Cloning of Thymidine Kinase Gene of Duck Plague Virus Using Degenerate PCR

The DNA of duck plague virus （DPV） thymidine kinase （TK） gene was cloned and sequenced from a vaccine virus in the study. Degenerate oligonucleotide primers for the consensus site of herpesvirus UL24, TK, and glycoprotein H（gH） gene were used in the polymerase chain reaction （PCR） to amplify DNA product with 3 741-base-pairs （bp） in size. DNA sequence analysis revealed a 1 077-base-pairs （bp） open reading frame （ORF） encoding a 358 amino acid polypeptide homologous to herpesvirus TK proteins. The predicted TK protein shared 31.2, 41.3, 35.7, 37.4, and 28.4% identity with herpes simplex virus typel, equine herpesvirus type 4, Marek＇s disease virus 2, herpesvirus turkey, and infectious laryngotracheitis virus, respectively. Comparison of the amino acid sequences of other herpesvirus TK proteins showed that these proteins were not conserved on the whole, otherwise the portion of the TK proteins corresponding to the nucleotide binding domain and the nucleoside binding site were highly conserved among herpesvirus. Comparison with the amino acid sequences of the conserved nucleotide and nucleoside binding domains of other eleven herpesvirus TK proteins to the predicted DPV peptide confirmed its identity as the DPV TK protein.

The modulation of radiation-induced cell death by genistein in K562 cells:Activation of thymidine kinase 1

Ionizing radiation is one of the most effective tools in cancer therapy. In a previous study, we reported that protein tyrosine kinase (PTK) inhibitors modulate the radiation responses in the human chronic myelogenous leukemia (CML)cell line K562. The receptor tyrosine kinase inhibitor, genistein, delayed radiation-induced cell death, while non-recepter tyrosine kinase inhibitor, herbimycin A (HMA) enhances radiation-induced apoptosis. In this study, we focused on the modulation of radiation-induced cell death by genistein and performed PCR-select suppression subtractive hybridization(SSH) to understand its molecular mechanism. We identified human thymidine kinase 1 (TK1), which is cell cycle regulatory gene and confirmed expression of TK1 mRNA by Northern blot analysis. Expression of TK1 mRNA and TK 1enzymatic activity were parallel in their increase and decrease. TK1 is involved in G1-S phase transition of cell cycle progression. In cell cycle analysis, we showed that radiation induced G2 arrest in K562 cells but it was not able to sustain. However, the addition of genistein to irradiated cells sustained a prolonged G2 arrest up to 120 h. In addition,the expression of cell cycle-related proteins, cyclin A and cyclin B 1, provided the evidences of G1/S progression and G2-arrest, and their relationship with TK1 in cells treated with radiation and genistein. These results suggest that the activation of TK1 may be critical to modulate the radiation-induced cell death and cell cycle progression in irradiated K562 cells.

Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase Gene Transfer Driver by KDR Promoter in Treatment of Experimental Human HepatocelLular Carcinoma in Nude Mice

Objective： To investigate the therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase （HSV-tk） gene transfer under the driving of KDR promoter （AdKDR-tk） in combination of ganciclovir （GCV） against human hepatocellular carcinoma in nude mice. Methods： HepG2 cell line was implanted subcutaneously into 32 nude mice, which were subsequently divided into 4 groups （n=8 each group）： Ganciclovir group （Ⅰ）, Ad group （Ⅱ）, AdCMV-tk/GCV group （under the driving of CMV promoter） （Ⅲ） and AdKDR-tk/GCV group （Ⅳ）. Then intratumoral injection of recombinant adenovirus or Ad was performed in all nude mice, and repeated 24 h later. For the following 10 d GCV was given at a dose of 100 mg/（kg· d）, ip. All the treated animals were killed to evaluate the tumor weight and the histopathological changes and the microvessel density of tumors after the treatment was determined. Results Compared with group Ⅰ, the tumor inhibitory rate was 12.3% in group Ⅲ and 24.5% in group Ⅳ; the inhibition rates were significantly different between group Ⅲand Ⅳ （P〈0.05）. The mean MVDs in group Ⅰ, Ⅱ, Ⅲ and Ⅳ were 37.4±8.6, 30.6±7.8, 27.6±7.1, and 10.7±4.1 （microvessels/mm^2）, respectively. Significant differences were found between group Ⅲ and Ⅱ （P〈0.05）, Ⅳ and Ⅱ （P〈0.01）, and Ⅳ and Ⅲ （P〈0.01）. Conclusion： Intratumoral injection of AdKDR-tk results in marked inhibition of HCC growth through inhibition angiogenesis in nude mice. It may be a new treatment approach for human HCC,

