Research progress in the study of protective effect of tanshinone IIA on cerebral ischemic stroke / 药学学报

Danshen is one of the traditional Chinese herbal medicines and nas a long history or being used clinically in the treatment of cardiovascular and cerebrovascular conditions such as coronary heart disease and angina pectoris. Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen. It has been reported to be the major bioactive compound of Danshen and has diverse biological effects. Recent studies demonstrated that tanshinone IIA had neuroprotective effects on experimental ischemic stroke through its antiinflammatory, anti-oxidant, anti-apoptosis effects and its inhibitory effect on excitatory amino acid toxicity. In this review, we summarized all the recent progresses on the protective effect of tanshinone IIA on cerebral ischemic stroke. Hopefully, this article will throw some light on further study and application of tanshinone IIA.

Effect of shenhuang ointment in promoting the rehabilitation of postoperative gastrointestinal dysfunction patients of Qi stagnation blood stasis syndrome: a clinical observation / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect and safety of plastering Chinese Compound Shenhuang Ointment (CSO) at Shenque (RN8) in promoting the rehabilitation of postoperative gastrointestinal dysfunction patients of qi stagnation blood stasis syndrome (QSBSS).</p><p><b>METHODS</b>A prospective, multi-centered, randomized, double-blinded, controlled trial was conducted in 220 postoperative gastrointestinal dysfunction patients of QSBSS. They were randomly assigned to two groups, the CSO group (110 cases) and the placebo group (110 cases). CSO was plastered at Shenque (RN8) for 5 days after operation. The time of exhaustion, defecation, the recovery of intestinal peristalsis, integrals of TCM syndrome, and serum levels of motilin (MOT)and somatostatin (SS) were observed.</p><p><b>RESULTS</b>Compared with the placebo group, the condition of exhaustion and defecation, the recovery of intestinal peristalsis on the 3rd day after operation was all improved (P < 0.05). The integrals of TCM syndrome at day 2, 3, and 4 were more significantly lowered in the CSO group than in the placebo group (P < 0.01, P < 0.05). The total effective rate of TCM syndrome was 95.3% in the CSO group, better than that in the placebo group (91.8%, P < 0.05). Compared with the placebo group, the serum MOT level increased and the serum SS level decreased at day 5 after operation in the CSO group (P < 0.05).</p><p><b>CONCLUSIONS</b>The plastering of CSO at Shenque (RN8) could advance the time of exhaustion and defecation, and improve patients' clinical symptoms. And patients could tolerate well.</p>

Double-mutated oncolytic adenovirus combined with gemcitabine for treating an orthotopic nude mouse model of bladder cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic efficacy of double-mutated oncolytic adenovirus AxdAdB-3 in combination with gemcitabine for treating bladder cancer in an orthotopic nude mouse model.</p><p><b>METHODS</b>The susceptibility to the adenovirus was evaluated in bladder cancer cell lines YTS-1, T24, 5637 and KK47, and normal cell lines HCV29 and WI38. The cells were infected with AxCAlacZ and stained with 5-bromo-4-chloro-3-indolyl-β-galactoside (X-Gal). Immunostaining against adenoviral hexon protein was performed to determine the selective replication of AxdAdB-3 in the cancer cells. Flow cytometry was used to determine the YTS-1 cells in S phase of cell cycle after adenovirus infection. Cell viability after AxdAdB-3 and/or gemcitabine was measured by CCK-8 assay. Orthotopic bladder cancer model was established in nude mice, and the inhibitory efficacy of intravesical instillation therapy with AxdAdB-3 or/and gemcitabine was assessed.</p><p><b>RESULTS</b>Gene transduction efficiency was different among the cell lines, and correlated with expression of CAR. 5637 and KK47 cells with high expression of CAR were more susceptible to the adenovirus, whereas YTS-1 and T24 cells with little CAR expression were resistant to adenoviral infection. Immunostaining showed that the expression levels of hexon protein varied among the cell lines. Normal cells infected with AxdAdB-3 expressed little hexon protein. The proportion of S-phase cells was (39 ± 3) % and (49 ± 5) % in the AxCAlacZ- and AxdAdB-3-infected bladder cancer cells, respectively. AxdAdB-3 effectively induced S-phase entry of cell cycle (P < 0.05). AxdAdB-3 combined with gemcitabine significantly inhibited the growth of bladder cancer cell lines. In vivo, the mean weight of the bladder tumors in mice treated with intravesical instillation of AxCAlacZ, gemcitabine, AxdAdB-3, and AxdAdB-3 + gemcitabine were 400.6, 126.4, 82. 0, 40.4 mg, respectively. Either AxdAdB-3 (P < 0.0001) and gemcitabine (P < 0.0001) suppressed the tumor growth in nude mice, and the combination therapy reduced tumors more effectively than either AxdAdB-3 (P < 0.0001) or gemcitabine (P < 0.0001) alone.</p><p><b>CONCLUSIONS</b>Intravesical instillation therapy with AxdAdB-3 in combination with gemcitabine can effectively inhibit the orthotopic bladder cancer in nude mouse, and further relevant clinical studies are guaranteed.</p>

