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
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 To establish a flow-injection chemiluminescence method for the determination of doxorubicin,epirubicin and mitoxantrone and study its reaction mechanism.Methods In alkaline medium,chemiluminescence of lumino...Objective To establish a flow-injection chemiluminescence method for the determination of doxorubicin,epirubicin and mitoxantrone and study its reaction mechanism.Methods In alkaline medium,chemiluminescence of luminol-potassium permanganate system could be inhibited obviously by anthracycline antibiotics.Combined with flow-injection technique,a new chemiluminescence method for determining the anthracycline antibiotics was set up.The chemiluminescence mechanism of the luminol-potassium permanganate system was also discussed.Results Under optimal conditions,the good linear ranges of doxorubicin,epirubicin and mitoxantrone were 5.0×10-9-1.0×10-6g/mL,1.0×10-9-1.0×10-5g/mL and 3×10-9-1.0×10-6g/mL,respectively.The detection limits of doxorubicin,epirubicin and mitoxantrone were 3.0×10-9g/mL,5.0×10-8g/mL and 2.0×10-9g/mL,respectively.During eleven repeated inter-day and intra-day precision tests of 1.0×10-6g/mL samples,the relative standard deviations corresponded to reference values of 3.0%,2.8% and 2.1%.Conclusion The developed method is sensitive,accurate,rapid and of low cost.It can be applied to determine doxorubicin hydrochloride,epirubicin hydrochloride and mitoxantrone hydrochloride in injection preparations.展开更多
Objective:To evaluate the effect of traditional Chinese medicine(TCM)on anthracycline-induced cardiotoxicity(AIC)in animal models.Methods:Separate systematic searches for preclinical studies were performed in the PubM...Objective:To evaluate the effect of traditional Chinese medicine(TCM)on anthracycline-induced cardiotoxicity(AIC)in animal models.Methods:Separate systematic searches for preclinical studies were performed in the PubMed,EMBASE,Web of Science,Chinese National Knowledge Infrastructure,Chinese Biomedical Database,Chinese Scientific Journal Database,and Wanfang Data from inception to August 2019.The primary outcomes were echocardiography,serum assays for myocardial enzymograms,histological assessments,and electrocardiograms.The secondary outcomes mainly included body weight and safety evaluations.The protocol is registered on PROSPERO(CRD42019145819).RevMan(V.5.3)was used for meta-analysis.Results:We identified 10 studies from 9 international scientific publications describing the efficacy of TCM on AIC animal models.All the included studies reported that,compared with animal model without any intervention,TCM significantly improved ventricular function,cardiac biomarkers,electrocardiograph results,and cardiac fibrosis.Improved survival rates and body mass indices were also observed with TCM.We further pooled the available data from four studies(63 animals)for the meta-analysis and the results showed that,compared with models without any intervention,TCM significantly increased the ejection fraction by 14.13%(95%CI,9.96e18.29)and fraction shortening by 8.66%(95%CI,6.05 e11.26).Creatine kinase-MB(SMD=2.49,95%CI:-3.12 to-1.85)and lactate dehydrogenase(SMD=-2.78,95%CI:-3.45 to-2.12)were also significantly decreased by TCM.Conclusions:TCM is effective in improving AIC in animal models and has tremendous potential to be translated to treat AIC in clinical practice.Additionally,the systematic review and meta-analysis of animal experiments may be valuable in enhancing and guiding animal experiments and promoting the transformation of the results.展开更多
A new Mutactimycin group antibiotic(XF-1)was isolated from the mycelium of Streptomyces sp.80-115 and its structure has been determined on the basis of its spectroscopical and chemical properties. XF-1 showed active a...A new Mutactimycin group antibiotic(XF-1)was isolated from the mycelium of Streptomyces sp.80-115 and its structure has been determined on the basis of its spectroscopical and chemical properties. XF-1 showed active against some Gram positive bacteria.展开更多
BACKGROUND Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment.The use of anthracycline is limited by dose-dependent cardiot...BACKGROUND Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment.The use of anthracycline is limited by dose-dependent cardiotoxicity,which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart failure.Despite baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents,there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity(AIC).CASE SUMMARY A 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70%determined by transthoracic and dobutamine stress echocardiogram.She underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery,and received a total of 450 mg/m2 doxorubicin at the end of her treatment course.She was evaluated regularly during chemotherapy without any cardiac or respiratory symptoms.Approximately two months after her last chemotherapy,the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory failure.Echocardiogram showed an ejection fraction of 5%-10%with severe biventricular failure.Despite attempts to optimize cardiac function,the patient’s hemodynamic status continued to decline,and resuscitation was not successful on the seventh day of hospitalization.The autopsy showed no evidence of osteosarcoma,and the likely cause of death was cardiac failure with the evidence of pulmonary congestion,liver congestion,and multiple body cavity effusions.CONCLUSION We present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m2 doxorubicin over 9 mo.Cardiac monitoring and management of patients receiving anthracycline chemotherapy have been an area of intense research since introduction of these agents in clinical practice.We have reviewed literature and recent advances in the prediction and prevention of AIC.Although risk factors currently identified can help stratify patients who need closer monitoring,there are limitations to our current understanding and further research is needed in this field.