HE TREATMENT OF HEPATIC CARCINOMA WITH HERPES SIMPLEX THYMIDINE KINASE GENE/ACYCLOVIR SYSTEM

A retroviral vector(LNHcTL)containing the herpes simplex virus type 1 thymldine kinase(HSVI-tk)gene was constructed and used for transduction of the gene into human hepatocellular carcinoma cells(SMMC-7721).Xenografted tumor on nude mice was produced with the injection of the transduced cells(SMMC- 7721/LN HcTL) inoculated subcutaneously and showed regression when treated with Acyclovir.The mean weight of the residual tumors was six times less than that of the controls'tumors. Patients with liver carcinoma were given an intratumoral injection of ampbotropic packing cells(PA317/LNHcTL)producing HSV1-tk recombinant retroviral particles,and then treated with Acyclovir intravenously, which showed a marked regression of the tumor.Our preliminary data suggest that HSV1-tk gene/Acyclovir system might be a useful therapeutic approach for the treatment of hepatic carcinoma in humans.

Vascular damage and anti-angiogenic effects of tumor vessel-targeted adenovirus-mediated herpes simplex virus thymidine kinase gene

AIM： To explore the therapeutic efficacy and mechanism of herpes simplex virus-thymidine kinase （HSV-tk） targeting angiogenesis against hepatocellular carcinoma in vivio and in vitro. METHODS： Recombinant adenovirus containing kinase domain insert with receptor （KDR） or cytomegalovirus （CMV） promoter-controlled HSV-tk gene （AdKDR-tk and AdCMV-tk） was constructed using pAdeasy system. The expression of KDR antigen in human umbilical venous endothelial cells （HUVEC） and HepG2 was detected with histological analysis of cells. The virus was used to infect HUVEC and HepG2. Following administration of ganciclovir （GCV）, the survival rate of gene-transfected HUVEC and HepG2 was evaluated by MTT method. To develop hepatocarcinomas in 32 Balb/C mice with HepG2 cells, the mice were divided into four groups： ganciclovir group （Ⅰ）, Ad group （Ⅱ）, AdCMV-tk group （Ⅲ） and AdKDR-tk group （Ⅳ）. Then selective administration of recombinant adenovirus or Ad via the intratumorial was given to all rats. Ganciclovir （GCV） was given at a dose of 100 mg·kg^-1·d^-1 （ip） started on the following day and lasted 10 d. Microvessel density （MVD） of tumor in all the treated animals were examined by the immunohistochemical methods and tumor burden was evaluated 10 d before and alter the last GCV dose.RESULTS： Immunocytochemical staining indicated the expression of KDR antigen in HUVEC. Under adenovirus infection index of 100, with increasing GCV concentration from 0 up to 50 mg/L, the survival rate of AdKDR-tk- transfected HUVEC and HepG2 decreased from 100% to （28.94 ± 5.67）% and （75.45 ± 2.91）% at proper order, respectively （P 〈 0.01）, while the survival rate of AdCMV- tk-transfected HUVEC and HepG2 declined from 100% to （17.56 ± 2.48）% and （23.15± 5.72）%, respectively （P 〉 0.05）. Compared with group I, there was a decrease of tumor weight by 14.7% in group Ⅲ and by 23.6% in group Ⅳ. And there was a distinct difference between group M and Ⅳ （P 〈 0.05）. The median MVD for all groups was 37.4 ± 8.6, 30.6 ± 7.8, 27.6 ± 7.1, and 10.7 ± 4.1 （microvessels/mm^2） in group Ⅰ, Ⅱ, M and IV, respectively. And there was a marked difference between group M and Ⅱ （P 〈 0.05）, Ⅳ and Ⅱ （P 〈 0.01）, and Ⅳ and M （P 〈 0.01）. CONCLUSION： KDR promoter-HSV-tk gene may effectually restrain the growth of tumor via targeting angiogenesis for hepatocellular carcinoma with treatment of GCV.

