A Contrast-Enhanced Tri-Modal MRI Technique for High-Performance Hypoxia Imaging of Breast Cancer.

Personalized radiotherapy strategies enabled by the construction of hypoxia-guided biological target volumes (BTVs) can overcome hypoxia-induced radioresistance by delivering high-dose radiotherapy to targeted hypoxic areas of the tumor. However, the construction of hypoxia-guided BTVs is difficult owing to lack of precise visualization of hypoxic areas. This study synthesizes a hypoxia-responsive T1, T2, T2 mapping tri-modal MRI molecular nanoprobe (SPION@ND) and provides precise imaging of hypoxic tumor areas by utilizing the advantageous features of tri-modal magnetic resonance imaging (MRI). SPION@ND exhibits hypoxia-triggered dispersion-aggregation structural transformation. Dispersed SPION@ND can be used for routine clinical BTV construction using T1-contrast MRI. Conversely, aggregated SPION@ND can be used for tumor hypoxia imaging assessment using T2-contrast MRI. Moreover, by introducing T2 mapping, this work designs a novel method (adjustable threshold-based hypoxia assessment) for the precise assessment of tumor hypoxia confidence area and hypoxia level. Eventually this work successfully obtains hypoxia tumor target and accurates hypoxia tumor target, and achieves a one-stop hypoxia-guided BTV construction. Compared to the positron emission tomography-based hypoxia assessment, SPION@ND provides a new method that allows safe and convenient imaging of hypoxic tumor areas in clinical settings.

Advances in the role of gut microbiota in the regulation of the tumor microenvironment (Review).

As a protector of human health, the gut microbiota plays an important role in the development of the immune system during childhood, and the regulation of dietary habits, metabolism and immune system during adulthood. Dysregulated gut flora is not pathogenic, but it can weaken the protective effect of the immune system and cause various diseases. The tumor microenvironment is a physiological environment formed during tumor growth, which provides nutrients and growth factors necessary for tumor growth. As an important factor affecting the tumor microenvironment, the intestinal microflora affects the development of tumors through the mechanisms of gut and microflora metabolites, gene toxins and signaling pathways. The present article aimed to review the components and mechanisms of action, clinical applications, and biological targets of gut microbiota in the regulation of the tumor microenvironment. The present review provides novel insights for the future use of intestinal flora, to regulate the tumor microenvironment, to intervene in the occurrence, development, treatment and prognosis of tumors.

Improved Boron Neutron Capture Therapy Using Integrin αvß3-Targeted Long-Retention-Type Boron Carrier in a F98 Rat Glioma Model.

Integrin αvß3 is more highly expressed in high-grade glioma cells than in normal tissues. In this study, a novel boron-10 carrier containing maleimide-functionalized closo-dodecaborate (MID), serum albumin as a drug delivery system, and cyclic arginine-glycine-aspartate (cRGD) that can target integrin αvß3 was developed. The efficacy of boron neutron capture therapy (BNCT) targeting integrin αvß3 in glioma cells in the brain of rats using a cRGD-functionalized MID-albumin conjugate (cRGD-MID-AC) was evaluated. F98 glioma cells exposed to boronophenylalanine (BPA), cRGD-MID-AC, and cRGD + MID were used for cellular uptake and neutron-irradiation experiments. An F98 glioma-bearing rat brain tumor model was used for biodistribution and neutron-irradiation experiments after BPA or cRGD-MID-AC administration. BNCT using cRGD-MID-AC had a sufficient cell-killing effect in vitro, similar to that with BNCT using BPA. In biodistribution experiments, cRGD-MID-AC accumulated in the brain tumor, with the highest boron concentration observed 8 h after administration. Significant differences were observed between the untreated group and BNCT using cRGD-MID-AC groups in the in vivo neutron-irradiation experiments through the log-rank test. Long-term survivors were observed only in BNCT using cRGD-MID-AC groups 8 h after intravenous administration. These findings suggest that BNCT with cRGD-MID-AC is highly selective against gliomas through a mechanism that is different from that of BNCT with BPA.

Biological target volume based on fluorine-18-fluorode-oxyglucose positron emission tomography/computed tomography imaging: a spurious proposition?

