Optimation of infiltration process of Pericarpium Citri Reticulatae in Huoxiang Zhengqi Liquid / 中草药

Objective: To optimize the infiltration process of Pericarpium Citri Reticulatae (PCR) in Huoxiang Zhengqi Liquid (HZL). Methods: Using the dissolution content of hesperidin as indicator, the infiltration process parameters for PCR such as soaking time, fineness of grind, degree of compaction, infiltration rate, and medicinal infiltration or not were studied, and considering the actual production efficiency, the optimal process conditions were determined. Results: The optimal infiltration process conditions were as follows: PCR was loaded into the extraction tank without soaking (there was no difference between 24 and 48 h of soaking time), spread evenly and compacted properly; The crude medicine fineness was about 0.5 cm × 0.5 cm; The infiltration solvent was 60% ethanol; The infiltration solvent was added to the extraction tank of crude medicines, the volume of solvent can not be too much, just inundating crude medicines; Adding solvent speed and infiltration speed were basically identical; The primary infiltration speed was 1 mL/(min·kg) and the continued infiltration speed was 2 mL/(min·kg). Conclusion: The optimal PCR infiltration process conditions of HZL are determined by evaluating the dissolution content of hesperidin.

Risk factors for postoperative seromas in Chinese breast cancer patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Seroma formation is one of the most common complications after breast cancer surgery. Various risk factors have been evaluated for their associations with the development of seromas in Western populations. However, similar data are not available in Chinese series. Therefore, we sought to investigate the potential risk factors for Chinese breast cancer patients.</p><p><b>METHODS</b>A prospective study of female breast cancer patients undergoing surgery was carried out in Cancer Hospital of Fudan University, Shanghai, China. Univariate analyses were performed by chi-square test or Student's t test or Mann-Whitney test and multivariate analyses by stepwise Logistic regression. The logistic model included age (years), total serum protein concentration (g/L), drainage volume on postoperative day 3 (POD 3; ml) and time to daily drainage volume not more than 30 ml (TTV30; days).</p><p><b>RESULTS</b>A total of 158 patients with breast cancer were studied. The mean age at diagnosis was (52.14 ± 10.77) years (range 25 - 92). During the follow-up period, 24 (15.2%) patients developed seromas. Calculated as continuous variables in the stepwise Logistic regression, age (OR = 1.090, 95%CI 1.028 - 1.155, P = 0.004), total serum protein concentration (OR = 0.886, 95%CI 0.791 - 0.992, P = 0.036), drainage volume on POD3 (OR = 1.013, 95%CI 1.002 - 1.023, P = 0.017) and TTV30 (OR = 1.273, 95%CI 1.039 - 1.561, P = 0.020) were independent risk factors for seroma formation. Additionally, significant difference in daily drainage volume was substantiated in the analysis by seroma formation (P = 0.034) rather than by type of surgery (P = 0.713).</p><p><b>CONCLUSIONS</b>Although the pathogenesis of seroma remains controversial, such risk factors as age, nutritional status, drainage volume on POD3 and TTV30 should be considered for prediction and prevention of seroma formation in Chinese breast cancer patients.</p>

Study on predictors of long term results for neo-adjuvant chemotherapy in locally advanced breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To identify predictive markers of the long-term outcome for neo-adjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) treated with intravenous vinorelbine (V) and epirubicin (E) combination regimen.</p><p><b>METHODS</b>One hundred and nineteen patients with LABC were treated from September 2001 to May 2006. All patients were diagnosed as invasive breast cancer by 14G core needle biopsy and treated with three cycles of VE regimen before the operation. The patients were subjected to surgery and subsequently were given other three cycles of VE or cyclophosphamide+epirubicin+fluorouracil (CEF) regimen according to the clinical responses. Local-regional radiotherapy was applied to all patients after the chemotherapy and followed by hormone-therapy according to hormone receptor status. The impact of clinical, pathological, and immunohistochemical features on disease free survival (DFS) and overall survival (OS) was evaluated.</p><p><b>RESULTS</b>All patients were evaluable for responses: clinical complete response was documented in 27 patients (22.7%), 78 patients (65.5%) obtained partial clinical response. The pathological complete response was found in 22 cases (18.5%). Of the patients, 115 cases (96.6%) were followed-up for a median time of 63.4 months (range, 9-76 months), the 5-year DFS rate and OS rate was 58.7% and 71.3%, respectively. On multivariate analysis, high pre-Ki-67 (P=0.012) and post-Ki-67 expression (P=0.045), no pathological complete response after NC (P=0.034) were associated with the higher risk of disease relapse; high pre-Ki-67 (P=0.017) and post-Ki-67 expression (P=0.001), negative pre-ER (P=0.002) and no pathological complete response after NC (P=0.034) were associated with a shorter survival.</p><p><b>CONCLUSION</b>Pathological response in primary tumor, pre-Ki-67 and post-Ki-67 expression, pre-ER expression are important predictors of long-term outcome for LABC patients with three cycles of VE regimen before operation.</p>

