Effects of Mitofusin-2 Gene on Cell Proliferation and Chemotherapy Sensitivity of MCF-7

In order to evaluate the effect of mitofusin-2 gene （mfn2） on proliferation and chemotherapy sensitivity of human breast carcinoma cell line MCF-7 in vitro, pEGFPmfn2 plasmid carrying full length of mitofusin-2 gene was transfected, by using sofast, into MCF-7 cells. Mitofusin-2 gene expression in MCF-7 cells transfected by sofast after 48 h was detected by PCR and Western blotting, and the stable expression of GFP protein in MCF-7 cells by Western blot analysis. The proliferation of MCF-7 cells was assayed by MTT and cell counting. By using PI method, the effects of mfn2 on the cell cycle distribution of MCF-7 were measured. Annexin-Ⅴ/PI double labeling method was employed to detect the changes in apoptosis induced by chemotherapeutics before and after transfection. The results showed that the MCF-7 cells transfected with mfn2 gene could stably and highly express GFP protein. MTT assay revealed that after transfection of mfn2 cDNA, the proliferation of MCF-7 cells was significantly inhibited. DNA histogram showed that cells arrested in S phase, and the percentage of S phase cells was 42.7, 17.2 and 19.6 in mfn2 cDNA transfection group, blank plasmid transfection group and blank control group, respectively （P〈0.05）. The apoptosis ratio of the cells transfected with mfn2 gene was increased from 3.56% to 15.95%, that of the cells treated with camptothecin （CAMP） followed by mfn2 gene transfection was 69.6%, and that in blank plasmid transfection group and blank control group was 31.0% and 23.4% respectively （P〈0.05）. It was suggested that transfection of mfn2 gene could significantly inhibit the proliferation of MCF-7 cells and promote their sensitivity to CAMP with a synergic effect.

A radiomics prognostic scoring system for predicting progression-free survival in patients with stageⅣnon-small cell lung cancer treated with platinum-based chemotherapy

Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.

Associations of genetic polymorphisms of the transporters organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATE1),and ATP-binding cassette subfamily C member 2(ABCC2) with platinum-based chemotherapy response and toxicity in non-small cel

Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this treatment.Four important transporter genes are expressed in the kidney,including organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATEl),ATP-binding cassette subfamily B member 1 {ABCB1),and ATP-binding cassette subfamily C member 2(ABCC2),and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs.This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC patients.Methods:A total of 403 Chinese NSCLC patients were recruited for this study.All patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based chemotherapy.The tumor response and toxicity were evaluated after two cycles of treatment,and the patients' genomic DNA was extracted.Seven single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and response.Results:OCT2 rs316019 was associated with hepatotoxicity(P = 0.026) and hematological toxicity(P = 0.039),and MATEl rs2289669 was associated with hematological toxicity induced by platinum(P = 0.016).In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response(P = 0.031).ABCB1 polymorphisms were associated with neither response nor toxicity.Conclusion:OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC patients.Trial registration Chinese Clinical Trial Registry

Surface-enhanced Raman spectroscopy of serum predicts sensitivity to docetaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer

Docetaxel-based chemotherapy,as the first-line treatment for metastatic castration-resistant prostate cancer(mCRPC),has succeeded in helping quite a number of patients to improve quality of life and prolong survival time.However,almost half of mCRPC patients are not sensitive to docetaxel chemotherapy initially.This study aimed to establish models to predict sensitivity to docetaxel chemotherapy in patients with mCRPC by using serum surface-enhanced Raman spectroscopy(SERS).A total of 32 mCPRC patients who underwent docetaxel chemo-therapy at our center from July 2016 to March 2018 were included in this study.Patients were dichotomized in prostate-specific antigen(PSA)response group(n=17)versus PSA failure group(n=15)according to the response to docetaxel.In total 64 matched spectra from 32 mCRPC patients were obtained by using SERS of serum at baseline(q0)and after 1 cycle of docetaxel chemotherapy(ql).Comparing Raman peaks of serum samples at baseline(q0)be-tween two groups,significant differences revealed at the peaks of 638,810,890(p<0.05)and 1136cm^(-1)(p<0.01).The prediction models of peak 1363 cm^(-1)and principal component anal-ysis and linear discriminant analysis(PCA-LDA)based on Raman data were established,re-spectively.The sensitivity and specificity of the prediction models were 71%,80%and 69%,78%through the way of leave-one-out cross-validation.According to the results of five-cross-valida-tion,the PCA-LDA model revealed an accuracy of 0.73 and AUC of 0.83.