PURPOSE: To assess whether the high metabolic region of fluorine-18-fluorode-oxyglucose (18F-FDG) in the primary lesion is the crux for recurrence in patients with nasopharyngeal carcinoma (NPC), to assess the feasibility and rationale for use of biological target volume (BTV) based on 18F-FDG positron emission tomography/computed tomography (18F-FDG-PET/CT). METHODS: The retrospective study included 33 patients with NPC who underwent 18F-FDG-PET/CT at the time of initial diagnosis as well as the time of diagnosis of local recurrence. Paired 18F-FDG-PET/CT images for primary and recurrent lesion were matched by deformation coregistration method to determine the cross-failure rate between two lesions. RESULTS: The median volume of the Vpri (primary tumor volume using the SUV thresholds of 2.5), the Vhigh (the volume of high FDG uptake using the SUV50%max isocontour), and the Vrecur (the recurrent tumor volume using the SUV thresholds of 2.5) were 22.85, 5.57, and 9.98 cm3, respectively. The cross-failure rate of Vrecur∩high showed that 82.82% (27/33) of local recurrent lesions had < 50% overlap volume with the region of high FDG uptake. The cross-failure rate of Vrecur∩pri showed that 96.97% (32/33) of local recurrent lesions had > 20% overlap volume with the primary tumor lesions and the median cross rate was up to 71.74%. CONCLUSION: 18F-FDG-PET/CT may be a powerful tool for automatic target volume delineation, but it may not be the optimal imaging modality for dose escalation radiotherapy based on applicable isocontour. The combination of other functional imaging could delineate the BTV more accurately.

KCNJ14 knockdown significantly inhibited the proliferation and migration of colorectal cells.

BACKGROUND: This study attempted to verify the potential of KCNJ14 as a biomarker in colorectal cancer (CRC). METHODS: Data on transcriptomics and DNA methylation and the clinical information of CRC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Biological information analysis methods were conducted to determine the role of KCNJ14 in the prognosis, diagnosis, immune cell infiltration, and regulation mechanism of CRC patients. The effect of KCNJ14 on the proliferation and migration of HCT116 and SW480 CRC cell lines was verified by in vitro experiments (MTT, colony-forming, wound healing, and transwell assays). Western blotting was performed to detect the effect of KCNJ14 on the levels of mTOR signalling pathway-related proteins. RESULTS: KCNJ14 expression was remarkably increased in CRC tissues and cell lines, which reduced the overall survival time of patients. KCNJ14 mRNA was negatively regulated by its methylation site cg17660703, which can also endanger the prognosis of patients with CRC. Functional enrichment analysis suggested that KCNJ14 is involved in the mTOR, NOD-like receptor, and VEGF signalling pathways. KCNJ14 expression was positively correlated with the number of CD4 + T cells and negatively correlated with that of CD8 + T cells in the immune microenvironment. KCNJ14 knockdown significantly reduced not only the proliferation and migration of CRC cell lines but also the levels of mTOR signalling pathway-related proteins. CONCLUSIONS: This study not only increases the molecular understanding of KCNJ14 but also provides a potentially valuable biological target for the treatment of colorectal cancer.

High throughput virtual screening (HTVS) of peptide library: Technological advancement in ligand discovery.

High-throughput virtual screening (HTVS) is a leading biopharmaceutical technology that employs computational algorithms to uncover biologically active compounds from large-scale collections of chemical compound libraries. In addition, this method often leverages the precedence of screening focused libraries for assessing their binding affinities and improving physicochemical properties. Usually, developing a drug sometimes takes ages, and lessons are learnt from FDA-approved drugs. This screening strategy saves resources and time compared to laboratory testing in certain stages of drug discovery. Yet in-silico investigations remain challenging in some cases of drug discovery. For the last few decades, peptide-based drug discoveries have received remarkable momentum for several advantages over small molecules. Therefore, developing a high-fidelity HTVS platform for chemically versatile peptide libraries is highly desired. This review summarises the modern and frequently appreciated HTVS strategies for peptide libraries from 2011 to 2021. In addition, we focus on the software used for preparing peptide libraries, their screening techniques and shortcomings. An index of various HTVS methods reported here should assist researchers in identifying tools that could be beneficial for their peptide library screening projects.

The Immune Pathogenesis of Acute-On-Chronic Liver Failure and the Danger Hypothesis.

