Preventive and therapeutic effects of NF-kappaB inhibitor curcumin in rats colitis induced by trinitrobenzene sulfonic acid.

AIM: To ascertain the molecule mechanism of nuclear factor-kappaB (NF-kappaB) inhibitor curcumin preventive and therapeutic effects in rats' colitis induced by trinitrobenzene sulfonic acid (TNBS). METHODS: Sixty rats with TNBS-induced colitis were treated with 2.0% curcumin in the diet. Thirty positive control rats were treated with 0.5% sulfasalazine (SASP). Thirty negative control rats and thirty model rats were treated with general diet. Changes of body weight together with histological scores were evaluated. Survival rates were also evaluated. Cell nuclear NF-kappaB activity in colonic mucosa was evaluated by using electrophoretic mobility shift assay. Cytoplasmic IkappaB protein in colonic mucosa was detected by using Western Blot analysis. Cytokine messenger expression in colonic tissue was assessed by using semiquantitative reverse-transcription polymerase chain reaction. RESULTS: Treatment with curcumin could prevent and treat both wasting and histopathologic signs of rats with TNBS-induced intestinal inflammation. In accordance with these findings, NF-kappaB activation in colonic mucosa was suppressed in the curcumin-treated groups. Degradations of cytoplasmic IkappaB protein in colonic mucosa were blocked by curcumin treatment. Proinflammatory cytokine messenger RNA expression in colonic mucosa was also suppressed. CONCLUSION: This study shows that NF-kappaB inhibitor curcumin could prevent and improve experimental colitis in murine model with inflammatory bowel disease (IBD). The findings suggest that NF-kappaB inhibitor curcumin could be a potential target for the patients with IBD.

[Modulation of intestinal mucosal inflammatory factors by curcumin in rats with colitis].

OBJECTIVE: To explore the mechanism of modulation of intestinal mucosal inflammatory factors by curcumin, the inhibitor of the transcriptional factor nuclear factor -kappaB (NF-kappaB), in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis, and screen for a targeted therapeutic agent for treatment of inflammatory bowel disease (IBD). METHODS: Rats with TNBS-induced colitis were fed with diet containing 2.0% curcumin (treatment group), 0.5% sulfasalazine (SASP, positive control group), and normal diet (model group and negative control group). Changes in colonic mucosal histological scores were evaluated and the cytokine mRNA expressions in the colonic tissue assessed by semiquantitative reverse transcriptional PCR (RT-PCR). RESULTS: Treatment with curcumin ameliorated the histopathologic signs in rats with TNBS-induced intestinal inflammation. Curcumin and sulfasalazine obviously suppressed the high expression of proinflammatory cytokine interleukin (IL)-1beta mRNA and increased the low expression of IL-10 mRNA in the colonic mucosa. Expression of the anti-inflammatory cytokine IL-4 mRNA was detected in none of the groups. CONCLUSIONS: Curcumin could modulate the expressions of IL-1beta and IL-10 mRNA in murine model of IBD, which suggests the potential of curcumin as a targeted therapeutic agent for IBD.

[Association between the survival time and high-expression of EGFR and HER-2 in breast cancer].

OBJECTIVE: To investigate the relationship between the survival time and the high-expression of epidermal growth factor receptor (EGFR) and human epidermal receptor 2 (HER2) in breast cancer patients, and assess the feasibility of using the two markers either alone or in combination for predicting the prognosis of the patients. METHODS: Breast cancer samples were obtained from 185 patients and measured for the expressions of EGFR and HER-2 by way of immunohistochemistry, and 120 patients (64.9%) were followed up and their survival time recorded. Sixty-five patients (35.1%) failed to be followed for various reasons. RESULTS: Of the 120 patients followed up, death occurred in 28 (15%). Positive HER2 expression was detected in 57.8% and EGFR expression in 40.5% of the all the samples examined. The over-expression of either HER2 or EGFR was in inverse correlation with the survival time (P<0.05 and P<0.01, respectively), and the over-expression of both related to the survival time in similar manner (P<0.05 and P<0.01). CONCLUSION: The high expression of HER2 or/and EGFR suggests a short survival time and an unfavorable prognosis.

