Tumor derived exosomal ENTPD2 impair CD8+ T cell function in colon cancer through ATP-adenosine metabolism reprogramming.

BACKGROUND: Extracellular ATP-AMP-adenosine metabolism plays a pivotal role in modulating tumor immune responses. Previous studies have shown that the conversion of ATP to AMP is primarily catalysed by Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39), a widely studied ATPase, which is expressed in tumor-associated immune cells. However, the function of ATPases derived from tumor cells themselves remains poorly understood. The purpose of this study was to investigate the role of colon cancer cell-derived ATPases in the development and progression of colon cancer. METHODS: Bioinformatic and tissue microarray analyses were performed to investigate the expression of ATPase family members in colon cancer. An ATP hydrolysis assay, high-performance liquid chromatography (HPLC), and CCK8 and colony formation assays were used to determine the effects of ENTPD2 on the biological functions of colon cancer cells. Flow cytometric and RNA-seq analyses were used to explore the function of CD8+ T cells. Immunoelectron microscopy and western blotting were used to evaluate the expression of ENTPD2 in exosomes. Double-labelling immunofluorescence and western blotting were used to examine the expression of ENTPD2 in serum exosomes and colon cancer tissues. RESULTS: We found that ENTPD2, rather than the well-known ATPase CD39, is highly expressed in cancer cells and is significantly positively associated with poor patient prognosis in patients with colon cancer. The overexpression of ENTPD2 in cancer cells augmented tumor progression in immunocompetent mice by inhibiting the function of CD8+ T cells. Moreover, ENTPD2 is localized primarily within exosomes. On the one hand, exosomal ENTPD2 reduces extracellular ATP levels, thereby inhibiting P2X7R-mediated NFATc1 nuclear transcription; on the other hand, it facilitates the increased conversion of ATP to adenosine, hence promoting adenosine-A2AR pathway activity. In patients with colon cancer, the serum level of exosomal ENTPD2 is positively associated with advanced TNM stage and high tumor invasion depth. Moreover, the level of ENTPD2 in the serum exosomes of colon cancer patients is positively correlated with the ENTPD2 expression level in paired colon cancer tissues, and the ENTPD2 level in both serum exosomes and tissues is significantly negatively correlated with the ENTPD2 expression level in tumor-infiltrating CD8+ T cells. CONCLUSION: Our study suggests that exosomal ENTPD2, originated from colon cancer cells, contributes to the immunosuppressive microenvironment by promoting ATP-adenosine metabolism. These findings highlight the importance of exosome-derived hydrolytic enzymes as independent entities in shaping the tumor immune microenvironment.

HIF-1α Mediates Immunosuppression and Chemoresistance in Colorectal Cancer by Inhibiting CXCL9, -10 and -11.

Uncertainty exists regarding the mechanisms by which hypoxia-inducible factors (HIFs) control CD8+T-cell migration into tumor microenvironments. Here, we found that HIF-1α knockdown or overexpression resulted in increased or decreased CXCL9, -10, and -11 expression in vitro, respectively. Gene Set Variation Analysis revealed that elevated HIF-1α levels correlated with a poor prognosis, severe pathological stage, and an absence of CD8+ T cells in the tumor microenvironment in colorectal cancer (CRC) patients. HIF-1α was inversely associated with pathways beneficial to anti-tumor immunotherapy and cytokine/chemokine function. In vivo, inhibiting HIF-1α or its upstream regulator BIRC2 significantly suppressed tumor growth and promoted CD8+ T-cell infiltration. CXCR3 neutralizing antibodies reversed these effects, implicating the involvement of CXCL9, -10, and -11/CXCR3 axis. The presence of HIF-1α weakened the upregulation of CXCL9, -10, and -11 by bleomycin and doxorubicin. Combining HIF-1α inhibition with bleomycin promoted CD8+ T-cell infiltration and tumor suppression in vivo. Moreover, doxorubicin could upregulate CXCL9, -10 and -11 by suppressing HIF-1α. Our findings highlight the potential of HIF-1α inhibition to improve CRC microenvironments and increase chemotherapy sensitivity.

Magnetic Hydroxyapatite-Coated Iron-Chromium Microspheres for Dental Surface Polishing and Plaque Removal.

