Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of t...Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of the first chemotherapeutic agents introduced in the 1960 s, has been the backbone for the last 30 years and has been used extensively so far. However, the cardiac toxicity and the concern for secondary hematological malignancy has always been a challenge. A better understanding of the tumor biology, role of Her2 expression and the discovery of trastuzumab and other anti-Her 2 agents along with other effective novel therapeutic options, have revolutionized the treatment for breast cancer. The role of anthracyclines has come under close scrutiny, especially in the adjuvant setting for patients with early stage breast cancer and those with low or intermediate risk of disease recurrence. Recent studies have highlighted such a shift in the use of anthracyclines in both the academic and community clinical practice. However, in patients with a high risk of relapse, anthracyclines still hold promise. Ongoing clinical trials are underway to further define the role of anthracyclines in such a patient population. This review highlights the development, clinical utility, limitations and potential future use of anthracyclinesin the adjuvant setting for patients with breast cancer. We consulted Pub Med, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review.展开更多
Chemoresistance remains the major barrier to cancer treatment.Metabolic and epigenetic reprogramming are involved in this process;however,the precise roles and mechanisms are largely unknown.Here,we report that lactat...Chemoresistance remains the major barrier to cancer treatment.Metabolic and epigenetic reprogramming are involved in this process;however,the precise roles and mechanisms are largely unknown.Here,we report that lactate-induced lactylation promotes chemoresistance to anthracyclines by regulating homologous recombination(HR)repair.Using the global lactylome,we revealed the landscape of differentially lactylated sites and proteins in cancer cells isolated from resistant and nonresistant tumors.Specifically,BLM,a crucial helicase in the HR repair process,is highly lactylated at Lys24 by AARS1 in response to chemotherapy.展开更多
Objective:To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines.Methods:Randomized controlled trials(RCTs)were identified by searching China National Knowledge Infra...Objective:To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines.Methods:Randomized controlled trials(RCTs)were identified by searching China National Knowledge Infrastructure(CNKI),Wanfang Database,Chinese Biomedical Literature Database(CBM),Pub Med,Cochrane Library,and Embase Databases from the inceptions until December 2020.The Cochrane Handbook was used to evaluate the risk of bias in the included studies.Data analysis was conducted using Rev Man 5.3 software.Results:Totally 19 RCTs with 2,331 participants were included in this review.Results showed that in improving arrhythmia(13 RCTs,n=1,877,RR=0.37,95%CI 0.25 to 0.52,P<0.00001),the treatment group was superior to the control group.In terms of reducing left ventricular end-diastolic diameter(LVEDD,2 RCTs,n=128,MD=-0.79,95%CI-0.93 to-0.65,P<0.00001)and left ventricular end systolic diameter(LVESD,2 RCTs,n=128,MD=-0.58,95%CI-0.82 to-0.35,P<0.00001),the treatment group was also better than the control group.In reducing myocardial enzymes such as creatine kinase(CK)[(3 RCTs,n=256,SMD=-0.80,95%CI-1.16 to-0.44,P<0.0001),(2 RCTs,n=126,SMD=-0.62,95%CI-0.98 to-0.26,P=0.0007)],the treatment group was superior to the control group.Conclusion:Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines.However,in the future,it is still necessary to conduct high-quality RCTs to verify its efficacy.展开更多
Background： Cardiotoxicity is one of the most serious chronic complications ofanthracyclines therapy. Assessment of the left ventricular ejection fraction （LVEF） fails to detect subtle cardiac dysfunction of left v...Background： Cardiotoxicity is one of the most serious chronic complications ofanthracyclines therapy. Assessment of the left ventricular ejection fraction （LVEF） fails to detect subtle cardiac dysfunction of left ventricular （LV）. This study aimed to detect and evaluate new parameters of subclinical anthracyclines＇ cardiotoxicity in children with solid tumor. Methods： A detailed echocardiographic examination was performed in 36 children with hepatoblastoma or rhabdomyosarcoma after receiving anthracyclines＇ chemotherapy and 36 healthy controls from January 2015 to December 2016. The LVEF, ratio of early diastolic peak velocity of transmitral flow （E） and septal diastolic e＇ mitral annular peak velocity （e＇）, tricuspid annular plane systolic excursion （TAPSE）, and LV global longitudinal strain （GLS） were evaluated using M-mode, tissue Doppler imaging （TDI）, and two-dimensional speckle tracking echocardiography （2D-STE）, respectively. Echocardiographic parameters were compared between patient group and healthy controls. All patients were divided into two subgroups based on their anthracyclines＇ cumulative dosage （〈300 mg/m^2 subgroup and ≥300 mg/m^2 subgroup）. Results： All patients had no presentation of heart failure and LVEF within normal range （65.7 ± 5.1%）. Compared with healthy controls, the mean E/e＇ increased significantly （7.9 ±0.7 vs. 10.2 ± 3.5, t = 3.72, P 〈 0.01 ）, mean TAPSE decreased significantly （ 17.2 ± 1.3 mm vs. 14.2 ± 3.0 mm, t = -4.03, P 〈 0.01）, and mean LV GLS decreased significantly （-22.2% ± 1.9% vs. -17.9% ± 2.9%, t = -5.58, P 〈 0.01） in patient group. Compared with subgroup with anthracyclines＇ cumulative dosage 〈 300 mg/m^2, mean LV GLS decreased significantly （- 18.7 ＋ 2.7% vs. - 16.5 ~ 2. 1%, t = 2.15, P = 0.04）, the mean E/e＇ increased significantly （9.1 ±1.5 vs. 11.5 ± 4.9, t = -2.17, P = 0.04）, and mean TAPSE decreased significantly （14.2±2.1 mm vs. 12.5±2.2 mm, t = -2.82, P = 0.02） in subgroup with anthracyclines＇ cumulative dosage 〉300 mg/m^2. Conclusions： LV GLS is helpful in the early detection of subclinical LV dysfunction using 2D-STE. E/e＇ and TAPSE are other sensitive parameters in detecting subclinical cardiac dysfunction of both ventricles by TD1. These parameters show significant change with different anthracyclines＇ cumulative dosage, so cumulative dosage should be controlled in clinical treatment.展开更多
The taxanes family of chemotherapy,which includes paclitaxel and docetaxel,has been incorporated in the adjuvant breast cancer treatments since 1990s.Sequential and concurrent use of taxanes was investigated with anth...The taxanes family of chemotherapy,which includes paclitaxel and docetaxel,has been incorporated in the adjuvant breast cancer treatments since 1990s.Sequential and concurrent use of taxanes was investigated with anthracyclines in many adjuvant early breast cancer randomized clinical trials.Results from taxanes trials showed inconsistent benefits.However,several meta-analyses showed significant survival benefit of adding taxanes.In this review article,data were collected and summarized from eleven large randomized trials and three meta-analyses to show and discuss the magnitude of benefit of taxanes-anthracyclines combination compared to anthracyclines only adjuvant regimens in early breast cancer.This article aims at providing the oncologists with a well-organized,inclusive and updated evidence.展开更多
Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effec...Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy(DIC);however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action.Through network medicine analysis, astragaloside Ⅳ(AsⅣ) and formononetin(FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsⅣ-FMT combination(AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsⅣ and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.展开更多
