Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

MicroRNA-409-5p Inhibits GIST Tumorigenesis and Improves Imatinib Resistance by Targeting KDM4D Expression

Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study aimed to explore the specific mechanism by which microRNA-409-5p(miR-409-5p)contributes to GIST.Methods To identify genes potentially involved in the development and progression of GIST,the differences of miR-409-5p between tumors and adjacent tissues were first analyzed.Following this analysis,target genes were predicted.To further investigate the function of miRNA in GIST cells,two GIST cell lines(GIST-T1 and GIST882)were transfected with lentiviruses that stably expressed miR-409-5p and scrambled miRNA(negative control).Later,the cells were subjected to Western blotting and ELSA to determine any differences in angiogenesis-related genes.Results In GISTs,there was a decrease in the expression levels of miR-409-5p compared to the adjacent tissues.It was observed that the upregulation of miR-409-5p in GIST cell lines effectively inhibited the proteins hypoxia-inducible transcription factor 1β(HIF1β)and vascular endothelial growth factor A(VEGF-A).Further investigations revealed that miR-409-5p acted as an inhibitor of angiogenesis by binding to the 3′-UTR of Lysine-specific demethylase 4D(KDM4D)mRNA.Moreover,the combination of miR-409-5p with imatinib enhanced its inhibitory effect on angiogenesis.Conclusion This study demonstrated that the miRNA-409-5p/KDM4D/HIF1β/VEGF-A signaling pathway could serve as a novel target for the development of therapeutic strategies for the treatment of imatinib-resistance in GIST patients.

Growth inhibition of hepatocellular carcinoma tumor endothelial cells by miR-204-3p and underlying mechanism

AIM: To investigate the mechanism by which miR-204-3p inhibits the growth of hepatocellular carcinoma (HCC) tumor endothelial cells (TECs).

PD-L1 Expression and Tumor Infiltrating Lymphocytes in Neurofibromatosis Type 1-Related Benign Tumors and Malignant Peripheral Nerve Sheath Tumors:An Implication for Immune Checkpoint Inhibition Therapy

Background Neurofibromatosis type 1(NF1)is an autosomal dominant inherited disorder.It can affect multiple systems of the body and cause severe disfigurement and discomfort in these patients.There are two types of neurofibromas,named cutaneous and plexiform neurofibromas.The latter type may transform into malignant peripheral nerve sheath tumors(MPNSTs).Surgical resection is difficult to perform owing to the complex tissue structure of neurofibromas;therefore,it is necessary to develop novel and effective therapies for the treatment of these tumors.Programmed cell death protein 1(PD-1)/programmed cell death-ligand 1(PD-L1)-related immune checkpoint inhibitors have been proven effective for various cancers,and the positive expression of PD-L1 and tumor-infiltrating lymphocytes(TILs)has been recognized as a biomarker for the response to immune checkpoint therapy.Methods We conducted immunohistochemistry(IHC)staining to detect PD-L1 expression in plexiform neurofibroma and MPNST tissue samples.Reverse transcription-polymerase chain reaction(RT-PCR)and western blotting were performed to detect PD-L1 and PD-1 expression in MPNST cell lines.IHC staining was used to show immune cell infiltration in NF1 and MPNST tissues.Results IHC staining showed PD-L1 positive expression in neurofibromas and MPNST tumor tissues.In addition,qPCR and western blotting showed high expression of PD-L1 in MPNST tumor cells.IHC staining revealed that aberrant T lymphocytes infiltrated the plexiform neurofibroma and MPNST tumor tissues.Conclusion These results indicate that immune checkpoint mechanisms may play a pivotal role in the development of NF1-related tumors,and immune checkpoint inhibitors may be effective for managing neurofibromas and MPNSTs.Combined therapy with other molecular agents may be explored in the future.