Detection of guanylate cyclase C mRNA and cytokeratin 20 mRNA in peripheral blood and analysis of prognosis in early to moderate colorectal cancer patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the associations of guanylate cyclase C (GC-C) mRNA and cytokeratin 20 (CK20) mRNA with metastasis and prognosis in early to moderate colorectal cancer patients.</p><p><b>METHODS</b>GC-C mRNA and CK 20 mRNA in peripheral blood of 74 colorectal cancer patients without distant metastasis were detected by fluorescent quantitative PCR (FQ-PCR). Based on their clinicopathological and postoperative follow-up data, the relationship and clinical significance of these data with metastasis hazards and prognosis factors were analyzed.</p><p><b>RESULTS</b>The positive rate of GC-C mRNA in 74 colorectal cancer patients was 33.8% (25/74), and CK20 mRNA was 31.1% (23/74). The 1-, 2-, 3- year disease-free survival rates of patients were 94.6%, 82.4% and 78.4% respectively. There were significant differences in positive rates of GC-C mRNA and CK20 mRNA, tumor differentiation, mesentery lymph node metastasis, tumor embolus in vessel and postoperative chemotherapy associated with 3-year disease free survival rate by Kaplan-Meier analysis (all P<0.05). While mesentery lymph node metastasis and tumor embolus in vessel were independent risk factors of 3-year disease-free survival (P<0.05). CK20 mRNA and tumor embolus in vessel were independent risk factors of 3-year disease-free survival by analysis stratified with clinical stage (P<0.05).</p><p><b>CONCLUSIONS</b>Detection of CK20 mRNA and GC-C mRNA in peripheral blood may be important for early detection of early metastasis of colorectal cancer.</p>

Detection and clinical significance of apoptosis related protein in local advanced rectal cancer patients with preoperative neoadjuvant therapy / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the mechanism of rectal cancer apoptosis induced by preoperative chemoradiotherapy and evaluate its effect by detection of apoptosis related proteins in locally advanced colorectal cancer patients who had received preoperative chemoradiation.</p><p><b>METHODS</b>To detect Bcl-XL and Bax expression in rectal cancer before and after chemoradiotherapy by EnVision method, combined with patients clinical and pathological index, statistically analysis and evaluation their relationship and clinical significance.</p><p><b>RESULTS</b>Patients with or without tumor shrinkage after preoperative chemoradiotherapy was 13 cases and 21 cases. While the positive rate of Bcl-XL in rectal cancer before and after chemoradiotherapy were 58.8% (20/34) and 52.9% (18/34), respectively. There were significant difference between Bcl-XL change before and after chemoradiation with tumor size, tumor cells shrinkage and operation pattern. The positive rate of Bax in rectal cancer before and after chemoradiotherapy were 32.4% (11/34) and 44.1% (15/34), respectively. There were no significant difference between Bax change before and after chemoradiotherapy with tumor cells shrinkage. There were statistically significant difference between Bax ratio (χ(2) = 9.607, P = 0.048) before and after chemoradiation while there were no significant difference between Bcl-XL/Bax ratio before and after chemoradiation with tumor shrinkage. According to layered analysis with preoperative therapy, there were statistically significant difference (χ(2) = 13.964, P = 0.007) between Bcl-XL change with operation pattern while the same of significant difference between Bax change with tumor infiltration and tumor shrinkage (χ(2) = 10.806 and 10.455, both P < 0.05).</p><p><b>CONCLUSIONS</b>Preoperative chemoradiation can influence rectal cancer cell's apoptosis and treatment effect by changing Bcl-XL and Bax expression. Bcl-XL downregulation and Bax upregulation have shown important function in colorectal cancer cell apoptosis which induced by preoperative chemoradiation, it can also improve the effection of chemoradiation in rectal cancer.</p>

