We have studied the patterns of P-glycoprotein expression before and after 3 cycles of induction chemotherapy (5-fluorouracil, adriamycin and cyclophosphamide) using immunohistochemically stained paraffin-embedded specimen of 28 patients with locally advanced breast cancer. The frequency of P-glycoprotein expression in untreated breast cancer turned out to be very low: only one out of 28 untreated, biopsy specimen at the time of diagnosis was positive. The frequency of P-glycoprotein expression was markedly increased from 9.1% before chemotherapy to 63.6% after induction chemotherapy (p = 0.006). After 3 cycles of induction chemotherapy, 25 patients had obtained clinical response to chemotherapy (4, CR; 21, PR). Eleven out of 25 tumors (44%) showing clinical response and all three tumors (100%) with minimal response have expressed P-glycoprotein. One out of 6 patients (16.7%) with microscopic residual tumor seen in mastectomy specimen expressed P-glycoprotein, whereas 13 of 22 patients (59.1%) with gross residual tumor showed the presence of P-glycoprotein (p = 0.08). The frequency of intrinsic P-glycoprotein expression in untreated breast cancer was quite low, but approximately half of the patients do acquire P-glycoprotein expression during the cycles of induction chemotherapy. Therefore, the results suggest that the immunohistochemical detection of P-glycoprotein on residual tumor cells after induction chemotherapy can predict acquired drug resistance in breast cancer.
Adult ; Aged ; Breast Neoplasms/chemistry/*drug therapy/pathology ; Breast Neoplasms/chemistry/*drug therapy/pathology ; Drug Resistance ; Drug Resistance ; Female ; Human ; Immunohistochemistry ; Membrane Glycoproteins/*analysis ; Middle Age ; P-Glycoprotein

Antineoplastic Agents, Hormonal ; therapeutic use ; Breast Neoplasms ; chemistry ; drug therapy ; Female ; Humans

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.
Humans ; Paclitaxel/pharmacology* ; Liposomes/chemistry* ; Ginsenosides/therapeutic use* ; Triple Negative Breast Neoplasms/drug therapy* ; Cardiotoxicity/drug therapy* ; Cell Line, Tumor

To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative breast cancer.We searched PubMed, the Cochrane Library, Web of Science, CNKI, Wanfang Database and the abstracts of major international conferences in recent 5 years to identify prospective randomized controlled clinical trials that met the inclusion and exclusion criteria. Study selection and analyses were undertaken according to the Cochrane Handbook. Meta-analysis was performed using RevMan 5.3 software.Six trials were identified with 4440 eligible patients. The results of this meta-analysis showed that the rate of pathological complete response (pCR) was higher in Her-2 negative breast cancer patients receiving bevacizumab combined with neoadjuvant chemotherapy than that in patients with neoadjuvant chemotherapy alone (24.7% vs 20.1%,=1.23, 95%:1.10-1.37,<0.01). In addition, the pCR rate rose up when bevacizumab was added to neoadjuvant chemotherapy both in hormone receptor-positive patients (13.1% vs 10.2%,=1.28, 95%:1.04-1.58,<0.05) and in hormone receptor-negative patients (46.3% vs 37.1%,=1.25, 95%:1.12-1.39,<0.01). Statistical differences were observed in the rate of relevant adverse events such as hypertention (3.2% vs 0.6%,=5.292, 95%:2.933-9.549,<0.01) and mucositis (10.5% vs 2.0%,=5.340, 95%:3.743-7.617,<0.01) between the combination group and the chemotherapy alone group. Differences in other toxicities such as febrile neutropenia, infection, surgical complications, neutropenia and hand-foot syndrome were also found to be statistically significant between the combination group and the chemotherapy alone group (all<0.05), while such difference was not found in the occurrence of peripheral neuropathy (>0.05).The addition of bevacizumab to neoadjuvant chemotherapy in Her2-negative breast cancer can significantly improve pathological complete response, but may bring more grade 3 and 4 toxicities.More neoadjuvant trials need to be done to define subgroups of Her2-negative breast cancer that would have clinically significant long-term benefit from bevacizumab treatment.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; toxicity ; Bevacizumab ; adverse effects ; therapeutic use ; toxicity ; Breast Neoplasms ; chemistry ; drug therapy ; Female ; Humans ; Neoadjuvant Therapy ; adverse effects ; methods ; Prospective Studies ; Receptor, ErbB-2 ; analysis ; Triple Negative Breast Neoplasms ; drug therapy

Four prenylated flavonoids compounds 1-4, named sinopodophyllines A-D, and a flavonoid glycoside (compound 13), sinopodophylliside A, together with 19 known compounds (compounds 5-12 and 14-24) were isolated from the fruits of Sinopodophyllum hexandrum. The structures of new compounds were elucidated by extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR. Compounds 1-6, 9-11, and 14-17 were tested for their cytotoxicity against human breast-cancer T47D, MCF-7 and MDA-MB-231 cells in vitro, and compounds 2, 5, 6, 10 and 11 showed significant cytotoxicity (IC values < 10 μmol·L) against T47D cells.
Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; pharmacology ; Berberidaceae ; chemistry ; Breast Neoplasms ; drug therapy ; physiopathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Flavonoids ; chemistry ; isolation & purification ; pharmacology ; Fruit ; chemistry ; Humans ; Molecular Structure

OBJECTIVETo study the anticancer effects of total alkaloid from Viscum coloratum in vivo and vitro.