Targeting BCRP/ABCG2 by RNA Interference Enhances the Chemotherapy Sensitivity of Human Colon Cancer Side Population Cells

Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics.This study isolated side population（SP） cells from a colon cancer cell line（Colo-320） and examined their self-renewal and differentiation abilities.Compared to non-SP（NSP） cells,SP colon cancer cells were more tumorigenic in vivo and exhibited more invasive characteristics and a greater ability to form colonies.Additionally,more cells were in G0/G1 phase and more highly expressed the multidrug resistance protein BCRP/ABCG2.We achieved enhanced chemotherapy sensitivity by transfecting SP cells with a hairpin-like,small interfering RNA（si RNA） eukaryotic expression plasmid targeting BCRP/ABCG2.

Weight Loss and Gastrointestinal Symptoms in Advanced Cancer Patients Treated with Platinum-based Chemotherapy

Objective This study assessed the weight loss changes and gastrointestinal symptoms in patients with advanced tumors receiving platinum-containing chemotherapy.Methods We retrospectively reviewed 297 patients with advanced cancers[124 gastrointestinal(GI)cancer patients,119 lung cancer patients and 54 head and neck cancer(HNC)patients]receiving first-line chemotherapy at Tongji Hospital.The patients’changes in body weight,body mass index(BMI),and biochemical parameters(serum haemoglobin and albumin levels)were compared before and after two chemotherapy cycles.Results More than half[54.88%(163/297)]of the patients had experienced unintentional weight loss in the 6 months before chemotherapy,and weight loss≥5%and≥10%of the body mass was noted in 35.69%and 20.20%of the patients,respectively.After two cycles of platinum-based chemotherapy,the proportions of patients with a>5%reduction in body weight among patients with GI,lung,and head and neck cancers were 47.5%(59/124),44.53%(53/119),and 46.2%(25/54),respectively.The patients with GI and lung cancers were more vulnerable to extreme weight loss(≥10%)than those with HNC(P=0.025).The serum hemoglobin levels were also remarkably decreased relative to those before chemotherapy(all P<0.05).Common GI symptoms reported by all patients included anorexia(61.28%),vomiting(52.53%),and nausea(51.18%).A higher proportion of patients with≥10%weight loss experienced anorexia and vomiting(OR=12.21 and 3.61,P=0.008 and 0.047,respectively).Conclusions For advanced cancer patients receiving platinum-based chemotherapy,the GI symptoms are the major factor related to their nutritional status.Appropriate nutritional screening,evaluation and treatment should be applied during the treatment of cancer in order to reduce GI symptoms and improve the patient’s nutritional status.

Research progress in the use of combinations of platinum-based chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors

In the past decade,the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)has dramatically influenced the therapeutic strategies for treating lung cancer,but with tumor progression and drug resistance,patients will ultimately develop reduced sensitivity to EGFR-TKIs.How can we delay the emergence of drug resistance? What is the next strategy after drug resistance? How to reasonably combine platinum-based chemotherapy and EGFR-TKIs? These questions are currently the focus of lung cancer research.Clinical studies have reported that platinum-based chemotherapy can increase the sensitivity to EGFR-TKIs.However,results of pre-clinical and clinical studies have been inconsistent.The mechanisms of platinum chemotherapy and EGFR-TKIs are still unknown due to the lack of systematic research.Therefore,systematic studies are required to show the mechanisms of EGFR-TKIs and chemotherapy agents and define the markers sensitive to their combinations when given concurrently or sequentially.