Anti-tumor effect of adenovirus-mediated Bcl-XL shRNA in vitro / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the anti-tumor effect of adenovirus-mediated Bcl-XL shRNA on colon cancer cells in vitro.</p><p><b>METHODS</b>A recombinant Bcl-xl adenovirus was constructed, amplified, and purified. The effect on mRNA expression of Bcl-XL was assessed by RT-PCR, and the effect on apoptosis-induction of colon cancer(Lovo cell line) in vitro was assessed by MTT assay and cell clonogenic assay.</p><p><b>RESULTS</b>RT-PCR showed that Ad/Bcl-XL shRNA significantly down-regulated the mRNA expression of Bcl-XL in Lovo cells. Ad/Bcl-XL shRNA suppressed the proliferation of Lovo cells in a dose-dependent as well as a time-dependent manner compared with Ad/GFP (P<0.05). Treatment with Ad/Bcl-XL shRNA dramatically suppressed the colony formation of Lovo cells in a dose-dependent manner (P<0.05). Ad/Bcl-XL shRNA showed no effect on normal human fibroblast.</p><p><b>CONCLUSION</b>Ad/Bcl-XL shRNA exhibits cytotoxic effect on Lovo cells and may have the potential value in the treatment of colon cancer.</p>

E1A, E1B double-restricted adenovirus enhances the cytotoxicity and antitumor activity of gemcitabine to renal cell carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Our previous studies have demonstrated potent oncolysis efficacy of the E1A, E1B double-restricted replication-competent oncolytic adenovirus AxdAdB-3 for treatment of bladder cancer. Here, we reported the feasibility and efficacy of AxdAdB-3 alone, or in combination with gemcitabine for treating renal cell carcinoma.</p><p><b>METHODS</b>Cytopathic effects of AxdAdB-3 were evaluated in human renal cell carcinoma cell lines TOS-1, TOS-2, TOS-3, TOS-3LN, SMKT-R3, SMKT-R4 and ACHN, and in normal human renal proximal tubule epithelial cells (RPTEC). AxdAdB-3 induced down-regulation of the cell cycle was determined by flow cytometry. Combination therapies of AxdAdB-3 with gemcitabine were evaluated in vitro and in vivo on subcutaneous TOS-3LN tumors in a severe combined immunodeficiency disease (SCID) mouse model.</p><p><b>RESULTS</b>AxdAdB-3 was potently cytopathic against the tested most renal cell carcinoma cell lines including TOS-2, TOS-3, TOS-3LN, SMKT-R3 and SMKT-R4, while normal human RPTEC were not destroyed. AxdAdB-3 effectively induced cell cycle S-phase entry. Combined therapy of AxdAdB-3 with gemcitabine demonstrated stronger antitumor effects in vitro and in vivo compared with either AxdAdB-3 or gemcitabine alone.</p><p><b>CONCLUSION</b>AxdAdB-3 alone, or in combination with gemcitabine may be a promising strategy against renal cell carcinoma.</p>

Efficacy and toxicity analysis of XELOX and FOLFOX4 regimens as adjuvant chemotherapy for stage III colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the efficacy and toxicity of capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin (5-Fu/LV) plus oxaliplatin (FOLFOX4) regimens as adjuvant chemotherapy for stage III colorectal cancer.</p><p><b>METHODS</b>The clinicopathological data of 118 patients with stage III colorectal cancer were studied retrospectively. The patients were assigned to receive either FOLFOX4 regimen (n = 76) or XELOX regimen (n = 42). 3-year disease-free survival (DFS) and adverse events as end points were compared between the two groups.</p><p><b>RESULTS</b>The number of patients that failed to finish 8 cycles was higher in FOLFOX4 group (28 vs. 8, P = 0.044). There was no significant difference for 3-year DFS and all grades adverse events between the two groups. However, the FOLFOX4 group showed more grade 3/4 neutropenia (31.6% vs. 14.3%, P = 0.039) and central venous catheter-associated complication (11.8% vs. 4.8%, P = 0.205), while XELOX showed more grade 3/4 thrombocytopenia (19.0% vs. 6.6%, P = 0.038) and hand-foot syndrome (11.9% vs. 1.3%, P = 0.012).</p><p><b>CONCLUSION</b>The results of this analysis indicate that XELOX and FOLFOX4 regimens have very similar efficacy as an adjuvant chemotherapy for stage III colon cancer, but XELOX may be safer than FOLFOX4.</p>

