Apmis

LIANG, TIE‐JUN; QIN, CHENG‐YONG

doi: 10.1111/j.1600-0463.2009.02520.xpmid: 19703123

MicroRNAs (miRNAs) are small RNA strands (20–25 nucleotides) that regulate gene expression by translational repression as well as by messenger RNA degradation. This review will examine the application and function of miRNAs in immune cell development and differentiation.

MÆHLE, BJØRN O.; COLLETT, KARIN; TRETLI, STEINAR; AKSLEN, LARS A.; GROTMOL, TOM

doi: 10.1111/j.1600-0463.2009.02510.xpmid: 19703124

Both subtypes of estrogen receptor (ER), ERα and ERβ, are normally present in the mammary gland. The role of ERα as a prognostic marker in breast cancer is well established due to the beneficial effect of providing tamoxifen as adjuvant therapy. The role of ERβ, however, is less clear. To gain insight into the importance of ERβ in breast cancer, 145 primary breast cancers were examined by immunohistochemistry for ERβ, and the expression level was compared with ERα and progesterone receptor (PR) status. Especially, we wanted to examine the significance of ERβ in the contrasting ERα+/PR+ and ERα−/PR− subgroups. In the ERα+/PR+ subgroup (dual positive), the survival difference between patients with low, medium and high ER β level was statistically significant (p = 0.004), with more than 70% of patients with medium and high ERβ levels surviving 100 months, compared with less than 30% in the group with low ERβ level. Further, for ERα+/PR+ patients there was a reduced risk of fatal outcome by multivariate analysis with increasing ERβ levels (p(trend) < 0.01 (univariate analysis); p(trend) = 0.05 (multivariate analysis)). The risk was 31% and 27% for medium and high ERβ levels, respectively, compared with low ERβ level, adjusting for standard prognostic factors such as tumor diameter, nuclear tumor grade (quantified by mean nuclear area), lymph node status, and patient age at operation. For patients with ERα−/PR− tumors (dual negative), however, there was no association between ERβ levels and patient outcome. Our findings indicate that ERβ expression provides independent prognostic information for breast cancers with ERα/PR‐positive status, a feature typical among screen‐detected breast cancers. The role of ERβ needs to be further evaluated especially in this group of breast cancers.

BOZKURT, SUHEYLA UYAR; AYAN, ERDOGAN; BOLUKBASI, FATIHHAN; ELMACI, ILHAN; PAMIR, NECMETTIN; SAV, AYDIN

doi: 10.1111/j.1600-0463.2009.02516.xpmid: 19703125

Meningioma is a common neoplasm that constitutes almost 30% of all primary central nervous system tumors and is associated with inconsistent clinical outcomes. The extracellular matrix proteins play a crucial role in meningioma cell biology and are important in tumor cell invasion and in progression to malignancy. SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) is a matricellular glycoprotein that regulates cell function by interacting with different extracellular matrix proteins. The aim of this study was to evaluate the expression of SPARC with proliferation index, p53 reactivity in WHO grade 1 (benign), grade 2 (atypical) and grade 3 (anaplastic) meningiomas and correlate with clinical features of the patients, including location of the tumor, recurrence of the tumor and survival of patients. We studied 111 meningiomas, 69 being benign, 34 being atypical and eight being anaplastic meningiomas of various histological types. Using immunohistochemical analysis, we evaluated the expression of SPARC, Ki‐67 (MIB‐1) and p53 in meningiomas. Immunohistochemical scores of SPARC were determined as the sum of frequency (0–3) and intensity (0–3) of immunolabeling of the tumor cells. A high immunohistochemical score (4–6) for SPARC was more frequent in atypical and in anaplastic meningiomas than in benign meningiomas (p < 0.01). MIB‐1 proliferation index showed significant association between tumor grades in meningiomas (p < 0.01). At the end of a follow‐up period of 47.53 ± 25.04 months, 30 tumors recurred. A high SPARC expression was significantly associated with tumor recurrence (p = 0.02). The immunoreactivity of p53 protein and MIB‐1 score were significantly higher in recurrent meningiomas than in non‐recurrent meningiomas. The cumulative survival of patients with high SPARC expression was significantly lower than patients with low SPARC expression. The high SPARC expression scores were predominantly identified in meningothelial, fibrous and chordoid meningiomas; low SPARC expression scores were mostly spotted in secretory and psammomatous meningiomas. Evaluating SPARC expression might help assessing recurrence risk and survival estimation in meningiomas.