Retrovirus-mediated herpes simplex virus thymidine kinase gene therapy approach for hepatocellular carcinoma

The therapeutic effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system on hepatocellular carcinoma was studied in this experiment. The tk-containing retroviral recombinants were used to infect hepatoma cells (BEL-7402) and the cells were treated with ganciclovir (0-1000 microg/ml). The results showed that HSV-tk gene could be efficiently transferred in vitro into hepatoma cells and stably expressed. The growth potential of the tk-containing cells was significantly inhibited by GCV (P

Cooperative Therapeutic Effects of Herpes Simplex Virus Thymidine Kinase Gene/Ganciclovir System and Chemotherapeutic Agents on Prostate Cancer in vitro

The killing effects of herpes simplex virus thymidine kinase gene/ganciclovir （HSV-tk/GCV） approach by the addition of several commonly clinical chemotherapeutic agents on hormone refractory prostate cancer （HRPC） cells PC-3m were investigated. After transferring of the HSV-tk gene into PC-3m cells, mRNA and protein expression of HSV-tk was detected by reverse-transcript polymerase chain reaction （RT-PCR） and strept avidin-biotin complex （SABC） im- munohistochemical method. The killing effect of GCV, cisplatin （CDDP）, etoposide （VP-16）, vincristine （VCR）, methotrexate （MTX）, 5-fluorouracil （5-Fu）, and suramin on PC-3m cells was evaluated by morphological assessment analysis, trypan blue exclusion assay and MTT assay respectively. Additionally, the cooperative effect of HSV-tk/GCV system combined with the above agents on the target cancer cells was determined by MTT. Furthermore, apoptosis and necrosis induced by GCV plus 5-Fu or suramin was analyzed by flow cytometry （FCM）. The results showed that that there was HSV-tk mRNA and protein expression in pDR2-tk plasmid transduced PC-3m cell. Combination of GCV with VP-16, VCR, 5-Fu or suramin led to an enhanced cellular killing effect, but with CDDP resulted in a reduced one and with MTX in an approximate one. FCM revealed that synergistic use of GCV and 5-fu or suramin resulted in a rather large proportion of apoptosis and necrosis with the apoptosis index being 36.38 % and 35.51%, and the proportion of necrosis being 33.05 % and 28.87 %, respectively. In conclusion, HSV-tk/CGV approach by addition of certain clinical available chemotherapeutic drugs brings on statistically significant enhanced cell killing over single-agent treatment. Our results highlight the potential for such new combination therapies for future treatments of HRPC.

Construction of the recombinant vector carrying herpes simplex virus thymidine kinase and cytokine genes expressed in cell line Tca8113

Objective: To construct expression vector containing fusion genes of herpes simplex virus thymidine kinase(Hsv-tk), Interleukin-2(IL-2) with internal ribosome entry sites(IRES), and to assess their expression in cell line Tca8113. Methods: IL-2 cDNA was obtained by reverse transcription. Hsv-tk, IL-2 and IRES genes were amplified by PCR. The purified amplification products were inserted into pGEM-T-Easy, and transformed into E.coli JM109. The purified recombinant plasmids were identified by restriction endonucleases. The recombinant plasmids were digested and pEGFP-N 3 were linearized, DNA fragments of Hsv-tk, IRES and IL-2 were ligated into linearized pEGFP-N 3, and then transferred into E.coli JM109. The recombinant tk-IL-2 genes were cloned separately and introduced into the expression vector pEGFP-N 3 containing GFP. The recombinant vectors were identified by their restriction sites through PCR. The plasmids pEGFP-TI was also transfected into Tca8113 cells by calcium phosphate method for the expression of fusion proteins. Fusion genes expressing vector PL(TI)SN was generated by the fusion of HSV-tk, IRES and IL-2 with the use of DNA recombination technology. The recombinant retroviruses were transferred into Tca8113 cells by lipofectamine. The positive clones were obtained after G418 selection and named Tca/TI respectively. Results: The pEGFP-TI pasmid was identified respectively by restriction endonucleases, and their fragment sizes were 1 120 bp and 450 bp. The pEGFP-TI pasmid as templates were amplified respectively by PCR, and their PCR products were 1 120 bp and 450 bp. The pEGFP-TI vectors were used to transfect Tca8113 cell, and the cells with fluorescence accounted for 60% of the total amount. Conclusion: pFGFP-tk-IRES-IL-2 expressing vector is easy to assess the expression of tk-IRES-IL-2-GFP fusion protein localization in transfected cells. The successful construction of expressing vector containing fusion genes of Hsv-tk, IRES and IL-2 may be beneficial for gene therapy in cell line Tca8113.