Study on the Correlation between the Detection of Tumor Markers in Abdominal Effusion and Chemotherapy Sensitivity

Since most patients with ovarian cancer are in the advanced stage when they are prone to recurrence,it is difficult to detect and treat ovarian cancer.There are tumor serum markers in the ascites.Therefore,the study explored the correlation between the serum marker levels of the ascites and chemotherapy sensitivity in patients with ovarian malignant tumors.First,50 patients with nested cancer were selected as research subjects and received treatment,and then immediately 200 mg carboplatin+100 mL normal saline was placed in the abdominal cavity of all patients,which was equivalent to an intraperitoneal chemotherapy.Carboplatin+docetaxel combined with intravenous chemotherapy was started 3 weeks after surgery,and chemotherapy was given every 3 weeks for a total of 5 to 6 courses.The serum levels of CA125,CA199,CEA and AFP in peripheral blood and peripheral blood were determined by ELISA.The results showed that the levels of CA125,CA199,CEA and AFP in serum and ascites after chemotherapy were lower than before chemotherapy(P<0.05).The short-term effective rate of 50 ovarian cancer patients(8 CR,28 PR,12 SD,2 PD)was 72.00%.Therefore,patients with ovarian malignant tumors had a good short-term curative effect after chemotherapy,which can reduce the ascites and serum levels of CA125,CA199,CEA,AFP for clinical reference value dual-mode MRI nanoparticle-mediated photothermal therapy showed good application potential in tumor treatment and diagnosis.

Targeting HMGCS1 restores chemotherapy sensitivity in acute myeloid leukemia

Acute myeloid leukemia(AML)is a common hematological malignancy with overall poor prognosis.Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory(RR)AML patients.Through clinical specimens,animal models and cell-level studies,we explored the specific mechanism of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1(HMGCS1)in AML and the mechanism of targeting HMGCS1 to attenuate cell proliferation,increase chemotherapy sensitivity and improve the occurrence and development of AML.Here,we reveal that HMGCS1 is overexpressed in RR patients and negatively related to overall survival(OS).Knocking out HMGCS1 in AML cells attenuated cell proliferation and increased chemotherapy sensitivity,while stable overexpression of HMGCS1 had the opposite effects.Mechanistically,we identified that knockout of HMGCS1 suppressed mitogen-activated protein kinase(MAPK)pathway activity,while overexpression of HMGCS1 could remarkably enhance the pathway.U0126,a MEK1 inhibitor,offset the effects of HMGCS1 overexpression,indicating that HMGCS1 promotes RR AML through the MAPK pathway.Further,we verified that hymeglusin,a specific inhibitor of HMGCS1,decreases cell growth both in AML cell lines and primary bone marrow cells of AML patients.Furthermore,combination of hymeglusin and the common chemotherapeutic drug cytarabine and adriamycin(ADR)had synergistic toxic effects on AML cells.Our study demonstrates the important role of HMGCS1 in AML,and targeting this protein is promising for the treatment of RR AML.

Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid

The application of paclitaxel(PTX) in clinic has been restricted due to its poor solubility.Several traditional nano-medicines have been developed to improve this defect,while they are still lack of tumor targeting ability and rapid drug release. In this work,an amphiphilic polymeric micelle of hyaluronic acid(HA) – all-trans-retinoid acid(ATRA) with a disulfide bond,was developed successfully for the co-delivery of PTX and ATRA. The combination chemotherapy of PTX and ATRA can strengthen the anti-tumor activity. Along with selfassembling to micelles in water,the delivery system displayed satisfying drug loading capacities for both PTX(32.62% ± 1.39%) and ATRA,due to directly using ATRA as the hydrophobic group. Rapid drug release properties of the PTX-loaded redox-sensitive micelles(HA-SS-ATRA) in vitro were confirmed under reducing condition containing GSH. Besides,HA-CD44 mediated endocytosis promoted the uptake of HA-SS-ATRA micelles by B16 F10 cells. Due to these properties,cytotoxicity assay verified that PTX-loaded HA-SS-ATRA micelles showed concentration-dependent cytotoxicity and displayed obvious combination therapy of PTX and ATRA. Importantly,HA-SS-ATRA micelles could remarkably prolong plasma circulation time after intravenously administration. Therefore,redox-sensitive HASS-ATRA micelles could be utilized and explored as a promising drug delivery system for cancer combination chemotherapy.

