Omega‐3 Fatty Acid Grafted PAMAM‐Paclitaxel Conjugate Exhibits Enhanced Anticancer Activity in Upper Gastrointestinal Cancer Cells

Upper Gastrointestinal Cancers (UGCs) are a leading cause of cancer‐related deaths worldwide. Paclitaxel (PTX) is frequently used for the treatment of UGCs; however, low bioavailability, reduced solubility, and dose‐dependent toxicity impede its therapeutic use. PAMAMG_4.0‐NH₂‐DHA is synthesized by linking amine‐terminated fourth‐generation poly(amidoamine) (PAMAMG_4.0‐NH₂) dendrimers with omega‐3 fatty acid docosahexaenoic acid (DHA). Next, PAMAMG_4.0‐NH₂‐DHA‐PTX (DHATX) and PAMAMG_4.0‐NH₂‐PTX (PAX) conjugates are synthesized by subsequent covalent binding of PTX with PAMAMG_4.0‐NH₂‐DHA and PAMAMG_4.0‐NH₂, respectively. ¹H‐NMR and MALDI‐TOF analyses are performed to confirm conjugation of DHA to PAMAMG_4.0‐NH₂ and PTX to PAMAMG_4.0‐NH₂‐DHA. The cell viability, clonogenic cell survival, and flow cytometry analyses are used to determine the anticancer activity of PTX, PAX, and DHATX in UGC cell lines. The in vitro data indicate that treatment with DHATX is significantly more potent than PTX or PAX at inhibiting cellular proliferation, suppressing long‐term survival, and inducing cell death in UGC cells.

     

FeOOH@Metal–Organic Framework Core–Satellite Nanocomposites for the Serum Metabolic Fingerprinting of Gynecological Cancers

High-throughput metabolic analysis is of significance in diagnostics, while tedious sample pretreatment has largely hindered its clinic application. Herein, we designed FeOOH@ZIF-8 composites with enhanced ionization efficiency and size-exclusion effect for laser desorption/ionization mass spectrometry (LDI-MS)-based metabolic diagnosis of gynecological cancers. The FeOOH@ZIF-8-assisted LDI-MS achieved rapid, sensitive, and selective metabolic fingerprints of the native serum without any enrichment or purification. Further analysis of extracted serum metabolic fingerprints successfully discriminated patients with gynecological cancers (GCs) from healthy controls and also differentiated three major subtypes of GCs. Given the low cost, high-throughput, and easy operation, our approach brings a new dimension to disease analysis and classification.     

Extracellular HSPs: The Potential Target for Human Disease Therapy

Heat shock proteins (HSPs) are highly conserved stress proteins known as molecular chaperones, which are considered to be cytoplasmic proteins with functions restricted to the intracellular compartment, such as the cytoplasm or cellular organelles. However, an increasing number of observations have shown that HSPs can also be released into the extracellular matrix and can play important roles in the modulation of inflammation and immune responses. Recent studies have demonstrated that extracellular HSPs (eHSPs) were involved in many human diseases, such as cancers, neurodegenerative diseases, and kidney diseases, which are all diseases that are closely linked to inflammation and immunity. In this review, we describe the types of eHSPs, discuss the mechanisms of eHSPs secretion, and then highlight their functions in the modulation of inflammation and immune responses. Finally, we take cancer as an example and discuss the possibility of targeting eHSPs for human disease therapy. A broader understanding of the function of eHSPs in development and progression of human disease is essential for developing new strategies to treat many human diseases that are critically related to inflammation and immunity.     

Electroporation and Electrochemotherapy in Gynecological and Breast Cancer Treatment

Gynecological carcinomas affect an increasing number of women and are associated with poor prognosis. The gold standard treatment plan is mainly based on surgical resection and subsequent chemotherapy with cisplatin, 5-fluorouracil, anthracyclines, or taxanes. Unfortunately, this treatment is becoming less effective and is associated with many side effects that negatively affect patients’ physical and mental well-being. Electroporation based on tumor exposure to electric pulses enables reduction in cytotoxic drugs dose while increasing their effectiveness. EP-based treatment methods have received more and more interest in recent years and are the subject of a large number of scientific studies. Some of them show promising therapeutic potential without using any cytotoxic drugs or molecules already present in the human body (e.g., calcium electroporation). This literature review aims to present the fundamental mechanisms responsible for the course of EP-based therapies and the current state of knowledge in the field of their application in the treatment of gynecological neoplasms.     

