Safety and efficacy of dendritic cell-based immunotherapy (DCVAC/LuCa) combined with carboplatin/pemetrexed for patients with advanced non-squamous non-small-cell lung cancer without oncogenic drivers.

BACKGROUND: Our prospective, open-label, single-arm phase II study investigated the safety and efficacy of DCVAC/LuCa (dendritic cell vaccines for lung cancer) combined with standard carboplatin/pemetrexed in advanced non-squamous (nsq) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients had stage IV nsq NSCLC without oncogenic drivers and had not received prior systemic cancer therapy. Treatment consisted of carboplatin/pemetrexed for up to 6 cycles followed by 21 cycles of pemetrexed maintenance or until progression or intolerance. Non-progression patients after two cycles of chemotherapy started to receive DCVAC/LuCa subcutaneously (s.c.) on day 15 of cycle 3, and thereafter q3w (day 15 of chemotherapy cycles) for up to 15 doses. Dosing of DCVAC/LuCa s.c. varied among patients depending on the baseline number of leucocytes but remained constant for each single patient. Safety was assessed by adverse events (AEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). Efficacy was measured by overall survival (OS), progression-free survival (PFS), time to progression (TTP), and objective response rate (ORR). RESULTS: Sixty-one patients were enrolled. In the safety population (n = 60), eight patients (13.33%) had grade 3 or greater TRAEs, and six patients (10.0%) showed SAEs which were not related to leukapheresis or DC vaccination. Six grade 1 AEs were considered to be related to leukapheresis. No AESIs or DCVAC/LuCa-induced AEs were observed. The 2-year survival rate in the modified intention-to-treat population (n = 44) was 52.57%. Median OS was not reached. Median PFS was 8.0 months, median TTP was 10.2 months, and the ORR was 31.82%. CONCLUSION: In treatment-naïve stage IV nsq NSCLC patients without oncogenic drivers, the combination of carboplatin/pemetrexed and DCVAC/LuCa was well tolerated and showed promising efficacy. Therefore, a study to prove our immunotherapeutic concept in a randomized phase III trial is planned.

[Clinicopathological features and prognosis of primary mediastinal large B-cell lymphoma: a series of sixty cases].

Objective: To investigate the clinicopathological features and prognostic factors of primary mediastinal large B-cell lymphoma (PMBL). Methods: The clinical data of 60 patients with PMBL including 44 biopsy cases and 16 consultation cases from September 2000 to November 2019 in the Department of Pathology, China-Japan Friendship Hospital (14 cases) and Peking Union Medical College Hospital (46 cases) were enrolled. Pathologic features, immunophenotype, immunoglobulin (Ig) gene rearrangement and microRNA expression profile were retrospectively studied. Results: Of the 60 patients, 23 were males and 37 were females, age ranged from 15 to 64 years (median 28 years). Immunohistochemical staining showed that the tumor cells were positive for pan-B cell antigens, CD30 (77.4%, 24/31), CD23 (73.1%, 19/26), MUM1 (45.8%, 11/24), Ki-67 index ≥70 % (90.6%, 29/32). EBER in situ hybridization was analyzed in 21 PMBL, only one case (4.8%) was positive. Ig gene rearrangement was performed in 20 cases, and seven were positive (35.0%). MicroRNA gene expression profiles were analyzed in seven cases of PMBL and nine cases of diffuse large B-cell lymphoma, and there were 33 microRNAs with significant difference (P<0.05). Univariate analysis indicated that the poor prognostic factors included serum lactate dehydrogenase (LDH) level,International Prognostic Index (IPI) score ≥3, stages Ⅲ-Ⅳ, chemotherapy not combined with rituximab and MUM1 positivity (P<0.05). Multivariate analysis showed that the treatment combined with rituximab was independently related to prognosis (P<0.05). Conclusions: PMBL is different from diffuse large B-cell lymphoma in clinicopathologic features, immunophenotypic presentation and molecular features. The prognostic factors, molecular genetics and immunological characteristics reveal that this study has enriched our understanding of the biology of PMBL, thus providing evidence and strategies for treatment.