[Clinical study of serum tissue polypeptide-specific antigen in breast cancer].

OBJECTIVE: To investigate the expression of serum tissue polypeptide-specific antigen (TPS) in breast cancer patients and its clinical value in such cases. METHODS: Altogether 160 subjects (90 patients with breast cancer, 40 with benign breast lesions, and 30 healthy subjects) were enrolled in this study. The serum TPS and CA153 levels were measured by ELISA in all the subjects. RESULTS: The levels and positivity rate of serum TPS and CA153 in breast cancer group were significantly higher than those in the normal subjects group and benign lesion group (P<0.01), and became even higher as the malignancy progressed. High serum TPS level was detected in the cancer patients in stage I. Serum TPS level was the most sensitive to bone metastasis of the malignancy, but its highest levels occurred in cases of lymphoid node metastasis (P<0.05). In patients who responded favorably to the treatment, serum TPS and CA153 levels were significantly reduced (P<0.05), but the reduction in TPS levels tended to be more obvious (P<0.05). CONCLUSION: Serum TPS can be used as a very useful and sensitive tumor marker in the diagnosis of breast cancer, especially in case of bone metastasis, and may be of great value in clinical decision-making and assessment of therapeutic effect.

Association of progesterone receptor and HER2 expressions with the survival time of patient with breast cancer.

OBJECTIVE: To investigate the relationship between the survival time and the expressions of progesterone receptor (PR) and HER2 in the tumor tissues of patients with breast cancer, thereby to explore the possibility of using the 2 indices as the indicator for the prognosis of the patients. METHOD: Immunohistochemical staining for PR and HER2 was performed on paraffin embedded tumor specimens obtained from 185 patients with breast cancer, and follow-up studies were conducted and the survival time of the patients recorded. RESULTS: In the 120 patients (64.9%) with complete followed-up data, 28 patients died (15%), with the record of the other 65 patients (35.1%) not available for this study. Immunohistochemical detection found that the positivity rates for HER2 and PR were 57.8% and 62.7% respectively in the total specimens examined, and HER2 and PR showed significant difference in their respective associations with the survival rate of the patients (P<0.01). Specifically, HER2 was inversely associated with the survival rate, to which PR was positively related. The univariant analysis suggested the hazards posed by HER2 expression to reduce the overall survival of the patients (P<0.01, OR=1.566), while PR, playing the protective role, was associated with a significantly longer overall survival time (P<0.01, OR=0.547). In the multivariate analysis, however, only PR expression was of significant prognostic value in the patients (P 0.012). CONCLUSION: Both HER2 and PR can be used as independent indicators for the prognosis of patients with breast cancer, and high HER2 expression may indicate poor prognosis, while PR is associated with a longer survival time and a higher survival rate.

[Interferon-gamma up-regulates Fas expression and increases Fas-mediated apoptosis in tumor cell lines].

OBJECTIVE: To investigate effect of interferon-gamma (IFN-gamma) on Fas expression and Fas-mediated apoptosis in tumor cell lines. METHODS: Fas expression was detected by flow cytometry, and the tumor cell apoptosis evaluated by enzyme-linked immunosorbent assay and AnnexinV staining assay. RESULTS: All the 4 tumor cell lines used in this study, e.g. gastric cancer cell lines Kato-III AGS, lung cancer cell line A549 and laryngeal cancer cell line Hep-2, expressed Fas protein to varied degrees. Fas expression was up-regulated by IFN-gamma (P<0.05), which alone was enough to induce apoptosis in tumor cells and increase the susceptibility of them to anti-Fas antibodies. IFN-gamma induced Fas expression up-regulation and tumor cell apoptosis in a time-dependent manner. CONCLUSION: Fas-mediated apoptosis is one of the mechanisms for IFN-gamma to exercise its anti-tumor effect.