Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

PPP1R14A is Associated with Immunotherapy Resistance in Head and Neck Squamous Cell Carcinoma Identified by Single-Cell and Bulk RNA-Sequencing

Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.

Advanced lung adenocarcinoma with EGFR 19-del mutation transforms into squamous cell carcinoma after EGFR tyrosine kinase inhibitor treatment

In this editorial we comment on the article by Ji et al.We focus specifically on the EGFR tyrosine kinase inhibitor(EGFR-TKI)treatment and the development of drug resistance to EGFR-TKIs.

Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.

Personalized targeted therapy for esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.

Integrated bioinformatics analysis of potential biomarkers and candidate drugs of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC),the major subtype of esophageal carcinoma(ESCA),is one of the most lethal malignancies worldwide.This study aimed to identify potential biomarkers and/or therapeutic targets for ESCC.The datasets GSE44021,GSE77861,GSE20347,and GSE29001 retrieved from the Gene Expression Omnibus(GEO)database contained 117 ESCC tissues and 109 normal tissues.Differentially expressed genes(DEGs)associated with ESCC were identified using the GEO2R tool.Dysregulated pathways associated with ESCC mainly included mitotic regulation,cell cycle,ECM-receptor interaction,DNA replication,etc.The protein-protein interaction(PPI)network of overlapping DEGs was constructed and nine key genes(KGs)were identified from the complex interaction network using Degree,maximum neighborhood component(MNC),and maximal clique centrality(MCC)algorithms.Expression patterns of KGs at the transcriptional and translational levels were validated using ESCC-related data from the Cancer Genome Atlas(TCGA),Oncomine,and Human Protein Atlas(HPA)databases.Genetic alterations calculation,immune cell infiltrates evaluation,methylation analysis,prognostic analysis,transcription factors(TFs)and miRNAs regulatory networks construction,and targeted drug prediction were further performed.It was also found that the knockout of these KGs affected the survival of more than two types of ESCC cells by genome-wide CRISPR-Cas9 dropout screens.In conclusion,we identified KGs,TFs,and miRNAs with biomarker potential(e.g.,NDC80,BUB1,TOP2A,AURKA,AURKB,TTK,UBE2C,TPX2,BUB1B,E2F1,and hsa-miR-483-5p)and 23 candidate targeted drugs for ESCC by utilizing an integrated multi-omics approach.These findings provide additional insights into uncovering the molecular mechanism and improving the efficiency of clinical diagnosis and treatment for ESCC.

Application of single-cell RNA sequencing in head and neck squamous cell carcinoma

Single-cell RNA sequencing has been broadly applied to head and neck squamous cell carcinoma(HNSCC) for characterizing the heterogeneity and genomic mutations of HNSCC benefiting from the advantage of single-cell resolution. We summarized most of the current studies and aimed to explore their research methods and ideas, as well as how to transform them into clinical applications. Through single-cell RNA sequencing, we found the differences in tumor cells’ expression programs and differentiation tracks. The studies of immune microenvironment allowed us to distinguish immune cell subpopulations, the extensive expression of immune checkpoints, and the complex crosstalk network between immune cells and non-immune cells. For cancerassociated fibroblasts(CAFs), single-cell RNA sequencing had made an irreplaceable contribution to the exploration of their differentiation status, specific CAFs markers, and the interaction with tumor cells and immune cells. In addition, we demonstrated in detail how single-cell RNA sequencing explored the HNSCC epithelial-tomesenchymal transition(EMT) model and the mechanism of drug resistance, as well as its clinical value.

Clinical Observation on Treatment of NonParvicellular Carcinoma of the Lung with Jin Fu Kang Oral Liquid

Jin Fu Kang Oral Liquid ([symbol: see text]), made of traditional Chinese drugs for supplementing qi and nourishing yin, was developed according to the common symptoms in lung carcinoma with deficiency of both qi and yin. Of the 96 cases in the Jin Fu Kang group, 1 case got complete remission (CR) after treatment, 8 cases partial remission (PR), 52 cases no change (NC), PR + NC covering 63.5%. Of the 52 cases in the group of Jin Fu Kang plus chemotherapy, 11 cases got PR after treatment, 26 cases NC, PR + NC covering 71.2%. Of the 25 cases in the chemotherapy group, 4 cases got PR after treatment, 11 cases NC, PR + NC covering 60.0%. The results show that the therapeutic effectiveness in the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy was better than that in the chemotherapy group. The one-year survival rate and the two-year survival rate after treatment in the Jin Fu Kang group were 67.3% and 67.3% respectively; 66.7% and 66.7% in the group of Jin Fu Kang plus chemotherapy; and 40.3% and 0.0% in the chemotherapy group. The improvement of clinical symptoms, increase of body weight and improvement of health situation (KPS marks) after treatment in both the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy were better than that in the chemotherapy group. Some indicators of immunology and hemogram after treatment were greatly improved in the Jin Fu Kang group, worse in the chemotherapy group, but no obvious improvement in the group of Jin Fu Kang plus chemotherapy.

