Anti-tumor activities of active ingredients in Compound Kushen Injection.

Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are matrine (MT) and oxymatrine (OMT) that exhibit a variety of pharmacological activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic and cardiovascular protective effects. Recent evidence shows that these compounds also produce anti-cancer actions, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- and/or radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this review, we summarize recent progress in studying the anti-cancer activities of MT, OMT and CKI and their potential molecular targets, which provide clues and references for further study.

[rh-endostatin in combination with docetaxel and carboplatin as adjuvant treatment for non-small lung cancer].

OBJECTIVE: To evaluate the efficacy of Endosteal(TM) (rh-endostatin, YH-16) combined with docetaxel and carboplatin (TP) regimen for the adjuvant treatment of non-small lung cancer (NSCLC) and its impact on circulating blood markers. METHODS: 36 patients with stage Ib-IIIa postoperative NSCLC, were randomly divided into the treatment group, Endosteal(TM) plus TP regimen, and the control group, TP regimen only, respectively. DFS and toxicities of patients were observed. The numbers of CEC and the levels of tumor marker CEA, NSE and CYFR21-1 were measured. RESULTS: The numbers of CEC and the levels of CEA, NSE and CYFR21-1 decreased after treatment. There were significant differences in CEC and NSE between treatment group and control group after four cycles of treatment, respectively (P = 0.016 and 0.013). Disease-free survival time (DFS) was longer in treatment group than control group but without significant difference. CEC was significantly increased in recurrent and metastasis cases and decreased after effective treatment. CONCLUSION: Endosteal(TM) combined with TP regimen seem to be superior to TP alone in some short term index for the treatment of postoperative NSCLC even though long-term survival is still anticipated. CEC, as a biomarker, may be useful in predicting the efficacy of the such synergistic treatment.

[Effect of potassium iodide on prevention of experimental lead nephropathy and expression of nuclear factor-kappaB and fibronectin].

OBJECTIVE: To investigate the effect of potassium iodide on the expression of nuclear factor-kappaB and fibronectin. METHODS: The experiment was performed with 72 SD rats weighing about 180-220 g. The animals were randomly assigned into nine groups. Group A, B, C (n=8) served as control and were fed with distilled water for 1 month, 2 month, 3 month respectively. Group D, E, F (n=8) served as lead exposed and were fed with water with 0.5% lead acetate for 1 month, 2 month, 3 month respectively. Group G, H, I (n=8) served as potassium iodide and lead exposed and were treated with 0.5% lead acetate simultaneously taking potassium iodide 3 mg/100 g weight by intragastric administration for 1 month, 2 month, 3 month respectively. Animals of different groups were sacrificed at the end of the treatment. Ultrastructure of kidney was observed by electron microscopy; Expression of NF-kappaB and FN protein and mRNA in kidney were measured respectively by immunohistochemistry and RT-PCR. RESULTS: Electron microscopic examination revealed potassium iodide could restrain the denaturalization in epithelial cells and mitochondrial cristae. The expressions of NF-kappaB protein (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839) and mRNA (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538) in all the lead exposed groups continuously increased compared with correspondent control groups; Group I was decreased obviously compared with group F. The expressions of FN protein (0.4243 +/- 0.0595, 0.4917 +/- 0.0891) and mRNA (0.8650 +/- 0.0880, 0.8714 +/- 0.0980) in group E and F increased compared with group B and C, but the expressions of FN protein in group I significantly decreased compared with group F; The expressions of FN mRNA in Group H and I significantly decreased compared with group E and F. CONCLUSION: The potassium iodide can ameliorate renal ultrastructure and degrade expression of nuclear factor-kappaB and fibronectin induced by lead.

Prognostic significance of preoperative and postoperative CK19 and CEA mRNA levels in peripheral blood of patients with gastric cardia cancer.