HALLANDER, HANS O.; LJUNGMAN, MARGARETHA; JAHNMATZ, MAJA; STORSAETER, JANN; NILSSON, LENNART; GUSTAFSSON, LENNART

doi: 10.1111/j.1600-0463.2009.02521.xpmid: 19703126

The anti‐Fim response and long‐term persistence after vaccination and infection may be of importance in understanding population immunity. Longitudinal serum samples (n = 1330) from 542 non‐infected children related to a Swedish vaccine trial showed that the post vaccination (DTPa5) antibody decay curve for pertussis ELISA IgG anti‐fimbriae2/3 (anti‐Fim2/3) was bi‐phasic. A slower one followed an initial rapid decay approximately 5–6 months after the third dose at 12 months of age. After 71 months, however, 60% still had concentrations above ≥5 EU/ml, a level that had been shown to correlate with decreased risk of disease. Booster responses after re‐vaccination with DTPa5 at 4, 5 and 6 years of age were strong and appeared within 1 week after vaccination, indicating immune memory. Ninety‐six young children with verified pertussis infection, for whom we had serum samples both before, during and after the infection, showed a high response if they had been primed with fimbriae (either DTPa5 or DTPwc). In contrast, 76% of infected children not primed with fimbriae (a DTPa2 or DT group) only had concentrations below the minimum level of detection in all samples taken during and after the infection. In two Swedish seroepidemiological surveys, one from 1997 just after reintroduction of universal childhood vaccination against pertussis and one from 2007, the proportion of children 2–3 years with anti‐Fim2/3 concentrations <5 EU/ml was similar and above 90%. This reflects that the two‐ or three‐component pertussis vaccines (DTPa2 and DTPa3) that were introduced in Sweden in 1996 do not induce anti‐Fim2/3 antibodies. In previous studies it was shown in multivariate analyses that levels of IgG anti‐Fim2/3 ≥5 EU/ml reduced short‐term risk of pertussis in small children. As the antibody response to Fim2/3 after infection is poor in children who have not been primed earlier in life, inclusion of immunogenic Fim2/3 in future pertussis vaccines should be considered.

SEIPEL, DANIELE; RIBEIRO‐Gomes, FLAVIA LIMA; BARCELOS, MICHELLE WILLMEN; RAMALHO, ANDRÉ VILLAÇA; KANASHIRO, MILTON M.; KIPNIS, THEREZA LIBERMAN; ARNHOLDT, ANDREA CRISTINA VETO

doi: 10.1111/j.1600-0463.2009.02519.xpmid: 19703127

Toxoplasma gondii is an obligate intracellular parasite that is able to disseminate into deep tissues and cross biological barriers, reaching immunoprivileged sites such as the brain and retina. The parasite is able to infect macrophages and dendritic cells and use them for dispersal throughout the body, but the activation state of those cells is unknown. We investigated the ability of human and murine cells from monocytic/macrophage lineages that had not previously been exposed to inflammatory cytokines to up‐regulate co‐stimulatory and adhesion molecules upon infection. Toxoplasma gondii‐infected human monocytes (freshly isolated and THP1 lineage) were unable to up‐regulate CD86, CD83, CD40 or CD1a. CD80 expression increased in infected cells but expression of l‐selectin and β2 integrin was unaltered. We evaluated the ability of infected macrophages from wild type C57/BL/6 or CD14−/− mice to migrate in 8 μm transwells. Infected cells from CD14−/− mice were more likely to de‐adhere than infected cells from wild type mice but they did not show any increase in migratory ability. The non‐stimulatory profile of these infected cells may contribute to parasite spread throughout the lymphatic circulation in the initial phases of infection.

HAO, LI SEN; ZHANG, XIAO LAN; AN, JUN YAN; KARLIN, JUSTIN; TIAN, XIAO PENG; DUN, ZHI NA; XIE, SHU RUI; CHEN, SHUANG

doi: 10.1111/j.1600-0463.2009.02515.xpmid: 19703128

The gene phosphatase and tensin homolog deleted on chromosome 10 (PTEN) codes for a tumor‐suppressor phospholipid phosphatase. Deletion, mutation or abnormal expression of PTEN is commonly found in many kinds of malignant tumors. At the time of this study, though, the role of PTEN expression in the pathology of hepatic fibrosis remains unclear. In this study, we investigate the dynamic expression of PTEN in a rat model of hepatic fibrosis, with special emphasis on the activation and proliferation of hepatic stellate cells (HSC) in vivo. The rat model of hepatic fibrosis used in this study employed common bile duct ligation. At four time points, the expression of PTEN in hepatic tissues and activated HSC in rat liver tissues was measured by immunohistochemical staining, Western blotting, real‐time fluorescent quantitative PCR and immunofluorescence confocal laser scanning microscopy, respectively. Further, α‐smooth muscle actin (α‐SMA), an activated HSC marker in rat liver tissues, was detected by immunohistochemical staining. This study showed that aggravation of hepatic fibrosis led to gradually decreasing expression of PTEN in the hepatic tissues. Further, as hepatic fibrosis worsens, PTEN‐expressing activated HSC accounts for an increasingly smaller percentage of all activated HSC. In contrast, the percentage of α‐SMA‐expressing HSC cells increases significantly. In conclusion, expression of PTEN mRNA and protein is down‐regulated in fibrogenic rat liver tissue, and its expression in HSC in vivo also decreases with progression of fibrosis. Thus, these results show that the dynamic expression of PTEN in hepatic tissues negatively correlates with activation and proliferation of HSC.