Acute-on-chronic liver failure (ACLF) is a group of clinical syndromes related to severe acute liver function impairment and multiple-organ failure caused by various acute triggering factors on the basis of chronic liver disease. Due to its severe condition, rapid progression, and high mortality, it has received increasing attention. Recent studies have shown that the pathogenesis of ACLF mainly includes direct injury and immune injury. In immune injury, cytotoxic T lymphocytes (CTLs), dendritic cells (DCs), and CD4+ T cells accumulate in the liver tissue, secrete a variety of proinflammatory cytokines and chemokines, and recruit more immune cells to the liver, resulting in immune damage to the liver tissue, massive hepatocyte necrosis, and liver failure, but the key molecules and signaling pathways remain unclear. The "danger hypothesis" holds that in addition to the need for antigens, damage-associated molecular patterns (DAMPs) also play a very important role in the occurrence of the immune response, and this hypothesis is related to the pathogenesis of ACLF. Here, the research status and development trend of ACLF, as well as the mechanism of action and research progress on various DAMPs in ACLF, are summarized to identify biomarkers that can predict the occurrence and development of diseases or the prognosis of patients at an early stage.

Expression and clinical significance of minichromosome maintenance protein 3(MCM3) in gastric cancer tissues / 国际生物医学工程杂志

Objective:To study the expression level and clinical significance of minichromosome maintenance protein 3(MCM3) in human gastric cancer.Methods:The expression levels of MCM3 mRNA and protein in gastric cancer and adjacent normal tissues were analyzed using public databases such as TCGA, CCLE and HPA. The clinicopathological features of 69 patients with gastric cancer were retrospectively analyzed, and the expression levels of MCM3 protein in tumor tissues and adjacent normal tissues were detected by immunohistochemical staining, and the relationship between it and clinicopathological features was analyzed. The interaction network of MCM3 proteins was analyzed using the STRING database.Results:The expression levels of MCM3 mRNA and protein in gastric cancer tissues were significantly higher than those in adjacent normal tissues ( P<0.05), and its high expression was correlated with the size of gastric cancer tumors ( P<0.05). In gastric cancer tissue, the expression of MCM3 was correlated with the expression level of proliferating cell nuclear antigen (PCNA) ( R=0.61, P<0.01), and there may be a protein-protein interaction. Conclusions:MCM3 plays an important role in gastric cancer by interacting with PCNA, and it is expected to become a new diagnostic and therapeutic target.

My 42-year Experience in Radiation Oncology.

In the present review, I provide an overview of the development of radiation therapy and short history of the Department of Radiation Oncology, Juntendo University. I also emphasize the importance of radiation therapy as a major treatment modality for cancers. Radiation therapy is a standard treatment for malignant tumors. It aims to deliver a sufficient radiation dose to a target volume to eradicate tumor cells or relieve symptoms of disease. Therapy can achieve good results in many types of cancers. Although radiation therapy sometimes causes undesirable adverse events, it is generally less invasive than other treatment modalities and does not alter the shape and function of healthy organs. When the author joined this field in 1981, radiation therapy techniques were highly primitive; however, during the past 42 years, treatment has advanced rapidly with the development of computer science, mechanical techniques and instrumentation. Currently, patients can be treated with precise radiation techniques, including intensity-modulated radiation therapy, image-guided radiation therapy, stereotactic irradiation, and brachytherapy. We also introduced a new treatment planning system that uses not only anatomical but also metabolic imaging, which permits correct delineation of the target volume. Therefore, it is crucial to stay up to date with advances and developments in rapidly emerging technologies to maintain high-quality treatment. The Department of Radiation Oncology at Juntendo University (Tokyo, Japan) is still small; however, it is gradually expanding and conducting research in both clinical and basic fields. It is the author's hope that many young investigators will join this field in the future.

Identification of biological targets through the correlation between cell line chemosensitivity and protein expression pattern.

Matching biological data sequences is one of the most interesting ways to discover new bioactive compounds. In particular, matching cell chemosensitivity with a protein expression profile can be a useful approach to predict the activity of compounds against definite biological targets. In this review, we discuss this correlation. First, we analyze case studies in which some known drugs, acting on known targets, show a good correlation between their antiproliferative activities and protein expression when a large panel of tumor cells is considered. Then, we highlight how the application of in silico methods based on the correlation between cell line chemosensitivity and gene/protein expression patterns might be a quick, cheap, and interesting approach to predict the biological activity of investigated molecules.

