Abstract
Introduction: Liver plasmacytoid dendritic cells (pDC) are considered to be weak stimulators of in vitro T cell responses. We sought to determine their ability to prime an antigen specific T ...cell response in vivo.
Methods: C57BL/6 murine spleen and liver pDC (CD11c+B220+NK1.1−CD19−CD11b−) were expanded in vivo with the use of an adenovirus encoding murine Flt3L cDNA and isolated by fluorescence activated cell sorting. CD45.2+ CFSE-labeled OT-I T cells were injected in the lateral tail vein of congenic recipient CD45.1 mice, pDC loaded with OVA257–264 (1μg/ml) or TRP-2181–188 (1μg/ml) were subsequently injected into the footpad. Three days later popliteal nodal lymphocytes were analyzed by flow cytometry for dissolution of CFSE fluorescence among CD3+CD8+CD45.2+cells.
Results: Flt3L expanded OVA257–264 loaded liver pDC and spleen pDC caused 70% and 79% respectively of the transferred T cells to divide. TRP-2181–188 loaded pDC induced no T cell division.
Conclusion: Liver pDC can initiate antigen specific T cell responses in vivo.
This work was supported by grant DK068346.
The present study was undertaken to define the clinical differences between leiomyosarcomas (LMS) occurring within the abdomen and retroperitoneum and gastrointestinal stromal tumors (GIST).
It was a ...retrospective, single-institution review of patients treated for intra-abdominal and retroperitoneal GIST and LMS from July 1, 1982 through August 1, 1999.
A total of 561 patients, 239 with GIST and 322 with LMS, were identified. Patients with GIST were older, with a median age of 58 years versus 54 years in the LMS group (P < .01). The majority of patients with GIST were male (58%), whereas 68% of LMS patients (excluding gender-specific sites) were female (P < .01). The 5-year disease-specific survival for GIST and LMS were 28% and 29%, respectively. The presentation status and ability to achieve a complete surgical resection were the main independent predictors of outcome for both GIST and LMS. Local and distant recurrence was common in both. The pattern of distant recurrence differed: 50% of all first-site GIST recurrences involved the liver, whereas 30% of all LMS first-site recurrences involved the lungs.
Although the two patient populations appear to be distinct, their clinical courses are similar. The pattern of distant spread follows the known patterns of hematogenous dissemination. Complete surgical resection is the cornerstone of treatment for primary GIST and LMS and in selected patients with local and distant recurrence.
Abstract
Introduction: Plasmacytoid dendritic cells (pDC) play a central role in innate immunity. While much is known about spleen pDC, liver pDC has only been recently identified and their function ...remains largely unknown. We sought to determine the ability of liver pDC to stimulate NK1.1+ cells in vitro in comparison to spleen pDC.
Methods: Liver and spleen pDC (CD11c+B220+NK1.1−CD19−CD11b−) from C57BL/6 mice were expanded in vivo with an adenovirus encoding murine Flt3L cDNA and isolated by fluorescence activated cell sorting. These cells were co-cultured with spleen NK1.1+ cells in the presence of CpG with or without a transwell insert. After 24 hours, supernatant IFN-γ level was determined by cytometric bead array. Additionally, α-GalCer –loaded liver and spleen pDC were stimulated with CpG and cultured with spleen NK1.1+ cells in the presence of CpG. IFN-γ production was measured after 24 hours.
Results: Flt3L-expanded liver pDC stimulated with CpG induced significantly higher CD69 expression on NK cells when compared to spleen pDC. CD69 expression by both groups was reduced by the presence of a transwell insert. Both liver and spleen pDC loaded with α-GalCer and stimulated with CpG induced large amounts of IFN-γ secretion by NK cells.
Conclusion: Upon expansion and stimulation, liver pDC are able to stimulate NK cells in vitro. This is partially mediated through cell-cell contact.
This work was supported by grant DK068346
Purpose The aim of this study was to build a molecular prognostic model based on gene signatures for patients with completely resected hepatic metastases from colorectal cancer (MCRC). Methods Using ...the Illumina HumanHT-12 gene chip, RNA samples from the liver metastases of 96 patients who underwent R0 liver resection were analyzed. Patients were randomly assigned to a training (n = 60) and test (n = 36) set. The genes associated with disease-specific survival (DSS) and liver-recurrence-free survival (LRFS) were identified by Cox-regression and selected to construct a molecular risk score (MRS) using the supervised principle component method on the training set. The MRS was then evaluated in the independent test set. Results Nineteen and 115 genes were selected to construct the MRS for DSS and LRFS, respectively. Each MRS was validated in the test set; 3-year DSS/LRFS rates were 42/32% and 79/80% for patients with high and low MRS, respectively (p = 0.007 for DSS and p = 0.046 for LRFS). In a multivariate model controlling for a previously validated clinical risk score (CRS), the MRS remained a significant predictor of DSS (p = 0.001) and LRFS (p = 0.03). When CRS and MRS were combined, the patients were discriminated better with 3-year DSS/LRFS rates of 90/89% in the low risk group (both risk scores low) vs 42/26% in the high risk group (both risk scores high), respectively (p = 0.002/0.004 for DSS/LRFS). Conclusion MRS based on gene expression profiling has high prognostic value and is independent of CRS. This finding provides a potential strategy for better risk-stratification of patients with liver MCRC.
Surgical treatment of malignant liver tumours DeMatteo, Ronald P.; Fong, Yuman; Blumgart, Leslie H.
Bailliere's best practice & research. Clinical gastroenterology,
12/1999, Letnik:
13, Številka:
4
Journal Article
Recenzirano
Surgical resection is the mainstay of treatment for malignant liver tumours and offers the only chance of cure. Advances in radiological imaging, surgical technique and peri-operative management have ...enabled liver resection to be performed safely. Partial hepatectomy is indicated for the treatment of hepatocellular carcinoma and hepatic metastases from colorectal cancer. In addition, it may be utilized for selected patients with liver metastases from other primary tumours. Total hepatectomy with transplantation may be of benefit in some patients with unresectable neuroendocrine metastases or small hepatocellular carcinomas. The role of cryosurgery has not been precisely defined, and it needs to be compared with other palliative therapies such as ethanol injection and hepatic artery embolization.
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