Diffuse glioma is a highly heterogeneous central nervous system tumor that is refractory to conventional therapy. Residual glioma cells escape from surgery and chemoradiotherapy, leading to lethal recurrence. Understanding the molecular mechanism of this recurrence process is critical to the development of successful therapies. Here, we analyzed whole-exome sequencing (WES) data of 97 paired primary and recurrent samples from 46 patients with glioma via a uniform pipeline. Clonality and phylogenetic analyses revealed that branching evolution was widespread in the recurrent process of gliomas. Recurrent tumors continued to evolve independently with chemoradiotherapy and harbored multiple recurrence-selected genetic alterations, such as amplification of PPFIBP1, PDE4DIP, and KRAS, deletion of TNFRSF14, DCC, CDKN2A, and MSH6, and mutations in ATRX, ARID1A, KEL, TP53, MSH6, and KMT2B. Meanwhile, truncal variants within partial driver genes were identified among primary and recurrent gliomas, suggesting that they might be ideal therapeutic targets. Intriguingly, the immunogenicity of recurrent gliomas did not increase significantly compared to the primary tumors. Genomic analysis of recurrent gliomas provided an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors.

UNASSIGNED: Chondrosarcoma is a common form of malignant bone tumor with limited treatment options. Approximately half of chondrosarcomas harbor gain-of-function mutations in isocitrate dehydrogenase (IDH), and mutant IDH produces 2-hydroxyglutarate (2-HG), which is an oncometabolite that contributes to malignant transformation. Therefore, inhibiting 2-HG production is a novel and promising treatment for advanced chondrosarcoma. 2-HG is also expected to be a useful biomarker for the diagnosis and treatment of IDH-mutant tumors. However, few studies have confirmed this using chondrosarcoma clinical specimens. Non-invasive monitoring of 2-HG levels is useful to infer that mutant IDH inhibitors reach therapeutic targets and to confirm their therapeutic efficacy in clinical practice.
UNASSIGNED: To evaluate the clinical utility of 2-HG as a surrogate biomarker for diagnosis and therapeutic efficacy, we measured intra-tumor and serum levels of 2-HG using frozen tissues and peripheral blood from patients with chondrosarcoma. We also developed a non-invasive method to detect intra-tumor 2-HG signals in vivo using magnetic resonance spectroscopy (MRS).
UNASSIGNED: Both intratumoral and serum 2-HG levels were significantly elevated in IDH-mutant tumors, and these levels correlated with decreased survival. Furthermore, we detected intratumoral 2-HG peaks using MR spectroscopy in a xenograft model of IDH-mutant chondrosarcoma, and observed that 2-HG peak signals disappeared after administering an inhibitor of mutant IDH1.
UNASSIGNED: Our findings suggest that both intratumoral and serum 2-HG levels represent potentially useful biomarkers for IDH-mutant tumors and that the 2-HG signal in MR spectra has potential value as a non-invasive biomarker. Taken together, these findings may positively impact the clinical development of mutant IDH inhibitors for the treatment of advanced chondrosarcoma.

UNASSIGNED: To investigate the clinical relevance of the radiotherapy (RT) dose bath in patients treated for lower grade glioma (LGG).
UNASSIGNED: Patients (n = 17) treated with RT for LGG were assessed with neurocognitive function (NCF) tests and structural Magnetic Resonance Imaging (MRI) and categorized in subgroups based on tumour lateralisation. RT dose, volumetric results and cerebral microbleed (CMB) number were extracted for contralateral cerebrum, contralateral hippocampus, and cerebellum. The RT clinical target volume (CTV) was included in the analysis as a surrogate for focal tumour and other treatment effects. The relationships between RT dose, CTV, NCF and radiological outcome were analysed per subgroup.
UNASSIGNED: The subgroup with left-sided tumours (n = 10) performed significantly lower on verbal tests. The RT dose to the right cerebrum, as well as CTV, were related to poorer performance on tests for processing speed, attention, and visuospatial abilities, and more CMB.In the subgroup with right-sided tumours (n = 7), RT dose in the left cerebrum was related to lower verbal memory performance, (immediate and delayed recall, r = -0.821, p = 0.023 and r = -0.937, p = 0.002, respectively), and RT dose to the left hippocampus was related to hippocampal volume (r = -0.857, p = 0.014), without correlation between CTV and NCF.
UNASSIGNED: By using a novel approach, we were able to investigate the clinical relevance of the RT dose bath in patients with LGG more specifically. We used combined MRI-derived and NCF outcome measures to assess radiation-induced brain damage, and observed potential RT effects on the left-sided brain resulting in lower verbal memory performance and hippocampus volume.