A preliminary PET radiomics study of brain metastases using a fully automatic segmentation method.

BACKGROUND: Positron Emission Tomography (PET) is increasingly utilized in radiomics studies for treatment evaluation purposes. Nevertheless, lesion volume identification in PET images is a critical and still challenging step in the process of radiomics, due to the low spatial resolution and high noise level of PET images. Currently, the biological target volume (BTV) is manually contoured by nuclear physicians, with a time expensive and operator-dependent procedure. This study aims to obtain BTVs from cerebral metastases in patients who underwent L-[11C]methionine (11C-MET) PET, using a fully automatic procedure and to use these BTVs to extract radiomics features to stratify between patients who respond to treatment or not. For these purposes, 31 brain metastases, for predictive evaluation, and 25 ones, for follow-up evaluation after treatment, were delineated using the proposed method. Successively, 11C-MET PET studies and related volumetric segmentations were used to extract 108 features to investigate the potential application of radiomics analysis in patients with brain metastases. A novel statistical system has been implemented for feature reduction and selection, while discriminant analysis was used as a method for feature classification. RESULTS: For predictive evaluation, 3 features (asphericity, low-intensity run emphasis, and complexity) were able to discriminate between responder and non-responder patients, after feature reduction and selection. Best performance in patient discrimination was obtained using the combination of the three selected features (sensitivity 81.23%, specificity 73.97%, and accuracy 78.27%) compared to the use of all features. Secondly, for follow-up evaluation, 8 features (SUVmean, SULpeak, SUVmin, SULpeak prod-surface-area, SUVmean prod-sphericity, surface mean SUV 3, SULpeak prod-sphericity, and second angular moment) were selected with optimal performance in discriminant analysis classification (sensitivity 86.28%, specificity 87.75%, and accuracy 86.57%) outperforming the use of all features. CONCLUSIONS: The proposed system is able i) to extract 108 features for each automatically segmented lesion and ii) to select a sub-panel of 11C-MET PET features (3 and 8 in the case of predictive and follow-up evaluation), with valuable association with patient outcome. We believe that our model can be useful to improve treatment response and prognosis evaluation, potentially allowing the personalization of cancer treatment plans.

Identification of the potential biological target of N-benzenesulfonyl-1,2,3,4-tetrahydroquinoline compounds active against gram-positive and gram-negative bacteria.

The development of new antibiotics with activity towards a broad spectrum of bacteria, including multiresistant strains, is a very important topic for global public health. As part of previous works, N-benzenesulfonyl-1,2,3,4-tetrahydroquinoline (BSTHQ) derivatives were described as antimicrobial agents active against gram-positive and gram-negative pathogens. In this work, experimental and molecular modelling studies were performed in order to identify their potential biological target in the light of structure-based design efforts towards further BSTHQ derivatives. First, a carboxyfluorescein leakage assay was performed using liposomes to mimic bacterial membranes, which found no significative membrane disruption effects with respect to control samples. These results support a non-surfactant antimicrobial activity of the tested compounds. In a second stage, the inhibition of potential antimicrobial targets was screened using molecular modelling methods, taking into account previously reported druggable targets deposited in the ChEMBL database for Escherichia coli and Staphylococcus aureus. Two enzymes, namely D-glutamic acid-adding enzyme (MurD) and N-acetylglucosamine-1-phophate-uridyltransferase (GlmU), both involved in bacterial membrane synthesis, were identified as potential targets. Pharmacodynamic interaction models were developed using known MurD and GlmU inhibitors by applying state-of-the-art chemoinformatic methods (molecular docking, molecular dynamics and free energy of interaction analyses). These models were further extended to the analysis of the studied BSTHQ derivatives. Overall, our results demonstrated that the studied BSTHQ derivatives elicit their antibacterial activity by interacting with a specific molecular target, GlmU being the highly feasible one. Based on the presented results, further structure-aided design efforts towards the obtaining of novel BSTHQ derivatives are envisioned.Communicated by Ramaswamy H. Sarma.

