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

Source: www.eurekalert.org 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 [...]

2020-03-28T19:03:40-07:00March, 2020|Oral Cancer News|
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Okayama University Research: disrupting blood supply to tumors as a new strategy to treat oral cancer

Source: www.prnewswire.com 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 [...]

2020-03-17T08:22:26-07:00March, 2020|Oral Cancer News|
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Identified: 15 genes that trigger rapid growth of head and neck squamous cell carcinoma

Source: medicalxpress.com 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 [...]

2020-03-13T18:53:30-07:00March, 2020|Oral Cancer News|
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Gabapentin shows efficacy as opioid alternative for patients with head and neck cancer

Source: www.healio.com 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 [...]

2020-03-13T06:43:56-07:00March, 2020|Oral Cancer News|
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Increasing ion channel function in cancer T cells could be new immunotherapy

Source: www.drugtargetreview.com 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 [...]

2020-03-12T10:53:22-07:00March, 2020|Oral Cancer News|
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Another vaping hazard: less-healthy mouths

Source: www.usnews.com/ Author: Serena Gordon, HealthDay Reporter Your lungs might not be your only concern if you're trying electronic cigarettes -- your mouth may pay the price, too. Vaping alters the natural bacteria found in the mouth, leaving you more vulnerable to oral infections and inflammation, a new study reports. The researchers said this study is the first to show that vaping can alter the natural balance of beneficial bacteria (microbiome) in the mouth, adding to the list of potential health effects associated with e-cigarette use. "Cells that are exposed to e-cigarettes are more susceptible to infections," said the study's senior author, Deepak Saxena. He's a professor of basic science and craniofacial biology at NYU College of Dentistry in New York City. Saxena said that e-cigarettes also lead to increased inflammation, which harms oral health. And once someone develops inflammation, it's possible to develop white patches in the mouth called leukoplakia that sometimes develop into cancer. However, this study doesn't have enough long-term evidence to show whether or not these changes could lead to oral cancers in the future, Saxena said. "Our study is just one piece of this big puzzle on e-cigarettes, and I would advise people to not use them. If you have not started, don't start. Nicotine is highly addictive," he said. A U.S. Centers for Disease Control and Prevention report from November suggested that as many as one out of every five U.S. high school students had vaped in the last month. That's especially concerning since [...]

2020-02-27T09:26:31-07:00February, 2020|Oral Cancer News|
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What’s coming down the pike in the dental profession?

Source: www.dentistryiq.com Author: Richard H. Nagelberg, DDS A plethora of dental research is underway in the US as well as globally. Some of these advancements will come to fruition and be commercially available, and some will die on the vine. There are innovations in essentially every dental discipline, with breakthroughs that have the potential to enhance oral health in ways we couldn’t imagine in the past. The impact of artificial intelligence (AI) will increase in the future. AI is already at work in hospitals to diagnose cancer and anticipate trends in health care. AI will have a significant effect in the dental profession on a daily basis, from evaluating images for pathology, to prosthetics and systemic care, among many others. AI promises to increase efficiency in dental practice by facilitating faster diagnosis, predictive analytics, and autocharting. Other areas of research and development include gene therapy and stem cells. Research is underway using gene therapy to restore salivary function in patients who have undergone radiation treatment, which could be a tremendous improvement in health for these individuals. The negative impact of dry mouth extends far beyond the discomfort associated with inadequate or complete lack of saliva. It has a significant effect on the quality of life of the individual and the health of the oral cavity. The ability to restore salivary function could be life-changing for many people. Other initiatives involve transformative research in periodontics, specifically agents operating on the host response and others applied to the diseased periodontal pockets. Some [...]

