Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

Effectiveness of complex decongestive therapy in management of breast cancer associated lymphedema

Background:To assess the edema relief effects of complex decongestive therapy(CDT)in patients with breast cancer associated lymphedema after axillary lymph node dissection(ALND).Methods:58 breast cancer patients with unilateral arm lymphedema after breast cancer ALND were enrolled.The patients were divided into three groups based on the difference of circumference between the affected and unaffected extremity:group 1,mild lymphedema in circumference difference;group 2,moderate lymphedema,and group 3,severe lymphedema.These patients received four weeks of CDT and self-administered home therapy.Arm circumference was measured before,right after CDT,3 months and 12 months of follow-up.Results:In the first group,the circumference difference was 1.53±0.73 cm prior to CDT,and 0.32±0.59 cm right after CDT,and the difference was statistically significant(P<0.001).At the 1-year-follow-up,we got an even higher value than the pre-CDT one,however,there was no significant difference(P=0.175).At the end of CDT,the circumference difference of the third group was 4.52±2.58 cm,significantly lower than the baseline level(8.76±3.07 cm)(P<0.001).In the third group,the reduction of circumference difference was persisted for 12 months.Conclusion:The effects of CDT were maintained for 12 months,while there were differences in progress of circumference difference among the three groups.The effects of patients with severe initial edema(>5 cm increased)last longer.

Interventional effect of cognitive behavioral therapy on cancer-related fatigue in breast cancer patients: A systematic review

Objective:To evaluate the effect of cognitive behavioral therapy on cancer-related fatigue in breast cancer patients.Methods:Computer search for CNKI,VIP,Wanfang database,CBM,PubMed,Embase,CINAHL,The Cochrane library as of 2019 randomized controlled trials on October 20 for cognitive behavioral therapy intervention for breast cancer due to fatigue.Results:A total of 6 RCTs were included,472 patients.Cognitive Behavioral Therapy has a strong effect on cancer related fatigue compared with the usual care[SMD=-1.19,95%CI(-1.86,-0.53),P=0.0004].Results:Available evidence suggests that CBT can alleviate cancer-related fatigue in breast cancer patients,and the above studies still need to continue to conduct relevant studies for validation.

Current status of therapy for breast cancer worldwide and in Japan

The results of clinical trials conducted in Europe and North America have been incorporated into treatment strategies for breast cancer in Japan.Despite the use of similar treatment regimens,why has mortality from breast cancer been increasing in Japan?Procedures for surgical treatment and sentinel lymph node biopsy in breast cancer do not differ between Japan and Western countries,but the strategies for radiotherapy differ slightly.Hormonal therapy is now selected on the basis of scientific evidence,and similar regimens are used in Japan and Western countries.As for postoperative adjuvant chemotherapy,an anthracycline plus cyclophosphamide and taxane-based regimens are standard treatments in Japan and Western countries.In 2009,however,the results of two large clinical studies designed to determine whether intravenous or oral treatment was superior for postoperative adjuvant chemotherapy were reported in Japan.Both studies showed that relapsefree survival and overall survival(OS)at 5 years after surgery were similar for a combination of cyclophosphamide,methotrexate,and 5-fluorouracil and for tegafur/uracil.Many chemotherapeutic agents that are used to treat recurrent or metastatic breast cancer have not yet been approved in Japan.As for molecular targeted therapy,some agents that target the human epidermal growth factor receptor family have been approved in Japan,whereas angiogenesis inhibitors have not.The results of many clinical trials have been incorporated into clinical practice in Japan,therefore,the outcomes of breast cancer therapy have surpassed those in other countries.Many pivotal clinical trials have been conducted outside Japan.Treatment regimens that have been developed on the basis of these studies might be suitable for the management of breast cancer in Western women,but not for Japanese women because of differences in genetic factors,physique,body mass index,pharmacokinetics,and drug metabolism.Such regimens should be modified on the basis of the characteristics of breast cancer in Japan to develop treatment that is optimally suited for Japanese women.In particular,local studies of pharmacokinetics,pharmacodynamics,and optimal dose levels and treatment intervals should be carefully performed.The establishment of treatment regimens optimally suited for Japanese patients with breast cancer could put the brakes on the trend towards increasing mortality from breast cancer in Japan.