长链非编码RNA GC1靶向微小RNA-551b-3p抑制食管癌的作用及分子机制研究

目的探讨长链非编码RNA(LncRNA)鸟苷酸环化酶1(GC1)对食管癌的影响,并探讨其靶向微小RNA-551b-3p(miR-551b-3p)的分子机制。方法建立食管癌荷瘤裸小鼠模型,随机分为GC1、miR-551b-3p上、下调组及其对应对照组与模型组共9组,每组8只。末次给药次日处死裸小鼠,称取瘤体质量,计算抑瘤率;取肿瘤组织检测LncRNA GC1、miR-551b-3p基因表达水平和细胞周期因子(CyclinD1)、p21、B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关x(Bax)基因与蛋白表达水平;观察肿瘤组织病理改变;采用流式细胞术检测肿瘤细胞凋亡率;采用双荧光素酶报告基因实验验证LncRNA GC1与miR-551b-3p的调控关系。另取人食管癌细胞株Eca109分为9组,每组3个复孔,其中基因干扰组命名同上,另设置空白组,培养48h后观察细胞LncRNA GC1、miR-551b-3p基因表达水平、形态学改变、凋亡率、CyclinD1、p21、Bcl-2、Bax基因与蛋白表达水平。结果动物实验:与模型组和相应对照组比较,GC1上调组与miR-551b-3p下调组瘤体质量、CyclinD1和Bcl-2基因与蛋白表达水平均上升,抑瘤率、细胞凋亡率、miR-551b-3p基因、p21和Bax基因与蛋白表达水平均下降;GC1下调组与miR-551b-3p上调组瘤体质量、CyclinD1和Bcl-2基因与蛋白表达水平均下降,抑瘤率和细胞凋亡率、miR-551b-3p基因、p21和Bax基因与蛋白表达水平均上升;GC1上调组LncRNA GC1基因表达水平上升,GC1下调组LncRNA GC1基因表达水平下降(P<0.05)。与转染野生型GC1的腺病毒载体相比,转染突变型GC1的腺病毒载体的miR-551b-3p荧光素酶相对活性上升(P<0.05)。细胞实验:LncRNA GC1和miR-551b-3p基因表达水平、细胞形态学改变与凋亡率、CyclinD1、p21、Bcl-2、Bax基因与蛋白表达水平变化趋势均与动物实验相同。结论下调LncRNA GC1、上调miR-551b-3p表达水平均可抑制食管癌进展,且下调LncRNA GC1可靶向上调miR-551b-3p,并降低CyclinD1和Bcl-2活性、上升p21和Bax活性。

Inhibition of tumor angiogenesis by TTF1 from extract of herbal medicine

AIM:To study the inhibition of tumor angiogenesis by 5,2,4'-trihydroxy-6,7,5'-trimethoxyflavone(TTF1) isolated from an extract of herbal medicine Sorbaria sorbifolia.METHODS:Angiogenic activity was assayed using the chick embryo chorioallantoic membrane(CAM) method.Microvessel density(MVD) was determined by staining tissue sections immunohistochemically for CD34 using the Weidner capillary counting method.The mRNA and protein levels of vascular endothelial growth factor(VEGF),vascular endothelialgrowth factor receptor 2(VEGFR2,Flk-1/KDR),basic fibroblast growth factor(bFGF),cyclo-oxygenase(COX)-2 and hypoxia-inducible factor(HIF)-1α were detected by quantitative real-time polymerase chain reaction and Western blotting analysis.RESULTS:The TTF1 inhibition rates for CAM were 30.8%,38.2% and 47.5% with treatment concentrations of 25,50 and 100 μg/embryo × 5 d,respectively.The inhibitory rates for tumor size were 43.8%,49.4% and 59.6% at TTF1 treatment concentrations of 5,10,and 20 μmol/kg,respectively.The average MVD was 14.2,11.2 and 8.5 at treatment concentrations of 5 μmol/kg,10 μmol/kg and 20 μmol/kg TTF1,respectively.The mRNA and protein levels of VEGF,KDR,bFGF,COX-2 and HIF-1α in mice treated with TTF1 were significantly decreased.CONCLUSION:TTF1 can inhibit tumor angiogenesis,and the mechanism may be associated with the down-regulation of VEGF,KDR,bFGF,HIF-1α and COX-2.

Preliminary Validation of Tumor Cell Attachment Inhibition Assay for Developmental Toxicants With Mouse S180 Cells

This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180cells attachment to Concanavalin A-coaed surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration tha reduced attachment by 50% ), of these 2 chemicals was 1.2×10-3mol/L and 1 .0 mol/L, respectively. Anoher developmental toxiant, hydmiortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally sindlar to those obtained with ascitic mouse ovdrian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not lindt attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an altemative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.

Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

Dicranostigma leptopodum (maxim) fedde induced apoptosis in SMMC-7721 human hepatoma cells and inhibited tumor growth in mice

Dicranostigma Leptopodum (Maxim) Fedde (DL- F), which had been previously documented to suppress oxidative hemolysis of erythrocytes and enhance immune functions of murine peri- toneal macrophages, was investigated for its effect on anti-tumor activity. Of alkaloids extracted from DLF, five have been identified with employment of chromatographic analysis. An antiproliferative role of these alkaloids was determined on SMMC-7721 Human Hepatoma Ce- lls in an apoptosis-inducing manner, through MTT assaying, Trypan blue exclusion assaying and cytometric analysis of cell cycle distribution. To further examine their inhibitory effects on tumor progression, murine H22 cells were inoculated into Kunming mice to determine the role of these alkaloids of DLF in inhibiting tumor growth in the tumor-implanted mice. It was found that these alkaloids of DLF enhanced the tumor shrinkage effectively wherein its tumor inhibitory rate and immunohistochemistry stain- ing of the tumor were determined and profiled, respectively.

Antitumor activity of miR-188-3p in gastric cancer is achieved by targeting CBL expression and inactivating the AKT/mTOR signaling

BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.

Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition

Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.

A proton-catalyzing prodrug for PDT and glycolysis inhibition-synergistic therapy of tumor in spatiotemporal dimensions

The reactive oxygen species(ROS)generation from photosensitizer in photodynamic therapy(PDT)is limited by tumor hypoxia.Even type-I photosensitizers,e.g.,sulfur-substituted Nile blue,still rely on oxygen as the main center for transferring electrons to generate ROS.Cutting off the pathway of oxygen consumption in tumor can help photosensitizers overcome the limitation of low oxygen,in order to efficiently generate more ROS.It is known that glycolysis inhibitor 3-bromopyruvic acid(3-BP),which could specially target mitochondria,can provide more oxygen by inhibiting oxidative phosphorylation.Herein,we successfully designed and synthesized a new 3-BP-coupled sulfur-substituted Nile blue as prodrug(NBBP)for chemical/photodynamic synergistic therapy.Major results indicated that the protons in tumor catalyzed the hydrolysis of NBBP,inhibited photoinduced electron transfer between 3-BP and the photosensitizer in NBBP and further assisted the photosensitizer to be localized in mitochondria,utilizing local oxygen as much as possible and kill tumor cells more efficiently.Moreover,the glycolysis inhibition-induced autophagy was combined with PDT-induced autophagy,which could promote the deaths of tumor cells.Unlike other remedies exploiting nanomaterials,this construction method of NBBP achieves the efficient synergy of photodynamic therapy and glycolysis inhibition,stronger than their theoretical addition,in spatiotemporal dimensions.Our study provides not only a highly efficient platform for tumor therapy but also a design approach for prodrugs with synergistic effects.

Trojan horses in tumor:engineered pyroelectric and photodynamic nanocomposites for NIR-induced cell apoptosis and tumor growth inhibition

It is desirable but always challenging to develop a cutting-edge tumor treatment strategy with high therapeutic efficacy,lesiontargeted precision and mild accessibility.Compared to traditional treatment modalities,photodynamic therapy has been widely studied since the generation of reactive oxygen species(ROS)at cancerous lesions unprecedentedly offers a convenient approach for localized tumor eliminations.Nevertheless,the consumption of oxygen for ROS production in a hypoxic tumor microenvironment has dramatically limited its feasibility and efficacy.Herein,the engineered nanocomposites of BTO@PDA-ICGHA with photodynamic and pyroelectric performances have been fabricated and applied to the photodynamic-pyroelectric dynamic treatments.The continuing ROS production derived from intracellular oxygen(O_(2))and water(H_(2)O)by laser irradiation contributed to the superb tumor cell apoptosis and significant tumor growth inhibition.Thus,this study has validated a new concept by depositing the engineered nanocomposites at the tumor just like Trojan horses,facilitating ROS release as killers and exerting the NIR-induced cell apoptosis and tumor growth inhibition with high therapeutic efficiency and expectable translational perspectives.