BACKGROUND The anthracycline chemotherapeutic drugs are cardiotoxic.Studies have found some indicators related to cardiotoxicity.However,there is currently no accurate indicator that can predict cardiac toxicity early...BACKGROUND The anthracycline chemotherapeutic drugs are cardiotoxic.Studies have found some indicators related to cardiotoxicity.However,there is currently no accurate indicator that can predict cardiac toxicity early.AIM To explore the diagnostic value of real-time three-dimensional echocardiography(RT3DE)in predicting cardiac toxicity in breast cancer patients undergoing chemotherapy.METHODS Female breast cancer patients who underwent radical mastectomy and postoperative chemotherapy at the Affiliated Hanzhou First People’s Hospital,Zhejiang University School of Medicine were recruited.All patients were routinely administered with chemotherapy for four cycles(T1-T4)after surgery.Two-dimensional(2D)echocardiography,RT3DE,and serological examinations were performed after each cycle of chemotherapy.Patients were divided into a toxic group and a non-toxic group based on whether patients hadΔleft ventricular ejection fraction>10%after one year of chemotherapy.Repeated measurement analysis of variance was used to compare the changes in 2D echocardiographic indicators,serological indicators,and RT3DE indicators before independent predictive indicators for cardiac toxicity in postoperative chemotherapy patients.Receiver operating characteristics(ROC)curve analysis was performed to analyze the diagnostic value of potential indicators in the diagnosis of cardiotoxicity.RESULTS A total of 107 female breast cancer patients were included in the study.T4 maximum peak velocity in early diastole(E peak)/mitral annulus lateral tissue Doppler(e'peak)(E/e'),serological indicators[T4 cardiac troponin I(cTnI)and T4 pro-brain natriuretic peptide(Pro-BNP)],T3 minimum left atrial volume(LAV),T4 LAVmin,T3 LAV before the start of the P wave(LAVprep),and T4 LAVprep in the toxicity group were significantly higher than those in the nontoxic group.Multivariate logistic regression found that T4 cTnI,T4 Pro-BNP,T3 LAVmin,T4 LAVmin,T3 LAVprep,and T4 LAVprep had potential predictive value for cardiac toxicity(P<0.05).ROC results showed that T4 LAVmin had the highest accuracy for diagnosing cardiac toxicity[area under the curve(AUC)=0.947;sensitivity=78.57%;specificity=94.62%],followed by T4 LAVprep(AUC=0.899;sensitivity=100%;specificity=66.67%).The accuracies of LAVprep and LAVprep in predicting cardiac toxicity were higher than those of T3 LAVmin and T3 LAVprep.CONCLUSION RT3DE of left atrial volume can be used to predict the cardiotoxicity caused by chemotherapy,and it is expected to guide the clinical adjustment of dose and schedule in time.展开更多
Acute myeloid leukemia (AML), a rapidly progressing hematopoietic malignancy, can only be cured hopefully by hematopoietic stem cells transplantation (HSCT). Before HSCT, we usually exert effects by attempting certain...Acute myeloid leukemia (AML), a rapidly progressing hematopoietic malignancy, can only be cured hopefully by hematopoietic stem cells transplantation (HSCT). Before HSCT, we usually exert effects by attempting certain regimens to induce these tumor cells to death. Administered in AML patients, the classic “3 + 7” intensive induction regimen including anthracyclines and cytarabine is recommended by guidelines worldwide. However, conventional regimens consist of anthracyclines, a category of drug limited by cumulative, dose-related, progressive myocardial damage and congestive heart failure occurs when its total doses break through the cut-off. Based on this background, mitoxantrone (MIT), an anthraquinone, was developed to a new form to reduce cardiotoxicity. Meanwhile, the nanomedicine, mitoxantrone liposome (Lipo-MIT), was characterized by improved bioavailability and limited toxicity. This drug has great therapeutic potential, but different side effects. We conclude the overall history and development of MIT and Lipo-MIT, which show controversial efficacy of MIT compared to doxorubicin and therapeutic potential of Lipo-MIT. This article reviewed the application of MIT and liposome forms in adult AML patients. .展开更多
In commenting on a case report of a 55-year-old man who suffered Takotsubo syndrome(TTS), in the setting of receiving chemotherapy with cytarabine and daunorubicin for acute myeloid leukemia, the author expresses his ...In commenting on a case report of a 55-year-old man who suffered Takotsubo syndrome(TTS), in the setting of receiving chemotherapy with cytarabine and daunorubicin for acute myeloid leukemia, the author expresses his views that TTS in the setting of chemotherapy for malignancies may not be chemotherapeutic drug-specific(like in the chemotherapeutic drug induced-cardiomyopathy), but may be due to the emotional and physical stresses resulting from the realization of having diagnosed with a malignancy, and the diagnostic testing, and therapeutic management which follows.展开更多
The number of women with heart disease who reach childbearing age in a good functional state increases continuously as advances in diagnosis and treatment improve overall health and prognosis. The cardiologist’s role...The number of women with heart disease who reach childbearing age in a good functional state increases continuously as advances in diagnosis and treatment improve overall health and prognosis. The cardiologist’s role is to give the woman an estimate of both maternal and fetal risk to allow her to make an informed decision about embarking on a pregnancy, and to provide appropriate antenatal care. There are only a few data about the natural history of anthracycline-induced cardiomyopathy during preg- nancy;we report our experience of a 29-year- old pregnant woman with a history of anthracycline-induced clinical heart failure.展开更多
BACKGROUND AND OBJECTIVES: The objective of this study was to assess the antitumor activity and toxicity profile of gemcitabine combined with epirubicin in patients with recurrent platinum refractory ovarian epithelia...BACKGROUND AND OBJECTIVES: The objective of this study was to assess the antitumor activity and toxicity profile of gemcitabine combined with epirubicin in patients with recurrent platinum refractory ovarian epithelial cancer. PATIENTS AND METHODS: Patients with recurrent platinum refractory ovarian cancer and with adequate hematologic, renal and hepatic function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 were enrolled. The regimen was Gemcitabine 1000 mg/m2 (day 1, 8) and Epirubicin 60 mg/m2 (day 1), the cycle was repeated at interval of 21 days. RESULTS: Twenty eight patients were recruited and received 156 cycles of gemcitabine-epirubicin combination chemotherapy (median 6 cycles). Overall response rate was 42.9% (95% CI equal 24.5 to 62.7) and tumor control rate was 75% (95% CI equal 55.1 to 89.3). No complete responses were observed. Median progression-free and median overall survival times were 7 and 15 months, respectively. The most common grade 3/4 hematological toxicities were neutropenia (57.1%), anemia (10.7%), and thrombocytopenia (7.1%), while the most common grade 3/4 non-hematological toxicities were mucositis (14.3%) and vomiting (3.6%). No treatment related deaths were observed. CONCLUSION: Gemcitabine combined with epirubicin regimen appeared to offer an acceptable clinical profile in patients with recurrent platinum-refractory epithelial ovarian cancer.展开更多
