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1.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 220-227, 2022.
Article in Chinese | WPRIM | ID: wpr-1011594

ABSTRACT

【Objective】 To analyze the gene expression profile of central nervous system primitive neuroectodermal tumors (CNS-PNETs) by bioinformatics methods so as to explore the possible pathogenesis of CNS-PNETs at the molecular level. 【Methods】 The gene expression profile of CNS-PNETs was downloaded from the GEO database, GSE35493 and GSE74195. The differentially expressed genes (DEGs) were screened by the online analysis tool of GEO2R and Venn software, DEGs were analyzed by using the online analysis tools of David database, such as Gene Ontology (GO) and pathway enrichment (KEGG). The protein interaction network analysis (PPI) of CNS-PNETs was made by using STRING online analysis tool, Cytoscape software and its plug-in cytohubba to find the key genes. 【Results】 We obtained 262 DEGs, including 49 upregulated genes and 213 downregulated genes. The analysis of GO function and KEGG signal pathway enrichment showed that DEG was involved in DNA transcription and mitosis, cell division, synaptic signal transmission and other biological processes, and associated with cell cycle, tumor-related pathway, p53 signal pathway, synapsis-related signal pathway, cAMP signal pathway and calcium ion signal pathway. Ten key genes, namely, CDK1, CDC20, MAD2L1, KIF11, ASPM, TOP2A, TTK, NDC80, NUSAP1 and DLGAP5 were screened out by STRING analysis. 【Conclusion】 Ten key genes including CDK1 may play an important role in the initiation and progression of CNS-PNETs, providing new clues for exploring the pathogenesis of CNS-PNETs.

2.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 592-596, 2021.
Article in Chinese | WPRIM | ID: wpr-1006695

ABSTRACT

【Objective】 To compare the efficacy and safety of oxycodone and sufentanil in transition analgesia after radical surgery of cervical cancer under general anesthesia. 【Methods】 A randomized, double-blind study was conducted. We randomly divided 68 patients on radical surgery of cervical cancer under general anesthesia into two groups: Group S (sufentanil in transition analgesia) (n=35) and Group O (oxycodone in transition analgesia) (n=33). Patients in Group S received sufentanil (0.1 μg/kg for endoscopy procedures or 0.15 μg/kg for laparotomy procedures), whereas patients in Group O received oxycodone (0.1 mg/kg for endoscopy procedures or 0.15 mg/kg for laparotomy procedures) 30 min before the end of operation as transition analgesia. We recorded the time of consciousness recovery and extubation, RSS restlessness score, the number of cough times, Ramsay score, Numerical Rating Scale (NRS) at rest in extubation immediately (T0), 30 min after extubation (T1), 1 h after extubation (T2), 2 h after extubation (T3), 4 h after extubation (T4), 12 h after surgery (T5), 24 h after surgery (T6), and the incidence of adverse complications within 24 h after operation. 【Results】 Compared with those in Group S, patients in Group O showed shorter time of consciousness recovery (4.28±3.35 vs. 5.53±2.25, P=0.027), shorter time of extubation (5.92±3.67 vs. 8.09±2.49, P=0.001), lower RSS restlessness score (0.38±0.49 vs. 0.83±0.63, P<0.001), smaller number of cough times (0.96±0.78 vs. 1.34±0.93, P=0.026), lower Ramsay score (2.3±0.58 vs. 2.63±0.85, P=0.017), and lower NRS score at rest in T3 and T4 (2.64±0.63 vs. 3.14±0.66; 2.86±0.81 vs. 3.69±0.75) (P<0.001). The incidence of nausea and vomiting was lower in Group O than in Group S (9.09% vs. 20%; 3.03% vs. 11.43%). 【Conclusion】 Both oxycodone and sufentanil provide adequate pain relief in transitional analgesia after radical surgery of cervical cancer under general anesthesia. However, oxycodone shows longer analgesia, faster recovery, and a lower incidence of side effects than sufentanil.