Advanced Lung Adenocarcinoma with EGFR 19-del Mutation Transformed into SCC after EGFR-tyrosine Kinase inhibitors Treatment:A Case report

BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.

The role of non-coding RNAs in drug resistance of oral squamous cell carcinoma and therapeutic potential

Oral squamous cell carcinoma(OSCC),the eighth most prevalent cancer in the world,arises from the interaction of multiple factors including tobacco,alcohol consumption,and betel quid.Chemotherapeutic agents such as cisplatin,5-fluorouracil,and paclitaxel have now become the first-line options for OSCC patients.Nevertheless,most OSCC patients eventually acquire drug resistance,leading to poor prognosis.With the discovery and identification of non-coding RNAs(ncRNAs),the functions of dysregulated ncRNAs in OSCC development and drug resistance are gradually being widely recognized.The mechanisms of drug resistance of OSCC are intricate and involve drug efflux,epithelial-mesenchymal transition,DNA damage repair,and autophagy.At present,strategies to explore the reversal of drug resistance of OSCC need to be urgently developed.Nano-delivery and self-cellular drug delivery platforms are considered as effective strategies to overcome drug resistance due to their tumor targeting,controlled release,and consistent pharmacokinetic profiles.In particular,the combined application of new technologies(including CRISPR systems)opened up new horizons for the treatment of drug resistance of OSCC.Hence,this review explored emerging regulatory functions of ncRNAs in drug resistance of OSCC,elucidated multiple ncRNA-meditated mechanisms of drug resistance of OSCC,and discussed the potential value of drug delivery platforms using nanoparticles and self-cells as carriers in drug resistance of OSCC.

Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma

Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC progression.By analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC patients.Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p sponge.MiR-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC cells.These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression.Therefore,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC development.These findings provide a new perspective for the development of OSCC treatments.

Research progress on the role and mechanism of circular RNA in drug resistance of head and neck squamous cell carcinoma

Drug resistance in tumors constitutes a significant obstacle to tumor therapy.Head and neck squamous cell carcinoma(HNSCC)presents a major challenge due to its deep anatomical location,limited space,and complex structure.These factors complicate surgical procedures and hinder the effectiveness of chemoradiotherapy,leading to poor prognosis and reduced quality of life.However,there is hope in the form of circular RNAs(circRNAs),non-coding RNA molecules with a closed-loop structure that exhibits superior stability and resistance to degradation compared to linear RNAs.Recent advances in high-throughput sequencing and bioinformatics technology revealed that circRNAs participate in tumor proliferation,invasion,migration,and drug resistance.This review aims to summarize current research progress on the involvement of circRNAs in drug resistance of HNSCC and provide valuable insights for the prevention and mitigation of drug resistance in HNSCC.

The Therapeutic Effects of the Radiotherapy Plus TCM Treatment Observed in Senile Non-Parvicellular Lung Cancer Patients at the Late Stage

47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases) treated only by radiotherapy for observation of the therapeutic effects.The patients in the treatment group orally took Chinese medicine during and after the radiotherapy.There was no obvious difference in short-term therapeutic effects between the two groups,but the long-term curative effects in the treatment group was obviously superior to that in the control group (P<0.05 or P<0.01).Conclusion:radiotherapy plus TCM can prolong the survival period for senile non-parvicellular lung cancer patients.