Doxorubicin is one of the anthracycline anti-neoplastic drugs widely used to treat leukemia, liver, breast, and ovarian cancers and other solid tumors. However, its clinical applications have been limited by its serio...Doxorubicin is one of the anthracycline anti-neoplastic drugs widely used to treat leukemia, liver, breast, and ovarian cancers and other solid tumors. However, its clinical applications have been limited by its serious cardio-cytotoxic effects. The aim of this study was to investigate the effect of neferine, a bisbenzylisoquinoline alkaloid extracted from the green embryo in the mature lotus seed, on the pharmacokinetics of doxorubicin. The levels of doxorubicin in plasma and tissues were measured using the high performance liquid chromatography（HPLC） method. The chromatographic separation was completed on a reversed-phase C18 column using acetonitrile–phosphate buffer（30：70, v/v） as the mobile phase at a flow rate of 1 mL /min and ultraviolet detection wave length was set at 233 nm. The pharmacokinetic study found that the co-administration of neferine and doxorubicin significantly affected the pharmacokinetics of doxorubicin. There were evident changes in area under the curve（AUC）, clearance（CL） and t1/2β in group of pretreatment neferine as compared with those in group treated with doxorubicin alone. Tissue distribution analysis showed that the concentrations of doxorubicin distributed to heart, liver and kidney were statistically significant higher in group of pretreatment with neferine plus doxorubicin than those in the doxorubicin alone-group at 0.5 h and 2 h after drug administration, respectively. While the doxorubicin concentrations in spleen and lung drug were slightly increased in the group of pretreatment with neferine plus doxorubicin as compared to that of group of doxorubicin alone, the difference between two groups were not statistically significant. Therefore, the dose of doxorubicin needs to be taken into consideration when it is administrated in combination with neferine.展开更多
Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment o...Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment of triple-negative breast cancer（TNBC） and human epidermal growth factor receptor-2-（HER2）-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.Methods： TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission（p CR）. Secondary endpoints included clinical response rate, event-free survival（EFS）, and overall survival（OS）.Results： A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of53（range, 8-76） months, the patients achieving p CR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without p CR（P〈0.05）. TAC treatment resulted in consistently better EFS than TC treatment：the estimated 5-year EFS was 66.1% vs. 29.8%（P=0.002）. Moreover, the estimated 5-year OS was also in favor of TAC： 88.4% vs. 51.6%（P〈0.001）. Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio（HR）, 0.48; 95%confidence interval（95% CI）, 0.26-0.90; P=0.021] and OS（HR, 0.20; 95% CI, 0.08-0.60; P=0.003）.Conclusions： The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.展开更多
All-trans retinoic acid(ATRA)and pre-upfront arsenic trioxide(ATO)have revolutionized the therapy of acute promyelocytic leukemia(APL).However,internal tandem duplication of FMS-like tyrosine kinase 3(FLT3-ITD)mutatio...All-trans retinoic acid(ATRA)and pre-upfront arsenic trioxide(ATO)have revolutionized the therapy of acute promyelocytic leukemia(APL).However,internal tandem duplication of FMS-like tyrosine kinase 3(FLT3-ITD)mutations is associated with increased risk of relapse.The aim of this study was to analyze the prognostic impact of FLT3-ITD on APL patients who received remission induction with ATRA,idarubicin(IDA)and/or ATO,followed by ATRA plus ATO along with anthracycline,as consolidation therapy.A total of 72 patients newly diagnosed with APL were included in this study.83.3%of the patients achieved complete remission(CR)after induction therapy.FLT3-ITD mutations were detected in 16(22.2%)patients and closely related to bcr-3 PML-RARa transcript(P<0.001).The 5-year overall survival(OS)rate was 100%in both FLT3-ITDposltlve and FLT3-ITD^(negatlve)groups,and there was no significant difference in 5-year event-free survival(EFS)between the two groups(78.3%vs.83.3%,P=0.85).ATRA plus ATO and anthracycline-based chemotherapy achieved great outcome in newly diagnosed APL regardless of the FLT3-ITD mutation status.展开更多
Anthracyclines (i.e., doxorubicin, daunorubicin) have significant impact on outcome in many pediatric chemotherapy protocols and therefore remain the mainstay of treatment. The objective of this study was to identify ...Anthracyclines (i.e., doxorubicin, daunorubicin) have significant impact on outcome in many pediatric chemotherapy protocols and therefore remain the mainstay of treatment. The objective of this study was to identify the risk factors for anthracycline induced cardiac dysfunction in pediatric patients. Multiple logistic regression model was applied to assess the risk factors for development of cardiac dysfunction. 110 pediatric oncology patients were available for final analysis. 75 (66%) children were males and mean age was 74 ± 44 months. ALL (n = 70, 64%) was the most common primary diagnosis followed by lymphoma (n = 19;17%) and AML (n = 12, 11%). Daunorubicin alone or in combination with doxorubicin was used in (n = 94, 85%) patients and cumulative dose n = 95;86%) children. 24 (22%) children received radiation therapy as per protocol and sepsis were observed in 47 (43%) cases. Post anthracycline, 15 (14%) children had cardiac dysfunction within a month;out of them 10/15 (67%) had isolated diastolic dysfunction, while 28 (25%) developed dysfunction within a year. 19 (17%) had pericardial effusion. 11 expired and out of them, 7 had significant cardiac dysfunction. Cumulative dose > 300 mg/m2 (p p = 0.009;AOR 3.5) and sepsis (p = 0.002;AOR 2.6) were found to be independent risk factors associated anthracycline induced cardiac dysfunction. At univariant level use of daunorubicin alone or in combination therapy (p p 0.048, OR 9.7) were also found statistically significant. In conclusion anthracycline induced cardiac dysfunction is mostly related to cumulative dose > 300 mg/m2, use of Daunorubicin alone or in combination with doxorubicin, mode of delivery, radiation therapy and sepsis. Regular long term follow-up with cardiologist is the key point for early diagnosis and therapy for a long term survival.展开更多
Objective Anthracycline chemotherapeutic agents have significant cardiotoxicity.The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular(LV)myocardial stiffness in breast cancer ...Objective Anthracycline chemotherapeutic agents have significant cardiotoxicity.The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular(LV)myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation(IVP),and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment.Methods A total of 68 newly diagnosed breast cancer patients,who were treated with anthracycline-based chemotherapy,were analyzed.Transthoracic echocardiography was performed at baseline(T0),and after 1,2,3,4 and 8 chemotherapeutic cycles(T1,T2,T3,T4 and T5,respectively).Then,the IVP,LV strain parameters[global longitudinal strain(GLS),longitudinal peak strain rate at systole(LSRs),longitudinal peak strain rate at early diastole(LSRe),longitudinal peak strain rate at late diastole(LSRa),and the E/LSRe ratio],and conventional echocardiographic parameters were obtained and further analyzed.A relative reduction of>15%in GLS was considered a marker of early LV subclinical dysfunction.Results Compared to the T0 stage,IVP significantly increased at the T1 stage.However,there were no significant changes in GLS,LSRs,or LSRe between the T0 and T1 stages.These parameters significantly decreased from the T2 stage.LSRa started to significantly decrease at the T5 stage,and the E/LSRe ratio started to significantly increase at the T3 stage(all P<0.05).At the T0 stage,IVP(AUC=0.752,P<0.001)had a good predictive value for LV subclinical dysfunction after chemotherapy.Conclusions IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.展开更多
Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing c...Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher mortality.Ki-67 is associated with the prognosis and response to therapy,and it changes after NAC.Methods A total of 105 BC patients who received anthracycline-containing NAC were enrolled.Then,the optimal model of Ki-67 was selected,and its predictive efficacy was analyzed.Immunohistochemistry(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 level.Fluorescent in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 decrease.The ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and ORR.The area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),respectively.Multivariate logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictors for anthracycline-containing NAC response,and that they may provide various information for further systematic therapy after surgery in clinical practice.展开更多
Objective： Anthracycline and taxane are the standard agents in combined chemotherapy of advanced breast cancer. However, when these agents based chemotherapy is failure, the selection of salvage regimen is still of p...Objective： Anthracycline and taxane are the standard agents in combined chemotherapy of advanced breast cancer. However, when these agents based chemotherapy is failure, the selection of salvage regimen is still of problem. Gemcitabine, an active agent in both lung cancer and pancreas cancer, is demonstrated effective in breast caner. But there have been relatively less data of gemcitabine in anthracycline and/or taxane-resistant breast cancer. Therefore we employe this study to explore the efficacy and safety of gemcitabine based combination regimen in this population. Methods： From May 2002 to March 2006, 28 patients with measurable lesion of advanced metastatic breast cancer who were resistant to prior anthracycline and taxane based chemotherapy were enrolled. Patients were treated with gemcitabine based combination chemotherapy with a median cycles of 3 （range 2-6）. Results： The overall response rate was 28.6% （8/28）, with 1 CR （Complete response 3.5%） and 7 PRs （Partial response 25%）. Stable disease was seen in 8 patients （28.6%） while disease progressed in 12 patiens （42.8%）. The median time to progression was 4.5 m （range, 2-23 m）. The main toxicity included bone marrow depression, alopecia, mucositis and peripheral neurotoxicity. The grade 3 to 4 clinical adverse effect was leukopenia in 5 cases （17.9%） and thrombocytopenia in 8 cases （30%）. Conclusion： Gemcitabine based combination regimens is feasible in anthracycline and taxane-resistant advanced breast cancer. The clinical response and TTP is acceptable with limited toxicity pattern.展开更多
OBJECTIVE To investigate the role of e IF3a in the regulation of DNA repair pathways in cancer chemotherapeutic response.METHODS Immunohistochemistry was used to determine the expression of e IF3a in lung and breast c...OBJECTIVE To investigate the role of e IF3a in the regulation of DNA repair pathways in cancer chemotherapeutic response.METHODS Immunohistochemistry was used to determine the expression of e IF3a in lung and breast cancer tissues followed by association analysis of e IF3a expression with patient′s response to chemotherapy.Ectopic overexpression and RNA interference knockdown of e IF3a were carried out in NIH3T3and H1299 cell lines,respectively,to determine the effect of altered e IF3a expression on cellular response to chemotherapeutic drugs by using MTT assay.The DNA repair capacity of these cells was evaluated by using host-cell reactivation,NHEJ and HR assay.Real-time reverse transcriptase PCR and Western Blot analyses were carried out to determine the effect of e IF3a on the DNA repair genes by using cells with altered e IF3a expression.RESULTS e IF3a expression associates with response of lung and breast cancer patients to platinum and anthracycline.e IF3a knockdown or overexpression,respectively,increased and decreased the cellular resistance to cisplatin and anthracycline anticancer drugs,DNA repair activity,and expression of NER and NHEJ DNA repair proteins.CONCLUSION e IF3a plays an important role in regulating the expression of NER and NHEJ DNA repair proteins which,in turn,contributes to cellular response to DNA-damaging anticancer drugs and patients′response to platinum and anthracycline chemotherapy.展开更多
BACKGROUND Cardiovascular side effects occur frequently during anti-cancer treatment, and there is a growing concern that they may lead to premature morbidity and death. CASE SUMMARY A 32-year-old woman was diagnosed ...BACKGROUND Cardiovascular side effects occur frequently during anti-cancer treatment, and there is a growing concern that they may lead to premature morbidity and death. CASE SUMMARY A 32-year-old woman was diagnosed with breast cancer. After comprehensive treatment with neoadjuvant chemotherapy, surgery, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy, and endocrine therapy, her breast cancer was cured. However, heart failure associated with anti-cancer treatment presented, most probably related to chemotherapy containing anthracycline. After active treatment, her cardiac function returned to normal. Unfortunately, follow-up visits revealed a second primary malignancy, lymphoma. After multiple courses of chemotherapy combined with targeted therapy, her lymphoma acquired complete remission and no cardiotoxicity was observed again. Heart failure related to breast treatment may be reversible. CONCLUSION Using alternatives to anthracycline in patients with lymphoma who are at risk of cardiac failure may preserve cardiac function.展开更多
文摘Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of the first chemotherapeutic agents introduced in the 1960 s, has been the backbone for the last 30 years and has been used extensively so far. However, the cardiac toxicity and the concern for secondary hematological malignancy has always been a challenge. A better understanding of the tumor biology, role of Her2 expression and the discovery of trastuzumab and other anti-Her 2 agents along with other effective novel therapeutic options, have revolutionized the treatment for breast cancer. The role of anthracyclines has come under close scrutiny, especially in the adjuvant setting for patients with early stage breast cancer and those with low or intermediate risk of disease recurrence. Recent studies have highlighted such a shift in the use of anthracyclines in both the academic and community clinical practice. However, in patients with a high risk of relapse, anthracyclines still hold promise. Ongoing clinical trials are underway to further define the role of anthracyclines in such a patient population. This review highlights the development, clinical utility, limitations and potential future use of anthracyclinesin the adjuvant setting for patients with breast cancer. We consulted Pub Med, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review.