Excellent effects and possible mechanisms of action of a new antibody–drug conjugate against EGFR-positive triple-negative breast cancer

Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR,ERK,MEK phosphorylation and tumor stemness marker gene expression.Results:LR004-VC-MMAE with a DAR of 4.02 were obtained.The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells(P<0.01).LR004-VC-MMAE inhibited the proliferation of EGFRpositive TNBC cells,and the ICvalues of MDA-MB-468 and MDA-MB-231 cells treated with LR004-VC-MMAE for 72 h were(0.13±0.02)nmol/L and(0.66±0.06)nmol/L,respectively,which were significantly lower than that of cells treated with MMAE[(3.20±0.60)nmol/L,P<0.01,and(6.60±0.50)nmol/L,P<0.001].LR004-VC-MMAE effectively inhibited migration and invasion of MDA-MB-468 and MDA-MB-231 cells.Moreover,LR004-VC-MMAE also killed tumor stem cells in EGFR-positive TNBC cells and impaired their tumorsphere-forming ability.In TNBC xenograft models,LR004-VC-MMAE at 10 mg/kg significantly suppressed tumor growth and achieved complete tumor regression on day 36.Surprisingly,tumor recurrence was not observed until the end of the experiment on day 52.In a mechanistic study,we found that LR004-VC-MMAE significantly induced cell apoptosis and cell cycle arrest at G/M phase in MDAMB-468[(34±5)%vs.(12±2)%,P<0.001]and MDA-MB-231[(27±4)%vs.(18±3)%,P<0.01]cells.LR004-VC-MMAE also inhibited the activation of EGFR signaling and the expression of cancer stemness marker genes such as Oct4,Sox2,KLF4 and EpCAM.Conclusions:LR004-VC-MMAE showed effective antitumor activity by inhibiting the activation of EGFR signaling and the expression of cancer stemness marker genes.It might be a promising therapeutic candidate and provides a potential therapeutic avenue for the treatment of EGFR-positive TNBC.

Self-adaptive hydrogel for breast cancer therapy via accurate tumor elimination and on-demand adipose tissue regeneration

The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment.Herein,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection inhibition.The hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed esterase.The bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose tissue.Moreover,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.

Metabolic reprogramming in triple-negative breast cancer

Since triple-negative breast cancer(TNBC)was first defined over a decade ago,increasing studies have focused on its genetic and molecular characteristics.Patients diagnosed with TNBC,compared to those diagnosed with other breast cancer subtypes,have relatively poor outcomes due to high tumor aggressiveness and lack of targeted treatment.Metabolic reprogramming,an emerging hallmark of cancer,is hijacked by TNBC to fulfill bioenergetic and biosynthetic demands;maintain the redox balance;and further promote oncogenic signaling,cell proliferation,and metastasis.Understanding the mechanisms of metabolic remodeling may guide the design of metabolic strategies for the effective intervention of TNBC.Here,we review the metabolic reprogramming of glycolysis,oxidative phosphorylation,amino acid metabolism,lipid metabolism,and other branched pathways in TNBC and explore opportunities for new biomarkers,imaging modalities,and metabolically targeted therapies.

Age exerts a continuous effect in the outcomes of Asian breast cancer patients treated with breast-conserving therapy

