海兔素对乳腺肿瘤大鼠肠道屏障损伤的保护作用△

目的 探讨海兔素对二甲基苯蒽(7,12-dimethylbenz(a)anthracene, DMBA)诱发的乳腺肿瘤大鼠肠道屏障损伤的保护作用。方法30只雌性SD大鼠按体质量随机分为正常对照组(C)、模型组(M)和海兔素干预组(A)。模型组及海兔素干预组大鼠右侧臀部皮下一次性注射100 mg/kg DMBA建立乳腺癌模型。观察各组大鼠乳腺癌发生率及抑瘤率;酶联免疫吸附实验(ELISA)检测血浆中IL-4、IL-10、IL-6、TNF-α 浓度及D-乳酸(D-LA)和二胺氧化酶(DAO)的水平;实时荧光定量PCR技术(Real-Time PCR)对大鼠粪便肠道菌群16s RDNA V3可变区进行定量分析。结果 与模型组比较,海兔素组大鼠肿瘤潜伏期延长,肿瘤发生率和平均瘤质量降低(P均<0.05),抑瘤率达到49.83%,且该组胸腺指数明显升高(P<0.05);ELISA结果显示,与模型组比较,海兔素干预组IL-4浓度显著升高(P<0.05),IL-6的浓度显著降低 (P<0.05),D-LA的浓度显著降低(P<0.05);RT-PCR结果显示,海兔素干预后,大肠杆菌显著性降低(P<0.05),柔嫩梭菌及乳酸杆菌显著性升高 (P<0.05)。 结论 海兔素对大鼠乳腺肿瘤生长具有一定抑制作用,其作用机制可能与修复乳腺癌大鼠肠道屏障相关。     

No one scans you and says ‘you’re alright now’: the experience of embodied risk for young women living with a history of breast cancer

The concept of ‘embodied’ risk has been used to understand the experience of being at risk of cancer, yet there has been less engagement of the concept in relation to those who have been diagnosed and treated for the disease. In this paper, I draw on young women’s accounts of living with breast cancer with the aim of developing analyses of embodied risk and expanding our understanding of the concept. Twenty women diagnosed with breast cancer while they were aged 18–44 took part in semi-structured interviews in the UK, and I analysed these interview data using social constructionist grounded theory. The findings illustrate how a sense of risk from within the body shaped the young women’s experiences and perceptions of their bodies, and how their body as risky was relational, becoming salient in interactions with others. I also explore new dimensions of embodied risk related to the age and social circumstances of the young women. Although the fear of cancer recurrence is well documented, this paper explores it as an embodied experience.     

A comprehensive review on Brigatinib – A wonder drug for targeted cancer therapy in non-small cell lung cancer

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.     

Isolation and identification of three new chromones from the leaves of Pimenta dioica with cytotoxic,oestrogenic and anti-oestrogenic effects

Context: Pimenta dioica (L.) Merr. (Myrtaceae) is used in Costa Rican traditional medicine for women’s health. Our previous work showed that P. dioica extracts were oestrogenic.

Objectives: This work identifies phytochemicals from P. dioica that are responsible for the plant’s oestrogen-like activities.

Materials and methods: P. dioica leaves were collected in Costa Rica in 2005. Fractions resulting from chromatographic separation of a methanol extract were tested at 50?μg/mL in a competitive oestrogen receptor-binding assay. Active compounds were isolated by HPLC and identified by NMR and MS. Pure compounds were tested at 1?μM in the oestrogen-responsive SEAP reporter gene assay. The effects on cell viability, cytotoxicity and apoptosis were investigated in breast cancer (MCF-7 and SK-BR3) and gastric cancer (AGS and NCI-N87) cell lines using the ApoTox-Glo and Caspase-Glo assays and qPCR.

Results: Quercitrin and three new chromones, including a 2-phenoxychromone, 6,8-di-C-methylcapillarisin (1) were isolated and identified. Compound 1 caused a 6.2-fold increase in SEAP expression at 1?μM (p?2 caused a 6.0-fold increase in SEAP, inhibited the growth of MCF-7, AGS and NCI-N87 cells (IC₅₀ 54.27, 38.13 and 51.22?μg/mL, respectively), and induced apoptosis via caspase 8 and increased the Bax/Bcl-2 mRNA ratio in MCF-7 cells. Compound 3 was anti-oestrogenic in MCF-7 cells.

Discussion and conclusions: Compounds from P. dioica have oestrogenic, anti-oestrogenic and cytotoxic effects that may explain the ethnomedical use of this plant.     

Clinical efficacy of ribociclib as a first-line therapy for HR-positive,advanced breast cancer

Introduction: Breast cancer (BC) remains the most frequently diagnosed cancer and the most common cause of cancer death among women of all races worldwide. Over 80% of BC cases are hormone receptor (HR)-positive, comprised of luminal A and luminal B per molecular subtypes, imposing an urgent need to fully understand the mechanisms behind progression. Ribociclib is a selective cycline-dependent kinase 4 and 6 inhibitor. A phase 1 and a phase 3 trial have established a definitive role of ribociclib as frontline in the treatment of endocrine-sensitive advanced BC.