Study of sensitivity of different chemotherapeutic agents on colon cancer cell line SW480

Objective:The aim of this study was to investigate the sensitivity of chemotherapeutic agents 5-FU,cisplatin(DDP) or TAXOL on colon cancer cell line SW480 with different methods,to find out the best examine time period for further study of chemotherapeutic sensitivities.Methods:The SW480 cell was treated with 5-FU(200μg/mL),DDP(150μg/mL) or TAXOL(50μg/mL) respectively for 4h,8h or 12h.MTT assay was used to examine the cell survival rate,Annexin V/PI assay was used to analysis the apoptosis rate,Western Blot assay was applied to examine the expression of apoptotic protein.Results:(1) Results of MTT assay showed that the survival rate of SW480 cells at 4h,8h or 12h was:5-FU(200μg/mL)96.0%±8.2%,85.4%±7.8%,74.4% ±10.2%(P<0.05);DDP(150μg/mL) 99.0%±6.4%,88.7%±4.7%(P<0.05),46.9%±2.6%(P<0.01);TAXOL(50μg/mL) 51.5%±4.2%(P<0.01),31.9%±3.1%,17.6%±2.3%,or blank group 97.2%±5.8%,98.7%±7.2%,97.5%±7.5% respectively.(2) The apoptosis rate of cancer cells at 4h,8h or 12h was:control group:3.4%±0.2%,6.2%±0.4%,7.0%±0.5%;5-FU(200μg/mL) 4.0%±0.3%,4.8%±0.4%,7.7%±0.7%;DDP(150μg/mL) 8.5%±0.9%,18.6%±1.6%(P<0.05),67.0%±6.2%(P<0.01);or TAXOL(50μg/mL) 32.0%±5.2%(P<0.01),76.6%±8.5%,94.0% ±8.2%,respectively.(3) Western Blot assay showed that the expression of apoptosis associated protein.PARP,X-linked inhibitor of apoptasis(XIAP),Caspase-9 and Bcl-xL were changed.Conclusion:The sensitivity of chemotherapy could be assessed by MTT assay,Annexin V/PI assay and Western Blot.The best examine time of the three chemotherapuc agents was 5-FU(200μg/mL):>12h,DDP(150μg/mL):8-12h,or TAXOL(50μg/mL):<4h.

pH-triggered dynamic erosive small molecule chlorambucil nano-prodrugs mediate robust oral chemotherapy

Currently,the dynamic erosive small molecule nano-prodrug is of great demand for oral chemotherapy,owing to its precise structure,high drug loading and improved oral bioavailability via overcoming various physiologic barriers in gastrointestinal tract,blood circulation and tumor tissues compared to other oral nanomedicines.Herein,this work highlights the successful development of pH-triggered dynamic erosive small molecule nano-prodrugs based on in vivo significant pH changes,which are synthesized via amide reaction between chlorambucil and star-shaped ortho esters.The precise nano-prodrugs exhibit extraordinarily high drug loading(68.16%),electric neutrality,strong hydrophobicity,and dynamic large-to-small size transition from gastrointestinal pH to tumoral pH.These favorable physicochemical properties can effectively facilitate gastrointestinal absorption,blood circulation stability,tumor accumulation,cellular uptake,and cytotoxicity,therefore achieving high oral relative bioavailability(358.72%)and significant tumor growth inhibition while decreasing side effects.Thus,this work may open a new avenue for robust oral chemotherapy attractive for clinical translation.