Differential expression of guanylin in colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of guanylin in colorectal cancer.</p><p><b>METHODS</b>The expression of guanylin was examined by RT-PCR and semiquantitative analysis in 20 cases of colorectal cancer, and its relationship with clinical characteristics was analyzed.</p><p><b>RESULTS</b>The positive expression of guanylin in normal tissue (80%, 16/20) was significantly higher than that in tumor tissue (35%, 7/20) (P<0.01). The same result was found in the semiquantitative analysis of 14 cases with differential expression. Differential expression of guanylin in colorectal cancer was associate with TNM stage (P<0.05), not with sex, Borrmann type and degree of differentiation (all P>0.05).</p><p><b>CONCLUSION</b>There is differential expression of guanylin in colorectal cancer, and this kind of differential expression is associated with tumor TNM stage.</p>

Detection of chromosomal aberration in sporadic colorectal cancer with comparative genomic hybridization / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the chromosomal aberration in sporadic colorectal carcinoma and its association with clinicopathological features.</p><p><b>METHODS</b>Comparative genomic hybridization(CGH) was used to screen the changes in the number of DNA sequence copies in 40 sporadic colorectal cancer patients in order to identify regions that contain genes important for the development and progression of colorectal cancer.</p><p><b>RESULTS</b>In 40 sporadic colorectal cancer, frequent gain at 20 q, 12 q, 13 q, 7 p, 7 q and 16 q were found, while loss was also found at 18 q, 5 q, 4 q, 8 pand 17 p. The number of chromosomal aberration was closely associated with tumor stage(P<0.05). No significant association was found between the number of chromosomal aberration and tumor site, histopathologic type and histologic grade.</p><p><b>CONCLUSIONS</b>Chromosomal aberration exists generally in sporadic colorectal carcinoma. The number of chromosomal aberration and gain of 20q are closely associated with tumor stage.</p>

Prognostic significance of metastatic lymph node ratio in colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic significance of metastatic lymph node ratio in patients with colorectal cancer.</p><p><b>METHODS</b>The clinicopathological data of 303 surgically treated patients with colorectal cancer were retrospectively analyzed. Spearman correlation analysis was used to determine the correlation coefficient. The survival was analyzed using Kaplan-Meier method, and the survival difference was assessed by Log-rank test. Multivariate analysis was performed using Cox proportional hazard regression model in forward stepwise regression. Receiver working characteristic curve was used to compare the accuracy of the metastatic lymph nodes ratio in predicting the death of patients at 5 years postoperatively with that of the number of metastatic lymph nodes.</p><p><b>RESULTS</b>The MLR was not correlated with the total number of dissected lymph nodes (Spearman correlation coefficient: -0.099, P > 0.05), but the positive rate of metastatic lymph nodes did (correlation coefficient: 0.107, P < 0.05). Kaplan-Meier survival analysis revealed that the MLR significantly influenced the postoperative survival time (Log-rank chi(2) = 42.878, P < 0.01), even in the patients with less than 12 resected lymph nodes. The 5-year survival rates for rN0, rN1, rN2 and rN3 were 90.9%, 68.9%, 54.7% and 39.4%, respectively. There was a significant difference between the different stages (P < 0.01). Cox proportional hazard regression model analysis showed that the metastatic lymph node ratio was an independent prognostic factor. (EXP(B) = 7.809, P < 0.01). There was no significant difference between metastatic lymph node ratio and the number of metastatic lymph nodes in predicting the death of patients at 5 years postoperatively based on the area under the receiver working characteristic curve.</p><p><b>CONCLUSION</b>The metastatic lymph node ratio in colorectal cancer patients is not correlated with the total number of dissected lymph nodes. The metastatic lymph node ratio is a major independent prognostic factor for patients with colorectal cancer. The ability of metastatic lymph node ratio in predicting the death of colorectal cancer patients at 5 years postoperatively is the same as that of the number of metastatic lymph nodes.</p>

Efficacy assessment of preoperative radiochemotherapy and analysis of associated factors in rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of preoperative radiochemotherapy and investigate the influencing factors in rectal cancer.</p><p><b>METHODS</b>Fifty-three patients with locally advanced rectal cancer were treated with radiochemotherapy before surgery. Three-field technique of radiation therapy was administered with 46 Gy, 2 Gy per fraction, five times a week. Two cycles of chemotherapy were carried out at day 1, 2 and day 21, 22 during the radiation course. Surgery was performed 4-6 weeks after the radiochemotherapy. Response of preoperative radiochemotherapy was evaluated in all the patients by endoscopic ultrasonography (EUS), spiral computed tomography (SCT) and pathology. Influencing factors of the efficacy of radiochemotherapy were evaluated by univariate and Logistic analysis.</p><p><b>RESULTS</b>Univariate analysis revealed that tumor size and histological grading were associated with the efficacy of preoperative radiochemotherapy. Logistic regression analysis showed that only tumor size was the significant predictive factor for response to preoperative radiochemotherapy. All patients underwent surgical resection after preoperative radiochemotherapy. The tumor was reduced by an average of 32.1%. T-level down-staging was 64.2%. Nodal negativity was 58.1%. Complete pathologic remission occurred in 11 patients.</p><p><b>CONCLUSIONS</b>Preoperative radiochemotherapy can shrink the primary tumor and decrease lymph node metastasis rate. Patient with small tumor may have better response to preoperative radiochemotherapy.</p>