An Oncolytic Adenovirus Expressing Herpes Simplex Virus-Thymidine Kinase for Targeting Cancer Therapy:An in vitro Evaluation

Objective： Oncolytic adenovirus, also called conditionally replicating adenovirus （CRAD）, has been developed for the treatment of cancer. However, there is a tremendous need to enhance their antitumor efficacy. Here we wish to evaluate whether a strategy that combines the herpes simplex virus-thymidine kinase with oncolytic effects offers a therapeutic advantage. Methods： A novel adenovirus Ad-ETK containing a sequentially positioned promoter of human telomerase reverse transcriptase （hTERT）, the coding sequence of E1A gene, an internal ribosome entry site sequence （IRES） and the coding sequence of herpes simplex virus-thymidine kinase （HSV-TK） was constructed. Infection of various cells with Ad-ETK followed by RT-PCR confirmed the expression of E1A and HSV-TK. The oncolytic ability and synergism between oncolytic effects and HSV-TK system was measured. The infection efficiency was determined by flow cytometry. Results： Ad-ETK deliverys E1A and HSV-TK gene, which selectively replicates in hTERT-positive tumor cells, and the progeny virus can reach up to 150 IU/cell. Our in vitro study showed that Ad-ETK plus ganciclovir （GCV） induced an obvious cell death. Conclusion： An oncolytic adenovirus plus the HSV-TK/GCV suicide gene system resulted in a significant improvement in treatment efficacy and it may offer important considerations in the development and preclinical assessments of oncolytic virotherapy.

Synergy in Rice Immunity:Exploring Strategies of Coordinated Disease Defense Through Receptor-Like Kinases and Receptor-Like Cytoplasmic Kinases

Receptor-like kinases(RLKs)and receptor-like cytoplasmic kinases(RLCKs)play an indispensable role in the perception and transmission of extracellular signals in plants.In rice,these kinases actively participate in immune responses against a variety of pathogens,including fungi,bacteria,and viruses.However,research on the specific response mechanisms and the spectrum of different kinase activities against various pathogens remains insufficient.This review provides an in-depth and comprehensive overview of the types and functions of RLKs and RLCKs involved in disease resistance,emphasizing the central role of certain RLKs and RLCKs in the plant immune system.These kinases can recognize specific molecular patterns of pathogens and rapidly initiate an immune response in rice.Furthermore,the activity and functional regulation of these key kinases are tightly controlled by various post-translational modifications,such as phosphorylation and ubiquitination.This meticulous regulation ensures that the rice immune system's response is both precise and timely,effectively balancing the intensity of the immune response and preventing potential issues caused by either hyperactivity or insufficiency.By synthesizing current research findings,this review not only broadens our understanding of the role of RLKs and RLCKs in plant immunity but also provides new perspectives and strategies for future research on disease resistance breeding in rice.Future studies are expected to delve deeper into the signaling networks and regulatory mechanisms of these kinases,exploring their potential in agricultural production to develop rice varieties with enhanced disease resistance.

Protein kinases are potential targets to treat inflammatory bowel disease

Protein kinases play a crucial role in the pathogenesis of inflammatory bowel disease(IBD), the two main forms of which are ulcerative colitis and Crohn's dis-ease. In this article, we will review the mechanisms of involvement of protein kinases in the pathogenesis of and intervention against IBD, in terms of their effects on genetics, microbiota, mucous layer and tight junc-tion, and the potential of protein kinases as therapeutic targets against IBD.

