Higher Expression of Receptor Tyrosine Kinase Axl,and Differential Expression of its Ligand,Gas6, Predict Poor Survival in Lung Adenocarcinoma Patients

Background

Downstream activation through receptor tyrosine kinases (RTKs) plays important roles in carcinogenesis. In this study, we assessed the clinical involvement of Axl, an RTK, and its ligand, Gas6, in surgically treated lung adenocarcinoma.

Methods

Axl and Gas6 mRNA and protein expression levels were quantified using quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, in completely resected lung adenocarcinoma tissues (n = 88) and were evaluated for correlation with clinicopathologic features and patient survival.

Results

Higher expressions of Axl mRNA/protein and Gas6 protein were significantly related to worse clinicopathological features and prognosis (5-year overall survival rates: Axl mRNA low: 72.3 %, high: 49.7 %, P = 0.047; Axl protein low: 77.5 %, high: 38.6 %, P < 0.001; and Gas6 protein low: 70.5 %, high: 48 %, P = 0.042). On the contrary, higher Gas6 mRNA expression was related to better clinicopathological features and prognosis (5-year overall survival rates: Gas6 mRNA low: 59.2 %, high: 81.8 %, P = 0.054). Multivariate analysis suggests that high Axl mRNA expression may be an independent factor for poor patient prognosis (P = 0.04).

Conclusions

In lung adenocarcinoma, Axl and Gas6 expression levels were associated with tumor advancement and patient survival, thus rendering them as reliable biomarkers and potential targets for treatment of lung adenocarcinoma.

     

Maximum Standard Uptake Value at the Biopsy Site during F-Fluorodeoxyglucose Positron Emission Tomography Does Not Predict the Proliferation Potential of Tumor Cells in Extranodal Natural Killer/T Cell Lymphoma, Nasal Type

No abstract available.     

Imbalance of coagulation and fibrinolysis can predict vascular access failure in patients on hemodialysis after vascular access intervention

Objective

For patients with end-stage renal disease on hemodialysis, the durability of vascular access (VA) is still far from optimal, and access survival after intervention for access failure is an important aspect. Procoagulant status is a leading cause of access failure. Coagulation-fibrinolysis imbalance can occur in hemodialyzed patients, but the influence of the imbalance has not been fully elucidated.

Potent and specific antitumor effect of CEA‐targeted photoimmunotherapy

Conventional photodynamic therapy (PDT) for cancer is limited by the insufficient efficacy and specificity of photosensitizers. We herein describe a highly effective and selective tumor‐targeted PDT using a near‐infrared (NIR) photosensitizer, IRDye700DX, conjugated to a human monoclonal antibody (Ab) specific for carcinoembryonic antigen (CEA). The antitumor effects of this Ab‐assisted PDT, called photoimmunotherapy (PIT), were investigated in vitro and in vivo. The Ab‐IRDye conjugate induced potent cytotoxicity against CEA‐positive tumor cells after NIR‐irradiation, whereas CEA‐negative cells were not affected at all, even in the presence of excess photoimmunoconjugate. We found an equivalent phototoxicity and a predominant plasma membrane localization of Ab‐IRDye after both one and six hours of incubation. Either no or little caspase activation and membrane peroxidation were observed in PIT‐treated cells and a panel of scavengers for reactive oxygen species showed only partial inhibition of the phototoxic effect. Strikingly, Ab‐IRDye retained significant phototoxicity even under hypoxia. We established a xenograft model, which allowed us to sensitively investigate the therapeutic efficacy of PIT by non‐invasive bioluminescence imaging. Luciferase‐expressing MKN‐45‐luc human gastric carcinoma cells were subcutaneously implanted into both flanks of nude mice. NIR‐irradiation was performed for only the tumor on one side. In vivo imaging and measurement of the tumor size revealed that a single PIT treatment, with intraperitoneal administration of Ab‐IRDye and subsequent NIR‐irradiation, caused rapid cell death and significant inhibition of tumor growth, but only on the irradiated side. Together, these data suggest that Ab‐IRDye‐mediated PIT has great potential as an anticancer therapeutics targeting CEA‐positive tumors.     

Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver

ABSTRACT— To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%, HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.     

Two-staged hepato-pancreatoduodenectomy and interventional pancreaticojejunostomy

Two-staged pancreatoduodenectomy, including exteriorization of the pancreatic juice and second-look pancreaticojejunostomy, has been recommended for high-risk patients to avoid pancreatic leakage, which often causes intra-abdominal hemorrhage. We present a new technique of interventional pancreaticojejunostomy under both fluoroscopy and endoscopy without second-look laparotomy. A 77-year-old woman with local recurrence and liver metastasis from colon cancer underwent hepato-pancreatoduodenectomy with the external drainage of pancreatic juice via the pancreatic duct tube without pancreaticojejunostomy. Two months later, the jejunum was punctured with the insertion of a 5-F needle-knife into the pancreatic fistula during endoscopic observation of jejunal lumen, followed by the insertion of two 0.35-inch guidewires into the jejunum and the pancreatic fistula. Finally, a 10-Fr stenting tube was placed between the jejunum and the pancreatic fistula. No complications developed.     

Phagocytosis of co-developing neutrophil progenitors by dendritic cells in a culture of human CD34<Superscript>+</Superscript> cells with granulocyte colony-stimulating factor and tumor necrosis factor-α

Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce the differentiation of CD34(+) cells toward dendritic cells (DCs). We have previously shown that DCs are co-generated from human CD34(+) cells during erythroid or megakaryocytic differentiation in the presence of TNF-alpha, and those DCs are able to stimulate autologous T cell proliferation. The aim of this study was to learn whether the co-stimulation of granulocyte colony-stimulating factor (G-CSF) and TNF-alpha would generate neutrophil progenitors and DCs together from human CD34(+) cells, and if this was the case, to clarify the phenotypic and functional characteristics of these DCs. When highly purified human CD34(+) cells were cultured for 7 days with G-CSF alone, the generated cells predominantly expressed a granulocyte marker, CD15, and then differentiated into neutrophils after 14 days of culture. The addition of TNF-alpha with G-CSF markedly decreased the number of CD15(+) cells without affecting the total number of cells during 7 days of culture. Almost one third of the generated cells were positive for CD11c and CD123. Furthermore, CD11c(+) cells were found to phagocytose CD15(+) cells and were able to induce allogeneic, but not autologous, T cell proliferation in the mixed lymphocyte reaction (MLR). On the other hand, the CD11c(+) cells generated by TNF-alpha and cytokines capable of inducing erythroid differentiation were able to stimulate autologous T cells. There was a difference in the expression of CD80, CD83 and CD86 among CD11c(+) cells induced by G-CSF plus TNF-alpha and those generated by interleukin-3, stem cell factor, and erythropoietin plus TNF-alpha. These results indicate that the co-stimulation of human CD34(+) cells with G-CSF and TNF-alpha induces the phagocytosis of co-developing neutrophil progenitors by DCs, and the stimulatory effects of these DCs on autologous T cells is different from that of DCs generated from CD34(+) cells during erythroid differentiation.