Immune cell infiltration features and related marker genes in lung cancer based on single-cell RNA-seq.

PURPOSE: Immune cells in the immune microenvironment of lung cancer have a great impact on the development of lung cancer. Our purpose was to analyze the immune cell infiltration features and related marker genes for lung cancer. METHODS: Single cell RNA sequencing data of 11,485 lung cancer cells were retrieved from the Gene Expression Omnibus. After quality control and data normalization, cell clustering was performed using the Seurat package. Based on the marker genes of each cell type from the CellMarker database, each cell was divided into G1, G2M, and S phases. Then, differential expression and functional enrichment analyses were performed. CIBERSORT was used to reconstruct immune cell types. RESULTS: Following cell filtering, highly variable genes were identified for all cells. 14 cell types were clustered. Among them, CD4 + T cell, B cell, plasma cell, natural killer cell and cancer stem cell were the top five cell types. Up-regulated genes were mainly enriched in immune-related biological processes and pathways. Using CIBERSORT, we identified the significantly higher fractions of naïve B cell, memory CD4 + T cell, T follicular helper cell, T regulatory helper cell and M1 macrophage in lung cancer tissues compared to normal tissues. Furthermore, the fractions of resting NK cell, monocyte, M0 macrophage, resting mast cell, eosinophil and neutrophil were significantly lower in tumor tissues than normal tissues. CONCLUSION: Our findings dissected the immune cell infiltration features and related marker genes for lung cancer, which might provide novel insights for the immunotherapy of lung cancer.

A polymorphic MYC response element in KBTBD11 influences colorectal cancer risk, especially in interaction with an MYC-regulated SNP rs6983267.

Background: MYC is a well-established cancer driver gene regulating the expression of numerous genes, indicating that polymorphisms in MYC response elements could affect tumorigenesis through altering MYC regulation. We performed integrative multistage study to evaluate the effects of variants in MYC response elements and colorectal cancer (CRC) risk. Patients and methods: We systematically integrated ChIP-Seq, DNase-Seq and transcription factor motif data to screen variants with potential ability to affect the MYC binding affinity. Then, we conducted a two-stage case-control study, totally consisting of 4830 CRC cases and 4759 controls in Chinese population to identify risk polymorphisms and interactions. The effects of risk variants were confirmed by functional assays in CRC LoVo, SW480 and HCT15 cells. Results: We identified a novel polymorphism rs11777210 in KBTBD11 significantly associated with CRC susceptibility (P = 2.43 × 10-12). Notably, we observed a significant interaction between rs11777210 and MYC nearby rs6983267 (P-multi = 0.003, P-add = 0.005), subjects carrying rs6983267 GG and rs11777210 CC genotypes showing higher susceptibility to CRC (2.83-fold) than those carrying rs6983267 TT and rs11777210 TT genotypes. We further demonstrated that rs6983267 T > G increased MYC expression, and MYC bound to and negatively regulated KBTBD11 expression when the rs11777210 C risk allele was present. KBTBD11 was downregulated in tumor tissues, and KBTBD11 knockdown promoted cell proliferation and inhibited cell apoptosis. Conclusion: The rs11777210 is a potential predictive biomarker of CRC susceptibility, and KBTBD11 functions as a putative tumor suppressor in tumorigenesis. Our study highlighted the high CRC risk of people carrying rs6983267 G and rs11777210 C alleles, and provided possible biological mechanism of the interaction.

Relationship between red blood cell distribution width, bilirubin, and clinical characteristics of patients with gastric cancer.