小剂量分次放疗增敏化疗在转移性结直肠癌治疗中的临床研究

目的:探究小剂量分次放疗增敏化疗在转移性结直肠癌(mCRC)治疗中的疗效及安全性。方法:根据治疗方式不同将72例一线化疗失败的mCRC患者分为观察组(n=37)和对照组(n=35)。对照组采用贝伐珠单抗^(+)化疗二线治疗。随访两年,比较两组患者的临床疗效、不良反应发生情况(白细胞、血小板)、治疗前后的血清肿瘤标志物水平[癌胚抗原(CEA)、糖类抗原199(CA199)]、免疫功能(CD3^(+)、CD4^(+)、CD8^(+))和生存情况[总生存期(OS)、无进展生存期(PFS)]。结果:观察组治疗后总有效率高于对照组(20.00%vs.43.24%,P<0.05);治疗后,两组CEA、CA199水平低于治疗前,且观察组低于对照组(P<0.05);两组CD3^(+)、CD4^(+)水平上升,且观察组高于对照组(P<0.05);CD8^(+)下降,且观察组低于对照组(P<0.05);两组白细胞下降、血小板减少等不良反应发生情况比较,差异无统计学意义(P>0.05);观察组两年OS、PFS分别为62.16%、40.54%,均高于对照组的37.14%、17.14%(P<0.05)。结论:小剂量分次放疗增敏化疗联合贝伐珠单抗^(+)化疗二线治疗mCRC具有较好的临床疗效,能改善患者的血清肿瘤标志物水平,提高其免疫功能,延长患者生存期,且具有一定安全性。

上调Numb通过调控铁死亡途径增加胃癌细胞化疗敏感性的机制研究

目的探究在胃癌细胞中上调细胞命运决定子Numb对胃癌细胞化疗敏感性的影响及其作用机制。方法通过脂质体转染技术将pcDNA3.1空质粒、pcDNA3.1-Numb质粒分别转染至胃癌细胞系BGC-823中,实时荧光定量PCR(qRT-PCR)和蛋白质印迹检测转染后细胞中Numb表达变化,采用不同浓度的多柔比星(doxorubicin,ADM)处理转染后的BGC-823细胞,MTT法检测细胞增殖抑制率。将BGC-823细胞分为对照组、NC组、Numb组、Numb+铁死亡抑制剂Ferrostatin-1(Fer-1)组,MTT法检测各组细胞增殖抑制率,DCFH-DA荧光探针法检测各组细胞活性氧(reactive oxygen species,ROS)水平,试剂盒检测各组细胞谷胱甘肽(glutathione,GSH)、丙二醛(malondialdehyde,MDA)含量及超氧化物歧化酶(superoxide dismutase,SOD)活力,铁离子检测试剂盒测定各组细胞内铁离子浓度,RT-qPCR和蛋白质印迹法检测各组细胞中铁死亡相关途径因子P53、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)和溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)表达水平。结果与对照组、NC组比较,Numb组细胞中Numb mRNA和蛋白相对表达量均显著上调(P<0.05),在不同浓度ADM处理下的细胞增殖抑制率显著升高(P<0.05)。使用Fer-1干预并进行分组处理后,与对照组、NC组比较,Numb组细胞增殖抑制率显著升高(P<0.05),细胞中ROS水平、MDA含量显著增加(P<0.05),GSH含量显著减少(P<0.05),SOD活性显著降低(P<0.05),Fe^(2+)浓度显著升高(P<0.05),P53 mRNA和蛋白相对表达量显著上调(P<0.05),GPX4、SLC7A11的mRNA和蛋白相对表达量显著下调(P<0.05);与Numb组比较,Numb+Fer-1组BGC-823细胞增殖抑制率显著降低(P<0.05),细胞中ROS水平和MDA含量显著减少(P<0.05),GSH含量显著增加、SOD活性显著升高(P<0.05),同时细胞内Fe^(2+)浓度显著降低(P<0.05),P53 mRNA和蛋白相对表达量显著下调(P<0.05),而GPX4、SLC7A11的mRNA和蛋白相对表达量显著上调(P<0.05)。结论上调Numb能够提高胃癌细胞对ADM的化疗敏感性,该机制可能与其调控P53/SLC7A11/GPX4通路诱导铁死亡的作用有关。

