Journal Watch

Cancer prevention drug also disables H. pylori bacterium

A medicine currently being tested as a chemoprevention agent for multiple types of cancer has more than one trick in its bag when it comes to preventing stomach cancer. Keith Wilson, MD, and J. Carolina Sierra, PhD, reported in the March 12 issue of Proceedings of the National Academy of Sciences that in addition to its ability to block the production of cell growth compounds, the drug difluoromethylornithine acts directly on Helicobacter pylori to reduce its virulence. H. pylori infection is the primary cause of gastric cancer.

Discovery points to new cancer immunotherapy option

Vanderbilt researchers have discovered a new “checkpoint” protein on immune system cells is active in tumors and that blocking it — in combination with other treatments — is a successful therapeutic approach in mouse models of cancer. The findings by Michael Korrer, PhD, and Young Kim, MD, PhD, were reported Dec. 13, 2018, in Cell.

Conventional wisdom on DNA shedding incorrect

Cells don’t shed DNA into the bloodstream in tiny vesicles called exosomes as previously thought. The findings by Dennis Jeppesen, PhD, and Robert Coffey, MD, reported April 4 in Cell, have important implications for the development of liquid biopsies for cancer biomarkers. The researchers determined that exosomes don’t carry DNA by employing high-resolution density gradient fractionation and other techniques they developed. They also found another way that cells secrete DNA, by forming novel hybrid organelles called amphisomes.

Breast cancer-killing RIG

Immune checkpoint inhibitors have had remarkable success in melanoma and lung cancer, but response rates to these immunotherapies in breast cancer have been disappointing. David Elion, Rebecca Cook, PhD, and colleagues are exploring approaches that activate innate immunity in breast cancer cells and the tumor microenvironment. They tested the use of a synthetic RIG-I agonist in breast cancer cells and in a mouse model of breast cancer. Reporting in the journal Cancer Research on Sept. 17, 2018, the team found that RIG-I activation increased tumor lymphocytes and decreased tumor growth and metastasis.

Novel genetic factors for colorectal cancer risk

A large-scale study conducted among East Asians and led by Vanderbilt researchers has identified multiple, previously unknown genetic risk factors for colorectal cancer. Wei Zheng, MD, PhD, said the research published in the April 2019 issue of Gastroenterology is the second largest discovery of novel genetic risk variants for colorectal cancer in a single study published to date. Zheng and colleagues identified previously unknown variants.

Pathways of radiosensitization

Androgen deprivation (hormone) therapy for prostate cancer sensitizes cancer cells to radiation and improves radiation’s tumor-killing power. Second-generation anti-androgen agents, such as enzalutamide, are used to treat both hormone-sensitive and -resistant metastatic prostate cancer and are being investigated as first-line therapeutics in combination with radiation therapy. Austin Kirschner, MD, PhD, and colleagues reported April 1 in PLOS ONE that enzalutamide radiosensitizes both androgen-sensitive and androgen-resistant cultured prostate cancer cells in vitro and in mouse models.

Cell death pathway implicated in bone marrow failure

Hematopoiesis, the production of blood cells in bone marrow, requires a careful balance between cell division, maturation and death. Sandra Zinkel, MD, PhD, and colleagues have discovered that disrupting that balance and pushing cells to die a certain way, by a pathway called necroptosis, leads to  bone marrow failure in mice that resembles the human disease myelodysplastic syndrome (MDS). The study published Jan. 10 in Blood implicates necroptotic signaling in MDS.