INTRODUCTION: Red blood cell distribution width (RDW) and bilirubin have been proved to be prognostic factors for various types of cancer. However, their prognostic value in patients with gastric cancer (GC) remains largely unknown. METHODS: To verify whether RDW and bilirubin are prognostic factors for patients with GC, we performed a cross-sectional study to analyze the relationship between RDW, bilirubin, and the clinical characteristics of patients with GC. Medical records of all newly diagnosed and pathologically proved patients with GC admitted to Changzheng Hospital between January 2016 and July 2016 were retrospectively reviewed. The relationship between RDW, bilirubin, and the clinical characteristics of patients with GC was analyzed. RESULTS: A total of 144 patients with GC were enrolled. Patients with GC had significantly higher RDW than healthy controls, even after adjusting for hemoglobin, while total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were significantly decreased. Furthermore, RDW and bilirubin were significantly correlated with tumor stage, as well as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). CONCLUSION: Our study indicated that RDW and bilirubin could be potential prognostic factors for patients of GC.

Effects of online cone-beam computed tomography with active breath control in determining planning target volume during accelerated partial breast irradiation.

PURPOSE: To test if active breath control during cone-beam computed tomography (CBCT) could improve planning target volume during accelerated partial breast radiotherapy for breast cancer. METHODS: Patients who were more than 40 years old, underwent breast-conserving dissection and planned for accelerated partial breast irradiation, and with postoperative staging limited to T1-2 N0 M0, or postoperative staging T2 lesion no larger than 3cm with a negative surgical margin greater than 2mm were enrolled. Patients with lobular carcinoma or extensive ductal carcinoma in situ were excluded. CBCT images were obtained pre-correction, post-correction and post-treatment. Set-up errors were recorded at left-right, anterior-posterior and superior-inferior directions. The differences between these CBCT images, as well as calculated radiation doses, were compared between patients with active breath control or free breathing. RESULTS: Forty patients were enrolled, among them 25 had active breath control. A total of 836 CBCT images were obtained for analysis. CBCT significantly reduced planning target volume. However, active breath control did not show significant benefit in decreasing planning target volume margin and the doses of organ-at-risk when compared to free breathing. CONCLUSION: CBCT, but not active breath control, could reduce planning target volume during accelerated partial breast irradiation.

PKR2 and ß-catenin genes regulates pancreatic cancer chemosensitivity.

OBJECTIVE: Pancreas is a well developed glandular organ lying behind the stomach. Cancer arises in this organ are difficult to identify in the initial stages, even in advanced stages it shows non-specific symptoms, and it is difficult to prognosis. Since they are identified and treated in the last stage, they are less responsive to chemotherapy. Therefore, it is important to study the proteins that are involved in regulating chemosensitivity and chemoresistance. MATERIALS AND METHODS: Initially, using KRAS mutant mice, we developed initial and advanced stage of pancreatic cancer. And we analyzed the expression of PKR2 and ß-catenin in different pathological stages of pancreatic cancer using Immunohistology and Western blotting. RESULTS: The histology of the tissue nature confirms and helps to categorize cancer, which shows enlarged nucleus in initial stages and shows clustering of cells in advanced stages. Immunohistological and Western blotting analyzes show prominent increasing in the expression of PKR2 and ß-catenin as the tumor develops to the next stages. On the course of initial treatment with cisplatin we find out that PKR2 and ß-catenin regulate the chemosensitivity with under-expression when compared with respective controls. In the advanced stages of pancreatic cancer with cisplatin treatment, we observed chemoresistance behavior with overexpression, especially for ß-catenin. CONCLUSIONS: The results conclude that using PKR2 and ß-catenin we are able to assess the chemosensitivity and chemoresistance nature of pancreatic cancer.

Effects of different sources of protein on the growth performance, blood chemistry and polypeptide profiles in the gastrointestinal tract digesta of newly weaned piglets.

