BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In thi...BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.展开更多
The mechanism of idiopathic ventricular tachycardia originating from the right ventricular outflow tract （RVOT） is not clear. Many clinical reports have suggested a mechanism of triggered activity. However, there ar...The mechanism of idiopathic ventricular tachycardia originating from the right ventricular outflow tract （RVOT） is not clear. Many clinical reports have suggested a mechanism of triggered activity. However, there are few studies investigating this be- cause of the technical difficulties associated with examining this theory. The L-type calcium current （/Ca-L）, an important in- ward current of the action potential （AP）, plays an important role in arrhythmogenesis. The aim of this study was to explore differences in the APs of right ventricular （RV） and RVOT cardiomyocytes, and differences in electrophysiological character- istics of the ICa-L in these myocytes. Rabbit RVOT and RV myocytes were isolated and their AP and Ic,-L were investigated us- ing the patch-clamp technique. RVOT cardiomyocytes had a wider range of AP duration （APD） than RV cardiomyocytes, with some markedly prolonged APDs and markedly shortened APDs. The markedly shortened APDs in RVOT myocytes were abolished by treatment with 4-AP, an inhibitor of the transient outward potassium current, but the markedly prolonged APDs remained, with some myocytes with a long AP plateau not repolarizing to resting potential. In addition, early afterdepolariza- tion （EAD） and second plateau responses were seen in RVOT myocytes but not in RV myocytes. RVOT myocytes had a high- er current density for/Ca-L than RV myocytes （RVOT （13.16±0.87） pA pF-1, RV （8.59±1.97） pA pF-1; P〈0.05）. The ICa-L and the prolonged APD were reduced, and the EAD and second plateau response disappeared, after treatment with nifedipine （10 μmol L^-1）, which blocks the Ica-L. In conclusion, there was a wider range of APDs in RVOT myocytes than in RV myocytes, which is one of the basic factors involved in arrhythmogenesis. The higher current density for ICa-L is one of the factors causing prolongation of the APD in RVOT myocytes. The combination of EAD with prolonged APD may be one of the mechanisms of RVOT-VT generation.展开更多
文摘BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.
文摘The mechanism of idiopathic ventricular tachycardia originating from the right ventricular outflow tract （RVOT） is not clear. Many clinical reports have suggested a mechanism of triggered activity. However, there are few studies investigating this be- cause of the technical difficulties associated with examining this theory. The L-type calcium current （/Ca-L）, an important in- ward current of the action potential （AP）, plays an important role in arrhythmogenesis. The aim of this study was to explore differences in the APs of right ventricular （RV） and RVOT cardiomyocytes, and differences in electrophysiological character- istics of the ICa-L in these myocytes. Rabbit RVOT and RV myocytes were isolated and their AP and Ic,-L were investigated us- ing the patch-clamp technique. RVOT cardiomyocytes had a wider range of AP duration （APD） than RV cardiomyocytes, with some markedly prolonged APDs and markedly shortened APDs. The markedly shortened APDs in RVOT myocytes were abolished by treatment with 4-AP, an inhibitor of the transient outward potassium current, but the markedly prolonged APDs remained, with some myocytes with a long AP plateau not repolarizing to resting potential. In addition, early afterdepolariza- tion （EAD） and second plateau responses were seen in RVOT myocytes but not in RV myocytes. RVOT myocytes had a high- er current density for/Ca-L than RV myocytes （RVOT （13.16±0.87） pA pF-1, RV （8.59±1.97） pA pF-1; P〈0.05）. The ICa-L and the prolonged APD were reduced, and the EAD and second plateau response disappeared, after treatment with nifedipine （10 μmol L^-1）, which blocks the Ica-L. In conclusion, there was a wider range of APDs in RVOT myocytes than in RV myocytes, which is one of the basic factors involved in arrhythmogenesis. The higher current density for ICa-L is one of the factors causing prolongation of the APD in RVOT myocytes. The combination of EAD with prolonged APD may be one of the mechanisms of RVOT-VT generation.