AIM: To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA levels in peripheral blood of patients with gastric cardia cancer (GCC). METHODS: We detected the preoperative and postoperative mRNA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors. RESULTS: Elevated preoperative and postoperative CK19 and CEA mRNA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 mRNA, and preoperative and postoperative CEA mRNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status (P = 0.018), preoperative CK19 (P = 0.035) and CEA (P = 0.011) mRNA levels were independent prognostic factors for overall survival (OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively (P < 0.001). CONCLUSION: Elevated preoperative CK19 and CEA mRNA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk.

[Expression of renal nuclear factor-kappaB, transforming growth factor-beta and fibronectin of rats exposed to lead].

OBJECTIVE: To investigate the role of lead in the expression of the renal fibrosis related nuclear factor kappaB (NF-kappaB), transforming growth factor (TGF-beta) and fibronectin (FN) in rat kidney and the possible molecule mechanism of lead induced renal fibrosis. METHODS: Thirty-two Sprague-Dawley rats were randomized into 4 groups. Group A was fed with distilled water as control group. Group B, C and D were fed with the water including 0.5% lead acetate continuously for 1, 2 or 3 months respectively. At the end of treatment, the expressions of renal NF-kappaB, TGF-beta and FN were detected by immunohistochemistry and RT-PCR. RESULTS: The immunohistochemistry analysis showed that expressions of NF-kappaB in group B, C and D (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839 respectively) were continuously increased as compared with that in group A (0.1464 +/- 0.0624). The RT-PCR analysis showed that expressions of NF-kappaB in group B, C and D (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538 respectively) were also increased as compared with that in group A (0.3608 +/- 0.0550). However, there was no change for TGF-beta in 4 groups except that it was increased markedly in group D (0.5225 +/- 0.0416) as compared with that in group A (0.4645 +/- 0.0461) by RT-PCR. The expressions of FN in group C and D (0.4243 +/- 0.0595 and 0.4917 +/- 0.0891 by immunohistochemistry; 0.8650 +/- 0.0880 and 0.8714 +/- 0.0980 by RT-PCR) were increased as compared with those in group A (0.3530 +/- 0.0490 by immunohistochemistry and 0.7432 +/- 0.0639 by RT-PCR). CONCLUSION: The lead can increase the expression of renal NF-kappaB, TGF-beta and FN in rats, which may be related to the lead induced renal fibrosis in rats.

Melatonin attenuates hypertension-induced renal injury partially through inhibiting oxidative stress in rats.

The aim of the present study was to investigate the protective effects of melatonin (MLT) on hypertension-induced renal injury and identify its mechanism of action. Twenty-four healthy male Wistar rats were divided into a sham control group (n=8), which was subjected to sham operation and received vehicle treatment (physiological saline intraperitoneally at 0.1 ml/100 g), a vehicle group (n=8), which was subjected to occlusion of the left renal artery and vehicle treatment, and the MLT group (n=8), which was subjected to occlusion of the left renal artery and treated with MLT (10 mg/kg/day). Pathological features of the renal tissues were determined using hematoxylin and eosin staining and Masson staining. Urine protein, serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Immunohistochemical analysis was performed to determine the expression of heme oxygenase­1 (HO­1), intercellular adhesion molecule­1 (ICAM­1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, reverse transcription polymerase chain reaction was conducted to determine the mRNA expression of HO­1, ICAM­1, eNOS and iNOS. A marked decrease in blood pressure was noticed in the MLT group at week 4 compared with that of the vehicle group (P<0.01). Furthermore, MLT treatment attenuated the infiltration of inflammatory cells and oedema/atrophy of renal tubules. MLT attenuated hypertension-induced increases in urine protein excretion, serum creatinine and MDA as well as decreases in SOD activity in renal tissues. Furthermore, MLT attenuated hypertension-induced increases in iNOS and ICAM­1 as well as decreases in eNOS and HO­1 expression at the mRNA and protein level. In conclusion, the results of the present study indicated that MLT had protective roles in hypertension­induced renal injury. Its mechanism of action is, at least in part, associated with the inhibition of oxidative stress.