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD0525700 to T.L.)the National Natural Science Foundation of China(82403698 to X.L.)+5 种基金the Postdoctoral Fellowship Program of CPSF grant(GZC20233348 to X.L.)the National Natural Science Foundation of China grant(82472779 to X.G.)the National Natural Science Foundation of China grant(82372881 to W.H.)the Chongqing Natural Science Foundation(CSTB2024NSCQ-MSX1030 to X.L.)the Chongqing Medical Youth Top Talent Project(YXQN202431 to X.L.)the Qiande Excellent Young Talent Project(2025QDYQ-06 to X.L.).
文摘Chemoresistance remains the major barrier to cancer treatment.Metabolic and epigenetic reprogramming are involved in this process;however,the precise roles and mechanisms are largely unknown.Here,we report that lactate-induced lactylation promotes chemoresistance to anthracyclines by regulating homologous recombination(HR)repair.Using the global lactylome,we revealed the landscape of differentially lactylated sites and proteins in cancer cells isolated from resistant and nonresistant tumors.Specifically,BLM,a crucial helicase in the HR repair process,is highly lactylated at Lys24 by AARS1 in response to chemotherapy.
基金Supported by the National Natural Science Foundation of China(No.81973689,No.82074254)the Beijing Natural Science Foundation of China(No.7202176)。
文摘Objective:To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines.Methods:Randomized controlled trials(RCTs)were identified by searching China National Knowledge Infrastructure(CNKI),Wanfang Database,Chinese Biomedical Literature Database(CBM),Pub Med,Cochrane Library,and Embase Databases from the inceptions until December 2020.The Cochrane Handbook was used to evaluate the risk of bias in the included studies.Data analysis was conducted using Rev Man 5.3 software.Results:Totally 19 RCTs with 2,331 participants were included in this review.Results showed that in improving arrhythmia(13 RCTs,n=1,877,RR=0.37,95%CI 0.25 to 0.52,P<0.00001),the treatment group was superior to the control group.In terms of reducing left ventricular end-diastolic diameter(LVEDD,2 RCTs,n=128,MD=-0.79,95%CI-0.93 to-0.65,P<0.00001)and left ventricular end systolic diameter(LVESD,2 RCTs,n=128,MD=-0.58,95%CI-0.82 to-0.35,P<0.00001),the treatment group was also better than the control group.In reducing myocardial enzymes such as creatine kinase(CK)[(3 RCTs,n=256,SMD=-0.80,95%CI-1.16 to-0.44,P<0.0001),(2 RCTs,n=126,SMD=-0.62,95%CI-0.98 to-0.26,P=0.0007)],the treatment group was superior to the control group.Conclusion:Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines.However,in the future,it is still necessary to conduct high-quality RCTs to verify its efficacy.
文摘Background： Cardiotoxicity is one of the most serious chronic complications ofanthracyclines therapy. Assessment of the left ventricular ejection fraction （LVEF） fails to detect subtle cardiac dysfunction of left ventricular （LV）. This study aimed to detect and evaluate new parameters of subclinical anthracyclines＇ cardiotoxicity in children with solid tumor. Methods： A detailed echocardiographic examination was performed in 36 children with hepatoblastoma or rhabdomyosarcoma after receiving anthracyclines＇ chemotherapy and 36 healthy controls from January 2015 to December 2016. The LVEF, ratio of early diastolic peak velocity of transmitral flow （E） and septal diastolic e＇ mitral annular peak velocity （e＇）, tricuspid annular plane systolic excursion （TAPSE）, and LV global longitudinal strain （GLS） were evaluated using M-mode, tissue Doppler imaging （TDI）, and two-dimensional speckle tracking echocardiography （2D-STE）, respectively. Echocardiographic parameters were compared between patient group and healthy controls. All patients were divided into two subgroups based on their anthracyclines＇ cumulative dosage （〈300 mg/m^2 subgroup and ≥300 mg/m^2 subgroup）. Results： All patients had no presentation of heart failure and LVEF within normal range （65.7 ± 5.1%）. Compared with healthy controls, the mean E/e＇ increased significantly （7.9 ±0.7 vs. 10.2 ± 3.5, t = 3.72, P 〈 0.01 ）, mean TAPSE decreased significantly （ 17.2 ± 1.3 mm vs. 14.2 ± 3.0 mm, t = -4.03, P 〈 0.01）, and mean LV GLS decreased significantly （-22.2% ± 1.9% vs. -17.9% ± 2.9%, t = -5.58, P 〈 0.01） in patient group. Compared with subgroup with anthracyclines＇ cumulative dosage 〈 300 mg/m^2, mean LV GLS decreased significantly （- 18.7 ＋ 2.7% vs. - 16.5 ~ 2. 1%, t = 2.15, P = 0.04）, the mean E/e＇ increased significantly （9.1 ±1.5 vs. 11.5 ± 4.9, t = -2.17, P = 0.04）, and mean TAPSE decreased significantly （14.2±2.1 mm vs. 12.5±2.2 mm, t = -2.82, P = 0.02） in subgroup with anthracyclines＇ cumulative dosage 〉300 mg/m^2. Conclusions： LV GLS is helpful in the early detection of subclinical LV dysfunction using 2D-STE. E/e＇ and TAPSE are other sensitive parameters in detecting subclinical cardiac dysfunction of both ventricles by TD1. These parameters show significant change with different anthracyclines＇ cumulative dosage, so cumulative dosage should be controlled in clinical treatment.