To determine the effects of different sources of protein on the growth performance of newly weaned piglets, 72 newly weaned piglets were randomly assigned to three groups fed different diets (soya bean, casein and dried distillers' grain with solubles (DDGS) feeds). Casein and DDGS feeds consisted of soya bean feed in which 5% of the CP was replaced with casein- or DDGS-derived CP respectively. Blood and chyme samples were collected from each piglet 2 h post-feeding on days 0 and 28 of the feeding period. The DDGS feed decreased DMI (p = 0.024) and increased FCR (p = 0.025) due to lower nitrogen utilization (p = 0.078) than those of other feeds. Total amino acid content in chyme demonstrated that casein feed digested rapidly in the duodenum (p = 0.005), whereas DDGS feed was digested primarily in the distal jejunum (p = 0.003) and ileocecum (p = 0.002). However, polypeptide profiles in chyme exhibited a pattern different from those of amino acids. There were no differences in the polypeptide profiles in the stomachs of piglets fed soya bean or casein feeds (p > 0.05), but soya bean group had greater amounts of small polypeptides (mass under m/z 3000 Da) in the duodenum (p = 0.052) than other groups. In contrast, the DDGS feed group had more large polypeptides (m/z 3000-4000 Da) in the stomach than the other groups (p < 0.001). In addition, 10 pairs of polypeptides with matching masses were identified in the plasma and digesta, indicating that polypeptides may have been transported across the intestinal epithelial cells and into the blood. Taken together, substitution of 5% of the CP in soya bean meal-based feed with DDGS-derived CP decreased the growth performance of newly weaned piglets due to poor digestibility and N utilization of DDGS feed, as well as untimely digestion of casein feed.

A case report of fetal malignant immature mediastinal teratoma.

PURPOSE: Fetal immature mediastinal teratoma is a rare disease. The pressure generated by the tumor mass can cause hydrops fetalis, pulmonary hypoplasia, pleural and peritoneal effusion, and polyhydramnios which cause the death of the fetus. Routine prenatal ultrasound has enabled accurate diagnosis. MATERIALS AND METHODS: The authors report a 26-year-old patient, gravida 4 para 1, who was referred to this hospital, carrying a fetus with immature mediastinal teratoma. RESULTS: At 27 weeks of gestation, a routine prenatal ultrasound suggested the fetus had a mass at the anterior mediastinum, accompanied by pulmonary hypoplasia, pleural and peritoneal effusion, subcutaneous edema of head and chest, and polyhydramnios. After the therapeutic abortion, the gross anatomy confirmed the mediastinal mass. The histological examination showed that the mass was a grade 2 immature teratoma. CONCLUSIONS: The mother of the fetus had been exposed to plaster, paint, and paint-thinner in the first trimester of pregnancy, suggesting that these chemical contacts may be one of the causes of the disorder.

[Association between genetic variants in p53 binding sites and risks of breast cancer in Chinese population].

OBJECTIVE: To investigate the association between breast tissue specified variants in p53 binding sites and the risk of BC in Chinese women. METHODS: ChIP-seq database on p53 binding sites in MCF-7 cell lines was extracted to identify the possible variants in p53 target genes. A hospital-based case-control study was then performed to investigate the association between variants in p53 binding sites and the risk of BC in a Chinese women population. RESULTS: Three variants were identified from the bioinformatics analysis. A total of 1 274 BC cases and 1 255 frequency-matched cancer-free controls were included in this case-control study. The average age was comparable between the case and the control groups, with the P value as 0.318. Meanwhile, distributions on menopausal status, smoking and alcohol intake between cases and controls were similar with the P values as 0.539, 0.258 and 0.131, respectively. The genotype distribution of rs1295925 was significantly different between the case and the control groups. Individuals that carrying rs1295925-CT and rs1295925-TT genotypes were significantly associated with an increased BC risk when compared with rs1295925-CC genotype after adjustment of age, menopausal status, smoking and alcohol intake (OR=1.32, 95%CI: 1.07-1.62 and OR=1.41, 95%CI: 1.13-1.78, respectively). Positive associations were also observed under the allelic, dominant and additive models. CONCLUSION: rs1295925 which located in VMP1 gene was associated with increased BC risk in the Chinese women population.

Real-time PCR assay with high resolution melting for EGFR and BIM mutation of lung cancer.