Endometriosis: A Disease with Few Direct Treatment Options

Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues inside and outside the pelvic cavity. The evolution of the disease can lead to infertility in addition to high treatment costs. Currently, available medications are only effective in treating endometriosis-related pain; however, it is not a targeted treatment. The objective of this work is to review the characteristics of the disease, the diagnostic means and treatments available, as well as to discuss new therapeutic options.     

宁波大学女教职工妇科普查分析

通过对宁波大学女教职工的妇科普查，发现患病率较高的3种疾病分别为慢性宫颈炎、阴道炎和子宫肌瘤．为保证女教职工的身心健康，应定期进行妇女常见病、多发病的普查普治．同时，也为不同年龄阶段女教职工妇科疾患的预防提供依据．     

Multiformat T‐Cell‐Engaging Bispecific Antibodies Targeting Human Breast Cancers

Four different formats of bispecific antibodies (bsAbs) were generated that consist of anti‐Her2 IgG or Fab site‐specifically conjugated to anti‐CD3 Fab using the genetically encoded noncanonical amino acid. These bsAbs varied in valency or in the presence or absence of an Fc domain. Different valencies did not significantly affect antitumor efficacy, whereas the presence of an Fc domain enhanced cytotoxic activity, but triggered antigen‐independent T‐cell activation. We show that the bsAbs can efficiently redirect T cells to kill all Her2 expressing cancer cells, including Her2 1+ cancers, both in vitro and in rodent xenograft models. This work increases our understanding of the structural features that affect bsAb activity, and underscores the potential of bsAbs as a promising therapeutic option for breast cancer patients with low or heterogeneous Her2 expression.     

Recent Developments in Targeting RAS Downstream Effectors for RAS-Driven Cancer Therapy

Aberrant activity of oncogenic rat sarcoma virus (RAS) protein promotes tumor growth and progression. RAS-driven cancers comprise more than 30% of all human cancers and are refractory to frontline treatment strategies. Since direct targeting of RAS has proven challenging, efforts have been centered on the exploration of inhibitors for RAS downstream effector kinases. Two major RAS downstream signaling pathways, including the Raf/MEK/Erk cascade and the phosphatidylinositol-3-kinase (PI3K) pathway, have become compelling targets for RAS-driven cancer therapy. However, the main drawback in the blockade of a single RAS effector is the multiple levels of crosstalk and compensatory mechanisms between these two pathways that contribute to drug resistance against monotherapies. A growing body of evidence reveals that the sequential or synergistic inhibition of multiple RAS effectors is a more convenient route for the efficacy of cancer therapy. Herein, we revisit the recent developments and discuss the most promising modalities targeting canonical RAS downstream effectors for the treatment of RAS-driven cancers.     

肺癌和癌旁组织中55个元素的原子光谱分析

建立了利用原子光谱技术测定人肺组织中55种元素的方法。样品采用冷消化过夜,温控电热板消解。其中49种元素利用电感耦合等离子体质谱(ICP-MS)进行测定;As和Se由原子荧光分光光度计(AFS)测定,K, Na, Ca和Mg由原子吸收分光光度计(AAS)测定。24个元素的测定值与牛肝和人发两种标准物质中的参考值基本吻合。除了Cr, Er和U三元素回收率略为偏高外,其余30种元素的加标回收率均在90％～110％之间。绝大多数元素的精密度在1.7％～10％之间。统计学分析结果表明,共有20种元素的含量在所测17对癌组织和癌旁组织之间具有显著性差异。此方法简便、快速、准确。     

伴有盆腔黏连的妇科腹腔镜手术临床分析

目的 分析伴有盆腔黏连的妇科腹腔镜手术临床应用价值。方法 选择2015年3月至2016年3月珠海市妇幼保健院收治的伴有盆腔黏连妇科疾病患者96例,随机分为两组,各48例。对照组采用传统开腹手术,观察组应用腹腔镜手术。比较两组手术疗效及手术情况。结果观察组手术总有效率为95.8%,明显高于对照组的83.2%,差异有统计学意义(P0.05);观察组手术时间、出血量及住院时间分别为(76.7±9.4)min、(45.6±4.7)m L、(4.6±1.3)d,均明显少于对照组[(89.3±10.2)min、(98.4±11.6)m L、(10.3±2.4)d],差异有统计学意义(P0.05)。结论 伴有盆腔黏连的妇科腹腔镜手术应用价值显著,是一种安全可靠的盆腔黏连治疗手段,值得推广。