Background:Asians are diagnosed with breast cancer at a younger age than Caucasians are.We studied the effect of age on locoregional recurrence and the survival of Asian breast cancer patients treated with breast-conserving therapy.Methods:Medical records of 2492 patients treated with breast-conserving therapy between 1989 and 2012 were reviewed.The Kaplan-Meier method was used to estimate locoregional recurrence,breast cancer-free survival,and breast cancer-specific survival rates.These rates were then compared using log-rank tests.Outcomes and age were modeled by Cox proportional hazards.Fractional polynomials were then used to test for non-linear relationships between age and outcomes.Results:Patients≤40 years old were more likely to have locoregional recurrence than were older patients(Hazard ratio[HR]=2.32,P<0.001).Locoregional recurrence rates decreased year-on-year by 4%for patients with luminal-type breast cancers,compared with 8%for those with triple-negative cancers.Similarly,breast cancer-free survival rates increased year-on-year by 4%versus 8%for luminal-type and triple-negative cancers,respectively.Breast cancer-spe-cific survival rates increased with age by 5%year-on-year.Both breast cancer-free survival and breast cancer-specific survival rates in patients with luminal cancers exhibited a non-linear(“L-shaped”)relationship-where decreasing age at presentation was associated with escalating risks of relapse and death.The influence of age on overall survival was confounded by competing non-cancer deaths in older women,resulting in a“U-shaped”relationship.Conclusions:Young Asian breast cancer patients have a continuous year-on-year increase in rates of disease relapse and cancer deaths compared with older patients with no apparent threshold.

Promestriene Affects <i>GREB</i>1 Expression in Estrogen Sensitive Breast Cancer Cells

Promestriene (3-propyl ethyl, 17B-methyl estradiol) is a synthetic estrogen analogue with reported minimal systemic absorption which has been suggested for topical treatment of vaginal atrophy. Promestriene’s ability to stimulate proliferation and estrogen responsive gene expression was analyzed in estrogen receptor (ER+) positive breast cancer cell lines MCF-7, T-47D, and BT-474 using CFSE flow cytometric analysis, and quantitative RT-PCR analysis of GREB1 RNA expression, an estrogen responsive gene involved in estrogen receptor alpha expression. In estrogen replete conditions, Promestriene did not stimulate proliferation even at high concentrations (100,000 pg/ml). However, anti-estradiol depletion allowed low dose Promestriene (2 - 10 pg/ml) to stimulate GREB1 expression in all three cell lines at levels equal to that induced by estradiol (BT-474) or significantly higher than estradiol (MCF7 and T-47D). These findings suggest that Promestriene has the potential to support estrogen like cell signaling, a possible contraindication for use in treatment of vaginal atrophy associated with breast cancer aromatase inhibitor therapy.

Quantitative Assessment of Chronic Skin Reactions Including Erythema and Pigmentation after Breast Conserving Therapy

Purpose: To evaluate long-term skin reactions following breast-conserving therapy by using the melanin-erythema index meter. Patients and Methods: 164 patients were followed for at least three years after breast-conserving therapy. For both the erythema and the melanin indices, the ratio of the irradiated-side index to the non-irradiated-side index was calculated. The time course of index ratios alternation was examined. Influences from additional therapies and patients’ age were also evaluated. Result: Both erythema and melanin index ratios of the breast skin were recovered to pre-radiation level three years after radiotherapy. However, both index ratios of the area administrated with 10-Gy boost irradiation were still high even after five years after radiotherapy. Endocrine therapy, chemotherapy and age had no significant influence on skin color reactions three years after radiotherapy. Conclusion: Quantitative assessment using the melanin-erythema index meter demonstrated that chronic skin reactions following breast conserving therapy had recovered to pre-radiation level for three years after irradiation except for the 10-Gy boost irradiated area.

Is surgical axillary staging necessary in women with T1 breast cancer who are treated with breast-conserving therapy?

Background:In the post-Z0011 trial era,the need to perform surgical axillary staging for early-stage breast cancer patients,who are treated with breast-conserving therapy(BCT),is being questioned.We conducted a retrospective cohort study using the Surveillance,Epidemiology,and End Results(SEER)database to evaluate the safety of waiving surgical axillary staging in patients with T1 breast cancer treated with BCT.Methods:A total of 166,615 eligible patients diagnosed between 2000 and 2012 were divided into staging(sentinel lymph node biopsy or axillary lymph node dissection)and non-staging(no lymph node examined or only needle aspiration biopsy of lymph nodes)groups.Propensity score matching(PSM)was performed to balance disparities between the two groups.Multivariate analysis with the Cox proportional hazards model was used to assess factors related to breast cancer-specific survival(BCSS).Results:Although the tumor size at time of presentation was decreasing over years,the rate of surgical axillary stag-ing increased from 93.3%to 96.9%.The 5-year BCSS rates of the whole cohort(before PSM)and matched cohort(after PSM)were 98.0%and 97.5%.Within the matched cohort,the BCSS was significantly longer in the staging group than in the non-staging group(P<0.001).However,surgical axillary staging did not benefit patients who were 50-79 years old,had tumor size<1 cm,histological grade I disease,or favorable histological types(tubular/mucinous/papillary)in stratified analyses(P>0.05).Race,marital status,hormone receptors,and chemotherapy were not associated with the favorable impact of surgical axillary staging on BCSS(P>0.05).Conclusion:Although surgical axillary staging remains important for T1 breast cancer patients treated with BCT,it might be unnecessary for patients with old age,small tumor,grade I disease,or favorable histological types.