3.
Journal of Breast Cancer ; : 129-140, 2020.
Article | WPRIM | ID: wpr-835607

ABSTRACT

As a standard treatment, endocrine therapy has dramatically enhanced the prognosis of patients with estrogen receptor (ER)-positive breast cancer, which accounts for nearly 70% of all breast cancers. Antiestrogen drugs such as tamoxifen and aromatase inhibitors are the standard treatment options for ERα-positive breast cancer. However, acquired antiestrogen resistance is still the leading cause of disease recurrence and progression. Evidence has shown that long noncoding RNAs (lncRNAs) play an essential role in the development of antiestrogen resistance in ER-positive breast cancer and can serve as biomarkers or potential therapeutic targets. This review highlights the role of lncRNAs in the development of antiestrogen resistance in breast cancer.

4.
Pakistan Journal of Pharmaceutical Sciences. 2018; 31 (3 Supp.): 985-990
in English | IMEMR | ID: emr-198707

ABSTRACT

To investigate the preventive effect of Kunlun snow chrysanthemum polysaccharides [KSCP] on acetaminophen [AP] induced liver damage and its possible mechanism. Mice acute liver injury model was established via intraperitoneal injection of AP [300 mg/kg]. The biochemical indicators of plasma and liver tissue were tested. The effects of KSCP on the liver index were examined. The liver pathological changes were investigated. The expressions of related protein were detected via Western blotting. In our study, compared with model group, the concentrations and contents of ALT, AST, TNF-alpha, IL-1beta and MDA were reduced and activities of SOD were increase in H-KSCP [1.2mg/10 g]-pretreated mice [P<0.01]. The liver index was significantly reduced in H-KSCP-pretreated mice compared with model group [4.89+/-0.22 vs 7.4+/-0.66, P<0.01]. Liver cellular swelling, degeneration and necrosis relieved, and pathological injury had been improved. Western blotting results showed that the caspase-3 protein level in H-KSCP group was significantly decreased, expression of Bcl-2 protein and Bcl-2/Bax ratio was increased, whereas which of Bax protein was decreased [P<0.01]. KSCP-pretreated at middle and high doses can prevent against the liver injury, its action mechanism may be related to its anti-inflammatory effects and regulation of apoptosis related proteins expression. Overall, our results showed that KSCP may be an effective preventive agent in preventing acute liver injury

5.
China Pharmacy ; (12): 4407-4411, 2017.
Article in Chinese | WPRIM | ID: wpr-667025

ABSTRACT

OBJECTIVE:To study the preventive effect and mechanism of Wei medicine Kunlun snow chrysanthemum polysac-charides(KSCP)on carbon tetrachloride(CCl4)-induced acute liver injury in mice. METHODS:96 mice were randomly divided in-to normal group(normal saline),model group(normal saline),Biphenyl diester dropping pill(positive control,1.5 mg/10 g)and KSCP low-dose,medium-dose,high-dose groups (0.3,0.6,1.2 mg/10 g),16 in each group,with intragastric administration, once a day,for 10 d. Except for normal group,mice in other groups were intraperitoneally injected 1%CCl4 rapeseed oil solution to induce liver injury. After 24 h of modeling,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),tu-mor necrosis factor α(TNF-α),interleukin 1(IL-1)in serum,levels of malondialdehyde(MDA),superoxide dismutase(SOD) in liver tissue were detected;the liver,spleen indexes were calculated. Pathological changes of liver tissue were observed,patho-logical scoring was conducted. The protein expressions of apoptosis-related genes Caspase-3,Bcl-2,Bax in liver tissue were detect-ed. RESULTS:Compared with normal group,levels of ALT,AST,TNF-α,IL-1 in serum,MDA level in liver tissue and liver, spleen indexes in model group were obviously increased(P<0.01);SOD level in liver tissue was decreased(P<0.01);pathologi-cal changes in hepatocellular necrosis,degeneration and inflammatory cell infiltration,and pathological score in model group was obviously increased(P<0.01);caspase-3 protein expression and Bcl-2/Bax ratio in liver tissue in model group were obviously de-creased (P<0.01). Compared with model group,above-mentioned indexes in each administration group were obviously improved (P<0.05 or P<0.01). CONCLUSIONS:KSCP has certain preventive effect on CCl4-induced acute liver injury in mice,and its mechanism may be associated with anti-oxidation,anti-inflammation and regulation of apoptosis-related protein expressions.

