STUDY ON RELATIONSHIP BETWEEN CHEMOSENSITIVITY OF BREAST CANCER AND EXPRESSION OF p73α AND p53

Objective： To investigate the relationship between the expression of p73α and p53 versus the chemosensitivity in breast cancer cells. Methods： Twelve surgical samples of breast cancer diagnosed by pathology were used. The cancer sample cells were separately cultured in the incubator at 37℃, 5% CO2 in vitro. The relative inhibition rate of cancer cells by 4 kinds of anticancer drugs, which were EPI, MMC, 5-Fu and DDP, were assayed by MTT method. Immunocytochemistry was used to detect the expression of p73α and p53 in the cancer cells. Results： The positive expression of p73α was found in 5/12 （41.67%）, and p53 positive expression rate was 50.0% （6/12）. The relative inhibition rate of MMC, EPI, 5-Fu and DDP were significantly higher in the p73α positive cancer cells than in the p73α negative cancer cells. A positive correlation was found between expression of p73α and chemosensitivity for all the four anticancer drugs. Condusion： The expression of p73α is related with the chemosensitivity of the breast cancer cells, and it may become one of the markers for judging the effect of chemotherapy in clinic.     

REVERSAL EFFECTS OF MIFEPRISTONE ON MULTIDRUG RESISTANCE(MDR) IN DRUG-RESISTANT BREAST CANCER CELL LINE MCF7/ADR IN VITRO AND IN VIVO

Breast cancer is one of the most common malignant tumors among women. Surgery is effective in the majority of cases but adjuvant or neoadjuvant chemotherapy plays an important role in the management of the patients with advanced and relapsed breast cancer[1]. However, cross-resistance to structurally and functionally unrelated anticancer agents, termed multidrug resistance(MDR), is a major obstacle to successful chemotherapy for breast cancer [2-3]. Although tens of reversal drugs have been f…     

Phase Ⅲ Clinical Trials of the Cell Differentiation Agent-2 （CDA-2）： Therapeutic Efficacy on Breast Cancer, Non-Small Cell Lung Cancer and Primary Hepatoma

OBJECTIVE The objective of this study was to explore the effect of CDA-2, a selective inhibitor of abnormal methylation enzymes in cancer cells, on the therapeutic efficacy of cytotoxic chemotherapy. METHODS Advanced cancer patients, all of whom had previously undergone chemotherapy, were randomly divided into 2 groups, one receiving chemotherapy only as the control group, and the other receiving CDA-2 in addition to chemotherapy as the combination group. The therapeutic efficacies and the toxic maniestations of the 2 groups were compared based on the WHO criteria. RESULTS Of 454 cancer patients enrolled in phase Ⅲ clinical trials of CDA-2, 80, 188, and 186 were breast cancer, NSCLC, and primary hepatoma patients, respectively. Among them 378 patients completed treatments according to the protocols. The results showed that the overall effective rate of the combination group was 2.6 fold that of the control group, 4.8 fold in the case of breast cancer, 2.3 fold in the case of primary hepatoma, and 2.2 fold in the case of NSCLC. Surprisingly, the combination therapy appeared to work better for stage Ⅳ than stage Ⅲ patients. CDA-2 did not contribute additional toxicity. On the contrary, it reduced toxic manifestations of chemotherapy, particularly regarding white blood cells, nausea and vomiting. CONCLUSION Modulation of abnormal methylation enzymes by CDA-2 is definitely helpful to supplement chemotherapy. It significantly increased the therapeutic efficacy and reduced the toxic manifestation of cytotoxic chemotherapy on breast cancer and NSCLC.     