OBJECTIVE: To establish and develop a reliable and simple Real-time PCR assay with high resolution melting (Real-time PCR-HRM) method for detection epidermal growth factor (EGFR) and BIM mutation of lung cancer and looking for effective targeted drugs to control lung cancer. PATIENTS AND METHODS: A total of 6858 participants (2538 cases with lung cancer and 4275 healthy controls who took part in the study by doing the physical examination in Shanghai Xuhui community) were recruited in the study. Clinical characteristics and 5 ml peripheral blood were collected from each participant, and the DNA has been extracted, which were determined the EGFR and BIM mutation by Real-time PCR-HRM. Data were recorded and Statistical analyses. RESULTS: All samples completed the study. BIM deletion polymorphism was no related with age, sex, and smoking or EGFR mutation. CONCLUSIONS: There were no relations among BIM deletion polymorphism, EGFR mutation or lung cancer risk. HRM is a novel procedure and provides rapid, sensitive, specific and simultaneous detection for gene mutation of cancer patients for predicting the efficacy of targeted therapy.

DIGRE: Drug-Induced Genomic Residual Effect Model for Successful Prediction of Multidrug Effects.

Multidrug regimens are a promising strategy for improving therapeutic efficacy and reducing side effects, especially for complex disorders such as cancer. However, the use of multidrug therapies is very challenging, due to a lack of understanding of the mechanisms of drug interactions. We herein present a novel computational approach-Drug-Induced Genomic Residual Effect (DIGRE) Computational Model-to predict drug combination effects by explicitly modeling drug response curves and gene expression changes after drug treatments. The prediction performance of DIGRE was evaluated using two datasets: (i) OCI-LY3 B-lymphoma cells treated with 14 different drugs and (ii) MCF breast cancer cells treated with combinations of gefitinib and docetaxel at different doses. In both datasets, the predicted drug combination effects significantly correlated with the experimental results. The results indicated the model was useful in predicting drug combination effects, which may greatly facilitate the discovery of new, effective multidrug therapies.

Effects of dietary supplementation with green tea polyphenols on digestion and meat quality in lambs infected with Haemonchus contortus.

Ujumqin sheep are susceptible to infection by the gastrointestinal nematode Haemonchus contortus, which reduces productivity and total meat yield in sheep. Thus, the effects of green tea polyphenol (GTP) supplements (0, 2, 4, or 6g of GTP/kg feed) on dietary nutrient digestibility and meat quality in lambs infected with H. contortus were examined; control lambs were not infected. H. contortus infections did not affect digestion but the apparent digestibilities of nutrients were decreased by dietary 2g of GTP/kg feed supplementation. There was an interaction between treatment and sampling time on plasma total protein, urea nitrogen, and amino acid concentrations. The antioxidant activity and meat color of INFGTP0 lambs decreased. In conclusion, H. contortus infections in lambs decreased meat quality, but appropriate levels of dietary GTP supplementation diminished these negative effects though lower dose of GTP supplement showed negative effects on digestion.

Meat quality, fatty acid composition of tissue and gastrointestinal content, and antioxidant status of lamb fed seed of a halophyte (Suaeda glauca).

Twenty-four Merino lambs were randomly assigned to four treatments: control diet (CT) consisting of 300g concentrates with ad libitum Leymus chinensis hay; C with 150g (T150), 300g (T300) and 450g (T450) Suaeda glauca seed, respectively. Meat quality, fatty acid composition of meat and lipid tissue and antioxidant status of lamb were evaluated. Inclusion of S. glauca seeds significantly increased selenium (Se) concentrations of muscle. The proportions of C18:1 trans-11 in muscle, C18:2 n-6, PUFA, n-6 series fatty acids, and the ratios of P:S in rumen contents, as well as the ratios of n-6:n-3 in adipose tissue, rumen and duodenum content have been significantly (P<0.05) improved with supplementation of S. glauca seeds to lamb diets. No significant effect was found on antioxidant status. The results suggest that S. glauca seed supplementation in lamb diets may change fatty acid composition in tissues and content of digestive tract.