6.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 226-229, 2016.
Article in Chinese | WPRIM | ID: wpr-487894

ABSTRACT

ABSTRACT:Objective To study the effects of propofol on the metastasis of tumor cells related PI3K/Akt signaling pathway.Methods The breast cancer model was established by transplanting human derived breast cancer cell lines into immunodeficient mice with naked gene.The mice,inoculated successfully,were randomly divided into 4 groups:control group (C group,n =6),propofol group (P group,n =6),propofol+PI3K inhibitor (BYL71 9)group (P+B group,n =6),and PI3K inhibitor group (BYL71 9)(B group,n =6).The expressions of PI3K,p-Akt and Akt were examined by Western blot at week 4 after administration;the gene levels of PI3KR1, Akt1 and Akt2 were detected by RT-PCR at week 4 after administration;the number of metastatic lung nodules from both lungs was also observed at week 4 after administration.Results Compared with those in C group,the expressions of PI3K and p-Akt were significantly higher in P group (P 0.05),but metastatic lung nodules significantly increased (P < 0.05 ).Compared with those in B group,in P+ B group the expressions of PI3K and p-Akt were markedly higher (P <0.05),the level of PI3KR1 mRNA but not Akt1 and Akt2 mRNA was significantly increased (P <0.05),and metastatic lung nodules significantly decreased (P <0.05).Conclusion Propofol can inhibit the metastasis of tumor cells through the upregulated and activated PI3K/Akt signaling pathway.

7.
Chinese Journal of Microbiology and Immunology ; (12): 343-348, 2014.
Article in Chinese | WPRIM | ID: wpr-451366

ABSTRACT

Objective To study the effects of Toll-like receptor 4(TLR4) on oxidized low density lipoprotein ( ox-LDL) induced macrophage apoptosis and its possible mechanism .Methods THP-1 derived macrophages were divided into four groups including untreated control group , ox-LDL treated group , ox-LDL+LPS treated group and tunicamycin treated group .MTT assay and flow cytometry analysis were performed to measure cell vitality and cell apoptosis , respectively .Oil red O staining was used to observe the phagocytosis of lipids by macrophages .The persistent and intense endoplasmic reticulum ( ER) stress markers were de-tected by analyzing the expression of glucose-regulated protein 78 ( GRP78 ) and CCAAT/enhancer-binding protein homologous protein ( CHOP) at mRNA and protein levels by q-RT-PCR and Western blot .Small in-terfering RNA ( siRNA) was used to silence the expression of TLR 4 to further elucidate its possible mecha-nism.Results Flow cytomotry and MTT assay showed that the number of apoptotic cells in ox-LDL+LPS treated group were increased more significantly than that in ox-LDL treated group (P<0.01), and cell apop-tosis in both two groups were greater than that in control group (P<0.01).Compared with control group, the expression of GRP78 and CHOP at mRNA and protein levels were up-regulated in ox-LDL+LPS treated group and ox-LDL treated group (P<0.01), and the expression of GRP78 and CHOP in ox-LDL+LPS treated group was significantly higher than that in ox-LDL treated group (P<0.01).Silenced expression of TLR4 al-leviated the endoplasmic reticulum stress (P<0.05).Conclusion Increased expression of CHOP contribu-ted to cell apoptosis .TLR4 might promote ox-LDL induced macrophage apoptosis through accelerating endo-plasmic reticulum stress .

8.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 361-363,384, 2014.
Article in Chinese | WPRIM | ID: wpr-599091

ABSTRACT

Objective To investigate the effects of propofol on the proliferation and apoptosis of lung cancer cells as well as the related molecular mechanisms.Methods HCC827 cells were seeded in well plates with a density of 1×106 and then randomly divided into 5 groups:control group (group C),intralipid group (group E),low-dose propofol group (1.5μL/mL,group P1),medium-dose propofol group (2.2μL/mL,group P2),and high-dose propofol group (3.2μL/mL,group P3).At 6 h,24 h and 48 h after propofol treatment,the cells were collected to detect their proliferation and apoptosis.At 6h after treatment,the cells were collected for the measurement of Nrf2 mRNA and protein by RT-PCR and Western blot.Results Cell inhibition rate (IR)and apoptosis as well as Nrf2 mRNA and protein expressions in group E did not differ significantly from those in group C (P>0 .0 5 ).Compared with those in groups C and E,IR and apoptosis and Nrf2 mRNA and protein expressions were significantly increased in groups P1,P2 and P3 (P<0.05).Conclusion Propofol can inhibit the proliferation of cancer cells and promote cell apoptosis,thereby inhibiting the reoccurrence and metastasis of cancer cells probably via regulating the activation of Nrf2 expression.