Arginine-solubilized lipoic acid-induced β-sheets of silkfibroin-strengthened hydrogel for postoperative rehabilitation ofbreast cancer

Breast cancer is the most common cancer among women worldwide, and adjuvant radiotherapy (RT) followingtumor removal is one of the most commonly used treatments for breast cancer. However, the high risk of tumorrecurrence and inevitable radiation skin injury after RT remain fatal problems, seriously challenging the patient’spostoperative rehabilitation. Herein, a multifunctional poly (lipoic acid)-based hydrogel is constructed throughone-step heating the mixture of α-lipoic acid (LA)/arginine (Arg)/silk fibroin (SF), without introducing any nonnaturalmolecules. The multiple synergistic interactions among LA, Arg, and SF not only enhance the solubilizationof LA in aqueous systems but also stabilize poly(lipoic acid) through strong salt bridge hydrogen bondsand ionic hydrogen bonds. Intriguingly, the LA-based surfactant induced β-sheet transformation of SF can furthermodulate the bulk strength of the hydrogel. Regulating the content of LA in hydrogels not only allows efficientcontrol of hydrogel bioactivity but also enables the evolution of hydrogels from injectable forms to adhesivepatches. Based on the different biological activities and forms of hydrogels, they can be implanted internally orapplied externally on the mice’s skin, achieving simultaneous prevention of tumor recurrence post-surgery andassistance in treating radiation-induced skin damage after radiotherapy.

Synthesis of Fluorinated Heterobicyclic Nitrogen Systems Containing 1,2,4-Triazine Moiety as CDK2 Inhibition Agents

New fluorine substituted heterobicyclic nitrogen system as imidozolopyrimidines (2,3), pyrimido- 1,2,4-triazinones (4-7), 1,2,4-triazinyl-1,2,4-triazine (12-16), 1,2,4-triazinyl-1,2,4-triazinones (14-17) and substituted thiobarbituric acids (19-20), have been synthesized using the reaction of 3- amino-5,6-di (4'-fluorophenyl)-1,2,4-triazine (1) with α,β–bifunctional compounds. Structures of the title compounds were characterized by UV, IR, 1H/13C-NMR and mass spectrometric method. The studied compounds were tested for CDK2 inhibiting activity in DNA damage, as well as in vitro anti-tumor activity.

Serum tumor markers:Can they clinically implicate in type 2 diabetes mellitus?

“Serum tumor markers expression(CA19-9,CA242,and CEA)and its clinical implications in type 2 diabetes mellitus”authored by Meng and Shi presents an observational case-control study investigating the correlation between tumor markers and type 2 diabetes mellitus(T2DM).The study explores the diagnostic accuracy of tumor markers,particularly cancer antigen 19-9(CA19-9),CA242,and carcinoembryonic antigen,in poorly controlled T2DM patients with hemoglobin A1c levels exceeding 9%,employing receiver operating characteristic curve analysis.Though study offers valuable insights into the potential utility of tumor markers in clinical practice,caution is advised regarding routine tumor marker testing due to challenges such as limited availability and cost.Additionally,the study overlooks potential confounding factors like smoking and alcohol consumption.Variations in CA19-9 and CA242 expression underscore the complex interplay between tumor markers and systemic diseases,warranting further investigation into their diagnostic and prognostic implications.While Meng and Shi represent a significant contribution to the field,more extensive research is needed to fully elucidate the role of tumor markers in diabetes management and beyond.