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:Cancer patients who are exposed to sepsis and had previous chemotherapy may have increased severity. Among chemotherapeutic agents, anthracyclines have been associated with cardiac toxicity. Like other chem...Background:Cancer patients who are exposed to sepsis and had previous chemotherapy may have increased severity. Among chemotherapeutic agents, anthracyclines have been associated with cardiac toxicity. Like other chemotherapeutic agents, they may cause endothelial toxicity. The aim of this study was to evaluate the effect of anthracycline treatment on the outcome of cancer patients with sepsis.Methods:Data from cancer patients admitted to intensive care units (ICUs) for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994-2015). Comparison between patients who received anthracycline and those who did not was performed using a propensity score, including confounding variables (age and underlying diseases). A competing risk adjusted for severity of illness (Sequential Organ Failure Assessment [SOFA] score) was used to analyze the duration of vasopressor requirement.Results:Among 2046 patients, 1070 (52.3%) patients who received anthracycline were compared with 976 (47.7%) who did not. The underlying disease was mostly acute hematological malignancy (49.2%). Sepsis, mostly pneumonia (47.7%), had developed 2 days (interquartile range [IQR]:1-4 days) prior to ICU admission. Most patients (n=1156/1980,58.4%) required vasopressors for 3 days (IQR: 2-6 days). Factors associated with the need for vasopressors were aplasia (hazard ratio [HR]=1.72, 95% confidence interval [CI]: 1.21 to 2.47, P=0.002) and day 1 respiratory SOFA score (HR=7.07, 95% CI: 2.75 to 22.1, P <0.001). Previous anthracycline treatment was not associated with an increased risk of vasopressor use. The duration of vasopressors was not different between patients who received anthracycline and those who did not (P=0.79). Anthracycline was not associated with ICU mortality.Conclusion:Previous anthracycline treatment did not alter the course of sepsis in a cohort of cancer patients admitted to intensive care with sepsis.展开更多
Chemotherapy-induced cardiovascular disease has become one of the main causes of death in cancer survivors.Several international authoritative societies have developed a number of guidelines to standardize clinical pr...Chemotherapy-induced cardiovascular disease has become one of the main causes of death in cancer survivors.Several international authoritative societies have developed a number of guidelines to standardize clinical practice for the emerging discipline of cardio-oncology,aiming to allow patients to receive cancer treatment while reducing the risk of cardio-vascular events.Anthracyclines,as the earliest first-line chemotherapy drugs,have attracted much attention from researchers due to their severe cardiotoxicity.Although targeted therapy and immunotherapy strategies improve anticancer efficacy,they also increase the risk of cardiotoxicity.Therefore,anthracyclines are still indispensable in cancer treatment,and in-depth understanding of the mechanism of cardiotoxicity will help to develop effective therapeutic strategies.This review aims to summarize the new mechanisms of cardiotoxicity caused by anthracyclines and cur-rent emerging therapeutic strategies.展开更多
Purpose Anthracyclines have been one of the standard therapies for breast cancer(BC),and dose-related cardiotoxicity is one serious side effect.Exercise is an effective strategy for the prevention and management of BC...Purpose Anthracyclines have been one of the standard therapies for breast cancer(BC),and dose-related cardiotoxicity is one serious side effect.Exercise is an effective strategy for the prevention and management of BC,endorsed by experts in both exercise and oncology.However,there is a great deal of confusion about the effectiveness of exercise on anthracycline-induced cardiotoxicity and the exercise prescription(i.e.,timing,type,and intensity)for cardiotoxicity,which limits its application in clinical settings.The aim of this article is to review the safety of exercise in BC patients receiving anthracy-clines and its effectiveness in preventing cardiotoxicity.Methods Six electronic databases were searched using terms related to exercise,BC,anthracyclines,and cardiotoxicity for retrieving clinical randomized controlled trials in either Chinese or English.A summary of the included literature was also provided.Results Of 202 records screened,10 were eligible.A total of 434 BC patients(stage I–IIIC,mean age ranged from 43.5 to 52.4 years)were included.The main findings were that:(1)Acute(a single bout)moderate-to-vigorous aerobic exercise could prevent NT-proBNP elevation beyond the threshold of acute myocardial injury;(2)Long-term(>8 weeks)moderate-to-high intensity aerobic exercise(continuous or interval)could improve or maintain left ventricular ejection fraction and cardiorespiratory fitness in BC patients.However,the optimal timing,type,and intensity of exercise for people with BC to prevent cardiotoxicity remain unclear.Conclusion Moderate-to-vigorous intensity exercise may be an effective non-pharmacological approach to mitigate cardio-toxicities induced by anthracyclines in women with BC.However,the optimal exercise prescription for preventing cardio-toxicity remains unclear.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
