Purpose: Hypoxia is common in breast cancer and may influence gene expression to promote malignancy. Estrogen receptor (ER) -? status is an important predictor for both prognosis and clinical response to endocrine therapy. The aim of our current study is to demonstrate the relationship between hypoxia and ER-? in breast cancer tissue. Methods: We have examined ER-a expression by immunohistochemistry in parallel with indicators of hypoxia in 51 ER-a ligand binding assay positive breast tumors for in vivo evidence of this phenomenon. Results: Overall, 49 tumors were ER-a positive by immunohistochemistry. Regional loss of ER-a expression was consistently present in peri-necrotic as compared to distant regions in both in situ (n =29, P

Objective To observe differences between repeat and written response in speech recognition tests of short Mandarin monosyllable lists. Methods 12 normal-hearing subjects were tested by 6 short monosyllabic lists. The subjects should repeat and write down.the contents of the tests at the same time, the tester monitors au-rally and records the subjects' reactions. The speech recognition scoring error under different responses at different presentation levels could be obtained by comparing the records of the subjects with the tester. Results The speech recognition scoring of repeat and written response were highly correlated with each other (P<0.01). However, 19(26.4%) out of 72 pairs of test records were inconsistent. The error range of them was from -5% to 10%. When the presentation level was 5 dB HL, the difference among the speech recognition scoring was significant statistically, but not significant when the presentation level at 20, 15, 10 and 0 dB HL. Conclusion The test results of speech audiometry are impacted by different respond methods. In the open-set test, it's supposed that the subjects should make notes while repeating the contents of the tests, then compare with the aural monitoring records of the tester to keep the reliability of the test.

Objective To investigate the clinical significance of fiberoptic ductoscopy-guided intraductal biopsy in diagnosing nipple discharge.Methods From May 2006 to April 2007,screening fiberoptic ductoscopy was performed for intraductal papillary lesions in 53 ducts among 51 patients.Fiberoptic ductoscopy-guided intraductal biopsy was carried out followed by open microdochectomy. Results Except for a failure in 5 ducts,biopsy found papilloma in 29 cases,ductal hyperplasia in 15 cases,severe ductal hyperplasia in 2 and carcinoma in 2.Microdochectomy revealed 43 benign diseases (12 solitary intraductal papillomas,12 multiple intraductal papillomas,and 25 ductal hyperplasia)and 4 malignancies (3 ductal carcinoma in situ,1 invasive ductal carcinoma).Surgeries performed for the 5 ducts failing a biopsy attempt revealed papilloma in one and adenosis in 4.Compared with conventional microdochectomy,fiberoptic ductoscopy-guided intraductal biopsy can significantly increase the detection rate of solitary papilloma(40.7% vs. 92.6%,P＜0.05).It might also underestimate multiple intraductal papilloma and breast cancer. Conclusion Fiberoptic ductoscopy-guided intraductal biopsy is microinvasive,safe,convenient with a high success rate,and could be as a routine procedure after intraductal lesion found by screening fiberoptic ductoscopy.

OBJECTIVE:To study the pharmacokinetics of recombinant staphylokinase(r-SAK)in a thrombosis model of femoral artery in rabbits.METHODS:Large glass plates were used for modified agar-well diffusion assay to measure r-SAK concentration in plasma of rabbits which had been administered different doses drug by different means respective?ly.RERULTS:The pharmacokinetics of r-SAK infusion in thrombosis model of the femoral artery in rabbits fits two-com?partment model,the plasma levels and the diameter of lytic circles showed a good linear correlation under the scope of20～2500IU/ml(r=0.9960),and the averaged recovery rate was(96.05?9.20)%.The peak concentrations of low,medial and high dose drop group and single iv group are(2.28?1.06),(3.54?0.32),(6.12?1.61)and(5.16?1.02)?g/ml.CONCLUSION:The biological assays is a simple,reliable method to determine the plasma level.

