^3H-thymidine渗入法测定Urocortin对大鼠血管平滑肌细胞增殖的影响

目的探讨Urocortin(UCN)对大鼠血管平滑肌细胞增殖的影响。方法分离、培养大鼠血管平滑肌细胞,分别加入不同浓度的UCN以及UCN+Astressin,UCN+Glybenclamide培养,采用3H-thymidine掺入法,观察不同浓度UCN对血管平滑肌细胞增殖的影响,及其相关作用机制。结果随着Urocortin浓度的增高,VSMC对3H-thymidine摄取率呈下降趋势,而该作用不受Astressin或Glybenclamide的影响。结论Urocortin具有抑制大鼠血管平滑肌细胞增殖的作用,其作用不是通过CRF受体或KATP通道。

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.

Relationship between the Expression of Thymidylate Synthase,Thymidine Phosphorylase and Dihydropyrimidine Dehydrogenase and Survival in Epithelial Ovarian Cancer

The mRNA and protein expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) and their relationship with prognosis were investigated. Real-time quantitative RT-PCR (Taqman) was used to detect the mRNA expression of TS, TP and DPD in formalin-fixed and paraffin-embedded 106 samples of epithelial ovarian cancer and 29 normal ovaries. A TATA box-binding protein (TBP) was used as an endogenous reference gene. A relationship between TS, TP, DPD expression and clinicopathologic features was investigated. The protein location and expression of TS, TP and DPD was examined in the same patients by an avidin-biotin-peroxidase immunohistochemistry. TS and TP mRNA expression levels were significantly higher in tumor group than in normal controls, with the average value of TS and TP mRNA being 6.14±0.62 and 0.59±0.06 in tumor tissue, and 0.71±0.14 and 0.16±0.04 in normal tissue, respectively. DPD mRNA expression levels were significantly lower in tumor group (0.11±0.02) than in normal controls (0.38±0.05). There was statistically significant difference in TS and TP mRNA expression levels among different pathological grades and clinical stages (P<0.05), but histological subtype was not significantly associated with TS and TP mRNA expression. DPD gene expression was not significantly associated with any clinicopathological parameters. Immunohistochemistry revealed that TP protein was mainly distributed in nucleus, and TS and DPD mainly in cytoplasm. The protein expression intensity of TS, TP and DPD was coincided with the mRNA expression levels. It was concluded that TS, TP mRNA and protein expression levels were significantly higher in epithelial ovarian cancer, and DPD mRNA and protein expression levels were significantly lower. The expression levels of TS and DPD were related to the patients’ prognosis and survival. Combined gene expression levels of TS, TP and DPD represent a new variable to predict the clinical outcome in ovarian cancer. The association of TS, TP and DPD expression levels with survival suggests an importance of these genes for tumor occurrence and progression.

Thymidylate synthase and thymidine phosphorylase gene expression as predictive parameters for the efficacy of 5-fluorouraci-based adjuvant chemotherapy for gastric cancer

AIM： To investigate the prognostic role of thymidylate synthase （TS） and thymidine phosphorylase （TP） mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouraci-based adjuvant chemotherapy. METHODS： Fifty-one patients with T3 or T4 gastric cancer received systemic 5-fluorouraci-based adjuvant chemotherapy, and intratumoral expression of TS and TP in 51 gastric cancer tissue samples was tested by realtime quantitative PCR.RESULTS： The median disease-free survival （DFS） time was 10.2 mo in the patients. There were no significant differences in DFS between the groups with high and low levels of TP. However, the group with low level of TS had a longer DFS （14.4 mo vs 8.3 mo, P = 0.017）. The median overall survival （OS） time was 18.5 mo, and there were significant differences in OS between the groups with high and low levels of TS or TP （for TS, 17.0 mo vs 21.3 mo, P = 0.010; for TP, 16.6 mo vs 22.5 too, P = 0.009）. Moreover, the coupled low expression of these two genes was strongly associated with a longer survival time of patients as compared with that of a single gene.CONCLUSION： Expression of TS and TP mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracilbased adjuvant chemotherapy.

Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma

AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.

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.

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.

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.

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.

