Publications by authors named "Kevin Bennewith"

Cancers can manifest large variations in tumor phenotypes due to genetic and microenvironmental factors, which has motivated the development of quantitative radiomics-based image analysis with the aim to robustly classify tumor phenotypes in vivo. Positron emission tomography (PET) imaging can be particularly helpful in elucidating the metabolic profiles of tumors. However, the relatively low resolution, high noise, and limited PET data availability make it difficult to study the relationship between the microenvironment properties and metabolic tumor phenotype as seen on the images.

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Oral squamous cell carcinoma (OSCC) remains an understudied and significant global cancer killer and dismal survival rates have not changed in decades. A better understanding of the molecular basis of OSCC progression and metastasis is needed to develop new approaches for treating this disease. The supportive network surrounding cancer tumor cells known as the tumor microenvironment (TME) has gained increasing interest lately since it performs essential protumorigenic functions.

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Article Synopsis
  • - Oral squamous cell carcinoma (OSCC) is a prevalent head and neck cancer with a low 5-year survival rate, highlighting the urgent need for improved treatment strategies and a deeper understanding of tumor development mechanisms.
  • - The tumor microenvironment (TME), especially cancer-associated fibroblasts (CAFs), plays a vital role in tumor progression, and recent studies are investigating how extracellular vesicles (EVs) from OSCC cells contribute to CAF activation.
  • - Research findings indicate that OSCC-derived EVs can activate oral fibroblasts into unique CAFs with distinct inflammatory profiles that differ from those activated by traditional pathways like TGFβ, suggesting alternative mechanisms and potential new therapeutic targets.
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Immunotherapy has changed the way many cancers are being treated. Researchers in the field of immunotherapy and tumor immunology are investigating similar questions: How can the positive benefits achieved with immunotherapies be enhanced? Can this be achieved through combinations with other agents and if so, which ones? In our view, there is an urgent need to improve immunotherapy to make further gains in the overall survival for those patients that should benefit from immunotherapy. While numerous different approaches are being considered, our team believes that drug delivery methods along with appropriately selected small-molecule drugs and drug candidates could help reach the goal of doubling the overall survival rate that is seen in some patients that are given immunotherapeutics.

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Organotypic cultures of murine brain slices are well-established tools in neuroscience research, including electrophysiology studies, modeling neurodegeneration, and cancer research. Here, we present an optimized brain slice invasion assay that models glioblastoma multiforme (GBM) cell invasion into organotypic brain slices. Using this model, human GBM spheroids can be implanted with precision onto murine brain slices and cultured to allow tumour cell invasion into the brain tissue.

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Metastatic breast cancer is challenging to effectively treat, highlighting the need for an improved understanding of host factors that influence metastatic tumor cell colonization and growth in distant tissues. The lungs are a common site of breast cancer metastasis and are host to a population of tissue-resident eosinophils. Eosinophils are granulocytic innate immune cells known for their prominent roles in allergy and Th2 immunity.

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Oxygen plays a fundamental role in respiration and metabolism, and quantifying oxygen levels is essential in many environmental, industrial, and research settings. Microdevices facilitate the study of dynamic, oxygen-dependent effects in real time. This review is organized around the key needs for oxygen measurement in microdevices, including integrability into microfabricated systems; sensor dynamic range and sensitivity; spatially resolved measurements to map oxygen over two- or three-dimensional regions of interest; and compatibility with multimodal and multianalyte measurements.

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Article Synopsis
  • Current lung cancer treatments don't work well for everyone, and researchers want to find out why so they can make better options.
  • They discovered that changes in lung cancer cells, like mutations in certain genes (EGFR and KRAS), can produce proteins that mess with how the immune system works.
  • By reducing a protein called CCL5 in mice with lung cancer, researchers found that the immune system was able to fight the tumor better, suggesting targeting CCL5 could help improve treatments for lung cancer patients.
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  • Some cancer cells in tumors can have low oxygen levels, making them tough against radiation treatment, which is what we studied.
  • We looked at two types of tumor cells to see how long they stay low on oxygen and how they react to radiation and a special drug that increases oxygen.
  • We found that certain low-oxygen cells can survive for a while after radiation, but high doses of radiation can actually harm these cells due to blood flow problems.
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Background: A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia).

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Article Synopsis
  • Scientists found that areas in the body called germinal centers (GCs) can become low in oxygen (hypoxic) when dealing with tumors in mice.
  • This lack of oxygen makes it harder for immune cells called B cells to grow and produce important antibodies.
  • They also discovered that this problem with low oxygen happens in humans with breast cancer too, which means it might be a big issue for fighting tumors.
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The ability of cancer cells to invade surrounding tissues requires degradation of the extracellular matrix (ECM). Invasive structures, such as invadopodia, form on the plasma membranes of cancer cells and secrete ECM-degrading proteases that play crucial roles in cancer cell invasion. We have previously shown that the protein tyrosine phosphatase alpha (PTPα) regulates focal adhesion formation and migration of normal cells.