Background and purpose: BRCA1 and BRCA2 mutation carriers have a high lifetime risk of developing breast and ovarian cancer. Through genetic counseling, mutation carriers can take the appropriate measures to reduce such cancer risk. At present, almost all related studies were conducted in Caucasian, while, the studies in Chinese population were rare. This study aimed to investigate the risk of breast cancer in BRCA1 and BRCA2 mutation carriers in Chinese Han population. Methods:Twenty unrelated families with BRCA1 or BRCA2 mutations were re-viewed. Kaplan-Meier analyses were used to estimate the cumulative risks of unilateral breast cancer and contralateral breast cancer for female BRCA1 and BRCA2 mutation carriers. Results:Breast cancer risk to 70 years (penetrance) was 67.2%(sx 0.100) for BRCA1 and 76.8%(sx 0.079) for BRCA2, respectively. Different from BRCA1 mutation carriers, the cumulative incidence of breast cancer in BRCA2 mutation carriers remained increasing after 70 years, reaching 93.1%at age 80. The 10-and 20-year risk for contralateral breast cancer was 19.4%(sx 0.089) and 50.3%(sx 0.155) for BRCA1/2 mutation carriers. Conclusion:BRCA1 and BRCA2 mutation carriers in Chinese Han population have a high risk of developing breast cancer. Thus, it has great clinical signiifcance to test mutations in BRCA1/2 genes in Chinese high-risk population.

OBJECTIVETo prepare a single chain antibody (ScFv) of mAb SZ-21 against platelet GPIIIa for its future clinical application.

METHODSThe expression vector pET20b-SZ-21ScFv was constructed and the fusion protein was expressed in E. coli BL21 (DE3) PlysS. The activated fusion protein was obtained after a series of purification steps, including cell breakage, inclusion body solubilization, His-bind resin affinity chromatography and protein refolding.

RESULTSThe fusion protein yields were up to 21% of the total amount of bacteria protein. The ScFv fragment could inhibit ADP-induced platelets aggregation in a dose-dependent manner in vitro and the maximal inhibition rate was obtained at a concentration of 20 micro g/ml. It also reacted with endothelial cells as detected by flow cytometry. Moreover, the ScFv fragment was able to inhibit the binding of fibrinogen to platelet.

CONCLUSIONThe SZ-21ScFv fragment had the activity to inhibit platelets aggregation and the binding of fibrinogen to platelet, being potentially useful for the treatment of thrombotic diseases.

Antibodies, Monoclonal ; pharmacology ; Blood Platelets ; metabolism ; Endothelium, Vascular ; cytology ; Fibrinogen ; metabolism ; Humans ; Immunoglobulin Fragments ; pharmacology ; Platelet Aggregation ; Platelet Glycoprotein GPIIb-IIIa Complex ; immunology ; Recombinant Fusion Proteins ; isolation & purification ; pharmacology

Background and purpose:Tumor suppressor gene P53 has long been studied in tumors, including breast cancer. More studies focused on the relationship between P53 and prognosis of breast cancer and found that P53 overexpression suggested a bad prognosis. However, the effect of P53 on early stage postmenopausal patients with ER-positive breast cancer has not been clariifed yet. This study was to investigate the role of P53 plays in aromatase inhibitor (AI) resistance among early stage postmenopausal patients with ER-positive breast cancer patients. Methods:A total number of 293 operable breast cancer patients who received surgical treatment during Jul. 2000 to Jul. 2006 in Fudan University Shanghai Cancer Center were enrolled into this study. All patients received AI treatment. The SPSS 12.0 software was used to estimate the survival rate. Univariate and multivariate analysis were also performed via above software. Results:The median follow-up time is 72 months (6-140 months). The 5 year disease free survival (DFS) of P53 positive and negative were 78%and 89%. The results showed that P53 overexpression (HR=1.729, 95%CI:1.038-2.880, P=0.035), pathological stage (HR=2.270, 95%CI:1.399-3.681, P=0.001);histological grade (HR=2.328, 95%CI:1.312-4.133, P=0.004); age (HR=1.988, 95%CI:1.511-2.617, P<0.005) were still the independent risk factors of recurrence and metastasis in breast cancer patients treated with AI. Conclusion:P53 overexpression correlated strongly with AI resistance in early stage postmenopausal patients with ER-positive breast cancer patients who were treated with AI and conifrmed the relevance of previously described prognostic factors. It is reasonable to take P53 expression into account when we evaluate the risk of breast cancer patients and decide the anti-cancer treatment strategy.

