Objective To explore the interaction of Anxa2 with P-Glycoprotein （P-gp） in the migration and invasion of the multidrug-resistant （MDR） human breast cancer cell line MCF-7/ADR. Methods A pair of short hairpin RNA ...Objective To explore the interaction of Anxa2 with P-Glycoprotein （P-gp） in the migration and invasion of the multidrug-resistant （MDR） human breast cancer cell line MCF-7/ADR. Methods A pair of short hairpin RNA （shRNA） targeting P-gp was transfected into MCF-7/ADR cells, and monoclonal cell strains were screened. The expression of P-gp was detected by Western blot. Transwell chambers were used to observe the cell migration capacity and invasion ability. The interaction between P-gp and Anxa2 was examined by immunoprecipitation and immunofluorescence confocal microscopy analyses. Results P-gp expression was significantly knocked down, and there were notable decreasing trends in the migration and invasion capability of MDR breast cancer cells （P〈0.05）. There was a close interaction between Anxa2 and P-gp. Conclusions MCF-7/ADR is an MDR human breast cancer cell line with high migration and invasion abilities. The knockdown of P-gp notably impaired the migration and invasion abilities of the tumor cells. The interaction of Anxa2 with P-pg may play an important role in time enhanced invasiveness of MDR human breast cancer cells.展开更多
Abnormal expression of long interspersed element-1(LINE-1)has been implicated in drug resistance,while our previous study showed that chemotherapy drug paclitaxel(PTX)increased LINE-1 level with unknown mechanism.Bioi...Abnormal expression of long interspersed element-1(LINE-1)has been implicated in drug resistance,while our previous study showed that chemotherapy drug paclitaxel(PTX)increased LINE-1 level with unknown mechanism.Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules(SGs).This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer(TNBC)cells.We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress,thereby adapting TNBC cells to chemotherapy drugs.Moreover,LINE-1 inhibitor efavirenz(EFV)could inhibit drug-induced SG to destabilize LINE-1.Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs.The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.展开更多
Objective： Early assessment of response to neoadjuvant chemotherapy （NAC） for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy ...Objective： Early assessment of response to neoadjuvant chemotherapy （NAC） for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy of automated breast ultrasound （ABUS） to predict pathological outcomes after NAC. Methods： A total of 290 breast cancer patients were eligible for this study. Tumor response after 2 cycles of chemotherapy was assessed using the product change of two largest perpendicular diameters （PC） or the longest diameter change （LDC）. PC and LDC were analyzed on the axial and the coronal planes respectively. Receiver operating characteristic （ROC） curves were used to evaluate overall performance of the prediction methods. Youden＇s indexes were calculated to select the optimal cut-off value for each method. Sensitivity, specificity, positive and negative predictive values （PPV and NPV） and the area under the ROC curve （AUC） were calculated accordingly.Results： ypT0/is was achieved in 42 patients （14.5%） while ypT0 was achieved in 30 patients （10.3%） after NAC. All four prediction methods （PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on coronal planes） displayed high AUCs （all〉0.82）, with the highest of 0.89 [95% confidence interval （95% CI）, 0.83-0.95] when mid-treatment ＆BUS was used to predict final pathological complete remission （pCR）. High sensitivities （85.7%-88.1%） were observed across all four prediction methods while high specificities （81.5%-85.1%） were observed in two methods used PC. The optimal cut-off values defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were observed when mid-treatment ABUS was used to predict poor pathological outcomes. Conclusions：ABUS is a useful tool in early evaluation of pCR after NAC while less reliable when predicting poor pathological outcomes.展开更多
AIM To evaluate the clinical value and efficiency of transarterial chemoperfusion(TACP) in patients with liver metastases from breast cancer(BC) and colorectal cancer(CRC).METHODS We treated 36 patients with liver met...AIM To evaluate the clinical value and efficiency of transarterial chemoperfusion(TACP) in patients with liver metastases from breast cancer(BC) and colorectal cancer(CRC).METHODS We treated 36 patients with liver metastases of BC(n = 19, 19 females) and CRC(n = 17; 8 females, 9 males) with repeated TACP. The treatment interval was 4 wk. TACP was performed with gemcitabine(1000 mg/m2) and mitomycin(10 mg/m2), administered within 1 h after positioning the catheter tip in the hepatic artery. Before treatment, the size, location, tumour volume, vascularization and number of liver tumours were evaluated using magnetic resonance imaging(MRI). Tumour response was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines.RESULTS TACP using gemcitabine and mitomycin for metastases from CRC and BC was performed without any serious side effects. The follow-up MRI showed a therapeutic response in 84.2% of the BC patients-stable disease 47.4% and partial response 36.8%. A progression was seen in 15.8%.CRC patients showed a therapeutic response in 52.9% of cases. A progression of the disease was documented in 47.1% of the patients with CRC. These data show that TACP in patients with liver metastases of BC leads to a significantly better therapeutic response compared with CRC patients(P = 0.042). The median survival time was 13.2 mo for the BC patients, which is significantly longer than for CRC patients at 9.3 mo(P = 0.001).CONCLUSION TACP for liver metastases of BC appears to be a safe and effective palliative treatment with improved outcomes in comparison to patients with CRC.展开更多
