Induction of immunogenic variant of a murine fibrosarcoma]

Immunogenic variant was induced from the methylcholanthrene induced fibrosarcoma (MCA-F) by in vitro treatment with the mutagen 1-methyl-3-nitro-1-nitrosoguanidine (MNNG). D-10 tumor cell which was cloned from MNNG treated MCA-F tumor cell was rejected by normal syngeneic C3H-HeJ mice but not by 650 rad irradiated immunosuppressed mice. Host which had rejected D-10 tumor growth, rejected parental MCA-F tumor cells. But active immunotherapy using D-10 tumor cell against MCA-F tumor cells. But active immunotherapy using D-10 tumor cell against MCA-F tumor bearing mice was not successful. Cytotoxic T cell (CTL) established from D-10 immunized spleen cells showed D-10 specific cytotoxic activity and not lysed parent MCA-F cells. CTL clone C-E-6 showed specific cytotoxic and proliferative activity against D-10 cell. In vivo tumor neutralizing assay also showed its specificity against D-10 tumor cell. Active immunotherapy and adoptive immunotherapy using immunogenic variant, D-10 was not successful. D-10 tumor cell possesses very strong neoantigen induced by MNNG treatment and parental MCA-F antigen.     

Endostatin inhibits the vascular endothelial growth factor-induced mobilization of endothelial progenitor cells

Circulating endothelial cells (CECs) are present in peripheral blood and have been shown to contribute to normal and pathological neovascularization. Antiangiogenic molecules can inhibit neovascularization in tumors and other sites, but their effect on CECs has not yet been determined. We hypothesize that angiogenic factors will increase the number of CECs, and conversely, antiangiogenic treatment will reduce these numbers. Mice treated with high levels of vascular endothelial growth factor (VEGF) showed increased numbers of Flk-1-positive cells in peripheral blood and endothelial cell colonies compared with vehicle-treated controls. These changes were accompanied by increased bone marrow neovascularization. In contrast, mice that received VEGF and endostatin had significantly lower numbers of CECs and reduced bone marrow vascularization. Endostatin-induced apoptosis was probably responsible for the decreased number of CECs. Systemic delivery of a VEGF antagonist, soluble Flt-1, also inhibited the VEGF-induced increase in CECs. These results were further confirmed in a Tie2/LacZ mouse model, in which endostatin reduced the number of beta-galactosidase-expressing peripheral blood mononuclear cells. We propose that endothelial progenitor cells are a novel target for endostatin and suggest that the relative numbers of CECs can serve as a surrogate marker for the biological activity of antiangiogenic treatment.     

The effects of serum from tumor-bearing mice on mitogen-induced blastogenesis of normal spleen cells

In order to detect the serum immunosuppressive factors of tumor bearer, the effects of normal C3H/He mice serum (NMS), serum from methylcholanthrene induced fibrosarcoma bearing mice (F4w serum) and sera fractionated by high performance liquid chromatography (HPLC) using anion exchange column were examined on mitogen-induced blastogenesis of normal murine spleen cells (Nspc). The addition of 5% of NMS suppressed the blastogenesis of Nspc. Less than 0.6% of F4w serum suppressed the blastogenesis. NMS was applied to HPLC and was separated to four peaks (A,B,C,D). In HPLC pattern of F4w serum, peak B was higher than that of NMS and new peak (E) was observed next to peak D. Peak D of NMS suppressed the blastogenesis. Not peak D but peak E of F4w serum suppressed the blastogenesis. The properties of those blastogenesis-suppressive fractions were discussed.     

Retardation of postsurgical metastases with the use of extracted tumor-specific transplantation antigens and cyclophosphamide

In a 3-methylcholanthrene [(MCA) CAS: 56-49-5]-induced tumor model of C3H/HeJ mice excision of a growing primary tumor decreased concomitant immunity and facilitated experimental lung metastases. Administration of tumor-specific transplantation antigens extracted from viable MCA-F cells with the use of single-phase (2.5%) 1-butanol [crude butanol extract (CBE)] augmented immunity after resection of the primary MCA-F tumor. Two weeks after footpad inoculation of 2 X 10(5) MCA-F cells, the tumor-bearing limbs were amputated and the mice were challenged subsequently with 5 X 10(4) cells of clone-9-4, a metastatic variant of MCA-F, via the tail vein. Whereas treatment with either 50 micrograms CBE sc or 20 mg cyclophosphamide (CY)/kg ip failed to retard lung colonization, combination therapy with the two agents reduced the incidence of lung colonies by 69.8% (26.5 vs. 8; P less than .001) compared with the incidence in the surgery-alone group and by 55.5% (18 vs. 8; P less than .001) compared with the incidence in the group treated with surgery and CY. Furthermore, the combined effects of CBE and CY were immunologically specific: The combined therapy with the non-cross-reactive MCA-D-CBE did not protect against iv challenge with clone-9-4. Treatment with antigenic extracts induced a 21.4% (4.2 vs. 3.3%) decrease in the ratio of Lyt 1+:Lyt 2+ cells in the spleens of tumor-resected mice, which suggested restoration to normal levels. Therefore, in the combined regimen, antigen may induce specific activation of helper lymphocytes, while CY inhibits activation of suppressor cells.     

