Breast Neoplasms ; drug therapy ; pathology ; surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Mammaplasty ; Mastectomy, Segmental ; methods ; Neoadjuvant Therapy ; Sentinel Lymph Node Biopsy ; methods

Triple-negative breast cancer (TNBC) is a heterogeneous disease.It has distinct risk factors,molecular biology features,clinical presentations and prognosis.TNBC recurrence is common after resection,and the survival rate is low and available treatment options are few after recurrence.To date,chemotherapy is the main treatment strategy for TNBC.There is a great need for new molecular predictive marks and drug targets for improving the efficacy of TNBC treatment.

AIM: To investigate the inhibitory effect of arsenic trioxide on human glioma cell line U251 growth, change of gene expression and intracellular calcium content. METHODS: MTT method was used to observe the growth inhibition effect. Cell cycle, positive rate of proliferation cell nuclear antigen (PCNA), apoptosis associated protein Fas and Bcl-2, and intracellular calcium ion (IECa~ 2+ ) levels were measured by flow cytometry in U251 cells treated with different doses of As_2O_3. Apoptosis was detected with annexin V-FITC+PI dual parameter. RESULTS: As_2O_3 inhibited the growth of U251 cells dramatically. There were obvious dosage-effect and time-effect correlations (P0.05). The cell cycle was arrested in G_2M phase. Apoptosis occurred in U251 cells treated with As_2O_3 by annexin V-FITC+PI dual parameter detection. CONCLUSION: As_2O_3 inhibits the growth of U251 cells in vitro dramatically and induces apoptosis. The mechanism is probably associated with the improvement of Fas expression and IECa~ 2+ levels, decrease in PCNA protein expression and cell cycle arrest.

Objective To investigate the efficacy and adverse reactions of SOX and GP combined with two chemotherapy methods.Methods From January 2014 to September 2016 came to our hospital for treatment of three advanced breast cancer patients with negative 84 cases as the research object of observation,were randomly divided into SOX group and GP group were given chemotherapy measures and clinical observation on the treatment of.Results Two groups of patients with CR,PR,SD,PD,the number of cases and the total effective rate comparison,P values were 0.693,0.637,0649,0.801,0.823; two groups of patients with diarrhea,liver damage,thrombocytopenia,nausea and vomiting,neurotoxicity,anemia,leukopenia,rash,renal toxicity,appetite the incidence rate of decline,P values were 0.374,0.629,0.643,0.374,0.645,0.434,0.450,0.693,0.645,0.815.Conclusion Standard chemotherapy regimens for advanced three negative breast cancer was not uniform,but the SOX and GP regimens are safe and effective,can be used for clinical treatment.

ObjectiveTo investigate the effect of the displacement of the selected silver clip in the different respiratory state achieved by active breathing control ( ABC ) system on the displacement of the geometry constituted by all of the silver clips at the border of the cavity in external-beam partial breast irradiation (EB-PBI).MethodsTwo sets of CT images in state of moderate deep inspiratory breathing hold (mDIBH),deep expiratory breathing hold (DEBH),and free breath (FB) were acquired in the same CT simulation assisted by ABC system for each of the 27 patients after breast conservative surgery.All silver clips in the cavity were delineated based on each set of CT images.Thereafter,the irregular geometry based on the silver clips as the vertices was automatically formed.Four selected clips located at the top,bottom,lateral border and medial border of the cavity were correspondingly manually registered based on automatic registration of the CT images acquired in the same or different state of respiration including mDIBH,FB,and DEBH.The displacement of center of the geometry in the direction of right-left (RL),anterior-posterior (AP),and superior-inferior (SI) separately based on automatic registration and manual registration was evaluated.The difference of the displacement was analyzed by Kruskal-Wallis H-test and Kolmogorov-Smirnov Z-test.Results When registered between mDIBH and mDIBH,FB and FB,DEBH and DEBH,the differences of the displacement of the center of geometry were not statistically significant (H =0.00 - 1.76,P=0.184-0.954). When registered between mDIBH and DEBH,the differences were statistically significant ( Z =11.31 - 23.00,P =0.000 - 0.001 ).There were statistically significant differences in the displacement of geometry center based on the selected silver clip between different registration forms in AP and SI directions (Z=4.76-25.54,P=0.000-0.029).ConclusionsThe difference of intrafraction displacement of the geometry constituted by the clips between the same respiratory states in the three dimensional direction is not statistically significant,but the difference is statistically significant between the different respiratory states in AP and SI directions.