载紫苏醇线粒体靶向脂质体(POH/DPT-LN)对乳腺癌MDA-MB-231细胞的作用研究

目的:制备载紫苏醇(POH)二硬脂酰基磷脂酰乙醇胺(DSPE)-聚乙二醇(PEG)-(3-丙羧基)三苯基溴化磷(TPP)脂质体(POH/DPT-LN),考察其理化特征、线粒体靶向性及对乳腺癌MDA-MB-231细胞的抑制作用。方法:采用薄膜分散法制备POH/DPT-LN,采用CCK-8、细胞划痕实验、Transwell、细胞凋亡实验、JC-1染色实验及western blotting实验对该载药系统线粒体靶向性及抑瘤作用进行评价。结果:POH/DPT-LN外观形态呈均一、完整的类球形,平均粒径为(141.0±0.8)nm,zeta电位为(29.5±2.8)m V,PDI为(0.185±0.006),包封率及载药量分别为(88.6±1.8)%和(17.7±0.3)%;POH/DPT-LN的IC50为63.32μg/mL,其对MDA-MB-231细胞生长抑制效果良好;与POH单药组相比较,POH/DPT-LN组的MDA-MB-231细胞迁移能力显著减弱,抑制细胞侵袭效果明显(P<0.01);POH/DPT-LN组使得线粒体内POH蓄积浓度,对细胞杀伤效果增强(P<0.01)。POH/DPT-LN可明显提高促凋亡P53、Bax、Caspase-3蛋白表达及降低抗凋亡Bcl-2蛋白表达。结论:POH/DPT-LN具有较高的包封率及载药量,能够将POH药物靶向传递至线粒体内,更有效的抑制MDA-MB-231乳腺癌细胞的增殖,增强药物抗肿瘤效果。

Inhibition of mouse tumors by heavy ion irradiation

Inhibition effects, control probabilities and pathology tissue changes of mouse transplanted tumors S180 after irradiation with 50 MeVu 12C6+ ions are reported. Doses of single irradiation were 0.5, 1, 2, 5, 10, 20, 40 Gy, respectivelyl at a dose rate of 3 Gy/min. Observing time was 24 days. The results show that each group had significant inhibition action on S180 tumors and all inhibitory probabilities were more than 90%; the initial time of inducing tumor inhibition effects were within one week in high dose groups （20, 40 Gy）, and after two weeks in medium dose groups （5, 10 Gy） and low dose groups （0.5, 1, 2 Gy）; also, inhibitory effects in high dose groups were obviously greater than other groups （p <0.05）; tumor control probabilities were different in each group) those in high dose groups （20, 40 Gy） were higher and TCD50 （50% tumor control dose） was 20Gy; the results for curing tumors are different in different doses; pathology inspection presented here were tumor tissue necrosis and degeneration in each dose group and they depended on doses.

紫铆素经EGFR-STAT3信号通路对荷宫颈癌裸鼠肿瘤生长的影响

目的探讨紫铆素对荷宫颈癌裸鼠肿瘤生长与肿瘤组织表皮生长因子受体(EGFR)、信号转导和转录激活因子3(signal transducer and activator of ranscription 3,STAT3)表达的影响。方法裸鼠左侧腑下接种宫颈癌SiHa细胞的方法构建宫颈癌模型,将成功构建的荷宫颈癌裸鼠随机分为模型组、阳性药组与低、中、高剂量组,每组各12只。低、中、高剂量组裸鼠分别给予11.5 mg/ml、46 mg/ml、115 mg/ml注射剂量的紫铆素注射,阳性药组给予4.3 ml/kg剂量的顺铂注射,模型组给予等量生理盐水;每天1次,连续注射7 d后,观察1周。测定各组裸鼠的抑瘤率及肝脏指数、肾脏指数;HE染色形态学观察肿瘤的病理特点,免疫组化、RT-qPCR检测肿瘤组织中EGFR、STAT3的表达水平。结果抑瘤率分析阳性药组(60.82±7.30%)和高剂量组(49.30±10.42)高于低、中剂量组,肿瘤体积与瘤重低于低、中剂量组和模型组;肾脏指数分析阳性药组(10.25±0.48)和高剂量组(10.13±0.47)低于模型组和低、中剂量组;EGFR蛋白表达阳性药组(0.002±0.002)、高剂量组(0.012±0.008)和STAT3蛋白表达阳性药组(0.063±0.011)、高剂量组(0.099±0.013)显著低于模型组和低、中剂量组;EGFR基因表达阳性药组(0.462±0.092)、高剂量组(0.524±0.115)和STAT3蛋白相对表达量阳性药组(0.435±0.123)、高剂量组(0.593±0.092)显著低于模型组和低、中剂量组;病理特点显示阳性药组、高剂量组肿瘤组织坏死情况较模型组和低、中剂量组明显降低;以上指标,差异有统计学意义(P<0.05)。结论紫铆素可有效抑制宫颈肿瘤的生长,且无明显毒性作用,其机制可能与宫颈肿瘤组织EGFR、STAT3表达相关。