Efficient gene transfer into macrophages and dendritic cells by in vivo gene delivery with mannosylated lipoplex via the intraperitoneal route

In this study, we developed an antigen-presenting cell (APC)-selective intraperitoneal (i.p.) gene delivery system with mannosylated cationic liposomes (Man-liposomes)/plasmid DNA complex (Man-lipoplex). An in vitro study using cultured peritoneal macrophages demonstrated that Man-liposomes could transfect luciferase-encoding plasmid DNA (pCMV-Luc) more efficiently than cationic liposomes via a mannose receptor-mediated mechanism. In vivo gene transfection studies revealed that Man-lipoplex showed a higher gene expression in the liver, spleen, peritoneal exuded cells, and mesenteric lymph nodes than cationic liposomes/plasmid DNA complex (lipoplex) or naked pCMV-Luc after i.p. administration, and this gene expression lasted for at least 24 h. The transfection activity of Man-lipoplex after i.p. administration was significantly higher than that after i.v. gene delivery with the Man-liposomes we developed previously, indicating that gene delivery via the i.p. route seems to be an efficient approach for in vivo gene delivery to APCs. Furthermore, it was demonstrated that Man-lipoplex could enhance gene expression in both F4/80+ and CD11c+ cells in the spleen. These results show that gene delivery with Man-liposomes via the i.p. route could be an effective approach for APC-selective gene transfection.     

Extent and contraindications for sacral amputation in patients with recurrent rectal cancer: a systematic literature review

Background  

Abdominosacral amputation is a potentially curative surgical approach for patients with recurrent rectal cancer. Previous reports have described differing extents of sacral resection. Most of these reports stated that high sacral involvement of the tumor is a contraindication for surgery; however, the basis for this is unclear.     

Prognostic impact of mitotic index of proliferating cell populations in cervical cancer patients treated with carbon ion beam

BACKGROUND:

The authors previously reported that the mitotic index of a proliferating cell population (pMI) was a potent prognostic factor in cervical cancer patients treated with photon beam therapy. In this study, they investigated whether the pMI accurately predicted prognosis in cervical cancer patients treated with carbon ion beam.

METHODS:

Tissue sections were obtained from 27 consecutively treated patients with stage IIIB bulky (19 patients) and stage IVA (8 patients) squamous cell carcinomas of the cervix treated with carbon ion beam at the National Institute of Radiological Sciences, Japan, as a phase I/II study with dose escalation methodology (52.8‐72 grays equivalent radiation dose/24 fractions). The mitotic index (MI) and Ki‐67 labeling index (Ki‐67‐LI) were determined by hematoxylin and eosin staining and immunohistochemical staining, respectively. The pMI was calculated using the following formula: pMI = MI/Ki‐67‐LI.

RESULTS:

The pMI ranged from 0.6 to 8.9 (mean, 3.9 ± 2.6; median, 3.2). Twelve of the 27 specimens had a pMI >3.5. The local control rate in tumors with a pMI >3.5 was 17%, significantly lower than the 73% in the tumors with a pMI <3.5 (P = .005). Multivariate analysis indicated that the pMI had the strongest impact on local control (standard regression coefficient = 0.48, P = .002) among the variables, including clinical stage, irradiated dose, age, and tumor volume.

CONCLUSIONS:

These results suggest that a high pMI is an indication of a poorer prognosis, and is a powerful prognostic factor in patients with squamous cell carcinomas of the cervix treated with carbon ion beam therapy. Cancer 2009. © 2009 American Cancer Society.     

Secondary correction of the wide nasal root in bilateral nasal deformity associated with cleft lip in five Oriental patients.

Secondary correction of bilateral nasal deformity associated with a cleft lip is common. However, few reports have referred to the correction of the wide nasal root. In this study we describe a technique other than osteotomy for the correction of the wide nasal root used in five Oriental patients with bilateral nasal deformity associated with cleft lip. Satisfactory results were obtained, and two representative cases are described.     

Nitric oxide synthase-containing neurons in the hippocampus are preserved in trimethyltin intoxication

We studied the effects of trimethyltin (TMT) (9 mg/kg, p.o.) on the nitric oxide synthase (NOS)-containing neurons in the rat hippocampus by NADPH-diaphorase histochemistry and a biochemical assay of NOS activity. TMT exposure caused the typical behavioral changes and a loss of the CA3/4 pyramidal cells, which were NADPH diaphorase-negative. The scattered interneurons and the CA1 pyramidal cells, which were NADPH diaphorase-positive, were spared. Hippocampal NOS activity showed no reduction in the TMT-treated rats compared with the controls. These results provide evidence of the preservation of the NOS-containing neurons in TMT intoxication.