High efficient generation of replication-defective adenoviruses containing thymidine kinase by homogeneous recombination in bacteria

Background Suicide gene therapy is a widely used molecular treatment for head and neck cancer. In this study, we try to use the method of homogenous recombination in bacteria to clone thymidine kinase gene （tk）-a kind of suicide gene to adenovirus backbone vectors for the construction of replication-defective adenoviruses. Methods pAdTrack-CMV/tk was constructed through subclone of a restriction endonuclease fragment including thymidine kinase gene from plasmid pCMV-tk to another plasmid pAdTrack-CMV, and then co-transfected with supercoiled pAdEasy-1, which was an adenoviral backbone vector except for deletions of E1 and E3, to competent E. coli BJ5183 for homogenous recombination using electroporation procedure. With the same method, pAdTrack-CMV was also co-transformed with pAdEasy-1 for homogenous recombination in BJ5183. Identified with restriction endonuclease Pad and polymerase chain reaction （PCR）, plasmids pAd-GFP/tk and pAd-GFP were successfully constructed. Each of them was digested with Pacl and sequently transfected into human embryo kidney 293 cells （HEK293） using Lipofectamine 2000. Results Comet-like adenovirus-producing foci of Ad-GFP/tk and Ad-GFP were observed after 5 to 7 days of cell culture After twelve days of packaging, the replication-defective adenoviruses were collected. Identified with PCR, thymidine kinase gene was successfully constructed into Ad-GFP/tk. Conclusion The replication-defective adenoviruses containing thymidine kinase can be constructed more easily by homogenous recombination in bacteria than conventional techniques.

Thymidine kinase gene mutation leads to reduced virulence of pseudorabies virus

To explore correlation between the tk gene structure of pseudorabies virus (PRV) and its virulence, to study the effect of the gene mutation on PRV biological properties, and to investigate mechinism of reduced virulence, thymidine kinase (TK)-deficient mutant of pseudorabies virus strain Hubei (PRV HB) was isolated by selection for resistance to 5-bromodeoxyuridine. The tk genes of PRV HB and its TK mutant were cloned and sequenced. 1587 base pairs of the tk gene and flanking regions of wild-type (wt) virus were sequenced, which included an open reading frame (ORF) of 1098 bp encoding a protein of 366 amino acids. The ORF contained two 137-bp repeated sequences, which were connected by an adenosine. 1458 bp of the tk and flanking regions of TK- mutant were sequenced. Analysis of the tk gene sequence of TK mutant indicated that one of 137 bp repeated sequence and the connecting adenosine in the tk gene of the wt virus was deleted and a repeated sequence of 8 nucleotides (GCGCGCC) was inserted. All

Expression and Clinical Significance of Cytokeratin-19 and Thymidine Kinase-1 in Advanced Gastrointestinal Cancer

Background： As the clinical value of cytokeratin-19 （CK 19） and thymidine kinase-1 （TK1 ） in advanced gastrointestinal cancer remains controversial, we investigated their expression and clinical significance in this disease. Methods： A total of 171 advanced gastrointestinal cancer patients were prospectively enrolled in this study. The mRNA level of CK 19 was detected using quantitative real-time reverse transcription-polymerase chain reaction （PCR） in all patients, along with a control group of fifty healthy individuals. Furthermore, detection of TK1 protein was carried out in 96 patients using a chemiluminescence dot blot assay. The primary endpoint was overall survival （OS） time. Results： Positive CKl 9 mRNA expression was detected in 74 （43.3%） of the 171 patients and positive TK1 expression was detected in 66 （68.8%） of the 96 patients. Furthermore, of the 96 patients, 36 （37.5%） were positive for both TK1 protein and CK19 mRNA, 30 （31.3%） were negative for TK1 protein, and 15 （15.6%） were negative for TKl protein and positive for CK19 mRNA. The results indicated that patients who were positive for CK 19 mRNA expression had significantly shorter OS times than those who were negative for it （median OS 7.7 vs. 9.7 months, respectively; P = 0.02）. Moreover, patients who were positive tbr CK 19 mRNA and TK 1 protein expression had shorter OS times （median OS 6.1 months） than those who were positive for CKl9 mRNA and negative for TKl protein expression （median OS 9.1 months; P： 0.028）. Positive CK 19 mRNA expression was significantly associated with shorter OS in the univariate analysis （P = 0.027）. Based on a multivariate Cox regression analysis, CK19 mRNA together with TK1 protein expression （P = 0.024） was an independent predictor for OS in gastrointestinal cancer patients. Conclusions： Our results suggest that positive expression ofCKl9 mRNA and TK1 protein is closely correlated with poor prognosis in advanced gastrointestinal cancer. Furthermore, both CKl9 and TKl are possible gastrointestinal cancer biomarkers.