Bone marrow mesenchymal stem cells and tongue squamous carcinoma cells: Promoting growth or targeting biotherapy / 中国组织工程研究

BACKGROUND: Currently, the treatment methods for tongue squamous cell carcinoma mainly adopt comprehensive sequence therapy mainly based on surgery, but the therapeutic effect is still unsatisfactory. In recent years, tumor targeted biotherapy has attracted increasing attention. Stem cell technology enables therapeutic factors to be selectively delivered to tumor sites to play corresponding roles. Bone marrow mesenchymal stem cells show great advantages in this respect. However, the effect and action mechanism of bone marrow mesenchymal stem cells on tongue squamous cell carcinoma are still unclear. OBJECTIVE: To review the research progress on the effect of bone marrow mesenchymal stem cells on tongue squamous carcinoma cells, and clarify its function and discuss its mechanism. METHODS: The computer was used to search literatures about bone marrow mesenchymal stem cells in PubMed database, Wanfang database and CNKI database. The key words were “bone marrow mesenchymal stem cells, tumor cells”, “bone marrow mesenchymal stem cells, tongue squamous cell carcinoma”, “bone marrow mesenchymal stem cells, proliferation”, “bone marrow mesenchymal stem cells, migration, invasion” in Chinese, and “bone marrow mesenchymal stem cells, cancer cells” and “bone marrow mesenchymal stem cells, tongue squamous cell carcinoma”, “bone marrow mesenchymal stem cells, proliferation”, “bone marrow mesenchymal stem cells, migration, invasion” in English. A total of 43 articles were included for analysis. RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells have strong proliferation characteristics and can migrate directionally and promote invasion of tongue squamous carcinoma cells, suggesting that even if bone marrow mesenchymal stem cells have the function of promoting defect repair, and can also express therapeutic factors by gene modification and migrate to tumor growth site to play a therapeutic role, they cannot be used for repair treatment of postoperative defects of tongue squamous cell carcinoma. Targeted biological therapy of mesenchymal stem cells is a brand-new and promising field, but its safety still needs to be taken into account, and its mechanism of action and potential risks still need our continuous exploration.

Checkpoint CD47 Function On Tumor Metastasis And Immune Therapy.

The success of cancer immunotherapy on recognition checkpoints for killing cancer cells has raised a great interest of scientists in understanding new and old methods of immunotherapeutic. CD47 (cluster of differentiation 47) is a cell surface glycoprotein and widely expressed on cells, which belongs to the immunoglobulin (Ig) superfamily as a cell membrane receptor which serves in immune therapy. CD47 is an inhibitory receptor expressed on tumor cell surface and interacts with signal receptor protein-alpha (SIPR-α, also named CD172a or SHPS-1) which may escape from immune cells such as macrophage and T cells. Meanwhile, tumor cells express high CD47 protein which may secrete exosomes with high CD47 expression. The high CD47 expression-exosomes could serve the tumor metastasis process and provide transfer convenience for tumors on the microenvironment. CD47 on cancer cells can also affect the migration and invasion of cells. The high CD47 expression on tumor or CTC (circulating tumor cell) surface means the stronger migration and invasion and makes them escape from immune cells for phagocytosis such as T cells, NK (natural killer) cells and macrophage, which could be used for diagnosis and prognosis on cancer patients. Meanwhile, targeting CD47 combined with other biomarkers such as EpCAM (epithelial cell adhesion molecule), CD44, etc on cancer surface could be used to isolate CTCs from patients' blood. In terms of treatment, anti-CD47 antibody combined with another antibody such as anti-PD-L1 (programmed death-ligand 1) antibody or drugs such as rituximab, DOX or oxaliplatin also has better therapeutic effects and antitumor function to tumors. Using nanomaterials as an intermediary for CD47-related immune therapy could greatly increase the therapeutic effect and overcome multiple biological barriers for anti-CD47 antibody in vivo. In this review, we discuss the important role and the function of CD47 in tumor metastasis and also provide a reference for related research.

Active contour algorithm with discriminant analysis for delineating tumors in positron emission tomography.