This research aimed to engineer magnetic hydroxyapatite-coated iron-chromium (HAp-FeCr) microspheres to enhance dental surface polishing and plaque elimination. Utilizing a tailored sol-gel approach, the HAp-FeCr microspheres were synthesized and exhaustively characterized via scanning electron microscopy, energy-dispersive X-ray spectroscopy, ζ-potential, X-ray diffractometry, and X-ray photoelectron spectroscopy methodologies. Key findings showcased that these microspheres retained their magnetic properties post-HAp coating, as evidenced by the magnetization curves. An innovative magnetic polishing system was developed, incorporating these microspheres and a 2000 rpm magnet. Comparative evaluations between traditional air-powder polishing and the proposed magnetic technique demonstrated the latter's superiority. Notably, the magnetic polishing led to a substantial reduction in dental plaque on the tooth surface, decreasing bacterial adhesion and early biofilm formation by Streptococcus gordonii and Lactobacillus acidophilus, where the most pronounced effects were observed in samples with elevated HAp content. A significant 60% reduction in dental plaque was achieved with the magnetic method relative to air-powder polishing. Furthermore, the HAp-FeCr microspheres' biocompatibility was verified through cytotoxicity tests and animal studies. In essence, the magnetic HAp-FeCr microspheres present a novel and efficient strategy for dental treatments, holding immense potential for improving oral health.

Targeting RPA promotes autophagic flux and the antitumor response to radiation in nasopharyngeal carcinoma.

BACKGROUND: Autophagy is involved in nasopharyngeal carcinoma (NPC) radioresistance. Replication protein A 1 (RPA1) and RPA3, substrates of the RPA complex, are potential therapeutic targets for reversing NPC radioresistance. Nevertheless, the role of RPA in autophagy is not adequately understood. This investigation was performed to reveal the cytotoxic mechanism of a pharmacologic RPA inhibitor (RPAi) in NPC cells and the underlying mechanism by which RPAi-mediated autophagy regulates NPC radiosensitivity. METHODS AND RESULTS: We characterized a potent RPAi (HAMNO) that was substantially correlated with radiosensitivity enhancement and proliferative inhibition of in vivo and in NPC cell lines in vitro. We show that the RPAi induced autophagy at multiple levels by inducing autophagic flux, AMPK/mTOR pathway activation, and autophagy-related gene transcription by decreasing glycolytic function. We hypothesized that RPA inhibition impaired glycolysis and increased NPC dependence on autophagy. We further demonstrated that combining autophagy inhibition with chloroquine (CQ) treatment or genetic inhibition of the autophagy regulator ATG5 and RPAi treatment was more effective than either approach alone in enhancing the antitumor response of NPC to radiation. CONCLUSIONS: Our study suggests that HAMNO is a potent RPAi that enhances radiosensitivity and induces autophagy in NPC cell lines by decreasing glycolytic function and activating autophagy-related genes. We suggest a novel treatment strategy in which pharmacological inhibitors that simultaneously disrupt RPA and autophagic processes improve NPC responsiveness to radiation.

Knockdown LIMP2 inhibits colorectal cancer cells migration, invasion, and metastasis.

Colorectal cancer (CRC) is a common malignancy worldwide nowadays and liver metastasis is the primary cause of death in patients with CRC. Although lysosomal integral membrane protein 2 (LIMP2) has been reported to play important roles in gastric cancer and prostate cancer, its role in CRC remains unclear. The aim of this study was to investigate the function of LIMP2 in CRC invasion and migration, along with the potential underlying molecular mechanisms. We found that LIMP2 levels were higher in CRC tissues compared to adjacent normal tissues. Kaplan-Meier survival analysis showed that high expression of LIMP2 was associated with worse prognosis in CRC patients. Knockdown of LIMP2 significantly inhibited invasion, migration, and wound healing abilities of CRC cells in vitro, and inhibited CRC liver metastasis in vivo. Additionally, LIMP2 knockdown inhibited autophagy in CRC. Therefore, LIMP2 plays an important role in CRC progression. High expression of LIMP2 was associated with worse prognosis in CRC patients. Knockdown LIMP2 can effectively inhibit CRC cell migration and invasion in vitro and prevent liver metastasis in vivo. These findings suggest that LIMP2 may serve as an independent prognostic factor and potential therapeutic target for CRC.

Jun-APOE-LRP1 axis promotes tumor metastasis in colorectal cancer.