菊苣酸通过FOXO3-FOXM1信号轴抑制肺癌细胞增殖和化疗敏感性并促进凋亡

目的:研究菊苣酸调节叉头框蛋白O3(FOXO3)-叉头蛋白M1(FOXM1)信号轴对肺癌细胞增殖、凋亡和化疗敏感性的影响。方法:构建人肺癌细胞顺铂(DDP)耐药细胞A549/DDP,用不同浓度菊苣酸处理后通过MTT法测定细胞活力,以不显著降低细胞活力的最大浓度作为菊苣酸的最佳作用浓度。将A549细胞随机分为对照组、空载组、菊苣酸组、菊苣酸+FOXO3敲低组,分组处理后分别采用MTT法、集落生成实验及流式细胞实验测定各组A549细胞增殖及凋亡;采用免疫印迹法检测各组A549细胞FOXO3-FOXM1通路、增殖(PCNA)与凋亡(Bcl-2、Bax)相关蛋白表达。将A549/DDP细胞随机分为对照组、DDP组、DDP+空载组、DDP+菊苣酸组、DDP+菊苣酸+FOXO3敲低组,分组处理后分别采用MTT法、集落生成实验及流式细胞实验测定各组A549/DDP细胞增殖及凋亡;采用免疫印迹法检测各组A549/DDP细胞FOXO3-FOXM1通路、增殖、耐药[P-糖蛋白(P-gp)]与凋亡相关蛋白表达。结果:与对照组相比,空载组A549细胞各指标无明显变化(P>0.05);菊苣酸组A549细胞凋亡率、Bax与FOXO3蛋白表达升高(P<0.05),集落生成率、细胞活力、Bcl-2与PCNA、FOXM1蛋白表达降低(P<0.05);FOXO3敲低可减弱菊苣酸对A549细胞上述各指标的作用。与对照组、DDP组相比,DDP+空载组A549/DDP细胞各指标均无明显变化(P>0.05);DDP+菊苣酸组A549/DDP细胞凋亡率、Bax与FOXO3蛋白表达均升高(P<0.05),集落生成率、细胞活力、Bcl-2与PCNA、P-gp、FOXM1蛋白表达均降低(P<0.05);FOXO3敲低可减弱菊苣酸对DDP处理下A549/DDP细胞上述各指标的作用。结论:菊苣酸可通过激活FOXO3-FOXM1信号而抑制肺癌细胞增殖和化疗敏感性并促进其凋亡,进而增强化疗药物DDP对其DDP耐药细胞的杀伤作用。

微肿瘤PTC药敏检测优化骨肉瘤二线化疗方案选择的作用研究

目的:探讨微肿瘤(PTC)药敏检测优化骨肉瘤二线化疗方案选择的作用研究。方法:收集医院内行二线化疗方案治疗的50例骨肉瘤患者,根据治疗方案不同分组,其中12例患者采用伊立替康+长春新碱(A组),15例患者采用白蛋白结合型紫杉醇(B组);13例患者采用吉西他滨+多西他赛治疗(C组),10例患者给予长春瑞滨(D组)。比较各组微肿瘤PTC药敏检测结果、临床疗效及不良反应。结果:B组患者微肿瘤PTC药敏有效率高于A组、B组、D组(P<0.05),A组、B组、D组患者微肿瘤PTC药敏有效率的差异无统计学意义(P>0.05);B组患者临床治疗总有效率高于A组、B组、D组(P<0.05),A组、B组、D组患者临床治疗总有效率的差异无统计学意义(P>0.05)。各组患者间不良反应的差异无统计学意义(P>0.05)。结论:微肿瘤PTC药敏检测与临床疗效结果相近,提示微肿瘤PTC药敏检测对骨肉瘤二线化疗方案选择具有指导价值。

