Objective To discuss the design of pedicled thoracodorsal artery perforator flap (TDAP flap),and to evaluate the aesthetic results and donor-site complications for immediate partial breast reconstruction (IPBR) after breast conserving surgery (BCS) for breast cancer patients.Method Clinical data of 13 breast cancer cases treated with BCS + IPBR using TDAP flap from November 2004 to November 2010 were retrospectively analyzed.Perforators were identified with Doppler preoperatively in all patients.Results All perforators originated within a median distance of 8.0 cm ( range,7.5 to 9.5 cm) from axillary plica at the posterior line of axilla.Median area of the flaps was 6.0 × 8.0 cm ( range,5.0 × 7.0 cm to 8.0 × 10.0 cm).One flap was muscle-sparing,while a small muscle strip was left embedding the perforators in other twelve flaps to increase the reliability of the vascular pedicle.Postoperatively patients were followedup from 4 to 71 months.Median follow-up time was 41 months.Flap necrosis and seroma in the donor-site were not found in all patients.Aesthetic results were graded as excellent or good in 9 patients,fair in 3,and poor in one.Conclusions TDAP flap is a good choice for IPBR after BCS for breast cancer patients whether lesions in outer quadrants or inner quadrants,especially for those patients with excisional biopsy.Preoperative mini-Doppler is helpful for determining the precise location of the main perforators,and decreasing the risk of vessels injury.

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 observe the expression of phospholipid scramblase 1 (PLSCR1) in matrine (MAT) induced differentiation of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) cells, and to explore its correlation to cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signal pathway.

METHODSNB4 (an APL cell line sensitive to ATRA) and NB4-R1 (a resistant strain of ATRA) were observed as subjects in this study. Effects of combined treatment of 0.1 mmol/L MAT and 1 [mol/L ATRA on the differentiation of two cell lines were detected using nitroblue tetrazolium (NBT) reduction test and flow cytometry (CD11b). Expressions of PML/RARot and PLSCR1 protein/gene were detected using Western blot and Real-time fluorescence quantitative PCR assay. Meanwhile, H89, PKA antagonist, was used to observe cell differentiation antigen and changes of aforesaid proteins and genes.

RESULTSMAT combined ATRA could significantly elevate positive rates of NBT and CD11 b in NB4-R1 cells, and significantly down-regulate the expression of PML/RARapha-fusion protein/gene (P < 0.05, P < 0.01). ATRA used alone could obviously enhance the expression of PLSCRI in NB4 cells at protein and mRNA levels (P < 0.01). But the expression of PLSCR1 was up-regulated in NB4-R1 cells, but with statistical.difference only at the protein level (P <0. 01). In combination of MAT, PLSCR1 protein expression was further elevated in the two cell lines (P < 0.01). Besides, there was statistical difference in mRNA expressions in NB4-R1 cells (P < 0.05). All these actions could be reversed by treatment of 10 micromol/L H89 (P < 0.05, P < 0.01).

CONCLUSIONMAT combined ATRA could significantly induce the differentiation of NB4-R1 cells, and inhibit the expression of PML/RARalpha fusion gene/protein, which might be associated with up-regulating PLSCR1 expression.

Alkaloids ; Antineoplastic Agents ; Cell Differentiation ; Cell Line, Tumor ; Down-Regulation ; Humans ; Leukemia, Promyelocytic, Acute ; metabolism ; Phospholipid Transfer Proteins ; metabolism ; Quinolizines ; RNA, Messenger ; Signal Transduction ; Tretinoin ; Tumor Cells, Cultured ; Up-Regulation

OBJECTIVETo evaluate the available surgical treatment modalities so as to explore the optimal strategy of managing early breast cancer.

METHODSThe 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 .

RESULTSThe 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%.