文摘The taxanes family of chemotherapy,which includes paclitaxel and docetaxel,has been incorporated in the adjuvant breast cancer treatments since 1990s.Sequential and concurrent use of taxanes was investigated with anthracyclines in many adjuvant early breast cancer randomized clinical trials.Results from taxanes trials showed inconsistent benefits.However,several meta-analyses showed significant survival benefit of adding taxanes.In this review article,data were collected and summarized from eleven large randomized trials and three meta-analyses to show and discuss the magnitude of benefit of taxanes-anthracyclines combination compared to anthracyclines only adjuvant regimens in early breast cancer.This article aims at providing the oncologists with a well-organized,inclusive and updated evidence.
基金supported by the National Natural Science Foundation of China(No.82173947).
文摘Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy(DIC);however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action.Through network medicine analysis, astragaloside Ⅳ(AsⅣ) and formononetin(FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsⅣ-FMT combination(AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsⅣ and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
基金Supported by Medical and Health Foundation Project of Zhejiang Province,China,No.2020KY690Natural Science Foundation of Zhejiang Province,China,No.LGF20H020004.
文摘BACKGROUND The anthracycline chemotherapeutic drugs are cardiotoxic.Studies have found some indicators related to cardiotoxicity.However,there is currently no accurate indicator that can predict cardiac toxicity early.AIM To explore the diagnostic value of real-time three-dimensional echocardiography(RT3DE)in predicting cardiac toxicity in breast cancer patients undergoing chemotherapy.METHODS Female breast cancer patients who underwent radical mastectomy and postoperative chemotherapy at the Affiliated Hanzhou First People’s Hospital,Zhejiang University School of Medicine were recruited.All patients were routinely administered with chemotherapy for four cycles(T1-T4)after surgery.Two-dimensional(2D)echocardiography,RT3DE,and serological examinations were performed after each cycle of chemotherapy.Patients were divided into a toxic group and a non-toxic group based on whether patients hadΔleft ventricular ejection fraction>10%after one year of chemotherapy.Repeated measurement analysis of variance was used to compare the changes in 2D echocardiographic indicators,serological indicators,and RT3DE indicators before independent predictive indicators for cardiac toxicity in postoperative chemotherapy patients.Receiver operating characteristics(ROC)curve analysis was performed to analyze the diagnostic value of potential indicators in the diagnosis of cardiotoxicity.RESULTS A total of 107 female breast cancer patients were included in the study.T4 maximum peak velocity in early diastole(E peak)/mitral annulus lateral tissue Doppler(e'peak)(E/e'),serological indicators[T4 cardiac troponin I(cTnI)and T4 pro-brain natriuretic peptide(Pro-BNP)],T3 minimum left atrial volume(LAV),T4 LAVmin,T3 LAV before the start of the P wave(LAVprep),and T4 LAVprep in the toxicity group were significantly higher than those in the nontoxic group.Multivariate logistic regression found that T4 cTnI,T4 Pro-BNP,T3 LAVmin,T4 LAVmin,T3 LAVprep,and T4 LAVprep had potential predictive value for cardiac toxicity(P<0.05).ROC results showed that T4 LAVmin had the highest accuracy for diagnosing cardiac toxicity[area under the curve(AUC)=0.947;sensitivity=78.57%;specificity=94.62%],followed by T4 LAVprep(AUC=0.899;sensitivity=100%;specificity=66.67%).The accuracies of LAVprep and LAVprep in predicting cardiac toxicity were higher than those of T3 LAVmin and T3 LAVprep.CONCLUSION RT3DE of left atrial volume can be used to predict the cardiotoxicity caused by chemotherapy,and it is expected to guide the clinical adjustment of dose and schedule in time.
文摘Acute myeloid leukemia (AML), a rapidly progressing hematopoietic malignancy, can only be cured hopefully by hematopoietic stem cells transplantation (HSCT). Before HSCT, we usually exert effects by attempting certain regimens to induce these tumor cells to death. Administered in AML patients, the classic “3 + 7” intensive induction regimen including anthracyclines and cytarabine is recommended by guidelines worldwide. However, conventional regimens consist of anthracyclines, a category of drug limited by cumulative, dose-related, progressive myocardial damage and congestive heart failure occurs when its total doses break through the cut-off. Based on this background, mitoxantrone (MIT), an anthraquinone, was developed to a new form to reduce cardiotoxicity. Meanwhile, the nanomedicine, mitoxantrone liposome (Lipo-MIT), was characterized by improved bioavailability and limited toxicity. This drug has great therapeutic potential, but different side effects. We conclude the overall history and development of MIT and Lipo-MIT, which show controversial efficacy of MIT compared to doxorubicin and therapeutic potential of Lipo-MIT. This article reviewed the application of MIT and liposome forms in adult AML patients. .
文摘In commenting on a case report of a 55-year-old man who suffered Takotsubo syndrome(TTS), in the setting of receiving chemotherapy with cytarabine and daunorubicin for acute myeloid leukemia, the author expresses his views that TTS in the setting of chemotherapy for malignancies may not be chemotherapeutic drug-specific(like in the chemotherapeutic drug induced-cardiomyopathy), but may be due to the emotional and physical stresses resulting from the realization of having diagnosed with a malignancy, and the diagnostic testing, and therapeutic management which follows.
文摘The number of women with heart disease who reach childbearing age in a good functional state increases continuously as advances in diagnosis and treatment improve overall health and prognosis. The cardiologist’s role is to give the woman an estimate of both maternal and fetal risk to allow her to make an informed decision about embarking on a pregnancy, and to provide appropriate antenatal care. There are only a few data about the natural history of anthracycline-induced cardiomyopathy during preg- nancy;we report our experience of a 29-year- old pregnant woman with a history of anthracycline-induced clinical heart failure.
