Study finds major anti-inflammatory immune activity that favors oral cancer tumors

Source: medicalxpress.com Author: Melisa Institute A collaborative research led by immunologist Estefania Nova-Lamperti from the Universidad de Concepción (Chile), with a branch of researchers from MELISA Institute and other international academic centers, made progress in the understanding of molecular mechanisms preventing an effective antitumor immune response in oral cancer; The latter due to the production of chemical mediators that induce an anti-inflammatory regulatory response that favors tumor development through the vitamin D signaling pathway. The study was published in Frontiers in Immunology on May 7, 2021. Oral cancer, 90% of which corresponds to the squamous cell type, is a neoplasm with a high mortality and morbidity rate, mainly because the diagnosis is made in late stages when metastases already exist, and where treatment produces serious physical and functional sequel among survivors. It is well known that the immune system plays a key role in the development of cancer, either by stimulating pathways that play an anti-tumor role or, conversely, by generating an anti-inflammatory environment that allows the tumor to grow and be spread. The main biological agents of the immune system are lymphocytes or T cells, which have different functions or phenotypes. In cancer, the presence of regulatory T cells (Tregs) and helper T cells type 2 (Th2) are associated with a worse prognosis, whereas the responses of helper T cells type 1 (Th1) within tumors, in general, show a better prognosis. Dr. Nova-Lamperti points out that a key question in oral cancer is how an anti-inflammatory microenvironment is induced, [...]

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 [...]

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 [...]

Scientists find new way to boost cancer drugs

Source: www.drbicuspid.com Author: DrBicuspid Staff Shutting down a specific pathway in cancer cells appears to improve the ability of common drugs to wipe those cells out, according to new research from scientists at Fox Chase Cancer Center (Cancer Discovery, January 2013, Vol. 3:1, pp. 96-111). The new approach appears to enhance the tumor-killing ability of a commonly prescribed class of drugs that includes cetuximab (Erbitux), used to treat head and neck cancers. These drugs work by blocking the activity of the epidermal growth factor receptor (EGFR), which sits on the cell surface and senses cues from the environment, telling cancer cells to grow and divide, according to co-author Igor Astsaturov, MD, PhD, an attending physician in the department of medical oncology at Fox Chase. In 2010, Dr. Astsaturov and his colleagues identified a pathway in the cell that, when blocked, completely suppressed EGFR activity. Interestingly, the pathway consists of a series of enzymes that, when working in concert, synthesize new molecules of cholesterol. Working with cancer cells in the lab, the researchers inactivated a key gene in the cholesterol synthesis pathway, and found the cells became more vulnerable to treatment with cetuximab. The same was true in mice that lacked this particular pathway, according to Dr. Astsaturov. "Most tumors are only moderately sensitive to inhibitors of EGFR, but when these tumors lack an essential gene in the cholesterol pathway, they become exquisitely sensitive to the anti-EGFR drugs," he said. "The cancers literally melt away in mice." The researchers then removed [...]

Researchers find potential new therapeutic strategy for head and neck cancer

Source: www.uab.edu Author: Beena Thannickal Shih-Hsin (Eddy) Yang, M.D., Ph.D., an assistant professor in the UAB Department of Radiation Oncology and associate scientist in the experimental therapeutics program at the UAB Comprehensive Cancer Center, found a way to prevent head and neck cancer cells from repairing damage to DNA as they grow. The findings, published by the Public Library of Science, showed that using the drug cetuximab can induce a DNA repair defect in head and neck cancer cells, and subsequently render the tumors susceptible to PARP inhibitors, which block enzymes that repair some types of DNA damage. This method prevents cancer cells from repairing the damage to the DNA as they grow, ultimately leading to cancer inhibition. Poly ADP-ribose polymerases, or PARPs, are enzymes that repair some types of damage done to DNA. If they are inhibited, a backup repair pathway is initiated. Cetuximab, which inhibits the epidermal growth factor receptor signaling pathway of cancer cells, blocks this backup pathway and thus induces cancer cell death. “The novelty of this finding is that we use targeted agents like cetuximab, in combination with a PARP inhibitor, ABT-888, both of which have already been tested to be safe in humans, to selectively kill tumors defective in DNA repair while potentially minimizing side effects,” says Yang. Cetuximab was pioneered by James Bonner, M.D., chair of the UAB Department of Radiation Oncology, in a landmark multi-institutional clinical trial in head and neck cancer patients. Because head and neck cancers are frequently aggressive, outcomes [...]

2011-09-23T16:29:08-07:00September, 2011|Oral Cancer News|
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