CONCLUSIONBreast 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.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; pathology ; surgery ; Carcinoma, Ductal, Breast ; pathology ; surgery ; Carcinoma, Intraductal, Noninfiltrating ; pathology ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Mastectomy ; methods ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paget's Disease, Mammary ; pathology ; surgery ; Reconstructive Surgical Procedures ; Retrospective Studies

Background and purpose:Rabs are members of Ras-related small GTPase superfamily. Rab27A is a unique member in the Rab family and has specific implications in human genetic diseases. We studied the potential role of Rab27A in proliferation, distribution of cell cycle, apoptosis and invasion of breast cancer cells and its mechanism(s). Methods:The eukaryotic expression vector containing Rab27A open reading frame (ORF) pcDNA3.1(+) - Rab27A was constructed and transfected into MDA-MB-231 breast cancer cells. Then we detected the changes in terms of cell growth, cell cycle distribution, apoptosis and in vitro invasion capability before and after transfection. We also applied RT-PCR to investigate the molecular basis.Results:① The expression of Rab27A was increased as invasive and metastatic ability increased in four human breast cancer cell lines. ② Overexpression of Rab27A can promote breast cancer cells to grow faster, increase the proportion of S phase cells, avoid apoptosis and invade in vitro. ③ Rab27A transfectants constitutively enhanced the expression of Cyclin D1, MMP-7 and MMP-9 in MDA-MB-231 cell lines, on the contrary, that of p16 were down-regulated constitutively. Reduced Rab27A expression by RNAi down-regulated the expression of Cyclin D1, MMP-7 and MMP-9, and up-regulated p16 expression.Conclusions:Rab27A can stimulate breast cancer cells to proliferate, increase the proportion of cells in S phase,avoid apoptosis and invade in vitro by regulating the expression of Cyclin D1, MMP-7, MMP-9 and p16.

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.

OBJECTIVETo evaluate the clinical value of mutated p53 in the peripheral blood of breast cancer patients.

METHODSPlasma DNA of 126 breast cancer patients and 92 healthy women was examined. DNA extraction from the tumor and tissue samples was performed by a nonorganic method. Plasma DNA was purified on Qiagen columns. PCR-SSCP analysis was performed to examine the point mutations in the conserved exons 5, 6, 7 and 8 of TP53.

RESULTSThe mean concentration of plasma DNA was 21 ng/ml in healthy women and 211 ng/ml in patients with breast cancer (P < 0.01). p53 mutations in the primary tumor were detected in 46 of 126 (36.5%) breast cancer patients. Of these 46 patients, 30 (65.1%) were also found to have p53 mutations in their plasma DNA. p53 mutation in plasma DNA was closely correlated with clinical stage, tumor size, lymph node (LN) metastasis and estrogen receptor status (P < 0.05). Survival of the patients with both primary tumor and plasma p53 mutations was the worst. Thirteen of the 22 (59.0%) patients with recurrence and/or metastasis had detectable p53 mutations in their plasma DNA.

CONCLUSIONp53 mutations in plasma DNA may be a useful prognostic factor and an early marker of recurrence or distant metastasis in breast cancer.

Adult ; Aged ; Breast Neoplasms ; genetics ; mortality ; Carcinoembryonic Antigen ; blood ; DNA ; blood ; Female ; Humans ; Middle Aged ; Mucin-1 ; blood ; Mutation ; Prognosis ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVETo explore the role of matrine (MAT) alleviating all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukemia (APL) and its mechanism.

METHODSATRA sensitive strain of APL (NB4) and resistant strain (NB4-R1, NB4-R2) were used in this study. The low toxic dosage of MAT was established by MTT test, and ATRA IC(50) of the cell strains (cultured with or without 0.1 mmol/L MAT) were obtained to confirm the reversal index (RI); the influence of MAT (10, 8, 6, 4, 2, 1, 0.1, 0.01, 0.001 mmol/L) combine with 1 µmol/L ATRA on the differentiation of the three cell strains were observed by nitro blue tetrazolium chloride (NBT) test and morphologic changes. The apoptosis rate of cells treated with different concentration of MAT combined with 1 µmol/L ATRA was tested by flow cytometry with Annexin V/PI staining.

RESULTS(1) The toxicity of MAT to NB4, NB4-R1, and NB4-R2 cells was increased with the concentration, IC(50) value was (0.661 ± 0.035) mmol/L, (0.673 ± 0.132) mmol/L and (0.329 ± 0.020) mmol/L, respectively; (2) After treated with 0.1 mmol/L MAT, the ATRA resistance factor of NB4-R1 decreased markedly (RI = 4.96 ± 1.15), but did not of NB4-R2(RI = 0.66 ± 0.17); (3) The differentiation capacity of NB4 and NB4-R1 was enhanced with increase of MAT, and peaked at 0.1 mmol/L (P < 0.05), but did not of NB4-R2; (4) After treated with MAT, the ATRA (1 µmol/L) induced apoptosis rate in NB4 and NB4-R1 increased significantly (P < 0.05 and P < 0.01, respectively).