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  • Scientists are finding connections between diseases like Parkinson's and cancer, specifically looking at a gene called LRRK2.
  • They discovered that when LRRK2 is less active in lung cancer patients, it is often linked to smoking and worse chances of survival.
  • In experiments with mice, removing LRRK2 made lung tumors grow more, showing that this gene might help protect against lung cancer.
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Purpose: To evaluate the 15-year impact of a transdisciplinary research training program for graduate students, postdoctoral fellows, and clinical trainees focused on radiation science, entitled Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21) with a primary objective to build capacity in radiation research.

Methods And Materials: Alumni (n = 128) and mentors (n = 41) who participated in STARS21 between 2003 and 2018 were sent an anonymized online survey designed to evaluate the program. Twelve alumni and 7 mentors also volunteered to participate in semistructured interviews.

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Hypoxic tumour cells are radiation-resistant and are associated with poor therapeutic outcome. A poorly understood source of tumour hypoxia is unstable perfusion, which exposes tumour cells to varying oxygen tensions over time creating "transiently" hypoxic cells. Evidence suggests that angiotensin II type 1 receptor blockers (ARBs) can improve tumour perfusion by reducing collagen deposition from cancer associated fibroblasts (CAFs).

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A Retraction to this paper has been published and can be accessed via a link at the top of the paper.

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Background: Solid tumors produce proteins that can induce the accumulation of bone marrow-derived cells in various tissues, and these cells can enhance metastatic tumor growth by several mechanisms. 4T1 murine mammary tumors are known to produce granulocyte colony-stimulating factor (G-CSF) and increase the numbers of immunosuppressive CD11bGr1 myeloid-derived suppressor cells (MDSCs) in tissues such as the spleen and lungs of tumor-bearing mice. While surgical resection of primary tumors decreases MDSC levels in the spleen, the longevity and impact of MDSCs and other immune cells in the lungs after tumor resection have been less studied.

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Tumours are complex systems of genetically diverse malignant cells that proliferate in the presence of a heterogeneous microenvironment consisting of host derived microvasculature, stromal, and immune cells. The components of the tumour microenvironment (TME) communicate with each other and with cancer cells, to regulate cellular processes that can inhibit, as well as enhance, tumour growth. Therapeutic strategies have been developed to modulate the TME and cancer-associated immune response.

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Article Synopsis
  • Hypoxia, or low oxygen levels, makes tumors more aggressive and patients have a harder time surviving.
  • Scientists found that tiny RNA molecules called piRNAs could help explain why some cancer patients do worse than others when they have tumors with low oxygen.
  • They discovered new piRNAs linked to hypoxic tumors and created a score to predict how likely it is for these tumors to come back, especially in early-stage lung cancer.
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Only 3% of the transcribed human genome is translated into protein, and small non-coding RNAs from these untranslated regions have demonstrated critical roles in transcriptional and translational regulation of proteins. Here, we provide a resource that will facilitate cell line selection for gene expression studies involving sncRNAs in cancer research. As the most accessible and tractable models of tumours, cancer cell lines are widely used to study cancer development and progression.

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  • The study looked at how a low dose of radiation (2.3 Gy) affects breast cancer cells, especially if it makes them move more, which is important in cancer spread.* -
  • They found that while the low dose didn't seem to change some cells much, it did make another type of cell (MDA-MB-231) move more without making them more invasive.* -
  • The researchers also discovered that the cells released special substances that could make other nearby cancer cells move more, suggesting that radiation might help cancer cells communicate and spread.*
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  • Malignant mesotheliomas are serious cancers caused by asbestos, making it hard for patients to get better.!
  • These cancers usually happen in the lining of the lungs or belly, and they have symptoms that are easy to confuse with other diseases.!
  • Researchers are studying how to fight these cancers better by focusing on their weak spots, especially how they deal with low oxygen levels inside the tumors.!
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Packaging of small molecular factors, including miRNAs, into small extracellular vesicles (SEVs) may contribute to malignant phenotypes and facilitate communication between cancer cells and tumor stroma. The process by which some miRNAs are enclosed in SEVs is selective rather than indiscriminate, with selection in part governed by specific miRNA sequences. Herein, we describe the selective packaging and removal via SEVs of four miRNAs (miR-142-3p, miR-150-5p, miR-451a, and miR-223-3p) in a panel of oral dysplasia and oral squamous cell carcinoma cell lines.

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Solid tumor perfusion is a proven variable of interest for predicting cancer aggression and response to therapy. Current methods for noninvasively imaging tumor perfusion with PET are limited by restricted accessibility and short half-lives of perfusion radiotracers. This study presents 2-F-fluoroethanol (2-F-FEtOH) as a perfusion reporter that can distinguish between tumors of varying perfusion levels and can be applied to screening drugs that modify tumor perfusion.

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