Apolipoprotein E (apoE) has previously been reported to play vital roles in tumor progression. However, the impact of apoE on colorectal cancer (CRC) metastasis remains largely unexplored. This study aimed to investigate the role of apoE in CRC metastasis and to identify the transcription factor and receptor of apoE involved in regulation of CRC metastasis. Bioinformatic analyses were conducted to examine the expression pattern and prognosis of apolipoproteins. APOE-overexpressing cell lines were utilized to explore the effects of apoE on proliferation, migration and invasion of CRC cells. Additionally, the transcription factor and receptor of apoE were screened via bioinformatics, and further validated through knockdown experiments. We discovered that the mRNA levels of APOC1, APOC2, APOD and APOE were higher in lymphatic invasion group, and a higher apoE level indicated poorer overall survival and progression-free interval. In vitro studies demonstrated that APOE-overexpression did not affect proliferation but promoted the migration and invasion of CRC cells. We also reported that APOE-expression was modulated by the transcription factor Jun by activating the proximal promoter region of APOE, and APOE-overexpression reversed the metastasis suppression of JUN knockdown. Furthermore, bioinformatics analysis suggested an interaction between apoE and low-density lipoprotein receptor-related protein 1 (LRP1). LRP1 was highly expressed in both the lymphatic invasion group and the APOEHigh group. Additionally, we found that APOE-overexpression upregulated LRP1 protein levels, and LRP1 knockdown attenuated the metastasis-promoting function of APOE. Overall, our study suggests that the Jun-APOE-LRP1 axis contributes to tumor metastasis in CRC.

Altered B cell immunoglobulin signature exhibits potential diagnostic values in human colorectal cancer.

Antibody-secreting B cells have long been considered the central element of gut homeostasis; however, tumor-associated B cells in human colorectal cancer (CRC) have not been well characterized. Here, we show that the clonotype, phenotype, and immunoglobulin subclasses of tumor-infiltrating B cells have changed compared to adjacent normal tissue B cells. Remarkably, the tumor-associated B cell immunoglobulin signature alteration can also be detected in the plasma of patients with CRC, suggesting that a distinct B cell response was also evoked in CRC. We compared the altered plasma immunoglobulin signature with the existing method of CRC diagnosis. Our diagnostic model exhibits improved sensitivity compared to the traditional biomarkers, CEA and CA19-9. These findings disclose the altered B cell immunoglobulin signature in human CRC and highlight the potential of using the plasma immunoglobulin signature as a non-invasive method for the assessment of CRC.

ICAT promotes colorectal cancer metastasis via binding to JUP and activating the NF-κB signaling pathway.

BACKGROUND: The inhibitor of ß-catenin and T-cell factor (ICAT) is a direct negative regulator of the canonical Wnt signaling pathway, which is an attractive therapeutic target for colorectal cancer (CRC). Accumulating evidence suggests that ICAT interacts with other proteins to exert additional functions, which are not yet fully elucidated. METHODS: The overexpression of ICAT of CRC cells was conducted by lentivirus infection and plasmids transfection and verified by quantitative real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) and Western blotting. The effect of ICAT on the mobility of CRC cells was assessed by wound healing assay and transwell assay in vitro and lung metastasis in vivo. New candidate ICAT-interacting proteins were explored and verified using the STRING database, silver staining, co-immunoprecipitation mass spectrometry analysis (Co-IP/MS), and immunofluorescence (IF) staining analysis. RESULT: Inhibitor of ß-catenin and T-cell factor overexpression promoted in vitro cell migration and invasion and tumor metastasis in vivo. Co-IP/MS analysis and STRING database analyses revealed that junction plakoglobin (JUP), a homolog of ß-catenin, was involved in a novel protein interaction with ICAT. Furthermore, JUP downregulation impaired ICAT-induced migration and invasion of CRC cells. In addition, ICAT overexpression activated the NF-κB signaling pathway, which led to enhanced CRC cell migration and invasion. CONCLUSION: Inhibitor of ß-catenin and T-cell factor promoted CRC cell migration and invasion by interacting with JUP and the NF-κB signaling pathway. Thus, ICAT could be considered a protein diagnostic biomarker for predicting the metastatic ability of CRC.

Potential roles of serum ATPase and AMPase in predicting diagnosis of colorectal cancer patients.