9.
Clinical Medicine of China ; (12): 18-21, 2014.
Article in Chinese | WPRIM | ID: wpr-444236

ABSTRACT

Objective To investigate toil-like receptor 4 (TLR4) expression and activity in peripheral blood mononuclear cells(PBMCs) of obese patients.Methods PBMCs from 16 obese patients and 16 normal control subjects were collected.TLR4 and IκBα protein concentrations were measured in PBMCs by western blotting.TLR4 and interleukin-6 (IL-6) mRNA expression levels in PBMCs were measured by quantitative realtime PCR.The blood levels of glucose,insulin,free fatty acids (FFA),IL-6 and tmnor necrosis factor-α (TNF-α) were measured after an overnight fast.Results The levels of FFA,IL-6,TNF-α and homeostasis model assessment of insulin resistance index (HOMA-IR) in obese patients were higher than that of control group (FFA:(879 ± 64) μmol/L vs.(458 ± 48) μmol/L; IL-6:(2.20 ± 0.35) ng/L vs.(1.26 ± 0.25) ng/L; TNF-α:(1.96±0.32) ng/Lvs.(1.38 ±0.24) ng/L;HOMA-IR:(1.8±0.2) vs.(0.4±0.1) ;t=24.613,P=0.000;t =14.993,P =0.000;t =9.128,P =0.000;t =32.254,P =0.000).Increased TLR4 gene and protein expression were observed in PBMCs of obese patients compared with control group(TLR4 mRNA:(3.13±0.21) vs.(0.99 ± 0.03),t =54.758,P < 0.05; TLR4 protein:(7.04 ± 0.42) vs.(2.53 ± 0.17),t =77.450,P <0.05).IκBα protein concentration in PBMCs of obese patients (2.52 ±0.16) was lower than in control group (4.00 ± 0.30,t =23.284,P < 0.05),indicating elevated IKKβ/NF-κB signaling.The increase in TLR4 and NF-κB signaling was accompanied by elevated expression of the NFκB-regulated gene IL-6 ((2.55 ±0.15) vs.(1.03 ±0.11),t =53.981,P <0.05).Conclusion TLR4 expression and activity are increased in the PBMCs of patients with obesity and might involve in the development and progress of insulin resistance.

10.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 357-360, 2014.
Article in Chinese | WPRIM | ID: wpr-448050

ABSTRACT

Objective To investigate the effects of propofol on the changes in myocardial Toll-like receptor 4 (TLR-4)and TNF-αand NF-κb protein expressions in ischemia-reperfusion injury (I/R).Methods Thirty healthy male SD rats weighing 250-320 g were randomly divided into 3 groups (n=10 for each):Group A,sham operation;Group B,I/R;and Group C,propofol + I/R.In Groups B and C myocardial I/R was induced by occlusion of the left anterior descending artery (LAD)for 30 min,followed by 120 min reperfusion.In Group C propofol was given intravenously 1 0 min before myocardial ischemia,followed by continuous infusion of propofol at 5 mg/(kg·h)until the end of 120 min reperfusion.In Groups A and B normal saline instead of propofol was given. The myocardial tissues were taken at the end of 120 min;ultrastructural changes of myocardial cells were observed under X-ray electron microscope and the expressions of TLR-4 mRNA as well as TNF-αand NF-κb protein were determined.Results Ultrastructural observation under electron microscope showed significantly worsened damage in myocardial tissue structure and mitochondria in Groups B and C compared with Group A.The myocardial expressions of TLR-4 and TNF-αand NF-κb protein were significantly higher in Groups B and C than in control Group A.The myocardial expressions of TLR-4 and TNF-αand NF-κb protein were down-regulated in Group C compared with Group B.Conclusion Intravenous injection of propofol can protect against myocardial damage.Propofol can suppress the increase in myocardial TLR-4 and TNF-αand NF-κb protein expressions induced by I/R.