细胞外囊泡在口腔鳞状细胞癌诊疗中的作用

背景:细胞外囊泡在不同的生理和病理生理条件下由多种细胞类型(包括肿瘤细胞)分泌到细胞外环境中,存在着广泛的生物学信号及细胞之间的信号传导。肿瘤衍生的细胞外囊泡可能会加剧癌症的进展、存活、侵袭和促进血管生成。目的:综述细胞外囊泡在口腔鳞状细胞癌诊疗中的研究进展。方法:由第一作者在Pub Med、万方和中国知网数据库中进行文献检索,关键词为“EVs,Oral squamous cell carcinoma,Diagnosis and treatment,Biopsy,Tissue engineering”及“细胞外囊泡,口腔鳞状细胞癌,诊疗,活检,组织工程”,最终纳入63篇文献进行分析。结果与结论:(1)在口腔鳞状细胞癌唾液活检中,细胞外囊泡作为肿瘤细胞与周围微环境间的信息传递工具,携带包括可溶性蛋白、脂质、DNA和RNA在内的多种生物分子,对口腔鳞状细胞癌的进展起着至关重要的作用,这些微小囊泡不仅在肿瘤的生长和扩散中扮演着关键角色,还提供了有关肿瘤生物学特性的重要信息。(2)唾液活检作为一种非侵入性诊断方法,通过分析其中的细胞外囊泡,可以为口腔鳞状细胞癌的早期诊断和靶向治疗开辟新的可能性。(3)研究发现,细胞外囊泡内含的生物活性分子,如micro RNAs(mi RNAs)和特定蛋白质,能作为口腔鳞状细胞癌的生物标志物,提高早期诊断的准确性。细胞外囊泡中的特定蛋白质如EHD2,CAVIN1,PF4V1和CXCL7等显示了作为新型预测性生物标志物的潜力。(4)此外,文章还强调了细胞外囊泡在口腔鳞状细胞癌治疗中的应用潜力,通过工程化改造,细胞外囊泡可以作为新一代纳米级药物输送系统,增强肿瘤靶向治疗的效率和特异性。(5)未来的研究将进一步深入探索细胞外囊泡在口腔鳞状细胞癌治疗中的作用及其机制,有望改善患者的生存率和生活质量。

小檗碱通过调控miR-30a对口腔鳞状细胞癌细胞5-氟尿嘧啶耐药性的影响

目的 观察小檗碱对口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)细胞5-氟尿嘧啶(5-fluorouracil,5-FU)耐药性的影响,并探讨可能的机制。方法 取对数期耐5-FU的人舌鳞癌CAL27细胞(human tongue squamous cell carcinoma CAL27cells resistant to 5-FU,CAL27/5-FU),将微小核糖核酸(micro ribonucleic acid,miR)-30a抑制质粒miR-30a inhibitor转染至CAL27/5-FU细胞上,将其随机分为inhibitor组和联合组,inhibitor组常规培养,联合组加入40μg·mL^(-1)小檗碱进行培养;另取对数期CAL27/5-Fu细胞分为空白组和小檗碱组,空白组常规培养,小檗碱组加入40μg·mL^(-1)小檗碱进行培养。用噻唑蓝(methyl thiazolyl tetrazolium,MTT)法检测细胞的增殖抑制率;实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)检测细胞miR-30a的表达水平;双染法检测细胞的凋亡率;双荧光素酶实验验证miR-30a与三结构域蛋白31(tripartite motif-containing protein 31,TRIM31)的靶向关系;免疫印迹法(Western blotting)检测细胞TRIM31蛋白的表达情况。结果 与空白组比较,小檗碱组的增殖抑制率、miR-30a的表达水平和凋亡率均升高,TRIM31蛋白的表达量降低(P<0.05),inhibitor组的增殖抑制率、miR-30a的表达水平和凋亡率均降低,TRIM31蛋白的表达量升高(P<0.05);与小檗碱组比较,联合组的增殖抑制率、miR-30a的表达水平和凋亡率均降低,TRIM31蛋白的表达量升高(P<0.05);与inhibitor组比较,联合组的增殖抑制率、miR-30a的表达水平和凋亡率均升高,TRIM31蛋白的表达量降低(P<0.05)。双荧光素酶实验结果显示,TRIM31是miR-30a的靶基因,两者的结合位点为TRIM31的3’-UTR片段。结论 小檗碱可逆转OSCC细胞的5-FU耐药性,促进细胞凋亡,其作用机制可能是通过上调miR-30a的表达来进一步靶向下调TRIM31的表达。