OBJECTIVE: Advanced biliary tract cancer (ABTC) is associated with a poor prognosis. Real-world data on the outcome of patients with ABTC undergoing sequential chemotherapies remain scarce, and little is known about treatment options beyond the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX. This study aimed to evaluate the outcome of patients with regard to different oncological therapies and to identify prognostic factors.
METHODS: From January 2010 until December 2019, 142 patients started palliative chemotherapy at our tertiary care liver center. Overall survival (OS) was calculated using Kaplan-Meier plots. Prognostic factors were evaluated using cox proportional-hazards.
RESULTS: Patients received a median number of 2 lines of chemotherapy. Median OS was 6.7, 15.2 and 18.2 months for patients who received 1, 2 and 3 lines of chemotherapy, respectively. Patients treated with FOLFIRINOX had a significantly extended OS of 23.8 months (log-rank test: p = 0.018). The univariate cox regression analysis identified several clinical parameters associated with survival (e.g. albumin, bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9 levels).
CONCLUSIONS: Our study provides real-world data on the prognosis of ABTC including survival times for patients receiving third and later lines of chemotherapy.
BACKGROUND: Real-world data depicting the outcome of patients with advanced biliary tract cancer outside the framework of controlled trials remain rare despite being extremely important for clinical decision-making. This study therefore provides important real-world data on the established first- and second-line treatments with gemcitabine + cisplatin and FOLFOX, as well as on other chemotherapy regimens or later lines of chemotherapy. It further demonstrates that the use of FOLFIRINOX is associated with promising survival and that there is an association between various clinical parameters such as pre-therapeutic albumin, bilirubin or carbohydrate antigen 19-9 levels and survival.

An important priority in the cardiovascular care of oncology patients is to reduce morbidity and mortality, and improve the quality of life in cancer survivors through cross-disciplinary efforts. The rate of survival in cancer patients has improved dramatically over the past decades. Nonetheless, survivors may be more likely to die from cardiovascular disease in the long term, secondary, not only to the potential toxicity of cancer therapeutics, but also to the biology of cancer. In this context, efforts from basic and translational studies are crucial to understanding the molecular mechanisms causal to cardiovascular disease in cancer patients and survivors, and identifying new therapeutic targets that may prevent and treat both diseases. This review aims to highlight our current understanding of the metabolic interaction between cancer and the heart, including potential therapeutic targets. An overview of imaging techniques that can support both research studies and clinical management is also provided. Finally, this review highlights opportunities and challenges that are necessary to advance our understanding of metabolism in the context of cardio-oncology.

Biliary tract cancers (BTCs) are aggressive epithelial malignancies that can arise at any point of the biliary tree. Albeit rare, their incidence and mortality rates have been rising steadily over the past 40 years, highlighting the need to improve current diagnostic and therapeutic strategies. BTCs show high inter- and intra-tumour heterogeneity both at the morphological and molecular level. Such complex heterogeneity poses a substantial obstacle to effective interventions. It is widely accepted that the observed heterogeneity may be the result of a complex interplay of different elements, including risk factors, distinct molecular alterations and multiple potential cells of origin. The use of genetic lineage tracing systems in experimental models has identified cholangiocytes, hepatocytes and/or progenitor-like cells as the cells of origin of BTCs. Genomic evidence in support of the distinct cell of origin hypotheses is growing. In this review, we focus on recent advances in the histopathological subtyping of BTCs, discuss current genomic evidence and outline lineage tracing studies that have contributed to the current knowledge surrounding the cell of origin of these tumours.

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BACKGROUND: Chondrosarcomas are malignant cartilage-producing tumors showing mutations and changes in gene expression in metabolism related genes. In this study, we aimed to explore the metabolome and identify targetable metabolic vulnerabilities in chondrosarcoma.
METHODS: A custom-designed metabolic compound screen containing 39 compounds targeting different metabolic pathways was performed in chondrosarcoma cell lines JJ012, SW1353 and CH2879. Based on the anti-proliferative activity, six compounds were selected for validation using real-time metabolic profiling. Two selected compounds (rapamycin and sapanisertib) were further explored for their effect on viability, apoptosis and metabolic dependency, in normoxia and hypoxia. In vivo efficacy of sapanisertib was tested in a chondrosarcoma orthotopic xenograft mouse model.
RESULTS: Inhibitors of glutamine, glutathione, NAD synthesis and mTOR were effective in chondrosarcoma cells. Of the six compounds that were validated on the metabolic level, mTOR inhibitors rapamycin and sapanisertib showed the most consistent decrease in oxidative and glycolytic parameters. Chondrosarcoma cells were sensitive to mTORC1 inhibition using rapamycin. Inhibition of mTORC1 and mTORC2 using sapanisertib resulted in a dose-dependent decrease in viability in all chondrosarcoma cell lines. In addition, induction of apoptosis was observed in CH2879 after 24 h. Treatment of chondrosarcoma xenografts with sapanisertib slowed down tumor growth compared to control mice.
CONCLUSIONS: mTOR inhibition leads to a reduction of oxidative and glycolytic metabolism and decreased proliferation in chondrosarcoma cell lines. Although further research is needed, these findings suggest that mTOR inhibition might be a potential therapeutic option for patients with chondrosarcoma.