A novel sub-class of S-adenosyl-L-methionine(SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines.Exemplified by RdmB from Streptomyces purpurascens,it was...A novel sub-class of S-adenosyl-L-methionine(SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines.Exemplified by RdmB from Streptomyces purpurascens,it was found with 10-decarboxylative hydroxylation activity on anthracyclines.We herein investigated the cata-lytic activities of RdmB and discovered a previously unknown 4-O-methylation activity.The site-directed mutagenesis studies proved that the residue at position R307 and N260 are vital for the decarboxylative hy-droxylation and 4-O-methylation,respectively,which define two distinct catalytic centers in RdmB.Further-more,the multifunctionality of RdmB activity was found as cofactor-dependent and stepwise.Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural di-versity and bioactivities of anthracyclines.展开更多
Background There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel...Background There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer （MBC） in older Chinese patients. Methods MBC patients aged 〉65 years pretreated with 1-5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m^2 twice daily, days 1-14, plus docetaxel 30 mg/m^2 on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles （median 4, range 2-8） and were evaluable for efficacy. Results The overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia （12%）, alopecia （7%）, grade 3 nausea and vomiting （2%） and grade 3 nail toxicity （2%）. Conclusions Capecitabine 825 mg/m^2 twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women 〉65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.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
Objectives: This article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetre...Objectives: This article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetrexed-based regimens. Methods: PubMed, Embase, OVID, and the Cochrane Library databases were searched from the beginning of each database without any limitations to the date of publication. Search terms were‘‘pemetrexed’’ or‘‘LY231514’’ or“Alimta”,“metastatic breast cancer”, and“advanced breast cancer”. Results: There were 15 studies (n ? 1002) meeting our criteria for evaluation. Eight single-agent trials (n ? 551) and seven using combinations with other agents (n ? 451) were identified that evaluated pemetrexed for use in patients with metastatic breast cancer. Response rates to pemetrexed as a single agent varied from 8%to 31%, and with combination therapy have been reported to be between 15.8% and 55.7%. With routine supplementation of patients with folic acid, dexamethasone, and vitamin B12, the toxicity profile of these patients was mild, including dose-limiting neutropenia and thrombocytopenia, as well as lower grades of reversible hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase (TS) and other biomarkers are associated with the prognosis and sensitivity for pemetrexed in breast cancer. Conclusion: Pemetrexed has shown remarkable activity with acceptable toxicities for treatment of metastatic breast cancer patients. Translational research on pemetrexed in breast cancer identified biomarkers as well as additional genes important to its clinical activity and toxicity. Further research is needed to clarify the role of pemetrexed in breast cancer treatment in order to guide oncologists. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Com-munications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).展开更多
Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably ass...Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably associated with recurrence of TNBC.This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival(DFS)of early-stage TNBC patients treated with anthracycline-and/or taxane-based chemotherapy.Methods:We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline-and/or taxane-based chemotherapy using the sequenom’s MassARRAY system.Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.Results:Three genotypes,AA,GA,and GG,were detected in the rs473543 of ATG5 gene.The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence(P=0.024).Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543(P=0.034).In addition,after adjust-ing for clinical factors,multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS(hazard risk[HR],1.73;95%confidence interval[CI],1.04-2.87;P=0.034).In addition,DFS was shorter in node-negative patients with the presence of A allele(AA/GA)than in those with the absence of A allele(P=0.027).Conclusion:ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.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 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.