文摘BACKGROUND AND OBJECTIVES: The objective of this study was to assess the antitumor activity and toxicity profile of gemcitabine combined with epirubicin in patients with recurrent platinum refractory ovarian epithelial cancer. PATIENTS AND METHODS: Patients with recurrent platinum refractory ovarian cancer and with adequate hematologic, renal and hepatic function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 were enrolled. The regimen was Gemcitabine 1000 mg/m2 (day 1, 8) and Epirubicin 60 mg/m2 (day 1), the cycle was repeated at interval of 21 days. RESULTS: Twenty eight patients were recruited and received 156 cycles of gemcitabine-epirubicin combination chemotherapy (median 6 cycles). Overall response rate was 42.9% (95% CI equal 24.5 to 62.7) and tumor control rate was 75% (95% CI equal 55.1 to 89.3). No complete responses were observed. Median progression-free and median overall survival times were 7 and 15 months, respectively. The most common grade 3/4 hematological toxicities were neutropenia (57.1%), anemia (10.7%), and thrombocytopenia (7.1%), while the most common grade 3/4 non-hematological toxicities were mucositis (14.3%) and vomiting (3.6%). No treatment related deaths were observed. CONCLUSION: Gemcitabine combined with epirubicin regimen appeared to offer an acceptable clinical profile in patients with recurrent platinum-refractory epithelial ovarian cancer.
基金The Scientific Research Fund Project of Heilongjiang University of Chinese Medicine(Grant No.201420)
文摘Doxorubicin is one of the anthracycline anti-neoplastic drugs widely used to treat leukemia, liver, breast, and ovarian cancers and other solid tumors. However, its clinical applications have been limited by its serious cardio-cytotoxic effects. The aim of this study was to investigate the effect of neferine, a bisbenzylisoquinoline alkaloid extracted from the green embryo in the mature lotus seed, on the pharmacokinetics of doxorubicin. The levels of doxorubicin in plasma and tissues were measured using the high performance liquid chromatography（HPLC） method. The chromatographic separation was completed on a reversed-phase C18 column using acetonitrile–phosphate buffer（30：70, v/v） as the mobile phase at a flow rate of 1 mL /min and ultraviolet detection wave length was set at 233 nm. The pharmacokinetic study found that the co-administration of neferine and doxorubicin significantly affected the pharmacokinetics of doxorubicin. There were evident changes in area under the curve（AUC）, clearance（CL） and t1/2β in group of pretreatment neferine as compared with those in group treated with doxorubicin alone. Tissue distribution analysis showed that the concentrations of doxorubicin distributed to heart, liver and kidney were statistically significant higher in group of pretreatment with neferine plus doxorubicin than those in the doxorubicin alone-group at 0.5 h and 2 h after drug administration, respectively. While the doxorubicin concentrations in spleen and lung drug were slightly increased in the group of pretreatment with neferine plus doxorubicin as compared to that of group of doxorubicin alone, the difference between two groups were not statistically significant. Therefore, the dose of doxorubicin needs to be taken into consideration when it is administrated in combination with neferine.
基金supported in part by the grants from the National Natural Science Foundation of China (Grant No. 81472462)Medical Guidance Foundation of Shanghai Municipal Science and Technology Commission (Grant No. 15411966400)Technology Innovation Act Plan of Shanghai Municipal Science and Technology Commission (Grant No. 14411950200, 14411950201) and Sanofi
文摘Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment of triple-negative breast cancer（TNBC） and human epidermal growth factor receptor-2-（HER2）-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.Methods： TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission（p CR）. Secondary endpoints included clinical response rate, event-free survival（EFS）, and overall survival（OS）.Results： A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of53（range, 8-76） months, the patients achieving p CR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without p CR（P〈0.05）. TAC treatment resulted in consistently better EFS than TC treatment：the estimated 5-year EFS was 66.1% vs. 29.8%（P=0.002）. Moreover, the estimated 5-year OS was also in favor of TAC： 88.4% vs. 51.6%（P〈0.001）. Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio（HR）, 0.48; 95%confidence interval（95% CI）, 0.26-0.90; P=0.021] and OS（HR, 0.20; 95% CI, 0.08-0.60; P=0.003）.Conclusions： The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.
文摘All-trans retinoic acid(ATRA)and pre-upfront arsenic trioxide(ATO)have revolutionized the therapy of acute promyelocytic leukemia(APL).However,internal tandem duplication of FMS-like tyrosine kinase 3(FLT3-ITD)mutations is associated with increased risk of relapse.The aim of this study was to analyze the prognostic impact of FLT3-ITD on APL patients who received remission induction with ATRA,idarubicin(IDA)and/or ATO,followed by ATRA plus ATO along with anthracycline,as consolidation therapy.A total of 72 patients newly diagnosed with APL were included in this study.83.3%of the patients achieved complete remission(CR)after induction therapy.FLT3-ITD mutations were detected in 16(22.2%)patients and closely related to bcr-3 PML-RARa transcript(P<0.001).The 5-year overall survival(OS)rate was 100%in both FLT3-ITDposltlve and FLT3-ITD^(negatlve)groups,and there was no significant difference in 5-year event-free survival(EFS)between the two groups(78.3%vs.83.3%,P=0.85).ATRA plus ATO and anthracycline-based chemotherapy achieved great outcome in newly diagnosed APL regardless of the FLT3-ITD mutation status.
文摘Anthracyclines (i.e., doxorubicin, daunorubicin) have significant impact on outcome in many pediatric chemotherapy protocols and therefore remain the mainstay of treatment. The objective of this study was to identify the risk factors for anthracycline induced cardiac dysfunction in pediatric patients. Multiple logistic regression model was applied to assess the risk factors for development of cardiac dysfunction. 110 pediatric oncology patients were available for final analysis. 75 (66%) children were males and mean age was 74 ± 44 months. ALL (n = 70, 64%) was the most common primary diagnosis followed by lymphoma (n = 19;17%) and AML (n = 12, 11%). Daunorubicin alone or in combination with doxorubicin was used in (n = 94, 85%) patients and cumulative dose n = 95;86%) children. 24 (22%) children received radiation therapy as per protocol and sepsis were observed in 47 (43%) cases. Post anthracycline, 15 (14%) children had cardiac dysfunction within a month;out of them 10/15 (67%) had isolated diastolic dysfunction, while 28 (25%) developed dysfunction within a year. 19 (17%) had pericardial effusion. 11 expired and out of them, 7 had significant cardiac dysfunction. Cumulative dose > 300 mg/m2 (p p = 0.009;AOR 3.5) and sepsis (p = 0.002;AOR 2.6) were found to be independent risk factors associated anthracycline induced cardiac dysfunction. At univariant level use of daunorubicin alone or in combination therapy (p p 0.048, OR 9.7) were also found statistically significant. In conclusion anthracycline induced cardiac dysfunction is mostly related to cumulative dose > 300 mg/m2, use of Daunorubicin alone or in combination with doxorubicin, mode of delivery, radiation therapy and sepsis. Regular long term follow-up with cardiologist is the key point for early diagnosis and therapy for a long term survival.