11.
Journal of Southern Medical University ; (12): 1775-1777, 2013.
Article in Chinese | WPRIM | ID: wpr-232704

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of palmitate on toll-like receptor 4 (TLR4) expression and signaling in vascular endothelial cells.</p><p><b>METHODS</b>Pig iliac endothelial cells (PIECs) were incubated with palmitate. TLR4 gene expression levels were measured by quantitative real-time PCR, and TLR4 and IκBα protein expressions by Western blotting. The expression levels of TLR4 protein on the surface of PIECs were quantified using flow cytometry. ELISA was employed to detect tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations in the cell medium.</p><p><b>RESULTS</b>Palmitate treatment significantly increased TLR4 mRNA and protein expression levels in PIECs compared with those in the control cells (4.73∓0.61 vs 1.25∓0.90, P<0.05; 5.79∓0.05 vs 4.07∓0.31, P<0.05). The expression levels of TLR4 on the cell surface significantly increased (38.070∓3.907 vs 29.390∓1.072, P<0.05), while IκBα protein level was significantly lowered in PIECs after palmitate treatment as compared with those in the control cells (2.04∓0.22 vs 3.98∓0.18, P<0.05). Palmitate treatment significantly elevated TNF-α (2.52∓0.30 vs 1.38∓0.26, P<0.05) and IL-6 (IL-6: 3.28∓0.32 vs 1.44∓0.28, P<0.05) concentrations in the cell culture medium.</p><p><b>CONCLUSION</b>Palmitate can enhance TLR4 expression and signaling in porcine vascular endothelial cells.</p>


Subject(s)
Animals , Blotting, Western , Endothelial Cells , Metabolism , I-kappa B Proteins , Metabolism , Interleukin-6 , Metabolism , NF-KappaB Inhibitor alpha , Palmitates , Pharmacology , RNA, Messenger , Real-Time Polymerase Chain Reaction , Signal Transduction , Swine , Toll-Like Receptor 4 , Metabolism , Tumor Necrosis Factor-alpha , Metabolism
12.
Practical Oncology Journal ; (6): 481-484, 2013.
Article in Chinese | WPRIM | ID: wpr-499293

ABSTRACT

Objective To evaluate the effect and the best concentration of Rg 3 combined with delaying tamoxifen resistance in breast cancer .Methods The tamoxifen-resistant(TAM-R)cell line with TAM was es-tablished.TAM-R cell line and WT -MCF-7 cell line were cultured in TAM at different concentrations and then detected the growth of cells .WT-MCF-7 cell line was cultured medium in TAM which contained Rg 3 at different levels .The growing situation of cells was detected with MTT method .Results Compared with wild -type WT-MCF-7 cells,TAM-R showed higher curves when they were both at TAM treatment .Rg3 could be associated with delaying the emergency of tamoxifen resistance and the best concentration was 1 ×10 -8 mol/L and 5 ×10 -8 mol/L.Conclusion It might be useful to reduce the tamoxifen resistance incidence by clinically com-bined Rg3 with TAM treatment .