文摘Objective To establish a flow-injection chemiluminescence method for the determination of doxorubicin,epirubicin and mitoxantrone and study its reaction mechanism.Methods In alkaline medium,chemiluminescence of luminol-potassium permanganate system could be inhibited obviously by anthracycline antibiotics.Combined with flow-injection technique,a new chemiluminescence method for determining the anthracycline antibiotics was set up.The chemiluminescence mechanism of the luminol-potassium permanganate system was also discussed.Results Under optimal conditions,the good linear ranges of doxorubicin,epirubicin and mitoxantrone were 5.0×10-9-1.0×10-6g/mL,1.0×10-9-1.0×10-5g/mL and 3×10-9-1.0×10-6g/mL,respectively.The detection limits of doxorubicin,epirubicin and mitoxantrone were 3.0×10-9g/mL,5.0×10-8g/mL and 2.0×10-9g/mL,respectively.During eleven repeated inter-day and intra-day precision tests of 1.0×10-6g/mL samples,the relative standard deviations corresponded to reference values of 3.0%,2.8% and 2.1%.Conclusion The developed method is sensitive,accurate,rapid and of low cost.It can be applied to determine doxorubicin hydrochloride,epirubicin hydrochloride and mitoxantrone hydrochloride in injection preparations.
基金This research was supported by the National Natural Science Foundation of China(81530100 and 81822049).
文摘Objective:To evaluate the effect of traditional Chinese medicine(TCM)on anthracycline-induced cardiotoxicity(AIC)in animal models.Methods:Separate systematic searches for preclinical studies were performed in the PubMed,EMBASE,Web of Science,Chinese National Knowledge Infrastructure,Chinese Biomedical Database,Chinese Scientific Journal Database,and Wanfang Data from inception to August 2019.The primary outcomes were echocardiography,serum assays for myocardial enzymograms,histological assessments,and electrocardiograms.The secondary outcomes mainly included body weight and safety evaluations.The protocol is registered on PROSPERO(CRD42019145819).RevMan(V.5.3)was used for meta-analysis.Results:We identified 10 studies from 9 international scientific publications describing the efficacy of TCM on AIC animal models.All the included studies reported that,compared with animal model without any intervention,TCM significantly improved ventricular function,cardiac biomarkers,electrocardiograph results,and cardiac fibrosis.Improved survival rates and body mass indices were also observed with TCM.We further pooled the available data from four studies(63 animals)for the meta-analysis and the results showed that,compared with models without any intervention,TCM significantly increased the ejection fraction by 14.13%(95%CI,9.96e18.29)and fraction shortening by 8.66%(95%CI,6.05 e11.26).Creatine kinase-MB(SMD=2.49,95%CI:-3.12 to-1.85)and lactate dehydrogenase(SMD=-2.78,95%CI:-3.45 to-2.12)were also significantly decreased by TCM.Conclusions:TCM is effective in improving AIC in animal models and has tremendous potential to be translated to treat AIC in clinical practice.Additionally,the systematic review and meta-analysis of animal experiments may be valuable in enhancing and guiding animal experiments and promoting the transformation of the results.
文摘A new Mutactimycin group antibiotic(XF-1)was isolated from the mycelium of Streptomyces sp.80-115 and its structure has been determined on the basis of its spectroscopical and chemical properties. XF-1 showed active against some Gram positive bacteria.
文摘BACKGROUND Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment.The use of anthracycline is limited by dose-dependent cardiotoxicity,which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart failure.Despite baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents,there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity(AIC).CASE SUMMARY A 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70%determined by transthoracic and dobutamine stress echocardiogram.She underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery,and received a total of 450 mg/m2 doxorubicin at the end of her treatment course.She was evaluated regularly during chemotherapy without any cardiac or respiratory symptoms.Approximately two months after her last chemotherapy,the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory failure.Echocardiogram showed an ejection fraction of 5%-10%with severe biventricular failure.Despite attempts to optimize cardiac function,the patient’s hemodynamic status continued to decline,and resuscitation was not successful on the seventh day of hospitalization.The autopsy showed no evidence of osteosarcoma,and the likely cause of death was cardiac failure with the evidence of pulmonary congestion,liver congestion,and multiple body cavity effusions.CONCLUSION We present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m2 doxorubicin over 9 mo.Cardiac monitoring and management of patients receiving anthracycline chemotherapy have been an area of intense research since introduction of these agents in clinical practice.We have reviewed literature and recent advances in the prediction and prevention of AIC.Although risk factors currently identified can help stratify patients who need closer monitoring,there are limitations to our current understanding and further research is needed in this field.