2020-02-25T08:26:05-07:00February, 2020|Oral Cancer News|
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Absent p53, oral cancers recruit and reprogram nerves to fuel tumor growth

Source: medicalxpress.com Author: by University of Texas M. D. Anderson Cancer Center Loss of an important tumor-suppressing gene allows head and neck cancer to spin off signals to nearby nerves, changing their function and recruiting them to the tumor, where they fuel growth and cancer progression, researchers from The University of Texas MD Anderson Cancer Center report in the journal Nature today. By cracking the mechanism that launches neuronal invasion of tumors, a known marker of poor prognosis for patients, the team has uncovered possible avenues to block the process, including the use of drugs commonly used to treat blood pressure and irregular heartbeat. "Tons of studies show that patients who have lots of nerves in their tumor are doing worse—recurrence rates are higher, survival is shorter," says co-first author Moran Amit, M.D., Ph.D., assistant professor of Head and Neck Surgery. "Nerve endings found in surgically removed tumors can't be easily characterized or tracked back to their source, so it's been a neglected field, a neglected hallmark of cancer." "When surgeons remove head and neck cancers and find a high degree of nerve invasion, post-surgical radiation sometimes is effective," said co-senior author Jeffrey Myers, M.D., Ph.D., chair of Head and Neck Surgery. "But we really haven't understood whether the tumor was growing into the nerves or the nerve growing into the tumor and what signaling drove those interactions." Co-senior author George Calin, M.D., Ph.D., professor of Experimental Therapeutics and an expert on non-coding RNAs added that the paper "puts together [...]

2020-02-13T08:56:02-07:00February, 2020|Oral Cancer News|
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FDA grants fast track designation to NBTXR3 in locally advanced head and neck cancers

Source: www.targetedonc.com Author: Nichole Tucker An FDA Fast Track Designation was granted to the first-in-class radioenhancer NBTXR3 with or without cetuximab (Erbitux) for the treatment of patients with locally advanced head and neck squamous cell cancer who are not eligible for platinum-based chemotherapy, according to a press release from Nanobiotix.1 NBTXR3 showed preliminary signals of antitumor activity in this patient population in a phase I study of 12 patients with advanced-stage head and neck squamous cell carcinoma (HNSCC). Specifically, 10 of the 11 evaluable patients had a complete response (CR) or a partial response to treatment, which included 2 CRs at dose levels ≤10% and 5 CRs at dose levels >10%.2 Treatment with NBTXR3 was also found to be safe and tolerable in patients with HNSCC. There were no serious adverse events or dose-limiting toxicities (DLTs) observed, which allowed patients to continue with their treatment as planned. The adverse events found to be related to injection with NBTXR3 included grade 1/2 injection pain and tumor hemorrhage. Patients in the study received either a single intratumor injection or single-arterial injection of NBTXR3 on day 1 followed by intensity-modulated radiation therapy 2 hours later, which lasted for up to 7 weeks. Radiotherapy was continued in all patients unless their tumor did not shrink by 50% of the baseline size. Those patients who did achieve the tumor shrinkage goals then received salvage tumor surgery. The primary end point of the study was the determination of the recommended dose of the drug and early [...]

2020-02-11T08:31:16-07:00February, 2020|Oral Cancer News|
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Surveillance of ctDNA in HPV-positive head and neck cancers may predict recurrence

Source: www.targetedonc.com Author: Nichole Tucker The detection of circulating tumor DNA (ctDNA) in human papillomavirus (HPV) with an experimental blood test has been associated with high positive predictive value (PPV) and negative predictive value (NPV) for identifying disease recurrence in HPV-positive oropharyngeal cancer, according to a press release from the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center.1 “The major utility of this test is it’s going to improve our ability to monitor patients after they complete treatment,” said Bhisham Chera, MD, associate professor in the UNC School of Medicine Department of Radiation Oncology. “Currently, our methods to assess whether the cancer has recurred are invasive, expensive and not always accurate.” In a prospective biomarker clinical trial published in the Journal of Clinical Oncology, investigators obtained 1006 blood samples for their analysis, 999 of which were evaluable for plasma circulating tumor human papillomavirus DNA (ctHPVDNA). The goal was to determine if surveillance of ctHPVDNA can facilitate earlier detection of recurrence compared with normal clinical follow-up.2 Patients were followed for a median of 23.7 months (range, 6.1-54.7 months), and out of 115 patients, 13% developed disease recurrence (n = 15). Of these recurrences, 1 was local only, 1 was regional only, 10 were distant only, 1 was local and distant, and the remaining 2 were regional and distant. Following treatment, 87 patients had undetectable ctHPVDNA, and none developed recurrence (95% CI, 96%-100%). The development of a positive ctHPVDNA occurred in 28 patients during post-treatment surveillance. The median time to abnormal [...]

2020-02-07T08:57:22-07:00February, 2020|Oral Cancer News|
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