In the context of cancer delineation using positron emission tomography datasets, we present an innovative approach which purpose is to tackle the real-time, three-dimensional segmentation task in a full, or at least nearly full automatized way. The approach comprises a preliminary initialization phase where the user highlights a region of interest around the cancer on just one slice of the tomographic dataset. The algorithm takes care of identifying an optimal and user-independent region of interest around the anomalous tissue and located on the slice containing the highest standardized uptake value so to start the successive segmentation task. The three-dimensional volume is then reconstructed using a slice-by-slice marching approach until a suitable automatic stop condition is met. On each slice, the segmentation is performed using an enhanced local active contour based on the minimization of a novel energy functional which combines the information provided by a machine learning component, the discriminant analysis in the present study. As a result, the whole algorithm is almost completely automatic and the output segmentation is independent from the input provided by the user. Phantom experiments comprising spheres and zeolites, and clinical cases comprising various body districts (lung, brain, and head and neck), and two different radio-tracers (18 F-fluoro-2-deoxy-d-glucose, and 11C-labeled Methionine) were used to assess the algorithm performances. Phantom experiments with spheres and with zeolites showed a dice similarity coefficient above 90% and 80%, respectively. Clinical cases showed high agreement with the gold standard (R2 = 0.98). These results indicate that the proposed method can be efficiently applied in the clinical routine with potential benefit for the treatment response assessment, and targeting in radiotherapy.

Dosimetric evaluation of radiotherapy planning with internal biological target volume of non-small cell lung cancer based on PET-CT and 4DCT / 中华放射医学与防护杂志

Objective To compare the size of the internal target volume (ITV),biological target volume (BTV) and internal biological target volume (IBTV) based on PET-CT and 4DCT for primary nonsmall cell lung cancer (NSCLC),as well as try to apply IBTV in radiotherapy planning.Methods A total of 15 patients with NSCLC were sequentially scanned by an axial enhanced 3DCT,4DCT and 18F-FDG PET-CT in the thoracic region.The gross target volumes (GTVs) of ten phases of 4DCT images were contoured,and ITV was obtained by fusion of ten GTVs.BTV based on PET-CT images was determined by the SUV 2.0.The IBTV was defined by fusion of ITV and BTV.Planning target volumes (PTVs) based on ITV,BTV,and IBTV (PITV,PBTV,PIBTV) were obtained by ITV,BTV and IBTV with a 10-mm expansion respectively.The metrics of PIBTV,PITV and PBTV were compared,and the planning parameters of target volumes and risk organs were evaluated.Results There was no significant difference between ITV and BTV,but there was significant difference between IBTV and ITV and BTV (F=22.533,P ＜ 0.05).To include more than 95％ volume of IBTV,it is necessary to expand the margin of 9.0(6.0,12.0)mm based on BTV or 10.00(7.0,12.0)mm based on ITV.There was no significant difference between the two groups (P ＞ 0.05).Dice's similarity coefficient of BTV and ITV was 0.72(0.54,0.79).The intensity modulated radiotherapy plan based on PBTV can guarantee 85.6％ (80.5％,91.2％) of PITV to reach the prescription dose,compared with 80.2％ (74.4％,87.6％) of PBTV by the plan from PITV.Additionally,the conformity index and homogeneity index were not ideal.The dosimetric parameters of PITV and PBTV in the PIBTV plan were much better than those in PBTV-and PITV plan.Conclusions The radiotherapy plan based on PET-CT or 4DCT could not guarantee a reasonable dose distribution of PTV expanded from ITV or BTV.Thus,using IBTV for radiotherapy is advised.

A smart and operator independent system to delineate tumours in Positron Emission Tomography scans.

Positron Emission Tomography (PET) imaging has an enormous potential to improve radiation therapy treatment planning offering complementary functional information with respect to other anatomical imaging approaches. The aim of this study is to develop an operator independent, reliable, and clinically feasible system for biological tumour volume delineation from PET images. Under this design hypothesis, we combine several known approaches in an original way to deploy a system with a high level of automation. The proposed system automatically identifies the optimal region of interest around the tumour and performs a slice-by-slice marching local active contour segmentation. It automatically stops when a "cancer-free" slice is identified. User intervention is limited at drawing an initial rough contour around the cancer region. By design, the algorithm performs the segmentation minimizing any dependence from the initial input, so that the final result is extremely repeatable. To assess the performances under different conditions, our system is evaluated on a dataset comprising five synthetic experiments and fifty oncological lesions located in different anatomical regions (i.e. lung, head and neck, and brain) using PET studies with 18F-fluoro-2-deoxy-d-glucose and 11C-labeled Methionine radio-tracers. Results on synthetic lesions demonstrate enhanced performances when compared against the most common PET segmentation methods. In clinical cases, the proposed system produces accurate segmentations (average dice similarity coefficient: 85.36 ±â€¯2.94%, 85.98 ±â€¯3.40%, 88.02 ±â€¯2.75% in the lung, head and neck, and brain district, respectively) with high agreement with the gold standard (determination coefficient R2 = 0.98). We believe that the proposed system could be efficiently used in the everyday clinical routine as a medical decision tool, and to provide the clinicians with additional information, derived from PET, which can be of use in radiation therapy, treatment, and planning.