CONCLUSIONMAT can reverse the ATRA resistance of NB4-R1, which may relate to the effect of MAT on differentiation and apoptosis. Treatment with MAT plus ATRA may exaggerate the cells resistance potency.

Alkaloids ; pharmacology ; therapeutic use ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Cell Differentiation ; drug effects ; Drug Resistance, Neoplasm ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Quinolizines ; pharmacology ; therapeutic use ; Tretinoin ; pharmacology ; Tumor Cells, Cultured

OBJECTIVETo evaluate the oncologic safety, indications and aesthetic results for skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR).

METHODOne hundred and twenty-nine breast cancer patients treated by SSM + IBR from October 1999 to May 2007 were reviewed. Reconstructive techniques included latissimus dorsi flaps (38 patients), implants only (2 patients), latissimus dorsi flaps plus implants (61 patients), pedicled transverse rectus abdominis myocutaneous (TRAM) flaps (25 patients) and deep inferior epigastric artery perforator (DIEP) flaps (3 patients). Aesthetic results were judged by patients' self-evaluation.

RESULTSMean duration of hospitalization was 18.6 days. Time of first chemotherapy was 5.2 days after operation. Eleven patients (11/63, 17.5%) developed capsular contracture and 24 patients (24/99, 24.2%) developed seroma in the donor site. Nine patients (9/28, 32.1%) developed partial fat necrosis in TRAM and DIEP flaps. The satisfaction with the aesthetic results of the reconstructive breast was significantly lower in irradiated patients than non-irradiated ones. Median follow-up time was 11 months. Five patients developed local recurrence and 7 patients with metastasis.

CONCLUSIONSSSM with IBR can be used for the 0 to II a stage breast cancer patients, with surgical oncologic and aesthetic satisfaction. Radiotherapy has an adverse effect on the reconstructive breast. Delayed or delayed-immediate reconstructions are recommended for patients indicated to postoperative radiotherapy.

Adult ; Breast Neoplasms ; surgery ; Female ; Follow-Up Studies ; Humans ; Mammaplasty ; methods ; Mastectomy, Subcutaneous ; Middle Aged ; Retrospective Studies ; Surgical Flaps ; Treatment Outcome

OBJECTIVETo summarize the clinical experience of trastuzumab treatment in neoadjuvant, adjuvant, metastatic setting of Chinese patients with Her-2 positive breast cancer and evaluate the efficacy of trastuzumab in combination with chemotherapy.

METHODSFrom January 2004 to December 2008, 141 outpatients with breast cancer treated with trastuzumab were investigated retrospectively. The follow-up time ranged from 3 to 319 months. The disease free survival time (DFS) of metastatic setting was calculated. The overall survival time (OS), time to treatment failure (TTF) and clinical response rate (CRR, including complete response, partial response and stable disease) of adjuvant, first-line, second-line therapy were analyzed statistically.

RESULTSIn the neoadjuvant regimen, paclitaxel plus carboplatin in combination with trastuzumab accounted for 66.7%, which achieved pathological complete response in 10 of 16 patients. In the adjuvant regimen, anthracycline or anthracycline followed by taxane accounted for 53.9%. The median DFS of 57 cases with metastatic diseases was 17 months. The CRR of first-line trastuzumab use in metastatic setting was 84.5%, compared with 44.4% of second-line use. The median TTF of first-line treatment was 24 months compared with 5 months of second-line treatment. Statistically significant differences were observed.

CONCLUSIONThe regimen of paclitaxel plus carboplatin in combination with trastuzumab deserves wide clinical use. In metastatic setting, first-line treatment of trastuzumab plus chemotherapy can achieve a higher response rate than second-line treatment. Continued trastuzumab therapy combined with different chemotherapy treatment after disease progression may obtain additive clinical advantage.

Adult ; Anthracyclines ; administration & dosage ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Bridged-Ring Compounds ; administration & dosage ; Carboplatin ; administration & dosage ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Paclitaxel ; administration & dosage ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; Survival Rate ; Taxoids ; administration & dosage ; Trastuzumab ; Treatment Failure