Human intrahepatic biliary epithelial cells engulf blebs from their apoptotic peers.

The phagocytic clearance of apoptotic cells is critical for tissue homeostasis; a number of non-professional phagocytic cells, including epithelial cells, can both take up and process apoptotic bodies, including the release of anti-inflammatory mediators. These observations are particularly important in the case of human intrahepatic biliary cells (HiBEC), because such cells are themselves a target of destruction in primary biliary cirrhosis, the human autoimmune disease. To address the apoptotic ability of HiBECs, we have focused on their ability to phagocytize apoptotic blebs from autologous HiBECs. In this study we report that HiBEC cells demonstrate phagocytic function from autologous HiBEC peers accompanied by up-regulation of the chemokines CCL2 [monocyte chemotactic protein-1 (MCP-1)] and CXCL8 [interleukin (IL)-8]. In particular, HiBEC cells express the phagocytosis-related receptor phosphatidylserine receptors (PSR), implying that HiBECs function through the 'eat-me' signal phosphatidylserine expressed by apoptotic cells. Indeed, although HiBEC cells acquire antigen-presenting cell (APC) function, they do not change the expression of classic APC function surface markers after engulfment of blebs, both with and without the presence of Toll-like receptor (TLR) stimulation. These results are important not only for understanding of the normal physiological function of HiBECs, but also explain the inflammatory potential and reduced clearance of HiBEC cells following the inflammatory cascade in primary biliary cirrhosis.

Effect of tea catechins on regulation of cell proliferation and antioxidant enzyme expression in H2 O2 -induced primary hepatocytes of goat in vitro.

Tea catechins (TC) are polyphenols that have potent antioxidant activity. The objectives of this study were to determine the effects of TC on antioxidant status of hepatocytes challenged with H2 O2 . Primary hepatocytes of goat were exposed to 1 mm H2 O2 without or with 5, 50 and 500 µg/ml TC. The cells were harvested at 48 h post-treatment to determine effects of TC on proliferation, apoptotic features and membrane integrity of cells, and expression of genes and activities of antioxidant enzymes. H2 O2 exposure caused damage to cells (p < 0.001). A lower concentration of TC (5 µg/ml) displayed a protective effect by inhibiting exorbitant cell proliferation and DNA degradation. Both H2 O2 exposure and TC pre-incubation affected expression of antioxidant enzymes at mRNA and protein levels (p < 0.001). The activities of catalase (CAT) (p = 0.027), CuZn-superoxide dismutase (CuZn-SOD) (p < 0.001) and glutathione peroxidase (GPx) (p < 0.001) increased with TC pre-incubation followed by H2 O2 challenge. Changes of CuZn-SOD activity induced by H2 O2 and TC basically paralleled the changes in the corresponding mRNA and protein levels, but the correlation in CAT and GPx expression displayed slightly different patterns at different concentrations of TC. These findings infer that oxidative stress can induce deleterious cellular responses and this unfavourable condition may be alleviated by treatment with TC.

Inflammatory myofibroblastic tumour of the maxillary sinus: CT and MRI findings.

AIM: To characterize the computed tomography (CT) and magnetic resonance imaging (MRI) findings of inflammatory myofibroblastic tumours (IMTs) of the maxillary sinus. MATERIALS AND METHODS: The imaging findings of eight patients with IMTs of the maxillary sinus were reviewed retrospectively. Of the eight patients, four patients underwent unenhanced and contrast-enhanced CT, and one patient underwent unenhanced CT only; three patients underwent unenhanced and contrast-enhanced MRI. RESULTS: Five cases of IMTs occurred in the left maxillary sinus, while three cases were right-sided. Four cases occupied the entire sinus, and the other four cases only partially occupied the sinus. Unenhanced CT images showed heterogeneous masses in four cases and a homogeneous mass in one case. One of the tumours showed some areas of calcification. T1-weighted MRI images showed isointense lesions. T2-weighted images showed mixed isointense and mild hyperintense lesions. All cases showed bone destruction and had infiltrated into the nasal fossa, orbit, infratemporal fossa, and other adjacent tissues. Seven cases showed mild to moderate heterogeneous enhancement on contrast-enhanced CT or T1-weighted MRI images. CONCLUSION: IMTs of the maxillary sinus can be characterized as a soft-tissue mass with bony destruction and infiltration of the adjacent tissues, with mild to moderate enhancement after the injection of contrast medium. CT and MRI can help to diagnose IMTs, determine the extent of the lesion and its relationship with adjacent tissues, and thus facilitate the prediction of surgical resectability.