Effects of enterostomy in treating locally advanced rectal cancer with combined chemoradiotherapy and operation / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of enterostomy in treatment of locally advanced rectal carcinoma patients with combined chemoradiotherapy and operation.</p><p><b>METHODS</b>Clinical data from 51 cases of locally advanced rectal cancer patients treated with preoperative chemoradiotherapy and operation were analyzed.</p><p><b>RESULTS</b>Thirty-three patients (64.9%) got staging down of their cancer after preoperative chemoradiotherapy, and 21.6% of patients (11 cases) had complete pathologic response. Thirty-seven patients received enterostomy, including extraperitoneal sigmoidostomy (29 cases), defunctioning ileostomy (8 cases) and double colostomy (3 cases with colon obstruction during preoperative therapy). One case experienced parastomal hernia and one stomal stenosis and 2 cases parastomal infection after enterostomy. No death of enterostomy occurred.</p><p><b>CONCLUSION</b>Colostomy can reduce the pressure of obstructed intestinal tract and contribute much to the preoperative chemoradiotherapy, ileostomy can protect the distal stoma from leakage in sphincter saving operation. Enterostomy could be selected when needed in the favor of locally advanced rectal cancer patients.</p>

Comparative study of endoluminal ultrasonography and spiral computed tomography in preoperative staging of rectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the efficacy of endoluminal ultrasonography (EUS) and spiral computed tomography (SCT) in preoperative staging of rectal carcinoma.</p><p><b>METHODS</b>Both EUS and SCT were performed prior to surgery in 68 patients with rectal carcinoma. After radical surgery, the preoperative findings were compared with histologic findings of the operative specimens, and the efficacy of EUS and SCT in staging the rectal carcinoma were evaluated.</p><p><b>RESULTS</b>For T stage, EUS accuracy was 86.8%, while SCT was 70.6%. The difference was significant (P<0.05). For N stage, EUS accuracy was 67.6% and SCT was 63.2%. The difference was not significant (P>0.05).</p><p><b>CONCLUSION</b>EUS is superior to SCT for the judgement of tumor infiltration depth, but neither is able to provide satisfactory assessment of lymph node metastases.</p>

Preoperative chemoradiotherapy as neoadjuvant therapy for 35 patients with locally advanced lower rectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the effect of combined preoperative chemotherapy with radiotherapy on locally advanced lower rectal carcinoma.</p><p><b>METHODS</b>Thirty- five patients with locally advanced lower rectal carcinoma were received a new regimen of combined preoperative chemotherapy with radiotherapy. Routine fr action of radiation was given with total dose of 46 Gy,2 Gy per fraction,five ti mes a week. Patients received oxaliplatin 130 mg/m(2) (infusion) on day 1, plus leu novorin 200 mg/m(2) and 5- FU 500 mg/m(2)(intravenous bolus) from day 1 to day 3 eve ry 3 weeks for total two cycles before irradiation. Operation was performed 4 to 6 weeks later after neoadjuvant therapy.</p><p><b>RESULTS</b>After neoadjuvant therapy,all patients underwent surgical resection with complete pathologic response in 7 patients,average tumor size decrease of in 34.4%, tumor stage decrease in 65.7% o f patients and nodal- negative change rate of 55.6%. Radical resection was per formed in 34 patients,in whom 18 patients received abdominoperineal resection(AP R) and 16 patients received sphincter- preserving surgery with 45.7% of anal preservation rate. One patient received palliative resection. No local recurrence occurred in all patients who received radical resection,but two cases had liver metastasis.</p><p><b>CONCLUSION</b>Combined preoperative chemotherapy with radiotherapy is a better neoadjuvant therapy for lower advanced rectal cancer,which can decrease tumor stage,improve resectability and anal sphincter preservation rate,therefore ,this new neoadjuvant therapy with tolerable toxicity will has a promising application in the clinical setting.</p>