基于尊严疗法的标准化护理模式对晚期肺癌患者的应用及效果评价

目的:探讨基于尊严疗法的标准化护理模式对晚期肺癌患者生活质量、心理状态及尊严水平的影响。方法:选取蚌埠医科大学第一附属医院收治的晚期肺癌患者(纳入时间:2023年1月至2023年12月;纳入例数:100例),采用摸球法随机分为两组:观察组(50例)和对照组(50例)。观察组采用基于尊严疗法的标准化护理模式,对照组采用常规护理。采用生活质量调查表、生命意义感量表、死亡态度描绘量表、心理痛苦量表和尊严量表对两组患者进行评估。结果:观察组患者的生活质量、心理状态及尊严水平均显著优于对照组(P<0.05)。结论:基于尊严疗法的标准化护理模式能有效提高晚期肺癌患者的生活质量,改善心理状态,提升尊严水平。

网络化认知行为疗法对乳腺癌化疗患者创伤后成长的影响

目的探讨网络化认知行为疗法(ICBT)对乳腺癌化疗患者创伤后成长的影响。方法选取84例乳腺癌化疗患者作为研究对象,分为对照组和观察组,每组42例。对照组采用常规护理干预,观察组在常规护理的基础上采用ICBT干预。比较两组患者干预前与干预4周后创伤后成长问卷(PTGI)评分、焦虑自评量表(SAS)评分、抑郁自评量表(SDS)评分及乳腺癌患者癌症治疗功能评价(FACT-B)量表评分。结果干预4周后,观察组PTGI评分、FACT-B量表各维度得分及总分高于干预前及对照组,SAS评分、SDS评分低于干预前及对照组(P<0.05)。结论ICBT可减轻乳腺癌化疗患者的焦虑、抑郁情绪,提高其创伤后成长水平,改善其生活质量。

新辅助内分泌治疗与新辅助化疗治疗激素受体阳性/人表皮生长因子受体2阴性乳腺癌的疗效比较

目的比较新辅助内分泌治疗与新辅助化疗治疗激素受体(HR)阳性(+)/人表皮生长因子受体2(HER2)阴性(-)乳腺癌的疗效。方法依据治疗方法的不同将110例HR+/HER2-乳腺癌患者分为对照组和观察组,每组55例,对照组患者给予新辅助化疗,观察组患者给予新辅助内分泌治疗,两组均于治疗后择期行手术治疗。比较两组患者的临床疗效、肿瘤标志物[糖类抗原125(CA125)、糖类抗原15-3(CA15-3)]水平、Ki-67表达情况、预后不良风险[术前内分泌预后指数(PEPI)]和不良反应发生情况。结果观察组患者的治疗总有效率为85.45%,高于对照组患者的69.09%,差异有统计学意义(P﹤0.05)。治疗后,观察组患者Ki-67高表达率低于对照组,差异有统计学意义(P﹤0.05)。治疗后,两组患者血清CA125、CA15-3水平均低于本组治疗前,观察组患者血清CA125、CA15-3水平均低于对照组,差异均有统计学意义(P﹤0.05)。观察组患者预后不良高风险发生率为12.73%,低于对照组患者的32.73%,不良反应总发生率为7.27%,低于对照组患者的36.36%,差异均有统计学意义(P﹤0.05)。结论新辅助内分泌治疗HR+/HER2-乳腺癌患者的疗效和预后均优于新辅助化疗,可抑制Ki-67的表达,降低肿瘤标志物水平,安全性较高。

