility treatments

Researchers studying infertility in mouse models found that, unlike similar types of cells that develop into sperm, the stem cells that express PAX7 can survive treatment with toxic drugs and radiation. If the findings hold true in people, they eventually could lead to new strategies to restore or protect fertility in men undergoing cancer treatment.

“Unfortunately, many cancer treatments negatively impact fertility, and men who receive such treatments are at high risk of losing their fertility. This is of great concern among cancer patients,” said Dr. Diego H. Castrillon, Associate Professor of Pathology and Director of Investigative Pathology. “The PAX7 stem cells we identified proved highly resistant to cancer treatments, suggesting that they may be the cells responsible for the recovery of fertility following such treatments.”

Infertility, which the Centers for Disease Control estimates affects as many as 4.7 million men in the United States, is a key complication of cancer treatments, such as chemotherapy and radiation therapy.

The new findings, presented in the Journal of Clinical Investigation, provide valuable insight into the process of sperm development. Known as spermatogenesis, sperm development is driven by a population of “immature” stem cells called progenitors in the testes. These cells gradually “mature” into fully differentiated sperm cells. Dr. Castrillon and his team tracked progenitor cells that express the protein PAX7 in mouse testes, and found that these cells gradually give rise to mature sperm.

“We have long known that male fertility is driven by rare stem cells within the testes, but the precise identity of these stem cells has been disputed,” said Dr. Castrillon, who holds the John H. Childers, M.D. Professorship in Pathology. “Our findings suggest that these rare PAX7 cells are the key cells within the testes that are ultimately responsible for male fertility.”

Importantly, even after exposure to toxic chemotherapy or radiation treatments, the PAX7-expressing cells continued to divide and thus could contribute to restoring sperm development.

source : http://www.sciencedaily.com/releases/2014/09/140904153805.htm

One-two punch for brain tumors? New clinical trial opens

The experimental approach, based on U-M research, delivers two different genes directly into the brains of patients following the operation to remove the bulk of their tumors.

The idea: trigger immune activity within the brain itself to kill remaining tumor cells — the ones neurosurgeons can’t take out, which make this type of tumor so dangerous.

It’s the first time this gene therapy approach is being tried in humans, after more than a decade of research in experimental models.

One of the genes is designed to kill tumor cells directly, and is turned on when the patient takes a certain drug. The other gene spurs the body’s own immune system to attack remaining cancer cells. Both are delivered into brain cells via a harmless virus.

The Phase I clinical trial has already enrolled two patients who have tolerated the gene delivery without complications. All patients in the study must have a presumptive diagnosis of WHO grade 3 or 4 malignant primary glioma, such as glioblastoma multiforme; patients must not have been treated yet by any therapy. They must also meet other criteria for inclusion in the trial.

More patients will be able to enroll at a pace of about one every three weeks, through a careful selection process. In addition to surgery and gene therapy at U-M, each will receive standard chemotherapy and radiation therapy as well as follow-up assessments for up to two years.

“We’re very pleased to see our years of research lead to a clinical trial, because based on our prior work we believe this combination of cell-killing and immune-stimulating approaches holds important promise,” says principal investigator Pedro Lowenstein, M.D., Ph.D., the U-M Medical School Department of Neurosurgery professor who has co-led the basic research effort to develop and test the strategy.

Co-leader Maria Castro, Ph.D., notes that the patients who agree to take part in the Phase I trial will be the first in the world to help establish the safety of the approach in humans. “Without them, and without our partners on the U-M Neurosurgery team, and donors to the Phase One Foundation that support our work, we wouldn’t be able to take this important step in testing this novel therapeutic approach.”

For more about the trial, visit http://umhealth.me/gliomatrial or call 1-800-865-1125.

source : http://www.sciencedaily.com/releases/2014/09/140902143230.htm

Carcinogenic role of protein in liver decoded

The EGF Receptor (Epidermal Growth Factor Receptor, EGFR) is a protein which, as a transmembrane receptor, controls a multitude of vital processes in the cell. In human beings, the EGF Receptor is present in many cells types and plays an important role in many types of cancer. It is present in various kinds of tumors in excessive amounts and/or in mutated form, which causes the tumor cells to grow and multiply. For this reason the EGFR serves as a point of attack in many treatment strategies. In the process, its function is inhibited with the objective of slowing down the growth of the tumor cell.

The liver cell carcinoma (hepatocellular carcinoma, short HCC) is one of the most frequent malignant tumors worldwide. Approximately six percent of all cancers in men and about three percent in women are liver cell carcinomas. It is the second most frequent cause of death associated with cancer. Risk factors for HCC include liver diseases through Hepatitis B and C infections as well as alcohol abuse or the classic “fatty liver.”

Up to now, the tumor-promoting role of EGFR has only been linked with its expression directly in the tumor cells. However, the study group of Maria Sibilia, Manager of the Institute for Cancer Research at the Medical University of Vienna and Deputy Manager of the Comprehensive Cancer Centre, in cooperation with the research groups of Michael Trauner and Markus Peck-Radosavljevic at the clinical division for gastroenterology and hepatology (Manager: Michael Trauner) as well as the Eastern Hepatobiliary Surgery Institute/Hospital in Shanghai discovered that EGFR plays a more decisive role in the macrophages of the liver (these are important cells of the immune system which are called Kupffer cells in the liver) with respect to the growth of the liver cell carcinoma than previously assumed.

“In this study we were able to prove that the inhibition of EGFR has a tumor inhibiting effect on the macrophages and not its inhibition on the tumor cell itself,” explains Maria Sibilia. However, if the EGFR conversely exists on these macrophages in an excessive number, it can promote the growth of the tumor. Its existence on the macrophages reduces the chance of survival for HCC patients.

This could explain why EGFR inhibitors utilised for cancer treatment and aiming directly for the tumor cells have achieved clinically disappointing results in the fight against the liver cell carcinoma in the past. For the first time, this study proves the tumor-promoting mechanism for EGFR in non-tumor cells, which could lead to more effective and precise treatment strategies with macrophages as a point of approach in the future.

source : http://www.sciencedaily.com/releases/2014/09/140901090303.htm