原代肿瘤细胞化疗药物敏感性检测指导下治疗对晚期癌症患者生存预后及肿瘤标志物的影响

目的探讨原代肿瘤细胞化疗药物敏感性检测指导下治疗对晚期癌症患者生存预后及肿瘤标志物的影响。方法以2022年1月至2023年4月在华南大学第一附属医院就诊的107例晚期癌症患者为研究对象,按不同化疗方案分为观察组(n=41例)和对照组(n=66例)。观察组:原代肿瘤细胞化疗药物敏感性检测指导下进行化疗;对照组:接受FOLFOX4(奥沙利铂+5⁃氟尿嘧啶+亚叶酸钙)方案化疗,随访12个月。比较两组完全缓解(CR)、部分缓解(PR)、稳定性疾病(SD)、病情进展(PD),计算有效缓解率(ORR)和疾病控制率(DCR);比较两组肿瘤标志物[鳞状上皮细胞癌抗原(SCC)、癌胚抗原(CEA)、糖类抗原125(CA125)、细胞角蛋白片段19(CYFRA21⁃1)];采用Kaplan⁃Meier生命曲线进行生存分析。结果观察组ORR率与DCR率均显著高于对照组,差异有统计学意义(P<0.05)。经治疗,两组血清SCC、CEA、CA125与CYFRA21⁃1水平均相应下降(P<0.05),且观察组低于对照组,差异有统计学意义(P<0.05)。Kaplan⁃Meier生命曲线分析结果显示,观察组PFS、OS与对照组比较差异有统计学意义(P<0.05)。结论原代肿瘤细胞化疗药物敏感性检测指导下治疗晚期癌症,改善患者预后,对癌症晚期个体化治疗方案具有一定的指导价值。

不同b值的MRI-DWI对乳腺癌术前新辅助化疗效果的评估价值

目的探讨不同扩散敏感系数(b值)的磁共振扩散加权成像(MRI-DWI)对乳腺癌术前新辅助化疗效果的评估价值。方法本研究为一项回顾性研究,采集2020年01月-2023年11月河南中医药大学第三附属医院75例完成4个周期新辅助化疗的乳腺癌患者资料。纳入的患者临床资料保存完整,查阅患者资料,记录研究所需资料数据。所有患者于化疗前完成不同b值(由低到高依次取600、1000、1500 s/mm^(2))的MRI-DWI检查,获取DWI相关参数:图像质量参数[图像信噪比(SNR)、对比信噪比(CNR)]、病变处表观扩散系数(ADC)。依据患者新辅助化疗前后穿刺活检病理Miller-Payne标准,将患者分为化疗敏感组和化疗耐药组。比较不同b值MRI-DWI检查获取的图像质量参数;比较两组不同b值MRI-DWI检查所测的ADC,并绘制受试者工作特征(ROC)曲线,分析不同b值MRI-DWI对乳腺癌患者新辅助化疗效果的预测评估价值。结果新辅助化疗4个周期后检查发现,75例患者化疗敏感53例,占70.67%;化疗耐药22例,占29.33%。b值取600、1000 s/mm^(2)时对应的SNR、CNR均高于b值取1500 s/mm^(2)时对应的SNR、CNR(P<0.05);b值取600、1000 s/mm^(2)时对应的SNR、CNR比较无显著差异(P>0.05)。化疗敏感组化疗前b值取600、1000、1500 s/mm^(2)时所测的ADC值均高于化疗耐药组(P<0.05)。绘制ROC曲线图结果显示,不同b值的MRI-DWI所测的ADC值用于预测评估化疗耐药风险的AUC均≥0.70,具有一定预测价值;其中b值取1000、1500 s/mm^(2)时对应的AUC均高于b值取600 s/mm^(2)时对应的AUC,差异有统计学意义(Z=2.142、2.512,P=0.032、0.012),b值取1000、1500 s/mm^(2)时对应的AUC比较,差异无统计学意义(Z=0.406,P=0.342)。结论使用MRI-DWI检查乳腺癌患者获取的ADC值可用于预测术前新辅助化疗效果,与b值取600、1500 s/mm^(2)比较,b值取1000 s/mm^(2)时,可兼顾DWI图像质量以及预测价值。

