The YAP signal plays a crucial role in head-and-neck cancer onset

Source: Author: press release, Kobe University Joint research between Kobe University and National Hospital Organization Kyushu Cancer Center has revealed that mice with mutations in the YAP signal pathway develop head-and-neck cancer over an extremely short period of time (world's fastest cancer onset mouse model), indicating that this pathway plays a crucial role in the onset of these cancers. This discovery may shed light on the development of new drugs for head-and-neck cancer. This research resulted from a collaboration between a research group led by Professor SUZUKI Akira and Associate Professor MAEHAMA Tomohiko at Kobe University Graduate School of Medicine, and Dr. MASUDA Muneyuki's team at Kyushu Cancer Center. These results were published in the American scientific journal 'Science Advances' on March 18. Main Points: >Deletion of MOB1 (*1, which represses YAP) in mouse tongues causes strong activation of YAP (*2), leading to the early onset of cancer (in about 1 week). >In humans, the expression of YAP increases during the development of dysplasia (pre-cancerous lesions), prior to the onset of head-and-neck cancer. YAP continues to increase with the development and progression of cancer. This high YAP activation is linked to poor patient prognosis. >The onset and progression of head-and-neck cancer in the mice in this study, and the proliferation of stem cells in this cancer in humans, are dependent on YAP. >These results suggest that cancer develops when the YAP activation exceeds a threshold. YAP may play a fundamental role in head-and-neck cancer onset and progression. These conclusions [...]

Okayama University Research: disrupting blood supply to tumors as a new strategy to treat oral cancer

Source: Author: press release provided by Okayama University Researchers at Okayama University have recently published a study in Cells in which they reduced the size of oral cancer tumors by damaging the blood vessels surrounding the tumor cells. Cancer cells have ingenious mechanisms of survival within the body. One strategy they adopt is developing a network of blood vessels around themselves as a source of blood supply. Scientists have long been investigating ways to prevent this blood flow to cancer cells. CXCR4 is a protein known to be closely involved with tumor growth. However, its exact role in tumor progression is unclear. A research team led by Assistant Professor KAWAI Hotaka and YOSHIDA Saori (graduate student, D.D.S.), Assistant Professor EGUCHI Takanori at Okayama University has now shown that CXCR4 is the main culprit maintaining the arrangement of tumor blood vessels. Firstly they found, immunohistochemistry on human clinical specimens revealed that tumor vessels expressed CXCR4 in human oral cancer specimens. The next question to arise was whether the CXCR4-rich blood vessels were promoting tumor growth. In order to investigate this further, the oral cancer cells were transplanted into mice. Once the tumor grew in mice body, they were given AMD3100—a drug that antagonises CXCR4. When the tumors were subsequently observed under a microscope, several areas were found to necrotic. A characteristic pattern of necrosis was observed in which the tumor tissue that were at a distance away from the blood vessel was necrotic, leaving the tumor tissue close to the [...]

Identified: 15 genes that trigger rapid growth of head and neck squamous cell carcinoma

Source: Author: Bob Yirka , Medical Xpress A team of researchers affiliated with several institutions in Canada has identified 15 tumor suppressor genes that can trigger rapid growth of human head and neck squamous cell carcinoma (HNSCC) when they mutate. In their paper published in the journal Science, the group describes their reverse genetic CRISPR screen, which allowed them to analyze almost 500 long-tail genetic mutations that lead to HNSCC. HNSCC is the sixth-most common type of human cancer, and sadly, has a low survival rate. As the researchers note, to date, most studies looking into a cure have focused on the few genes that mutate at a very high rate. This has given them a high profile. But there is another class of slower mutating gene that can lead to tumors in low numbers of patients. Prior research has shown that there are hundreds of these so called "long tail" genes, many of which have not been identified. In this new effort, the researchers used a reverse genetic CRISPR screen that allowed them to identify 15 of them. The work focused on tumor suppressor genes that regulate cell division. When something goes wrong with them, such as a mutation, they lose their function and thus cannot prevent the cells they were regulating from mutating out of control. More specifically, the team focused their attention on the genes in cells that are part of the notch signaling pathway—in particular, those cells that develop into HNSCC tumors. All mammals have [...]

Gabapentin shows efficacy as opioid alternative for patients with head and neck cancer

Source: Author: Jennifer Byrne For many patients with head and neck cancer, treatment-associated oral mucositis is a source of severe pain. Managing this pain is a priority for physicians and interdisciplinary care teams. Although opioid painkillers historically have been used for this purpose, researchers at Roswell Park Comprehensive Cancer Center investigated the use of gabapentin, a drug used to alleviate nerve pain, as an alternative to narcotics for this patient population. “Virtually all patients will require some type of pain relief or analgesic medication during the course of chemotherapy and radiation,” study author Anurag K. Singh, MD, professor of oncology and director of radiation research at Roswell Park, told Healio. “We’ve been studying better ways to improve pain control in this population because standard narcotics just don’t work that well. Patients tend to use a lot and they still experience pain, but they are sleepier.” A dose-dependent effect In their study, published in Cancer, Singh and colleagues randomly assigned 60 patients with head and neck squamous cell carcinoma to one of two treatment regimens: high-dose gabapentin (2,700 mg daily), progressing sequentially to hydrocodone-acetaminophen and fentanyl when needed (n = 31), or low-dose gabapentin (900 mg daily) progressing to methadone as needed (n = 29). Safety and toxicity served as the study’s primary endpoints. Pain, opioid requirement and quality of life served as secondary endpoints. Results showed no difference in pain between the treatment groups, but more patients in the high-dose gabapentin group did not need an opioid while receiving [...]

Increasing ion channel function in cancer T cells could be new immunotherapy

Source: Author: Ameet Chimote et al. A previously unknown T cell mechanism that could explain the reason behind decreased immune function in cancer patients has been discovered. According to the researchers, their finding may present a new immunotherapeutic target for patients with head and neck cancers. The study, conducted at the University of Cincinnati (UC), US, revealed that a reduced interaction between a molecule called calmodulin and the ion channel KCa3.1 in the immune cells of cancer patients plays an important role in the limited function of these cells. The team performed experiments on cytotoxic T cells taken from the blood of patients with head and neck cancer. “Cytotoxic T cells are like the soldiers of our immune system and are our body’s first line of defence against cancerous tumours,” said first author Ameet Chimote. “These cytotoxic T cells are expected to penetrate the solid tumours by migrating within the tumour mass and then secreting chemicals called cytokines to kill these tumour cells. Sadly, for some reason, these cells do not function properly in patients with cancer and they do not penetrate the tumours and attack the tumour cells, causing the cancerous tumours to grow uncontrollably.” Lead researcher Professor Laura Conforti, explained: “Identifying the mechanism of this underlying dysfunction can help us identify molecules that we can target with drugs and ultimately restore the ability of these cells to enter and kill the tumours.” Molecules, known as ion channels, are present in the T-cell membranes and are essential for [...]

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