妊娠乳腺癌患者2例终止妊娠前或后行首程化疗的疗效分析并文献复习(英文)

Pregnancy-associated breast cancer (PABC) is defined as breast cancer occurring anytime during gestation, lactation, or within 1 year after delivery. The incidence is between 1 in 3000 and 1 in 10,000 pregnancies and comprises about 0.2% to 3.8% of all breast cancers diagnosed in women under the age of 50 years. As women tend to delay childbearing into their third and fourth decades, the incidence of PABC is expected to increase. Here we reported two PABC patients with similar clinic and pathologic characters received chemotherapy before or after termination of pregnancy respectively, and found that the former got pathologic complete response. Based on the phenomena and the fact that endocrine hormones may have chemosensitization role in cancer chemotherapy, which is called hormonosensitizing chemotherapy (HSCT), endocrinosensitizing chemotherapy (ESCT) or neoendocrinochemotherapy (NECT), suggestion is proposed that chemotherapy should be taken before or immediately after termination for PABC, especially for the patients who prefer to artificial abortion, which may possibly acquire improved chemotherapeutic effect.     

Breast-conserving surgery and combined therapy for women breast cancer： a report of 216 cases

Objective： To explore the therapeutic effect and associated techniques of breast-conserving therapy on patients with clinical stage Ⅰ and stage Ⅱ breast cancer. Methods： 216 female patients with breast cancer underwent breast-conserving therapy from December 1993 to October 2004. Their data were analyzed retrospectively. The breast-conserving therapy consisted of lumpectomy or quadrant removal of the breast, postoperative radiotherapy, chemotherapy and endocrine therapy. Of them, 209 patients underwent axillary lymph node dissection. Results： There were no operative complications. 216 patients were followed-up 3 to 147 months, the medial follow-up time was 78 months. The local recurrence rate was 1.85%. Two patients died and one of them was not related with breast cancer. Presence or absence of fibrosis, shape of breast, asymmetry, pigmentation and handle were taken into consideration for cosmetic evaluation by the patients and experienced breast surgeon. Breasts were scored cosmetically as excellent and good in 199 patients, the rate of satisfactory was 92.13%. Conclusion： Breast-conserving therapy for early breast cancer is e safe end effective therapy. It has less trauma end less complications and can also raise the quality of life in the patients. But we must obey the strict indications and reasonable techniques.     

Expression of sIL-2R before and after chemotherapy in patients with breast cancer

Objective:To investigate the difference of peripheral blood sIL-2R before and after chemotherapy in breast cancer patients,and evaluate the clinical value of the sIL-2R in breast cancer's diagnosis and therapy.Methods:The peripheral blood sIL-2R levels of the breast cancer patients with or without chemotherapy were detected by ELISA.The healthy persons were made as the control group.Results:The slL-2R levels of the breast cancer patients were higher than that of the control group(P＜0.05);the slL-2R's levels in Ⅰ～Ⅱ stage breast cancer were lower than that in Ⅲ～Ⅳ stag e breast cancer (P＜0.05);the sIL-2R levels of the patients before chemotherapy were higher than that of the patients undergone chemotherapy(P＜0.05);The level of the patient with chemotherapy was still higher than that of the control group(P＜0.05);the sIL-2R levels of the patients whose chemotherapies were noneffective were higher than that of the patients received effective chemotherapies(P＜0.05).There was no significant difference between the group with ER( )or PR( )and the group with ER(-)or PR(-)(P＞0.05).Conclusion:The breast cancer patients have the high slL-2R levels.There is a close relationship between the cancer incidence and the patients,immune situation.The level of slL-2R could be a clinical index which Can be used for evaluating the cancer degree,because the higher levels of slL-2R can indicate that the immune ability of patient is worse.There is a significant difference between the slL-2R levels of the patients before chemotherapy and that of the patients undergone chemotherapy.     

ACETYLATOR PHENOTYPE AND ITS RELATIONSHIP TO BREAST TUMOR

The patterns of acetylator phenotypes has been determined in 102 women with breast tumors, including 25 with benign breast disease and 77 with breast cancer, and compared to that in 59 healthy controls. There was significant increase (16.2%) of rapid acetylators in 77 patients with breast cancer, P<0.05. As a result of the effect of therapy on the rate of acetylation, it was found that in 39 patients with breast cancer the level of acetylation was decreased after mastectomy. The difference of percentage acetylation between preoperation and post-operation was statistically significant, P<0.05. A similar change in 8 patients with breast cancer could be observed after chemotherapy, P<0.01. The results obtained in the present study indicated that there was a significant association between rapid phcnotype and breast cancer of women. The mastectomy or inhibition of tumor growth may bring about a decrease in the level of acetylation.     

