新辅助化疗对乳腺癌ER PR HER-2及Ki-67表达影响的研究进展

目前乳腺癌已成为女性发病率最高的恶性肿瘤,新辅助化疗(neoadjuvant chemotherapy,NAC)后雌激素受体(estrogen re-ceptor,ER)、孕激素受体(progesterone receptor,PR)和人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)、Ki-67表达情况会有不同程度变化,这种变化机制是否会影响后续治疗方案的选择尚无定论。本文将就NAC对乳腺癌ER、PR、HER-2及Ki-67表达影响的研究进展进行综述。

三阴性乳腺癌靶向治疗进展

三阴性乳腺癌(triple-negative breast cancer,TNBC)是雌、孕激素受体和HER-2表达均为阴性的乳腺癌,侵袭性强,与其他分子分型乳腺癌相比复发率较高,生存率低。临床上内科治疗主要以化疗为主,随着对TNBC分子分型的深入探索,靶向治疗的研究逐渐成为关注的焦点。近些年,多种靶向药物进入临床试验,取得一定疗效,不良反应相对较轻,部分药物已批准上市。本文将对TNBC的靶向治疗应用进展进行综述。

Benefit of everolimus as a monotherapy for a refractory breast cancer patient bearing multiple genetic mutations in the PI3K/AKT/mTOR signaling pathway

A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient's tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases(PI3 K) signaling pathway were detected via next-generation sequencing(NGS)-based liquid biopsy, including a p. G1007 R missense mutation in exon 21 of PIK3 CA(33.61%), a p.L70 fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten(PTEN)(49.14%), and a p. D1542 Y missense mutation in exon 32 of mammalian target of rapamycin(m TOR)(1.66%). Therefore, only the m TOR inhibitor everolimus was administered to the patient. Partial remission(PR) was observed after 2 months, and sustained stable disease(SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3 CA decreased to 4.17%, and that the PTEN and m TOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3 K/ARK/m TOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.

哌柏西利联合内分泌治疗对78例激素受体阳性HER-2阴性晚期乳腺癌的疗效观察

目的:分析哌柏西利联合内分泌治疗的激素受体(hormone receptor,HR)阳性、HER-2阴性晚期乳腺癌临床疗效。方法:回顾性分析2018年9月至2019年12月78例于天津医科大学肿瘤医院行哌柏西利联合内分泌治疗HR阳性、HER-2阴性晚期乳腺癌患者的临床资料,并对其疗效与安全性进行分析。结果:78例患者的中位年龄为58岁,中位无进展生存期(progression-free survival,PFS)为7个月,总体客观缓解率(objective response rate,ORR)为36.7%(22/60),临床获益率(clinical benefit rate,CBR)为73.3%(44/60)。既往使用解救治疗<2线和≥2线的ORR分别为71.4%(20/28)和6.3%(2/32),两者比较差异具有统计学意义(P<0.001)。采用Cox比例风险回归模型多因素分析显示,转移部位数目、既往解救治疗线数和是否行解救化疗是哌柏西利联合内分泌治疗疗效的独立影响因素。不良事件中的中性粒细胞减少为96.2%(75/78)最常见,3~4级占62.8%(49/78),14.1%(11/78)患者因3~4级的白细胞减少/中性粒细胞减少而调整用药剂量。最常见的非血液学不良事件是乏力,占23.1%(18/78)。不良事件引起的停药发生率为7.7%(6/78)。结论:哌柏西利联合内分泌治疗更适合既往解救治疗线数少、未行解救化疗的患者,较后线使用有更好的疗效,且不良事件可控。

Therapeutic window of Qingkailing injection for focal cerebral ischemia/reperfusion injury

The time window in which a drug is effective varies between drugs. The present study investigated the therapeutic window of Qingkailing injection for focal cerebral ischemia/reperfusion in mice. Animals underwent middle cerebral artery occlusion and were injected with Qingkailing (1.5, 3, 6 mL/kg). Infarct volume and neurological function were assessed after 24 hours of ischemia. In addition, to establish the therapeutic time window, mice were injected with 3 mL/kg Qingkailing at 0, 1, 3, 4, 6, 9 and 12 hours after occlusion. Results revealed that Qingkailing injection significantly reduced infarct volume and improved neurological function in model mice after cerebral infarction for up to 9 hours, demonstrating that the therapeutic window of Qingkailing injection can extend to 9 hours for cerebral ischemia/reperfusion in mice.

