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Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely fragile making it an attractive therapeutic target. A subset of small-molecule tubulin binding agents cause disaggregation of the endothelial cytoskeleton leading to enhanced vascular permeability generating increased interstitial pressure. The resulting vascular collapse and ischemia cause downstream hypoxia, ultimately leading to cell death and necrosis. Thus, local damage generates massive amplification and tumor destruction. The tumor vasculature is readily accessed and potentially a common target irrespective of disease site in the body. Development of a therapeutic approach and particularly next generation agents benefits from effective non-invasive assays. Imaging technologies offer varying degrees of sophistication and ease of implementation. This review considers technological strengths and weaknesses with examples from our own laboratory. Methods reveal vascular extent and patency, as well as insights into tissue viability, proliferation and necrosis. Spatiotemporal resolution ranges from cellular microscopy to single slice tomography and full three-dimensional views of whole tumors and measurements can be sufficiently rapid to reveal acute changes or long-term outcomes. Since imaging is non-invasive, each tumor may serve as its own control making investigations particularly efficient and rigorous. The concept of tumor vascular disruption was proposed over 30 years ago and it remains an active area of research.

The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha . Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha . We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza . The wild rice species can be used as germplasm resources for this crop’s genetic improvement. Here Chen and colleagues report the de novo sequencing of the O. brachyantha genome, and identify the origin of genome size variation, the role of gene movement and its implications on heterochromatin evolution in the rice genome.

Longitudinal MRI was applied to monitor intracranial initiation and development of brain metastases and assess tumor vascular volume and permeability in a mouse model of breast cancer brain metastases. Using a 9.4T system, high resolution anatomic MRI and dynamic susceptibility contrast (DSC) perfusion MRI were acquired at different time points after an intracardiac injection of brain-tropic breast cancer MDA-MB231BR-EGFP cells. Three weeks post injection, multifocal brain metastases were first observed with hyperintensity on T2-weighted images, but isointensity on T1-weighted post contrast images, indicating that blood-tumor-barrier (BTB) at early stage of brain metastases was impermeable. Follow-up MRI revealed intracranial tumor growth and increased number of metastases that distributed throughout the whole brain. At the last scan on week 5, T1-weighted post contrast images detected BTB disruption in 160 (34%) of a total of 464 brain metastases. Enhancement in some of the metastases was only seen in partial regions of the tumor, suggesting intratumoral heterogeneity of BTB disruption. DSC MRI measurements of relative cerebral blood volume (rCBV) showed that rCBV of brain metastases was significantly lower (mean= 0.89±0.03) than that of contralateral normal brain (mean= 1.00±0.03; p<0.005). Intriguingly, longitudinal measurements revealed that rCBV of individual metastases at early stage was similar to, but became significantly lower than that of contralateral normal brain with tumor growth (p<0.05). The rCBV data were concordant with histological analysis of microvascular density (MVD). Moreover, comprehensive analysis suggested no significant correlation among tumor size, rCBV and BTB permeability. In conclusion, longitudinal MRI provides non-invasive in vivo assessments of spatial and temporal development of brain metastases and their vascular volume and permeability. The characteristic rCBV of brain metastases may have a diagnostic value.

Background Ovarian cancer (OC) is the most lethal gynecological malignancy. The objective of this study was to establish and validate an individual aging‐related gene signature and a clinical nomogram that can powerfully predict independently the overall survival rate of patients with ovarian cancer. Methods Data on transcriptomic profile and relevant clinical information were retrieved from The Cancer Genome Atlas (TCGA) database as a training group, and the same data from three public Gene Expression Omnibus (GEO) databases as validation groups. Univariate Cox regression analysis, lasso regression analysis, and multiple multivariate Cox analysis were analyzed sequentially to select the genes to be included in the aging‐associated signature. A risk scoring model was established and verified, the predictive value of the model was evaluated, and a clinical nomogram was established. Results We found eight genes that were most relevant to prognosis and constructed an eight‐mRNA signature. Based on the model, each OC patient's risk score was able to be calculated and patients were split into groups of low and high risks with a distinct outcome. Survival analysis confirmed that the outcome of patients in the high‐risk group was dramatically shorter than that of those in the low‐risk group, and the eight‐mRNA signature can be considered as a powerful and independent predictor that could predict the outcome of OC patient. Additionally, the risk score and age can be used to construct a clinical nomogram as a simpler tool for predicting prognosis. We also explored the association between the risk score and immunity and drug sensitivity. Conclusion This study suggested that the aging‐related gene signature could be used as an intervention point and latent prognostic predictor in OC, which may provide new perceptions for postoperative treatment strategies. We constructed a prognostic signature of eight aging‐related genes and a clinical nomogram that provides potential biomarkers for predicting the prognosis of patients with OC, helps to understand the potential pathogenesis of OC, and can possibly be used to develop new approaches for the clinical treatment of ovarian cancer.

IntroductionPatient-reported outcome-based symptom monitoring and alerting have been attractive for patient care after a tumour-removal surgery. However, the implementation parameters of this patient-centred symptom management system in perioperative patients with lung cancer are still lacking. We aim to develop a perioperative symptom scale (PSS) for monitoring, to determine the optimal time points for symptom assessment and to define the alert thresholds for medical intervention.Methods and analysisThis study will prospectively recruit 300 patients undergoing lung cancer surgery in six hospitals. The MD Anderson Symptom Inventory–Lung Cancer Module (MDASI-LC) is used to collect longitudinal symptom data preoperatively, daily postoperatively during in-hospital stay and weekly after discharge until 4 weeks or the start of postoperative oncological therapy. Symptoms that change significantly over time will be generated as the PSS. We will determine the optimal time points for follow-up using the generalised linear mixed-effects models. The MDASI-LC interference-measured functional status will be used as the anchor for the alert thresholds.Ethics and disseminationEthics Committee of Sichuan Cancer Hospital approved this study on 16 October 2017 (No. SCCHEC-02-2017-042). The manuscript is based on the latest protocol of Version 3.0, 15 September 2019. The results of this study will be presented at medical conferences and published in peer-reviewed journals.Trials registration number NCT03341377.