Effects of neoadjuvant chemotherapy on MDR1 and MRP gene expression in primary breast cancer

Objective: To investigate the effects of neoadjuvant chemotherapy on the expression of drug resistance genes, multidrug resistance-1 (MDR1) and multidrug resistance-associated protein (MRP), in patients with primary breast cancer. Methods: MDR1 and MRP expression were detected by semi-quantitative RT-PCR in 20 patients with primary breast cancer, before and after chemotherapy. Results: Before chemotherapy, MDR1 and MRP expression can be detected in 15 cases (75%) and 18 cases (90%) respectively. After chemotherapy, expression of MDR1 is not significantly different from that before chemotherapy, but expression of MRP is significantly different from that before chemotherapy. Conclusion: Expression of drug resistance gene MRP, but not MDR1, is enhanced in patients with primary breast cancer submitted to neoadjuvant chemotherapy.     

HPV16感染与P21基因失活在胃癌发生及预后中的意义

Objective： To investigate whether there is a synergistic carcinogenesis between the infection of human papilloma virus （HPV） and the P21 gene mutation in gastric cancer tissue and their relationship with prognosis of the patients with gastric cancer. Methods： By using PCR technique, HPV16 infection in 46 gastric cancer tissue samples was measured and by using immunohistochemical S-P method, the P21 gene mutation in gastric cancer was detected. All patients were regularly followed up for 3 years by writing letter or clinics, to detect the infection of HPV16 by PCR and the p21 gene mutation by immunohistochemical method in 46 gastric cancer tissue specimens. Results： The positive rate of HPV16 was 41.3% and the gene mutation rate of p21 was 52.17% respectively. The recurrence or remote metastasis was observed in 21 of 46 patients. The recurrence rate was 73.68% in the patients positive for HPV16 and 66.6% in those positive for p21 gene mutation. In 8 cases positive for both HPV16 and P21, 6 had recurrence or remote metastasis. Conclusion： The HPV16 infection may be one factor causing gastric cancer and it has a synergistic carcinogenesis with the p21gene mutation. The latter may be one of the prognostic indices in gastric cancer.     

The significance of minimally invasive core needle biopsy and immunohistochemistry analysis in 235 cases with breast lesions

OBJECTIVE To evaluate core needle biopsy （CNB） as a minimally invasive method to examine breast lesions and discuss the clinical significance of subsequent immunohistochemistry （IHC） analysis. METHODS The clinical data and pathological results of 235 patients with breast lesions, who received CNB before surgery, were analyzed and compared. Based on the results of CNB done before surgery; 87 out of 204 patients diagnosed as invasive carcinoma were subjected to immunodetection for p53, c-erbB-2, ER and PR. The morphological change of cancer tissues in response to chemo- therapy was also evaluated. RESULTS In total of 235 cases receiving CNB examination, 204 were diagnosed as invasive carcinoma, reaching a 100% consistent rate with the surgical diagnosis. Sixty percent of the cases diagnosed as non-invasive carcinoma by CNB was identified to have the presence of invading elements in surgical specimens, and similarly, 50% of the cases diagnosed as atypical ductal hyperplasia by CNB was confirmed to be carcinoma by the subsequent result of excision biopsy. There was no significant difference between the CNB biopsy and regular surgical samples in positive rate of immunohistochemistry analysis （p53, c-erbB-2, ER and PR; P 〉 0.05）. However, there was significant difference in the expression rate of p53 and c-erbB-2 between the cases with and without morphological change in response to chemotherapy （P 〈 0.05）. In most cases with p53 and c-erbB-2 positive, there was no obvious morphological change after chemotherapy. CONCLUSION CNB is a cost-effective diagnostic method with minimal invasion for breast lesions, although it still has some limitations. Immunodetection on CNB tissue is expected to have great significance in clinical applications.     