Smac多肽对食管鳞状细胞癌耐药性调节机制的研究

目的探究Smac多肽(Smac-N7)对食管癌鳞状细胞系Eca-109和紫杉醇(PTX)耐药株(Eca-109/PTX)耐药性的影响和作用机制。方法采用小剂量间歇诱导法建立Eca-109/PTX细胞株,CCK-8法检测PTX对Eca-109和Eca-109/PTX的半数抑制浓度(IC_(50))。使用PTX和Smac-N7分别或联合处理Eca-109或Eca-109/PTX细胞,并将细胞分为:Eca-109组、Eca-109+PTX组、Eca-109+Smac-N7组、Eca-109+PTX+Smac-N7组;Eca-109/PTX组、Eca-109/PTX+PTX组、Eca-109/PTX+Smac-N7组、Eca-109/PTX+PTX+Smac-N7组。采用流式细胞术、试剂盒和Western blot法分别检测各组Eca-109和Eca-109/PTX细胞的凋亡率和细胞中caspase-3活性与Bcl-2、Bax蛋白的表达水平。结果CCK-8法检测结果显示,随浓度的增加,PTX对Eca-109与Eca-109/PTX的生长抑制率均明显增加(P<0.05),且PTX对Eca-109的IC_(50)[(0.08±0.01)μg/mL]显著低于其对Eca-109/PTX的IC_(50)[(2.47±0.11μg/mL)](P<0.01)。与Eca-109组或Eca-109/PTX组相比,Eca-109+PTX组、Eca-109+PTX+Smac-N7组和Eca-109/PTX+Smac-N7组、Eca-109/PTX+PTX+Smac-N7组细胞中Bcl-2蛋白表达水平显著降低(P<0.05),但细胞凋亡率、细胞中caspase-3活性和Bax蛋白表达水平明显升高(P<0.05)。与Eca-109+PTX组或Eca-109/PTX+PTX组相比,Eca-109+PTX+Smac-N7组和Eca-109/PTX+PTX+Smac-N7组细胞中Bcl-2蛋白表达水平明显降低(P<0.05),而细胞凋亡率、细胞中caspase-3活性和Bax蛋白表达水平明显升高(P<0.05)。结论Smac-N7可在体外通过促进细胞凋亡来改善Eca-109细胞及其耐药株对PTX的敏感度。

信迪利单抗联合白蛋白结合型紫杉醇和铂类对Ⅲ B~Ⅳ期肺鳞状细胞癌的疗效及对肿瘤标志物的影响

目的 探究信迪利单抗联合紫杉醇(白蛋白结合型)、铂类化疗对ⅢB~Ⅳ期肺鳞状细胞癌(LSCC)的临床疗效及其对肿瘤标志物的影响。方法 回顾性分析2021年6月至2023年3月乐山市人民医院收治的87例ⅢB~Ⅳ期LSCC患者的临床资料,根据用药方案不同分为对照组(39例)和观察组(48例),对照组采用紫杉醇(白蛋白结合型)、铂类化疗,观察组在对照组的基础上联合信迪利单抗治疗。对比两组患者治疗12周后的临床疗效、肿瘤标志物、不良反应及生存情况。结果 治疗12周后,观察组的客观缓解率和疾病控制率分别为41.67%和81.25%,高于对照组(20.51%和61.54%),差异具有统计学意义(χ^(2)=4.412,4.185,均P<0.05);观察组癌胚抗原、血清细胞角蛋白19片段21-1、鳞状上皮细胞癌抗原水平[分别为(5.78±1.51) ng·m L^(-1)、(4.34±1.21) ng·m L^(-1)、(16.78±3.45) ng·m L^(-1)]低于对照组[分别为(8.45±1.87) ng·m L^(-1)、(6.02±2.02) ng·m L^(-1)、(25.48±4.31) ng·m L^(-1)],差异具有统计学意义(均P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05);观察组的中位无进展生存期(PFS)、中位总生存期(OS)分别为14.09个月和17.59个月,长于对照组(10.82个月和12.88个月),差异具有统计学意义(均P<0.05)。结论 信迪利单抗联合紫杉醇(白蛋白结合型)、铂类化疗对ⅢB~Ⅳ期LSCC的疗效较好,可以改善肿瘤标志物的表达,安全性可控。

吉西他滨载药微球经支气管动脉化疗栓塞治疗中晚期不可切除肺鳞状细胞癌的临床研究

目的探讨吉西他滨载药微球经支气管动脉化疗栓塞治疗中晚期不可切除肺鳞状细胞癌的临床疗效与安全性。方法收集2020年10月至2022年5月马鞍山市人民医院收治的32例中晚期不可切除肺鳞状细胞癌患者的临床资料,根据治疗方案的不同将患者分为A组(n=16,采用吉西他滨+顺铂或卡铂化疗)、B组(n=8,给予支气管动脉灌注化疗,即白蛋白结合型紫杉醇200 mg+顺铂60 mg)和C组(n=8,给予支气管动脉灌注化疗,即吉西他滨600 mg+顺铂60 mg,灌注化疗后使用载药微球吉西他滨600 mg,之后静脉补充顺铂60 mg+吉西他滨800~1200 mg)。比较3组患者的治疗结局,包括客观缓解率(ORR)、疾病控制率(DCR)、临床疗效及总生存期。结果治疗后,3组患者ORR、DCR、临床疗效以及总生存期超过12个月的比例比较,差异均无统计学意义(P﹥0.05)。治疗后,部分患者发生药物相关不良反应,其中,3组患者恶心呕吐、腹泻、骨髓抑制、肝功能损伤及肾功能损伤的发生率比较,差异均无统计学意义(P﹥0.05);3组患者食欲减退和脱发的发生率比较,差异均有统计学意义(P﹤0.05)。结论吉西他滨载药微球经支气管动脉化疗栓塞治疗中晚期不可切除肺鳞状细胞癌的疗效、安全性与单纯全身化疗和支气管动脉灌注化疗相近,可以作为后两种治疗方案的替代方案。

