1.The latest developments in targeted therapy for triple-negative breast cancer
China Oncology 2017;27(1):36-40
Triple-negative breast cancer (TNBC) is a special type of breast cancer, accounting for 15%-20% of all diagnosed breast cancer cases. Its estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) expression is negative, with unique biological characteristics, clinicopathological features and tumor heterogeneity. Its clinical features include high incidence of relapse, early metastasis and poor prognosis. Currently, it lacks effective treatment. This review described the clinicopathological features of TNBC, its molecular subtypes, several important pathways and targets, as well as presented the progress in clinical studies of targeted drugs in the hope of generating new ideas for the treatment of TNBC in the future.
2.Clinical signiifcance of ICAM-1 expression and its correlation with prognosis of triple-negative breast cance r
Zimei LIU ; Wenxi YU ; Chu SUN ; Yuan YUAN ; Zan SHEN
China Oncology 2017;27(2):121-127
Background and purpose:Triple negative breast cancer (TNBC) is with high invasion, poor prognosis and lack of usefull treatment. This study investigated expression status of ICAM-1 protein in TNBC in order to explore its relationship with clinicopathological features and outcome in patients.Methods:Fifty-nine tissue samples of TNBC were collected while 50 cases of para-carcinoma tissue samples were used as negative controls. Immunohistochemical staining was conducted to detect expression level of ICAM-1 protein. The relationship of ICAM-1 protein expression with clinicopathological features (age, tumor size, subtype, grade, status of lymph node metastasis, TNM stage, vascular tumor thrombus, nerve inifltration, Ki-67, p53 and E-cadherin expression) and outcome in patients were analyzed.Results:The ICAM-1 protein expression of TNBC was signiifcantly higher than that in adjacent tissues (P=0.000). ICAM-1 expression was related to status of lymph node metastasis, grade and TNM stage (with aP-value of 0.036, 0.027 and 0.048, respectively), while demonstrated an undeifned relationship with tumor size, subtype, vascular tumor thrombus and expression of Ki-67, p53 and E-cadherin. The disease-free survival (DFS) of ICAM-1 high expression set was shorter than that of the lower one but has nothing to do with overall survival (OS). In addition, Cox proportional hazards model showed that ICAM-1 expression and lymph node metastasis were independent risk factors of DFS in patients (HR=3.2, 95%CI: 1.6 to 6.4, HR=2.7, 95%CI: 1.28 to 5.9,P<0.05).Conclusion:ICAM-1 could serve as a predictive factor for differentiation status of TNBC. The high expression of ICAM-1 in TNBC may indicate poorer prognosis.
3.The inlfuence of diagnostic interval and other clinicopathological factors on the prognosis of triple-negative breast cancer
Chu SUN ; Hongtao LI ; Zimei LIU ; Yuan YUAN ; Zan SHEN
China Oncology 2016;26(6):538-545
Background and purpose:The time from ifrst onset of symptoms or signs to a deifnitive diagnosis is deifned as diagnostic interval (DI). The relation of DI to other clinicopathological parameters andthe impact of DI on prognosis of patients with triple-negative breast cancer (TNBC) remain unclear.This article plans to make an intensive study of these questions.Methods:The clinical records of a series of 83 consecutively presenting unselected patients referred to the Shanghai Sixth People’s Hospital with diagnosed TNBC between September 2009 and September 2015 were retrospectively reviewed. Clinical and pathological factors included were investigated by univariate analysis using the Kaplan-Meier method, the factors associated with prognosis were further evaluated by multivariable analysis with Cox progression model.t-test and Kruskal-Wallis test were used to study the correlation between DI and other characters.Results:DI: stage T3>T1 (P=0.01), stageⅢ>Ⅱ (P=0.03) andⅠ (P=0.01). Compared with patients of DI≥3 months, the <3 months group had earlier age (P=0.028) and TNM stage (P=0.035). T stage, N stage, neoadjuvant chemotherapy, TNM stage and DI are inlfuencing factors of overall survival (OS). Age, T stage, N stage, TNM stage, menstrual status and neoadjuvant chemotherapy are inlfuencing factors of progression-free survival (PFS). TNM staging is an independent inlfuencing factor for OS and PFS.Conclusion:Patients with later disease stage were more likely to have a longer DI; The shorter DI, the earlier age and stage of disease; DI is the inlfuence factor of OS; TNM stage is an independent inlfuencing factor for OS and PFS.