Areas covered: Herein, the authors provide an overview of the data on ribociclib covering all aspects of the drug from its pharmacokinetics to efficacy and safety. The authors also provide their perspectives for the future.

Expert opinion: Ribociclib is offering an opportunity to explore a new compound at the crossroads of different molecular activity and cell targets, which focus on endocrine-resistance reversal in multiple settings including early BC. Moreover, its activity against different subtypes of BC is being studied as is its immune-modulating effect. One cautionary note is that, in a market of concomitant similar competitors, a financial discussion will be mandatory.     

Abemaciclib for the treatment of breast cancer

Introduction: There have been numerous clinical trials of CDK4/6 inhibitors performed on various carcinomas including breast cancer. One such inhibitor tested and which has ongoing clinical trials for breast cancer is abemaciclib. Abemaciclib is a molecular-targeted agent that targets basic cell cycle regulatory mechanisms.

Areas covered: This review discusses the available clinical data and ongoing clinical trials of abemaciclib in breast cancer.

Expert opinion: Abemaciclib has demonstrated a clear anti-tumour effect and manageable toxicity against HR-positive, HER2-negative breast cancer in many clinical trials and is expected to be an important standard therapy. However, currently, besides oestrogen receptor expression, there is a definite lack of predictive biomarkers for response and/or tolerance to abemaciclib, which is important for patient selection. Another problem is that its contribution to overall survival (OS) has not been shown. And while two large the phase 3 study highlighted the anti-tumour effect of abemaciclib, the OS results are awaited. Furthermore, the effect on brain metastases is expected to be unique to abemaciclib as the response of brain metastasis in HR-positive breast cancer patients has been confirmed in a few cases with case collection still ongoing.     

前哨淋巴结活检在早期浸润性乳腺癌保乳手术中的应用价值

目的分析前哨淋巴结活检术(SLNB)对早期浸润性乳腺癌腋窝淋巴结转移的诊断效能及其在保乳手术中的应用价值。方法回顾性分析2012年7月-2015年5月该院收治的217例早期浸润性乳腺癌患者的临床资料,均行SLNB和保乳手术治疗,以术后病理为金标准分析SLNB对腋窝淋巴结转移的诊断效能。同时,根据患者意愿将前哨淋巴结(SLN)阴性者分为两组,清扫腋窝淋巴结者为对照组,未清扫者为观察组,对比其手术情况、术后转归及生存质量。结果 SLNB诊断腋窝淋巴结转移的灵敏度、特异度、漏诊率、误诊率和准确度分别为92.1%、100.0%、7.9%、0、94.4%。观察组手术时间短,术中出血量和术后引流量少,拔管时间早,与对照组相比差异均有统计学意义(均P<0.05)。观察组并发症发生率低于对照组(P<0.05);复发率、转移率及死亡率比较,差异均无统计学意义(均P>0.05)。治疗前,两组患者的欧洲癌症研究与治疗组织生存质量问卷(EORTC QLQ-C30)和欧洲生命质量协作组乳腺癌专用生命质量量表(QLQ-BR23)评分比较,差异均无统计学意义(均P>0.05);治疗后,观察组功能和症状评分低于对照组,总生存质量评分高于对照组,差异均有统计学意义(均P<0.05)。结论SLNB对早期浸润性乳腺癌腋窝淋巴结转移的诊断效能较高,用以指导保乳手术可降低术后并发症,提高患者的生存质量,具有较好的应用价值。     

Breast milk transmission of flaviviruses in the context of Zika virus: A systematic review

Background

Since the Zika virus epidemic in the Americas began in 2015, Zika virus transmission has occurred throughout the Americas. However, limited information exists regarding possible risks of transmission of Zika virus and other flaviviruses through breast feeding and human milk. We conducted a systematic review of the evidence regarding flaviviruses detection in and transmission through milk, specifically regarding Zika virus, Japanese encephalitis virus, tick‐borne encephalitis virus, Powassan virus, West Nile virus, dengue virus, and yellow fever virus.

Methods

Medline, Embase, Global Health, CINAHL , Cochrane Library, Scopus, Popline, Virtual Health Library, and WorldCat were searched through June 2017. Two authors independently screened potential studies for inclusion and extracted data. Human and nonhuman (animal) studies describing: 1) confirmed or suspected cases of mother‐to‐child transmission through milk; or 2) the presence of flavivirus genomic material in milk.

Results

Seventeen studies were included, four animal models and thirteen observational studies. Dengue virus, West Nile virus, and Zika virus viral ribonucleic acid was detected in human milk, including infectious Zika virus and dengue virus viral particles. Human breast‐feeding transmission was confirmed for only yellow fever virus. There was evidence of milk‐related transmission of dengue virus, Powassan virus, and West Nile virus in animal studies.

Conclusions

Because the health advantages of breast feeding are considered greater than the potential risk of transmission, the World Health Organization recommends that mothers with possible or confirmed Zika virus infection or exposure continue to breast feed. This review did not identify any data that might alter this recommendation.