活性氧响应型鬼臼毒素聚合物前药胶束的制备及其抗口腔癌活性

目的制备基于透明质酸(HA)活性氧(ROS)响应型鬼臼毒素(POD)聚合物前药胶束(HTP-M),并考察其抑制口腔鳞状细胞癌(OSCC)效果。方法采用两步酯化法合成基于HA的ROS响应型POD聚合物前药HA-TK-POD,采用透析法制备聚合物前药胶束HTP-M,并对其形态特征、粒径、电位和载药量进行表征,同时考察ROS响应性药物释放。以SCC-9细胞和荷瘤小鼠为模型,考察HTP-M体内外抗肿瘤效果。结果磁共振氢谱(^(1)H-NMR)证实HA-TK-POD聚合物前药成功合成。所得HTP-M胶束呈类球形,粒径(126.1±3.5)nm,分布均一,Zeta电位(-26.8±1.9)mV。HTP-M载药量(12.3±0.8)%,具有良好ROS响应性。HTP-M可特异性靶向CD44高表达的SCC-9细胞,具有良好的体内外抗肿瘤效果。结论制备了一种基于HA的ROS响应型POD聚合物前药胶束HTP-M,其具有良好的ROS响应性,并可有效抑制OSCC,为临床OSCC的治疗提供了新策略。

靶向抑制GOT1介导的铁死亡途径逆转食管鳞癌细胞顺铂耐药的机制

目的:探究靶向抑制谷氨酸草酰乙酸转氨酶1(GOT1)是否通过介导铁死亡途径影响食管鳞癌细胞顺铂(DDP)耐药性,并探究分子机制。方法:CCK-8法和细胞集落形成实验检测DDP敏感细胞株Eca-109与DDP耐药细胞株Eca-109/DDP的存活率、集落形成数目,RT-qPCR和Western blot检测Eca-109细胞和Eca-109/DDP细胞中GOT1表达水平差异;将Eca-109/DDP细胞分为对照组、siNC组、siGOT1组、siGOT1+铁死亡抑制剂Ferrostatin-1(Fer-1)组,CCK-8法检测不同浓度DDP处理下各组细胞存活率,细胞集落形成实验检测各组细胞集落形成数目,流式细胞术检测各组细胞凋亡率,DCFH-DA染色法检测各组细胞内活性氧(ROS)水平,比色法检测各组细胞中铁离子(Fe2+)浓度,Western blot检测各组细胞中铁死亡效应因子酰基辅酶A合成酶长链家族成员4 (ACSL4)、谷胱甘肽过氧化物酶4(GPX4)、溶质载体家族7成员11(SLC7A11)的蛋白表达水平。结果:与Eca-109细胞比较,不同浓度DDP处理下Eca-109/DDP细胞存活率增高(P<0.05),细胞集落形成数目增加(P<0.05),细胞中GOT1 mRNA与蛋白相对表达量上调(P<0.05)。与对照组比较,siGOT1组Eca-109/DDP细胞在不同浓度DDP处理下的存活率降低(P<0.05),细胞集落形成数目减少(P<0.05),细胞凋亡率增加(P<0.05),细胞中ROS水平和Fe2+浓度升高(P<0.05),ACSL4蛋白相对表达量上调(P<0.05),GPX4和SLC7A11蛋白相对表达量下调(P<0.05);与siGOT1组比较,siGOT1+Fer-1组Eca-109/DDP细胞在不同浓度DDP处理下的存活率升高(P<0.05),细胞集落形成数目增加(P<0.05),细胞凋亡率减少(P<0.05),同时,细胞中ROS水平和Fe2+浓度降低(P<0.05),ACSL4蛋白相对表达量下调而GPX4和SLC7A11蛋白相对表达量上调(P<0.05)。结论:靶向抑制GOT1能够提高食管鳞癌耐药细胞Eca-109/DDP对DDP的敏感性,促进该耐药细胞凋亡,这一作用与促进铁死亡途径有关。