Inhibition of cyclooxygenase-2-mediated matriptase activation contributes to the suppression of prostate cancer cell motility and metastasis.

Chronic inflammation plays an important role in cancer development and progression. Cyclooxygenases-2 (COX-2) is a key enzyme in generating prostaglandins causing inflammation, is often found to be overexpressed in prostate cancer (PCa) and is correlated with PCa cell invasion and metastasis. We aim to investigate the molecular mechanism of how COX-2 promotes PCa cell invasion and metastasis and to evaluate the effect of COX-2 inhibitors in a selected model of PCa progression. Our results showed that the expression of COX-2 and Interleukin 1ß (IL-1ß) was upregulated in highly invasive PCa cells and was correlated with the activated levels of membrane-anchored serine protease matriptase. The expression levels of COX-2 were increased and were correlated with matriptase levels in PCa specimens. Moreover, results showed that COX-2 overexpression or a COX-2 product Prostaglandin E2 (PGE2) caused an increase in matriptase activation and PCa cell invasion, whereas COX-2 silencing antagonized matriptase activation and cell invasion. In addition, the inhibition of COX-2-mediated matriptase activation by Celebrex and sulindac sulfide suppressed the androgen-independent and COX2-overexpressing PCa PC-3 cell invasion, tumor growth and lung metastasis in an orthotopic xenograft model. Our results indicate that COX-2/matriptase signaling contributes to the invasion, tumor growth and metastasis of COX-2-overexpressing and androgen-independent PCa cells.

HAI-2 suppresses the invasive growth and metastasis of prostate cancer through regulation of matriptase.

Dysregulation of cell surface proteolysis has been strongly implicated in tumorigenicity and metastasis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer (PCa) cell migration, invasion, tumorigenicity and metastasis using a human PCa progression model (103E, N1, and N2 cells) and xenograft models. N1 and N2 cells were established through serial intraprostatic propagation of 103E human PCa cells and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was revealed to gradually increase throughout the serial isolations (103E

Antibiotic-resistant Propionibacterium acnes among acne patients in a regional skin centre in Hong Kong.

BACKGROUND: There has been no study on antibiotic-resistant Propionibacterium acnes in Hong Kong. OBJECTIVE: We investigated the prevalence and pattern of antibiotic-resistant P. acnes and to identify any associated factors for harbouring the resistant strains. METHODS: Culture and sensitivity testing of P. acnes to commonly used antibiotics were performed. Resistance to tetracycline was defined at a minimal inhibitory concentration (MIC) of 2 µg/mL or more; erythromycin at an MIC of 0.5 µg/mL or more; clindamycin at an MIC of 0.25 µg/mL or more according to EUCAST. For breakpoints of doxycycline and minocycline, those with an MIC of 1 µg/mL or more were defined as resistant strains. RESULTS: Among the 111 specimens collected from 111 patients, 86 strains of P. acnes were recovered, one from each specimen. Twenty-five specimens had no growth. Forty-seven (54.8%) strains were found to be resistant to one or more antibiotics. Forty-six (53.5%), 18 (20.9%), 14 (16.3%), 14(16.3%) and 14 (16.3%) strains were resistant to clindamycin (CL), erythromycin (EM), tetracycline (TET), doxycycline (DOX) and minocycline (MR) respectively. Ten strains (11.6%) had cross resistance between the MLS antibiotics (erythromycin or clindamycin), one strain (1.2%) had cross resistance among the cyclines and 14 strains (16.4%) had cross resistance between the MLS and cycline antibiotics. Binary logistic regression showed an association between MLS antibiotic resistance with an increased age whereas cycline resistance was associated with the duration of treatment. CONCLUSION: Antibiotic-resistant P. acnes is prevalent in Hong Kong. Dermatologists should be more vigilant in prescribing antibiotics for acne patients.

Rac2 expression and mutation in human brain tumors.

BACKGROUND: Rac1 and Rac2 are interchangeable in NADPH oxidase activation. Rac1 plays an important role in regulating nuclear signalling and in the activation of transcriptional factors that regulate gene expression and cell growth. Our previous study observed mutation in effector region of Rac1 gene in brain tumors. Little is known about the expression and mutation of Rac2 in human brain tumors. METHOD: We examined the expression of Rac2 by using reverse transcriptase-polymerase chain reaction (RT-PCR) and northern blot analysis and the mutation of Rac2 gene by using DNA sequence analysis. FINDINGS: The decreased expression of Rac2 was found in 15 cases (57.7%) including 8 of 10 astrocytomas, 2 of 8 meningiomas, and 5 of 8 pituitary adenomas. Two of 13 cases with decreased expression of Rac2 had gene mutation. Only two of 26 cases had Rac2 overexpression in which no Rac2 gene mutation was found. Four of 8 cases with normal Rac2 expression had Rac2 gene mutation. The site of Rac2 gene mutation had no hot spots and was not concentrated in the effector region. CONCLUSIONS: Our results showed a low frequency of mutation and no hot spots of mutation in Rac2 gene in brain tumors, suggesting a decreased possibility of Rac2 in the brain tumorigenesis. The role of high frequency of decreased Rac2 expression in brain tumors, particularly in malignant astrocytomas, needs further investigations to be elucidated.