Genetic polymorphism and natural fertility in women

Objective: To investigate the cooperative interaction among five genetic systems (phosphoglucomutase locus 1, adenosine deaminase locus 1, acid phosphatase locus 1, adenylate kinase locus 1, and haptoglobin) concerning their effects on natural fertility in humans. Natural fertility has been evaluated by a model of age related differences between the distributions of types among pregnant women. Methods: A total of 137 nonsmoking consecutive puerperaes from the white population who had delivered their first born baby in the Maternity Department of S. Massimo Hospital of Penne were studied. The phenotypes of the five systems studied were determined by starch gel electrophoresis. Statistical analysis was performed using the statistical package for the social science. Results: There was a highly significant negative correlation between maternal age and the number of genetic factors showing a lower maternal age at the birth of the first child, which suggested a positive cooperative interaction among these factors concerning their effects on fertility. Conclusions:In the relationship of mother-fetus, besides nutritional factors, genetic factors involved in immunological interaction of the embryo with the mother are of paramount importance. Haptoglobin and adenosine deaminase locus 1 polymorphisms are involved in immune reactions and our data indicate that genetic variability within these systems gives a more important contribution to variation of human fertility as compared to acid phosphatase locus 1, phosphoglucomutase locus 1 and adenylate kinase locus 1 that are mainly involved in metabolic functions.

Thymidine Kinase 1(TK1)重组蛋白的表达、纯化及鉴定

为获得具有免疫原性的TK1重组蛋白。通过构建能够表达TK1蛋白的重组菌BL21-pET32a-TK1,采用大肠杆菌pET32a表达系统,优化IPTG浓度、诱导温度、诱导时间使BL21-pET32a-TK1重组菌表达目的蛋白的作用条件最佳。表达产物用镍离子亲和层析纯化获得TK1蛋白,并用SDS-PAGE和Western blot进行检测。用TK1重组蛋白免疫BALB/c小鼠制备单克隆抗体,检测蛋白质免疫原性。实验结果表明,成功构建能够表达TK1蛋白的重组菌BL21-pET32aTK1,在37℃条件下,IPTG浓度为0.2mmol/L、诱导6h时重组蛋白TK1表达量最高。镍离子亲和层析梯度洗脱在80mmol/L咪唑条件下TK1蛋白纯度最大,灰度分析为87.3%,浓缩后蛋白质浓度为5.96mg/ml。用该蛋白质制备杂交瘤共获得10株稳定分泌TK1抗体的阳性单克隆细胞株,表明TK1重组蛋白具有较好的免疫原性。成功获得可溶性、抗原活性高、免疫原性强的TK1重组蛋白,为肿瘤科学及临床应用研究提供物质支撑。

预后营养指数及血清suPAR、TK1在晚期肝癌预后中的预测价值

目的探索预后营养指数(PNI)及血清可溶性尿激酶型纤溶酶原激活物受体(suPAR)、胸苷激酶1(TK1)在晚期肝癌表达意义以及在预后评估中预测的应用价值。方法选取2019年2月至2021年2月收集的92例晚期肝癌患者进行回顾性分析,均进行PNI评估及血清suPAR、TK1检测,比较两组PNI、suPAR、TK1水平。同时,根据患者是否死亡,分为预后不良组(n=28,死亡),预后良好组(n=64,生存),经多因素Cox回归模型分析影响晚期肝癌患者预后独立危险因素,经受试者操作特征(ROC)曲线分析PNI、suPAR、TK1的诊断价值。结果经单因素分析,血管侵犯、门静脉癌栓会对晚期肝癌预后造成影响(P<0.05),且预后不良组PNI低于预后良好组,suPAR、TK1水平高于预后良好组,差异有统计学意义。Kaplan-Meier生存分析显示,PNI高表达、suPAR低表达、TK1低表达、无血管侵犯、无门静脉癌栓者生存时间显著高于PNI低表达、suPAR高表达、TK1高表达、有血管侵犯、有门静脉癌栓者,差异有统计学意义(P<0.05);经多因素Cox回归模型分析,PNI低表达、suPAR高表达、TK1高表达是影响晚期肝癌患者预后的独立危险因素(P<0.05)。经ROC曲线分析,PNI、suPAR、TK1及3项联合诊断晚期肝癌预后的曲线下面积分别为0.818、0.827、0.801、0.957。结论晚期肝癌患者血清suPAR、TK1水平升高,PNI降低,PNI、suPAR、TK1可作为一项简捷而有效的指标,来协助评估晚期肝癌患者的病情严重程度及预后。