13.
Chinese Journal of Neurology ; (12): 109-112, 2011.
Article in Chinese | WPRIM | ID: wpr-384416

ABSTRACT

Objective To investigate serum uric acid (UA) levels and related clinical features in patients with high risk syndrome of neuromyelitis optica. Methods UA levels were measured in 51 patients with high risk syndrome of neuromyelitis optica including 34 with longitudinally extensive transverse myelitis (LETM) and 17 with optic neuritis (ON), 48 with neuromyelitis optica (NMO), 45 with other neurological diseases (OND) and 65 with healthy controls (HC). The disability severity was assessed by the expanded disability status scale (EDSS). Spinal lesions were viewed by MRI. Serum aquaporin-4(AQP4) antibody was tested in cell based immunofluorescence assay. Results Serum UA levels in LETM ( ( 189. 84 ±85. 65) μmol/L) and ON patients ( (222. 12 ±61.68) μmol/L) were significantly lower than that in OND ((315.90±71.36) μ mol/L) and HC ((291.05 ±76.64) μ mol/L) subjects (P<0.01). No difference was found between LETM, ON and NMO groups. UA levels were significantly lower in females ( ( 158.24 ±55.92), (187.00±47.52), (198.21 ±62.62), (274.51 ±70.66)and (243.26±60.65) μmol/L)than in males ( ( 262. 09 ± 101.63 ), ( 262. 45 ± 62. 13 ), ( 298.90 ± 74. 14 ), ( 355.37 ± 50. 30 ) and (340. 34 ±58. 23) μmol/L) in all groups (t=3. 183, 2.578, 4.356, 4.365 and 6.579, all P<0.05).UA levels in patients with high risk syndrome of NMO were not correlated with mono or relapse course,duration or status of serum AQP4 antibody. UA were negatively correlated with EDSS in patients with LETM (r= -0.714, P<0.01). Conclusion Lower serum UA levels were found in patients with high risk syndrome of NMO and related to more severe symptoms in LETM group.

14.
Chinese Journal of Internal Medicine ; (12): 935-938, 2010.
Article in Chinese | WPRIM | ID: wpr-386323

ABSTRACT

Objective To investigate serum uric acid (UA) levels and related clinical characteristics of neuromyelitis optica (NMO). Methods The serum uric acid levels were measured in 65 patients with NMO, compared to control groups which were 76 cases with multiple sclerosis ( MS), 126 cases with cerebral vascular diseases (CVD) and 130 healthy controls(HC). The disability severity in NMO was assessed by the Expanded Disability Status Scale (EDSS). Magnetic resonance imaging ( MRI ) was performed to strengthen assessment the involved lesions. Serum AQP4 antibody was tested in a cell based immunofluorescence assay. Results In male groups, serum UA levels in NMO patients [ (298.90±74.14) μmol/L] were significantly lower than that in CVD [ (355.37 ±50. 30) μmol/L] and HC subjects [ (340.33 ± 58.23 ) μmol/L, P < 0.05 ]. No difference was found between NMO and MS [ ( 292.36 ±92.95) μmol/L] groups. In female groups, serum UA levels in NMO patients [(198.21 ± 62.62)μmol/L] were significantly lower than that in CVD [(274.51 ± 70.66) μmol/L] and HC subjects [(243.26 ±60.65) μmol/L,P <0.05]. No difference was found between NMO and MS [(232.29 ±71.95 ) μmol/L ] groups. UA levels were significantly lower in females [ ( 198.21 ± 62. 62) μ mol/L] than in males [ (298.90 ±74.14) μmol/L]. UA levels were significantly lower in patients with EDSS≥5 [ ( 195.48 ± 83.70 )μmol/L] than EDSS < 5 [ (241.00 ± 63.20)μmol/L] NMO patients. In our study UA levels were not correlated with longitude of spinal lesions, activity revealed by MRI and AQP4 antibody tires.Conclusion Lower serum UA levels were found in patients with NMO and related to more severe symptoms.

15.
China Oncology ; (12)2006.
Article in Chinese | WPRIM | ID: wpr-546962

ABSTRACT

Background and purpose:Angiogenesis plays an important part in growth and metastases of breast cancer. Nowadays researchers put more concern about whether endocrine therapy adjusts tumor angiogenesis in breast cancer. Here we investigated the regulation of vascular endothelial growth factor(VEGF) expression in breast cancer in response to various stimuli:estradiol(E2) ,ICI182780 and tamoxifen. Methods:We studied the regulation of VEGFmRNA expression in MCF-7 cells stimulated by E2 at different doses and duration by semiquantitative RT-PCR. When ICI182780 and Tamoxifen used alone or in combination with E2,the expression of VEGFmRNA was detected respectively. Results:Dose-dependent experiments indicated that the maximum VEGF mRNA level(0.125?0.006) -(0.112?0.014) was obtained at 1-10 nmol/L.The response of VEGFmRNA expression to E2(1 nmol/L) occurred in a time-dependent manner;the level of VEGF transcripts(0.105?0.009) signifi cantly increased within 2 h and reached a maximum at 6 h(0.140?0.024)(P