Objective To investigate the relationship between the single nucleotide polymorphisms (SNPs) in has-mir-125a-5p rs12975333 and the expression of has-mir-125a-5p and clinicopathological cheracteristics of female breast cancer in Han Chinese women. Methods Genomic DNA was extracted from peripheral blood lymphocytes. taqman-MGB assay was used to type breast cancer of 338 cases and 338 controls. Expression levels of has-mir-125a-5p in 289 biopsies were examined using stem-loop real-time RTPCR and the clinicopathological cheracteristics of breast cancer were evaluated. Result The gene frequencies (GG,GT,TT) of rsl2975333 in the patients were GG 273 (94. 5% ), GT 16 (5.5%),TT 0(0%), while in breast fibroadenoma and controls there were GG 49 ( 100% ), 338 (100%). The expression level of has-mir-125a-5p in breast cancer(0. 19 ±0. 04) was lower than that in the matched nontumor adjacent tissue specimens (0. 37 ± 0. 05 ) ( P = 0. 04 ) .The expression level of minor T allele of mature miR-125a in breast cancer patients was lower than that in has-mir-125a-5p-GG carying(P =0.022). The expression of has-mir-125a-5p was down-regulated in primary breast cancer, especially in elder patients ( P = 0. 036) and lymph node metastasis groups (P = 0. 001) and with negative ERBB2 (P = 0. 007), ERBB3 (P =0. 04). Conclusions rs12975333 polymorphisms in has-mir-125a-5p gene may work as a risk factor of breast cancer in Han Chinese women. The altered expression of has-mir-125a-5p might play a role in the pathogenesis and progression of breast carcinoma.

ObjectiveTo investigate the role of OPN in human breast cancer cell line ( MDA-MB-231) by using small interfering RNA to specifically knockdown OPN expression. MethodsOPN ShRNA expression vector was stably transfected to MDA-MB-231 cell line.The expression of OPN mRNA and protein were analyzed using reverse transcription polymerase chain reaction (RT-PCR)and Western blot,respectively.The growth of MDA-MB-231 cells were observed by MTT.The effect of OPN siRNA on the transplanted tumor growth and tumor hypoxia were assessed in nude mice. ResultsThe expression level of OPN in MDA-MB-231 cells were significantly lower under hypoxia or normoxia(P ＜ 0.05 ).OPN silence with RNAi significantly inhibited the invasion ability and proliferation of MDA-MB-231 cell lines (P ＜ 0.01 ).Inhibition of OPN with RNAi significantly inhibited the growth ability of MDA-MB-231 cells in vivo(P ＜0.05).The tumor hypoxia significantly decreased(P ＜ 0.05). ConclusionsOPN silence with RNAi can effectively inhibit cell proliferation and tumor growth of MDA-MB-231 cells,and decrease the bypoxia level of MDA-MB-231 transplanted tumor in nude mice.

Objective To observe the influence of lysyl oxidase(LOX)downregulation via RNAi on hypoxic metastasis of human lung cancer cell 95D and stduy its molecular mechanism.Methods LOX siRNA was used to transfect 95D cell line in normoxia (19％ O2 ).After 24-hour incubation,the cells were cultured in hypoxic incubator (0.5％ O2 ) for 24h.Real-time PCR assay was applied to detect LOX mRNA and Snail mRNA expression.Levels of Src,phosphorylation of Src (P-Src Y418 ) and Snail protein were determined by Western blot assay.Transwell chamber was used to evaluate the cellular invasion potential.Results Compared with 95D cells under normoxic conditions,hypoixa treatment increased LOX mRNA expression by 14 times and invasion ability by 2.12 times respectively.Compared with siRNA control group,LOX siRNA transfection decreased LOX mRNA expression,the invasion ability of hypoxic cells,and the protein expression of P-Src Y418 and Snail by 70％ - 75％,about 30％,and about 40％ respectively (P ＜ 0.05).However,it didn't affect the expression level of Src protein or Snail mRNA ( P ＞ 0.05).Conclusions Impaired metastatic potential of hypoxic human lung cancer cell induced by LOX downregulation is associated with reduced expression level of Src activation and Snail protein.The present data provids experimental evidence for LOX as a potential target for prevention and treatment of lung cancer metastasis under hypoxia.

ObjectiveTo explore the feasibility,efficacy and cosmetic effect of three-dimensional conformal external beam partial breast irradiation (EB-PBI) after breast-conserving surgery for the selected Chinese early stage breast cancer patients.MethodsFrom June 2003 to December 2010,Forty-four early stage breast cancer patients underwent EB-PBI after breast-conserving surgery.Twenty patients had CT simulation scan in moderate deep inspiration breathing hold,and twenty-four patients in free breathing.EB-PBI was planned and delivered by three-dimensional conformal radiotherapy (3DCRT)with four noncoplanar beams.The prescribed dose was 3.40 Gy per fraction in thirty-nine patients and 3.85 Gy per fraction in five patients,twice per day at an interval of at least six hours,in five consecutive days.Results The number of patients with follow up time of 2,3 and 5 years were 39,31 and 16.Grade 1 acute radiationinduced dermatitis was observed in 17 patients (39％) at three months.Cosmesis was good or excellent in all cases at six months after radiotherapy and in 95％ cases at two years after radiotherapy.The 2-,3-and 5-year local control rates were 100％,99％ and 94％,respectively.The 2-,3-,and 5-year survival rates were all 100％ and no metastases occurred.Conclusions EB-PBI delivered by 3DCRT is feasible for selected Chinese early stage breast cancer patients after breast-conserving surgery.The cosmetic effect,local control rate and long-term survival rate are satisfactory,and acute radiation toxicity is very low.