Objective： In patients with chemotherapy-induced amenorrhea （CIA）, the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menop...Objective： In patients with chemotherapy-induced amenorrhea （CIA）, the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausalstatus of breast cancer patients with CIA.Methods： This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution andaccumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potentialconfounding factors including age, serum concentration of estradiol （E2） and follicle-stimulating hormone （FSH）,feeding, pregnancy, parity, abortions, and body mass index （BMI）. The odds ratio （OR） and 95% confidenceinterval （95% CI） of different risk factors were estimated.Results： A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 （65.42%） werepremenopausal patients and 621 （34.58%） were post-menopause patients. Five hundred and fifty patients wereincluded in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age （OR： 1.856, 95% CI：1.732-1.990）, serum concentration of E2 （OR： 0.976, 95% CI： 0.972-0.980） and FSH （OR： 1.060, 95% CI：1.053-i.066）, and menarche age （OR： 1.074, 95% CI： 1.009-1.144） were found to be associated with the patients＇menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status isLogit （P）=-28.396＋0.536Age-0.014E2＋0.031FSH. The sensitivities for this model were higher than 85%, and itsspecificities were higher than 89%.Conclusions： The discriminative model obtained from this study for predicting menstrual state is important forpremenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.展开更多
Objective: To analyze the clinical course and treatment result of lung metastases from breast cancer Method: 122 cases with lung metastases from breast cancer were treated with chemotherapy or chemotherapy plus end...Objective: To analyze the clinical course and treatment result of lung metastases from breast cancer Method: 122 cases with lung metastases from breast cancer were treated with chemotherapy or chemotherapy plus endocrine therapy, response was assessed according to WHO criteria and survival rate estimated using the life Table Results: The median time from initial treatment of primary tumor to lung metastases was 22 months Sites of common consecutive metastases were lung, liver and bone The overall response rate was 48% with a CR rate of 15% Compared to non DDP encompassing regimen, the CR rate was higher in DDP based chemotherapy (7% versus 21%, P <0 05) with a longer median survival time (MST) The PR rate was higher in regimens containing anthracycline (48%) than in those without anthracycline (20%, P <0 01) The response rate was similar between chemotherapy and chemotherapy plus endocrine therapy ( P >0 05) No difference in MST was observed between patients receiving anthracycline and non anthracycline encompassing regimens The 1 , 3 , 5 , and 10 year survival rate was 77%, 22%, 11%, and 10%, respectively Conclusion: Size of primary tumor, the length of disease free interval, the number of lung metastases may provide additional information for predicting patients survival after treatment of lung metastases Combination chemotherapy, especially DDP based chemotherapy may prolong survival time of patients with lung metastases from breast cancer展开更多
OBJECTIVE To examine fatigue and quality of life (QOL) inbreast cancer patients undergoing chemotherapy or radiotherapy.METHODS A self-report survey derived from the Chineseversion of Brief Fatigue Inventory, the Func...OBJECTIVE To examine fatigue and quality of life (QOL) inbreast cancer patients undergoing chemotherapy or radiotherapy.METHODS A self-report survey derived from the Chineseversion of Brief Fatigue Inventory, the Functional Assessmentof Chronic Illness Therapy for Breast Cancer, and the MedicalOutcomes Study Social Support Survey. Descriptive statisticswas used to examine the intensity of fatigue and the prevalenceof severe fatigue. Multivariate analysis of variance was used todetermine factors that affect the five domains of QOL among theparticipants.RESULTS The majority of the participants (n = 261) perceiveda mild level of fatigue, but 35.6% of them suffered severe fatigue.Fatigue had a significantly negative association with all domainsof QOL except social/family wellbeing. The participants whowere receiving chemotherapy, undergoing curative treatment andhaving inadequate social support were more likely to have poorerQOL in all five domains (after adjustment for age).CONCLUSION Although the majority of the participantsexperienced a mild level of fatigue, there was a substantial groupof breast cancer patients who perceived their fatigue as severe. Thefindings of this study showed that fatigue had a detrimental effecton the various aspects of the participants' QOL. Demographic andclinical characteristics of breast cancer patients who were at riskof getting poorer QOL were identified. The results of the studydemonstrate that we should enhance healthcare professionals'awareness of the importance of symptom assessment, andprovide them with information for planning effective symptom-management strategies among this study population.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81071731 and 81001188)the Changjiang Scholars and Innovative Research Team(No.IRT1076)the Tianjin Higher Education Science & Technology Fund Planning Project(No.20100120)
