Novel anti-melanoma treatment: focus on immunotherapy.

Melanoma is an intractable cancer that is aggressive, lethal, and metastatic. The prognosis of advanced melanoma is very poor because it is insensitive to chemotherapy and radiotherapy. The incidence of melanoma has been ascending stably for years worldwide, accompanied by increasing mortality. New approaches to managing this deadly disease are much anticipated to enhance the cure rate and to extend clinical benefits to patients with metastatic melanoma. Due to its high degree of immunogenicity, melanoma could be a good target for immunotherapy, which has been developed for decades and has achieved certain progress. This article provides an overview of immunotherapy for melanoma.

[Molecular characterization of vancomycin-resistant enterococci isolates].

OBJECTIVE: To investigate the prevalence and genotype of vancomycin-resistant enterococci (VRE)faecium and faecalis isolates. METHODS: Thirty-eight non duplicate vancomycin -resistant enterococci isolates were collected from 2003 to 2007 in Beijing Chaoyang hospital. The prevalence of VRE was analyzed using WHONET software. These strains were processed by brain heart infusion agar screening in the presence of vancomycin (6 mg/L), and were analyzed for genotypic characteristics using multiplex PCR. The homology of the isolates was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Most VRE strains were isolated from the ICU patients (34.2% , 13/38). The vancomycin resistance rate (vancomycin MIC> or =16 mg/L) was 2.6% in 2003, 1.8% in 2004, 0.7% in 2005, 6. 8% in 2006, and 3.3% in Jan - Mar 2007. Fifteen vancomycin-resistant Enterococci faecalis isolates were identified as vanB genotype by PCR and sequencing. (the vancomycin MIC ranged from 16 to 48 mg/L and the teicoplanin MIC ranged from 0.38 to 0.5 mg/L). The vanA gene was confirmed by PCR and sequencing in twenty-three vancomycin-resistant Enterococcus faecium (vancomycin MIC > or =256 kg/L, teicoplanin MIC = 2-32 mg/L). Twelve vancomycin-resistant Enterococcus faecium isolates showed incongruence between phenotype and genotype for glycopeptides resistance (vanA genotype and vanB phenotype). The PFGE analysis revealed 10 different PFGE types. Fourteen vancomycin-resistant Enterococci faecalis isolates belonged to the same clone. 21 vancomycin-resistant Enterococci faecium isolates belonged to 9 PFGE types. The four most prevalent clones was A, D, E and F. CONCLUSION: The VRE strains isolated from Beijing Chaoyang Hospital belong to vanA and vanB genotypes. Vancomycin -resistant Enterococci faecalis is monoclonal, and vancomycin-resistant Enterococci faecium is polyclonal. Some of the vancomycin-resistant Enterococcus faecium isolates show incongruence between phenotype and genotype.

Characterization of FGFR signaling pathway as therapeutic targets for sarcoma patients.

The fibroblast growth factor receptor (FGFR) family plays important roles in regulating cell growth, proliferation, survival, differentiation and angiogenesis. Deregulation of the FGF/FGFR signaling pathway has been associated with multiple development syndromes and cancers, and thus therapeutic strategies targeting FGFs and FGFR in human cancer are currently being explored. However, few studies on the FGF/FGFR pathway have been conducted in sarcoma, which has a poor outcome with traditional treatments such as surgery, chemotherapy, and radiotherapy. Hence, in the present review, we provide an overview of the role of the FGF/FGFR pathway signal in sarcoma and FGFR inhibitors, which might be new targets for the treatment of sarcomas according to recent research.

[Plasmid-mediated cephalosporinase among extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae].