Colorectal cancer (CRC) is a common gastrointestinal cancer with high incidence and mortality rates. CRC may be associated with regulation of circulating nucleotides. This study aimed to evaluate the serum levels of nucleotide-metabolizing enzymes (ATPase and AMPase) in patients with CRC and to explore the clinical diagnostic value of these enzymes. The gene set variation analysis (GSVA) score of the ATP-adenosine signature was calculated using tumor samples from The Cancer Genome Atlas (TCGA). ATP-adenosine signaling plays a central role in CRC progression. A total of 135 subjects, including 87 patients with CRC and 48 healthy controls, were included. The serum levels of ATPase and AMPase in the CRC group were significantly higher than those in the control group (P < 0.05). Furthermore, ATP and AMP hydrolysis levels significantly increased in the advanced CRC group (P < 0.05). ATP and AMP hydrolysis was decreased by the ENTPDase inhibitors (POM-1 and ARL67156) and CD73 inhibitor (APCP). The sensitivities of ATPase and AMPase were 95.4% and 75.9%, respectively, which were higher than those of CEA (67.8%) and CA19-9 (72.4%). The specificities of ATPase and AMPase were 69.9% and 73.9%, respectively, which were higher than that of CA19-9 (47.8%). The combination of CEA, ATPase, and AMPase demonstrated high sensitivity (92.0%) and specificity (87.0%). Collectively, ATPase and AMPase activities are upregulated in CRC with considerable diagnostic significance. The combination of CEA, ATPase, and AMPase may provide a novel approach for CRC screening.

Overexpression of ICAT Inhibits the Progression of Colorectal Cancer by Binding with ß-Catenin in the Cytoplasm.

Inhibitor of ß-catenin and T-cell factor (ICAT) was first found as a polypeptide that blocks ß-catenin-TCF interaction. Abundant evidence has shown that ICAT has different functions in diverse cancers' progression. Nevertheless, the roles it plays in colorectal cancer (CRC) have not been described. Here, we documented that ICAT expression was higher in CRC tissue than in the adjacent normal tissue and that prognosis was better in high-ICAT expression patients. The overexpression of ICAT inhibited CRC cell proliferation both in vitro and in vivo. Wnt pathway transcriptional activity was suppressed in the CRC cells with ICAT overexpression, where the CCND1 and MYC expression, which occurs downstream of the Wnt signaling pathway, was inhibited. Co-immunoprecipitation experiments showed that ICAT bound with ß-catenin in stable overexpression cell lines; immunofluorescence showed the co-localization of ICAT and ß-catenin in the cytoplasm. Overall, our study reveals that ICAT inhibits CRC cell proliferation by binding to cytoplasm-located ß-catenin, and prevents its translocation, which results in Wnt signaling pathway inactivation. It may provide a scientific foundation for focusing on ICAT in treatments for CRC.

Improved diagnostic value by combining plasma PON1 level with tumor biomarkers in Colorectal Cancer patients.

The incidence of colorectal cancer (CRC) ranks third among all cancers in China and improvements in screening for CRC have an important impact on prevention and control of the disease. Paraoxonase 1 (PON1) is a calcium ion-dependent hydrolase that is widely distributed in tissue. Its diagnostic value in colorectal cancer has been reported, but the diagnostic value of combining PON1 with carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 12-5 (CA12-5) in colorectal cancer has not been evaluated. Experiments were carried out in a total of 284 CRC patients and 90 healthy controls. The primary cohort was randomly divided into training and validation sets. The levels of PON1 in plasma of CRC patients were significantly lower than that in the healthy controls (P < 0.001). It showed excellent diagnostic value with the AUC reaching 0.750 for the training set and 0.742 for the validation set. Furthermore, combining PON1 with CEA, CA12-5, CA19-9 could better classify CRC patients (AUC rising from 0.821, 0.716, 0.712 to 0.875, 0.817 and 0.814, respectively, in the training set, from 0.818, 0.581, 0.593 to 0.854, 0.770, and 0.772 in the validation set). In conclusion, PON1 can serve as a diagnostic biomarker for CRC and raise the sensitivity and specificity when incorporated with traditional tumor biomarkers.

Exosomal transfer of p-STAT3 promotes acquired 5-FU resistance in colorectal cancer cells.

