Summary

SummaryDendritic cells (DCs) can acquire unique features or phenotypes in different tissue microenvironments and decide whether immunity or tolerance develops. DCs observed within the decidua have been implicated in pregnancy maintenance. However, the precise distribution of decidual DC subsets and their phenotypic characteristics are largely unknown. Using flow cytometry, we identified three DC subsets in normal human first-trimester decidua:myeloid DC type 2 (MDC2) and BDCA-2 + CD123 + plasmacytoid DC (PDC). The percentage of MDC1 to mononuclear cells in the decidua was similar to that in the peripheral blood controls. The percentage of MDC2 in the decidua was significantly higher than that in the peripheral blood controls, whereas the percentage of PDC was significantly lower. Both MDC1 and MDC2 subsets expressed human leucocyte antigen D-related, CD86 and CD80 at low levels, suggesting a characteristic of immature myeloid DCs. Immunoglobulin-like transcript 3, suggested to be involved in immune tolerance induction, was also expressed on decidual MDC1 and MDC2 subsets. In addition, as gestational age increased from 6 to 9 weeks, the numbers of MDC1 decreased but MDC2 increased significantly. This is the first study to demonstrate the presence of three previously unidentified BDCA-1 + , BDCA-3 + and BDCA-2 + DC subsets in human decidua, these decidual DCs might play important role in the maintenance of pregnancy.

Pharmacokinetics and bio-distribution are crucial factors affecting the performance of an intravenous drug. In this study, we explore the combined use of glucose and polyethylene glycol (PEG) ligands to further improve gold nanoparticle (GNP) pharmacokinetics and bio-distribution, with the aim of using the drug for in-vivo radiotherapy. The inclusion of PEG was found to significantly prolong the half-life period, where PEG-Glu-GNPs achieved 6.17 +/- 3.71 h, compared to 1.23 +/- 0.14 h for Glu-GNPs and 1.07 +/- 0.22 h for uncoated GNPs. Our data indicates that nanoparticle size impacts cell uptake performance, with 20 nm being the optimal diameter for cancer treatment applications. Although PEG-Glu-GNPs mainly distributed in the spleen, liver, lung, and kidneys, the concentration of PEG-Glu-GNPs in tumour tissue was 20 times higher than healthy cells in the uterus and ovaries, reaching 9.22 +/- 2.41 microg/g cancer tissue at 48 h after injection. This difference in uptake holds promise for selective tumor targeting which can in turn lead to more effective radiotherapy through the interaction of X-rays and GNPs. Specifically tumor size after 47 days of treatment had reduced to (769 +/- 92) mm3 compared to (1432 +/- 269) mm3 using X-rays alone and (3514 +/- 1818) mm3 without any treatment. Moreover, the mice remained healthy without statistically significant weight loss. Results of our pharmacokinetic and bio-distribution study as well as therapeutic data for PEG-Glu-GNPs in our tumor bearing animal model demonstrate that PEG-Glu-GNPs provide excellent in-vivo stability, tumor targeting function, and radiotherapeutic enhancement effects, providing useful insights for further clinical studies.

Objectives: To evaluate the clinical outcomes of gonadotropin-releasing hormone analog (GnRHa) combined with implantation of a levonorgestrel-releasing intrauterine system (LNG-IUS) in adenomyosis patients with significantly enlarged uteruses. Subjects and Methods: Twenty-one adenomyosis patients whose uterine volumes were greater in size than at 12 weeks' gestation were recruited for the study. Subcutaneous injection of GnRHa was administrated at an interval of 28 days for a total of 3-4 cycles when uterine length was determined to be less than 10 cm by ultrasound measurement. At 3, 6 and 12 months after LNG-IUS implantation, follow-up was performed to document the clinical values such as uterine volume, degree of dysmenorrhea and menstrual flow. Results: Twelve months after implantation, the menstrual flow was significantly lower than baseline values (53.8 ± 11.7 vs. 100, p = 0.03). The degree of dysmenorrhea (pain) was relieved 12 months after implantation (58.2 ± 11.5 vs. 93.7 ± 0.2, p = 0.005). Uterine volume was also below pre-GnRHa levels after implantation (276.6 ± 32.1 vs. 311.4 ± 32.3, p = 0.005). LNG-IUS was expelled in 3 patients, giving an expulsion rate of 14%. Side effects of GnRHa combined with LNG-IUS implantation were few. Conclusion: The findings indicate that combined GnRHa and LNG-IUS treatment was efficacious in patients with enlarged adenomyosis.

Testis derived transcript (TES) is a candidate tumor suppressor gene located at the human chromosome 7q31, and its function in ovarian cancer is still unknown. Using ovarian cancer cell lines and tissue samples, we demonstrated that both loss of heterozygosity and hypermethylation of the TES gene occurred in ovarian cancer at high frequencies, and there were significant correlations between TES expression and hypermethylation or loss of heterozygosity. We also detected methylation in ovarian cancer cell line A2780 after treatment with 5-aza-2-deoxycytidine. The expression level of TES was enormously up-regulated, then caused changes to the biological behaviors of A2780 cells: cell growth properties were greatly impaired, colony formatting abilities were suppressed to very low levels, and the apoptosis rate was highly raised compared to the control group. Our findings suggest that the TES gene functions as a tumor suppressor gene and is frequently silenced by hypermethylation and loss of heterozygosity in ovarian cancers. (Cancer Sci 2010; 101: 1255-1260 N owadays, we realize that tumors are a complex process made up of multiple steps. In past decades, a great number of genes was proved to be involved in the development and progression of tumors. In recent years, several genes were identified to be able to suppress tumor growth (as tumor suppressor genes), such as P53,(1) phosphatase and tensin homologue,and p16, (3) highlighting the optimistic prospect of research into these genes. A great many studies showed that alterations of tumor suppressor genes like loss of heterozygosity (4,5) and promoter hypermethylation (6,7) were detected in almost every type of cancers.Ovarian cancer is the third most frequent female cancer type and the leading cause of death by cancer among women in China. More than 70% of patients were already in the late stage on diagnosis, and lost the chance to have an operation, which then required a great deal of money and medical resources.It has also been demonstrated that some tumor suppressor genes play a notable role in ovarian cancer; the testis derived transcript (TES) gene is one of them. The TES gene is located at 7q31, within the fragile chromosomal region FRA7G.(8,9) It spans about 48 kb encompassing seven exons. There are three isoforms of human TES, which differ from each other in the 3-untranslated region (3-UTR).(10) At its COOH terminal, the TES protein has three zinc-binding domain present in Lin-11, Isl-1 and Mec-3 domains which play a very important role in focal adhesion targeting.(11) TES was proved to be a putative tumor suppressor gene; (12) in the past few years, much evidence has indicated TES anticancer functions in the mechanisms of tumorigenesis, angiogenesis, and metastasis. Frequent loss of heterozygosity at 7q31 happened in a variety of malignances, implying that loss of gene expression within this region had a relationship with cancer. Moreover, studies also reported a great rate of TES hypermethylation in glioblastomas and other malignances, leading to the TES...