The feeling of fatigue--fatigue severity by unidimensional versus composite questionnaires

The authors' purpose in this study was to compare the perception of fatigue severity as measured by different fatigue questionnaires. The authors evaluated 3 groups of patients in a cross-sectional study: chronic fatigue syndrome (CFS, n = 20), non-CFS fatigue (n = 20), and familial Mediterranean fever (FMF n = 25). In addition, the authors tracked 7 patients with CFS longitudinally for severity of fatigue. The severity of fatigue-related symptoms was assessed with 2 questionnaires: the unidimensional Chalder's Fatigue Severity Scale (CH) and the composite Fatigue Impact Scale (FI) which has 3 subscales--cognitive, physical, and social--and a total score. In the cross-sectional study, correlations between CH and FI cognitive scores were r = .78 (p < .0001), CH versus FI physical scores r = .603 (p < .0001), CH versus FI social scores r = .66 (p < .0001), and CH versus FI total scores r = .74 (p < .0001). In the longitudinal survey of CFS patients, the authors compared 30 questionnaires revealing correlations of CH versus FI cognitive scores r = .64 (p = .0004), CH versus FI physical r = .68 (p = .0001), CH versus FI social r = .87 (p < .0001), and CH versus FI total r = .90 (p < .0001). Fatigue severity as assessed by the unidimensional CH scale and the composite FI scale is comparable. The simple CH scale may be adequate for the assessment of the feeling of fatigue, in general, and for monitoring the severity of fatigue in CFS, in particular.     

A Trinity regimen with aflibercept for treatment-naïve neovascular age-related macular degeneration: 2-year outcomes

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the advantages of the Trinity regimen for treatment-naïve neovascular age-related macular degeneration (nAMD)....     

Clinical significance of elevated osteopontin levels in head and neck cancer patients

OBJECTIVES: Osteopontin (OPN) is associated with several human malignancies, but the role of OPN in head and neck cancer (HNC) remains unclear. We investigated the clinicopathologic relevance of serum OPN levels in HNC patients. METHODS: Serum OPN levels in HNC patients were determined by quantitative sandwich enzyme immunoassay (EIA). OPN levels and their correlation with clinical features were examined. In addition, serum squamous cell carcinoma (SCC) antigen was examined simultaneously. RESULTS: The mean OPN level was significantly higher in HNC patients (99.5 ng/ml) than in control subjects (55.3 ng/ml). OPN levels were significantly higher in patients with advanced stage HNC than in patients with early stage HNC. OPN levels did not correlate with SCC antigen levels. CONCLUSIONS: OPN may play a role in the pathogenesis of head and neck cancer (HNC), and serum OPN may be a potential biomarker of HNC.     

Research progress on the relationship between human cartilage glycoprotein 39 (YKL-40) and cardiovascular disease

Background Cardiovascular disease (CVD) is a common cause of death in China.There have been many evidences that inflammatory factors and acute phase reactants p...     

Clinical importance of B7-H3 expression in human pancreatic cancer

Background:

B7-H3 is a new member of the B7 ligand family and regulates T-cell responses in various conditions. However, the role of B7-H3 in tumour immunity is largely unknown. The purpose of this study was to evaluate the clinical significance of B7-H3 expression in human pancreatic cancer and the therapeutic potential for cancer immunotherapy.

Methods:

We investigated B7-H3 expression in 59 patients with pancreatic cancer by immunohistochemistry and real-time PCR. Furthermore, we examined the anti-tumour effect of B7-H3-blocking monoclonal antibody in vivo in a murine pancreatic cancer model.

Results:

Tumour-related B7-H3 expression was abundant in most human pancreatic cancer tissues and was significantly higher compared with that in non-cancer tissue or normal pancreas. Moreover, its expression was significantly more intense in cases with lymph node metastasis and advanced pathological stage. B7-H3 blockade promoted CD8⁺ T-cell infiltration into the tumour and induced a substantial anti-tumour effect on murine pancreatic cancer. In addition, the combination of gemcitabine with B7-H3 blockade showed a synergistic anti-tumour effect without overt toxicity.

Conclusion:

Our data show for the first time that B7-H3 may have a critical role in pancreatic cancer and provide the rationale for developing a novel cancer immunotherapy against this fatal disease.