BACKGROUND: Acquired resistance remains a limitation of the clinical use of 5-fluorouracil (5-FU). Because exosomes, are important vesicles participating in intercellular communication, their contribution to the development of acquired 5-FU resistance needs to be elucidated. In this study, we aimed to examine the underlying mechanisms of exosomes from 5-FU resistant cells (RKO/R) in sustaining acquired 5-FU resistance in sensitive cells (RKO/P). METHODS: Exosomes from a 5-FU-resistant cell line (RKO/R) and its parental cell line RKO/P were isolated and co-cultured with 5-FU-sensitive cells. Real-time cellular analysis (RTCA) and FACS analysis were used to examine cell viability and apoptosis. Exosomal protein profiling was performed using shotgun proteomics. Inhibitors and siRNAs were applied to study the involvement of selected proteins in 5-FU resistance. The effect of exosomal p-STAT3 (Tyr705) on the caspase cascade was examined by western blotting (WB) and high content analysis. Xenograft models were established to determine whether exosomal p-STAT3 can induce 5-FU resistance in vivo. RESULTS: Our results indicated that exosomes from RKO/R cells significantly promoted cell survival during 5-FU treatment. Proteomics and WB analysis results indicated that GSTP1 and p-STAT3 (Tyr705) were enriched in exosomes from RKO/R cells. Inhibition of p-STAT3 re-sensitized RKO/P cells to 5-FU via caspase cascade. Furthermore, p-STAT3 packaged by exosomes from RKO/R cells increased resistance of tumor cells to 5-FU in vivo. CONCLUSIONS: Our results reveal a novel mechanism by which p-STAT3-containing exosomes contribute to acquired 5-FU resistance in CRC. This study suggests a new option for potentiating the 5-FU response and finding biomarkers for chemotherapy resistance.

[Effects of low temperature exposure on dermal microvascular endothelial cells function].

OBJECTIVE: To explore the damage effects and expression of vascular endothelial growth factor (VEGF) exposed with different low-temperatures on rat dermal microvascular endothelial cells (DMVECs). METHODS: Primary DMVECs were obtained by discontinuous Percoll gradient centrifugation. The DMVECs were identified by phase contrast microscope and immunofluorescence studies for CD31 antigen. Applied 28 degrees C, 12 degrees C and 0 degrees C to interfere with rat DMVECs as cold-exposure model. The changes of cells morphology were observed under invert microscope. The membrane integrity was determined by lactate dehydrogenase (LDH) activity. RT-PCR was used to examine the expression of vascular endothelial growth factor mRNA in cells. RESULTS: The monolayer of cultured PMVECs displayed the shape of pavingstone. CD31 antigen and binding BSI results by fluorescence microscope identified the cultured cells were DMVECs. After 24 h cold exposure, the cell morphology of 0 degrees C group was shrunken, the other groups were "Fibroblast-like". The LDH activity (U/L) in the medium of 28 degrees C, 12 degrees C and 0 degrees C groups was 54.17 +/- 3.02, 64.66 +/- 3.03, 82.13 +/- 10.91 respectively, which was significantly higher than that of 37 degrees C group (12.23 +/- 3.0, P < 0.01). The VEGF mRNA expression level was up-regulated in 28 degrees C group and 12 degrees C group versus control group (P < 0.05), but unchanged in 0 degrees C group. CONCLUSION: The rat DMVECs injury severity are deteriorated with temperature decreasing, and VEGF might be involved in the regulation of membrane permeability in this period.

[The damage effects of hypothermia combined with hypoxia on rat pulmonary microvascular endothelial cells].

OBJECTIVE: To study the synergistic effects of hypothermia and hypoxia on the damage of pulmonary microvascular endothelial cells (PMVEC) in rat. METHODS: Primary PMVECs were obtained by complex phosphoesterasum digesting from isolated lung tissues of Wistar rats, the PMVECs were identified by phase contrast microscope and immunofluorescence studies for CD31 antigen and bandeiraea simplicifolia isolectin (BSI) binding test. Factorial design was adopted in trial according to hypothermia and hypoxia existing or not. Using corresponding kit measured the levels of lactate dehydrogenase (LDH) activity in cell medium. Level of nitric oxide (NO) concentration was measured by Griess Assay. RT-PCR was used to examine the expression of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) mRNA in PMVECs. RESULTS: The monolayer of cultured PMVECs displayed the shape of pavingstone. CD31 antigen and binding BSI results by fluorescence microscope identified the cultured cells were PMVECs. Compared to the control group, LDH activity and VEGF, ET-1 expression levels were significantly increased in hypothermia group, hypoxia group and hypoxia combined with hypothermia group. And the levels of NO concentration were reduced in these three groups. The results of One-way ANOVA showed that there was a synergistic effect between hypothermia and hypoxia. CONCLUSION: Hypothermia and hypoxia both have an effect on PMVECs whether in altering the cell permeability or in releasing of vasoactive substances including NO and ET-1. In addition, there is a synergistic effect between hypothermia and hypoxia.

[Changes of protein kinase A expressions in central amygdaloid nuclei during the process of chronic morphine-induced conditioned place aversion in rats].

