A constant annoyance in reading through reports for this column is the tendency of so many writers to use terminology that can likely be interpreted only by a minority of experts. Coming from a profession that insisted any writing be understood by the average, literate 12-year-old, it’s an annoying habit.
However the news, once deciphered, is usually encouraging…..`dysphagia’ by the way means `difficulty swallowing’.
Swallowing Exercise May Improve Chronic Dysphagia
(Netherlands) — A novel rehabilitative swallowing exercise program aids long-term head and neck cancer survivors with chronic dysphagia, according to a study published in Head & Neck.
Sophie AC Kraaijenga, MD, PhD, from The Netherlands Cancer Institute in Amsterdam, and colleagues evaluated an intensive strength training program in 17 head and neck cancer survivors with chronic dysphagia. Swallow and non-swallow exercises were performed for 6-8 weeks, allowing for progressive muscle overload, including chin tuck, jaw opening, and effortful swallow exercises.
The researchers found that the program was feasible, with an 88% completion rate. Exercise compliance was 97%. After the training period, there were substantial
improvements in chin tuck, jaw opening, and anterior tongue strength. All but one patient reported benefiting from the exercises.
"Some objective and subjective effects of progressive load on muscle strength and swallowing function could be demonstrated," the authors wrote.
(U.S.) Patients with head and neck squamous cell carcinoma who are positive for human papilloma virus (HPV-positive) have been observed to respond significantly better to chemo-radiotherapy than HPV-negative patients. This observation is surprising because HPV infection leads to an increased risk of developing oropharyngeal cancer. To date, the reason for this dichotomy has not been well understood.
In an article in the August 2017 issue of EMBO: Molecular Medicine, researchers and clinicians at the Medical University of South Carolina (MUSC) Hollings Cancer Center report having identified one of the underlying mechanisms—expression of the viral protein E7 leads to cell death through mitophagy, a process that destroys the mitochondria. They went on to develop a novel peptide that mimics this pathway and improves therapeutic intervention in HPV-negative head and neck cancers.
"This study looked at both the clinical aspects as well as the mechanistic and therapeutic aspects of oral cancer. We are very excited about these findings because they represent what is happening in the clinic," says Besim Ogretmen, Ph.D., senior author for this study, director of the Lipidomics Shared Resource Center and professor of Biochemistry and Molecular Biology at MUSC.
Ogretmen's laboratory has a history of studying mitochondria as well as a specific lipid, ceramide. Association of ceramide with mitochondria elicits a decrease in energy production as well as an increase in the production of toxic molecules called reactive oxygen species. The findings described in their recent work bridges these two areas of study and describes a mechanism of cell death termed ceramide-induced mitophagy, which plays an important role in killing oral cancer cells.
Ceramide-induced mitophagy is a two-pronged approach to killing cancer cells. The first prong involves treating cancer cells with cisplatin, a chemotherapeutic agent that mimics ceramide. The treated cells accumulate ceramide at the mitochondria. The second prong involves the viral protein E7. The E7 protein liberates the cellular protein E2F5, which is then capable of binding another cellular protein called dynamin related protein 1 (DRP1). This complex is then targeted to the mitochondria. Importantly, it is the combined presence of ceramide and DRP1 at mitochondria that prompts mitochondrial degradation and ultimately cell death.
Having described the mechanism by which HPV-positive cancer cells succumb to chemotherapy, the Ogretmen lab next wanted to determine if they could apply these findings to HPV-negative cancers, since patients with these cancers are much more likely to succumb to their disease relative to patients with HPV-related cancer.
"Based on these mechanistic findings, we developed a peptide that can mimic the HPV effects without the HPV infection," says Ogretmen.
In order to accomplish this, they developed a peptide that mimics the interaction of the cellular proteins E2F5 and DRP1. Treatment of HPV- oral cancer cells with cisplatin and this novel peptide led to increased cell death in a manner that was similar to treatment of HPV-positive cancer cells with cisplatin. Further experiments showed that this peptide was effective at killing HPV cancer cells in a mouse model.
Future studies are aimed at better understanding the mechanism by which ceramide is incorporated into mitochondria. How does ceramide enter the cell? How is ceramide transported to the mitochondria? Better understanding of this pathway may provide further avenues for improved treatment with cisplatin or other ceramide-like compounds.
Overall, these results demonstrate that chemotherapy is much more effective in HPV-positive cancer cells and that this improved efficacy can be achieved in HPV-negative cancer cells through co-treatment with an E2F5 peptide.
"We are very excited about the potential therapeutic aspects of this peptide; however, developing a drug and taking that drug to the clinic takes a lot of effort and a lot of funding," says Ogretmen.
There are many hurdles that have to be overcome before this novel treatment becomes available in the clinic. One of the first hurdles is manufacturing large quantities of the peptide using good laboratory practices, which is a requirement of the Food and Drug Administration
New cancer drug reduces tumor size by 'up to 50 percent'
(U.K.) New research from the University of Southampton in the United Kingdom investigates the way in which cancer takes over certain cell types and uses them as a life support. Finding a way to target these turncoat cells could help to reduce a tumor's success.
One of the many reasons that cancer is so difficult to treat is its ability to hijack normal cellular components and switch them from useful to deadly. Cancer can therefore turn vital, natural cell types against the body.
As Dr. Aine McCarthy, Cancer Research UK's senior science information officer, says, "Some cancers are incredibly difficult to treat and can use the body's own cells to help them grow, evade treatment, and spread around the body. Researchers have been trying to unlock the secrets behind this for many years."
The findings of the most recent study in this field, carried out by researchers at the University of Southampton, are published this week in the Journal of the National Cancer Institute.
An example of the repurposing of the body's biological mechanisms involves fibroblasts. Normally, these cells make a range of products, such as collagen and elastic fibers, helping to fix organs and cells together.
However, cancer can utilize these cells for its own purpose, turning them into cancer-associated fibroblasts (CAFs).
CAFs support a tumor as it grows and can help it spread. Earlier studies carried out at the University of Southampton have demonstrated that increased CAF levels are associated with poorer survival rates in a number of cancers, including bowel and head and neck cancers.
They have also shown that CAFs protect cancer cells from chemotherapy and suppress the immune system's anti-cancer response.
The relationship between CAF levels and survival could make them a potential target for pharmacological intervention. To date, however, attempts to interact with them have been unsuccessful.