Thymidine Glycol: The Effect on DNA Structure and DNA Binding by Site-Specific Proteins

Thymidine glycol (5,6-dihydroxy-5,6-dihydrothymidine, Tg) is a major type of oxidative damage in DNA. During chemical oligonucleotide synthesis, Tg residue was incorporated in the different positions of 17 b.p. DNA duplexes, which differ in one base pair in the internal part. According to UV-melting curves, Tg destabilizes the double helix in a sequence independent manner. In contrast, the localized alterations in duplex structure were shown by CD spectroscopy to depend on the type of base pairs flanking the Tg lesion. Molecular dynamics simulations demonstrate that Tg is partially out of the double helix. For the first time, Tg impact on several site-specific DNA-binding proteins is studied, namely p50 and p65 subunits of nuclear factor kappa-B (NF-κB) and DNA methyltransferase SsoII (M.SsoII). Our results show that p50/p50 and p65/p65 homodimers of NF-κB can tolerate a single Tg residue in the binding site quite well. Nevertheless the homodimers have different affinities to the oxidized κB site depending on the Tg position. M.SsoII can act as a transcription repressor when bound to the regulatory site. M.SsoII demonstrates decreased affinity and lowered methylation efficiency when its methylation site contains Tg in the central position. Single Tg in one half of the regulatory site decreases M.SsoII affinity to the oxidized DNA, whereas Tg presence in both half-sites prevents M.SsoII binding to such ligand.

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

DFT-Based Chemical Reactivity Descriptors, Pharmacokinetics and Molecular Docking Studies of Thymidine Derivatives

Thymidine-containing derivatives are considered to be among the most significant derivatives in medicinal chemistry. In this study, we employed a combined computational approach involving density-functional theory (DFT) calculations, molecular docking simulations, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) property predictions. Prediction of activity spectra for substances (PASS) revealed promising antiviral, antimicrobial and anti-carcinogenic activities of these thymidine derivatives. Using Gaussian 09, we optimized the molecular structures of the thymidine derivatives to obtain their stable conformations and calculate their electronic properties. Subsequently, molecular docking simulations were performed to explore the binding interactions between the thymidine derivatives and the active site of the Candida albicans (PDB: 1IYL and 2Y7L) proteins. The docking results were evaluated based on docking scores, hydrogen bonding, and hydrophobic interactions and revealed favorable binding interactions between the thymidine derivatives and the proteins, suggesting their potential as antifungal agents. The thermodynamic properties, including binding free energy, enthalpy, and entropy changes were determined to assess the stability and strength of the ligands-protein complexes. The calculated pharmacokinetic parameters, such as ADMET properties, provided insights into the drug-likeness and potential bioavailability of the thymidine derivatives. These results offer a foundation for further experimental investigations and the design of novel antifungal agents targeting Candida albicans infections.

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.

Synthesis and Properties of D-Thymidylyl (3'→5')L-Thymidine (D/L-TpT)

The synthesis and properties of D-thymidylyl (3'→5')L-thymidine (D/L-TpT) aredescribed.

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.

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。

血清TFF1 TK1与晚期乳腺浸润性小叶癌患者白蛋白结合型紫杉醇化疗疗效及预后

目的研究血清三叶因子1(TFF1)、胸苷激酶1(TK1)与晚期乳腺浸润性小叶癌(ILC)患者白蛋白结合型紫杉醇化疗疗效和预后的关系。方法选取2018年4月至2020年7月邯郸市中心医院诊治的97例晚期ILC患者纳入ILC组,以同期我院诊治的70例女性乳腺良性疾病患者纳入良性对照组,70例健康体检的女性志愿者纳入健康对照组。检测并比较3组研究对象血清TFF1、TK1水平。比较不同临床病理特征ILC患者血清TFF1、TK1水平差异;多因素logistic回归分析影响化疗疗效的因素;Kaplan-Meier曲线分析不同血清TFF1、TK1表达对晚期ILC患者预后的影响。结果ILC组患者血清TFF1、TK1水平高于良性对照组及健康对照组,差异有统计学意义(P<0.05)。组织学分级Ⅲ级、肿瘤最大径>4 cm的ILC患者血清TFF1、TK1水平高于组织学分级Ⅰ~Ⅱ级、肿瘤最大径≤4 cm患者,差异具有统计学意义(P<0.05)。根据化疗后疗效分为有效组51例,无效组46例。无效组患者组织学分级Ⅲ级比例、血清TFF1、TK1水平高于有效组,差异有统计学意义(P<0.05),组织学分级Ⅲ、血清TFF1、TK1水平是影响ILC患者化疗疗效的独立危险因素(OR=1.885、1.716、1.205;P<0.001、0.017、0.011)。TFF1高表达组和低表达组患者的3年生存率分别为44.19%(19/43),72.22%(39/54);TK1高表达组和低表达组患者的3年生存率分别为43.48%(20/46),74.51%(38/51)。TFF1、TK1高表达组患者3年累积生存率分别低于TFF1、TK1低表达组,差异具有统计学意义(P<0.05)。结论晚期ILC患者血清TFF1、TK1水平升高,两者水平升高是影响白蛋白结合型紫杉醇化疗疗效的危险因素,且与晚期ILC患者预后密切相关。