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Antibody drug conjugations (ADCs) are a new class of drugs with both targeted specificity and high activity of chemotherapy drugs, which has gradually become a novel generation of therapeutic models with great clinical application prospects. In recent years, ADCs composed of monoclonal antibodies against different tumor cell surface antigens and small molecule potent cytotoxic drugs have shown superior therapeutic effects on recurrent / metastatic breast cancer. This article reviews the clinical application and research progress of ADCs with different molecular targets in the field of breast cancer.
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Objective@#To investigate the clinicopathological characteristic and risk factors for recurrence in different subtypes of mucinous breast cancer(MBC).@*Methods@#Clinical data of 97 MBC patients at Zhejiang Cancer Hospital from August 2005 to November 2012 were retrospectively analyzed. All of patients were divided into 3 subtypes according to the mucinous components in the tumors, named as partial mixed MBC with less than 50% of mucinous components, main mixed MBC where the mucinous component accounted for 50% to 90%, and pure MBC with more than 90% of mucinous components. In this study, 43, 16 and 38 patients were included in partial mixed MBC, main mixed MBC, and pure MBC, respectively. Follow-up was collected by out-patient, in-patient system and phone call. The relationship between different subtypes and clinicopathological significance were analyzed by χ2 test. Kaplan-Meier curve combined with Log-rank test was used to evaluate the risk factors of relapse free survival(RFS) at 3- and 5-year. Cox proportional hazard regression model was used for multivariate analysis.@*Results@#The median follow-up time was 65 months (range 24-125). Of the 97 patients, 14 patients were relapse or metastasis at the end point. The 3- and 5-year RFS were 90.7% and 85.7%, respectively. Tumor size, number of involved lymph nodes (LN), axillary LN metastasis, TNM stages and p53 mutant status were all related with subtypes of MBC(all of P<0.05). There was no correlation between subtypes of MBC and the other parameters, including age at surgery, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor-2 (HER-2) overexpression, menstruation status, and the relapse of disease(all of P>0.05). Univariate analysis showed menstruation status and TNM stages were associated with the relapse of breast cancer(P<0.05). The patients with menopause and stage Ⅲ-Ⅳ showed significantly shorter RFS time(both of P<0.05). Multivariate Cox proportional hazard regression analysis revealed that tumor size, PR status and postoperative radiotherapy were the independent prognostic factors for the relapse of MBC.@*Conclusions@#Tumor size, status of axillary LN metastasis, TNM stages, and p53 mutation status are differ among different subtypes of MBC. The tumor size (>30 mm), PR status and postoperative radiotherapy are the independent risk factors for recurrence, whereas the proportion of the mucinous component is not associated with relapse in MBC patients.
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It has been shown that the PIK3CA mutation in HER2 positive breast cancer is up to 25%, and thus activates PI3K-Akt signaling pathway,promotes HER2 mediated tumor cell epithelial transformation, alters the intrinsic phenotype of HER2 overexpression breast cancer,and finally leads to resistance to anti HER2 targeted therapy.Some studies have shown that the PIK3CA gene mutation is associated with the efficacy of anti-HER2 targeted therapy.Therefore,real-time monitoring of PIK3CA gene mutation will promote indivi-dualized anti-HER2 targeted therapy.
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With the development and clinical use of the molecular targeted drugs and individualized treatment,cancer research has been focused on gene targeting diagnosis and treatment.Especially for the epidermal growth factor receptor (EGFR) signaling pathway-related genes,DNA replication-related genes,spindle apparatus format-related genes,cell metabolism-related genes and other molecular targeted detection and treatment,the polymorphism of targeting genes/molecules determines the clinical efficiency of the therapies.
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Objective Carbonic anhydrase 1 (CA1) not only enhances the hydration reaction but also promotes the formation of CaCO3,which is an essential step for new bone formation in vitro.However,there is no direct evidence to demonstrate the involvement of CA1 in bio-mineralization in cells and tissues.This study is aimed to evaluate the important role of CA1 in bio-mineralization and ossification in cultured cells.Methods Calcification in Saos-2 cells was induced using osteogenic medium (OM) and the calcification was determined by Alizarin Red-S staining.The expressions of ossification protein marker Runt-related transcription factor-2 (Runx2),osterix (OSX),alkaline phosphatase (ALP),osteocalcin (OCN) and bone sialoprotein (BSP) were detected in the process of bone formation by real-time PCR.The expression of CA 1 in the calcified cells were measured using real-time PCR and Western blotting.We also detected calcification in Saos-2 cells in the presence of acetazolamide,an anti-carbonic anhydrase drug to CA1,to determine the role of CA1 in biomineralization in culture cells.T test analysis was used to compare the two groups,M-ANOVA of repeated measurs was conducted for different time point.Results Following the stimulation of OM,Saos-2 cells produced a great amount of calcium-rich deposits [0.68±0.03 vs 2.76±0.13,P＜0.01].Increased transcriptions of ossification protein markers were also detected in these stimulated Saos-2 cells,indicating that the OM launched the process of bone formation in the cells.CA1 had a significantly increased expression during this process [0.25±0.03 vs 0.94±0.06,P＜0.01].Following treatment with acetazolamide,the expression of CA1 evidently declined [1.09±0.05 vs 0.55±0.07,P＜0.05],and the mineralized nodule formation was declined [2.76±0.13 vs 2.19±0.07,P＜0.01].Conclusion These findings indicate that CA1 participates in the biomineralization and ossification,and may play an important roles in bone formation.
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Objective To determine long-term survival of 214 patients of lung cancer with brain metastases and to detect the potential prognostic factors.Methods A retrospective review was pedormed evaluating patients diagnosed as lung cancer with brain metastasis from Jan 1992 to Dec 2001 at Zhejiang Cancer Hospital.Two hundred and fourteen cases were enrolled.All hospital records were thoroughly reviewed in a retrospective manner.The management of the brain metastases were as follows: 8 patients underwent surgical resection and postoperative whole brain radiotherapy (WBRT); 2 cases received resection and chemotherapy; 10 had resection alone; 10 underwent WBRT alone,36 had chemotherapy alone; 15 received the combination of resection,chemotherapy and WBRT; 104 were performed with chemotherapy combined with WBRT; 29 had only supportive care.Survival time was measured from the date of the first treatment for malignancy to the date of death or the last follow-up.Seven further potential prognostic factors were investigated for survival including age,gender,T or N status,number of extra cranial metastases,pathological type and treatment modality.Statistical analysis was performed using the Kaplan-Meier method and Cox-regression analysis.Results The overall median survival time was 10 months (95% CI9.06--10.94) and the 1,3,5 year survival rates were 7.46%,1.14% and 0,respectively.In the univariate model,none of the following variables had effect on survival: age,gender,T stage of the tumor,nodal status,number of extra cranial metastases and histological type.Univariate analysis showed a better survival for the combination of surgical resection,chemotherapy and radiation (P=0.00).Based on Cox-regression analysis,treatment modality was the only independent predictor of survival Conclusions Aggressive combined therapy of brain metastases may achieve a survival advantage.Excellent overall survival of lung cancer with brain metastases has been achieved with a combination of WBRT with surgical resection and chemotherapy.
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Objective: To observe the effect of Shenfu Injection on carcinemia and study its mechanism.Methods: Mice C57 Lewis lung cancer model were established.The changes of physiological conditions(body weight,food and water intake),the serum levels of tumor necrosis factor-?(TNF-?),interleukin-6(IL-6) and interleukin-1(IL-1) were observed in the experiment.Results: Shenfu Injection can signifi cantly increase water and food intake of carcinemia mice,and inhibited the loss of body weigh(P