4.The effect of ZDY102 on brain M receptor in dementia model rats
Zimei WANG ; Qixiang SUN ; Qingfeng LIU ; Yaer HU ; Zongqin XIA
Chinese Pharmacological Bulletin 2003;0(09):-
Aim To observe the effect of ZDY102, a C25 stereo-isomer of ZMS, the active component of Zhimu, on brain M receptor density of dementia model animals and the correlation with its effect on learning/memory ability. Methods The rats were randomly divided into five groups: control group, model group, model given orally for 2 months with 3.6 mg?kg -1?d -1 of ZDY102 treatment, model treated with 9.0 mg?kg -1?d -1 of ZDY102, and model treated with 18.0 mg?kg -1?d -1 of ZDY102. Dementia model was produced by single unilateral injection of 4 ?l of normal saline containing 4 ?g of ?-amyloid (25~35) and 1 ?g of ibotenic acid into right basal ganglion region with the aid of a stereotaxic equipment. The brain muscarinic receptor density was analyzed with single-site binding assay using 3H-quinuclidinyl benzilae(QNB). The learning/memory ability was measured by Y-maze performance. Results Two months after model production, the learning and memory ability as well as the density of muscarinic receptor in brain were significantly decreased in model rats compared with those in control rats. Parallel models treated with daily oral administration of ZDY102 for two months improved in learning and memory ability and their muscarinic receptor density was significantly increased when compared with model rats. The correlation coefficient between total M receptor densities and the learning/memory ability was significant when examined with linear regression. Conclusion ZDY102 can significantly improve the learning and memory ability and increase the brain muscarinic receptor density of the model. Since brain muscarinic receptors are closely correlated to learning and memory, up-regulation of M receptor density might play a very important role in the therapeutic effect of ZDY102.
5.The analysis of X-ray manifestations and clinical pathology in triple negative breast cancer
Shujing LIU ; Guang YANG ; Nanya LI ; Zimei GAO ; Lijing ZHANG ; Haiping LI
Journal of Practical Radiology 2016;32(7):1043-1047
Objective To discuss the X-ray characteristics of triple negative breast cancer(TNBC)for improving the diagnostic level.Methods 105 cases of TNBC which confirmed by pathology and immunohistochemistry were analyzed their X-ray performance and clinical pathology.Results (1)The main pathologic types of TNBC was infiltrating ductal carcinoma(64 cases,61.0%),secondly was medullary carcinoma(24 cases,22.9%).(2)The X-ray manifestations of this group were mainly the mass shape(78.1 %).Nearly half of them had clear edge(46.3%).And 24.4% were tumor with calcification.(3)The calcification in TNBC was rare and the distribu-tion mainly for regional or cluster,while the morphology was mainly for malignant and suspicious for malignancy.(4)The X-ray per-formance characteristics of infiltrating ductal carcinoma and medullary carcinoma in TNBC had differences in tumor morphology and edge(P <0.05).Conclusion (1)The X-ray manifestations were always the circular similarity of tumor with clear edge in TNBC.(2) The proportion of medullary carcinoma is larger in TNBC,and the X-ray manifestations is more likely show as benign lesions.(3) The calcification probability is lower in TNBC,and the calcification form is mainly as suspicious for malignancy and malignant.
6.Preparation of CI-921 mixed micelles and determination of its entrapment efficiency by method of dialysis and fitting
Weisai ZHOU ; Zimei WU ; Bruce C BAGULEY ; Caibin LI ; Wenli ZHANG ; Jianping LIU
Journal of China Pharmaceutical University 2016;47(5):575-580
The aim of this research were to prepare CI-921 mixed micelles(CI-Micelles), to establish a method for determining the entrapment efficiency of CI-Micelles, to optimize the formulation and to evaluate their in vitro properties. CI-Micelles were prepared by film dispersion. Dialysis and fitting were used to calculate true entrapment efficiency(EE)and drug loading(DL)of CI-Micelles. The influences of polymer concentration, polymer radio and hydrating media on the entrapment efficiency, drug loading and particle-size were investigated. The stability at 4 °C in 6 days was evaluated. The optimal formulation of CI-921-Micelles consisting of polymer concentration of 72 mg/mL, a mass radio of Pluronic F127/Solutol HS15 at mass ratio of 1 ∶2 and 5% glucose solution as hydrating medium, showed a EE of more than 90%, and mean particle-size of 17-25 nm and PDI< 0. 210. There were no significant changes to CI-Micelles in EE and particle-size after treatment at 4 °C for 6 days. The applied method of dialysis and fitting could be used to determine EE for micelles loaded with weakly basic drug which was difficult to meet sink conditions. Adjustment of the mass radio of Pluronic F127 to Solutol HS15 had resulted in uniform particle size distribution, high entrapment efficiency and drug loading capacity and better stability of CI-Micelles.