Objective: To investigate the effect of cinobufacini on proliferation, celly cycle distribution, invasion capability of MDA-MB-231 breast cancer cell line in vitro and possible mechanism. Methods: The effect of cinobufacini on cell growth was measured by CCK-8 reagent kit. Cell cycle distribution was determined by flow cytometry. The invasion capability in vitro was detected by Transwell chamber assay. The mRNA expressions of cell cycle related factors (cyclin) and p21 were tested by RT-PCR. Results: Cinobufacini inhibited proliferation of MDA-MB-231 cells. The half inhibition concentration (IC50) was 0.31 mg/mL. The inhibitory effect was timE-dependent (P<0.05). Cinobufacini significantly decreased invasion capability of MDA-MB-231 cells in vitro compared with control group (P<0.05). Cinobufacini induced S-phase arrest of MDA-MB-231 cells in a concentration-dependent manner (P<0.000 1). Cinobufacini down-regulated the expression levels of cyclin A1, cyclin D1, and cyclin E1, while up-regulated that of p21 in MDA-MB-231 cell line. However, there was no marked change in the expression of cyclin B1. Conclusion: Cinobufacini inhibits cell proliferation and influences the cell cycle distribution in vitro by regulating the expression of cyclin A1, cyclin D1, cyclin E1 and p21 in breast can-cer cells.

OBJECTIVETo evaluate the accuracy of sentinel lymph node biopsy (SLNB) to predict the axillary lymph node status in breast cancer patients and its clinical significance.

METHODSSeventy patients with clinical TNM status T(1 - 2)N(0)M(0) underwent sentinel lymph node biopsy using Tc-99m sulfur colloid radiotracer and gamma probe, which was followed by standard axillary dissection. SLNB was compared with standard axillary dissection for its ability to reflect the final pathological status of the axillary nodes. The SLNs that were tumor negative in conventional HE staining were further evaluated using immunohistochemical stains for CK8, CK19 and KP-1 antibodies.

RESULTSThe sentinel lymph node (SLN) was successfully identified in 67 (95.7%) out of 70 patients. The number of sentinel nodes harvested ranged from 1 to 5 (average 1.6). The nonsentinel nodes ranged from 5 to 20 (average 12.3). Of the 67 patients, 29 (43.3%) had histologically positive axillary lymph nodes. SLN was positive in 24 patients with metastasis (35.8%), and in 7 patients without metastasis (10.4%). In 5 patients, SLN was negative for tumor with positive nodes. The accuracy of sentinel lymph node biopsy to predict the axillary lymph node status was 92.5% and the false negative rate was 7.5%. For tumors with diameter less than or equal to 2 cm, the accuracy was 100%. 65 SLNs that were negative for HE stain were also non-reactive to immunostain for CK8 and CK19 antibody.

CONCLUSIONSSLNB can accurately predict the axillary lymph node status in most of breast cancer patients. The accuracy is about 100% in patients with T(1) lesions. Immunohistochemical staining at the same level of HE stain can not increase the detection of lymph node micrometastasis.

Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms ; pathology ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Middle Aged ; Sentinel Lymph Node Biopsy

Objective To explore the influencing factors for postoperative adjuvant chemotherapy effects in elderly patients with breast cancer. Methods Five hundred and ninety female patients aged 65 years or older with invasive breast cancer were treated in our hospital, and the influencing factors for postoperative adjuvant chemotherapy effects were analyzed by chi-square test and logistic regression. Results Two hundred and thirty-one (39.2%) patients received postoperative adjuvant chemotherapy. The results showed that diabetes, age, patterns of operation and pathological characteristics of tumor had significant influences on postoperative adjuvant chemotherapy effects (χ2=4.49,88. 27,23.49 and 9.40, all P<0.05). Logistic regression analysis showed that age, tumor size, lymph node status(pN) and estrogen receptor (ER) status were related to postoperative adjuvant chemotherapy effects(χ2=68.857,15. 284,43. 540 and 7.009 ,all P<0.01). Forty-four patients (66.7%) with pN(+)/ER(-) received adjuvant chemotherapy. Conclusions Age, tumor size, lymph node status and ER status were independent predictive factors for postoperative adjuvant chemotherapy effects in elderly patients with breast cancer.