It is recognized that cancer cells exhibit highly elevated glucose metabolism compared to non-tumor cells. We have applied in vivo optical imaging to study dynamic uptake of a near-infrared dye-labeled glucose analogue, 2-deoxyglucose (2-DG) by orthotopic glioma in a mouse model. The orthotopic glioma model was established by surgically implanting U87-luc glioma cells into the right caudal nuclear area of nude mice. Intracranial tumor growth was monitored longitudinally by bioluminescence imaging and MRI. When tumor size reached >4 mm diameter, dynamic fluorescence imaging was performed after an injection of the NIR labeled 2-DG, IRDye800CW 2-DG. Real-time whole body images acquired immediately after i.v. infusion clearly visualized the near-infrared dye circulating into various internal organs sequentially. Dynamic fluorescence imaging revealed significantly higher signal intensity in the tumor side of the brain than the contralateral normal brain 24 h after injection (tumor/normal ratio, TNR = 2.8+/-0.7). Even stronger contrast was achieved by removing the scalp (TNR = 3.7+/-1.1) and skull (TNR = 4.2+/-1.1) of the mice. In contrast, a control dye, IRDye800CW carboxylate, showed little difference (1.1+/-0.2). Ex vivo fluorescence imaging performed on ultrathin cryosections (20 microm) of tumor bearing whole brain revealed distinct tumor margins. Microscopic imaging identified cytoplasmic locations of the 2-DG dye in tumor cells. Our results suggest that the near-infrared dye labeled 2-DG may serve as a useful fluorescence imaging probe to noninvasively assess intracranial tumor burden in preclinical animal models.

Hypoxia is associated with prostate tumor aggressiveness, local recurrence, and biochemical failure. Magnetic resonance imaging (MRI) offers insight into tumor pathophysiology and recent reports have related transverse relaxation rate (R2*) and longitudinal relaxation rate (R1) measurements to tumor hypoxia. We have investigated the inclusion of oxygen-enhanced MRI for multi-parametric evaluation of tumor malignancy. Multi-parametric MRI sequences at 3 Tesla were evaluated in 10 patients to investigate hypoxia in prostate cancer prior to radical prostatectomy. Blood oxygen level dependent (BOLD), tissue oxygen level dependent (TOLD), dynamic contrast enhanced (DCE), and diffusion weighted imaging MRI were intercorrelated and compared with the Gleason score. The apparent diffusion coefficient (ADC) was significantly lower in tumor than normal prostate. Baseline R2* (BOLD-contrast) was significantly higher in tumor than normal prostate. Upon the oxygen breathing challenge, R2* decreased significantly in the tumor tissue, suggesting improved vascular oxygenation, however changes in R1 were minimal. R2* of contralateral normal prostate decreased in most cases upon oxygen challenge, although the differences were not significant. Moderate correlation was found between ADC and Gleason score. ADC and R2* were correlated and trends were found between Gleason score and R2*, as well as maximum-intensity-projection and area-under-the-curve calculated from DCE. Tumor ADC and R2* have been associated with tumor hypoxia, and thus the correlations are of particular interest. A multi-parametric approach including oxygen-enhanced MRI is feasible and promises further insights into the pathophysiological information of tumor microenvironment.

Genetic sex determination by W and Z chromosomes has developed independently in different groups of organisms. To better understand the evolution of sex chromosomes and the plasticity of sex-determination mechanisms, we sequenced the whole genomes of a male (ZZ) and a female (ZW) half-smooth tongue sole (Cynoglossus semilaevis). In addition to insights into adaptation to a benthic lifestyle, we find that the sex chromosomes of these fish are derived from the same ancestral vertebrate protochromosome as the avian W and Z chromosomes. Notably, the same gene on the Z chromosome, dmrt1, which is the male-determining gene in birds, showed convergent evolution of features that are compatible with a similar function in tongue sole. Comparison of the relatively young tongue sole sex chromosomes with those of mammals and birds identified events that occurred during the early phase of sex-chromosome evolution. Pertinent to the current debate about heterogametic sex-chromosome decay, we find that massive gene loss occurred in the wake of sex-chromosome 'birth'.

We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.

Background: Dynamic contrast-enhanced (DCE) MRI may provide prognostic insights into tumour radiation response. This study examined quantitative DCE MRI parameters in rat tumours, as potential biomarkers of tumour growth delay following single high-dose irradiation. Methods: Dunning R3327-AT1 prostate tumours were evaluated by DCE MRI following intravenous injection of Gd-DTPA. The next day tumours were irradiated (single dose of 30 Gy), while animals breathed air ( n =4) or oxygen ( n =4); two animals were non-irradiated controls. Growth was followed and tumour volume-quadrupling time (T 4 ) was compared with pre-irradiation DCE assessments. Results: Irradiation caused significant tumour growth delay (T 4 ranged from 28 to 48 days for air-breathing rats, and 40 to 75 days for oxygen-breathing rats) compared with the controls (T 4 =7 to 9 days). A strong correlation was observed between T 4 and extravascular-extracellular volume fraction ( v e ) irrespective of the gas inhaled during irradiation. There was also a correlation between T 4 and volume transfer constant ( K trans ) for the air-breathing group alone. Conclusions: The data provide rationale for expanded studies of other tumour sites, types and progressively patients, and are potentially significant, as many patients undergo contrast-enhanced MRI as part of treatment planning.