秋水仙碱对胶质瘤细胞系化疗敏感性的影响

目的探讨秋水仙碱对胶质瘤细胞系化疗敏感性的影响及其机制。方法采用不同浓度的替莫唑胺(TMZ)处理人脑胶质瘤细胞系U87和A172细胞,构建TMZ耐药细胞系U87/TR和A172/TR,再使用秋水仙碱(10、30 ng/ml)干预1、2、3 d,采用细胞计数法、BrdU法和流式细胞术检测细胞活力、细胞增殖和细胞周期。生物信息学方法分析胶质瘤组织差异表达的微小RNA(miRNAs),并预测其靶基因;然后,采用qRT-PCR检测U-87/TR和A172/TR细胞中这些miRNAs的表达情况,调控miRNAs的表达以观察秋水仙碱效应的变化。结果秋水仙碱显著抑制U87/TR和A172/TR细胞的增殖活力(P<0.05),呈时间依赖性和剂量依赖性(P<0.05),而且显著阻滞U87/TR和A172/TR的有丝分裂,使细胞阻滞在G0/G1期。30ng/ml秋水仙碱显著增加TMZ对U87/TR和A172/TR细胞增殖的抑制效果(P<0.05),明显降低TMZ的IC50值(P<0.05)。生信分析显示,胶质瘤组织miR-330-3p、miR-491-5p、miR-6782-5p、miR-31-5p、miR-330-5p、miR-137和miR-433-3p呈差异表达,秋水仙碱明显上调U87/TR和A172/TR细胞miR-330-3p的表达(P<0.05)、明显抑制miR-330-3p靶基因ErbB的表达(P<0.05)。抑制miR-330-3p表达明显逆转秋水仙碱的生物学效应(P<0.05)。结论秋水仙碱可以抑制TMZ耐药的胶质瘤细胞的增殖,其机制可能涉及到miR-330-3p/ErbB信号通路的调节。

恩度联合埃克替尼对晚期非小细胞肺癌患者化疗敏感性、肿瘤标志物及预后的影响

目的 探讨恩度联合埃克替尼对晚期非小细胞肺癌(NSCLC)患者化疗敏感性、肿瘤标志物及预后的影响。方法 选取2019年1月至2020年8月我院收治的88例晚期NSCLC患者,随机分为观察组和对照组,每组44例。2组均采取培美曲塞^(+)顺铂(PP)化疗,同时对照组给予埃克替尼治疗,观察组给予恩度联合埃克替尼治疗。观察2组临床疗效、肿瘤标志物[糖类抗原(CA) 50、癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA) 21-1]、T淋巴细胞亚群、miR-34b、miR-204-5p、miR-158-5p表达水平,以及酪氨酸蛋白激酶2(JAK2)/信号转导和转录激活因子3 (STAT3)信号通路和不良反应。结果 2组临床总缓解率比较无统计学差异(P>0.05)。治疗后,观察组血清CA50、CEA、CYFRA21-1水平低于对照组(P <0.05);CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)水平高于对照组,CD8^(+)低于对照组(P <0.05);miR-34b、miR-204-5p、miR-158-5p表达水平高于对照组,JAK2、STAT3 mRNA表达水平低于对照组(P <0.05);无进展生存期高于对照组(P <0.05)。结论 恩度联合埃克替尼治疗晚期NSCLC疗效确切,可提高患者化疗敏感性及免疫功能,其作用机制可能与抑制JAK2/STAT3信号通路有关。