OBJECTIVE: To explore neurobiological mechanisms of the withdrawal-induced aversion. The changes of protein kinase A were measured in central amygdaloid nucleic (CeA) of conditioned place aversion (CPA) model rats. METHODS: (1) All 72 male SD rats were divided into three groups, model group (MN group), and control group (MS group and SN group). MN group was injected with morphine,6.5 days, 10 mg/kg, intraperitoneally (ip), twice per day, naloxone injection, 0.3 mg/kg, ip, along with conditioned place aversion training, to develop the CPA model. The MS group was administrated equivalent volume of morphine and saline. Also the SN group was injected with equivalent volume of saline and naloxone. (2) During the process of morphine-induced CPA, the expression of protein kinase A was assayed with immunohistochemistry in the CeA. RESULTS: In the MN group, protein kinase A expressions in the CeA occurred adaptive changes at different points of CPA (P < 0.05). Protein kinase A expressions after establishment(Day7,134.43 +/- 4.481, P < 0.05), and after extinction (Day 13, 141.01 +/- 3.360, P < 0.01), and after reinstatement (Day 14,137.18 +/- 40.330, P < 0.05) were also lower than those before the establishment of the CPA (Day 5, 124.48 +/- 6.722). However, PKA expressions were not significantly different both in MS group (P > 0.05)and SN group (P > 0.05). CONCLUSION: (1) Protein kinase A expression, in turn regulating the aversion expression, in the CeA probably is a key pathway contributing to the development of CPA. (2) The neuroadaptation mediated by protein kinase A may be one of the important molecular underpinnings of CPA.

[Protective effects of SUR2B/Kir6.1 potassium channel opener natakalim against RAVECs injuries induced by hypoxia].

OBJECTIVE: To investigate the protective effects of natakalim against rat aortic vascular endothelial cells (RAVECs) injuries induced by hypoxia and its mechanisms. METHODS: Selecting RAVECs as a cell model injured by hypoxia, these RAVECs were divided into 5 groups: i.e. control group, hypoxia group, natakalim low, medium and high group. The cell survival rate was determined by MTT assay, con was measured using Griess Assay, RT-PCR was used to examine t he expression of intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) mRNA in RAVEC. RESULTS: Natakalim could reverse hypoxia-induced changes in endothelial cell function, including increased endothelial cell survival rate and level of NO concentration, significantly inhibited the hypoxia-induced endothelial ICAM-1, ET-1, VEGF mRNA expression levels increased. CONCLUSION: Natakalim have protective effects on hypoxia-induced changes in endothelial cell function, increasing of permeation, excess expression of cell adhesion molecules.

Precise segmentation of multiple organs in CT volumes using learning-based approach and information theory.

In this paper, we present a novel method by incorporating information theory into the learning-based approach for automatic and accurate pelvic organ segmentation (including the prostate, bladder and rectum). We target 3D CT volumes that are generated using different scanning protocols (e.g., contrast and non-contrast, with and without implant in the prostate, various resolution and position), and the volumes come from largely diverse sources (e.g., diseased in different organs). Three key ingredients are combined to solve this challenging segmentation problem. First, marginal space learning (MSL) is applied to efficiently and effectively localize the multiple organs in the largely diverse CT volumes. Second, learning techniques, steerable features, are applied for robust boundary detection. This enables handling of highly heterogeneous texture pattern. Third, a novel information theoretic scheme is incorporated into the boundary inference process. The incorporation of the Jensen-Shannon divergence further drives the mesh to the best fit of the image, thus improves the segmentation performance. The proposed approach is tested on a challenging dataset containing 188 volumes from diverse sources. Our approach not only produces excellent segmentation accuracy, but also runs about eighty times faster than previous state-of-the-art solutions. The proposed method can be applied to CT images to provide visual guidance to physicians during the computer-aided diagnosis, treatment planning and image-guided radiotherapy to treat cancers in pelvic region.

Multi-stage learning for robust lung segmentation in challenging CT volumes.

Simple algorithms for segmenting healthy lung parenchyma in CT are unable to deal with high density tissue common in pulmonary diseases. To overcome this problem, we propose a multi-stage learning-based approach that combines anatomical information to predict an initialization of a statistical shape model of the lungs. The initialization first detects the carina of the trachea, and uses this to detect a set of automatically selected stable landmarks on regions near the lung (e.g., ribs, spine). These landmarks are used to align the shape model, which is then refined through boundary detection to obtain fine-grained segmentation. Robustness is obtained through hierarchical use of discriminative classifiers that are trained on a range of manually annotated data of diseased and healthy lungs. We demonstrate fast detection (35s per volume on average) and segmentation of 2 mm accuracy on challenging data.