Imaging of the treated breast post breast conservation surgery/oncoplasty: Pictorial review

Mammographic appearance of the normal breast is altered in the post-operative setting. It is essential to be aware of the normal findings as well as to identify features of recurrent disease with particular emphasis on radiologicalpathological concordance. Digital breast tomosynthesis and volumetric breast density add incremental value in this clinical setting. We present a pictorial review of various cases to illustrate normal post-operative findings as well as mammographic features suspicious for recurrent disease.

经筋推拿联合肌内效贴对乳腺癌术后上肢水肿患者上肢功能和生活质量的影响

目的观察经筋推拿联合肌内效贴治疗乳腺癌根治术后上肢水肿(BCRL)的临床疗效。方法选取74例BCRL患者,按照随机数字表法分为对照组(n=37)和治疗组(n=37),对照组采用空气波压力治疗仪治疗,治疗组在对照组基础上采用经筋推拿联合肌内效贴治疗,2组均治疗2周后统计疗效。比较2组治疗前后中医证候评分、患侧与健侧上肢周径差、患侧上肢软组织厚度,臂、肩、手功能障碍(DASH)量表评分,健康调查简表(SF-36)评分。结果治疗后,2组各项中医证候评分和总分均较本组治疗前降低(P<0.05),且治疗组均低于对照组(P<0.05)。治疗后,2组患侧与健侧上肢周径差、患侧上肢软组织厚度及DASH评分均较本组治疗前减少(P<0.05),且治疗组均少于对照组(P<0.05)。治疗后,2组SF-36各维度评分均较本组治疗前升高(P<0.05),且治疗组均高于对照组(P<0.05)。治疗组总有效率94.59%(35/37),对照组总有效率78.38%(29/37),治疗组总有效率高于对照组(P<0.05)。结论经筋推拿联合肌内效贴能有效促进BCRL患者上肢功能恢复,改善患者生活质量,疗效良好。

舒乳解郁汤联合穴位贴敷治疗乳腺癌术后抑郁失眠临床疗效观察

目的:对舒乳解郁汤联合中药穴位贴敷治疗乳腺癌术后抑郁失眠进行临床观察。方法:选取乳腺癌术后抑郁患者137例,分为观察组(68例)与对照组(69例)。对照组予常规西医治疗方案治疗,观察组在此基础上联合舒乳解郁汤及穴位贴敷治疗,连续干预6周。评价工具为匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)量表、汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD),同时比较两组临床疗效及血清P物质(Substance P,SP)、血清5羟色胺(5-hydroxytryptamine,5-HT)、神经肽Y(neuropeptide Y,NPY)水平,并进行安全性评价。结果:PSQI评分、HAMD评分治疗后两组均显著低于治疗前(P<0.01),且观察组下降幅度大于对照组(P<0.05)。治疗后血清SP水平观察组明显低于对照组(P<0.01),5-HT、NPY水平观察组明显高于对照组(P<0.01)。观察组总有效率[92.65%(63/68)]高于对照组[83.82%(57/68)](P<0.01)。观察组不良反应发生率[10.29%(7/68)]低于对照组[30.43%(21/69)](P<0.01)。结论:舒乳解郁汤联合穴位贴敷治疗乳腺癌术后抑郁失眠安全有效,能够显著提升患者的睡眠质量和生活质量。

