Hepatic arterial infusion plus systemic chemotherapy as third-line or later treatment in colorectal liver metastases.

BACKGROUNDS: The present study aimed to evaluate benefit of hepatic arterial infusion chemotherapy (HAI) combined with systemic chemotherapy (SCT) for patients with colorectal liver metastases (CLMs) in a palliative setting. METHODS: This was a retrospective single-center study including 43 consecutive patients with CLM after failure of standard SCT. Among them, 20 (47 %) patients underwent HAI combined with SCT (Group A) and 23 historical control patients who had received SCT with or without targeted agent treatment (Group B). RESULTS: The two groups had similar characteristics. Compared with SCT alone, HAI combined with SCT prolonged survival (median 19.8 vs. 9.0 months; P = 0.045). Median hepatic progression-free survival was significantly longer for HAI combined with SCT vs. SCT alone (median 8.1 vs. 4.7 months; P = 0.027), as were response rates (25 and 0 %; P = 0.038) and progression-free survival (median 5.7 vs. 3.0 months; P = 0.02). Three patients (15 %) achieved conversion to potentially curative surgery. Grade 3/4 toxicities for Group A and Group B were neutropenia (5 and 8.7 %, respectively), anemia (5 and 0 %, respectively), and hyperbilirubinemia (0 and 4.3 %, respectively). Other complications were mostly grade 1 or 2. CONCLUSIONS: HAI combined with SCT treatment can improve overall survival compared with SCT alone in highly advanced CLM refractory to intravenous chemotherapy.

Molecular cloning and expression of drought-induced protein 3 (DIP3) encoding a class III chitinase in upland rice.

A drought-induced gene, DIP3, encoding a chitinase III protein was isolated from the roots of upland rice by reverse transcription-polymerase chain reaction (RT-PCR). Sequence analysis demonstrated that the cDNA and deduced protein showed high identity to Oryza sativa class III chitinase. The deduced protein contained a signal peptide sequence in the N-terminal region of 21aa and a conserved glycosyl hydrolase (GH) 18 domain. The secondary and 3D structures were analyzed and showed that it contained α-helix, ß-sheets, extended strand and random coil structures and that it was approximately spheroidal. Real-time quantitative PCR analysis revealed that expression levels accumulated rapidly under different forms of abiotic stress (drought, salt and low temperature), peaked at different times and then decreased. These results implied that as a member of class III chitinases, DIP3 may function as a stress-induced protein involved in the regulation of plant stress response.

Effects of beta-glucanase and xylanase supplementation on gastrointestinal digestive enzyme activities of weaned piglets fed a barley-based diet.

The effects of supplementing a barley-based diet for weaned piglets withexogenous beta-glucanase and xylanase on gastrointestinal digestiveenzyme activities were investigated. Thirty-six cross-bred weaned pigletswere randomly assigned to two groups with three pens based on sexand mass. Each group was fed on the diet based on barley with or withoutadded beta-glucanase and xylanase (0.15%) for a 4-week period. Theresults showed that enzyme supplementation improved growth performanceof piglets significantly (p < 0.05), but had no effect (p = 0.091)on average daily feed intake. The results also showed that supplementationof beta-glucanase and xylanase had no effect on pepsin activity in gastriccontents but slightly decreased (p = 0.092) the pepsin activity ingastric mucosa. Meanwhile, no effect of enzyme supplementation ontrypsin activity in duodenal contents was observed. However, the activitiesof amylase and lipase in duodenal contents were significantly(p < 0.05) decreased, whereas the activities of maltase, sucrase andgamma-glutamyl transpeptidase (gamma-GT) in jejunal and ileal mucosa wereenhanced significantly (p < 0.05). The improvement of disaccharidaseand gamma-GT activity may be attributed to the positive impacts of exogenousenzymes on digestion and absorption of the nutrients. In conclusion,the current results indicated that supplementation with enzymes in barley-based diets could improve the growth performance of piglets,decrease the activities of amylase and lipase in duodenal contents andincrease the activities of disaccharidase and gamma-GT in jejunal and ilealmucosa.

Specificity and function of monoclonal antibodies directed against Ewing sarcoma cells.

A selection of 16 monoclonal antibodies has been produced against a fresh Ewing's sarcoma (ES) tumor mixed with a permanent ES cell line. The majority of antibodies identify an 80-kDa molecule, which is not detected on healthy tissues except on certain cultured monocytes. One antibody recognizes the CD2 ligand MIC2 and 2 antibodies (numbers 13 and 16) define a higher-molecular-mass antigen. Antibody 16 is also expressed on mesenchymal fibroblasts of bone marrow or fetal origin. Tumor-specific antigen expression is potentially linked to the chromosome 22 abnormality described in Ewing's sarcoma, products altered expression in tumors with the chromosome 11/22 translocation has not been shown. The putative chimeric protein on chromosome 11 is apparently not expressed to a great extent, as tested by Northern blotting; however, the fusion protein initiated on chromosome 22 and ending on chromosome 11 is readily seen on Northern blots. The altered expression of a number of cellular genes in addition to a novel gene product(s) originating from translocation events were expected to be identified by monoclonal antibodies selected by their unique binding pattern to Ewing's sarcoma (ES) cells.

Monoclonal anti-human T cell antibody and PAP-s conjugate--preparation and selective cytotoxic properties on leukemic cell.

Pokeweed antiviral protein (PAP-s) was prepared from seeds of Phytolacca americana. Monoclonal antibody against human pan-T lymphocyte Wu71 was linked to PAP-s by a disulfide bond. The results of SDS-PAGE, double immunodiffusion of active monoclonal antibody and PAP-s showed that the conjugate was highly cytotoxic to the human T-leukemic cell line CEM, but not to antigen-negative cell line SP2/O. At a concentration of 10(-9) mol/L, 76.4% of the target cells were killed, as compared with 10.1% at 10(-9) mol/L of free PAP-s. Treatment of the CEM cells with conjugate at 10(-9) mol/L reduced their rate of protein synthesis by 72.4%, as determined with 14C-leucine incorporation. The immunotoxin may be useful for the in-vitro eradication of leukemic cells in autologous bone marrow transplantation to leukemia patients.

Generation of CD4-positive suppressor T cells from mixed lymphocyte cultures in the presence of interleukin 2 receptor antibody TU69. An in vitro model for transplantation tolerance induction.

The specificity of a novel monoclonal antibody (moAB), TU69, directed to the interleukin 2 receptor (IL-2R) was verified by sequential immunoprecipitation with anti-Tac. TU69 cross-competed with anti-Tac in binding analyses. When TU69 was added during the sensitization of normal peripheral blood mononuclear cells (PBMC) to allogeneic HLA-class I or -class II mismatched stimulator PBMC, alloproliferative responses and specific cytotoxicity were no longer detectable and the generation of natural killer (NK)-like effector cells was partially inhibited. Remarkably, however, the generation of CD4+ nonspecific suppressor T cells in such mixed lymphocyte cultures (MLC) was not inhibited--but, in contrast, was strongly enhanced in the presence of TU69. These suppressor cells inhibited unrelated allospecific responses in vitro to background levels even at a ratio of 50:1 responder:irradiated suppressor T cell lines. Such a potent experimental suppressor system suggests a possible application of TU69 for in vivo tolerance induction after transplantation, by down-regulating allospecific effector cells and allowing the generation of tolerance to graft antigens.