5589del8: the recurrent mutation of BRCA1 gene in Chinese breast cancer patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the "hot spot" of BRCA1/2 gene mutations in Chinese mainland breast cancer population.</p><p><b>METHODS</b>The known BRCA1/2 gene mutations in author's previous studies were reanalyzed by denaturing high performance liquid chromatography and DNA sequencing method in 177 patients with early onset breast cancer or affected relatives and 426 sporadic breast cancer patients from four breast cancer centers in China.</p><p><b>RESULTS</b>Three cases were found with BRCA1 5589del8 mutation out of 247 hereditary-predisposing breast cancer patients (70 patients in previous study and 177 patients in current study) and 2 cases with BRCA1 5589del8 mutation out of 426 sporadic breast cancer patients. They had similar even same haplotype.</p><p><b>CONCLUSION</b>BRCA1 5589del8 mutation is likely to be the "founder mutation" in Chinese population, but it should be confirmed by further studies.</p>

Surgical management of early breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the available surgical treatment modalities so as to explore the optimal strategy of managing early breast cancer.</p><p><b>METHODS</b>The clinical data of 2173 consecutive early-stage breast cancer patients treated by surgery treatments were retrospectively reviewed in order to clarify the indications and contraindications of different modalities. Therapeutic outcome of different surgical treatment modes were compared in terms of recurrence-free survival ( RFS) , disease-free survival ( DFS) , overall survival (OS). The cosmetic results of breast conservation and reconstruction were also evaluated .</p><p><b>RESULTS</b>The median age of these patients was 51 years ranging from 18 to 91. Of 2173 patients, 547 had stage 0- I lesions and 1626 stage II , and 1155 (53. 2% ) premenopausal. The proportion of patients who received radical surgery, breast conservation and reconstruction after mastectomy was 83. 6% (1817/2173), 10. 5% (229/2173) and 2. 5% (55/2173) , respectively. Younger and premenopausal patients prefer conservative and reconstructive surgeries, which are reasonable for stage 0-I and non-invasive breast cancer patients. Conservative surgery was not suitable for Paget's disease of breast (P = 0. 004) , mastectomy followed by reconstruction in this type of cancer was up to 38. 5%. The recurrence and metastasis rate of conservation or mastectomy were similar with a comparable 3-year RFS of 97. 4% and 95. 4% , respectively; there were also no significant differences in RFS(P =0. 2435) , DFS( P =0. 1395) and OS(P =0. 9406) after having been followed for 3 to 64 months. Similarly, immediate reconstruction did not show any negative effects with only 1 recurrence and 1 metastasis. Aesthetic outcomes were assessed as excellent or good in 90. 0% of breast conservation surgery, and the acceptability of reconstruction was 94. 5%.</p><p><b>CONCLUSION</b>Breast conserving surgery not only has comparable survival as mastectomy, but also has better cosmetic outcomes. Immediate breast reconstruction can be a suitable option without compromising survival. It is very important in the management for early breast cancer by selecting the most suitable surgery mode for every individual patient not only to cure her disease but also to satisfy the patient psychologically. Conservation should be preferred prior to reconstruction whenever possible.</p>

Protective effects and its mechanisms of total alkaloids from rhizoma Coptis chinensis on Helicobacter pylori LPS induced gastric lesion in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects and its possible mechanisms of total alkaloids (TA) from rhizoma Coptis chinensis on H. pylori LPS induced gastric lesion in rats.</p><p><b>METHOD</b>H. pylori lipopolysaccharide was applied to rat intragastrically for 4 days to induce a pattern of mucosal responses resembling that of acute gastritis. After treatment with 50, 100, 200 mg x kg(-1) TA, we identified the changes on gastric histopathology, the effects on the activities of cNOS and NOS-2, the contents of TNF-alpha and the gastric mucus epithelial cell apoptosis.</p><p><b>RESULT</b>H. pylori LPS could significantly induce the epithelial cell apoptosis of gastric mucus, increase the expression of NOS-2 and decline the expression of cNOS, and enhance the content of TNF-alpha in serum. Treatment with 50, 100, 200 mg x kg(-1) TA led to reduction in the extent of mucosal inflammatory changes elicited by H. pylori LPS and decrease in epithelial cell apoptosis. Furthermore, this effect of TA was associated with decrease in content of TNF-alpha in serum, decline in NOS-2, and increase in cNOS.</p><p><b>CONCLUSION</b>The findings suggest that TA is a potent protective agent against H. pylori LPS induced gastric mucosal inflammation. The concerned mechanisms may be related to its inhibition on epithelial cell apoptosis, and the suppression of the inflammatory responses by upregulating cNOS and interfering with the events propagated by NOS-2, and reducing the content of TNF-alpha.</p>

