Publications by authors named "Fran Balkwill"

Background: Lockdown measures, including school closures, due to the COVID-19 pandemic have caused widespread disruption to children's lives. The aim of this study was to explore the impact of a national lockdown on children's physical activity using seasonally matched accelerometry data.

Methods: Using a pre/post observational design, 179 children aged 8 to 11 years provided physical activity data measured using hip-worn triaxial accelerometers worn for 5 consecutive days prepandemic and during the January to March 2021 lockdown.

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TNF-α is a major inflammatory cytokine named for its ability to induce rapid hemorrhagic necrosis of experimental cancers. During efforts to harness this antitumor activity in cancer treatments in the 1980s, a paradoxical tumor-promoting role of TNF became apparent. The cellular and molecular complexity of mammalian tumor microenvironments makes these opposing effects difficult to study.

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The chemokine receptor CXCR4 is expressed by malignant cells in ovarian cancer and is implicated in their growth and spread. We report here a unique mechanism of action of a small peptide antagonist of CXCR4 on ovarian cancer cells: induction of cell death by mitotic catastrophe. CTCE-9908 inhibited ovarian cancer cell migration to CXCL12, but on longer incubation, caused cell death in CXCR4-positive cells.

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IFN-gamma has direct anti-proliferative effects on ovarian cancer cell lines and tumour cells isolated from ovarian cancer ascites. The aim of this study was to further elucidate the mechanisms involved. An IFN-gamma-mediated cell cycle blockade was detectable in synchronised cell populations.

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Immunologists need to establish a vibrant dialogue with young people. This is not only important for the continuation and progress of biomedical research, but it can also contribute to the fight against diseases such as HIV/AIDS and can help young people to make informed decisions about lifestyle, medical treatment and ethical issues. Good communication skills are crucial to any scientific career, and the lessons learned from talking with non-scientists can also be useful when writing scientific papers and grants.

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Cytokine and chemokine gradients are central to the directed movement of cells in both homeostatic and pathological processes. Most cancers have a complex chemokine network which can influence immune responses to the tumor, direct the extent and cellular composition of the leukocyte infiltrate and also play a role in angiogenesis. Tumor cells can also hijack the chemokine system and gain expression of certain chemokine receptors and respond to specific chemokine gradients.

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Malignant cells from at least 23 different types of cancer express the chemokine receptor CXCR4 and respond to its ligand CXCL12. This receptor ligand pair appears to be involved in directed migration of cancer cells to sites of metastasis, increased survival of cancer cells in sub optimal conditions and establishment of a tumour promoting cytokine/chemokine network. Preliminary data from animal models suggest that CXCR4 may be an important therapeutic target in a range of cancers.

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A network of inflammatory cytokines and chemokines is found in epithelial cancer. There is evidence that these mediators contribute not only to tumour cell growth and survival, but also to communication between the cancer cells and stromal elements. Tumour cell production of the inflammatory cytokine tumour necrosis factor alpha (TNFalpha) is one critical factor in this autocrine and paracrine network.

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Purpose: The purpose of this study was to compare in vitro and in vivo responses of primary human tumor cells to IFN-gamma.

Experimental Design: IFN-gamma may have therapeutic activity in patients with ovarian cancer. We showed previously that this cytokine had direct antiproliferative activity against human ovarian cancer cell lines and xenografts in nude mice.

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Chemokine biology in cancer.

Semin Immunol

February 2003

Many human cancers possess a complex chemokine network that may influence the extent and phenotype of the leukocyte infiltrate, angiogenesis, tumor cell growth, survival and migration. Restricted expression of chemokine receptors on leukocytes may allow concise control of cell movement and retention at the tumor site. Restricted and specific expression of chemokine receptors on tumor cells may be involved in the characteristic patterns of metastasis, and may promote tumor cell growth and survival.

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The epithelial tumour microenvironment is a complex tissue comprising variable numbers of tumour cells, fibroblasts, endothelial cells and infiltrating leucocytes. Cytokines are key molecules controlling autocrine or paracrine communications within and between these individual cell types. Under some circumstances, endogenous cytokines may orchestrate host responses against the tumour, but there is increasing evidence that the cytokine network contributes to tumour growth, progression and host immuno-suppression.

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Purpose: Ascitic disease is a common occurrence in human ovarian cancer, but it is unclear how the cellular composition of ascitic fluid is determined. Because chemokines can determine host cell infiltration in solid ovarian cancer, we assessed CC chemokine protein and CC chemokine receptor expression in ovarian cancer ascites.

Experimental Design: We used reverse transcription-PCR and RNase protection assay to determine CC chemokine and chemokine receptor mRNA expression and ELISA to measure CC chemokine protein levels.

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