N -butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumours

Abnormalities in glycosphingolipid (GSL) biosynthesis have been implicated in the oncogenesis and malignancy of brain tumours. GSLs comprise the gangliosides and the neutral GSLs and are major components of the cell surface glycocalyx. N -butyldeoxynojirimycin (N B-DNJ) is an imino sugar that inhibits the glucosyltransferase catalysing the first step in GSL biosynthesis. The influence of N B-DNJ was studied on the growth and ganglioside composition of two 20-methylcholanthrene-induced experimental mouse brain tumours, EPEN and CT-2A, which were grown in vitro and in vivo. N B-DNJ (200 μM) inhibited the proliferation of the EPEN and CT-2A cells by 50%, but did not reduce cell viability. The drug, administered in the diet (2400 mg kg−1) to adult syngeneic C57BL/6 mice, reduced the growth and ganglioside content of subcutaneous and intracerebral EPEN and CT-2A tumours by at least 50% compared to the untreated controls. N B-DNJ treatment also shifted the relative distribution of tumour gangliosides in accordance with the depletion of metabolic substrates. Side effects of N B-DNJ treatment were generally mild and included reductions in body and spleen weights and intestinal distension. We conclude that N B-DNJ may inhibit tumour growth through an effect on ganglioside biosynthesis and may be useful as a new chemotherapy for brain tumours. © 2001 Cancer Research Campaign http://www.bjcancer.co

Exploration of 2-deoxy-D-ribose and 17β-Estradiol as alternatives to exogenous VEGF to promote angiogenesis in tissue-engineered constructs

Aim: In this study, we explored the angiogenic potential and proangiogenic concentration ranges of 2-deoxy-D-ribose (2dDR) and 17β-Estradiol (E2) in comparison with VEGF. The 2dDR and E2 were then loaded into tissue engineering (TE) scaffolds to investigate their proangiogenic potential when released from fibers. Materials & methods:Ex ovo chick chorioallantoic membrane (CAM) assay was used to evaluate angiogenic activity of 2dDR and E2. Both factors were then introduced into scaffolds via electrospinning to assess their angiogenic potential when released from fibers. Results: Both factors were approximately 80% as potent as VEGF and showed a dose-dependent angiogenic response. The sustained release of both agents from the scaffolds stimulated neovascularization over 7 days in the chorioallantoic membrane assay. Conclusion: We conclude that both 2dDR and E2 provide attractive alternatives to VEGF for the functionalization of tissue engineering scaffolds to promote angiogenesis in vivo

A framework to guide planetary health education

People around the world are increasingly facing the pressing challenges of today's interconnected environmental, social, and health crises. The COVID-19 pandemic has been an important wake-up call reminding us that we need a healthy planet to ensure the health of all people. The emerging field of planetary health is a framework for understanding these interconnections and identifying solutions to the complex challenges confronting our civilization. Building on the unique role and responsibility of education institutions in shaping our futures, embedding planetary health education in curricula is an essential step to achieving the transformative change needed. Planetary health education across all levels and disciplines will equip and enable learners to drive transdisciplinary and mutually reinforcing actions to protect and restore planetary health and achieve the Sustainable Development Goals

Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors

BACKGROUND: Somatic mutations in the mitochondrial genome occur in numerous tumor types including brain tumors. These mutations are generally found in the hypervariable regions I and II of the displacement loop and unlikely alter mitochondrial function. Two hypervariable regions of mononucleotide repeats occur in the mouse mitochondrial genome, i.e., the origin of replication of the light strand (O(L)) and the Arg tRNA. METHODS: In this study we examined the entire mitochondrial genome in a series of chemically induced brain tumors in the C57BL/6J strain and spontaneous brain tumors in the VM mouse strain. The tumor mtDNA was compared to that of mtDNA in brain mitochondrial populations from the corresponding syngeneic mouse host strain. RESULTS: Direct sequencing revealed a few homoplasmic base pair insertions, deletions, and substitutions in the tumor cells mainly in regions of mononucleotide repeats. A heteroplasmic mutation in the 16srRNA gene was detected in a spontaneous metastatic VM brain tumor. CONCLUSION: None of the mutations were considered pathogenic, indicating that mtDNA somatic mutations do not likely contribute to the initiation or progression of these diverse mouse brain tumors

Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model

Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30–40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13 Kcal day−1, respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cell-induced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers

Ganglioside composition and histology of a spontaneous metastatic brain tumour in the VM mouse

Glycosphingolipid abnormalities have long been implicated in tumour malignancy and metastasis. Gangliosides are a family of sialic acid-containing glycosphingolipids that modulate cell–cell and cell–matrix interactions. Histology and ganglioside composition were examined in a natural brain tumour of the VM mouse strain. The tumour is distinguished from other metastatic tumour models because it arose spontaneously and metastasizes to several organs including brain and spinal cord after subcutaneous inoculation of tumour tissue in the flank. By electron microscopy, the tumour consisted of cells (15 to 20 μm in diameter) that had slightly indented nuclei and scant cytoplasm. The presence of smooth membranes with an absence of junctional complexes was a characteristic ultrastructural feature. No positive immunostaining was found for glial or neuronal markers. The total ganglioside sialic acid content of the subcutaneously grown tumour was low (12.6 ± 0.9 μg per 100 mg dry wt, n= 6 separate tumours) and about 70% of this was in the form of N-glycolylneuraminic acid. In contrast, the ganglioside content of the cultured VM tumour cells was high (248.4 ± 4.4 μg, n= 3) and consisted almost exclusively of N-acetylneuraminic acid. The ganglioside pattern of the tumour grown subcutaneously was complex, while GM3, GM2, GM1, and GD1a were the major gangliosides in the cultured tumour cells. This tumour will be a useful natural model for evaluating the role of gangliosides and other glycolipids in tumour cell invasion and metastasis. © 2001 Cancer Research Campaign http://www.bjcancer.co