Background: B7-H3 is an immune checkpoint member that belongs to B7-CD28 families and plays a vital role in the inhibition of T-cell function. Importantly, B7-H3 is widely overexpressed on solid tumors, making it become an attractive target for cancer immunotherapy. To clarify the expression panel of B7-H3 in glioma, we explored the clinical and immune features of B7-H3 expression in a large-scale study. Methods and patients: Totally, 1323 glioma samples from Chinese Glioma Genome Atlas (CGGA) dataset, including 325 RNAseq data and 301 mRNA microarray data, and The Cancer Genome Atlas (TCGA) dataset, including 697 RNAseq data, were gathered into our research. The statistical analysis and graphical work were mainly realized by R language. Results: B7-H3 expression was found positively correlated with the grade of malignancy, which might be caused by hypomethylation. The expression level of B7-H3 was consistently up-regulated in IDH wild-type glioma and highly enriched in mesenchymal subtype. GSEA analysis suggested that B7-H3 related genes were more involved in immune response and angiogenesis in glioma. Moreover, B7-H3 showed a consistent positive relationship with stromal and immune cell populations. Further analysis confirmed that B7-H3 played an important role in T-cell-mediated immunity, especially in T-cell-mediated immune response to tumor cell. Circos plots revealed that B7-H3 was tightly associated with most B7 members and other immune checkpoints. Univariate and multivariate cox analysis demonstrated that B7-H3 was an independent prognosticator for glioma patients. Conclusion: B7-H3 represents the malignant phenotype of glioma and independently predicted worse prognosis in glioma patients. Moreover, B7-H3 collaborating with other checkpoint members may contribute to the dysfunctional phenotype of T cell. These findings will be helpful for further optimizing immunotherapies for glioma.

The effect of livingstone potato (Plectranthus esculenthus N.E.Br) on serum glucose, glycated hemoglobin (HbA1C), serum triglyceride, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), hepatic malic enzyme (ME), isocitrate dehydrogenase (IDH) and catalase activities of Streptozotocin induced diabetic rats were investigated using standard techniques. The atherogenic index (AI) and coronary risk index (CRI) of the rats were calculated as the ratios of LDL to HDL and total cholesterol to HDL, respectively. The serum glucose of the non-diabetic, diabetic control and diabetic rats given livingstone potato incorporated feeds (test feed) were 92.58 ± 3.97, 352.30 ± 4.88 and 165.50 ± 7.88 mg/dl, respectively. Intake of the test feed by the diabetic rats of group 3, resulted in significant (P < 0.05) decrease of their serum glucose, HbA1c, triglyceride, cholesterol, LDL, VLDL, AI and CRI but significant increase (P < 0.05) of hepatic levels of ME, IDH, catalase and serum HDL compared with the diabetic control rats that had significant alteration of these parameters (P < 0.05) compared with the non-diabetic rats. The feed intakes of the non-diabetic, diabetic control and diabetic rats given the test feed were 133.34 ± 1.32, 137.84 ± 5.77 and 146.38 ± 4.33 g/rat/week by the last week of experimentation. The diabetic control rats recorded significant loss of weight (P < 0.05) compared with the non diabetic rats despite increased feed intake. Chemical analysis of the standard and test feeds showed that the standard rat feed contained 15.00 ± 0.78% protein, 7.24 ± 1.20% fat, 31.55 ± 2.62% carbohydrates, energy value of 290.65 ± 4.77 kcal/100 g, 10% crude fiber and 0.12 ± 0.04 mg Gallic Acid Equivalent while the test feed contained 40.10 ± 0.16% carbohydrates, 17.22 ± 0.40% protein, 22.16 ± 0.34% fat, energy value of 428.70 ± 2.12 kcal/100 g, 8.51 ± 0.16% crude fiber, 1.3 ± 0.2 mg Gallic Acid Equivalent/g of sample and strong antioxidant activity comparable to standard quercetin. The study shows the potentials of livingstone potato in the management of diabetes and hyperlipidemia.