OBJECTIVE: To investigate the prevalence and genotype of plasmid-mediated cephalosporinase (AmpC) beta-lactamase in extended-spectrum-beta-lactamase-producing (ESBL) Escherichia coli and Klebsiella pneumoniae. METHODS: 24 strains of cefoxitin-resistant ESBL-producing E. coli and 8 strains of K. pneumoniae were collected from January to December 2001 at Beijing Chaoyang Hospital. Analytical isoelectric focusing electrophoresis was used to measure the pI of the beta-lactamase. Conjugation experiment was used to study the transfer of cefoxitin resistance. The homology of the isolates was determined by pulsed field gel electrophoresis (PFGE). Plasmid-mediated AmpC enzyme genes were amplified and sequenced by using multiplex PCR. RESULTS: The prevalence of ESBL-producing E. coli and K. pneumoniae were 16.8% (49/292) and 16.5% (35/212), respectively. The prevalence of AmpC enzyme among ESBL-producing E. coli and K. pneumoniae isolates were 2.0% (1/49) and 17.1% (6/35), respectively. These 7 isolates produced DHA-1 AmpC enzyme. One strain of K. pneumoniae could transfer cefoxitin resistance to the recipient. Among 7strains, 5 strains produced CTX-M-3 and 2 produced SHV-12 ESBL. These 7 strains also produced TEM-1 broad-spectrum enzymes. These strains harbored 2 - 5 plasmids and one of them were 33 - 36 kb. PFGE showed these strains came from a variety of clones. CONCLUSIONS: In this hospital, 7 strains of the ESBL-positive E. coli and K. pneumoniae produced both DHA-1AmpC enzyme and CTX-M-3/SHV-12 ESBL. These 7 strains were from different clones.

Antagonism of estrogen-mediated cell proliferation by raloxifene in prevention of ageing-related prostatic hyperplasia.

Estrogen has important roles in the initiation and development of benign prostatic hyperplasia (BPH). Regulators of the estrogen receptor (ER) are tissue- and cell-specific. We evaluated the effect of estrogen antagonist, raloxifene (Ral), on the prevention and treatment of BPH by investigating its effect on the proliferation of two different prostate cell lines: a stromal cell line, WPMY-1, and a benign prostatic hyperplasia epithelial cell line, BPH-1. We additionally evaluated its effect on prostatic hyperplasia induced by estrogen and androgen in a rat model. The effect of Ral on the prevention of prostatic hyperplasia was analyzed by haematoxylin and eosin staining and quantitative immunohistochemistry (IHC) for proliferating cell nuclear antigen and alpha-smooth muscle actin. In vitro and in vivo, tamoxifen (Tam), another anti-estrogen drug, and finasteride (Fin), a drug for the clinical treatment of BPH, served as efficacy controls. The in vitro data showed that neither Ral nor Tam alone affected the proliferation of WPMY-1 and BPH-1, but both antagonized the effect of oestradiol in promoting the proliferation of the two cells. Results from the IHC staining of the rat prostates indicated that, similar to Tam and Fin, Ral inhibited the proliferation of stromal cells in vivo. Interestingly, in contrast to Tam, both Ral and Fin inhibited the proliferation of epithelial cells. Furthermore, Ral treatment much strongly decreased the number of prostatic acini and the surrounding layers of smooth muscle cells than Fin (P < 0.05). Our data showed for the first time that Ral may have a role in the response of the rat prostate to selective ER modulators.

Proliferation and phenotypic changes of stromal cells in response to varying estrogen/androgen levels in castrated rats.

It is known that human benign prostatic hyperplasia might arise from an estrogen/androgen (E/T) imbalance. We studied the response of castrated rat prostate to different ratios of circulating E/T. The castrated male Wistar rats were randomly injected with E/T at different ratios for 4 weeks. The prostates of E/T (1:100) group showed a distinct prostatic hyperplasia response by prostatic index, hematoxylin and eosin staining, and quantitative immunohistochemical analysis of alpha-smooth muscle actin (SMA). In this group, cells positive for Vimentin, non-muscle myosin heavy chain (NMMHC) and proliferating cell nuclear antigen (PCNA) increased in the stroma and epithelium. Furthermore, the mRNA levels of smooth muscle myosin heavy chain (SMMHC) and NMMHC increased. So E/T at a ratio of 1:100 can induce a stromal hyperplastic response in the prostate of castrated rats. The main change observed was an increase of smooth muscle cells, whereas some epithelial changes were also seen in the rat prostates.