文摘Objective To explore the interaction of Anxa2 with P-Glycoprotein （P-gp） in the migration and invasion of the multidrug-resistant （MDR） human breast cancer cell line MCF-7/ADR. Methods A pair of short hairpin RNA （shRNA） targeting P-gp was transfected into MCF-7/ADR cells, and monoclonal cell strains were screened. The expression of P-gp was detected by Western blot. Transwell chambers were used to observe the cell migration capacity and invasion ability. The interaction between P-gp and Anxa2 was examined by immunoprecipitation and immunofluorescence confocal microscopy analyses. Results P-gp expression was significantly knocked down, and there were notable decreasing trends in the migration and invasion capability of MDR breast cancer cells （P〈0.05）. There was a close interaction between Anxa2 and P-gp. Conclusions MCF-7/ADR is an MDR human breast cancer cell line with high migration and invasion abilities. The knockdown of P-gp notably impaired the migration and invasion abilities of the tumor cells. The interaction of Anxa2 with P-pg may play an important role in time enhanced invasiveness of MDR human breast cancer cells.
基金supported by the National Natural Science Foundation of China(Grant No.82072580 and No.81572789).
文摘Abnormal expression of long interspersed element-1(LINE-1)has been implicated in drug resistance,while our previous study showed that chemotherapy drug paclitaxel(PTX)increased LINE-1 level with unknown mechanism.Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules(SGs).This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer(TNBC)cells.We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress,thereby adapting TNBC cells to chemotherapy drugs.Moreover,LINE-1 inhibitor efavirenz(EFV)could inhibit drug-induced SG to destabilize LINE-1.Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs.The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.
文摘Objective： Early assessment of response to neoadjuvant chemotherapy （NAC） for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy of automated breast ultrasound （ABUS） to predict pathological outcomes after NAC. Methods： A total of 290 breast cancer patients were eligible for this study. Tumor response after 2 cycles of chemotherapy was assessed using the product change of two largest perpendicular diameters （PC） or the longest diameter change （LDC）. PC and LDC were analyzed on the axial and the coronal planes respectively. Receiver operating characteristic （ROC） curves were used to evaluate overall performance of the prediction methods. Youden＇s indexes were calculated to select the optimal cut-off value for each method. Sensitivity, specificity, positive and negative predictive values （PPV and NPV） and the area under the ROC curve （AUC） were calculated accordingly.Results： ypT0/is was achieved in 42 patients （14.5%） while ypT0 was achieved in 30 patients （10.3%） after NAC. All four prediction methods （PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on coronal planes） displayed high AUCs （all〉0.82）, with the highest of 0.89 [95% confidence interval （95% CI）, 0.83-0.95] when mid-treatment ＆BUS was used to predict final pathological complete remission （pCR）. High sensitivities （85.7%-88.1%） were observed across all four prediction methods while high specificities （81.5%-85.1%） were observed in two methods used PC. The optimal cut-off values defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were observed when mid-treatment ABUS was used to predict poor pathological outcomes. Conclusions：ABUS is a useful tool in early evaluation of pCR after NAC while less reliable when predicting poor pathological outcomes.
文摘AIM To evaluate the clinical value and efficiency of transarterial chemoperfusion(TACP) in patients with liver metastases from breast cancer(BC) and colorectal cancer(CRC).METHODS We treated 36 patients with liver metastases of BC(n = 19, 19 females) and CRC(n = 17; 8 females, 9 males) with repeated TACP. The treatment interval was 4 wk. TACP was performed with gemcitabine(1000 mg/m2) and mitomycin(10 mg/m2), administered within 1 h after positioning the catheter tip in the hepatic artery. Before treatment, the size, location, tumour volume, vascularization and number of liver tumours were evaluated using magnetic resonance imaging(MRI). Tumour response was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines.RESULTS TACP using gemcitabine and mitomycin for metastases from CRC and BC was performed without any serious side effects. The follow-up MRI showed a therapeutic response in 84.2% of the BC patients-stable disease 47.4% and partial response 36.8%. A progression was seen in 15.8%.CRC patients showed a therapeutic response in 52.9% of cases. A progression of the disease was documented in 47.1% of the patients with CRC. These data show that TACP in patients with liver metastases of BC leads to a significantly better therapeutic response compared with CRC patients(P = 0.042). The median survival time was 13.2 mo for the BC patients, which is significantly longer than for CRC patients at 9.3 mo(P = 0.001).CONCLUSION TACP for liver metastases of BC appears to be a safe and effective palliative treatment with improved outcomes in comparison to patients with CRC.
