Immunization during a cerebrospinal meningitis epidemic in the Mongolian People's Republic, 1974-75.

An epidemic of cerebrospinal meningitis (CSM) in the Mongolian People''s Republic, starting in 1969, reached its peak in 1974. In that year and in early 1975, 65 000 children in the 0-8-years age group in the main towns and in the provinces were immunized with meningococcal vaccine of serogroup A. The morbidity rates due to CSM were 12 times higher in the non-immunized than in the immunized children. This result demonstrates the value of an immunization programme to control epidemics of CSM.     

Targeted pharmacogenetic analysis of antipsychotic response in the CATIE study

Aim: This study evaluated the impact of 6789 SNPs on treatment response to antipsychotics in Caucasian patients from the CATIE study.Materials & methods: An Illumina (CA, USA) BeadChip was designed that targeted genes potentially impacting disease risk, disease presentation or antipsychotic response. SNPs tagged regions of linkage disequilibrium or functional variants not detectable using previous genotypes for CATIE. Change in Positive and Negative Syndrome scale total score was modeled using a mixed model repeated measures method that assumed a 30-day lag period. Genetic association analysis was performed using linear regression. Results: Association analysis identified 20 SNPs with p-values of ≤5 × 10(-4). Many of these are in genes previously implicated in schizophrenia and other neuropsychiatric diseases.Conclusion: The targeted approach identified SNPs possibly influencing response to antipsychotic drugs in Caucasian patients suffering from schizophrenia. The findings support a biological link between disease risk and presentation and antipsychotic response. Original submitted 10 April 2012; Revision submitted 7 June 2012.     

Tumor necrosis factor‐α induces prostate cancer cell migration in lymphatic metastasis through CCR7 upregulation

Understanding the mechanism of lymph node metastasis, a poor prognostic sign for prostate cancer, and the further dissemination of the disease is important to develop novel treatment strategies. Recent studies have reported that C‐C chemokine receptor 7 (CCR7), whose ligand is CCL21, is abundantly expressed in lymph node metastasis and promotes cancer progression. Tumor necrosis factor‐α (TNF‐α) is chronically produced at low levels within the tumor microenvironment. The aim of this study was to determine whether TNF‐α promotes prostate cancer dissemination from metastatic lymph nodes through activation of the CCL21/CCR7 axis. First, human prostate cancer cells were determined to express both TNF‐α and CCR7. Second, low concentrations of TNF‐α were confirmed to induce CCR7 in prostate cancer cells through phosphorylation of ERK. Finally, CCL21 was found to promote the migration of prostate cancer cells through phosphorylation of the protein kinase p38. Our results suggest that TNF‐α leads to the induction of CCR7 expression and that the CCL21/CCR7 axis might increase the metastatic potential of prostate cancer cells in lymph node metastasis.     

CCL2 induces resistance to the antiproliferative effect of cabazitaxel in prostate cancer cells

Understanding the mechanism of chemoresistance and disease progression in patients with prostate cancer is important for developing novel treatment strategies. In particular, developing resistance to cabazitaxel is a major challenge in patients with docetaxel‐resistant and castration‐resistant prostate cancer (CRPC) because cabazitaxel is often administered as a last resort. However, the mechanism by which cabazitaxel resistance develops is still unclear. C‐C motif chemokine ligands (CCL) were shown to contribute to the castration resistance of prostate cancer cells via an autocrine mechanism. Therefore, we focused on CCL as key factors of chemoresistance in prostate cancer cells. We previously established a cabazitaxel‐resistant cell line, DU145‐TxR/CxR, from a previously established paclitaxel‐resistant cell line, DU145‐TxR. cDNA microarray analysis revealed that the expression of CCL2 was upregulated in both DU145‐TxR and DU145‐TxR/CxR cells compared with DU145 cells. The secreted CCL2 protein level in DU145‐TxR and DU145‐TxR/CxR cells was also higher than in parental DU145 cells. The stimulation of DU145 cells with CCL2 increased the proliferation rate under treatments with cabazitaxel, and a CCR2 (a specific receptor of CCL2) antagonist suppressed the proliferation of DU145‐TxR and DU145‐TxR/CxR cells under treatments of cabazitaxel. The CCL2‐CCR2 axis decreased apoptosis through the inhibition of caspase‐3 and poly(ADP‐ribose) polymerase (PARP). CCL2 is apparently a key contributor to cabazitaxel resistance in prostate cancer cells. Inhibition of the CCL2‐CCR2 axis may be a potential therapeutic strategy against chemoresistant CRPC in combination with cabazitaxel.     

Mycoplasma penetrans is capable of activating V gamma 9/V delta 2 T cells while other human pathogenic mycoplasmas fail to do so

While most mycoplasma species appear to have evolutionarily lost the ability to synthesize isoprenoid precursors, Mycoplasma penetrans has retained the nonmevalonate pathway that proceeds via the immunogenic intermediate (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP). Consequently, this pathogen is capable of stimulating human V gamma 9/V delta 2 T cells.