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:Cancer patients who are exposed to sepsis and had previous chemotherapy may have increased severity. Among chemotherapeutic agents, anthracyclines have been associated with cardiac toxicity. Like other chemotherapeutic agents, they may cause endothelial toxicity. The aim of this study was to evaluate the effect of anthracycline treatment on the outcome of cancer patients with sepsis.Methods:Data from cancer patients admitted to intensive care units (ICUs) for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994-2015). Comparison between patients who received anthracycline and those who did not was performed using a propensity score, including confounding variables (age and underlying diseases). A competing risk adjusted for severity of illness (Sequential Organ Failure Assessment [SOFA] score) was used to analyze the duration of vasopressor requirement.Results:Among 2046 patients, 1070 (52.3%) patients who received anthracycline were compared with 976 (47.7%) who did not. The underlying disease was mostly acute hematological malignancy (49.2%). Sepsis, mostly pneumonia (47.7%), had developed 2 days (interquartile range [IQR]:1-4 days) prior to ICU admission. Most patients (n=1156/1980,58.4%) required vasopressors for 3 days (IQR: 2-6 days). Factors associated with the need for vasopressors were aplasia (hazard ratio [HR]=1.72, 95% confidence interval [CI]: 1.21 to 2.47, P=0.002) and day 1 respiratory SOFA score (HR=7.07, 95% CI: 2.75 to 22.1, P <0.001). Previous anthracycline treatment was not associated with an increased risk of vasopressor use. The duration of vasopressors was not different between patients who received anthracycline and those who did not (P=0.79). Anthracycline was not associated with ICU mortality.Conclusion:Previous anthracycline treatment did not alter the course of sepsis in a cohort of cancer patients admitted to intensive care with sepsis.
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0502605)the National Natural Science Foundation of China(82374420 and 82174364)+3 种基金the Beijing-Tianjin-Hebei Basic Research Cooperation project(J230033)the Science and Technology Department of Beijing University of Chinese Medicine(2022-JYB-JBZR-001)the Science and Technology Department of Beijing University of Chinese Medicine(BZY-BZX-2022-08)the Beijing University of Chinese Medicine Graduate Independent Project(ZJKT2023042).
文摘Chemotherapy-induced cardiovascular disease has become one of the main causes of death in cancer survivors.Several international authoritative societies have developed a number of guidelines to standardize clinical practice for the emerging discipline of cardio-oncology,aiming to allow patients to receive cancer treatment while reducing the risk of cardio-vascular events.Anthracyclines,as the earliest first-line chemotherapy drugs,have attracted much attention from researchers due to their severe cardiotoxicity.Although targeted therapy and immunotherapy strategies improve anticancer efficacy,they also increase the risk of cardiotoxicity.Therefore,anthracyclines are still indispensable in cancer treatment,and in-depth understanding of the mechanism of cardiotoxicity will help to develop effective therapeutic strategies.This review aims to summarize the new mechanisms of cardiotoxicity caused by anthracyclines and cur-rent emerging therapeutic strategies.
基金supported by the National Key Research and Development Program Project(2020YFC2006705).