基金supported by Chinese Medical Foundation (CMF, No. 313.2215)
文摘Objective： In patients with chemotherapy-induced amenorrhea （CIA）, the menopausal status is ambiguous anddifficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausalstatus of breast cancer patients with CIA.Methods： This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution andaccumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potentialconfounding factors including age, serum concentration of estradiol （E2） and follicle-stimulating hormone （FSH）,feeding, pregnancy, parity, abortions, and body mass index （BMI）. The odds ratio （OR） and 95% confidenceinterval （95% CI） of different risk factors were estimated.Results： A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 （65.42%） werepremenopausal patients and 621 （34.58%） were post-menopause patients. Five hundred and fifty patients wereincluded in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age （OR： 1.856, 95% CI：1.732-1.990）, serum concentration of E2 （OR： 0.976, 95% CI： 0.972-0.980） and FSH （OR： 1.060, 95% CI：1.053-i.066）, and menarche age （OR： 1.074, 95% CI： 1.009-1.144） were found to be associated with the patients＇menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status isLogit （P）=-28.396＋0.536Age-0.014E2＋0.031FSH. The sensitivities for this model were higher than 85%, and itsspecificities were higher than 89%.Conclusions： The discriminative model obtained from this study for predicting menstrual state is important forpremenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.
文摘Objective: To analyze the clinical course and treatment result of lung metastases from breast cancer Method: 122 cases with lung metastases from breast cancer were treated with chemotherapy or chemotherapy plus endocrine therapy, response was assessed according to WHO criteria and survival rate estimated using the life Table Results: The median time from initial treatment of primary tumor to lung metastases was 22 months Sites of common consecutive metastases were lung, liver and bone The overall response rate was 48% with a CR rate of 15% Compared to non DDP encompassing regimen, the CR rate was higher in DDP based chemotherapy (7% versus 21%, P <0 05) with a longer median survival time (MST) The PR rate was higher in regimens containing anthracycline (48%) than in those without anthracycline (20%, P <0 01) The response rate was similar between chemotherapy and chemotherapy plus endocrine therapy ( P >0 05) No difference in MST was observed between patients receiving anthracycline and non anthracycline encompassing regimens The 1 , 3 , 5 , and 10 year survival rate was 77%, 22%, 11%, and 10%, respectively Conclusion: Size of primary tumor, the length of disease free interval, the number of lung metastases may provide additional information for predicting patients survival after treatment of lung metastases Combination chemotherapy, especially DDP based chemotherapy may prolong survival time of patients with lung metastases from breast cancer
基金supported by grants from the University of Hong Kong and School of Nursing of University of Colorado.
文摘OBJECTIVE To examine fatigue and quality of life (QOL) inbreast cancer patients undergoing chemotherapy or radiotherapy.METHODS A self-report survey derived from the Chineseversion of Brief Fatigue Inventory, the Functional Assessmentof Chronic Illness Therapy for Breast Cancer, and the MedicalOutcomes Study Social Support Survey. Descriptive statisticswas used to examine the intensity of fatigue and the prevalenceof severe fatigue. Multivariate analysis of variance was used todetermine factors that affect the five domains of QOL among theparticipants.RESULTS The majority of the participants (n = 261) perceiveda mild level of fatigue, but 35.6% of them suffered severe fatigue.Fatigue had a significantly negative association with all domainsof QOL except social/family wellbeing. The participants whowere receiving chemotherapy, undergoing curative treatment andhaving inadequate social support were more likely to have poorerQOL in all five domains (after adjustment for age).CONCLUSION Although the majority of the participantsexperienced a mild level of fatigue, there was a substantial groupof breast cancer patients who perceived their fatigue as severe. Thefindings of this study showed that fatigue had a detrimental effecton the various aspects of the participants' QOL. Demographic andclinical characteristics of breast cancer patients who were at riskof getting poorer QOL were identified. The results of the studydemonstrate that we should enhance healthcare professionals'awareness of the importance of symptom assessment, andprovide them with information for planning effective symptom-management strategies among this study population.
