ABSTRACT
Purpose@#Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis. @*Materials and Methods@#One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included. @*Results@#Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea. @*Conclusion@#Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.
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Background and purpose:The third generation of aromatase inhibitors (AI) in postmenopausal hormone receptor-positive patients is the routine treatments in endocrine therapy. The 500 mg fulvestrant showed clini-cal beneifts in patients with previous AI treatment. This study aimed to access the effcacy and safety of 500 mg fulves-trant in estrogen receptor (ER) positive postmenopausal patients who had previous AI treatments with locally advanced and metastatic breast cancer.Methods:This study retrospectively analyzed the clinical data from 188 post-AI ER positive and (or) progesterone receptor (PR)-positive locally advanced and metastatic breast cancer patients treated with 500 mg fulvestrant in Fudan University Shanghai Cancer Center from Jul. 2011 to Dec. 2015. Primary end point was progression-free survival (PFS). Secondary end points were objective response rate (ORR), clinical beneift rate (CBR) and safety proifle.Results:After the median follow-up of 11.3 months, median PFS was 5.9 months (95%CI: 4.2-7.5), CBR was 40.0% and ORR was 3.4%. COX proportional hazards regression analysis indicated that PFS was correlated with the number of metastatic sites (HR=1.92, 95% CI: 1.2-2.9,P =0.002) and previous lines of chemotherapy (HR=1.52, 95%CI:1.0-2.1,P=0.022). Six patients stopped the treatment for intolerable adverse events.Conclusion:The treatment of 500 mg fulvestrant has a favorable effcacy and safety in treatment of post-AI ER positive postmenopausal patientswith metastatic breast cancer.
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Background and purpose:Gemcitabine-based chemotherapy has been shown to have signiifcant activity and favourable safety in metastatic breast cancer patients, but the effectiveness is limited due to drug resistance. MicroRNAs are a family of small non-coding RNA molecules, acting as oncogenes or tumor suppressors. Although various mechanisms of chemoresistance have been uncovered, the aberrant microRNA expression and its relationship with drug resistance of breast cancer are still unclear. This study explored the potential role and underlying mechanism of microRNA-21 in gemcitabine resistant breast cancer. Methods:MDA-MB-231 cells were continuously exposed to the increasing concentrations of gemcitabine to induce drug resistance to gemcitabine, which was 10 times more resis-tant. Then multiple methods were used including real-time PCR (RT-PCR), CCK-8, Western blot, transfection, wound healing and Transwell assay to observe the effect of microRNA-21 on epithelial-mesenchymal transition (EMT) and chemosensitivity. Results:The expression of microRNA-21 was up-regulated in gemcitabine resistant breast cancer cell line and inversely correlated with gemcitabine sensitivity. Manipulation of microRNA-21 status could change microR-NA-21 level, and could result in corresponding changes in EMT status and drug sensitivity. Conclusion:MicroRNA-21 induces gemcitabine resistance possibly via EMT process in breast cancer.
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Objective To investigate the value of transvaginal ultrasound for the diagnosis of endometrial polyps .Methods The ultrasonographic characteristics in 56 cases of endometrial polyp diagnosed by transvaginal ultrasound were performed the retro-spective analysis and the situation of the hysteroscopic examination in consistent with the pathological examination was analyzed . Results Among 56 cases ,50 cases of endometrial polyps were verified by the pathological examination ,the coincidence rate of transvaginal ultrasound diagnosis was 89 .3% ,in which 6 cases were misdiagnosed with the misdiagnosis rate was 10 .7% . Conclusion The transvaginal ultrasound has the high accuracy rate for diagnosing endometrial polyps .
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Objective To construct the stable stathmin-overexpression SMMC-7721 hepatocellular carcinoma cells and to explore the effect of stathmin-overexpression on the cell proliferation and metastasis in SMMC-7721 cells .Methods By using liposome , Flag-pcDNA3 .1 and Flag-pcDNA3 .1-stathmin plasmid were transfected into SMMC-7721 cells respectively ,the stable Flag-pcD-NA3 .1 expression cells(control group) and the stable stathmin-overexpression cells(experimental group) were established after an-tibiotic resistant gene screening ,and the cell lines were identified by Western Blot .Subsequently ,the cell proliferation was detected by cell count kit(CCK-8) and the soft agar assay ,the apoptosis and cell cycle were determined by the flow cytometry (FCM ) ,and the cell motility and invasion were analyzed by the Transwell assay in vitro .Results The stathmin protein expression of the experi-mental group was significantly increased compared with the control group (0 .76 ± 0 .12 vs .0 .16 ± 0 .05 ,P<0 .05) ,which indicated that the stathmin-overexpression human SMMC-7721 hepatocellular carcinoma cell line was successfully constructed .CCK-8 and the soft agar assay showed that the cell proliferation of the experimental group was higher than that of the control group (0 .29 ± 0 .03 vs .0 .60 ± 0 .05 ,P< 0 .01);additionally ,the apoptotic ratio of the experimental group was decreased compared with the control group[(11 .57 ± 1 .09)% vs .(5 .80 ± 0 .33)% ,P<0 .05] ,the cell cycle was arrested in the stage G2/M ;the Transwell experiment results verified that the cell motility and the invasive ability of the experimental group were obviously reinforced compared with the control group[transmenbrane cell numbers in migrant assay :(54 .03 ± 7 .21) vs .(130 .45 ± 14 .13);transmenbrane cell numbers in invasive assay :(17 .75 ± 2 .52) vs .(57 .76 ± 8 .50) respectively] ,the differences had statistical significance(P<0 .01) .Conclusion The overexpression of stathmin promotes the cell proliferation and the invasive ability in SMMC-7721 hepatocellular carcinoma cells .