一例接受阿那曲唑和预防性那屈肝素治疗的乳腺癌妇女发生肺动脉栓塞

Hormonal treatment is widely accepted for the adjuvant treatment of breast carcinoma, in order to get a reduction in the synthesis of estrogen or to block estrogen receptors in tumors that are hormone dependent. There are multiple risk factors that contribute to hypercoagulability in cancer patients. Hormonal therapy and chemotherapy are the main one. Type and stage of malignancy are other risk factors; so age, immobility and surgery are. The main antineoplastic therapy with definitive hypercoagulable effect is tamoxifen, because it can cause reduction in the concentrations of antithrombin Ⅲ and protein C. Here, we explain the case of a 75-year-old postmenopausal woman presenting with breast carcinoma who suffered from pulmonary thromboembolism during the treatment with anastrozole although she was taking nadroparin.     

Investigation of the Effect of Neoadjuvant Chemotherapy on Stage Ⅱ Breast Cancer

OBJECTIVE To investigate the effect of neoadjuvant chemotherapy in treatment of Stage Ⅱ breast cancer. METHODS The data from 113 patients with breast cancer of the same pathologic type in Stage Ⅱ,during the period of 1995 to 2001,were analyzed retrospectively.Among the patients,47 were treated with neoadjuvant chemotherapy,and 66 received no adjuvant therapy before surgery（control group）.After the patients of the neoadjuvant chemotherapy group had received 2 courses of chemotherapy with the CMF regimen,the surgical procedure was conducted. RESULTS Complete remission（CR）was attained in 9 of the 47 cases receiving neoadjuvant chemotherapy and partial remission（PR）was reached for 22 cases.The rate of breast-conserving surgery was enhanced from 22.73%to 46.81%（P〈0.05）in the neoadjuvant treatment group. There was no difference in the 5-year overall survival（OS）and disease-free survival（DFS）rate between the two groups（P〉0.05）,but the 5-year OS and DFS of the cases with clinical tumor remission was higher compared to the control group（P〈0.05）. CONCLUSION Neoadjuvant chemotherapy can enhance the rate of breast conservation for Stage Ⅱ breast cancer and may improve the prognosis of the cases with clinical remission.     

Mitochondrial DNA mutations---candidate biomarkers for breast cancer diagnosis in Bangladesh

Breast cancer is a major health problem that affects more than 24% of women in Bangladesh. Furthermore, among low-income countries including Bangladesh, individuals have a high risk for developing breast cancer. This study aimed to identify candidate mitochondrial DNA (mtDNA) biomarkers for breast cancer diagnosis in Bangladeshi women to be used as a preventive approach. We screened the blood samples from 24 breast cancer patients and 20 healthy controls to detect polymorphisms in the D-loop and the ND3-and ND4-coding regions of mtDNA by direct sequencing. Among 14 distinct mutations, 10 polymorphisms were found in the D-loop, 3 were found in the ND3-coding region, and 1 was found in the ND4-coding region. The frequency of two novel polymorphisms in the D-loop, one at position 16290 (Tins) and the other at position 16293 (A-del), was higher in breast cancer patients than in control subjects (position 16290: odds ratio = 6.011, 95% confidence interval = 1.2482 to 28.8411, P = 0.002; position 16293: odds ratio = 5.6028, 95% confidence interval = 1.4357 to 21.8925, P = 0.010). We also observed one novel mutation in the ND3-coding region at position 10316 (A > G) in 69% of breast cancer patients but not in control subjects. The study suggests that two novel polymorphisms in the D-loop may be candidate biomarkers for breast cancer     

PROMOTER HYPERMETHYLATION OF p16 GENE AND DAPK GENE IN SERA FROM HEPATOCELLULAR CARCINOMA （HCC） PATIENTS

Objective： To analyze the aberrant methylation of p16 gene and DAPK gene in sera from primary liver cancer patients ad to evaluate the clinical significance. Methods： A methylation-specific PCR was performed for the detection of promoter hypermethylation of p16 gene and DAPK gene in blood DNA from 64 cases of HCC patients, and to analyze the relation of the aberrant methylation of p16 gene and KAPK gene and the clinical pathological data. Results： 76.6%（49/64） of the sera from 64 cases of HCC patients showed hypermethylation for p16 promoter and 40.6% （26/64） for KAPK promoter, whereas no methylated p16 gene promoter and DAPK gene promoter were found in sera from benign liver diseases patients and normal control. Methylated p16 gene and KAPK gene promoters in sera did not strongly correlated with HBsAg, stage, metastasis and differentiation in HCC; but strongly correlated with AFP. Conclusion： Detection of the aberrant methylation of p16 gene and KAPK gene in blood DNA from HCC patients might offer an effective means for the earlier auxiliary diagnosis of the malignancy.     