扶正驱邪方联合新辅助化疗对三阴性乳腺癌患者肿瘤复发、血清TK1 水平及免疫功能的影响

【目的】探究扶正驱邪方联合新辅助化疗对三阴性乳腺癌(TNBC)患者肿瘤复发、血清胸苷激酶1(TK1)水平及免疫功能的影响。【方法】将80例TNBC气阴两虚型患者随机分为联合组和对照组,每组各40例。对照组给予AC-T序贯化疗方案(多柔比星与环磷酰胺联合并序贯多西他赛)治疗,联合组在对照组的基础上加用扶正驱邪方治疗。1个疗程为21 d,连续治疗4个疗程。观察2组患者治疗前后中医证候积分、生活质量Karnofsky功能状态(KPS)评分、肿瘤标志物[糖类抗原125(CA125)、糖类抗原153(CA153)、TK1]水平及T淋巴细胞亚群的变化情况,比较2组患者的临床疗效以及肿瘤的转移、复发情况。【结果】(1)治疗4个疗程后,联合组的总有效率为87.50%(35/40),对照组为67.50%(27/40),组间比较(χ2检验),联合组的疗效明显优于对照组(P<0.05)。(2)治疗后,2组患者的中医证候积分均较治疗前明显降低(P<0.05),KPS评分均较治疗前明显升高(P<0.05),且联合组对中医证候积分的降低幅度及对KPS评分的升高幅度均明显优于对照组(P<0.05或P<0.01)。(3)治疗后,2组患者的血清CA125、CA153、TK1水平均较治疗前明显降低(P<0.05),且联合组对血清CA125、CA153、TK1水平的降低幅度均明显优于对照组(P<0.01)。(4)治疗后,2组患者的T细胞CD3+、CD4+水平和CD4+/CD8+比值均较治疗前明显升高(P<0.05),CD8+水平均较治疗前明显降低(P<0.05),且联合组对T细胞CD3+、CD4+水平和CD4+/CD8+比值的升高幅度及对CD8+水平的降低幅度均明显优于对照组(P<0.05或P<0.01)。(5)经过1年的随访调查,联合组的肿瘤复发率和肿瘤转移率分别为7.50%(3/40)和12.50%(5/40),明显低于对照组的25.00%(10/40)和35.00%(14/40),组间比较,差异均有统计学意义(P<0.05)。【结论】扶正驱邪方联合新辅助化疗对于TNBC气阴两虚型患者的治疗效果较好,能有效改善患者的免疫功能,降低血清肿瘤标志物水平,提高患者的生活质量,降低肿瘤复发和转移的发生率。

单操作孔电视胸腔镜肺癌根治术治疗非小细胞肺癌患者的疗效观察

目的观察单操作孔电视胸腔镜(VATS)肺癌根治术对非小细胞肺癌(NSCLC)血管内皮生长因子受体2(VEGFR2)、胸苷激酶1(TK1)水平的影响。方法我院收治的245例NSCLC患者,按手术方式分为对照组(三孔胸腔镜肺癌根治术,n=115)和观察组(单操作孔VATS肺癌根治术,n=130),比较两组围术期指标、视觉模拟(VAS)评分、肺功能、炎性因子、肿瘤标志物、VEGFR2、TK1水平及并发症。结果观察组术中出血量较对照组少(P<0.05);术后,观察组VAS评分、炎性因子、肿瘤标志物和VEGFR2、TK1水平低于对照组,肺功能高于对照组(P<0.05)。结论单操作孔VATS肺癌根治术治疗NSCLC出血量少、疼痛轻,可改善肺功能,降低炎性因子、肿瘤标志物和VEGFR2、TK1水平,且不增加术后并发症,值得临床推广。