The Current Understanding of MicroRNA's Therapeutic, Diagnostic, and Prognostic Role in Chordomas: A Review of the Literature.

Chordomas are primary low-grade bone tumors derived from the embryonic notochord that make up less than 5% of all osseous malignancies and commonly affect the spine at its vertebral body and at its two ends i.e., skull base and the sacrum. Although histologically defined to be low-grade, chordoma is locally destructive, metastatic, and has a serious recurrence rate, which all contribute to the dismal median survival rate of six years. Its locally destructive nature places the adjacent vital neurovascular structures at risk, making an en-bloc resection a challenge. This tumor is also known to show high resistance to currently available chemoradiotherapy, although the benefit of proton beam therapy for skull base chordoma has been demonstrated. There is an additional need to focus our attention on investigating the molecular biology of this chemoradiotherapy-resistant tumor to develop a more targeted therapy, which has additional diagnostic and prognostic values. In this paper, we discuss the therapeutic, diagnostic, and prognostic role of microRNAs (miRNAs) in chordomas.

Comparison of biological target volume metrics based on FDG PET-CT and 4DCT for primary non-small-cell lung cancer.

Fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) and four-dimensional CT (4DCT) are used in several methods for defining the biological target volume (BTV) in primary non-small cell lung cancer (NSCLC). Disagreements between the assessments using these methodologies make the use of BTV for radiotherapy planning controversial. In this study, we compared existing methods with our proposed internal biological target volume (IBTV) metric, derived by combining internal target volume (ITV) and BTV metrics. We defined the IBTV from ITV (IBTVi) or BTV (IBTVb) based on ITV or BTV with symmetrical margin expansion. We detected large differences between IBTV, IBTVi and IBTVb (p < 0.001), but no difference between ITV and BTV. A margin expansion of about 13 mm was necessary for ITV or BTV to encompass > 95% IBTV. The conformity index correlated negatively with IBTV/ITV, IBTV/BTV, IBTVi/ITV, and IBTVb/BTV volume ratios (p < 0.05). VR also increased the margins of IBTVi and IBTVb. Indeed, IBTV was much smaller than IBTVi or IBTVb, suggesting that using IBTV for radiotherapy planning could improve treatment by minimizing the radiation exposure of healthy tissue and organs surrounding tumors.

Patterns-of-failure guided biological target volume definition for head and neck cancer patients: FDG-PET and dosimetric analysis of dose escalation candidate subregions.

BACKGROUND: To identify the radio-resistant subvolumes in pretreatment FDG-PET by mapping the spatial location of the origin of tumor recurrence after IMRT for head-and-neck squamous cell cancer to the pretreatment FDG-PET/CT. METHODS: Patients with local/regional recurrence after IMRT with available FDG-PET/CT and post-failure CT were included. For each patient, both pre-therapy PET/CT and recurrence CT were co-registered with the planning CT (pCT). A 4-mm radius was added to the centroid of mapped recurrence growth target volumes (rGTV's) to create recurrence nidus-volumes (NVs). The overlap between boost-tumor-volumes (BTV) representing different SUV thresholds/margins combinations and NVs was measured. RESULTS: Forty-seven patients were eligible. Forty-two (89.4%) had type A central high dose failure. Twenty-six (48%) of type A rGTVs were at the primary site and 28 (52%) were at the nodal site. The mean dose of type A rGTVs was 71Gy. BTV consisting of 50% of the maximum SUV plus 10mm margin was the best subvolume for dose boosting due to high coverage of primary site NVs (92.3%), low average relative volume to CTV1 (41%), and least average percent voxels outside CTV1 (19%). CONCLUSIONS: The majority of loco-regional recurrences originate in the regions of central-high-dose. When correlated with pretreatment FDG-PET, the majority of recurrences originated in an area that would be covered by additional 10mm margin on the volume of 50% of the maximum FDG uptake.