对比常规放疗与三维适形放射治疗(3D-CRT)乳腺癌的临床疗效、毒副作用

目的对比常规放疗与三维适形放射治疗(3D-CRT)乳腺癌的临床疗效、毒副作用。方法选定本院2018年1月至2021年1月住院的90例乳腺癌患者,以随机法将其分组(每组n=45),对比组给予常规放疗治疗,观察组给予3D-CRT治疗,对比两组局部复发率、血清肿瘤标志物、毒副反应总发生率,统计危及器官照射剂量。结果观察组局部复发率(2.22%)低于对比组(22.22%),P<0.05(差异有统计学意义)。观察组治疗后血清糖类抗原199(CA199)、糖类抗原125(CA125)、癌胚抗原(CEA)均低于对比组,P<0.05(差异均具有统计学意义)。观察组毒副反应总发生率(8.89%)低于对比组(28.89%),P<0.05(差异具有统计学意义)。患侧肺V20、患侧肺V30、患侧肺V40、患侧肺V50、左侧心脏V30、左侧心脏V40、左侧心脏V50、分别是(15.28±2.62)cm^(3)、(10.15±3.96)cm^(3)、(1.85±0.62)cm^(3)、(0.54±0.26)cm^(3)、(2.52±1.25)cm^(3)、(2.24±0.99)cm^(3)、(0.45±0.13)cm^(3)。结论3D-CRT可有效抑制乳腺癌患者肿瘤病灶生长,降低局部复发率、血清肿瘤标志物浓度,同时可减少危及器官照射剂量,减轻毒副反应。

曲妥珠单抗与帕妥珠单抗联合化疗在HER2阳性乳腺癌患者辅助治疗中的安全性分析

目的 探究曲妥珠单抗与帕妥珠单抗联合化疗应用于人类表皮生长因子受体2(HER2)阳性乳腺癌患者辅助治疗中的安全性。方法 回顾性分析80例HER2阳性乳腺癌患者的临床资料,所有患者均给予TCbHP方案[曲妥珠单抗(H)+帕妥珠单抗(P)联合多西他赛(T)+卡铂(Cb)]进行辅助治疗。分析患者毒副反应发生情况。结果 所有患者均按计划完成全部治疗,超声心动图监测未出现左心室射血分数(LVEF)降低超过基线10%的现象。80例患者恶心呕吐、骨髓抑制、乏力、心悸、皮疹瘙痒、失眠、骨骼肌肉疼痛、手足麻木、腹泻、便秘发生率分别为60.0%、30.0%、71.3%、5.0%、12.5%、27.5%、55.0%、30.0%、27.5%、16.3%。其中3级恶心呕吐10例、3级骨髓抑制8例,乏力、心悸、皮疹瘙痒、失眠、骨骼肌肉疼痛、手足麻木、腹泻、便秘均为1~2级。结论 曲妥珠单抗、帕妥珠单抗联合多西他赛和卡铂用于HER2阳性乳腺癌患者的辅助治疗, 3级以上严重毒副反应发生率低、安全可控。

Injectable“cocktail”hydrogel with dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic effect

The combination of the first-line standard chemotherapeutic drug doxorubicin hydrochloride(DOX)and the molecular-targeted drug Herceptin(HCT)has emerged as a promising strategy for human epidermal growth receptor 2(HER-2)overexpressing breast cancer treatment.However,insufficient drug accumulation and severe cardiotoxicity are two major challenges that limit its clinical application.Herein,an in situ forming gold nanorods(AuNRs)-sodium alginate(ALG)hybrid hydrogel encapsulating DOX and HCT was engineered for tumor synergistic therapy involving injectable,dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic therapy.The photothermal agent AuNRs,anticancer drug DOX,and anticancer antibody HCT were mixed in ALG solution,and after injection,the soluble ALG was quickly transformed into a hydrogel in the presence of Ca^(2+)in the body.Significantly,the hybrid hydrogel exhibits an extremely high photothermal conversion efficiency of 70%under 808 nm laser irradiation.The thermal effect can also provide photothermal stimulation to trigger the drug release from the gel matrix.In addition,the drug release rate and the releasing degree are also sensitive to the pH.In vitro studies demonstrated that the PEI-AuNR/DOX/HCT/ALG hydrogel has facilitated the therapeutic efficiency of each payload and demonstrated a strong synergistic killing effect on SK-BR-3 cells.In vivo imaging results showed that the local drug delivery system can effectively reduce the nonspecific distribution in normal tissues and increase drug concentration at tumor sites.The proposed hydrogel system shows significant clinical implications by easily introducing a sustainable photothermal therapy and a potential universal carrier for the local delivery of multiple drugs to overcome the challenges faced in HER-2 overexpressing cancer therapy.