三阴乳腺癌在新辅助化疗中相关预测因子的Meta分析(英文)

Objective: Neoadjuvant chemotherapy (NAC) was increasingly used as a systemic therapy for triple-negative breast cancer (TNBC). The pathological complete response (PCR) rates of neoadjuvant chemotherapy in TNBC were higher than other types of breast cancer with fluctuate data. Predictors to identify which subgroup TNBC was more likely to achieve PCR in neoadjuvant chemotherapy would give us some hints on how to improve outcomes of TNBC patients. The meta-analysis was conducted to contrast the prognostic function of some clinicopathological parameters in the PCR rates of neoadjuvant chemotherapy for TNBC. Methods: Studies were selected from the PubMed database. The relevant parameters to PCR rates in TNBC group were recorded. Review Manager and MIX were used to estimate prognostic function of some biological markers and clinicopathological parameters in PCR rates of TNBC. Results: The analysis included 6 studies with 723 patients, the aggregate PCR rate was 27.9% in TNBC group. The association of lymph nodes metastasis, Ki-67 expression, p53 expression and CK5/6 expression with PCR rate of TNBC was investigated in the analysis, and the odds ratios were 0.50, 9.87, 1.17 and 0.53 respectively. Conclusion: This meta-analysis demonstrated that Ki-67 expression and lymph nodes metastasis were predictors of PCR rate for TNBC in neoadjuvant chemotherapy, while p53 and CK5/6 expression could not be confirmed for the prognostic function.     

PROMOTER HYPERMETHYLATION OF p16 GENE IN PRE- AND POST-OPERATIVE PLASMA OF PATIENTS WITH GASTRIC ADENOCARCINOMA

Objective: To detect promoter hypermethylation of p16 gene in matched pre- and post-operative plasma of patients with gastric adenocarcinoma for evaluating the effectiveness of therapeutic intervention. Methods: Tissue samples, pre- and post-operative plasma of 84 patients were collected. Plasma of 15 healthy people was collected as control. After sodium-bisulfite treatment, extracted DNA was amplified for p16 promoter by methylation-specific polymerase chain reaction (MSP). The PCR products were detected by both gel-ethidium bromide electrophoresis and high performance liquid chromatogram (HPLC). Results: Among 84 patients, p16 hypermethylation was detected in 26 (31.0%) cancer tissues and 2 (0.02%) tumor-adjacent tissues and 12 (14.3%) pre-operative plasma, while negative in plasma of healthy people. For positive plasma cases, the paired tumor tissues were confirmed to be methylated.Within available 30 pairs of matched pre- and post-operative plasma, 6 pre-operative plasma was positive, and only 1 of 6 plasma remained hypermethylated after surgery. The results detected by HPLC exactly matched those by gel-electrophoresis. Conclusion: The alteration of status of p16 hypermethylation in post-operative plasma is considered the consequences of surgical intervention. Although p16 hypermethylation has no role in pre-operative staging of gastric cancer, detecting hypermethylated p16 in plasma could be utilized in monitoring patients after surgery.     

The relationship between the pathological changes and response rate (RR) in non-small cell lung cancer treated by neoadjuvant chemotherapy with mitomycin (MMC), vindesine (VDS) and cisplatin (DDP) combination

Lung cancer is the leading cause of male cancer death in the big cities in China. The mortality is growing recent years. It has been confirmed that the best treatment for non-small cell lung cancer is the surgery-based multimodality therapy. But only 20% of NSCLC patients present with stage I and II disease and can be resected completely when the diagnosis is established. It is a trend for stage II and IIIa patients to use adjuvant chemotherapy in order to improve the 5-year survival rat…