METHODIn vitro, MTT assays were used t o measure the inhibitory effect. Cells at period of logarithmic growth were incubated for 24 hours. Then total alkaloid of various concentrations were added. 24 hours later, supernatant was removed and MTT was added. 4 hours after that, DMSO was added, then 30 minutes later, A value was measured. In vivo, suspension of carcinoma cells was implanted in the mice's limbs subcutaneously, 0.2mL each. 24 hours later, the mice were grouped randomly. Fed by total alkaloid continuously for 7 days, the mice were sacrificed. The tumors were weighed and calculated the inhibitory rates.

RESULTIn vitro, it shows that total alkaloid has prominent inhibitory effect on the growth of carcinoma cells. In vivo, it shows that total alkaloid can inhibit the growth of tumors and prolong the survival days of the mice bearing tumors.

CONCLUSIONTotal alkaloid from Viscum coloratum has the activities of anticancer.

Alkaloids ; isolation & purification ; pharmacology ; Animals ; Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Breast Neoplasms ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Esophageal Neoplasms ; pathology ; Female ; Humans ; Liver Neoplasms, Experimental ; drug therapy ; pathology ; Mice ; Neoplasm Transplantation ; Plants, Medicinal ; chemistry ; Viscum ; chemistry

BACKGROUNDIt is now recognized that Cimicifuga foetida (C. foetida) extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. The aim of this study was to investigate the effects of C. foetida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women.

METHODSThis was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment.

RESULTSIn comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A (11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P > 0.05); in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs. 11.84 ± 2.72 mm and 11.90 ± 3.33 mm, P < 0.05) after treatment, the same as Group C (11.56 ± 3.03 mm vs. 12.5 ± 3.57 mm and 12.22 ± 4.39 mm P < 0.05). In comparing breast duct width before and after 1 and 2 years of treatment, no significant difference was seen in Group A (1.07 ± 0.19 mm vs. 1.02 ± 0.18 mm and 0.98 ± 0.21 mm, P > 0.05); in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P < 0.05), the same as Group C (1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P < 0.05). The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment: There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum target check.

CONCLUSIONSIn early postmenopausal patients, C. foetida extract therapy and estrogen and progesterone therapy at low doses did not increase the incidence of malignant breast tumors.

Adult ; Breast ; drug effects ; Breast Neoplasms ; drug therapy ; Cimicifuga ; chemistry ; Estrogens ; therapeutic use ; Female ; Hormone Replacement Therapy ; Humans ; Male ; Middle Aged ; Plant Extracts ; pharmacology ; Postmenopause ; Progestins ; therapeutic use ; Software

Vincristine is a dimer-indo-alkaloid which is extracted from the leaves of Catharanthus roseus. It is effective to treat acute lymphocytic cell leukemia, Hodgkin disease and non-Hodgkin disease clinically. But the severe side effects, such as neurotoxic and tissue damage, limit its application. In this paper, we summarize physical, chemical, pharmacological and pharmacokinetical properties of VCR and advances in decreasing its side effects. In clinic, association with other medication is adopted. In pharmaceutics, people adopt some new methods and technology such as conjugation with the antibody, encapsulation in liposomes or controlled release films.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; isolation & purification ; therapeutic use ; Breast Neoplasms ; drug therapy ; Catharanthus ; chemistry ; Humans ; Liposomes ; Liver Neoplasms ; drug therapy ; Plants, Medicinal ; chemistry ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Stomach Neoplasms ; drug therapy ; Vincristine ; administration & dosage ; isolation & purification ; therapeutic use

To evaluate the efficacy of adjuvant endocrine therapy (AET) in breast cancer patients with a positive-to-negative switch of hormone receptor status after neoadjuvant chemotherapy (NAC).One hundred and six patients who presented with hormone receptor (HR)-positive breast cancer at diagnosis and turned to HR-negative after NAC during December 2000 and December 2013 in Jiaxing Maternity and Child Health Care Hospital were retrospectively identified. Kaplan-Meier analysis and log-rank test were used for univariate analyses of factors related to disease free survival (DFS) and overall survival (OS). Multivariate analysis was carried out using the Cox proportional hazards model in patients with DFS and OS.All the patients were categorized into two groups on the basis of the administration of AET:61 AET-administered patients (57.5%) and 45 AET-naïve patients (42.5%). After a median follow-up of 68 months (range 14-103 months), human epidermal growth factor receptor 2 (HER-2) status, initial clinical stage, pathological axillary lymph node status and the use of AET were identified as the variables affecting DFS and OS (all<0.05). Patients treated with AET had a significantly improved 5-year DFS rate when compared with that without AET (77.1%53.5%,<0.05). The 5-year OS of AET-administered patients was also better than that of AET-naïve patients (80.9%71.0%,<0.05). Cox regression analysis showed that AET-administered or not was the independent predictor for 5-year DFS (=2.096, 95%:1.081-4.065,<0.05).Patients with HR altered from positive to negative after NAC may still gain benefit from AET.
Antineoplastic Agents, Hormonal ; therapeutic use ; Axilla ; Breast Neoplasms ; chemistry ; classification ; drug therapy ; mortality ; Chemotherapy, Adjuvant ; methods ; statistics & numerical data ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes ; Lymphatic Metastasis ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Neoplasms, Hormone-Dependent ; drug therapy ; Proportional Hazards Models ; Receptor, ErbB-2 ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Triple Negative Breast Neoplasms ; drug therapy

Animals ; Antineoplastic Agents, Alkylating/pharmacology* ; Breast Neoplasms/drug therapy* ; Cell Line ; Cell Line, Tumor ; Cyclophosphamide/pharmacology* ; Ginkgo biloba/chemistry* ; Mammary Neoplasms, Animal/drug therapy* ; Mice ; Plant Extracts/administration & dosage*