基金the Hubei Province Health and Famliy Planning Scientific Research Project(No.WJ2023M011)the Department of Finance of Hubei Province(No.3890750).
文摘Objective Anthracycline chemotherapeutic agents have significant cardiotoxicity.The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular(LV)myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation(IVP),and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment.Methods A total of 68 newly diagnosed breast cancer patients,who were treated with anthracycline-based chemotherapy,were analyzed.Transthoracic echocardiography was performed at baseline(T0),and after 1,2,3,4 and 8 chemotherapeutic cycles(T1,T2,T3,T4 and T5,respectively).Then,the IVP,LV strain parameters[global longitudinal strain(GLS),longitudinal peak strain rate at systole(LSRs),longitudinal peak strain rate at early diastole(LSRe),longitudinal peak strain rate at late diastole(LSRa),and the E/LSRe ratio],and conventional echocardiographic parameters were obtained and further analyzed.A relative reduction of>15%in GLS was considered a marker of early LV subclinical dysfunction.Results Compared to the T0 stage,IVP significantly increased at the T1 stage.However,there were no significant changes in GLS,LSRs,or LSRe between the T0 and T1 stages.These parameters significantly decreased from the T2 stage.LSRa started to significantly decrease at the T5 stage,and the E/LSRe ratio started to significantly increase at the T3 stage(all P<0.05).At the T0 stage,IVP(AUC=0.752,P<0.001)had a good predictive value for LV subclinical dysfunction after chemotherapy.Conclusions IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.
基金supported by grants from the Beijing Hospitals Authority Youth Programme,China(No.QML20231602)the Young Elite Scientist Sponsorship Program by Beijing Association for Science and Technology(BAST)(No.BYESS2023226).
文摘Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher mortality.Ki-67 is associated with the prognosis and response to therapy,and it changes after NAC.Methods A total of 105 BC patients who received anthracycline-containing NAC were enrolled.Then,the optimal model of Ki-67 was selected,and its predictive efficacy was analyzed.Immunohistochemistry(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 level.Fluorescent in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 decrease.The ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and ORR.The area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),respectively.Multivariate logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictors for anthracycline-containing NAC response,and that they may provide various information for further systematic therapy after surgery in clinical practice.
文摘Objective： Anthracycline and taxane are the standard agents in combined chemotherapy of advanced breast cancer. However, when these agents based chemotherapy is failure, the selection of salvage regimen is still of problem. Gemcitabine, an active agent in both lung cancer and pancreas cancer, is demonstrated effective in breast caner. But there have been relatively less data of gemcitabine in anthracycline and/or taxane-resistant breast cancer. Therefore we employe this study to explore the efficacy and safety of gemcitabine based combination regimen in this population. Methods： From May 2002 to March 2006, 28 patients with measurable lesion of advanced metastatic breast cancer who were resistant to prior anthracycline and taxane based chemotherapy were enrolled. Patients were treated with gemcitabine based combination chemotherapy with a median cycles of 3 （range 2-6）. Results： The overall response rate was 28.6% （8/28）, with 1 CR （Complete response 3.5%） and 7 PRs （Partial response 25%）. Stable disease was seen in 8 patients （28.6%） while disease progressed in 12 patiens （42.8%）. The median time to progression was 4.5 m （range, 2-23 m）. The main toxicity included bone marrow depression, alopecia, mucositis and peripheral neurotoxicity. The grade 3 to 4 clinical adverse effect was leukopenia in 5 cases （17.9%） and thrombocytopenia in 8 cases （30%）. Conclusion： Gemcitabine based combination regimens is feasible in anthracycline and taxane-resistant advanced breast cancer. The clinical response and TTP is acceptable with limited toxicity pattern.
基金The project supported by National High-tech R&D Program of China 863 Program Grant(2009AA022704)National Natural Science Foundation of China(81573463,81173129,81202595 and NIH Grant CA 94961)
文摘OBJECTIVE To investigate the role of e IF3a in the regulation of DNA repair pathways in cancer chemotherapeutic response.METHODS Immunohistochemistry was used to determine the expression of e IF3a in lung and breast cancer tissues followed by association analysis of e IF3a expression with patient′s response to chemotherapy.Ectopic overexpression and RNA interference knockdown of e IF3a were carried out in NIH3T3and H1299 cell lines,respectively,to determine the effect of altered e IF3a expression on cellular response to chemotherapeutic drugs by using MTT assay.The DNA repair capacity of these cells was evaluated by using host-cell reactivation,NHEJ and HR assay.Real-time reverse transcriptase PCR and Western Blot analyses were carried out to determine the effect of e IF3a on the DNA repair genes by using cells with altered e IF3a expression.RESULTS e IF3a expression associates with response of lung and breast cancer patients to platinum and anthracycline.e IF3a knockdown or overexpression,respectively,increased and decreased the cellular resistance to cisplatin and anthracycline anticancer drugs,DNA repair activity,and expression of NER and NHEJ DNA repair proteins.CONCLUSION e IF3a plays an important role in regulating the expression of NER and NHEJ DNA repair proteins which,in turn,contributes to cellular response to DNA-damaging anticancer drugs and patients′response to platinum and anthracycline chemotherapy.
文摘BACKGROUND Cardiovascular side effects occur frequently during anti-cancer treatment, and there is a growing concern that they may lead to premature morbidity and death. CASE SUMMARY A 32-year-old woman was diagnosed with breast cancer. After comprehensive treatment with neoadjuvant chemotherapy, surgery, postoperative adjuvant chemotherapy, postoperative adjuvant radiotherapy, and endocrine therapy, her breast cancer was cured. However, heart failure associated with anti-cancer treatment presented, most probably related to chemotherapy containing anthracycline. After active treatment, her cardiac function returned to normal. Unfortunately, follow-up visits revealed a second primary malignancy, lymphoma. After multiple courses of chemotherapy combined with targeted therapy, her lymphoma acquired complete remission and no cardiotoxicity was observed again. Heart failure related to breast treatment may be reversible. CONCLUSION Using alternatives to anthracycline in patients with lymphoma who are at risk of cardiac failure may preserve cardiac function.