16.
Chinese Journal of Lung Cancer ; (12): 181-185, 2005.
Article in Chinese | WPRIM | ID: wpr-326800

ABSTRACT

<p><b>BACKGROUND</b>Recently a number of preclinical studies have sparked interest in the concept of exploiting conventional chemotherapeutic drugs as antiangiogenics. Such antiangiogenic activity is achieved by metronomic-dosing (low-dose) protocols. This new target may have some advantages in avoiding toxicity and resistance caused by chemotherapeutic drugs. This study is to test the efficacy of continuous low-dose cyclophosphamide (CTX) for antiangiogenic effect on Lewis lung carcinoma, and investigate its antitumor effect and toxicity.</p><p><b>METHODS</b>C57/BL6 mice bearing Lewis lung carcinoma were randomly divided into three groups, receiving low-dose metronomic (LDM) CTX, maximum tolerated dose (MTD) CTX therapy and saline respectively. Tumor growth, weight loss, peripheral white blood cell counts and survival of mice were monitored in each group. At the end of experiment, tumors were resected for immunohistochemical staining. Tumor microvascular density (MVD) and vascular endothelial growth factor (VEGF) level were detected by immunohistochemical staining.</p><p><b>RESULTS</b>MVD and VEGF expression of tumors were much lower in the mice received LDM CTX therapy than those in control group and MTD CTX group (P < 0.05). During the experiment, growth delays of tumor were found in the mice received LDM CTX therapy, without apparent body weight loss or leukopenia, and the survival of mice was remarkably prolonged, compared with mice received MTD CTX therapy (P < 0.05).</p><p><b>CONCLUSIONS</b>The continuous low-dose regimen of CTX can significantly increase the therapeutic activity with decreased toxicity and prolonged animal survival for lung cancer. It may act as an antiangiogenic and lead to less drug resistance.</p>

17.
Chinese Journal of Integrated Traditional and Western Medicine ; (12): 730-733, 2005.
Article in Chinese | WPRIM | ID: wpr-269913

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the anti-angiogenetic effect of the combination of low-dose cyclophosphamide(CTX) and ginsenoside Rg3 in mice with Lewis lung carcinoma, and to observe the anti-tumor effect, toxicity, adverse reaction of the treatment and survival time of the tumor bearing mice.</p><p><b>METHODS</b>Holland C57/ BL6 Lewis lung carcinoma mice were taken as the model and randomly divided into 5 groups, i.e. the low-dose CTX (LDCTX) group, the maximum tolerable dose CTX (MTDCTX) group, the ginsenoside Rg3 (Rg3) group, the low-dose CTX combined with ginsenoside Rg3 group (LDCTX + Rg3), and the model group. Tumor volume, weight of mice, peripheral white blood cell counts and survival time of mice were observed, tumor microvascular density (MVD) and vascular endothelial growth factor (VEGF) gene expression were determined during the therapeutic course.</p><p><b>RESULTS</b>In the LDCTX group, tumor grew comparatively slow, no significant decrease in body weight or peripheral white blood cells, and survival time was prolonged. In the LDCTX + Rg3 group, the tumor inhibitory effect was more persistent and steady without any increase of toxicity or adverse reaction. Besides, the survival time of mice was prolonged (P < 0.01). MVD was lower in the LDCTX group than that in the MTDCTX group (P< 0. 05). Compared with the model group, MVD and VEGF expression were lower in the LDCTX and the Rg3 group, and the lowering action was more significant when the two drugs were used in combination (P < 0.05).</p><p><b>CONCLUSION</b>The combination of low-dose CTX and Rg3 has obvious synergetic action of anti-angiogenesis, it shows significant and persistent tumor inhibitory effect, with less toxic and adverse reaction, and could induce longer survival time than treatment of CTX or Rg3 alone.</p>


Subject(s)
Animals , Female , Mice , Angiogenesis Inhibitors , Therapeutic Uses , Antineoplastic Agents, Phytogenic , Therapeutic Uses , Carcinoma, Lewis Lung , Drug Therapy , Pathology , Cyclophosphamide , Drug Therapy, Combination , Ginsenosides , Therapeutic Uses , Mice, Inbred C57BL , Neovascularization, Pathologic , Random Allocation
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