A study of the combination of vinorelbine and epirubicin as neoadjuvant chemotherapy regimen in the treatment of locally advanced breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and toxicity of vinorelbine (N) and epirubicin (E) as the neoadjuvant chemotherapy regimen in the treatment of locally advanced breast cancer (LABC).</p><p><b>METHODS</b>From September 2001 to December 2004, 158 patients with LABC were treated with NE chemotherapy before operation. Neoadjuvant chemotherapy containing vinorelbine (N), 25 mg/m(2) (days 1 and 8) and epirubicin (E), 60 mg/m(2) (days 1) was administered every 3 weeks for three cycles before local treatment.</p><p><b>RESULTS</b>Response in the breast: the clinical objective response was 81.6% [23.4% (37/158) cCR and 58.2% (92/158) PR], 16.5% (26/158) SD and 1.9% (3/158) PD. Pathological complete response was found in 29 cases (18.3%). Eighteen cases (26.5%) who have positive FNA result in the axillary lymphnode before chemotherapy showed negative result in the surgery specimen. The most common toxicities were neutropenia, alopecia and nausea/vomiting. Neutropenia grade 3 - 4 was reported in 111 patients (70.3%) and there was no toxic deaths.</p><p><b>CONCLUSIONS</b>The combination of vinorelbine and epirubicin is a very active and well-tolerated regimen as neoadjuvant chemotherapy for the LABC.</p>

Biological significance of E-cadherin in an inflammatory breast carcinoma cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects of E-cadherin on the biologic behavior of SUM149, an inflammatory breast cancer cell line.</p><p><b>METHODS</b>SUM149 cells were transfected with dominant-negative mutant E-cadherin expressing plasmid. The positive clones with higher expression of dominant-negative E-cadherin mutant were identified by RT-PCR and fluorescent flow cytometry method. The differences in cell growth, proliferation and invasion between positive clones and controls were compared.</p><p><b>RESULTS</b>Whereas the proliferation of positive clones was of no change, compared with controls, the ability of invasion was decreased and the mRNA levels of MMP-1 and MMP-9 were downregulated. Gelatin zymography analysis also confirmed the decreasing expression of MMP-9 in the positive clones.</p><p><b>CONCLUSION</b>In this cell line model, down-regulation of E-cadherin can inhibit the ability of invasion of this inflammatory breast cancer cell line.</p>

Clinicopathological significance of aromatase expression in breast cancers / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effects of aromatase on breast cancer proliferation and invasive ability, so as to detect the relationship between in situ estrogen levels and molecular biological characteristics of breast cancer.</p><p><b>METHODS</b>By immunohistochemistry staining, the expression of aromatase, matrix metalloproteinases 2 (MMP2) and matrix metalloproteinases (MMP 9) in the primary breast cancers were detected, the associations between aromatase and MMPs as well as clinical-pathological factors were analyzed.</p><p><b>RESULTS</b>The positive rates of aromatase were 25.0% (+) and 29.9% (++). Aromatase status was associated with MMP2, MMP9 and co-expression of MMP2 and MMP9 (P < 0.05), but not associated with tumor size, ER/PR status, menopausal status and tumor grade (P > 0.05). In the postmenopausal patients there was a relationship between aromatase and tumor size (P < 0.05), but not in the premenopausal patients (P > 0.05); there was a relationship between aromatase and co-expression of MMP2/MMP9 in the patients with ER and/or PR positive (P < 0.05), but not in the patients with ER and PR negative (P > 0.05).</p><p><b>CONCLUSIONS</b>In the breast cancer in situ estrogen produced by tumor aromatase may promote the cancer cells proliferation and invasiveness and maybe through ER pathway especially in the postmenopausal patients.</p>