Acupuncture enhances anticancer effects of cyclophosphamide on 4T1 tumors via suppression of angiogenesis in BALB/c mice

Objective:Acupuncture is considered an important part of the alternative medical treatment of tumors.However,it is still unclear whether acupuncture has a direct effect on inhibition of tumor growth.The purpose of this study was to evaluate the effects of acupuncture treatment on tumors in BALB/c mice that were or were not administered cyclophosphamide.Methods:A 4T1 breast carcinoma mouse model for this study was established.When the mice developed 5 mm × 5 mm visible subcutaneous tumors,they were subjected to acupuncture and/or cyclophosphamide (CTX) treatment for 15 days.Results:Acupuncture and CTX treatment both reduced the size of the solid tumors.When used in conjunction,the tumor size reduction was even more obvious.Hematoxylin and eosin staining showed that acupuncture had a significant effect on induction of tumor cell necrosis and inhibition of angiogenesis.Immunohistochemistry showed that the expression of CD34 and matrix metalloproteinase-9 (MMP-9),which were related to angiogenesis,decreased after treatment with either acupuncture or CTX.However,when the two treatments were used in conjunction,they showed a synergistic effect on inhibiting the expression of CD34.However,the synergistic effect was not observed onMvMP-9 expression.Conclusion:Acupuncture plays an important role in improving the effect of chemotherapy by inhibiting angiogenesis.

Inverse design on terahertz multilevel diffractive lens based on 3D printing[Invited]

Terahertz(THz)lenses have numerous applications in imaging and communication systems.Currently,the common THz lenses are still based on the traditional design of a circular convex lens.In this work,we present a method for the design of a 3D-printed multilevel THz lens,taking advantage of the benefits offered by 3D printing technology,including compact size,lightweight construction,and cost-effectiveness.The approach utilizes an inverse design methodology,employing optimization methods to promise accurate performance.To reduce simulation time,we employ the finite-difference time-domain method in cylindrical coordinates for near-field computation and couple it with the Rayleigh-Sommerfeld diffraction theory to address far-field calculations.This technology holds great potential for various applications in the field of THz imaging,sensing,and communications,offering a novel approach to the design and development of functional devices operating in the THz frequency range.

Integrative analysis of LncRNA-mRNA signature reveals a functional LincRNA in triple-negative breast cancer

Purpose:Triple-negative breast cancer(TNBC)is an aggressive subtype of breast cancer.It is still unclear that the mechanisms by which long non-coding RNA(lncRNA)regulates tumorigenesis of TNBC.In this study,we explored the function and regulation of lncRNA in TNBC.Methods:The diferentially expressed and overlapped lncRNAs were obtained from two microarray datasets of breast cancer.The cancer genome atlas(TCGA)data was applied to validate the roles of top diferentially expressed lncRNAs.The potential relationship among lncRNAs,miRNAs,and mRNAs and the efects of them on the TNBC tumorigenesis were further explored through multiple bioinformatic methods.Results:Long intergenic non-protein coding RNA 1351(LINC01351)was frst discovered to play an oncogenic role in TNBC.The highly expressed LINC01351 was signifcantly related to aggressive subtypes,advanced stages and metastasis of breast cancer.The overexpressed LINC01351 was associated with adverse prognosis of patients with TNBC.LINC01351 was found to negatively regulate ELK4 which was involved in the transcriptional regulation in cancer.The high expression of ELK4 showed favorable prognosis of patients with basal-like 1 subtype and luminal androgen receptor subtype of TNBC.Conclusion:The dysregulation of LINC01351 played an important role in triple-negative breast cancer.LINC01351 could be a poor prognostic marker and a potential target for patients with TNBC.