7. Application of contrast enhanced ultrasound in TN staging of pancreas cancer: comparison with contrast enhanced computed tomography
Zimei LIN ; Qing WEN ; Yongyuan XU ; Chao ZHANG ; Caoxin YAN ; Guoqiang MO ; Minqiang PAN ; Chunmei LIU ; Pintong HUANG
Chinese Journal of Ultrasonography 2018;27(7):614-617
Objective:
To assess value of contrast enhanced ultrasound (CEUS) in TN staging of pancreatic cancer and compared with contrast enhanced computed tomography(CECT).
Methods:
Seventy-eight cases with pancreatic cancer confirmed by pathology were enrolled in this study. All patients were examined using CEUS and CECT and staged according to the 8th guideline of pancreas tumors of AJCC. The diagnostic accuracies of CEUS in TN staging of pancreas tumors were compared with CECT.
Results:
The diagnostic accuracies of CEUS in T staging and N staging of pancreatic cancer were 80.8%, and 78.2%, respectively. For CECT, the diagnostic accuracies in T staging and N staging were 88.5%, and 88.5%, respectively. There was no significant difference in the diagnostic accuracies between CEUS and CECT in T staging(χ2=1.56,
8.The qualitative and quantitative features of contrast-enhanced ultrasound in biomarker expression of breast cancer
Zimei LIN ; Yang SUN ; Yunxia GAO ; Chunmei LIU ; Huifang WENG ; Yao WANG ; Pintong HUANG
Chinese Journal of Ultrasonography 2021;30(7):569-574
Objective:To evaluate the relationships among contrast-enhanced ultrasound (CEUS) features, molecular type, and biomarker expression of breast cancer.Methods:A retrospectively analysis of breast cancer patients confirmed by pathology were performed using Breast Imaging Report And Data System (BI-RADS) ultrasound category lesions in the Second Affiliated Hospital Zhejiang University School of Medicine from May 2020 to April 2021. All patients underwent conventional ultrasound and CEUS before biopsy and/or surgery. The relationships among BI-RADS category, quantitative and qualitative CEUS features and biomarker expression of breast cancer were evaluated.Results:All 149 patients with 149 breast lesions were included. The numbers of BI-RADS category 4A, 4B, 4C, and 5 were 8, 60, 49, and 32, respectively. Among them, the numbers of Luminal A like, Luminal B like (human epidermal growth factor receptor-2 (HER-2) positive), Luminal B like (HER-2 negative), HER-2 overexpression and triple negative type were 81, 29, 17, 15, and 7. No significant correlations were found among BI-RADS category, molecular types, and biomarker estrogen receptor (ER), progesterone receptor (PR), HER-2, and antigen Ki-67 (Ki-67) expression (all P>0.05). There were no correlations between quantitative or qualitative CEUS features and molecular types of breast cancer (all P>0.05). There were no correlations between qualitative CEUS variables and ER, PR, HER-2, and Ki-67 expression (all P>0.05). Ascending slope (AS) were negatively correlated with ER and PR expression( r=-0.40, P=0.01; r=-0.35, P=0.03). Descending slope (DS) were positively correlated with ER and PR expression( r=0.42, P=0.01; r=0.36, P=0.03). Arrive time (AT) were positively correlated with HER-2 expression( r=0.37, P=0.02). Conclusions:AS and DS are correlated with ER and PR expression.Arrive time (AT) is correlated with HER-2 expression. The quantitative variables of CEUS are helpful for evaluation of biomarker expression in breast cancer.
9.Contrast enhanced ultrasonography vs.contrast enhanced computed tomography for the diagnosis of focal lesions of the pancreas
Zimei LIN ; Minqiang PAN ; Yongyuan XU ; Qing WEN ; Chunmei LIU ; Yao WANG ; Caoxin YAN ; Qinghai LI ; Pintong HUANG
Chinese Journal of General Surgery 2018;33(10):849-852
Objective To assess the characterization and usefulness of contrast enhanced ultrasound (CEUS) to diagnose focal lesions of pancreas in comparison to contrast enhanced computed tomography (CECT).Methods 177 cases of focal solid lesions of the pancreas confirmed by pathology were collected.The enhanced patterns and diagnostic capability of CEUS were analyzed,and these results were compared with those of CECT.Results The diagnostic accuracies of ultrasound,CEUS and CECT were 61.6% (109/177),89.3% (158/177),and 92.1% (163/177),respectively.There was no significant difference between the diagnostic accuracies of CEUS and CECT (P =0.071).The sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV),and accurate rate for CEUS were 90.9%,63.6%,73.8%,86.2%,82.5% (the areas under the curve,AUC =0.820),and 89.8%,69.3%,76.7%,85.9%,84.7% for CECT (AUC =0.847),respectively,when the hypo-enhanced was regarded as the cut value.No significant difference was found between these results from CEUS and CECT (P =0.071).Conclusions The diagnostic ability of CEUS in focal lesions of the pancreas is similar to that of CECT.