98例局部晚期乳腺癌介入化疗并发症的临床分析

目的：分析局部晚期乳腺癌介入化疗的主要并发症,探讨其原因和防治措施。方法：局部晚期乳腺癌98例,在DSA室于局麻下经尺动脉或股动脉穿刺插管,将导管尖端送至锁骨下动脉与胸廓内动脉开口交界处近端并固定,经导管灌注化疗药物。结果：20例发生了较明显的并发症,其中患侧上肢、肩背部疼痛11例,局部皮肤损伤6例,上肢肌肉萎缩1例,穿刺部位出血2例。结论：出现上述并发症的原因可能与介入途径、留管时间、化疗疗程、化疗药物种类、用量、浓度、推药速度及推注药物时操作不当等因素有关。     

Super Magnetic Niosomal Nanocarrier as a New Approach for Treatment of Breast Cancer: A Case Study on SK-BR-3 and MDA-MB-231 Cell Lines

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe₂O₄ core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe₂O₄@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe₂O₄@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.     

LANSCLC预后因素的临床研究

目的：观察74例局部晚期非小细胞肺癌（locally advanced non-small cell lung cancer,LANSCLC）患者综合治疗后的1年、2年和3年总生存率,总结临床因素对患者疗效及预后的影响。方法：收集74例在重庆医科大学附属第一医院肿瘤科施行化疗和放射治疗的LANSCLC患者病史及随访资料,计算生存率,筛选预后不良因素。结果：全组治疗后1年,2年,3年总生存率（0S）为79.7%,2年总生存率为49.0%,3年总生存率为18.8%,中位生存时间为24个月。单因素和多因素分析显示放化疗方式及手术与否各组间患者的生存率曲线分布差异有统计学意义（p〈0.05）;而不同化疗方案,化疗周期数各组间患者的生存率曲线分布差异无统计学意义（p〉0.05）。结论：放化疗结合方式,手术与否对LANSCLC患者预后有影响。     

Protein Profiling of WERI-RB1 and Etoposide-Resistant WERI-ETOR Reveals New Insights into Topoisomerase Inhibitor Resistance in Retinoblastoma

Chemotherapy resistance is one of the reasons for eye loss in patients with retinoblastoma (RB). RB chemotherapy resistance has been studied in different cell culture models, such as WERI-RB1. In addition, chemotherapy-resistant RB subclones, such as the etoposide-resistant WERI-ETOR cell line have been established to improve the understanding of chemotherapy resistance in RB. The objective of this study was to characterize cell line models of an etoposide-sensitive WERI-RB1 and its etoposide-resistant subclone, WERI-ETOR, by proteomic analysis. Subsequently, quantitative proteomics data served for correlation analysis with known drug perturbation profiles. Methodically, WERI-RB1 and WERI-ETOR were cultured, and prepared for quantitative mass spectrometry (MS). This was carried out in a data-independent acquisition (DIA) mode. The raw SWATH (sequential window acquisition of all theoretical mass spectra) files were processed using neural networks in a library-free mode along with machine-learning algorithms. Pathway-enrichment analysis was performed using the REACTOME-pathway resource, and correlated to the molecular signature database (MSigDB) hallmark gene set collections for functional annotation. Furthermore, a drug-connectivity analysis using the L1000 database was carried out to associate the mechanism of action (MOA) for different anticancer reagents to WERI-RB1/WERI-ETOR signatures. A total of 4756 proteins were identified across all samples, showing a distinct clustering between the groups. Of these proteins, 64 were significantly altered (q < 0.05 & log2FC |>2|, 22 higher in WERI-ETOR). Pathway analysis revealed the “retinoid metabolism and transport” pathway as an enriched metabolic pathway in WERI-ETOR cells, while the “sphingolipid de novo biosynthesis” pathway was identified in the WERI-RB1 cell line. In addition, this study revealed similar protein signatures of topoisomerase inhibitors in WERI-ETOR cells as well as ATPase inhibitors, acetylcholine receptor antagonists, and vascular endothelial growth factor receptor (VEGFR) inhibitors in the WERI-RB1 cell line. In this study, WERI-RB1 and WERI-ETOR were analyzed as a cell line model for chemotherapy resistance in RB using data-independent MS. Analysis of the global proteome identified activation of “sphingolipid de novo biosynthesis” in WERI-RB1, and revealed future potential treatment options for etoposide resistance in RB.     

The Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 Promotes Ovarian Cancer Pathogenesis

Syndecans are transmembrane heparan sulfate proteoglycans that integrate signaling at the cell surface. By interacting with cytokines, signaling receptors, proteases, and extracellular matrix proteins, syndecans regulate cell proliferation, metastasis, angiogenesis, and inflammation. We analyzed public gene expression datasets to evaluate the dysregulation and potential prognostic impact of Syndecan-3 in ovarian cancer. Moreover, we performed functional in vitro analysis in syndecan-3-siRNA-treated SKOV3 and CAOV3 ovarian cancer cells. In silico analysis of public gene array datasets revealed that syndecan-3 mRNA expression was significantly increased 5.8-fold in ovarian cancer tissues (n = 744) and 3.4-fold in metastases (n = 44) compared with control tissue (n = 46), as independently confirmed in an RNAseq dataset on ovarian serous cystadenocarcinoma tissue (n = 374, controls: n = 133, 3.5-fold increase tumor vs. normal). Syndecan-3 siRNA knockdown impaired 3D spheroid growth and colony formation as stemness-related readouts in SKOV3 and CAOV3 cells. In SKOV3, but not in CAOV3 cells, syndecan-3 depletion reduced cell viability both under basal conditions and under chemotherapy with cisplatin, or cisplatin and paclitaxel. While analysis of the SIOVDB database did not reveal differences in Syndecan-3 expression between patients, sensitive, resistant or refractory to chemotherapy, KM Plotter analysis of 1435 ovarian cancer patients revealed that high syndecan-3 expression was associated with reduced survival in patients treated with taxol and platin. At the molecular level, a reduction in Stat3 activation and changes in the expression of Wnt and notch signaling constituents were observed. Our study suggests that up-regulation of syndecan-3 promotes the pathogenesis of ovarian cancer by modulating stemness-associated pathways.     

Biocompatible,Uniform, and Redispersible Mesoporous Silica Nanoparticles for Cancer‐Targeted Drug Delivery In Vivo

Engineering multifunctional nanocarriers for targeted drug delivery shows promising potentials to revolutionize the cancer chemotherapy. Simple methods to optimize physicochemical characteristics and surface composition of the drug nanocarriers need to be developed in order to tackle major challenges for smooth translation of suitable nanocarriers to clinical applications. Here, rational development and utilization of multifunctional mesoporous silica nanoparticles (MSNPs) for targeting MDA‐MB‐231 xenograft model breast cancer in vivo are reported. Uniform and redispersible poly(ethylene glycol)‐incorporated MSNPs with three different sizes (48, 72, 100 nm) are synthesized. They are then functionalized with amino‐β‐cyclodextrin bridged by cleavable disulfide bonds, where amino‐β‐cyclodextrin blocks drugs inside the mesopores. The incorporation of active folate targeting ligand onto 48 nm of multifunctional MSNPs (PEG‐MSNPs48‐CD‐PEG‐FA) leads to improved and selective uptake of the nanoparticles into tumor. Targeted drug delivery capability of PEG‐MSNPs48‐CD‐PEG‐FA is demonstrated by significant inhibition of the tumor growth in mice treated with doxorubicin‐loaded nanoparticles, where doxorubicin is released triggered by intracellular acidic pH and glutathione. Doxorubicin‐loaded PEG‐MSNPs48‐CD‐PEG‐FA exhibits better in vivo therapeutic efficacy as compared with free doxorubicin and non‐targeted nanoparticles. Current study presents successful utilization of multifunctional MSNP‐based drug nanocarriers for targeted cancer therapy in vivo.     

The Utilization of the Immune System in Lung Cancer Treatment: Beyond Chemotherapy

Lung cancer is ranked first worldwide as one of the main cancers in terms of prevalence and mortality rate. The development of effective treatment strategies against lung cancer is therefore of paramount importance. Traditionally, chemotherapy was employed in the treatment of various cancers. However, the non-specific nature of the actions of chemotherapeutic drugs and the potential for tumors to develop resistance to these drugs may render chemotherapy a less favorable option for cancer treatment. Immunotherapy provides an alternative strategy for this purpose. It involves the utilization of the immune system and the immune effector cells to elicit an immune response to the tumors, thereby eliminating them. Strategies include the administration of pro-inflammatory cytokines for immune stimulation, the removal of immunological checkpoints using monoclonal antibodies, and the use of cancer vaccines to enhance immunity against tumors. This article summarizes the above strategies, highlights the reasons why immunotherapy is superior to chemotherapy for the purpose of tumor removal, and reviews the recent clinical studies comparing the clinical outcomes of patients undergoing immunotherapy and chemotherapy. The article also describes advances in immunotherapeutic strategies for the treatment of lung cancer.     

Gold‐Coated Fe3O4 Nanoroses with Five Unique Functions for Cancer Cell Targeting,Imaging, and Therapy

The development of nanomaterials that combine diagnostic and therapeutic functions within a single nanoplatform is extremely important for molecular medicine. Molecular imaging with simultaneous diagnosis and therapy will provide the multimodality needed for accurate diagnosis and targeted therapy. Here, gold‐coated iron oxide (Fe₃O₄@Au) nanoroses with five distinct functions are demonstrated, integrating aptamer‐based targeting, magnetic resonance imaging (MRI), optical imaging, photothermal therapy. and chemotherapy into one single probe. The inner Fe₃O₄ core functions as an MRI agent, while the photothermal effect is achieved through near‐infrared absorption by the gold shell, causing a rapid rise in temperature and also resulting in a facilitated release of the anticancer drug doxorubicin carried by the nanoroses. Where the doxorubicin is released, it is monitored by its fluorescence. Aptamers immobilized on the surfaces of the nanoroses enable efficient and selective drug delivery, imaging, and photothermal effect with high specificity. The five‐function‐embedded nanoroses show great advantages in multimodality.