SU-E-T-539: The Effect of the Scattering Volume of Phantom on Dose Calculation Accuracy Using Elekta's Cone-Beam Computed Tomography (CBCT) for Head-Neck Radiotherapy.

PURPOSE: To analyze the scattering volume effect of phantom on HU values and dose calculation accuracy utilizing Elekta's cone-beam computed tomography (CBCT) for head and neck radiotherapy. METHODS: A water phantom was designed to simulate different scattering volume by varying its lengthfrom 5cm to 30cm.A CIRS density reference phantom combined with the water phantom was used to measure the CBCT HU values. HU-ED correction curves for 30cm length (Correction-A) and 5cm length (Correction-B) were generated for CBCT dose calculation, respectively. A four-field-box plan was designed both on CBCT and conventional CT of a head-neck anatomical phantom to compare the dosimetric difference. RESULTS: The maximum HU variance in the CBCT of the water phantom was up to 10% with varying phantom length. For the combined CIRS phantom, the HU value in CBCT was found to decrease in high-density inserts, but increase in low-density inserts with increasing scatter length.For dense-bone insert, the change in HU values was up to 1422HU. For head-neck anatomical phantom, the dose results showed an average difference of 0.3% of cGy /MU, 2-3mm of isodose discrepancy,and 97% of 2%/2mm DTA index for each beam with Correction-A; and 3.7% of cGy /MU,1.5-3cm of isodose discrepancy,and 59.5% of 2%/2mm DTA index for each beam with Correction-B. CONCLUSIONS: The scattering volume of phantom has a significant impact on the HU value and further HU-D calibration of Elekta's CBCT. Excellent dosimetric agreement between CBCT and conventional CT was found when the HU-D calibration phantom volume is close to patient volume imaged by CBCT.

The role of CD11c(+) hepatic dendritic cells in the induction of innate immune responses.

The role of the liver in the initiation and maintenance of tolerance is a critical immune function that involves multiple lineages of immune cells. Included within these populations are liver dendritic cells (DCs). Although there has been significant work on the phenotypic and functional roles of splenic and bone marrow dendritic cells, as well as their subsets, comparable studies in liver have often been difficult. To address this issue we have isolated, from C57BL/6 mice, relatively pure populations of DCs and compared phenotype and function to the data from spleen using flow cytometry, cell sorter assisted purification and culture, morphology by cytospin and May-Giemsa staining, cell cycle progression, antigen uptake, cytokine production and allo-activation potential. natural killer (NK)1.1(-)CD11c(+) liver DC subsets (conventional DCs, T cell receptor (TcR)beta(-)NK1.1(-)CD11c(+)B220(-) and plasmacytoid DCs, TcRbeta(-)NK1.1(-)CD11c(+)B220(+)) efficiently endocytose dextran and produce significant levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-12 p40 in response to Toll-like receptor (TLR) ligands, with responses higher than splenic DCs. There is also a differential capability of hepatic DCs to respond to innate signals. Indeed, CD11c(+) hepatic DCs have a greater capacity to respond to innate stimulation but are less capable of inducing CpG activated-allogeneic T cells. These data suggest that hepatic dendritic cells function as a critical bridge between innate and adaptive immunity and are capable of inducing stronger innate responses with a lower capacity for allo-stimulation than splenic dendritic cells. These properties of liver dendritic cells contribute to their unique role in the induction of tolerance.