Expression of ER alpha in chemically induced MDA-MB-435 cells and its responsiveness to endocrine / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of ER alpha in chemically induced, ER alpha-negative human breast cancer MDA-MB-435 cells and its restoration of the responsiveness to endocrine therapy.</p><p><b>METHODS</b>MDA-MB-435 cells were treated with HDAC inhibitor trichostatin A(TSA)and DNMT1 inhibitor 5-AZA-CdR (AZA). The mRNA level of ER alpha, PR and PS2 in treated MDA-MB-435 cells was detected by RT-PCR. The WST-8 (water-soluble tetrazolium salt-8) method was used to analyze the proliferation rate of the cells. Xenograft in female nude mice was used to further explore the change of proliferation rate of treated MDA-MB-435 cells in vivo.</p><p><b>RESULTS</b>After treatment with AZA and TSA, mRNA expression of ER alpha, PR and pS2 was up-regulated in MDA-MB-435 cells. The mRNA level of ER alpha was the hightest when MDA-MB-435 cells were treated with 2.5 micromol/L AZA and 100 ng/ml TSA. The treated MDA-MB-435 cells showed different proliferation rate in various media containing different concentration of estrodial. The MDA-MB-435 cells showed down-regulated proliferation rate after treatment with the combination of 2.5 micromol/L AZA and 100 ng/ml TSA, and 4-OH tamoxifen could suppress the growth rate of the induced MD-MBA-435 cells but not the untreated cells. The treated MDA-MB-435 cells showed slower proliferation rate than that of untreated cells in vivo (P <0. 01), and the proliferation rate of the treated MDA-MB-435 cells became lower when the nude mice were deprived of estrogen by castration (P <0. 01).</p><p><b>CONCLUSION</b>After treatment with TSA and AZA, ER alpha-negative MDA-MB-435 cells can express functional ER alpha and regain responsiveness to estrogen both in vitro and in vivo. HDAC inhibitor and DNMT1 inhibitor may play an important role in restoration of sensitivity of ER alpha-negative breast cancers to endocrine therapy.</p>

In vitro study of the effects of estrogen receptor beta expression on the biological behavior of a human breast cancer cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study effects of estrogen receptor beta (ER beta) on the biological behavior of a human breast cancer cell line MDA-MB-435.</p><p><b>METHODS</b>Human ER beta cDNA was introduced into MDA-MB-435 cells by stable transfection. Effects of ER beta expression on cell proliferation and invasion were investigated by MTT, flow cytometry and transwell techniques. Cyclin A, cyclin E, cyclin D1, p21, MMPs, Ets-1, VEGF and b-FGF were detected by RT-PCR and/or Western blot or gelatin zymography.</p><p><b>RESULTS</b>ER beta was shown to be able to significantly increase the proliferation and invasion of MDA-MB-435 cells in an estradiol-independent manner. The S phase distribution of the cells with ER beta overexpression was 46.8%, significantly higher than that of wild type (29.9%) and mock transfected cells (27.6%) (P = 0.01). In ER beta transfected cells, the expression of p21 decreased by 33.3% at mRNA level (P = 0.03) and by 47.4% at protein level (P = 0.02), respectively. The expression of MMP-9 increased by 91.3% at mRNA level (P < 0.01) and its activity was up-regulated by 67.3% (P = 0.02). Furthermore, the mRNA and protein levels of Ets-1 increased 62.2% (P = 0.01) and 51.0% (P = 0.01), respectively. No significant difference was observed in the mRNA levels of cyclin A, cyclin E, cyclin D1, MMP-1, MMP-2, MMP-7, VEGF and b-FGF among these cells.</p><p><b>CONCLUSION</b>ER beta can enhance proliferation and invasion of breast cancer cells. Down-regulation of p21 and up-regulation of MMP-9 and Ets-1 may be involved in its mechanisms.</p>

Analysis of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives.</p><p><b>METHODS</b>Genomic DNA from 41 patients' peripheral blood mononuclear cells was studied by using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and DNA sequencing. BRCA1 mutations were detected in the whole gene sequence.</p><p><b>RESULTS</b>Disease-related BRCA1 mutations were detected in 3 of the 41 patients studied. Two of the 3 patients were younger than 35 years old, and one patient with family history.</p><p><b>CONCLUSION</b>The incidence of BRCA1 mutations in Chinese patients with early onset breast cancer is similar to that reported from western countries, but the incidence of mutations in Chinese breast cancer patients with affected relatives is comparatively low.</p>