文摘Purpose Anthracyclines have been one of the standard therapies for breast cancer(BC),and dose-related cardiotoxicity is one serious side effect.Exercise is an effective strategy for the prevention and management of BC,endorsed by experts in both exercise and oncology.However,there is a great deal of confusion about the effectiveness of exercise on anthracycline-induced cardiotoxicity and the exercise prescription(i.e.,timing,type,and intensity)for cardiotoxicity,which limits its application in clinical settings.The aim of this article is to review the safety of exercise in BC patients receiving anthracy-clines and its effectiveness in preventing cardiotoxicity.Methods Six electronic databases were searched using terms related to exercise,BC,anthracyclines,and cardiotoxicity for retrieving clinical randomized controlled trials in either Chinese or English.A summary of the included literature was also provided.Results Of 202 records screened,10 were eligible.A total of 434 BC patients(stage I–IIIC,mean age ranged from 43.5 to 52.4 years)were included.The main findings were that:(1)Acute(a single bout)moderate-to-vigorous aerobic exercise could prevent NT-proBNP elevation beyond the threshold of acute myocardial injury;(2)Long-term(>8 weeks)moderate-to-high intensity aerobic exercise(continuous or interval)could improve or maintain left ventricular ejection fraction and cardiorespiratory fitness in BC patients.However,the optimal timing,type,and intensity of exercise for people with BC to prevent cardiotoxicity remain unclear.Conclusion Moderate-to-vigorous intensity exercise may be an effective non-pharmacological approach to mitigate cardio-toxicities induced by anthracyclines in women with BC.However,the optimal exercise prescription for preventing cardio-toxicity remains unclear.
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 Key Research and Development Program of China(2019YFA0905400 and 2019YFA0905700)the National Natural Science Foundation of China(U2106227 and 82022066)+1 种基金the Shandong Provincial Natural Science Foundation(ZR2021ZD28)the Shenzhen Fundamental Research Program(20220523121619003)。
文摘A novel sub-class of S-adenosyl-L-methionine(SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines.Exemplified by RdmB from Streptomyces purpurascens,it was found with 10-decarboxylative hydroxylation activity on anthracyclines.We herein investigated the cata-lytic activities of RdmB and discovered a previously unknown 4-O-methylation activity.The site-directed mutagenesis studies proved that the residue at position R307 and N260 are vital for the decarboxylative hy-droxylation and 4-O-methylation,respectively,which define two distinct catalytic centers in RdmB.Further-more,the multifunctionality of RdmB activity was found as cofactor-dependent and stepwise.Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural di-versity and bioactivities of anthracyclines.
文摘Background There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer （MBC） in older Chinese patients. Methods MBC patients aged 〉65 years pretreated with 1-5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m^2 twice daily, days 1-14, plus docetaxel 30 mg/m^2 on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles （median 4, range 2-8） and were evaluable for efficacy. Results The overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia （12%）, alopecia （7%）, grade 3 nausea and vomiting （2%） and grade 3 nail toxicity （2%）. Conclusions Capecitabine 825 mg/m^2 twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women 〉65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.
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Objectives: This article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetrexed-based regimens. Methods: PubMed, Embase, OVID, and the Cochrane Library databases were searched from the beginning of each database without any limitations to the date of publication. Search terms were‘‘pemetrexed’’ or‘‘LY231514’’ or“Alimta”,“metastatic breast cancer”, and“advanced breast cancer”. Results: There were 15 studies (n ? 1002) meeting our criteria for evaluation. Eight single-agent trials (n ? 551) and seven using combinations with other agents (n ? 451) were identified that evaluated pemetrexed for use in patients with metastatic breast cancer. Response rates to pemetrexed as a single agent varied from 8%to 31%, and with combination therapy have been reported to be between 15.8% and 55.7%. With routine supplementation of patients with folic acid, dexamethasone, and vitamin B12, the toxicity profile of these patients was mild, including dose-limiting neutropenia and thrombocytopenia, as well as lower grades of reversible hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase (TS) and other biomarkers are associated with the prognosis and sensitivity for pemetrexed in breast cancer. Conclusion: Pemetrexed has shown remarkable activity with acceptable toxicities for treatment of metastatic breast cancer patients. Translational research on pemetrexed in breast cancer identified biomarkers as well as additional genes important to its clinical activity and toxicity. Further research is needed to clarify the role of pemetrexed in breast cancer treatment in order to guide oncologists. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Com-munications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
文摘Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably associated with recurrence of TNBC.This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival(DFS)of early-stage TNBC patients treated with anthracycline-and/or taxane-based chemotherapy.Methods:We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline-and/or taxane-based chemotherapy using the sequenom’s MassARRAY system.Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.Results:Three genotypes,AA,GA,and GG,were detected in the rs473543 of ATG5 gene.The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence(P=0.024).Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543(P=0.034).In addition,after adjust-ing for clinical factors,multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS(hazard risk[HR],1.73;95%confidence interval[CI],1.04-2.87;P=0.034).In addition,DFS was shorter in node-negative patients with the presence of A allele(AA/GA)than in those with the absence of A allele(P=0.027).Conclusion:ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.
