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Human growth hormone (hGH) is a pleiotropic cytokine targeting a variety of tissues. Its protective effects on haematopoiesis during treatment with chemotherapeutic drugs were investigated. Sprague-Dawley rats were intraperitoneally administered with both carboplatin and 5-fluorouracil together with or without recombinant hGH (rhGH) at a dose of 1 IU/kg/day. Body weight, full blood count, bone marrow differential count and expression of proliferating cell nuclear antigen (PCNA) in bone marrow were measured weekly for 4 weeks in chemotherapy-treated (CT) or chemotherapy plus rhGH-treated (CT+GH) animals. During the first week, body weight, white blood cell count, haematopoietic count and reticulocyte count were decreased in the CT group as well as in the CT+GH group, but to a lesser extent in the latter group (CT vs. CT+GH group, p < 0.05). Further decreases were also prevented in the CT+GH group. Myeloid cells were extremely hypoplastic in the CT group, while in the CT+GH group, myeloid cells recovered from obviously hypoplastic to excessively hyperplastic in the first 2 weeks, and the myeloid karyocyte count increased significantly (CT+GH vs. CT group, p < 0.05). PCNA-positive cell count in the CT+GH group was also significantly higher than in the CT group (CT+GH vs. CT group, p < 0.05). Thus, rhGH showed a promising protective effect on body weight loss and haematopoietic recovery of chemotherapy-treated rats, which may be useful in clinic to reduce the side effects of chemotherapy. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

ZnO nanoparticles (ZnONPs) and carbon nanotubes (CNTs) are frequently used nanoparticles with unique features. Aquatic organisms are exposed to a combination of contaminants in natural water systems, so the combination effect of two or more nanomaterials has caused much concern. In this study, the toxicity to the liver of common carp was explored under four weeks of exposure to single ZnONPs or in combination with multi-walled CNTs (MWCNTs). The results demonstrated that ZnONPs induced pathological changes and apoptosis in the liver. In combination, decreased pathological changes were observed in the LSC-ZnONPs group (50 mg L-1 ZnONPs and 0.25 mg L-1 MWCNTs) at the microscopic level and ultrastructural level, and increased pathological changes in the HSC-ZnONPs group (50 mg L-1 ZnONPs and 2.5 mg L-1 MWCNTs). A 52% reduction in the percentage of TUNEL-positive nuclei in the LSC-ZnONPs group and a 33% increase in the HSC-ZnONPs group were observed compared to the ZnONPs group. The mRNA expression of apoptosis-related genes, including caspase3, BAX, and XBP1, were significantly up-regulated in the exposure groups, confirming the occurrence of apoptosis. Significantly decreased caspase 3 and BAX mRNA levels in the co-exposure groups were detected compared to the ZnONPs group. Nevertheless, the XBP1 mRNA level was significantly upregulated in the LSC-ZnONPs group, but downregulated in the HSC-ZnONPs group, indicating multiple signal pathways involved in the apoptosis. In conclusion, a low concentration of MWCNTs (0.25 mg L-1) decreased the toxic effect of ZnONPs on common carp, but a high concentration of MWCNTs (2.5 mg L-1) enhanced it. This study will contribute to developing future risk assessment and management strategies for nanomaterials. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of small interfering RNA (siRNA) targeting human growth hormone receptor (hGHR) combined with 5-fluorouracil (5-FU) on the hepatic metastasis of colon cancer. The animal model of liver metastases using human SW480 colon cancer cells was established on BALB/c mice and the siRNA interfering plasmid targeting hGHR gene was constructed. The tumor-bearing mice were randomly divided into the saline control, plasmid, growth hormone (GH), 5-FU, 5-FU+plasmid and 5-FU+plasmid+GH groups. The liver metastasis in each group was observed. All the animals showed liver metastases and using siRNA-interfering plasmid treatment the incidence of liver metastases was significantly reduced in the tumor groups compared to the saline or GH group. The combined treatment of interfering plasmid and 5-FU slightly decreased the incidence of liver metastases in the tumor groups compared to the plasmid alone or 5-FU alone treatment, although the findings were not statistically significant. On the basis of the combination of interfering plasmid and 5-FU, the additional GH did not increase the incidence of liver metastases (P>0.05), but improved the weight loss of the mice (P<0.05) induced by the inhibition of GHR and toxicity of 5-FU. The present results showed that siRNA targeting hGHR is able to reduce the incidence of liver metastases of human SW480 colon cancer cells in mice. Thus, GHR may be important in tumor metastasis. [ABSTRACT FROM AUTHOR]